(navigation image)
Home American Libraries | Canadian Libraries | Universal Library | Community Texts | Project Gutenberg | Children's Library | Biodiversity Heritage Library | Additional Collections
Search: Advanced Search
Anonymous User (login or join us)
Upload
See other formats

Full text of "Advisory Committee on Human Radiation Experiments : final report"


Advisory 

Committee 

on 

Human 

Radiation 

Experiments 



NATIONAL IjVSTITi 
NIHLIBR 









JAN 2 2 

BLDG 10, 10 CENTER DR 
BETHESDA, MD 20892-1150 



Advisory Committee 

on Human Radiation 

Experiments 

Final Report 



October 1995 



Additional copies of the Final Report of the Advisory Committee on Human 
Radiation Experiments (stock number 061-000-00-848-9) as well as copies of the 
Executive Summary and Guide to Final Report (stock number 061-000-00849-7) 
and the three supplemental volumes (061-000-00850-1, 061-000-00851-9, and 
061-000-00852-7) may be purchased from the Superintendent of Documents, U.S. 
Government Printing Office. 

All telephone orders should be directed to: 

Superintendent of Documents 

U.S. Government Printing Office 

Washington, D.C. 20402 

(202) 512-1800 

FAX (202) 512-2250 

8 a.m. to 4 p.m., Eastern time, M-F 

All mail orders should be directed to: 

U.S. Government Printing Office 
P.O. Box 371954 
Pittsburgh, PA 15250-7954 



An Internet site containing ACHRE information (replicating the Advisory 
Committee's original gopher) will be available at George Washington University. 
The site contains complete records of Advisory Committee actions as approved; 
complete descriptions of the primary research materials discovered and analyzed; 
complete descriptions of the print and non-print secondary resources used by the 
Advisory Committee; a copy of the Interim Report of October 21, 1994, and a 
copy of the Final Report; and other information. The address is 
http://www.seas.gwu.edu/nsarchive/radiation. The site will be maintained by the 
National Security Archive at GWU. 



Printed in the United States of America 



Contents 

PREFACE 1 

INTRODUCTION The Atomic Century 19 

PART I Ethics of Human Subjects Research: A Historical Perspective 

Overview 81 

1 Government Standards for Human Experiments: The 1940s and 1950s 83 

2 Postwar Professional Standards and Practices for Human Experiments .... 130 

3 Government Standards for Human Experiments: The 1960s and 1970s .... 171 

4 Ethics Standards in Retrospect 196 

PART II Case Studies 

Overview 227 

5 Experiments with Plutonium, Uranium, and Polonium 233 

6 The AEC Program of Radioisotope Distribution 283 

7 Nontherapeutic Research on Children 320 

8 Total-Body Irradiation: Problems When Research and Treatment Are 
Intertwined 366 

9 Prisoners: A Captive Research Population 42 1 

10 Atomic Veterans: Human Experimentation in Connection with Bomb 

Tests 454 

1 1 Intentional Releases: Lifting the Veil of Secrecy 506 

12 Observational Data Gathering 563 

13 Secrecy, Human Radiation Experiments, and Intentional Releases 619 

PART III Contemporary Projects 

Overview 669 

14 Current Federal Policies Governing Human Subjects Research 675 

1 5 Research Proposal Review Project 694 

16 Subject Interview Study 724 

Discussion of Part III 758 

PART IV Coming to Terms with the Past, Looking Ahead to the Future 

Overview 769 

1 7 Findings 777 

18 Recommendations 801 

Statement By Committee Member Jay Katz 847 

Official Documents 

Executive Order 857 

Charter | 862 

Appendices 

Acronyms and Abbreviations 869 

Glossary 878 

Selected Bibliography 886 

Public Comment Participants 892 

A Citizen's Guide to the Nation's Archives: Where the Records Are 

and How to Find Them 897 

iii 




advisory committee on human radiation Experiments 

1726 M STREET, N.W., SUITE 600 

WASHINGTON, D.C. 20036 _ . innc 

October 1995 

To the Members of the Human Radiation Interagency Working Group: 

Secretary Hazel O'Leaiy, Department of Energy 

Secretary William Perry, Department of Defense 

Attorney General Janet Reno, Department of Justice 

Secretary Donna Shalala, Department of Health and Human Sen-ices 

Secretary Jesse Brown. Department of Veterans Affairs 

Director Alice Rivlin, Office of Management and Budget 

Director John Deutch, Central Intelligence Agency 

Administrator Daniel Goldin, National Aeronautics and Space Administration 

On behalf of the Advisory Committee on Human Radiation Experiments, it is my 
privilege to transmit to you our Final Report. 

Since the Committee's first meeting in April 1994 we have been able to conduct 
an intensive inquiry into the history of government-sponsored human radiation 
experiments and intentional environmental releases of radiation that occurred between 
1944 and 1974. We have studied the ethical standards of that time and of today and have 
developed a moral framework for evaluating these experiments. Finally, we have 
examined the extent to which current policies and practices appear to protect the rights 
and interests of today's human subjects. This report documents our findings and makes 
recommendations for your consideration. 

The committee listened to the testimony of more than 200 public witnesses who 
appeared before us. We are deeply grateful to all these witnesses, who overcame the 
obstacles of geography and emotions to assist us. 

Our work and this report would not have been possible without the extraordinary 
effort the President and you put forward to open the government's records to our inquiry 
and thus to the nation. We are especially pleased that, through our joint efforts, the 
American people now have access to the tens of thousands of documents that bear on this 
important history. 

None of our conclusions came easily. We endeavored, both as individuals and as 
a committee, to live up to the responsibility with which we were entrusted. This report 
represents the consensus of fair-minded people who gave the best they had to offer to 
their fellow citizens. 

We thank President Clinton for this opportunity and for his courage and 
leadership in appointing the Advisory Committee. 



Ruth R. Faden 

Chair, Advisory Committee 

on Human Radiation Experiments 



® 



Printed with soy ink on recycled paper 



Advisory Committee on Human Radiation Experiments 

Ruth R. Faden. Ph.D.. M.RH.-Chair 

Philip Franklin Wagley Professor of Biomedical Ethics and Director 

The Bioethics Institute 

Johns Hopkins University 

Baltimore, Maryland 

Senior Research Scholar 

Kennedy Institute of Ethics 

Georgetown University 

Washington, D.C. 



Kenneth R. Feinberg, J.D. 

Kenneth R. Feinberg & Associates 
Washington, D.C. 

Eli Glatstein, M.D. 

Professor and Chair 
Department of Radiation Oncology 
The University of Texas 
Southwestern Medical Center at Dallas 
Dallas, Texas 

Jay Katz, M.D. 

Elizabeth K. Dollard Professor Emeritus 

of Law, Medicine and Psychiatry 
Harvey L. Karp Professorial Lecturer in Law 

and Psychoanalysis 
Yale Law School 
New Haven, Connecticut 

Patricia A. King, J.D. 

Professor of Law 

Georgetown University Law Center 

Washington, D.C. 

Susan E. Lederer, Ph.D. 

Associate Professor 

Department of Humanities 

The Pennsylvania State University College of Medicine 

Hershey, Pennsylvania 

Ruth Macklin, Ph.D. 

Professor of Bioethics 

Department of Epidemiology & Social Medicine 

Albert Einstein College of Medicine 

Bronx, New York 



Nancy L. Oleinick, Ph.D. 

Professor of Radiation Biochemistry 

Division of Radiation Biology 

Case Western Reserve University School of Medicine 

Cleveland, Ohio 

Henry D. Royal, M.D. 

Professor of Radiology 

Associate Director; Division of Nuclear Medicine 

Mallinckrodt Institute of Radiology 

Washington University Medical Center 

St. Louis, Missouri 

Philip K. Russell, M.D. 

Professor, Department of International Health 
Johns Hopkins University 
School of Hygiene and Public Health 
Baltimore, Maryland 

Mary Ann Stevenson, M.D., Ph.D. 

Assistant Professor of Radiation Oncology 
Joint Center for Radiation Therapy 
Harvard Medical School 
Boston, Massachusetts 

Deputy Chief 

New England Deaconess Hospital 
Department of Radiation Oncology 
Boston, Massachusetts 

Duncan C. Thomas, Ph.D. 

Director, Biostatistics Division 

Department of Preventive Medicine 

University of Southern California School of Medicine 

Los Angeles, California 



Lois L. Norris 

Second Vice President of Omaha National Bank 
and Omaha National Corporation (Retired) 
Omaha, Nebraska 



Reed V. Tuckson, M.D. 

President 

Charles Drew University of Medicine and Science 

Los Angeles, California 



Advisory Committee on Human Radiation Experiments 



Jeffrey Kahn 

Associate Director 



Dan Guttman 

Executive Director 



Anna Mastroianni 

Associate Director 



Stephen Klaidman 

Director of Communications 
Counselor to the Committee 



Sarah Flynn 

Editor 



Staff* 



Senior Policy and Research Analysts 

Barbara Berney 
James David 
John Harbert 
Gregg Herken 
Jonathan Moreno 
Ronald Neumann 
Gary Stem 
Jeremy Sugarman 
Donald Weightman 
Gilbert Whittemore 

Research Analysts 

Jonathan Engel 
Patrick Fitzgerald 
Mark Goodman 
Deborah Holland 
Denise Holmes 
Michael Jasny 
Gail Javitt 
Wilhelmine Miller 
Patricia Perentesis 
Kathy Taylor 
Sandra Thomas 
Faith Weiss 



Research Associates 

Miriam Bowling 
Praveen Fernandes 
Sara Chandros Hull 
Valerie Hurt 
John Kruger 
Ellen Lee 

Shobita Parthasarathy 
Noel Theodosiou 

Information Services 

David Saumweber, Director 
Robin Cochran, Librarian 
Tom Wisner, Senior Technology 
Consultant 

Communications and Outreach 

Lanny Keller 
Kristin Crotty 

Committee and Staff Affairs 

Jerry Garcia 
Jeanne Kepper 



Consultants 



Jeffrey Botkin 
Allen Buchanan 
Gwen Davis 
Gail Geller 
Steve Goodman 
Jon Harkness 
Rebecca Lowen 



Suzanne White Junod 
Nancy Kass 
Charles McCarthy 
Monica Schoch-Spana 
Patricia Stewart-Henney 
John Till 
E.W. Webster 



*includes both full-time and part-time staff 



acknowledgments 



T t 



he Committee's work over the past year and a half would have been 
impossible without the assistance of an extraordinary number of individuals and 
groups from all corners of the United States, and beyond. We wish to express the 
depth of our gratitude to the many people who assisted, informed, and advised us. 

Some of these people are identified by name elsewhere in this report and 
its supplemental volumes. An appendix in this volume lists the more than 200 
witnesses who appeared before the Committee at our public meetings in 
Washington, D.C., Cincinnati, Knoxville, San Francisco, Santa Fe, and Spokane. 
The supplemental volumes identify the dozens of individuals who agreed to 
formal, taped interviews in connection with the Committee's oral history projects. 
We thank all these people and many more: 

• The hundreds of people who contacted the Committee with information 
about their own experiences or the experiences of their family members. 
Many of these people shared not only their personal stories but also the 
information they had collected in the course of conducting their own 
research into government archives. 

• The representatives of many groups whose interests coincided with the 
work of the Committee. These include organizations of former subjects of 
biomedical radiation experiments (and their families), downwinders, 
atomic veterans, uranium miners, and workers in and around atomic 
energy communities. These groups, as well, shared the accumulated 
information and perspective of years of experience and research. 

• The numerous professionals in fields related to our research who gave of 
their time and expertise to provide information or comment on the myriad 
factual, technical, and policy questions before the Committee. These 
experts provided help in understanding areas ranging from military and 
human rights law to the laws of the atom, from the history of the 
government's use of secrecy to the history of radiation science. 

• The dozens of universities and independent hospitals, located in all 
regions of the country, that willingly provided us with the documents we 
needed to conduct our Research Proposal Review Project. 



vn 



A ckn o wledgm en (s 



The nearly 1,900 individuals who graciously participated in our Subject 
Interview Study, and the university hospitals, veterans hospitals, and 
community hospitals that permitted us to conduct the study. 

The numerous chairs of institutional review boards and radiation safety 
committees who were kind enough to share with us their views about the 
current status of human subject protections. 

Archivists at public and private libraries, universities, and research 
institutions, who assisted the Committee in our search for information. 

The many journalists and scholars who have previously researched and 
written about the subjects covered in this report, for sharing the 
knowledge and wisdom embodied in their own many years of inquiry and 
reflection. 

A variety of state and local agencies for sharing with the Committee the 
results of their own reviews of activities that we explored. 

Members of Congress and congressional staff, including the staffs of the 
General Accounting Office and the Office of Technology Assessment, for 
sharing the product of their own prior inquiries into many of the areas 
discussed in this report. 

The members of the Human Radiation Interagency Working Group, who 
provided invaluable assistance. We are particularly grateful to the many 
employees at the Department of Energy, the Department of Defense, the 
Department of Health and Human Services, the Department of Veterans 
Affairs, the National Aeronautics and Space Administration, and the 
Central Intelligence Agency, who aided us in the search and retrieval of 
the many thousands of documents that provide the backbone for the 
Committee's review of human radiation experiments that took place 
between 1944 and 1974 and the history of government requirements for 
the conduct of that research. We are also grateful to the staffs of the 
Nuclear Regulatory Commission and the National Archives and Records 
Administration for their invaluable assistance. Many of the same people, 
as well as others, also provided advice and information as we undertook 
our evaluation of the conduct of research involving human subjects today. 



We wish to thank both the professional and administrative members of our 
staff who worked so hard and showed such dedication to our task. Their talent, 
energy, and commitment provided the foundation for our work. It is impossible 
to overstate our gratitude and appreciation for their extraordinary efforts. 

Finally, we wish to acknowledge our indebtedness to President Clinton for 
the honor he bestowed upon us when he selected us to serve on the Advisory 
Committee. 



Vlll 



Documentary Note 



In fulfilling its mandate, the Advisory Committee on Human Radiation 
Experiments (ACHRE) relied on several thousand separate sources: primary and 
secondary published monographs, journal articles, historical records and 
manuscripts, original correspondence and surveys, interviews, specially 
constructed databases, searches of public and commercial databases, and 
documentary films. Only a fraction of these, however, is represented in the final 
report. More extensive information may be found in the supplemental volume 
Sources and Documentation, which contains a full account of the ACHRE 
research program, a finding aid to the complete research document collection, a 
bibliography of published sources used, an index to significant documents and 
identified experiments, and other auxiliary materials. Further information both 
about the sources used by the Advisory Committee generally and about the 
particular sources cited in this volume should be sought there. 

The unpublished documents referenced in this report are identified by 
their places in the ACHRE Research Document Collection. These identifiers, or 
ACHRE document numbers, have four parts: originating institution, date of 
receipt, order of receipt, and document number. For example, DOE-05 1094-A- 
123 is the 123d document described in the first ("A") Department of Energy 
("DOE") shipment (or accession) received on May 10, 1994 ("051094"). One of 
the appendices, A Citizen's Guide to the Nation's Archives, provides instructions 
for using references to the ACHRE collection to find documents there and in the 
collections of the National Archives and at the agencies. 



IX 



FINAL REPORT 



Preface 



Un January 15, 1994, President Clinton created the Advisory Committee 
on Human Radiation Experiments in response to his concern about the growing 
number of reports describing possibly unethical conduct of the U.S. government, 
and institutions funded by the government, in the use of, or exposure to, ionizing 
radiation in human beings at the height of the Cold War. He directed us to 
uncover the history of human radiation experiments and intentional environmental 
releases of radiation; to identify the ethical and scientific standards for evaluating 
these events; and to make recommendations to ensure that whatever wrongdoing 
may have occurred in the past cannot be repeated. 

The Advisory Committee is composed of fourteen members: a citizen 
representative and thirteen experts in bioethics, radiation oncology and biology, 
epidemiology and statistics, public health, history of science and medicine, 
nuclear medicine, and law. We report to a Cabinet-level group convened by the 
President (the Human Radiation Interagency Working Group), whose members 
are the secretaries of defense, energy, health and human services, and veterans 
affairs; the attorney general; the administrator of the National Aeronautics and 
Space Administration; the director of the Central Intelligence Agency; and the 
director of the Office of Management and Budget. 

On April 21, 1994, at the end of the first day of our opening meeting, 
President Clinton invited us to the White House to personally communicate his 
commitment to the process we were about to undertake. He urged us to be fair, 
thorough, and unafraid to shine the light of truth on this hidden and poorly 
understood aspect of our nation's past. Our most important task, he said, was to 
tell the full story to the American public. At the same time, we were also to 
examine the present, to determine how the conduct of human radiation research 
today compares with that of the past and to assess whether, in the light of this 
inquiry, changes need to be made in the policies of the federal government to 
better protect the American people. This report and the accompanying 

1 



Preface 

supplemental volumes constitute the Committee's attempt to tell the story of the 
past and to report on our inquiry into the present. 

WHY THE COMMITTEE WAS CREATED 

Past research with human subjects, including human radiation research, 
has been a source of life-saving knowledge. Research involving human subjects 
continues to be essential to the progress of medical science, since most advances 
in medicine must at some point in their development be tested in human subjects. 
Every one of us who has been either a patient or a loved one of a patient has 
benefited from knowledge gained through research with human subjects. But 
medical science, like all science, does not proceed or progress without the taking 
of risks. In medical research, these risks often fall on the human subject, who 
sometimes does not stand to benefit personally from the knowledge gained. This 
is the source of the moral tension at the core of the enterprise of research 
involving human subjects. In order to secure important collective goods- 
scientific knowledge and advances in medicine-individuals are put in harm's 
way. The moral challenge is how to protect the rights and interests of these 
individuals while enabling and encouraging the advancement of science. 

The Committee had its origins when public controversy developed 
surrounding human radiation experiments that were conducted half a century 
ago. In November 1993, the Albuquerque Tribune published a series of articles 
that, for the first time, publicly revealed the names of Americans who had been 
injected with plutonium, the man-made material that was a key ingredient of the 
atom bomb. Reporter Eileen Welsome put a human face to what had previously 
been anonymous data published in official reports and technical journals. As 
World War II was ending, she wrote, doctors in the United States injected a 
number of hospitalized patients with plutonium, very likely without their 
knowledge or consent. The injections were part of a group of experiments to 
determine how plutonium courses through the human body. The experiments, 
and the very existence of plutonium, were shrouded in secrecy. They were 
conducted at the direction of the U.S. government, with the assistance of 
university researchers in Berkeley, Chicago, and Rochester (New York), with the 
expectation that the information gained could be used to limit the hazards to the 
thousands of workers laboring to build the bomb. 

On reading the articles, Secretary of Energy Hazel O'Leary expressed 
shock, first to her staff, and then in response to a question posed at a press 
conference. She was particularly concerned because the Department of Energy 
had its earliest origins in the agencies responsible for building the atomic bomb 
and sponsoring the plutonium experiments. During the Cold War, these agencies 
had continued to do much of their work in the twilight zone between openness 
and secrecy. Now, the Cold War was over. The time had come, Secretary 



Preface 

O'Leary determined, to make public anything that remained to be told about the 
plutonium experiments. 

Subsequent press reports soon noted that the plutonium injections were 
not the only human radiation experiments that had been conducted during the war 
and the decades that followed. In Massachusetts, the press reported that members 
of the "science club" at the Fernald School for the Retarded had been fed oatmeal 
containing minute amounts of radioactive material. In Ohio, news articles revived 
an old controversy about University of Cincinnati researchers who had been 
funded by the Defense Department to gather data on the effects of "total-body 
irradiation" on cancer patients. In the Northwest, the papers retold the story of 
Atomic Energy Commission funding of researchers to irradiate the testicles of 
inmates in Oregon and Washington prisons in order to gain knowledge for use in 
government programs. The virtually forgotten 1986 report prepared by a 
subcommittee headed by U.S. Representative Edward Markey, "American 
Nuclear Guinea Pigs: Three Decades of Radiation Experiments on U.S. 
Citizens," was also recalled to public attention. 1 

Coincidentally, the fact that the environment had also been used as a 
secret laboratory became a subject of controversy. A November 1993 
congressional report uncovered thirteen cases in which government agencies had 
intentionally released radiation into the environment without notifying the 
affected populations. 2 At various times, tests were conducted in Tennessee, Utah, 
New Mexico, and Washington state. This report had been prepared at the request 
of Senator John Glenn in his capacity as chair of a committee that had undertaken 
a comprehensive oversight investigation of the nuclear weapons complex. As a 
young marine in 1945, the senator was in a squadron being trained for possible 
deployment to Japan when the atomic bomb ended the war; as an astronaut, he 
had been the subject of constant testing and medical monitoring by space 
administration flight surgeons; as a senator he was at the center of the country's 
efforts to understand and control nuclear weapons. Senator Glenn understood the 
importance of national security, but he found it "inconceivable . . . that, even at 
the height of the communist threat, some of our scientists and doctors and military 
and perhaps political leaders approved some of these experiments to be conducted 
on an unknowing and unwitting public." 3 

In the immediate aftermath of Secretary O'Leary's press conference and 
the further press reports, thousands of callers flooded the Department of Energy's 
phone lines to recount their own experiences and those of friends and family 
members. 

Underlying the outrage and concern expressed by government officials 
and members of the public were many unanswered questions. How many human 
radiation experiments were conducted? No one knew if the number was closer to 
100 or 1,000. Were all the human radiation experiments done in secret, and were 
any of them still secret? Are any secret or controversial studies still ongoing? 



Preface 

Scientists and science journalists pointed out that some of the highly publicized 
experiments had long ago been the subject of technical journal articles, even press 
accounts, and were old news; other commentators countered that, for most of the 
public, articles in technical journals might as well be secret. 

How, why, and from what population groups were subjects selected for 
experiments? Some suspected that subjects were disproportionately chosen from 
the most vulnerable populations-children, hospitalized patients, the retarded, the 
poor—those too powerless to resist the government and its researchers. 

Did the experiments benefit the American people through the 
advancement of science and the enhancement of the ability to treat disease? 

How many intentional releases took place, and how many people were 
unknowingly put at risk? The answer here was sketchy; the releases identified in 
the November 1993 Glenn report had all been performed in secret, and much 
information about them was still secret. 

How great were the risks to which people were exposed? Many pointed 
out that radiation is not only present in our natural environment, but that, as a 
result of biomedical research, most people routinely rely on radiation as a means 
of diagnosing and treating disease. Others noted that while this is so, radiation 
can be abused, and the potential dangers of low-level exposure are still not well 
understood. 

What did our government and the medical researchers it sponsored do to 
ensure that the subjects were informed of what would be done to them and that 
they were given meaningful opportunities to consent? Today, federal government 
rules require the prior review of proposed experiments, to ensure that the risks 
and potential benefits have been considered and that subjects will be adequately 
informed and given the opportunity to consent. But the standards of today, many 
historians and scholars of medical ethics noted, are not those of yesterday. 
Others, however, declared that it was self-evident that no one should be 
experimented upon without his or her voluntary consent. Indeed, it was pointed 
out that this very principle was proclaimed aloud to the world in 1947, as the 
plutonium experiments were coming to a close. It was the American judges at the 
international war crimes trials in Nuremberg, Germany, who invoked the 
principle in finding doctors guilty of war crimes for their vile experiments on 
inmates of Nazi concentration camps. How could yesterday's standard have been 
less strict than that of today? How, moreover, could the standard not have been 
known by the government that sponsored the experiments and the researchers 
who conducted them? 

Finally, there were questions about how human experiments are 
conducted today. Insofar as wrong things happened in the past, how confident 
should we be that they could not happen again? Have practices changed? Do we 
have the right rules, and are they implemented and enforced? 



4 



Preface 
THE PRESIDENT'S CHARGE 

The Advisory Committee was created under the Federal Advisory 
Committee Act of 1972, which provides that committee meetings and basic 
decision making be conducted in the open. The Committee's charter 4 defined 
human radiation experiments to include 

(1) experiments on individuals involving intentional exposure to 
ionizing radiation. This category does not include common and 
routine clinical practices. . . . 

(2) experiments involving intentional environmental releases of 
radiation that (A) were designed to test human health effects of 
ionizing radiation; or (B) were designed to test the extent of human 
exposure to ionizing radiation. 

The Committee was mandated to review experiments conducted between 
1944 and 1974, the latter being the year that the U.S. Department of Health, 
Education, and Welfare issued rules for the protection of human subjects of 
federally sponsored research. The Committee was asked to determine the ethical 
and scientific standards by which to evaluate the pre- 1974 experiments and the 
extent to which these experiments were consistent with such standards. We were 
also to "consider whether (A) there was a clear medical or scientific purpose for 
the experiments; (B) appropriate medical follow-up was conducted; and (C) the 
experiments' design and administration adequately met the ethical and scientific 
criteria, including standards of informed consent, that prevailed at the time of the 
experiments and that exists today." The charter also directed that, upon 
completing our review, the Committee may recommend that subjects (or families) 
be notified of potential health risks and the need for medical follow-up and also 
that we "may recommend further policies, as needed, to ensure compliance with 
recommended ethical and scientific standards for human radiation experiments." 

In order to inform the public about the conduct of research involving 
human subjects taking place today, we were authorized to sample and consider 
examples of research with human subjects currently under way. 

In essence, we were to answer several fundamental questions: (1) What 
was the federal government's role in human radiation experiments conducted from 
1944 to 1974? (2) By what standards should the ethics of these experiments be 
evaluated? and (3) What lessons learned from studying past and present research 
standards and practices should be applied to the future? 

In addition, while the Committee was not expressly charged with 
considering issues relating to remedies, including financial compensation, we 
have felt obliged to address the type of remedies that we believe the government, 



Preface 

as an ethical matter, should provide to subjects of experiments where the 
circumstances warranted such a response. 

THE COMMITTEES APPROACH 

When those of us selected by President Clinton to serve on the Committee 
read about human radiation experiments in our hometown newspapers during the 
1993 holiday season, none of us imagined that within months we would be 
embarking on such an intense and challenging investigation of an important 
aspect of our nation's past and present, requiring new insights and difficult 
judgments about enduring ethical questions. 

On April 2 1 and 22, 1 994, the Committee held its first meeting, and most 
of us met each other for the first time. As we listened to opening statements by 
Cabinet members and members of Congress, as well as the first witness from the 
general public, it became clear how daunting a task we were undertaking. We 
realized that our ability to reconstruct the story of past radiation experiments 
required both the capacity to join with the agencies in the search through 
thousands of boxes for documents and the intuition to recognize which documents 
were important. We knew that the ability to tell that story depended on our ability 
to understand the full range of technically complex, often emotionally charged 
issues related to human radiation experiments. We could not understand, much 
less tell, the story until we sought out all who could enhance our understanding, a 
difficult job because the voices to which we had to listen spoke in the varied 
languages of medicine, a multiplicity of scientific disciplines, the military, 
policymakers, philosophers, patients, healthy subjects, family members of former 
subjects, and individuals in a variety of other roles. 

Finally, we were also convinced that an important determinant of our 
success in keeping faith with the American people would be to understand not 
only how human subject research was conducted in the past but also how it is 
being conducted in the present. 

Reaching In and Reaching Out 

As we began our work, Committee members first sought to educate one 
another. Early meetings included basic presentations on such topics as research 
ethics, radiation, the history of human experimentation, the law of remedies, and 
the debate over the effects of low levels of radiation. 

Then we determined to search broadly for those who could contribute to 
our understanding. We hired a staff with the expertise and experience need for 
the Committee's myriad tasks. Finally, we sought to make ourselves available to 
those who wanted to speak to us directly, especially people who felt they or their 
loved ones were harmed, or might have been harmed, by human radiation-related 



Preface 



research or exposure. Each of the Committee's meetings reserved a period for 
public comment. Since April 1994, the full Committee held sixteen public 
meetings, each of two to three days' duration. Fifteen of those meetings were held 
in Washington, D.C., and one was in San Francisco. In addition,; subsets of 
Committee members presided over public forums in Cincinnati, Knoxville, Santa 
Fe and Spokane. We traveled to these different cities in order to hear from 
people who could not come to Washington, D.C., and lived in communities 
where, or near where, experiments or intentional releases of interest to the 
Committee had taken place. We further sought to reach out to those who could 
not attend our meetings. By phone, mail, and personal visit, we and our staff 
communicated with members of the public, researchers, attorneys, investigative 
reporters, authors, and representatives of dozens of groups of interested people 
who shared some aspect of the Committee's concern. 

The Records of Our Past: The Search for Documents 

One of the most difficult tasks before the Committee was determining how 
many federally sponsored human radiation experiments occurred between 1944 
and 1974 and who conducted them. When President Clinton established the 
Committee, he also directed the Human Radiation Interagency Working Group to 
provide us with all relevant documentary information in each of the agencies 
files Teams were formed to identify the hundreds of government sites where 
relevant documents might be located. We discovered there was no easy way to 
identify how many experiments had been conducted, where they took place and 
which government agencies had sponsored them. The location and retrieval of 
documents thus required an extraordinary effort, and we appreciate the assistance 

of all our collaborators. . , ... 

We began with documents that were assembled during the 1980s and that 
provided the basis for the Markey report. But review of those materials 
confirmed that, even for this relatively well-known group of u ex P^ m ^ ; basic 
information was lacking. We found that the Department of Health ; an Humm 
Services (DHHS), which is the primary government sponsor of research involving 
human subjects, reported that, as permitted by federal records laws it had long 
since discarded files on experiments performed decades ago. Furthermore, the 
capsule descriptions of research that remained sometimes did not make clear 
whether the subjects of research had been humans or animals To complicate 
matters further, the DHHS also pointed out that much research documentation had 
originated and been retained only in the files of nonfederal grantee institutions 
and investigators. Other agencies did provide some lists of experiments, in many 
cases however, there was no information on basic questions of concern (tor 
example, who the subjects were and what, if anything, they were told). 

What rules or policies, if any, existed to govern federally sponsored 



Preface 

experiments in the pre- 1974 period? The prevailing assumption was that, with a 
few notable exceptions, it was not until the mid-1960s that federal agencies began 
to develop such policies in any significant way. Most scholarship focused on 
divisions of the (then) Department of Health, Education, and Welfare. Little was 
known about approaches to human experimentation at the Atomic Energy 
Commission and the Department of Defense. Yet it was clear from the outset of 
our inquiry that these agencies, as well as the DHEW, were central to the story of 
human radiation experiments and that many of the experiments of interest 
predated by decades the mid-1960s' interest in human subject protections. 

As we began our search into the past, we found that it was necessary to 
reconstruct a vanished world. The Committee and the agencies had to collect 
information scattered in warehouses throughout the country. At the same time, 
we had to create and test the framework needed to ensure that there would be a 
"big picture" into which all the pieces of the puzzle would fit. 

After a few months, the outlines of a world that had been almost lost 
began to reemerge. Working with the Defense Department, we discovered that 
long-forgotten government entities had played central roles in the planning of 
midcentury atomic warfare-related medical research and experimentation. These 
groups, the piecing together of long-lost or forgotten records would show, 
debated the ethics of human experimentation and discussed possible human 
radiation experimentation: Similarly, working with the Department of Energy, we 
pieced together the minutes, and even many transcripts, of the key medical 
advisory committee to the Atomic Energy Commission. We sought to mine 
agency histories, when th£y existed: for example, at the Committee's request, the 
Defense Nuclear Agency (the heir to the part of the Manhattan Project that was 
transferred to the Defense Department) made public portions of the more than 500 
internal histories that chronicle its story, most of which had previously been 
available only to those with security clearances. 

Despite these successes, it became evident that the records of much of our 
nation's recent history had been irretrievably lost or simply could not be located. 
The Department of Energy told the Committee that all the records of the 
Intelligence Division of its predecessor, the Atomic Energy Commission, had 
been destroyed— mainly during the 1970s, but in some cases as late as 1989. The 
CIA explained, as had been previously reported, that records of the program 
known as MK.ULTRA, in which unwitting subjects were experimented upon with 
a variety of substances, had been destroyed during the 1970s, when the program 
became a widely publicized scandal. Though documents related to the program 
referred to radiation, the CIA concluded that human experiments using ionizing 
radiation never took place under that program, based on currently available 
evidence. 

We also turned to nongovernmental archives throughout the country. 
Cryptic notes and fragments of correspondence located in private and university 

8 



Preface 

archives were fitted into our growing outline. For example, a copy of an 
important 1954 Army surgeon general research policy statement, referenced in 
Defense Department documents, was found at Yale University among the papers 

of a Nobel laureate. . , 

Bv the end of our term, the Committee had received, organized, and 
reviewed hundreds of thousands of pages of documents from public and private 
archives This collection will be available to individuals and scholars who wish 
to pursue the great many stories that remain to be told, and we view this as one of 
our most significant contributions. 

The Records of Our Past: The Memories of the People 

The Committee listened to the testimony of more than 200 public 
witnesses who appeared before us. We heard from people or their family 
members who had been subjects in controversial radiation experiments, including 
the plutonium injections, total-body irradiation experimen ts and ex Penments 
involving the use of radioactive tracers with institutionalized children. We heard 
from "atomic veterans": soldiers who had been marched to ground zero at atomic 
bomb tests, sailors who had walked the decks of ships contaminated by 
radioactive mist, and pilots who had flown through radioactive mushroom clouds. 
We also heard from their widows. We heard from people who lived "downwind 
from nuclear weapons tests in Nevada and intentional releases of radioactive 
material in Washington state. We heard from Navajo miners who had served the 
Country in uranium mines filled with radioactive dust, from native Alaskans who 
had been experimented upon by a military cold weather research . lab, and I from 
Marshall Islanders, whose Pacific homeland had been contaminated by fallout 
after a 1954 hvdrogen bomb test. 

We heard from officials and researchers responsible for human t research 
today and from those who were present at or near the dawn of the Cold War. We 
heard from individuals who, on their own time, had long been seeking to piece 
together the story of human radiation experiments and offered to share their 
findings. We heard from scholars, from members of Congress, and from people 
who wanted to bear witness for those who could no longer speak We heard from 
a woman who, as a high-school student intern decades ago, attended at the 
bedside while a terminally ill patient was injected with uranium and from a 
powerfully spoken veteran of the nuclear weapons work force who told of the 
"bodv snatching" of dead friends in the name of science. 

Most important, we heard from many people who believed that something 
involving the government and radiation happened to them or their loved ones 
decades ago; most had been unable to find out exactly what had happened, or 
whv and now they wanted to know the truth. These witnesses spoke eloquent y 
of their pain, their frustration, and the reasons they do not trust the government. 



Preface 

Their very appearance before the Committee testified to a commitment to the 
country and to the value of the nation's effort to understand its past. We are 
deeply grateful to all of these witnesses, who overcame the obstacles of 
geography and emotions to participate in this work. 

We combined our public meetings with additional efforts to interview, and 
record for the nation's archives, those who could shed light on Cold War human 
radiation experiments and on the ethics of biomedical experimentation. Dozens 
of interviews were conducted with former government officials responsible for 
programs that included radiation research, as well as with radiation researchers. 

In Mississippi we talked with a retired general who served as a military 
assistant to secretaries of defense in the 1940s and 1950s; in Berkeley, we talked 
with the chemist who was one of the discoverers of plutonium; in Rhode Island 
we talked with the physicist who served as the link between the civilian health 
and safety agencies and the Cold War military research efforts; in Florida we 
talked with a pioneer in health physics, a discipline created to provide for the 
safety of nuclear weapons workers; in San Francisco and Washington, D.C., we 
talked to the lawyers who advised the Atomic Energy Commission at its postwar 
creation; in New York we talked with the Navy radiation researcher who was 
rousted from his Maryland laboratory to respond to the emergency created by the 
exposure of the Marshall Islanders; in San Diego we talked with a researcher 
whose own career and massive history of radiation research had covered much of 
the Committee's territory. 

We also launched a special effort, called the Ethics Oral History Project, 
to learn from eminent physicians who were beginning their careers in academic 
medicine in the 1940s and 1950s about how research with human subjects was 
then conducted. The Ethics Oral History Project also included interviews with 
two people who had been administrators of the National Institutes of Health 
during the 1950s, since they were intimately involved with ethical and legal 
aspects of research involving human subjects at the time. 

We listened to all these people and more, and through their testimony, this 
report is informed. 

Bounds of Our Inquiry 

In the course of listening to public testimony, it became clear to us that 
confusion exists about what an experiment is and whether it can be distinguished 
from other activities in which people are put at risk and information is gathered 
about them. The biomedical community, for example, struggles with the 
distinction between scientific research and related activities. In a medical setting, 
it is sometimes hard to distinguish a formal experiment designed to test the 
effectiveness of a treatment from ordinary medical care in which the same 
treatment is being administered outside of a research project. The patient 



10 



Preface 



receiving the treatment may discern no difference between the two but the 
Sn is relevant to questions of ethics. The physician-investigator may face 
conflicts between the obligation to do what is best for each individual patient .and 
the requirements of scientific research, whereas the physician involved only in 
clinical care has a responsibility solely to the patient. 

Similarly, in an occupational setting in which employees are put at risk, it 
is often difficult to distinguish formal scientific efforts to study effects on the 
health of employees fromroutine monitoring of employees exposure to hazards 
in the work place for purposes of ensuring worker safety. In the first case, the 
r^les of research ethics apply; in the second they do not. And yet here too, the 
worker may discern no difference between the two activities. A further 
complication for the Committee to consider was the fact that research in 
occupational settings rarely takes the form of a classic experiment, in which the 
investigator controls the variable under study and then randomly assigns subjects 
to be in the "treatment" or "control" group. Instead, most occupational research 
employs observational and statistical methods, drawing most heavily from the 
field of epidemiology. These distinctions were unimportant, however to Mhe 
representatives of atomic veterans, uranium miners, and residents of the Marshall 
Islands, who told us of their belief that they, or those they spoke for, were 

subjects of research. j-„*:„„ 

The Committee struggled with how strictly to define human radiation 
experiments for purposes of our inquiry. There is no sin gle clear definition of an 
experiment that is widely subscribed to by every member of the biomedical 
community. Even our description above of a classic experiment is open to 
contest Today, as well as in the past, the scientific community has rarely 
employed the term experiment in discussions of biomedical research; other terms, 
not necessarily synonymous-such as clinical study, clinical investigation, quasi 
Zeriment, and case control study--** all used. We concluded that it was not 
possible to interpret our charge by stipulating an artificial definition of human 
radiation experiment. Instead, in keeping with the realities of bl0 ™ e ? ical 
research, we decided to interpret our charge broadly, as including both research 
involving human subjects in which the research design called for exposing 
subjects to ionizing radiation and research designed to study the effects of 
radiation exposure resulting from nonexpenmental activities. 

This latter category includes the research involving uranium miners and 
Marshall Islanders. In these cases we quickly determined that it was in some 
respects impossible to isolate the ethical questions raised by the research from the 
ethics of the context in which the research was conducted. A centra issue was 
the exposure of people to risk, regardless of whether they were clearly understood 
to be subjects of research. This characterization is true, as well, of the experience 
of atomic veterans. As a consequence, we considered events that might be said to 
be on the boundary between research and some other activity. Our inquiry 

11 



Preface 

underscored the importance for social policy of the need to keep focused on 
questions of risk and well-being regardless of what side of that boundary the 
activity producing the risk falls. 

Human Experimentation Today 

In tandem with the reconstruction of the past, we undertook three projects 
to examine the current state of human radiation experiments. 

First, we studied how each agency of the federal government that 
currently conducts or funds research involving human subjects regulates this 
activity and oversees it. We surveyed what the operative rules are, how they are 
implemented, and how they are enforced. 

Second, from among the very large number of research projects involving 
human subjects currently supported by the federal government, we randomly 
selected 125 research projects for scrutiny by the Committee. For each of these 
projects, we reviewed all available relevant documentation to assess how well it 
appeared the rights and interests of the subjects participating in these projects 
were being protected. The success of this review required the cooperation of 
private research institutions all over the country, on whom we were dependent for 
access to important documents. We had expected that perhaps no more than half 
of those asked to cooperate would agree to do so, but with little hesitation, all of 
the research centers that we approached agreed to cooperate. 

Third, to learn from the subjects themselves, the Committee interviewed 
almost 1,900 patients receiving medical care in outpatient facilities of private and 
federal hospitals throughout the country. We asked patients about their attitudes 
toward medical research with human subjects and about the meaning they attach 
to the different terms used to explain medical research to potential subjects. We 
ascertained, and attempted to verify, how many of these patients were currently or 
ever had been subjects of research. Patient-subjects were asked about their 
reasons for agreeing to join research projects; patients who reported having 
refused offers to enter research projects were asked why they had decided against 
participating. 

In all three of these projects, we focused not only on human radiation 
experiments but on human research generally. In critical (but not all) respects, 
the government regulations that apply to human radiation research do not differ 
from those that govern other kinds of research involving human subjects. 
Moreover, the underlying ethical principles that should guide the conduct of 
research are identical, whether one is considering human radiation research or all 
research with human subjects. Finally, the Committee hoped to learn whether, in 
practice, there are any differences between the conduct of radiation and 
nonradiation experiments. 



12 



Preface 
LESSONS FROM HISTORY: LOOKING TO THE FUTURE 

What we have found is a story about the government's attempt to serve 
two critical purposes: safeguarding national security and advancing medical 
knowledge. One-half century ago, the U.S. government and its experts in the 
fields of radiation and medicine were seeking to learn more about radiation in 
order to protect workers, service personnel, and the general public against 
potential atomic war and individuals against the menace of disease. 

Toward these laudable ends, the government used patients, workers, 
soldiers, and others as experimental subjects. It acted through the experts to 
whom we regularly entrust the well-being of our country and our selves: elected 
officials, civil servants, generals, physicians, and medical researchers. 

Moreover, the government acted with full knowledge that the use of 
individuals to serve the ends of government raises basic ethical questions. If, as 
we look back, there could be doubt about the importance of the matter to the 
leaders of the time, we need only look to the appearance before the U.S. Senate of 
David Lilienthal, who had been nominated to serve as the first chairman of the 
Atomic Energy Commission, the civilian successor to the Manhattan Project and 
the predecessor to today's Department of Energy. In his testimony, Lilienthal 
forcefully stated: 

... all Government and private institutions must be 
designed to promote and protect and defend the 
integrity and the dignity of the individual. . . . Any 
forms of government . . . which make men means 
rather than ends in themselves ... are contrary to 
this conception; and therefore I am deeply opposed 
to them. . . . The fundamental tenet of communism 
is that the state is an end in itself, and that therefore 
the powers which the state exercises over the 
individual are without any ethical standards to limit 
them. This I deeply disbelieve. 6 

What did happen when individuals were sometimes used as means to 
achieve national goals? How well were the national goals of preserving the peace 
and advancing medical science reconciled with the equally important end of 
respect for individual dignity and health? What rules were followed to protect 
people, and how well did they work? Was the public let in on the balancing of 
collective and individual interest? In what sense did the public, in general, and 
individuals, in particular, know what was happening and have the opportunity to 
provide their meaningful consent? 

In this report we try to convey our understanding of how, when only good 

13 



Preface 

was sought, when its pursuit was entrusted to the experts on whom we most 
relied, and when missions were substantially accomplished, distrust, as well as 
accomplishment, remains. 

We focus on the ways in which the government and its experts recognized 
the interest of individual dignity and sought to strike a balance with the national 
interests being pursued. We focus equally on the extent to which the public was 
privy to this balancing. In particular, we try to show how individuals' 
understanding and participation were limited by the conjunction of government 
secrecy and expert knowledge. 

All Americans should experience immense satisfaction in the strides that 
have been made toward accomplishing both our national security and our medical 
research goals. However, as attested to by the many thousands of letters and calls 
that led to the Committee's creation, and the eloquent statements of the witnesses 
who appeared before us, this pride is diluted by a bitter aftertaste-distrust by 
many Americans of the federal government and those who served it. 

The government has the power to create and keep secrets of immense 
importance to us all. Secret keeping is a part of life. Secret keeping by the 
government may be in the national interest. However, if government is to be 
trusted, it is important to know, at the very least, the basic rules of secrecy and to 
know that they are reasonable and that they are being followed. 

Similarly, experts, by training and experience, have knowledge that 
individual people must, as a practical matter, rely on. However, legitimate 
questions arise when experts wear multiple hats or when they are relied on in 
areas beyond their expertise. 

Where official secrecy is coupled with expert authority, and both are 
focused on a public that is not privy to secrets and does not speak the languages 
of experts, the potential for distrust is substantial. 

In telling the story, and asking the questions, we have kept our eyes open 
for ways in which lost trust can be restored. It might be presumed that the past 
we report on here is so different from the present that it will be of little use in 
understanding research involving human subjects today. In fact, as we shall see, 
basic questions posed by the story of human radiation experiments conducted 
during the 1944-1974 period are no less relevant today. Then, as now, there were 
standards; the question is how they worked to protect individuals and the public. 
Then, as now, the ethical impulse was complexly alloyed with concerns for legal 
liability and public image. Then, as now, the most difficult questions often 
concerned the scope and practical meaning of ethical rules, rather than their 
necessity. The country has come to recognize, from its experience of the past half 
century, that tinkering with the regulations that govern publicly supported 
institutions, imposing ethical codes on experts, and altering the balance between 
secrecy and openness are important but not always sufficient means of reform. 
The most important element is a citizenry that understands the limits of these 



14 



Preface 

activities. That is why the purpose of this story is not simply to leam which 
changes to make in rules or policies that apply to government or professionals, 
but to begin to learn something more about how the Cold War world worked, as 
the most important means to making the world of tomorrow work better. 

HOW THIS REPORT IS ORGANIZED 

Though this report is addressed largely to those who can affect future 
policy in light of the information the Advisory Committee has gathered, 
specifically the Human Radiation Interagency Working Group, it has been written 
in such a way that it should be accessible to a wide range of interested readers. 

We begin with an introduction, titled "The Atomic Century," which 
describes the intersection of several developments: the birth and remarkable 
growth of radiation science; the parallel changes in medicine and medical 
research; and the intersection of these changes with government programs that 
called on medical researchers to play important new roles beyond that involved in 
the traditional doctor-patient relationship. The introduction concludes with a 
section titled "The Basics of Radiation Science" for the lay reader. 

The remainder of the text is divided into four parts. Each part is preceded 
by an overview. 

Part I, "Ethics of Human Subjects Research: A Historical Perspective," 
which contains four chapters, explores how both federal government agencies and 
the medical profession approached human experimentation in the period 1944 
through 1974. We begin with the story of the principles stated at midcentury at 
the highest levels of the Cold War medical research bureaucracies and what we 
have ascertained about whether these principles were translated into federal rules 
or requirements. We then turn to the norms and practices engaged in at the time 
by medical researchers themselves. It is in this chapter that we report the results 
of our Ethics Oral History Project. In chapter 3, we review the development of 
formal and public regulations concerning research involving human subjects in 
the 1960s and 1970s. In the last chapter in part I we present our framework for 
evaluating the ethics of human radiation experiments, grounded in both history 
and philosophical analysis. 

Part II, "Case Studies," approaches particular experiments from several 
angles, each of which raises overlapping ethical questions. The chapters on the 
plutonium injections and total-body irradiation consider the use of sick patients to 
provide data needed to protect the health of workers engaged in the production of 
nuclear weapons; the chapter on prisoners considers the use of healthy subjects 
for this purpose; the chapter on children considers experimentation with 
particularly vulnerable people; and the chapter on the AEC program of 
radioisotope distribution considers the institutional safeguards that underlay the 
conduct of thousands of human radiation experiments. The chapters on 

15 



Preface 

intentional releases, atomic veterans, and observational studies consider, in 
common, situations in which entire groups of people were exposed to risk as a 
consequence of government-sponsored Cold War programs. The section 
concludes with a review of the degree to which secrecy impaired, and may still 
impair, our ability to understand human radiation experiments and intentional 
releases conducted in the 1944-1974 period. 

Part III, "Contemporary Projects," reports the findings of our three 
inquiries into the present. We begin by describing what we have learned about 
how the different federal agencies that sponsor human research regulate and 
oversee this activity. Next, we report the results of our Research Proposal 
Review Project, followed by the results of our Subject Interview Study. Part III 
concludes with the Committee's synthesis of the implications of the results of all 
three of these projects for the current state of human subject research. 

Part IV, "Coming to Terms with the Past, Looking Ahead to the Future," 
reports the Committee's findings and recommendations. 

A FINAL NOTE 

The Committee's findings and recommendations represent our best efforts 
to distill almost eighteen months of inquiry into, debate about, and analysis of 
human radiation experiments. But what they cannot fully express is the 
appreciation we developed for how much damage was done to individuals and to 
the American people during the period we investigated and how this damage 
endures today. The damage we speak of here is not physical injury, although this 
too did occur in some cases. Rather, the damage is measured in the pain felt by 
people who believe that they or their loved ones were treated with disrespect for 
their dignity and disregard for their interests by a government and a profession in 
which they had placed their trust. It is measured in a too-often cynical citizenry, 
some of whom have lost faith in their government to be honest brokers of 
information about risks to the public and the purposes of government actions. 
And it is measured in the confusion among patients that remains today about the 
differences between medical research and medical care— differences that can 
impede the ability of patients to determine what is in their own best interest. 

In the period that we examined, extraordinary advances in biomedicine 
were achieved and a foundation was laid for fifty years without a world war. At 
the same time, however, it was a time of arrogance and paternalism on the part of 
government officials and the biomedical community that we would not under any 
circumstances wish to see repeated. 

As we listened to the heart-rending testimony of many public witnesses, 
we came to feel great sorrow about the suffering they described. Our most 
difficult task was determining what to recommend as the appropriate national 
response to these emotions and the events that stimulated them. What can best 



16 



Preface 

precipitate the healing of wounds and the restoration of trust? Appropriate 
remedies for those who were wronged or harmed were of critical importance, but 
remedies alone speak only to the past, not the future. It is equally important that, 
the historical record having been spelled out and appropriate remedies identified, 
we as a nation move forward and take action to prevent similar occurrences from 
happening in the future. In the end, if trust in government is to be restored, those 
in power must always act in good faith in their dealings with the citizenry. At the 
same time, however, we must recognize that unless we have expectations of 
honesty and fairness from our government and unless we are vigilant in holding 
the government to those expectations, trust will never be restored. 

Finally, we hope that this report conveys the sense of gratitude and honor 
that we experienced as citizens serving on the Advisory Committee. We were 
provided by the President with extraordinary access to the records of our past and 
given complete liberty to deliberate on what we found. Although some of what 
we report is a matter for national regret, our freedom of inquiry, and the 
cooperation we received from officials and fellow citizens of all perspectives, 
confirms that our nation's highest traditions are not things of the past but live very 
much in the present. 



17 



ENDNOTES 



1 . U.S. House of Representatives, Committee on Energy and Commerce, 
Subcommittee on Energy Conservation and Power, November 1986, "American Nuclear 
Guinea Pigs: Three Decades of Radiation Experiments on U.S. Citizens" (ACHRE No. 
CON-050594-A-1). 

2. U.S. Senate, Committee on Governmental Affairs, 1 1 November 1993, 
"Nuclear Health and Safety: Examples of Post World War II Radiation Releases at U.S. 
Nuclear Sites," GAO/RCED-94-51-FS (ACHRE No. CON-042894-A-4). 

3. Advisory Committee on Human Radiation Experiments, proceedings of 21 
April 1994, transcript, 112-113. 

4. The full text of the Committee's charter appears at the end of this report. See 
table of contents for page number. 

5. For further information on access to this collection, see "A Citizen's Guide to 
the Nation's Archives" at the end of this report. 

6. David E. Lilienthal, The Journals of David E. Lilienthal: 1945-1950, 2 vols. 
(New York: Harper and Row, 1964), as quoted in David McCullough, Truman (New 
York: Simon and Schuster, 1992), 537-538. 



18 



INTRODUCTION 

The Atomic Century 



One hundred years ago, a half century before the atomic bombing of 
Hiroshima and Nagasaki, the discovery of x rays spotlighted the extraordinary 
promise, and peril, of the atom. From that time until 1942, atomic research was in 
private hands. The Second World War and the Manhattan Project, which planned 
and built the first atomic bombs, transformed a cottage industry of researchers 
into the largest and one of the most secretive research projects ever undertaken. 
Scientists who had once raced to publish their results learned to speak in codes 
accessible only to those with a "need to know." Indeed, during the war the very 
existence of the man-made element plutonium was a national secret. 

After the war's end, the network of radiation researchers, government and 
military officials, and physicians mobilized for the Manhattan Project did not 
disband. Rather, they began working on government programs to promote both 
peaceful uses of atomic energy and nuclear weapons development. 

Having harnessed the atom in secret for war, the federal government 
turned enthusiastically to providing governmental and nongovernmental 
researchers, corporations, and farmers with new tools for peace-radioisotopes- 
mass-produced with the same machinery that produced essential materials for the 
nation's nuclear weapons. Radioisotopes, the newly established Atomic Energy 
Commission (AEC) promised, would create new businesses, improve agricultural 
production, and through "human uses" in medical research, save lives. 

From its 1947 creation to the 1974 reorganization of atomic energy 
activities, the AEC produced radioisotopes that were used in thousands of human 
radiation experiments conducted at universities, hospitals, and government 
facilities.' This research brought major advances in the understanding of the 



19 



Introduction 

workings of the human body and the ability of doctors to diagnose, prevent, and 
treat disease. 

The growth of radiation research with humans after World War II was part 
of the enormous expansion of the entire biomedical research enterprise following 
the war. Although human experiments had long been part of medicine, there had 
been relatively few subjects, the research had not been as systematic, and there 
were far fewer promising interventions than there were in the late 1940s. 

With so many more human beings as research subjects, and with 
potentially dangerous new substances involved, certain moral questions in the 
relationship between the physician-researcher and the human subject—questions 
that were raised in the nineteenth century-assumed more prominence than ever: 
What was there to protect people if a researcher's zeal for data gathering 
conflicted with his or her commitment to the subjects' well-being? Was the age- 
old ethical tradition of the doctor-patient relationship, in which the patient was to 
defer to the doctor's expertise and wisdom, adequate when the doctor was also a 
researcher and the procedures were experimental? 

While these questions about the role of medical researchers were fresh in 
the air, the Manhattan Project, and then the Cold War, presented new ethical 
questions of a different order. 

In March 1946, former British Prime Minister Winston Churchill told an 
audience in Fulton, Missouri, that an "iron curtain" had descended between 
Eastern and Western Europe—giving a name to the hostile division of the 
continent that had existed since the end of World War II. By the following year. 
Cold War was the term used to describe this state of affairs between the United 
States and its allies on the one hand and the Soviet bloc on the other. A quick 
succession of events underscored the scope of this conflict, as well as the stakes 
involved: In 1948 a Soviet blockade precipitated a crisis over Berlin; in 1949, the 
American nuclear monopoly ended when the Soviet Union exploded its first 
atomic bomb; in 1950, the Korean War began. 

The seeming likelihood that atomic bombs would be used again in war, 
and that American civilians as well as soldiers would be targets, meant that the 
country had to know as much as it could, as quickly as it could, about the effects 
of radiation and the treatment of radiation injury. 

This need for knowledge put radiation researchers, including physicians, 
in the middle of new questions of risk and benefit, disclosure and consent. The 
focus of these questions was, directly and indirectly, an unprecedented public 
health hazard: nuclear war. In addressing these questions, medical researchers 
had to define the new roles that they would play. 

As advisers to the government, radiation researchers were asked to assist 
military commanders, who called for human experimentation to determine the 
effects of atomic weapons on their troops. But these researchers also knew that 
human experimentation might not readily provide the answers the military 
needed. 

20 



The Atomic Century 

As physicians, they had a commitment to prevent disease and heal. At the 
same time, as government advisers, they were called upon to participate in 
making decisions to proceed with weapons development and testing programs 
that they knew could put citizens, soldiers, and workers at risk. As experts they 
were asked to ensure that the risks would not be excessive. And as researchers 
they saw these programs as an opportunity for gathering data. 

As researchers, they were often among the first to volunteer to take the 
risks that were unavoidable in such research. But the risks could not always be 
disclosed to members of the public who were also exposed. In keeping with the 
tradition of scientific inquiry, these researchers understood that their work should 
be the subject of vigorous discussion, at least among other scientists in their field. 
But, as government officials and advisers, they understood that their public 
statements had to be constrained by Cold War national security requirements, and 
they shared in official concern that public misunderstanding could compromise 
government programs and their own research. 

Medical researchers, especially those expert in radiation, were not 
oblivious to the importance of the special roles they were being asked to play. 
"Never before in history," began the 1949 medical text Atomic Medicine, "have 
the interests of the weaponeers and those who practice the healing arts been so 
closely related." 2 This volume, edited by Captain C. F. Behrens, the head of the 
Navy's new atomic medicine division, was evidently the first treatise on the topic. 
It concluded with a chapter by Dr. Shields Warren, the first chief of the AEC's 
Division of Biology and Medicine, who would become a major figure in setting 
policy for postwar biomedical radiation research. While the atomic bomb was not 
"of medicine's contriving," the book began, it was to physicians "more than to any 
other profession" that atomic energy had brought a "bewildering array of new 
problems, brilliant prospects, and inescapable responsibilities." The text, a 
prefatory chapter explained, treats "not of high policy, of ethics, of strategy or of 
international control [of nuclear materials], as physicians these matters are not for 
us." 3 Yet what many readers of Atomic Medicine could not know in 1949 was 
that Behrens, along with Warren and other biomedical experts, was already 
engaged in vigorous but secret discussions of the ethics underlying human 
radiation experiments. At the heart of these discussions lay difficult choices at 
the intersection of geopolitics, science, and medicine that would have a 
fundamental impact on the federal government's relationship with the American 
people. 

This chapter provides a brief survey of the development of radiation 
research and the changing roles of the biomedical researcher, from the discovery 
of x rays by a single individual to the complex world of government-sponsored 
human radiation experimentation. Finally, at the end of this chapter, an aid to the 
reader titled "The Basics of Radiation Science" provides information needed to 
understand technical concepts in this report. 



21 



Introduction 



BEFORE THE ATOMIC AGE: "SHADOW PICTURES," 
RADIOISOTOPES, AND THE BEGINNINGS OF HUMAN 
RADIATION EXPERIMENTATION 

Radiation has existed in nature from the origins of the universe, but was 
unknown to man until a century ago. Its discovery came by accident. On a 
Friday evening, November 8, 1895, the German physicist Wilhelm Roentgen was 
studying the nature of electrical currents by using a cathode ray tube, a common 
piece of scientific equipment. When he turned the tube on, he noticed to his 
surprise that a glowing spot appeared on a black paper screen coated with 
fluorescent material that was across the room. Intrigued, he soon determined that 
invisible but highly penetrating rays were being produced at one end of the 
cathode ray tube. The rays could expose photographic plates, leaving shadows of 
dense objects, such as bone. 

After about six weeks of experimenting with his discovery, which he 
called x rays, Roentgen sent a summary and several "shadow pictures" to a local 
scientific society. The society published the report in its regular journal and 
wisely printed extra copies. News spread rapidly; Roentgen sent copies to 
physicists throughout Europe. One Berlin physicist "could not help thinking that 
I was reading a fairy tale . . . only the actual photograph proved to everyone that 
this was a fact." 4 

Physicians immediately recognized these rays as a new tool for diagnosis, 
a window into the interior of the body. The useless left arm of German Emperor 
Wilhelm II was x-rayed to reveal the cause of his disability, while Queen Amelia 
of Portugal used x rays of several of her court ladies to vividly display the 
dangers of "tightlacing." 5 Physicians began to use x rays routinely for examining 
fractures and locating foreign objects, such as needles swallowed by children or 
bullets shot into adults. 6 During World War I, more than 1.1 million wounded 
soldiers were treated with the help of diagnostic x rays. 7 

In 1 896, Roentgen's insight led to the discovery of natural radioactivity. 
Henri Becquerel, who had been studying phosphorescence, discovered that 
shadow pictures were also created when wrapped photographic plates were 
exposed to crystals partly composed of uranium. Could this radioactive property 
be concentrated further by extracting and purifying some as-yet-unknown 
component of the uranium crystals? Marie and Pierre Curie began laborious 
chemical analyses that led to the isolation of the element polonium, named after 
Marie's native Poland. 8 Continuing their work, they isolated the element radium. 
To describe these elements' emission of energy, they coined the word radio- 
activity!' 

As with x rays, popular hopes and fears for natural radioactivity far 
exceeded the actual applications. One 1905 headline captures it all: "Radium, as 
a Substitute for Gas, Electricity, and as a Positive Cure for Every Disease." 10 

22 



The Atomic Century 

Following initial enthusiasm that radiation could, by destroying tumors, provide a 
miracle cure for cancer, the reappearance of irradiated tumors led to 
discouragement. Despite distressing setbacks, research into the medical uses of 
radiation persisted. In the 1920s French researchers, performing experiments on 
animals, discovered that radiation treatments administered in a series of 
fractionated doses, instead of a single massive dose, could eliminate tumors 
without causing permanent damage. With the new method of treatment, doctors 
began to report impressive survival rates for patients with a variety of cancers.^ 
Fractionation became, and remains, an accepted approach to cancer treatment. 

Along with better understanding of radiation's benefits came a better 
practical appreciation of its dangers. Radiation burns were quickly apparent, but 
the greater danger took longer to manifest itself. Doctors and researchers were 
frequently among the victims. Radiation researchers were also slow to take steps 
to protect themselves from the hidden danger. One journal opened its April 1914 
issue by noting that "[w]e have to deplore once more the sacrifice of a radiologist, 
the victim of his art." 12 

Clear and early evidence of tragic results sharpened both expert and public 
concern. By 1924, a New Jersey dentist noticed an unusual rate of deterioration 
of the jawbone among local women. On further investigation he learned that all 
at one time had jobs painting a radium solution onto watch dials. Further studies 
revealed that as they painted, they licked their brushes to maintain a sharp point. 
Doing so, they absorbed radium into their bodies. The radium gradually revealed 
its presence in jaw deterioration, blood disease, and eventually, a painful, 
disfiguring deterioration of the jaw. 13 There was no question that radium was the 
culprit. The immediate outcome was a highly publicized crusade, investigation, 
lawsuits, and payments to the victims. Despite the publicity surrounding the dial 
painters, response to the danger remained agonizingly slow. Patent medicines 
containing radium and radium therapies continued. 14 

The tragedy of the radium dial painters and similar cases of patients who 
took radium nostrums have provided basic data for protection standards for 
radioactive substances taken into the body. One prominent researcher in the new 
area of radiation safety was Robley Evans. Evans was drawn into the field by the 
highly publicized death in 1932 of Eben Byers, following routine consumption of 
the nostrum Radiothor. Byers's death spurred Evans, then a California Institute of 
Technology physics graduate student, to undertake research that led to a study of 
the effects on the body of ingesting radium; this study would continue for more 
than half a century. 15 

Evans's study and subsequent studies of the effects of radium treatments 
provided the anchor in human data for our understanding of the effects of 
radiation within the human body. As the dangers of the imprudent use of x rays 
and internal radiation became clear, private scientific advisory committees sprang 
up to develop voluntary guidelines to promote safety among those working with 
radiation. When the government did enter the atomic age, it often referred to the 

23 



Introduction 

guidelines of these private committees as it developed radiation protection 
standards."' 

The Miracle of Tracers 

In 1913, the Hungarian chemist Georg von Hevesy began to experiment 
with the use of radioactive forms of elements (radioisotopes) to trace the behavior 
of the normal, nonradioactive forms of a variety of elements. Ten years later 
Hevesy extended his chemical experiments to biology, using a radioisotope of 
lead to trace the movement of lead from soil into bean plants. In 1943, Hevesy 
won the Nobel Prize for his work on the use of radioisotopes as tracers. 

Previously, those seeking to understand life processes of an organism had 
to extract molecules and structures from dead cells or organisms, and then study 
those molecules by arduous chemical procedures, or use traceable chemicals that 
were foreign to the organism being studied but that mimicked normal body 
chemicals in some important way. Foreign chemicals could alter the very 
processes being measured and, in any case, were often as difficult to measure 
precisely as were normal body constituents. The radioactive tracer— as Our 
Friend the Atom, a book written by Dr. Heinz Haber for Walt Disney productions, 
explained in 1956 to readers of all ages—was an elegant alternative: "Making a 
sample of material mildly radioactive is like putting a bell on a sheep. The 
shepherd traces the whole flock around by the sound of the bell. In the same way 
it is possible to keep tabs on tracer-atoms with a Geiger counter or any other 
radiation detector." 17 

By the late 1920s the tracer technique was being applied to humans in 
Boston by researchers using an injection of dissolved radon to measure the rate of 
blood circulation, an early example of using radioactivity to observe life 
processes. 18 However, research opportunities were limited by the fact that some 
of the elements that are most important in living creatures do not possess 
naturally occurring radioactive isotopes. 

The answer to this problem came simultaneously at faculty clubs and 
seminars in Berkeley and Boston in the early 1930s. Medical researchers realized 
that the famed "atom smasher," the cyclotron invented by University of California 
physicist Ernest Lawrence, could be used as a factory to create radioisotopes for 
medical research and treatment. "Take an ordinary needle," Our Friend the Atom 
explained, "put it into an atomic reactor for a short while. Some of the ions 
contained in the steel will capture a neutron and be transformed into a radio- 
isotope of iron. . . . Now that needle could be found in the proverbial haystack 
without any trouble." 19 

In 1936, two of Lawrence's Berkeley colleagues, Drs. Joseph Hamilton 
and Robert Stone, administered radiosodium to treat several leukemia patients. In 
1937, Ernest Lawrence's brother, physician John Lawrence, became the first to 
use radiophosphorus for the treatment of leukemia. This application was 

24 



The Atomic Century 

extended the following year to the treatment of polycythemia vera, a blood 
disease. This method soon became a standard treatment for that disease. In 1938, 
Hamilton and Stone also began pioneering work in the use of cyclotron-produced 
neutrons for the treatment of cancer. The following year, not long before the war 
in Europe began, Ernest Lawrence unveiled a larger atom smasher, to be used to 
create additional radioisotopes and hence dubbed the "medical cyclotron." 20 The 
discovery that some radioisotopes deposited selectively in different parts of the 
body—the thyroid, for example-inspired a spirited search for a radioactive "magic 
bullet" that might treat, or even cure, cancer and other diseases. 

In Cambridge, the age of "nuclear medicine" is said to have begun in 
November 1936 with a lunchtime seminar at Harvard, at which MIT President 
Karl Compton talked on "What Physics Can Do for Biology and Medicine." 
Robley Evans, by that time at MIT, is reported to have helped prepare the portion 
of the talk from which medical researchers at the Massachusetts General 
Hospital's thyroid clinic came to realize that MIT's atom smasher could produce a 
great research tool for their work—radioisotopes. Soon, doctors at the thyroid 
clinic began a series of experiments, including some involving humans, that 
would lead to the development of radioiodine as a standard tool for diagnosing 
and treating thyroid disease. 21 

In late 1938, the discovery of atomic fission in Germany prompted 
concern among physicists in England and the United States that Nazi Germany 
might be the first to harness the power of the atom— as a propulsion method for 
submarines, as radioactive poison, or most worrisome of all, as a bomb capable of 
unimagined destruction. In the United States, a world-famous physicist, Albert 
Einstein, and a recent emigre from Hungary, Leo Szilard, alerted President 
Franklin D. Roosevelt to the military implications of the German discovery in an 
August 1939 letter. 

Assigning his own science adviser, Vannevar Bush, to the task of 
determining the feasibility of an atomic bomb, Roosevelt's simple "O.K.," 
scrawled on a piece of paper, set in motion the chain of events that would lead to 
the largest and most expensive engineering project in history. Soon, Ernest 
Lawrence's Radiation Laboratory and its medical cyclotron were mobilized to aid 
in the nationwide effort to build the world's first atomic bomb. In a related effort, 
Drs. Stone and Hamilton, and others, would turn their talents to the medical 
research needed to ensure the safety of those working on the bomb. 

THE MANHATTAN PROJECT: A NEW AND SECRET 
WORLD OF HUMAN EXPERIMENTATION 

In August 1942, the Manhattan Engineer District was created by the 
government to meet the goal of producing an atomic weapon under the pressure 
of ongoing global war. Its central mission became known as the Manhattan 
Project. Under the direction of Brigadier General Leslie Groves of the Army 

25 



Introduction 

Corps of Engineers, who recently had supervised the construction of the 
Pentagon, secret atomic energy communities were created almost overnight in 
Oak Ridge, Tennessee, at Los Alamos, New Mexico, and in Hanford, 
Washington, to house the workers and gigantic new machinery needed to produce 
the bomb. The weapon itself would be built at the Los Alamos laboratory, under 
the direction of physicist J. Robert Oppenheimer. 

Plucked from campuses around the country, medical researchers came 
face to face with the need to understand and control the effect upon the thousands 
of people, doctors included, of radioactive materials being produced in previously 
unimaginable quantities. 

In November 1942 General Groves, through the intermediation of an 
Eastman Kodak official, paid a call on University of Rochester radiologist 
Stafford Warren. Rochester, like MIT and Berkeley, was another locale where 
radiation research had brought together physicists and physicians. "They wanted 
to know what I was doing in radiation. So I discussed the cancer work and some 
of the other things," Warren told an interviewer in the 1960s. Then "[w]e got 
upstairs and they looked in the closet and they closed the transom and they looked 
out the window. . . . Then they closed and locked the door and said, 'Sit down.'" 22 

Soon thereafter, Dr. Warren was made a colonel in the U.S. Army and the 
medical director of the Manhattan Project. As his deputy, Warren called on Dr. 
Hymer Friedell, a radiologist who had worked with Dr. Stone in California. Dr. 
Stone himself had meanwhile moved to the University of Chicago, where he 
would play a key role in Manhattan Project-related medical research. 

Initially, researchers knew little or nothing about the health effects of the 
basic bomb components, uranium, plutonium, and polonium. 23 But, as a secret 
history written in 1946 stated, they knew the tale of the radium dial painters: 

The memory of this tragedy was very vivid in the 
minds of people, and the thoughts of potential 
dangers of working in areas where radiation hazards 
existed were intensified because the deleterious 
effects of radiation could not be seen or felt and the 
results of over-exposure might not become apparent 
for long periods after such exposure. 24 

The need for secrecy, Stafford Warren later recalled, compounded the 
urgency of understanding and controlling risk. Word of death or toxic hazard 
could leak out to the surrounding community and blow the project's cover. 25 

The need to protect the Manhattan Project workers soon gave rise to a new 
discipline, called health physics, which sought to understand radiation effects and 
monitor and protect nuclear worker health and safety. The Project was soon 
inundated with data from radiation-detection instruments, blood and urine 
samples, and physical exams. The "clinical study of the personnel," Robert Stone 

26 



The Atomic Century 

wrote in 1943, "is one vast experiment. Never before has so large a collection of 
individuals been exposed to so much radiation." 26 Along with these data- 
gathering efforts came ethical issues. 

Would disclosure of potential or actual harm to the workers, much less the 
public, impair the program? For example, a July 1945 Manhattan Project memo 
discussed whether to inform a worker that her case of nephritis (a kidney disease) 
may have been due to her work on the Project. The issue was of special import 
because, the memo indicated, the illness might well be a precursor of more cases. 
The worker, the memo explained, "is unaware of her condition which now shows 
up on routine physical check and urinalysis." 27 

As this memo showed, there was an urgent need for decisions on how to 
protect the workers, while at the same time safeguard the security of the project: 
"The employees must necessarily be rotated out, and not permitted to resume 
further exposure. In frequent instances no other type of employment is available. 
Claims and litigation will necessarily flow from the circumstances outlined." 
There were also, the memo concluded, "Ethical considerations": 

The feelings of the medical officers are keenly 
appreciated. Are they in accordance with their 
canons of ethics to be permitted to advise the 
patient of his true condition, its cause, effect, and 
probable prognosis? If not on ethical grounds, are 
they to be permitted to fulfill their moral obligations 
to the individual employees in so advising him? If 
not on moral grounds, are those civilian medical 
doctors employed here bound to make full 
disclosure to patients under penalty of liability for 
malpractice or proceeding for revocation of license 
for their failure to do so? 28 

It is not clear what was decided in this case. However, the potential 
conflict between the government doctors' duty to those working on government 
projects and the same doctors' obligations to the government would not disappear. 
Following the war, as we see in chapter 12, this conflict would be sharply posed 
as medical researchers studied miners at work producing uranium for the nation's 
nuclear weapons. 

Another basic question was the extent to which human beings could or 
should be studied to obtain the data needed to protect them. The radium dial 
painter data served as a baseline to determine how the effects of exposures in the 
body could be measured. But this left the question of whether plutonium, 
uranium, and polonium behaved more or less like radium. Research was needed 
to understand how these elements worked in the body and to establish safety 
levels. A large number of animal studies were conducted at laboratories in 

27 



Introduction 

Chicago, Berkeley, Rochester, and elsewhere; but the relevance of the data to 
humans remained in doubt. 

The Manhattan Project contracted with the University of Rochester to 
receive the data on physical exams and other tests from Project sites and to 
prepare statistical analyses. While boxes of these raw data have been retrieved, it 
is not clear what use was made of them. 29 Accidents, while remarkably few and 
far between, became a key source of the data used in constructing an 
understanding of radiation risk. But accidents were not predictable, and their 
occurrence only enhanced the immediacy of the need to gain better data. 

In 1944, the Manhattan Project medical team, under Stafford Warren and 
with the evident concurrence of Robert Oppenheimer, made plans to inject 
polonium, plutonium, uranium, and possibly other radioactive elements into 
human beings. As discussed in chapter 5, the researchers turned to patients, not 
workers, as the source of experimental data needed to protect workers. By the 
time the program was abandoned by the government, experimentation with 
plutonium had taken place in hospitals at the Universities of California, Chicago, 
and Rochester, and at the Army hospital in Oak Ridge, and further 
experimentation with polonium and uranium had taken place at Rochester. 

The surviving documentation provides little indication that the medical 
officials and researchers who planned this program considered the ethical 
implications of using patients for a purpose that no one claimed would benefit 
them, under circumstances where the existence of the substances injected was a 
wartime secret. Following the war, however, the ethical questions raised by these 
experiments would be revisited in debates that themselves were long kept secret. 

In addition to experimentation with internally administered radioisotopes, 
external radiation was administered in human experiments directed by Dr. Stone 
at Chicago and San Francisco and by others at Memorial Hospital in New York 
City. Once again, the primary subjects were patients, although some healthy 
subjects were also involved. In these cases, the researchers may have felt that the 
treatment was of therapeutic value to the patients. But, in addition to the question 
of whether the patients were informed of the government's interest, this research 
raised the question of whether the government's interest affected the patients' 
treatment. As discussed in chapter 8, these questions would recur when, 
beginning in 1 95 1 , and for two decades thereafter, the Defense Department would 
fund the collection of data from irradiated patients. 

Ensuring safety required more, however, than simply studying how 
radioactive substances moved through and affected the human body. It also 
involved studying how these substances moved through the environment. While 
undetectable to the human senses, radiation in the environment is easily 
measurable by instruments. When General Groves chose Hanford, on the 
Columbia River in Washington state, as a site for the plutonium production 
facility, a secret research program was mounted to understand the fate of 
radioactive pollution in the water, the air, and wildlife. 30 

28 



The Atomic Century 

Outdoor research was at times improvisational. Years after the fact, 
Stafford Warren would recall how Manhattan Project researchers had deliberately 
"contaminated the alfalfa field" next to the University of Rochester medical 
school with radiosodium, to determine the shielding requirements for radiation- 
measuring equipment. Warren's associate Dr. Harold Hodge recalled that a 
shipment of radiosodium was received by plane from Robley Evans at MIT, 
mixed with water in a barrel, and poured into garden sprinklers: 

We walked along and sprinkled the driveway. This 
was after dark. . . . The next thing, we went out and 
sprayed a considerable part of the field. ... It was 
sprayed and then after a while sprayed again, so 
there was a second and third application. We were 
all in rubber, so we didn't get wet with the stuff . . . 
then Staff [Warren] said that one of the things we 
needed was to see what would be the effect on the 
inside of a wooden building. So we took the end of 
the parking garage, and we sprinkled that up about 
as high as our shoulders, and somebody went inside 
and made measurements, and we sprinkled it again. 
Then we wanted to know about the inside of a brick 
building, and so we sprinkled the side of the animal 
house. ... I had no idea what the readings were. . . I 
hadn't the foggiest idea of what we were doing, 
except that obviously it was something 
radioactive. 31 

Outdoor releases would put at risk unsuspecting citizens, even 
communities, as well as workers. There were no clear policies and no history of 
practice to guide how these releases should be conducted. As we explore in 
chapter 1 1, this would be worked out by experts and officials in secret, on behalf 
of the workers and citizens who might be affected. 

THE ATOMIC ENERGY COMMISSION AND POSTWAR 
BIOMEDICAL RADIATION RESEARCH 

On August 6, 1945, when the atomic bomb was dropped on Hiroshima, 
the most sensitive of secrets became a symbol for the ages. A week later, the 
bomb was the subject of a government report that revealed to the public the uses 
of plutonium and uranium. 32 Immediately, debate began over the future of atomic 
energy. Could it be controlled at the international level? Should it remain 
entirely under control of the military? What role would industry have in 
developing its potential? Although American policymakers failed to establish 

29 



Introduction 

international control of the bomb, they succeeded in creating a national agency 
with responsibility for the domestic control of atomic energy. 

The most divisive question in the creation of the new agency that would 
hold sway over the atom was the role of the military. Following congressional 
hearings, the Atomic Energy Commission was established by the 1946 McMahon 
Act, to be headed by five civilian commissioners. President Truman appointed 
David Lilienthal, former head of the Tennessee Valley Authority, as the first 
chairman of the AEC, which took over responsibilities of the Manhattan Engineer 
District in January 1947. 

Also in 1947, under the National Security Act, the armed services were 
put under the authority of the newly created National Military Establishment 
(NME), to be headed by the secretary of defense. In 1949 the National Security 
Act was amended, and the NME was transformed into an executive department— 
the Department of Defense. 33 The Armed Forces Special Weapons Project, which 
would coordinate the Defense Department's responsibilities in the area of nuclear 
weapons, became the military heir to the Manhattan Engineer District. The 
Military Liaison Committee was also established as an intermediary between the 
Atomic Energy Commission and the Defense Department; it was also to help set 
military requirements for the number and type of nuclear weapons needed by the 
armed services. 

Even before the AEC officially assumed responsibility for the bomb from 
the Manhattan Project, the Interim Medical Advisory Committee, chaired by 
former Manhattan Project medical director Stafford Warren, began meeting to 
map out an ambitious postwar biomedical research program. Former Manhattan 
Project contractors proposed to resume the research that had been interrupted by 
the war and to continue wartime radiation effects studies upon human subjects. 34 

In May 1947, Lilienthal commissioned a blue-ribbon panel, the Medical 
Board of Review, that reported the following month on the agency's biomedical 
program. In strongly recommending a broad research and training program, the 
board found the need for research "both urgent and extensive." The need was 
"urgent because of the extraordinary danger of exposing living creatures to 
radioactivity. It is urgent because effective defensive measures (in the military 
sense) against radiant energy are not yet known." The board, pointing to the 
AEC's "absolute monopoly of new and important tools for research and important 
knowledge," noted the commensurate responsibilities-both to employees and 
others who could suffer from "its negligence or ignorance" and to the scientific 
world, with which it was obliged to "share its acquisitions . . . whenever security 
considerations permit." 35 In the fall of 1947, as recommended by the Medical 
Board of Review, the AEC created a Division of Biology and Medicine (DBM) to 
coordinate biomedical research involving atomic energy and an Advisory 
Committee for Biology and Medicine (ACBM), which reported directly to the 
AEC's chairman. 36 

Not surprisingly, the DBM and ACBM became gathering places for the 

30 



The Atomic Century 

luminaries of radiation science. The ACBM was headed by a Rockefeller 
Foundation official, Dr. Alan Gregg. It settled on Dr. Shields Warren, a Harvard- 
trained pathologist, to serve as the first chief of the DBM. Warren, as we shall 
see, would play a central role in developments related to radiation research and 
human experimentation. In the 1930s, focusing on cancer research, and 
influenced by the work of Hevesy and the pioneering radioisotope work being 
done in Berkeley and Boston, Warren turned to the question of the effects of 
radiation on animals and the treatment of acute leukemia, the "most hopeless . . . 
of tumors at that time." As the war neared, Warren enlisted in the Naval Reserve. 
He continued medical work for the Navy, turning down an invitation to join 
Stafford Warren (no relation) on "a project . . . that he couldn't tell me anything 
about [the Manhattan Project]."" 

While most of the AEC's budget would be devoted to highly secret 
weapons development and related activities, the biomedical research program 
represented the commission's proud public face. Even before the AEC opened its 
doors, Manhattan Project officials and experts had laid the groundwork for a bold 
program to encourage the use of radioisotopes for scientific research, especially in 
medicine. This program was first presented to the broad public in a September 
1946 article in the New York Times Magazine. The article began dramatically by 
describing the use of "radioactive salt" to measure circulation in a crushed leg, so 
that a decision on whether to amputate below or above the knee could be made. 

By November 1946, the isotope distribution program was well under way, 
with more than 200 requests approved, about half of which were designated for 
"human uses." From the beginning, the AEC's Isotope Division at Oak Ridge had 
in its program director, Paul Aebersold, a veritable Johnny Appleseed for 
radioelements. 39 In presentations before the public and to researchers, Aebersold, 
dubbed "Mr. Isotope," touted the simplicity and low cost with which scientists 
would be provided with radioisotopes: "The materials and services are made 
available . . . with a minimum of red tape and under conditions which encourage 
their use." 40 At an international cancer conference in St. Louis in 1947, the AEC 
announced that it would make radioisotopes available without cost for cancer 
research and experimental cancer treatment. This, Shields Warren later recalled, 
had a "tremendous effect" and "led to a revolution in the type of work done in this 

field." 41 c . .__, 

To AEC administrators, Aebersold emphasized the benefits to the AhC s 
public image: "Much of the Commission's success is judged by the public and 
scientists ... on its willingness to carry out a wide and liberal policy on the 
distribution of materials, information, and services," he wrote in a memo to the 
AEC's general manager. 42 

The AEC biomedical program as a whole also provided for funding ot 
cancer research centers, research equipment, and numerous other research 
projects. Here, too, were advances that would save many lives. Before the war, 
radiotherapy had reached a plateau, limited by the cost of radium and the inability 

31 



Introduction 

of the machines of the time to focus radiation precisely on tumors to the exclusion 
of surrounding healthy tissue. AEC facilities inherited from the Manhattan 
Project could produce radioactive cobalt, a cheaper substitute for radium. As 
well, the AEC's "teletherapy" program funded the development of new equipment 
capable of producing precisely focused high-energy beams. 43 

The AEC's highly publicized peacetime medical program was not immune 
to the pressures of the Cold War political climate. Even the lives of young 
researchers in the AEC Fellowship Program conducting nonclassified research 
were subject to Federal Bureau of Investigation review despite protests from 
commission members. Congressionally mandated Cold War requirements such as 
loyalty oaths and noncommunist affidavits, Chairman Lilienthal declared, would 
have a chilling effect on scientific discussion and could damage the AEC's ability 
to recruit a new generation of scientists. 44 The reach of the law, the Advisory 
Committee for Biology and Medicine agreed, was like a "blighting hand; for 
thoughtful men now know how political domination can distort free inquiry into a 
malignant servant of expediency and authoritarian abstraction." 45 Nonetheless, 
the AEC accepted the congressional conditions for its fellowship program and 
determined to seek the program's expansion. 46 

The AEC's direct promotional efforts were multiplied by the success of 
Aebersold and his colleagues in carrying the message to other government 
agencies, as well as to industry and private researchers. This success led, in turn, 
to new programs. 

In August 1947, General Groves urged Major General Paul Hawley, the 
director of the medical programs of the Veterans Administration, to address 
medical problems related to the military's use of atomic energy. Soon thereafter, 
Hawley appointed an advisory committee, manned by Stafford Warren and other 
medical researchers. The advisers recommended that the VA create both a 
"publicized" program to promote the use of radioisotopes in research and a 
"confidential" program to deal with potential liability claims from veterans 
exposed to radiation hazards. 47 The "publicized" program soon mushroomed, 
with Stafford Warren, Shields Warren, and Hymer Friedell among the key 
advisers. By 1974, according to VA reports, more than 2,000 human radiation 
experiments would be performed at VA facilities, 48 many of which would work in 
tandem with neighboring medical schools, such as the relationship between the 
UCLA medical school, where Stafford Warren was now dean, and the Wadsworth 
(West Los Angeles) VA Hospital. 

While the AEC's weapons-related work would continue to be cloaked in 
secrecy, the isotope program was used by researchers in all corners of the land to 
achieve new scientific understanding and help create new diagnostic and 
therapeutic tools. It was, however, only a small part of an enormous institution. 
By 1951 the AEC would employ 60,000 people, all but 5,000 through contractors. 
Its land would encompass 2,800 square miles, an area equal to Rhode Island and 
Delaware combined. In addition to research centers throughout the United States, 

32 



The Atomic Century 

its operations "extended] from the ore fields of the Belgian Congo and the Arctic 
region of Canada to the weapons proving ground at Enewetak Atoll in the Pacific 
and the medical projects studying the after-effects of atomic bombing in . . . 
Japan " 49 The Isotope Division, however, would employ only about fifty people 
and, when reactor production time was accounted for, occupy only a fraction of 
its budget and resources. 50 

THE TRANSFORMATION IN GOVERNMENT-SPONSORED 
RESEARCH 

The AEC's decision to proceed with a biomedical research program was 
part of an even greater transformation, in which government continued and 
expanded wartime support for research in industry and at universities. Before 
World War II, biomedical research was a small enterprise in which the federal 
government played a minor role. During the war, however, large numbers of 
American biomedical researchers were mobilized by the armed forces. These 
researchers played an important role in advancing military medicine in a wide 
range of areas, including blood substitutes, antimalarial drugs and, as noted 
above in nurturing the infant science of nuclear medicine. 

' As the war was drawing to a close, President Roosevelt asked for advice 
from his Office of Scientific Research and Development (OSRD) on how to 
convert the nation's military research effort to a peacetime footing, and whether 
the government should take an activist role in promoting research. The OSRD, 
under Vannevar Bush, responded in July 1945, after Roosevelt's death, with a 
report called "Science, the Endless Frontier." Bush and his colleagues 
recommended among other things the establishment of a National Science 
Foundation (NSF) to support basic research in all areas including the biomedical 
sciences. While the principle that the federal government should fund medical 
research came to seem self-evident, this was hardly the case at the time. In a 
personal reminiscence published in 1970, Bush wrote: 

To persuade the Congress of these pragmatically 
inclined United States to establish a strong 
organization to support fundamental research would 
seem to be one of the minor miracles. We in this 
country have supported well those pioneers who 
have created new gadgetry for our use or our 
amusement. But we have not had during our 
formative years the respect for scientific endeavors, 
for scholarship generally, to the extent it had been 
present in Europe. 51 

Congress worked Bush's small miracle and passed relevant legislation, but 

33 



Introduction 

President Harry Truman vetoed the bill. When the bill passed again, however, 
Bush persuaded Truman to sign it. 52 

At the new AEC, and elsewhere, a key element of the support for science 
was the determination to fund extramural research, that is, research outside the 
agency. Prior to the war, federal support for private researchers was limited. The 
Manhattan Project was only one of several wartime efforts that drew private 
researchers into government service and that provided federal funds for those who 
remained in private research centers. Following the war, as researchers returned 
to universities, laboratories, and hospitals, the continued federal support of their 
efforts transformed the relationship between government and science and the 
dimensions of the scientific effort. 53 

During the war, the Committee on Medical Research (CMR) of the OSRD 
operated entirely by funding external research. In 1 944, Congress empowered the 
surgeon general of the Public Health Service to make grants to universities, 
hospitals, laboratories, and individuals, which provided the legislative basis for 
the postwar National Institute of Health (NIH) extramural program. 54 In 1948, 
Congress authorized the National Heart Institute to join the decade-old National 
Cancer Institute, and NIH became the National Institutes of Health. 

By the late 1960s, the annual appropriations of NIH exceeded $1 billion. 55 
Research involving medical uses of radioisotopes and external radiation was 
among the newer fields benefiting from the increased funding. As discussed in 
more detail in chapter 6, government-supported radioisotope research has proved 
profoundly important in the development of techniques for medical diagnosis and 
treatment. 

Federal research funding has also continued to be essential to the 
development of the use of external sources of radiation. For example, the crude 
images made possible by Roentgen's discovery of x rays have been replaced by 
higher resolution, three-dimensional pictures, such as those produced by 
computerized tomographic (CT) scanning and magnetic resonance imaging 
(MRI). 

Today, the benefits of federally sponsored medical research are often 
taken for granted. To many of those in the midst of the postwar planning and 
advocacy, however, the result was not foreordained. "Fortunately," Shields 
Warren recalled years later, postwar "momentum" kept AEC research budgets on 
track until, in 1957, the Soviet launch of Sputnik (the first space satellite) jolted 
the American people into a renewed commitment to the support of scientific 
research. 56 



34 



The Atomic Century 

THE AFTERMATH OF HIROSHIMA AND NAGASAKI: THE 
EMERGENCE OF THE COLD WAR RADIATION RESEARCH 
BUREAUCRACY 

While promoting the beneficial uses of radiation, the government also 
wished to continue and expand research on its harmful effects. Three days after 
the destruction of Hiroshima, Robert Stone wrote two letters to Stafford Warren's 
deputy, and Stone's former student, Hymer Friedell. The first expressed hope that 
the contribution of medical researchers could now be made public, so that people 
would know what they had done during the war. 57 The second letter described 
Stone's "mixed feelings" at the success that had been achieved and his fear that 
the lingering effects of radiation from the bomb had been underestimated: "I 
could hardly believe my eyes," Stone wrote, "when I saw a series of news releases 
said to be quoting Oppenheimer, and giving the impression that there is no 
radioactive hazard. Apparently all things are relative." 58 

Friedell and other researchers, including Stafford Warren and Shields 
Warren, soon traveled to Hiroshima and Nagasaki to begin what became an 
extensive research program on survivors. The data from that project quickly 
became and still remain the essential source of information on the long-term 
effects of radiation on populations of human beings. It was not long, however, 
before there were additional real-life data on the bomb, from postwar atomic tests. 
In 1946, the United States undertook the first peacetime nuclear weapons tests at 
Bikini Atoll in the Marshall Islands. Operation Crossroads, conducted before 
journalists and VIPs from around the world, was intended to test the ability of a 
flotilla of unmanned ships to withstand the blast. Since most of the ships 
remained afloat, the Navy declared Crossroads a triumph. 59 

Behind the scenes, however, Crossroads medical director Stafford Warren 
expressed horror at the level of contamination on the ships due to the underwater 
atomic blast. 60 When the ships returned to the West Coast from the Pacific, they 
were extensively studied to assess the damage and contamination from the atomic 
bombs. The government created the Naval Radiological Defense Laboratory 
(NRDL) to study the effects of atomic bombs on ships and to design ways to 
protect them. "Crossroads," according to an NRDL history, "left no doubt that 
man was faced with the necessity for coping with strange and unprecedented 
problems for which no solutions were available." 6 ' 

Hiroshima and Nagasaki, it now seemed, were only the beginning, not the 
end, of human exposure to bomb-produced radiation. As Crossroads confirmed 
with the lingering problem of contaminated ships, what the bomb did not 
obliterate it might still damage by radiation over the course of days or years. It 
was no longer enough to know about the effects of radioactive materials on 
American nuclear weapons workers; now there was the urgent need to understand 
the effects on American soldiers, sailors, and even citizens as well. 

Largely invisible to the public, an ad hoc bureaucracy sprang up to 

35 



Introduction 

address the medical and radiation research problems of atomic warfare. This 
bureaucracy brought together former wartime radiation researchers, who were 
joined by junior colleagues, to advise, and participate in, the government's 
growing radiation research program. Other, already established groups-such as 
the AEC's Division of Biology and Medicine and its advisory committee-also 
had important places in the new network. 

Beyond considering fallout from the testing of atomic bombs, these groups 
also looked at how radiation itself might be used as a weapon. During the war, 
scientists like J. Robert Oppenheimer had speculated on the possibility that fission 
products (radioactive materials produced by the bomb or by reactors) could be 
dispersed in the air and on the ground to kill or incapacitate the enemy. In 1946, 
the widespread contamination of ships at Crossroads by radioactive mist gave 
dramatic evidence of the potential of so-called radiological warfare, or RW. In 
1947, the military created a committee of experts to study the problem. The 
following year, a blue-ribbon panel of physicians and physicists looked at the 
prospects, both offensive and defensive, of what the Pentagon termed "Rad War." 
The work of these panels would lead to dozens of intentional releases of radiation 
into the environment at the Army's Dugway, Utah, testing grounds from the late 
1940s to the early 1950s. The very fact that the government was engaged in RW 
tests was a secret. Indeed, the records of the RW program-including, as we shall 
see in chapter 1 1, the debate on what the public should be told about the 
program-would remain largely secret for almost fifty years. 

In 1 949, a military program to build a nuclear-powered airplane led to a 
set of proposed human radiation experiments. The NEPA (Nuclear Energy for the 
Propulsion of Aircraft) program had its origins in 1946 as a venture that included 
the Manhattan Project's Oak Ridge site, the military, and private aircraft 
manufacturers. Robert Stone, as we shall see in chapter 8, was a leading 
proponent of experiments involving healthy volunteers, as a key to answering 
questions about the radiation hazard faced by the crew of the proposed airplane. 

The NEPA and RW groups considered important, but still discrete, 
projects. Where did the "big picture" discussions take place? The Advisory 
Committee has pieced together the records of the Armed Forces Medical Policy 
Council, the Committee on Medical Sciences, and the Joint Panel on the Medical 
Aspects of Atomic Warfare." These three Defense Department groups, all 
chaired by civilian doctors, guided the government on both the broad subject of 
military-related biomedical research and the new and special problems posed by 
atomic warfare. 

If the surviving records are an indication, from its creation in 1949 to its 
evident demise with the reorganization of the Defense Department in 1953, the 
Joint Panel quickly became the hub of atomic warfare-related biomedical 
research. The Joint Panel gathered information about relevant research from all 
corners of the government, provided guidance for Defense Department programs, 



36 



The Atomic Century 

and reviewed and coordinated policy in the matter of human experimentation 
using atomic energy. 

By charter, the group was to be headed by a civilian. Harvard's Dr. Joseph 
Aub, a long-standing member of the Boston-based medical research community 
who had worked with Robley Evans on the study of the radium dial painters and 
had also studied lead toxicity, served as chair. Those who served with Aub 
included Evans, Hymer Friedell, and Louis Hempelmann, Oppenheimer's 
Manhattan Project medical aide. Other government participants came from the 
AEC, the Public Health Service, the National Institutes of Health, the Veterans 
Administration, and the CIA. (The charter provided that the Joint Panel should 
collect information on relevant research conducted abroad, which the CIA 
evidently provided.) 63 

This bureaucracy provided the venue for secret discussions that linked the 
arts of healing and war in ways that had little precedent. At one and the same 
time, for example, doctors counseled the military about the radiation risk to troops 
at the site of atomic bomb tests, advised on the need for research on the 
"psychology of panic" at such bomb tests, and debated the need for rules to 
govern atomic warfare-related experimentation. (See chapter 10.) 

The records of the Joint Panel show that, during the height of the Cold 
War, the resources of civilian agencies were part of the mobilization of resources 
to serve national security interests. For example, Dr. Howard Andrews, trained as 
a physicist, was the National Institutes of Health's representative to the Joint 
Panel, and in the 1950s he worked with the DOD and the AEC in monitoring 
safety measures and measuring fallout from nuclear tests. 64 

In 1950 President Truman ordered federal agencies, including the Public 
Health Service and NIH, to focus their resources on activities that would benefit 
national security needs. On paper, at least, PHS and NIH policymakers sought to 
direct resources to questions of radiation injury, civil defense, and worker health 
and safety. 65 For example, a 1952 internal planning memo explained that NIH 
"will not wait for formal requests by the armed forces ... to undertake research 
which NIH staff knows to be of urgent military and civilian defense significance. 
Limited selective conversion of research to work directly related to biological 
warfare, shock, radiation injury and thermal burns will begin immediately. . . ." 66 
The fragmentary surviving documentation, however, does not show the extent to 
which PHS- and NIH-funded researchers actually redirected their investigations 
or merely recast the purpose of ongoing work. 

NEW ETHICAL QUESTIONS FOR MEDICAL 
RESEARCHERS 

As medical researchers became fixtures in the Cold War research 
bureaucracy, they assumed roles that, if not entirely new, raised ethical questions 
with which they had rarely dealt before. The surviving records of the period 

37 



Introduction 

reveal that frank and remarkable discussions took place among military and 
civilian officials and researchers, all of whom had to balance the benefits of 
gaining knowledge needed to fight and survive an atomic war with the risks that 
had to be taken to gain this knowledge. They had to consider, and even debated, 
whether human radiation experimentation was justified, what kinds of risks entire 
populations could be exposed to, and what the public could and should be told. 

Whether to Experiment with Humans: The Debate Is Joined 

Spurred by proposals for human radiation experiments connected with the 
nuclear-powered airplane (NEPA) project, AEC and DOD medical experts in 
1949 and 1950 engaged in debate on the need for human experimentation. The 
transcript of a 1950 meeting among AEC biomedical officials and advisers and 
military representatives provides unique insight into the mix of moral principles 
and practical concerns. 67 

The participants in the debate included many of the key medical figures in 
the Manhattan Project and the postwar radiation research bureaucracy. For the 
Navy, for example, Captain Behrens, the editor of Atomic Medicine, made the 
point that an atomic bomb might contaminate, but not sink, ships. The Navy 
would need to know the risk of sending rescue or salvage parties into the 
contaminated area. There were questions of "calculated risk which all of the 
services are interested in, and not only the services but probably the civilians as 
well." 68 Brigadier General William H. Powell, Jr., of the Office of the Air Force 
Surgeon General, added further questions: How does radiation injure tissue? Can 
equipment protect against the bomb's effects? Is there a way to treat radiation 
injury? How should mass casualties be handled? 69 

These questions were hardly abstract. Operation Crossroads had 
demonstrated that postblast contamination of Navy ships was a serious hazard. 
The use of the atomic bomb as a tactical weapon, declared Brigadier General 
James Cooney of the AEC's Division of Military Applications, "has now gone 
beyond the realm of possibility and into the realm of probability." 70 This meant 
that "we have a responsibility that is tremendous," Cooney added. "If this weapon 
is used tactically on a corps or division, and we have, say, 5,000 troops who have 
received 100 Roentgens] radiation, the Commander is going to want from me, 'Is 
it all right for me to reassemble these men and take them into combat?' I don't 
know the answer to that question." 71 Commanders needed to know "How much 
radiation can a man take?" 72 

Cooney argued that human experimentation was necessary. He invoked 
the military's tradition of experimentation with healthy volunteers, dating back to 
Walter Reed's famous work on yellow fever at the turn of the century. Cooney 
urged that the military seek volunteers within its ranks--"both officer and 
enlisted"--to be exposed to as much as 150 R of whole-body radiation. 73 

The AEC's Shields Warren took the other side in this debate. Warren 

38 



The Atomic Century 

raised two basic points in response to Cooney. First, human experimentation was 
not essential because animal research would be adequate to find the answers. 
Second, data from human experimentation would likely be scientifically useless. 
"We have," Warren declared, "learned enough from animals and from humans at 
Hiroshima and Nagasaki to be quite certain that there are extraordinary variables 
in this picture. There are species variables, genetics variables within species, 
variations in condition of the individual within that species." The danger of 
failing to provide data had to be weighed against the danger of providing 
misleading data: "It might be almost more dangerous or misleading to give an 
artificial accuracy to an answer that is of necessity an answer that spreads over a 
broad range in light of these variables." 74 

There were, moreover, political obstacles to the program Cooney had 
proposed. Satisfactory answers, Warren concluded, would require "going to tens 
of thousands of individuals." But America was not the Soviet Union: "If we were 
considering things in the Kremlin, undoubtedly it would be practicable. I doubt 
that it is practicable here." 75 

At the heart of Warren's objections to Cooney's proposal was a concern 
about employing "human experimentation when it isn't for the good of the 
individual concerned and when there is no way of solving the problem." 76 To 
Cooney's invocation of Walter Reed, Warren responded that, in the case of yellow 
fever, humans were needed as subjects because there was no nonhuman host to 

Cooney did not disagree with Warren "that statistically we will prove 

nothing." But, he pointed out, "[G]enerals are hard people to deal with If we 

had 200 cases whereby we could say that these men did or did not get sick up to 
150 R, it would certainly be a great help to us." 77 

Even then, Warren rejoined, the data might not be of great use: "I can 
think in terms of times when even if everybody on a ship was sea-sick, you would 
still have to keep the ship operating." 78 

The 1950 debate over NEPA provides clear evidence that midcentury 
medical experts gave thought before engaging in human experimentation that 
involved significant risk and was not intended to benefit the subject. On paper, 
the debate was decided in Shields Warren's favor. Following Warren's and 
DBM's opposition, Cooney and the military agreed that "human experimentation" 
on healthy volunteers would not be approved. However, even as this policy was 
declared, the Defense Department, with Warren's apparent acquiescence, 
proceeded to contract with private hospitals to gather data on sick patients who 
were being treated with radiation. The government's use of sick patients for 
research, as we shall see in chapter 8, raised difficult ethical questions of its own. 

Whether to Put Populations at Risk: The Debate Continues 

As the medical experts debated the issue of whether to put individual 

39 



Introduction 

human subjects at risk in radiation experiments on behalf of NEPA, they were 
also engaged in secret discussions about whether to proceed with the testing of 
nuclear weapons, which might put whole populations at risk. 

It was also in 1950 that the decision was made to carry out atomic bomb 
testing at a site in the continental United States. President Truman chose the 
Nevada desert as the location for the test site. Shields Warren's Division of 
Biology and Medicine was assigned the job of considering the safety of early 
tests. Like the earlier transcript, an account of a May 1951 meeting at Los 
Alamos, convened by Warren, provides a window onto the balancing of risks and 
benefits by medical researchers. 

The meeting focused on the radiological hazards to populations downwind 
from underground testing planned at the Nevada Test Site. Those in attendance 
realized that the testing could be risky. "I would almost say from the discussion 
this far," Warren summarized, "that in light of the size and activity of some of 
these particles, their unpredictability of fallout, the possibility of external beta 
burns is quite real." 79 Committee members considered the testing a "calculated 
risk" for populations downwind, but they thought that the information they could 
gain made the risk worthwhile. According to the record of the meeting, Warren 
summarized the view of Dr. Gioacchino Failla, a Columbia University 
radiological physicist: "[T]he time has come when we should take some risk and 
get some information ... we are faced with a war in which atomic weapons will 
undoubtedly be used, and we have to have some information about these 
things ... if we look for perfect safety we will never make these tests." 80 Worried 
about the potential consequences of miscalculation, the AEC's Carrol Tyler 
observed, "We have lost a continental site no matter where we put it." Still, Tyler 
argued, "If we are going to gamble it might as well be done where it is 
operationally convenient." 1 " A proposed deep underground test did not take place, 
and a test evidently considered less risky was substituted. Ultimately, in a 
summary prepared at the end of the 1951 test series, the Health Division leader of 
the AEC's Los Alamos Laboratory recorded that perhaps only good fortune had 
averted significant contamination: "Thanks to the kindness of the winds, no 
significant activity was deposited in any populated localities. It was certainly 
shown however," he wrote, "that significant exposures at considerable distances 
could be acquired by individuals who actually were in the fallout while it was in 
progress." 82 

The NEPA debate and the advent of nuclear testing confronted biomedical 
experts with a set of conflicting, and even contradictory, objectives. First, they 
were called upon to offer advice on decisions that might inevitably put people at 
some risk. The risk had to be balanced against the benefit, which in most 
instances was defined as connected with the nation's security. In many cases, the 
experts agreed, it was better to bear the lesser risk now, in order to avoid a greater 
risk later. Second, these experts were also called upon, as in the 1951 Nevada 
test, to provide advice on minimizing risk. Third, as in the Nevada test, these 

40 



The Atomic Century 

same experts saw the tests as opportunities to gather data that might ultimately be 
used to reduce risk for all. 

Whether and What the Public Should Be Told About Government-Created 
Radiation Risk 

Scientific research had a long and celebrated tradition of open publication 
in the scientific literature. But several factors caused Cold War researchers to 
limit their public disclosures. These included, preeminently, concern with 
national security, which necessarily required secrecy. But they also included the 
concern that the release of research information would undermine needed 
programs because the public could not understand radiation or because the 
information would embarrass the government. 

The tension between the publicizing of information and the limits on 
disclosure was a constant theme in Cold War research. When, in June 1 947, the 
Medical Board of Review appointed by David Lilienthal reported on the AEC's 
biomedical program, it declared that secrecy in scientific research is "distasteful 
and in the long run contrary to the best interests of scientific progress." 83 As 
shown by its organization of the medical isotope program, the AEC acted quickly 
to make sure that the great preponderance of biomedical research done under its 
auspices would be published in the open literature. 

However, recently retrieved documents show that the need for secrecy was 
also invoked where national security was not endangered. At the same time that 
biomedical officials, such as those on the Medical Board of Review, spoke openly 
of the need to limit national security restrictions, internally they sometimes sided 
with those who would restrict information from the public even where release 
admittedly would not directly endanger national security. Thus, as we shall see in 
chapter 13, Shields Warren and other AEC medical officials agreed to withhold 
data on human experiments from the public on the grounds that disclosure would 
embarrass the government or could be a source of legal liability. 

A further important qualification to what the public could know related to 
research connected with the atomic bomb-including the creation of a worldwide 
network to gather data on the effects of fallout from nuclear tests. In 1949, the 
AEC undertook Project Gabriel, a secret effort to study the question of whether 
the tests could threaten the viability of life on earth. In 1953, Gabriel led to 
Project Sunshine, a loose confederation of fallout research projects whose human 
data-gathering efforts, as we see in chapter 13, operated in the twilight between 
openness and secrecy. 

Finally, while documents show that medical experts and officials shared 
an acute awareness of the importance of public support to the success of Cold 
War programs, this awareness was coupled with concern about the American 
public's ability to understand the risks that had to be borne to win the Cold War. 
The concern that citizens could not understand radiation risk is illustrated by a 

41 



Introduction 

recently recovered NEPA transcript. In July 1949, the nuclear airplane project 
gathered radiation experts and psychologists to consider psychological problems 
connected to radiation hazard. To the assembled experts the greatest unknown 
was not radiation itself, but the basis for public fear and misunderstanding of 
radiation. 

"I believe," General Cooney proposed, "that the general public is under 
the opinion that we don't know very much about this condition [radiation]. . . . We 
know," he ventured, "just about as much about it as we do about many other 
diseases that people take for granted . . . even tuberculosis." 84 

Yet, said the Navy's Captain Behrens, "there are some peculiar ideas 
relative to radiation that are related to primitive concepts of hysteria and things in 
that category. . . . There is such a unique element in it; for some it begins to 
border on the mystical." 85 A good deal of the public's fear of radiation, declared 
Berkeley's Dr. Karl M. Bowman, a NEPA medical adviser, "is essentially the fear 
of the unknown. The dangers have been enormously magnified." As Dr. 
Bowman and others noted, the public's perception was not without reason, for "we 
have emphasized for purposes of getting funds for research how little we know." 86 

The perspective expressed in the NEPA transcript would lead, as shown in 
chapter 10, to the use of atomic bomb tests to perform human research on the 
psychology of panic and, as shown in other case studies, to decisions to hold 
information closely out of concern that its release could create public 
misunderstanding that would imperil important government programs. 

CONCLUSION 

In the atomic age, Captain Behrens's Atomic Medicine pointed out, 
radiation research was both the agent and the beneficiary of dramatic 
developments at the intersection of government and medicine. When ethical 
questions were raised by these developments, radiation researchers would be on 
the front line in having to deal with them. The burgeoning government- funded 
biomedical research, including human radiation research, required a 
reexamination of the traditional doctor-patient relationship. At the same time, the 
evolving role of medical researchers as government officials and advisers also 
posed questions about the place of doctors, and more generally of scientists, in 
service to government. 



42 



The Atomic Century 

The Basics of Radiation Science 

The ethical and historical issues of human radiation experiments cannot be 
understood without a basic grasp of the underlying science. This requires more 
than a glossary defining technical terms. At least an intuitive understanding of 
the natural laws and scientific techniques of radiation science is necessary. 
Obviously, acquiring a professional level of knowledge would require far more 
time than most readers can afford; indeed, entire careers are devoted to studying 
just one aspect of the field. To serve the interests of democracy in a technological 
world, however, we must provide sufficient technical background for all citizens 
to become active participants in considering the ethical and political dimensions 
of scientific research. 

What follows is an attempt to provide such a background for the events 
and issues discussed in this report, directed toward those readers less familiar 
with "the basics" of radiation science. This task was deemed important enough to 
deserve a distinct section of this Introduction. 

What Is Ionizing Radiation? 

What is radiation! 

Radiation is a very general term, used to describe any process that 
transmits energy through space or a material away from a source. Light, sound, 
and radio waves are all examples of radiation. When most people think of 
radiation, however, they are thinking of ionizing ra<//arto«--radiation that can 
disrupt the atoms and molecules within the body. While scientists think of these 
emissions in highly mathematical terms, they can be visualized either as 
subatomic particles or as rays. Radiation's effects on humans can best be 
understood by first examining the effect of radiation on atoms, the basic building 
blocks of matter. 

What is ionization! 

Atoms consist of comparatively large particles (protons and neutrons) 
sitting in a central nucleus, orbited by smaller particles (electrons): a miniature 
solar system. Normally, the number of protons in the center of the atom equals 
the number of electrons in orbit. An ion is any atom or molecule that does not 
have the normal number of electrons. Ionizing radiation is any form of radiation 
that has enough energy to knock electrons out of atoms or molecules, creating 
ions. 

How is ionizing radiation measured? 

Measurement lies at the heart of modern science, but a number by itself 
conveys no information. Useful measurement requires both an instrument for 
measurement (such as a stick to mark off length) and an agreement on the units to 

43 



Introduction 

be used (such as inches, meters, or miles). The units chosen will vary with the 
purpose of the measurement. For example, a cook will measure butter in terms of 
tablespoons to ensure the meal tastes good, while a nutritionist may be more 
concerned with measuring calories, to determine the effect on the diner's health. 

The variety of units used to measure radiation and radioactivity at times 
confuses even scientists, if they do not use them every day. It may be helpful to 
keep in mind the purpose of various units. There are two basic reasons to 
measure radiation: the study of physics and the study of the biological effects of 
radiation. What creates the complexity is that our instruments measure physical 
effects, while what is of interest to some are biological effects. A further 
complication is that units, as with words in any language, may fade from use and 
be replaced by new units. 

Radiation is not a series of distinct events, like radioactive decays, which 
can be counted individually. Measuring radiation in bulk is like measuring the 
movement of sand in an hourglass; it is more useful to think of it as a continuous 
flow, rather than a series of separate events. The intensity of a beam of ionizing 
radiation is measured by counting up how many ions (how much electrical 
charge) it creates in air. The roentgen (named after Wilhelm Roentgen, the 
discoverer of x rays) is the unit that measures the ability of x rays to ionize air; it 
is a unit of exposure that can be measured directly. Shortly after World War II, a 
common unit of measurement was the roentgen equivalent physical (rep), which 
denoted an ability of other forms of radiation to create as many ions in air as a 
roentgen of x rays. It is no longer used, but appears in many of the documents 
examined by the Advisory Committee. 

What are the basic types of ionizing radiation? 

There are many types of ionizing radiation, but the most familiar are 
alpha, beta, and gamma/x-ray radiation. Neutrons, when expelled from atomic 
nuclei and traveling as a form of radiation, can also be a significant health 
concern. 

Alpha particles are clusters of two neutrons and two protons each. They 
are identical to the nuclei of atoms of helium, the second lightest and second most 
common element in the universe, after hydrogen. Compared with other forms of 
radiation, though, these are very heavy particles—about 7,300 times the mass of 
an electron. As they travel along, these large and heavy particles frequently 
interact with the electrons of atoms, rapidly losing their energy. They cannot even 
penetrate a piece of paper or the layer of dead cells at the surface of our skin. But 
if released within the body from a radioactive atom inside or near a cell, alpha 
particles can do great damage as they ionize atoms, disrupting living cells. 
Radium and plutonium are two examples of alpha emitters. 

Beta particles are electrons traveling at very high energies. If alpha 
particles can be thought of as large and slow bowling balls, beta particles can be 
visualized as golf balls on the driving range. They travel farther than alpha 

44 



The Atomic Century 

particles and, depending on their energy, may do as much damage. For example, 
beta particles in fallout can cause severe burns to the skin, known as beta burns. 
Radiosotopes that emit beta particles are present in fission products produced in 
nuclear reactors and nuclear explosions. Some beta-emitting radioisotopes, such 
as iodine 131, are administered internally to patients to diagnose and treat disease. 

Gamma and x-ray radiation consists of packets of energy known as 
photons. Photons have no mass or charge, and they travel in straight lines. The 
visible light seen by our eyes is also made up of photons, but at lower energies. 
The energy of a gamma ray is typically greater than 100 kiloelectron volts (keV— 
"k" is the abbreviation for kilo, a prefix that multiplies a basic unit by 1 ,000) per 
photon, more than 200,000 times the energy of visible light (0.5 eV). If alpha 
particles are visualized as bowling balls and beta particles as golf balls, photons 
of gamma and x-radiation are like weightless bullets moving at the speed of light. 
Photons are classified according to their origin. Gamma rays originate from 
events within an atomic nucleus; their energy and rate of production depend on 
the radioactive decay process of the radionuclide that is their source. X rays are 
photons that usually originate from energy transitions of the electrons of an atom. 
These can be artificially generated by bombarding appropriate atoms with high- 
energy electrons, as in the classic x-ray tube. Because x rays are produced 
artificially by a stream of electrons, their rate of output and energy can be 
controlled by adjusting the energy and amount of the electrons themselves. Both 
x rays and gamma rays can penetrate deeply into the human body. How deeply 
they penetrate depends on their energy; higher energy results in deeper 
penetration into the body. A 1 MeV ("M" is the abbreviation for mega, a prefix 
that multiplies a basic unit by 1,000,000) gamma ray, with an energy 2,000,000 
times that of visible light, can pass completely through the body, creating tens of 
thousands of ions as it does. 

A final form of radiation of concern is neutron radiation. Neutrons, along 
with protons, are one of the components of the atomic nucleus. Like protons, they 
have a large mass; unlike protons, they have no electric charge, allowing them to 
slip more easily between atoms. Like a Stealth fighter, high-energy neutrons can 
travel farther into the body, past the protective outer layer of the skin, before 
delivering their energy and causing ionization. 

Several other types of high-energy particles are also ionizing radiation. 
Cosmic radiation that penetrates the Earth's atmosphere from space consists 
mainly of protons, alpha particles, and heavier atomic nuclei. Positrons, mesons, 
pions, and other exotic particles can also be ionizing radiation. 

What Is Radioactivity? 

What causes radioactivity? 

As its name implies, radioactivity is the act of emitting radiation 
spontaneously. This is done by an atomic nucleus that, for some reason, is 

45 



Introduction 

unstable; it "wants" to give up some energy in order to shift to a more stable 
configuration. During the first half of the twentieth century, much of modern 
physics was devoted to exploring why this happens, with the result that nuclear 
decay was fairly well understood by 1 960. Too many neutrons in a nucleus lead 
it to emit a negative beta particle, which changes one of the neutrons into a 
proton. Too many protons in a nucleus lead it to emit a positron (positively 
charged electron), changing a proton into a neutron. Too much energy leads a 
nucleus to emit a gamma ray, which discards great energy without changing any 
of the particles in the nucleus. Too much mass leads a nucleus to emit an alpha 
particle, discarding four heavy particles (two protons and two neutrons). 

How is radioactivity measured? 

Radioactivity is a physical, not a biological, phenomenon. Simply stated, 
the radioactivity of a sample can be measured by counting how many atoms are 
spontaneously decaying each second. This can be done with instruments 
designed to detect the particular type of radiation emitted with each "decay" or 
disintegration. The actual number of disintegrations per second may be quite 
large. Scientists have agreed upon common units to use as a form of shorthand. 
Thus, a curie (abbreviated "Ci" and named after Pierre and Marie Curie, the 
discoverers of radium 87 ) is simply a shorthand way of writing "37,000,000,000 
disintegrations per second," the rate of disintegration occurring in 1 gram of 
radium. The more modern International System of Measurements (SI) unit for the 
same type of measurement is the becquerel ( abbreviated "Bq" and named after 
Henri Becquerel, the discoverer of radioactivity), which is simply a shorthand for 
"1 disintegration per second." 

What is radioactive half-life"! 

Being unstable does not lead an atomic nucleus to emit radiation 
immediately. Instead, the probability of an atom disintegrating is constant, as if 
unstable nuclei continuously participate in a sort of lottery, with random drawings 
to decide which atom will next emit radiation and disintegrate to a more stable 
state. The time it takes for half of the atoms in a given mass to "win the lottery"-- 
that is, emit radiation and change to a more stable state—is called the half-life. 
Half-lives vary greatly among types of atoms, from less than a second to billions 
of years. For example, it will take about 4.5 billion years for half of the atoms in 
a mass of uranium 238 to spontaneously disintegrate, but only 24,000 years for 
half of the atoms in a mass of plutonium 239 to spontaneously disintegrate. 
Iodine 131, commonly used in medicine, has a half-life of only eight days. 

What is a radioactive decay chain? 

Stability may be achieved in a single decay, or a nucleus may decay 
through a series of states before it reaches a truly stable configuration, a bit like a 
Slinky toy stepping down a set of stairs. Each state or step will have its own 

46 



The Atomic Century 

unique characteristics of half-life and type of radiation to be emitted as the move 
is made to the next state. Much scientific effort has been devoted to unraveling 
these decay chains, not only to achieve a basic understanding of nature, but also 
to design nuclear weapons and nuclear reactors. The unusually complicated 
decay of uranium 238, for example— the primary source of natural radioactivity on 
earth— proceeds as follows:" 8 

U-238 emits an alpha 

I 

Thorium 234 emits a beta 

I 

Protactinium 234 emits a beta 

I 
Uranium 234 emits an alpha 

1 
Thorium 230 emits an alpha 

1 
Radium 226 emits an alpha 

I 

Radon 222 emits an alpha 

! 

Polonium 2 1 8 emits an alpha 

1 

Lead 214 emits a beta 

1 

Bismuth 214 emits a beta 

I 

Polonium 214 emits an alpha 

I 

Lead 210 emits a beta 

1 

Bismuth 210 emits a beta 

1 

Polonium 210 emits an alpha 

I 

Lead 206, which is stable 



How can radioactivity be caused artificially? 

Radioactivity can occur both naturally and through human intervention. 
An example of artificially induced radioactivity is neutron activation. A neutron 
fired into a nucleus can cause nuclear fission (the splitting of atoms). This is the 
basic concept behind the atomic bomb. Neutron activation is also the underlying 

47 



Introduction 

principle of boron-neutron capture therapy for certain brain cancers. A solution 
containing boron is injected into a patient and is absorbed more by the cancer than 
by other cells. Neutrons fired at the area of the brain cancer are readily absorbed 
(captured) by the boron nuclei. These nuclei then become unstable and emit 
radiation that attacks the cancer cells. Simple in its basic physics, the treatment 
has been complex and controversial in practice and after half a century is still 
regarded as highly experimental. 

What Are Atomic Number and Atomic Weight? 

What is an element? 

Chemical behavior is what originally led scientists to classify matter into 
various elements. Chemical behavior is the ability of an atom to combine with 
other atoms. In more technical terms, chemical behavior depends upon the type 
and number of the chemical bonds an atom can form with other atoms. In 
classroom kits for building models of molecules, atoms are usually represented by 
colored spheres with small holes for pegs and the bonds are represented by the 
small pegs that can connect the spheres. The number of peg holes signifies the 
maximum number of bonds an atom can form; different types of bonds may be 
represented by different types of pegs. Atoms that have the same number of peg 
holes may have similar chemical behavior. Thus, atoms that have identical 
chemical behavior are regarded as atoms of the same element. For example, an 
atom is labeled a "carbon atom" if it can form the same number, types, and 
configurations of bonds as other carbon atoms. Although the basics are simple to 
explain, how atoms bind to each other becomes very complex when studied in 
detail; new discoveries are still being made as new types of materials are formed. 

What is atomic number? 

An atom may be visualized as a miniature solar system, with a large 
central nucleus orbited by small electrons. The bonding capacity of an atom is 
determined by the electrons. For example, atoms that in their normal state have 
one electron are hydrogen atoms and will readily (and sometimes violently) bond 
with oxygen. This bonding capacity of hydrogen was the cause of the explosion 
of the airship Hindenburg in 1937. Atoms that in their normal state have two 
electrons are helium atoms, which will not bond with oxygen and would have 
been a better choice for filling the Hindenburg. 

We can pursue the question back one step further: What determines the 
number of electrons? The number of protons in the nucleus of the atom. Here, 
the analogy between an atom and the solar system breaks down. The force that 
holds the planets in their orbits is the gravitational attraction between the planets 
and the sun. However, in an atom what holds the electrons in their orbit is the 
electrical attraction between the electrons and the protons in the nucleus. The 

48 



The Atomic Century 

basic rule is that like charges repel and opposite charges attract. Although a 
proton has more mass than an electron, they both have the samf amount of 
electrical charge, but opposite in kind. Scientists have designated electrons as 
having a negative charge and protons as having a positive charge. One positive 
proton can hold one negative electron in orbit. Thus, an atom with one proton in 
its nucleus normally will have one electron in orbit (and be labeled a hydrogen 
atom); an atom with ninety-four protons in its nucleus will normally have ninety- 
four electrons orbiting it (and be labeled a plutonium atom). 

The number of protons in a nucleus is called the atomic number and 
always equals the number of electrons in orbit about that nucleus (in a nonionized 
atom). Thus, all atoms that have the same number of protons~the atomic 
number— are atoms of the same element. 

What is atomic weight? 

The nuclei of atoms also contain neutrons, which help hold the nucleus 
together. A neutron has no electrical charge and is slightly more massive than a 
proton. Because a neutron can decay into a proton plus an electron (the essence 
of beta decay), it is sometimes helpful to think of a neutron as an electron and a 
proton blended together, although this is at best an oversimplification. Because a 
neutron has no charge, a neutron has no effect on the number of electrons orbiting 
the nucleus. However, because it is even more massive than a proton, a neutron 
can add significantly to the weight of an atom. The total weight of an atom is 
called the atomic weight. It is approximately equal to the number of protons and 
neutrons, with a little extra added by the electrons. The stability of the nucleus, 
and hence the atom's radioactivity, is heavily dependent upon the number of 
neutrons it contains. 

What notations are used to represent atomic number and weight? 

Each atom, therefore, can be assigned both an atomic number (the number 
of protons equals the number of electrons) and an atomic weight (approximately 
equaling the number of protons plus the number of neutrons). A normal helium 
atom, for example, has two protons and two neutrons in its nucleus, with two 
electrons in orbit. Its chemical behavior is determined by the atomic number 2 
(the number of protons), which equals the normal number of electrons; the 
stability of its nucleus (that is, its radioactivity) varies with its atomic weight 
(approximately equal to the number of protons and neutrons). The most well- 
known form of plutonium, for example, has an atomic number of 94, since it has 
94 protons, and with the 145 neutrons in its nucleus, an atomic weight of 239 (94 
protons plus 145 neutrons). In World War II, its very existence was highly 
classified. A code number was developed: the last digit of the atomic number 
(94) and the last digit of the atomic weight (239). Thus, in some of the early 
documents examined by the Advisory Committee, the term 49 refers to 
plutonium. 

49 



Introduction 

Styles of notation vary, but usually isotopes are written as: 

atcic numb e r Chemical abbreviation at ™8 ht 

or as 
atomic weight chemical abbreviation 

Thus, the isotope of plutonium just discussed would be written as: 



94 



Pu 239 or as 239 Pu 



Since the atomic weight is what is often the only item of interest, it might also be 
written simply as Pu-239, plutonium 239, or Pu 239 . 



Radioisotopes: What Are They and How Are They Made? 

What are isotopes? 

The isotopes of an element are all the atoms that have in their nucleus the 
number of protons (atomic number) corresponding to the chemical behavior of 
that element. However, the isotopes of a single element vary in the number of 
neutrons in their nuclei. Since they still have the same number of protons, all 
these isotopes of an element have identical chemical behavior. But since they 
have different numbers of neutrons, these isotopes of the same element may have 
different radioactivity. An isotope that is radioactive is called a radioisotope or 
radionuclide. Two examples may help clarify this. 

The most stable isotope of uranium, U-238, has an atomic number of 92 
(protons) and an atomic weight of 238 (92 protons plus 146 neutrons). The 
isotope of uranium of greatest importance in atomic bombs, U-235, though, has 
three fewer neutrons. Thus, it also has an atomic number of 92 (since the number 
of protons has not changed) but an atomic weight of 235 (92 protons plus only 
143 neutrons). The chemical behavior of U-235 is identical to all other forms of 
uranium, but its nucleus is less stable, giving it higher radioactivity and greater 
susceptibility to the chain reactions that power both atomic bombs and nuclear 
fission reactors. 

Another example is iodine, an element essential for health; insufficient 
iodine in one's diet can lead to a goiter. Iodine also is one of the earliest elements 
whose radioisotopes were used in what is now called nuclear medicine. The most 
common, stable form of iodine has an atomic number of 53 (protons) and an 
atomic weight of 127 (53 protons plus 74 neutrons). Because its nucleus has the 
"correct" number of neutrons, it is stable and is not radioactive. A less stable 
form of iodine also has 53 protons (this is what makes it behave chemically as 

50 



The Atomic Century 

iodine) but four extra neutrons, for a total atomic weight of 131 (53 protons and 
78 neutrons). With "too many" neutrons in its nucleus, it is unstable and 
radioactive, with a half-life of eight days. Because it behaves chemically as 
iodine, it travels throughout the body and localizes in the thyroid gland just like 
the stable form of iodine. But, because it is radioactive, its presence can be 
detected. Iodine 131 thus became one of the earliest radioactive tracers. 

How can different isotopes of an element be produced? 

How can isotopes be produced-especially radioisotopes, which can serve 
many useful purposes? There are two basic methods: separation and synthesis. 

Some isotopes occur in nature. If radioactive, these usually are 
radioisotopes with very long half-lives. Uranium 235, for example, makes up 
about 0.7 percent of the naturally occurring uranium on the earth.* 9 The challenge 
is to separate this very small amount from the much larger bulk of other forms of 
uranium. The difficulty is that all these forms of uranium, because they all have 
the same number of electrons, will have identical chemical behavior: they will 
bind in identical fashion to other atoms. Chemical separation, developing a 
chemical reaction that will bind only uranium atoms, will separate out uranium 
atoms, but not distinguish among different isotopes of uranium. The only 
difference among the uranium isotopes is their atomic weight. A method had to 
be developed that would sort atoms according to weight. 

One initial proposal was to use a centrifuge. The basic idea is simple: 
spin the uranium atoms as if they were on a very fast merry-go-round. The 
heavier ones will drift toward the outside faster and can be drawn off. In practice 
the technique was an enormous challenge: the goal was to draw off that very 
small portion of uranium atoms that were lighter than their brethren. The 
difficulties were so enormous the plan was abandoned in 1942. 90 Instead, the 
technique of gaseous diffusion was developed. Again, the basic idea was very 
simple: the rate at which gas passed {diffused) through a filter depended on the 
weight of the gas molecules: lighter molecules diffused more quickly. Gas 
molecules that contained U-235 would diffuse slightly faster than gas molecules 
containing the more common but also heavier U-238. This method also presented 
formidable technical challenges, but was eventually implemented in the gigantic 
gas diffusion plant at Oak Ridge, Tennessee. In this process, the uranium was 
chemically combined with fluorine to form a hexafluoride gas prior to separation 
by diffusion. This is not a practical method for extracting radioisotopes for 
scientific and medical use. It was extremely expensive and could only supply 
naturally occurring isotopes. 

A more efficient approach is to artificially manufacture radioisotopes. 
This can be done by firing high-speed particles into the nucleus of an atom. 
When struck, the nucleus may absorb the particle or become unstable and emit a 
particle. In either case, the number of particles in the nucleus would be altered, 
creating an isotope. One source of high-speed particles could be a cyclotron. A 

51 



Introduction 

cyclotron accelerates particles around a circular race track with periodic pushes of 
an electric field. The particles gather speed with each push, just as a child swings 
higher with each push on a swing. When traveling fast enough, the particles are 
directed off the race track and into the target. 

A cyclotron works only with charged particles, however. Another source 
of bullets are the neutrons already shooting about inside a nuclear reactor. The 
neutrons normally strike the nuclei of the fuel, making them unstable and causing 
the nuclei to split (fission) into two large fragments and two to three "free" 
neutrons. These free neutrons in turn make additional nuclei unstable, causing 
further fission. The result is a chain reaction. Too many neutrons can lead to an 
uncontrolled chain reaction, releasing too much heat and perhaps causing a 
"meltdown." Therefore, "surplus" neutrons are usually absorbed by "control 
rods." However, these surplus neutrons can also be absorbed by targets of 
carefully selected material placed in the reactor. In this way the surplus neutrons 
are used to create radioactive isotopes of the materials placed in the targets. 

With practice, scientists using both cyclotrons and reactors have learned 
the proper mix of target atoms and shooting particles to "cook up" a wide variety 
of useful radioisotopes. 

How Does Radiation Affect Humans? 

Radiation may come from either an external source, such as an x-ray 
machine, or an internal source, such as an injected radioisotope. The impact of 
radiation on living tissue is complicated by the type of radiation and the variety of 
tissues. In addition, the effects of radiation are not always easy to separate from 
other factors, making it a challenge at times for scientists to isolate them. An 
overview may help explain not only the effects of radiation but also the 
motivation for studying them, which led to much of the research examined by the 
Advisory Committee. 

What effect can ionizing radiation have on chemical bonds? 

The functions of living tissue are carried out by molecules, that is, 
combinations of different types of atoms united by chemical bonds. Some of 
these molecules can be quite large. The proper functioning of these molecules 
depends upon their composition and also their structure (shape). Altering 
chemical bonds may change composition or structure. Ionizing radiation is 
powerful enough to do this. For example, a typical ionization releases six to 
seven times the energy needed to break the chemical bond between two carbon 
atoms. 91 This ability to disrupt chemical bonds means that ionizing radiation 
focuses its impact in a very small but crucial area, a bit like a karate master 
focusing energy to break a brick. The same amount of raw energy, distributed 
more broadly in nonionizing form, would have much less effect. For example, the 
amount of energy in a lethal dose of ionizing radiation is roughly equal to the 

52 



The Atomic Century 

amount of thermal energy in a single sip of hot coffee. 92 The crucial difference is 
that the coffee's energy is broadly distributed in the form of nonionizing heat, 
while the radiation's energy is concentrated in a form that can ionize. 

What is DNA? 

Of all the molecules in the body, the most crucial is DNA (deoxyribose 
nucleic acid), the fundamental blueprint for all of the body's structures. The DNA 
blueprint is encoded in each cell as a long sequence of small molecules, linked 
together into a chain, much like the letters in a telegram. DNA molecules are 
enormously long chains of atoms wound around proteins and packed into 
structures called chromosomes within the cell nucleus. When unwound, the DNA 
in a single human cell would be more than 2 meters long. It normally exists as 
twenty-three pairs of chromosomes packed within the cell nucleus, which itself 
has a diameter of only 10 micrometers (0.00001 meter). 93 Only a small part of 
this DNA needs to be read at any one time to build a specific molecule. Each cell 
is continually reading various parts of its own DNA as it constructs fresh 
molecules to perform a variety of tasks. It is worth remembering that the 
structure of DNA was not solved until 1953, nine years after the beginning of the 
period studied by the Advisory Committee. We now have a much clearer picture 
of what happens within a cell than did the scientists of 1944. 

What effect can ionizing radiation have on DNA? 

Ionizing radiation, by definition, "ionizes," that is, it pushes an electron 
out of its orbit around an atomic nucleus, causing the formation of electrical 
charges on atoms or molecules. If this electron comes from the DNA itself or 
from a neighboring molecule and directly strikes and disrupts the DNA molecule, 
the effect is called direct action. This initial ionization takes place very quickly, 
in about 0.000000000000001 of a second. However, today it is estimated that 
about two-thirds of the damage caused by x rays is due to indirect action. This 
occurs when the liberated electron does not directly strike the DNA, but instead 
strikes an ordinary water molecule. This ionizes the water molecule, eventually 
producing what is known as zfree radical. A free radical reacts very strongly 
with other molecules as it seeks to restore a stable configuration of electrons. A 
free radical may drift about up to 10,000,000,000 times longer than the time 
needed for the initial ionization (this is still a very short time, about 0.00001 of a 
second), increasing the chance of it disrupting the crucial DNA molecule. This 
also increases the possibility that other substances could be introduced that would 
neutralize free radicals before they do damage. 94 

Neutrons act quite differently. A fast neutron will bypass orbiting 
electrons and occasionally crash directly into an atomic nucleus, knocking out 
large particles such as alpha particles, protons, or larger fragments of the nucleus. 
The most common collisions are with carbon or oxygen nuclei. The particles 
created will themselves then set about ionizing nearby electrons. A slow neutron 

53 



Introduction 

will not have the energy to knock out large particles when it strikes a nucleus. 
Instead, the neutron and the nucleus will bounce off each other, like billiard balls. 
In so doing, the neutron will slow down, and the nucleus will gain speed. The 
most common collision is with a hydrogen nucleus, a proton that can excite or 
ionize electrons in nearby atoms. 95 

What immediate effects can ionizing radiation have on living cells? 

All of these collisions and ionizations take place very quickly, in less than 
a second. It takes much longer for the biological effects to become apparent. If 
the damage is sufficient to kill the cell, the effect may become noticeable in hours 
or days. Cell "death" can be of two types. First, the cell may no longer perform 
its function due to internal ionization; this requires a dose to the cell of about 100 
gray (10,000 rad). (For a definition of gray and rad, see the section below titled 
"How Do We Measure the Biological Effects of Radiation?") Second, 
"reproductive death" (mitotic inhibition) may occur when a cell can no longer 
reproduce, but still performs its other functions. This requires a dose of 2 gray 
(200 rad), which will cause reproductive death in half the cells irradiated (hence 
such a quantity is called a "mean lethal dose.") 96 Today we still lack enough 
information to choose among the various models proposed to explain cell death in 
terms of what happens at the level of atoms and molecules inside a cell. 97 If 
enough crucial cells within the body totally cease to function, the effect is fatal. 
Death may also result if cell reproduction ceases in parts of the body where cells 
are continuously being replaced at a high rate (such as the blood cell-forming 
tissues and the lining of the intestinal tract). A very high dose of 100 gray 
( 1 0,000 rad) to the entire body causes death within twenty-four to forty-eight 
hours; a whole-body dose of 2.5 to 5 gray (250 to 500 rad) may produce death 
within several weeks. 98 At lower or more localized doses, the effect will not be 
death, but specific symptoms due to the loss of a large number of cells. These 
effects were once called nonstochastic; they are now called deterministic.™ A 
beta burn is an example of a deterministic effect. 

What long-term effects can radiation have? 

The effect of the radiation may not be to kill the cell, but to alter its DNA 
code in a way that leaves the cell alive but with an error in the DNA blueprint. 
The effect of this mutation will depend on the nature of the error and when it is 
read. Since this is a random process, such effects are now called stochastic.™ 
Two important stochastic effects of radiation are cancer, which results from 
mutations in nongerm cells (termed somatic cells), and heritable changes, which 
result from mutations in germ cells (eggs and sperm). 

How can ionizing radiation cause cancer? 

Cancer is produced if radiation does not kill the cell but creates an error in 
the DNA blueprint that contributes to eventual loss of control of cell division, and 

54 



The Atomic Century 

the cell begins dividing uncontrollably. This effect might not appear for many 
years. Cancers induced by radiation do not differ from cancers due to other 
causes, so there is no simple way to measure the rate of cancer due to radiation. 
During the period studied by the Advisory Committee, great effort was devoted to 
studies of irradiated animals and exposed groups of people to develop better 
estimates of the risk of cancer due to radiation. This type of research is 
complicated by the variety of cancers, which vary in radiosensitivity. For 
example, bone marrow is more sensitive than skin cells to radiation-induced 
cancer. 101 

Large doses of radiation to large numbers of people are needed in order to 
cause measurable increases in the number of cancers and thus determine the 
differences in the sensitivity of different organs to radiation. Because the cancers 
can occur anytime in the exposed person's lifetime, these studies can take seventy 
years or more to complete. For example, the largest and scientifically most 
valuable epidemiologic study of radiation effects has been the ongoing study of 
the Japanese atomic bomb survivors. Other important studies include studies of 
large groups exposed to radiation as a consequence of their occupation (such as 
uranium miners) or as a consequence of medical treatment. These types of 
studies are discussed in greater detail in the section titled "How Do Scientists 
Determine the Long-Term Risks from Radiation?" 

How can ionizing radiation produce genetic mutations? 

Radiation may alter the DNA within any cell. Cell damage and death that 
result from mutations in somatic cells occur only in the organism in which the 
mutation occurred and are therefore termed somatic or nonheritable effects. 
Cancer is the most notable long-term somatic effect. In contrast, mutations that 
occur in germ cells (sperm and ova) can be transmitted to future generations and 
are therefore called genetic or heritable effects. Genetic effects may not appear 
until many generations later. The genetic effects of radiation were first 
demonstrated in fruit flies in the 1920s. Genetic mutation due to radiation does 
not produce the visible monstrosities of science fiction; it simply produces a 
greater frequency of the same mutations that occur continuously and 
spontaneously in nature. 

Like cancers, the genetic effects of radiation are impossible to distinguish 
from mutations due to other causes. Today at least 1,300 diseases are known to 
be caused by a mutation. 102 Some mutations may be beneficial; random mutation 
is the driving force in evolution. During the period studied by the Advisory 
Committee, there was considerable debate among the scientific community over 
both the extent and the consequences of radiation-induced mutations. In contrast 
to estimates of cancer risk, which are based in part on studies of human 
populations, estimates of heritable risk are based for the most part upon animal 
studies plus studies of Japanese survivors of the atomic bombs. 

The risk of genetic mutation is expressed in terms of the doubling dose: 

55 



Introduction 

the amount of radiation that would cause additional mutations equal in number to 
those that already occur naturally from all causes, thereby doubling the naturally 
occurring rate of mutation. 

It is generally believed that mutation rates depend linearly on dose and 
that there is no threshold below which mutation rates would not be increased. 
Spontaneous mutation (unrelated to radiation) occurs naturally at a rate of 
approximately 1/10,000 to 1/1,000,000 cell divisions per gene, with wide 
variation from one gene to another. 

Attempts have been made to estimate the contribution of ionizing 
radiation to human mutation rates by studying offspring of both exposed and 
nonexposed Japanese atomic bomb survivors. These estimates are based on 
comparisons of the rate of various congenital defects and cancer between exposed 
and nonexposed survivors, as well as on direct counting of mutations at a small 
number of genes. For all these endpoints, no excess has been observed among 
descendants of the exposed survivors. 

Given this lack of direct evidence of any increase in human heritable 
(genetic) effects resulting from radiation exposure, the estimates of genetic risks 
in humans have been compared with experimental data obtained with laboratory 
animals. However, estimates of human genetic risks vary greatly from animal 
data. For example, fruit flies have very large chromosomes that appear to be 
uniquely susceptible to radiation. Humans may be less vulnerable than previously 
thought. Statistical lower limits on the doubling dose have been calculated that 
are compatible with the observed human data. Based on our inability to 
demonstrate an effect in humans, the lower limit for the genetic doubling dose is 
thought to be less than 100 rem. 103 

How Do We Measure the Biological Effects of External Radiation? 

The methods of measuring radiation and radioactivity, purely physical 
events, were discussed earlier. In studying the effect of radiation on living 
organisms, a biological event, the crucial data are the amount of energy absorbed 
by a specific amount and type of tissue. This requires first measuring the amount 
of energy left behind by the radiation in the tissue and, second, the amount and 
type of tissue. 

What is an absorbed dose of radiation? 

The risk posed to a human being by any radiation exposure depends partly 
upon the absorbed dose, the amount of energy absorbed per gram of tissue. 
Absorbed dose is expressed in rad. A rad is equal to 100 ergs of energy 
absorbed by 1 gram of tissue. The more modern, internationally adopted unit is 
the gray (named for the English medical physicist L. H. Gray); one gray equals 
100 rad. Almost all the documents from the time period studied by the Advisory 
Committee use the term rad rather than gray. It is important to realize that 

56 



The Atomic Centwy 

absorbed dose refers to energy per gram of absorbing tissue, not total energy. 
Someone absorbing 1 gray (100 rad) in a small amount of tissue, such as a thyroid 
gland, will absorb much less total energy than someone absorbing 1 gray (100 
rad) throughout his or her entire body. Thus, when speaking of absorbed dose, it 
is crucial to know the amount of tissue being exposed, not simply the number of 
gray or rad. 

What is an equivalent dose of radiation? 

Even the rad or gray, though, are still units that measure a purely physical 
event: the amount of energy left behind in a gram of tissue. It does not directly 
measure the biological effect of that radiation. The biological effect of the same 
amount of absorbed energy may vary according to the type of radiation involved. 
This biological effect can be computed by multiplying the absorbed dose (in rad 
or gray) by a number indicating the quality factor of the particular type of 
radiation. For photons and electrons the quality factor is defined to be 1; for 
neutrons it ranges from 5 to 20 depending on the energy of the neutron; for alpha 
particles it is 20. m Thus, 1 gray (100 rad) of alpha particles is currently judged to 
have an effect on living tissue that is twenty times more than 1 gray ( 1 00 rad) of x 
rays. Multiplying the absorbed dose (in rad or gray) by the quality factor (also 
known as the radiation weighting factor) produces what is called the equivalent 
dose. For the period studied by the Advisory Committee, this was expressed in 
terms of a unit called the rem, an acronym for roentgen equivalent man. 105 (The 
term equivalent simply meant that an absorbed dose expressed in rem would have 
equivalent biological effects, regardless of the type of radiation. Thus, 10 rem of 
x rays should have the same biological effect as 10 rem of neutrons absorbed by 
the same part of the body.) The modern unit is the sievert (abbreviated Sv and 
named for the prominent Swedish radiologist, Rolf Sievert), which is equal to 100 
rem. Thus, an equivalent dose of 200 rem would today be expressed as 2 sievert. 

What is an effective dose of radiation? 

Finally, the biological effect of radiation depends on the type of tissue 
being irradiated. As with different types of radiation, a weighting or quality 
factor is introduced depending on the type of tissue. The more sensitive the tissue 
is to radiation, the higher the factor. The effective dose is the sum of the 
equivalent doses of the various types of irradiated tissue, each properly weighted 
for its sensitivity to radiation. Tissue weighting factors are determined from the 
relative incidence of cancers in different tissues in the Japanese survivors of the 
atomic bombs. 

Calculating the effective dose makes it possible to readily compare 
different exposures, as illustrated by the accompanying graphs. 



57 



Experimental and Nonexperimental Doses* 



Thyroid Studies with lodine-131 

Effective Dose Equivalant (millirems, thyroid excluded) 
350 





Study 1 Study 2 Study 3 Study 4 Background 



Largest Dose 



Smallest Dose 



Thyroid Studies with lodine-131 

Dose to Thyroid Gland (rads) 
600 





Study 1 Study 2 Study 3 
■ Largest Thyroid Dose H 



Study 4 Medical Scan 
Smallest Thyroid Dose 



*The experiments themselves are discussed in chapter 7. These graphs are reproduced with permission 
from Task Force on Human Subject Research, Commonwealth of Massachusetts Department of Mental 
Retardation, April 1994, "A Report on the Use of Radioactive Materials in Human Subject Research that 
Involved Residents of State-Operated Facilities within the Commonwealth of Massachusetts from 1942- 
1973" (ACHRENo. MASS-072194-A), 17, and the Working Group on Human Subject Research, 
Commonwealth of Massachusetts Department of Mental Retardation, June 1994, "The Thyriod Studies: 
A Follow-up Report on the Use of Radioactive Materials in Human Subject Research that Involved 
Residents of State-Operated Facilities within the Commonwealth of Massachusetts from 1942-1973" 
(ACHRENo. MASS-072194-A), 14. 



Fernald School Nutrition Study: Ca Tracer 

Effective Dose Equivalent (millirems) 
500 




Smallest Dose Largest Dose 

|H Annual Natural Background | 



Denver Resident 
Study 



Fernald School Nutrition Study: Fe Tracer 

Effective Dose Equivalent (millirems) 
500 




Smallest Dose Largest Dose Denver Resident 

MB Annual Natural Background H] Study 



Common Medical Procedures 

Whole Body Effective Dose Equivalent (millirems) 
1000 




Chest X-Ray BackX-Ray Colon X-Ray Brain Scan 
H| Annual Natural Background HH Procedure 



Introduction 

How Do We Measure the Biological Effects of Internal Emitters? 

The general principles just described require further refinement when 
applied to doses from internal emitters. 

What information is needed to calculate absorbed dose of a 
radionuclide inside the body? 

Calculating the absorbed dose from a radionuclide inside the body is 
complex since it involves both the physics of radioactive decay and the biology of 
the body's metabolism. Six important factors that must be considered are these: 

1. The amount of the radionuclide administered. 

2. The type of radiation emitted during the decay process. 

3. The physical half-life of the radionuclide. 

4. The chemical form of the radionuclide. 

5. The fraction of the radionuclide that accumulates in each organ. 

6. The length of time that the radionuclide remains in the organ (the 
biological half-life). 

How varied are the types of radiation that different radionuclides 
emit? 

Radionuclides can emit several types of radiation (e.g., gamma rays, beta 
or alpha particles). Each radionuclide emits its own unique mixture of radiations; 
indeed, scientists identify radioactive materials by using these unique mixtures as 
if they were fingerprints. The mix of radiations for a specific radionuclide is 
always the same, regardless of whether the radionuclide is located on a bench in a 
physicist's laboratory or inside the human body. This means that the type of 
radiation of each radionuclide can be measured outside the body with great 
precision by laboratory instruments. A quality factor, discussed earlier, is used to 
adjust for the difference in the biological effects of different types of radiation. 

What determines how long a radionuclide will irradiate the body? 

The combination of the physical and biological half-life (the effective 
half-life) determines how long a radionuclide will continue to pump out energy 
into surrounding tissue. If the physical and biological half-lives of a particular 
chemical form of a radionuclide are very long, the radionuclide will continue to 
expose an individual to radiation over his or her lifetime. The total lifetime 
radiation exposure, expressed in rem, is called the committed dose equivalent. 

The physical half-life is the length of time it will take for half of the atoms 
in a sample to decay to a more stable form. The physical half-life of each 
radionuclide can be measured precisely in the laboratory. A shorter half-life 
means that the miniature power source will "run down" sooner. Sometimes, 
however, a radionuclide will not decay immediately to a stable form, but to a 

60 



The Atomic Century 

second, still unstable, form. A full calculation, therefore, must also include the 
types of radiation and physical half-lives of any decay products. 

The biological half-life does not depend on the radionuclide but rather on 
the chemical form of the radionuclide. One chemical form of the radionuclide 
might be rapidly eliminated from the body whereas other chemical forms may be 
slowly eliminated. 

To measure the biological half-life of a particular chemical form of a 
radionuclide, that chemical form needs to be studied in animals. Since the 
biological processes of different animals vary considerably, an accurate 
determination of the biological half-life requires that each chemical form of the 
radionuclide be studied in each animal of interest. Prior to studying a chemical 
form of a radionuclide in a human being, animal studies are performed to get 
some idea of what to expect. 

Once the results of animal studies are available, scientists are able to 
predict what amount of that chemical form of the radionuclide can be safely 
injected into humans. An accurate determination of what fraction of each 
chemical form of the radionuclide accumulates in each organ and how long it 
stays in each organ in humans can only be determined by studying humans. 
These type of studies are called biodistribution studies. 

What is the tissue weighting factor? 

Some chemical forms of radionuclides are highly concentrated in one 
small organ (e.g., iodine in the thyroid gland). When this happens, that organ will 
absorb most of the radiated energy, and little energy will be deposited in the 
remainder of the body. Thus, for each chemical form of a radionuclide, there is 
an organ that will receive the highest dose from that radionuclide. Since organs 
also vary greatly in their sensitivity to radiation, the biological consequences of 
the radiation dose differ depending on the organ. This difference in sensitivity to 
radiation is represented by what is called a tissue weighting factor. 

What is the difference between committed equivalent dose and 
committed effective dose? 

An estimate of the risk posed by a radionuclide in the body depends on its 
chemical form, its biodistribution, its physical properties (how it decays), and the 
sensitivity of the organs exposed. When all these factors are considered in the 
calculation of risk for a single radionuclide, the total lifetime exposure is called 
the committed equivalent dose. If more than one radioisotope is present, the sum 
of all the committed equivalent doses is called the committed effective dose. Both 
are expressed in rem or the more modern units sieverts. m These calculations 
provide a basis for comparing the risk posed by different isotopes. 

How do radiation risks compare with chemical risks? 

It should be noted that radiation is not the only possible hazard resulting 

61 



Introduction 

from the medical use of radionuclides. Few radioisotopes, whether intentionally 
or accidentally introduced into the body, enter in a chemically pure form. The 
radioactive atoms are usually part of a larger chemical compound. The chemical 
form of the radioisotope may pose its own hazards of chemical toxicity. Chemical 
toxicity depends upon the chemical effect of the compound on the body, quite 
independent of any effects of radiation. Determining chemical toxicity is an 
entire field of science on its own. 

How Do Scientists Determine the Long-Term Risks from Radiation? 

Where did the risk estimates in this report come from? 

Throughout this report, the reader will find numerous statements 
estimating the risks of cancer and other outcomes to individuals exposed to 
various types of radiation. These estimates were obtained from various scientific 
advisory committees that have considered these questions in depth. 107 Their 
estimates in turn are based on syntheses of the scientific data on observed effects 
in humans and animals. 

How are risk estimates expressed? 

Epidemiologists usually express the risk of disease in terms of the number 
of new cases {incidence rate) or deaths (mortality rate) in a population in some 
period of time. For example, an incidence rate might be 100 new cases per 
100,000 people per year; a mortality rate might be 15 deaths per 100,000 people 
per year. These rates vary widely by age, conditions of exposure, and various 
other factors. To summarize this complex set of rates, government regulatory 
bodies often consider the lifetime risk of a particular outcome like cancer. When 
relating a disease, such as cancer, to one of its several causes, a more useful 
concept is the excess lifetime risk expected from one particular pattern of 
exposure, such as continuous exposure to 1 rad per year. 

It is well established that cancer rates begin to rise above the normal 
background rate only some time after exposure, the latent period, which varies 
with the type of cancer and other factors such as age. Even after the latent period 
has passed and radiation effects begin to appear, not all effects are due to 
radiation. The excess rate may still vary by age, latency, or other factors, but for 
many cancers it tends to be roughly proportional to the rate in the general 
population. This is known as the constant relative risk model, and the ratio of 
rates at any given age between exposed and unexposed groups is called the 
relative risk. Many advisory committees have based their risk estimates on 
models for the relative risk as a function of dose and perhaps other factors. Other 
committees, however, have based their estimates on the difference in rates 
between exposed and unexposed groups, a quantity known as the absolute risk. 
This quantity also varies with dose and other factors, but when this variation is 
appropriately accounted for, either approach can be used to estimate lifetime risk. 

62 



The Atomic Century 

What are the types of data on which such estimates are based? 

Human data are one important source, discussed below. Two other 
important sources of scientific data are experiments on animals and on cell 
cultures. Because both types of research are done in laboratories, scientists can 
carefully control the conditions and many of the variables. For the same reason, 
the experiment can be repeated to confirm the results. Such research has 
contributed in important ways to our understanding of basic radiobiological 
principles. It also has provided quantitative estimates of such parameters as the 
relative effectiveness of different types of radiation and the effects of dose and 
dose rate. In some circumstances, where human data are limited or nonexistent, 
such laboratory studies may provide the only basis on which risks can be 
estimated. 

Why are human data preferable to data on animals or tissue cultures 
for most purposes? 

Most scientists prefer to base risk estimates for humans on human data 
wherever possible. This is because in order to apply animal or tissue culture data 
to humans, scientists must extrapolate from one species to another or from simple 
cellular systems to the complexities of human physiology. This requires adjusting 
the data for differences among species in life span, body size, metabolic rates, and 
other characteristics. Without actual human data, extrapolation provides no 
guarantee that there are no unknown factors also at work. It is not surprising that 
there is no clear consensus as to how to extrapolate risk estimates from one 
species to another. This problem is not unique to radiation effects; there are 
countless examples of chemicals having very different effects in different species, 
and humans can differ quite significantly from animals in their reaction to toxic 
agents. 

How have human data been obtained? 

There are serious ethical issues with conducting experiments on humans, 
as discussed elsewhere in the report. However, most of the human data that are 
used to estimate risks, not just risk from radiation, come from epidemiologic 
studies on populations that already have been exposed in various ways. For 
radiation effects, the most important human data come from studies of the 
Japanese atomic bomb survivors carried out by the Radiation Effects Research 
Foundation (formerly the Atomic Bomb Casualty Commission) in Hiroshima. 
Other valuable sources of data include various groups of medically exposed 
patients (such as radiotherapy patients) and occupationally exposed workers (such 
as the uranium miners, discussed in chapter 12). I08 



63 



Introduction 

Why is it necessary to compare exposed populations with unexposed 
populations? 

Unlike a disease caused by identifiable bacteria, no "signature" has yet 
been found in cancerous tissue that would link it definitively to prior radiation 
exposure. Radiogenic cancers are identical in properties, such as appearance 
under a microscope, growth rate, and potential to metastasize, to cancers 
occurring in the general population. Finding cancers in an exposed population is 
not enough to prove they are due to radiation; the same number of cancers might 
have occurred due to the natural frequency of the disease. The challenge is to 
separate out the effects of radiation from what would otherwise have occurred. A 
major step in this direction is to develop follow-up (or cohort) studies, in which 
an exposed group is followed over time to observe their disease rates, and these 
rates are then compared with the rates for the general population or an unexposed 
control group. 109 

Why is the analysis of epidemiologic data so complicated? 

Simply collecting data on disease rates in exposed and control populations 
is not enough; indeed, casual analysis may lead to serious errors in understanding. 
Sophisticated data-collection techniques and mathematical models are needed to 
develop useful risk estimates for several reasons: 

1 . Random variation due to sample size. 

2. Multiple variables. 

3. Limited time span of most studies. 

4. Problems of extrapolation. 

In addition, individual studies may also be biased in their design or 
implementation. 

What is random variation? 

The observed proportion of subjects developing disease in any randomly 
selected subgroup (sample) of individuals with similar exposures is subject to the 
vagaries of random variation. 

A simple-minded example of this is the classic puzzle of determining, in a 
drawer of 100 socks, how many are white and how many are black, by pulling out 
one sock at a time. Obviously, if we pull out all the socks, we know for certain. 
In most areas of study, though, "pulling out all the socks" is far too expensive and 
time-consuming. But if we pull only 10, with what degree of confidence can we 
predict the color of the others? If we pull 20, we will have more confidence. In 
other words, the larger the sample, the greater our confidence. Using statistical 
techniques, our degree of confidence can be calculated from the size of the entire 
population (in this case 100 socks) and the size of the actual sample. The result is 
popularly called the margin of error. 

64 



The Atomic Century 

The most common examples of this in everyday life are the public opinion 
polls continually quoted in the news media. As can be seen in the simple example 
of the drawer of socks, the highest degree of confidence can be achieved simply 
by pulling all the socks out of the drawer. For public opinion polls, this would be 
far too expensive; instead, a small sample is selected at random from the 
population. Nowadays it is common to report not only the actual results, but also 
the sample size and the margin of error. The margin of error depends not only on 
the sample size, but also on how high a degree of confidence we desire. The 
degree of confidence is the probability that our sample has provided a true picture 
of the entire population. For example, the margin of error will be smaller for 80 
percent degree of confidence than for 95 percent. Even where a study covers an 
entire exposed population, such as the atomic bomb survivors, the issue of 
random variation remains when we wish to generalize the findings to other 
populations. 

What are multiple variables'! 

The effects of radiation will depend upon, or vary, with the dose of 
radiation received. However, these effects also may vary with other factors- 
other variables-thai are not dependent upon the radiation dose itself. Examples 
of such variables are age, gender, latency (time since exposure), and smoking. 
Data on these other variables must be collected as well as data on the basic 
elements of radiation dose and disease. The challenge is to then distinguish 
between disease rates due to radiation and those due to other factors. For 
example, if the population studied were all heavy smokers, this might explain in 
part a higher rate of lung cancer. Much of the science of epidemiology is devoted 
to choosing what factors to collect data on and then developing the multivariate 
mathematical models needed to separate out the effect of each variable. 
Radiation effects vary considerably across subgroups and over time or age. 
Because of this, direct estimates of risk for particular subgroups would be very 
unstable. Mathematical models must be used. These models allow all the data to 
be used to develop risk estimates that, while based on sufficiently large estimates 
to be stable, will be applicable to particular subgroups. 

A more subtle problem is mis specification of the model finally chosen to 
calculate risks. The model may weigh selected factors in a manner that best fits 
the data from a statistical viewpoint. This model, while fitting the data, may not 
actually be a "correct" view of nature; another model that does not fit the data 
quite as well may actually better describe the as-yet-unknown underlying 
mechanisms. 

Why does a limited time span reduce the value of a study? 

The most pronounced effects of large exposures to radiation manifest 
themselves quickly in symptoms loosely termed radiation sickness. 

However, another concern is understanding the effects of much lower 

65 



Introduction 

levels of radiation. Unlike the more acute effects of large exposures, these may 
not appear for some time. Some cancers, for example, do not appear until many 
years after the initial exposure. These latent effects may continue to appear in a 
population throughout their entire lifetimes. Calculating the lifetime risk of an 
exposure requires following the entire sample until all its members have died. 
Thus far, none of the exposed populations have yet been followed to the ends of 
their lives, although the radium dial painter study for the group painting before 
1930 essentially has been completed, and the follow-up has been closed out." 

Why does extrapolation among human populations pose problems? 

As discussed earlier, extrapolating results from one species to another is 
problematic due to differences in how species respond to radiation. 

Even though humans are all members of the same species, there are 
similar problems when extrapolating results from one group of humans to another 
group. Within the human species, different groups can have different rates of 
disease. For example, stomach cancer is much more common and breast cancer 
much rarer among Japanese than among U.S. residents. 

How then should estimates of the radiation-induced excess of cancer 
among the atomic bomb survivors be applied to the U.S. population? 
Assumptions are needed to "transport" risk estimates from one human population 
to another human population that may have very different "normal" risks. 

Why does extrapolation from high to low doses pose problems? 

Acquiring high-quality human data on low-dose exposure is difficult. Past 
studies indicate that the effects of low doses are small enough to be lost in the 
"noise" of random variation. In other words, the random variation due to sample 
size may be greater than the effects of the radiation. Thus, to estimate the risks of 
low doses, it is necessary to extrapolate from the effects of high doses down to 
the lower range of interest. As with extrapolation among species or among 
human populations, assumptions must be made. 

The basic assumption concerns the dose effect. Is the effect of a dose 
linear? This would mean that half the dose would produce half the effect; one- 
tenth of the dose would produce one-tenth of the effect, and so forth. Nature is 
not always so reasonable, however. There are many instances in nature of 
nonlinear relationships. A nonlinear dose effect, for example, could mean that 
half the dose would produce 75 percent of the effects. Or, going in the other 
direction, a nonlinear dose effect could mean that half the dose would produce 
only 10 percent of the effect. Reliable data are too sparse to settle the issue 
empirically. Much of the ongoing controversy over low-dose effects concerns 
which dose effect relationship to assume. Concerning dose response, most 
radiation advisory committees assume that radiation risks are linear in doses at 
low levels, although these risks may involve nonlinear terms at higher doses. 

Another assumption concerns the effect of dose rate. It is generally 

66 



The Atomic Century 

agreed that the effect of high-dose x rays is reduced if the radiation is received 
over a period of time instead of all at once. (This reduction in acute effects, due 
to the cell's ability to repair itself in between exposures, is one of the reasons that 
modern protocols for radiotherapy use several fractionated doses.) The degree to 
which this also happens at low doses is less clear. There are few human data on 
the effect of dose rate on cancer induction. Most estimates of the effect come 
from animal or cell culture experiments. There is also evidence of quite different 
dose-rate effects for alpha radiation and neutrons. 

How can a specific study be biased? 

When applied to an epidemiologic study, the term bias does not refer to 
the personal beliefs of the investigators, but to aspects of the study design and 
implementation. There are several possible sources of bias in any study. 

What is called a confounding bias may result if factors other than radiation 
have affected disease rates. Such factors, as mentioned earlier, might be a rate of 
smoking higher than the general population. 

A selection bias may result if the sample was not truly a random selection 
from the population under study. For example, the results of a study that includes 
only employed subjects might not be applicable to the general population, since 
employed people as a group are healthier than the entire population. 

An information bias may result from unreliability in a source of basic 
data. For example, basing the amount of exposure on the memory of the subjects 
may bias the study, since sick people may recall differently than healthy people. 
Dose, in particular, can be difficult to determine when studies are conducted on 
populations exposed prior to the study, since there usually was no accurate 
measurement at the time of exposure. Sometimes when dose measurements were 
taken, as in the case of the atomic veterans, the data are not adequate by today's 
standards." 1 

Finally, any study is subject to the random variation discussed earlier, 
which depends on how large the sample is. This is more important for low-dose 
than for high-dose studies, since the low-dose effects themselves are small 
enough to be lost amid random variations if the sample is too small. 

To summarize, multiple studies may produce somewhat different results 
because there is an actual difference in the response between populations or 
because studies contain spurious results due to their own inadequacies. In 
addition, it must be recognized that the entire body of scientific literature is itself 
subject to a form of bias known as publication bias, meaning an overreporting of 
findings of excess risk. This is because studies that demonstrate an excess risk 
may be more likely to be published than those that do not. 



67 



Introduction 

In view of all these uncertainties, what risk estimates did the 
Committee choose? 

Despite all these uncertainties, it must be pointed out that more is known 
about the effects of ionizing radiation than any other carcinogen. 

The BEIR V Committee of the National Academy of Sciences estimated 
in 1990 that the lifetime risk from a single exposure to 10 rem of whole-body 
external radiation was about 8 excess cancers (of any type) per 1,000 people. 
(This number is actually an average over all possible ages at which an individual 
might be exposed, weighted by population and age distribution.) For continuous 
exposure to 0.1 rem per year throughout a lifetime, the corresponding estimate 
was 5.6 excess cancers (that is, over and above the rate expected in a similar, but 
nonexposed population) per 1 ,000 people. It is widely agreed that for x rays and 
gamma rays, this latter figure should be reduced by some factor to allow for a 
cell's ability to repair DNA, but there is considerable uncertainty as to what figure 
to use; a figure of about 2 or 3 is often suggested." 2 

The estimates of lifetime risk from the BEIR V report have a range of 
uncertainty due to random variation of about 1.4-fold. The additional 
uncertainties, due to the factors discussed earlier, are likely to be larger than the 
random variation. 

In comparison, for most chemical carcinogens, the uncertainties are often 
a factor of 10 or more. This agreement among studies of radiation effects is quite 
remarkable and reflects the enormous amount of scientific research that has been 
devoted to the subject, as well as the large number of people who have been 
exposed to doses large enough to show effects. 



68 



ENDNOTES 



1 . In 1974 the AEC's regulatory activities for civilian nuclear power and the use 
(including medical research) of radioisotopes produced in nuclear reactors were 
transferred to the Nuclear Regulatory Commission and its research and weapons- 
development activities to the Energy Research and Development Administration 
(ERDA) In 1 977 ERDA was incorporated into the new Department of Energy. 

2. Captain C. F. Behrens, ed., Atomic Medicine (New York: Thomas Nelson and 
Sons, 1949), 3. 

3. Ibid., 7. 

4 Otto Glasser, William Conrad Roentgen and the Early History oj the 
Roentgen Rays (Springfield, 111., and Baltimore: Charles C. Thomas, 1934), 29; Glasser is 
quoting O. Lummer of Berlin. 

5. Ibid., 271. 

6. Ibid., 244-282. 

7. Robert Reid, Marie Curie (New York: E. P. Dutton, 1974), 241. 

8. Ibid., 86-87. 

9. P. Curie and M. S. Curie, "Radium: A New Body, Strongly Radio-Active, 
Contained in Pitchblende," Scientific American (28 January 1899): 60. The term 
hyperphosphorescence was suggested by Silvanus Thompson. Reid, Marie Curie, 87. 
See also Susan Quinn, Marie Curie: A Life (New York: Simon and Schuster, 1995). 

10. New York Journal, 21 June 1905, reproduced in David J. DiSantis, M.D., 
and Denise M. DiSantis, "Radiologic History Exhibit: Wrong Turns on Radiology's Road 
of Progress," Radiographics (1991): 1 121-1 138, figure 17. 

11. Henry S. Kaplan, "Historic Milestones in Radiobiology and Radiation 
Therapy," Seminars in Oncology 6, no. 4 (December 1979): 480. 

12. "Autopsy of a Radiologist," Archives of the Roentgen Ray 18 

(April 1914): 393. . 

13 Reid, Marie Curie, 274; Barton C. Hacker, The Dragon's Tail: Radiation 
Safety in the Manhattan Project, 1942-1946 (Berkeley, Calif: University of California 

Press, 1987), 22-23. 

14. The marketing of one nostrum containing radium, Radiothor, was not 
officially shut down by the Federal Trade Commission until 1932. "With the institution 
of regulations, the radioactive patent medicine industry collapsed overnight." Roger M. 
Macklis, "The Great Radium Scandal," Scientific American 269 (March 1993): 94-99. 
In the 1920s, the use of capsules containing radium inserted into the nose was introduced 
as a means of shrinking lymphoid tissue in children to treat middle ear obstructions and 
infections. During World War II this procedure was used on submariners and Air Force 
personnel as treatment and, in the case of several hundred submariners, on an 
experimental basis to test the effectiveness of nasopharyngeal irradiation in shrinking 
lymphoid tissue and equalizing external and middle ear pressure. In the late 1940s, the 
observation that no controlled study had ever been conducted to test the treatment's 
effectiveness in preventing deafness in children led Johns Hopkins researchers to begin 
the experimental treatment of several hundred children. As the Advisory Committee 
began its work in 1994, controversy over the long-term effects of this treatment still 
swirled. Samuel Crane, "Irradiation of Nasopharynx," Annals of Otology, Rhinology, and 
Laryngology 55 (1946): 779-788; H. L. Holmes and J. D. Harris, "Aerotitis Media in 

69 



Submariners," Annals of Otology, Rhinology, and Laryngology 55 (1946): 347-371. See 
chapter 7 and ACHRE Briefing Book, vol. 13, tab E, April 1995, for fuller discussion. 

15. Macklis, "The Great Radium Scandal," 94-99. 

16. The National Council on Radiation Protection began as the American 
Committee on X Ray and Radium Protection in 1928, under the aegis of the International 
Congress of Radiology. A private organization, its members were physicians, physicists, 
and representatives of the equipment manufacturers. Prior to World War II its main 
function was to issue recommendations on radiological safety, which were published by 
the National Bureau of Standards (a federal agency). At times this arrangement created 
confusion, leading people to believe the publications were official recommendations. 
After the war, the private group was revived as the National Committee on Radiation 
Protection. In 1956 it was renamed the National Committee on Radiation Protection and 
Measurements. In the early 1 960s, it received a congressional charter and was renamed 
the National Council on Radiation Protection and Measurements. Throughout its history 
it has coordinated its activities with other groups, such as the International Commission 
on Radiological Protection' and committees of the National Academy of Sciences (known 
as the BEAR and BEIR Committees). The most complete record of the NCRP's activities 
is Lauriston S. Taylor, Organization for Radiation Protection: The Operations of the 
ICRPandNCRP, 1928-1974 (Washington, D.C.: Office of Technical Information, U.S. 
Department of Energy.) Lauriston Taylor, a physicist at the National Bureau of 
Standards, served as the executive director of the organization from its founding in 1 928 
to 1974. For further background on the history of radiation protection, see Daniel P. 
Serwer, The Rise of Radiation Protection: Science, Medicine and Technology in Society, 
1896-1935 (Ph.D. diss, in the History of Science, Princeton University, 1976) (Ann 
Arbor: University Microfilms 77-14242, 1977); Gilbert F. Whittemore, The National 
Committee on Radiation Protection, 1928-1960: From Professional Guidelines to 
Government Regulation (Ph.D. diss, in the History of Science, Harvard University, 1986) 
(Ann Arbor: University Microfilms 87-04465, 1987); J. Samuel Walker, "The 
Controversy Over Radiation Safety: A Historical Overview," Journal of the American 
Medical Association 262 (1989): 664-668; D. C. Kocher, "Perspective on the Historical 
Development of Radiation Standards," Health Physics 61, no. 4 (October 1994). 

17. Heinz Haber, The Walt Disney Story of Our Friend the Atom (New York: 
Simon and Schuster, 1956), 152. The German-born Dr. Haber had come to the United 
States in 1947 to work for the Air Force School of Aviation Medicine and was a 
cofounder of the field of space medicine. In the early 1950s he joined the faculty of the 
University of California at Los Angeles. As Spencer Weart, a historian of the images of 
the atomic age has recorded, the accompanying Walt Disney movie Our Friend the Atom, 
which was shown on television and in schools beginning in 1957, was probably the most 
effective of educational films on the perils and potential of atomic energy. "The great 
storyteller introduced the subject as something 'like a fairy tale,' indeed the tale of a genie 
released from a bottle. The cartoon genie began as a menacing giant. . . . But scientists 
turned the golem into an obedient servant, who wielded the 'magic power' of 
radioactivity. . . ." Spencer R. Weart, Nuclear Fear: A History of Images (Cambridge, 
Mass.: Harvard University Press, 1988), 169. 

18. Marshall Brucer, Chronology of Nuclear Medicine (St. Louis: Heritage 
Publications, 1990), 199-200. Radon is a gas at room temperature. Doctors developed 
an innovative system for capturing radon from used cancer therapy vials and dissolving 
it in a saline solution, which was then injected. 



70 



19. Haber, Our Friend the Atom, 152. 

20. J. L. Heilbron and Robert W. Seidel, Lawrence and His Laboratory: A 
History of the Lawrence Berkeley Laboratoiy, vol. 1 (Los Angeles: University of 
California Press, 1989). The birth and development of nuclear medicine at the University 
of California's Berkeley and San Francisco branches is the subject of a case study in a 
supplemental volume to this report. 

21. John Stanbury, A Constant Ferment (Ipswich, N.Y.: Ipswich Press, 1991), 
57-67. 

22. Stafford Warren, interview by Adelaide Tusler (Los Angeles: University of 
California), 23 June 1966 in An Exceptional Man for Exceptional Challenges, Vol. 2 
(Los Angeles: University of California, 1983) (ACHRE No. UCLA-101794-A-1), 421- 
422. 

23. Manhattan Project researchers focused on polonium in the development of 
the initiator for the bomb. See Richard Rhodes, The Making of the Atomic Bomb (New 
York: Simon and Schuster, 1986), 578-580. 

24. Manhattan District Program, 31 December 1946 (book 1, "General," volume 
7, "Medical Program") (ACHRE No. NARA-052495-A-1), 2.2. 

25. Stafford Warren in Radiology in World War II, ed. Arnold Lorentz Ahnfeldt 
(Washington, D.C.: GPO, 1966), 847. 

26. Robert Stone, 10 May 1943 ("Health Radiation and Protection") (ACHRE 
No. DOE-011195-B-1). 

27. Philip J. Close, Second Lieutenant, JAGD, to Major C. A. Taney, Jr., 26 
July 1945 ("Determination of Policy on Cases of Exposure to Occupational Disease") 
(ACHRE No. DOE-120894-E-96), 1. 

28. Ibid., 3. 

29. Response to ACHRE Request No. 012795-B, Oak Ridge Associated 
Universities, D. M. Robie to A. ("Tony") P. Polendak, 15 June 1979 ("Storage of records- 
-Shipment 1161"). 

30. The story of this early Hanford research is told in Neal D. Hines, Proving 
Ground: An Account of the Radiobiological Studies in the Pacific 1946-61 (Seattle: 
University of Washington Press, 1962). As Hines explains, the initial study of the effect 
of radioactivity on aquatic organisms was undertaken by a University of Washington 
researcher. The program could not be identified with the Columbia River, and the 
research was to be conducted in a normal campus setting. The project's name ("Applied 
Fisheries Laboratory") was selected to disguise its work. The primary researcher initially 
did not know the true purpose, and the university accepted the work for undisclosed 
purpose on the assurance that national security required it. 

3 1 . Harold Hodge, interview by J. Newell Stannard, transcript of audio 
recording, 22 October 1980 (ACHRE No. DOE-061794-A-4), 21-22. Stafford Warren, 
interview by J. Newell Stannard, transcript of audio recording, 7 February 1979 (ACHRE 
No. DOE-061794-A), 3. 

32. Henry DeWolf Smyth, Atomic Energy for Military Purposes: The Official 
Report on the Development of the Atomic Bomb under the Auspices of the United States 
Government, 1940-45 (Princeton, N.J.: Princeton University Press, 1945). 

33. The organizational history of the Department of Defense is chronicled in 
The Department of Defense: Documents on Establishment and Organization 1944-1978, 
eds. Alice C. Cole, Alfred Goldberg, Samuel A. Tucker, Rudolf A. Winnacker 
(Washington, D.C.: Office of the Secretary of Defense, Historical Office, 1978). 



71 



34. The program expanded from the base of Manhattan Project research sites 
such as Oak Ridge, Hanford, Chicago, and the Universities of California, Chicago, and 
Rochester to take in a growing portion of the university research establishment. The 
minutes of the January 1947 meeting record an ambitious program to focus on the 
physical measurement of radiation, the biological effects of radiation, methods for the 
detection of radiation damage, methods for the prevention of radiation injury, and 
protective measures. There followed an itemized list of the work to be done at Argonne 
National Laboratory, Los Alamos, Monsanto, Columbia University, and the Universities 
of Michigan, Rochester, Tennessee, California, and Virginia. 

The University of Rochester was to be the largest university contractor, receiving 
more than $1 million, followed by the University of California (about one-half million 
for UCLA, where Stafford Warren was dean of the new medical school, and Berkeley, to 
which Stone had returned to join Hamilton), Western Reserve (to which Warren's deputy 
Hymer Friedell was headed), and Columbia (more than $100,000). Argonne received an 
amount comparable to Rochester; other labs, including Los Alamos National Laboratory 
and Clinton Laboratories (now Oak Ridge National Laboratory), were scheduled for 
$200,000 or less. Stafford Warren, Interim Medical Committee, proceedings of 23-24 
January 1947 (ACHRE No. UCLA-1 1 1094-A-26). See also ACHRE Briefing Book, vol. 
3, tab F, document H. 

35. "Report of the Board of Review," 20 June 1947, attached to letter from 
David Lilienthal, Chairman, AEC, to Dr. Robert F. Loeb, Chairman, AEC Medical Board 
of Review, 27 June 1947 ("At the conclusion of the deliberations . . .") (ACHRE No. 
DOE-051094-A-191), 3-4. 

36. The Advisory Committee has assembled the minutes of the meetings, and 
such transcripts as have been retrieved. 

37. Shields Warren, interview by Dr. Peter Olch, National Library of Medicine, 
transcript of audio recording, 10-11 October 1972, 59. 

38. Harry H. Davis, "The Atom Goes to Work for Medicine," New York Times 
Magazine, 26 September 1946 (ACHRE No. DOE-051094-A-408). 

39. Marshall Brucer, M.D., Chairman, Medical Division, Oak Ridge Institute 
for Nuclear Studies, wrote: 

Paul Aebersold's isotopes division was the only safely nonsecret part of 
AEC. Aebersold had unlimited funds, unlimited radioisotopes, and 
seemingly unlimited energy to promote the unlimited cures that had been 
held back from the American public for too long. The liberal 
establishment was in the depths of shame for having ended the war by 
killing people. Radioisotopes didn't kill people; they cured cancer. 

Aebersold spoke at every meeting of one person or more that had one 
minute or more available on its program. No matter what the meeting's 
subject, Aebersold's topic was always the same. He sold isotopes. 

Marshall Brucer, "Nuclear Medicine Begins with a Boa Constrictor," Journal of Nuclear 

Medicine 19, no. 6 (1978): 595. 

40. Isotopes Division, prepared for discussion with general manager, "Present 
and Future Scope of Isotope Distribution," 4 March 1949 (ACHRE No. DOE-01 1895-B- 
1). 

41. Interview with Shields Warren, 10-11 October 1972, 76. 



72 



42. Isotopes Division, 4 March 1949, 2. 

43. See Kaplan, "Historic Milestones," 480. 

44. "Summary of Congressional Hearings on Fellowship Issue," 16 May 1949 
(ACHRE No. DOE-061395-D-1). 

45. Advisory Committee for Biology and Medicine, proceedings of 10 
September 1949 (ACHRE No. DOE-072694-A), 18. 

46. Ibid, 19. 

47. For a further discussion of the contemplated secret record keeping by the 
VA, see chapter 10. As noted there, a VA investigation concluded that the "confidential" 
division was never activated. 

48. The VA provided the Advisory Committee with capsule descriptions of 
experiments, which appeared in periodic VA reports of the time. In fact, the number of 
descriptions exceeded 3,000 for the portion of the 1944-74 period the reports covered. 
However, further information on the vast majority of the experiments was typically 
unavailable, and the VA noted that some of the descriptions may be redundant (or reflect 
refunding of a single experiment), and some may not have involved humans. Therefore, 
the "more than 2,000" reflects a very rough estimate adjusted for these considerations. 

49. Paul C. Aebersold, address before Rocky Mountain Radiological Society, 9 
August 1951 ("The United States Atomic Energy Program: Part I-Overall Progress") 
(ACHRE No. TEX- 101294- A- 1), 6. 

50. By 1955 the program was receiving 8,000 applications a year, including 
hundreds from abroad. A July 1955 Aebersold summary of accomplishments pronounced 
that, as a result of the program, there were now 1 00 companies in the radiation instrument 
business, two dozen suppliers of commercially labeled compounds, pharmaceutical 
companies, hundreds of isotope specialists, a half-dozen waste disposal firms, and ten 
safety monitoring companies. Also, 2,693 U.S. institutions had received isotope 
authorization, including 1,126 industrial firms, 1,019 hospitals and private physicians, 
220 colleges and universities, 244 federal and state laboratories, and 47 foundations. 
"Capsule Summary of Isotopes Distribution Program," July 1955 (ACHRE No. TEX- 
101294-A-2). 

5 1 . Vannevar Bush, Pieces of the Action (New York: William Morrow and 
Company, 1970), 65. 

52. Ibid. 

53. In addition to direct grants to private institutions the AEC pioneered the 
creation of research consortia. In 1946, for example, the University of Tennessee and a 
consortium of southeastern universities urged the Manhattan Project to establish the Oak 
Ridge Institute of Nuclear Studies (ORINS). Following the creation of the AEC, ORINS 
operated under AEC contract to train researchers and to operate a clinical research facility 
focused on cancer. In 1966 ORINS became known by the name of its operating 
contractor, the Oak Ridge Associated Universities, and the research facility is now known 
as the Oak Ridge Institute for Science and Education (ORISE). 

54. Donald C. Swain, "The Rise of a Research Empire: NIH, 1930 to 1950," 
Science 138, no. 3546 (14 December 1962): 1235. The National Institutes of Health 
began as the Laboratory of Hygiene in 1887. It was renamed the National Institutes of 
Health in 1948. 

55. Assistant Director, Office of Extramural Research, National Institutes of 
Health, to Anna Mastroianni, Advisory Committee, 16 July 1995 ("Comments on Draft 
Chapters of ACHRE Final Report"). 



73 



56. Interview with Shields Warren, 10-1 1 October 1972, 78. 

57. Robert S. Stone, M.D., to Lieutenant Colonel H. L. Friedell, U.S. Engineer 
Corps, Manhattan District, 9 August 1945 ("In reading through the releases . . .") 
(ACHRE No. DOE-121494-D-2). 

58. Robert S. Stone, M.D., to Lieutenant Colonel H. L. Friedell, U.S. Engineer 
Corps, Manhattan District, 9 August 1945 ("As you and many others are aware, a great 
many of the people . . .") (ACHRE No. DOE-121494-D-1). 

59. Jonathan M. Weisgall, Operation Crossroads: The Atomic Tests at Bikini 
Atoll (Annapolis, Md.: Naval Institute Press, 1994). For a contemporary account by a 
doctor who served as a radiation monitor, see David Bradley, No Place to Hide (Boston: 
Little, Brown and Co., 1948). 

60. Weisgall, Operation Crossroads, 266-270. 

61. "History of the U.S. Naval Radiological Defense Laboratory, 1946-58" 
(ACHRE No. DOD-071494-A-1), 1. 

62. The Joint Panel was the child of the Committee on Medical Science and 
Committee on Atomic Energy (hence the term Joint), both of which, in turn, were 
committees of the Defense Department's Research and Development Board. That board 
served as the secretary of defense-level coordinator of departmentwide R&D. 

63. The Committee has assembled the charter, agenda, reports, and available 
minutes of the Joint Panel. ACHRE Research Collection Series, Library File, 
Compilation of the Minutes of the Joint Panel on Medical Aspects of Atomic Warfare, 
1948-1953(1994). 

64. Howard Andrews, interview by Gilbert Whittemore (ACHRE staff), 
transcript of audio recording, 3 December 1994 (ACHRE Reseach Project, Interview 
Series, Targeted Interview Project). 

65. In a February 1950 paper, the Public Health Service explained its role in 
national defense: 

During and since WW II, science and technology have 
introduced new weapons and whole new industries 
whose effects on human health have not been precisely 
determined and effective methods against these hazards 
have not yet been developed. 

If, for example, an atomic bomb were to burst over a 
large city in this country, tens of thousands of burned and 
injured people could not be given effective treatment 
because science has not yet found the practical means. . . . 
The operation of atomic piles and related facilities also 
presents a variety of problems as to human tolerance of 
radiation and the disposition of radioactive substances. 

"The U.S. Public Health Service and National Defense," February 1950 (ACHRE No. 

HHS-071394-A-2), 1. 

66. National Institutes of Health, 2 August 1952 ("Assumptions Underlying 
NIH Defense Planning") (ACHRE No. HHS-071394-A-1). 

67. Advisory Committee for Biology and Medicine, transcript (partial) of 
proceedings of 10 November 1950 (ACHRE No. DOE-012795-C-1). While the 
document is undated, discussion of the meeting appears in the November 1950 ACBM 



74 



minutes (12); a letter from Alan Gregg, Chairman, ACBM, to Gordon Dean, Chairman, 
AEC, 30 November 1950 ("The Advisory Committee for Biology and Medicine held 
their twenty-fourth . . .") (ACHRE No. DOE-072694-A); and a letter from Marion W. 
Boyer, AEC General Manager, to Honorable Robert LeBaron, Chairman, Military 
Liaison Committee, 10 January 1951 ("As you know, one of the important problems . . 
.") (ACHRE No. DOE-040395-A-1). 

68. Behrens, transcript, proceedings of 10 November 1950, 2. 

69. Powell, transcript, proceedings of 10 November 1950, 8-10. 

70. Cooney, transcript, proceedings of 10 November 1950, 6. 

71. Ibid., 7. 

72. Ibid., 6. 

73. Ibid., 7-8. 

74. Warren, transcript, proceedings of 10 November 1950, 13. 

75. Ibid., 14. 

76. Ibid., 15. 

77. Cooney, transcript, proceedings of 10 November 1950, 15. 

78. Ibid., 16. 

79. "Notes on the Meeting of a Committee to Consider the Feasibility and 
Conditions for a Preliminary Radiological Safety Shot for Operation 'Windsquall,'" 2 1 - 
22 May 1951 (ACHRE No. DOE-030195-A-1), 41. 

80. Ibid., 40. 

81. Ibid., 19. 

82. T. L. Shipman, Health Division Leader, to Alvin Graves, J-Division Leader, 
27 December 1951 ("Summary Report Rad Safe and Health Activities at Buster- Jangle") 
(ACHRE No. DOE-033195-B-1). 

83. [AEC] Board of Review to the Atomic Energy Commission, 20 June 1947 
("Report of the Board of Review") (ACHRE No. DOE-071494-A-4), 10. 

84. NEPA Medical Advisory Panel, Subcommittee No. IX, "An Evaluation of 
Psychological Problem of Crew Selection Relative to the Special Hazards of Irradiation 
Exposure," 22 July 1949 (ACHRE No. DOD-121494-A-2), 20. 

85. Ibid., 27. 

86. Ibid., 22. 

87. Definition of "curie," The Compact Edition of the Oxford English Dictionaiy 
(Oxford, England: Oxford University Press, 1971), 3937. 

88. J. Newell Stannard, Radioactivity and Health: A History (Oak Ridge, Tenn.: 
Office of Scientific and Technical Information, 1988), 9. 

89. Hanson Blatz, ed., Radiation Hygiene Handbook (New York: McGraw-Hill 
Book Co., 1959), 6-185. 

90. Richard G. Hewlett and Oscar E. Anderson, The New World: A Histo>y of 
the Atomic Energy Commission, Vol. I: 1939-1946 (Berkeley: University of California 
Press, 1990), reprint of 1962 edition, 107-108. 

91. Eric Hall, Radiobiology for the Radiologist, 4th ed. (Philadelphia: J. B. 
Lippincott, 1994), 3. 

92. Ibid., 5. 

93. The DNA strand would be about 5 centimeters (cm) long; the average cell 
diameter is about 20 microns (0.002 cm). Bruce Alberts et al., eds., Molecular Biology of 
the Cell (New York: Garland, 1983), 385-388. 

94. Hall, Radiobiology for the Radiologist, 4th ed., 9-10. 



75 



95. 


Ibid. 




96. 


Ibid., 


30. 


97. 


Ibid., 


32-33. 


98. 


Ibid., 


312. 


99. 


Ibid., 


324. 


100 


. Ibid 





101. International Commission on Radiological Protection, Recommendations: 
ICRP Publication No. 60 (New York: Pergamon Press, 1991), cited in Hall, 
Radiobiology for the Radiologist, 4th ed., 456. 

102. Hall, Radiobiology for the Radiobiologist, 4th ed., 355. 

103. Committee on the Biological Effects of Ionizing Radiation, National 
Research Council, Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR 
V (Washington, D.C.: National Academy Press, 1990), 2-4. 

104. International Commission on Radiological Protection, Recommendations: 
ICRP Publication No. 60, quoted in Hall, Radiobiology for the Radiologist, 4th ed., 455. 

105. ". . . roentgen equivalent man, or mammal (rem). The dose of any ionizing 
radiation that will produce the same biological effect as that produced by one roentgen of 
high-voltage x-radiation." Blatz, ed., Radiation Hygiene Handbook, 2-19. 

106. Hall, Radiobiology for the Radiobiologist, 4th ed., 458. 

107. These include the National Council on Radiation Protection and 
Measurement (NCRP), the International Commission on Radiation Protection (ICRP), the 
United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), 
the Committee on the Biological Effects of Ionizing Radiation (BEIR) of the National 
Research Council, and the Environmental Protection Agency (EPA). 

108. In addition, there have been a number of studies of people exposed to low 
levels of radiation, including military personnel and residents subject to fallout from 
nuclear weapons testing, workers at and residents near nuclear facilities, patients given 
diagnostic x rays, and regions with high natural background radiation. Most of these 
either have not produced convincing positive results or are unsuitable for risk assessment 
because of the statistical instability of their estimates. 

109. Some indirect estimates have been based on "case control" studies, in which 
diseased cases are compared with unaffected controls to look for differences in their past 
exposures that could account for their different outcomes. 

General reference works include D. G. Kleinbaum, W. Kupper, and H. 
Morgenstern, Epidemiologic Research: Principles and Quantitative Methods (Belmont, 
Calif.: Lifetime Learning Publications, 1982), and J. D. Boice, Jr., and J. E. Fraumeni, Jr., 
Radiation Carcinogenesis: Epidemiology and Biological Significance (New York: Raven 
Press, 1984). 

110. Dr. Shirley Fry to Bill LeFurgy, 31 August 1995 ("HRE Draft Final 
Report"), 8, contained in Ellyn Weiss, Special Counsel and Director, Office of Human 
Radiation Experiments, DOE, to Anna Mastroianni, ACHRE, 1 1 September 1995. 

111. "[T]he NTPR dose data are not suitable for dose-response analysis." 
Institute of Medicine, "A Review of the Dosimetry Data Available in the Nuclear Test 
Personnel Review (NTPR) Program, An Interim Letter Report of the Committee to Study 
the Mortality of Military Personnel Present at Atmospheric Tests of Nuclear Weapons to 
the Defense Nuclear Agency" (Washington, D.C.: Institute of Medicine, May 15, 1995), 
2. 



76 



1 12. Committee on the Biological Effects of Ionizing Radiation, National 
Research Council, Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR 
V (Washington, D.C.: National Academy Press, 1990), 22, 162. 



77 



Part I 

ETHICS OF HUMAN SUBJECTS 

RESEARCH: A HISTORICAL 

PERSPECTIVE 



PartI 
Overview 



W hen the Advisory Committee began work in April 1994 we were 
charged with determining whether "the [radiation] experiments' design and 
administration adequately met the ethical and scientific standards, including 
standards of informed consent, that prevailed at the time of the experiments and 
that exist today" and also to "determine the ethical and scientific standards and 
criteria by which it shall evaluate human radiation experiments." 

Although this charge seems straightforward, it is in fact difficult to 
determine what the appropriate standards should be for evaluating the conduct 
and policies of thirty or fifty years ago. First, we needed to determine the extent 
to which the standards of that time are similar to the standards of today. To the 
extent that there were differences we needed to determine the relative roles of 
each in making moral evaluations. 

In chapter 1 we report what we have been able to reconstruct about 
government rules and policies in the 1940s and 1950s regarding human 
experiments. We focus primarily on the Atomic Energy Commission and the 
Department of Defense, because their history with respect to human subjects 
research policy is less well known than that of the Department of Health, 
Education, and Welfare (now the Department of Health and Human Services). 
Drawing on records that were previously obscure, or only recently declassified, 
we reveal the perhaps surprising finding that officials and experts in the highest 
reaches of the AEC and DOD discussed requirements for human experiments in 
the first years of the Cold War. We also briefly discuss the research policies of 
DHEW and the Veterans Administration during these years. 

In chapter 2 we turn from a consideration of government standards to an 
exploration of the norms and practices of physicians and medical scientists who 
conducted research with human subjects during this period. We include here an 



81 



Part I 

analysis of the significance of the Nuremberg Code, which arose out of the 
international war crimes trial of German physicians in 1947. Using the results of 
our Ethics Oral History Project, and other sources, we also examine how 
scientists of the time viewed their moral responsibilities to human subjects as well 
as how this translated into the manner in which they conducted their research. Of 
particular interest are the differences in professional norms and practices between 
research in which patients are used as subjects and research involving so-called 
healthy volunteers. 

In chapter 3 we return to the question of government standards, focusing 
now on the 1960s and 1970s. In the first part of this chapter, we review the well- 
documented developments that influenced and led up to two landmark events in 
the history of government policy on research involving human subjects: the 
promulgation by DHEW of comprehensive regulations for oversight of human 
subjects research and passage by Congress of the National Research Act. In the 
latter part of the chapter we, review developments and policies governing human 
research in agencies other than DHEW, a history that has received comparatively 
little scholarly attention. We also discuss scandals in human research conducted 
by the DOD and the CIA that came to light in the 1970s and that influenced 
subsequent agency policies. 

With the historical context established in chapters 1 through 3, we turn in 
chapter 4 to the core of our charge. Here we put forward and defend three kinds 
of ethical standards for evaluating human radiation experiments conducted from 
1944 to 1974. We embed these standards in a moral framework intended to 
clarify and facilitate the difficult task of making judgments about the past. 



82 



Government Standards for 

Human Experiments: 

The 1940s and 1950s 



W hen the Advisory Committee began its work, a central task was the 
reconstruction of the federal government's rules and policies on human 
experiments from 1944 through 1974. The history of research rules at the 
Department of Health, Education, and Welfare (DHEW) was well known, at least 
from 1953 on, when DHEW's National Institutes of Health (NIH) adopted a 
policy on human subjects research for its newly opened research hospital, the 
Clinical Center. In the 1960s, the DHEW and some other executive branch 
agencies undertook regulation of research involving human subjects. These were 
early steps of a process that culminated, in 1991, in the comprehensive federal 
policy known as the "Common Rule."' The historical background of this process, 
including a well-publicized series of incidents and scandals that motivated it, was 
also widely known and much discussed (see chapter 3). 2 

By contrast to DHEW, much less was known about the history of research 
rules for other agencies also involved in research with human subjects during this 
period, including the Department of Defense (DOD), the Atomic Energy 
Commission (AEC), and the Veterans Administration (VA). From the 
perspective of the charge to the Advisory Committee, these agencies were at least 
as important as DHEW. It was known that in 1953 the secretary of defense 
issued, in Top Secret, a memorandum on human subjects based on the Nuremberg 
Code. 3 In 1947 an international tribunal had declared the Nuremberg Code the 
standard by which a group of doctors in Nazi Germany should be judged for their 



83 



Parti 

horrific wartime experiments on concentration camp inmates. However, the 
actual impact of the Nuremberg Code on the biomedical community in the United 
States, both inside and outside of government, is a matter of some disagreement 
(see chapter 2). The general view was that, despite some developments in the 
1940s and 1950s, there was little activity within the federal government on issues 
of human subjects research before the 1960s. 

But while scholars have known of the 1953 secretary of defense 
memorandum, which was declassified in 1975, other relevant Department of 
Defense documents remained classified or had lain buried in archives. Moreover, 
relevant records of the Atomic Energy Commission were largely unexplored and 
in some cases still classified. These records are important because, from its 
creation in 1947, the AEC distributed radioisotopes that would be used in 
thousands of human radiation experiments, and it was a funding source for many 
other experiments (see Introduction). Along with the DOD, also created in 1 947, 
the AEC was searching for biomedical information needed to understand the 
effects of radiation as it prepared for the possibility of atomic warfare. Although 
the AEC was thus the catalyst for a considerable amount of human 
experimentation after World War II, there has been literally no scholarship on the 
AEC's position on the use of human beings in radiation-related research. 

Now that previously obscure, even classified, records are being made 
public, it appears that in the first years of the Cold War, officials and experts in 
the AEC and DOD did discuss the requirements for human experiments. In this 
chapter we tell what we have learned about those discussions. 

We begin by telling the story of the AEC general manager's early 
declarations on human research, which included a requirement that consent be 
obtained from patient-subjects. This story requires a careful look at a series of 
letters and memorandums exchanged in the late 1940s. Together these documents 
paint a clearly important but nonetheless confusing picture of a new agency's 
attempts to come to grips with the complexities of human experimentation. We 
consider not only what these documents say, but what we can piece together 
about what they meant in the context of the times. Central questions include the 
precise scope of the activities covered by the requirements and whether and how 
these 1 947 statements were communicated and put into effect in the AEC's 
burgeoning contract research and radioisotope distribution programs. 

We turn next to the Department of Defense, where we trace the history of 
rules on the use of healthy "normal volunteer" subjects in military research from 
the time of Walter Reed through the secretary of defense's 1953 memorandum, 
and beyond. This memorandum is the earliest known instance in which a federal 
agency that sponsored human experiments adopted the Nuremberg Code. What is 
known about how the memorandum was interpreted and implemented by the 
military establishment takes up much of the rest of this chapter. Here, as in the 
case of the AEC, key questions concern the scope of the activities covered by 
requirements and the extent to which they were put into effect. 

84 



Chapter 1 

Finally, we briefly discuss how research involving human subjects was 
addressed at the National Institutes of Health and the Veterans Administration in 
the 1950s. The evolution of policies governing human research at DHEW has 
been well documented and is only summarized here. 4 We now know that NIH's 
1953 policy was not the earliest federal requirement that consent be obtained from 
patients as well as healthy subjects. However, in contrast with the 1940s 
declarations by the AEC, it was a far more visible statement issued by an agency 
that was emerging as the leading sponsor of human subjects research. In contrast 
with what is known about NIH, the extent to which there were research rules at 
the VA in the 1940s and 1950s remains unclear. 

A recurring theme in this chapter is the uncertainty about the significance 
within government agencies of many of the official statements that are discussed. 
While these statements emanated from high and responsible officials and 
committees, often they cannot be linked to fuller expressions of commitment by 
the agencies. Some of these statements were not widely disseminated, and there 
were no implementing guidelines or regulations and no sanctions for failures to 
abide by them. Thus, it is sometimes unclear what formal, legal significance 
these statements had. We are no less interested, however, in what these 
statements can tell us about how government officials and advisers saw human 
research at the time and how they understood the obligations surrounding it. 

THE ATOMIC ENERGY COMMISSION: A REQUIREMENT 
FOR "CONSENT" IS DECLARED AT THE CREATION 

Even before the AEC came into existence on January 1, 1947, Manhattan 
Project researchers and officials had begun to lay the groundwork for the 
expansion of the government's support of biomedical radiation research 
conducted under federal contract. By the time the AEC began operations, the 
parallel program to distribute federally produced radioisotopes to research 
institutions throughout the country was already well under way. 

The planning for these undertakings required both reflection on high-level 
matters of policy and attention to matters of small but critical legal and 
bureaucratic detail. Both legal rules and administrative processes were uncharted. 
For example, who would be responsible if things went awry and subjects were 
injured? When could the government tell private doctors or researchers how to 
conduct treatment or research? The need for rules seemed obvious, but the 
particular rules that would be arrived at were not. 

In April 1947 and again in November, Carroll Wilson, the general 
manager of the new agency, wrote letters first to Stafford Warren and then to 
Robert Stone, both of whom played prominent roles in Manhattan Project medical 
research, Warren as medical director, and Stone as a key member of the Chicago 
branch of the project. In these letters, Wilson maintained that "clinical testing" 
with patients could go forward only where there was a prospect that the patient 

85 



Part I 

could benefit medically and only after that patient had been informed about the 
testing and there was documentation that the patient had consented. What was the 
origin of this position, and what was its reach? It appears that these letters were 
the products of an agency that was not only seeking to devise rules for new 
programs but also was trying to glean lessons from the experience with the secret 
research that had been conducted during the Manhattan Project. In the course of 
setting rules for the future, the AEC and its research community had to confront 
whether and how to proceed with human experimentation in the face of human 
experiments, including plutonium injections, conducted under the auspices of the 
Manhattan Project, experiments that were conducted in secret and that had the 
potential for both negative public reaction and litigation. 

The First Wilson Letter 

General Manager Wilson's first 1947 letter on human research, dated April 
30, was, at least in part, a straightforward effort to define the rules according to 
which the AEC would provide contractors with research funding. The need for 
such rules had been discussed by the AEC's Interim Medical Advisory 
Committee, chaired by Stafford Warren, in January 1 947 when it met to consider 
whether "clinical testing" should be part of the AEC contract research program. 
The report of the meeting records projects involving human subjects at the 
University of Rochester and the University of California at Berkeley, and perhaps 
others. 5 In a January 30 letter to General Manager Wilson, Stafford Warren 
reported the committee's conclusion that in the study of health hazards and the use 
of fissionable and radioactive materials, "final investigations by clinical testing of 
these materials" would be needed. Warren therefore requested that the AEC legal 
department determine the "financial and legal responsibility" of the AEC when 
such "clinical investigations" are carried out under AEC-approved and -financed 
programs. 6 (The term experiment was not used, and the precise meaning of 
clinical testing is not clear.) 

A month later, in early March, Warren met with Major Birchard M. 
Brundage, chief of the AEC's Medical Division, and two AEC lawyers to consider 
the terms for the resumption of "clinical testing." In a memorandum for the 
record, the lawyers summarized the meeting. In the case of "clinical testing" the 
lawyers 

expressed the view that it was most important that it 
be susceptible of proof that any individual patient, 
prior to treatment, was in an understanding state of 
mind and that the nature of the treatment and 
possible risk involved be explained very clearly and 
that the patient express his willingness to receive 
the treatment. 7 

86 



Chapter 1 

Initially, the lawyers had proposed that researchers obtain a "written 
release" from patients. However, "on Dr. Warren's recommendation," the lawyers 
agreed that it would be sufficient if "at least two doctors certify in writing to the 
patient's state of mind to the explanation furnished him and to the acceptance of 

the treatment."" 

In his April 30 letter to Stafford Warren, Wilson announced that the AEC 
had approved Warren's committee's recommendations for a "program for 
obtaining medical data of interest to the Commission in the course of treatment of 
patients, which may involve clinical testing." 9 Wilson's letter spelled out ground 
rules that were agreed upon. The commission understood that "treatment (which 
may involve clinical testing) will be administered to a patient only when there is 
expectation that it may have therapeutic effect." In addition, the commission 
adopted the requirement for documentation of consent agreed upon in Warren's 
meeting with the lawyers: 

[I]t should be susceptible of proof from official 
records that, prior to treatment, each individual 
patient, being in an understanding state of mind, 
was clearly informed of the nature of the treatment 
and its possible effects, and expressed his 
willingness to receive the treatment. 10 

The commission deferred to Warren's request that written releases from 
the patient not be required. However, 

it does request that in every case at least two 
doctors should certify in writing (made part of an 
official record) to the patient's understanding state 
of mind, to the explanation furnished him, and to 
his willingness to accept the treatment." 

Carroll Wilson's April letter was sent to Stafford Warren as head of the 
Interim Medical Advisory Committee, which was responsible for advising the 
AEC on its contract research program, and forwarded to Major Brundage at the 
Oak Ridge office. 12 Stafford Warren was at this point dean of the medical school 
at the University of California at Los Angeles, one of the dozen research 
institutions involved in the AEC contract research program. With one exception 
the Advisory Committee on Human Radiation Experiments did not locate 
documentation that the letter or its contents were communicated to any other 
research institutions involved with the AEC's contract research program. The 
exception is the University of California at San Francisco, where there is indirect 
evidence that someone at that institution had been apprised of Wilson's April 
letter. Of the eighteen plutonium injections, only the last one, that involving 

87 



Parti 

Elmer Allen, or "CAL-3," took place after the April letter. In Mr. Allen's 
medical chart, there is a notation signed by two physicians indicating that the 
"experimental nature" of the procedure was explained and that the patient 
"agreed." 13 Although the note in Mr. Allen's chart suggests an effort on the part 
of the researchers to comply with Wilson's April letter, the researchers did not 
comply with the other provision of the Wilson letter, that "treatment (which may 
involve clinical testing) will be administered to a patient only when there is 
expectation that it may have therapeutic effect." 14 As is discussed in more detail 
in chapter 5, there was no expectation at the time that Mr. Allen would benefit 
medically from an injection of plutonium. 15 

The Second Wilson Letter 

The context of the second Wilson letter, as well as its precise terms, further 
indicates that the April 1947 letter was given little distribution and effect. In the 
fall of 1947, the AEC laboratory at Oak Ridge requested advice from Carroll 
Wilson's office on the rules for experiments involving human subjects. Just as the 
AEC's Washington headquarters had embarked on the funding of a new research 
program, Oak Ridge was also in the midst of considering the rules governing the 
expansion of its own medical research program and the distribution of isotopes, 
which was then headquartered at Oak Ridge. In September 1 947, the manager of 
Oak Ridge Operations wrote to Wilson, asking, "What responsibilities does the 
AEC bear for human administration of isotopes (a) by private physicians and 
medical institutions outside the Project, and (b) by physicians within the project. . . 
What are the criteria for future human use?" 16 

Two weeks later. Oak Ridge sent a memorandum to the Advisory 
Committee for Biology and Medicine (ACBM). The ACBM had succeeded both 
Stafford Warren's Interim Medical Advisory Committee and the Medical Board of 
Review, a group appointed by AEC Chairman David Lilienthal to review the 
AEC's medical program. The memorandum emphasized the need for "medico- 
legal criteria" for "future human tracer research" because some of that research 
would be "of no immediate therapeutic value to the patient." The memorandum 
outlined the pros and cons of "tracer studies": 

Pro - 

( 1 ) Tracer research is fundamental to toxicity 
studies. 

(2) The adequacy of the health protection which we 
afford our present employees may in a large 
measure depend upon information obtained using 
tracer techniques. 

(3) New and improved medical applications can 

88 



Chapter 1 

only be developed through careful experimentation 
and clinical trial. 

(4) Tracer techniques are inherent in the 
radioisotope distribution program. 

Con - 

(1) Moral, ethical and medico-legal objections to 
the administration of radioactive material without 
the patient's knowledge or consent. 

(2) There is perhaps a greater responsibility if a 
federal agency condones human guinea pig 
experimentation. 

(3) Publication of such researches in some 
instances will compromise the best interests of the 
Atomic Energy Commission. 

(4) Publication of experiments done by Atomic 
Energy Commission contractor's personnel may 
frequently be the source of litigation and be 
prejudicial to the proper functioning of the Atomic 
Energy Commission Insurance Branch. 17 

The questions raised by Oak Ridge were discussed by the ACBM at its 
October 11, 1947, meeting, which decided to give the "matter more study." 18 The 
minutes of the October 1 1 meeting record that "human experimentation" was then 
discussed in the context of a request by Dr. Robert Stone to release "classified 
papers containing certain information on human experimentation with 
radioisotopes conducted within the AEC research program." 19 The request was 
part of a continuing effort by Stone and other scientists to obtain permission to 
publish the research, including the plutonium experiments, that they had 
conducted in secret during the Manhattan Project. Earlier in 1947, the AEC had 
reversed a decision to declassify a report on the plutonium injections, citing the 
potential for public embarrassment and legal liability (see chapter 5). The 
question of what to do with these requests continued to fester. 

The minutes explain that the "problem" raised by Stone had been dealt 
with by Chairman Lilienthal's Medical Board of Review in June. In a cryptic 
statement, the minutes record the ACBM's agreement that papers on human 
experiments "should remain classified unless the stipulated conditions laid down 
by the Board of Review were complied with." 20 

The "stipulated conditions" referred to are contained in General Manager 

89 



Part I 

Wilson's November 5, 1947, letter to Stone. According to Wilson's letter, at a 
June meeting the Medical Board of Review concluded that "the matter of human 
experimentation" would remain classified where certain "conditions" were not 
satisfied. Wilson then quoted from the "preliminary unpublished and restricted 
draft of the [Medical Board] report read to the Commissioners" as follows: 

The atmosphere of secrecy and suppression makes 
one aspect of the medical work of the Commission 
especially vulnerable to criticism. We therefore 
wish to record our approval of the position taken by 
the medical staff of the AEC in point of their 
studies of the substances dangerous to human life. 
We [the Medical Board of Review] believe that no 
substances known to be, or suspected of being, 
poisonous or harmful should be given to human 
beings unless all of the following conditions are 
fully met: (a) that a reasonable hope exists that the 
administration of such a substance will improve the 
condition of the patient, (b) that the patient give his 
complete and informed consent in writing, and (c) 
that the responsible next of kin give in writing a 
similarly complete and informed consent, revocable 
at any time during the course of such treatment 
[emphasis added]. 21 

In other words, the opinion of the Medical Board of Review was presented 
by Wilson in his November letter as both a prescription for the future conduct of 
human experiments and a presentation of the criteria that must be met for the 
declassification of past research. Wilson again referenced these conditions in a 
letter to ACBM Chairman Alan Gregg, also on November 5. "I am sure," Wilson 
wrote Gregg, "that this information will assist Dr. Stone in evaluating the present 
problem and inform him as to the conditions that must be met in future 
experiments." 22 Thus, as discussed in more detail in chapters 5 and 13, the 
requirement that research proceed only with consent appears to have been 
coupled with the decision to withhold from the public information about 
experiments that failed to meet that standard. 

Two points should be made about the term informed consent, which 
appears in the November letter from Wilson to Stone. First, it is not clear what 
meaning Wilson and the members of the Medical Board of Review attributed to 
the term. No further explanation was given. Second, it is nevertheless a matter of 
some historical interest that this term is used at all. Previous scholarship had 
attributed its first official usage to a landmark legal opinion in a medical 
malpractice case that was issued a decade later. 23 - 

90 



Chapter 1 

The April and November 1947 Wilson letters have some common 
elements, in spite of their differences in detail. They both provided that research 
with humans proceed (1) only where there is reasonable hope of therapeutic effect; 
and (2) with documentary proof that the patient-subject was informed of the 
treatment and its possible effects and had consented to its administration. 

But there are many remaining mysteries about the AEC's 1947 statements. 
In interviews with Advisory Committee staff, Joseph Volpe, who served as an 
AEC attorney in its early days and became general counsel in 1949, explained 
that a letter authored by General Manager Wilson could state AEC policy and 
confidently recollected that informed consent from research subjects would have 
been required by the first AEC general counsel. This requirement, Volpe 
maintained, should be reflected in the commission's minutes. 24 However, 
Committee and DOE review of the commission's minutes did not reveal evidence 
that the "consent" policy was expressly addressed. 

Even more troubling is that both Wilson letters precluded research that did 
not offer patient-subjects a prospect of direct medical benefit. In the context of 
the concern about the plutonium injections and the other "nontherapeutic" 
research conducted during the Manhattan Project experiments, this provision 
readily makes sense. Yet, as Oak Ridge's inquiry to Washington noted, 
nontherapeutic research in the form of tracer studies had been, and would 
continue to be, a mainstay of AEC-sponsored isotope research. How could it be 
that the Wilson letters were intended to ban exactly the kind of research that at the 
same time the AEC was so actively promoting? It is conceivable that the 
requirement of the isotope distribution program for risk review prior to the human 
use of radioisotopes was a means of addressing this notion. However, if the 
equation between that risk review procedure and the provision in the November 
Wilson letter seems implicit, the documentary evidence does not provide an 
express link between the requirement stated in the Wilson letter and the rules of 
the isotope distribution program. 

From Statements to Policy: A Failure of Translation 

Despite the fact that they were developed in response to a need for clarity 
in the way that human research should be conducted, we have found little 
evidence of efforts to communicate or implement the rules stated by Wilson in 
coordination with the AEC's biomedical advisory groups and other AEC officials. 
In some cases the evidence described in the following paragraphs suggests that 
policies for consent from subjects were established and implemented, while in 
other cases it suggests that, if there were any such policies, they were unknown or 
lost. Taken together, however, this evidence further supports the view that the 
ideas present in General Manager Wilson's 1947 statements were available to 
those working in the field during this time, albeit perhaps in a primitive form. 

Consider, for example, a 1951 exchange between the AEC's Division of 

91 



Parti 

Biology and Medicine (DBM), which directed the AEC's medical research 
program, and the commission's Los Alamos Laboratory, which was in routine 
contact with Washington. An information officer at Los Alamos, Leslie Redman, 
who was charged to review papers that involved human experimentation, asked 
the DBM for a "definite AEC policy" on "human experimentation." In the course 
of his work, Redman wrote, he had been advised by "various persons" at Los 
Alamos that "regulations or policies of the AEC" on human experimentation were 
available, but he had been unable to locate more than general information about 
these regulations. According to his letter, his understanding was that 

these regulations are comparable to those of the 
American Medical Association: that an experiment 
be performed under the supervision of an M.D., 
with the permission of the patient, and for the 
purpose of seeking a cure. 25 

Redman's characterization of the American Medical Association's guidelines, as 
we shall see in chapter 2, is partly incorrect. The requirement of a therapeutic 
intent is absent from the AM A guidelines. The possibility of direct therapeutic 
benefit for the patient was, however, a condition of research according to both of 
General Manager Wilson's 1947 letters. 

Shields Warren, the DBM chief, responded to Redman by citing Wilson's 
November 5, 1947, letter to Stone and by excerpting the conditions quoted 
above. 26 But Warren did not term these conditions "standards" or "requirements." 
Rather, Warren's response to Los Alamos "urges" compliance with these "guiding 
principles." 27 

Though Los Alamos was provided with the criteria stated by Wilson in 
November 1947, General Manager Wilson's statements were not routinely 
communicated in response to requests for guidance from non-AEC researchers. 
In an April 1948 letter to the DBM, a university researcher explained that the 
Isotopes Division had approved his request to use phosphorus 32 for 
"experimental procedures in the human . . . simply for investigational purposes 
and not for treatment of disease." What, the researcher wanted to know, should 
be done about "medical-legal aspects" and "permission forms"? 28 The request 
could have been answered by referring to Wilson's 1 947 statements about 
consent. Instead, the DBM simply referred the researcher to the Isotopes Division 
at Oak Ridge. 29 In its response, the Isotopes Division did not indicate that consent 
should be solicited, as Wilson had stipulated. The Isotopes Division, stating it 
could be "of little assistance," declined to provide "legal advice," save to note that 
"we understand that most hospitals do require patients to sign general releases 
before entering into treatment." 30 

From 1947 onward, the AEC had ample opportunity to disseminate a 
research policy. The AEC routinely provided educational and administrative 

92 



Chapter 1 



materials to applicants for AEC funding and to the far greater number of 
ZlTcan s foTAEC-produced radioisotopes. The isotopes distribution program, 
np Sat included a sophisticated structure of regulation, repkte with ; review 
oSmttees, training courses, and informational brochures (see chapter -t ) At the 
federal level this included the Subcommittee on Human Applications of the 
Cotmi ^ilitopc Distribution, whose very purpose was "to review all initial 
« for radioisotopes to be used experimentally or otherwise in human beings 
remohasis added]." 31 The AEC Subcommittee on Human Applications was 
supplemented by similar committees at the research institutions where the work 

WaS C °fn U p C nnciple, there does not seem to be any reason these local committees 
could not have been instructed by the Isotopes Division on consent 
eautemenL- Some evidence suggests that in March 1948 the Subcommittee on 
Human Applications discussed consent requirements for healthy subjects and 
"Sheets. In a document dated March 29, 1948, the Subcommittee on 
Human Applications appeared to resolve that 

1 Radioactive materials should be used in experiments 
involving human subjects when information obtained will 
have diagnostic value, therapeutic significance, or will 
contribute to knowledge on radiation protection. 

2. Radioactive materials may be used in normal human 
subjects provided 

a. The subject has full knowledge of 
the act and has given his consent to 
the procedure. 

b. Animal studies have established 
the assimilation, distribution, 
selective localization and excretion 
of the radioisotope or derivative in 
question. 

3. Radioactive materials may be used in patients 
suffering from diseased conditions of such nature 
that there is no reasonable probability of the 
radioactivity employed producing manifest injury 
provided: 

a. Animal studies have established the 
assimilation, distribution, selective 

93 



Part I 

localization and excretion of the 
radioisotope or derivative in 
question. 

b. The subject is of sound mind, has 
full knowledge of the act and has 
given his consent to the procedure. . . . 

4. Investigations are approved ( 1 ) by medical 
director or his equivalent at the installation 
responsible for the investigation, (2) by the 
Director, Division of Biology and Medicine, and (3) 
full written descriptions of experimental procedures 
and calculated estimates of radiation to be received 
by body structure and organs must be submitted. 31 

We were unable to locate any further references to this document and do not 
know whether it represented a policy that was adopted. Perhaps it represents the 
consensus of the Subcommittee on Human Applications, as it had met shortly 
before that, or perhaps it is simply a draft document prepared by staff. 

Whatever the ultimate disposition of this document, it provides some idea 
of the problems that were under consideration at the time and indicates that views 
on human use were unsettled. The first numbered item, for example, appears to 
recommend human radiation experiments when they will offer diagnostic value 
and therapeutic significance or knowledge about radiation protection. If the 
document had in fact been adopted, the recognition that isotope experimentation 
could be undertaken to "contribute to knowledge" (item 1) would appear to revise 
the Wilson letters' prohibition of nontherapeutic experimentation. The third item 
also addresses consent and risk of injury to patient-subjects without indicating 
that there should be any potential benefit. Another peculiarity is found in the 
second item, which refers to consent from normal human subjects but does not 
rule out experiments that present risk to the subject. 

In any event, at a 1948 meeting the Subcommittee on Human Applications 
articulated a consent requirement as part of a decision to permit patients suffering 
from serious diseases to receive "larger doses for investigative purposes." 34 This 
requirement was disseminated to all radioisotope purchasers in 1949. 35 The 
subcommittee allowed investigators to administer "larger doses" to seriously ill 
patients but only with the patient's consent. While it is possible that the basis for 
permitting larger doses was an assumption that smaller ones would be of no 
potential benefit to subjects, item 3 of the just-quoted March 1948 document 
suggests the assumption was rather that in seriously ill patients other disease 
processes would be more likely to take their course before radiation injury was 
manifested. 

94 



Chapter 1 

There is evidence that at least one AEC-funded entity did routinely 
provide some form of disclosure and consent in the early 1950s. From its opening 
in 1950 the AEC-sponsored Oak Ridge Institute for Nuclear Studies (ORINS), a 
research hospital, advised incoming patients that procedures were experimental. 
Additionally, patients were given written information that advised them that 
"probable benefit, if any, cannot always be predicted in advance." 36 Patients were 
also asked to sign a form that indicated that they were "fully advised" about the 
"character and kind of treatment and care," which would be "for the most part 
experiments with no definite promise of improvement in my physical 
condition." 37 Thus, at least in the case of ORINS, and perhaps at other AEC 
facilities, a local process was instituted apart from any known communication of 
the statements by AEC officials. 

Nonetheless, there is other evidence that the AEC did not communicate 
the requirements detailed in General Manager Wilson's 1 947 letters to its own 
contract research organizations, which, as in the cases of Argonne, Los Alamos, 
Brookhaven, and Oak Ridge, ;had significant biomedical programs and were 
engaged in human research. When the Division of Biological and Medical 
Research at Argonne National Laboratory met in January 1951 to discuss 
beginning a program of human experimentation in cancer research, one of its 
members asserted that the ACBM had not established a "general policy 
concerning human experimentation." The minutes of the meeting at Argonne 
record that the ACBM "has been approached several times in the past for a 
general policy and has refused to formulate one." 38 

In 1956, Los Alamos asked the DBM to "restate its position on the 
experimental use of human volunteer subjects" for tracer experiments. 39 The 
DBM responded by stating that tracer doses might be administered under certain 
conditions, which included the provision that subjects be volunteers who were 
fully informed. The focus of this position seems to have been research with 
healthy people and not patients, and no reference was made to the provisions of 
the Wilson letters. 40 The DBM's 1956 formulation was given "staff distribution" 
by Los Alamos and restated in 1962. 4 ' 

Also in 1956, the Isotopes Division did state a requirement for healthy 
subjects. All subjects were to be informed volunteers. As part of its 
"Recommendations and Requirements" guidebook for the medical uses of 
radioisotopes, which was distributed to all medical users of radioisotopes, the 
Isotopes Division stated: 



Uses of radioisotopes in normal subjects for 
experimental purposes shall be limited to: 

a. Tracer doses which do not exceed the 
permissible total body burden for the radioisotope 



95 



Part I 

in question. In all instances the dose should be kept 
as low as possible. 

b. Volunteers to whom the intent of the study and 
the effects of radiation have been outlined. 

c. Volunteers who are unlikely to be exposed to 
significant additional amounts of radiation. 42 

These requirements apparently applied to all uses of AEC radioisotopes, whether 
government or private researchers were involved. The "experimental or 
nonroutine" use of radioisotopes in any human subjects was limited to 
institutional programs where local review committees existed to oversee the risk 
to which subjects were exposed. In stating these requirements, the AEC reiterated 
that "patients" in whom "there is no reasonable probability of producing manifest 
injury" may be used in some experiments not normally permitted, but did not 
reiterate the requirement that consent should be obtained from these patients, as 
was stated in 1948. 

What, then, can be said about the rules and policies of the AEC in the 
1940s and 1950s? General Manager Wilson's 1947 letters clearly stipulate a 
requirement of "informed consent" from patient-subjects, at least where 
potentially "poisonous or harmful" substances are involved. But with the 
exception of ORINS there is little indication that this requirement was imposed as 
binding policy on any AEC facility, contractor, or recipient of radioisotopes. By 
contrast, later requirements that healthy subjects be informed volunteers and that 
seriously ill patients be permitted to receive higher doses only with their consent 
appear to have been more broadly communicated and enforced. The only 
evidence of general attention to matters of consent from patient-subjects comes 
from ORINS, whose policies and practices show a striking similarity to those that, 
as we shall see, were being contemporaneously employed at another facility 
essentially devoted to experimental work, the NIH's Clinical Center. At the same 
time, there is evidence of considerable attention in both policy and practice to 
issues of safety and acceptable risk (see chapter 6). Questions of subject 
selection, as in the case of seriously ill patients, emerge only in this context of 
safety; there is no evidence that issues of fairness or concerns about exploitation 
in the selection of subjects figured in AEC policies or rules of the period. 

THE DEPARTMENT OF DEFENSE: CONSENT IS 
FORMALIZED 

The story of research involving human subjects in the U.S. military began 
at least a century ago. Well before 1944, the beginning of the period of special 
interest to the Advisory Committee, the military needed healthy subjects to test 

96 



Chapter 1 

means to prevent and treat infectious diseases to which military personnel might 
be exposed. The notion that consent should be obtained from human subjects was 
clearly part of this tradition; less clear is how consistently this was applied and 
what consent actually meant to those in authority. 

The most famous example of the early use of subject consent in the 
military took place at the turn of the century. Walter Reed's successful research 
on yellow fever, the mosquito-borne disease that bedeviled Panama Canal 
construction efforts, employed healthy subjects who signed forms indicating their 
agreement. Whether the practice was required by the Army or self-imposed by 
Reed is unknown. In 1925 an Army regulation to promote infectious disease 
research noted that "volunteers" should be used in "experimental" research. 43 

The Navy also provided early requirements for human subject research. 
In 1932, the secretary of the Navy granted permission for the conduct of an 
experiment involving divers on condition that the subjects were "informed 
volunteers." 44 In 1943 the secretary of the Navy also required that all 
investigators seeking to conduct research with service personnel obtain prior 
approval from the secretary. 45 

As we have noted in the Introduction, during World War II, federally 
funded biomedical research related to the war effort (outside the Manhattan 
Project) was coordinated by the Committee on Medical Research (CMR) of the 
Office of Scientific Research and Development, which was part of the Executive 
Office of the President. The CMR supported a program of human research, 
during which the question of the rules for the conduct of human research was 
addressed. In 1942 a University of Rochester researcher, seeking to "work out a 
human experiment on the chemical prophylaxis of gonorrhea," asked the CMR for 
"an opinion that such human experimentation is desirable." 46 In an October 9, 
1942, response, the CMR's chairman offered the following general statement, 
which was endorsed by the full committee: 

[HJuman experimentation is not only desirable, but 
necessary in the study of many of the problems of 
war medicine which confront us. When any risks 
are involved, volunteers only should be utilized as 
subjects, and these only after the risks have been 
fully explained and after signed statements have 
been obtained which shall prove that the volunteer 
offered his services with full knowledge and that 
claims for damage will be waived. An accurate 
record should be kept of the terms in which the 
risks involved were described. 47 

In spite of the CMR's statement in response to this researcher's query, it supported 
other experiments that involved subjects whose capacity to give valid consent to 

97 



Part I 

participation was doubtful, including institutionalized people with cognitive 
disabilities. 4 * 

During the war, the Navy used consent forms in wartime experiments 
using prisoners and conscientious objectors, as a proposal for research on an 
influenza vaccine with prisoners at San Quentin in 1943 shows. 49 The form used 
in this case indicates that the subject is "acting freely and voluntarily without any 
coercion on the part of any person whomever." 50 To be sure, the forms located by 
the Advisory Committee were called "waiver" or "release" rather than "consent" 
forms. Thus, the attestation to voluntary participation was punctuated by the 
release of experimenters from liability. However, at a time when free young men 
were routinely conscripted into the military, the requirement that subjects, 
including prisoners and conscientious objectors, must be volunteers seems 
remarkable. 

In sharp contrast with these procedures, the Navy, too, sometimes 
functioned in a manner inconsistent with a voluntary consent policy for healthy 
subjects. Surviving subjects have reported that harmful mustard gas experiments 
on naval personnel at the Naval Research Laboratory in Washington, D.C., during 
World War II failed to adequately inform subjects and seem to have involved 
manipulation or coercion of "volunteers." 51 The lack of medical follow-up on the 
subjects of these experiments was sharply criticized in a 1993 report by the 
Institute of Medicine of the National Academy of Sciences. 52 

The NEPA Debate on the Ethics of Prisoner Experiments 

Many of the researchers and officials who had been involved in Manhattan 
Project human experiments during the war and then in the 1947 AEC 
deliberations about human research policy also were engaged in 1949 and 1950 in 
discussions of the ground rules for research with human subjects in the 
development of new military technology. This time the forum was the joint AEC- 
DOD project on Nuclear Energy for the Propulsion of Aircraft (NEPA). The 
DOD convened an advisory panel of private and public officials to determine how 
to obtain data needed to answer questions such as whether the air crew would be 
put at undue risk by the nuclear-powered engine. The participants in the 
discussion included university researchers Hymer Friedell, Stafford Warren, 
Robert Stone, and Joseph Hamilton, and AEC officials Shields Warren and Alan 
Gregg. Shields Warren argued that human experimentation was not appropriate 
because the research could be done on animals and human data was not likely to 
produce scientifically valid results (see Introduction). 

Robert Stone, the recipient of the November 1947 letter in which AEC 
General Manager Wilson called for "informed consent," emerged as the primary 
proponent of human experiments. In a January 1950 discussion paper, he focused 
on the "ethics of human experimentation." 53 After a recitation of a tradition that 
included Walter Reed's experience and the historical use of prisoners and medical 

98 



Chapter 1 

students as research subjects, Stone cited requirements that had been publicized 
by the American Medical Association in 1946. These rules provided that subjects 
must give voluntary consent, that animal experimentation must precede human 
experimentation, and that human experiments should be "performed under proper 
medical protection and management." 54 (See chapter 2.) Stone argued that it 
would be possible to conduct NEPA-related experiments with prisoners in 
compliance with all three of these requirements. 

Stone's proposal generated considerable discussion among DOD and AEC 
experts and officials. In April 1950, the DOD's Joint Panel on the Medical 
Aspects of Atomic Warfare endorsed the use of prisoners of "true volunteer 
status" as meeting "the requirements of accepted American standards for the use 
of human subjects for research purposes." 55 

However, AEC officials were less than enthusiastic. "Doesn't the prisoner 
proposal," ACBM Chairman Alan Gregg asked a military official in the course of 
one discussion, "fall in the category of cruel and unusual punishment?" 5 "Not," 

the official replied, "if they would carry out the work as they proposed It 

would be on an absolutely voluntary basis, and under every safety precaution that 
could be built up around it ... it didn't strike me as being cruel and unusual." To 
which Shields Warren retorted: "It's not very long since we got through trying 
Germans for doing exactly the same thing." 57 

In December 1950 the AEC convened a panel to discuss what was known 
about potential radiation effects on service personnel and whether human research 
was needed. Joseph Hamilton, Robert Stone's colleague at the University of 
California, was unable to attend the meeting, and in his regrets he offered his 
thoughts on the matter. In a letter to Shields Warren, he noted that the proposal to 
use prisoner volunteers "would have a little of the Buchenwald touch" and 
reported that he had no "very constructive ideas as to where one would turn for 
such volunteers should this plan be put into effect." 58 He suggested using large 
primates, even though, from a purely scientific viewpoint, the data collected 
would not be as useful as data from humans. 59 

Apparently Stone lost the debate. A decision was made not to conduct 
experiments with prisoners or other healthy subjects in connection with the NEPA 
project. However, as will be discussed in more detail in chapter 8, the military 
contracted with a private hospital to study patients who were being irradiated for 
cancer treatment, in the hopes of answering the same kinds of questions that 
would have been addressed if NEPA research with prisoners had gone forward. 

Congress Provides for DOD Contractor Indemnification in the Case of 
Injury 

In the aftermath of World War II, the military continued its long-standing 
program of infectious disease research using human subjects. During the late 
1940s and early 1950s the Army Epidemiological Board (AEB) and its 1949 

99 



Parti 

successor, the Armed Forces Epidemiological Board (AFEB), which was 
established to advise on medical research funded by the DOD and to direct some 
research undertaken with Army funds, sponsored studies with healthy subjects 
that focused on hepatitis, dengue fever, and other infectious diseases. Consistent 
with military tradition, at least some AEB-sponsored researchers were using 
written permission forms. The forms, frequently referred to as an "Agreement 
with Volunteer," or a "release," outlined the study and the risks to the subject and 
protected the DOD from liability. 60 

In the late 1 940s, some university researchers expressed concern that they 
were not adequately protected from liability in the case of injury or death of their 
prisoner-subjects. The ensuing dialogue provides a window on the role of the 
written releases and the understanding of the rules governing human subject 
research. In response to a researcher's request to be reimbursed by the Army for a 
disability policy for the subjects, the Army lawyers replied that the Army could 
not provide indemnification in the absence of clear congressional authority. 
Army legal advisers recommended that the researcher "protect himself, the State 
of New Jersey [the research locale], and the Government by means of the usual 
waiver." 61 

In a February 1948 letter, the AEB director, John R. Paul, explained that 
the "world situation" had placed the rules for human experimentation up for 
grabs. 62 

At this stage in the world situation one should 
proceed cautiously, until standards are set by what 
ever body is in 'authority.' I am not sure just what 
the rules are but I understand that . . . some type of 
vigilance committee has laid down certain 
principles about volunteers in order to protect this 
country from the criticisms brought up in Germany 
during the Nuremberg trials. . . . During the war we 
more or less made our own policies on this, but I 
am not sure that this is possible today. . . , 63 

The allusion to a "vigilance committee" is unclear. It may be a reference to a 
committee established by the governor of Illinois to examine the use of prisoners 
as research subjects in that state and chaired by Andrew Ivy, the principal expert 
witness for the prosecution at the Nuremberg Medical Trial (see chapter 2). 
Given the date of the letter, February 18, 1948, it seems likely that Paul had just 
skimmed through his new copy of the Journal of the American Medical 
Association— the report of Ivy's committee was published in the February 14, 
1948, issue. 64 

In April 1948, an AEB official made it plain to the researchers that the fact 
that state authorities or the prison warden gave permission for the experiment 

100 



Chapter 1 

should be of little comfort to them. In case of a lawsuit, responsibility "would 
devolve entirely upon the individual experimenter." 65 Only Congress could 
provide a solution, but it would be a "dangerous course" to raise the matter 
publicly. "I have," the AEB official wrote, 

given considerable thought to the matter of whether 
it would be advisable to approach individuals or 
groups in Congress with the idea of having laws 
passed relating to payment of compensation for 
disability or release of the experimenter from 
liability. I am afraid that this would be a dangerous 
course, and that it might in fact injure clinical 
investigations generally. There is a very real 
possibility that unfavorable publicity would quickly 
result. 66 

It appears that the relief sought by researchers was provided by Congress 
in 1952, however, under the umbrella of a law that provided indemnification for 
DOD research and development activities as a whole. In October 1952, following 
the death of a prisoner-subject in an AFEB-sponsored hepatitis study 67 and 
questions raised by the Army Chemical Corps about release forms for "human 
'guinea pigs,'" 68 the AFEB administrator queried the DOD Legal Office about a 
recently passed federal law. The law provided authority for the military to 
indemnify contractors for risks undertaken in "research and development 
situations." Did the new law "afford relief to the immediate dependents of 

prison volunteers when as [a] result of these experiments they should die[?]" 6 
The answer was yes, but only by providing relief to the researchers first. "From 
the wording of the law, and from ... the legislative history," the Legal Office 
replied, "it is a direct indemnification to the contractor and not to the individual 

human guinea pig." 70 

Thus, what appears to have been the first Cold War congressional 
enactment to deal with human subjects of research addressed the government's 
obligation to its contractors, not the government's and its researchers' obligations 
to the subjects. Moreover, the record indicates that a more direct approach was 
not sought by the DOD because of concerns about public relations. At the same 
time Congress was acting, however, the DOD itself was secretly debating a new 
policy for human experiments. 

The Secretary of Defense Issues the Nuremberg Code in Top Secret 

As the Korean War began in mid- 1950, the military's interest in human 
experimentation-in connection with chemical and biological as well as atomic 
and radiation warfare-intensified. The need for a DOD-wide policy on the use of 

101 



Part I 

human subjects in research was noted by Colonel George Underwood, the 
director of the Office of the Secretary of Defense, in a February 1953 
memorandum to the incoming administration of Dwight D. Eisenhower: "There 
is no DOD policy on the books which permits this type of research [human 
experiments in the field of atomic, biological, and chemical warfare]." 71 

From 1950 to 1953 discussions about human research and human research 
policy were held in several high-level DOD panels, including the Armed Forces 
Medical Policy Council (AFMPC), the Committee on Medical Sciences (CMS), 
and the Joint Panel on the Medical Aspects of Atomic Warfare. These groups 
were headed by civilian researchers, and, in at least the latter two cases, included 
representatives of the AEC, CIA, NIH, VA, and Public Health Service. 

At its September 8, 1952, meeting, the AFMPC heard a presentation from 
the chief of preventive medicine of the Army Surgeon General's Office on the 
topic of biological warfare research: 

It was pointed out that the research had reached a 
point beyond which essential data could not be 
obtained unless human volunteers were utilized for 
such experimentation. . . . Following detailed 
discussion, it was unanimously agreed that the use 
of human volunteers in this type of research be 
approved. 72 

At its October 13, 1952, meeting the AFMPC again took up the question 
of human experimentation. "It was resolved," the chairman wrote to the secretary 
of defense, "that the ten rules promulgated at the Nuremberg trials be adopted as 
the guiding principles to be followed. An eleventh rule [barring experiments with 
prisoners of war] was added by the legal advisor to the Council, Mr. Stephen S. 
Jackson." 73 

DOD attorney Jackson evidently was responsible for the inclusion of the 
Nuremberg Code in the AFMPC's proposed policy. In an October 13, 1952, 
memo to the chairman of the AFMPC, Jackson 

recommended: that the attached principles and 
conditions for human experimentation, which were 
laid down by the Tribunal in the Nuremberg Trials, 
be adopted instead of those previously submitted by 
me. 74 

As an addendum to the Nuremberg Code, Jackson proposed a requirement 
that "consent be expressed in writing before at least one witness." This 
recommendation followed from the suggestion of Anna Rosenberg, assistant 



102 



Chapter 1 



The Nuremberg Code 

1. The voluntary consent of the human subject is absolutely essential. 

This means that the person involved should have legal capacity to give consent; should be so 
situated as to be able to exercise free power of choice, without the intervention of any element of 
force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or coercion; and 
should have sufficient knowledge and comprehension of the elements of the subject matter 
involved as to enable him to make an understanding and enlightened decision. The latter element 
requires that before the acceptance of an affirmative decision by the experimental subject there 
should be made known to him the nature, duration, and purpose of the experiment; the method and 
means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; 
and the effects upon his health or person which may possibly come from his participation in the 
experiment. The duty and responsibility for ascertaining the quality of the consent rest upon each 
individual who initiates, directs or engages in the experiment. It is a personal duty and 
responsibility which may not be delegated to another with impunity. 

2. The experiment should be such as to yield fruitful results for the good of society, 
unprocurable by other methods or means of study, and not random and unnecessary in nature. 

3. The experiment should be so designed and based on the results of animal 
experimentation and a knowledge of the natural history of the disease or other problem under 
study that the anticipated results will justify the performance of the experiment. 

4. The experiment should be so conducted as to avoid all unnecessary physical and 
mental suffering and injury. 

5. No experiment should be conducted where there is an a priori reason to believe that 
death or disabling injury will occur; except, perhaps, in those experiments where the experimental 
physicians also serve as subjects. 

6. The degree of risk to be taken should never exceed that determined by the 
humanitarian importance of the problem to be solved by the experiment. 

7. Proper preparations should be made and adequate facilities provided to protect the 
experimental subject against even remote possibilities of injury, disability, or death. 

8. The experiment should be conducted only by scientifically qualified persons. The 
highest degree of skill and care should be required through all stages of the experiment of those 
who conduct or engage in the experiment. 

9. During the course of the experiment the human subject should be at liberty to bring the 
experiment to an end if he has reached the physical or mental state where continuation of the 
experiment seems to him to be impossible. 

10. During the course of the experiment the scientist in charge must be prepared to 
terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the 
good faith, superior skill, and careful judgment required of him, that a continuation of the 
experiment is likely to result in injury, disability, or death to the experimental subject. 



103 



Parti 

secretary of defense for manpower and personnel, who was an expert on labor 
relations. 75 

A letter written by the administrator of the Armed Forces Epidemiological 
Board documents Mr. Jackson's role and motivation: 

It was on Mr. Jackson's insistence that the 
'Nuremberg Principles' were used in toto in the 
document, since he stated, these already had 
international judicial sanction, and to modify them 
would open us to severe criticism along the line— 
"see they use only that which suits them." 76 

Thus, the DOD's counsel cited the 1947 Nuremberg military tribunal 
ruling as establishing an international legal precedent to which American 
researchers should be held. 

It appears that in succeeding months the AFMPC proposal was received 
unenthusiastically by other DOD committees that reviewed it. In a November 12, 
1952, memorandum, the executive director of the Committee on Medical Sciences 
pointed out that "human experimentation has been carried on for many years." He 
contended that 

to issue a policy statement on human 
experimentation at this time would probably do the 
cause more harm than good; for such a statement 
would have to be "watered down" to suit the 
capabilities of the average investigator. 77 

"Human experimentation," the CMS executive director asserted, "has, in 
years past, and is at present governed by an unwritten code of ethics," which is 
"administered informally by fellow workers in the field [and] is considered to be 
satisfactory. ... To commit to writing a policy on human experimentation would 
focus unnecessary attention on the legal aspects of the subject." 78 

Notwithstanding the reservations of the CMS and others, 79 the Nuremberg 
Code proposal had the support of President Truman's secretary of defense, Robert 
A. Lovett. 80 However, the secretary's aide, George V. Underwood, wrote in 
January 1953, "Since consequences of this policy will fall upon Mr. Wilson 
[President Eisenhower's nominee for secretary of defense, Charles Wilson], it 
might be wise to pass to him as a unanimous recommendation from the 
'alumni.'" 81 

In a January 13, 1953, memorandum for the new secretary, the AFMPC 
"strongly recommended that a policy be established for the use of human 
volunteers (military and civilian employees) in experimental research at Armed 



104 



Chapter 1 

Forces facilities." The policy would render the research "subject to the principles 
and conditions laid down as a result of the Nuremberg trials." 82 



The Wilson Memorandum 

26 Feb 1953 



Memorandum for the Secretary of the Army 

Secretary of the Navy 
Secretary of the Air Force 

Subject: Use of Human Volunteers in Experimental Research 

1. Based upon a recommendation of the Armed Forces Medical Policy Council, that 
human subjects be employed, under recognized safeguards, as the only feasible means for realistic 
evaluation and/or development of effective preventive measures of defense against atomic, 
biological or chemical agents, the policy set forth below will govern the use of human volunteers 
by the Department of Defense in experimental research in the fields of atomic, biological and/or 
chemical warfare. 

2. By reason of the basic medical responsibility in connection with the development of 
defense of all types against atomic, biological and/or chemical warfare agents. Armed Services 
personnel and/or civilians on duty at installations engaged in such research shall be permitted to 
actively participate in all phases of the program, such participation shall be subject to the 
following conditions: 

a. The voluntary consent of the human subject is absolutely essential. 

( 1 ) This means that the person involved should have legal capacity to 
give consent; should be so situated as to be able to exercise free power of choice, 
without the intervention of any element offeree, fraud, deceit, duress, over- 
reaching, or other ulterior form of constraint or coercion; and should have 
sufficient knowledge and comprehension of the elements of the subject matter 
involved as to enable him to make an understanding and enlightened decision. 
This latter element requires that before the acceptance of an affirmative decision 
by the experimental subject there should be made known to him the nature, 
duration, and purpose of the experiment; the method and means by which it is to 
be conducted; all inconveniences and hazards reasonably to be expected; and the 
effects upon his health or person which may possibly come from his 
participation in the experiment. 

(2) The concept [sic] of the human subject shall be in writing; his 
signature shall be affixed to a written instrument setting forth substantially the 
aforementioned requirements and shall be signed in the presence of at least one 
witness who shall attest to such signature in writing. 



105 



Parti 

(a) In experiments where personnel from more than one 
Service are involved the Secretary of the Service which is exercising 
primary responsibility for conducting the experiment is designated to 
prepare such an instrument and coordinate it for use by all the Services 
having human volunteers involved in the experiment. 
(3) The duty and responsibility for ascertaining the quality of the 
consent rests upon each individual who initiates, directs or engages in the 
experiment. It is a personal duty and responsibility which may not be delegated 
to another with impunity. 

b. The experiment should be such as to yield fruitful results for the good of 
society, unprocurable by other methods or means of study, and not random and 
unnecessary in nature. 

c. The number of volunteers used shall be kept at a minimum consistent with 
item b., above. 

d. The experiment should be so designed and based on the results of animal 
experimentation and a knowledge of the natural history of the disease or other problem 
under study that the anticipated results will justify the performance of the experiment. 

e. The experiment should be so conducted as to avoid all unnecessary physical 
and mental suffering and injury. 

f. No experiment should be conducted where there is an a priori reason to 
believe that death or disabling injury will occur. 

g. The degree of risk to be taken should never exceed that determined by the 
humanitarian importance of the problem to be solved by the experiment. 

h. Proper preparation should be made and adequate facilities provided to protect 
the experimental subject against even remote possibilities of injury, disability, or death. 

i. The experiment should be conducted only by scientifically qualified persons. 
The highest degree of skill and care should be required through all stages of the 
experiment of those who conduct or engage in the experiment. 

j. During the course of the experiment the human subject should be at liberty to 
bring the experiment to an end if he has reached the physical or mental state where 
continuation of the experiment seems to him to be impossible. 

k. During the course of the experiment the scientist in charge must be prepared 
to terminate the experiment at any stage, if he has probable cause to believe, in the 
exercise of the good faith, superior skill and careful judgment required of him that a 
continuation of the experiment is likely to result in injury, disability, or death to the 
experimental subject. 

1. The established policy, which prohibits the use of prisoners of war in human 
experimentation, is continued and they will not be used under any circumstances. 
3. The Secretaries of the Army, Navy and Air Force are authorized to conduct 
experiments in connection with the development of defenses of all types against atomic, biological 
and/or chemical warfare agents involving the use of human subjects within the limits prescribed 
above. 



106 



Chapter 1 

4. In each instance in which an experiment is proposed pursuant to this memorandum, 
the nature and purpose of the proposed experiment and the name of the person who will be in 
charge of such experiment shall be submitted for approval to the Secretary of the military 
department in which the proposed experiment is to be conducted. No such experiment shall be 
undertaken until such Secretary has approved in writing the experiment proposed, the person who 
will be in charge of conducting it, as well as informing the Secretary of Defense. 

5. The addresses will be responsible for insuring compliance with the provisions of this 
memorandum within their respective Services. 

/signed/ 
C. E. Wilson 
copies furnished: 

Joint Chiefs of Staff 

Research and Development Board 

Downgraded to 
UNCLASSIFIED 
22 Aug 75 
TOP SECRET 



On February 26, 1953, Secretary of Defense Wilson signed off on the 
AFMPC policy. It was issued in a Top Secret memorandum to the secretaries of 
the Army, Navy, and Air Force. The Wilson memorandum reiterates the 
principles of the Nuremberg Code, requires written and witnessed informed 
consent of research subjects, and prohibits the use of prisoners of war. The policy 
was to "govern the use of human volunteers by the Department of Defense in 
experimental research in the fields of atomic, biological, and/or chemical warfare 
for defensive purposes." 83 

The basis for the classification of the 1953 memorandum is not clear. 
Since the memorandum dealt with atomic and other unconventional forms of 
warfare, its classification may have been routine. There is evidence that the DOD 
had a general desire to keep hidden from public view any indication that it was 
involved in biological and chemical warfare-related research; the Wilson 
memorandum, of course, was just such an indication. In September 1952, the 
Joint Chiefs of Staff advised the services to "[e]nsure, insofar as practicable, that 
all published articles stemming from BW [biological warfare] and CW [chemical 
warfare] research and development programs are disassociated from anything 
which might connect them with U.S. military endeavor." 84 

In one sense the memorandum is a landmark in its official recognition of 
the Nuremberg Code, but in another sense it also generates important questions. 
Having determined to recognize international principles of human rights, why, or 
how, could the secretary have limited their application to some, but not all, human 

107 



Parti 

experiments? Why was the policy directed exclusively to experiments related to 
"atomic, biological, and chemical warfare"? Moreover, was the policy intended 
to govern such research wherever it was conducted; for example, when it was 
performed by private contractors, as well as by intramural researchers? How was 
a directive issued in secret implemented? 

Communicating the 1953 Wilson Memorandum 

That there were problems in the dissemination of Secretary Wilson's Top 
Secret memorandum is evidenced in a memorandum containing queries by 
officials of the Armed Forces Special Weapons Project (AFSWP), within a year 
of the Wilson memorandum's issuance. The AFSWP, now the Defense Nuclear 
Agency (DNA), was at the hub of DOD nuclear weapons research. In the course 
of a routine review of research reports, an AFSWP official learned that 
"volunteers were injured as a consequence of taking part in [a] field experiment" 
of flashblindness conducted at an atomic bomb test before the Wilson 
memorandum was issued (see chapter 10). The AFSWP reviewer immediately 
concluded that a "definite need exists for guidance in the use of human volunteers 
as experimental subjects." 85 

On further inquiry, the AFSWP reviewer found that a policy already 
existed, but had not been disseminated to investigators. A follow-up 
memorandum, evidently written in early 1954, records: 

In November 53 it was learned that there existed a 
T/S [Top Secret] document signed by the Secretary 
of Defense which listed various requirements and 
criteria which had to be met by individuals 
contemplating the use of human volunteers in Bio- 
medical or other types of experimentation. ... It 
was learned that although this document details 
very definite and specific steps which must be taken 
before volunteers may be used in experimentation, 
no serious attempt has been made to disseminate the 
information to those experimenters who have a 
definite need-to-know. 86 

"The lowest level at which it had been circulated," the AFSWP reviewer 
learned, "was that of the three Secretaries of the Services." Efforts by an assistant 
secretary to "downgrade" the document had "not been able to obtain 
concurrence." The reviewer hoped that "this letter shall point up the need for 
some relaxation of the grip in which this document is now held, at least on a 
definite need-to-know basis." 87 (The application of the Wilson memorandum to 
further experiments conducted at atomic bomb tests is discussed in chapter 10.) 

108 



Chapter 1 
Implementation in the Army 

The Army did take substantial steps to put into effect the Wilson 
memorandum. In June 1953 the Army chief of staff, John C. Oakes, issued a 
memorandum implementing the secretary of defense's policy in toto. Referred to 
in the Army as CS:385, this memorandum was initially classified Top Secret, but 
was declassified the following year. In addition to the provisions of the Wilson 
memorandum, the Army document required the prior review and approval of both 
the surgeon general and the secretary of the Army. The Army's memorandum 
also contained legal analysis that explained the source of the Army's authority to 
perform human experiments in the first place and the limits that this authority put 
on the selection of subjects. 81 * Even in the midst of the Korean War, the Army 
did not view it as self-evident that the DOD could engage in human experiments 
or choose any subjects it wished. The memorandum explained that the authority 
to experiment on humans came from congressional enactments, including 
provisions for research and development. 1 * 9 

Interestingly, choice of subjects was to be governed by the Army's ability 
to ensure compensation in the case of death or disability. 90 This could be 
provided, the lawyers declared, only upon express congressional action. In the 
case of military personnel and contractor employees there was such provision. 
But there was no such authority in the case of private citizens who offered their 
services. The Army lawyers recommended, and the CS:385 policy provided, that 
private citizens not employed by Army contractors could not serve as research 
subjects. 91 

On March 12, 1954, the Army Office of the Surgeon General (OSG) 
issued an unclassified statement entitled "Use of Human Volunteers in Medical 
Research: Principles, Policies, and Rules." 92 This document too restated the 
Nuremberg principles. In contrast with the Wilson and Oakes memorandums, it 
was not restricted to research related to atomic, biological, or chemical warfare. 
Instead, the OSG statement was directed to "medical research" with human 
volunteers generally. 93 

Moreover, while CS:385 did not state directly whether it applied to 
contract researchers, the 1954 OSG statement was transmitted to at least some 
university researchers with the prefatory note, "To be used as far as applicable as 
a non-mandatory guide for planning and conducting contract research." 94 There is 
evidence that the OSG's requirements were sometimes more than "non-mandatory 
guides." For example, in a June 27, 1956, letter to the the Armed Forces 
Epidemiological Board, a Tulane University public health researcher agreed that 
his vaccine experiments with prisoner subjects would be conducted only after 
written consent was obtained from the subjects. 95 The Tulane researcher 
indicated that, with respect to his application for funding, "I have held it up since 
Dr. Dingle indicated I be familiar with the statement of the Office of the Surgeon 
General re the use of human volunteers I have read it and believe that our 

109 



Parti 

past and future work have [sic] and will comply with the rules stipulated." 96 
Moreover, this researcher provided a written statement to supplement his original 
proposal that explained how the OSG requirements would be met. In another 
case, a proposal involving measles and normal children, an AFEB official advised 
the researcher to "take [the OSG policy] into consideration in writing the 
proposal." 97 

As discussed earlier, in 1952 the Army obtained congressional authority to 
indemnify contract researchers in the event that an experiment caused injury or 
death. There is evidence that the Army sought to link the grant of an 
indemnification clause (ASPR 7.203.22, "Insurance-Liability to Third Persons") 
to contractor acceptance of the principles stated by the Army surgeon general. In 
a March 1957 letter to the University of Pittsburgh, which was proposing to use 
medical student-volunteers in a (nonradiation) experiment, the Army told 
Pittsburgh that the provision of the clause was "contingent upon your adhering to 
the following [March 1954 Office of the Surgeon General] principles, policies, 
and rules for the use of human volunteers in performing subject medical research 
contracts." 98 

While the evidence clearly shows that Army officials sought to apply the 
Nuremberg Code policy to contractors, it did not meet with complete success, and 
the full extent of its efforts remains unclear. As we see in chapter 2, in the early 
1960s Harvard successfully resisted the inclusion of the Nuremberg Code 
language in its medical research contracts with the Army. As we see in chapter 8, 
which discusses DOD funding of research on the effects of total-body irradiation, 
the indemnification language was included in at least some contracts in which the 
surgeon general's policy was not mentioned. By 1969, however, the policy may 
have become standard in Army contracts under the authority of the Medical 
Research and Development Command. 99 

There are several possible explanations for the seeming absence of 
widespread inclusion of the surgeon general's memo as a contractual requirement, 
at least where indemnification was provided for. First, as discussed below, it is 
possible that the 1954 policy was meant to apply to research with healthy 
subjects, and not sick patients. (However, even if that were generally the case, 
the provision of indemnification might be expected to have triggered reflection on 
this limitation.) Second, as a related matter, the evidence we are reviewing shows 
a tension between the government's declaration of a principle and its readiness to 
actively insist that the principle be honored within the privacy of the doctor- 
patient relationship. 

Finally, Army imposition of the surgeon general's principles may also 
have depended on the nature of its interest in the research being done. An April 
3, 1957, memo distinguished cases where the institution "because of its primary 
interest, would conduct the research even without support of the OSG," from 
cases where "the study is conducted at the insistence of OSG." In the former case 
the strategy would be to seek cost-sharing contracts, in which the institution 

110 



Chapter 1 

would "assume all responsibility for any possible effects resulting from the 
experimentation." In the latter case, the indemnification clause would be 
provided, but the March 1954 policy would also be required and included in the 
contract directly or by reference. ino 

It is not clear that the 1954 OSG policy on human volunteers was intended 
to apply to research with patients. The term volunteer is ambiguous but at the 
time was commonly used to refer to healthy subjects. Nonetheless, a 1 962 Army 
memorandum that declared that since World War II "by and large research has 
been conducted in strict accordance with the Nuremberg Code" mentions 
patients. I0 ' The memo reported that a recent survey of contract research found 
that the volunteers treated in accord with the Nuremberg Code included "3,000 
students, 250 patients, and 300 prisoners." It is not known what kind of research 
these 250 patients were involved in, nor is it known what proportion of the 
patients who had been subjects of research supported or conducted by the Army 
since World War II were represented by these 250. 

Unfortunately, the 1962 review's confident declaration that Army research 
complied with the Nuremberg Code was too sanguine. In 1975, following public 
revelations that the Army and the CIA had conducted LSD experiments on 
unwitting subjects, the Army inspector general reviewed the application of the 
June 1953 policy to drug testing. The inspector general's review led to the 
declassification of the 1953 Wilson memorandum. The inspector general found 
that the Army had, with one or two exceptions, used only "volunteers" for its 
drug-testing program. However, the "volunteers were not fully informed, as 
required, prior to their participation, and the methods of procuring their services 
in many cases appeared not to have been in accord with the intent of Department 
of the Army policies governing use of volunteers in research." 102 

Additional DOD Research Requirements 

While the Navy is not known to have taken specific action in response to 
the 1953 Wilson memorandum, we have already noted that the Navy had long 
since provided for prior review and voluntary participation in some cases. The 
1951 Navy "Manual of the Medical Department" required secretarial approval of 
human experimentation and the use of volunteers. These requirements applied to 
"experimental studies of a medical nature" involving "personnel of the Naval 
Establishment (military and civilian)." 103 Participation was to be "on a voluntary 
basis only." 104 The manual also mandated prior review for research with patient- 
subjects. "Clinical research," including "research projects and therapeutic trials," 
was to be "authorized by" the Bureau of Medicine and Surgery. 105 

At least for research with radioisotopes, the requirement for voluntary 
participation may have applied to patient-subjects as well as healthy subjects. In 
1951 the Navy debated adoption of a permission form for the use of radioisotopes 
for patients at naval hospitals. 106 This form, to be signed by either the patient or 

111 



Parti 

the responsible next of kin, authorized the use of "tracer-therapeutic" doses 
"obtained from the Atomic Energy Commission for research purposes." 107 

Although it is not clear that the Army rules implementing the 1953 Wilson 
memorandum applied to patient-subjects, there is some evidence that consent 
forms that were usually used for surgical procedures were used in patient-related 
experimental settings involving radioisotopes. In 1955 an official from the 
Letterman Army Hospital in San Francisco asked the Walter Reed Hospital about 
the need for written "permission" forms for "test doses" of radioisotopes. 108 In 
response, the Army indicated that a standard form used for operations and 
anesthesia should also be employed, at the physician's discretion, when 
"authorization for administration of radioisotope therapy is desired." 109 

In the Air Force, a 1952 regulation on clinical research mandated safety 
and administrative procedures for the use of humans in experiments at Air Force 
medical facilities." This regulation required prior group review but did not 
mention consent provisions or refer to the subjects as volunteers. In 1958 a letter 
from the Air Force's Air Research and Development Command describes the 
policy for the use of humans in "hazardous research and development tests." This 
policy reiterated the requirement for prior review discussed in the 1952 
regulation. In this context, however, subjects were to be "volunteers]" who 
"understood] the degree of risk involved in the experiment."" 1 

What, then, were the operative rules in the Department of Defense for 
research involving human subjects in the 1940s and 1950s? By the mid-1950s, 
for the entire DOD for research related to atomic, biological, and chemical 
warfare, and for all research involving "human volunteers" in the Army, the 
formal rules were the ten principles of the Nuremberg Code and the additions 
included in the secretary of defense's 1953 policy. According to the 1975 
testimony of the surgeon general of the Army before the U.S. Senate and the 
internal review conducted by the Army inspector general, these principles were 
Army "policy."" 2 At the same time, as the inspector general reported in 1975 and 
as we discuss further in chapter 10, these requirements were not always known or 
followed. While there were attempts to implement the Army surgeon general's 
1954 policy, it is not known how the policy's provisions, including the 
requirement to obtain voluntary consent, were interpreted. The Navy's 1951 
requirements for prior review and voluntariness applied to all research involving 
Navy personnel. 

The extent to which research rules applied to patient-subjects in the 
clinical setting is less clear. There is some indication that in some cases standard 
consent forms, akin to the surgical permits in use at the time, were employed with 
patients at military hospitals who were administered "test doses" of radioisotopes. 



112 



Chapter 1 

THE NATIONAL INSTITUTES OF HEALTH AND THE 
VETERANS ADMINISTRATION 

During the late 1940s and 1950s, the AEC and DOD were by no means 
the only agencies sponsoring research involving human subjects. The Department 
of Health, Education, and Welfare (DHEW), through two of its components, the 
Public Health Service and the NIH, was emerging during this period as the 
dominant government agency sponsoring human biomedical research. The 
Veterans Administration (VA) as well conducted a large medical research 
program that involved the use of radioisotopes in numerous human experiments. 

In the early 1950s NIH participated in some of the discussions preceding 
the issuance of the 1953 secretary of defense memorandum. At the request of a 
DOD official for information on NIH's approach to the use of human subjects, 
NIH responded with an April 1952 letter that included a draft statement on the 
"Ethical Principles Underlying Investigations Involving Human Beings." Among 
its other provisions, the April 28, 1952, draft states that 

[t]he person who is competent to give consent to an 
investigative procedure must do so. He must have legal 
capacity to give consent and be able to exercise free choice, 
without the intervention of any element of force, fraud, 
deceit, duress, constraint or coercion. He must have 
sufficient knowledge and comprehension of the nature of 
the investigation to enable him to make an understanding 
and enlightened decision. He must therefore be told the 
nature, duration, and purpose of the experiment; the 
method and means by which it is to be conducted; the 
inconveniences and hazards reasonably to be expected; and 
the effects upon his health or person which can reasonably 
be expected to come from his participation in the 
investigation. He should understand, furthermore, that by 
his participation he becomes a co-investigator with the 
physician." 3 

Although it is not known what became of this draft statement, around this 
time NIH had good reason to develop a policy on the use of human subjects. In 
1953 NIH opened the Clinical Center, a state-of-the-science research hospital. 
The center adopted a policy requiring "voluntary agreement based on informed 
understanding" from all research subjects and written consent from some patient- 
subjects involved in research that the physician believed to be unusually 
hazardous." 4 Written consent was required from all healthy, "normal" subjects of 
research beginning in 1954." 5 Additionally, NIH began a system of group review 
of proposed research that became a model for today's institutional review boards 

113 



Part I 

(IRBs)." 6 Thus, the NIH policy appears to be the first instance of a single policy 
that expressly provides for consent from all subjects, be they healthy or sick. 
Even so, the policy was still limited to research at the Clinical Center and did not 
apply to the considerable amount of NIH-funded research being undertaken by 
grantees (extramural research). 

The question of whether "patients," as well as healthy, "normal" 
volunteers, should give written consent arose in the development of the NIH 
policy. Legal counsel at NIH advised that, "from a legal point of view," there 
should be a "written statement . . . indicating the patient's awareness of the nature 
of the particular investigation in which he was to participate and acceptance of 
any particular inconvenience or risk inherent in his participation."" 7 A signed 
form offered the best proof that a "policy" of "informed consent" was followed for 
all subjects enrolled in studies at the center. 

The NIH attorney wrote that while the Clinical Center's Medical Advisory 
Board did not disagree with the principle, it did disagree with the need for a 
written statement: 

[0]f the members that expressed their views, and 
most did so, all rejected such a proposal. The 
rejection was due, as I understand it, not to any 
particular detail but rather a more basic objection to 
written, as opposed to oral, statements. There was 
apparently, therefore, no objection to providing the 
patient with enough information to permit him to 
exercise an informed choice of participation or 
refusal as long as not reduced to writing for his 
signature." 8 

Nonetheless, the principle that all research subjects, including healthy subjects in 
the "normal volunteer" program and patient-subjects, should make an informed 
choice seems to be acknowledged in the Medical Advisory Board's position. 

The NIH Clinical Center approach adopted by the mid-1950s-written 
consent from healthy subjects and from only certain patient-subjects— persisted 
through the early 1960s and was paralleled in policies of the DOD and the AEC. 
The view that written consent from patients might unnecessarily interfere with 
doctor-patient relationships prevailed. 

Within the NIH, dialogue continued throughout the 1950s, setting the 
stage for the leading role DHEW was to take in formulating human research 
regulations in the 1960s (see chapter 3)." 9 

Although the NIH was by far the dominant agency in research involving 
human subjects, a significant amount of radioisotope research occurred at the VA. 
The VA research program employing radioisotopes at VA medical centers began 
in 1948. 120 This program was limited to VA hospitals affiliated with medical 

114 



Chapter 1 

schools. From its inception, this program involved a system of prior group review 
by local radioisotope committees, normally composed of non-VA-affiliated 
teaching staff of the affiliated medical school. 121 These committees reviewed all 
research proposals and approved all research conducted at VA radioisotope units. 

In its formative years, the advisers to the new VA program included 
Stafford Warren, Shields Warren, and others who were likely to be familiar with 
the consent principles articulated by the AEC. Nonetheless, the earliest evidence 
of a consent policy at the VA comes in the form of a 1958 general counsel's 
opinion on whether the VA could participate in certain research. The general 
counsel asserted that 

persons who participate [in human subject research] 
must voluntarily consent to the experiment on 
themselves. Such consent must rest upon an 
understanding of the hazards involved. The 
volunteer may withdraw from the experiment at any 
time. Moreover, before the experiment, steps to 
reduce the hazard, as for example, indicated 
research on animals, must be made. 122 

This opinion was written in response to two proposed research projects, and it is 
not known if it was implemented in the projects or applied to others. 

CONCLUSION 

Records now available show that at the highest reaches of Cold War 
bureaucracies officials discussed conditions under which human experimentation 
could take place. These discussions took place earlier and in greater, although by 
today's standards uncritical and less searching, detail than might have been 
assumed. Nonetheless, the stated positions that resulted were often developed in 
isolation from one another, were neither uniform nor comprehensive in their 
coverage, and were often limited in their effectuation. Several interrelated factors 
seem to have been prominent in causing these discussions to take place and in 
determining the scope of the requirements that were declared and the efforts that 
were undertaken to implement them. We summarize these key factors below. 

Administrative and Legal Circumstance 

The creation of new programs, or the qualitative expansion of old ones, 
impelled officials, lawyers, and researchers to reflect on the rules to govern them. 
While these rules were sometimes cast as "legal" or "financial" requirements, they 
often included provisions, such as a requirement for written consent, that appear 
similar to statements in requirements that govern the conduct of research today. 

115 



Parti 

The language used to describe these rules was often that of law or administration, 
such as "waiver" or "release" forms, or it may have had particular meaning to 
researchers at the time, such as "clinical testing." As a result, it is often hard to 
compare these rules to current requirements, which have benefited from 
intervening decades of linguistic and conceptual refinement. 

Professional Cultures 

Differing professions brought their own tools and perspectives to 
discussions of conditions under which human subjects research could proceed. 
For example, lawyers were likely to insist on obtaining documented evidence of 
patient consent, while medical professionals emphasized the importance of the 
trust that underlay the relationship between doctor and patient; they sometimes 
objected to the use and implications of written consent forms. 

If consent procedures were a source of disagreement, the need to minimize 
risk to subjects was not. In creating and administering the AEC's radioisotope 
distribution program, physician investigators and other researchers placed a 
premium on controlling and minimizing risk in the "human use" of radioisotopes. 
This emphasis on the establishment of administrative and educational procedures 
to control risk, the details of which are discussed in chapter 6, embodied an 
essential principle of ethical research. 

The requirement for prior review included in the isotope distribution 
program was, as we have seen, also present elsewhere. Even before 1944, 
approval of the secretary of the Navy was required for research with human 
subjects. The secretary of the Army required prior approval of research related to 
atomic, biological, and chemical warfare in 1953. In the Air Force, secretarial 
approval of human experiments was codified in 1952. At NIH, prior group 
review was employed as a policy from 1953 on. The VA, whose program 
developed under the eye of AEC experts and advisers, relied on local isotope 
committees. 

The Nature of the Subjects 

While voluntary consent was acknowledged as a condition of human 
research by some government agencies well before 1944, it was not as broadly 
applied as it is today. Requirements of voluntary consent were asserted most 
clearly and consistently where the subjects were healthy. As a practical matter, 
healthy subjects are not likely to participate in experiments without specific 
request, and as a legal matter the invasion of a person's body in the absence of a 
prior relationship that might justify it has long been unacceptable. Still more 
important, the arbitrary use of people in experiments is incompatible with respect 
for human dignity. 



116 



Chapter 1 

The use of patients in medical research appeared in a different historical 
context from that of healthy subjects, and the agencies appear to have responded 
accordingly. From the perspective of the medical profession, the age-old tradition 
of the doctor-patient relationship, as we shall see in the next chapter, provided a 
justification for research with the potential to benefit patients, but not, of course, 
for healthy subjects who were not under medical care. There is little evidence 
that the agencies questioned whether research with patients that did not offer a 
prospect of benefit warranted a different response. An exception is the position 
articulated by the AEC's general manager in 1947, which made the possibility of 
benefit to the patient-subject a condition of permissible research, at least where 
the research involved "poisonous or harmful" substances. However, there is little 
indication that this provision was ever implemented. 

The period we reviewed in this chapter led to considerable public disquiet 
about the use of healthy subjects and about the use of ill and institutionalized 
people in research from which they could not possibly benefit. It was this 
disquiet, in the wake of several well-publicized incidents, that formed the basis of 
the mid-1960s reforms of federal policy governing research with human subjects 
(see chapter 3). The focus on the way that patient-subjects were used in clinical 
research that offered some prospect of benefit, and particularly on consent issues, 
came much later. The latter discussion is one that continues today, as is evident 
from the Advisory Committee's work on current research regulation that is 
described in part III. 

The Degree of Risk 

To the extent that there was discussion in the 1940s and the 1950s of 
consent for patient-subjects, it seemed to arise mainly in circumstances in which 
those who were ill would be put at unusual risk from the research. 

As we have seen, the AEC's radioisotope distribution division concluded 
that consent was required where patients were being subjected to "larger doses for 
investigative purposes" that apparently posed unusually hazardous or unknown 
risks. Similarly, from its establishment at midcentury, the AEC's hospital at Oak 
Ridge, which focused on new and potentially risky experimental cancer treatment, 
did have routine requirements for consent. Likewise, from its 1953 birth, the 
NIH's Clinical Center established a policy that recognized that patient choice was 
important for all kinds of research with patients, and written consent was required 
when an experiment involved' an unusual hazard. 

Formal Policies and Public Morality 

It is important not to get lost in the details of the various documents we 
have cited in this chapter. What is most significant about the discussions that 
took place in federal agencies from the mid- 1940s through the 1950s is the fact 

117 



Part I 

that so many of the ideas and values with which we are familiar were apparent 
then. That does not mean that the same words were used or that when they were 
used they had the same meaning as they do for us today. But it does mean that 
there were certainly more or less rough ideas about voluntary consent and 
minimization of risk. As we have seen in this chapter, these ideas were very 
much in play in the culture of the time. 



118 



ENDNOTES 



1. The "Common Rule" applies requirements for voluntary consent, prior 
review, and risk analysis to all federally sponsored research. This rule is discussed in 
chapter 14. 

2. David Rothman, Strangers at the Bedside: A History of How Law and 
Bioethics Transformed Medical Decision Making (New York: Basic Books, 1991), and 
Ruth Faden and Tom Beauchamp, A History and Theoiy of Informed Consent (New 
York: Oxford University Press, 1986). 

3. George J. Annas and Michael A. Grodin, eds.. The Nazi Doctors and the 
Nuremberg Code; Human Rights in Human Experimentation (New York: Oxford 
University Press, 1992). 343-345. 

4. See Faden and Beauchamp, A Histoiy and Theory of Informed Consent, and 
Mark S. Frankel, "Public Policymaking for Biomedical Research: The Case of Human 
Experimentation" (Ph.D. diss., George Washington University, 9 May 1976). 

5. Stafford L. Warren, Chairman, Interim Medical Advisory Board ("Report of 
the 23-24 January 1947 Meeting of the Interim Medical Committee of the United States 
Atomic Energy Commission") (ACHRE No. UCLA-1 1 1094-A-26). The report 
summarized "specific projects" at twelve institutions. The projects at the University of 
Rochester included "Study of the Metabolism of Plutonium, polonium, radium, etc. in 
human subjects" (p. 8). In the case of Berkeley, the projects identified to Dr. Stone were 

(1 ) Studies in whole-body radiation of human subjects by external and internal 
radiation. 

(2) Studies on the metabolism of radioactive iodine in animals and man. 

(3) Joint studies with Dr. Joseph G. Hamilton to evaluate the therapeutic 
applications ' 

of the fission products and the fissionable elements. 

(4) Exploration and therapeutic application of other radioactive elements and 
compounds (p. 1 1). 

A 14 March 1947 memorandum from Austin Brues, director of the Biology Division of 
the Argonne National Laboratory, records that "clinical testing programs" had only been 
authorized, at least for the time being, at Berkeley and Rochester. However, Brues urged 
that Argonne also be included. On behalf of this request he cited the University of 
Chicago's "work using human subjects" with specific reference to a report on plutonium 
injections. He further noted that human subject work also included the Argonne project 
list provided at the January meeting. A. M. Brues, Director, Biology Division, to N. 
Hilberry, Associate Laboratory Director, 14 March 1947 ("Clinical Testing") (ACHRE 
No. DOE-050195-B). 

6. Stafford Warren, Chairman, Interim Medical Advisory Committee, to Carroll 
Wilson, General Manager, AEC, 30 January 1947 ("The opinion on Clinical Testing . . .") 
(ACHRE No. DOE-051094-A-439), 1. 



19 



7. John L. Burling, Deputy General Counsel's Office, AEC, to Edwin 
Huddleson, Jr., Deputy General Counsel, AEC, 7 March 1947 ("Clinical Testing") 
(ACHRE No. DOE-051094-A-468), 2-3. 

8. Ibid., 3. 

9. Carroll L. Wilson, General Manager of the AEC, to Stafford Warren, the 
University of California at Los Angeles, 30 April 1947 ("This is to inform you that the 
Commission is going ahead with its plans . . .") (ACHRE No. DOE-051094-A-439), 2. 

10. Ibid. 

11. Ibid. 

12. Robert J. Buettner, Assistant to Chairman, Interim Medical Advisory 
Committee, AEC, to B. M. Brundage, Chief, Medical Division, AEC, 12 May 1947 
("Transmitted herewith for your information . . .") (ACHRE No. DOE-05 1 094-A-439), 
1. 

13. Note in medical chart of Cal-3, dated 18 July 1947 ("Elmer Allen chart") 
(ACHRE No. DOE-05 1 094- A-6 1 5). For more information on this case, see chapter 5. 

14. Wilson to Warren, 30 April 1947. 

15. University of California at San Francisco, February 1995 ("Report of the 
UCSF Ad Hoc Fact Finding Committee ") (ACHRE No. UCSF-022495-A-6), 27. 

16. J. C. Franklin, Manager, Oak Ridge Operations, to Carroll Wilson, General 
Manager, AEC, 26 September 1947 ("Medical Policy") (ACHRE No. DOE-1 13094-B- 
3), 2. Although the motivation for Oak Ridge's inquiry is not entirely clear, it seems to 
have come in part from concerns of Albert Holland, M.D., who became the acting 
medical adviser at Oak Ridge after Major Brundage retired. Holland served on the 
committee that oversaw the use of radioisotopes in human research, discussed in chapter 
6. In November 1947 Holland wrote, in regard to the isotopes distribution program: 
"How far does the AEC's moral responsibility extend in this program?" Albert Holland, 
Jr., Medical Adviser, Oak Ridge, to J. C. Franklin, Manager of Oak Ridge Operations, 7 
November 1947 ("Medical and Operational Decisions") (ACHRE No. DOE-1 13095-B- 
10), 2. 

1 7. Unknown author to the Advisory Committee for Biology and Medicine, 8 
October 1947 ("It is the desire of the Medical Advisor's Office . . .") (ACHRE No. DOE- 
05 1094-A-502). 

18. Atomic Energy Commission, Advisory Committee for Biology and 
Medicine, minutes of 1 1 October 1947 (ACHRE No. DOE-072694-A-1), 10. 

19. Ibid. 

20. Ibid. 

21 . Carroll Wilson, General Manager, AEC, to Robert Stone, University of 
California, 5 November 1947 ("Your letter of September 18 regarding the 
declassification of biological and medical papers was read at the October 1 1 meeting of 
the Advisory Committee for Biology and Medicine.") (ACHRE No. DOE-052295-A-1). 

22. Carroll Wilson, General Manager, AEC, to Alan Gregg, Chairman of the 
AEC Advisory Committee for Biology and Medicine, 5 November 1947 ("I want to 
thank you for your letter of October 14 concerning the questions raised by Dr. Stone in 
his letter to me of September 18 regarding declassification of biological and medical 
papers containing information on the experimental use of radioisotopes in human beings 
conducted under AEC sponsorship.") (ACHRE No. DOE-052295-A-I). 

23. Salgo v. Leland Stanford Jr. University Board of Trustees, 317 P. 2d 170 
(1957). 



120 



24. Joseph Volpe, interview by Gregg Herken, Dan Guttman, and Debra Holland 
(ACHRE), transcript of audio recording, 6 October 1994 (ACHRE Research Project 
Series, Interview Program Files, Targeted Interview Project), 24-42. 

In a May 1995 interview, Volpe agreed that a letter written by the general 
manager constituted a "policy." The transcript of the interview records: 

Interviewer: . . . today there are regular procedures for getting 

something recognized as a policy, including publication 
and so forth. In 1947, when the general manager writes 
a letter, is that a policy? 

Mr. Volpe: Yes, Yes. 

Mr. Volpe noted that while the question of the precise authority of the general manager 
was not without controversy. Chairman Lilienthal "believed in delegation of authority 
and so always took measures to strengthen the general manager's hand on these things." 
Joseph Volpe, interview by Barbara Berney, Steve Klaidman, Dan Guttman, Lanny 
Keller, Jonathan Moreno, Patrick Fitzgerald, and Gilbert Whittemore (ACHRE), 
transcript of audio recording, 18 May 1995 (ACHRE Research Project Series, Interview 
Program Files, Targeted Interview Project), 37-38. 

25. Leslie M. Redman, Los Alamos Laboratory, to Dr. Alberto F. Thompson, 
Chief, Technical Information Service, DBM, 22 January 1951 ("I find myself concerned 
in the course of duty with the review of papers relating to human experimentation.") 
(ACHRE No. DOE-051094-A-609). 

26. Warren did not cite the context for Wilson's discussion of these conditions, 
that is, the need for criteria for declassification. 

27. Shields Warren, Director, DBM, to Leslie Redman, "D" Division, Los 
Alamos National Laboratory, 5 March 1951 (". . . to reply to your letter of January 22, 
1951, concerning policies on human experimentation.") (ACHRE No. DOE-051094-A- 
603). 

28. Everett Idris Evans, M.D., Medical College of Virginia, to John Z. Bowers, 
M.D., Assistant to the Director, DBM, AEC, 8 April 1948 ("We have recently obtained 
approval from the Isotopes Division for human use of P 32 . . .") (ACHRE No. DOE- 
051094-A-64). 

29. John Z. Bowers, Assistant to Director, DBM, AEC, to Everett Idris Evans, 
M.D., Medical College of Virginia, 27 April 1948 ("Thank you for recent letter 
requesting information regarding isotopes.") (ACHRE No. DOE-050194-A-480). 

30. Nathan H. Woodruff, Chief Technical Division, Isotopes Division, to Everett 
I. Evans, M.D., Medical College of Virginia, 14 May 1948 ("Your letter of April 8 to Dr. 
Bowers has been referred to me for answer.") (ACHRE No. NARA-082294-A-10). 

3 1 . U.S. Atomic Energy Commission, Advisory Committee for Biology and 
Medicine, agenda of 14 February 1948 (ACHRE No. DOE-072694-A), 2. 

32. In addition to the document discussed above, there is some indication that 
the AEC Isotopes Division was charged with ensuring that consent was obtained. In the 
early 1970s, when the AEC conducted an investigation into the plutonium experiments. 
Shields Warren told the investigators that his recollection was that ethical issues were 
addressed at the time by the issuance of prospective policies. Warren stated: 

I think the way it [concern about the plutonium 

121 



injections] was handled was that Alan Gregg and 1 
agreed the best way to do [it] was to see that the rules 
were properly drawn up by the . . . Human Applications 
Isotope Committee, which had then come into being, so 
that use without full safeguards could not occur, and that 
we saw no point in bringing this up after the fact as long 
as we were sure that nothing of this sort could happen in 
the future. 

Shields Warren, interview by L. A. Miazga, Sidney Marks, Walter Weyzen (AEC), 
transcript of audio recording, 9 April 1974, 10-11 (ACHRE No. DOE-121294-D-14). 

33. Unknown author, unpublished draft, 29 March 1948 ("The Experimental 
Use of Radioactive Materials in Human Subjects at AEC Establishments") (ACHRE No. 
DOE-050194-A-267). 

34. Subcommittee on Human Applications, minutes of 22-23 March 1948, as 
discussed in the minutes of the 13 March 1949 meeting. S. Allan Lough, Chief, 
Radioisotopes Branch, to H. L. Friedell, G. Failla, J. G. Hamilton, and A. H. Holland, 19 
July 1949 ("Revised Tentative Minutes of March 13, 1949 Meeting of the Subcommittee 
on Human Applications of Committee of U.S. Atomic Energy Commission, AEC 
Building, Washington, DC") (ACHRE No. DOE-101 194-A-13), 5. 

35. The subcommittee was not definitive about when larger doses were 
permitted, however. The policy was to apply in "instances in which the disease from 
which a patient is suffering permits the administration of larger doses for investigative 
purposes." U.S. Atomic Energy Commission, Isotopes Division, September 1949 
("Supplement No. 1 to Catalogue and Price List No. 3, July 1949") (ACHRE No. DOD- 
122794-A-l), 3-4. 

36. While these statements were perhaps more than was told to patient-subjects 
in other institutions, they did not necessarily provide details about the research. In the 
application for admission, the applicant agreed to "such operations and biopsies as are 
deemed necessary and advisable by the hospital." Oak Ridge Institute of Nuclear 
Studies, 1950 ("Application for Admission to the Medical Division Hospital") (ACHRE 
No. DOE-121494-C-1), 1. 

Upon admission, the applicant was required to sign a "Waiver and Release" that 
did not describe the treatment, but included a lengthy release from the patient, the 
patient's "heirs, executors, administrators, and assigns," for any "causes of action, claims, 
demands, damages, loss, costs, and expenses, whether direct or consequential," associated 
with or resulting from the care of the hospital. This form notes that the hospital has 
described the "character and kind of treatment." Oak Ridge Institute of Nuclear Studies, 
1950 ("Waiver and Release") (ACHRE No. DOE-121494-C-3), 1. 

37. Oak Ridge Institute for Nuclear Studies, 1950 ("Waiver and Release") 
(ACHRE No. DOE-121494-C-3). 

38. Program Committee of the Division of Biological and Medical Research of 
the Argonne National Laboratory, minutes of 22 January 1951 (ACHRE No. DOE- 
051095-B), 3. 

39. Thomas Shipman, M.D., Health Division Leader, Los Alamos Laboratory, 
AEC, to Dr. Charles Dunham, Director, DBM, AEC, 18 June 1956 ("Two questions have 
recently arisen— one of them specific, the other general— wherein we need an opinion 
from you.") (ACHRE No. DOE-091994-B-1). 



122 



40. Charles Dunham, Director, DBM, AEC, to Thomas Shipman, Health 
Division Leader, Los Alamos Laboratory, 5 July 1956 ("This is in response to your letter 
of June 18.") (ACHRE No. DOE-091994-B-2). In addition to consent, Dunham indicated 
that the research should proceed so long as (a) the doses were small, "true tracer doses"; 
(b) the proposal was approved by a senior medical officer; and (c) the work was 
supervised by a licensed physician. 

41. T. L. Shipman, Health Division Leader, Los Alamos Laboratory, to Staff 
Distribution, 12 July 1956 ("Administration of Tracer Doses to Humans") (ACHRE No. 
DOE-091994-B-3), 1. Also, T. L. Shipman, Health Division Leader, Los Alamos 
Laboratory, to "Distribution," 3 September 1963 ("Administration of Tracer Doses to 
Humans For Experimental Purposes") (ACHRE No. DOE-091994-B-4), 1. 

42. Isotopes Extension, Division of Civilian Application, U.S. AEC, "The 
Medical Uses of Radioisotopes, Recommendations and Requirements of the Atomic 
Energy Commission" (Oak Ridge, Tenn.: AEC, Februaiy 1956), 15. 

43. U.S. Department of the Army, AR 40-210, The Prevention of Communicable 
Diseases of Man— General (21 April 1925). 

44. Charles W. Shilling, Medical Corps, USN. Retired, undated paper ("History 
of the Research Division, Bureau of Medicine and Surgery, USN") (ACHRE No. DOD- 
080295-A), 74. 

45. The Secretary of the Navy to All Ships and Stations, 7 April 1943 
("Unauthorized Medical Experimentation on Service Personnel") (ACHRE No. DOD- 
091494-A-2). 

46. J. E. Moore, M.D., to Dr. A. N. Richards, excerpt of letter dated 6 October 
1942 ("I have recently received an inquiry from Dr. Charles M. Carpenter of the 
University of Rochester School of Medicine who believes that he may be able to work 
out a human experiment on the chemical prophylaxis of gonorrhea.") (ACHRE No. 
NARA-060794-A-1). 

47. A. N. Richards to J. E. Moore, 31 October 1942 (" Revision of Dr. Richards' 
letter of October 9, 1942") (ACHRE No. NARA-060794-A-1 ). Stafford Warren, the 
Manhattan Project medical director, also came from the University of Rochester. It is not 
clear how, if at all, the CMR's views on human experiments were accounted for in 
Manhattan Project research. 

48. Rothman, Strangers at the Bedside, 30-50. 

49. The Chief of the Bureau of Medicine and Surgery to the Officer-in-Charge, 
Naval Laboratory Research Unit No. 1, University of California, Berkeley, California, 6 
March 1943 ("Proposed Clinical Evaluation of Influenza Antiserum, and Messages 
concerning Influenza Virus Specimens") (ACHRE No. DOD-062194-C-1). 

50. Ibid., 2. 

51. Institute of Medicine, National Academy of Sciences, Veterans at Risk: The 
Health Effects of Mustard Gas and Lewisite (Washington, D.C.: National Academy 
Press, 1993), 66-69. 

52. Ibid., 214. 

53. Robert S. Stone, unpublished paper, "Irradiation of Human Subjects as a 
Medical Experiment," 31 January 1950 (ACHRE No. NARA-070794-A). 

54. American Medical Association, Judicial Council, "Supplementary Report of 
the Judicial Council," Journal of the American Medical Association 132 (1946): 1090. 

55. The Under Secretary of the Navy to the Secretary of Defense, 24 April 1950 
("Recommendation that the Armed Service conduct experiments on human subjects to 



123 



determine effects of radiation exposure") (ACHRE No. NARA-070794-A). 

56. Atomic Energy Commission, Advisory Committee for Biology and 
Medicine, transcript (partial) of meeting, 10 November 1950 (ACHRE No. DOE-0 12795- 
C-l), 28. 

57. Ibid., 28-29. 

58. J. G. Hamilton, University of California, to Shields Warren, DBM, AEC, 28 
November 1950 ("Unfortunately, it will not be possible for me to be at the meeting on 
December 8 . . .") (ACHRE No. DOE-072694-B-45), 1. 

59. Ibid. 

60. Adam J. Rapalski, Administrator, the Armed Forces Epidemiological Board, 
DOD, to Chief, Legal Office, 5 January 1952 ("Draft of 'Agreement with Volunteer'") 
(ACHRE No. DOD-040895-A). 

61. Lieutenant Colonel Robert J. O'Connor, Chief, Legal Officer, JAGD, to 
Colonel Frank L. Baier, Army Medical Research and Development, 23 October 1947 
("Protection of Research Project Volunteers") (ACHRE No. NARA-012395-A-4). 

62. John R. Paul, Director, AEB, DOD, to Dr. Joseph Stokes, Jr., Children's 
Hospital, Philadelphia, Pennsylvania, 18 February 1948 ("This is in reply to your hand 
written request for a comment [from] me re your letter to Dr. Macleod dated 1 1 February 
on the subject of funds for the reimbursement of volunteer prisoners . . .") (ACHRE No. 
NARA-012395-A-1). 

63. Ibid. 

64. Committee Appointed by Governor Dwight H. Green of Illinois, "Ethics 
Governing the Service of Prisoners As Subjects In Medical Experiments," Journal of the 
American Medical Association 136, no. 7 (1948): 457-458. 

65. C. J. Watson, M.D., Commission on Liver Disease, Army Epidemiological 
Board, to Colin MacLeod, President of the Board, AEB, 5 April 1948 ("I have given 
considerations in the past few weeks to the matter of using volunteers in penal 
institutions for experimentation . . .") (ACHRE No. NARA-012395-A-2). 

66. Ibid. 

67. "Prisoner Dies After Injection in Disease Study," Washington Post, 6 May 
1952,3. 

68. L. M. Harff, Contract Insurance Branch, to File, 25 April 1952 ("Research 
and Development Contracts-Medical Investigations) (ACHRE No. DOD-012295-A). 

69. Adam J. Rapalski, Administrator, AEB, to Chief Legal Office, 14 October 
1952 ("Applicability of Section 5, Public Law 557-82d Congress") (ACHRE No. NARA- 
012395-A). 

70. Adam J. Rapalski, Administrator, AEB, to Members of the AEB, undated 
memorandum ("Applicability of Section 5, Public Law 557-82nd Congress") (ACHRE 
No. NARA-012395-A). In congressional hearings, the activities used to illustrate the 
purpose of the indemnification provision included test piloting, damage that might be 
caused by cloud modification research, and cataracts caused by the operation of a 
cyclotron. In addition, however, biomedical human experimentation was specifically 
addressed in the following exchange between Representative Edward Hebert and Colonel 
W. S. Triplet, from the Army Research and Development Division: 

Mr. Hebert. Colonel, would you expand on the proposal to make 
the Government liable for losses and damages? . . . 



124 



Colonel Triplet. There have been some experiments or types of 
research in the past which would have come under section 5 [the 
indemnification provision]. There are more coming up in the 
future. One of the early cases, long before the time of the bill, I 
would cite as an example is Dr. Reed in Cuba in 1900 utilized 
the services of 21 volunteers to study yellow fever, an extremely 
dangerous experiment. Two of these volunteers died. Eighteen 
of the others became seriously ill. As a result a special medal 
was awarded these people by Congress. That is an example of 
the type of experiment that at the present time is going on in the 
medical service. 
Subcommittee Hearings on H. R. 1 1 80 to Facilitate the Performance of Research and 
Development Work by and on Behalf of the Departments of the Army, the Navy, and the 
Air Force, and for Other Purposes; House of Representatives, Committee on Armed 
Services, Subcommittee no. 3, 6 June 1952, 621 (ACHRE No. NARA-10495-D). 

71. Colonel George V. Underwood, Director, Executive Office, Office of the 
Secretary of Defense, to Mr. Kyes, Deputy Secretary of Defense, 5 February 1953 ("Use 
of Human Volunteers in Experimental Research") (ACHRE No. DOD-062194-A). 

72. Melvin Casberg, Chairman, AFMPC, to the Secretary of Defense, 24 
December 1952 ("Human Volunteers in Experimental Research") (ACHRE No. NARA- 
101294-A-3). 

73. Ibid. 

74. Jackson recommended changes to the Nuremberg Code: the elimination of 
the Nuremberg Code exception for self-experimentation by physicians and the express 
provision that prisoners, but not prisoners of war, could be used. We do not know what 
Jackson had "previously submitted." See Stephen Jackson, Assistant General Counsel in 
the Office of the Secretary of Defense and Counsel for the AFMPC, to Melvin Casberg, 
undated memorandum ("The standards and requirements to be followed in human 
experimentation") (ACHRE No. NARA-101294-A-3). 

75. Ms. Rosenberg, a high-ranking official in the DOD, was an expert in labor 
relations and a New Dealer. Her role was recorded in Stephen Jackson to Melvin 
Casberg, Chairman, AFMPC, 22 October 1952 ("I discussed the attached with Mrs. 
Rosenberg . . .") (ACHRE No. NARA-101294-A-3). 

76. Colonel Adam J. Rapalski, Administrator, Armed Forces Epidemiological 
Board, DOD, to Colin MacCleod, President, Armed Forces Epidemiological Board, 
DOD, 2 March 1953 ("The attached copy of letter I believe is self-explanatory.") 
(ACHRE No. NARA-012395-A-5). 

77. F. Lloyd Mussells, Executive Director, Committee on Medical Sciences, 
RDB, DOD, to Floyd L. Miller, Vice Chairman, Research and Development Board, 
DOD, 12 November 1952 ("Human Experimentation") (ACHRE No. NARA-071 194-A- 
2). 

78. Ibid. 

79. In a 10 November 1952 meeting the Committee on Chemical Warfare was 
read a draft of the AFMPC policy. One member remarked to general laughter: "If they 
can get any volunteers after that I'm all in favor of it." Committee on Chemical Warfare, 
RDB, DOD, transcript of the meeting of 10 November 1952 (ACHRE No. NARA- 
102594-A), 128. H. N. Worthley, Executive Director, Committee on Chemical Warfare, 
RDB, DOD, to the Director of Administration, Office of the Secretary of Defense, 9 



125 



December 1952 ("Use of Volunteers in Experimental Research") (ACHRE No. NARA- 
101 294- A), 1. 

80. This, at least, was the 1994 recollection of Lovett's military assistant. 
General Carey Randall, who served in the same role for Lovett's predecessor and 
successor. General Carey Randall, interview by Lanny Keller (ACHRE), transcript of 
audio recording, 20 September 1994 (ACHRE Research Project Series, Interview 
Program File, Targeted Interview Project), 17. 

81 . George V. Underwood, Director of the Executive Office of the Secretary of 
Defense, to Deputy Secretary of Defense Foster, 4 January 1953 ("I believe that Mr. 
Lovett has a considerable awareness of this proposed policy.") (ACHRE No. NARA- 
101294-A-l), 1. 

82. Melvin A. Casberg, Chairman, Armed Forces Medical Policy Council, DOD, 
to the Secretary of Defense, 13 January 1953 ("Digest 'Use of Human Volunteers in 
Experimental Research"') (ACHRE No. DOD-042595-A), 1. 

83. Secretary of Defense to the Secretary of the Army, Secretary of the Navy, 
Secretary of the Air Force, 26 February 1953 ("Use of Human Volunteers in 
Experimental Research") (ACHRE No. DOD-082394-A). The second paragraph of the 
memorandum stipulates its application to "Armed Services personnel and/or civilians on 
duty at installations engaged in such research. . . ." The Advisory Committee takes this 
stipulation to be in recognition of the separate authority of the medical services, as 
distinct from research and development commands. 

84. W. G. Lalor. Secretary, Joint Chiefs of Staff, to Chief of Staff, U.S. Army, 
Chief of Naval Operations, Chief of Staff, U.S. Air Force, 3 September 1952 ("Security 
Measures on Chemical Warfare and Biological Warfare") (ACHRE No. NARA-0 12495- 
A-l). 

85. Irving L. Branch, Colonel, USAF, Acting Chief of Staff, to the Assistant 
Secretary of Defense (Health and Medicine), 3 March 1954 ("Status of Human 
Volunteers in Bio-medical Experimentation") (ACHRE No. DOD-090994-C), 2. 

86. Ibid.. 3. 

87. Ibid. 

88. Brigadier General John C. Oakes, GS, Secretary of the General Staff, 
Department of the Army, to the Chief Chemical Officer and the Surgeon General, 30 
June 1953 ("CS:385-Use of Volunteers in Research") (ACHRE No. DOD-022295-B-1) 
(CS385). This document was originally classified as Top Secret then downgraded to 
Confidential and declassified in June 1954. "Research Report Concerning the Use of 
Volunteers in Chemical Agent Research." Inspector General and Auditor General, 1975 
(Army IG report), 77. 

89. Oakes, sec. 3(a). 

90. A series of memorandums from the Office of the Judge Advocate General 
preceded and shed light on the 30 June 1953 memorandum: 

Colonel Robert H. McCaw, JAGC, Chief, Military Affairs Division, to the Chief, 
Research and Development, Office of the Chief of Staff, 6 April 1953 ("Volunteers for 
Biological Warfare Research") (ACHRE No. DOD-082294-B). 

Colonel Robert H. McCaw, JAGC, Chief, Military Affairs Division, to the Chief, 
Research and Development, Office of the Chief of Staff, 10 April 1953 ("Volunteers for 
Biological Warfare Research") (ACHRE No. DOD-082294-B). 



126 



Colonel A. W. Betts, GS, Executive for the Chief of Research and Development, to 
Mr. J. N. Davis, Office of the Under Secretary of the Army, 15 April 1953 ("Use of 
Volunteers in Experimental Research") (ACHRE No. DOD-082294-B). 

91. CS:385, sec. 3(d). 

92. Army Office of the Surgeon General, 12 March 1954 ("Use of Volunteers in 
Medical Research, Principles, Policies, and Rules of the Office of the Surgeon General") 
(ACHRE No. DOD-1 20694- A-4). 

93. Ibid., 1 . A copy of this document was found in the files of John Enders, 
Ph.D., Nobel Laureate in Medicine and Physiology, 1954, Yale University. 

94. Ibid. 

95. John Fox, M.D., Professor of Epidemiology, Tulane University School of 
Medicine, to Captain R. W. Babione, Executive Secretary, AFEB, 27 June 1956 ("Finally 
I am able to complete and send to you the application for a research contract to study . . . 
") (ACHRE No. NARA-012395-A). 

96. Ibid. 

97. W. McD. Hammon, M.D., Director, Commission on Viral Infections, AFEB, 
to John Enders, Children's Medical Center, 20 November 1958 ("This is to confirm our 
telephone call this morning, November 20th, regarding approval of the AFEB for the 
protocol of the experiment which you propose to carry out . . .") (ACHRE No. NARA- 
032495-B), 1. 

98. Max H. Brown, Contracting Officer, to Vice Chancellor, Schools of the 
Health Professions, University of Pittsburgh, 12 March 1957 ("This is in reply to letter . . 
.") (ACHRE No. DOD NARA-012395-A-6) The DOD has not located the Pittsburgh 
contract itself, which may have been long since routinely destroyed; therefore, it cannot 
be said for certain that the 1 954 surgeon general provisions were made a contract 
requirement. 

99. Herbert L. Ley to Colonel Howie, 8 January 1969 ("Review of Department 
of the Army Policy on Use of Human Subjects in Research") (ACHRE No. DOD- 
063094-A). 

100. Max H. Brown to Contracting Officer, OTSG, 5 August 1957 ("The Use of 
Human Test Subjects in Medical Research Supported by the Office of the Surgeon 
General") (ACHRE No. NARA-012395-A). 

101. Donald L. Howie, Assistant Chief, Medical Research, 10 July 1962 
("Memorandum for the Record, Use of Volunteers for Army Medical Research") 
(ACHRE No. DOD-1 20694- A-3). It is worth noting that prior to this memorandum, in 
March 1 962, the Army promulgated its first regulation specifically directed to the 
conduct of clinical research. This regulation (AR 70-25, 26 March 1962) specifically 
exempted "clinical research," which apparently included research conducted on patients. 
See chapter 3. 

102. Army IG report, 1975. 

103. Department of the Navy, Bureau of Medicine and Surgery, "Manual of the 
Medical Department," sec. IV, research article 1-17 (26 September 1951). 

104. On the question of written documentation, interestingly, the manual 
stipulated: "[Vjolunteers" should not "execute a release for future liability for negligence 
attributable to the Navy," but the manual required that a statement be "entered into the 
Individual's Health Record" indicating the project number and the physical and 
psychological effects, or lack of same, resulting from the investigation. "Manual of the 
Medical Department," sec. IV, art. 1-17. 



127 



105. Ibid. 

106. Loren B. Poush, Code 1 1, USN, to Code 74, USN (Bureau of Medicine and 
Surgery), 18 October 1951 ("Legal comments relative to proposed means of proper 
authorization and safeguard in use of radioisotopes") (ACHRE No. NARA-070794-A-4). 

107. Code 74, USN, to Code 1 1, USN, 18 September 1951 ("Proposed Means 
of Proper Authorization and Use of Radioisotopes") (ACHRE No. NARA-070794-A-4) 
2. 

108. Paul O. Wells, Chief, Radiological Service, Letterman Army Hospital, to 
Elmer A. Lodmell, Chief, Radiological Service, Walter Reed Army Hospital, 14 January 
1955 ("I am writing this letter at the suggestion of General Gillespie after having 
discussed with him the matter of requiring patients to sign a permit for radioisotope 
therapy.") (ACHRE No. DOD-012295-A). 

109. Standard Form 522 (SF-522), "Clinical Record-Authorization for 
Administration of Anesthesia and Performance of Operations and Other Procedures," was 
proposed for use "in those instances when authorization for administration of 
radioisotope therapy is desired." Eugene L. Hamilton, Chief, Medical Statistics Division, 
to the Chiefs of the Medical Plans and Operations Division and the Legal Office, 3 
August 1955 ("Permit for Radioisotope Therapy") (ACHRE No. DOD-012295-A). 

In response to an inquiry from Walter Reed Army Hospital concerning the use of 
consent forms for patients, the Medical Statistics Division, recommending the use of SF- 
522, indicated that consent should be obtained when a procedure "carries an unusual 
risk." Additionally, the Medical Statistics Division recommended that patients should be 
"counselled as to the nature, expected results of, and risks involved in procedures." 
Eugene L. Hamilton, Chief, Medical Statistics Division, to the Chiefs of the Professional 
Division, Medical Plans and Operations Division, and the Legal Office, undated 
memorandum (probably November 1956) ("Forms for Authorization of Radiation 
Therapy") (ACHRE No. DOD-012295-A). 

110. U.S. Air Force, Research and Development, "Clinical Research," AFR 80- 
22(11 July 1952). 

111. The Deputy Commander for Research and Development of the Air Force 
R&D Command to RADC, WADC, APGC, AFCRC, AFSWC, AFMTC, AFMDC, 
AFFTC, AFBMD (ARDC), AFOSR, 12 September 1958 ("Conduct of Hazardous 
Human Experiments") (ACHRE No. HHS-090794-A). 

112. Richard R. Taylor, Surgeon General of the Department of the Army, 
testimony before the Subcommittee on Administrative Practice and Procedure of the 
Judiciary Committee and the Subcommittee on Health of the Labor and Public Welfare 
Committee, U.S. Senate, 94th Cong., 1st Sess., 10 September 1975 (ACHRE No. DOD- 
063094-A), 1. 

See also, U.S. Army Inspector General, Use of Volunteers in Chemical Agent 
Research (Washington D.C.: GPO, 1975), 77. 

1 13. Charles V. Kidd, Director, Research and Planning Division, NIH, to Rear 
Admiral Winfred Dana, Medical Corps, USN, 30 April 1952 ("In accordance with our 
telephone conversation of this afternoon I am enclosing a copy of draft statement which 
we have developed.") (ACHRE No. DOD-1 1 1594-A), 2-3. The context of this statement 
is not known. Perhaps it was formulated in response to an inquiry from the DOD about 
the NIH's research requirements during the discussions that led to the drafting of the 
Wilson memorandum. 



128 



1 14. National Institutes of Health, 17 November 1953 ("Group Consideration of 
Clinical Research Procedures Deviating from Accepted Medical Practice or Involving 
Unusual Hazard") (ACHRE No. HHS-090794-A), 4. 

115. Director, N1H, to Institute Directors, 15 November 1954 ("Participation by 
NIH Employees as Normal Controls in Clinical Research Projects") (ACHRE No. HHS- 
090794-A), 1. Although this memorandum referred only to NIH employees, Advisory 
Committee' staff and NIH staff have concluded it applied to all healthy volunteer subjects. 

116. National Institutes of Health, policy statement of 17 November 1953 
("Group Consideration of Clinical Research Procedures Deviating From Accepted 
Medical Practice Or Involving Unusual Hazard") (ACHRE No. HHS-090794-A). 

117. Edward J. Rourke, Legal Adviser, NIH, to Mr. John A. Trautman, Director, 
Clinical Center, 5 December 1952 ("At your invitation, I presented to the Medical Board 
of the Clinical Center on December 2 a proposal that, in view of several factors in some 
degree peculiar to the Clinical Center, it would be advisable from the legal point of view 
among others to accept certain procedures relating to patient admission that are more 
formal than might otherwise be considered necessary") (ACHRE No. DOD-1 1 1 594- A), 
1. 

118. Ibid. 

119. For a more detailed review of this history see Faden and Beauchamp, A 
Histoiy and Theoiy of Informed Consent, and Frankel, "Public Policymaking for 
Biomedical Research: The Case of Human Experimentation." 

120. George M. Lyon, M.D., Assistant Chief Medical Director for Research and 
Education, presentation to the Committee on Veterans Medical Problems, National 
Research Council, 8 December 1952 ("Appendix II, Medical Research Programs of the 
Veterans Administration") (ACHRE No. VA-052595-A). 

121. Ibid., 558. 

122. Guy H. Birdsall, General Counsel, Veterans Administration, to Chief 
Medical Director, 25 June 1958, ("Op. G.C. 28-58, Legal Aspects of Medical Research") 
(ACHRE No. VA-052595-A). 



129 



Postwar Professional 

Standards and Practices for 

Human Experiments 



In chapter 1, we explored government discussions of research involving 
human subjects in the 1940s and 1950s. We found that, at several junctures, 
government officials exhibited an awareness of the Nuremberg Code, the product 
of an international war crimes tribunal in 1947. If a requirement of voluntary 
consent of the subject was endorsed by the Nuremberg judges and was recognized 
at the highest reaches of the new Cold War bureaucracy, then how, a citizen 
might now ask, could there be any question about the use of this standard to judge 
experiments conducted during this time in the United States? And yet precisely 
this question has been raised in connection with human radiation experiments. 
Did American medical scientists routinely obtain consent from their subjects in 
the 1940s and 1950s, including those who were patients, and if not, how did these 
scientists square their conduct with the demands of the Nuremberg Code? 

This chapter describes the Advisory Committee's efforts to answer these 
questions and what we learned. We begin with an examination of what, in fact, 
was argued at Nuremberg. We focus particularly on the testimony of Andrew 
Ivy, the American Medical Association's (AMA) official consultant to the 
Nuremberg prosecutors, and on the AMA's response to the report Dr. Ivy 
prepared about the trial for the organization. 

We turn next to an analysis of the actual practices of American medical 
scientists during this period. In addition to reviewing contemporary 
documentation and present-day scholarship, the Advisory Committee conducted 



130 



Chapter 2 

interviews with leading medical scientists and physicians who were engaged in 
research with human subjects in the 1940s and 1950s. These sources suggest a 
different, more nuanced picture of the principles and practices of human research 
than that presented at Nuremberg. 

Of particular importance in this picture are the practical and moral 
distinctions that many researchers made between investigations with healthy 
subjects and those with sick patients. Those working with healthy subjects could 
cite a tradition of consent that dated, at least, to Walter Reed's turn-of-the-century 
experiments; those working with sick patients were in a clinical context that was 
conditioned by a tradition of faith in the wisdom and beneficence of physicians, a 
tradition that was dominant until at least the 1 970s. Closely related to these 
distinctions was the tension between being a scientist and being a physician. This 
tension confronted members of a new, and rapidly growing, breed of medical 
professionals in the United States working to make careers in clinical research. 
The chapter goes on to explore whether these distinctions and tensions were 
reflected in the Nuremberg Code and why the trial may not have had much impact 
on the treatment of patient-subjects. 

The rest of the chapter explores the emerging awareness of the moral 
complexities of research at the bedside and the limitations of the Nuremberg Code 
to address them. We close with a brief discussion of the Declaration of Helsinki, 
the international medical community's attempt to produce a code of conduct 
compatible with the realities of medical research. 

THE AMERICAN EXPERT, THE AMERICAN MEDICAL 
ASSOCIATION, AND THE NUREMBERG MEDICAL TRIAL 

In the fall of 1943, the United States, Great Britain, and the Soviet Union 
agreed that, once victorious, they would prosecute individuals among the enemy 
who might have violated international law during the war. On August 8, 1945-- 
exactly three months after V.E. Day and two days after the bombing of 
Hiroshima-representatives of the American, British, French, and Soviet 
governments officially established the International Military Tribunal in 
Nuremberg, Germany. An assemblage of Allied prosecutors presented cases 
against twenty-four high-ranking German government and military officials, 
including Hermann Goering and Rudolph Hess, before this international panel of 
judges. Quite early in the course of these initial Nuremberg trials, which ran from 
October 1945 to October 1946, "it became apparent," according to the recent 
recollections of American prosecutor Telford Taylor, "that the evidence had 
disclosed numerous important Nazis, military leaders, and others" who should 
also be tried.' In January 1946, President Harry Truman approved a 
supplementary series of war crimes trials. These trials were to take place in the 
same Nuremberg courtroom, and international law would continue to be the 



131 



Parti 

standard by which guilt or innocence would be determined. America's wartime 
allies would not, however, participate; responsibility for prosecuting and judging 
defendants in the second set of Nuremberg trials was left exclusively to the 
United States. 

The first of twelve cases that would eventually make up this second series 
of trials in Nuremberg is technically called United States v. Karl Brandt et al. 
More popularly, this trial is known by a variety of other names such as "The 
Doctors' Trial" and "The Medical Case." For the sake of convenience and 
consistency we will refer to the trial by another common name: the Nuremberg 
Medical Trial. This case began on December 9, 1946, when U.S. Chief of 
Counsel for War Crimes Telford Taylor delivered the prosecution's opening 
statement against the twenty-three defendants (twenty of whom were physicians). 
To one degree or another, Taylor charged the defendants with "murders, tortures, 
and other atrocities committed in the name of medical science." The trial ended in 
late August 1947 when the judges handed down a ruling that included the so- 
called Nuremberg Code and seven death sentences. 2 

In the spring of 1946, the American prosecution team preparing for the 
Medical Trial, which was made up of lawyers commissioned in the Army, cabled 
Secretary of War Robert P. Patterson with a request for a medical expert. 
Patterson consulted with Army Surgeon General Norman T. Kirk, who suggested 
turning to the American Medical Association. Kirk contacted the AMA, and, 
after some internal consultation, the association's Board of Trustees voted in May 
1946 to appoint Dr. Andrew C. Ivy as the AMA's official consultant to the 
Nuremberg prosecutors. 3 Dr. Ivy was one of America's leading medical 
researchers at the time. Early in the war, Ivy was the civilian scientific director of 
the Naval Medical Research Institute in Bethesda, Maryland. 4 During the 
summer of 1946, he was in the process of moving from a position as head of the 
Division of Physiology and Pharmacology at Northwestern University Medical 
School to the University of Illinois, where he would serve as a vice president with 
responsibility for the university's professional schools in Chicago. 

The precise rationale behind Ivy's selection as the AMA's adviser to the 
Nuremberg prosecutors remains unclear, but it is likely that the AMA turned to 
Ivy for at least two reasons. First, his wartime research interests corresponded in 
topic, though not in style, to some of the most shocking experiments that had 
taken place in the Nazi concentration camps. Ivy supervised and carried out 
experiments in seawater desalination, sometimes using human subjects, with the 
intent of developing techniques to aid Allied pilots and sailors lost at sea. He also 
conducted some pioneering human experiments in aviation medicine dealing with 
the physiological challenges posed by high altitudes. These are two of the areas 
in which Nazi researchers had conducted especially gruesome human 
experiments. Second, Ivy was well known for his energetic defense of animal 
experimentation against American antivivisectionists. For example, he served for 



132 



Chapter 2 

eight years as the founding secretary-treasurer of the National Society for Medical 
Research, an organization formed by scientists in 1946 to ward off challenges to 
medical research posed by antivivisectionists. It seems likely that the AMA 
Board of Trustees would have recognized Ivy as someone who possessed an 
unusual combination of familiarity with the scientific aspects of experiments 
carried out in the concentration camps and broad understanding of the moral 
issues at stake in medical research, whether the experimental subjects were 
animals or humans. Also, Ivy was almost certainly perceived as someone who 
could be trusted to look out for the interests of the American medical research 
community during the Nuremberg Medical Trial. The AMA Board of Trustees 
probably realized that the entire enterprise of medical research would, to some 
degree, be on trial in Germany. 

In July or early August of 1946, Ivy went to Germany to meet with the 
Nuremberg prosecution team. Ivy offered technical assistance to the lawyers 
struggling with the scientific details of the experiments, but he also recognized, as 
he put it, that the prosecutors "appeared somewhat confused regarding the ethical 
and legal aspects" of human experimentation. 5 

After returning from his initial trip to Europe in aid of the Nuremberg 
prosecutors, Ivy offered a preliminary oral report to the Board of Trustees of the 
American Medical Association at the board's August 1946 meeting. After his 
presentation, the trustees asked Ivy to provide a written summary of his findings, 
so that the AMA's Judicial Council (a committee of five whose duties included 
deliberating on matters of medical ethics) could "make a report as to the manner 
in which these [Nazi] experiments [were] infringements of medical ethics." 6 

In mid-September, Ivy submitted a written report to the AMA as he had 
been directed. 7 At roughly the same time, he also turned over a copy of the 
twenty-two-page typescript to the Nuremberg prosecution team. In this piece, Ivy 
laid out "the rules" of human experimentation. He stated without equivocation 
that these standards had been "well established by custom, social usage and the 
ethics of medical conduct." Ivy's rules read as follows: 

1 . Consent of the human subject must be obtained. 
All subjects must have been volunteers in the 
absence of coercion in any form. Before 
volunteering the subjects have been informed of the 
hazards, if any. (In the U.S.A. during War, accident 
insurance against the remote chance of injury, 
disability and death was provided. [This was not 
true in all cases.]) 

2. The experiment to be performed must be so 
designed and based on the results of animal 



133 



Parti 

experimentation and a knowledge of the natural 
history of the disease under study that the 
anticipated results will justify the performance of 
the experiment. That is, the experiment must be 
such as to yield results for the good of society 
unprocurable by other methods of study and must 
not be random and unnecessary in nature. 

3. The experiment must be conducted 

(a) only by scientifically qualified persons, and 

(b) so as to avoid all unnecessary physical and mental 
suffering and injury, and 

(c) so, that, on the basis of the results of previous 
adequate animal experimentation, there is no a priori 
reason to believe that death or disabling injury will occur, 
except in such experiments as those on Yellow Fever where 
the experimenters serve as subjects along with non- 
scientific personnel. 8 

A comparison of these rules with the Nuremberg Code, which the 
Nuremberg Tribunal issued as part of its judgment on August 19, 1947, reveals 
that the three judges extracted important elements of clause 1 from Ivy's first rule 
and clauses 2, 3, 4, 5, and 8 almost verbatim from the rest of Ivy's formulation. 
Significantly, the judges also reiterated Ivy's assertion that these rules were 
already widely understood and followed by medical researchers. 9 

It is possible that the Nuremberg judges never read Ivy's report directly. 
During his testimony at the trial, Ivy essentially read his set of rules into the court 
record. 10 Also, the judges could have gained exposure to Ivy's thinking through 
two additional indirect sources. First, another medical expert who aided the 
prosecution, an American Army psychiatrist named Leo Alexander, submitted on 
April 15, 1947, a memorandum to the prosecutors entitled "Ethical and Non- 
Ethical Experimentation on Human Beings." In this memorandum, which would 
have been passed to the judges, Alexander repeated in very similar language 
significant portions of Ivy's rules as outlined in the September 1946 report." 
Second, American prosecutor James McHaney closely followed the text of Ivy's 
rules when setting before the judges the "prerequisites to a permissible medical 
experiment on human beings" during the prosecution's closing statement on July 
14, 1947. 12 

But Ivy's standards for human experimentation served as even more than 
the primary textual foundation for the Nuremberg Code; his set of rules also 
undergirded the AMA's first formal statement on human experimentation. As the 
Board of Trustees had directed when asking Ivy to prepare his written report, the 



134 



Chapter 2 

finished document was immediately forwarded to the AMA Judicial Council. 
The board gave the Judicial Council three months to prepare a presentation for the 
House of Delegates, the large policy-making body of the AMA that was 
scheduled to hold an annual meeting in early December 1946. 13 Unfortunately, 
records of the Judicial Council's consideration of Ivy's report have not survived, 
but published proceedings of the House of Delegates meeting reveal the results of 
the council's deliberations. 14 Dr. E. R. Cunniffe, chair of the Judicial Council, 
summarized his panel's response to Ivy's report at an executive session of the 
House of Delegates on December 10, 1946 (the day immediately following the 
prosecution's opening statement in the Nuremberg Medical Trial). Cunniffe 
condemned the Nazi experiments described in Ivy's report as gross violations of 
standards that were already inherent in the existing "Principles of Medical Ethics 
of the American Medical Association," which had undergone only minor revision 
since the AMA adopted them in 1847, the first year of the association's existence. 
But in recognition of the fact that guidelines for human experimentation were not 
explicitly laid out in these "Principles," the Judicial Council offered the following 
distillation of Ivy's rules: 

In order to conform to the ethics of the American 
Medical Association, three requirements must be 
satisfied: (1) the voluntary consent of the person on 
whom the experiment is to be performed [must be 
obtained]; (2) the danger of each experiment must 
be previously investigated by animal 
experimentation, and (3) the experiment must be 
performed under proper medical protection and 
management. 15 

These three rules became the official policy of the AMA when the House 
of Delegates voted its approval "section by section and as a whole" on the 
morning of December 1 1, 1946. The AMA's official governing body also added a 
general admonition: "This House of Delegates condemns any other manner of 
experimentation on human beings than that mentioned herein." 16 It is worth 
noting that in 1946 roughly 70 percent of American physicians belonged to the 
AMA. In absolute terms, 126,835 physicians belonged to the association, but it 
must be acknowledged that membership in the national association came 
automatically with membership in county and state medical societies, which was 
often necessary for professional privileges at local hospitals. 17 Each member of 
the AMA would have received a regular subscription to the Journal of the 
American Medical Association, and all of these subscribers would have had an 
opportunity to read the three rules for human experimentation approved by the 
House of Delegates. At the same time, however, these rules were not published 



135 



Parti 

prominently; they were set in small type along with a variety of other 
miscellaneous business items in the lengthy published minutes of the meeting. 
Only an exceptionally diligent member, or one with a special interest in medical 
ethics, is likely to have located this item. 

In mid-June 1947, Ivy took the stand late in the Nuremberg Medical Trial 
as a rebuttal witness for the prosecution to counter the claims of the defense that 
standards for proper conduct in human experimentation had not been clearly 
established before the initiation of the trial. The contents of Ivy's September 1946 
report, and the AMA standards that arose from it, played a major role during his 
three days of testimony. At one point, prosecution associate counsel Alexander 
G. Hardy carefully walked Ivy through a verbatim oral recitation of the rules for 
human experimentation contained in Ivy's report and the condensed version of his 
rules as approved by the AMA. After a reading of the AMA principles, Hardy 
and Ivy had the following exchange: 

Q. . . . Now, [do these rules] purport to be the principles 
upon which all physicians and scientists guide themselves 
before they resort to medical experimentation on human 
beings in the United States? 

A. Yes, they represent the basic principles approved by the 
American Medical Association for the use of human beings 
as subjects in medical experiments. 18 

Hearing this specific, and obviously important, claim about research with 
human subjects in the United States, Judge Harold E. Sebring interjected with a 
broad question about the international significance of Ivy's assertion: "How do the 
principles which you have just enunciated comport with the principles of the 
medical profession over the civilized world generally?" Ivy responded: "They 
are identical, according to my information." 19 

Later in his testimony, Ivy faced cross-examination by Fritz Sauter, 
counsel for two of the German medical defendants. Sauter pushed Ivy to 
acknowledge that the AMA guidelines had come into formal existence only as the 
Nuremberg Medical Trial was getting under way. In response to this attempt to 
diminish the legal force of the AMA standards with the obvious suggestion that 
the rules had been made up too recently to be of relevance, Ivy made an explicit 
claim in court that the ideas inherent in the AMA standards significantly predated 
their official formulation: 

Q. You told us that ... an association had made a 
compilation regarding the ethics of medical experiments on 
human beings. . . . Can you recall what I am referring to? 
A. Yes. 



136 



Chapter 2 

Q. That was in December 1946, 1 believe. 

A. Yes, I remember. . . . 

Q. Did that take place in consideration of this trial? 

A. Well, that took place as a result of my relations 

to the trial, yes. 

Q. Before December of 1946 were such instructions 

in printed form in existence in America? 

A. No. They were understood only as a matter of 

common practice. 20 

Thus, if Ivy is to be taken literally, the standards he forcefully articulated 
during the Nuremberg Medical Trial, which were affirmed by the AMA House of 
Delegates as the trial was just beginning and codified by three American judges 
as the trial came to an end, were the standards of practice at the time. 

THE "REAL WORLD" OF HUMAN EXPERIMENTATION 

It would be historically irresponsible, however, to rely solely on records 
related directly to the Nuremberg Medical Trial in evaluating the postwar scene in 
American medical research. The panorama of American thought and practice in 
human experimentation was considerably more complex than Ivy acknowledged 
on the witness stand in Nuremberg. In general, it does seem that most American 
medical scientists probably sought to approximate the practices suggested in the 
Nuremberg Code and the AMA principles when working with "healthy 
volunteers." Indeed, a subtle, yet pervasive, indication of the recognition during 
this period that consent should be obtained from healthy subjects was the 
widespread use of the term volunteer to describe such research participants. Yet, 
as Advisory Committee member Susan Lederer has recently pointed out, the use 
of the word volunteer cannot always be taken as an indication that researchers 
intended to use subjects who had knowingly and freely agreed to participate in an 
experiment; it seems that researchers sometimes used volunteer as a synonym for 
research subject, with no special meaning intended regarding the decision of the 
participants to join in an experiment. 21 

Even with this ambiguity it is, however, quite clear that a strong tradition 
of consent has existed in research with healthy subjects, research that generally 
offered no prospect of medical benefit to the participant. In the United States 
much of this tradition has rested on the well-known example of Walter Reed's 
turn-of-the-century experiments, when he employed informed volunteers to 
establish the mosquito as the vector of transmission for yellow fever. 22 Indeed, it 
seems that a tradition of research with consenting subjects has been particularly 
strong among Reed's military descendants in the field of infectious disease 
research (which has frequently required the use of healthy subjects). For 



137 



Part I 

example, Dr. Theodore Woodward, a physician-researcher commissioned in the 
Army, conducted vaccine research during the 1950s with healthy subjects under 
the auspices of the Armed Forces Epidemiological Board. In a recent interview 
conducted by the Advisory Committee, Woodward recalled that the risks of 
exposure to diseases such as typhus were always fully disclosed to potential 
healthy subjects and that their consent was obtained. Since some of these studies 
were conducted in other countries with non-English-speakers, the disclosure was 
given in the volunteer's language. 23 Of his own values during this time, 
Woodward stated: "If I gave someone something that could make them sick or kill 
them and hadn't told them, I'm a murderer." 24 Similarly, Dr. John Arnold, a 
physician who conducted Army-sponsored malaria research on prisoners from the 
late 1940s through the mid-1950s, recalled that he always obtained written 
permission from his subjects. 25 

Not all the evidence on consent and healthy subjects comes from the 
military tradition. A particularly compelling general characterization of research 
with "normal volunteers" during this period comes from the "Analytic Summary" 
of a conference on the "Concept of Consent in Clinical Research," which the 
Law-Medicine Research Institute (LMRI) of Boston University convened on 
April 29, 1961. At this conference, twenty-one researchers from universities, 
hospitals, and pharmaceutical companies across the country were brought 
together "to explore problems arising from the legal and ethical requirements of 
informed consent of research subjects." 26 The LMRI project was what one might 
now call a fact-finding mission; the LMRI staff was attempting "to define and to 
analyze the actual patterns of administrative practice governing the conduct of 
clinical research in the United States" during the early 1960s. 27 Anne S. Harris, 
an LMRI staff member and author of the conference's final report, offered a 
simple but significant assessment of the handling of healthy participants in 
nontherapeutic research as expressed by the researchers at the meeting, whose 
careers included the decade and a half since the end of World War II: "The 
conferees indicated that normal subjects are usually fully informed." 28 

Even so, researchers who almost certainly knew better sometimes 
employed unconsenting healthy subjects in research that offered them no medical 
benefits. For example, Dr. Louis Lasagna, who has since become a respected 
authority on bioethics, stated in an interview conducted by the Advisory 
Committee that between 1952 and 1954, when he was a research fellow at 
Harvard Medical School, he helped carry out secret, Army-sponsored experiments 
in which hallucinogens were administered to healthy subjects without their full 
knowledge or consent: 

The idea was that we were supposed to give 
hallucinogens or possible hallucinogens to healthy 
volunteers and see if we could worm out of them 



138 



Chapter 2 

secret information. And it went like this: a 
volunteer would be told, 'Now we're going to ask 
you a lot of questions, but under no circumstances 
tell us your mother's maiden name or your social 
security number,' I forget what. I refused to 
participate in this because it was so mindless that a 
psychologist did the interviewing and then we'd 
give them a drug and ask them a number of 
questions and sure enough, one of the questions was 
'What is you mother's maiden name?' Well, it was 
laughable in retrospect . . . [The subjects] weren 't 
informed about anything [emphasis added]. 29 

Lasagna, reflecting "not with pride" on the episode, offered the following 
explanation: "It wasn't that we were Nazis and said, 'If we ask for consent we lose 
our subjects,' it was just that we were so ethically insensitive that it never 
occurred to us that you ought to level with people that they were in an 
experiment." 30 This might have been true for Lasagna the young research fellow, 
but the explanation is harder to understand for the director of the research project, 
Henry Beecher. Beecher was a Harvard anesthesiologist who, as we will see later 
in this chapter and in chapter 3, would emerge as an important figure in 
biomedical research and ethics during the mid-1960s. 31 

If American researchers experimenting on healthy subjects sometimes did 
not strive to follow the standards enunciated at Nuremberg, research practices 
with sick patients seem even more problematic in retrospect. Advisory 
Committee member Jay Katz has recently argued that this type of research still 
gives rise to ethical difficulties for physicians engaged in research with patients, 
and he has offered an explanation: "In conflating clinical trials and therapy, as 
well as patients and subjects, as if both were one and the same, physician- 
investigators unwittingly become double agents with conflicting loyalties." 

It is likely that such confusion and conflict would have been as 
troublesome several decades ago, if not more troublesome, than it is today. The 
immediate postwar period was a time of vast expansion and change in American 
medical science (see Introduction). Clinical research was emerging as a new and 
prestigious career possibility for a growing number of medical school graduates. 
Most of these young clinical researchers almost certainly would have absorbed in 
their early training a paternalistic approach to medical practice that was not 
seriously challenged until the 1970s. This approach encouraged physicians to 
take the responsibility for determining what was in the best interest of their 
patients and to act accordingly. The general public allowed physicians to act with 
great authority in assuming this responsibility because of an implicit trust that 
doctors were guided in their actions by a desire to help their patients. 



139 



Parti 

This paternalistic approach to medical practice can be traced to the 
Hippocratic admonition: "to help, or at least do no harm." 33 Another long- 
standing medical tradition that can be found in Hippocratic medicine is the belief 
that each patient poses a unique medical problem calling for creative solution. 
Creativity in the treatment of individuals, which was not commonly thought of as 
requiring consent, could be— and often was—called experimentation. This tradition 
of medical tinkering without explicit and informed consent from a patient was 
intended to achieve proper treatment for an individual's ailments; but it seems also 
to have served (often unconsciously) as a justification for some researchers who 
engaged in large-scale clinical research projects without particular concern for 
consent from patients. 

Members of the medical profession and the American public have today 
come to better understand the intellectual and institutional distinctions between 
organized medical research and standard medical practice. There were significant 
differences between research and practice in the 1950s, but these differences were 
harder to recognize because they were relatively new. For example, randomized, 
controlled, double-blind trials of drugs, which have brought so much benefit to 
medical practice by greatly decreasing bias in the testing of new medicines, were 
introduced in the 1950s. The postwar period also brought an unprecedented 
expansion of universities and research institutes. Many more physicians than ever 
before were no longer solely concerned, or even primarily concerned, with aiding 
individual patients. These medical scientists instead set their sights on goals they 
deemed more important: expanding basic knowledge of the natural world, curing 
a dread disease (for the benefit of many, not one), and in some cases, helping to 
defend the nation against foreign aggressors. At the same time, this new breed of 
clinical researchers was motivated by more pragmatic concerns, such as getting 
published and moving up the academic career ladder. But these differences 
between medical practice and medical science, which seem relatively clear in 
retrospect, were not necessarily easy to recognize at the time. And coming to 
terms with these differences was not especially convenient for researchers; using 
readily available patients as "clinical material" was an expedient solution to a 
need for human subjects. 

As difficult and inconvenient as it might have been for researchers in the 
boom years of American medical science following World War II to confront the 
fundamental differences between therapeutic and nontherapeutic relationships 
with other human beings, it was not impossible. Otto E. Guttentag, a physician at 
the University of California School of Medicine in San Francisco, directly 
addressed these issues in a 1953 Science magazine article. Guttentag's article, and 
three others that appeared with it, originated as presentations in a symposium held 
in 1951 on "The Problem of Experimentation on Human Beings" at Guttentag's 
home institution. Guttentag constructed his paper around a comparison between 
the traditional role of the physician as healer and the relatively new role of 



140 



Chapter 2 

physician as medical researcher. Guttentag referred to the former as "physician- 
friend" and the latter as "physician-experimenter." He explicitly laid out the 
manner in which medical research could conflict with the traditional doctor- 
patient relationship: 

Historically, . . . one human being is in distress, in 
need, crying for help; and another fellow human 
being is concerned and wants to help and the desire 
for it precipitates the relationship. Here both the 
healthy and the sick persons are . . . fellow- 
companions, partners to conquer a common enemy 
who has overwhelmed one of them. . . . Objective 
experimentation to confirm or disprove some 
doubtful or suggested biological generalization is 
foreign to this relationship ... for it would involve 
taking advantage of the patient's cry for help, and of 
his insecurity. 34 

Guttentag worried that a "physician-experimenter" could not resist the 
temptation to "tak[e] advantage of the patient's cry for help." 35 To prevent the 
experimental exploitation of the sick that he envisioned (or knew about), 
Guttentag suggested the following arrangement: 

Research and care would not be pursued by the 
same doctor for the same person, but would be kept 
distinct. The physician-friend and the physician- 
experimenter would be two different persons as far 
as a single patient is concerned. . . . The 
responsibility for the patient as patient would rest, 
during the experimental period, with the physician- 
friend, unless the patient decided differently. 

Retaining his original physician as personal adviser, 
the patient would at least be under less conflict than 
he is at present when the question of 
experimentation arises. 36 

Among physicians, Guttentag was nearly unique in medicine in those days 
in raising such problems in print. Another example of concern about the moral 
issues raised by research at the bedside comes from what might be an unexpected 
source: a Catholic theologian writing in 1945. In the course of a general review 
of issues in moral theology, John C. Ford, a prominent Jesuit scholar, devoted 



141 



Parti 

several pages to the matter of experimentation with human subjects. Ford was not 
a physician, but his thoughts on this topic-published a year before the beginning 
of the Nuremberg Medical Trial-suggest that a thoughtful observer could 
recognize, even decades ago, serious problems with conducting medical research 
on unconsenting hospital patients: 

The point of getting the patient's consent [before 
conducting an experiment] is increasingly 
important, I believe, because of reports which 
occasionally reach me of grave abuses in this 
matter. In some cases, especially charity cases, 
patients are not provided with a sure, well-tried, and 
effective remedy that is at hand, but instead are 
subjected to other treatment. The purpose of 
delaying the well-tried remedy is, not to cure this 
patient, but to discover experimentally what the 
effects of the new treatment will be, in the hope, of 
course, that a new discovery will benefit later 
generations, and that the delay in administering the 
well-tried remedy will not harm the patient too 
much. . . . This sort of thing is not only immoral, 
but unethical from the physician's own standpoint, 
and is illegal as well. 37 

The transcripts and reports produced in the Law-Medicine Research 
Institute's effort during the early 1 960s to gather information on ethical and 
administrative practices in research in medical settings suggest that by this time 
more researchers had come to recognize the troubling issues associated with using 
sick patients as subjects in research that could not benefit them. The body of 
evidence from the LMRI project also suggests that problems with this type of 
human experimentation had been widespread before the early 1960s and remained 
common at that time. The transcript of a May 1, 1961, closed-door meeting of 
medical researchers organized by LMRI to explore issues in pediatric research 
shows a medical scientist from the University of Iowa offering a revealing 
generalization from which none of his colleagues dissented. In order to 
understand this transcript excerpt one must know that item "Al" on the meeting 
agenda related to research "primarily directed toward the advancement of medical 
science" and item "A2" referred to "clinical investigation . . . primarily directed 
toward diagnostic, therapeutic and/or prophylactic benefit to patients." 

We have done a thousand things with an implied 
feeling [of consent]. . . . We wear two hats. Item 



142 



Chapter 2 

A2 allows us to do A 1 but we feel uncomfortable 
about it. The responsibility of the physician 
includes responsibility to advance in knowledge. 
Things are different now and this problem of a 
secondary role [i.e., to advance knowledge] is 
increasingly in front stage [emphasis added]. 38 

This researcher acknowledged that many physicians during the period let 
themselves slide into nontherapeutic research with patients. He provided the 
additional, and significant, assessment that he and his colleagues felt guilty about 
this behavior, even though it was quite common. 

An even more probing analysis of these issues had taken place two days 
earlier at the April 29, 1961, LMRI conference on "The Concept of Consent," 
referred to above in our discussion of research with healthy subjects. The 
participants at this meeting recognized that research with sick patients could be 
both therapeutic and nontherapeutic. Interestingly, they suggested that patients 
employed for research in which "there was the possibility of therapeutic benefit 
with minimal or moderate risk" were "usually informed" of the proposed study. 
The author of the conference report offered the plausible explanation that 
informing subjects in potentially beneficial research "is psychologically more 
comfortable for investigators [because] the [therapeutic] expectations of potential 
subjects coincide with the purpose and expected results of the experiment." 39 The 
conferees identified research in which "patients are used for studies unrelated to 
their own disease, or in studies in which therapeutic benefits are unlikely" as the 
most problematic. Those at the meeting "indicated that it is most often subjects in 
this category to whom disclosure is not made." 40 The conference report outlined 
an approach employed by many researchers (including some at the meeting), in 
which, rather than seeking consent from patients for research that offers them no 
benefit, 

[t]he therapeutic illusion is maintained, and the 
patient is often not even told he is participating in 
research. Instead, he is told he is "just going to 
have a test." If the experimental procedure involves 
minimal risk, but some discomfort, such as hourly 
urine collection, "All you do is tell the patient: 'We 
want you to urinate every hour.' We merely let them 
assume that it is part of the hospital work that is 
being done." 41 

Again, it is important to note that the conference participants displayed 
some moral discomfort with this pattern of behavior, as can be seen from the 



143 



Part I 

following exchange: 

Dr. X: There is a matter here of whether the patient 
is not informed because the risk is too trivial, or 
because it's too serious. 

Dr. Y: I think you're getting right at it. There's a 
great difference in not telling the patient because 
you're afraid he won't participate and not telling him 
because you don't think there is a conceivable risk, 
and it's so trivial you don't bother to inform him. 
Dr. Z: On the question of whether it's [acceptable] 
not to tell, we would say that it is not permissible on 
the grounds of refusal potential. 42 

It is also important to draw out of this transcript excerpt the general point 
that most researchers in this period appear not to have had great ethical qualms 
about enrolling an uninformed patient in a research project if the risk was deemed 
low or nonexistent. Of course, the varying definitions of "low risk" could lead to 
problems with this approach. Indeed, the participants at the "Concept of Consent" 
conference grappled at length with this very issue without ever reaching 
consensus. A minority steadfastly asserted that participants in an experiment 
should be asked for consent even if the risk would be extremely low, such as in 
only taking a small clipping of hair. 

The Advisory Committee's Ethics Oral History Project 43 has provided 
extensive additional evidence that medical researchers sometimes (perhaps even 
often) took liberties with sick patients during the decades immediately following 
World War II. The element of opportunism was recounted in several interviews. 
Dr. Lasagna, who was involved in pain-management studies in postoperative 
patients at Harvard in the 1950s, explained rather bluntly: 

[Mjostly, I'm ashamed to say, it was as if, and I'm 
putting this very crudely purposely, as if you'd 
ordered a bunch of rats from a laboratory and you 
had experimental subjects available to you. They 
were never asked by anybody. They might have 
guessed they were involved in something because a 
young woman would come around every hour and 
ask them how they were and quantified their pain. 
We never made any efforts to find out if they 
guessed that they were part of it. 44 

Other researchers told similar tales, with a similar mixture of matter-of- 



144 



Chapter 2 

fact reporting and regretful recollection. Dr. Paul Beeson remembered a study he 
conducted in the 1940s, while a professor at Emory University, on patients with 
bacterial endocarditis, an invariably fatal disease at the time. He recalled that he 
thought it would be interesting to use the new technique of cardiac catheterization 
to compare the number of bacteria in the blood at different points in circulation: 

[This is] something I wouldn't dare do now. It 
would do no good for the patient. They had to 
come to the lab and lie on a fluoroscopic table for a 
couple of hours, a catheter was put into the heart, a 
femoral needle was put in so we could get femoral 
arterial blood and so on. . . . All I could say at the 
end was that these poor people were lying there and 
we had nothing to offer them and it might have 
given them some comfort that a lot of people were 
paying attention to them for this one study. I don't 
remember ever asking their permission to do it. I 
did go around and see them, of course, and said, 
"We want to do a study on you in the X-ray 
department, we'll do it tomorrow morning," and 
they said yes. There was never any question. Such 
a thing as informed consent, that term didn't even 
exist at that time. . . . [I]f I were ever on a hospital 
ethics committee today, I wouldn't ever pass on that 
particular study. 45 

Radiologist Leonard Sagan recalled an experiment in which he assisted 
during his training on a metabolic unit at Moffett Hospital in San Francisco in 
1956-1957. 

At the time, the adrenal gland was hot stuff. ACTH 
[adrenocorticotropic hormone] had just become 
available and it was an important tool for exploring the 
function of the adrenal gland. . . . This was the project 
I was involved in during that year, the study of adrenal 
function in patients with thyroid disease, both hypo- 
and hyperthyroid disease. So what did we do? I'd find 
some patients in the hospital and I'd add a little ACTH 
to their infusion and collect urines and measure output 
of urinary corticoids. ... I didn't consider it dangerous. 
But I didn't consider it necessary to inform them 
either. So far as they were concerned, this was part of 



145 



Parti 

their treatment. They didn't know, and no one had 
asked me to tell them. As far as I know, informed 
consent was not practiced anyplace in that hospital at 
the time. 46 

Sagan viewed the above experiment as conforming not only with the 
practices of the particular hospital but also in accord with the high degree of 
professional autonomy and respect that was granted to physicians in this era: 

In 1945, '50, the doctor . . . was king or queen. It 
never occurred to a doctor to ask for consent for 
anything. . . . People say, oh, injection with 
plutonium, why didn't the doctor tell the patient? 
Doctors weren't in the habit of telling the patients 
anything. They were in charge and nobody 
questioned their authority. Now that seems 
egregious. But at the time, that's the way the world 

47 

was. 

Another investigator, Dr. Stuart Finch, who was a professor of medicine at 
Yale during the 1950s and 1960s, recalled instances when oncologists there were 
overly aggressive in pursuing experimental therapies with terminal patients. 

[I]t's very easy to talk a terminal patient into taking 
that medication or to try that compound or whatever 
the substance is. . . . Sometimes the oncologists 
[got] way overenthused using it. It's very easy 
when you have a dying patient to say, "Look, you're 
going 

to die. Why don't you let me try this substance on 
you?" I don't think if they have informed consent or 
not it makes much difference at that point. 48 

Economically disadvantaged patients seem to have been perceived by 
some physicians as particularly appropriate subjects for medical experimentation. 
Dr. Beeson offered a frank description of a quid pro quo rationale that was 
probably quite common in justifying the use of poor patients in medical research: 
"We were taking care of them, and felt we had a right to get some return from 
them, since it wouldn't be in professional fees and since our taxes were paying 
their hospital bills." 49 

Another investigator, Dr. Thomas Chalmers, who began his career in 
medical research during the 1940s, identified sick patients as the most vulnerable 



146 



Chapter 2 

type of experimental subjects-more vulnerable even than prisoners: 

One of the real ludicrous aspects of talking about a 
prisoner being a captive, and therefore needing 
more protection than others, is, there's nobody more 
captive than a sick patient. You've got pain. You 
feel awful. You've got this one person who's going 
to help you. You do anything he says. You're a 
captive. You can't, especially if you're sick and 
dying, discharge the doctor and get another one 
without a great deal of trauma and possible loss of 
lifesaving measures. 50 

Thus, as compared with prisoners, who are now generally viewed to be 
vulnerable to coercion, those who are sick may be even more compromised in 
their ability to withstand subtle pressure to be research subjects. Appropriate 
protection for the sick who might be candidates for medical research has proved 
to be an especially troublesome issue in the era following Nuremberg. 

NUREMBERG AND RESEARCH WITH PATIENTS 

The record of conducting nontherapeutic research with unconsenting sick 
patients during the postwar period discussed above seems to stand in particularly 
sharp contrast with the claims about the conduct of research involving human 
subjects in the United States that Andrew Ivy made during his testimony in 
Nuremberg. We have seen how some observers, even before Nuremberg, 
recognized that employing uninformed, vulnerable sick patients solely as a means 
to a scientific end was simply wrong. We must, however, also acknowledge that 
the particulars of the Nuremberg Medical Trial did not call for careful attention to 
the issues surrounding research with sick patients. None of the German 
physicians at Nuremberg stood accused of exploiting patients for experimental 
purposes. 

Nonetheless, it is likely that Andrew Ivy would have argued that consent 
was appropriate in virtually all instances of medical research. Dr. Herman 
Wigodsky, who worked closely under Ivy at Northwestern in the late 1930s and 
early 1940s, explicitly commented during an Ethics Oral History Project 
interview that he did not believe that his mentor drew any sort of ethical line 
between various types of clinical research: "I don't think he made any distinction 
[between research with sick patients and research with healthy subjects]. 
Research was research. It didn't make any difference." 51 

Additional evidence that Ivy would have supported standards of consent 
for research with ill as well as with healthy subjects comes from his response to a 



147 



Parti 

set of rules for human experimentation put forth by the German Ministry of 
Interior in 1931, presented to him after he had prepared his written report for the 
AM A in the fall of 1946. These rules appear to be considerably more 
comprehensive and sophisticated than the Nuremberg Code itself. 52 Most 
significantly, the 1931 German standards cover both therapeutic and 
nontherapeutic research, calling for consent in both types of medical 
investigation. For reasons that are not clear, the prosecution team at Nuremberg 
did not choose to place much emphasis on these German standards in constructing 
the case. Ivy did, however, attempt (without much help from the prosecution) to 
initiate a discussion of the 1931 standards during his testimony. It is clear from 
the trial transcript that Ivy saw a rough equivalence between the more detailed and 
extensive German rules and those formulated by the AMA, with his assistance. 
Shortly after discussing the AMA principles on the witness stand, Ivy had the 
following exchange with prosecutor Alexander G. Hardy: 

Q. Do you have any further statements to make 
concerning rules of medical ethics concerning 
experimentation in human beings? 
A. Well, I find that since making [my] report to the 
American Medical Association that a decree of the 
Minister of Public Welfare [Ivy should have said 
"the Minister of the Interior"] of Germany in 1931 
on the subject of "Regulations for Modern Therapy 
for the Performance of Scientific Experiments on 
Human Beings" contains all the [AMA] principles 
which I have read. 53 

Hardy did not take what now seems an obvious opportunity to allow Ivy to 
expand further on these rules. However, a few minutes later, Ivy brought up the 
German standards again on his own (and again Hardy did not pursue the topic 
further). At this point, Ivy stated his general agreement with the German 
standards of 1931 even more firmly: 

I cited the principles . . . from the Reich Minister of 
the Interior dated February 28, 193 1 to indicate that 
the ethical principles for the use of human beings as 
subjects in medical experiments in Germany in 
1931 were similar to these which I have enunciated 
and which have been approved by the House of 
Delegates of the American Medical Association. 54 

Ivy's assertion of "similarity" between the AMA principles and those in the 1931 



148 



Chapter 2 

German document may not meet with agreement among those who compare the 
two. Though they may be viewed as similar in philosophy and intent, the German 
interior ministry document is, far more detailed and comprehensive than that of 

theAMA. 

Contrary to Ivy's claims at Nuremberg, and the positioning of Ivy by the 
prosecution, he cannot in any full sense be taken as the embodiment of the entire 
American medical profession in the years immediately following World War II. 
Again, Dr. Wigodsky spoke to this point in his recent interview: 

Well, I've always felt that that stuff that Ivy wrote 
up during the time of the trials was pretty much an 
expression of his personal philosophy about 
research. And ... it was the kind of understanding 
that we had in working with him about how he felt. 
Voluntariness being number one--you had to 
volunteer and had to be in a situation where you 
could volunteer. And consent in the sense that you 
didn't do anything to anybody that they didn't know 
what you were doing. That you explained to people 
what it was you were going to do and why you were 
going to do it and that sort of thing [emphasis 
added]. 55 

Even if it is true that Andrew Ivy would have wholeheartedly endorsed the 
notion of obtaining consent from any research subject- whether an experiment 
held the possibility of personal benefit or not; whether the subjects were sick or 
healthy-it seems likely that the AMA House of Delegates would have been 
hesitant to endorse a condensation of Ivy's principles of research ethics if they had 
been explicitly extended to cover all categories of clinical investigation. 
Obtaining consent from patients within the normal clinical relationship was not a 
common practice in late 1946. At that time, and for many years to come, patient 
trust and medical beneficence were viewed as the unshakable moral foundations 
on which meaningful interactions between professional healers and the sick 
should be built. In fact, it was not until 1981 that the AMA's Judicial Council 
specifically endorsed "informed consent" as an appropriate part of the therapeutic 
doctor-patient relationship. 56 

But, in the end, it must be acknowledged that the facts of the Nuremberg 
Medical Trial did not force Andrew Ivy, the AMA House of Delegates, the 
Nuremberg prosecutors, or the judges to grapple with the distinctions between 
research with sick patients and research with healthy subjects, or therapeutic and 
nontherapeutic research. The Nuremberg defendants stood accused of ghastly 
experimental acts that were absolutely without therapeutic intent, and their 



149 



Parti 

unfortunate subjects were never under any illusion that they were receiving 
medical treatment. To rebut the claims of some of the medical defendants that 
obtaining consent from research subjects was not a clearly established principle, 
Ivy could, and did, offer a variety of examples on the witness stand from a long 
tradition of human experimentation on consenting healthy subjects. 57 Ivy and the 
members of the prosecution team were not faced with what might have been a 
more troubling process: finding examples of well-organized nontherapeutic 
experiments on sick patients in which the subjects had clearly offered consent. 
Simply put, the Nuremberg Medical Trial did not demand it. 

AMERICAN MEDICAL RESEARCHERS' REACTIONS TO 
NEWS OF THE NUREMBERG MEDICAL TRIAL 

It is important to have some understanding of the extent to which 
American medical scientists paid attention to the events of the Nuremberg 
Medical Trial and made connnections with the messages that emanated from the 
courtroom in Germany. The Nuremberg Medical Trial received coverage in the 
American popular press, but it would almost certainly be an exaggeration to refer 
to this attention as exhaustive. Historian David Rothman has provided the 
following summary of the trial's coverage in the New York Times: 

Over 1945 and 1946 fewer than a dozen articles 
appeared in the New York Times on the Nazi 
[medical] research; the indictment of forty-two 
doctors in the fall of 1946 was a page-five story and 
the opening of the trial, a page-nine story. (The 
announcement of the guilty verdict in August 1 947 
was a front-page story, but the execution of seven 
of the defendants a year later was again relegated to 
the back pages.) 58 

The Advisory Committee's Ethics Oral History Project suggests that 
American medical researchers, perhaps like the American public generally, were 
not carefully following the daily developments in Nuremberg. For example, Dr. 
John Arnold, a researcher who, during the Medical Trial, was involved in malaria 
experiments on prisoners at Stateville Prison in Illinois, offered a particularly 
vivid (if somewhat anachronistic) recollection of the scant attention paid to the 
Nuremberg Medical Trial among American medical scientists: "We were dimly 
aware of it. And as you ask me now, I'm astonished that we [were not] hanging 
on the TV at the time, watching for each twist and turn of the argument to 
develop. But we weren't." 59 It might have been expected that the researchers at 
Stateville would have been particularly concerned with the events at Nuremberg 



150 



Chapter 2 

because some of the medical defendants claimed during the trial that the wartime 
malaria experiments at the Illinois prison were analogous to the experiments 
carried out in the Nazi concentration camps. 

The strongest statement of awareness came from Dr. Herbert Abrams, a 
radiologist who was in his residency at Montefiore Hospital in the Bronx 
throughout most of the trial: 

[The Nuremberg Medical Trial] was part of the 
history of the day. And there was extensive 
reportage ... so that the manner of human 
experimentation as it had been done by the Nazis 
was very much in the news. We were all aware of 
it. I think that people experienced this kind of 
revulsion about it that you might anticipate. ... It 
was surely something, at least in the environment I 
was in, we were aware of and that affected the 
thinking of everyone who was involved in clinical 
investigation. 60 

It seems likely, however, that the "environment" this young physician was in 
would have caused a heightened awareness of a trial dealing with Nazi medical 
professionals. Montefiore is a traditionally Jewish hospital that was home to 
many Jewish refugee physicians who had fled the terror and oppression of the 
Nazi regime. 61 A trial of German physicians almost certainly would have been of 
particular interest in this setting. 

Even among American medical researchers who might have been aware of 
events at Nuremberg, it seems that many did not perceive specific personal 
implications in the Medical Trial. Rothman has enunciated this historical view 
most fully. He asserts that "the prevailing view was that [the Nuremberg medical 
defendants] were Nazis first and last; by definition nothing they did, and no code 
drawn up in response to them, was relevant to the United States." 62 Jay Katz has 
offered a similar summation of the immediate response of the medical community 
to the Nuremberg Code: "It was a good code for barbarians but an unnecessary 
code for ordinary physicians." 63 

Several participants in the Ethics Oral History Project affirmed the 
interpretations of Rothman and Katz, using similar language. Said one physician: 
"There was a disconnect [between the Nuremberg Code and its application to 
American researchers]. . . . The interpretation of these codes [by American 
physicians] was that they were necessary for barbarians, but [not for] fine 
upstanding people." 64 This same physician later acknowledged that, in a sense, 
some American researchers did not pay attention to the lessons of the Nuremberg 
Medical Trial because it was not convenient to do so: 



151 



Parti 

The connection between those horrendous acts 
[carried out by German medical scientists in the 
concentration camps] and our everyday 
investigations was not made [by American medical 
researchers] for reasons of self-interest, to be 
perfectly frank. As I see it now, I'm saddened that 
we didn't see the connection, but that's what was 
done. . . . It's hard to tell you now . . . how we 
rationalized, but the fact is we did/' 5 

The popular press mirrored the view that human experimentation as 
practiced in the United States was not a morally troubling enterprise—it was as 
American as apple pie. Between 1948 and 1960 magazines such as the Saturday 
Evening Post, Reader's Digest, and the American Mercury ran "human interest" 
stories on "human guinea pigs." These stories generally focused on specific 
groups of healthy subjects— prisoners, conscientious objectors, medical students, 
soldiers— and described them as "volunteers." The articles explained the ordeals 
to which the volunteers had submitted themselves. "Among these men and 
women," the New York Times informed its Sunday readership in 1958, "you will 
find those who will take shots of the new vaccines, who will swallow radioactive 
drugs, who will fly higher than anyone else, who will watch malaria infected 
mosquitos feed on their bare arms." 6 ' 1 The articles assured the public that the 
volunteers had plausible, often noble, reasons for volunteering for such seemingly 
gruesome treatment. The explanations included social redemption (especially in 
the case of prisoners), religious or other beliefs (particularly for conscientious 
objectors), the advancement of science, service to society, and thrill-seeking. 67 In 
sum, most articles in the popular press were uncritical toward experimentation on 
humans and assumed that those involved had freely volunteered to participate. 

However, a smaller number of press reports in the late 1940s and 1950s 
did suggest some tension between the words at Nuremberg and the practices in 
America. As early as 1948, for example, Science News reported the Soviet claim 
that Americans were using "Nazi methods" in the conduct of prisoner 
experiments. 68 Concern also began to be voiced about the dangers to volunteer 
"guinea pigs." In October 1954, for another example, the magazine Christian 
Century called on the Army to halt, at the first sign of danger, experiments at the 
Fitzsimmons Hospital in Denver, where soldiers were called upon to eat foods 
exposed to cobalt radiation. 69 

It is also possible that press accounts of experiments with patients rather 
than healthy subjects were more inclined to be critical, even in the late 1940s. A 
Saturday Evening Post article from the January 15, 1949, issue describes how a 
VA physician kept quiet about streptomycin trials involving the medical 
departments of the Army, Navy, and VA 



152 



Chapter 2 

because of the risk of congressional chastisement 
from publicity-conscious members of the House and 
Senate who might have screamed: 'You can't 
experiment on our heroes,' if it had been known that 
Army and Navy veterans of former wars were being 
used in the medical investigation. This was a real 
worry of the doctors who formulated the clinical 
program.™ 

Evidence suggests that some American researchers were genuinely and 
deeply concerned with the issues surrounding human experimentation during the 
years immediately following World War II. One source of insight into the 
thinking of American physicians engaged in clinical research during the 1950s is 
found in the ground-breaking work of medical sociologist Renee C. Fox. For two 
five-month periods between September 1951 and January 1953, Fox spent long 
days "in continuous, direct, and intimate contact with the physicians and patients" 
in a metabolic research ward that she pseudonymously called "Ward F-Second." 
In 1959 Fox reported with remarkable sensitivity and eloquence on the ethical 
dilemmas faced by the physicians conducting research on this ward. She did not 
suggest that the scientists under her observation were unaware of the Nuremberg 
Code; instead she offered a point-by-point paraphrasing of the Code, which she 
identified as "the basic principles governing research on human subjects which 
the physicians of the Metabolic Group [her collective term for the researchers 
whom she studied] were required to observe." Rather than being unconscious or 
contemptuous of a set of principles intended for barbarians, Fox reported that the 
researchers on "Ward F-Second" were sometimes troubled by their inability to 
apply the high, but essentially unquestioned, standards enunciated at the 
Nuremberg Medical Trial: 

The physicians of the Metabolic Group were deeply 
committed to these principles and conscientiously 
tried to live up to them in the research they carried 
out on patients. However like most norms, the 
"basic principles of human experimentation" are 
formulated on such an abstract level that they only 
provide general guides to actual behavior. Partly as 
a consequence, the physicians of the Metabolic 
Group often found it difficult to judge whether or 
not a particular experiment in which they were 
engaged "kept within the bounds" delineated by 
these principles. 71 



153 



Parti 

Sometimes private discussions among researchers about the ethical 
aspects of human experimentation led to public events. A good example from the 
early 1950s is the symposium held on October 10, 1951, at the University of 
California School of Medicine in San Francisco at which Otto Guttentag made the 
presentation discussed earlier. One of Guttentag's colleagues, Dr. Michael B. 
Shimkin, organized the symposium in response to some confidential criticism that 
he had received for research carried out under his direction with patients at the 
University of California's Laboratory of Experimental Oncology. The exact 
nature of this criticism is unclear from the records that remain of the episode, but 
Shimkin reported in a memoir that "remedial steps" were taken, including 
"written protocols for all new departures in clinical research, which we asked the 
cancer board of the medical school to review." 72 In his memoirs Shimkin also 
recalls that patients were screened carefully before they were admitted to the 
Laboratory of Experimental Oncology: 

They had to understand the experimental nature of 
our work, and every procedure was again explained 
to them; the initial release form even included 
agreement to an autopsy. The understanding did 
not absolve us of negligence, nor deprive patients of 
recourse to legal actions, but did set the tone and 
nature of our relationships. In all our 5 years of 
operations, not a single threat or implied threat of 
action against us was voiced. Two patients did 
instruct us to terminate our attempts at therapy. 73 

The criticism Shimkin experienced also demonstrated to him that a more open 
discussion of clinical research might be of benefit to his colleagues. According 
to his recollection, "There was an almost visible thawing of attitude by the airing 
of the problem" at the symposium. 74 

Less than a year after Shimkin's 1 95 1 San Francisco symposium, the 
organizers of the "First International Congress of the Histopathology of the 
Nervous System," which was held in Rome, were sufficiently concerned with 
ethical issues that they invited Pope Pius XII to address "The Moral Limits of 
Medical Methods of Research and Treatment." In a speech before 427 medical 
researchers from around the world (including 62 Americans), the pope firmly 
endorsed the principle of obtaining consent from research subjects— whether sick 
or healthy. He also pointed his audience to the relatively recent lessons of the 
Nuremberg Medical Trial, which he summed up as teaching that "man should not 
exist for the use of society; on the contrary, the community exists for the good of 
man." 75 In an interview in 1961, Dr. Thomas Rivers, a prominent American virus 
researcher, recalled that the pope's words had been influential among medical 



154 



Chapter 2 

scientists working during the 1950s: 

[I]n September 1952, Pope Pius XII had given a 
speech at the First International Congress on the 
Histopathology of the Nervous System in which he 
outlined the Roman Catholic Church's position on 
the moral limits of human experimentation for 
purposes of medical research. That speech had a 
very broad impact on medical scientists both here 
and abroad. 76 

The growing influence of the Nuremberg Medical Trial can be seen by 
looking at two editions of the best-known textbook of American medical 
jurisprudence in the midtwentieth century. In the 1949 edition of Doctor and 
Patient and the Law, Louis J. Regan, a physician and lawyer, offered very little 
under the heading "Experimentation," and what he did offer made no reference to 
Nuremberg: 

The physician must keep abreast of medical 
progress, but he is responsible if he goes beyond 
usual and standard procedures to the point of 
experimentation. If such treatment is considered 
indicated, it should not be undertaken until 
consultation has been had and until the patient has 
signed a paper acknowledging and assuming the 
risk. 77 

However, in Regan's next edition of the same text, published in 1956, his few 
lines on human experimentation had been expanded to three pages. He presented 
a lengthy paraphrasing of the Nuremberg Code, and he repeated verbatim 
(without quotation marks) the judges' preamble to the Code, stating that "all 
agree" about these principles. Regan characterized the standards enunciated by 
the judges at Nuremberg as "the most carefully developed set of precepts 
specifically drawn to meet the problem of human experimentation." Immediately 
following his discussion of Nuremberg, Regan laid out the 1946 standards of the 
American Medical Association, which, as he put it, researchers needed to meet 
"in order to conform with the ethics of the American Medical Association." 78 

NEW TIMES, NEW CODES 

In the spring of 1959 the National Society for Medical Research (NSMR), 
an organization that Andrew Ivy had helped to found in 1946, sponsored a 



155 



Parti 

"National Conference on the Legal Environment of Medicine" at the University of 
Chicago. Human experimentation was one of the major topics presented for 
discussion by the 148 conference participants, primarily medical researchers, 
from around the country. The published report of this conference reveals that the 
many researchers who gathered in Chicago understood the Nuremberg Code well 
enough to use it as a point of departure for discussion. As a group, the conferees 
acknowledged that "[t]he ten principles [of the Nuremberg Code] have become 
the principal guideposts to the ethics of clinical research in the western world." 
Not all those in attendance, however, seemed to have been entirely pleased with 
this state of affairs. A "Committee on the Re-Evaluation of the Nuremberg 
Experimental Principles" reported general agreement with "the spirit of these 
precautions" but discomfort with a number of "particulars." For example, they 
suggested that the absolute requirement for consent in the Code's first principle 
might be softened by inserting "either explicit or reasonably presumed" before the 
word "consent." They also added a clause that would allow for third-party 
permission for "those not capable of personal consent." 79 

The 1959 NSMR conference strongly suggests that by the late 1950s many 
and perhaps even most American medical researchers had come to recognize the 
Nuremberg Code as the most authoritative single answer to an important question: 
What are the rules for human experimentation? The same conference also 
provides compelling evidence that many researchers who were giving the ethical 
issues surrounding human experimentation serious attention at this time were not 
entirely happy with the prospect of living by the letter of the Code. The sources 
of discomfort with the Nuremberg Code can be grouped, retrospectively, into 
three broad categories. First, some recognized the discrepancies between what 
they had come to know as real practices in research on patient-subjects and what 
they read in the lofty, idealized language of the Code. Others simply disagreed 
with some elements of the Code. Still others disliked the very idea of a single, 
concrete set of standards to guide behavior in such a complex matter as human 
experimentation. 

Henry Beecher, the Harvard-based medical researcher who was Louis 
Lasagna's mentor in the early 1950s, published a paper, "Experimentation in 
Man," in the Journal of the American Medical Association only a few months 
before the NSMR conference in Chicago. In this lengthy piece, Beecher 
addressed a mixture of all three sources of discomfort with the Nuremberg Code. 
Beecher offered the assertion that "it is unethical and immoral to carry out 
potentially dangerous experiments without the subject's knowledge and consent" 
as the "central conclusion" of his paper. 80 But, even with this strong statement, he 
was not entirely happy with the first clause of the Code; he viewed the 
Nuremberg consent clause as too extreme and not squaring with the realities of 
clinical research: 



156 



Chapter 2 

It is easy enough to say, as point one [of the 
Nuremberg Code] does, that the subject "should 
have sufficient knowledge and comprehension of 
the elements of the subject matter involved as to 
enable him to make an understanding and 
enlightened decision." Practically, this is often 
quite impossible ... for the complexities of 
essential medical research have reached the point 
where the full implications and possible hazards 
cannot always be known to anyone and are often 
communicable only to a few informed investigators 
and sometimes not even to them. Certainly the full 
implications of work to be done are often not really 
communicable to lay subjects. . . . [P]oint one states 
a requirement very often impossible of fulfillment 
[emphasis added]. 81 

Beecher's second form of difficulty with the Code can be found in his 
opinion of another Nuremberg clause, which states, in part, that a human 
experiment should not be "random and unnecessary in nature." Beecher cited 
"anesthesia, x-rays, radium, and penicillin" as important medical breakthroughs 
that had resulted from "random" experimentation. He further stated that he 
"would not know how to define experiments 'unnecessary in nature. " ,82 Finally, 
Beecher expressed skepticism in general that any code could provide effective 
moral guidance for researchers working with human subjects. Near the beginning 
of his paper he wrote that "the problems of human experimentation do not lend 
themselves to a series of rigid rules." 83 Later in the piece, he expanded on this 
thought: 

[I]t is not my view that many rules can be laid down 
to govern experimentation in man. In most cases, 
these are more likely to do harm than good. Rules 
are not going to curb the unscrupulous. Such abuses 
as have occurred are usually due to ignorance and 
inexperience. The most effective protection for all 
concerned depends upon a recognition and an 
understanding of the various aspects of the 
problem. 84 

Another episode involving Henry Beecher further clarifies the medical 
profession's dissatisfaction with the construction of the Nuremberg Code. In the 
fall of 1961, Beecher and other members of the Harvard Medical School's 



157 



Parti 

Administrative Board, the school's governing body, were presented with a set of 
"rigid rules" that had begun to appear in Army medical research contracts. The 
members of the board quickly recognized the "Principles, Policies and Rules of 
the Surgeon General, Department of the Army, Relating to the Use of Human 
Volunteers in Medical Research" awarded by the Army as little more than a 
restatement of the Nuremberg Code. The Army Office of the Surgeon General's 
provisions, as we discussed in chapter 1, originally appeared in 1954. Given what 
we have just read of Beecher, it is not surprising that he was uncomfortable with 
the prospect of working in strict accordance with the Nuremberg Code if he were 
to receive funding from the Army, nor, as we see from the minutes of the 
Administrative Board meetings in which this matter came up for discussion, was 
Beecher alone in his opposition. At the October 6, 1961, meeting of the board, 
when the Army contract insertion was first mentioned, "some members . . . felt 
that with the minor changes the regulations were acceptable, while others 
described the regulations as vague, ambiguous and, in many instances, impossible 
to fulfill."" 5 

One of Beecher's fellow board members, Assistant Medical School Dean 
Joseph W. Gardella, M.D., produced a thoroughgoing written critique of the 
"Principles, Policies, and Rules of the Surgeon General" (and, thus, of the 
Nuremberg Code) following the October 1961 meeting for the consideration of 
the other board members. Gardella opened his analysis with some general 
comments on the intended meaning of the Nuremberg Code: 

The Nuremberg Code was conceived in reference to 
Nazi atrocities and was written for the specific 
purpose of preventing brutal excesses from being 
committed or excused in the name of science. The 
code, however admirable in its intent, and however 
suitable for the purpose for which it was conceived, 
is in our opinion not necessarily pertinent to or 
adequate for the conduct of medical research in the 
United States. 86 

After questioning the pertinence of the Nuremberg Medical Trial to American 
medical science, Gardella went on to raise a general question about the scope of 
the Nuremberg Code; he strongly suggested that the code was not meant to cover 
what he perceived as the morally distinct enterprise of conducting potentially 
therapeutic research with sick patients: 

Does it refer only to healthy volunteers who have 
nothing to gain in terms of their health by 
participating as research subjects? Or does it 



158 



Chapter 2 

include the sick, whose physicians foresee for them 
the possibility of personal benefit through their 
participation? The distinction is important in that 
we believe that it would be difficult and might 
prove to be impossible to devise one set of guiding 
principles that would apply satisfactorily to both of 
these two different categories. 87 

Gardella offered a variety of specific objections to the Army surgeon 
general's "Principles," but several of these points related directly to the general 
questions raised above. The first rule of the Army "Principles" stated (in a clear 
example of borrowing from the Nuremberg Code) that "the voluntary consent of 
the human subject is absolutely essential." Gardella, like Beecher, did not 
question the general spirit of this stricture; he worried about the practical 
application of this seemingly simple idea. Some of Gardella's worries arose 
specifically in the context of research with sick patients: 

The concept of "voluntary consent" is of central 
importance in any code relating to experimentation 
on humans. . . . And yet the concept of "consent" is 
not satisfactorily defined [in the Army 
"Principles"]. . . . The quality of the subject's 
consent depends . . . upon an interpretation ... of a 
factual situation which will frequently be complex. 
Could the subject comprehend what he was told? 
Did he in fact comprehend? How far was his 
consent influenced by his condition or by his trust 
in his physician? These questions may be easily 
answered in the case of the [healthy] volunteer. 
They may be more difficult for the sick [emphasis 
added]. 88 

Perhaps the most significant addition to the Nuremberg Code found in the 
Army "Principles" was the requirement for written consent from research 
subjects. Gardella objected to this requirement in research on patients in a firm, 
and revealing, fashion: 

This condition is . . . inappropriate except in 
connection with healthy normal volunteers. The 
legal overtones and implications attendant to such a 
requirement have no place in [a] patient-physician 
relationship based on trust. Here such faith and 



159 



Parti 

trust serve as the primary basis of the subject's 
consent. Moreover being asked to sign a somewhat 
formal paper is likely to provoke anxiety in the 
subject [i.e., patient] who can but wonder at the 
need for so much protocol. 89 

Dr. Gardella presented his analysis of the Army "Principles" to the other 
members of the Harvard Medical School Administrative Board on March 23, 
1962. The minutes of that meeting document that Gardella's views were not 
extreme or exceptional among leading medical scientists in the early 1960s, at 
least at Harvard University: "The members of the Board were in general 
agreement with the objections and criticisms expressed in [Gardella's] critique." 90 
At this same meeting, Henry Beecher "agreed, in an expansive moment, to 
attempt to capture in a paragraph or so the broad philosophical and moral 
principles that underlie the conduct of research on human beings at the Harvard 
Medical School." 91 The members of the board hoped that such a statement might 
satisfy the Army and that it would allow Harvard, as Gardella put it, "to avert the 
catastrophic impact of the Surgeon General's regulation." 92 

A few months later, Beecher had completed a two-and-a-half-page 
"Statement Outlining the Philosophy and Ethical Principles Governing the 
Conduct of Research on Human Beings at Harvard Medical School." At the June 
8, 1962, board meeting, Beecher's colleagues "commended" and "reaffirmed" the 
views expressed in Beecher's document. 93 In this statement, as in his 1959 
published paper, Beecher emphasized the significance of consent, but he also 
asserted that "it is folly to overlook the fact that valid, informed consent may be 
difficult to the point of impossible to obtain in some cases." More than consent, 
Beecher believed in the significance of "a special relationship of trust between 
subject or patient and the investigator." In the end, Beecher concluded that the 
only reliable foundation for this relationship was a virtuous medical researcher, 
with virtuous peers: 

It is this writer's point of view that the best 
approach [to research with human subjects] 
concerns the character, wisdom, experience, 
honesty, imaginativeness and sense of responsibility 
of the investigator who in all cases of doubt or 
where serious consequences might remotely occur, 
will call in his peers and get the benefit of their 
counsel. Rigid rules will jeopardize the research 
establishments of this country where 
experimentation in man is essential. 94 



160 



Chapter 2 

Available evidence suggests that, by offering Henry Beecher's 
replacement for the Nuremberg Code, representatives of Harvard Medical School 
were able to extract a clarification during a meeting with Army Surgeon General 
Leonard D. Heaton, on July 12, 1962, that the "Principles" being inserted into 
Harvard's research contracts with the Army were "guidelines" rather than "rigid 
rules." 95 

While the Harvard Medical School discussion of the Army's "Principles" 
took place behind closed doors and involved a policy of limited applicability, the 
leaders of the international medical community were simultaneously engaged in a 
far more visible and global attempt to bring the standards enunciated in the 
Nuremberg Code into line with the realities of medical research. The 1964 
statement by the World Medical Association (WMA), commonly known as the 
Declaration of Helsinki, created two separate categories in laying out rules for 
human experimentation: "Clinical Research Combined with Professional Care" 
and "Non-therapeutic Clinical Research." 96 In the former category, physicians 
were required to obtain consent from patient-subjects only when "consistent with 
patient psychology." In the latter type of research, the consent requirements were 
more absolute: "Clinical research on a human being cannot be undertaken 
without his free consent, after he has been fully informed." Another noteworthy 
deviation from the Nuremberg Code is Helsinki's allowance (in both therapeutic 
and nontherapeutic research) for third-party permission from a legal guardian. 97 

As one might predict from the similarity between the changes introduced 
by the Declaration of Helsinki and the changes to the Nuremberg Code suggested 
by the American participants at the NSMR conference in 1959, the WMA 
document met with widespread approval among researchers in this country. 
Organizations including the American Society for Clinical Investigation, the 
American Federation for Clinical Research, and the American Medical 
Association offered their quick and enthusiastic endorsements. 98 Compared with 
the lofty, idealized language of the Nuremberg Code, the Helsinki Declaration 
may have seemed more sensible to many researchers in the early 1 960s because it 
offered rules that more closely resembled research practice in the clinical setting. 

CONCLUSION 

In the late 1940s American medical researchers seldom recognized that 
research with patient-subjects ought to follow the same principles as those applied 
to healthy subjects. Yet, as we have seen in this chapter, some of those few who 
asked themselves hard questions about their research work with patients 
concluded that people who are ill are entitled to the same consideration as those 
who are not. That some did in fact reach this conclusion is evidence that it was 
not beyond the horizon of moral insight at that time. Nevertheless, they were a 
minority of the community of physician researchers, and the organized medical 



161 



Parti 

profession did not exhibit a willingness to reconsider its responsibilities to 
patients in the burgeoning world of postwar clinical research. 

While a slowly increasing number of investigators reflected on the ethical 
treatment of human subjects during the 1950s, it was not until the 1960s and a 
series of highly publicized events with names like "Thalidomide," 
"Willowbrook," and "Tuskegee" that it became apparent that a professional code, 
whether it originated in Nuremberg or Helsinki, did not provide sufficient 
protection against exploitation and abuse of human subjects of research. In the 
next chapter we examine how the federal government became intimately, 
extensively, and visibly involved in the regulation of research with human 
subjects. 



162 



ENDNOTES 



1 . A detailed recounting of the first series of Nuremberg Trials can be found in 
Telford Taylor, The Anatomy of the Nuremberg Trials: A Personal Memoir (New York: 
Alfred A. Knopf, 1992). Taylor describes the motivation for the second series of 
Nuremberg Trials in the introduction to this book (p. xii). He also mentions that he 
"hope[s] later to write a description of these subsequent trials" (p. xii). Taylor served as 
an assistant to chief American prosecutor Robert H. Jackson at the first series of trials; he 
was the chief prosecutor for the second series, which eventually included twelve separate 

trials. 

2. United States v. Karl Brandt et al, "The Medical Case, Trials of War 
Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10" 
(Washington, D.C.: U.S. Government Printing Office, 1949). This two-volume set 
contains an abridged set of transcripts from the Nuremberg Medical Trial. A general 
timeline for the trial can be found on p. 3 of volume 1 ; the quotation of Taylor's charges 
can be found in the reproduction of his opening statement in volume 1, p. 27. The 
published trial transcripts provide extensive detail on the experiments carried out by 
German medical scientists on inmates at Nazi concentration camps. These experiments 
included a long list of brutalities carried out in the name of medical science. Some of 
these were specifically related to the Nazi war effort. German investigators conducted 
high-altitude tolerance tests for the Luftwaffe using a low-pressure chamber. Scientists 
forced prisoners to enter the chamber and subjected them to extreme pressure changes 
that resulted in excruciating pain and, sometimes, death. Among these experiments were 
human twin studies related to genetics and germ warfare. For example, a series of 
experiments involved injecting one twin with a potential germ warfare agent to test the 
effects of that agent. If the twin injected with the germ died, the other twin was 
immediately killed to compare the the organs between the healthy and the sick twin. 
Another series of experiments related to downed airman and shipwrecked sailors who 
were faced with deprivation of potable water. In these tests, prisoners were divided into 
four groups: the first received no water; a second set was forced to drink ordinary 
seawater; the third would drink seawater processed to remove the salty taste (but not the 
actual salt); and fourth group could drink desalinated seawater. Many of the subjects in 
the first three groups died. German researchers also compelled prisoners to engage in a 
variety of other cruel experiments, many of which were concerned with infectious 
diseases such as malaria, epidemic jaundice, and typhus. More information can be 
found on the Nazi prison camp experiments in several sources including Robert Jay 
Lifton, The Nazi Doctors: Medical Killing and the Psychology of Genocide (New York: 
Basic Books, 1986); Robert N. Proctor, Racial Hygiene: Medicine under the Nazis 
(Cambridge, Mass.: Harvard University Press, 1988); and George J. Annas and Michael 
A. Grodin, eds., The Nazi Doctors and the Nuremberg Code: Human Rights in Human 
Experimentation (New York: Oxford University Press, 1992). 

Japanese medical scientists, especially those associated with a biological warfare 
(BW) research corps known as Unit 731, also conducted many cruel medical experiments 
during the war. Until recently, these experiments were virtually unknown because 
American military and medical officials struck a postwar deal with leading Japanese 
scientists associated with Unit 73 1 : immunity from war crimes prosecution in exchange 
for exclusive American access to the results of the Japanese BW experiments. The 

163 



Japanese experiments and the American cover-up have recently received coverage in 
Sheldon Harris's Factories of Death: Japanese Biological Warfare, 1932-1945, and the 
American Cover Up (London/New York: Routledge, 1994). See also Peter Williams and 
David Wallace, Unit 731: The Japanese Army's Secret of Secrets (London: Hodder and 
Stoughton, 1989); and John W. Powell, Jr., "Japan's Biological Weapons, 1930-1945," 
Bulletin of the Atomic Scientists 37 (October 1981): 44-53. 

3. American Medical Association, Board of Trustees, minutes of the May 1946 
meeting, AMA Archive, Chicago, Illinois (ACHRE No. IND-072595-A), 156-157. 

4. A full-blown biography of Ivy remains to be written, but some biographical 
information can be found in the following brief notices: Carl A. Dragstedt, "Andrew 
Conway Ivy," Quarterly Bulletin of the Northwestern University Medical School 1 8 
(Summer 1944): 139-140; Morton I. Grossman, "Andrew Conway Ivy (1893-1978)," 
Physiologist 21 (April 1978): 1 1-12; D. B. Bill, "A. C. Ivy-Reminiscences," 
Physiologist 22 (October 1979): 21-22. 

5. The quotation is taken from Andrew C. Ivy, "Nazi War Crimes of a Medical 
Nature," Federation Bulletin 33 (May 1947): 133. Ivy first publicly offered this view of 
the Nuremberg prosecutors' confusion about the ethics and legality of human 
experimentation when he presented this paper at an annual meeting of the Federation of 
State Medical Boards of the United States on 10 February 1947-just a few months after 
the start of the Medical Trial. In this presentation Ivy said that he traveled to Germany 
in August 1946. In a similar description of his experiences with the Nuremberg 
prosecution team published a few years later Ivy reiterates a similar story except that the 
date of his initial travel is given as July 1946: A. C. Ivy, "Nazi War Crimes of a Medical 
Nature," Journal of the American Medical Association 139(15 January 1 949): 131. An 
editorial in JAMA confirms some of the essential elements of Ivy's early work with the 
Nuremberg prosecutors (his selection by the AMA Board of Trustees at the request of the 
federal government and his travel to Germany "a few months" before November 1946): 
"The Brutalities of Nazi Physicians," JAMA 132 (23 November 1946): 714. The basic 
narrative of Ivy's selection by the Board of Trustees and his travel to Europe can also be 
found in R. L. Sensenich, "Supplementary Report of the Board of Trustees," JAMA 132 
(21 December 1946): 1006. 

6. American Medical Association, Board of Trustees, minutes of the 16 August 
1946 meeting, AMA Archive, Chicago, Illinois (ACHRE No. IND-072595-A), 8-9. 

7. American Medical Association, Board of Trustees, minutes of the 19 
September 1946 meeting, AMA Archive, Chicago, Illinois (ACHRE No. IND-072595- 
A), 51-52. 

8. A. C. Ivy, "Report on War Crimes of a Medical Nature Committed in 
Germany and Elsewhere on German Nationals and the Nationals of Occupied Countries 
by the Nazi Regime during World War II," 1946. This report was not published, but it is 
available at the National Library of Medicine. A copy also exists in the AMA Archive 
(ACHRE No. DOD-063094-A). 

9. United States v. Karl Brandt et ah, "The Medical Case, Trials of War 
Criminals before the Nuremberg Military Tribunals under Control Council Law No. 10" 
(Washington, D.C.: U.S. Government Printing Office, 1949), 2: 181-182. The judges' 
preamble to the Code states that "[a]ll agree . . . that certain basic principles must be 
observed in order to satisfy the moral, ethical and legal" aspects of human 
experimentation. 



164 



10. Ivy's recitation of his own set of rules does not appear in the published 
abridged transcripts of the trial. See the complete transcripts of the trial, which are 
available on microfilm at the National Archives (National Archives Microfilm, M887, 
reel 9, 13 June 1947, pp. 9141-9142). Throughout this chapter, we cite the abridged 
transcripts wherever possible and the full transcripts only if necessary. 

11. Leo Alexander later reproduced his 1 5 April 1 947 memo in two 
publications: "Limitations in Experimental Research on Human Beings," Lex et Scientia 
3 (January-March 1966): 20-22, and "Ethics of Human Experimentation," Psychiatric 
Journal of the University of Ottawa 1 (1976): 42-44. In the 1976 article, Alexander made 
a seemingly exaggerated claim to be "the original author of the Nuremberg Code" (p. 40). 
Side-by-side comparison of Ivy's rules, Alexander's memo, and the Nuremberg Code 
does, however, suggest that the judges drew two original contributions from Alexander's 
memo: clauses 6 and 7 of the Nuremberg Code are embedded in the 15 April memo (they 
do not appear in Ivy's rules). 

12. McHaney's closing statement can be found in the complete microfilm 
transcripts of the trial available through the National Archives. McHaney's closing 
statement and Alexander's memorandum (and Alexander's claim to authorship of the 
Code) are also reproduced in Michael A. Grodin's "Historical Origins of the Nuremberg 
Code," in The Nazi Doctors and the Nuremberg Code: Human Rights in Human 
Experimentation, 134-137. 

13. American Medical Association, Board of Trustees, minutes of the 19 
September 1946 meeting, AM A Archive, Chicago, Illinois (ACHRE No. IND-072595- 

A). 

14. The AM A reports that the records of the Judicial Council for all of the 1940s 
have been lost. Personal communication between Marilyn Douros, of the AM A 
Archives, and Jon M. Harkness (ACHRE), 19 January 1995. 

15. "Supplementary Report of the Judicial Council," proceedings of the House 
of Delegates Annual Meeting, 9-1 1 December 1946, JAMA 132 (28 December 1946): 
1090. The bracketed addition to rule 1 was added in the final version of statement, which 
was approved by the House of Delegates on 1 1 December 1946. 

16. William A. Coventry, "Report of the Reference Committee on 
Miscellaneous Business," proceedings of the House of Delegates Meeting, 9-1 1 
December 1946, JAMA 133 (4 January 1947): 35. 

17. Robert Williamson, an AMA archivist, reports that in 1942, 65 percent of 
American physicians were members of the AMA, and in 1949, 75 percent of American 
physicians were members; he did not have percentage figures available for 1946. 
Williamson also provided the absolute number of members for 1946. Personal 
communication between Jon M. Harkness (ACHRE) and Robert Williamson, 4 January 
1995. 

1 8. United States v. Karl Brandt et al. , "The Medical Case, Trials of War 
Criminals before the Nuremberg Military Tribunal under Control Council Law No. 10," 
voi. 2, 83. 

19. Ibid. 

20. Complete transcripts of the Nuremberg Medical Trial, National Archives 
Microfilm, M887, reel 9, 13 June 1947, pp. 9168-9170. 

2 1 . Susan E. Lederer, Subjected to Science: Experimentation in America before 
the Second World War (Baltimore: Johns Hopkins University Press, 1995), 105. 

165 



22. Lederer recounts the historical details of the yellow fever experiment (pp. 
19-23) and explores Reed's powerful legacy (pp. 132-134) in Subjected to Science. 

23. Theodore Woodward, interview by Gail Javitt and Suzanne White-Junod 
(ACHRE), transcript of audio recording, 14 December 1994 (ACHRE Research Project 
Series, Interview Program File, Ethics Oral History Project), 6. 

24. Interview with Woodward, 14 December 1994, 10. 

25. John D. Arnold, interview by Jon M. Harkness (ACHRE), transcript of 
audio recording, 6 December 1994 (ACHRE Research Project Series, Interview Program 
File, Ethics Oral History Project), 18. 

26. The list of participants exists in the extant records of the LMRI project 
available at the Center for Law and Health Sciences, School of Law, Boston University. 
The quotation explaining the goal of the meeting is taken from the first page of a 
summary of the conference prepared for the project's final report, which was not 
published: Anne S. Harris, "The Concept of Consent in Clinical Research: Analytic 
Summary of a Conference," chapter 6 in A Study of the Legal, Ethical, and 
Administrative Aspects of Clinical Research Involving Human Subjects: Final Report of 
Administrative Practices in Clinical Research, fNIHJ Research Grant No. 7039 Law- 
Medicine Research Institute, Boston University, 1963 (ACHRE No. BU-053194-A). 

27. The National Institutes of Health awarded LMRI almost $100,000 on 1 
January 1960 to begin this project, which concluded 31 March 1963. The general 
statement of the project's purpose appears in LMRI final report, chapter 1 ("Focus of the 
Inquiry"), 1. 

28. LMRI final report, chapter 6, 48. 

29. Louis Lasagna, interview by Jon M. Harkness and Suzanne White-Junod 
(ACHRE), transcript of audio recording, 13 December 1994 (ACHRE Research Project 
Series, Interview Program File, Ethics Oral History Project), 5. 

30. Ibid., 11. 

31. Extensive newspaper clippings related to the Nuremberg Medical Trial exist 
in Beecher's personal papers in the Special Collections Department, Countway Library, 
Harvard University. Beecher's first major publication on research ethics appeared in early 
1959: Henry K. Beecher, "Experimentation in Man," JAMA 169 (31 January 1959): 461- 
478. Of course, he is best known for a 1966 article: Henry K. Beecher, "Ethics and 
Clinical Research," New England Journal of Medicine 274 (16 June 1966): 1354-1360. 
Significantly, Beecher acknowledged in a manuscript copy of the original version of the 
NEJM paper, which he presented at a conference for science journalists on 22 March 
1965, that "in years gone by work in my laboratory could have been criticized." Beecher, 
"Ethics and the Explosion of Human Experimentation," 2a, Beecher Papers, Countway 
Library (ACHRE No. IND-072595-A). 

32. Jay Katz, "Human Experimentation and Human Rights," St. Louis University 
Law Journal 38 (1993): 28. 

33. Stanley Joel Reiser, Arthur J. Dyck, and William J. Curran, eds., Ethics in 
Medicine: Historical Perspectives and Contemporarv Concerns (Cambridge, Mass.: The 
MIT Press, 1977), 7. 

34. Otto E. Guttentag, "The Physician's Point of View," Science 1 17 (1953): 
207-210; the quotation is from 208. Guttentag's article appeared in Science with three 
others that had been presented at the 1951 symposium: Michael B. Shimkin, "The 
Researcher Worker's Point of View," 205-207; Alexander M. Kidd, "Limits of the Right 



166 



of a Person to Consent to Experimentation on Himself," 211-212; and W. H. Johnson, 
"Civil Rights of Military Personnel Regarding Medical Care and Experimental 
Procedures," 212-215. 

35. Guttentag, "The Physician's Point of View," 208. 

36. Ibid., 210. 

37. John C. Ford, "Notes on Moral Theology," Theological Studies 6 (December 
1945): 534-535. Ford's discussion of human experimentation arose in a lengthy and 
discursive review of issues and ideas in moral theology. For several years, he contributed 
a similar review to each volume of Theological Studies. 

38. Transcripts of "Social Responsibility in Pediatric Research" conference, 1 
May 1961, 7. LMRI records, Center for Law and Health Sciences, School of Law, Boston 
University (ACHRE No. BU-053194-A). 

39. "LMRI Final Report," chapter 6, 43. 

40. Ibid., 43-44. 

41. Ibid., 44. 

42. Ibid., 46-47. 

43. Committee member and historian Susan Lederer took principal 
responsibility for organizing the Ethics Oral History Project, with assistance from several 
members of the staff including two historians experienced in the techniques of oral 
history. The Committee also drew on advice from several outside experts, including 
historians and ethicists, to create a list of potential interviewees and to refine the list of 
questions that we wanted to explore during interviews. In total, the Committee 
conducted twenty-two interviews in the Ethics Oral History Project. Most of the subjects 
were medical researchers whose careers began in the late 1940s or early 1950s, but we 
also spoke with some research administrators. In general, we chose to interview 
researchers who had exhibited some particular interest in research ethics during their 
careers. But this does not mean that we held interviews only with researchers who 
viewed recent developments in research ethics in a positive fashion. The interviews were 
all recorded on audio tape and professionally transcribed. Interview subjects had an 
opportunity to review the transcripts. Complete sets of all transcripts can be found in the 
archival records of the Advisory Committee. 

44. Interview with Lasagna, 13 December 1994, 13. 

45. Paul Beeson, interview by Susan E. Lederer (ACHRE), transcript of audio 
recording, 20 November 1994 (ACHRE Research Project Series, Interview Program 
File, Ethics Oral History Project), 16-17. 

46. Leonard Sagan, interview by Gail Javitt, Suzanne White-Junod, Sandra 
Thomas, and John Kruger (ACHRE), transcript of audio recording, 17 November 1994 
(ACHRE Research Project Series, Interview Program File, Ethics Oral History Project), 
13-14. 

47. Ibid., 19-20. 

48. Stuart Finch, interview by Gail Javitt, Suzanne White-Junod, and Valerie 
Hurt (ACHRE), transcript of audio recording, 6 December 1994 (ACHRE Research 
Project Series, Interview Program File, Ethics Oral History Project), 52. 

49. Interview with Paul Beeson, 20 November 1994, 39. 

50. Thomas Chalmers, interview by Jon Harkness (ACHRE), transcript of audio 
recording, 9 December 1994 (ACHRE Research Project Series, Interview Program File, 
Ethics Oral History Project), 75. 

167 



5 1 . Herman Wigodsky, interview by Gail Javitt and Suzanne White-Junod 
(ACHRE), transcript of audio recording, 17 January 1995 (ACHRE Research Project 
Series, Interview Program File, Ethics Oral History Project), 14. 

52. For an analysis and translation of the 1931 German rules see Hans-Martin 
Sass, "Reichsrundschreiben 1931: Pre-Nuremberg German Regulations Concerning New 
Therapy and Human Experimentation," Journal of Medicine and Philosophy 8 ( 1 983): 
99-1 1 1 . A similar analysis and translation of the same set of rules appears in Grodin, 
"Historical Origins of the Nuremberg Code," 129-132. 

53. Full trial transcripts, 9142. 

54. Abridged trial transcripts, 83. 

55. Interview with Dr. Herman Wigodsky, 17 January 1995, 16-17. 

56. Ruth Faden and Tom Beauchamp, A History and Theory of Informed 
Consent (New York: Oxford University Press, 1986), 96. 

57. Ivy's several examples ranged from Walter Reed's turn-of-the-century 
experiments with yellow fever to wartime malaria experiments in American state and 
federal prisons. See page 91 19 of the full trial transcripts for Ivy's discussion of the 
Reed experiments and pages 9125-9129 for his description of the malaria experiments 
that had taken place in the United States during the war. 

58. David J. Rothman, Strangers at the Bedside: A Histoiy of How Law and 
Bioethics Transformed Medical Decision Making (New York: Basic Books, 1994), 62. 

59. Interview with John Arnold, 6 December 1 994, 9- 1 0. 

60. Herbert Abrams, interview by Jon Harkness (ACHRE), transcript of audio 
recording, 12 January 1995 (ACHRE Research Project Series, Interview Program File, 
Ethics Oral History Project), 25. 

61. Dorothy Levenson, Montefwre: The Hospital as Social Instrument, 1884- 
1984 (New York: Farrar, Straus & Giroux, 1984). For information on the presence of 
Jewish refugee physicians at Montefiore, see pages 154-155. 

62. Rothman, Strangers at the Bedside, 62-63. 

63. Katz, "The Consent Principle of the Nuremberg Code," 228. 

64. William Silverman, interview by Gail Javitt (ACHRE), transcript of audio 
recording 14 February 1995 (ACHRE Research Project Series, Interview Program File, 
Ethics Oral History Project), 61-62. 

65. Ibid., 87-88. 

66. "Why Human 'Guinea Pigs' Volunteer," New York Times Magazine, 13 
April 1958,62. 

67. See, for example, John L. O'Hara, "The Most Unforgettable Character I've 
Met," Reader's Digest, May 1948, 30-35; Thomas Koritz, "I Was a Human Guinea Pig," 
Saturday Evening Post, 25 July 1953, 27, 79-80, 82; Don Wharton, "A Treasure in the 
Heart of Every Man,'" Reader's Digest, December 1954, 49-53 (condensed from 
"Prisoners Who Volunteer, Blood, Flesh-and Their Lives," American Mercuiy, 
December 1954, 51-55); Howard Simons, "They Volunteer to Suffer," Saturday Evening 
Post, 26 March 1960, 33, 87-88. 

68. "Experiments on Prisoners," Science Newsletter (also Science News), 2 1 
February 1948,53, 117. 

69. "C.O.'s Offer Selves for Atomic Experiments," Christian Century, 20 
October 1954, 1260. 



168 



70. Robert D. Potter, "Are We Winning the War Against TB?" Saturday 
Evening Post, 15 January 1949. Cited in Marcel C. LaFollette, Making Science Our 
Own: Public Images of Science 1910-1955 (Chicago: University of Chicago Press, 1990), 
138-140. 

71 . Renee C. Fox, Experiment Perilous: Physicians and Patients Facing the 
Unknown (Philadelphia: University of Pennsylvania Press, 1974, first published 1959). 
Fox describes her long days of observation on page 15; she discusses the Nuremberg 
Code at 46-47. 

72. Michael B. Shimkin, As Memory Serves: Six Essays on a Personal 
Involvement with the National Cancer Institute, 1938-1978 (Bethesda, Md.: U.S. 
Department of Health and Human Services, 1983), 127. 

73. Ibid., 128. 

74. Ibid., 127. 

75. The quotation is a translation from the French in which Pius XII delivered 
the address: "II faut remarquer que l'homme dans son etre personnel n'est pas ordonne en 
fin de compte a l'utilite de la societe, mais au contraire, la communaute est la pour 
rhomme." The French text can be found in the Atti del Primo Congresso Internazionale 
di Istopatologia del Sistema Nervosa/Proceedings of the First International Congress of 
Neuropathology, Rome, 8-13 September 1952. English translations of the pope's address 
appear in a variety of publications including The Linacre Quarterly: Official Journal of 
the Federation of Catholic Physicians' Guilds 19 (November 1952): 98-107 and The 
Irish Ecclesiastical Record 86 (1954): 222-230. 

76. Saul Benison, Tom Rivers: Reflections on a Life in Medicine and Science 
(Cambridge, Mass.: MIT Press, 1967), 498. 

77. Louis J. Regan, Doctor and Patient and the Law, 2d ed. (St. Louis: C. V. 
Mosby, 1949), 398. 

78. Louis J. Regan, Doctor and Patient and the Law, 3d ed. (St. Louis: C. V. 
Mosby, 1956), 370-372. 

79. Report on the National Conference on the Legal Environment of 
Medicine,27-28 May 1959 (Chicago: National Society for Medical Research, 1959); the 
quotations are from pages 91 and 88, respectively. 

80. Henry K. Beecher, "Experimentation in Man," Journal of the American 
Medical Association 169(1959): 118/470. 

81. Ibid., 121/473. 

82. Ibid., 122/474. 

83. Ibid., 109/461. 

84. Ibid., 119/471. 

85. Harvard Medical School, Harvard Medical School Administrative Board, 
proceedings of the 6 October 1961 meeting (ACHRE No. HAR-062394-A-3). 

86. Memorandum to "GPB" [Harvard Medical School Dean Berry] from "JWG" 
[Assistant Dean Gardella] ("Criticisms of 'Principles, Policies and Rules of the Surgeon 
General, Department of the Army, relating to the use of Human Volunteers in Medical 
Research Contracts awarded by the Army'") (ACHRE No. IND-072595-A), 1. 

87. Ibid., 2. 

88. Ibid. 

89. Ibid., 3. 



169 



90. Harvard Medical School, Harvard Medical School Administrative Board, 
proceedings of 23 March 1962 (ACHRE No. HAR-062394-A-3). 

91. Joseph W. Gardella, Assistant Dean, Harvard Medical School to Henry K. 
Beecher, Massachusetts General Hospital, 27 March 1962 ("I write to confirm my 
impression . . .") (ACHRE No. HAR-062394-A-4). 

92. Ibid. 

93. Harvard Medical School, Harvard Medical School Administrative Board, 
proceedings of 8 June 1962 (ACHRE No. HAR-062394-A-3). 

94. Henry Beecher, undated ("Statement Outlining the Philosophy and Ethical 
Principles Governing the Conduct of Research on Human Beings at the Harvard Medical 
School") (ACHRE No. IND-072595-A). 

95. Henry K. Beecher to Lieutenant General Leonard D. Heaton, 12 July 1962 
("I have just returned to Boston . . .") (ACHRE No. HAR-062394-A-2). 

96. World Medical Association, "Declaration of Helsinki: Recommendations 
Guiding Medical Doctors in Biomedical Research Involving Human Subjects," adopted 
by the Eighteenth World Medical Assembly, Helsinki, Finland, 1964. 

97. "Draft Code of Ethics on Human Experimentation," British Medical Journal 
2 (1962): 1119; "Human Experimentation: Code of Ethics of the World Medical 
Association," British Medical Journal 2 (1964): 177. 

98. Faden and Beauchamp, A History and Theory of Informed Consent, 1 56- 1 57, 
and Paul M. McNeill, The Ethics and Politics of Human Experimentation (Cambridge, 
U.K.: Press Syndicate of the University of Cambridge, 1993), 44-47. For a more detailed 
comparison between the Nuremberg Code and the Declaration of Helsinki, see Jay Katz, 
"The Consent Principle of the Nuremberg Code," 231-234. 



170 



Government Standards for 

Human Experiments: 

The 1960s and 1970s 



1 he year 1974 marks the upper bound for the period of the Advisory 
Committee's historical investigation. That year two landmark events in the 
history of government policy on research involving human subjects took place: 
the promulgation by the Department of Health, Education, and Welfare (DHEW) 
of comprehensive regulations for oversight of human subject research and 
passage by Congress of the National Research Act. The DHEW regulations set 
rules for oversight of human subject research supported by the single largest 
funding source for such research, and the National Research Act authorized the 
establishment of the National Commission for the Protection of Human Subjects 
of Biomedical and Behavioral Research (also known as the National 
Commission), which was charged with examining the conduct of research 
involving human subjects. In the years following 1974, many of the rules 
promulgated by DHEW were subsequently adopted by various other government 
agencies, culminating in governmentwide regulations under the Common Rule in 
1991.' 

In the first part of this chapter, we trace the developments in the 1960s and 
early 1970s that influenced and led up to the DHEW regulations and the National 
Research Act. These developments included congressional hearings on the 
practices of the drug industry and the thalidomide tragedy, critical scholarly 
writings, interim policies at DHEW, public outcry over controversial cases of 
medical research, and the congressional hearings these cases occasioned. People 



171 



Parti 

were surprised and shocked to learn about practices and behaviors they knew to 
be wrong. While the ethical principles such practices violated may not have been 
well articulated specific to the enterprise of human research, they were part of 
individuals' moral consciousness. The history of these events has been well told 
before, and we only summarize it here, drawing heavily on the previous work of 
other authors. 2 

The 1974 regulations were promulgated by DHEW and applied only to 
that agency. Likewise, the National Research Act authorized the establishment of 
the National Commission and directed it to make recommendations to the 
secretary of DHEW. In the latter part of this chapter, we review developments in 
policies governing human research during this period in agencies other than 
DHEW. This is a history that has received comparatively little scholarly 
attention. 

In the 1970s, just as DHEW was moving ahead with broad new 
regulations, scandal rocked the Department of Defense and the CIA. It was 
revealed that, with cooperation from university researchers, these agencies had 
engaged in secret experimentation on military and civilian subjects without their 
knowledge, sometimes with tragic results. 3 The discovery of the existence of 
these secret programs led to further congressional investigations and to a 1975 
Department of the Army review of the effectiveness of the 1953 Secretary of 
Defense Wilson memorandum adopting the Nuremberg Code. This Army review 
led to the eventual declassification of the Wilson memorandum, which had been 
Top Secret upon its issuance and remained classified until 1975. It also led, much 
later, to litigation in which justices of the U.S. Supreme Court for the first time 
commented on the applicability of the Nuremberg Code to actions undertaken by 
the U.S. government. 4 The chapter concludes with a discussion of these 
important events. 

THE DEVELOPMENT OF HUMAN SUBJECT RESEARCH 
POLICY AT DHEW 

As the largest funding source in the federal government for human subject 
research, DHEW led the way in developing regulations aimed at protecting the 
rights and welfare of subjects. The evolution of the regulations, which would 
eventually be adopted on a government wide basis, was influenced by revelations 
of unethical research, congressional reaction to the revelations, and concern over 
public perception of such research. That regulations were eventually adopted at 
all by DHEW was influenced by the political realities of the time and the lack of 
congressional support for a standing regulatory body to oversee human subject 
research, as had been recommended by an influential federally appointed panel, 
the Tuskegee Syphilis Study Ad Hoc Panel. In a trade-off that would have major 
influence on the future of human subject research oversight, the proposed bill 
creating the standing regulatory body was withdrawn in exchange for the National 

172 



Chapter 3 

Research Act, establishing the National Commission, and an understanding that 
DHEW would promulgate the aforementioned regulations. This historical 
backdrop is outlined in the rerhainder of this chapter. 

The Thalidomide Tragedy and the Congressional Requirement for Patient 
Consent 

In 1959 a Senate subcommittee chaired by Senator Estes Kefauver of 
Tennessee began hearings into the conduct of pharmaceutical companies. 
Testimony revealed that it was common practice for drug companies to provide 
samples of experimental drugs, whose safety and efficacy had not been 
established, to physicians, who were then paid to collect data on their patients 
taking these drugs. Physicians throughout the country prescribed these drugs to 
patients without their knowledge or consent as part of this loosely controlled 
research. These practices and others prompted calls by Kefauver and other 
senators for an amendment to the Food, Drug, and Cosmetic Act of 1938 to 
address the injuriousness and ineffectiveness of certain drugs. In 1961 the 
dangers of new drug uses were vividly exemplified by the thalidomide disaster in 
Europe, Canada, and to a lesser degree, the United States. 5 Starting in late 1957, 
the sedative thalidomide was given to countless pregnant women and caused 
thousands of birth defects in newborn infants (most commonly, missing or 
deformed limbs). The thalidomide disaster was widely covered by the television 
networks, and the visual impact of these babies stunned viewers and caused 
Americans to question the protections afforded those receiving investigational 
agents. 

It is in large measure because of the thalidomide episode that the 1962 
Kefauver-Harris amendments to the Food, Drug, and Cosmetic Act were passed, 6 
requiring that informed consent be obtained in the testing of investigational 
drugs. 7 While such testing occurred mainly with patients, Congress carefully 
avoided interfering in the doctor-patient relationship and in the process severely 
reduced the effectiveness of the requirement. Consent was not required when it 
was "not feasible" or was deemed not to be in the best interests of the patient— 
both judgments made "according to the best judgment of the doctors involved." 8 
Despite their being limited in scope, the Kefauver-Harris amendments were 
influential in advancing considerations of protections of research subjects first 
within the DHEW and later throughout the rest of the government. 

NIH and PHS Develop a Uniform Policy to Protect Human Subjects 

In late 1963, concerns were raised within NIH by Director James Shannon 
after disturbing revelations about two research projects funded in part by the 
Public Health Service and NIH. One was the unsuccessful transplantation of a 
chimpanzee kidney into a human being at Tulane University, a procedure that 

173 



Parti 

promised neither benefit to the recipient nor new scientific information. The 
transplant was reportedly done with the consent of the patient, but without 
consultation or review by anyone other than the medical team involved." 

The second was research undertaken in mid- 1963 at the Brooklyn Jewish 
Chronic Disease Hospital. There, investigators (the chief investigator, Dr. 
Chester M. Southam was a physician at the Sloan-Kettering Cancer Research 
Institute, and he received permission to proceed with the work from the hospital's 
medical director, Dr. Emmanuel E. Mandel) had undertaken a research project in 
which they injected live cancer cells into indigent elderly patients without their 
consent. The research went forward without review by the hospital's research 
committee and over the objections of three physicians consulted, who argued that 
the proposed subjects were incapable of giving adequate consent to participate. 10 
The disclosure of the experiment served to make both PHS officials like Shannon 
and the Board of Regents of the University of the State of New York, which had 
jurisdiction over licensure of physicians, aware of the shortcomings of procedures 
in place to protect human subjects. They were further concerned over the public's 
reaction to disclosure of the research and the impact it would have on research 
generally and the institutions in particular. After a review, the Board of Regents 
censured the researchers. They suspended the licenses of Drs. Mandel and 
Southam, but subsequently stayed the suspension and placed the physicians on 
probation for one year." There were no immediate repercussions for the hospital, 
Sloan-Kettering, the university, or PHS, but the case nonetheless profoundly 
affected the subsequent development of federal guidelines to protect research 
subjects. 

To add to the ferment, NIH officials had closely followed the work of the 
Law-Medicine Research Institute at Boston University, which issued survey 
findings in 1 962 showing that few institutions had procedural guidelines covering 
clinical research. 12 And in the year after both the above-mentioned cases came to 
light, the World Medical Association issued its Declaration of Helsinki, which set 
standards for clinical research and required that subjects give informed consent 
prior to enrolling in an experiment. 13 Thus national and world opinion on matters 
related to the ethics of human subject research created a climate ripe for changes 
in policies and approaches toward research ethics. 

Concern over disturbing cases and the growing attention paid to research 
ethics prompted NIH director James Shannon to create a committee in late 1 963 
under the direction of the NIH associate chief for program development, Robert 
B. Livingston, whose office supported centers at which NIH-funded research took 
place. The internal committee was charged with studying problems of inadequate 
consent and the standards of self-scrutiny involving research protocols and 
procedures. The committee was also to recommend a suitable set of controls for 
the protection of human subjects in NIH-sponsored research. The Livingston 
Committee recognized that ethically questionable research—exemplified by the 
research at the Jewish Chronic Disease Hospitals-could wreak havoc on public 

174 



Chapter 3 

perception, increase the likelihood of liability, and inhibit research. 14 These 
problems made it worthwhile to reconsider central oversight~or lack thereof-for 
research contracted out. However, the committee expressed concern over NIH 
taking too authoritarian a posture toward research oversight and so argued that it 
would be difficult for the agency to assume responsibility for ethics and research 
practices. When it issued its report in late 1964, the committee did not 
recommend any changes in the current NIH policies and, moreover, cautioned 
that "whatever NIH might do by way of designating a code or stipulating 
standards for acceptable clinical research would be likely to inhibit, delay, or 
distort the carrying out of clinical research. . . ."' 5 In deference to physician 
autonomy and traditional regard for the sanctity of the doctor-patient relationship, 
the report concluded that NIH was "not in a position to shape the educational 
foundations of medical ethics. . . ." 16 

Director Shannon did not think the conclusions of the Livingston 
Committee went far enough, feeling as he did that NIH should take a position of 
increased responsibility for research ethics. 17 Especially in light of the Jewish 
Chronic Disease Hospital case and its implications for the NIH, both internally 
and in terms of public perception, he felt that a stronger reaction was needed. 
Thus, despite the committee's limited conclusions, Shannon and Surgeon General 
Luther Terry together decided in 1965 to propose to the National Advisory Health 
Council (NAHC), an advisory committee to the surgeon general of the Public 
Health Service, 1S that in light of recent problems, the NIH should assume 
responsibility for formal controls on individual investigators. 19 At the NAHC 
meeting, Shannon argued for impartial prior peer review of the risks research 
posed to subjects and questioned the adequacy of the protections of the rights of 
subjects. 20 

The council's members mostly agreed with Shannon's concerns and three 
months later issued a "resolution concerning research on humans" following 
Shannon's broad recommendations and endorsing the importance of obtaining 
informed consent from subjects: 

Be it resolved that the National Advisory Health 
Council believes that Public Health Service support 
of clinical research and investigation involving 
human beings should be provided only if the 
judgment of the investigator is subject to prior 
review by his institutional associates to assure an 
independent determination of the protection of the 
rights and welfare of the individual or individuals 
involved, of the appropriateness of the methods 
used to secure informed consent, and of the risks 
and potential medical benefits of the investigation. 21 



175 



Parti 

What this statement did not do, however, was explain what would count as 
informed consent. The NAHC recommendations were accepted by the new 
surgeon general, William H. Stewart, and in February 1966 he issued a policy 
statement requiring PHS grantee institutions to address three topics by committee 
prior review for all proposed research involving human subjects: 

This review should assure an independent 
determination (1) of the rights and welfare of the 
individual or individuals involved, (2) of the 
appropriateness of the methods used to secure 
informed consent, and (3) of the risks and potential 
medical benefits of the investigation. 22 

The 1966 PHS policy required that institutions give the funding agency a 
written "assurance" of compliance, but like the NAHC recommendations, the 
policy spoke strictly to the procedural aspects of informed consent and not to its 
meaning and criteria. Substantive informed consent criteria were established for 
research at the NIH Clinical Center shortly after the PHS policy was issued, but 
this new policy applied only to intramural research, that is, to research undertaken 
at the Clinical Center. The Clinical Center policy was important as the first 
federal research policy with a specific definition of what constituted informed 
consent requirements in the research context. The inclusion of specific consent 
requirements in policies applying to extramural research would not occur, 
however, until the mid-1970s. 

The 1966 PHS policy is significant both for its recognition that patient- 
subjects, like healthy subjects, should be included in the consent provisions for 
federally sponsored human experimentation and for its attempt to strike a balance 
between federal regulation and local control, which continues to this day. Such a 
balancing continued the work begun by the AEC, in its provision for local human 
use committees as a condition for the use of AEC-supplied isotopes, and the 
DOD, in the provision for high-level review of proposed experimentation. 
Although a landmark in the government regulation of biomedical research, the 
1966 policy was to be revised and changed throughout the decade as biomedical 
research drew greater attention and informed consent grew in importance. 

While, from the outset, the PHS policy was revised periodically, 23 site 
visits by PHS employees to randomly selected institutions revealed a wide range 
of compliance. 24 These site visits found widespread confusion about how to 
assess risks and benefits, refusal by some researchers to cooperate with the policy, 
and in many cases, indifference by those charged with administering research and 
its rules at local institutions. Complaints of overworked review committees and 
requests for clarification and guidance came from research institutions all over the 
country. 25 

In response to continued questions about the scope and meaning of the 

176 



Chapter 3 

policy, DHEW in 1971 produced The Institutional Guide to DHEW Policy on 
Protection of Human Subjects. 2 * Better known as the "Yellow Book" because of 
its cover's color, this substantial guide contained both the requirements and 
commentary on how the requirements were to be understood and implemented. 
The guide provided that informed consent was to be obtained from anyone who 
"may be at risk as a consequence of participation" in research-including both 
patients and healthy volunteers. 27 

As the 1960s progressed, increased discussion of research practices 
appeared in both professional literature and the popular press. One person who 
advanced the debate in both arenas was Henry Beecher of Harvard Medical 
School. 

Henry Beecher: The Medical Insider Speaks Out 

Henry Beecher, as noted in chapter 2, was an active participant in 
professional discussions of ethics in research during the late 1950s and early 
1960s. In March 1965, Beecher focused attention on the issues at a conference 
for science journalists sponsored by the Upjohn pharmaceutical company. There 
Beecher presented a paper discussing twenty-two examples of potentially serious 
ethical violations in experiments that he had found in recent issues of medical 
journals. 28 (Among them was the Brooklyn Jewish Chronic Disease Hospital 
study.) He explained this research had not taken place "in a remote corner, but 
[in] . . . leading medical schools, university hospitals, top governmental military 
departments, governmental institutes and industry." 29 He also acknowledged that 
his own conscience was not entirely clear: "Lest I seem to stand aside from these 
matters I am obliged to say that in years gone by work in my laboratory could 
have been criticized." 30 Beecher also explained the consciousness-raising purpose 
of these revelations with stark clarity: "It is hoped that blunt presentation of these 
examples will attract the attention of the uninformed or the thoughtless and 
careless, the great majority of offenders." 31 

In making this presentation to a group of journalists, Beecher was clearly 
breaking with a professional expectation that such matters should be addressed 
within the biomedical community. After some reservations on the part of medical 
journals, the March 1965 paper having been rejected by at least the Journal of the 
American Medical Association (JAMA), Beecher published a revised version in 
the New England Journal of Medicine in June 1966. 32 That article, like his 
presentation at the conference, indicted the entire biomedical research community 
and the journals that published biomedical research results. 

Beecher's efforts to focus professional, press, and therefore public 
awareness on the conduct of research involving human subjects met with some 
success. A July 1965 article in the New York Times Magazine was headlined 
"Doctors Must Experiment on Humans~But What Are the Patient's Rights?" 33 In 
February 1966, as the PHS issued its first uniform policy for biomedical research, 

177 



Parti 

more headlines, this time in the Saturday Review, asked, "Do We Need New 
Rules for Experimentation on People?" 34 In July 1966, following Beecher's 
article in the New England Journal of Medicine and an editorial in JAMA, 35 
another article declared "Experiments on People— The Growing Debate." 36 Thus, 
by the mid- to late 1960s, professional, governmental, and public attention was all 
being drawn to issues of research on human subjects. Revelations of purportedly 
unethical treatment of research subjects would not be over by this time, but 
changes in policy largely driven by attention from so many corners were 
beginning to move toward a more comprehensive approach to research oversight. 

Public Attention Is Galvanized: Willowbrook and Tuskegee 

From 1956 to 1972 Dr. Saul Krugman of New York University led a study 
team at the Willowbrook State School for the Retarded, on Staten Island, New 
York. The study was not secret or hidden. (It was one of the twenty-two projects 
Beecher discussed as ethically troublesome in his 1966 article.) The 
Willowbrook study was discovered by the media beginning in the late 1 960s 37 and 
was the subject of further discussion of the case in separate places by Beecher, 38 
theologian Paul Ramsey, 39 and physician Stephen Goldby. 40 Noting the high 
incidence of hepatitis among the residents of the school, nearly all of whom were 
profoundly mentally impaired children and adolescents, Krugman and his 
colleagues injected some of them with a mild form of hepatitis serum. The 
researchers justified their work on the grounds that the subjects probably would 
have become infected anyway, and they hoped to find a prophylaxis for the virus 
by studying it from the earliest stages of infection. Before beginning the work, 
Krugman discussed it with many physician colleagues and sought approval from 
the Armed Forces Epidemiological Board, which approved and funded the 
research, 41 and the executive faculty of the New York University School of 
Medicine, who approved the research. A review committee for human 
experimentation did not exist in 1955, 42 but later, when such a committee was 
formed, it too approved the research. 

According to Krugman, the parents of each subject signed a consent form 
after receiving a detailed explanation of the research, without any pressure to 
enroll their child. 43 Some critics argued that the content of the consent form was 
itself deceiving, since it seemed to say that children were to receive a vaccine 
against the virus. Moreover, charges of coercion arose. It is alleged that parents 
who enrolled their children in the study were initially offered more rapid 
admission to the school through the hepatitis unit and later found, due to 
overcrowding, that the only route for admission of new patients was through the 
hepatitis unit. 44 Commentators further argued that the fault in the doctors' study 
lay in their deliberate attempt to infect the children, with or without parental 
consent, as opposed to studying the course of disease in children who naturally 
became sick. 

178 



Chapter 3 

Soon after Willowbrook, another research project, the Tuskegee syphilis 
study, provoked widespread public outcry when it was revealed the study had 
exposed people to unnecessary and serious harm with no prospect of direct 
benefit to them. Beginning in 1 932, PHS physicians sought to trace the natural 
history of syphilis by observing some 400 African- American men affected by the 
disease and another group of approximately 200 African- American men without 
syphilis serving as controls. All the subjects lived in or around Tuskegee, 
Alabama. Originally designed to be a short-term study in the range of six to eight 
months, some investigators successfully argued that the potential scientific value 
of longer-term study was so great that the research ought to go on indefinitely. 
The subjects were enticed into the study with offers of free medical examinations. 
Many of those who came from around the area to be tested by "government 
doctors" had never had a blood test before and had no idea what one was. 45 Once 
selected to be subjects in the study, the men were not informed as to the nature of 
their disease or of the fact that the research held no therapeutic benefit for them. 
Subjects were asked to appear for "special free treatments," which included 
purely diagnostic procedures such as lumbar punctures. 46 

By the mid- 1940s it was becoming clear that the death rate for the infected 
men in the study was twice as high as for those in the control group. This was the 
period in which penicillin was discovered and soon after began to be used to treat 
syphilis, at least in its primary stage. The study was reviewed by PHS officials 
and medical societies and reported by a number of journals from the early 1930s 
to 1970. In the 1960s a growing number of criticisms began to appear, although 
the study was not stopped until 1973. 

Thus, men with a confirmed disease were not told of their diagnosis and 
were deceived into participating in the study under the guise of its being 
therapeutic for unspecified maladies. In addition to exposing the subjects to the 
additional harms of participation in the study, the false belief that treatment was 
being administered prevented subjects from otherwise seeking medical care for 
their disease. As at Willowbrook, a justification given after the fact for the 
research was that the disease had appeared in a way that was natural and 
inevitable and that the study would be of immense benefit to future patients. 47 
Over this forty-year history, at least 28 participants died and approximately 100 
more suffered blindness and insanity from untreated syphilis before the study was 
stopped. 

In 1972, an account of the study was published on the front page of the 
New York Times. 4 * In response, DHEW appointed the Tuskegee Syphilis Study 
Ad Hoc Panel to review the Tuskegee study as well as the department's policies 
and procedures for the protection of human subjects. The work of the ad hoc 
panel-which consisted of physicians, a university president, a theologian, an 
attorney, and a labor representative-contributed in large measure to the passage 
of the first comprehensive regulations for federally sponsored human subjects 
research. One member of the ad hoc panel who is also a member of the Advisory 

179 



Parti 

Committee, Jay Katz, expressed his dismay over the unwillingness or incapacity 
of society to mobilize the necessary resources for "treatment" at the beginning of 
the study and the deliberate efforts of the investigators to "obstruct the 
opportunity for treatment." 49 

Despite the fact that the PHS Policy for the Protection of Human Subjects 
had been in place for six years by the time the Tuskegee study was revealed, it 
was exposed by a journalist rather than by a review committee. Although an 
institutional committee had allegedly reviewed the Tuskegee study, the study was 
not discontinued until after the recommendation of the ad hoc panel. 50 The human 
rights abuses of the Tuskegee study demonstrated the need for both prior and 
ongoing review, in that the study was undertaken before prior review 
requirements were in place, and the prevailing review policies during the period 
of the study were so flawed that the study was allowed to continue. 

As a result of their deliberations, the ad hoc panel found that neither 
DHEW nor any other agency in the government had adequate policies for 
oversight of human subjects research. The panel recommended that the Tuskegee 
study be stopped immediately and that remaining subjects be given necessary 
medical care resulting from their participation. 51 The panel also recommended 
that Congress establish "a permanent body with the authority to regulate at least 
all federally supported research involving human subjects." 52 In summary, the 
panel concluded that despite the lessons of Nuremberg, the Jewish Chronic 
Disease Hospital case, and the Declaration of Helsinki, human subject research 
oversight and mechanisms to ensure informed consent were still inadequate and 
new approaches were needed to adequately protect the rights and welfare of 
human subjects. 

Congressional Response to Abuses of Human Subjects: The National 
Research Act 

Public attention to abuses such as those inflicted on the subjects of the 
Tuskegee study increased during the late 1960s and early 1970s. Following the 
initial revelations about the Tuskegee syphilis study, several bills were introduced 
in Congress to regulate the conduct of human experimentation. In February 1973 
Senator Edward Kennedy held hearings on these bills; 53 the Tuskegee study; 
experimentation with prisoners, children, and poor women; and a variety of other 
issues related to biomedical research and the need for a national body to consider 
the ethics of research and advancing medical technology. 54 After the hearings, 
Senator Kennedy introduced an unsuccessful bill to create a National Human 
Experimentation Board, as recommended by the Tuskegee Syphilis Study Ad Hoc 
Panel. When it became clear, however, that the bill would not be successful, 
Senator Kennedy introduced the bill that would become the National Research 
Act, endorsing the regulations about to be promulgated by DHEW and 
establishing the National Commission for the Protection of Human Subjects of 

180 



Chapter 3 

Biomedical and Behavioral Research, in return for DHEW's issuance of human 
subject research regulations. 55 The trade-off was clear: no national regulatory 
body in return for regulations applying to the research funded or performed by the 
government agency responsible for the greatest proportion of human subject 
research. This meant that the goal of oversight of all federally funded research 
would not be achieved and that whatever oversight did exist was left to the 
funding agencies rather than an independent body. 

On May 30, 1974, DHEW published regulations for the use of human 
subjects in the Federal Register. 5 " These regulations required that each grantee 
institution form a committee (what became known as an institutional review 
board, or IRB) to approve all research proposals before they were passed to 
DHEW for funding consideration. These committees were charged with 
reviewing the safety of the proposals brought to them as well as the adequacy of 
the informed consent obtained from each subject prior to participation in the 
research. Additionally, the regulations defined not only the procedure for 
obtaining informed consent but substantive criteria for it as well. Shortly after the 
announcement of the DHEW regulations, in July 1974, the National Research Act 
was passed, and with it came the establishment of the National Commission. 57 

The National Commission-charged with advising the secretary of DHEW 
(though the National Research Act did not require the secretary to follow the 
commission's recommendations)--existed over the next four years and published 
seventeen reports and appendix volumes. During its tenure, the commission did 
pioneering work as it addressed issues of autonomy, informed consent, and third- 
party permission, particularly in relation to research involving vulnerable subjects 
such as prisoners, children, and people with cognitive disabilities. It was also 
charged with examining the IRB system and procedures for informed consent, as 
background for proposing guidelines that would ensure that basic ethical 
principles were instituted in the research oversight system and in research 
involving vulnerable populations. 

In the course of its deliberations, the commission identified three general 
moral principles-respect for persons, beneficence, and justice-as the appropriate 
framework for guiding the ethics of research involving human subjects. These 
three are known as the Belmont principles because they appeared in The Belmont 
Report, one of the commission's major publications. 58 

The National Commission was required to examine the "nature and 
definition" of informed consent as well as the "adequacy" of current practices. In 
its reports, the commission decisively argued that the basic justification for 
obligations to obtain informed consent is the moral principle of respect for 
persons. This emphasis on respect for persons meant a great premium was put on 
autonomous decision making by the research subject, an emphasis that continues 
to the current day. 

While it may not have been the intent of those who sponsored it, the 
National Research Act-because it was limited to DHEW-funded research-did 

181 



Parti 

not ensure that all federally sponsored research would be subject to requirements 
for informed consent and prior review. Nonetheless, by this time, as described 
below, published policies within the DOD, the AEC, the VA, and NASA did meet 
these requirements. 

The passage of the National Research Act and the promulgation of 
DHEW's regulations were important milestones in the development of federal 
standards for the protection of human subjects of research. They represented the 
first national recognition of the need to protect human subjects. Moreover, they 
attempted to provide for that protection through the IRB requirement and 
establishment of the National Commission. The Advisory Committee's charter 
requires that it examine the standards for research between 1944 and 1974. These 
two landmark events in 1974 ushered in a new era in which the conduct and 
oversight of biomedical experimentation with humans remained a topic of 
national scrutiny and debate. Eventually, the approaches required by the 1974 
DHEW regulations would be applied to nearly all federally sponsored human 
research, as described in chapter 14. 

THE DEVELOPMENT OF REQUIREMENTS FOR HUMAN 
SUBJECT RESEARCH IN OTHER FEDERAL AGENCIES 

The history and evolution of human subject research policy in the federal 
government is well documented for DHEW. However, many other agencies, 
most notably the military services, have important but less well-documented and 
less well-studied histories. Some of this history is described in chapter 1 of this 
report. Here we continue with a brief treatment of that history in the context of 
the evolution of human subject research policy. 

Army Policy 

In 1962 the Army, for the first time, issued as a formal regulation, Army 
Regulation (AR) 70-25, the 1953 policy embodied in the Wilson memorandum. 
The regulation made explicit, as the 1953 DOD and Army policies had only left 
implicit, basic issues about the scope of the DOD's rules. Unlike the Wilson 
memorandum, the new regulation applied to all types of research, not simply that 
related to atomic, biological, and chemical warfare. However, the regulation 
specifically excluded clinical research, that is, the research likely to be performed 
with patients at the Army's many hospitals. In 1963, an ad hoc committee of 
Army and civilian personnel concluded that the rule applied where research was 
done by contractors; however, tracer research (which arguably posed minimal 
risk) was excluded. 59 Despite the committee's recommendations, no immediate 
changes were made to the regulation. In 1963, however, the Army issued a 
regulation for radioisotope use that required local institutions to convene review 
committees and obtain approval from the secretary of the Army pursuant to AR 

182 



Chapter 3 

70-25 when radioisotopes were to be used with "volunteer" experimental 
subjects. 60 

The regulatory void apparently persisted until 1973, when another rule 
(AR 40-38, "Medical Services-Clinical Investigation Program") closed the gap. 
That rule clearly applied to "any person who may be at risk because of 
participation . . . [in] clinical investigation," including "patients" and "normal 
individuals." 61 It required that subjects of research be given an explanation of the 
proposal in understandable language and sign a "volunteer agreement." 62 
Moreover, clinical research with patients, as well as healthy people, was to be 
reviewed by a "Human Use Committee." 63 

Navy Policy 

As we saw in chapter 1 , the Navy had required oral consent from research 
volunteers since at least 195 1. Some evidence suggests that written consent was 
required in the mid-1960s; in a 1964 proposal to study the effects of hypoxia on 
service personnel it is indicated that a "signed Consent to Voluntarily Participate 
in Research Experiment (NMRI Form 3)" would be used. 64 In 1967 a clear 
requirement for written consent appeared in the Navy's Medical Department 
manual. 65 It is unclear whether the policy drew a distinction between research on 
patients and research on healthy subjects. In 1969, in any event, the secretary of 
the Navy issued a comprehensive policy requiring written informed consent of 
research subjects, which appeared to cover both groups. 66 

Air Force Policy 

In 1965 the Air Force promulgated AFR 169-8, "Medical Education and 
Research— Use of Volunteers in Aerospace Research," which required voluntary 
and written informed consent from all subjects in any "research, development, 
test, and evaluation" that may involve "distress, pain, damage to health, physical 
injury, or death." 67 As such, it seems inclusive of both healthy and patient- 
subjects. 68 Updating the language of the Nuremberg Code's first principle, the 
policy was based on the idea that the "voluntary informed consent of the human 
subject is absolutely essential." 69 Additionally, the regulation provided for the 
appointment of a committee to review all human research proposals at each 
originating facility. 

NASA Policy 

The National Aeronautics and Space Administration (NASA), created in 
1958, inherited staff and research expertise from the DOD and other federal 
agencies. Before 1968, local centers at which research using radioisotopes was 
conducted-notably the Ames Research Center and the Manned Spacecraft Center 

183 



Part I 

(MSC)-were essentially autonomous. Each center established medical use 
subcommittees, as required by AEC rules.™ Reorganization within NASA in 
1 968 combined the medical operations functions and the medical research 
functions at MSC into one medical research and operations directorate headed by 
Dr. Charles A. Berry. 

By 1968, Ames had a policy requiring informed consent. 71 By definition, 
of course, the work of astronauts is frequently risky and experimental. The 
question of the proper boundary between experimental and occupational activities 
was one that could not be drawn easily. Consequently, the policy authorized the 
director of Ames to waive the consent requirement in several instances, including 
when obtaining consent would seriously hamper the research or when test pilots 
or astronauts were involved. 72 

Between 1968 and 1970, prior review for risk and subject consent was 
adopted at Ames in the form of the Human Research Experiments Review Board 
and indirectly at the MSC in accordance with the AEC requirements for a medical 
use committee. 73 In 1972 the prior review provisions and consent requirements of 
Ames and the MSC were reformulated in a NASA-wide policy. 74 This policy 
required voluntary and written informed consent from subjects prior to 
participation. The policy continued to provide waivers for "exceptional cases," as 
in the Ames policy, and did not apply to research conducted by NASA contractors 
or grantees. 

The development of NASA's polices, like those at the PHS, NIH, and the 
DOD, appeared at a time when the public was becoming increasingly interested in 
biomedical research. In contrast with the 1940s and 1950s, bureaucratic 
developments during the 1960s and 1970s were mirrored by growing public 
debate about the adequacy of protections for human subjects. 

SUPREME COURT DISSENTS INVOKE THE NUREMBERG 
CODE: CIA AND DOD HUMAN SUBJECTS RESEARCH 
SCANDALS 

As we have seen, the development of federal legislation for government- 
sponsored research with human subjects arose in part because of institutional and 
governmental concern and public reaction to perceived abuses and failures by the 
government. Around the same time that the 1974 National Research Act was 
enacted, a scandal arose surrounding the discovery of secret Cold War chemical 
experiments conducted by the CIA and DOD. The review of these experiments 
led to the rediscovery of the previously secret 1953 Wilson memorandum and 
later to the first Supreme Court decision in which comment was made, in dissent, 
on the application of the Nuremberg Code to the conduct of the U.S. government. 

In December 1974, the New York Times reported that the CIA had 
conducted illegal domestic activities, including experiments on U.S. citizens, 
during the 1 960s. That report prompted investigations by both Congress (in the 

184 



Chapter 3 

form of the Church Committee) and a presidential commission (known as the 
Rockefeller Commission) into the domestic activities of the CIA, the FBI, and 
intelligence-related agencies of the military. In the summer of 1975, 
congressional hearings and the Rockefeller Commission report revealed to the 
public for the first time that the CIA and the DOD had conducted experiments on 
both cognizant and unwitting human subjects as part of an extensive program to 
influence and control human behavior through the use of psychoactive drugs 
(such as LSD and mescaline) and other chemical, biological, and psychological 
means. They also revealed that at least one subject had died after administration 
of LSD. Frank Olson, an Army scientist, was given LSD without his knowledge 
or consent in 1953 as part of a CIA experiment and apparently committed suicide 
a week later. 75 Subsequent reports would show that another person, Harold 
Blauer, a professional tennis player in New York City, died as a result of a secret 
Army experiment involving mescaline. 76 

The CIA program, known principally by the codename MKULTRA, 
began in 1950 and was motivated largely in response to alleged Soviet, Chinese, 
and North Korean uses of mind-control techniques on U.S. prisoners of war in 
Korea. Because most of the MKULTRA records were deliberately destroyed in 
1973 by order of then-Director of Central Intelligence Richard Helms, it is 
impossible to have a complete understanding of the more than 150 individually 
funded research projects sponsored by MKULTRA and the related CIA 
programs. 77 Central Intelligence Agency documents suggest that radiation was 
part of the MKULTRA program and that the agency considered and explored uses 
of radiation for these purposes. 78 However, the documents that remain from 
MKULTRA, at least as currently brought to light, do not show that the CIA itself 
carried out any of these proposals on human subjects. 

The congressional committee investigating the CIA research, chaired by 
Senator Frank Church, concluded that "[p]rior consent was obviously not 
obtained from any of the subjects." 7 " The committee noted that the "experiments 
sponsored by these researchers . . . call into question the decision by the agencies 
not to fix guidelines for experiments." 80 (Documents show that the CIA 
participated in at least two of the DOD committees whose discussions, in 1952, 
led up to the issuance of the Wilson memorandum.) Following the 
recommendations of the Church Committee, President Gerald Ford in 1976 issued 
the first Executive Order on Intelligence Activities, which, among other things, 
prohibited "experimentation with drugs on human subjects, except with the 
informed consent, in writing and witnessed by a disinterested party, of each such 
human subject" and in accordance with the guidelines issued by the National 
Commission. 81 Subsequent orders by Presidents Carter and Reagan expanded the 
directive to apply to any human experimentation. 82 

Following on the heels of the revelations about CIA experiments were 
similar stories about the Army. In response, in 1975 the secretary of the Army 
instructed the Army inspector general to conduct an investigation. 83 Among the 

185 



Part I 

findings of the inspector general was the existence of the then-still-classified 1953 
Secretary of Defense Wilson memorandum. In response to the inspector general's 
investigation, the Wilson memorandum was declassified in August 1975. The 
inspector general also found that the requirements of the 1953 memorandum had. 
at least in regard to Army drug testing, been essentially followed as written. The 
Army used only "volunteers" for its drug-testing program, with one or two 
exceptions." 4 However, the inspector general concluded that the "volunteers were 
not fully informed, as required, prior to their participation; and the methods of 
procuring their services, in many cases, appeared not to have been in accord with 
the intent of Department of the Army policies governing use of volunteers in 
research." 85 The inspector general also noted that "the evidence clearly reflected 
that every possible medical consideration was observed by the professional 
investigators at the Medical Research Laboratories." 86 This conclusion, if 
accurate, is in striking contrast to what took place at the CIA. 

The revelations about the CIA and the Army prompted a number of 
subjects or their survivors to file lawsuits against the federal government for 
conducting illegal experiments. Although the government aggressively, and 
sometimes successfully, sought to avoid legal liability, several plaintiffs did 
receive compensation through court order, out-of-court settlement, or acts of 
Congress. Previously, the CIA and the Army had actively, and successfully, 
sought to withhold incriminating information, even as they secretly provided 
compensation to the families. 87 One subject of Army drug experimentation, 
James Stanley, an Army sergeant, brought an important, albeit unsuccessful, suit. 
The government argued that Stanley was barred from suing it under a legal 
doctrine—known as the Feres doctrine, after a 1950 Supreme Court case, Feres v. 
United States—that prohibits members of the Armed Forces from suing the 
government for any harms that were inflicted "incident to service." 88 

In 1987, the Supreme Court affirmed this defense in a 5-4 decision that 
dismissed Stanley's case. 89 The majority argued that "a test for liability that 
depends on the extent to which particular suits would call into question military 
discipline and decision making would itself require judicial inquiry into, and 
hence intrusion upon, military matters." 90 In dissent, Justice William Brennan 
argued that the need to preserve military discipline should not protect the 
government from liability and punishment for serious violations of constitutional 
rights: 

The medical trials at Nuremberg in 1947 deeply 
impressed upon the world that experimentation with 
unknowing human subjects is morally and legally 
unacceptable. The United States Military Tribunal 
established the Nuremberg Code as a standard 
against which to judge German scientists who 
experimented with human subjects. . . . [I]n 

186 



Chapter 3 

defiance of this principle, military intelligence 
officials . . . began surreptitiously testing chemical 
and biological materials, including LSD. 91 

Justice Sandra Day O'Connor, writing a separate dissent, stated: 

No judicially crafted rule should insulate from 
liability the involuntary and unknowing human 
experimentation alleged to have occurred in this 
case. Indeed, as Justice Brennan observes, the 
United States played an instrumental role in the 
criminal prosecution of Nazi officials who 
experimented with human subjects during the 
Second World War, and the standards that the 
Nuremberg Military Tribunals developed to judge 
the behavior of the defendants stated that the 
'voluntary consent of the human subject is 
absolutely essential ... to satisfy moral, ethical, and 
legal concepts.' If this principle is violated, the very 
least that society can do is to see that the victims are 
compensated, as best they can be, by the 
perpetrators. 92 

This is the only Supreme Court case to address the application of the 
Nuremberg Code to experimentation sponsored by the U.S. government. 93 And 
while the suit was unsuccessful, dissenting opinions put the Army-and by 
association the entire government-on notice that use of individuals without their 
consent is unacceptable. The limited application of the Nuremberg Code in U.S. 
courts does not detract from the power of the principles it espouses, especially in 
light of stories of failure to follow these principles that appeared in the media and 
professional literature during the 1960s and 1970s and the policies eventually 
adopted in the mid-1970s. 

CONCLUSION 

The 1960s and early 1970s witnessed an extraordinary growth in 
government, institutional, and public awareness of issues in the use of human 
subjects, fueled by scandals and an increasing emphasis on individual expression. 
The branches of the military had articulated policies during this period, in spite of 
numerous problems in implementation. By 1974 the DHEW had established a set 
of regulations and a system of local review, and Congress had established a 
commission to issue recommendations for further change to the DHEW. 
Together, these advances created a model and laid the groundwork for human 

187 



Parti 

subjects protections for all federal agencies. 

Many conditions coalesced into the framework for the regulation of the 
use of human subjects in federally funded research that is the basis for today's 
system. Described further in chapter 14, this framework is undergirded by the 
three Belmont principles that were identified by the National Commission as 
governing the ethics of research with human subjects: respect for persons, 
beneficence, and justice. The federal regulations and the conceptual framework 
built on the Belmont principles became so widely adopted and cited that it might 
be argued that their establishment marked the end of serious shortcomings in 
federal research ethics policies. Whether this position is well supported is 
evaluated in light of the Advisory Committee's contemporary studies in part III. 

By 1974, DHEW had extensive policies to protect human subjects within 
its purview. Policies were more variable among other government agencies. By 
1975, the branches of the military set about developing their own more 
comprehensive policies for human subject research, and the CIA was required by 
executive order to comply with consent requirements in human subject research in 
light of scandalous practices in the past. In order to evaluate the adequacy of the 
efforts taken to protect people before these policies were established, we must 
take into account both the government's policies and rules and the norms and 
practices of medicine reviewed in chapters 1 through 3. The Advisory 
Committee's framework for the consideration of these factors is presented in the 
next chapter. 



188 



ENDNOTES 



1 For a discussion of the development of the Common Rule, see chapter 1 4. 

2 We relied particularly on Ruth R. Faden and Tom L. Beauchamp, A History 
and Theory of Informed Consent (New York: Oxford University Press, 1986). Other 
excellent sources include Jay Katz, Experimentation with Human Beings (New York: 
Russell Sage Foundation, 1972), and Robert Levine, Ethics and Regulation of Clinical 
Research (Baltimore: Urban and Schwarzenberg, 1981). 

3 U S. Congress, The Select Committee to Study Governmental Operations 
with Respect to Intelligence Activities, Foreign and Military Intelligence [Church 
Committee report], report no. 94-755, 94th Cong., 2d Sess. (Washington, D.C.: GPO, 
1976). Also, U.S. Army Inspector General, Use of Volunteers in Chemical Agent 
Research [Army IG report] (Washington, D.C.: 1975). 

4 In dissenting opinions, four justices of the U.S. Supreme Court (Brennan, 
Marshall, Stevens, and O'Connor) cited the Nuremberg Code. United States et al. v. 

Stanley, 483 U.S. 669, 687, 710 (1987). u ,,-^ t t tW 

" 5. Thalidomide was only available in clinical trials in the United States at that 
time but was approved for use in a number of other countries. 

6 Louis Lasagna, interview by Susan White-Junod and Jon Harkness 
(ACHRE) transcript of audio recording, 13 December 1994 (ACHRE Research Project 
Series Interview Program Files, Ethics Oral History Project), 37-38. See also, Louis 
Lasagna "1938-1968: The FDA, the Drug Industry, the Medical Profession, and the 
Public," in Safeguarding the Public: Historical Aspects of Medicinal Drug Control, ed. 
John B. Blake (Baltimore: The Johns Hopkins Press, 1970), 173. 

7 Food Drug and Cosmetic Act amendments, 21 U.S.C. § 355 (1962). 

8* Congressional Record, 87th Cong, 2d Sess., 22042, as cited in an attached 
memorandum, C. Joseph Stetler, Pharmaceutical Manufacturers Association, to James L. 
Goddard M.D., Commissioner of Food and Drugs, DHEW, 1 1 October 1966 
("Regarding Statement Appearing in August 30, 1966 Federal Register Concerning 
Clinical Investigation of Drugs") (ACHRE No. HHS-090794-A). 

9 Keith Reemtsma et al., "Reversal of Early Graft Rejection after Renal 
Heterotransplantation in Man," Journal of the American Medical Association 1 87 

(1964): 691-696. 

1 This research, conducted by Dr. Chester Southam of Sloan-Kettenng 
Institute and Dr. Emmanuel Mandel of the Jewish Chronic Disease Hospital in 1963 and 
funded by the U.S. Public Health Service and the American Cancer Society, raised 
concern within PHS and brought about an investigation by the hospital. Drs. Mandel and 
Southam were subject to a disciplinary hearing before the Board of Regents of the 
University of the State of New York. The hospital's internal review and a suit against 
the hospital prompted concern and debate at the NIH. Edward J. Rourke, Assistant 
General Counsel, NIH, to Dr. Luther L. Terry, Surgeon General, 16 September 1965 
("Research Grants-Clinical-PHS responsibility-Fin* v. Jewish Chronic Disease 
Hospital [New York Supreme Court, Kings County]") (ACHRE No. HHS-090794-A). 

For a more thorough discussion of this case, see Katz, Experimentation with 

Human Beings, 9-65. 

11. In 1967 Dr. Southam was elected vice president of the American 
Association for Cancer Research and became president the following year. Katz, 

189 



Experimentation with Human Beings, 63 and 65. 

12. For a fuller discussion of the Law-Medicine Research Institute, see chapter 
2. 

13. The development of the Declaration of Helsinki is discussed briefly in 
chapter 2. 

14. Robert B. Livingston, Associate Chief for Program Development, 
Memorandum to the Director, NIH, 4 November 1964 ("Progress Report on Survey of 
Moral and Ethical Aspects of Clinical Investigation" [the Livingston report]) (ACHRE 
No. HHS-090795-A), 3. 

15. Ibid., 7. 

16. Ibid. 

17. Mark S. Frankel, "Public Policymaking for Biomedical Research: The Case 
of Human Experimentation" (Ph.D. diss., George Washington University, 9 May 1976), 
50-51. 

1 8. The NAHC discussed the "general question of the ethical, moral, and legal 
aspects of clinical investigation" at its meetings of September and December 1965. 
Terry's interest in this was motivated in part by the concern of Senator Jacob K. Javits 
that the informed consent provisions of the 1962 Drug Amendments were not applicable 
to nondrug-related research. See (a) draft letter to Senator Javits from the Surgeon 
General, 15 October 1965; (b) Senator Javits to Luther L. Terry, Surgeon General, 15 
June 1965; and (c) Edward J. Rourke, Assistant General Counsel, to William H. Stewart, 
Surgeon General, 26 October 1965. All in ACHRE No. HHS-090794-A. 

19. Transcript of the NAHC meeting, Washington, D.C., 28 September 1965. 
See Faden and Beauchamp, A History and Theory of Informed Consent, 208. 

20. Ibid. 

21 . Dr. S. John Reisman, the Executive Secretary, NAHC, to Dr. James A. 
Shannon, 6 December 1965 ("Resolution of Council") (ACHRE No. HHS-090794-A). 

22. Surgeon General, Public Health Service to the Heads of the Institutions 
Conducting Research with Public Health Service Grants, 8 February 1966 ("Clinical 
research and investigation involving human beings") (ACHRE No. HHS-090794-A). 
This policy was distributed through Bureau of Medical Services Circular no. 38, 23 June 
1966 ("Clinical Investigations Using Human Beings As Subjects") (ACHRE No. HHS- 
090794-A). 

23. In December 1966 the policy was expanded to include behavioral as well 
as medical research. William H. Stewart, Surgeon General, Public Health Service, to 
Heads of Institutions Receiving Public Health Service Grants, 12 December 1966 
("Clarification of procedure on clinical research and investigation involving human 
subjects") (ACHRE No. HHS-072894-B), 2. 

In 1967 the Public Health Service required that intramural research, including 
that conducted at NIH, abide by similar requirements. William H. Stewart, Surgeon 
General of the Public Health Service, to List, 30 October 1967 ("PHS policy for 
intramural programs and for contracts when investigations involving human subjects are 
included") (ACHRE No. HHS-072894-B), 2. 

24. Frankel, "Public Policymaking for Biomedical Research: The Case of 
Human Experimentation," 161. 

25. Ibid., 161-162. 

26. U.S. Department of Health, Education, and Welfare, The Institutional 
Guide to DHEW Policy on Protection of Human Subjects (Washington, D.C.: GPO, 



190 



1971) (ACHRE No. HHS-090794-A). 

27. Ibid., 1-2. 

28. Beecher's criticism involved many aspects of the research, including the 
risk assessment, usefulness of the research, and the question of informed consent. On 
this last point, Beecher argued that while consent was important, he disputed the belief 
that it was easily obtainable. In his talk at Brook Lodge, Beecher questioned the "naive 
assumption implicit in the Nuremberg Code," that consent was readily obtainable. 
Beecher indicated the difficulty of obtaining truly informed consent may have led many 
researchers to treat the provision cavalierly and often to ignore it. Henry K. Beecher, 
"Ethics and the Explosion of Human Experimentation," unpublished manuscript of paper 
presented 22 March 1965, "a," Beecher Papers, Countway Library (ACHRE No. IND- 
072595-A). 

29. lbid.,"a" and "b." 

30. Ibid., 2a. 

31. Ibid., 2. 

32. H. K. Beecher, "Ethics and Clinical Research," New England Journal of 
Medicine 274(1966): 3354-1360. 

33. W. Goodman, "Doctors Must Experiment on Humans~But What are 
Patients Rights?" New York Times Magazine, 2 July 1965, 12-13, 29-33, as cited in 
Faden and Beauchamp, A History and Theory of Informed Consent, 1 88. 

34. J. Lear, "Do We Need New Rules for Experimentation on People?" 
Saturday Review, 5 February 1966, 61-70. 

35. Henry K. Beecher, "Consent in Clinical Experimentation: Myth and 
Reality," Journal of the American Medical Association 1 95 ( 1 966): 34-35. 

36. J. Lear, "Experiments on People-The Growing Debate," Saturday Review, 
2 July 1966,41-43. 

37. Both the New York Times and the Wall Street Journal ran stories on 24 
March 1971. See Medical World News, 15 October 1971, "Was Dr. Krugman Justified 
in Giving Children Hepatitis?" 

38. Beecher, Research and the Individual: Human Studies (Boston: Little, 
Brown, and Company, 1970), 122-127. 

39. Paul Ramsey, The Patient as Person: Explorations in Medical Ethics (New 
Haven: Yale University Press, 1970), 51-55. 

40. In a letter to the Lancet, Dr. Stephen Goldby called the work "unjustifiable" 
and asked, "Is it right to perform an experiment on a normal or mentally retarded child 
when no benefit can result to the individual?" (S. Goldby, "Letters to the Editor," Lancet 
7702 [1971]: 749). The Lancet editors agreed with Goldby. On this side of the Atlantic, 
however, the editors of NEJM and JAMA, among others, defended Krugman's work. 

41. Armed Forces Epidemiological Board, minutes of 24 May 1957 (ACHRE 
No. NARA-032495-B). 

42. S. Krugman, "Ethical Practices in Human Experimentation," text of lecture 
presented at the Fifth Annual Midwest Student Medical Research Forum, 1 March 1974 
(ACHRE No. IND-072895-A). 

43. Ibid., 3-4. 

44. Louis Goldman, "The Willowbrook Debate," World Medicine (September 
1971 and November 1971): 23, 25. 

45. James H. Jones, Bad Blood (New York: Free Press, 1993 edition), 1 14. 



191 



46. Jones, Bad Blood (1981), 69-7 1 ; Levine, Ethics and Regulation of Clinical 
Research, 70. 

47. Charles J. McDonald, "The Contribution of the Tuskegee Study to Medical 
Knowledge," Journal of the National Medical Association (January 1 974): 1 - 1 1 , as cited 
in Faden and Beauchamp, A History and Theory of Informed Consent, 194-195. 

48. Jean Heller, "Syphilis Victims in U.S. Study Went Untreated for 40 
Years," New York Times (26 July 1972) 1, 8, as cited in Faden and Beauchamp, A 
History and Theory of Informed Consent, 195. 

49. U.S. Department of Health, Education, and Welfare, Final Report of the 
Tuskegee Syphilis Study Ad Hoc Panel (Washington, D.C.: GPO, 1 973), Jay Katz 
Concurring Opinion, 14. 

50. Ibid. 

51. Ibid., 21-32. 

52. Ibid., 23. 

53. Senator Jacob Javits introduced legislation that would have made the 
DHEW policy a regulation backed by federal law. S. 878 and S. 974, 93d Cong., 1st 
Sess. (1973). 

Senator Hubert Humphrey introduced a bill to create a National Human 
Experimentation Standards Board~a separate federal agency with authority over research 
similar to the Security and Exchange Commission's authority over securities transactions. 
S. 934, 93d Cong., 1 st Sess. ( 1 973). 

Also, Senator Walter Mondale introduced a resolution to provide for a "study 
and evaluation of the ethical, social, and legal" aspects of biomedical research. S.J. Res. 
71, 93d Cong., 1st Sess. (1973). 

54. It is worth noting here that Senator Kennedy had convened similar hearings 
two years previously, in 1971, to consider the establishment of a national commission to 
examine "ethical, social, and legal implications of advances in biomedical research." 
Among the topics mentioned in this hearing was the total-body irradiation research 
sponsored by the Department of Defense at the University of Cincinnati, which we 
discuss in chapter 8. 

55. Jay Katz, "Human Experimentation: A Personal Odyssey," IRB 9, no. 1 
(January/February 1987): 1-6. 

56. Protection of Human Subjects, 39 Fed. Reg. 105, 18914-1 8920 (1974) (to 
be codified at 45 C.F.R. §46). 

57. National Research Act of 1974. P.L. 348, 93d Cong., 2d Sess. (12 July 
1974). 

58. U.S. Department of Health, Education, and Welfare, Office for Protection 
from Research Risks, 18 April 1979, OPPR Reports [The Belmont Report] (ACHRE No. 
HHS-011795-A-2), 4-20. 

59. Interestingly, this committee included Henry Beecher, who, as was 
discussed in part I, chapter 3, had objected to the imposition of these requirements to 
contract research in 1961 . Beecher's presence on the committee testifies to the common 
relationship between military and private research during this time. Like many of the 
AFEB members and commissioners, many of the members of the ad hoc panel were 
nonmilitary consultants to the DOD. 

60. Department of the Army, Army Regulation 40-37, 12 August 1963 
("Radioisotope License Program [Human Use]"). 



192 



61. Department of the Army, AR 40-38, 23 February 1973 ("Medical Services- 
Clinical Investigation Program"). 

62. Ibid. 

63. Ibid. 

64. Commanding Officer, Naval Medical Research Institute, National Naval 
Medical Center, to Secretary of the Navy, 30 November 1964 ("Authorization to use 
human volunteers as subjects for study of effects of hypoxia on the visual field; request 
for") (ACHRE No. DOD-091494-A), 2. 

65. Department of the Navy, "Manual of the Medical Department," 20-8, 
Change 36, 7 March 1967 ("Use of Volunteers in Medical or Other Hazardous 
Experiments") (ACHRE No. DOD-091494-A). 

66. Department of the Navy, SecNav Instruction 3900.39, 28 April 1969 ("Use 
of volunteers as subjects of research, development, tests, and evaluation"). 

67. Department of the Air Force, AFR 169-8, 8 October 1965 ("Medical 
Education and Research—Use of Volunteers in Aerospace Research"). 

68. Ibid. 

69. Ibid. 

70. National Aeronautics and Space Administration, Manned Spacecraft 
Center, MSCI 1860.2, 12 May 1966 ("Establishment of MSC Radiological Control 
Manual and Radiological Control Committee") (ACHRE No. NASA-022895-A), 3. 

National Aeronautics and Space Administration, "Ames Management Manual 
7170-1," 15 January 1968 ("Human Research Planning and Approval") (ACHRE No. 
NASA- 120894- A), 3. 

71 . Ames required the voluntary, written informed consent of the subject and 
stipulated that consent be informed by an 

explanation to the subject in language understandable to 
him . . . [including] the nature, duration, and purpose of 
the human research; the manner in which it will be 
conducted; and all foreseeable risks, inconveniences and 
discomforts. 
"Ames Management Manual 7170-1," 15 January 1968, 3. 

72. The Ames director was authorized to waive the consent requirements (a) 
when the requirements would "not be necessary to protect the subject"; (b) when the 
research uses "classes of trained persons who knowingly follow a specialized calling or 
occupation which is generally recognized as hazardous," including "test pilots and 
astronauts"; and (c) when the research "would be seriously hampered" by compliance. 
"Ames Management Manual 7170-1," 15 January 1968, 3. 

73. For example, one review from this group recommended changes in a 
consent form to include 

[T]he part of the procedure you are consenting to which 
principally benefits the research program and is not part 
of your treatment is known as arterial puncture. . . . 
These risks will be explained to you in detail if you so 
desire. The entire procedure, including the diagnostic 
radioscan, takes about an hour. 



193 



Although this proposed consent form does not delineate the medical risks posed by the 
procedure, its statement that the patient's participation is incidental to treatment may 
provide a greater opportunity for the patient to make an informed decision about 
participation. George A. Rathert, Jr., Chairman, Human Research Experiments Review 
Board, ARC, to Director, 20 January 1969 ("Proposed Investigation entitled 
'Measurement of Cerebral Blood Flow in Man by an Isotopic Technique Employing 
External Counting,' by Dr. Leo Sapierstein, Stanford University") (ACHRE No. NASA- 
022895-A), 4. 

At MSC, the instruction establishing the Medical Uses Subcommittee was 
rescinded in 1968. In 1969, formal combination of the medical operations and medical 
research functions at MSC led to the reestablishment of the instruction as the Medical 
Isotopes Subcommittee at MSC. No evidence suggests what factors, other than risk, 
were considered in this form of prior review is available currently. National Aeronautics 
and Space Administration, Manned Spacecraft Center, MSCI 1860.2, 12 May 1966 
("Establishment of MSC Radiological Control Manual and Radiological Control 
Committee"); and National Aeronautics and Space Administration, NMI 1 156.19, 28 
August 1969 ("Medical Isotopes Subcommittee of the MSC Radiation Safety 
Committee") (ACHRE No. NASA-022895-A). 

74. National Aeronautics and Space Administration, NMI 71008.9, 2 February 
1972 ("Human Research Policy and Procedures") (ACHRE No. NASA-022895-A). See 
also, National Aeronautics and Space Administration, NMI 7100.9 ("Power and 
Authority - To Authorize Human Research and to Grant Certain Related Exceptions and 
Waivers") (ACHRE No. NASA-022895-A). 

75. Commission on CIA Activities within the United States, Report to the 
President, (Washington, D.C.: GPO, 1975). 

76. U.S. Congress, The Select Committee to Study Governmental Operations 
with Respect to Intelligence Activities, Foreign and Military Intelligence [Church 
Committee report], report no. 94-755, 94th Cong., 2d Sess. (Washington, D.C.: GPO, 
1976), 394. 

77. For general information on the CIA program, see the Church Committee 
report, 385-422, and J. Marks, The Search for the "Manchurian Candidate": The CIA 
and Mind Control (New York: Times Books, 1978). 

78. Church Committee report, book 1, 389. 

79. Church Committee report, book 1, 400, 402. In 1963 the CIA inspector 
general (IG) recommended that unwitting testing be terminated, but Deputy Director for 
Plans Richard Helms (who later became director of Central Intelligence) continued to 
advocate covert testing on the ground that "positive operational capability to use drugs is 
diminishing, owing to a lack of realistic testing. With increasing knowledge of the state 
of the art, we are less capable of staying up with the Soviet advances in this field." The 
Church Committee noted that "Helms attributed the cessation of the unwitting testing to 
the high risk of embarrassment to the Agency as well as the 'moral problem.' He noted 
that no better covert situation had been devised than that which had been used, and that 
'we have no answer to the moral issue.'" 

80. Ibid., 402. 

8 1 . Executive Order 11905(19 February 1 976). 

82. Executive Order 12036, section 2-301 (26 January 1978) and Executive 
Order 12333, section 2.10 (4 December 1981). 



194 



83. U.S. Army Inspector General, Use of Volunteers in Chemical Agent 
Research [Army IG report] (Washington, D.C.: GPO, 1975), 2. 

84. One noted exception involved using LSD as an interrogation devise on ten 
foreign intelligence agents, and one U.S. citizen suspected of stealing classified 
documents. Army IG report, 143. 

85. Army IG report, 87. 

86. Ibid. 

87. The CIA paid death benefits to the Olson family after Frank Olson's death, 
and the Army secretly paid half of an $18,000 settlement that the Blauer family 
negotiated with the state of New York in 1955. The state ran the psychiatric institute 
that administered the drugs, but which never disclosed the Army's involvement. Both 
agencies feared that the resulting embarrassment and adverse publicity might undermine 
their ability to continue their secret research programs. Barrett v. United States, 6660 F. 
Supp. 1291 (E. D. N.Y., 1987). 

88. Feres v. United States, 340 U.S. 1 46 ( 1 950). 

89. United States v. Stanley, 483 U.S. 669 ( 1 987). 

90. 483 U.S. 669, 682. 

91. 483 U.S. 669, 687-88. 

92. 483 U.S. 669, 709-10. 

93. George Annas, a scholar of human experimentation and biomedical ethics, 
has traced the history of the Nuremberg Code in the U.S. courts. The first express 
reference in a majority opinion, Annas found, was in a 1973 decision in the Circuit Court 
in Wayne County, Michigan. The decisions in which the Code has since been cited, 
Annas concluded, reflect the proposition that the Nuremberg Code is a "document 
fundamentally about nontherapeutic experimentation." Thus, the "types of experiments 
that U.S. judges have found the Nuremberg Code useful for setting standards have 
involved nontherapeutic experiments often conducted without consent. . . . Many of 
these experiments were justified by national security considerations and the cold war." 
George J. Annas, "The Nuremberg Code in U.S. Courts: Ethics versus Expediency," in 
George J. Annas and Michael A. Grodin, eds.. The Nazi Doctors and the Nuremberg 
Code: Human Rights in Human Experimentation (New York: Oxford University Press, 
1992), 218. 



195 



4 

Ethics Standards 
in Retrospect 



/\ccording to the mission set out in our charter, the Advisory Committee 
is in essence a national ethics commission. In this capacity we were obliged to 
develop an ethical framework forjudging the human radiation experiments. This 
proved to be one of our most difficult tasks, for we were not only dealing with 
complex events that occurred decades ago, but also with some of the most 
controversial issues in moral philosophy. This chapter sets out the standards that 
we believe are appropriate for evaluating human radiation experiments and offers 
reasons for relying on them. It then applies these standards to the results of the 
historical research we have conducted and draws ethical conclusions.* 

Fulfilling our charge to "determine the ethical and scientific standards and 
criteria" to evaluate human radiation experiments that took place between 1 944 
and 1974 requires consideration of a complex question: Is it correct to evaluate 
the events, policies, and practices of the past, and the agents responsible for them, 
against ethical standards and values that we accept as valid today but that may not 



"Some of the features of the moral framework presented in this chapter pertain to 
biomedical experiments only and not to intentional releases. A moral analysis of 
intentional releases involves somewhat different elements than a moral analysis of 
biomedical experiments, because they engage different ethical issues. For example, a 
requirement of individual informed consent is not applicable to the intentional releases, 
and the concepts of risk and benefit and national security have different implications for 
them. Ethical and policy issues specific to intentional releases are discussed in chapter 
11. 

196 



Chapter 4 

have been widely accepted then? Or must we limit our ethical evaluation of the 
past to those standards and values that were widely accepted at the time? This is 
the problem of retrospective moral judgment. 

Quite apart from the issue of the validity of projecting current standards 
onto the past, there is another question that this chapter must address: In a 
pluralistic society such as ours, is there at present a sufficiently broad consensus 
on ethical standards to make possible a public evaluation that is not simply the 
arbitrary imposition of one particular moral point of view among several or even 
many? This is the problem of value pluralism. The ethical framework the 
Advisory Committee employs takes both these issues into account. 

This chapter is divided into two parts. In the first part we present and 
defend the ethical framework adopted by the Committee for the evaluation of 
human radiation experiments conducted from 1944 to 1974 and the agents 
responsible for them. We begin by identifying the types of moral judgments with 
which the Committee is concerned and the different kinds of ethical standards 
against which these judgments can be made. We next address two challenges to 
the position that the Advisory Committee can use these, or any other, standards to 
make valid ethical judgments. These challenges are (1) that the diversity of views 
about ethics in American society invalidates any effort by a public body such as 
the Advisory Committee to make moral judgments and (2) that the diversity of 
views about ethics across time similarly invalidates our making defensible moral 
judgments about the past. Although the Committee does not accept these 
challenges as definitive, we discuss these as well as other factors that influence or 
limit ethical evaluation. We include here a discussion of an issue of particular 
relevance to our charge: what role, if any, considerations of national security 
should play in the Committee's ethical framework. We also consider factors that 
can mitigate the blame we would otherwise place on agents (whether individuals 
or collective entities) for having conducted morally wrong actions. 

In the second part of the chapter, we explore how the Committee's ethical 
framework can be used to evaluate both experiments conducted in the past and the 
people and institutions that sponsored and conducted them. Drawing on the 
history presented in chapters 1 through 3, we illustrate how, when applied, the 
framework is specified by context and detail. This specification of the framework 
continues in part II of the report, when the framework is used to evaluate specific 
cases. 

AN ETHICAL FRAMEWORK 
Two Types of Moral Judgment 

For purposes of the Committee's charge, there are two main types of moral 
judgment: judgments about the moral quality of actions, policies, practices, 
institutions, and organizations; and judgments about the praiseworthiness or 

197 



Parti 

blameworthiness of individual agents and in some cases entities such as 
professions and governments (insofar as these can be viewed as collective agents 
with powers and responsibilities). The first type contains several kinds of 
judgments. Actions may be judged to be obligatory, wrong, or permissible. 
Institutions, policies, and practices can be characterized as just or unjust, 
equitable or inequitable, humane or inhumane. Organizations can be said to be 
responsible or negligent, fair-dealing or exploitative. 

The second type of judgment about the praiseworthiness or 
blameworthiness of agents also contains a diversity of determinations. Agents, 
whether individual or collective, can be judged to be culpable or praiseworthy for 
this or that action or policy, to be generous or mean-spirited, responsible or 
negligent, to respect the moral equality of people or to discriminate against 
certain individuals or groups, and so on. 

Three Kinds of Ethical Standards 

A recognized way to make moral judgments is to evaluate the facts of a 
case in the context of ethical standards. The Committee identified three kinds of 
ethical standards as relevant to the evaluation of the human radiation 
experiments: 1 

1 . Basic ethical principles that are widely accepted and generally 
regarded as so fundamental as to be applicable to the past as 
well as the present; 

2. The policies of government departments and agencies at the 
time; and 

3. Rules of professional ethics that were widely accepted at the 
time. 

Basic Ethical Principles 

Basic ethical principles are general standards or rules that all morally 
serious individuals accept. The Advisory Committee has identified six basic 
ethical principles as particularly relevant to our work: "One ought not to treat 
people as mere means to the ends of others"; "One ought not to deceive others"; 
"One ought not to inflict harm or risk of harm"; "One ought to promote welfare 
and prevent harm": "One ought to treat people fairly and with equal respect"; and 
"One ought to respect the self-determination of others." These principles state 
moral requirements; they are principles of obligation telling us what we ought to 
do. 2 

Every principle on this list has exceptions, because all moral principles 

198 



Chapter 4 

can justifiably be overridden by other basic principles in circumstances when they 
conflict. To give priority to one principle over another is not a moral mistake; it 
is a reality of moral judgment. The justifiability of such judgments depends on 
many factors in the circumstance; it is not possible to assign priorities to these 
principles in the abstract. 

Far more social consensus exists about the acceptability of these basic 
principles than exists about any philosophical, religious, or political theory of 
ethics. This is not surprising, given the central social importance of morality and 
the fact that its precepts are embraced in some form by virtually all major ethical 
theories and traditions. These principles are at the deepest level of any person's 
commitment to a moral way of life. 

It is important to emphasize that the validity of these basic principles is 
not typically thought of as limited by time: we commonly judge agents in the past 
by these standards. For example, the passing of fifty years in no way changes the 
fact that Hitler's extermination of millions of people was wrong, nor does it erase 
or even diminish his culpability. Nor would the passing of a hundred years or a 
thousand do so. 

This is not to deny that it might be inappropriate to apply to the distant 
past some ethical principles to which we now subscribe. It is only to note that 
there are some principles so basic that we ordinarily assume, with good reason, 
that they are applicable to the past as well as the present (and will be applicable in 
the future as well). We regard these principles as basic because any minimally 
acceptable ethical standpoint must include them. 

Policies of Government Departments and Agencies 

The policies of departments and agencies of the government can be 
understood as statements of commitment on the part of those governmental 
organizations, and hence of individuals in them, to conduct their affairs according 
to the rules and procedures that constitute those policies. In this sense, policies 
create ethical obligations. When a department or agency adopts a particular 
policy, it in effect promises to make reasonable efforts to abide by it. 3 

At least where participation in the organization is voluntary, and where the 
organization's defining purpose is morally legitimate (it is not, for example, a 
criminal organization), to assume a role in the organization is to assume the 
obligations that attach to that role. Depending upon their roles in the 
organization, particular individuals may have a greater or lesser responsibility for 
helping to ensure that the policy commitments of the organization are honored. 
For example, high-level managers who formulate organizational policies have an 
obligation to take reasonable steps to ensure that these policies are effectively 
implemented. If they fail to discharge these obligations, they have done wrong 
and are blameworthy, unless some extenuating circumstance absolves them of 
responsibility. One sort of extenuating circumstance is that the policy in question 

199 



Parti 

is unethical. In that case, we would hold an individual blameless for not 
attempting to implement it (at least if the individual did so because of a 
recognition that the policy was unethical). Moreover, we might praise the 
individual for attempting an institutional reform at some professional or personal 
risk. 

Different types of organizations have different defining purposes, and 
these differences determine the character of the department's or agency's role- 
derived obligations. All government organizations have special responsibilities to 
act impartially and to fairly protect all citizens, including the most vulnerable 
ones. These special obligations constitute a standard for evaluating the conduct 
of government officials. 

Rules of Professional Ethics 

Professions traditionally assume responsibilities for self-regulation, 
including the promulgation of certain standards to which all members are 
supposed to adhere. These standards are of two kinds: technical standards that 
establish the minimum conditions for competent practice, and ethical principles 
that are intended to govern the conduct of members in their practice. In exchange 
for exercising this responsibility, society implicitly grants professions a degree of 
autonomy. The privilege of this autonomy in turn creates certain special 
obligations for the profession's members. 

These obligations function as constraints on professionals to reduce the 
risk that they will use their special power and knowledge to the detriment of those 
whom they are supposed to serve. Thus, physicians, whose special knowledge 
gives them opportunities for exploiting patients or breaching confidentiality, are 
obligated to act in the patient's best interest in general and to follow various 
prescriptions for minimizing conflicts of interest. 

Unlike basic ethical principles that speak to the whole of moral life, rules 
of professional ethics are particularized to the practices, social functions, and 
relationships that characterize a profession. Rules of professional ethics are often 
justified by appeal to basic ethical principles. For example, as we discuss later in 
this chapter, the obligation to obtain informed consent, which is a rule of research 
and medical ethics, is grounded in principles of respect for self-determination, the 
promotion of others' welfare, and the noninfliction of harm. 

In one respect, rules of professional ethics are like the policies of 
institutions and organizations: they express commitments to which their members 
may be rightly held by others. That is, rules of professional ethics express the 
obligations that collective entities impose on their members and constitute a 
commitment to the public that the members will abide by them. Absent some 
special justification, failure to honor the commitment to fulfill these obligations 
constitutes a wrong. To the extent that the profession as a collective entity has 



200 



Chapter 4 

obligations of self-regulation, failure to fulfill these obligations can lead to 
judgments of collective blame. 

Ethical Pluralism and the Convergence of Moral Positions 

Although we have argued that there is broad agreement about and 
acceptance of basic ethical principles in the United States, such as principles that 
enjoin us to promote the welfare of others and to respect self-determination, 
people nevertheless disagree about the relative priority or importance of these 
principles in the moral life. For example, although any minimally acceptable 
ethical standpoint must include both these principles, some approaches to 
morality emphasize the importance of respecting self-determination while others 
place a higher priority on duties to promote welfare. These differences in 
approaches to morality pose a problem for public moral discourse. How can a 
public body, such as the Advisory Committee, purport to speak on behalf of 
society as a whole and at the same time respect this diversity of views about 
ethics? The key to understanding how this is possible is to appreciate that 
different ethical approaches can and often do converge on the same ethical 
conclusions. People can agree about what ought to be done without necessarily 
appealing to the same moral arguments to defend their common position. 

This phenomenon of convergence has been observed in the work of other 
public bodies whose charge was to make ethical evaluations on research 
involving human subjects, including the National Commission for the Protection 
of Human Subjects of Biomedical and Behavioral Research and the President's 
Commission for the Study of Ethical Problems in Medicine and Biomedical and 
Behavioral Research. 4 For example, both those who take the viewpoint that 
emphasizes obligations to promote welfare and to refrain from inflicting harm and 
those who accord priority to self-determination can agree that law and medical 
and research practice should recognize a right to informed consent for competent 
individuals. The argument for a requirement of informed consent based on 
promoting welfare and refraining from inflicting harm assumes that individuals 
are generally most interested in and knowledgeable about their own well-being. 
Individuals are thus in the best position to discern what will promote their welfare 
when deciding about participation in research or medical care. Allowing 
physicians or others to decide for them runs too great a risk of harm or loss of 
benefits. By contrast, an approach based on self-determination assumes that, at 
least for competent individuals, being able to make important decisions 
concerning one's own life and health is intrinsically valuable, independent of its 
contribution to promoting one's well-being. The most compelling case for 
recognizing a right of informed consent for competent subjects and patients draws 
upon both lines of justification, emphasizing that this requirement is necessary 
from the perspective of self-determination considered as valuable in itself and 
from the standpoint of promoting welfare and refraining from doing harm. 

201 



Part I 

Therefore, although people may have different approaches to the moral 
life, which reflect different priorities among basic moral principles, these 
differences need not result in a lack of consensus on social policy or even on 
particular moral rules such as the rule that competent individuals ought to be 
allowed to accept or refuse participation in experiments. On the contrary, the fact 
that the same moral rules or social policies can be grounded in different basic 
moral principles and points of view greatly strengthens the case for their public 
endorsement by official bodies charged to speak for society as a whole. 

The three kinds of ethical standards upon which the Committee relies for 
our ethical evaluations-the basic moral principles, government policies, and rules 
of professional ethics—also enjoy a broad consensus. They are not idiosyncratic 
to a particular ethical value system. Thus it would be a mistake to think that in 
order to fulfill our charge of ethical evaluation, the Advisory Committee must 
assume that there is only one uniquely correct ethical standpoint. A broad range 
of views can acknowledge that the medical profession should be held accountable 
for moral rules it publicly professes and that individual physicians can be held 
responsible for abiding by these rules of professional ethics. Likewise, regardless 
of whether one believes that the ultimate justification for government policies is 
the goal of promoting welfare and minimizing harms or respect for self- 
determination, one can agree that policies represent commitments to action and 
hence generate obligations. Moreover, any plausible ethical viewpoint will 
recognize that when individuals assume roles in organizations they thereby 
undertake role-derived obligations. 

We have already argued that the basic ethical principles that we employ in 
evaluating experiments are widely accepted and command significant allegiance 
not only from our contemporaries but also from reflective and morally sensitive 
individuals and ethical traditions in the past. It would be very implausible to 
construe any of them as parochial or controversial. 

Retrospective Moral Judgment and the Challenge of Relativism 

Some may still have reservations about the project of evaluating the ethics 
of decisions and actions that occurred several decades ago. The worry is that it is 
somehow inappropriate, if not muddled, to apply currently accepted standards to 
earlier periods when they were not accepted, recognized, or viewed as matters of 
obligation. This is an important worry, though one that does not apply to our 
framework. 

The position that the values and principles of today cannot be validly 
applied to past situations in which they may not have been accepted is called 
historical ethical relativism. This is the thesis that moral judgments across time 
are invalid because moral judgments can be justified only by reference to a set of 
shared values, and the values of a society change over time. According to this 
view, one historical period differs from another by virtue of lacking the relevant 

202 



Chapter 4 

values contained in the other historical period, namely, those that support or 
justify the particular moral judgments in question. Understood in this way, 
historical ethical relativism, if true, would explain why some retrospective moral 
judgments are invalid, namely, where the past society about which the judgments 
are made lacked the values that, in our time, support our judgments. In other 
words, the claim is that moral judgments made about actions and agents in one 
period of history cannot be made from the perspective of the values of another 
historical period. 

The question of whether historical ethical relativism limits the validity of 
retrospective moral judgment is not a mere theoretical puzzle for moral 
philosophers. It is an eminently practical question, since how we answer it has 
direct and profound implications for what we ought to do now. Most obviously, 
the position we adopt on the validity of retrospective moral judgment will 
determine whether we should honor claims that people now make for remedies for 
historical injustices allegedly perpetrated against themselves or their ancestors. 
Similarly, we must know whether there is any special circumstance resulting from 
the historical context in which the responsible parties acted that mitigates 
whatever blame would be appropriate. We return to this question later in the 
chapter. 

In addition, something even more fundamental is at stake in the debate 
over retrospective moral judgment: the possibility of moral progress. The idea of 
moral progress makes sense only if it is possible to make moral judgments about 
the past and to make them by appealing to some of the same moral standards that 
we apply to the present. Unless we can apply the same moral yardstick to the past 
and the present, we cannot meaningfully say either that there has been moral 
progress or that there has not. For example, unless some retrospective moral 
judgments are valid, we cannot say that the abolition of slavery is a case of moral 
progress, moral regression, or either one. More specifically, unless we can say 
that slavery was wrong, we cannot say that the abolition of slavery was a moral 
improvement. 

For these and other reasons, the acceptance of historical ethical relativism 
has troubling implications. But even if we were to accept historical ethical 
relativism as the correct position, it would not follow from this alone that there is 
anything improper about making judgments about radiation experiments 
conducted decades ago based on the three kinds of ethical standards the 
Committee has identified. Two of these kinds of standards-government policies 
and rules of professional ethics-are standards used at the time the experiments 
were conducted. Neither of these kinds of standards involves projecting current 
cultural values onto a different cultural milieu. 

We have already argued that basic ethical principles, the third kind of 
standard adopted by the Committee, are not temporally limited. Although there 
have been changes in ethical values in the United States between the mid- 1940s 
and the present, it is implausible that these changes involved the rejection or 

203 



Part I 

affirmation of principles so basic as that it is wrong to treat people as mere means, 
wrong to inflict harm, or wrong to deceive people. Thus, the Advisory 
Committee's evaluations of the human radiation experiments in light of these 
basic principles is based on a simple and we think reasonable assumption that, 
even fifty years ago, these principles were pervasive features of moral life in the 
United States that were widely recognized and accepted, much as we recognize 
and accept them today. 5 

Factors That Influence or Limit Ethical Evaluation 

Several considerations influence and can limit the ability to reach ethical 
conclusions about Tightness and wrongness and praise and blame. Some of these 
may be more likely to be present in efforts to evaluate the past, but all can arise 
when attempts are made to evaluate contemporary events as well. The most 
important such limitations relevant to the Advisory Committee's evaluations are 
these: 

( 1 ) Lack of evidence as to whether ethical 
standards were followed or violated and if so, 
by whom, and 

(2) The presence of conflicting obligations. 

The three kinds of ethical standards adopted by the Committee can yield 
the conclusion that an individual or collective agent had or has a particular 
obligation. But this conclusion is not by itself sufficient to determine in any 
particular case whether anything wrong was done or whether any individual or 
collective agent deserves blame. 

Lack of Evidence 

Sound evaluations cannot be made without sufficient evidence. 
Sometimes it cannot be determined if anything wrong was done because key facts 
about a case are missing or unclear. Other times there may be sufficient evidence 
that a wrong was done, but insufficient evidence to determine who performed the 
action that was wrong or who authorized the policy that was wrong or who was 
responsible for a practice that was wrong. This is why the Advisory Committee 
strove during our tenure to reconstruct the details of the circumstances under 
which the human radiation experiments themselves took place. However, these 
records are incomplete, and even the copious documentation we have gathered 
does not tell as complete a story as sometimes was needed to make ethical 
evaluations. 



204 



Chapter 4 

Conflicting Obligations 

Because we all have more than one obligation, because they can conflict 
with one another, and because some obligations are weightier than others, a 
particular obligation that is otherwise morally binding may not be binding in a 
particular circumstance, all things considered. For example, a government 
official might be obligated to follow certain routine procedures, but in a time of 
dire emergency he or she might have a weightier obligation to avert great harm to 
many people by taking direct action that disregards the procedures. Similarly, a 
physician is obligated to keep his patient's condition confidential, but in some 
cases it is permissible and even obligatory to breach this confidence (for example, 
in order to prevent the spread of deadly infectious diseases). In such cases, the 
agent has done nothing wrong in failing to do what he or she would ordinarily be 
morally obligated to do; that obligation has been validly overridden by what is in 
the particular circumstances a weightier obligation. 

The presence of conflicting obligations may limit our ability to make 
moral judgments when, for example, it is difficult to determine, in a particular 
case, which obligation should take precedence. At the same time, however, if it 
can be determined which obligation is weightier, then the presence of this factor 
does not serve as an impediment to evaluation; rather, it can lead to the 
conclusion that nothing morally wrong was done and that no one should be 
blamed. 

An example of a potentially overriding obligation that is especially 
important for the Advisory Committee's work is the possibility that, during the 
period of the radiation experiments, obligations to protect national security were 
sometimes more morally weighty than obligations to comply with standards for 
human subjects research. If the threat were great enough, considerations of 
national security grounded in the basic ethical principle that one ought to promote 
welfare and prevent harm could justifiably override the basic ethical principle of 
not using people as mere means to the ends of others, as well as the more specific 
rule of research ethics requiring the voluntary consent of human subjects. Had 
such an overriding obligation to protect national security existed during the period 
we studied, it also would have relieved responsible individuals of any blame 
otherwise attributable to them for using individuals in experiments that were 
crucial to the national defense. 

Especially during the late 1940s and early 1950s, and then again in the 
first years of the early 1960s, our country was engaged in an intense competition 
with the Soviet Union. A high premium was placed upon military superiority, not 
only in "conventional" warfare but also in atomic, biological, and chemical 
warfare. The DOD's Wilson memorandum, when originally promulgated in 1953, 
declared that it was directed toward the need to pursue atomic, biological, and 
chemical warfare experiments "for defensive purposes" in these fields. 

It would not be surprising, therefore, to discover that, in the government's 

205 



Parti 

policies and rules for human subject research, provisions had been made for the 
possibility that obligations to protect national security might conflict with and 
take priority over obligations to protect human subjects, and thus that such 
policies would have included exceptions for national security needs. The moral 
justification would also not be surprising: that, in order to preserve the American 
way of life with its precious freedoms, some sacrifices of individual rights and 
interests would have to be made for the greater good. The very phrase Cold War 
expressed the conviction that we already were engaged in a life-or-death struggle 
and that in war actions may be permissible that would be impermissible in 
peacetime. Survival in the treacherous and heavily armed post-World War II era 
might demand no less, repugnant as those actions otherwise might be to many 
Americans. 

The Advisory Committee did not undertake an inquiry to determine 
whether during either World War II or the Cold War there were ever 
circumstances in which considerations of national security might have justified 
infringements of the rights and protections that would otherwise be enjoyed by 
American citizens in the context of human experimentation. Our sources for 
answering this question were limited to materials pertinent to specific human 
radiation experiments and declassified defense-related memorandums and 
transcripts. With regard to the experiments, particular cases are reviewed in part 
II of this report. In those experiments that took place under circumstances most 
closely tied to national security considerations, such as the plutonium injections 
(see chapter 5), it does not appear that such considerations would have barred 
satisfying the basic elements of voluntary consent. Thus, for instance, although 
the word plutonium was classified until the end of World War II, subjects could 
still have been asked their permission after having been told that subjects in the 
experiment would be injected with a radioactive substance with which medical 
science had had little experience and which might be dangerous and that would 
not help them personally, but that the experiment was important to protecting the 
health of people involved in the war effort or safeguarding the national defense. 

With regard to defense-related documents, in none of the memorandums 
or transcripts of various agencies did we encounter a. formal national security 
exception to conditions under which human subjects may be used. In none of 
these materials does any official, military or civilian, argue for the position that 
individual rights may be justifiably overridden owing to the needs of the nation in 
the Cold War. In none of them is an official position expressed that the 
Nuremberg Code or other conventions concerning human subjects could be 
overridden because of national security needs. 

Some government officials, military and civilian, may have personally 
advocated the view that obligations to protect national security were more 
important than obligations to protect the rights and interests of human subjects. 
It is, of course, possible that the priority placed on national security was so great 
in some circles of government that the ability of security interests to override 

206 



Chapter 4 

other national interests was implicitly assumed, rather than explicitly articulated. 
It is a matter of historical record that some initiatives undertaken by government 
officials at some agencies during this period adopted the view that greater 
national purposes justified the exploitation of individuals. Notorious examples 
are the CIA's MKULTRA project and the Army's psychochemical experiments, 
which subjected unsuspecting people to experiments with LSD and other 
substances (see chapter 3). A However, even the internal investigation of the 
Department of Defense into these incidents in the 1970s concluded that these 
incidents were violations of government policy, not recognized legitimate 
exceptions to it. 7 

During the era of the Manhattan Project, the United States and its allies 
were engaged in a declared and just war against the Axis powers. Regarding the 
possibility of a wartime exception, it is well documented that during World War II 
the Committee on Medical Research (CMR) of the Executive Office of the 
President funded research on various problems confronting U.S. troops in the 
field, including dysentery, malaria, and influenza. This research involved the use 
of many subjects whose capacity to consent to be a volunteer was questionable at 
best, including children, the mentally retarded, and prisoners. K However, when 
the CMR considered proposed gonorrhea experiments that would have involved 
deliberately exposing prisoners to infection, the resulting discussion about the 
ethics of research exhibited a cautious attitude. The conclusion was that only 
"volunteers" could be used and that they had to be carefully informed about the 
risks and benefits of participation. In these and other classified conversations, the 
CMR took the position that care is to be taken with human subjects, including 
conscientious objectors and military personnel. 9 

It is difficult to reconcile these deliberations with the fact that many 
subjects of CMR-funded research were not true volunteers. Whether the CMR 
believed that the needs of a country at war justified the use of people who could 
not be true volunteers as research subjects is not known. 

It would, however, be an error to conclude that, even in contexts where 
important national security interests are at stake, such as during wartime, a 
conflict between obligations to protect national defense and obligations to protect 
human subjects ought always to be resolved in favor of national security. The 
question of whether any and all means are morally acceptable for the sake of 
national security and the national defense is a complex one. Even in the case of a 
representative democracy that is not an aggressor, it would be wrong to assume 
that there are no moral constraints in time of war. All of the major religious and 
secular traditions concerning the morality of warfare recognize that there are 
substantial limitations upon the manner in which even a just war is conducted. 10 
The issue of the morality of "total warfare" for a just cause, including the use of 
medical science, was beyond the scope of the Advisory Committee's charter, 
deliberations, and expertise. 



207 



Part I 

Distinguishing Between the Wrongness of Actions and Policies and the 
Blameworthiness of Agents 

Factors That Influence or Limit Judgments About Blame 

The factors we have just discussed—lack of evidence and the presence of 
conflicting obligations-place limits on our ability to make judgments about both 
the Tightness and wrongness of actions and the blameworthiness of the agents 
responsible for them. Some factors, however, place limits only on our ability to 
make judgments about the blameworthiness of agents. Even in cases where 
actions or policies are clearly morally wrong, it may be uncertain how 
blameworthy the agents who conducted or promulgated them are, or in fact, 
whether they are blameworthy at all. Some factors make it difficult to affix 
blame; other factors can mitigate or lessen the blame actors deserve. Four such 
factors are of particular concern to the Committee: ' ' 

(1) Factual ignorance; 

(2) Culturally induced ignorance about relevant moral considerations; 

(3) Evolution in the interpretations and specification of moral principles; 
and 

(4) Indeterminacy in an organization's division of labor, with the result 
that it is unclear who has responsibility for implementing the 
commitments of the organization. 

Factual Ignorance 

Factual ignorance refers to circumstances in which some information 
relevant to the moral assessment of a situation is not available to the agent. There 
are many reasons that this may be so, including that the information in question is 
beyond the scope of human knowledge at the time or that there was no good 
reason to think that a particular item of information was relevant or significant. 
However, just because an agent's ignorance of morally relevant information leads 
him or her to commit a morally wrong act, it does not follow that the person is not 
blameworthy for that act. The agent is blameworthy if a reasonably prudent 
person in that agent's position should have been aware that some information was 
required prior to action, and the information could have been obtained without 
undue effort or cost on his or her part. Some people are in positions that obligate 
them to make special efforts to acquire knowledge, such as those who are directly 
responsible for the well-being of others. Determinations of culpable and 
nonculpable factual ignorance often turn on whether the competent person in the 

208 



Chapter 4 

field at that time had that knowledge or had the means to acquire it without undue 
burdens. 

Culturally Induced Moral Ignorance 

Sometimes cultural factors can prevent individuals from discerning what 
they are morally required to do and can therefore mitigate the blame we would 
otherwise place on individuals for failing to do what they ought to do. In some 
cases these factors may have been at work in the past but are no longer operative 
in the present, because of changes in culture over time. 

An individual may, like other members of the culture, be morally 
ignorant. Because of features of his or her deeply enculturated beliefs, the 
individual may be unable to recognize, for example, that certain people (such as 
members of another race) deserve equal respect or even that they are people with 
rights. Moral ignorance can impair moral judgment and hence may result in a 
failure to act morally. 

In extreme cases, a culture may instill a moral ignorance so profound that 
we may speak of cultural moral blindness. In some societies the dominant culture 
may recognize that it is wrong to exploit people but fail to recognize certain 
classes of individuals as being people. Some of those committed to the ideology 
of slavery may have been morally blind in just this way, and their culture may 
have induced this blindness. 

Here it is crucial to distinguish between culpable and nonculpable moral 
ignorance. The fact that one's moral ignorance is instilled by one's culture does 
not by itself mean that one is not responsible for being ignorant; nor does it 
necessarily render one blameless for actions or omissions that result from that 
ignorance. What matters is not whether the erroneous belief that constitutes the 
moral ignorance was instilled by one's culture. What matters is the extent to 
which the individual can be held responsible for maintaining this belief, as 
opposed to correcting it. Where opportunities for remedying culturally induced 
moral ignorance are available, a person may rightly be held responsible for 
remaining in ignorance and for the wrongful behavior that issues from his or her 
mistaken beliefs. 

People who maintain their culturally induced moral ignorance in the face 
of repeated opportunities for correction typically do so by indulging in 
unjustifiable rationalizations, such as those associated with racist attitudes. They 
show an excessive partiality to their own opinions and interests, a willful rejection 
of facts that they find inconvenient or disturbing, an inflated sense of their own 
self-worth relative to others, a lack of sensitivity to the predicament of others, and 
the like. These moral failings are widely recognized as such across a broad 
spectrum of cultural values and ethical traditions, both religious and secular. 

Only if an agent could not be reasonably expected to remedy his or her 
culturally induced moral ignorance would such ignorance exculpate his conduct. 

209 



Parti 

But even in cases in which the individual could not be blamed for persisting in 
ignorance, this would do nothing to show that the actions or omissions resulting 
from his or her ignorance were not wrong. Nonculpable moral ignorance only 
exculpates the agent; it does not make wrong acts right. 

Evolution in Interpretations of Ethical Principles 

There is another respect in which the dependence of our perceptions of 
right and wrong on our cultural context has a bearing on the Advisory 
Committee's evaluations. While basic ethical principles do not change, 
interpretations and applications of basic ethical principles as they are expressed in 
more specific rules of conduct do evolve over time through processes of cultural 
change. 

Recognizing that more specific moral rules do change has implications for 
how we judge the past. For example, the current requirement of informed consent 
is the result of evolution. Acceptance of the simple idea that medical treatment 
requires the consent of the patient (at least in the case of competent adults) seems 
to have preceded by a considerable interval the more complex notion that 
informed consent is required. 12 Furthermore, the notion of informed consent itself 
has undergone refinement and development through common law rulings, through 
analyses and explanations of these rulings in the scholarly legal literature, through 
philosophical treatments of the key concepts emerging from legal analyses, and 
through guidelines in reports by government and professional bodies. 13 For 
example, as early as 1914, the duty to obtain consent to medical treatment was 
established in American law: "Every human being of adult years and sound mind 
has a right to determine what shall be done with his own body; and a surgeon who 
performs an operation without his patient's consent commits an assault." 14 
However, it was not until 1957 that the courts decreed that consent must be 
informed, 15 and this 1957 ruling was only the beginning of a long debate about 
what it means for a consent to be informed. Thus it is probably fair to say that the 
current understanding of informed consent is more sophisticated, and what is 
required of physicians and scientists more demanding, than both the preceding 
requirement of consent and earlier interpretations of what counts as informed 
consent. As the content of the concept has evolved, so has the scope of the 
corresponding obligation on the part of these professionals. For this reason it 
would be inappropriate to blame clinicians or researchers of the 1940s and 1950s 
for not adhering to the details of a standard that emerged through a complex 
process of cultural change that was to span decades. At the same time, however, 
it remains appropriate to hold them to the general requirements of the basic moral 
principles that underlie informed consent—not treating others as mere means, 
promoting the welfare of others, and respecting self-determination. 



210 



Chapter 4 

Inferring Bureaucratic Responsibilities 

It is often unclear in complex organizations such as government agencies 
who has responsibility for implementing the organization's policies and rules. 
This is particularly common in new and changing organizations, where it is more 
likely than in stable organizations that there will be interconnecting lines of 
authority among employees and officials, and job descriptions that are not explicit 
with respect to responsibility for implementation of policies and initiatives. When 
policies are not properly implemented in organizations that fit this description, it 
often is difficult to assign blame to particular individuals. An employee or 
official of an agency cannot fairly be blamed for a failed or poorly executed 
policy unless it can be determined with confidence that the person had 
responsibility for implementing that policy and should have known that he or she 
had this responsibility. 

The Importance of Distinguishing Wrongdoing from 
Blameworthiness 

Judgments of wrongdoing and judgments of blameworthiness have very 
different implications. Even where a wrong was done, it does not follow that 
anyone should be blamed for the wrong. This is because there are factors, 
including the four we have just described, that can lessen or remove blame from 
an agent for a morally wrong act but that cannot in any way make the wrong act 
right. If experiments violated basic ethical principles, institutional or 
organizational policies, or rules of professional ethics, then they were and will 
always be wrong. Whether and how much anyone should be blamed for these 
wrongs are separate questions. 16 

The distinction between the moral status of experiments and that of the 
individuals who were involved with conducting, funding, or sponsoring them also 
has important implications for our own time. For a society to make moral 
progress, individuals must be able to exercise moral judgment about their actions. 
It is important for social actors to be critical about their activities, even those in 
which they have been engaged for some time. It is important for them to be able 
to step back and analyze their actions as right or wrong. If we did not distinguish 
between actions and agents, then people may feel that, once they have perceived 
their moral error, it is "too late" for them to change their ways, to object to the 
ongoing activity, and to try to rally others in support of reform. 

For any generation to initiate morally indicated reforms, it must be able to 
take this critical stance. As we see in part III of this report, even now there are 
aspects of our society's use of human subjects that should be critically examined. 
The actions we ourselves have performed do not condemn us as moral agents 
unless we refuse to open ourselves to the possibility that we have in some ways 
been in error. As we have said, even if we are exculpated by our own culturally 

211 



Parti 

induced moral ignorance, that does not make our wrong acts right. Even if we 
must accept a measure of blame for our actions, we are free to achieve a critical 
assessment and to initiate and participate in needed change. 

The Significance of Judgments About Blameworthiness 

The Committee believes that its first task is to evaluate the Tightness or 
wrongness of the actions, practices, and policies involved in the human radiation 
experiments that occurred from 1944 to 1974. However, it is also important to 
consider whether judgments ascribing blame to individuals or groups or 
organizations can responsibly be made and whether they ought to be made. 

There are three main reasons forjudging culpability as well as wrongness.. 
First, a crucial part of the Committee's task is to make recommendations that will 
reduce the risk of errors and abuses in human experimentation in the future, on 
the basis of its diagnoses of what went wrong in the past. A complete and 
accurate diagnosis requires not only stating what wrongs were done, but also 
explaining who was responsible for the wrongs occurring. To do this is likely to 
yield the judgment that some individuals were morally blameworthy. Second, 
unless judgments of culpability are made about particular individuals, one 
important means of deterring future wrongs will be precluded. People 
contemplating unethical behavior will presumably be more likely to refrain from 
it, other things being equal, if they believe that they, as individuals, may be held 
accountable for wrongdoing than if they can assure themselves that at most their 
government or their particular government agency or their profession may be 
subject to blame. Third, ethical evaluation generally involves both evaluation of 
the Tightness or wrongness of actions and the praiseworthiness or 
blameworthiness of agents. In the absence of any explicit exemption of the latter 
sorts of judgment in our mandate, the Committee believes it would be arbitrary to 
exclude them. 

Having made a case for judgments of culpability as well as wrongness, the 
Committee believes it is very important to distinguish carefully between judging 
that an individual was culpable for a particular action and judging that he or she is 
a person of bad moral character. Justifiable judgments of character must be based 
on accurate information about long-standing and stable patterns of action in a 
number of areas of a person's life, under a variety of different situations. Such 
patterns cannot usually be inferred from information about a few isolated actions 
a person performs in one particular department of his or her life, unless the 
actions are so extreme as to be on the order of heinous crimes. 

APPLYING THE ETHICAL FRAMEWORK 

The three kinds of standards presented in this chapter provide a general 
framework for evaluating the ethics of human radiation experiments. In this 

212 



Chapter 4 

section of the chapter, we revisit those standards in the specific context of human 
radiation experiments conducted between 1944 and 1974 and what we have 
learned about the policies and practices involving human subjects during that 
period. 

Basic Ethical Principles 

Earlier in this chapter we identified six basic ethical principles as 
particularly relevant to our work: "One ought not to treat people as mere means to 
the ends of others"; "One ought not to deceive others"; "One ought not to inflict 
harm or risk of harm"; "One ought to promote welfare and prevent harm"; "One 
ought to treat people fairly and with equal respect"; and "One ought to respect the 
self-determination of others." 

These principles are central to our analysis of the cases we present in part 
II of the report, although not every case we evaluate engages every principle. 
Two of the principles, however, recur repeatedly as we consider the ethics of past 
experiments. These are "One ought not to treat people as mere means to the ends 
of others" and "One ought not to inflict harm or risk of harm." Whether an 
experiment involving human subjects violates the principle not to use people as 
mere means generally depends on two factors-consent and therapeutic intent. An 
individual may give his or her consent to being treated as a means to the ends of 
others. If a person freely consents, then he or she is no longer being used as a 
mere means, that is, as a means only. Thus, if a person is used as a subject in an 
experiment from which the person cannot possibly benefit directly, but the 
person's consent to that use is obtained, the person is not being used as a mere 
means to the ends of others. By contrast, if a person is used as a subject in such 
an experiment but the person's consent is not obtained for that use, the person is 
being used as a mere means to the ends of the investigator conducting the 
experiment and the institutions funding or sponsoring the experiment. 

If an action that involves the use of a person is undertaken in whole or in 
part for that person's benefit, then the person is not being used as a mere means 
toward the ends of others. Thus, if a person is used as a subject in an experiment 
that is intended to offer the subject a prospect of direct benefit, then, even if the 
subject's consent has not been obtained, the subject is not being used as a mere 
means to the ends of others. This is because the experiment is intended to serve 
the subject's interests as well as the interests of the investigator and funding 
agency. It may be wrong not to obtain the subject's consent in this case, but the 
wrong does not stem from a violation of the principle not to use people as mere 
means. Instead, the wrong reflects the violation of other basic principles such as 
the principles enjoining us to respect self-determination and to promote welfare 
and prevent harm. 

These two factors-the obtaining of consent and an intention to benefit- 
also can transform the moral quality of an act that involves the imposition of harm 

213 



Part I 

or risk of harm. One important way to make the imposition of a risk of harm 
justifiable is to obtain the person's permission for the imposition. The imposition 
of risk on a person also is more justifiable when the risk is imposed to secure a 
benefit for that person, although even in the presence of a prospect of offsetting 
benefit, the imposition of risk on another without that person's consent is morally 
questionable because it appears to violate the principle of respect for self- 
determination. 17 

Consider the following example of how the factors of therapeutic intent 
and consent can transform a morally questionable action into a morally acceptable 
one. Patients are enrolled in an experiment in which they are given a new drug 
that is unproven in humans, induces substantial discomfort or even suffering, and 
may produce irreversible damage to vital organs. There is, however, no effective 
treatment for the condition from which these patient-subjects suffer, and the 
condition is life threatening. The drug is theoretically promising compared with 
related drugs used in similar diseases, and it has proven effective in animals. 
Further, the opportunity to participate in the experiment is offered to patients 
while they are lucid, comfortable, and at ease. Under these circumstances the 
imposition of harm may be transformed into a caring and respectful act. 

Policies of Government Agencies 

Where agencies of the government had policies on the conduct of research 
involving human subjects, and where these policies included requirements or 
rules that are morally sound, these policies constitute standards against which the 
conduct of the agencies and the people who worked there, as well as the 
experiments the agencies sponsored or conducted, can be evaluated. Government 
agencies must be held responsible for failures to implement their own policies. 
To do otherwise is to break faith with the American people, who have a 
reasonable expectation that an agency will conduct its affairs in accord with the 
agency's stated policies. As we noted in chapter 1 , it is not always clear, 
however, whether statements made in letters or memorandums constitute agency 
policy. When there is little evidence that a statement by a government official 
was ever implemented, it is often difficult to determine whether this was an 
instance of an agency failing to implement its own policies or an instance where a 
statement by a government official was not perceived as agency policy in the first 
place. 

Among the general conclusions that can be drawn from the discussions 
about policies during the late 1940s and early 1950s is that the AEC, DOD, and 
NIH required investigators to obtain the consent of the healthy or "normal" 
subject, and prior group review was required for risk in research using 
radioisotopes for all private and publicly financed research (and, in the NIH, for 
all hazardous procedures). Also, in 1953, the Department of Defense adopted the 
Nuremberg Code as the policy for research related to atomic, biological, and 

214 



Chapter 4 

chemical warfare, and the NIH Clinical Center articulated a consent requirement 
for patient-subjects in intramural research (see chapter 1). 

Two questions that arise at this juncture are whether an experiment was 
wrong if it violated one of these policies but took place at another government 
agency, and whether an experiment was wrong if it took place under the auspices 
of an agency before it promulgated the policy. The answer to both questions is 
the same: Even if such an experiment was not wrong according to the policy of 
the agency sponsoring the experiment at the time, the experiment may 
nevertheless have been unethical based on one or more basic ethical principles or 
rules of professional ethics. 

As is the case today, decades ago government officials had obligations to 
take reasonable steps to see that policies were adequately implemented. 18 Policies 
constitute organizational commitments, and organizational commitments generate 
obligations on the part of the organization and its members. In some cases, 
however, it is not clear that conditions stated by individual officials rise to a level 
that all would be comfortable calling "policies." Accordingly, it is not clear 
whether corresponding obligations to implement can be inferred. The two letters 
signed by AEC General Manager Carroll Wilson in April and November 1947 are 
the best examples of this problem. Nevertheless, if it is correct to say that high 
officials have an obligation to exert due efforts to implement and communicate 
the rules they are empowered to establish, then they may reasonably be blamed 
for failures in this regard. Further, if they do not even attempt to articulate rules 
that are indicated by basic ethical principles and that are clearly relevant to 
organizational activities that fall under their authority, they are also subject to 
moral blame. 

The mitigating condition of culturally induced moral ignorance does not 
apply to government officials who failed to exercise their responsibilities to 
implement or communicate requirements that clearly fell within the ambit of their 
office and of which they were aware. The very fact that these requirements were 
articulated by the agencies in which they worked is evidence that officials could 
not have been morally ignorant of them. 

We have observed, however, that, especially with regard to research 
involving patients, policies were frequently unclear. When this research offered 
patient-subjects a chance to benefit medically, the widespread discretion granted 
physicians to make decisions on behalf of their patients is a mitigating factor in 
judging the blameworthiness of government officials for failing to impose consent 
requirements on physician-investigators. This failure could be attributed to a 
cultural moral ignorance concerning the proper limits to the authority of 
physicians over their patients. 

The same cannot be said of government officials for failing to impose 
consent requirements on physician-investigators who used patient-subjects in 
research from which the patients could not benefit medically. This use of human 
subjects took place outside of the therapeutic context that defines the doctor- 

215 



Parti 

patient relationship and therefore also was outside of the authority then ceded to 
physicians. In this case responsible agency officials had a ready analogy to 
healthy subjects for whom there was a lengthy tradition of policies and rules 
requiring the use of "volunteers" and the obtaining of consent. Government 
officials could and should have perceived the morally identical nature of these 
cases— that, without consent, both cases involved violation of the principle not to 
use people as mere means to the ends of others. Those who were ill should have 
been granted the same protections as those who were well. 

In contrast to requirements for consent, requirements intended to ensure 
that risks to experimental subjects were acceptable were far more clearly stated. 
Government officials are blameworthy if they permitted research to continue that 
was known to entail unusual risks to the subjects, in direct violation of agency 
policy. 

Finally, some lessons that can be drawn from the experience of the human 
radiation experiments we considered speak to the conduct of government itself as 
a collective agent, rather than simply to individual government officials. In too 
many instances, as we saw in chapter 1, we found a lack of clarity about the status 
within an agency of specific declarations by responsible officials. Particularly 
when agencies are engaged in activities that may compromise the rights or 
interests of citizens, it is critically important that agencies be clear about their 
commitments and policies and that they not remain passive in the face of 
questionable practices for which they may bear some responsibility. In chapter 3 
we saw an effective response to such a situation in the 1960s by the PHS. This 
example attests to the fact that institutional clarity and active reform measures can 
succeed and that when they do they can be great forward strides. 

Rules of Professional Ethics 

Even if the federal government had adopted no formal human research 
ethics policy whatsoever, the medical profession and its members would still have 
moral obligations to those who entrust themselves to their care. The successes of 
modern medical research, regardless of its funding source, are ultimately due to 
the efforts of talented and dedicated medical scientists. These investigators bear a 
profound ethical burden in their work with human subjects. Society entrusts them 
with the privilege of using other human beings to advance their important work. 
Although society must not discourage them from the pursuit of new information, 
it also must diligently pursue signs that medical scientists have not exercised their 
ethical responsibility with the care and sensitivity that society has good reason to 
expect from them. 

Without reference to the policies adopted by federal agencies, what rules 
of professional ethics were seen by the medical profession during the 1944-1974 
period as relevant to the conduct of its members engaged in human subjects 
research? The answer to this question depends upon which kind of experimental 

216 



Chapter 4 

situation is under discussion: an experiment on a healthy subject; an experiment 
on a patient-subject without a scientific or clinical basis for an expectation of 
benefit to the patient-subject; or an experiment on a patient-subject with a 
scientific or clinical basis for an expectation of benefit to the patient-subject. 

Experiments on Healthy Subjects: By the mid- 1 940s it was common to 
obtain the voluntary consent of healthy subjects who were to participate in 
biomedical experiments that offered no prospect of medical benefit to them. 
Sophisticated philosophical analysis is not required to reach the conclusion that 
using a human being in a medical experiment that offers the person no prospect of 
personal benefits without that person's consent is wrong. As we have already 
noted, such conduct violates the basic ethical principle that one ought not use 
people as mere means to the ends of others. 

Experiments on Patient-Subjects Without a Scientific or Clinical Basis for 
an Expectation of Benefit to the Patient-Subject: The Hippocratic tradition of 
medical ethics inherited by physicians in the 1940s holds that, unless the 
physician is reasonably sure that his or her treatment is, on balance, likely to do 
the patient more good than harm, the treatment should not be introduced. The 
heart of the Hippocratic ethic is the physician's commitment to putting the 
interests of the patient first. Subjecting one's patient to experimentation that 
offers no prospect of benefit to the patient without his or her consent is a direct 
repudiation of this commitment. (If the patient consents to this use, the moral 
warrant for proceeding with the experiment comes from the patient's permission, 
not from the Hippocratic ethic.) 

Experiments on Patient-Subjects with a Scientific or Clinical Basis for an 
Expectation of Benefit to the Patient-Subject: Even in Hippocratic medicine it is 
recognized that physicians should attempt to use unproven or experimental 
methods to benefit the patient, whether through efforts at cure or palliation, but 
only so long as there is no efficacious standard therapy available and innovative 
measures are compatible with the obligation to avoid doing harm without the 
prospect of offsetting benefit. Interventions in this category should be based on 
scientific reasoning and conservative clinical judgment. Arguably, so long as 
these conditions prevailed, it was not thought morally necessary within the 
medical profession to obtain the patient's consent to such experimentation prior to 
the 1960s. But the physician assumed a corresponding obligation to base his or 
her deviation from standard practice on the reasonable likelihood of patient 
benefit, sufficient to outweigh the risks associated with being in the experiment. 
This type of reasoning, too, has been available to and accepted by physicians for 
many years, even though the ability to assess and calculate risks has developed 
greatly. 



217 



Part I 

Although the professional ethics of the period thus had relevant moral 
rules for each of these three experimental situations, compliance with these rules 
is a separate matter. There may be many reasons for specific failures by 
physicians to adhere to the requirements of their ethical tradition, some of which 
may render them nonculpable, and there are various limitations on our ability to 
assign blame for particular cases of a physician's failure to adhere to professional 
ethics. However, any use of human subjects that did not proceed in accordance 
with these rules of professional ethics was wrong in the sense that it was a 
violation of sound professional ethical standards. Moreover, even if there was 
then or is now a lack of clarity about the rules of professional ethics, recognition 
by morally serious individuals of basic ethical principles is enough to identify 
certain sorts of human experiments as morally unacceptable. 

The special moral responsibilities of the medical profession as a whole, 
whether decades ago or in our own time, deserve careful consideration, especially 
insofar as previous experience can help formulate lessons for the future. Like the 
government, the medical profession as a whole must be held to a higher standard 
than individuals in society. Confidence in the medical profession is important 
because individuals put their very lives, and the lives of their loved ones, in the 
hands of those whom the profession has certified as competent to practice. 
Unlike government officials, members of the medical profession are explicitly 
bound to a moral tradition in their professional relations, based on which society 
grants the medical profession the privilege of largely policing itself. This 
authority is part of what constitutes the medical profession as a profession, but the 
authority is granted by society on the condition that the profession will adhere to 
the high moral rules it professes and that, if necessary, the medical profession will 
reform or encourage the reform of relevant institutions to ensure that those rules 
will be honored in practice. 

Moreover, many of the privileges that devolve on the medical profession 
are granted on the condition that it is sufficiently well organized to police itself, 
with minimal intervention by the government and the legal system. Therefore, 
members of the medical profession are further legitimately expected to engage in 
organizational conduct that constitutes sound moral practices. Implicit in this 
arrangement is also the assumption that it will be self-critical even about its 
relatively well-entrenched attitudes and beliefs, so that it will be prepared to 
undertake reforms. Without this commitment to self-criticism, self-regulation 
cannot be effective and the public's trust in the professional's ability to self- 
regulate would be unwarranted. 

Today we regard subjects of biomedical research whose consent was not 
obtained to have been wronged; under conditions of significant risk, the wrong is 
greater, and in the absence of the potential for offsetting medical benefit, greater 
still. The historical silence of the medical profession with respect to 
nontherapeutic experiments was perhaps based on the rationale that those who are 
ill and perhaps dying may be used in experiments because they will not be 

218 



Chapter 4 

harmed even though they will not benefit. But this rationale overlooks both the 
principle that people should never be used as mere means and the principle of 
respect for self-determination; it may also provide insufficient protection against 
harm, given the position of conflict of interest in which the physician-researcher 
may find him-or herself. Nevertheless, until the mid-1960s medical conventions 
were silent on experiments with patient-subjects that offered no direct benefit but 
which physicians believed to pose acceptable risk. This silence was a failure of 
the profession. 

One defense of the profession in this regard is that it was as subject to the 
phenomenon we have called cultural moral ignorance as any other group in 
society at the time, including the arguably excessive deference to physician 
authority on the part of the government and possibly the public at large. 
However, the medical profession was in a wholly different position from the 
others, in several respects. First, it insisted upon and was given the privilege of 
policing its own behavior. Second, the profession was the direct beneficiary of 
the deference paid to it. Third, there were already examples of experiments that 
had involved subject consent that could have served as models of reform. Under 
these conditions the profession had an obligation to be self-critical concerning the 
norms and rules it thought appropriate to govern its members' conduct. 

The medical profession could and should have seen that healthy subjects 
and patient-subjects in nontherapeutic experiments were in similar moral 
positions—neither was expected to benefit medically. Just as physicians had no 
moral license to determine an "acceptable risk" for healthy subjects without their 
voluntary consent, they had no moral license to do so in the case of other subjects 
who also could not benefit from being in research, even if they were patients. The 
prevailing standards for healthy subject groups could easily have been applied to 
patient-subjects for whom there was no expectation of medical benefit. The moral 
equivalence of the use of healthy people and ill people as subjects of experiments 
from which no subject could possibly benefit directly was perceptible at the time. 

This moral equivalence would have made it clear that no one, well or sick, 
should be used as a mere means to advance medical science without voluntary 
consent. Thus, this moral ignorance could have and should have been remedied at 
the time. Indeed, it is arguably the case that physicians could and should have 
seen that using patients in this way was morally worse than using healthy people, 
for in so doing one was violating not only the basic ethical principle not to use 
people as a mere means but also the basic ethical principle to treat people fairly 
and with equal respect. 

American physicians are members of a society that places a high value on 
these basic moral principles, still more vital than the advancement of medical 
science. These principles are as easily known to physicians as to anyone else, and 
it is unacceptable to single oneself out as an exception to these principles simply 
because one is a member of an esteemed profession. Someone who is ill deserves 
to be treated with the same respect as someone who is well. Accordingly, a 

219 



Parti 

physician who failed to tell a patient that what was proposed was an experiment 
with no therapeutic intent was and is blameworthy. To the extent that the 
experiment entailed significant risk, the physician is more blameworthy; where it 
was reasonable to assume that the experiment imposed no risk or minimal risk or 
inconvenience, the blame is less. 

We argue here that the use of patients in nontherapeutic experiments 
without their consent was not only a violation of these basic moral principles but 
also a violation of the Hippocratic principle that was the cornerstone of 
professional medical ethics at that time. That principle enjoins physicians to act 
in the best interests of their patients and thus would seem to prohibit subjecting 
patients to experiments from which they could not benefit. It might be argued 
that a widespread practice that is not in conformity with a principle of 
professional ethics invalidates the principle, since the practice shows that the 
profession was not really committed to the principle in the first place. This is a 
misunderstanding, however, of what it means for a profession to adopt and 
espouse a moral principle. Even if many or most physicians sometimes fail or 
even often fail to comply with the principle, it is still coherent to say that the 
principle is accepted by the profession, if the principle has been publicly 
pronounced and affirmed by the profession, as was clearly the case with respect to 
the Hippocratic ethic. 

To characterize a great profession as having engaged over many years in 
unethical conduct-years in which massive progress was being made in curbing 
some of mankind's greatest ills-may strike some as arrogant and unreasonable. 
However, fair assessment indicates that the circumstance was one of those times 
in history in which wrongs were committed by very decent people who were in a 
position to know that a specific aspect of their interactions with others should be 
improved. Wrongs are not less egregious because they were committed by a 
member of a certain profession or by people who are very decent in their 
relationships with other parties. It is common for us to look back at such conduct 
in amazement that so many otherwise good and decent people could have 
engaged in it without a high level of self-awareness. Moral consistency requires 
the Advisory Committee to conclude that, if the use of healthy subjects without 
consent was understood to be wrong at the time, then the use of patients without 
consent in nontherapeutic experiments should also have been discerned as wrong 
at the time, no matter how widespread the practice. 

It should be emphasized, however, that often these nontherapeutic 
experiments on unconsenting patients constituted only minor wrongs. Often there 
was little or no risk to patient-subjects and no inconvenience. Although it is 
always morally offensive to use a person as a means only, as the burden on the 
patient-subject decreased, so too did the seriousness of the wrong. 

Much the same can be said of experiments that were conducted on 
patient-subjects without their consent but that offered a prospect of medical 
benefit. To the extent that such experiments were conducted within the moral 

220 



environment of the doctor-patient relationship, that is, based on the physician's 
considered and informed judgment that it was in the patient's best interests to be 
enrolled in the research, then the less blameworthy the physician was for failing 
to obtain consent. However, where the risks were great or where there were 
viable alternatives to participation in research, then the physician was more 
blameworthy for failing to obtain consent. 

It is often difficult to establish standards and make judgments about right 
and wrong, and about blame and exculpation. Our charge was all the more 
difficult because the context of the actions and agents we were asked to evaluate 
differs from our own. In arriving at this moral framework for evaluating human 
radiation experiments, we have tried to be fair to history, to considerations of 
ethics, and above all, to the people affected by our analysis-former subjects, 
physician-investigators, and government officials. 



221 



ENDNOTES 



1 . International declarations of human rights that would otherwise be relevant 
to an evaluation of human experimentation, such as the Covenant on Civil and Political 
Rights (1966), were articulated after the human radiation experiments with which we are 
mainly concerned, with the significant exception of the Nuremberg Code, as discussed in 
chapter 2. 

2. The Advisory Committee is aware that questions such as precisely what 
ethical principles should be considered "basic," how they are related to those less basic, 
and how the basic ethical principles are known are among the most controversial and 
difficult in moral philosophy. For the Advisory Committee's limited purposes, a 
comprehensive and systematic moral theory is not required and is, in any case, far 
beyond the scope of this report. We have rather settled on a list of immediately 
recognizable and widely accepted ethical principles that are not usually thought to 
require justification themselves and that should be included in any adequate moral 
theory. 

3. Some view promise keeping as a basic ethical principle on a par with the 
prohibition against deception. It may also be seen as grounded in one or more of the 
basic ethical principles on our list of six, such as those concerning deception and treating 
people as mere means. 

4. The President's Commission functioned from 1978 to 1983, under the Carter 
and Reagan administrations, and produced a number of influential reports and 
recommendations concerning medical ethics and health care policy. 

5. It may be argued that historical ethical relativism reduces to cultural ethical 
relativism. On this position, the notion that even basic ethical principles vary by era is 
part of a more general claim that what is really at stake is different "world views," and 
these different world views may exist at the same time but in cultures that are different 
from one another in certain crucial respects. On this analysis, in other words, the 
temporal factor is not the essential one. However, some find it easier to reject historical 
ethical relativism than cultural ethical relativism, for they find it plausible that essentially 
the same values operative in, say, the United States in the 1990s were operative in the 
1950s, but not that essentially the same values that are operative in the United States in 
the 1990s are also operative in China in the 1990s. 

6. In its report on the CIA and Army psychochemical experiments, the U.S. 
Senate found that 

[i]n the Army's tests, as with those of the CIA, individual 

rights were . . . subordinated to national security 

considerations; informed consent and follow-up 

examinations of subjects were neglected in efforts to 

maintain the secrecy of the tests. 
U.S. Congress, The Select Committee to Study Governmental Operations with Respect 
to Intelligence Activities, Foreign and Military Intelligence [Church Committee report], 
report no. 94-755, 94th Cong., 2d Sess. (Washington, D.C.: GPO, 1976), book 1,4111. 
However, even in the light of the Army's own analysis of its LSD experiments, presented 
in a 1959 staff study by the U.S. Army Intelligence Corps (USAINTC), the operative 
legal principles should not have permitted the resulting practices to take place: 



222 



It was always a tenet of Army intelligence that the basic 
American principle of dignity and welfare of the 
individual will not be violated ... In intelligence, the 
stakes involved and the interests of national security 
may permit a more tolerant interpretation of moral- 
ethical values, but not legal limits, through necessity . . . 
[emphasis added]. 
USAINTC Staff Study, Material Testing Program EA 1 729 ( 1 5 October, 1959), 26. The 
staff study's distinction between the flexibility of "moral-ethical values" and "legal 

limits" is puzzling. 

7. U.S. Army Inspector General, Use of Volunteers in Chemical Agent Research 

(Army IG report) (Washington D.C.: GPO, 1975). 

8. David J. Rothman, Strangers at the Bedside: A History of How Law and 
Bioethics Transformed Medical Decision Making (New York: Basic Books, 1991), 32- 

9. Rothman writes of the CMR's deliberations on the gonorrhea proposal: It 
[the CMR] conducted a remarkably thorough and sensitive discussion of the ethics of 
research and adopted procedures that satisfied the principles of voluntary and informed 
consent. Indeed, the gonorrhea protocols contradict blanket assertions that in the 1940s 
and 1950s investigators were working in an ethical vacuum." Ibid., 42-43. 

10. Michael Walzer, Just and Unjust Wars (New York: Basic Books, 1977). 

11. Another factor often important in assessments of blame is duress. All 
systems of ethics recognize that people cannot be blamed for actions that violate basic 
ethical principles if they acted under duress. Duress includes manipulation, blackmail, 
or threats of physical harm. There is no evidence that any particular individual involved 
in the human radiation experiments functioned under conditions of duress. 

12. Ruth Faden and Tom Beauchamp, A History and Theory of Informed 
Consent (New York: Oxford University Press, 1986). 

13. For example, the National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research published ten reports. Many of these 
recommendations were enacted into federal regulation. U.S. Congress, Office of 
Technology Assessment, Biomedical Ethics in U.S. Public Policy-Background Paper, 
OTA-BP-BBS-105 (Washington, D.C.: GPO, June 1993), 10. 

14. Scholendorffv. Society of New York Hospital, 2 1 1 N.Y. 2d ( 1 9 1 4). 

1 5. Salgo v. Leland Stanford, Jr., University Board of Trustees. 3 1 7 P.2d 1 70 

(1957). 

1 6. In each case we assume that the principles or policies in question were 
morally sound; if not, anyone who refused to take part in unethical experiments 
performed in accordance with them acted, in retrospect, in a praiseworthy manner. 

1 7. Again, with regard to the elements of an ethical framework suited to the 
intentional releases, we note that different justifications are used to evaluate the risks to 
collectives or communities as against those used to evaluate risks to individuals. 

18. Note, however, that the intended scope of the policy was not always clear. 
Also, if the government or an agency had no policy at all concerning the use of human 
subjects but did conduct such research, then the absence of a policy would itself be 
objectionable. 



223 



PART II 



CASE STUDIES 



Part II 
Overview 



W hen we began our work, the Advisory Committee was aware of 
several dozen human radiation experiments and the thirteen intentional releases in 
our charter. Soon, however, we found that these represented a fraction of the 
several thousand government-sponsored human radiation experiments and 
hundreds of intentional releases conducted from 1944 to 1974. 

It was clear that the Committee would have to decide how to proceed in 
examining the experiments. Our ability to review all of the experiments and 
releases in detail was limited not only by time and resources, but even more so by 
the information available. For the majority of experiments identified, only the 
barest descriptions remained. It appeared that the vast majority of experiments 
involved trace amounts of radioisotopes, as are routinely used today for the study 
of bodily processes and the diagnosis of disease. However, where reports or other 
data were available, they did not routinely provide information needed to assess 
the precise risks to which subjects were exposed. These reports were even less 
likely to identify what kinds of people were chosen as subjects and why and how 
they were selected. 

Since the Committee could not review all experiments, we decided to 
prepare a series of case studies focused on groups of experiments. We quickly 
found that there was no one right way to organize the experiments for purpose of 
case study. For example, the case studies could have been defined by the type of 
radiation to which subjects were exposed. This would likely have yielded 
groupings of experiments with differing purposes, differing populations, and 
differing risks and benefits. Likewise, grouping all experiments according to the 
characteristics of the people who were the subjects of the research would have 
lumped together experiments with differing purposes, risks, and scientific 
procedures. 



227 



Part II 



The ACHRE Experiments Database 

By Cabinet directive on January 19, 1994, federal agencies were ordered to "establish 
forthwith an initial procedure for locating records of human radiation experiments conducted by 
the Agency or under a contract or grant of the Agency." The agencies most closely associated 
with these activities-the DOD, DOE, DHHS, NASA, CIA, and VA (and later the NRC)--in 
cooperation with Advisory Committee staff, identified record collections of importance and 
provided ACHRE with copies of documents potentially containing information on human radiation 
experiments. The documents were analyzed to identify individual experiments, which were then 
described according to a protocol developed by ACHRE members and staff, given unique 
identifiers, and recorded in an electronic database. Experiments were also identified by Advisory 
Committee staff in the published literature, discovered through a search of the National Library of 
Medicine databases and bibliographies, and documented by individuals who came forward with 
information for the Advisory Committee. 

The database contains records for approximately 4,000 human radiation experiments. 
Information was collected, to the extent it was available, on the identity of the experiment 
(including investigators, location, dates, title, and documentation); funding, program approval and 
classification; the type and dose of radiation used; various characteristics of the experimental 
subjects; and the nature of the consent obtained. The experiments were in addition categorized by 
various themes and characteristics developed by Advisory Committee members and staff to reflect 
ACHRE research interests. 

Documentation for individual experiments varies widely, sometimes including significant 
primary protocol documentation, often including only a journal article or abstract and, for the 
greatest number, just an investigator's name, a location, a date, and a title. As a result, although 
the database and the records it abstracts constitute an impressive and unique collection of 
information on human radiation experiments, that collection is not a comprehensive information 
resource on human radiation experiments but really just the best place to start to look for 
information. 

The supplemental volume titled Sources and Documentation contains a more extensive 
and detailed description of the database and its sources. 



After extensive deliberation, the Committee settled on eight case studies, 
which together address the charges to and priorities of the Committee. For 
example, we were charged to consider both intentional releases of radiation into 
the environment and the question of whether any former subjects of human 
radiation experiments would benefit medically from notification of their 
involvement. In addition, the Committee saw a responsibility to address those 
experiments that had received significant public attention at the time of the 
Committee's creation as well as those brought to our attention by members of the 
public. These experiments either offered no prospect of medical benefit to 
subjects or they involved interventions alleged to be controversial at the time. We 

228 



Overview 

also, however, recognized the importance of considering the far larger group of 
experiments that received no such attention but that also may have involved no 
prospect of benefit to subjects. We also placed a priority on experiments that 
were conducted on behalf of secret programs and for national security reasons; 
experiments that posed the greatest risk of harm; and experiments in which the 
subjects selected for experimentation were particularly powerless to resist or 
exercise independent judgment about participation. Together, these 
considerations formed the basis for the selection of the case studies. 

In chapter 5, we look at the Manhattan Project plutonium-injection 
experiments and related experimentation. Sick patients were used in sometimes 
secret experimentation to develop data needed to protect the health and safety of 
nuclear weapons workers. The experiments raise questions of the use of sick 
patients for purposes that are not of benefit to them, the role of national security 
in permitting conduct that might not otherwise be justified, and the use of secrecy 
for the purpose of protecting the government from embarrassment and potential 

liability. 

In contrast to the plutonium injections, the vast majority of human 
radiation experiments were not conducted in secret. Indeed, the use of 
radioisotopes in biomedical research was publicly and actively promoted by the 
Atomic Energy Commission. Among the several thousand experiments about 
which little information is currently available, most fall into this category. The 
Committee adopted a two-pronged strategy to study this phenomenon. In chapter 
6, we describe the system the AEC developed for the distribution of isotopes to be 
used in human research. This system was the primary provider of the source 
material for human experimentation in the postwar period. In studying the 
operation of the radioisotope distribution system, and the related "human use" 
committees at local institutions, we sought to learn the ground rules that governed 
the conduct of the majority of human radiation experiments, most of which have 
received little or no public attention. Also in this chapter we review how research 
with radioisotopes has contributed to advances in medicine. 

The Committee then selected for particular consideration, in chapter 7, 
radioisotope research that used children as subjects. We determined to focus on 
children for several reasons. First, at low levels of radiation exposure, children 
are at greater risk of harm than adults. Second, children were the most 
appropriate group in which to pursue the Committee's mandate with respect to 
notification of former subjects for medical reasons. They are the group most 
likely to have been harmed by their participation in research, and they are more 
likely than other former subjects still to be alive. Third, when the Committee 
considered how best to study subject populations that were most likely to be 
exploited because of their relative dependency or powerlessness, children were 
the only subjects who could readily be identified in the meager documentation 
available. By contrast, characteristics such as gender, ethnicity, and social class 
were rarely noted in research reports of the day. 

229 



Part II 

Moving from case studies focused on the injection or ingestion of 
radioisotopes, chapter 8 shifts to experimentation in which sick patients were 
subjected to externally administered total-body irradiation (TBI). The Committee 
discovered that the highly publicized TBI experiments conducted at the 
University of Cincinnati were only the last of a series in which the government 
sought to use data from patients undergoing TBI treatment to gain information for 
nuclear weapons development and use. This experimentation spanned the period 
from World War II to the early 1970s, during which the ethics of experimentation 
became increasingly subject to public debate and government regulation. In 
contrast with the experiments that flowed from the AEC's radioisotope program, 
the use of external radiation such as TBI did not in its earlier years involve a 
government requirement of prior review for risk. The TBI experimentation raises 
basic questions about the responsibility of the government when it seeks to gather 
research data in conjunction with medical interventions of debatable benefit to 
sick patients. 

In chapter 9 we examine experimentation on healthy subjects, specifically 
prisoners, for the purpose of learning the effects of external irradiation on the 
testes, such as might be experienced by astronauts in space. The prisoner 
experiments were studied because they received significant public attention and 
because a literally captive population was chosen to bear risks to which no other 
group of experimental subjects had been exposed or has been exposed since. This 
research took place during a period in which the once-commonly accepted 
practice of nontherapeutic experimentation on prisoners was increasingly subject 
to public criticism and moral outrage. 

Chapter 10 also explores research involving healthy subjects: human 
experimentation conducted in conjunction with atomic bomb tests. More than 
200,000 service personnel—now known as atomic veterans— participated at atomic 
bomb test sites, mostly for training and test-management purposes. A small 
number also were used as subjects of experimentation. The Committee heard 
from many atomic veterans and their family members who were concerned about 
both the long-term health effects of these exposures and the government's 
conduct. This case study provided the opportunity to examine the meaning of 
human experimentation in an occupational setting where risk is the norm. 

In chapter 1 1 we address the thirteen intentional releases of radiation into 
the environment specified in the Committee's charter, as well as additional 
releases identified during the life of the Committee. In contrast with biomedical 
experimentation, individuals and communities were not typically the subject of 
study in these intentional releases. Rather, the releases were to test intelligence 
equipment, the potential of radiological warfare, and the mechanism of the atomic 
bomb. While the risk posed by intentional releases was relatively small, the 
releases often took place in secret and remained secret for years. 

The final case study, in chapter 1 2, looks at two groups that were put at 
risk by nuclear weapons development and testing programs and as a consequence 

230 



Overview 

became the subjects of observational research: workers who mined uranium for 
the Atomic Energy Commission in the western United States from the 1 940s to 
1960s and residents of the Marshall Islands, whose Pacific homeland was 
irradiated as a consequence of a hydrogen bomb test in 1954. While these 
observational studies do not fit the classic definition of an experiment, in which 
the investigator controls the variable under study (in this case radiation exposure), 
they are instances of research involving human subjects. The Committee elected 
to examine the experiences of the uranium miners and Marshallese because they 
raise important issues in the ethics of human research not illustrated in the 
previous case studies and because numerous public witnesses impressed on the 
Committee the significance of the lessons to be learned from their histories. 

Part II concludes with an exploration of an important theme common to 
many of the case studies-openness and secrecy in the government's conduct 
concerning human radiation research and intentional releases. In chapter 13 we 
step back and look at what rules governed what the public was told about the 
topics under the Committee's purview, whether these rules were publicly known, 
and whether they were followed. 



231 



Experiments with Plutonium, 
Uranium, and Polonium 



In August 1944, at the secret Los Alamos Laboratory in New Mexico, a 
twenty-three-year-old chemist was trying to learn what he could about the 
properties of a radioactive metal. One year later, the new "product"-one of 
several code words for this three-year-old element with a classified name-would 
power the bomb dropped on Nagasaki. That day the young scientist, Don 
Mastick, was working with the entire Los Alamos supply of the material, 10 
milligrams. It was sealed in a glass vial several inches long and about a quarter 
inch in diameter. Unknown to Mastick, a chemical reaction was causing pressure 
to build up inside the vial. Suddenly it burst, firing an acidic solution against the 
wall from where it splattered into Mastick's face, some of it entering his mouth.' 

Realizing the importance to the war effort of the plutonium he had just 
ingested, Mastick hurried directly to the office of Louis Hempelmann, the health 
director at Los Alamos. Hempelmann pumped Mastick's stomach and instructed 
the young scientist to retrieve the plutonium from the expelled contents. 
Hempelmann expressed a concern related to worker safety: there was no way 
available to determine how much plutonium remained in Mastick's body. He 
immediately pressed the lab's director, J. Robert Oppenheimer, for authorization 
to conduct studies to develop ways of detecting plutonium in the lungs, and in 
urine and feces, and of estimating the level of plutonium in the body from the 
amount found in excreta. 2 

Looming over Mastick's accident was the well-known tragedy of the 
radium dial workers more than a decade earlier. Like Mastick, they had ingested 
radioactive material through their mouths, as they licked the brushes they used to 



233 



Part II 

apply radium paint to watch dials. As time passed, many suffered from a 
gruesome bone disease localized in the jaw, and some bone cancers developed. 
Could plutonium cause a similar tragedy? If so, how much plutonium needed to 
be ingested before harmful effects might arise? How could one tell how much 
plutonium a person had already ingested? The answers to these questions were 
crucial, not only in the case of accidents such as Mastick's, but also, in the long 
run, to establish occupational health standards for the hundreds of workers who 
would soon be mass-producing plutonium for atomic bombs. Several pounds of 
radium, handled without recognition of the dangers, had led to dozens of deaths; 
what might plutonium cause? 

A starting point was to examine the available data on radium poisoning, 
compare the characteristics of the radiation emitted by radium and plutonium, and 
try to extrapolate from radium to plutonium. However, plutonium had already 
revealed unexpected physical properties, which were posing problems for the 
bomb designers. Could plutonium also have unexpected biochemical properties? 
Extrapolation from radium was a good starting point, but could never be as 
reliable as data on plutonium itself. 

Oppenheimer agreed that this research was critical. In an August 16, 
1944, memorandum to Hempelmann, Oppenheimer authorized separate programs 
to develop methods to detect plutonium in the excreta and in the lung. With 
respect to biological studies, which Oppenheimer speculated might involve 
human experimentation, he wrote: "I feel that it is desirable if these can in any 
way be handled elsewhere not to undertake them here." 3 The reason 
Oppenheimer did not want these experiments conducted at Los Alamos remains 
obscure. Nine days later, Hempelmann met with Colonel Stafford L. Warren, 
medical director of the Manhattan Project, and others. They agreed to conduct a 
research program using both animal and human subjects. 4 

Mastick, who reported no ill effects from the accident when Advisory 
Committee staff interviewed him in 1995, 5 was not the first alert to the potential 
hazards of plutonium. Human experiments to study the metabolism and retention 
of plutonium in the body had been contemplated from the earliest days of the 
Manhattan Project. On January 5, 1944, Glenn Seaborg, who in 1941 was the 
first to recognize that plutonium had been created in the cyclotron at the 
University of California at Berkeley, wrote to Dr. Robert Stone, health director of 
the Metallurgical Laboratory in Chicago (a Manhattan Project contractor) and a 
central figure in efforts to understand the health effects of plutonium: 

It has occurred to me that the physiological hazards 
of working with plutonium and its compounds may 
be very great. Due to its alpha radiation and long 
life it may be that the permanent location in the 
body of even very small amounts, say one 
milligram or less, may be very harmful. The 

234 



Chapter 5 

ingestion of such extraordinarily small amounts as 
some few tens of micrograms might be unpleasant, 
if it locates itself in a permanent position. 6 

Seaborg urged that a safety program be set up. In addition, "I would like 
to suggest that a program to trace the course of plutonium in the body be initiated 
as soon as possible. In my opinion such a program should have the very highest 
priority." 7 Stone reassured Seaborg that human tracer studies "have long since 
been planned. . . . although never mentioned in official descriptions of the 
program." 8 The work began at Berkeley with studies on rats conducted by Dr. 
Joseph Hamilton. 9 

Even as these studies on the biological effects of plutonium were 
beginning, the amount of plutonium being produced was dramatically increasing. 
Most of the effort at Oak Ridge was devoted to the separation of isotopes of 
uranium. However, the X- 10 plant at Oak Ridge was a larger version of the very 
small plutonium-producing reactor developed at the University of Chicago. The 
X-10 plant began operating on November 4, 1943, and by the summer of 1944 
was sending small amounts of plutonium to Los Alamos. 10 By December 1944 
large-scale production of plutonium began at the Hanford, Washington, reactor 
complex. ' ' 

By late 1944, in the wake of the Mastick accident, the need to devise a 
means of estimating the amount of plutonium in the body became acute. It 
seemed that the only way to estimate how much plutonium remained in a worker's 
body would be to measure over time the amount excreted after a known dose and, 
from this, estimate the relationship between the amount excreted and the amount 
retained in the body. 12 



Maximum Permissible Body Burden (MPBB) for Plutonium 

The plutonium injections were part of a larger research project intended to provide data 
for an occupational safety program riddled with uncertainty. Not only was there a need for ways to 
monitor the exposure of personnel-the driving force behind the plutonium injections-but the 
maximum permissible body burden (MPBB) for plutonium, the maximum amount of plutonium 
that would be permitted in the bodies of workers, was still under debate. 

The concept of "maximum permissible body burden" had begun to develop before the 
war in light of the known hazards of radium. Just prior to the war, primarily at the request of the 
Navy, a committee of experts was formed to establish occupational health standards for the 
factories producing dials illuminated by radium paint. After examining the data on radium dial 
painters, this committee agreed that 0. 1 microgram fixed in the body should be the "tolerance 
level" for radium: an amount that, in the words of the committee chairman, Robley Evans, would 



235 



Part II 

be "at such a level that we would feel comfortable if our own wife or daughter were the subject." 8 
After the war the term maximum permissible body burden was adopted and defined more precisely 
as the amount of a radioisotope that, when continuously present inside the body, would produce a 
dose equivalent to the allowable occupational exposure (the maximum permissible dose). For 
radioisotopes that, like radium, primarily reside in bone, biological data and mathematical models 
were used to determine how much of another bone seeker would produce the same dose as the 
original 0. 1 -microgram radium standard. 

Between 1943 and the spring of 1945, based on the body burden for radium and 
preliminary results of animal experiments, a tentative MPBB for plutonium of 5 micrograms was 
adopted by the Manhattan District. b This level was derived by direct comparison of the relative 
energies of plutonium and radium. 

By the spring of 1945, differences between the deposition of radium and plutonium in the 
body were becoming clearer. Animal data indicated that plutonium deposited in what was called at 
the time the "organic matrix" of the bone-the part of the bone most associated with bone growth. 
This was different from radium, which seemed to deposit instead in the mineralized bone. Wright 
Langham wrote to Hymer Friedell supporting the choice of 1 microgram as an operating limit in 
lieu of a more formal policy. Langham wrote that with the adoption of this lower limit "the 
medico-legal aspect will have been taken care of and of still greater importance, we will have 
taken a relatively small chance of poisoning someone in case the material proves to be more toxic 
than one would normally expect."" This level was adopted and held until the Tripartite Permissible 
Dose Conference at Chalk River, Canada, in September 1 949. 

At this conference, representatives from the United States, United Kingdom, and Canada 
agreed on tolerance doses for many radioactive isotopes, including a maximum body burden of 0. 1 
microgram for plutonium. This reduced by a factor of 10 the value under which Los Alamos 
production had been operating. This reduction was based on the results of acute toxicological 
experiments with animals, which indicated that plutonium was as much as fifteen times more toxic 
than radium. 

On January 20, 1950, Wright Langham wrote to Shields Warren, then the director of the 
AEC's Division of Biology and Medicine, alerting him to the problems caused by the Chalk River 
Conference's new "extremely conservative tolerances [which] may have a drastic effect on the 
efficiency and productivity of the Los Alamos Laboratory. Their official adoption will 
undoubtedly force major alteration in both present and future laboratory facilities and may add 
millions of dollars to the cost of construction of the permanent building program now in the 



a. Robley Evans, "Inception of Standards for Internal Emitters, Radon and Radium," Health 
Physics 41 (September 1981): 437-448. 

b. W. H. Langham et al., "The Los Alamos Scientific Laboratory's Experience with Plutonium in 
Man," Health Physics 8 (1962): 753. 

C. Wright Langham, Los Alamos Scientific Laboratory Health Division, to Hymer Friedell, 21 
May 1945 ("Since the Chicago Meeting, 1 am somewhat lost as to what our program should be in the 
future . . .") (ACHRE No. DOE-1 13094-B-7), 1. 

236 



Chapter 5 

planning phases.'" 1 Langham continued with reasons for regarding the Chalk River value of 0.1 
micrograms of plutonium as "unnecessarily low." He cited, among other things, differences 
between acute and chronic toxicity and new analysis of data from the radium watch dial painters. 

On January 24, 1950, Shields Warren, Austin Brues of Argonne National Laboratory, 
Robley Evans, Karl Morgan, and Wright Langham met in Washington. Langham wrote later: "As 
a result of this meeting, Dr. Shields Warren of the Division of Biology and Medicine authorized 
0.5 ug (0.033 uc) of Pu 2 " as the AEC's official operating maximum permissible body burden." 
There were no minutes or transcripts taken of this meeting. The calculation of this level was again 
based on the body burden for radium, this time modified by the 1/15 toxicity factor (since 
experiments had indicated that plutonium was up to fifteen times more toxic than radium), by the 
relative retention of plutonium and radium in rodents, and by the energy ratios modified by radon 
retention. 

Thus far, the entire debate had occurred behind the closed doors of the AEC. 
Consideration of all the complex issues applied in setting a permissible body burden had been 
within a small circle of scientists and administrators. While the MPBB for plutonium accepted at 
the January 1950 meeting has held until today, its derivation has changed over the years. 



By March 1945, there was disturbing news that urine samples from Los 
Alamos workers were indicating, based on models developed from animal 
experimentation, that some might be approaching or had exceeded a body burden 
of 1 microgram. 13 A March 25 meeting led to Hempelmann's recommendation 
that the Project "help make arrangements for a human tracer experiment to 
determine the percentage of plutonium excreted daily in the urine and feces. It is 
suggested that a hospital patient at either Rochester or Chicago be chosen for 
injection of from one to ten micrograms of material and that the excreta be sent to 
the laboratory for analysis." 14 The overall program, as it was envisioned by Dr. 
Hymer Friedell, deputy medical director of the Manhattan Engineer District, 
Oppenheimer, and Hempelmann, consisted of three parts: improvement of 
methods to protect personnel from exposure to plutonium; development of 
methods for diagnosing overexposure of personnel; and study of methods of 
treatment for overexposed personnel. On March 29, Oppenheimer forwarded the 
recommendation to Stafford Warren, with his "personal endorsement." 15 



d. The letter went on to say that "operations of the Los Alamos Laboratory would be curtailed or 
stopped if such action were necessary to the reasonable and sensible protection of the personnel. The 
seriousness of this action, however, seems to be adequate reason for requesting that official adoption of the 
tolerances by the AEC be postponed until they have been carefully reviewed in order to make certain that the 
values are not unnecessarily conservative." Wright Langham, Los Alamos Laboratory Health Division, to 
Shields Warren, Director of AEC Division of Biology and Medicine, 20 January 1950 ("Radiation 
Tolerances Proposed by the Chalk River Permissible Dose Conference of September 29-30, 1949") (ACHRE 
No. DOE-020795-D-6), 1. 

e. W. H. Langham et al„ "The Los Alamos Scientific Laboratory's Experience with Plutonium in 
Man," Health Physics 8 (1962): 754. 

237 



Part II 

The accident at Los Alamos was part of the prelude to experiments 
conducted between 1945 and 1947 in which eighteen hospital patients were 
injected with plutonium to determine how excreta (urine and feces) could be used 
to estimate the amount of plutonium that remained in an exposed worker's body. 
One patient was injected at Oak Ridge Hospital in Oak Ridge, Tennessee; eleven 
were injected at the University of Rochester, three at the University of Chicago, 
and three at the University of California. 

The results of these experiments contributed to the development of a 
monitoring method that, with small changes, is still used today. The experimental 
data were used to develop a model relating body burden to short-term excretion 
rate. Known as the "Langham model," it was based on short-term excretion data, 
long-term excretion data that were collected in 1950 from two injection subjects, 
and worker excretion data. This model has been used almost universally to 
monitor plutonium workers since 1950, although it has been modified over the 
years as longer-term and more extensive data were accumulated. While now, fifty 
years later, not every question concerning the quality of the science or the basis 
for estimating risk can be answered with precision, there is general agreement 
among radiation scientists that the experiments were useful. 

Although this would be the first time that plutonium would be injected 
into human beings, the plutonium experiments were not viewed at the time as 
being extremely risky, and for good reason. Based on experience with other 
bone-seeking radioisotopes such as radium, the investigators had firm basis for 
believing, even in the 1940s, that the amount of material to be injected was likely 
too small to produce any immediate side effects or reactions. No one was 
expected to feel ill or have any negative reaction to the injection, and apparently 
no one did. Because acute effects were not expected, the plutonium injections 
were viewed as posing no short-term risks to human subjects. There was concern, 
however, about long-term risk. A draft report, written by one of the primary 
investigators within a few years of the injections, records that "acute toxic effects 
from the small dose of pu [plutonium] administered were neither expected nor 
observed." The document also recognized that "with regard to ultimate effects, it 
is too early to predict what may occur." 16 Based largely on the experience of the 
radium dial painters, it was recognized that exposure to plutonium could result, 
perhaps ten or twenty years later, in the development of cancer in a human 
subject. This was viewed as a significant risk but also as a risk that could be 
minimized by the use of small doses and wholly avoided if the subjects were 
expected to die well before a cancer had a chance to materialize. 

Even if the plutonium injections had been entirely risk free, an 
impossibility in human experimentation, they could still be morally problematic. 
As we discussed in chapter 2, it was not uncommon in the 1940s for physicians 
to use patients as subjects in experiments without their knowledge or consent. 
This occurred frequently in research involving potential new therapies, where 
there was at least a chance that the patient-subjects might benefit medically from 

238 



Chapter 5 

being in an experiment. But it also occurred even in experiments-like the 
plutonium injections- where there was never any expectation and no chance that 
the experiment might be of benefit to the subjects. 

The conduct of the plutonium experiments raises a number of difficult 
ethics and policy questions: Who should have been the subjects of an experiment 
designed to protect workers vital to bomb production in wartime? What should 
the subjects have been told about the risks of the secret substance with which they 
were being injected? What should they have been told about the purpose of the 
experiment? What were the subjects told? Did they know they were part of an 
experiment in which there was no expectation that they would benefit medically? 

An inquiry initiated by the AEC commissioners in 1974 investigated some 
of these questions. That inquiry focused on whether consent was obtained from 
the subjects, either at the time of the plutonium injections or during 1973 follow- 
up studies funded by the AEC's Argonne National Laboratory in Chicago, 
designed to determine the long-term effects of the injections. Sixteen patient 
charts were examined for evidence of consent at the time of injection; the other 
two charts had been either lost or destroyed. Of the sixteen charts examined, only 
one chart-that of the only subject injected after the April 1947 directive of AEC 
General Manager Carroll Wilson (discussed in chapter 1) that required 
documented consent-contained evidence of some form of consent. The other 
fifteen contained no record of consent. 17 According to AEC investigators, oral 
testimony pointed to failure to obtain consent in the case of the Oak Ridge 
injection and to some form of disclosure to patients for the California and 
Chicago experiments. The AEC concluded that testimony was inconclusive for 
the Rochester experiments. 11 * With regard to the follow-up studies conducted with 
three surviving subjects in 1973, the investigation concluded that two subjects had 
deliberately not been informed of the purpose of the follow-up and that one 
subject had actually been misled about the purpose. 19 

As we will see later in this chapter, the AEC's conclusion that consent was 
not obtained from the surviving subjects for the 1973 follow-up studies was 
correct. Moreover, additional documentary evidence and testimony suggests that 
patient-subjects at the Universities of Rochester and California were never told 
that the injections were part of a medical experiment for which there was no 
expectation that they would benefit, and they never consented to this use of their 
bodies. 

The rest of this chapter provides a chronological account of the plutonium 
injection experiments and follow-up studies conducted over the course of many 
years, assesses the influence of secrecy on the conduct of the experiments, and 
examines the motivating factors behind the prolonged secrecy of the experiments 
and the continued deception of surviving subjects. We also consider the conduct 
of experimentation with uranium and polonium. Finally, we render judgments 
where we can about the ethical conduct of these experiments. 



239 



Part II 

THE MANHATTAN DISTRICT EXPERIMENTS 

The First Injection 

A few days after Hempelmann's March 26, 1945, recommendation that a 
hospital patient be injected with plutonium, Wright Langham, of the Los Alamos 
Laboratory's Health Division, sent 5 micrograms of plutonium to Dr. Friedell, 
with instructions for their use on a human subject. 20 The subject, as it turned out, 
was already in the Oak Ridge Army hospital, a victim of an auto accident that had 
occurred on March 24, 1945. 2I He was a fifty-three-year-old "colored male" 22 
named Ebb Cade, 23 who was employed by an Oak Ridge construction company as 
a cement mixer. The subject had serious fractures in his arm and leg, but was 
otherwise "well developed [and] well nourished." 24 The patient was able to tell 
his doctors that he had always been in good health. 25 

Mr. Cade had been hospitalized since his accident, but the plutonium 
injection did not take place until April 10. On this date, "HP- 12" (the code name 
HP— "human product" 26 --was later assigned to this patient and to patients at the 
University of Rochester) was reportedly injected with 4.7 micrograms of 
plutonium. (It is important here to distinguish between administered dose and 
retained dose; not all of the injected dose would remain fixed in the body. It was 
not known with certainty, however, how much of the 4.7 micrograms of 
plutonium would remain in his body.) 

The small amount of material injected into Mr. Cade would not be 
expected to produce any acute effects, and there is no indication that any were 
experienced. However, except for his fractures, Mr. Cade was apparently in good 
health and at age fifty-three could reasonably have been expected to live for 
another ten to twenty years. Thus, in Mr. Cade's case, the risk of a plutonium- 
induced cancer could not be ruled out. 

Dr. Joseph Howland, an Army doctor stationed at Oak Ridge, told AEC 
investigators in 1974 that he had administered the injection. There was, he 
recalled, no consent from the patient. He acted, he testified, only after his 
objections were met with a written order to proceed from his superior, Dr. 
Friedell. 27 Dr. Friedell told Advisory Committee staff in an interview that he did 
not order the injection and that it was administered by a physician named Dwight 
Clark, not Dr. Howland. 28 The Committee has not been able to resolve this 
contradiction. 

Measurements were to be taken from samples of Mr. Cade's blood after 
four hours, his bone tissue after ninety-six hours, and his bodily excretions for 
forty to sixty days thereafter. 29 His broken bones were not set until April 1 5— five 
days after the injection~when bone samples were taken in a biopsy. 30 Although 
this was several weeks after his injury, during this era when antibiotics were only 
beginning to become available, it was common practice to delay surgery if there 
was any sign of possible infection. One document records that Mr. Cade had 

240 



Chapter 5 

"marked" tooth decay and gum inflammation/ 1 and fifteen of his teeth were 
extracted and sampled for plutonium. The Committee has not been able to 
determine whether the teeth were extracted primarily for medical reasons or for 
the purpose of sampling for plutonium. In a September 1945 letter, Captain 
David Goldring at Oak Ridge informed Langham that "more bone specimens and 
extracted teeth will be shipped to you very soon for analysis." 32 It remains 
unclear whether these additional bone specimens were extracted at the time of the 
April 15 operation or later. 

According to one account, Mr. Cade departed suddenly from the hospital 
on his own initiative; one morning the nurse opened his door, and he was gone." 
Later it was learned that he moved out of state and died of heart failure on April 
13, 1953, in Greensboro, North Carolina. 34 

The experiment at Oak Ridge did not proceed as planned. "Before" and 
"after" urine samples were mistakenly commingled, so no baseline data on kidney 
function was available. 35 Thus, the subject's kidney function would be difficult to 
assess. In May 1945, 36 Dr. Stone convened a "Conference on Plutonium" in 
Chicago to discuss health issues related to plutonium, including the relationship 
between dose and excretion rate, the permissible body burden, and potential 
therapy and protective measures. 37 Wright Langham spoke about the Oak Ridge 
injection at the conference, carefully qualifying the reliability of the excretion 
data obtained from Mr. Cade. Langham observed that "the patient might not have 
been an ideal subject in that his kidney function may not have been completely 
normal at the time of injection" 38 as indicated by protein tests of his urine. 

The Chicago Experiments 

On April 1 1, the day after the Oak Ridge injection, Hymer Friedell 
transmitted the protocol describing the experiment on Mr. Cade to Louis 
Hempelmann at Los Alamos. "Everything went very smoothly," he wrote, "and I 
think that we will have some very valuable information for you." 39 He then went 
on to discuss the injection of more patients: "I think that we will have access to 
considerable clinical material here, and we hope to do a number of subjects. At 
such time as we line up several patients I think we will make an effort to have Mr. 
Langham here to review our setup." 40 

Subsequently, between late April and late December of 1945, three cancer 
patients, code-named CHI-1, 2, and 3, were injected with plutonium. At least two 
and possibly all three were injected at the Billings Hospital of the University of 
Chicago. The doses to subjects CHI-2 and CHI-3 were the highest doses 
administered to any of the eighteen injection subjects-approximately 95 
micrograms. 41 However, the amount of material injected was still below what 
would be expected to produce acute effects. Moreover, unlike Mr. Cade, all three 
of these patients were seriously ill and at least two of them died within ten months 
of receiving the injection. That the selection of seriously ill patients was an 

241 



Part II 

intentional strategy to contain risk is indicated in a 1946 report on CHI-1 and 
CHI-2: "Some human studies were needed to see how to apply the animal data to 
the human problems. Hence, two people were selected whose life expectancy 
was such that they could not be endangered by injections of plutonium." 42 It 
remains a mystery why CHI-3 was not included in this report. 

On April 26, 1945, CHI-1, a sixty-eight-year-old man who had been 
admitted to Billings Hospital in March, was injected with 6.5 micrograms of 
plutonium. At the time of injection he was suffering from cancer of the mouth 
and lung. The patient reportedly "remained in fair condition until August 1945, 
when he complained of pain in the chest." 4 ' 1 His lung cancer had apparently 
spread, and he died on October 3, 1945. 44 

The next injection took place eight months later. CHI-2 was a fifty-five- 
year-old woman with breast cancer who had been admitted to Billings Hospital in 
December 1945 after the cancer had already spread throughout her body. The 
1 946 report recorded that "the patient's general condition was poor at the time of 
admission and deteriorated steadily throughout the period of hospitalization." 45 
She was injected with 95 micrograms of plutonium on December 27 and died on 
January 13, 1946. 46 

There is little known about the condition of CHI-3, the other subject who 
was injected with approximately 95 micrograms. He was a young man suffering 
from Hodgkin's disease, reportedly injected on the same date as CHI-2. 47 His 
condition at the time of injection remains unknown, as does his date of death. 
There is some question whether he was injected at Billings hospital or at another 
hospital in the Chicago area. 4 * 

There was no discussion of consent in the original reports on the Chicago 
experiments. However, a draft report on an interview conducted with E. R. 
Russell for the 1974 AEC investigation into the experiments (Russell was 
coauthor of the 1946 report on the Chicago experiments) summarized Russell's 
description of consent as follows: "[H]e prepared the plutonium solutions for 
injection and acted together with a nurse as witness to the fact that the patient was 
or had been informed that a radioactive substance was going to be injected. The 
administration of this substance, according to what was said in obtaining consent, 
was not necessarily for the benefit of the patients but might help other people." 49 
To say that the injection was "not necessarily" for the benefit of the patient 
implies that there was some chance these patients might benefit; in fact, there was 
no expectation that this would occur. 

Russell's account was obtained in the context of an official inquiry into his 
conduct and the conduct of the other investigators and officials involved in the 
plutonium injections, an inquiry that focused on whether consent was obtained 
from the subjects. We have no way of corroborating this account or of assessing 
what Dr. Russell's motivations were in explaining the plutonium injections to the 
subjects in the way claimed. 



242 



Chapter 5 
The Rochester Experiments 

By the time the war began, the University of Rochester, which had a 
cyclotron, had assembled a group of first-rate physicists and medical researchers 
who were pioneering the new radiation research. Following the selection of the 
university's Stafford Warren to head its medical division, the Manhattan Project 
turned to Rochester for an increasing share of its biomedical research-including, 
in particular, research needed to set standards for worker safety. 50 

The university's metabolism ward, at what is now the Strong Memorial 
Hospital, became the central Manhattan District site for the administration of 
isotopes to human subjects. The two-bed ward, headed by Dr. Samuel Bassett, 
was part of the Manhattan District's "Special Problems Division," which worked 
on the health monitoring of production plants, the development of monitoring 
instruments, and research on the metabolism and toxicology of long-lived 
radioactive elements. 51 An experimental plan called for fifty subjects altogether, 
in five groups often subjects each. Each group would receive plutonium, radium, 
polonium, uranium, or lead. 52 Although the exact number of subjects remains 
unknown, at least twenty-two patients were administered long-lived isotopes in 
experiments with plutonium (eleven subjects), polonium (five subjects), and 
uranium (six subjects). 

At the time the experiment was being designed, the main selection 
criterion for the subjects chosen at Rochester for the plutonium experiment was 
that they have a metabolism similar to healthy Manhattan Engineer District 
workers. In a work plan for the plutonium study based on a September 1 945 
meeting with a representative of Colonel Warren's office and the Rochester 
doctors, Langham wrote: 

The selection of subjects is entirely up to the 
Rochester group. At the meeting it seemed to be 
more or less agreed that the subjects might be 
chronic arthritics [patients with serious collagen 
vascular diseases, such as scleroderma] or 
carcinoma patients without primary involvement of 
bone, liver, blood or kidneys. 

It is of primary importance that the subjects have 
relatively normal kidney and liver function, as it is 
desirable to obtain a metabolic picture comparable 
to that of an active worker. 

Undoubtedly the selection of subjects will be 
greatly influenced by what is available. The above 
points, however, should be kept in mind. 53 

243 



Part II 

Although this protocol specifies cancer patients as potential subjects, 
evidently the deliberate choice was made later by the experimenters to select 
patients without malignant diseases in the hope of ensuring normal metabolism. 54 
Thus no cancer patients were included among the plutonium subjects at 
Rochester. Preference appears to have been given to patients the doctors believed 
would benefit from additional time in the hospital. 55 

An additional perspective on the selection of subjects for the plutonium 
experiments is provided in three retrospective reports written by Wright 
Langham. In a 1950 report on the plutonium project, including the experiments 
conducted at Rochester, Langham wrote that "as a rule, the subjects chosen were 
past forty- five years of age and suffering from chronic disorders such that 
survival for ten years was highly improbable." 56 In subsequent reports, Langham 
refers to the plutonium subjects as having been "hopelessly sick" 57 and 
"terminal." 58 

Documents retrieved for the Advisory Committee show that all but one of 
the plutonium subjects at Rochester suffered from chronic disorders such as 
severe hemorrhaging secondary to duodenal ulcers, heart disease, Addison's 
disease, cirrhosis, and scleroderma. 59 One subject, Eda Schultz Charlton, did not 
have any such condition. According to the draft of the 1950 report, she was 
misdiagnosed: "a woman aged 49 years may have a greater life expectancy than 
originally anticipated due to an error in the provisional diagnosis." 60 

Most of the subjects at Rochester were not terminally ill, and at least some 
of them had the potential to live more than ten years. Three of the Rochester 
subjects were known to still be living at the time of the 1974 AEC investigation 
into the plutonium experiments. Whether the inclusion of subjects at Rochester 
with the potential to live more than ten years is an indication that the investigators 
were not using Langham's criterion to select subjects or that they erred in their 
predictions is unclear. Judgments about the life expectancy of the chronically ill 
are difficult to make and often in error, even today. 

The likelihood that long-term risks can be altogether eliminated does 
exist, however, if the subject is in the terminal stages of an illness and death is 
imminent. This was recognized by the plutonium investigators, and it led to the 
observation that the use of a terminal patient permitted a larger dose, which would 
make analysis easier. The first terminal patient at Rochester was injected toward 
the end of that series, and the possibility of further injections into terminal 
patients was discussed explicitly. In a March 1946 letter, Wright Langham wrote 
to Dr. Bassett, the primary physician-investigator at Rochester: 

In case you should decide to do another terminal 
case, I suggest you do 50 micrograms instead of 5. 
This would permit the analysis of much smaller 
samples and would make my work considerably 
easier. ... I feel reasonably certain there would be 

244 



Chapter 5 

no harm in using larger amounts of material if you 
are sure the case is a terminal one [as was done in 
two of the three Chicago injections]. 61 

As was the case at Oak Ridge and Chicago, there was no expectation that 
the patient-subjects at Rochester would benefit medically from the plutonium 
injections. The Advisory Committee found no documents that bear directly on 
what, if anything, the subjects were told about the injections and whether they 
consented. The recollections of at least some of those intimately involved have 
survived, however, and these recollections all suggest that the patients did not 
know they had been injected with radioactive material or even that they were 
subjects of an experiment. 

Milton Stadt, the son of a Rochester subject, told the Advisory Committee 
the following at a meeting in Santa Fe, New Mexico, on January 30, 1995: 

My mother, Jan Stadt, had a number, HP-8. She 
was injected with plutonium on March 9th, 1946. 
She was forty-one years old, and I was eleven years 
old at the time. My mother and father were never 
told or asked for any kind of consent to have this 
done to them. 

My mother went in [to the hospital] for scleroderma 
. . . and a duodenal ulcer, and somehow she got 
pushed over into this lab where these monsters 
were. 

Dr. Hempelmann, in an interview for the 1974 AEC investigation, said he 
believed that the patients injected with plutonium were deliberately not informed 
about the contents of the injections. 62 Dr. Patricia Durbin, a University of 
California researcher who in 1968 undertook a scientific reanalysis of the 
experiments, reported on a visit with Dr. Christine Waterhouse in 1971 . Dr. 
Waterhouse was a medical resident at Rochester at the time of the plutonium 
injections. Durbin wrote the following regarding the Rochester subjects who 
were still alive: 

She [Dr. Waterhouse] believes that all three persons 
would be agreeable to providing excretion samples 
and perhaps blood samples, but they are all quite 
old~in their middle or late 70's and cannot travel 
far. More important, they do not know that they 
received any radioactive material. 63 



245 



Part II 

In notes on a 1971 telephone conversation with Wright Langham, Dr. 
Durbin wrote: "He is, I believe, distressed by . . . the fact that the injected people 
in the HP series were unaware that they were the subjects of an experiment." 64 
This recollection is even more troubling than the recollections of Drs. Waterhouse 
and Hempelmann, as it indicates not only that the subjects did not know that they 
were being injected with plutonium or a radioactive substance, but also that they 
did not know even that they were subjects of an experiment. 

Even the doctors in charge of some of the injections at Rochester may not 
have known what they were injecting into patients. In 1974, Dr. Hempelmann 
suggested that the physician who actually injected the solution quite possibly did 
not know of its contents. 65 

Further evidence suggesting that the patient-subjects were never told what 
was done to them comes from 1 950 correspondence between Langham and the 
physicians at Rochester. These physician-investigators were looking for signs of 
long-term skeletal effects in follow-up studies with two of the subjects at 
Rochester. Langham wrote to Rochester that he was "very glad to hear that you 
will manage to get follow-ups on the two subjects. The x-rays seem to be the all- 
important thing, but please get them in a completely routine manner. Do not 
make the examination look unusual in any way." 66 

Moreover, a letter from Langham to Dr. Bassett discussed the 
undesirability of recording plutonium data in the Rochester subjects' hospital 
records: 

I talked to Col. [Stafford] Warren on the phone 
yesterday and he recommended that I send copies of 
all my data to Dr. [Andrew] Dowdy where it would 
be available to you and Dr. [Robert M.] Fink to 
observe. He thought it best that I not send it to you 
because he wanted it to remain in the Manhattan 
Project files, instead of taking a chance on it finding 
its way into the hospital records. I think this is 
probably a sensible suggestion. 



67 



Uranium Injections at Rochester 

Under the Manhattan Engineer District program, physicians at the 
Rochester metabolism ward also injected six patients with uranium (in the form of 
uranyl nitrate enriched in the isotopes uranium 234 and uranium 235) to establish 
the minimum dose that would produce detectable kidney damage due to the 
chemical toxicity of uranium metal, and to measure the rate at which uranium was 
excreted from the body. To achieve the first objective, the experimenters used a 
higher dose with each new subject until the first sign of minimal kidney damage 
occurred. Damage occurred in the sixth and last subject (at a calculated amount 

246 



Chapter 5 

of radioactivity of 0.03 microcuries), indicated by protein tests of his urine. 
Unlike the plutonium injections, this was an experiment that evidently was 
designed not only to obtain excretion data but to cause actual physical harm, 
however minimal. Thus, although the investigators could reasonably view the 
plutonium injections as an experiment that was extremely unlikely to produce 
acute effects, this was not true of the uranium experiment, which was intended to 
produce acute effects. As with the plutonium injections, the uranium injections 
also posed a long-term risk of the development of cancer. The Committee does 
not know in this case how long subjects survived after injection; there is no 
documentation of follow-up with these subjects as there is for some of the 
subjects of the plutonium injections. 

The subjects of this experiment, like some of the plutonium-injection 
subjects, were not at risk of imminent death, but did suffer from chronic medical 
conditions such as rheumatoid arthritis, alcoholism, malnutrition, cirrhosis, and 
tuberculosis. According to Dr. Bassett, again the primary investigator, the 
subjects "were chosen from a large group of hospital patients. Criteria of 
importance in making the selection were reasonably good kidney function with 
urine free from protein and with a normal sediment on clinical examination. The 
probability that the patient would benefit from continued hospitalization and 
medical care was also a factor in the choice." 68 

The 1948 report on the experiment did not discuss the question of consent. 
We were not able to locate any documents that bear on what, if anything, the 
subjects were told about the uranium injections, nor have any relevant 
recollections about the experiment survived. Two 1946 documents, however, 
discussing whether Dr. Bassett should be permitted to give a departmental 
seminar on the excretion rate of uranium in humans, illustrate the secrecy that 
surrounded these injections and suggest that the subjects were not informed of the 
experiment. By the time of this correspondence, the uranium research with 
animals at Rochester had been declassified. The first document, a letter written by 
Andrew Dowdy, the director of the Manhattan Department at the University of 
Rochester, to a Manhattan District Area engineer requesting permission for 
Bassett to give the seminar, included the following: "I feel that there is no reason 
why he should not discuss this matter, and I believe that the fact that this 
information was actually obtained on his own patients is of more concern to 
himself than to the District." 69 In the second document, an intraoffice 
memorandum, the area engineer discussed this point, and more: 

Dr. Dowdy states that the patients were Dr. 
Bassett's, but it should be borne in mind that all the 
work performed by Dr. Bassett was performed at 
the request of the Manhattan District Medical 
Section. This seminar is to be conducted for persons 
who are all Doctors of Medicine and it is doubtful if 

247 



Part II 

this information would get out to any of the families 
of the patients or the patients on whom the 
experiments were performed. . . . 

At the time these experiments were started, this 
office was given strict orders that the information 
should not be released to any but authorized 
persons. Almost all the correspondence and result 
of experiments were exchanged between Dr. Wright 
Langham at Santa Fe and Dr. Bassett of the 
University of Rochester. This rule is still in effect 
on some of the material that Dr. Bassett is using and 
knowledge of the experiments is kept from 
personnel at the Rochester Area. 70 

Polonium Injections at Rochester 

In addition to the subjects injected with plutonium and uranium at 
Rochester, five subjects were chosen for an experiment with polonium. The 
purpose of the experiment was to determine the excretion rate of polonium after a 
known dose, as well as to analyze the uptake of polonium in various tissues. The 
primary investigator for these experiments was Dr. Robert M. Fink, assistant 
professor of radiology and biophysics at the University of Rochester. Four 
patients were injected with the element, and one ingested it. 71 All five patients 
selected for this study were suffering from terminal forms of cancer: 
lymphosarcoma, acute lymphatic leukemia, or chronic myeloid leukemia. It is 
unclear why patients with malignant diseases were chosen as subjects in this 
experiment but excluded from the subject pools for the plutonium and uranium 
experiments. There is no discussion in the 1950 final report on the polonium 
experiments of the possibility that patients with malignant diseases might have 
abnormal metabolism, and the excretion data were employed right away in the 
establishment of occupational safety standards. 72 

The final report, unlike other reports on the Manhattan District 
metabolism studies, briefly discusses the question of consent: "the general 
problem was outlined to a number of hospital patients with no previous or 
probable future contact with polonium. Of the group that volunteered as subjects, 
four men and one woman were selected for the excretion studies outlined 
below." 73 This statement leaves no clear impression of what the subjects actually 
were told; like the experiments with plutonium and uranium, the human polonium 
experiment was a classified component of the metabolism program. Still, this 
report provides a contrast to the contemporaneous reports on the Manhattan 
District plutonium and uranium experiments, which make no mention of consent 
and which do not refer to the patient-subjects as "volunteers." 

248 



Chapter 5 
The California Experiments 

While the University of Rochester had been conducting experiments for 
the Manhattan Engineer District, a related effort was under way at the University 
of California at Berkeley. 74 Before the war, Drs. Joseph Hamilton and Robert 
Stone had been exploring medical applications of radioisotopes with the aid of the 
University of California's cyclotron. Hamilton and his colleagues had pioneered 
in using radioisotopes to treat cancer, in particular iodine 131 in the 1930s. At the 
time the United States entered the war, they were investigating another isotope for 
cancer therapy, strontium 89. Indeed, it was this area of Hamilton's expertise that 
attracted the : interest of the Manhattan Project. While Stone moved to the Chicago 
Metallurgical Laboratory during the war, Hamilton remained at the University of 
California's Radiation Laboratory, or "Rad Lab," at Berkeley. A colleague of both 
men, Dr. Earl Miller, a radiologist at the University of California, reported 
regularly to Stone on the progress of the Berkeley plutonium project. 

Under the Manhattan District contract, Hamilton's studies originally had 
involved exposing rats to plutonium in an effort to determine its metabolic fate 
and thereby project the risk to workers at atomic plants. Toward the end of the 
war, Hamilton began to conduct plutonium studies on humans for the 
government. 75 Experiments with humans could be handled expeditiously, 
Hamilton wrote, because of the close relationship between the Rad Lab and the 
medical school at the University of California at San Francisco. 76 In January 
1945, Hamilton confirmed to the Manhattan District that he planned "to 
undertake, on a limited scale, a series of metabolic studies with [plutonium] using 
human subjects." 77 The purpose of this work, Hamilton wrote, "was to evaluate 
the possible hazards ... to humans who might be exposed to them, either in the 
course of the operation of the [Chicago] pile, or in the event of possible enemy 
action against the military and civilian population." 78 

Subsequently, three subjects, two adults and one child (known as CAL-1, 
2, and 3), were injected with plutonium. In addition, in April 1947 a teenage boy 
(CAL-A) was injected with americium, and in January 1948 a fifty-five-year-old 
female cancer patient (CAL-Z) was injected with zirconium. 79 

On May 10, 1945, Hamilton reported he was awaiting "a suitable patient" 
for the plutonium experiment. 80 Four days later, fifty-eight-year-old Albert 
Stevens, designated CAL-1, was injected with plutonium, becoming the first 
human subject in the California portion of the project. 81 Albert Stevens was 
chosen in the belief that he was suffering from advanced stomach cancer. 82 
Shortly after the injection, however, a biopsy revealed a benign gastric ulcer 
instead of the suspected cancer. The researchers collected excreta daily for almost 
one year, analyzing them for plutonium content. 83 Evidently, by two months after 
the injection, Mr. Stevens was considering moving out of the Berkeley area; this 
would have prevented further collection of excretion specimens. Dr. Hamilton 
proposed to Drs. Stone and Stafford Warren that he be permitted to "pay the man 

249 



Part II 

fifty dollars per month" in order to keep Mr. Stevens in the area. Hamilton 
recognized, however, that there were "possible legal and security situations which 
may present insurmountable obstacles." 84 In response to this request, Dr. Joe 
Howland (who was reportedly involved with the Oak Ridge plutonium injection) 
wrote the following to the California area engineer: 

Possible solutions to this problem could be: 

a. Pay for his care in a hospital or nursing home as 
a service. 

b. Place this individual on Dr. Hamilton's payroll in 
some minor capacity without release of any 
classified information. 

It is not recommended that he be paid as an 
experimental subject only." 5 

According to a 1979 oral history of Kenneth Scott, an investigator at 
Berkeley who evidently was responsible for the analysis of Mr. Stevens's 
excretion specimens, the patient was paid some amount each month to keep him 
in the area. However, Dr. Scott also recalled that he never told Mr. Stevens what 
had happened to him: "His sister was a nurse and she was very suspicious of me. 
But to my knowledge he never found out." 86 

In addition, an April 1946 report on the experiment records that "several 
highly important tissue samples were secured including bone." 87 It appears that 
these tissue specimens, which included specimens of rib and spleen, were 
removed four days after the injection in an operation for the patient's suspected 
stomach cancer. 88 

Four months after Mr. Stevens was injected, Dr. Hamilton told the 
Manhattan District that the next subject would be injected "along with Pu238 
[plutonium], small quantities of radio-yttrium, radio-strontium, and radio- 
cerium." The purpose of this experiment was to "compare in man the behavior of 
these three representative long-lived Fission Products with their metabolic 
properties in the rat, and second, a comparison can be made of the differences in 
their behavior from that of Plutonium." 89 This research would provide data to 
improve extrapolation from higher-dose animal experiments. 

Despite Hamilton's hope to have a second patient by the fall, CAL-2 was 
not selected until April 1946. Simeon Shaw was a four-year-old Australian boy 
suffering from osteogenic sarcoma, a rare form of bone cancer, who was flown 
from Australia to the University of California for treatment. According to 
newspaper articles at the time, Simeon's family had been advised by an Australian 
physician to seek treatment at the University of California. 90 Arrangements then 
were made by the Red Cross and the U.S. Army for Simeon and his mother to fly 
by Army aircraft to San Francisco. Within days, he had been injected with a 

250 



Chapter 5 

solution containing plutonium, yttrium, and cerium by physicians at the 
university. 91 

Following his discharge on May 25, about a month after his injection, the 
boy returned to Australia, and no follow-up was conducted. He died in January 
1947. In February 1995 an ad hoc committee at the University of California at 
San Francisco (UCSF) concluded that probably at least part of the motivation for 
this experiment was to gather scientific data on the disposition of bone-seeking 
radionuclides with bone cancers. 92 

One piece of evidence indicating that there was a secondary research 
purpose for the injection of CAL-2 was a handwritten note in the boy's medical 
record saying that the surgeons removed a section of the bone tumor for 
pathology and for "studies to determine the rate of uptake of radioactive materials 
that had been injected prior to surgery, in comparison to normal tissues." 93 

It is likely that the CAL-2 experiment was designed both to acquire data 
for the Manhattan District and also to further the physicians' own search for 
radioisotopes that might treat cancer in future patients. The California researchers 
themselves noted the dual purpose of their research at the time. Hamilton wrote in 
a report to the Army in the fall of 1945 that there were "military considerations 
which can be significantly aided by the results of properly planned tracer 
research." 94 

As the February 1995 UCSF report on the experiments concluded, 
however, the "injections of plutonium were not expected to be, nor were they, 
therapeutic or of medical benefit to the patients." 95 This corresponds with the 
evidence of a letter, written by Hamilton in July 1946, three months after the 
injection of CAL-2, to the author of an article on the peacetime implications of 
wartime medical discoveries: 

To date no fission products, aside from radioactive 
iodine, have been employed for any therapeutic 
purposes. There is a possibility that one or more of 
the long list of radioactive elements produced by 
uranium fission may be of practical therapeutic 
value. At the present time, however, we can do no 
more than speculate. 96 

Documentary evidence suggests that consent for the injections likely was 
not obtained from at least some of the subjects at the University of California. A 
1946 letter from T. S. Chapman, with the Manhattan District's Research Division, 
said the following regarding preparations for injections: 

. . . preparations were being made for injection in 
humans by Drs. [Robert] Stone and [Earl] Miller. 
These doctors state that the injections would 

251 



Part II 

probably be made without the knowledge of the 
patient and that the physicians assumed full 
responsibility. Such injections were not divergent 
from the normal experimental method in the 
hospital and the patient signed no release. A release 
was held to be invalid. 

The Medical Division of the District Office has 
referred "P" reports for project 48A to Colonel 
Cooney for review and approval is withheld 
pending his opinion. 97 

Chapman does not specify whether the "injections" referred to in this letter 
were injections of plutonium or of some other substance. It is unclear whether "'P' 
reports" refers to Hamilton's overall progress reports on his tracer research, which 
had reported mostly on research with plutonium (but also on research with cerium 
and yttrium), or whether "P" referred specifically to reports on work with 
plutonium. As we noted at the outset of this chapter, Chapman's claim that it was 
commonplace at the time to use patients in experiments without their knowledge 
and without asking them to sign a "release" is correct. 

In the case of Albert Stevens (CAL-1), no documentary evidence that 
bears on disclosure or consent has been found. Simeon Shaw's (CAL-2's) medical 
file contains a standard form "Consent for Operation and/or Administration of 
Anaesthetic." This form, however, was signed by a witness attesting to consent of 
Simeon's mother one week after the injection and therefore probably applies to a 
biopsy done a week after the injection, not to the injection itself. 98 

On December 24, 1946, at the prompting of Major Birchard M. Brundage, 
who was chief of the Manhattan District's Medical Division, Colonel K. D. 
Nichols, commander of the Manhattan District, ordered a halt to injections of 
"certain radioactive substances'' into human subjects at the University of 
California. 99 "Such work," Nichols wrote, "does not come under the scope of the 
Manhattan District Programs and should not be made a part of its research plan. It 
is therefore deemed advisable by this office not only to recommend against work 
on human subjects but also to deny authority for such work under the terms of the 
Manhattan contract." The following week, the civilian AEC took over 
responsibility for all Manhattan District research and temporarily reaffirmed the 
Manhattan District's suspension of human experimentation at the University of 
California. 100 It is unclear why this action was taken. 

THE AEC'S REACTION: PRESERVING SECRECY WHILE 
REQUIRING DISCLOSURE 

When the civilian Atomic Energy Commission took over for the 

252 



Chapter 5 

Manhattan District on January 1, 1947, the plutonium injections provoked a 
strong reaction at the highest levels. One immediate result was the decision to 
keep information on the plutonium injections secret, evidently for reasons not 
directly related to national security, but because of public relations and legal 
liability concerns. The other immediate result, as we saw in chapter 1, was the 
issuing of requirements for future human subjects research as articulated in letters 
by the AEC's general manager, Carroll Wilson. 

In December 1946, as the civilian AEC was about to open its doors, 
Hymer Friedell, who had been deputy medical director of the Manhattan Engineer 
District, recommended the declassification of one of the plutonium reports, "CH 
[Chicago]-3607--The Distribution and Excretion of Plutonium in Two Human 
Subjects." The report, Friedell argued, "will not in my opinion result in the release 
of information beyond that authorized for disclosure by the current 
Declassification Guide." 101 

Friedell's recommendation was soon reversed. Officials with the new AEC 
had learned of the human injection experiments, and on February 28, 1947, an 
AEC declassification officer concluded that declassification was out of the 
question. The reasons are revealed in a previously classified document recently 
found at Oak Ridge: 

The document [CH-3607] appears to be the most 
dangerous since it describes experiments performed 
on human subjects, including the actual injection of 
the metal plutonium into the body. The locations of 
these experiments are given and the results, even to 
the autopsy findings in the two cases. It is unlikely 
that these tests were made without the consent of 
the subjects, but no statement is made to that effect 
and the coldly scientific manner in which the results 
are tabulated and discussed would have a very poor 
effect on the public. Unless, of course, the legal 
aspects were covered by the necessary documents, 
the experimenters and the employing agencies, 
including the U.S., have been laid open to a 
devastating lawsuit which would, through its 
attendant publicity, have far reaching results. 102 

It is not clear to the Advisory Committee on what basis the 
declassification officer who wrote this comment concluded that it was unlikely 
that consent was not obtained from the Chicago subjects. This statement could be 
read as careful bureaucratic language, intended to leave an appropriate paper trail 
in the event of subsequent legal problems. On the other hand, the statement does 



253 



Part II 

support the claim, noted earlier, made by one of the Chicago doctors in 1974 that 
some form of oral consent for the injections had been obtained from the Chicago 
subjects. It is clear that there was no documentation of disclosure or consent on 
which the AEC could rely. As a consequence, secrecy was to be maintained, not 
as a defense against foreign powers, but to avoid a "devastating lawsuit" and 
"attendant publicity." Upon further review the report was "reclassified 
'Restricted' on 3/31/47." 103 In a March 19, 1947, memorandum, Major Brundage, 
by that time chief of the AEC's Medical Division, explained: 

The Medical Division also agrees with Public 
Relations that it would be unwise to release the 
paper 'Distribution and Excretion of Plutonium' 
primarily because of medical legal aspects in the 
use of plutonium in human beings and secondly 
because of the objections of Dr. Warren and 
Colonel Cooney that plutonium is not available for 
extra Commission experimental work, and thus this 
paper's distribution is not essential to off Project 104 
experimental procedures. 105 

In July 1947, Argonne National Laboratory's declassification officer, 
Hoylande D. Young, inquired about possible declassification of this report as well 
as Hamilton's report on the CAL-1 injection. She stated that the directors of 
Argonne's Biology and Health Divisions (including J. J. Nickson, one of the 
authors of the Chicago report on the injections) believed that declassification of 
these reports would not be "prejudicial to the national interests." 106 The AEC 
continued to withhold declassification of these reports, however, on the grounds 
that they involved "experimentation on human subjects where the material was 
not given for therapeutic reasons." 107 Thus, there was clearly no expectation at 
the time that the plutonium injections would benefit the patient-subjects but some 
expectation that the general public might be disturbed by human experimentation 
in the absence of a prospect of offsetting benefit. 

In 1950, Wright Langham and the Rochester doctors undertook to prepare 
a "Plutonium Report" 101 * that would be "the last word on the plutonium 
situation." 109 It would be the "last word" to only a select few. In 1947, Rochester's 
Andrew Dowdy had urged Los Alamos to give advance notice of declassification 
of the Rochester part of the experiment "because of possible unfavorable public 
relations and in an attempt to protect Dr. [Samuel] Bassett from any possible legal 
entanglements." 110 This is likely a reference to the same concern raised in the 
discussion of Dr. Bassett's seminar about his having experimented upon his own 
patients, except in this case the context is the plutonium rather than the uranium 
injections. "We think," Langham wrote to Stafford Warren, "the classification will 
be 'Secret,' and the circulation limited, depending on Dr. Shields Warren's [the 

254 



Chapter 5 

head of AEC's Division of Biology and Medicine] wishes."" 1 In August, Shields 
Warren approved the report for "CONFIDENTIAL classification and limited 
circulation as [Dr. Langham] requested."" 2 

Even though its data and analysis were the basis for widespread plutonium 
safety procedures, the report remained unavailable to the public until 1971 when, 
at the urging of Dr. Patricia Durbin, it was downgraded to "Official Use Only."" 3 
(This categorization means that while the document was not likely to be released 
to the public absent specific request, it could be disclosed.) 

What was it that was so potentially embarrassing about the plutonium 
experiments? The answer appears to lie in the 1947 letters from General Manager 
Wilson, discussed in detail in chapter 1 . These letters state rules for both the 
conduct of human experiments and the declassification of previously conducted 
secret experiments." 4 

In his April 1947 letter, Wilson stated the requirements that there be 
expectation that research "may have therapeutic effect" and that at least two 
doctors "certify in writing (made part of an official record) to the patient's 
understanding state of mind, to the explanation furnished him, and to his 
willingness to accept the treatment."""' In his November 1947 letter, Wilson 
reiterated these terms for human experiments, again calling for "reasonable 
hope . . . that the administration of such a substance will improve the condition of 
patient" and this time calling for "informed consent in writing" by the patient." 6 
All of the seventeen plutonium injections conducted prior to the letters violated 
both these terms. As a consequence, they would have to stay secret. The only 
secret experiments that could be declassified were those that satisfied these 
requirements; to do otherwise was to risk adverse public reaction. Thus, the 
decision to keep the plutonium reports secret was itself an example of the way in 
which the AEC's assertion of conditions for human experimentation was coupled 
with the decision to keep secret those experiments that evidently did not adhere to 
these conditions (see chapter 13). 

HUMAN EXPERIMENTATION CONTINUES 

In March 1947, just as he was declaring that "public relations" required 
the reclassification of plutonium data. Medical Division chief Major Brundage 
approved a 1947-48 "Research Program and Budget" for Rochester that provided 
for metabolism studies with polonium, plutonium, uranium, thorium, radiolead, 
and radium." 7 The program was put on hold by the AEC soon after." 8 

The future of the metabolism work at Rochester apparently was decided 
when Shields Warren was named the first chief of the AEC's Division of Biology 
and Medicine in fall 1947. In his private diary for December 30, 1947, Warren 
tersely noted: "Ordered abandonment of human isotope program at Rochester.""' 
The program at the University of California at Berkeley, however, continued. On 
December 4, 1947, Shields Warren had met with Hamilton and Stone; 120 the 

255 



Part II 

decision to allow the program to continue clearly was not a hasty one. A 1 974 
recollection of Shields Warren indicates that his decision to allow the program to 
continue may have been due to Hamilton's assertion in December 1947 that it had 
been the University of California's practice to obtain some form of 
(undocumented) consent. 121 

According to Warren, Hamilton had said that subjects were told "they 
would receive an injection of a new substance that was too new to say what it 
might do but that it had some properties like other substances that had been used 
to control growth processes in patients, or something of that general sort." 122 
Warren went on to observe that "you could not call it informed consent because 
they did not know what it was, but they knew that it was a new and to them 
unknown substance." 123 Warren's observation does not go far enough, however. If 
Warren's secondhand account is accurate and this is indeed what the patient- 
subjects at the University of California were told, then they were more misled 
than informed. Analogizing plutonium to substances that "control growth 
processes in patients," even in prospect, might reasonably lead patients to believe 
that they would be receiving a substance with some hope of treating their cancer. 
Certainly such a remark would not communicate to patients that the experiment to 
be performed was not for their own benefit. It would have been appropriate that 
these patients be told that their participation might benefit future patients with the 
same conditions. It would have been crucial to distinguish, however, between 
this legitimate explanation of potential benefit to future cancer patients and 
misleading the patient into believing the experiment might benefit him or her. 

Human Experimentation Continues at the University of California 

By the summer of 1947, human experimentation had resumed at the 
University of California under AEC contract. In June, "CAL-A," a teenage Asian- 
American bone cancer patient at Chinese Hospital in San Francisco, was injected 
with americium. An instruction in the patient's file by one of Hamilton's assistants 
specifies that "we will use the same procedure as with Mr. S,"' 24 evidently a 
reference to Albert Stevens. Dr. Durbin, Hamilton's associate, believes that CAL- 
A's guardian was informed of the procedure followed in that case. 125 The 
Advisory Committee received incomplete records for CAL-A that contained no 
evidence of disclosure or consent; UCSF has told the Committee that records at 
Chinese Hospital from the 1950s and earlier have been destroyed. I2(1 

A thirty-six-year-old African-American railroad porter named Elmer 
Allen, code-named CAL-3, was believed to be suffering from bone cancer and 
was injected with plutonium at the University of California in July 1947. His left 
leg was amputated shortly thereafter. There is a note in his medical chart signed 
by two physicians, stating that the experimental nature was "explained to the 
patient, who agreed to the procedure" and that "the patient was in fully oriented 
and in sane mind." 127 It is likely that this note was intended to fulfill one of the 

256 



Chapter 5 

April 1947 conditions for human experimentation, which allowed for such a 
procedure as documentation of having obtained the patient-subject's consent. It is 
not clear from the note, however, whether in explaining about the experimental 
nature of the procedure the physicians told the patient about the potential effects 
of the injection, as required by the Wilson letter, or that the injection was not 
intended to be of medical benefit to the patient. On this second point, the 
injection was in violation of the Wilson letter, which also required that there be an 
"expectation that it may have therapeutic effect." 128 As acknowledged by the 
February 1995 UCSF report, there was never any expectation on the part of the 
experimenters that the injection would be of therapeutic benefit to Mr. Allen. 

Mr. Allen lived until 1991. According to UCSF's 1995 review of patient- 
subjects' medical charts, upon biopsy of his tumor a pathologic diagnosis was 
made of chondrosarcoma, a type of malignant bone tumor. UCSF reported that 
patients with this type of tumor "frequently surviv[e] many years beyond 
diagnosis if there is complete excision of the primary tumor."' 29 This pathology 
finding suggests that Mr. Allen was a long-term cancer survivor. A note in his 
patient chart recorded that the tumor was "malignant but slow growing and late to 
metastasize. Prognosis therefore moderately good." 130 

On March 15, 1995, Elmerine Whitfield Bell, the daughter of Elmer Allen, 
told the Advisory Committee in Washington, D.C., that she 

continue[s] to be appalled by the apparent attempts 
at cover-ups, the inferences that the nature of the 
times, the 1940s, allowed scientists to conduct 
experiments without getting a patient's consent or 
without mentioning risks. We contend that my 
father was not an informed participant in the 
plutonium experiment. 

He was asked to sign his name several times while a 
patient at the University of California hospital in 
San Francisco. Why was he not asked to sign his 
name permitting scientists to inject him with 
plutonium? Why was his wife, who was college 
trained, not consulted in this matter? 

On January 5, 1948, a fifty-five-year-old woman with cancer was injected 
with zirconium at the University of California. '■" The patient record for this case 
has not yet been located, nor have any other documents that might bear on 
whether this experiment was conducted in compliance with the consent 
requirements of the Wilson letters. We do know that the injection of zirconium 
was not expected to benefit the subject herself. 132 

A secret report on the zirconium injection was reviewed by the AEC in 

257 



Part II 

light of public relations and liability concerns. In August of that year, the report 
was denied declassification with the approval of Shields Warren, who wrote, 
"This document should not be declassified for general medical publication [and] it 
would be very difficult to rewrite it in an acceptable manner." 113 Warren was 
responding to a memorandum from Albert H. Holland, Jr., medical adviser at Oak 
Ridge, which specified that the concern about rewriting had to do with public 
relations and the fact that the report "specifically involves experimental human 
therapeutics." 134 

Follow-up of the Patient-Subjects at Rochester 

The investigators at Rochester and the AEC were interested in obtaining 
long-term data from surviving subjects on excretion levels and the distribution of 
plutonium in various tissues. Follow-up studies at Rochester continued at least 
through 1953 with two of the subjects in the HP series, Eda Charlton and John 
Mousso. We have already noted Wright Langham's 1950 instruction to the 
physicians at Rochester suggesting that they were not to give these patients any 
indication of the true purpose of the follow-up studies. 135 In addition, Langham 
sought help in early 1950 to locate Ebb Cade (the man injected at Oak Ridge 
Hospital) for follow-up excretion studies. Langham asked Dr. Albert Holland at 
Oak Ridge to try to locate Mr. Cade and to keep his "eyes open for a possible 
autopsy." 136 It is unclear to the Committee whether follow-up of any kind was 
ever done with Mr. Cade. 

On June 8, 1953, Eda Charlton's rib was removed during exploratory 
surgery for cancer and analyzed for plutonium. Louis Hempelmann, who by that 
time had moved from Los Alamos to Strong Memorial Hospital at Rochester, 
wrote to Charles Dunham of the AEC's Division of Biology and Medicine in 
advance of the procedure: 

The patient in question was brought in for a skeletal 
survey, and turned out to have a 'coin-like' lesion 
inside the chest wall. ... It is undoubtedly an 
incidental finding, but she must be explored by the 
chest surgeon here at Strong. In the course of the 
operation, he will remove a rib which we can 
analyze. Her films show the same type of minimal 
indefinite change in the bone that the others have 
had. 137 

It was standard practice at the time to remove a section of rib incidental to 
lung surgery. It is clear that the patient was still being followed for long-term 
effects of plutonium and that some subclinical bone changes of unclear 
significance had already been observed by this time. Therefore, the examination 

258 



Chapter 5 

of this rib segment would have included special tests to determine whether 
plutonium was present. 

On August 31, 1950, an internal DBM memorandum recorded the 
understanding of some AEC officials that Wright Langham and Rochester doctors 
were engaged in follow-up studies. 13 " In a 1974 interview, however, Shields 
Warren recalled that he had no knowledge that the patients were the subjects of 
follow-up studies: "I did not learn of this continuing contact while I was in office 

at AEC I had assumed because I had been told that they were incurable 

patients that they all had died by the time we talked." 139 

Additional Follow-up Studies and the Argonne Exhumation Project 

In 1968 Dr. Patricia Durbin undertook an investigation of the plutonium- 
injection subjects, which included a reevaluation of the original plutonium data. 
Her goal was to pursue "some elusive information on Pu in man and the 
information or assumptions about physiology needed to create a believable Pu 
model for man." She "decided to look at all the old Pu patients as individuals 

rather than in a lump " 14 ° Durbin was surprised to find in her search for the 

original experimental data that the University of California data were drawn from 
three subjects who received plutonium and one who received americium; the data 
from only one plutonium subject from California had previously been reported in 
the open scientific literature. 141 Durbin asked the original researchers why these 
data had not been analyzed. She wrote: "I understand from Wright Langham that 
this problem has been discussed before and discarded as too messy." 14 

In 1972, after the classified report on the experiments had been 
downgraded to "Official Use Only," she went on to publish "Plutonium in Man: 
A New Look at the Old Data," a landmark paper in the plutonium story. 143 This 
was the first review in the open literature to analyze Langham's results in light of 
the actual medical conditions of the patient-subjects. Because of the prolonged 
secrecy surrounding the experiments, it was generally not known that two of the 
three University of California cases had been omitted from the 1950 analysis. 
The report also revealed in retrospect that all the patients were not hopelessly or 
terminally ill, as had been suggested in Langham's later public references, that 
some were still alive, and that some had been misdiagnosed. 

In December 1972, Argonne National Laboratory's Center for Human 
Radiobiology (CHR), to whom Durbin had provided the names of surviving 
subjects, began a review of the data from all eighteen people who were injected 
with plutonium between 1945 and 1947. CHR was the national center designated 
by the AEC to do long-term follow-up of individuals with internally deposited 
radionuclides, primarily the radium dial painters. Argonne's follow-up plan for the 
plutonium experiments was to uncover the postinjection medical histories of all 
the subjects, obtain biological material from those still living, and exhume and 
study the bodies of those deceased in order to "provide data on the organ contents 

259 



Part II 

at long times after acquisition of plutonium." 144 

In 1973, three patients--Eda Charlton, John Mousso, and Elmer Allen- 
were admitted to the University of Rochester's metabolic ward for more excretion 
studies paid for by CHR. Elmer Allen had first been brought to Argonne, where 
an unsuccessful attempt had been made to detect plutonium by external counting 
techniques. In the course of his examination, however, CHR found subclinical 
bone "changes" that an Argonne radiologist characterized as "suggestive of 
damage due to radiation." 145 

Again there was no disclosure to the subjects that they were now being 
followed because they had been subjects of an experiment that had been unrelated 
to their medical care, an experiment in which there was continuing scientific 
interest. The 1974 AEC investigation concluded that, in the case of the surviving 
Rochester subjects, Dr. Waterhouse, who conducted the follow-up studies with 
these patients for Argonne, had not told them the purpose of the studies in 1973 
because she believed "that disclosure might be harmful to them in view of their 
advanced age and ill health." 146 This suggests that Dr. Waterhouse had well- 
intentioned motivations for not being straightforward with the Rochester subjects. 
It also suggests that these subjects had not been told the truth about the 
experiments at the time the injections occurred, or that they had forgotten. 
According to Dr. Waterhouse, the studies were feasible without the subjects' 
knowledge of the true purpose of the research since these two patients "were 
accustomed to participating in clinical studies, unrelated to this matter, involving 
the collection of excretion specimens." 147 Elmer Allen's physician was told by 
CHR that the purpose of bringing Mr. Allen to Argonne's CHR and the University 
of Rochester for follow-up was interest in the treatment he received at the 
University of California in 1947 for his cancer. 148 This use of the term treatment 
in the information provided Mr. Allen's physician, which he presumably relayed 
to Mr. Allen and his family, was deceptive and manipulative; it implied that the 
injection Mr. Allen received had been given as therapy for his benefit. 

The second component of this follow-up study was research on the 
exhumed bodies of deceased subjects. The 1974 AEC investigation concluded 
that the families were not informed that plutonium had been injected. Instead, 
they were told that "the purpose of exhumation was to examine the remains in 
order to determine the microscopic distribution of residual radioactivity from past 
medical treatment" and that the subjects had received an "unknown" mixture of 
radioactive isotopes. 149 The investigation concluded that such disclosure "could be 
judged misleading in that the radioactive isotopes were represented as having 
been injected as an experimental treatment for the patient's disease." 150 Thus, the 
families of the deceased subjects as well as those subjects still surviving were 
deceived by officials of the AEC. 

A December 1972 intralaboratory memorandum, written by an Argonne 
investigator, instructs that "outside of CHR we will never use the word plutonium 
in regard to these cases. 'These individuals are of interest to us because they may 

260 



Chapter 5 

have received a radioactive material at some time' is the kind of statement to be 
made, if we need to say anything at all." 151 Robert E. Rowland, the author of this 
memorandum, told Advisory Committee staff in 1995 that he had written this 
after he had been instructed earlier that month by Dr. James Liverman, director of 
the AEC's Division of Biomedical and Environmental Research, that "I could not 
tell the individuals that they were given plutonium. I protested that they must be 
given a reason for our interest in them, and I was told to tell them that they had 
received an unknown mixture of radioisotopes in the past, and that we wanted to 
determine if it was still in their bodies. Further, we were not to divulge the names 
of the institutions where they received this unknown mixture." 152 Dr. Rowland 
said he had received these instructions during a trip to Washington, D.C., to 
obtain approval and funding for the study. 153 Dr. Liverman told Advisory 
Committee staff that he has "no recollection of discussions with anyone in which 
some stricture would have been placed on what could be discussed with the 
patients. That is a medical ethics issue which would have been left to the 
physicians." 154 

This study was not brought to the attention of the Argonne Human Use 
Committee until November 1973, even though it had been established in January 
1973. (See chapter 6 for a discussion of human use committees.) In a briefing for 
the 1974 AEC investigation, Dr. Liverman attributed this failure to bring the 
study before the Human Use Committee to the following factors: "( 1 ) [Argonne's] 
opinion that the studies came under the scope of a protocol approved by that 
Committee in 1971. (2) The nature of the studies was to be suppressed to avoid 
embarrassing publicity for AEC." 155 

In 1974 the AEC informed at least two of the four living subjects— Eda 
Charlton and John Mousso— of the plutonium injections and had them sign 
documents to this effect. These documents did not provide any information on 
possible effects of the injections, although they did describe the purpose as having 
been "to determine how plutonium, a man-made radioactive material, is deposited 
and excreted in the human body." 156 One living patient, Jan Stadt, was not told, 
because it was her attending physician's opinion that her condition was precarious 
and that disclosure in this case would be "medically indefensible." 157 This 
judgment, like that of Dr. Waterhouse's, exemplifies how physicians of the time 
commonly managed the information they shared with their patients. Physicians 
typically told patients only what they thought it was helpful for them to know; if 
in the physician's judgment information might cause the patient to become upset 
or distressed, this was often considered reason enough to withhold it. 15X The 
judgment also suggests that Ms. Stadt, like Ms. Charlton and Mr. Mousso, had not 
been told the truth about the experiments at the time the injections occurred or 
that she had forgotten. 

The AEC recommended that exhumations continue, but only with full 
disclosure to the subjects' next of kin. 



261 



Part II 

The Boston Project Uranium Injections 

Human experiments conducted to measure the excretion and distribution 
of atomic weapons materials did not stop with the last of the injections at the 
University of California. The Boston Project human uranium-injection 
experiments were conducted from 1953 to 1957 at Massachusetts General 
Hospital (MGH) as part of a cooperative project between the hospital and the 
Health Physics Division of Oak Ridge National Laboratory. Eleven patients with 
terminal conditions were injected with uranium, although data obtained from 
three of these subjects were never published. 159 The ORNL and the AEC 
undertook the Boston Project to obtain better data for the development of worker 
safety standards. One of the investigators wrote that the Boston Project would 
provide "a wonderful opportunity to secure 'human data' for the analysis and 
interpretation of industrial exposures." 160 The occupational standards for uranium 
at the time were based on animal data and on the experiment conducted at 
Rochester in the 1940s. No autopsy data were obtained from this earlier 
experiment at Rochester, however, since none of the patients had terminal 
diseases. Thus, wrote a Boston Project investigator, "the uncertainty, in so far as 
the distribution of uranium was concerned, was not reduced [by the Rochester 
experiment] or could not even be determined." 161 

The Boston Project involved a second purpose—the search for a 
radioisotope that would localize in a certain type of brain tumor—called 
glioblastomas— and destroy them when activated by a beam of neutrons. This had 
long been the research interest of Dr. William Sweet at MGH; at the time, these 
tumors were clearly diagnosable and 100 percent fatal, and there was no effective 
treatment. This research involved many radioisotopes over the years, most 
notably isotopes of boron and phosphorus. It is unclear whether Dr. Sweet would 
have tested uranium without ORNL's involvement— or whether it would have been 
made available to him by the AEC. Dr. Sweet has indicated to the Committee that 
he was interested in the potential of uranium as a therapeutic agent prior to being 
approached by the AEC about the possibility of conducting a joint project. 162 

The Boston Project produced data on the distribution of uranium in the 
human body that the earlier Manhattan District uranium studies had not provided. 
The data obtained indicated that uranium, at least at the dose levels used in the 
Boston Project, localized in the human kidney at higher concentrations than small 
animal data had predicted and that therefore the maximum permissible levels for 
uranium in water and air might be unsafe. Recommendations made by the 
investigators of the Boston Project for more conservative occupational standards 
were apparently not heeded, however. The accepted occupational levels for 
uranium became less rather than more conservative over the years, despite the 
findings of the Boston Project. 163 

Hopes that uranium would localize sufficiently in brain tumors to be of 
potential therapeutic use were unfulfilled. In a 1979 interview, Robert Bernard, 

262 



Chapter 5 

one of the health physicists at ORNL most intimately involved with the study, 
was asked if during the experiment uranium was showing any promise as a 
treatment. "No, it concentrated in the kidney just like Rochester said back in the 
'40's. . . . They got brain tumor samples. There was very little uranium present, 
but Sweet was still wondering: maybe [it was] not a high enough dose." 164 

In a 1995 interview, Karl Morgan, head of the Health Physics Division of 
ORNL at the time of the Boston Project, indicated that the project was ultimately 
discontinued in 1957 165 because of the concerns of an ORNL health physicist: 

He felt that the patients were given very large doses 
of uranium which our data had indicated— that is, 
the data we collected [at ORNL] in setting 
permissible doses—would be very harmful. ... I 
immediately cancelled our participation in the 
program. Apparently, they were given doses that 
were many times the . . . permissible body 
burden. 166 

In their application to their radioisotope committee, MGH investigators clearly 
recorded that the proposed dose of 2.12 rem per week "exceeds maximum 
permissible exposure rate of 0.3 rem/week but [patients] are terminal." 16 

At least one of the subjects was selected for the distribution part of the 
study only. Reports describe the patients as "virtually all" having malignant brain 
tumors; newly available documents indicate that at least one patient injected with 
uranium did not have a brain tumor at all. An unidentified male, identity and age 
still unknown at the time of his death, became Boston Project subject VI when he 
"was brought to the Emergency Ward after being found unconscious. ... No other 
information was obtainable." I6X According to his autopsy report, this patient was 
suffering from a subdural hematoma~a severe hemorrhage— on his brain. There 
was clearly no benefit intended for this patient from the injection of uranium, but 
there is evidence of harm attributable to the injection. His autopsy report records 
clinical evidence of mild kidney failure 169 and pathological evidence of kidney 
nephrosis (damage to the kidney tubules) from the chemical toxicity of uranium 
metal. 170 The report also records that "the liver, spleen, kidneys and bone marrow 
showed evidence of radiation." 171 

Even for the patient-subjects with brain cancer, there was no expectation 
on the part of investigators that the experiment would benefit the subjects 
themselves. The object of the experiment was to test whether uranium would 
localize sufficiently in brain tumors to be of therapeutic value in the future. In 
order for uranium to have had therapeutic potential for patient-subjects, exposure 
to a reactor's neutron beam would have been necessary to then activate the 
uranium, if it had localized sufficiently in the tumors, which it did not. There was, 
however, no plan to expose these particular patient-subjects to a neutron beam; 

263 



Part II 

the goal was to see whether the concentration would justify further research that 
would involve exposure to a neutron beam. Most of the subjects were already 
comatose and "in the terminal phase of severe irreversible central nervous system 
disease." 172 

The doses used in the Boston Project were high; the lowest dose was 
comparable to the highest used in the earlier Rochester uranium experiment— a 
dose that had caused detectable kidney damage in one of the Rochester subjects. 
One document records that at least two Boston Project subjects, in addition to 
subject VI, had kidney damage at the time of death, although this document does 
not directly link this damage to the uranium injections.' 73 

There is no discussion of consent in any of the Boston Project reports. It 
appears that ORNL left such considerations to Dr. Sweet and MGH. In an interim 
report, ORNL discusses the division of responsibility in the experiment: "It was 
agreed that the Y-12 Health Physics Department [at Oak Ridge] would prepare 
injection solutions and perform the analytical work associated with this joint 
effort. Massachusetts General Hospital agreed to select the patients, perform the 
injections, and care for the patients during the period of study." 174 

Dr. Sweet told the Advisory Committee in 1995 that it was his practice to 
obtain consent from patients or from their families and "scrupulously to give a 
patient all the information we had ourselves." 175 The Committee has not been 
able to locate any documents that bear on questions of disclosure or consent for 
this experiment. I7A The case of the Boston Project subject who was brought into 
the hospital after being found unconscious, and who, according to his autopsy 
report, was never identified and never regained consciousness, indicates that this 
rule was not applied universally. 

CONCLUSION 

From 1945 through 1947 Manhattan Project researchers injected eighteen 
human subjects with plutonium, five human subjects with polonium, and six 
human subjects with uranium to obtain metabolic data related to the safety of 
those working on the production of nuclear weapons. All of these subjects were 
patients hospitalized at facilities affiliated with the Universities of Rochester, 
California, and Chicago or at Oak Ridge. Another set of experiments took place 
between 1953 and 1957 at Massachusetts General Hospital, in which human 
subjects were injected with uranium. In no case was there any expectation that 
these patient-subjects would benefit medically from the injections. 

At fifty years' remove, it is in some respects remarkable that so much 
information has survived that bears on the question of what the patient-subjects 
and their families were told. Particularly for the Manhattan Project plutonium 
experiments information is available, in large part because of the 1974 AEC 
inquiry in which interviews with principals of these experiments were conducted 
and records of these interviews maintained. At the same time, however, there are 

264 



Chapter 5 

significant gaps in the record for all the experiments. Particularly where the 
evidence is skimpy, it is possible that some of the patient-subjects agreed to be 
used in nontherapeutic experiments., But the picture that emerges suggests 
otherwise. This picture is bolstered by the historical context. As we discussed in 
chapter 2, it was not uncommon in the 1940s and 1950s for physician- 
investigators to experiment on patients without their knowledge or consent, even 
where the patients could not benefit medically from the experimental procedures. 
This context is referenced in a 1946 letter about the University of California 
injections: "These doctors state that the injections would probably be made 

without the knowledge of the patient Such injections were not divergent from 

the normal experimental method in the hospital. . . ."' 77 

Here we present our conclusions about the ethics of these experiments, 
first for the set of experiments conducted between 1945 and 1947 and then for the 
experiment conducted from 1953 to 1957. Because the facts appear to be 
different in the different institutions at which these experiments took place, we 
summarize what we have learned about risk, disclosure, and consent at each 
location. We also analyze the ethical issues the experiments raise in common. In 
our analysis, we focus on whether the subjects consented to being used in 
experiments from which they could not benefit medically, and the extent to which 
the subjects were exposed to risk of harm. We also focus on the particular ethical 
considerations raised when research is conducted on patients at the end of their 
lives. All but one member of the Advisory Committee believe that what follows 
is the most plausible interpretation of the available evidence in light of the 
historical context. 

With one exception, the historical record suggests that these patients- 
subjects were not told that they were to be used in experiments for which there 
was no expectation they would benefit medically, and as a consequence, it is 
unlikely they consented to this use of their person. 

In the case of the plutonium experiments, there was no reason to think that 
the injections would cause any acute effects in the subjects. This was not true, 
however, in the case of the Rochester uranium experiments. Both the plutonium 
and the Rochester uranium experiments put the subjects at risk of developing 
cancer in ten or twenty years' time. In some cases, this risk was eliminated by the 
selection of subjects who were likely to die in the near future. The selection of 
subjects with chronic illnesses was also an apparent strategy to contain this long- 
term risk of cancer. However, some of these subjects lived for far longer than ten 
years, and some were misdiagnosed altogether. On the basis of available 
evidence, we could not conclude that any individual was or was not physically 
harmed as a result of the plutonium injections. There is some evidence that there 
were observable, subclinical bone changes of unclear significance in at least two 
surviving subjects who were followed up in 1953 and 1973 and in one deceased 
subject who was exhumed in 1973. The uranium injections at Rochester were 
designed to produce minimal detectable harm-that was the endpoint of the 

265 



Part II 

experiment. Such minimal damage is reported to have occurred in the sixth 
patient of the series. 

In the case of Mr. Cade at Oak Ridge, a physician claiming to have 
injected Mr. Cade reported that his consent was not obtained. An apparently 
healthy man in his early fifties, Mr. Cade was put at some (probably small) risk of 
cancer by the plutonium injection. 

At the University of Chicago, the only evidence that bears on disclosure 
and consent comes from an interview with a Chicago investigator conducted as 
part of the AEC's 1974 inquiry. The investigator was recorded as saying that in 
obtaining consent patients were told that the radioactive substance to be injected 
"was not necessarily for the benefit of the patients but might help other people." 178 
This statement is misleading. It suggests that there was some chance these 
patient-subjects might benefit when there was no such expectation. At the same 
time, however, this statement suggests that the subjects at Chicago were told 
something. These subjects also were all apparently terminally ill and thus at no 
risk of developing plutonium-induced cancer; at least two of the three were 
known to have died within one year of the injection. 

Misleading language was purportedly also used with subjects at the 
University of California, where a secondhand account suggests that subjects were 
told they were to be injected with a new substance that "had some properties like 
other substances that had been used to control growth processes in patients." 179 
Language in a 1946 letter suggests that at least some of the injections at the 
University of California may have occurred altogether without the knowledge of 
the patients. In the case of Mr. Allen, one of the California subjects, two 
physicians attested that the experimental nature of the procedure had been 
explained to Mr. Allen and that he had consented. And yet Mr. Allen's physician 
was subsequently informed that the follow-up studies were in relation to 
treatment Mr. Allen had received at the University of California. This suggests 
that, while Mr. Allen may have been told the procedure was experimental, it is 
not likely that he was told that the procedure was part of an experiment in which 
there was no expectation that he would benefit medically. Both Mr. Allen and 
Mr. Stevens survived long enough after injection to be at risk of plutonium- 
induced cancer. 

All the available evidence suggests that none of the subjects injected with 
either plutonium or uranium at Rochester knew or consented to their being used 
as subjects in experiments from which they could not benefit. This evidence 
comes from recollections of some of the individuals who were involved with the 
plutonium injections, as well as documents about seminars and follow-up studies 
in the early 1950s suggesting that information about the experiments should be 
concealed from the subjects. Most of the subjects at Rochester had serious 
chronic illnesses. It is unclear how likely it was at the time that these patients 
would not survive more than ten years. A few of these subjects were still alive 
more than twenty years after the injections. None of the plutonium subjects but all 

266 



Chapter 5 

of the uranium subjects were put at risk of acute effects from the experiment. 

The purpose of the 1973 follow-up studies was withheld from two 
surviving subjects. Also, both Elmer Allen's physician and family members of 
deceased subjects were misled by AEC officials about the purpose of the follow- 
up studies. They were told that the follow-up was in relation to past medical 
treatment, which was not true. 

It is unlikely that AEC officials would have lied about or otherwise 
attempted to conceal the purpose of the follow-up studies if at the outset the 
subjects had known and agreed to their being used as subjects in nontherapeutic 
experiments. It is also relevant that when the Atomic Energy Commission 
succeeded the Manhattan Project on January 1, 1947, officials decided to keep the 
plutonium injections secret. It appears that this decision was based on concerns 
about legal liability and adverse public reaction, not national security. The 
documents show that the AEC responded to the possibility that consent was not 
obtained in the plutonium experiments, as well as their lack of therapeutic benefit, 
by stating requirements for informed consent and therapeutic benefit for future 
research, while still keeping the experiments secret. As a result of the decision to 
keep the injections secret, the subjects and their families, as well as the general 
public, were denied information about these experiments until the 1970s. 

The one likely exception to this picture of patients not knowing that they 
were used as subjects in experiments that would not benefit them is the polonium 
experiment conducted at Rochester. This is the one instance in which the patient- 
subjects are said to have volunteered after being told about "the general problem." 
Although there is no direct evidence that these subjects were told that the 
experiment was not for their benefit, the language of volunteering suggests a more 
forthright disclosure was made, more in keeping with the conventions in 
nontherapeutic research with healthy subjects than in research with patients (see 
chapter 2). We cannot reconcile the account of the polonium experiment with the 
historical record on the other injections. 

The Advisory Committee is persuaded that these experiments were 
motivated by a concern for national security and worker safety and that, 
particularly in the case of the plutonium injections, they produced results that 
continue to benefit workers in the nuclear industry today. 180 However, with the 
possible exception of the polonium experiments, we believe that these 
experiments were unethical. In the conduct of these experiments, two basic moral 
principles were violated-that one ought not to use people as a mere means to the 
ends of others and that one ought not to deceive others-in the absence of any 
morally acceptable justification for such conduct. National security 
considerations may have required keeping secret the names of classified 
substances, but they would not have required using people as subjects in 
experiments without their knowledge or giving people the false impression that 
they or their family members had been given treatment when instead they had 
been given a substance that was not intended to be of benefit. 

267 



Part II 

The egregiousness of the disrespectful way in which the subjects of the 
injection experiments and their families were treated is heightened by the fact that 
the subjects were hospitalized patients. Their being ill and institutionalized left 
them vulnerable to exploitation. As patients, it would have been reasonable for 
them to assume that their physicians were acting in their best interests, even if 
they were being given "experimental" interventions. Instead, the physicians 
violated their fiduciary responsibilities by giving the patients substances from 
which there was no expectation they would benefit and whose effects were 
uncertain. This is clearest at Rochester where at least the uranium subjects, and 
perhaps the plutonium subjects, were apparently the personal patients of the 
principal investigator. 

Concern for minimizing risk of harm to subjects is evident in several of 
the planning documents relating to the experiments, an obligation that many of 
those involved apparently took seriously. At Chicago, for example, where the 
highest doses of plutonium were used, care was taken to ensure that all the 
subjects had terminal illnesses. In those cases where this concern for risk was 
less evident and subjects were exposed to more troubling risks, the moral wrong 
done in the experiments was greater. Where it was not reasonable to assume that 
subjects would be dead before a cancer risk had a chance to materialize, or in the 
case of the uranium injections at Rochester where acute effects were sought, the 
experiments are more morally offensive. 

Consideration for the basic moral principle that people not be put at risk of 
harm is apparently what animated the decision to give higher doses to only 
"terminal" patients who could not survive long enough for harms to materialize. 
A person who is dying may have fewer interests in the future than a person who is 
not. This does not mean, however, that a dying person is owed less respect and 
may be used, like an object, as a mere means to the ends of others. There are 
many moral questions about research on patients who are dying; the desperation 
of their circumstances leaves them vulnerable to exploitation. At a minimum, 
nontherapeutic research on a dying patient without the patient's consent or the 
authorization of an appropriate family member is clearly unethical. 

Uranium was also injected in eleven patients with terminal conditions at 
Massachusetts General Hospital in an experiment conducted jointly by the 
hospital and Oak Ridge National Laboratory from 1953 to 1957. ORNL's purpose 
was to obtain data for setting nuclear worker safety standards. A second purpose 
was to identify a radioisotope that would localize in brain tumors and destroy 
them when activated by a neutron beam. Although all but one of the patient- 
subjects had brain cancer, the limited purpose of the experiment— to establish 
whether uranium would localize sufficiently—meant that there was no expectation 
that patient-subjects might benefit medically from the uranium injections. 

The uranium doses in the Boston experiment were comparable to or higher 
than the one that caused measurable physical harm in the Rochester subject. 
Boston subjects were apparently subjected to brain biopsies, presumably solely 

268 



Chapter 5 

for scientific purposes. At least three Boston subjects showed kidney damage at 
the time of death. In one of these cases, a trauma victim who was found 
unconscious, the autopsy report recorded clinical evidence of some amount of 
kidney failure and pathological evidence of kidney damage due to the chemical 
toxicity of uranium. 

The only evidence available about what the Boston subjects were told 
comes from 1995 testimony of one of the investigators, Dr. William Sweet, who 
said it was his practice to "give a patient all the information we had ourselves." 
Presumably this would have included that the injections had no prospect of 
benefiting the patient. The Boston Project was an instance in which high doses 
were given to dying patients. Some of these patients were comatose or otherwise 
suffering from severe, irreversible central nervous system disease. Unless these 
patients, or the families of comatose or incompetent patients, understood that the 
injections were not for their benefit and still agreed to the injections, this 
experiment also was unethical. There was no justification for using dying 
patients as mere means to the ends of the investigators and the AEC. In at least 
one case, this disrespectful treatment clearly occurred. The trauma victim who 
arrived at the hospital unconscious was used as a subject despite the fact that his 
identity was never known. Presumably he was not accompanied by any family or 
friends who might have authorized such a use of his body. 

Only extraordinary circumstances can justify deception and the use of 
people as mere means by government officials and physicians in the conduct of 
research involving human subjects. In the case of the injection experiments, we 
see no reason that the laudable goals of the research could not have been pursued 
in a morally acceptable fashion. There is no reason to think that people would not 
have been willing to serve as subjects of radiation research for altruistic reasons, 
and indeed there is evidence of people writing to the AEC to volunteer 
themselves for just such efforts (see chapter 13). 

That people are not likely to live long enough to be harmed does not 
justify failing to respect them as people. Concerns about adverse public relations 
and legal liability do not justify deceiving subjects, their families, and the public. 
Insofar as basic moral principles were violated in the conduct of the injection 
experiments, the Manhattan Engineer District, the AEC, the responsible officials 
of these agencies, and the medical professionals responsible for the injections are 
accountable for the moral wrongs that were done. 



269 



ENDNOTES 



1. Don Mastick, telephone interview with Steve Klaidman (ACHRE), 23 July 1995 
(ACHRENo. IND-072395-F), 1. 

2. L. H. Hempelmann, Los Alamos Laboratory Health Division Leader, to J. R. 
Oppenheimer, Director, Los Alamos Laboratory, 16 August 1944 ("Health Hazards 
Related to Plutonium") (ACHRE No. DOE-051094-A-17), 1. 

3. J. R. Oppenheimer, Director, Los Alamos Laboratory, to L. H. Hempelmann, 
Los Alamos Laboratory Health Division Leader, 16 August 1944 ("Your memorandum 
of August 16, 1944") (ACHRE No. DOE-051094-A-17), 1. 

4. L. H. Hempelmann, Los Alamos Laboratory Health Division Leader, to J. R. 
Oppenheimer, Director of the Los Alamos Laboratory, 29 August 1944 ("Medical 
Research Program") (ACHRE No. DOE-051094-A-17), 1. 

5. Interview with Mastick, 23 July 1995, 1. 

6. Glenn Seaborg, head of Chemistry Section C-l of the Metallurgical 
Laboratory, to Robert Stone, Health Director of the Metallurgical Laboratory, 5 January 
1944 ("Physiological Hazards of Working with Plutonium") (ACHRE No. DOE-070194- 
A-3), 1. 

7. Ibid. 

8. Robert Stone, Health Director of the Metallurgical Laboratory, to Glenn 
Seaborg, Head of the Chemistry Section C-l of the Metallurgical Laboratory, 8 January 
1944 ("Hazards of Working with Plutonium") (ACHRE No. DOE-070194-A-4), 1. 

9. Seaborg suggested that several milligrams of the first shipment of plutonium 
from Oak Ridge be sent on to Dr. Hamilton at Berkeley. A minute amount of plutonium 
was sent to Hamilton, who began his studies on rats in February 1944. Next came more 
animal work at Chicago, focusing on the toxic effects of plutonium, as well as its 
distribution in various tissues. These studies showed that plutonium, like radium, was a 
"bone-seeking" element, the potential deadly consequences of which radium had already 
demonstrated. Furthermore, these studies demonstrated that in rats, plutonium distributed 
itself in bone in a potentially more hazardous way than radium. J. Newell Stannard, 
Radioactivity and Health: A History (Oak Ridge, Tenn.: Office of Scientific and 
Technical Information, 1988), 1424. 

10. Richard Rhodes, The Making of the Atomic Bomb (New York: Simon and 
Schuster, 1986), 547-548. 

11. Ibid., 560. 

12. The most likely route of worker exposure to plutonium would be inhalation. 
Hempelmann and others wrote to Oppenheimer in March 1945 that "the very important 
and difficult problem of detection of alpha active material in the lungs has been studied 
only at this project and here only on a very limited scale. This problem should be given 
much higher priority here and at other projects." L. H. Hempelmann, Los Alamos 
Laboratory Health Division Leader et al., to J. R. Oppenheimer, Director of the Los 
Alamos Laboratory, 15 March 1945 ("Medical Research of Manhattan District concerned 
with Plutonium") (ACHRE No. DOE-051094-A-17), 1. Inhalation experiments with 
rodents were undertaken, starting in 1944, at the University of California's Radiation 
Laboratory and the University of Chicago's Metallurgical Laboratory, although these 
studies did not result in extensive analysis of data until the latter half of the 1940s. W. H. 

270 



Langham and J. W. Healy, "Maximum Permissible Body Burdens and Concentrations of 
Plutonium: Biological Basis and History of Development," in Uranium - Plutonium - 
Transplutonic Elements, eds. H. C. Hodge et al. (New York: Springer- Verlag, 1973), 
576. Wright Langham wrote in 1945 that "if a limited amount of human tracer data are to 
form the basis of a method of diagnosing internal body contamination," it would be 
necessary "to assume that [plutonium] is metabolized in the same way regardless of the 
route of absorption or administration." Wright Langham, Los Alamos Laboratory Health 
Division, 28 July 1945 ("Report of Conference on Plutonium-May 14th and 15th") 
(ACHRE No. DOE-05 1 094-A-427), 29. Since the time of the experiments, it has become 
clearer that the deposition of plutonium in the body can differ in cases of chronic 
inhalation exposure versus other types of exposures. 

13. Langham and Healy, "Maximum Permissible Body Burdens and 
Concentrations of Plutonium," 576. 

14. L. H. Hempelmann, Los Alamos Laboratory Health Division Leader, to J. 
R. Oppenheimer, Director of the Los Alamos National Laboratory, 26 March 1945 
("Meeting of Chemistry Division and Medical Group") (ACHRE No. DOE-05 1094-A- 
17), 1. 

15. J. R. Oppenheimer, Director, Los Alamos Laboratory, to Colonel S. L. 
Warren, 29 March 1945 ("We are enclosing a record of discussions . . .") (ACHRE No. 
DOE-05 1094-A- 17), 1. 

16. Samuel Bassett [attr.], undated ("Excretion of Plutonium Administered 
Intravenously to Man. Rate of Excretion in Urine and Feces with Two Observations of 
Distribution in Tissues") (ACHRE No. DOE-121294-D-10), 29. 

17. Division of Biomedical and Environmental Research and Division of 
Inspection, AEC, 13 August 1974 ("Disclosure to Patients Injected with Plutonium") 
(ACHRE No. DOE-05 1094-A-586), 11. 

18. Ibid. 

19. Ibid., 10. 

20. Wright Langham, Los Alamos Laboratory Health Division, to Hymer 
Friedell, Executive Officer of the Manhattan District's Medical Section, 6 April 1945 
("Although we sent you directions for the 49 experiment along with the material . . .") 
(ACHRE No. DOE-120894-E-1), 1. 

2 1 . Wilson O. Edmonds, AEC Resident Investigator, to Jon D. Anderson, 
Director, Division of Inspection, 15 July 1974 ("Division of Biomedical and 
Environmental Research, Headquarters-Request to Locate Mr. Ebb Cade") (ACHRE 
No. DOE-05 1 094- A-6 11), 2. 

22. Undated document ("Experiment I on P. 49+4") (ACHRE No. DOE- 
113094-B-5), 1. 

23. The Committee uses names of subjects in this chapter only where the names 
were already a matter of public record. 

24. "Experiment I on P. 49+4," 1. 

25. Ibid. 

26. Hannah E. Silberstein, University of Rochester, to Wright Langham, Los 
Alamos Laboratory Health Division, 25 October 1945 ("This letter is to report the 
injection on the second human product subject, HP-2 . . .") (ACHRE No. DOE-121294- 
D-19), 1. 



271 



27. W. H. Weyzen, 25 April 1974 ("Visit with Dr. Joe Howland, Chapel Hill 
Holiday Inn, April 24, 1974") (ACHRE No. DOE-121294-D-18), 1. 

28. Hymer Friedell, interviewed by Steve Klaidman and Ron Neumann 
(ACHRE), transcript of audio recording, 23 August 1994 (ACHRE Research Project 
Series, Interview Program File, Targeted Interview Project), 49-50. 

29. "Experiment I on P. 49+4," 3. 

30. Ibid. 

31. Ibid., 2. 

32. Captain David Goldring, Medical Corps, to Wright Langham, Los Alamos 
Laboratory Health Division, 19 September 1945 ("Enclosed is a brief resume of E. C.'s 
medical history . . .") (ACHRE No. NARA-082294-A-47), 1. 

33. Karl Morgan, interviewed by Gil Whittemore and Miriam Bowling 
(ACHRE), transcript of audio recording, 6 January 1995 (ACHRE Research Project 
Series, Interview Program File, Targeted Interview Project), 147. 

34. Edmonds to Anderson, 15 July 1974, 3. 

35. "Experiment I on p. 49+4," 3. 

36. On 7 May 1945 Germany had surrendered to the Allied forces. The 
Manhattan Engineer District continued on with the building and testing of the first 
atomic bomb (the first test was scheduled for July of that year). 

37. Robert Stone, Health Director of the Metallurgical Laboratory, to Stafford 
Warren, Hymer Friedell et al., undated ("On Monday, May 14th, we plan to have an all 
day meeting dealing with plutonium . . .") (ACHRE No. N ARA-082294-A-5 1 ), 1 . 

38. Wright Langham, Los Alamos Laboratory Health Division, 28 July 1945 
("Report of Conference on Plutonium-May 14th and 15th") (ACHRE No. DOE-051094- 
A-427), 29. 

39. Colonel Hymer Friedell, Executive Officer of the Manhattan District's 
Medical Section, to L. H. Hempelmann, 1 1 April 1945 ("Enclosed is a protocol of the 
clinical experiment as we intend to carry it out . . .") (ACHRE No. DOE-121294-D-1), 1. 

40. Ibid. 

41. J. J. Nickson to R. S. Stone, 23 January 1946 ("Abstract of Monthly Report 
for January, 1946") (ACHRE No. DOE-051094-A), 1. 

42. E. R. Russell and J. J. Nickson, 2 October 1946 ("The Distribution and 
Excretion of Plutonium in Two Human Subjects") (ACHRE No. DOE-051094-A-370), 
1. 

43. Ibid. 

44. Ibid. 

45. Ibid., 2. 

46. Ibid. 

47. Nickson to Stone, 23 January 1946, 1. 

48. Sidney Marks, 3 May 1974 ("Interview with Dr. Leon Jacobson ... by 
Marks and Miazga at about 1:30 p.m. on 4/16/74") (ACHRE No. DOE-121294-D-15), 2. 

49. W. H. Weyzen, 25 April 1974 ("Visit with Edwin R. Russell, Savannah 
River Plant, April 23, 1974") (ACHRE No. 121294-D-17), 1. 

50. Andrew H. Dowdy, Director of AEC Rochester Project ("Proposed Research 
Program and Budget: July 1, 1947 - July 1, 1948") (ACHRE No. DOE-061794-B-16). 



272 



51. William F. Bale, Head of Special Problems Division, undated 
("Contributions of the Division of Special Problems to the Manhattan Project") (ACHRE 
No. DOE-113094-B), 1. 

52. L. H. Hempelmann and Wright H. Langham, undated ("Detailed Plan of 
'Product' Part of Rochester Experiment") (ACHRE No. 121294-D-2), 5. 

53. W. H. Langham. undated ("Revised Plan of 'Product' Part of Rochester 
Experiment") (ACHRE No. DOE-121294-D-3), 2. 

54. The choice not to use subjects suffering from malignant conditions is 
discussed retrospectively in a partial draft version of the 1950 report (probably written 
by Dr. Bassett). This discussion was not included in the final version of the report: 

The individuals chosen as subjects for the experiment 
were a miscellaneous group of male and female hospital 
patients for the most part with well established 
diagnoses. Preference was given to those who might 
reasonably gain from continued residence in the hospital 
for a month or more. . . . Patients with malignant disease 
were also omitted from the group on the grounds that 
their metabolism might be affected in an unknown 
manner. 
Bassett, "Excretion of Plutonium Administered Intravenously to Man," 2. 

55. Ibid. 

56. Wright Langham et al., 20 September 1950 ("Distribution and Excretion of 
Plutonium Administered Intravenously to Man") (ACHRE No. DOE-070194-A-18). 10. 

57. Wright Langham. 27 September 1957 ("Proceedings of the Second Annual 
Meeting on Bio- Assay and Analytical Chemistry: October 1 1 and 12, 1956 ~ Panel 
Discussion of Plutonium") (ACHRE No. DOE-120894-C-1), 80. 

58. W. H. Langham et al.. "The Los Alamos Scientific Laboratory's Experience 
with Plutonium in Man," Health Physics 8 (1962): 755. 

59. Addison's disease is an endocrine disease produced by adrenal gland failure. 
Today this disease is treated with steroid therapy that was developed in the 1940s and 
that was extremely expensive at the time of the experiments. HP-6, diagnosed with 
Addison's, was given steroid treatment as part of his care at the University of Rochester; 
he lived until 1984. 

Scleroderma is a collagen-vascular disease that can produce extreme pain, 
especially in the hands; can affect eating and swallowing if the esophagus is involved; 
and eventually leads to organ failure and death. Steroids are the treatment of choice 
today, but if this disease is not well controlled it can still be fatal. HP-8, who was 
diagnosed with scleroderma, lived until 1975. 

60. Bassett, "Excretion of Plutonium Administered Intravenously to Man," 2. 
Her provisional diagnosis according to this report was mild hepatitis and malnutrition. 
Ibid, 18. Her medical records indicate, however, that she had symptoms related to 
nutritional deficiencies, which appear to have been alleviated with proper diet and rest. 
Strong Memorial Hospital, 20 December 1945 ("Discharge Summary Form") (ACHRE 
No. DOE-051094-A-612), 1. 

61 . Wright Langham, Los Alamos Laboratory Health Division, to Samuel 
Bassett, Head of Metabolism Ward of Strong Memorial Hospital, 13 March 1946 ("Your 



273 



letter of February 27 regarding Hp 1 1 was startling, to say the least . . .") (ACHRE No. 
DOE-121294-D-4), 1. 

62. Document dated 17 April 1974 ("Comments on Meeting with Dr. 
Hempelmann on April 17, 1974") (ACHRE No. DOE-121294-D-16), 1. 

A 1955 letter from Dr. Hempelmann to the AEC's Division of Biology and 
Medicine (discussed in more detail in chapter 13) indicates Hempelmann's belief that, in 
general, patients could be easily deceived about the true research purpose of a medical 
intervention. In this letter, Hempelmann (who was by then professor of experimental 
radiology at Rochester) is proposing that researchers present themselves as life insurance 
agents to AEC workers as a ruse, in order to conceal the true purpose of follow-up 
medical examinations. He observes that it would be more difficult to deceive workers 
than it would be to mislead patients in a hospital: 

If you feel that the physical examinations are vital to the 
survey, then, perhaps, you could offer to pay the people 
to compensate them for the time and effort that they will 
spend on the part of your alleged survey for the 
insurance company. They would think they were getting 
something for nothing and might not feel that you were 
worried or they were seriously ill. I don't know if these 
ideas are helpful at all. It is more difficult to find an 
excuse for these individual workers than it is in the case 
of patients who were treated for something or other at a 
hospital. 
Louis Hempelmann, University of Rochester, to Charles Dunham, Director, AEC 
Division of Biology and Medicine, 2 June 1955 ("I did not have an opportunity . . ." ) 
(ACHRE No. DOE-092694-A), 1. 

63. Patricia Durbin, 9 December 1971 ("Report on Visit to Rochester") 
(ACHRE No. DOE-121294-D-I2), 1. 

64. Patricia Durbin, 10 December 1971 ("Dr. Wright Langham, of the Los 
Alamos Scientific Laboratory, was the biochemist who performed the Pu analyses . . .") 
(ACHRE No. DOE-121294-D-13), 1. 

65. "Comments on Meeting with Dr. Hempelmann on April 17, 1974," 1. 

66. Langham further instructed Rochester to look for the following longer-term 
"symptoms" in the examination of the patients: "Judging from the recent observations 
that Robley Evans has made, a generalized osteitis with rarefaction of the bones of the 
feet, the jaw and the heads of the long bones with coarsening of the trabeculae are the 
most likely symptoms." Wright Langham, Los Alamos Health Division, to Dr. Joe 
Howland, Chief of University of Rochester's Division of Medical Services, 2 October 
1950 ("I am very glad to hear that you will manage to get follow-ups on the two subjects 
. . .") (ACHRE No. DOE- 1 2 1 294-D- 1 1 ), 1 . 

67. Wright Langham, Los Alamos Laboratory Health Division, to Samuel 
Bassett, Head of Metabolism Ward of Strong Memorial Hospital, 25 October 1946 ("I 
just received a shipment of samples which I am sure are the ones you collected on HP-3 . 
. .") (ACHRE No. DOE-121294-D-5), 1. 

68. Samuel Bassett et al., 19 July 1948 ("The Excretion of Hexavalent Uranium 
Following Intravenous Administration II. Studies on Human Subjects") (ACHRE No. 
CON-030795-A-1), 8. 

274 



69. Andrew H. Dowdy, Director, Manhattan Department, University of 
Rochester, to the Area Engineer, Rochester Area, 22 October 1946 ("Clearance of 
Material for Seminar") (ACHRE No. DOE-120994-A-4), 1. 

70. Madison Square Area Engineer, 24 October 1946 ("Uranium Studies in 
Humans") (ACHRE No. DOE 120994-A-4), 1. 

71. Robert M. Fink ("Biological Studies with Polonium, Radium, and 
Plutonium") (ACHRE No. CON-030795-A-2), 122. 

72. K. Z. Morgan, Oak Ridge National Laboratory Health Physics Division, to 
R. S. Stone, Health Director of the Metallurgical Laboratory, 5 May 1945 ("Tolerance 
Values for Polonium Used at Clinton Laboratories") (ACHRE No. DOE-1 13094-B-6), 2. 

73. Fink, "Biological Studies with Polonium, Radium, and Plutonium," 122. 

74. A supplemental volume contains a chapter on the development of human 
subject research at the University of California at Berkeley and San Francisco. 

75. Hamilton's work with plutonium had begun in 1 942 with support from the 
Office of Scientific Research and Development; it was later supported by the Manhattan 
Engineer District. 

76. Joseph Hamilton, Radiation Laboratory of University of California at 
Berkeley, to Colonel E. B. Kelly, 28 August 1946 ("Summary of Research Program for 
Contract #W-7405-eng-48-A") (ACHRE No. DOE-1 13094-B-8), 2. 

77. Joseph Hamilton, 1 1 January 1945 ("Proposed Biochemical Program at 
University of California") (ACHRE No. IND-071395-A-14), 2. 

78. Ibid. 

79. At least eleven patients were injected with columbium (later renamed 
niobium) or zirconium between 1 948 and 1 950. These experiments appear to have been 
outside the federal effort. 

80. Joseph Hamilton, 10 May 1945 ("Progress Report for Month of May 1945") 
(ACHRE No. DOE-072694-B-65), 4. 

81. Joseph Hamilton, 14 June 1945 ("Progress Report for Month of June 1945") 
(ACHRE No. DOE-072694-B-66), 4. 

82. Ibid. 

83. Joseph G. Hamilton, Radiation Laboratory, University of California, 
Berkeley, to Captain Joe W. Howland, 23 April 1946 ("The problems of the research 
program . . .") (ACHRE No. DOE-120894-E-40), 2. 

84. Joseph G. Hamilton, Radiation Laboratory, University of California, 
Berkeley, to Robert Stone, Metallurgical Laboratory, 7 July 1945 ("I am writing 
concerning our experimental subject . . .") (ACHRE No. IND-071395-A), 1. 

85. Joe W. Howland, First Lieutenant. Medical Corps, to the Area Engineer, 
California Area, 12 July 1945 ("Status of Experimental Subject") (ACHRE No. IND- 
071395-A), 1. 

86. Kenneth Scott, interviewed by Sally Hughes (University of California Oral 
History Project), transcript of audio recording, 17 December 1979, 49-50. 

87. Ibid. 

88. Hamilton, "Progress Report for Month of June 1945," 4. 

89. Joseph Hamilton, 14 September 1945 ("Progress Report for Month of 
September 1945") (ACHRE No. DOE-072694-B-67), 5. 



275 



90. "Mercy Flight Brings Aussie Boy Here: Suffering From Rare Bone Ailment, 
He Seeks U.S. Treatment," San Francisco Examiner, 16 April 1946, 1. 

91. In addition to this injection, which was not performed for his benefit, the 
child also received superficial external radiation (five doses of 250 rad over five days) 
for palliation of his pain. A 1995 report written by an ad hoc committee at the University 
of California at San Francisco (UCSF) described the child's prognosis as having been 
"grave with palliation the only option." With that in mind, superficial irradiation was 
performed to reduce the patient's pain, not to destroy the sarcoma of the right leg. 
University of California at San Francisco, February 1995 ("Report of the USCF Ad Hoc 
Fact Finding Committee on World War II Human Radiation Experiments, February 1995, 
Appendix 19: Summary of the medical record of CAL-2") (ACHRE No. UCSF-022495- 
A-6), 3. 

92. UCSF, "Report of the USCF Ad Hoc Fact Finding Committee," 27. 

93. Loren J. Larson, Assistant in Orthopedic Surgery, University of California 
Hospital, 1 1 June 1946 ("To Whom It May Concern . . .") (ACHRE No. DOE-05I094-A- 
605), 2. 

94. Joseph Hamilton, Radiation Laboratory of the University of California at 
Berkeley, to Samuel K. Allison, 1 1 September 1945 ("Plans for Future Biological 
Research") (ACHRE No. IND-071395-A-2), 3. 

95. UCSF, "Report of the USCF Ad Hoc Fact Finding Committee," 27. 

96. Joseph Hamilton, Radiation Laboratory of the University of California at 
Berkeley, to John Fulton, Historical Library, Yale University Medical Center, 19 July 
1946 ("Inasmuch as both the Lawrence brothers are away at the moment, I thought it 
best that I answer your letter of July 16, 1946, to John . . .") (ACHRE No. DOE-122294- 
A-3), 1. 

97. T. S. Chapman, Chief of Operations Branch, Research Division, to Area 
Engineer, Berkeley Area, 30 December 1946 ("Human Experiments") (ACHRE No. 
DOE-112194-D-3), 1. 

98. Form dated 2 May 1946 ("Consent for Operation and/or Administration of 
Anaesthetic") (ACHRE No. DOE-051094-A-604), 1. 

99. Colonel K. D. Nichols, Corps of Engineers, to the Area Engineer, California 
Area, 24 December 1946 ("Administration of Radioactive Substances to Human 
Subjects") (ACHRE No. DOE-1 I3094-B-2), 1. This order followed a renewed request to 
the Army by Hamilton for additional plutonium, "to be used for certain human studies," 
and a further progress report on the injection of Albert Stevens. 

100. John L. Burling, AEC Legal Division, to Edwin E. Huddleson, AEC 
Deputy General Counsel, 7 March 1947 ("Clinical Testing.") (ACHRE No. DOE- 
051094-A-468), 1. 

101. Undated document ("CH-3607 . . . Excerpts from statements of reviewers") 
(ACHRE No. 113094-B-9), I. 

102. Ibid. 

103. Ibid. For discussion of classification levels, see chapter 13. 

104. "Off Project" probably refers to work not sponsored by the AEC. 

105. Major B. M. Brundage, Chief, Medical Division, to Declassification 
Section, 19 March 1947 ("Clearance of Technical Documents") (ACHRE No. DOE- 
113094-B-4), 1. 



276 



106. Hoylande D. Young, Argonne National Laboratory, to Charles A. Keller, 
25 July 1947 ("Declassification has been refused for the following reports . . .") (ACHRE 
No. NARA-050995-A-6), 1. 

107. Carroll Wilson, AEC General Manager, to Robert Stone, University of 
California Medical Center, 12 August 1947 ("Declassification of Biological and Medical 
Papers") (ACHRE No. DOE-061394-A-1 11), 1. 

108. Wright Langham, Los Alamos Laboratory Health Division, to Stafford 
Warren, University of California, 1 July 1950 ("Dr. Bassett has been here and helped me 
finish the semi-final draft of the Plutonium Report . . .") (ACHRE No. DOE-082294-B- 
72), 1. 

109. Wright Langham, Los Alamos Laboratory Health Division, to Joe W. 
Howland, Chief, Division of Medical Services, University of Rochester School of 
Medicine and Dentistry, 15 April 1950 ("1 am curious to hear your reaction to the names 
that I sent you . . .") (ACHRE No. DOE-082294-B-73), 1 . 

1 10. Andrew H. Dowdy, Director of the Manhattan Department, University of 
Rochester, to Norris E. Bradbarry [sic], Director of the Los Alamos Laboratory, 18 
February 1947 ("Dr. Wright Langham and Dr. Samuel Bassett were discussing with me 
today the technical details relative to writing the report . . .") (ACHRE No. DOE-121294- 
D-6), 1. 

111. Langham to Warren, 1 July 1950, 1. 

112. Walter D. Claus, Acting Chief, Biophysics Branch, AEC Division of 
Biology and Medicine, to Wright Langham, Los Alamos Laboratory Health Division, 30 
August 1950 ("You will be pleased to learn that Dr. Shields Warren has approved your 
report for CONFIDENTIAL classification . . .") (ACHRE No. DOE-082294-B-2), 1 . 

113. It is not clear when CH-3607, the report Dr. Friedell recommended for 
declassification in December 1946, was declassified. The copy retrieved by the 
Committee bears a 31 December 1946 declassification date and no indication of 
subsequent reclassification. Russell and Nickson, "The Distribution and Excretion of 
Plutonium in Two Human Subjects," 1 . In 1956 Dr. Langham made a brief reference to 
fifteen experimental subjects at an unclassified technical conference. Langham, 
"Proceedings of the Second Annual Meeting on Bio-Assay and Analytical Chemistry," 
80. In 1951, a report, based on Metallurgical Laboratory Memorandum MUC-ERR-209 
("Distribution and Excretion of Plutonium") appeared in a volume of the public 
Manhattan District research history. 

1 14. While the Wilson letters do not expressly reference the plutonium 
experiments, the context seems to leave little question that the policies stated in the 
letters were arrived at with the plutonium experiments in mind. In 1974, when asked 
what steps had been taken when the plutonium injections had been brought to the 
attention of the AEC, Shields Warren, who became director of the AEC's Division of 
Biology and Medicine in late 1947, said that it had been decided "that the rules [should 
be] properly drawn up by the ... Human Applications Isotope Committee ... so that 
use without full safeguards could not occur, and that . . . nothing of the sort could 
happen in the future." Shields Warren, interviewed by L. A. Miazga, Sidney Marks, and 
Walter Weyzen (AEC), transcript of audio recording, 9 April 1974 (ACHRE No. DOE- 
121294-D-14), 10. 

115. Carroll Wilson, AEC General Manager, to Stafford Warren, University of 
California, 30 April 1947 ("This is to inform you that the Commission is going ahead 



277 



with its plans to extend the medical research contracts . . .") (ACHRE No. DOE-051094- 
A-439), 2. 

1 16. Carroll Wilson, AEC General Manager, to Robert Stone, University of 
California Medical School, 5 November 1947 ("Your letter of September 18 regarding 
the declassification of biological and medical papers was read . . .") (ACHRE No. DOE- 
061395-A-112), 1. 

1 17. Dowdy, "Proposed Research Program and Budget: July 1, 1947-July 1, 
1948," 25. 

1 18. A December 1947 memorandum from Dr. Bassett recorded: 

In the autumn of 1 945 the Section on Human 
Metabolism was activated under your direction at the 
request of the Manhattan Engineer District to carry out 
certain tracer studies with long-lived isotopes. As you 
know, this program was discontinued in the spring of 
1 947 under a directive from the Atomic Energy 
Commission although we were instructed to keep the 
personnel of the section intact. When this directive was 
received, it was anticipated that follow-up studies on the 
several subjects of the original investigation would 
provide occupation for the employees of the section. 
Samuel H. Bassett, Section on Human Metabolism, University of Rochester, to William 
F. Bale, Head of Special Problems Division, University of Rochester, 2 December 1947 
("Proposal of Work for Metabolism Section") (ACHRE No. DOE-121294-D-7), 1. 
Dr. Bassett proposed an interim activity for the employees of the section— a 
study of certain aspects of radiation injury. This was approved by Bale until "the project 
research program of the Metabolism Section . . . with regard to tracer studies with heavy 
elements is clarified." William F. Bale, Head of Special Problems Division, University 
of Rochester, to Andrew H. Dowdy, Director of AEC's Rochester Project, 3 December 
1947 ("Program of Work for Metabolism Section") (ACHRE No. DOE-121294-D-8), 1. 

1 19. Gilbert Whittemore, 3 March 1995 ("Shields Warren Papers: A Cumulative 
Update of Excerpts") (ACHRE No. BU-030395-A-1), 3. 

120. Ibid. 

121. Interview with Warren, 9 April 1 974, 1 1 . 

122. Ibid. 

123. Ibid. According to Dr. Durbin, it is likely that the "other substances" 
referred to were probably phophorus 32 and strontium 89, which were used at the 
University of California between 1941 and 1944 as experimental tracers or for palliation 
of pain. Dr. Patricia Durbin, telephone interview with Miriam Bowling (ACHRE), 2 
August 1995 (ACHRE No. ACHRE-081095-A), 1. 

124. Undated note in medical record of CAL-A from "K..G.S." (Ken G. Scott 
[attr.]) ("The day after solution is injected . . .") (ACHRE No. UCLA-1 1 1094-A-l), 1. 

125. Telephone interview with Durbin, 2 August 1995, 1. 

126. Lori Hefner; telephone interview by John Kruger (ACHRE), 6 July 1995 
(ACHRE No. IND-070695-A), 1. 

127. Note in medical record of CAL-3 dated 1 8 July 1 947 ("Elmer Allen 
Chart") (ACHRE No. DOE-051094-A-615), 2. 



278 



128. Wilson to Warren, 30 April 1947, 2. 

129. UCSF, "Report of the USCF Ad Hoc Fact Finding Committee, Appendix 
20: Summaries of the medical record of CAL-3," 3-4. 

130. Ibid., 4. If the diagnosis was correct, surgical amputation would have been 
appropriate treatment at the time to completely excise the tumor. 

131. B. V. Low Beer et al., Radiation Laboratory, University of California, 
Berkeley, 15 March 1948 ("Comparative Deposition of Zr-95 in a Reticulo-Endothelial 
Tumor to Normal Tissues in a Human Patient") (ACHRE No. DOE- 101 194-B-4), 4. 

1 32. Ibid. The test dose was administered to the patient just twenty-four hours 
prior to the midthigh amputation of her leg for cancer. 

133. Shields Warren, Director of AEC's Division of Biology and Medicine, to 
Albert H. Holland, Jr., AEC Medical Adviser, 19 August 1948 ("Review of Document") 
(ACHRE No. DOE-101494-B), 1. 

134. Albert H. Holland, Jr., AEC Medical Adviser, to Shields Warren, Director 
of AEC's Division of Biology and Medicine, 9 August 1948 ("Review of Document") 
(ACHRE No. DOE-051094-A), I. 

135. Langham to Howland, 2 October 1950, 1. 

136. Wright Langham, Los Alamos Laboratory Health Division, to Albert H. 
Holland, AEC Director of Research and Medicine, 20 March 1950 ("It seems that I 
really fouled up regarding my promise to you at the Washington meeting . . .") (ACHRE 
No. NARA-082294-A-155), 1. 

137. L. H. Hempelmann. University of Rochester, to Charles Dunham, AEC 
Division of Biology and Medicine, 23 May 1953 ("There are several things on my mind 
that I would like to bring to your attention . . .") (ACHRE No. DOE-041495-A-1), 1. 

138. Walter D. Claus, Acting Chief of the Biophysics Branch, AEC Division of 
Biology and Medicine, to Charles L. Dunham, Chief, Medical Branch, 31 August 1950 
("Physical Examinations at Rochester") (ACHRE No. DOE-051094-A-471), 1. 

139. Interview with Warren, 9 April 1974, 8. 

140. Patricia W. Durbin, University of California, to William E. Lotz, AEC 
Division of Biology and Medicine, 13 September 1968 ("You will never guess what I 
found today . . .") (ACHRE No. DOE-051094-A-606), 1. 

141. Ibid. 

142. Ibid. 

143. Patricia Durbin, 1 972 ("Plutonium in Man: A New Look at the Old Data") 
(ACHRE No. DOE-051094-A-160), 469. 

144. R. E. Rowland, Argonne National Laboratory's Center for Human 
Radiobiology, 8 November 1973 ("Plutonium Studies at the Center for Human 
Radiobiology [CHR]") (ACHRE No. DOE-051094-A-608), 4. 

145. I. E. Kirch, Radiological and Environmental Research Division, Argonne 
National Laboratory, 13 June 1973 ("Center for Human Radiobiology: Radiologist's 
Report") (ACHRE No. DOE-051094-A-616), 1. The report records: "In the proximal 
portions of both humeri as well as in the adjacent acromions, there are some changes in 
the trabeculae which are consistent with findings in early radium deposition, but not yet 
completely specific. The mandible shows abnormal trabeculae, suggestive of damage 
due to radiation." 

Subclinical bone changes were also observed in a deceased subject who was 
exhumed for the Argonne study. The same radiologist summarized that an "abnormality 

279 



is present, namely, that there are very many very small very dense deposits on the 
surfaces of a number of the bones, and other such deposits in the soft tissues very close 
to the bone surfaces. This abnormality is attributed to the plutonium which has been 
administered during the subject's life. The radiographic pattern is unique." I. E. Kirch, 
Radiological and Environmental Research Division, Argonne National Laboratory, 15 
November 1974 ("Center for Human Radiobiology: Radiologist's Report") (ACHRE No. 
DOE-051094-A-618), 1. 

146. AEC Division of Biomedical and Environmental Research and Division of 
Inspection, 13 August 1974 ("Disclosure to Patients Injected With Plutonium") (ACHRE 
No. DOE-051094-A-586), 10. 

147. Ibid. 

148. Ibid. 

149. Ibid. 

150. Ibid. 

151. Robert E. Rowland, Argonne National Laboratory, to H. A. Schultz, 21. 
December 1972 ("Plutonium Cases") (ACHRE No. DOE-080795-A), 1. 

152. Robert E. Rowland to Miriam Bowling (ACHRE Staff), 7 August 1995 
("Attached is the memo of December 2 1 , 1972 . . .") (ACHRE No. DOE-080795-A), 1. 

153. Ibid. 

154. James L. Liverman to Miriam Bowling (ACHRE Staff), 20 August 1995 
("With your fax of August 9 was included . . .") (ACHRE No. IND-082095-A), 1. 

155. James L. Liverman, 29 April 1974 ("Briefing on Plutonium Project by Dr. 
James L. Liverman on April 29, 1974") (ACHRE No. DOE-051094-A-I96), 8. The 1971 
protocol referred to in this briefing had covered a follow-up project involving the radium 
dial painters. Although the procedures for the two follow-up studies were similar, the 
original conditions of exposure were quite different. The radium dial painters, unlike the 
plutonium-injection subjects, had not been chosen as subjects in a carefully planned 
medical experiment organized by the government. They had been exposed either 
occupationally as dial painters or therapeutically as patients receiving one of a variety of 
prewar radium treatments. 

156. Signed form dated 28 August 1974 ("Acknowledgement of Disclosure") 
(ACHRE No. DOE-051094-A-619), 1. 

157. Document dated 24 May 1974 ("Patients Injected with Plutonium [Draft 
Report of 5-24-74]") (ACHRE No. DOE-051094-A-607), 1. 

158. There is some evidence suggesting that at least one subject had a serious 
emotional reaction to the news, many years after the fact, that she had been injected with 
plutonium. This suggests that physicians involved in the follow-up had cause to be 
concerned about how at least some patients might respond to knowledge of the injections. 

159. K. F. Eckerman to Barry A. Berven, 7 January 1994 ("The Boston-Oak 
Ridge Uranium Study") (ACHRE No. DOE-051094-A-425), 1. 

160. John C. Gallimore, Associate Health Physicist, to Dr. W. H. Sweet, 
Massachusetts General Hospital, 22 March 1954 ("First Results of Uranium Distribution 
and Excretion Study") (ACHRE No. NARA-082294-A-35), 1. 

161. S. R. Bernard, "Maximum Permissible Amounts of Natural Uranium in the 
Body, Air and Drinking Water Based on Human Experimental Data," Health Physics 1 
(1958): 288-305. 



280 



162. According to the 1957 interim report on the study, it was Harold Hodge of 
the University of Rochester's Atomic Energy Project, who had been involved with the 
MED metabolism work at Rochester, who ultimately coordinated the beginning of the 
joint research. S. R. Bernard and E. G. Struxness, 4 June 1957 ("A Study of the 
Distribution and Excretion of Uranium in Man: An Interim Report") (ACHRE No. DOE- 
051094-A-369), 3. 

163. Bernard, "Maximum Permissible Amounts of Natural Uranium in the 
Body, Air and Drinking Water Based on Human Experimental Data," 296-298; Standards 
for Protection Against Radiation, 9 C.F.R. 20 (1958-1994). 

1 64. Robert Bernard, interviewed by J. Newell Stannard, transcript of audio 
recording, 17 April 1979 (ACHRE No. DOE-061794-A), 8. 

1 65. A continuation of the study at lower doses was proposed by the ORNL in 
1958; it is unclear whether this project went forward. Karl Morgan, Director of ORNL's 
Health Physics Division, to William Sweet, Massachusetts General Hospital, 16 July 
1958 ("Your help in our cooperative study on the distribution and excretion of uranium 
in man has been of great value to us . . .") (ACHRE No. DOE-021695-A-1 ), 1. A study 
similar to the one proposed by the ORNL in 1958 may have taken place during the mid- 
1960s at Argonne Cancer Research Hospital. K. Z. Morgan to W. H. Jordan, 3 
September 1963 ("Proposed Study of Distribution and Excretion of Enriched Uranium 
Administered to Man") (ACHRE No. DOE-051094-A-620), 1. 

166. Interview with Morgan, 6 January 1995, 118-119. 

1 67. Form dated 3 November 1 953 ("Application for Approval of Radioactive 
Isotopes: Massachusetts General Hospital") (ACHRE No. MGH-030395-A-1), 4. 

1 68. Leonard Atkins, M.D., 26 June 1 954 ("Necropsy No. : June 26, 1 954 at 

12:30 p.m.") (ACHRE No. DOE-050895-D-1), 6. 

169. Ibid., 1. 

170. Ibid. The "Anatomic Diagnoses" include "Uranium nephrosis, acute." 

171. Ibid., 5. 

172. Bernard and Struxness, "A Study of the Distribution and Excretion of 
Uranium in Man: An Interim Report," 6. 

173. Undated document ("#l Cloudy swelling of the epithelium of proximal 
and distal convoluted tubules . . .") (ACHRE No. DOE-050895-D-2), 1. The document 
records a diagnosis for the two additional patients as "acute nephrosis," and for subject 
VI, as "severe subacute nephrosis." 

174. Bernard and Struxness, "A Study of the Distribution and Excretion of 
Uranium in Man: An Interim Report," 4. 

175. William Sweet, interviewed by Gil Whittemore (ACHRE), transcript of 
audio recording, 8 April 1995 (ACHRE Research Project Series, Interview Program File, 
Targeted Interview Project), 46. 

176. By the end of the Committee's deliberations, MGH had not yet completed 
its search for the patient records of the Boston Project subjects. 

177. Chapman to Area Engineer, Berkeley Area, 30 December 1946, 1 . 

178. Weyzen, "Visit with Edwin R. Russell, Savannah River Plant, April 23, 
1974," 1. 

179. Interview with Warren, 9 April 1974, 1 1 . 

180. The relatively small population that has been exposed to substantial levels 
of plutonium precludes definitive conclusions about risks to humans, but the available 

281 



evidence clearly suggests that an epidemic of cancer of the magnitude that afflicted the 
radium dial painters from an earlier era has not occurred in plutonium workers. In the 
case of the radium dial painters, the unprotected handling of only a few pounds of 
radium led to hundreds of deaths; in contrast, studies of plutonium workers suggest that 
to date there is no definite excess mortality in this population. A forty-two-year follow- 
up of twenty-six Manhattan Project workers who worked with plutonium found a total of 
seven deaths, including three cancers (two lung and one osteogenic sarcoma), a 
substantially lower mortality rate than expected based on the U.S. population. The 
authors concluded that "the diseases and physical changes noted in these persons are 
characteristic of a male population in their 60s." G. L. Voelz and J. N. Lawrence, "A 42- 
year Medical Follow-up of Manhattan Project Plutonium Workers," Health Physics 61 
(1991): 181-190. A larger study of 15,727 LANL workers followed through 1990, some 
of whom had plutonium exposures, found no cause of death significantly elevated among 
the plutonium-exposed workers compared with unexposed workers, although there was a 
nonsignificant 78 percent elevation in lung cancer (a site that is directly exposed) and a 
single osteogenic sarcoma, a rare cancer that has been associated with plutonium 
exposure in animal studies. L. D. Wiggs, E. R. Johnson, C. A. Cox-DeVore and G. L. 
Voelz, "Mortality Through 1990 Among White Male Workers at the Los Alamos 
National Laboratory: Considering Exposures to Plutonium and Ionizing Radiation," 
Health Physics 67 (1994): 577-588. Another study of 5,413 workers at the Rocky Flats 
Nuclear Weapons Plant found elevated risks for various cancers comparing workers with 
body burdens of 2 nanocuries (nCi) or greater, but with wide uncertainties; no excesses 
were seen for bone or liver cancers. . The authors concluded that "these findings suggest 
that increased risks for several types of cancers cannot be ruled out at this time for 
individuals with plutonium body burdens of > 2 nCi. Plutonium-burdened individuals 
should continue to be studied in future years." G. S. Wilkinson et al., "Mortality Among 
Plutonium and Other Radiation Workers at a Plutonium Weapons Facility," American 
Journal of Epidemiology 125 (1987): 231-250. 



282 



6 

The AEC Program of 
Radioisotope Distribution 



At the dawn of the atomic age, many people hoped for dramatic 
advances in medicine, akin to the new miracle drug penicillin. Many of these 
hopes have been fulfilled. Radioisotopes have become remarkable tools in three 
areas. First, as their travels within the body are "traced," radioisotopes provide a 
map of the body's normal metabolic functions. Second, building on tracer 
research, diagnostic techniques distinguish between normal and abnormal 
functioning. Finally, radioisotopes, carried by the body's own processes to 
abnormal or cancerous cells, can deliver a lethal dose of radiation to those 
undesirable cells. By supplying radioisotopes and supporting their use, the 
Atomic Energy Commission (AEC) actively promoted the research needed to 
achieve this progress. 

The growth in the applications of radioisotopes involved thousands of 
experiments using radioisotopes. No feasible method was found to review in 
detail the vast number of individual radioisotope experiments in the Advisory 
Committee's database. This was due not only to the large number of experiments, 
but also to the scarcity of information about many of the individual experiments. 
Both consent and exact dose levels were often not discussed in published work; 
no federal repository was found that had collected records documenting these 
aspects of experiments. Given the decentralized structure of American medicine, 
it is not surprising that the Committee found that records on consent and exact 
dose, if they exist, would still be held at the local institutions conducting research 
or perhaps even in the private papers of physicians and scientists. Even when 



283 



Part II 

records were found at the local level, there was little documentation about 
consent. 

Thus, for the largest group of human radiation experiments, little 
documentation remains, and a meaningful examination of all such experiments 
was not possible. The Committee instead chose to focus its energies in two 
directions: examining the overall system of oversight created by the federal 
government and examining small subsets of radioisotope experiments that posed 
significant ethical issues. The first effort led to this chapter, an overview of the 
system created by the federal government to monitor radioisotope experiments. 
The second effort led to the case study on experiments involving children (chapter 
7) since those raised questions of both additional biological risk and justification 
for doing nontherapeutic research on minors. 

The AEC's isotope distribution program was faced with three essential 
ethical questions. The most immediate question concerned the allocation of a 
scarce resource. Given the likelihood that demand for radioisotopes would exceed 
supply, how should priorities be set? The question involved not simply the choice 
among competing proposals for "human uses" (including experimentation, 
treatment of disease, and diagnosis), but between human uses and other kinds of 
uses (for example, basic scientific research or industrial uses). 

Another immediate question was the safety with which this new material 
would be used. Since the government was actively promoting the use of 
radioactive isotopes, it had an obligation to ensure their safe use. Harm to 
patients, physicians, and others involved could arise from inexperienced and 
untrained users of radioisotopes. When properly used in trace amounts, 
radioisotopes posed risks well below those deemed acceptable in occupational 
settings. Balancing risks versus benefits—and seeking means to decrease risks and 
increase benefits as the field developed— was a major ethical obligation. 

Finally, there was the question of the relationship between researcher and 
subject— more precisely, the question of the authorization for use in humans and 
the process of disclosure and consent, if any, to be followed. These uses can be 
divided into (1) therapeutic/diagnostic uses, (2) therapeutic/diagnostic research, 
and (3) nontherapeutic research. 

As we shall see, great attention was paid initially to the question of 
resource allocation; but supply soon proved far greater than expected, and the 
need for this attention evaporated. The control of the risk posed by the use of 
AEC-provided radioisotopes was also a source of intense focus from the outset 
and remained so as the program grew. By contrast, notwithstanding the 1947 
declarations by AEC General Manager Carroll Wilson on the importance of 
consent, the matter of consent received only limited attention in the early years of 
the program. 



284 



Chapter 6 

ORIGINS OF THE AEC RADIOISOTOPE DISTRIBUTION 
PROGRAM IN THE MANHATTAN PROJECT 

The medical importance of radioisotopes was recognized before World 
War II but distribution was unregulated by government. The postwar program 
for distributing radioisotopes grew out of the part of the Manhattan Project that 
had developed the greatest technical expertise during the war: the Isotopes 
Division of the Research Division at Oak Ridge. 1 Production of useful 
radioisotopes required extensive planning for both their physical creation and 
their chemical separation from other materials. Plans to distribute radioisotopes 
to medical researchers outside the Manhattan Project were developed in the final 

year of the Project. 

In June 1946, the Manhattan Project publicly announced its program tor 
distributing radioactive isotopes. The new world of radioisotope research was to 
be shared with all. Most research would be unclassified. 2 An enthusiastic Science 
magazine reported: "Production of tracer and therapeutic radioisotopes has been 
heralded as one of the great peacetime contributions of the uranium 
chain-reacting pile. This use of the pile will unquestionably be rich in scientific, 
medical, and technological applications." 3 An article in the New York Times 
Magazine told readers that "properly chosen atoms can become a powerful and 
highly selective weapon for the destruction of certain types of cancer." Until 
now "the doctors and biologists have had to plea for samples of isotope material 
from their brothers in the cyclotron laboratories. ... Now the picture has changed 
in a revolutionary way. The Government has adapted one of the Oak Ridge 
uranium piles to the mass production of radioactive 'by-product material."' 

Extensive planning led up to this public announcement. Although the 
initial expectations were that basic research would precede extensive medical 
applications, from the very beginning officials planned for "clinical investigation 
with humans. In doing so, they recognized that the "administration to humans 
places extreme demands, both moral and legal, upon the specifications and timing 
of the radioisotope material supplied." 6 The recognition of special moral and 
legal aspects of human experimentation and reliance on the professional 
competency of those administering radioisotopes formed the cornerstones of the 
radioisotope distribution system's oversight of experiments. Significantly, 
however, the system was not designed to oversee consent from subjects prior to 
the administration of radioisotopes. 

Radioisotopes could not simply be ordered from the Manhattan Engineer 
District; each purchase had to be reviewed and approved. For human applications, 
each application was reviewed by a special group of experts: the Advisory 
Subcommittee on Human Applications of the Interim Advisory Committee on 
Isotope Distribution Policy of the Manhattan Project. According to one of the 
initial planners, "The chief reason for setting this group up as a separate entity 
from the Research group [another subcommittee] is that of medico-legal 

285 



Part II 

responsibility involved in the use or treatment of humans, experimentally or 
otherwise." 7 (When the AEC began its work, this subcommittee continued but 
was renamed the "Subcommittee on Human Applications of the Committee on 
Isotope Distribution of the AEC." In 1959 it was absorbed into the "Advisory 
Committee on Medical Uses of Isotopes." 8 In 1974, the AEC's responsibilities 
were transferred to the Nuclear Regulatory Commission.) Coupled with this 
review was a requirement that those wishing to purchase radioisotopes 
demonstrate the special competence required for working with radioactive 
materials. This mechanism for centralized, nationwide review was unusual at the 
time it was begun. 

The breadth of the subcommittee's purview can be seen in the range of 
proposals examined. Although the Advisory Committee is concerned primarily 
with medical research, the AEC subcommittee review extended well beyond this 
realm. Apparently, the subcommittee reviewed all proposed uses for 
radioisotopes that might result in the exposure of humans to radiation. These 
included, for example, using cobalt 60 in nails in wooden survey stakes (probably 
to assist in later locating them), sulfur 35 in firing underground coal mines, and 
yttrium 90 as a tracer in gasoline in simulated airplane crashes. 9 (Its jurisdiction 
was limited to by-product material, however, and did not extend to fissionable 
materials such as plutonium and uranium.) 

Soon after the Manhattan Project's public announcement, both the 
radioisotope distribution system and its oversight structure began operation. On 
June 28, 1946, the Subcommittee on Human Applications held its first meeting. 
Attending as members were Dr. Andrew Dowdy, chairman, and biophysicist 
Gioacchino Failla. Dowdy was director of the University of Rochester's 
Manhattan Project division, while Failla was a professor at Columbia University 
and consultant to the Metallurgical Laboratory in Chicago. Not attending was the 
third member of the subcommittee, Dr. Hymer Friedell, executive officer of the 
Manhattan Project's Medical Section. Attending as nonvoting secretary was Paul 
Aebersold, in charge of the production of radioisotopes at Oak Ridge (later to 
head the AEC's Isotopes Division). His efforts to promote the use of 
radioisotopes later earned him the nickname "Mr. Isotope." Also attending as 
advisers from Oak Ridge were W. E. Cohn, the author of the original 
memorandum proposing a system for distributing radioisotopes, and Karl 
Morgan, director of Health Physics at Oak Ridge, who would, over the years, 
become a leading figure in the establishment of occupational exposure limits for 
radioisotopes. 10 

Although the primary task of the subcommittee was to oversee safety, at 
the time, many expected a shortage of radioisotopes. Thus, much of this first 
meeting was taken up with a discussion of priorities for allocation." (As it 
happened, supply exceeded demand within one year.) It was in the context of this 
discussion of allocation, not a discussion of safety or ethics, that a system of 
local committees was suggested. Each local committee (also called "local isotope 

286 



Chapter 6 

committee" at this meeting) would include "(a) a physician well versed in the 
physiology and pathology of the blood forming organs; (b) a physician well 
versed in metabolism and metabolic disorders; (c) a competent biophysicist, 
radiologist, or radiation physiologist qualified in the techniques of 
radioisotopes."' 2 The main advantages of a system of local committees were ^ 
administrative efficiency and delegation of prioritization for scarce isotopes. 
The primary functions of each local isotope committee were coordination, 
allocation, and safety. Evidently no mention was made of overseeing subject 

consent. . 

At this first meeting, the subcommittee had before it no actual requests to 
evaluate. Even so, members did agree on the general principles on which they 
would deny a request: 

a. The requestors are not sufficiently qualified to 
guarantee a safe and trustworthy investigation. 

b. Insufficient knowledge exists to permit a safe 
application of the material in the proposed human 

14 

cases. 

There was no elaboration of crucial terms such as qualified, safe and trustworthy, 
insufficient knowledge, and safe application. Although no standards of adequate 
consent were mentioned, this degree of oversight was unusual in medical research 
during this time and even later. 

Although it had no specific requests before it, the subcommittee did 
consider the anticipated uses of some isotopes. The uses of some isotopes were 
apparently rejected, not only because of the hazards of radiation, but also because 
of chemical toxicity and the availability of less-hazardous alternatives. For 
others, specific limits were set. For example, the subcommittee was especially 
cautious concerning isotopes of strontium because it concentrated in bone, as did 
radium, which was known to be hazardous from the prewar experience of the dial 
painters. The subcommittee set a specific exposure limit: "the Sr 90 (and Y 90 
daughter) should not contribute in excess of 1% to the total rate of beta 

disintegration." 16 . • 

Such general guidelines have little effect unless a procedure is established 
for their implementation. At its first meeting, the subcommittee set out in detail 
the mechanism for its own future operation. What the subcommittee would be 
reviewing were requests to purchase isotopes for any use in human beings. Only 
after the subcommittee approved a request would the isotope be sold and shipped 
to the researcher. The need for speed in responding to requests for human uses 

was recognized. 17 

Details of the procedure for purchasing isotopes were disseminated to 
potential users through a brochure issued in October 1946 by the Isotopes Branch 
at Oak Ridge. 18 Most of the brochure concerned the paperwork, which, among 



287 



Part II 

other things, ensured that the Subcommittee on Human Applications would 
actually be notified of all applications for human use. 

The last stage of the purchase procedure indicates the underlying concern 
with legal liability. Although Manhattan Project approval was required, the 
actual purchase was from the private contractor-operator of the Clinton 
Laboratories (later designated the Oak Ridge National Laboratory) in Oak Ridge, 
at that time Monsanto Chemical Company. The final purchase agreement 
contained a clause relieving both the government and the private contractor from 
any responsibility for "injury to persons or other living material or for any 
damage to property in the handling or application of this material. . . ."' 9 The 
Manhattan Project also required the purchaser to file with the Isotopes Office a 
statement required by section 505(i) of the Federal Food, Drug, and Cosmetic 
Act. However, the Advisory Committee found no evidence of direct involvement 
by the FDA at that time in the planning or operation of the radioisotope 
distribution program. 20 

By October 1 946, the distribution program was well under way: 2 1 7 
requests had been received. Of these, 21 1 had been approved. Human use requests 
totaled 94, of which 90 had been approved. 21 

THE AEC ASSUMES RESPONSIBILITY FOR 
RADIOISOTOPE DISTRIBUTION 

When the AEC took over responsibility for the program on January 1, 
1947, the structure of the radioisotopes distribution system remained intact. The 
Subcommittee on Allocation and the Subcommittee on Human Applications 
remained as standing subcommittees of the Interim Committee on Isotopes 
Distribution Policy, which became known as the Advisory Committee on Isotope 
Distribution Policy. The forms developed by the Manhattan Project were reissued 
as AEC forms without substantial revision. The system of application from 
private users, review, purchase, and distribution continued to operate. 

At first, there appears to have been some confusion over the responsibility 
of the AEC for its own research program and for its program to distribute 
radioisotopes to private researchers. As discussed in chapter 1, two 1947 letters 
from AEC General Manager Carroll Wilson describe strong consent 
requirements. The April letter to Stafford Warren was expressly directed to the 
terms on which research conducted by AEC contractors (including universities) 
would be approved. The November letter was sent to Robert Stone. As we have 
discussed, those clear statements to contract researchers do not seem to have been 
made to those applying for radioisotopes. This confusion about the relationship 
between contract research and isotope distribution is discussed in a September 26, 
1947, memorandum from J. C. Franklin, manager of Oak Ridge Operations, to 
Carroll Wilson. 22 Other correspondence also indicates confusion over whether the 
AEC's own labs (which were themselves often operated by contractors) were to 

288 



Chapter 6 

follow the procedures for the radioisotope distribution program, which would 
have placed their human use requests before the Subcommittee on Human 

Applications. 

Initially, requests for by-product materials from within the AEC used a 
form that did not specify whether the radioisotope was to be used on humans. 23 
By August 1949, Shields Warren, director of the AEC's Division of Biology and 
Medicine, had directed that human use by AEC laboratories be subject to review 
by the Subcommittee on Human Applications. 24 However, when regulations 
governing radioisotope distribution were first promulgated, AEC-owned facilities 
were specifically exempted from all such regulations. 25 Warren's goal was 
achieved instead by a memorandum from Carroll Wilson in July 1950. This 
memorandum discontinued use of the earlier form and directed that all requests 
use the same form used by outside purchasers, which directed human use requests 
to the Subcommittee on Human Applications. 26 

The AEC Subcommittee on Human Applications 

At the heart of overseeing the expansion of the use of radioisotopes was 
the Subcommittee on Human Applications of the AEC's Advisory Committee on 
Isotope Distribution. Applications had to have been approved by a local isotope 
committee before even being considered by the subcommittee. 27 The 
subcommittee itself conducted most of its reviews by mail. Unfortunately, only 
fragmentary records of this correspondence have been found. 

The subcommittee formally met only once a year to discuss general issues. 
By its second meeting, in March 1948, membership had grown to four. Dowdy 
was no longer on the subcommittee; Joseph Hamilton and A. H. Holland had been 
added. Hamilton was, as described in chapter 5, a physician-investigator with the 
University of California's Radiation Laboratory in Berkeley. Holland was a 
physician-investigator who became medical director at the AEC's Oak Ridge 
Operations in late 1947. (As we shall see in chapter 13, he played a central role 
in the question of the declassification of secret experiments.) As the 
subcommittee continued to "examine each case on its own merits" it began to 
generate principles for "general guidance." In doing so, it began to categorize 
experiments, apparently according to the degree of hazard posed. 

One category was tracer studies in "normal adult humans" using beta and 
gamma emitters with half-lives of twenty days or fewer. Applications needed to 
include information on biodistribution and biological half-life of the radioisotope, 
based on either animal studies or references to the literature. 28 

A second category was studies in "normal children." In 1948 the 
subcommittee did not issue detailed guidelines, but instead simply stated that such 
applications "would be given special scrutiny by the Subcommittee on Human 
Applications." 29 In 1949 it issued more detailed guidelines, which indicate that 
the concern was with minimizing risk, not requiring or overseeing consent: 

289 



Part II 

In general the use of radioisotopes in normal 
children should be discouraged. However, the 
Subcommittee will consider proposals for use in 
important researches, provided the problem cannot 
be studied properly by other methods and provided 
the radiation dosage level in any tissue is low 
enough to be considered harmless. It should be 
noted that in general the amount of radioactive 
material per kilogram of body weight must be 
smaller in children than that required for similar 
studies in adults. 30 

Coupled with the children's category in 1 949 were studies on pregnant women: 
"The use of radioactive materials in all normal pregnancies should be directly 
discouraged where no therapeutic benefit is to be derived." 31 Although not 
specifically mentioned in the minutes, such a policy may, like research in "normal 
children," have been waived for "important researches" that could not otherwise 
be undertaken. 

One recurring difficulty was the problem of deciding when an application 
could be considered "safe." There was no simple, mechanical process for making 
such a judgment. This can be seen in the subcommittee's detailed consideration of 
an application for phosphorus 32 to be used in a blood volume study of children. 
The amount of radioactivity proposed ranged from 1/4 to 1 microcurie per 
kilogram of body weight. Initially, three of the four members approved the 
application and the allocation was made. However, the fourth member, replying 
late, reopened the question. Following reconsideration by the entire 
subcommittee, three of the four members concluded the original application for 
use on children should be turned down and the investigator asked to revise the 
application to "state the importance of making the study in children" and to keep 
the amount of activity less than 1/2 microcurie per kilogram. 32 The reduction in 
allowable amount of activity illustrates both the diligence with which the 
subcommittee pursued its task and the inherent difficulties in making judgments 
about what constituted "safe" practices in a rapidly developing field of research. 

The subcommittee's task was made a bit easier when considering 
applications with adults, where it could draw upon occupational guidelines. 
Requests for "long-lived radioisotopes" were placed in a third category, defined 
as those with a biological half-life greater than twenty days. In contrast with 
experiments on children, here the subcommittee was willing to set a general dose 
limit: "The dosage in the critical tissue should be such as to conform to the 
limitations stated by the National Committee on Radiation Protection." 33 (The 
NCRP, now the National Council on Radiation Protection and Measurements, is 
an independent organization that publishes occupational radiation protection 
guidelines based on expert reviews of contemporary scientific knowledge.) As 

290 



Chapter 6 

with children, such applications "must be reviewed separately." The 
subcommittee did not wish this limit to be ironclad: "In special cases, however, 
the Subcommittee on Human Applications may permit the use of radioisotopes in 
higher dosages." 34 At this point the subcommittee appears to have been 
establishing general principles; no specific radioisotopes or particular research 
proposals are mentioned. 

A final category was applications using radioisotopes with long half-lives 
in patients with short life expectancies. The term moribund was used in 
correspondence by Paul Aebersold prior to the second meeting of the 
subcommittee in March 1948. He wrote to the subcommittee members explaining 
that the item was on the agenda because requests for such work had been 
received. He referred to a written request from a physician at Massachusetts 
General Hospital to use calcium 45 and an oral request from a staff member at 
Presbyterian Hospital in Chicago to use testosterone labeled with carbon 14. 
Aebersold did not provide any details as to the purposes of the proposed research. 
The issue was what policy to adopt when the patients were predicted not to live 
long enough for long-term hazards to develop. Aebersold told the subcommittee 
that "this office feels that such requests should be allowed if a satisfactory 
mechanism for determining the 'moribundness' of the patients in question is 
established. We believe that this question should be decided by a group of doctors 
and written evidence signed by the group filed with the Isotopes Division prior to 
use of the material." 35 

The subcommittee had no objection to the basic principle of applying 
larger doses to patients with short life expectancies, but its language was more 
oblique than Aebersold's letter: "It is recognized that there may be instances in 
which the disease from which the patient is suffering permits the administration 
of larger doses for investigative purposes." 36 Safeguards were to be provided by 
reliance on the judgment of local physicians, not a precise definition of moribund. 
Indeed, the subcommittee did not even use the term. Applications would be 
approved providing: 

1. Full responsibility for conduct of the work is 
assumed by a special committee of at least three 
competent physicians in the institutions in which 
the work is to be done. This will not necessarily be 
the local Radioisotope Committee. 

2. The subject has given his consent to the 
procedure. 

3. There is no reasonable likelihood of producing 
manifest injury by the radioisotope to be 
employed. 37 

No further explanation was given of how the second requirement, giving consent, 

291 



Part II 

would be fulfilled by a "moribund" patient, nor was additional guidance provided 
to clarify the third criterion. 

One instance in which this policy was applied took place at the Walter E. 
Fernald State School in Massachusetts (see chapter 7). Correspondence between 
the researchers and the AEC indicates that the AEC allowed the administration of 
50 microcuries of calcium 45 (fifty times the amount the AEC allowed the 
researchers to administer to other subjects in the study) to a ten-year-old patient 
with a life expectancy of a few months, suffering from Hurler-Hunter syndrome 
(a degenerative disease of the nervous system). In applying for the radioisotope, 
Dr. Clemens Benda, the researcher, noted that "permission for the use of higher 
doses administered to moribund patients has been granted by you to other 
investigators . . . ." 38 This subject was part of a study of calcium metabolism 
approved by the superintendent of the school. Students had been described as 
"voluntarily participating" in a letter sent earlier to the parents asking if they 
objected, but that did not mention the use of radioactive tracers. Lack of response 
from a parent was presumed to be approval. 39 The subject with Hurler-Hunter 
syndrome was found to have abnormal calcium metabolism, but died before the 
study could be completed. 40 

Even as it developed procedures for unusual cases, the subcommittee 
recognized that some existing uses were becoming routine and did not need to be 
continuously reviewed by the subcommittee itself. The subcommittee delegated 
the review of such requests to the Isotopes Division, setting out the criteria to be 
applied: 

Such applications should be justified by: 

a) A commensurate increase in patient load. 

b) An expanded research program. 

c) Provision of adequate storage and handling facilities. 

d) Assurance that personnel protection and supervision are 
adequate for the larger amounts requested. 41 

An additional simplification occurred with the introduction in 1951 of "general 
authorizations," which delegated more authority to the local radioisotope 
committees of approved institutions. 42 These authorizations enabled research 
institutions to obtain some radioisotopes for approved purposes after filing a 
single application each year, therefore eliminating the need to file a separate 
application for each radioisotope order. As such, they also reduced the oversight 
of the AEC's Subcommittee on Human Applications, as each order was no longer 
reviewed individually. However, at first the general authorizations did not apply 
to human use, and when they were expanded to human use in 1952, they were 
limited to certain radioisotopes for clinical use and excluded radioisotopes in 
cancer research, therapy, and diagnosis. 43 

Both the AEC and the subcommittee reacted strongly when proper 

292 



Chapter 6 

bureaucratic procedures were not followed. One example was a private industrial 
lab that used iodine 131 for a human study that had not been properly reviewed. 
Even though no one was harmed, the AEC threatened to suspend shipments of all 
radioisotopes, not just iodine 131; such action would have put the company out of 
business. 44 Aebersold, at the direction of the subcommittee, notified the company 
president that while the incident "did not lead to any unfortunate results from the 
standpoint of radiation hazard ... a recurrence of this type of violation should 
result in cessation of all shipment of radioactive materials to Tracerlab, Inc." 45 
For his part, the company president reacted by notifying employees that such 
action would be grounds for automatic dismissal. 46 

Thus, as it proceeded in its work of evaluating individual applications, the 
subcommittee developed more general principles such as categories of human 
uses based upon risk and updating of criteria based upon developing knowledge. 
The goal, as the AEC's director of research, K. S. Pitzer, stated in 1950, was "to 
make radioisotopes as nearly as possible ordinary items of commerce in the 
technical world." 47 For example, cancer researchers initially received 
radioisotopes at no charge. 48 This free program was changed to an 80 percent 
discount program in 1952 49 and ended in July 1961. 50 

AEC Regulations and Published Guidelines 

An important step toward making the use of radioisotopes a component of 
medical practice routine was formally enacting regulations governing the use of 
isotopes. The first regulations were enacted in 1951. 5 ' These early regulations 
essentially promulgated facility and personnel requirements without establishing 
dose limits or mentioning the consent requirement established in 1949 for 
administering larger doses to very sick patients. Throughout the 1950s, changes in 
the regulations dealt with administrative procedures. Other concerns about 
radioisotope use, such as consent requirements, were disseminated through 
circulars, brochures, and guides of the Isotopes Division. In 1948 the circular 
describing medical applications was only three pages long; by 1956 it had been 
replaced by a twenty-four-page guide that provided detailed requirements for 
many different applications of isotopes. 52 

This greater precision can be seen, for example, in the guidelines for 
terminal patients. By the time of the 1956 guide, the use of radioisotopes with 
half-lives greater than thirty days ordinarily would not be permitted without prior 
animal studies establishing metabolic properties, unless patients had a short life 
expectancy. The judgment of local physicians was now to be guided by a more 
exact definition: exceptions would be "limited to patients suffering from diseased 
conditions of such a nature (life expectancy of one year or less) that there is no 
reasonable probability of the radioactivity employed producing manifest injury." 53 
However, while a more precise definition of terminal was now provided, there 
was no longer explicit mention of a specific requirement for consent from these 

293 



Part II 

patient subjects, as had been made earlier. 

Consent was required, though, in the section of the 1956 guide on the "use 
of radioisotopes in normal subjects for experimental purposes." (Presumably, 
"normal" here means "healthy.") This section included the earlier provisions that 
the tracer dose not exceed the permissible body burden and that such experiments 
not normally be conducted on infants or pregnant women. It also, however, 
included a new provision that such experiments were to be limited to "volunteers 
to whom the intent of the study and the effects of radiation have been outlined." 54 
The term volunteer would seem to imply a requirement that consent be obtained 
following a disclosure of information to potential subjects. The disclosure 
requirement dops not include, however, all of the elements of information that 
today are included in duties to obtain informed consent. 

This 1956 consent requirement now governed all radioisotope 
experiments in normal subjects, a substantial expansion of the earlier requirement 
of consent only from terminal patients receiving larger-than-usual doses. It also 
explicitly required that both the purpose and effects of radiation be explained. It 
is unclear whether the failure to mention consent in the section on terminal 
patients was an oversight in drafting or a deliberate distinction between patients 
and "normal" subjects. The Advisory Committee has not found documents 
revealing the history of this provision, nor any explanation of the choice to limit 
the broad consent requirement to "normal" subjects. 55 

This broad requirement continued over the next decade as part of AEC 
policy. In 1965, the AEC published the "Guide for the Preparation of Applications 
for the Medical Use of Radioisotopes." The guide described the application 
process and specific policies for the "Non-Routine Medical Uses of Byproduct 
Material." This policy statement reiterated the exclusion of pregnant women and 
required that subject characteristics and selection criteria be clearly delineated in 
the application. Another requirement stated that applications should include 
"confirmation that consent of human subjects, or their representatives, will be 
obtained to participate in the investigation except where this is not feasible or in 
the investigator's professional judgment, is contrary to the best interests of the 
subjects." 56 

During the 1960s, the entire system of oversight of radioisotope research 
began to change as the Food and Drug Administration began developing a more 
active role in supervising the development of radiopharmaceuticals. 57 The 
regulatory history of this shift in authority is complex and beyond the scope of 
this report. Suffice it to say that by the mid-1960s the regulation of radioisotope 
research was beginning to merge with the regulation of pharmaceutical research 
in general. 



294 



Chapter 6 
LOCAL OVERSIGHT: RADIOISOTOPE COMMITTEES 

From its inception, the AEC distribution system required each local 
institution to establish a "local radioisotope committee," later termed a "medical 
isotopes committee." Initially, the primary purpose was to simplify the allocation 
process by having local institutions establish their own priorities before applying 
to the AEC. 5X Soon after the program began, supply increased and no dramatic 
new uses developed, so allocation was no longer a major issue. These local 
committees also took on responsibilities for physical safety, usually working 
closely with radiation safety offices. By October 1949 this requirement also 
applied to the AEC's national labs. 59 When "general authorizations" were issued 
in 1951, granting broader discretion to qualifying local institutions, local isotope 
committees assumed greater responsibility. 60 

By 1956, the functions of the local radioisotope committees included 
reviewing applications, prescribing any special precautions, reviewing reports 
from their radiological safety officers, recommending remedial action when 
safety rules were not observed, and keeping records of their own activities. The 
basic focus on radiological safety remained, although in reviewing applications a 
local medical isotopes committee could also consider "other factors which the 
[local medical isotopes] Committee may wish to establish for medical use of these 
materials." 61 Exactly what these "other factors" might be was not specified. 

These local committees together reviewed thousands of applications over 
the next decades. Although not federal agencies, they were required by the AEC, 
and their proper functioning was an important part of the oversight system 
envisioned by the AEC. To fully assess whether this system fulfilled its goals 
would be an enormous task, requiring the retrieval and examination of thousands 
of local records. However, to make a preliminary assessment of whether the 
system as a whole generally appeared to function as planned, the Advisory 
Committee did examine the records of several public and private institutions: the 
Veterans Administration (VA), the University of Chicago, the University of 
Michigan, and Massachusetts General Hospital (MGH). 62 Doing so provided us 
with an understanding of the techniques of risk management used at the local 
level on a day-to-day basis. We specifically examined whether local radioisotope 
committees in fact were established as directed and what techniques they 
developed to monitor consent and ensure safety. 

Establishment of Local Isotope Committees 

Overall, the federal requirement seems to have been an effective means of 
instituting a reasonably uniform structure across the nation for local radioisotope 
committees. The AEC's requirements for local committees were followed in all 
the institutions studied, and there is no reason for believing they were exceptional. 
One local radioisotope committee, that of Massachusetts General Hospital, was 

295 



Part II 

established in May 1946, prior to the AEC requirement. 63 The other institutions 
established a local radioisotope committee when required to do so by the AEC. 

Local committees also could have broader tasks than those required by the 
AEC. For example, the Radiation Policy Committee at the University of Michigan 
regulated all radioactive substances used on campus, not just those purchased 
from the AEC. These included reactor products, transuranic elements, and 
external sources of radiation. 64 

The Veterans Administration added another level of oversight in the form 
of a systemwide Central Advisory Committee. 65 In 1947 the VA embarked on a 
radioisotope research program that would take place within newly established 
radiation units in the hospitals that would be the recipients of AEC-supplied 
isotopes. 66 Among early research projects were the treatment of toxic goiter and 
hyperthyroidism with iodine 131 and treatment of polycythemia rubra vera 
(overproduction of red blood cells) with phosphorus 32 at Los Angeles, 
radioactive iron tracers of erythrocytes at Framingham, and sodium 24 circulatory 
tracers in Minneapolis. 67 By the end of 1948, radioisotope units had been 
established in eight VA hospitals. 68 Each of the eight was asked to establish a 
radioisotope committee (as required by the AEC) to be appointed by the Dean's 
Committee of each hospital, while representatives from affiliated universities 
agreed to serve as consultants in the various units. 

Local Monitoring of Consent 

Generally, although local institutions created clear procedures to monitor 
safety, these local radioisotope committees did not establish procedures to 
monitor or require consent. 69 (See part I for discussion of the broader historical 
context of consent in medical research.) The standard application form to the 
Massachusetts General Hospital committee, as of 1953, had no place to describe 
an informed consent procedure. This does not, of course, resolve the question of 
whether consent was given. According to one prominent neurosurgeon 
interviewed by the Advisory Committee staff, William Sweet, at that time, in the 
case of brain tumor patients, oral consent was obtained from both the patient and, 
since mental competency could later be an issue, the next of kin. 70 

Similarly, no mention of the 1947 AEC requirements stated in General 
Manager Wilson's letters is contained in the advice Shields Warren gave in 1948 
to the VA, even though Warren, as director of the AEC's Division of Biology and 
Medicine, must have known of discussions about consent requirements. An issue 
that arose before the VA Central Advisory Committee was whether patient- 
subjects should sign release slips. This issue posed the question of whether the 
radioisotope units in the VA hospitals were treatment wards or clinical research 
laboratories. If wards, patients need not sign consent forms, for they were simply 
being treated in the normal course of an illness. Shields Warren agreed with this 
presumption and felt that there was no need for the patients to sign release slips: 

296 



Chapter 6 

"The proper use of radioisotopes in medical practice is encompassed in the 
normal responsibilities of the individual and of the institution or hospital." 71 In 
addition, he felt that the practice would draw "undue and unwholesome attention 
to the use of radioisotopes." 72 

Movement toward more formal consent requirements gradually arose at 
the local level. In 1956 the University of Michigan's own Human Use 
Subcommittee directed that in an experiment using sodium 22 and potassium 42, 
each "volunteer would be required to sign a release indicating that he has full 
knowledge of his being subjected to a radiation exposure." Since the local 
committee was concerned about what it termed "unnecessary" radiation, the 
volunteers presumably were healthy subjects not otherwise receiving radiation for 
treatment or diagnosis. The committee appended a recommended "release" form 
to its minutes: 

I, the undersigned, hereby assert that I am 

voluntarily taking an injection of at a dose 

level which I understand to be considered within 
accepted permissible dose limits by the University 
of Michigan Radio-isotope Human Use Sub- 
Committee. 73 

By 1967, the Michigan subcommittee also required that the subject 
explain the experiment to the researcher to clarify any doubts or 
misunderstandings. The following statement was incorporated into all 
applications to the university's Human Use Subcommittee: 

The opinion of the Committee is that INFORMED 
CONSENT is the legal way of describing a 
"meeting of the minds" in a contract. In this 
situation it means that the subject clearly 
understands what the experiment is, what the 
potential risks are, and has agreed, and without 
pressure of any kind, elected to participate. The best 
way to ascertain that the consent is informed, is to 
have the subject explain back fully to the 
interviewer, exactly what he thinks he is submitting 
to and what he believes the risks might be. This 
facilitates clarification of any doubts, spoken or 
unspoken. The content of this discussion will be 
recorded in detail below. 74 

During the 1960s, as explained in chapter 3, concern was growing over the 
adequacy of consent from subjects. Although not intended by the AEC to 

297 



Part II 

monitor the obtaining of consent from subjects, over the years the local 
radioisotope committees may have come to take on this task. By requiring such 
local committees, the AEC had, probably unwittingly, provided an institutional 
structure that allowed later concern for informed consent to be implemented at the 
local level. 

Local Monitoring of Risk 

This local and informal approach to consent is in sharp contrast to the 
detail and documentation with which risk was assessed. As discussed earlier, 
monitoring risk was the major task of the AEC's Subcommittee on Human 
Applications. The local committees mirrored this task, examining in detail the 
various experiments presented to them. As with the AEC subcommittee, local 
committees developed a variety of methods, none especially surprising, to ensure 
what they believed was adequate safety. 75 

The basic dilemma facing local committees was to allow exploration of 
new territory while attempting to guard against hazards that, precisely because 
new territory was being explored, were not totally predictable. This dilemma was 
apparent at the local level, as well as at the level of the AEC's Subcommittee on 
Human Applications. For example, in the minutes of the Massachusetts General 
Hospital local radioisotope committee in 1955, during a discussion of new and 
experimental radiotherapies for patients, one member of the committee declared 
that the safety of the patient was of "paramount importance." 76 Yet, other 
members suggested that a risk-benefit analysis needed to be an integral 
component of such a policy decision. The committee as a whole concluded 
merely that it was a complicated issue and that "it is not wise in any way to inhibit 
investigators with ideas, and yet the safety of the patient must come first." 77 

Requiring prior animal studies was a basic method of assessing risk. For 
example, the twenty-two studies reviewed by the University of Chicago's local 
committee in 1953 included multiple therapeutic and tracer studies involving 
brain tumors, the thyroid gland, metastatic masses, and tissue differentiation. 
Those the Chicago committee viewed as involving any risk to the patient were 
preceded by extensive animal studies. 78 

Animal studies were usually tailored to each project and also raised the 
question of the differences between how humans and animals might respond to a 
particular radioisotope. A more uniform standard directly applicable to humans 
was the system of dose limits established by the National Committee on Radiation 
Protection for occupational purposes: the maximum permissible dose for each 
isotope. In addition, although no national system existed for reporting their 
decisions, local committees drew upon their knowledge of what had been 
approved at other institutions. 79 At least one local committee issued its own dose 
limits. The Massachusetts General Hospital local committee in 1949 issued a 
seven-point policy on human use of beta- and gamma-emitting radioisotopes. 80 

298 



Chapter 6 

By 1956, the Michigan committee provided explicit limits for exposure of 
volunteers/ 1 

At other times, the condition of subjects who were patients was accepted 
as justification for higher doses. For example, in 1953 the Chicago committee 
approved a tracer study using mercury 203 "to study uptake by malignant renal 
tissue." Although admitted to be unusual, it was approved as potentially 
efficacious in patients suffering hypernephroma (a kidney cancer). Total dose 
would not exceed 10 milligrams of ionic mercury, a high dose for most tracer 
studies, which was approved as reasonable given the illness of the patients. 82 
Similarly, the Harvard Medical School committee in 1956 stipulated that "the risk 
of incurring any type of deleterious effect due to the radiation received should be 
comparable to the normal everyday risks of accidental injury." For seriously ill 
patients receiving experimental treatment, however, the committee stated, "the 
estimated deleterious effect from radiation should be offset by the expected 
beneficial effects of the procedure." 83 

In addition to setting limits, local committees encouraged the use of 
technical methods to reduce risk. Use of different detection techniques could 
reduce the dose required. In 1955, for example, the Michigan committee 
considered an application to administer to normal volunteers up to 30 microcuries 
of sodium 22 and up to 350 microcuries of potassium 42, resulting in internal 
radiation doses of up to 300 millirem per week. (The purpose was to study 
sodium-potassium exchanges.) The committee asked itself: "Is it justifiable to 
subject the volunteers to an exposure in excess of the maximum permissible? 
This Committee did not resolve this question but came forward with the 
suggestion that more-sensitive counting techniques might permit this 
investigation at lower dose levels." 84 

Another method of reducing risk was to restrict the type of subjects to 
those whose life expectancy was too short for long-term effects to appear. This 
has already been seen regarding terminal patients. Another variation of the same 
technique was to restrict the use of volunteers to those over a certain age. At 
Michigan, age restrictions on who would be acceptable as a volunteer began 
appearing in the 1960s. 85 

When a worthwhile experiment also involved novel risks, another method 
to control risk was to require additional monitoring by the local committee as the 
experiment proceeded. At times, the Michigan committee required preliminary 
reports before allowing experiments to proceed further. 86 In another instance, the 
Michigan committee required the researcher to obtain long-term excretion data 
because of concern that "the usual biologic half-life data might not be 
sufficient." 87 Similar additional oversight was required at the University of 
Chicago in 1953. A proposal was made to use tritium-labeled cholesterol to study 
steroid-estrogen metabolism in women. The question of the distribution of 
estrogenic hormones in humans was unexplored at the time and deemed worthy of 
research. While the risk appeared low, the committee ultimately approved the 

299 



Part II 

study for the first round of the experiment only for nonpregnant women who were 
sterile or pregnant women who planned to be sterilized postabortion. If data from 
the first round suggested minimal risk to the women and the fetuses, the program 
could be expanded. 88 

Thus, in establishing a system of local radioisotope committees, the AEC 
effectively increased the detail with which each proposed experiment was 
reviewed. Often, it appears, experimental protocols were revised at the local level 
before being approved and sent on to the AEC. Thus, the system created by the 
AEC did some of its most effective risk management out of sight of direct federal 
oversight. 

GENERAL BENEFITS OF RADIOISOTOPE RESEARCH 

The system for distribution of radioisotopes worked well and encouraged 
researchers to explore new applications. There are two striking aspects of the 
application of radioisotopes to medicine since World War II: rapid expansion and 
complexity. Practices that at the end of the war were limited to fewer than four 
dozen practitioners have now become mainstays of modern medicine. 89 The 
second major aspect of the field is its complexity. Just as nature at times is best 
regarded as a seamless web, not unconnected scientific fields, knowledge 
nurtured in one field often provides unexpected benefits in another. A few 
examples can illustrate how some of the hopes at the dawn of the atomic age have 
actually been realized. 90 

Improved Instrumentation to Detect Radiation 

Improved instruments, the basic tools for all biological research using 
radioisotopes, were developed through the interaction of biology and medicine 
with physics and engineering. Improvements not only provide greater precision, 
they also allow the same amount of information to be gathered with lower doses 
of radiation, thereby reducing the risk. 

Perhaps the best-known example is the application of the "whole-body 
counter" to biological problems. The device was originally developed as a tool 
for physics, enabling measurements of minute amounts of radiation by combining 
sensitive detectors with extensive shielding to eliminate extraneous radiation. 
The result was similar to placing a sensitive microphone in a sound-proofed room, 
allowing lower levels of radioactivity to be detected than was previously possible. 
For some research, no radioisotope at all was administered; the counters could 
measure naturally occurring radioisotopes. Whole-body counters also greatly 
simplified metabolic studies. In some studies, subjects who previously would 
have had to reside continuously in a metabolic ward could now schedule visits to 
the whole-body counter for their natural radioactivity to be measured on an 
outpatient basis. 91 This device was later adapted for whole-body counting after 

300 



Chapter 6 

administration of tracer amounts of radioisotopes and is the basis for a number of 
fundamental nuclear medicine tests. 

In the early 1 970s, computerized tomographic scanning (CT) was 
introduced. This technique was first applied to x-ray imaging by taking multiple 
x-ray "slices" through a region of the body, then programming a computer to 
construct a three-dimensional image from the information. Thus, internal 
structures of the body may be imaged noninvasively. Newer types of 
tomographic scanning include positron emission tomography (PET), in which 
various metabolites or drugs are labeled with a very short half-life positron- 
emitting radioisotope, such as fluorine 18, and the passage of the labeled material 
is tracked throughout the body by taking multiple images over several minutes or 
hours. 

Diagnostic Procedures 

The first medical application of any radiation was the use of x rays for 
diagnostic purposes, such as locating broken bones inside the patient. 
Radioisotopes later opened another window into the body. The natural tendency 
of certain organs to preferentially absorb specific radioisotopes, coupled with 
ever-improving detection techniques, allowed radioisotopes to be used to increase 
the contrast between different parts of the body. X rays could distinguish 
between hard and soft tissues because of their different densities. Radioisotopes 
could go one step further and distinguish different kinds of tissues from one 
another based upon their metabolic function, not merely their physical density. 

Radioisotopes also could go beyond detecting different types of tissues. 
Since they were distributed throughout the body by the body's own metabolism, 
their location provided a picture not only of structure, but also of processes. 
Tracing radioisotopes was a means of observing the body in action. The earliest 
success was using radioiodine to measure the activity of the thyroid. The gland 
cannot distinguish between radioactive and nonradioactive forms of iodine and 
therefore preferentially absorbs all isotopes of iodine. Thus, the activity of the 
gland can be assessed by observing its absorption of radioiodine. Largely as a 
result of these advances, the thyroid gland is arguably the best understood of all 
human endocrine organs, and its hormones the best understood of all endocrine 
secretions. Since the incidence of thyroid disease is second only to diabetes 
mellitus among human endocrine diseases, this understanding is basic to therapy 
in large numbers of patients. 92 

Because the brain is a crucial and delicate organ, techniques for 
diagnosing brain tumors without surgery were vital. In 1948 radioactive isotopes 
were applied to this task. Using radiotagged substances that were preferentially 
absorbed by brain tumors, physicians could more accurately detect and locate 
brain tumors, allowing better diagnosis and more precise surgery. Similar 
"scanning" techniques were later developed for the liver, spleen, gastrointestinal 

301 



Part II 

system, gall bladder, lymphomas, and bone. 

As mentioned, a recently developed technique is PET scanning, which is 
especially helpful in studying the human brain in action. Glucose is the primary 
food for the brain; by tagging a glucose analog with fluorine 18, investigators can 
identify the actively metabolizing portions of the brain and relate that to function. 
This technique, has opened a new era of studies of the brain. Outwardly 
observable functions, such as language, object recognition, and fine motor 
coordination can now be linked with increased activities in specific areas of the 
brain. 

Radioisotopes allow investigators to increase the sensitivity for analyzing 
biological samples, such as tissue and blood components, especially when 
separating out the material of interest using chemical processes would be difficult. 
Because instruments to measure radioactivity are so sensitive, radioisotopes are 
frequently used in tests to detect particular hormones, drugs, vitamins, enzymes, 
proteins, or viruses. 

Therapeutic Techniques 

Radioisotopes are energy sources that emit one or more types of radiation 
as they decay. If radioisotopes are deposited in body tissues, the radiation they 
emit can kill cells within their range. This may be harmful to the individual if the 
exposed cells are healthy. However, this same process may be beneficial if the 
exposed cells are abnormal (cancer cells, for example). 

The potential for radiation to treat cancer had been recognized in the early 
days of work with radiation, but after World War II the effort to develop radiation 
therapy for cancer increased. Iodine 1 3 1 treatment for thyroid cancer was 
recognized as an effective alternative to surgery, both at the primary and 
metastatic sites. Cancer is not the only malady susceptible to therapy using 
radioisotopes. The use of radioiodine to treat hyperthyroidism is perhaps the 
most widespread example. It illustrates the progression from using a radioisotope 
to measure a process (thyroid activity) to actually correcting an abnormal process 
(hyperthyroidism). 93 

Not all experimental applications of radioisotopes are successful. Some 
experiments end in blind alleys, an important result because this prevents 
widespread application of useless or even harmful treatments. Negative results 
also help researchers to redirect their efforts to more promising areas. The 
importance of negative results is sometimes not appreciated because they do not 
lead to effective treatments. Negative results may range from simply not 
obtaining an anticipated beneficial effect to the development of severe side 
effects. Such side effects may or may not have been anticipated; they may occur 
simultaneously with beneficial effects, such as the killing of cancer cells. 
Occasionally negative results include earlier-than-anticipated deaths of severely 
ill subjects. An example is the experimental use of gallium 72 in the early 1950s 

302 



Chapter 6 

on patients diagnosed with malignant bone tumors. 94 

Another radioisotope, cobalt 60, has been used successfully to irradiate 
malignant tumors, but in this case the radioisotope is not administered internally 
to the patient; rather, the cobalt 60 forms the core of an external irradiator, and the 
gamma radiation emanating from the radioisotope source is focused on the 
patient's tumor. Although cobalt 60 irradiators have been largely replaced by 
linear accelerators, they were developed under AEC sponsorship and were 
responsible for many advances in radiation therapy. 

Recent efforts to utilize radioisotopes in cancer diagnosis and treatment 
are based on the ability of antibodies to recognize and bind to specific molecules 
on the surface of cancer cells and the ability of biomedical scientists to custom- 
design and manufacture antibodies, thus improving their specificity. These fields 
are now contributing to a hybrid technique: cloning antibodies and tagging them 
with radioactive isotopes. As the antibody selectively binds to its target on the 
surface of the cancer cell, the radioactive isotopes attached to the antibody can 
either tag the cell for detection and diagnosis or deliver a fatal dose of radiation to 
the cancer cell. The Food and Drug Administration recently approved the first 
radiolabeled antibody, to be used to diagnose colorectal and ovarian cancers. 95 

Even in the case of widespread metastases where cure is no longer 
possible, radiation treatments will often produce tumor regression and ease the 
pain caused by cancer. Phosphorus 32 has been used to ease (palliate) the bone 
pain caused by metastatic prostate and breast cancers. Recently, the FDA 
approved the use of strontium 89 for similar uses. 9 '' 

Metabolic Studies 

Studies of the basic processes within the body may not have any 
immediate application in diagnosis or therapy, but they can indirectly lead to 
practical applications. One example is in the study of the metabolism of iron in 
the body. Iron is an important part of hemoglobin, which carries oxygen from the 
lungs to all cells in the body. Studies using radioactive iron established the 
pathway iron takes, from its ingestion in food to its use in the blood's hemoglobin 
and its eventual elimination from the body; these studies had practical 
applications in blood disease, nutrition, and the importance of iron metabolism 
during pregnancy. 

Radioisotopes have also been used to study how the weightlessness of 
space travel affects the human body. Radioisotopes have allowed more precise 
observation of effects of space travel on blood plasma volume, total body water, 
extracellular fluid, red cell mass, red cell half-life, and bone and muscle tissue 
turnover rates. 

Other uses of radioisotopes are in studies of the transport and metabolism 
of drugs through the body. New drugs for any clinical application, whether 
diagnostic or therapeutic, must be understood in detail before the FDA will 

303 



Part II 

approve them for general use. One method for readily determining how a drug 
moves through the blood to various tissues, and is metabolically changed in 
structure, is to incorporate a radioactive isotope into the structure of the drug. 

Unexpected results from an experiment can at times have widespread 
consequences. An example is how the work of Rosalyn Yalow and Solomon 
Berson of the Bronx VA Medical Center opened up the field of 
radioimmunoassay. In the early 1950s, it was discovered that adult diabetics had 
both pancreatic and circulating insulin. This appeared odd; previously, it had 
been believed that all diabetics lacked insulin. To explain the presence of 
diabetes in people with pancreatic insulin, Yalow and Berson decided to study 
how rapidly insulin disappeared from the blood of diabetics. To do this, they 
synthesized radioiodine-labeled insulin. This would act as a radioactive tag, 
making it much easier to measure the presence of insulin in blood. To their 
surprise, they found that insulin disappeared more slowly from diabetic patients 
than from nondiabetic people. 97 

Their work had an impact beyond the study of diabetes, however. In the 
process of studying the plasma of patients who had been injected with insulin, 
they discovered that the radioactively tagged insulin was bound to an antibody, a 
defensive molecule that had been produced by the patient's body and custom- 
designed to attach itself to the foreign insulin molecule. This was a surprise, since 
prevalent doctrine held that the body did not produce antibodies to attack small 
molecules such as insulin. To study the maximum binding capacity of the 
antibodies, they did saturation tests, using fixed amounts of radiolabeled insulin 
and of antibody to measure graded concentrations of insulin. With this technique 
Yalow and Berson realized they could measure with great precision the quantities 
of insulin in unknown samples. They thus developed the first 
radioimmunoassay. This technique, for which Rosalyn Yalow was awarded the 
Nobel Prize in Medicine in 1977, has become a basic tool in many areas of 
research. Radioimmunoassay revolutionized the ability of scientists to detect and 
quantify minute levels of tissue components, such as hormones, enzymes, or 
serum proteins, by measuring the component's ability to bind to an antibody or 
other protein in competition with a standard amount of the same component that 
had been radioactively tagged in the laboratory. This technique has permitted the 
diagnosis of many human conditions without directly exposing patients to 
radioactivity. 

No discussion of the impact of radioisotopes on biomedical science would 
be complete without a recognition of their fundamental importance in basic 
biological investigations. The ability of radioisotopically labeled metabolites to 
act like, and therefore trace, their nonradioactive counterparts has allowed 
scientists to follow virtually every aspect of metabolism in cells of bacteria, 
yeasts, insects, plants, and animals, including human cells. Among the benefits of 
such studies are (a) an understanding of the similarities in metabolism of 
organisms throughout the evolutionary scale, (b) identification of sometimes 

304 



Chapter 6 

subtle differences in cell structure and function between organisms and thus the 
ability of drugs to kill bacteria, fungi, or insects without harming humans, and (c) 
elucidation of the fundamental properties of genetic material (DNA), The last of 
these examples has important implications today, as the human genes controlling 
many important bodily functions are being identified and cloned and gene therapy 
is just beginning to find its way into clinical application. Many benefits of 
understanding the human genetic code have already been realized, and others will 
likely accrue in the next few years. These benefits are the result of fundamental 
advances in genetics and molecular biology of the past half century, which in turn 
depended heavily on studies with lower organisms and with radioisotopically 
labeled materials. Thus, human health is benefiting from both human and 
nonhuman research with radioisotopes. 

The grandest dream of the early pioneers—a simple and complete cure for 
cancer-remains unfulfilled. Promising paths at times proved to be dead ends. 
However, the AEC's widespread provision of radioisotopes, coupled with support 
for new techniques to apply them, laid the foundation stones for much of modern 
medicine and biology. This section has only skimmed the field of nuclear 
medicine, with its vast array of diagnostic and therapeutic techniques, and the use 
of radioisotopes in many areas of basic research. 



An Example of Hopes Unfulfilled: The Gallium 72 Experiments 

Human experiments with gallium 72, as discussed in the section titled "General Benefits 
of Radioisotope Research," were conducted at the Oak Ridge Institute of Nuclear Studies in the 
early 1950s. The experiments used gallium 72 because of its short half-life (14.3 hours) and 
because an earlier animal study indicated it concentrated in new bone, making it useful as a tumor 
marker and possibly for therapy." The 1953 published report stated that the purpose of the study 
was "to investigate the therapeutic possibilities in human tumors involving the skeletal system. " b 
In 1995 one of the original researchers stated to Advisory Committee staff a somewhat broader 
purpose: "to exploit to the fullest possible extent any possible use of this isotope as a bone seeking 
element rather than to seek a cure for a specific malignant bone tumor, such as osteogenic 
sarcoma. . . . While the GalIium-72 studies did include osteogenic sarcomas, they only represented 



a. Herbert D. Herman. M.D., FACR, to Dan Guttman, Executive Director, Advisory Committee 
on Human Radiation Experiments, 19 May 1995 ("It has come to my attention . . ."), 2. Dr. Kerman cites as 
the preceding study: H. C. Dudley and G. E. Maddox, "Deposition of radiogallium (Ga-72) in skeletal 
tissues," Journal of Pharmacology,' and Experimental Therapeutics 96 (July 1949): 224-227. 

b. Gould A. Andrews, M.D., Samuel W. Root, M.D.. and Herbert D. Kerman, M.D.. "Clinical 
Studies with Gallium-72," 570, in Marshall Brucer, M.D. (ed.), Gould Andrews, M.D., and H. D. Bruner, 
M.D., "Clinical Studies with Gallium-72," Radiology 66 (1953): 534-613. 

305 



Part II 

less than half (9/21 ), 43%, of all the other primary and metastatic skeletal malignancies studied.'" 

Patients were chosen who had been diagnosed with "ultimately fatal neoplasms not 
amenable to curative surgery or radiotherapy.'" 1 The diagnosis later proved to be accurate in all but 
one of the fifty-five subjects. In one part of the study, thirty-four patients were given trace 
amounts of gallium. Both external radiation measurements and a variety of excreta, blood, and 
tissue samples were analyzed to determine the localization of gallium. In another part of the study, 
twenty-one other patients were given doses that the researchers hoped would be in the therapeutic 
range. Total doses ranged from 50 to 777 microcuries. 1 The gallium was administered in 
fractionated doses biweekly. According to the medical investigators, these patients "were, in 
general, in a more advanced stage of disease and were completely beyond even palliation from 
conventional forms of therapy." 6 For these patients, "doses which were believed to be moderate 
were given and gradually increased to toxic level. " h The conclusion of the report notes that "most 
of the patients in whom gallium therapy was attempted were given maximum amounts of the 
isotope. Only the hopelessness of their prognoses justified a trial of doses so damaging to the 
hematopoietic tissues.'" 

A major difficulty was lack of knowledge about both the chemical toxicity of stable (that 
is, nonradioactive) gallium and the radiation toxicity of gallium 72. Calculations and small animal 
studies indicated that dosimetry techniques used for other radioisotopes would "be of little value." 1 
During the study, close monitoring was done of many bodily functions to observe toxic effects as 
soon as they began to appear. Blood tests revealed changes that "were prominent and were usually 
of primary importance in determining when the treatments should be discontinued. " k Other effects 
included drowsiness, then anorexia, nausea, vomiting, and skin rash. 

One problem was determining whether these effects were due to chemical toxicity, 
radiation toxicity, or a combination. Due to technical difficulties in separating out pure gallium 



c. Kerman to Guttman, 19 May 1995, 2. Dr. Kennan presumably was referring to the twenty-one 
subjects who received doses in the therapeutic range, not the thirty-four who received trace doses. 

d. Andrews, Root, and Kerman, "Clinical Studies with Gallium-72," 570. 

e. A patient was diagnosed with osteogenic sarcoma in his leg, which was amputated. X rays also 
revealed dense nodules in his lung, which were diagnosed as inoperable but typical pulmonary metastases. 
He was discharged after the gallium study. When he later returned to the hospital, an operation revealed that 
the nodules were not typical metastases, but unidentifiable lesions "not characteristic of any specific lesion." 
This could not have been known prior to the study, when only x rays were available for diagnosis. Ibid., 585. 

f. The researchers reported that these doses were equivalent to 8.5-89.2 mg/kg of body weight. 
Ibid., 574-577. 

g. Ibid., 570. 
h. Ibid., 571. 
i. Ibid., 587. 

j. The investigators wrote that "[njormal tissue and whole-body tolerances for amounts of 
radiogallium necessary to produce a significant effect upon malignant tissues were unknown. Preliminary 
calculations and small animal experiments had indicated that accepted radiation dosimetry as applied to other 
isotopes would be of little value in calculating radiation dosage to tissues. It was therefore necessary to 
utilize the hematologic picture to assess the damaging effects of whole-body irradiation, and clinical and 
roentgenographic experience in evaluating a therapeutic response." Ibid., 571. 

k. Ibid., 573. 

306 



Chapter 6 

72. the radioactive gallium was injected with larger amounts of stable gallium, so both chemical 
and radiation effects could be present. To distinguish them, one patient was administered an 
amount of stable gallium equal to a therapeutic dose, but with only an insignificant amount of 
radioactive tracer (to determine localization). Observed toxic effects in this patient did not include 
bone marrow depression. The researchers concluded, therefore, that the "profound bone marrow 
depression is characteristic of radiation damage and is probably chiefly caused by radiation, 
though an element of stable metal toxicity may also be contributory." 1 

Bone marrow depression gradually ended after gallium injections were stopped. While it 
lasted, bone marrow depression led to greater susceptibility to infection and bleeding. Two 
subjects died sooner than anticipated, one from infection and bleeding and the other from 
infection, while their bone marrow was still depressed. "These two patients died in spite of 
antibiotics, blood transfusions, and toluidine-blue therapy.'"" The researchers reported that "in two 
patients our estimates of safe dosage limits were in error and radiogallium is believed to have 
hastened death."" One researcher, writing in 1995, stated that "since 'safe dosage' levels were only 
estimates and seven other patients had survived with even higher dosages, our choice of language 
[citing the preceding quotation] was unfortunate. It must be emphasized that this portion of the 
study must be likened to a current clinical Phase I trial where in a limited fashion [a] broad range 
of toxicity levels may at best be only estimated." 

The major conclusion of the experiment was that hopes for gallium therapy were 
unfulfilled. Even though the maximum tolerated doses had been administered, the researchers 
reported that "we were impressed with the almost complete lack of any clinical improvement 
following gallium treatment, even in patients who showed evidence of striking differential 
localization of gallium in tumor tissue." 

Concerning patient consent, the published study says nothing, which was normal for 
scientific articles at that time. Near the end of the Advisory Committee's deliberations, ORINS 
reportedly found consent forms signed by subjects in the gallium study. 4 One of the researchers in 
1995 did offer his recollections regarding consent to the Committee: 

Forty-five years ago all of our patients and their families were 
given a booklet of information explaining how radioisotopes 
were used in medicine and more specific information about 



I. Ibid., 575. 

m. Ibid., 573. Neither had suffered from osteogenic sarcoma; one had suffered from 
adenocarcinoma of the kidney with lytic bone metastases and another from cancer of the prostate with 
metastatic skeletal involvement, Kerman to Guttman, 19 May 1995, 3. 

n. Andrews, Root, and Kerman, "Clinical Studies with Gallium-72," 571. 

o. Ibid. 

p. Ibid., 587. Researchers reported evidence of concentration in tumors as being one of the 
following: "no data," "none." "little," "moderate," or "pronounced." Ibid., 574. 

q. Dr. Shirley Fry, telephone interview with Dan Guttman (ACHRE), 30 August 1995, I. The 
Advisory Committee did not have enough time to review the forms and related file materials once they were 
identified, which, because ORINS deemed them privacy-protected material, would have required review at 
Oak Ridge. 

307 



Part II 



their own involvement including the possible known risks. 
Signed applications for admission and waiver and release 
forms were demanded for all patients. When, as in the ongoing 
gallium studies, toxicity or enhanced risks were encountered, 
these were immediately made clear to the patients and their 
families if they were known in that time frame. Very often 
toxicity is only apparent after review of the clinical data. In the 
gallium studies, when on review of the data it was determined 
that no therapeutic benefit had occurred, the study was 
immediately terminated/ 



CONCLUSION 

At the end of World War II, radioisotopes were regarded as the most 
promising peacetime application of our new knowledge of the atom. Venturing 
into new fields carried with it substantial risks: risks due to our ignorance of what 
lay ahead, and risks due to the lack of training of many would-be explorers. The 
AEC consistently accepted and acted upon its responsibility to manage this risk. 
An extensive administrative system was created to oversee the safety of human 
radiation experiments that used radioisotopes supplied by the AEC. At the heart 
of the system was the AEC's Subcommittee on Human Applications of the 
Advisory Committee on Isotopes Distribution Policy. This system regulated the 
types of uses allowed according to their hazard and the extent of our knowledge 
of the risks. It required and provided training of those who would use 
radioisotopes. It required the establishment of local radioisotope committees, 
which not only reviewed proposals but suggested changes at the local level in 
experimental design to reduce risk. 

While extensive measures were taken to minimize risk, few measures 
were taken to ensure that all the explorers, subjects as well as researchers, were 
fully informed and willing members of the expedition. No evidence has yet been 
found that the standards for documented consent, articulated by AEC General 
Manager Carroll Wilson in 1947, were applied by the AEC Isotopes Distribution 
Division. A limited consent requirement was instituted only for the administration 
of larger-than-usual doses to very sick patients. Only in the late 1950s did a 
consent requirement for normal volunteers appear in the AEC guidelines. 

Based on the records examined by the Advisory Committee, the adjunct 



r. Kerman to Guttman, 19 May 1995, 3. The booklet, "ORINS Patient Information Booklet" 
(circa May 1950). is discussed in chapter 1 . ORINS hospital was known to be dedicated to experimental 
work with radiation and radioisotopes. Patients were admitted to the hospital only if they were willing to be 
experimental subjects. It is not as clear, however, whether the details of any particular experiment were 
always explained adequately to patients. 

308 



Chapter 6 

system of local radioisotope committees appears to have functioned as planned. 
The records of local institutions indicate that they established their own local 
radioisotope committees, as required by the AEC, and that these local committees 
closely assessed the risks of experiments. At times, this system went beyond 
what the AEC had planned. Some local committees had jurisdictions that 
extended to all radiation-related work, not merely to radioisotopes supplied by the 
AEC. The local committees also provided, probably unintentionally, a ready- 
made vehicle for administering greater oversight of consent practices, as concern 
developed in the 1960s. Requirements for consent on a federal level changed only 
in the late 1960s, as part of a governmentwide concern. 



309 



ENDNOTES 



1. The first complete proposal for radioisotope distribution is contained in a 
memo dated 3 January 1946. Radioisotope Committee of Clinton Laboratories (Oak 
Ridge, Tennessee) to Colonel S. L. Warren, Medical Director of the Manhattan Project, 
3 January 1946 ("Specific Proposals for the National Distribution of Radioisotopes 
Produced by the Manhattan Engineer District") (ACHRE No. NARA-082294-A-31). 
This memo, in turn, was derived from a more extensive document prepared by Waldo 
Cohn, a member of the lab staff. W. E. Cohn, 3 January 1946 ("The National 
Distribution of Radioisotopes from the Manhattan Engineer District") (ACHRE No. 
DOE-051094-A-317). 

2. The press release announcing the program noted that, in addition to technical 
qualifications of researchers, "An additional qualification will require all groups using 
the isotopes for fundamental research or applied science to publish or otherwise make 
available their findings, thereby promoting further applications and scientific advances." 
Headquarters, Manhattan District (Oak Ridge, Tennessee), 14 June 1946 ("For Release 
in Newspapers Dated June 14, 1946") (ACHRE No. NARA-082294-A-31), 1. 

3. "Availability of Radioactive Isotopes: Announcement from Headquarters, 
Manhattan Project, Washington, D.C.," Science 103 (14 June 1946): 697-705. 

4. Harry H. Davis, New York Times Magazine (typescript), 22 September 1946 
("The Atom Goes to Work for Medicine") (ACHRE No. DOE-051094-A-408), 2. 

5. Ibid., 6. 

6. Cohn, 3 January 1946, 10. 

7. Ibid., 14. 

8. R. E. Cunningham, 20 February 1971 ("Historical Summary of the 
Subcommittee on Human Applications") (ACHRE No. NRC-012695-A), 6. 

9. AEC Subcommittee on Human Applications of the Committee on Isotope 
Distribution, 13 March 1949 ("Revised Tentative Minutes of March 13, 1949, Meeting 
of Subcommittee on Human Application of the Committee on Isotope Distribution of 
U.S. Atomic Energy Commission: AEC Building, Washington, D.C.") (ACHRE No. 
NARA-082294-A-62), 7. 

10. Advisory Subcommittee on Human Applications of the Interim Advisory 
Committee on Isotope Distribution Policy, 1 1 July 1946 ("Minutes of Initial Meeting- 
Held June 28, 1946; Oak Ridge, Tennessee") (ACHRE No. NARA-082294-A-84), 1. 

11. Ibid., 2-8. 

12. Ibid., 5. 

13. Ibid., 6. 

14. Ibid., 10. 

15. For example, proposals to study possible therapeutic uses of UX1/ UX2, a 
"naturally radioactive pair [that] behaves chemically as UX1, a thorium isotope 

(Th 234). . . . Aside from the danger of bone damage, the material would have to be used 
with much caution because of likely kidney damage. No advantage could be seen in the 
use of radiothorium over the use of certain other beta ray emitting radioisotopes which 
deposit in bone." Ibid., 9. 

16. Ibid. 

17. "In general, there is more of a need for speed in handling requests for human 
applications than for others because: (1) therapeutic action may be needed urgently, (2) 



310 



the case may be an exceptionally good one for some purpose and may only be available 
for study immediately (for example, the chance to obtain tracer samples resulting from a 
special operation)." Ibid., 10. 

18. Isotopes Branch, Research Division, Manhattan District, Oak Ridge, 
Tennessee, 3 October 1946 ("Details of Isotope Procurement") (ACHRE No. 
NARA-082294-A-31). 

19. Isotopes Branch, Research Division, Manhattan District, Oak Ridge, 
Tennessee, 3 October 1946 ("Agreement and Conditions for Order and Receipt of 
Radioactive Materials") (ACHRE No. NARA-082294-A-31), 2. 

20. The statement read: 

This is to certify that the undersigned has adequate facilities for the 
investigation to be conducted by him as proposed in the 'Interim 

Period Request for Radioelement, Form 313,' Serial Number , 

and that such drug will be used solely by him or under his direction 
for the investigation, unless and until an application becomes 
effective with respect to such drug under section 505 of the Federal 
Food, Drug and Cosmetic Act, Isotopes Branch, Research Division, 
Manhattan District, Oak Ridge, Tenn. 
Isotopes Branch, Research Division, Manhattan District, Oak Ridge, Tennessee, 3 
October 1946 ("Certificate . . . EIDM Form 465") (ACHRE No. NARA-082294-A-31), 
1. 

21. Isotopes Branch, Research Division, Manhattan District ("Report of 
Requests Received to July 31,1 946," "2nd Report of Request Received August 1 to 3 1 , 
1946," "3rd Report of Request Received September 1 to 30, 1946," "4th Report of 
Requests Received October 1 to 31, 1946") (ACHRE No. NARA-082294-A-31). 

22. Franklin asked: 

What is the relationship of the Atomic Energy Commission Medical 
Division to the Isotopes Branch and the medical and biological aspects 
of the isotope distribution program? 

(1) Will allocations for human administration be subject to medical 
review and what control will be exercised? 

(2) What responsibilities does the Atomic Energy Commission bear 
for the human administration of isotopes (a) by private physicians and 
medical institutions outside of the Project, and (b) by physicians within 
the Project? This latter category includes contractor personnel 
employing Atomic Energy Commission funds (indirectly) to perform 
tracer research, some of which is of no immediate therapeutic value to 
the patient. What are the criteria for future human tracer research? 

(3) What responsibilities does the Atomic Energy Commission bear 
for the safe handling by the recipient of the more hazardous 
radioisotopes? 

(4) What responsibilities does the Atomic Energy Commission bear 
for radioactive waste disposal outside the Project? 

J. C. Franklin, Manager, Oak Ridge Operations, to Carroll Wilson, AEC General 
Manager, 26 September 1947 ("Medical Policy") (ACHRE No. DOE-1 13094-B-3), 2. 



311 



23. Research Division, Manhattan District, 3 October 1946 ("Isotope Request, 
For Manhattan Project Use Only . . . EIDM Form 558") (ACHRE No. NARA-082294-A- 
31), 1. 

24. In a 5 October 1949 memorandum to Carroll Tyler, Manager of Los Alamos, 
Paul Aebersold, Chief of the Isotopes Division, noted that "Dr. [Shields] Warren 
instructed that such allocations would be made by the Isotopes Division only after 
review and approval by the Subcommittee on Human Applications of the Commission's 
Committee on Isotope Distribution. It should be emphasized that the instruction applies 
even though the radiomaterial is produced in the laboratory where it is to be used. 

"Since this procedure has not been uniformly followed in the past, we are 
writing to acquaint you with the appropriate details." Paul Aebersold, Chief, Isotopes 
Division, to Carroll Tyler, Manager, Los Alamos, 5 October 1949 ("Use of Radioisotopes 
in Human Subjects") (ACHRE No. DOE-021095-B-4), 1 . An identical memo was also 
sent to the manager of the AEC's New York office regarding requirements for 
Brookhaven National Laboratory. Paul Aebersold, Chief, Isotopes Division, to W. E. 
Kelley, Manager, New York, 5 October 1949 ("Use of Radioisotopes in Human 
Subjects") (ACHRE No. DOE-012795B). 

25. Presumably codifying existing practice, 10 C.F.R. 30.10 (1951 supplement 
to 1949 edition) states: 

The regulations in this part do not apply to persons to 
the extent that such persons operate Commission-owned 
facilities in carrying out programs on behalf of the 
Commission. In such cases, the acquisition, transfer, 
use, and disposal of radioisotopes are governed by the 
contracts between such persons and the Commission, 
and internal bulletins, instructions and directives issued 
by the Commission. 

26. Carroll L. Wilson, AEC General Manager, to Principal Staff, Washington, 
and Managers of Operations, 7 June 1950 ("Bulletin GM-161, Procedure for Securing 
Isotopic Materials and Irradiation Services") (ACHRE No. NARA-122994-B), 1. 

27. Subcommittee on Human Applications, 13 March 1949, 1. 

28. Ibid., 3. 

29. Ibid. These minutes include a review of the minutes of the 22-23 March 
1948, meeting. 

30. Ibid., 10-11. 

31. Ibid., 10. 

32. Ibid., 12-13. 

33. Ibid., 4. 

34. Ibid. 

35. Paul Aebersold, Chief, Isotopes Division, Oak Ridge Operations, to Hymer 
Friedell, G. Failla, Joseph G. Hamilton, and A. H. Holland, Jr., 9 March 1948 ("Meeting 
of Subcommittee on Human Applications in Washington, March 22 and 23") (ACHRE 
No. NARA-082294-A-17), 2. 

36. Subcommittee on Human Applications, 13 March 1949, 5-6. 

37. Ibid. 

38. Clemens Benda, Director of Research and Clinical Psychiatry, to AEC 
Subcommittee on Human Applications, 29 September 1953 ("This letter is written in 



312 



order to elicit your permission to administer a dose of 50 uc Ca45 to a moribund gargoyle 
patient now hospitalized in our institution . . ."), 1 . Reproduced at appendix B-27, Task 
Force on Human Subject Research, to Philip Campbell, Commissioner, Commonwealth 
of Massachusetts Executive Office of Health and Human Services, Department of Mental 
Retardation, April 1994 ("A Report on the Use of Radioactive Materials in Human 
Subject Research that Involved Residents of State-Operated Facilities within the 
Commonwealth of Massachusetts from 1943 to 1973") (ACHRE No. MASS-072194-A). 

39. Clemens Benda, Clinical Director, to "Parent," 28 May 1953 ("In previous 
years we have done some examinations in connection with the nutritional department of 
the Massachusetts Institute of Technology . . ."), 1. Reproduced at appendix B-23, Task 
Force on Human Subject Research, to Philip Campbell, April 1994. 

40. Task Force on Human Subject Research, to Philip Campbell, April 1994, 16. 

41. Subcommittee on Human Applications, 13 March 1949, 8. 

42. AEC Isotopes Division, "General Authorizations for Procurement of 
Radioisotopes," Isotopics: Announcements of the Isotopes Division 1 (April 1951): 1-3. 

43. AEC Isotopes Division. "General Authorizations for Clinical Use of 
Radioisotopes," Isotopics: Announcements of the Isotopes Division 2 (April 1952): 1-2. 

44. Subcommittee on Human Applications, 13 March 1949, 1 1. 

45. Paul C. Aebersold, Chief, AEC Isotopes Division, to William E. Barbour, 
Jr., President, Tracerlab, Inc., 1 1 April 1949 ("Violation of 'Acceptance of Terms and 
Conditions for Order and Receipt of Byproduct Materials [Radioisotopes]'") (ACHRE 
No. NARA-082294-A-4), 1. 

46. William Barbour, President, Tracerlab, Inc., to Employees, April 1949 
("Violation of AEC Regulations") (ACHRE No. NARA-082294-A-4), 1 . Barbour stated 
that a recurrence would 

mean cessation of all radiochemical operations of the 
Company. In turn this would jeopardize the investments 
of several thousand new stockholders who have placed 
great faith in the integrity and ability of the management. 
A violation of a specific agreement with the AEC would 
be a breach of that faith and could only result in the 
automatic dismissal of anyone contributing to such a 
violation. 

47. AEC Isotopes Division, 23 March 1950 ("Meeting of the Advisory 
Committee on Isotope Distribution, March 23 and 24, 1950, Washington, D.C., 
Minutes") (ACHRE No. NARA- 1 22994-B- 1 ), 4. 

48. AEC Isotopes Division, September 1949 ("Supplement No. 1 to Catalogue 
and Price List No. 3") (ACHRE No. DOD-122794-A-1), 1. 

49. Paul C. Aebersold, Director, Isotopes Division, to T. H. Johnson, Director, 
Division of Research, 2 November 1954 ("Providing Radioisotopes at Reduced Prices 
for Medical, Biological, or Other Research Uses") (ACHRE No. TEX-101294-A-4), 1 . 

50. 10 C.F.R. 37(1961). 

51. A conscious decision was made not to include detailed standards in the 
regulations. The discussion is summarized in Advisory Committee on Isotope 
Distribution, 23 March 1950, 7-8. The regulations were first promulgated in 10 C.F.R. 
30.50(1951 supplement to 1949 edition). 



313 



52. AEC Isotopes Division, 6 December 1948 ("Isotopes Division Circular D-4: 
Radioisotopes for Use in Medicine") (ACHRE No. DOE-101 194-A-5); Isotopes 
Division, "Supplement No. 1," September 1949; Isotopes Extension, Division of Civilian 
Application, U.S. Atomic Energy Commission, "The Medical Use of Radioisotopes: 
Recommendations and Requirements by the Atomic Energy Commission," RC- 1 2 
(February 1956). 

53. Isotopes Extension, February 1956, 14. 

54. Ibid., 15. 

55. R. E. Cunningham, "Historical Summary," 5. 

56. AEC Division of Materials Licensing, "Non-Routine Medical Uses of 
Byproduct Material," A Guide for the Preparation of Applications for the Medical Use of 
Radioisotopes (November 1965), 47-48. 

57. See, for example, Bryant L. Jones, Division of Oncology and 
Radiopharmaceuticals, Bureau of Medicine, Food and Drug Administration, 1 8 May 
1967 ("FDA Responsibility in Radiopharmaceutical Research") (ACHRE No. DOE- 
051094-A-236). 

58. Advisory Subcommittee on Human Applications, 1 1 July 1946, 6. 

59. This requirement is stated in Aebersold's memo of 5 October 1949, quoted 
earlier in endnote 24, which notified AEC labs that their applications for human use 
would now be reviewed by the Subcommittee on Human Applications of the AEC's 
Committee on Isotope Distribution. Concerning local isotope committees, the memo 
states: "It should be emphasized that each application should be accompanied by a 
formal, written endorsement, signed by the Chairman of the local "Isotopes Committee," 
the recommended membership of which is outlined on pages 30 and 31 of the catalog." 
Paul Aebersold, Chief, Isotopes Division, to Carroll Tyler, Manager, Los Alamos, 5 
October 1949 ("Use of Radioisotopes in Human Subjects") (ACHRE No. DOE-021095- 
B-4); Paul Aebersold, Chief, Isotopes Division, to W. E. Kelley, Manager, New York, 5 
October 1949 ("Use of Radioisotopes in Human Subjects") (ACHRE No. DOE-0 12795- 

B). 

60. AEC Isotopes Division, Isotopics 1,1. 

61. Isotopes Extension, February 1956, 7. The full description of the functions 
of the Medical Isotope Committee is: 

1. Formation of a Medical Isotopes Committee. The 
Medical Isotope Committee shall include at least three 
members. Membership should include physicians expert 
in internal medicine (or hematology), pathology, or 
therapeutic radiology and a person experienced in assay 
of radioisotopes and protection against ionizing 
radiations. It is often appropriate that a qualified 
physicist be available to the Committee, at least in 
consulting capacity. It is recognized that the 
composition of local isotope committees may vary from 
institution to institution depending upon the individual 
interests of a particular medical facility. 

2. Duties of the Medical Isotopes Committee 



314 



Generally, the Committee should have the following 
responsibilities: 

a. Review and grant permission for, or disapprove, the 
use of radioisotopes within the institution from the 
standpoint of radiological health safety and other factors 
which the Committee may wish to establish for medical 
use of these materials. 

b. Prescribe special conditions which may be necessary, 
such as physical examinations, additional training, 
designation of limited area or location of use, disposal 
methods, etc. 

c. Review records and receive reports from its 
radiological safety officer or other individual responsible 
for health-safety practices. 

d. Recommend remedial action when a person fails to 
observe safety recommendations and rules. 

e. Keep a record of actions taken by the Committee. 

62. The Advisory Committee also reviewed materials from the AEC's Oak 
Ridge, Los Alamos, Argonne, and Brookhaven laboratories, the Air Force School of 
Aviation Medicine, and the University of California. The development of research at the 
University of California at Berkeley and San Francisco is the subject of a case study 
appearing in a companion volume to this report. 

63. N. W. Faxon, Director, Massachusetts General Hospital, to Drs. Aub, 
Moore, Shulz, and Rawson, 3 May 1946 ("At the meeting of the General Executive 
Committee held on May 1, 1946, consideration of the use of radioactive isotopes was 
discussed . . .") (ACHRE No. H AR- 100394- A- 1), 1. 

64. "It should be emphasized that the University Radiation Policy Committee 
was established to deal with all types of radiation problems at the University and was not 
limited to the scope of 'radioisotope committees' suggested by the AEC for radioisotope 
procurement. In fact this Committee predated the earliest suggestions of the AEC by 
almost a year." W. W. Meinke, Chairman, University of Michigan Radiation Policy 
Committee, to I. Lampe, 27 February 1956 ("On October 13, 1950, the President of the 
University of Michigan established the Radiation Policy Committee . . .") (ACHRE No. 
MIC-010495-A-2), 1. 

65. Consisting of Hugh Morgan (Vanderbilt University), Stafford Warren 
(University of California at Los Angeles), Hymer Friedell (Case Western Reserve 
University ), Shields Warren (AEC Division of Biology and Medicine), and Perrin Long 
(Johns Hopkins University). 

66. There was some debate at the beginning as to the name of the units. With 
"radioactive" still a charged word for much of the population, an early memo suggested 
that "it could to advantage be called a Metabolism Ward." Veterans Administration, 15 
September 1948 ("Minutes of the Meeting, Central Advisory Committee on 
Radioisotopes, U.S. Veterans Administration") (ACHRE No. UCLA- 100794- A), 23. 

67. The chairman listed the already-achieved benefits to thyroid gland research 
and blood volume diagnosis, and claimed, "It is not an overstatement to say that progress 
can be expected to be rapid and on a wide front as greater use is made in medical and 
biological research when this new tool is applied in attempts to solve such problems." 



315 



Ibid., 3. 

68. Framingham, Massachusetts; Bronx, New York; Cleveland, Ohio; Hines, 
Illinois; Minneapolis, Minnesota; Van Nuys, California; Los Angeles, California; and 
Dallas, Texas. 

69. Joseph C. Aub et. a!., to the Executive Committee, Massachusetts General 
Hospital, 17 June 1946 ("The Radioactive Isotope Committee had its first meeting on 
June 15th . . .") (ACHRE No. HAR-100394-A-2), 1-2. 

70. William Sweet, interviewed by Gilbert Whittemore (ACHRE), transcript of 
audio recording, 8 April 1995 (ACHRE Research Project Series, Interview Program File, 
Targeted Interview Project), 20. 

7 1 . VA Central Advisory Committee on Radioisotopes, 1 5 September 1 948, 26. 

72. Ibid. 

73. University of Michigan Subcommittee on Human Use of Isotopes, 10 
December 1956 ("Minutes, Meeting of the Subcommittee on Human Use of Isotopes") 
(ACHRE No. MIC-010495-A-3), 1. 

74. William H. Beierwaltes to Edward A. Carr, Chairman, University of 
Michigan Subcommittee on Human Use of Radioisotopes, 20 May 1968 ("Enclosed are 
our calculations to date on our first two patients studied in the Clinical Research Unit . . 
.") (ACHRE No. MIC-010495-A-6), 3. The form includes space for a signature by a 
witness as well as the patient. 

75. In an effort to develop an overall assessment of the possible harm from 
radioisotope experiments conducted in the past, the Advisory Committee extracted dose 
data from our Experiment Database, whenever available, in order to perform risk 
analyses using contemporary standards. Unfortunately, most of the data recovered by the 
Committee was fragmentary and did not provide a sufficient basis for an analysis of 
possible harm in most cases. 

76. Massachusetts General Hospital Radioactive Isotope Committee, 15 March 
1955 ("Meeting of the Massachusetts General Hospital Radioactive Isotope Committee") 
(ACHRE No. HAR-100394-A-4), 1. 

77. Ibid. 

78. One proposal, for example, involved saturating gelfoam with silver 1 1 1 or 
yttrium 90, and then implanting the gelfoam into the tumor. Preliminary work had been 
done on animals in the previous year on normal brain tissue. After extensive animal 
testing, the procedure was to be attempted on those humans who already suffered brain 
cancer and had undergone surgery. Theodore Rasmussen, 29 May 1952 ("Local 
Application of Beta Ray Isotopes to Brain Tumors") (ACHRE No. DOE-122194-A). 

79. For example, in 1 953 the Chicago committee approved a proposal to use 
tritium and C-14-labeled acetate to trace the development of adrenal cholesterol in 
advanced cancer patients as well as a control group. The committee noted that the doses 
"are smaller than have been used in human studies at other institutions and in no case 
involve amounts which will produce internal radiation in excess of maximum permissible 
dose." George V. LeRoy, Chairman, Radioisotope Committee, 24 February 1953 
("Minutes of the Radioisotope Committee Meeting") (ACHRE No. DOE- 122 1 94- A), 1. 

80. This included recommendations for using the minimum amounts of isotopes 
possible, a limitation of 1 rep [roentgen equivalent physical] for tracers, mandatory blood 
tests before administration and forty-eight hours after, and a listing of dose 
recommendations. The policy on patients and children was specific: "Adult humans who 
are ill and who are expected to receive benefit from the procedure, shall not receive tracer 



316 



doses of radioactive material giving off radiation in excess of a total of 4 rep. Children 
(all patients below 15 years of age) shall not receive more than a total of 0.8 rep." J. C. 
Aub, A. K. Solomon, and Shields Warren, Harvard Medical School, 7 May 1949 ("Tracer 
Doses of Radioactive Isotopes in Man") (ACHRE No. HAR-100394-A-3), 1. 

81 . The committee stated that all volunteers receiving Na-22 and K-42 should 
be subjected to doses no more than 100 millirads for the whole body, nor more than one- 
third the maximum permissible values to a specific organ. University of Michigan 
Subcommittee on Human Use of Isotopes, 10 December 1956, 1. 

82. W. F. to University of Chicago Radioisotope Committee, 28 September 
1953 ("Permission is requested to administer intravenously 500 microcuries, or less, of 
radio-mercury to a patient . . .") (ACHRE No. DOE-122194-A-2), 1 . 

83. Harvard Medical School Committee on Medical Research in Biophysics, 
August 1957 ("Tracer Doses of Radioactive Isotopes in Man") (ACHRE No. HAR- 
100394-A-5), 2. 

84. University of Michigan Subcommittee on Human Use of Isotopes, 27 
September 1955 ("Minutes of Human Use Committee Meeting") (ACHRE No. MIC- 
010495-A), 2. 

85. A 1963 memorandum indicates the committee's unwillingness to allow a 
procedure involving selenium 75-labeled methionine for parathyroid scanning limited to 
use in patients over forty years old, while in a 1 966 letter Carr stated that he was 
"strongly inclined to refuse to permit the use of radioisotopes in all volunteers below the 
age of 21, unless there are special mitigating circumstances approved by the whole 
subcommittee." Ronald C. Bishop, Acting Chairman, Subcommittee on Human Use, 13 
August 1963 ("Dr. E. A. Carr has asked me to act as chairman of the Subcommittee on 
Human Use in his absence . . .") (ACHRE No. MIC-010495-A-4), 1; Edward A. Carr to 
Dr. Bishop, 3 September 1966 ("To Members of the Subcommittee on Human Use of 
Radioisotopes") (ACHRE No. MIC-010495-A-5), 1. 

86. In 1 968 the committee approved a proposal for an experiment that involved 
doses of NM-125 labeled with 1-131 or 1-125 for patients with melanomas or a reasonable 
clinical suspicion of melanoma for thirty patients, and then wished to see results before 
approving of further administration. Likewise, the committee gave approval to a closely 
related experiment involving use of the same substances in patients with lung cancer. For 
that regime, the committee demanded feedback after fifteen patients. For a further 
related matter involving the same substances in patients with pulmonary carcinoma, the 
committee limited the work to five patients. In each case the dose was to exceed 2 
millicuries per patient. Edward A. Carr, Chairman, Subcommittee on Human Use, to 
William H. Beierwaltes, Director, Nuclear Medicine, 27 September 1968 ("This is to 
inform you that the Sub-committee on Human Use of Radioisotopes, at its meeting of 
September 26, 1968, approved the use of a single dose of NM-1 13 . . .") (ACHRE No. 
M1C-010495-A-6), 1. 

87. A researcher had applied to use sodium 22 in a tracer procedure with several 
patients. The committee was concerned that "a small but significant fraction of one of 
the radioisotopes might remain localized in the body for a long period of time . . ." 
Edward A. Carr, 3 June 1968 ("Sub-committee on Human Use of Radioisotopes, Minutes 
of the Meeting of June 3, 1968") (ACHRE No. MIC-010495-A-7), 1 . 

88. George V. LeRoy, 3 November 1953 ("Minutes of the Radioisotope 
Committee Meeting") (ACHRE No. DOE-122194-A-3), 1. 



317 



89. Paul C. Aebersold, Chief, Isotopes Division, to John Z. Bowers, Assistant to 
Director, Division of Biology and Medicine, 18 March 1948 ("Investigation of Patients 
Who Have Received Radioactive Isotopes") (ACHRE No. DOE-061395-E-1), 1. 

90. A comprehensive history of the application of radioisotopes is well beyond 
the scope of this chapter and would needlessly duplicate substantial histories already 
written. See, for example, J. Newell Stannard, Radioactivity and Health: A History 
(Springfield, Va.: Office of Scientific and Technical Information, 1988). 

91. An example is Konstantin N. Pavlou, William P. Steffee, Robert H. Lerman, 
and Belton A. Burrows, "Effects of Dieting and Exercise on Lean Body Mass, Oxygen 
Uptake, and Strength," Medicine and Science in Sports and Exercise 17(1 985): 466-47 1 . 
The study was conducted at the Boston University Medical School and the Boston VA 
Medical Center. 

92. There is a vast literature on radioiodine and the thyroid. Government studies 
specifically noted by the Veterans Administration as significant are the following: H. C. 
Allen, R. A. Libby, and B. Cassen, "The Scintillation Counter in Clinical Studies of 
Human Thyroid Physiology Using 1-131," Journal of Clinical Endocrinology and 
Metabolism 1 1 (1951): 492-51 1; B. A. Burrows and J. A. Ross, "The Thyroid Uptake of 
Stable Iodine Compared with the Serum Concentration of Protein-Bound Iodine in 
Normal Patients and in Patients with Thyroid Disease," Journal of Clinical 
Endocrinology and Metabolism 13 (1953): 1358-1368; S. A. Berson and R. S. Yalow, 
"Quantitative Aspects of Iodine Metabolism: The Exchangeable Organic Iodine Pool, 
and the Rates of Thyroidal Secretion, Peripheral Degradation and Fecal Excretion of 
Endogenously Synthesized Organically Bound Iodine," Journal of Clinical Investigation 
33 (1954): 1533-1552; M. A. Greer and L. J. DeGroot, "The Effect of Stable Iodide on 
Thyroidal Secretion in Man," Metabolism 5 (1956): 682-696; K. Sterling, J. C. Lashof, 
and E. B. Man, "Disappearance from Serum of 1-131 Labeled I-Thyroxine and 1- 
Triiodothyronine in Euthyroid Subjects," Journal of Clinical Investigation 33 (1954): 
1031; K. Sterling and R. B. Chodos, "Radiothyroxine Turnover Studies in Myxosema, 
Thyrotoxicosis, and Hypermetabolism Without Endocrine Disease," Journal of Clinical 
Investigation 35 (1956): 806-813. 

93. See, for example, J. F. Ross, "Cooperative Study of Radioiodine Therapy for 
Hyperthyroidism," Bulletin of the Committee on Veterans Medical Problems (National 
Academy of Sciences) (1952): 576-578. 

94. Gould A. Andrews, M.D., Samuel W. Root, M.D., and Herbert D. Kerman, 
M.D., "Clinical Studies with Gallium-72," 570-588 in Marshall Brucer, M.D. (ed.), 
Gould Andrews, M.D., and H.D. Bruner, M.D., "Clinical Studies with Gallium-72," 
Radiology 66 (1953): 534-613. 

95. OncoScint, developed by Cytogen, was approved by the FDA for diagnosis 
of colorectal and ovarian cancers on 29 December 1992, Product License Application no. 
89-0601, with Amendment no. 90-0278. The use of monoclonal antibodies to treat cancer 
is discussed in Oliver W. Press, M.D., Ph.D., et al., "Radiolabeled-Antibody Therapy of 
B-Cell Lymphoma with Autologous Bone Marrow Support," New England Journal of 
Medicine 329 (21 October 1993): 1219-1224. Progress in the field is reviewed in an 
accompanying editorial, Robert C. Bast, Jr., M.D., "Progress in Radioimmunotherapy," 
New England Journal of Medicine 329(21 October 1993): 1266-1268. 

96. Strontium 89, commercially available as Metastron from Amersham- 
Mediphysics, was approved on 18 June 1993, New Drug Application no. 20134. One of 
its therapeutic uses is described in an article by Arthur T. Porter. M.D., and Lawrence P. 



318 



Davis, M.D., "Systemic Radionuclide Therapy of Bone Metastases with Strontium-89," 
Oncology 8 (February 1994): 93-96. 

97. R. S. Yalow and S. A. Berson, "Assay of Plasma Insulin in Human Subjects 
by Immunological Methods," Nature 184 (1959): 1648. 



319 



nontherapeutic research on 

Children 



In the late 1940s and again in the early 1950s, Massachusetts Institute of 
Technology scientists conducting research fed breakfast food containing minute 
amounts of radioactive iron and calcium to a number of students at the Walter E. 
Fernald School, a Massachusetts institution for "mentally retarded" children. 1 
The National Institutes of Health, the Atomic Energy Commission, and the 
Quaker Oats Company funded the research, which was designed to determine 
how the body absorbed iron, calcium, and other minerals from dietary sources and 
to explore the effect of various compounds in cereal on mineral absorption. 

In 1961, researchers from Harvard Medical School, Massachusetts 
General Hospital, and Boston University School of Medicine administered small 
amounts of radioactive iodine to seventy children at the Wrentham State School, 
another Massachusetts facility for mentally retarded children. With funding from 
the Division of Radiologic Health of the U.S. Public Health Service, the scientists 
conducting this experiment used Wrentham students to test a proposed 
countermeasure to nuclear fallout. Specifically, the study was meant to determine 
the amount of nonradioactive iodine that would effectively block the uptake of 
radioactive iodine that would be released in a nuclear explosion. 

Recently, these two studies have received considerable media attention, 
and an official Massachusetts state task force has reported on both episodes in 
some detail. 2 Although they represent special cases because they involve 
institutionalized children, the Fernald and Wrentham experiments nonetheless are 
the most widely known examples of a category of research that raises particular 
concerns for the Committee: nontherapeutic experimentation on children. 



320 



Chapter 7 

Experiments involving children are important to the Committee for two 
reasons. First, children are more susceptible than adults to harm from low levels 
of radiation, and thus as a group they are more likely than adults to have been 
harmed as a consequence of their having been subjects of human radiation 
experiments. Second, an evaluation of research with children is critical to 
determining whether any former subjects of radiation experiments should be 
notified in order to protect their health, one of our specific charges. 3 Subjects 
who were children at the time of their exposure are more likely than adults to be 
candidates for such notification, both because of their increased biological 
sensitivity and because they are more likely to still be alive. (See chapter 18 for 
the Committee's recommendations with respect to notification and follow-up.) 

We elected to focus on pediatric research that offered subjects no prospect 
of medical benefit, so-called nontherapeutic research, because it is this kind of 
research that has generated the most public concern and is the most ethically 
problematic. This is not to say, however, that experiments on children in which 
the children stand to benefit medically never raise ethical issues; such research 
certainly can and does. But in deciding how to allocate our limited resources, we 
chose to concentrate where the issues are mostly sharply drawn. Also, because 
most nontherapeutic research with children involved tracer doses of radioisotopes, 
focusing on this work allowed us a window into radioisotope research generally. 

We begin the chapter by setting the context for nontherapeutic radiation 
experiments on children. We review those factors that make nontherapeutic 
research on children ethically problematic and how such research has been 
viewed historically. We next consider what the practices and standards were for 
research on children in the 1940s, 1950s, and 1960s. This is a continuation of the 
discussion in chapter 2, which focused on professional standards and practices for 
human research. 

The next three sections address human radiation experiments in terms of 
the central ethical issues raised by nontherapeutic research involving children- 
level of risk, authorization for the involvement of children, and selection of 
subjects. To address the question of risk, we analyzed twenty-one nontherapeutic 
radiation experiments with children conducted during the 1944-1974 period. The 
focus of this analysis is whether it is likely that any of the subjects of these 
experiments was harmed or remains at risk of harm attributable to research 
exposures. A table summarizing these experiments and our risk estimates can be 
found at the end of this chapter. The twenty-one experiments were selected from 
eighty-one pediatric radiation research projects identified by the Committee from 
government documents and the medical literature. Although these eighty-one by 
no means constitute all the pediatric radiation research conducted during this 
time, they include what are likely fairly typical examples of such research. Of the 
eighty-one, thirty-seven studies were judged to be nontherapeutic, and twenty-one 
of these were conducted or funded by the federal government and thus fell under 
the charge of the Committee. Included within these twenty-one studies were the 

321 



Part II 

two nutrition experiments conducted at the Fernald School and one fallout-related 
study conducted at the Wrentham School discussed in the introduction to this 
chapter. All twenty-one studies employed radioisotopes to explore human 
physiology and pathology. 

We turn next to a consideration of how authorization for the inclusion of 
the children in these experiments was obtained and who these children were. 
Unfortunately, for most of these experiments, little is known about either of these 
issues. The last section of the chapter focuses specifically on the experiments at 
the Fernald School where, thanks to the work of the Massachusetts Task Force on 
Human Subject Research, relevant information is available. Throughout the 
chapter, we focus only on research in which children could not have benefited 
medically. The Committee did not have the resources to pursue two related areas 
of research—nontherapeutic research on pregnant women and therapeutic research 
on children. We include two capsule descriptions of examples of these types of 
research at the end of this chapter. 

THE CONTEXT FOR NONTHERAPEUTIC RESEARCH WITH 
CHILDREN 

Children as Mere Means 

In both law and medical ethics, it has long been recognized that children 
may not authorize medical treatment for themselves, except in special 
circumstances. 4 Instead, authorization must be sought from the parent. 
Historically, the source of this respect for parental authority rested upon the view 
that children were the property of their parents, and thus parents had the right to 
determine how their "property" Was to be treated. Today, we still speak of 
parental rights, although the justification for these rights no longer rests on an 
analysis of children as property. Instead, respect for the rights of parents is 
viewed as a mechanism for valuing and fostering the institution of the family and 
the freedom of adults to perpetuate family traditions and commitments. Another 
important line of justification for respecting the authority of parents relies not on 
a recognition of parental rights but on the view that the interests of the child are 
generally best served by ceding decisional authority to the parent. The parent is 
thought not only to be in the best position to determine what is in the interests of 
the child but is also thought to be generally motivated to act in the child's best 
interests. 5 

When research involving children offers a prospect of medical benefit to 
the child-subject, the application of the above analysis is straightforward. Parents 
are generally thought to have the authority to determine whether their children 
should be made subjects of such research. Certainly today, any use of a child in 
research would not be ethically acceptable or legally permissible without the 
parent's permission/' Where the research does not offer any prospect of benefit to 

322 



Chapter 7 

the child, however, the legitimacy of the parent as authorizer is less clear. 

Respect for the authority of parents to make decisions for their children 
and otherwise control their children's lives is not without bounds. The law 
recognizes several exceptions, designed primarily to protect the child from what 
society at large considers to be unacceptable or unjustifiable harm or risk of 
harm. 7 Laws against the physical abuse of children are perhaps the most obvious 
example of such limitations on parental authority. In the context of research, the 
question arises of whether a parent has the authority to permit a child to be put at 
risk of harm in an experiment from which the child could not possibly benefit 
medically. In this case, the child is to be used as a means to the ends of others. 
Children are not in a position to determine for themselves whether they wish to 
agree to such a use and thus cannot themselves render the use morally acceptable. 
Should parents have such authority? Should anyone? 

This question was resolved as a matter of public policy in the 1970s 
through the work of the National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research and the subsequent adoption, in 
1983, of federal regulations governing research involving children that were 
guided by the recommendations of the National Commission. 8 These regulations 
state that children can participate in federally funded research that poses greater 
than minimal risks to the subject if a local review committee (an institutional 
review board, or IRB) finds that the potential risk is "justified by the anticipated 
benefit to the subjects"; "the relation of the anticipated benefit to the risk is at 
least as favorable to the subjects as that presented by available alternative 
approaches"; and "adequate provisions are made for soliciting the assent of the 
children and permission of their parents or guardians." 9 The word consent is 
purposely avoided in these regulations to distinguish parental permission and 
minor assent from the autonomous, legally valid consent of a competent adult. 

Federal regulations do allow nontherapeutic research on children if an IRB 
determines that the research presents "no greater than minimal risk" to the 
children who would serve as subjects, although no clear definition of what 
constitutes minimal risk is provided. 10 As with therapeutic pediatric research, 
parents or guardians must grant "permission" and children who are deemed 
capable must offer "assent." 

The regulations also allow for nontherapeutic research with children that 
does present more than minimal risk, again with parental permission and assent of 
the child (as appropriate), but only if 'the risk represents a minor increase over 
minimal risk, the procedures involved are commensurate with the general life 
experiences of subjects, and the research is likely to yield knowledge of "vital 
importance" about the subjects' disorder or condition." Research with children 
that is not otherwise approvable may be permitted, but only under special, and 
presumably rare, circumstances. In addition to local IRB review, such research 
must withstand the special scrutiny of the secretary of the agency sponsoring the 
research, who is to be advised by a special IRB. 12 The secretary must also allow 

323 



Part II 

the opportunity for "public review and comment" on a proposed nontherapeutic 
research project that is not otherwise approvable. 

The regulations thus draw a sharp distinction between therapeutic and 
nontherapeutic research. Nontherapeutic research, while severely restricted, is 
not banned. The decision to permit parents to authorize the use of their children in 
nontherapeutic research reflects both the recognition that some important 
advances in pediatrics could come only from research with children that was of no 
benefit to them and the recognition that we all—as parents, as potential future 
parents, and as members of society— share in the interest of advancing the health 
of the young. At the same time, however, parental authority to permit such use of 
a child is generally restricted to research judged to pose little risk; as important as 
it is to promote the welfare of children (as a class), this interest justifies only 
minor infringements of the principle not to use people as mere means to the ends 
of others. 

These 1983 regulations, and the reasoning behind them, were the 
culmination of considerable public debate and scholarly analysis, much of which 
occurred in the 1970s. To situate properly the experiments of interest to the 
Committee, it is necessary to examine the social and professional roots of the 
issues and arguments that ultimately led to the federal regulations. 

Public Attitudes, Professional Practices 

Attitudes and Practices Prior to 1944 

There was significant research interest in infants and children as early as 
the eighteenth century, as scientists began to experiment with vaccines and 
immunization. Children were particularly valuable subjects for this type of 
research because in general, they were less likely than adults to have been 
exposed to the disease being studied. 13 A child's response to immunizations was 
also of great interest because most immunizations are performed during 
childhood. 

During the nineteenth century, the Industrial Revolution greatly increased 
the number of child laborers, and the public began to acknowledge the need for 
laws to protect children from abuse. 14 Physicians started to specialize in 
pediatrics, studying specifically the health problems and diseases that afflicted 
children. Simultaneously, as social reformers were creating a wide range of 
institutions for children, such as orphanages, schools, foundling homes, and 
hospitals, scientists recognized the value of research conducted in these types of 
institutions. In the late nineteenth and early twentieth centuries, Alfred F. Hess, 
the medical director of the Hebrew Infant Asylum in New York City, conducted 
pertussis vaccine trials and undertook extensive studies of the anatomy and 
physiology of digestion in infants at the asylum. According to Advisory 
Committee member and historian Susan Lederer, Hess sought to take advantage 

324 



Chapter 7 

of the conditions in the asylum as they approximated those "conditions which are 
insisted on in considering the course of experimental infection among laboratory 
animals, but which can rarely be controlled in a study of infestation in man." 15 

Although many shared Hess's laudable goal of improving the health of 
asylum children, many people drew the line at the pediatrician's investigations of 
scurvy and rickets. In order to study the disease, Hess and his colleagues 
withheld orange juice from infants at the asylum until they developed lesions 
characteristic of scurvy. Responding to the public discussion of the ethics of 
using children in such nontherapeutic experiments, the editors of one American 
medical journal insisted that such investigations gave the children an opportunity 
to repay their debt to society, even as they conceded that experimentation on 
human beings should be limited to "children as may be utilized with parental 
consent." 16 

Hess's work was not the only case in which experiments involving 
children attracted negative public opinion. In 1896, for example, American 
antivivisectionists attacked a Boston pediatrician, Arthur Wentworth, who 
performed lumbar punctures on infants and children in order to establish the 
safety and utility of the procedure. The antivivisectionists were particularly 
alarmed because this procedure, which caused pain and discomfort, did not confer 
any benefits to the subjects. John B. Roberts, a physician from Philadelphia, 
labeled Wentworth's procedures "human vivisection," saying that "using the 
children in the hospital without explaining his plan to their mothers or gaining 
their permission intensified public fear of hospitals." 17 

The twentieth century brought new drugs and advanced technologies, 
which allowed for increased research on children. The conduct of this 
experimentation, however, was largely left to the individual investigator. When 
his experimental gelatin injections provoked "alarming symptoms of prostration 
and collapse in three normal children (including a 'feeble-minded' four-year-old 
girl), the physician Isaac Abt stopped his pediatric experiments and began 
experimenting on rabbits." 18 Meanwhile, legislation was being proposed 
throughout the country to protect children and pregnant women from 
experimenting physicians. Two proposals were introduced in the U.S. Senate in 
1900 and 1902; proposals '"to prohibit such terrible experiments on children, 
insane persons and pregnant women . . . ,' and to ensure 'that no experiment 
should be performed on any other human being without his intelligent written 
consent' were introduced in the Illinois legislature" in 1905 and 1907; in 1914 and 
1923, the New York legislature considered bills that prohibited exoerimentation 
with children. 19 Although these bills did not become law, it is clear that some 
unease concerning nontherapeutic research on children existed among the public 
and elected officials. 

Reaction to the polio vaccine trials conducted during the 1930s further 
demonstrated the growing discomfort over pediatric experimentation as thousands 
of American children were involved in what some considered at the time to be 

325 



Part II 

premature human trials of the polio vaccine. Although it appears that parental 
consent was obtained for a number of these studies, the controversy over these 
trials stalled polio vaccine research for almost two decades and generally made 
investigators ambivalent about the use of human subjects. 20 

Although there are no legal cases that bear directly on nontherapeutic 
research with children during this period, an appellate court ruling in 1941, 
Bonner v. Moran, involving the performance of a nontherapeutic medical 
procedure on a child without parental consent, suggests how such a case might 
have been decided. 21 John Bonner, a fifteen-year-old African-American boy from 
Washington, D.C., had undergone an experimental skin graft for the benefit of 
Clara Howard, a cousin suffering from severe burns. When he discovered that 
John Bonner had the same blood type as the burn victim, Howard's plastic 
surgeon, Robert Moran, persuaded Bonner to allow him to fashion "a tube of 
flesh" by cutting from the boy's "arm pit to his waist line." 22 This procedure, 
however, was conducted without the consent of a parent, as "his mother, with 
whom he lived, was ill at the time and knew nothing about the arrangement." 23 
Moran then attached the free end of Bonner's flesh tube to Clara Howard, hoping 
that the flesh-and-blood link would bring benefit to the burned girl. Due to poor 
circulation in the tube, the procedure did not help the burn patient and put the 
healthy boy, who was required to stay in the hospital for two months, at 
significant risk (and left him with permanent scars). Bonner's mother brought suit 
against Moran for assault and battery. 

The appellate court based its ruling against Moran on what it perceived as 
a disturbing combination of a lack of direct benefit for John Bonner and a lack of 
permission from the boy's mother: 

[H]ere we have a case of a surgical operation not 
for the benefit of the person operated on but for 
another. . . . We are constrained, therefore, to feel 
. . . that the consent of the parent was necessary. 24 

The court did not refer to the episode as an instance of experimentation, but the 
parallels between this novel procedure performed for the benefit of another and a 
nontherapeutic medical experiment are quite powerful. 25 

Attitudes and Practices 1944-1974 

As best the Committee can establish, there were no written rules of 
professional ethics for the conduct of research on children prior to 1964. Taken 
literally, the Nuremberg Code, which requires that all subjects of research "have 
legal capacity to give consent," precludes all research with children. 26 There is no 
reason to believe, however, that the judges at Nuremberg meant to impose such a 
prohibition, and the Nuremberg Code did not result in a ban on research with 

326 



Chapter 7 

children. 

Pediatric research flourished after World War II, as did biomedical 
research in general. What is less clear is how this research was conducted, and on 
whom. One source of evidence about legal thinking on pediatric research, if not 
actual practice, is the writings of Irving Ladimer, a lawyer who, in 1958, was 
completing a doctoral degree in juridical science at the same time he was 
employed as an administrator at the National Institutes of Health. Ladimer 
concluded his doctoral dissertation, "Legal and Ethical Implications of Medical 
Research on Human Beings," with an appendix devoted to the issues surrounding 
"Experimentation on Persons Not Competent to Provide Personal Consent," 
whom he defined broadly as minors and mental incompetents. 27 Ladimer argued 
that it was "permissible to employ minors and incompetents as subjects of 
medical investigations . . . where there is informed consent by a parent or 
guardian (including the state) for procedures which also significantly benefit or 
may be expected to benefit the individual. " 2X Ladimer was less sanguine, 
however, about nontherapeutic research with these populations. He expressed 
particular concern about the use of institutionalized children— even with proxy 
permission—in research that did not hold the possibility of personal benefit: 
"Permission given by parents or the state to utilize institutionalized children, 
without any suggestion of benefit to the children, may well be beyond the ambit 
of parental or guardianship rights." 29 

Ladimer did, however, leave open a window for the use of legally 
incompetent subjects in nontherapeutic research, but he clearly harbored great 
discomfort with his own suggestion: 

[T]he availability of certain persons, not able to 
consent personally, may constitute a strategic 
resource in terms of time or location not otherwise 
obtainable. It must be remembered, however, that 
the Nazis hid behind this rationalization in 
explaining certain highly questionable or 
clandestine medical experiments. Such justification 
should not even be considered except in dire 
circumstances. If ever employed, it should not be 
assimilated into the concept of personal benefit, else 
there may be no legal or ethical control for the 
protection of both prospective subject and 
investigator and their individual integrity. 30 

As part of the Committee's Ethics Oral History Project, we interviewed 
two pediatricians who were beginning their careers in academic medicine in the 
late 1940s. One of these respondents, Dr. Henry Seidel, had some research 
experience with institutionalized children. He noted that "we got access [to the 

327 



Part II 

children] very easily," and although his research was merely observational, it was 
"not hard to imagine" that experimental research with these children could have 
been conducted. 31 When asked about the studies conducted by Dr. Saul Krugman 
on institutionalized children at the Willowbrook State School (discussed later in 
this chapter), Seidel observed, "I didn't have any problem imagining that 
possibility. In retrospect, I'm sure it could happen, you know. There was 
something about those reports that rang true. . . ." 32 William Silverman, the other 
pediatrician interviewed, had clear recollections of how research was conducted 
in pediatrics at that time. He recalled that, in the 1950s, many pediatricians, 
including himself, believed that it was not necessary to obtain the permission of 
parents before using a pediatric patient as a subject in research-even if the 
research was nontherapeutic (he has since become a strong proponent of the 
parental permission requirement in pediatric research). 33 He also asserted that 
performing nontherapeutic experiments on children without authorization from 
parents was part of a broader "ethos of the time" in which "everyone was a 
draftee" in a national war on disease. 34 Dr. Silverman's account squares with the 
picture that emerged in chapter 2 of practices in research with adults, in which it 
was not uncommon to use adult patients as subjects of research without their 
knowledge or consent. 

Silverman was among the researchers invited by Boston University's Law- 
Medicine Research Institute (LMRI) to participate in a conference on "Social 
Responsibility in Pediatric Research" held in May 1961. 35 This meeting was one 
in a series of closed-door conferences organized by LMRI to investigate actual 
practices among clinical researchers. The transcripts of the conference provide an 
important window onto practices and attitudes of the time; in large measure, they 
confirm Silverman's recollection of his own position some thirty-five years ago. 
Early in the meeting, Silverman asserted that "there is an unwritten consent by 
being a living person at this time to participate in this kind of advancement of 
knowledge [that is, nontherapeutic pediatric research]." 3 ' 1 Some of the other 
participants employed the same analogy to the military draft that Silverman 
recently used to relate his recollections. 

However, there was by no means unanimity about the appropriateness of 
this view: 

Dr. A: [Dr. B] says that this [research without 

consent] is like military conscription. 

Dr. C: Not comparable. We voted to do military 

conscription. 37 

The proceedings of the conference suggest that while it may not have been 
uncommon for pediatric patients to be used as subjects of nontherapeutic research 
without the permission of their parents, at least some physician-investigators, 
including investigators who followed this practice, thought it was morally wrong 

328 



Chapter 7 

to do so. Consider, for example, a story relayed by one pediatrician-investigator 
at the conference who seemed to embrace with particular earnestness the desire of 
the conference organizers to learn the unvarnished reality of clinical research. In 
the opening minutes of the meeting, this researcher reminded his colleagues that 
"the question for us to discuss here today is how we operate on a daily basis." 38 
He offered for discussion a provocative case from his personal experience in 
which he and his associates "wanted [to do] lumbar punctures on newborns. " 39 
He explicitly noted that "this study [was] not of benefit to the individual; it was an 
attempt to learn about normal physiology." 40 One of the other conferees asked, 
"Did you ask [parental] permission?" The researcher responded, "No. We were 
afraid we would not get volunteers." 41 The case prompted a great deal of 
discussion at the conference, but perhaps most tellingly this researcher frankly 
acknowledged toward the end of the discussion— in a meeting that had begun with 
an assurance of confidentiality from the organizers—that he had "sinned" in 
carrying out these lumbar punctures in "normal infants" without parental 
permission. 42 

The proceedings of the conference also suggest that at least some 
pediatrician investigators routinely obtained the permission of parents before 
embarking on research with their children. It is perhaps significant that the 
pediatric researcher who articulated this position at the conference was from 
Canada— and the conference transcript seems to suggest that he was providing a 
general characterization of practices in his country: 

Dr. A: Let's ask [Dr. B] from Canada. 
Dr. B: We have been quite sticky on consent. If we 
want a biopsy or a radioactive exposure and the 
parent says "no" then we don't do it. . . . The 
question of morals is too valuable. 43 

If this statement represents the sensitivity of Canadian pediatrician-investigators 
to issues of parental permission (which this single quotation does not prove), 
there is no obvious explanation as to why many of their colleagues in the United 
States behaved differently. 

The LMRI conference is noteworthy not only for what it reveals about the 
range of views and practices concerning parental permission for nontherapeutic 
research, but also for the unanimity expressed about the importance of obligations 
to prevent or minimize harm to pediatric subjects of research. Minimizing risk 
was recognized by those at the conference as the most important (and, for some 
participants, the only) moral duty of pediatric investigators. 44 

Three years after the LMRI conference, in the summer of 1964, the World 
Medical Association ratified a code of ethics for human experimentation at a 
meeting in Helsinki. Unlike the Nuremberg Code, this statement, known as the 
Declaration of Helsinki, recognizes that research may be conducted on people 

329 



Part II 

with "legal incapacity to consent." 45 The Declaration distinguishes between two 
kinds of research: "Clinical Research Combined with Professional Care" and 
"Non-therapeutic Clinical Research." 46 It permits the use of people with legal 
incapacity to consent as subjects in both kinds of research, provided that the 
consent of the subject's legal guardian is procured. 

Subjects of the first kind of research are referred to as patients; disclosure 
to and consent from patient-subjects are required by the Declaration, "consistent 
with patient psychology." 47 The Declaration does not specify whether 
considerations of "patient psychology" also could justify not obtaining the 
consent of the guardian where the subject does not have the legal capacity to 
consent. 

The subjects of "non-therapeutic clinical research" are not referred to as 
patients but as human beings who must be "fully informed" and whose "free 
consent" must be obtained. 48 The Declaration also requires that nontherapeutic 
research be discontinued if in the judgment of the investigators to proceed would 
"be harmful to the individual." 49 Thus, although the Declaration permits parents 
to authorize the use of their children as subjects in nontherapeutic research, such 
research is not intended to be "harmful" to the subjects. 

The language and reasoning of the Declaration was unclear and confusing 
with regard to clinical research, both therapeutic and nontherapeutic, on legally 
incapacitated individuals. It was revised in 1 975, at a time when the ethics of 
research with human subjects was receiving considerable public attention in the 
United States (see chapter 3). 

Both in the 1960s and early 1970s, public controversies erupted about 
several cases of research involving human subjects, controversies that led to the 
establishment of the National Commission and publication of the federal 
regulations (see chapter 3). One of the most well known of these cases involved 
research on institutionalized children. During the 1950s and 1960s, Dr. Saul 
Krugman of New York University conducted studies of hepatitis at the 
Willowbrook State School, an institution for the severely mentally retarded. 50 To 
study the natural history, effects, and progression of the disease, Krugman and his 
staff systematically infected newly arrived children with strains of the virus. 
Although the investigators did obtain the permission of the parents to involve 
their children in the research, critics of the Willowbrook experiments maintained 
that the parents were manipulated into consenting because, at least in the later 
years of the research, the institution was overcrowded and the long waits for 
admittance were allegedly shorter for children who were entering the research 
unit. Henry Beecher, a Harvard anesthesiologist whose impact on the history of 
research ethics is detailed in chapter 3, condemned Krugman and his staff for not 
properly informing the parents about the risks involved in the experiment. 51 
Beecher also challenged the legal status of parental consent when no therapeutic 
benefit for the child was anticipated. A New York state senator, Seymour R. 
Thaler, criticized the Willowbrook research on the pages of the New York Times 

330 



Chapter 7 

in 1967, only to come to its defense later in 1971. Also in the early 1970s 
Willowbrook became the subject of a heated debate in the medical literature. 52 

Interestingly, Dr. Krugman was one of the participants at the LMRI 
"Social Responsibility in Pediatric Research" conference where he expressed 
pride that he routinely obtained permission from the parents of the children in his 
studies. In that group in 1961, Krugman was thus among those pediatric 
investigators most sympathetic to the position that children could not be used as 
mere means to the ends of the researcher without the authorization of the parent. 

AEC Requirements for Radiation Research With Children 

Although in the 1940s and 1950s there were apparently no written rules of 
professional ethics for pediatric research in general, there were guidelines for the 
investigational use of radioisotopes in children. In 1949, the Subcommittee on 
Human Applications of the Atomic Energy Commission's Isotope Division 
established a set of rules to judge proposals submitted by researchers for the use 
of radioisotopes in medical experiments with human subjects, including "normal 
children."" These standards appeared in the fall 1949 supplement to the AEC's 
isotope catalogue and price list. Under the heading "Normal Children" the 
isotope catalogue offered the following statement: 

In general the use of radioisotopes in normal 
children is discouraged. However, the 
Subcommittee on Human Applications will 
consider proposals for such use in important 
researches, provided the problem cannot be studied 
properly by other methods and provided the 
radiation dosage level in any tissue is low enough to 
be considered harmless. It should be noted that in 
general the amount of radioactive material per 
kilogram of body weight must be smaller in 
children than that required for similar studies in the 
adult. 54 

These guidelines did not mention consent--of parents, guardians, or 
children. 55 Instead, this statement simply discouraged nontherapeutic experiments 
with children. The guidelines did not, however, suggest that the practice was 
completely inappropriate; the subcommittee asserted that "important" research 
using "harmless" levels of radiation dosage with children was acceptable. The 
crucial terms important and harmless were left undefined. 

It seems reasonable to expect that "important" pediatric research would 
address a significant medical problem affecting children or would explore key 
aspects of normal human physiology-relevant to health promotion or disease 

331 



Part II 

prevention— for which research on children is indispensable. By these standards, 
the twenty-one nontherapeutic radiation experiments with children whose risks 
we review in the next section of this chapter could all be said to address important 
questions relevant to pediatric health care. This judgment is not based on a 
determination of whether a given study proved important in the subsequent 
development of a particular field. Such retrospective analysis would place an 
unreasonable burden on investigators of the past, as research is an inherently 
speculative enterprise. Many experiments that prove to be of little value in the 
advance of medical knowledge are, at the time they are implemented, well 
designed and appropriate attempts to address important research questions. 

It is easier to infer what the members of the AEC Subcommittee on 
Human Applications would have considered "important" research than what the 
subcommittee would have considered "harmless" radioisotope research. Acute 
toxicity is not seen following administration of nontherapeutic (tracer) doses of 
radioisotopes. Thus, the principal potential harm from radiation exposure at 
lower doses is the subsequent development of cancer. In the 1940s and 1950s, 
some in the field apparently discounted the risk, while others were wary of a 
prevailing uncertainty. Dr. John Lawrence, an early radioisotope researcher at the 
University of California, described how some researchers conducted public 
demonstrations of tracers, using an "unsuspecting physician out of the audience to 
act as the guinea pig," presumably to reassure the audience that tracers were 
innocuous. 56 By contrast, other investigators focused on the tragedy of the radium 
dial painters, concerned that this might be repeated with man-made radionuclides. 

Evidence of how well the AEC enforced its 1949 guidelines with respect 
to research on children is elusive (see chapter 6). AEC correspondence with 
researchers at the Fernald School suggests that in at least one case there was 
oversight of research in which children were administered radioisotopes. 57 

RISK OF HARM AND NONTHERAPEUTIC RESEARCH 
WITH CHILDREN 

The Twenty-One Case Examples 

During the 1944-1974 period, there was an explosion of interest in the use 
of radioisotopes in clinical medicine and medical research, including pediatrics. 
The twenty-one research projects we review here include only a small number of 
all those that were likely conducted. These twenty-one do include, however, 
every nontherapeutic study that was funded by the federal government and fell 
into our original group of eighty-one pediatric radiation experiments. The table 
that appears at the end of the chapter provides information about the number of 
children involved in each of the experiments, the radioisotopes used, and risk 
estimates for cancer incidence. These twenty-one represent a subset of eighty-one 
studies identified in documents of the Atomic Energy Commission and a review 

332 



Chapter 7 

of the medical literature that met the criteria described above." 

All twenty-one projects analyzed in detail involve the administration of 
radioisotopes to children in order to better understand child physiology or to 
develop better diagnostic tools for pediatric disease. In this respect, the studies 
supported by the federal government do not differ from those reviewed that had 
other funding sources. With the exception of the study at the Wrentham school to 
evaluate protective measures for fallout, none of the twenty-one experiments 
reviewed was related to national defense concerns. Seventeen of the twenty-one 
experiments involved the use of iodine 131 for the evaluation of thyroid function. 
Three examples of research reviewed by the Committee will help illustrate 
the nature of the experiments and the risks posed to children. In the first example 
investigators at Johns Hopkins in 1953 injected iodine 131 into thirty-four 
children from ages two months to fifteen years with hypothyroidism and an 
unknown number of healthy "control" children in order to better understand the 
cause of this disease. 59 Iodine is normally taken up and used by the thyroid gland 
for hormone production. In this experiment, a radiation detector was placed over 
the thyroid to detect the amount of iodine 1 3 1 taken up. Most children with 
hypothyroidism have an underdeveloped thyroid gland, in which case only very 
low levels of iodine 131 uptake will occur. Indeed, this is what the investigators 
found in this experiment, which was one of the first projects to use iodine 131 
uptake as a measure of thyroid function in children. Hypothyroidism is a 
relatively common condition (1 per 4,000 births) that can cause profound mental 
retardation if untreated. Today, better diagnostic tests for thyroid function 
including radioimmunoassay and effective thyroid hormone replacement have 
virtually eliminated hypothyroidism as a cause of mental retardation in the 
developed world. 

A second example of research reviewed by the Committee is an 
experiment by investigators at the University of Minnesota in 1951 in which four 
children with nephrotic syndrome were injected with an amino acid labeled with 
sulfur 35, along with two "control" children hospitalized for other conditions. 60 
Nephrotic syndrome is a serious pediatric condition in which protein is excreted 
by the kidneys in large quantities. There was controversy at the time over 
whether children with nephrotic syndrome have low blood protein levels solely 
because of renal losses or whether they also have impaired protein production 
This experiment looked at the incorporation of the radioisotope-labeled amino 
acid into protein, and the results suggested that the protein production in children 
with nephrotic syndrome is normal. 

A third example of research reviewed by the Committee is a study of 
iodine 125 and iodine 131 uptake by eight healthy children performed at the Los 
Alamos Laboratory in 1963. 61 The purpose of the study was to evaluate the use of 
radioisotopes in very small doses (nanocurie levels) as a measure of thyroid 
function. The study demonstrated that the technique was scientifically valid and 
exposed the children to smaller radiation doses than earlier methods 



333 



Part II 
Estimating Risk 

How can the risks posed to children in these types of experiments be 
estimated? The primary risk posed by the administration of radioisotopes is the 
potential development of cancer years, even decades, after the exposure. As will 
be discussed further, the risk of cancer following external radiation exposure was 
not well documented until the late 1950s and the early 1960s. Thus, the published 
reports of research projects prior to that time rarely discuss the issue of long-term 
risks. 

The principles of risk assessment for radioisotopes are laid out in "The 
Basics of Radiation Science" at the end of "Introduction: The Atomic Century." 62 
To review: the increased risk of cancer is generally assumed to be proportional to 
the dose of radiation delivered to the various organs of the body. This dose 
depends upon a number of factors, including the amount of radioactivity 
administered, its chemical form (which determines which organs will be 
exposed), and how long it stays in the body, which in turn depends upon the 
radioactive decay rate and the body's normal excretion rate for that substance. 
For many radioisotopes, the overall personal dose can be derived by the 
"effective-dose method," in which the doses to the ten most sensitive organs are 
computed and added together, weighting the various organs in proportion to their 
radiosensitivity. Thus, this effective dose can be thought of as producing the 
same excess risk of cancer (all sites combined) as if the whole body had received 
that amount as a uniform dose. This risk is then computed by multiplying the 
effective dose by established risk estimates per unit dose for various ages. For 
this chapter, the Advisory Committee has adopted the effective doses and risk 
estimates tabulated by the International Commission on Radiation Protection and 
the National Council on Radiation Protection. 63 The lifetime-risk estimate used in 
this chapter is 1/1,000 excess cancers per rem of effective dose for children and 
fetuses exposed to slowly delivered radiation doses, like those from radioactive 
tracers. 

The risks of thyroid cancer following exposure to radioactive iodine 
(generally 1-131) represent a special case for three reasons. First, use of the 
effective-dose method is inappropriate because the dose is much greater to the 
thyroid than for other organs, and the lifetime risk is therefore dominated by the 
thyroid cancer risk. Therefore, risk is best calculated using only the thyroid dose 
and its associated risk. Second, the thyroid cancer risk varies even more by age 
than for other cancers. Third, the risk for iodine 1 3 1 has not been measured 
directly, but several lines of evidence suggest that it may be substantially lower 
than for external radiation. For this chapter, the Advisory Committee has adopted 
estimates provided by three follow-up studies of external irradiation of the thyroid 
by x rays or gamma rays in childhood: 2,600 children who received x-ray 
treatment for enlarged thymus glands in the first year of life; 64 1 1,000 children 
who were treated by x rays in Israel for ringworm under age ten; 65 and Japanese 

334 



Chapter 7 

atomic bomb survivors under age twenty. 66 The risk estimates from these studies 
were divided by three to convert them to internal iodine 131 exposures. 67 The 
estimates from these studies are for cancer incidence; for mortality we have 
divided them by 10, since 90 percent of thyroid cancers are curable. The resulting 
estimates are summarized in table 1 . These are the same estimates used by the 
Massachusetts Task Force, which investigated the Fernald and Wrentham 
experiments. 68 

We can use data from the previously described Johns Hopkins iodine 1 3 1 
study as an example. In this study, the amount of radioactivity administered was 
1.75 microcuries per kilogram body weight; equivalent to 44 microcuries in a 
seven-year-old child weighing 25 kilograms. Based on interpolation of the tables 
in ICRP 53, and assuming a 13 percent thyroid uptake, this would produce a 
thyroid dose of 1 15 rem to a child aged seven. In this age range (5-9), the lifetime 
risk of developing thyroid cancer would be calculated by multiplying this dose by 
20 per million person rems to produce an estimate of 2.3 cases per 1,000 exposed 
individuals, or 0.23 percent for a particular child. The risk of dying of thyroid 
cancer would be one-tenth of this, or 0.023 percent. 

The twenty-one experiments subjected to the Committee's detailed risk 
analysis included approximately 800 children. Eleven of the studies produced 
estimates of average risk of cancer incidence within the range of 1 and 0.1 
percent; eight studies ranged within 0.09 and 0.01 percent, and the remaining two 
studies produced average risk estimates of 0.001 percent. The maximum potential 
risk estimate was 2.3 percent in a few children aged one to two years at the time 
of exposure. The average risk of cancer incidence for the Fernald radioiron and 
radiocalcium studies were 0.03 percent and 0.001 percent respectively, and for the 
Wrentham fallout (iodine 131) study, 0. 10 percent. All of the highest-risk 
experiments involved iodine 131, and hence the risks of dying of cancer would be 
about ten times smaller. (See table 2 at the end of this chapter for further details.) 

Based on the average risk estimate for each of the twenty-one 
experiments, we would estimate an excess cancer incidence of 1 .4 cases for the 
entire group of 792 subjects. However, given the uncertainties built into the risk 
analysis, it is also possible that no excess cases resulted. Furthermore, since most 
of that excess would have been thyroid cancer, it is particularly unlikely that any 
cancer deaths would have been caused. Finally, as thyroid cancer does occur in 
the general population, it would be difficult to attribute these cases to an 
individual's involvement in research. In addition, any cases of thyroid cancer 
among former subjects attributable to their participation in research conducted in 
the 1940s and 1950s are likely to have occurred already, although there is little 
long-term follow-up data to know for certain what the ultimate lifetime risk might 
be. 



335 



Part II 



Table 1. Summary of Risk Estimates for Thyroid Cancer 

from Iodine 131 



EXPOSURE AT VARIOUS AGES 


Age 


0-4* 


5-9 + 


10-14* 


15-19 § 


Lifetime risk" of cancer incidence per million exposed per rem 


Males 


27 


13 


6.7 


1.9 


Females 


53 


27 


13 


3.7 


Both 


40 


20 


10 


2.8 


Lifetime risk of cancer mortality per million exposed per rem 


Males 


2.7 


1.3 


0.7 


0.2 


Females 


5.3 


2.7 


1.3 


0.4 


Both 


4.0 


2.0 


1.0 


0.3 



* From R. E. Shore et al., "Thyroid Tumors Following Thymus Irradiation," 
Journal of the National Cancer Institute 74 ( 1 985): 1 1 77- 1 1 84, based on 2.9 cases per 
million person-year-rem. 

t From E. Ron and B. Modon, "Thyroid and Other Neoplasms Following 
Childhood Scalp Irradiation," in J. D. Boice, Jr., and J. F. Fraumeni, Jr., eds., Radiation 
Carcinogenesis: Epidemiology and Biological Significance (New York: Raven, 1984), 
139-151, based on the risk in this age group being half that in the 0-4 age group. 

\ From R. L. Prentice et al., "Radiation Exposure and Thyroid Cancer Incidence 
Among Hiroshima and Nagasaki Residents," National Cancer Institute Monographs 62 
(1982): 207-212, based on the risk in this age group being one-third of that in the 0-9 age 
group. 

§ Ibid., based on 0.21 per million person-year-rem. 

I Based on an assumed forty-year period at risk from five to forty-five years 
after exposure and assuming females have twice the excess risk of males. 



336 



Chapter 7 

How do these risk figures compare with what is acceptable in 
nontherapeutic research today? As noted earlier in this chapter, the contemporary 
regulatory standard permits children to be involved in nontherapeutic research if 
the research poses no more than "minimal risk" to the subjects. "Minimal risk" is 
defined by analogy only: "A risk is minimal where the probability and magnitude 
of harm or discomfort anticipated in the proposed research are not greater, in and 
of themselves, than those ordinarily encountered in daily life or during the 
performance of routine physical or psychological tests. "^ The regulations also 
allow for nontherapeutic research with children that does present more than 
minimal risk, but only //"the risk represents a minor increase over minimal risk, 
the procedures involved are commensurate with the general life experiences of 
subjects, and the research is likely to yield knowledge of "vital importance" about 
the subjects' disorder or condition. 70 The regulations do not specify what would 
count as a minor increase over minimal risk. With this general guidance, it is the 
obligation of individual institutional review boards (IRBs) to determine whether a 
nontherapeutic study involving children is acceptable. 71 It is likely that a cancer 
risk of greater than 1 per 1 ,000 subjects would be considered by most, if not all 
IRBs to be unacceptable by a minimal-risk standard, even for nonfatal cancers. It 
is less clear whether this risk would be considered unacceptable by the "minor 
increase over minimal risk" standard (assuming the research satisfied the "vital 
importance" condition). The difficulty of establishing an acceptable level of risk 
in nontherapeutic radiation research with children is currently being debated in 
the medical literature, 72 a debate that will likely continue at least until federal 
guidelines become more specific. 

What Was Known at the Time About Risk in Children 

Assuming that any study that posed risks of greater than 1 excess case of 
cancer per 1,000 subjects would be judged to be more than minimal risk, eleven 
of the twenty-one research projects reviewed by the Committee exposed children 
to higher risk than is acceptable today for nontherapeutic experiments. From a 
moral perspective, a crucial question is whether investigators at the time could or 
should have known that they were putting their pediatric subjects at greater than 
minimal risk. If they could have known, then, arguably, these investigators were 
not conforming to the AEC's requirement permitting nontherapeutic research in 
children provided that "the radiation dosage level in any tissue is low enough to 
be considered harmless." 

It is clear that the medical community's understanding of the nature and 
magnitude of risks posed to children by radiation exposure is not what it is today. 
Researchers did not positively associate prior exposure to external radiation with 
an increased risk of cancer until the mid to late 1950s. In 1950, Duffy and 
Fitzgerald raised the question as to whether there might be cause to investigate a 
possible association between therapeutic thymic irradiation during childhood and 

337 



Part II 

subsequent development of thyroid or thymic cancers: 

To pose a cause and effect relationship between 
thymic irradiation and the development of cancer 
would be quite unjustified on the basis of data at 
hand when one considers the large number of 
children who have had irradiation of an "enlarged 
thymus." However, the potential carcinogenic 
effects of irradiation are becoming increasingly 
apparent, and such relationships as those of thymic 
irradiation in early life and the subsequent 
development of thyroid or thymic tumors might be 
profitably explored. 73 

By 1959, several studies had reported an association between radiation 
exposure and the subsequent development of leukemia. 74 Saenger et al. 
performed an epidemiologic study of several thousand children in 1960 to 
evaluate the association between radiation exposure and cancer. 75 They stated: 

The question of whether or not radiation can be 
indicted as the principal causative factor in the 
induction of neoplasia following radiation exposure 
for either diagnostic or therapeutic purposes has 
been of increased interest over the past several 
years. 76 

In completing their analysis, they concluded: "It remains a fact, indisputable in 
all respects, that the rate of thyroid cancers in the irradiated group is 
disproportionately high." 77 

In 196U Beach and Dolphin prepared a detailed analysis of the literature 
on the relationship between radiation and thyroid cancer in children. 78 They 
reported: 

The thyroid has always been considered to be an 
organ comparatively radio-resistant to alteration 
and subsequent tumor development. Although no 
definite development of radiogenic tumor has been 
reported in adults after therapeutic administration of 
iodine-131, Jelliffe and Jones (1960) discuss a total 
of 10 cases of thyroid cancer reported in the 
literature in persons treated early in life by x-ray 
irradiation in the neck region. [T]he total of 
malignant thyroid tumors which develop in children 

338 



Chapter 7 

given a dose of x-radiation to the thyroid that is of 
the same order of magnitude as the incidence 
estimated for other tumors if a linear dose-response 
relationship is assumed. No biologic significance is 
attached to this point, apart from noting the fact that 
the child's thyroid appears to be more radio- 
sensitive than an adult's but not more sensitive than 
some adult tissues. 79 

This lack of appreciation for the potential long-term effects of radiation in 
children is further reflected in institutional policy development for use of 
radioisotopes at the time. The Massachusetts General Hospital developed 
standards for tracer doses of radioisotopes in May 1949. Dr. Shields Warren 
director of the AEC Division of Biology and Medicine, assisted in the 
development of the MGH standard: 

Tracer doses in humans will always be kept to the 
absolute minimum required to make the 
observation. 

Adult humans who are ill and who are expected to 
benefit from the procedure, shall not receive tracer 
doses of radioactive material giving off radiation in 
excess of a total of 4 rep. Children (all patients 
below 15 years of age) shall not receive more than a 
total of 0.8 rep. sn 

In any other cases, tracer doses will be limited to 
radioactive material giving off radiation in an 
amount less than a total of 1 rep. 

In the case of iodine, the thyroid, which retains 
most of the radioactivity, is radioresistant. In this 
case, the permitted dosage may be increased by a 
factor of 100. 81 

Despite the cautious tone of this document, the policy illustrates the 
complete lack of understanding of the true radiosensitivity of the thyroid gland 
especially in the pediatric population. Further allowances must be made with ' 
regard to what was known about the distribution of radioisotopes in children at 
the time. It is evident that investigators using radioisotopes in children were not 
employing available information on organ weights in children to calculate tissue 
exposures at least until the mid-1960s. When "standard man" assumptions were 

339 



Part II 

used to calculate pediatric exposures before pediatric standards were developed, 
investigators may have significantly and systematically underestimated effective 
tissue dosages in children. It is notable that the highest levels of risk posed in the 
experiments reviewed were to infants administered iodine 131. 

Iodine 131 was routinely used for diagnostic procedures in the pediatric 
population until the 1980s, when it was replaced by 1-123, a newly available 
radioisotope with a significantly shorter half-life, which reduced the thyroid dose 
markedly. The Wrentham fallout study, performed in 1 96 1 , employed doses of 
iodine 131 that resulted in an average dose of 44 rad to the gland, slightly less 
than the dose that would have been received for a diagnostic thyroid scan during 
this time. , 

Although the doses of radioisotopes subsequently declined during these 
years for both therapeutic medicine and nontherapeutic research, these guidelines 
were not based on long-term outcome studies of exposed individuals but rather 
on conservative extrapolations from high-dose studies and on the dosages 
necessary to enable detection with the available equipment. 

The debate over the potential risks of low-dose exposure continues today, 
as epidemiological studies of thyroid cancer incidence subsequent to iodine 131 
administration in both the diagnostic as well as therapeutic dose range have been 
largely negative. Risks as a result of iodine 131 exposure are still unclear, and 
risk analyses for exposure to radioisotopes are thus based on extrapolations from 
studies involving external irradiation. 

In summary, during the period in which children were exposed to the 
highest levels of risk from nontherapeutic research involving radioisotopes, 
investigators had a limited understanding of the potential long-term risks of low- 
dose radiation and of methods to accurately calculate the tissue doses in children. 
Today, we cautiously assume that any exposure to radiation likely produces some 
small increase in cancer risk, so that no exposure is absolutely harmless. Instead, 
the concept of minimal or acceptable risk is commonly used, as discussed earlier. 
Some of the studies during this period involved risks that would be judged as 
minimal even today, whereas others would be clearly viewed as unacceptable 
today. Should the investigators then have viewed any of these studies as 
harmless? Though an understanding of the association between exposure to 
external radiation and subsequent development of cancer was emerging during 
this time, a similar association had not been made for exposure to low dose levels 
of radioisotopes. In addition, the relative radiosensitivity of many pediatric 
tissues, including thyroid, had not been established, and most researchers during 
this period subscribed to the "threshold" theory of risk, which assumed that 
sufficiently low doses were probably harmless. In the face of such widespread 
factual ignorance, it is difficult to hold these investigators culpable for imposing 
risks on their subjects that were not appreciated at the time. 



340 



Chapter 7 

BEYOND RISK: OTHER DIMENSIONS OF THE ETHICS OF 
NONTHERAPEUTIC RESEARCH ON CHILDREN 

The level of risk to which children are exposed is critical in evaluating the 
ethics of nontherapeutic research on children. Also important, however, is 
whether and how the authorization of parents was solicited, and also which 
children were selected to be so used. For nineteen of the twenty-one studies 
reviewed by the Committee, we know almost nothing about whether the 
permission of parents was sought or what the parents were told about their 
children's involvement. Two of the studies conducted at the Fernald School were 
the exceptions, as a result of extensive historical and archival research by the 
Massachusetts Task Force on Human Subjects Research. 

There is a reference to parents in the published literature on only one of 
the remaining nineteen studies, a 1954 iodine uptake experiment at the University 
of Tennessee. This paper included the following line: "The procedure was 
described to the mothers of the infants studied, and the mothers gave consent for 
the study before the tests were made."* 2 (The inclusion of this line is noteworthy 
for it suggests that at least some investigators thought parental permission was 
worth mentioning in published reports of their research.) 

If the Committee had devoted extensive investigatory resources to these 
nineteen studies, it is likely we would have learned more about whether or how 
parental authorization was obtained in at least some cases. It is also almost 
certain that even the deepest archival digging would have produced no useful 
information about parental authorization for some of these experiments. The 
recent experience of the Massachusetts Task Force demonstrates the possibility of 
both outcomes: for some of the experiments conducted at the Fernald School, the 
task force's diligent historical research uncovered a variety of documents that 
shed important light on what both parents and children were told; for the 
experiments at Wrentham, similar efforts did not produce any significant 
information on questions of parental authorization. 

Again with the exception of the experiments conducted at Fernald and 
Wrentham, we know almost nothing about who the children were who served as 
subjects in these experiments. The journal articles on these remaining studies do 
not describe the sociodemographic characteristics of the subjects. They do 
sometimes mention whether the subjects had relevant medical conditions and 
usually that the children, including the "control" subjects, were hospitalized 
patients. In some of the experiments reviewed by the Committee, the scientific 
research questions of interest could have been pursued only in children who were 
ill and hospitalized. In other instances, however, the hospitalized children were 
likely samples of convenience. This is particularly plausible in the case of control 
subjects, when a sample of healthy, nonhospitalized children might have made a 
better control group from a scientific perspective. As we saw in chapter 2, 
hospitalized patients were often viewed by physician-investigators as a 

341 



Part II 

convenient source of research subjects. 

Because so little is known, the Committee cannot draw conclusions about 
the ethics of most of the nontherapeutic studies involving children we reviewed, 
apart from the important issue of risk of harm to the children involved. We turn 
now to an analysis of the studies where relevant information about parental 
authorization, disclosure, and subject selection is available: the studies conducted 
at the Fernald School. 

THE STUDIES AT THE FERNALD SCHOOL 

Researchers from the Massachusetts Institute of Technology, working in 
cooperation with senior members of the Fernald staff, carried out nontherapeutic 
nutritional studies with radioisotopes at the state school in the late 1940s and 
early 1950s. The subjects of these nutritional research studies were young male 
residents of Fernald, who were members of the school's "science club." In 1946, 
one study exposed seventeen subjects to radioactive iron. The second study, 
which involved a series of seventeen related subexperiments, exposed fifty-seven 
subjects to radioactive calcium between 1950 and 1953. It is clear that the doses 
involved were low and that it is extremely unlikely that any of the children who 
were used as subjects were harmed as a consequence. These studies remain 
morally troubling, however, for several reasons. First, although parents or 
guardians were asked for their permission to have their children involved in the 
research, the available evidence suggests that the information provided was, at 
best, incomplete. Second, there is the question of the fairness of selecting 
institutionalized children at all, children whose life circumstances were by any 
standard already heavily burdened. 

Parental Authorization 

The Massachusetts Task Force found two letters sent to parents describing 
the nutrition studies and seeking their permission. The first letter, a form letter 
signed by the superintendent of the school, is dated November 1949." The letter 
refers to a project in which children at the school will receive a special diet "rich" 
in various cereals, iron, and vitamins and for which "it will be necessary to make 
some blood tests at stated intervals, similar to those to which our patients are 
already accustomed, and which will cause no discomfort or change in their 
physical condition other than possibly improvement." The letter makes no 
mention of any risks or the use of a radioisotope. Parents or guardians are asked 
to indicate that they have no objection to their son's participation in the project by 
signing an enclosed form. 84 



342 



Chapter 7 
The second letter, dated May 1953, we quote in its entirety: 
Dear Parent: 

In previous years we have done some 
examinations in connection with the nutritional 
department of the Massachusetts Institute of 
Technology, with the purposes of helping to 
improve the nutrition of our children and to help 
them in general more efficiently than before. 

For the checking up of the children, we 
occasionally need to take some blood samples, 
which are then analyzed. The blood samples are 
taken after one test meal which consists of a special 
breakfast meal containing a certain amount of 
calcium. We have asked for volunteers to give a 
sample of blood once a month for three months, and 
your son has agreed to volunteer because the boys 
who belong to the Science Club have many 
additional privileges. They get a quart of milk daily 
during that time, and are taken to a baseball game, 
to the beach and to some outside dinners and they 
enjoy it greatly. 

I hope that you have no objection that your 
son is voluntarily participating in this study. The 
first study will start on Monday, June 8th, and if 
you have not expressed any objections we will 
assume that your son may participate. 

Sincerely yours, 

Clemens E. Benda, M.D. 
[Fernald] Clinical Director 

Approved:. 



Malcom J. Farrell, M.D. 
[Fernald] Superintendent 85 



Again, there is no mention of any risks or the use of a radioisotope. It was 
believed then that the risks were minimal, as indeed they appear to have been, and 
as a consequence, school administrators and the investigators may have thought it 
unnecessary to raise the issue of risks with the parents. There was no basis, 
however, for the implication in both letters that the project was intended for the 

343 



Part II 

children's benefit or improvement. This was simply not true.* 6 

The conclusion of the Massachusetts Task Force was that these 
experiments were conducted in violation of the fundamental human rights of the 
subjects. This conclusion is based in part on the task force's assessment of these 
letters. Specifically, the task force found that 

1 [t]he researchers failed to satisfactorily inform the 
subjects and their families that the nutritional 
research studies were non-therapeutic; that is, that 
the research studies were never intended to benefit 
the human subjects as individuals but were intended 
to enhance the body of scientific knowledge 
concerning nutrition. 

The letter in which consent from family members 
was requested, which was drafted by the former 
Fernald superintendent, failed to provide 
information that was reasonably necessary for an 
informed decision to be made. 87 

Fairness and the Use of Institutionalized Children 

The Fernald experiments also raise quite starkly the particular ethical 
difficulties associated with conducting research on members of institutionalized 
populations-especially where some of the residents have mental impairments. 
Living conditions in most of these institutions (including Fernald and Wrentham) 
have improved considerably in recent years, and sensitivity toward people with 
cognitive impairments has likewise increased. As Fred Boyce, a subject in one of 
these experiments has put it, "Fernald is a much better place today, and in no way 
does it operate like it did then. That's very important to know that." ss 

The Massachusetts Task Force describes conditions in state-operated 
facilities like Fernald, particularly as they bear on human experimentation, as 
follows: 

Until the 1970s, the buildings were dirty and in 
disrepair, staff shortages were constant, brutality 
was often accepted, and programs were inadequate 
or nonexistent. There were no human rights 
committees or institutional review boards. If the 
Superintendent (in those days required to be a 
medical doctor) "cooperated" in an experiment and 
allowed residents to be subjects, few knew and no 
one protested. If nothing concerning the 

344 



Chapter 7 

experiments appeared in the residents' medical 
records, if "request for consent" letters were less 
than forthright, or if no consent was obtained there 
was no one in a position of authority to halt or 
challenge such procedures. 89 

Although public attitudes toward people who are institutionalized are 
admittedly different today than they were fifty years ago, it is likely that this state 
of affairs would have been troubling to most Americans even then. Historian 
Susan Lederer has revealed several episodes of experimentation with 
institutionalized children in America that caused considerable public outcry even 
before 1940, presaging the concern generated by Willowbrook when this research 
became a public issue in the 1960s. 90 

The LMRI staff reported in the early 1960s that the pediatric researchers 
whom they had gathered agreed in principle that the convenience of conducting 
research on institutionalized children did not outweigh the moral problems 
associated with this practice: 

Several investigators spoke about the practical 
advantages of using institutionalized children who 
are already assembled in one location and living 
within a standard, controlled environment. But the 
conferees agreed that there should be no differential 
recruitment of ward patients rather than private 
patients, of institutionalized children rather than 
children living in private homes, or of handicapped 
rather than healthy children. 91 

A particularly poignant dimension of the unfairness of using 
institutionalized children as subjects of research is that it permits investigators to 
secure cooperation by offering as special treats what other, noninstitutionalized 
children would find far less exceptional. The extra attention of a "science club," a 
quart of milk, and an occasional outing were for the boys at Fernald extraordinary 
opportunities. As Mr. Boyce put it: 

I won't tell you now about the severe physical and 
mental abuse, but I can assure you, it was no Boys' 
Town. The idea of getting consent for experiments 
under these conditions was not only cruel but 
hypocritical. They bribed us by offering us special 
privileges, knowing that we had so little that we 
would do practically anything for attention; and to 
say, I quote, "This is their debt to society," end 

345 



Part II 

quote, as if we were worth no more than laboratory 
mice, is unforgivable. 92 

Even when a child was able to resist the offers of special attention and 
refused to participate in the experiment, the investigators seem to have been 
unwilling to respect the child's decision. One MIT researcher, Robert S. Harris, 
explicitly noted that "it seemed to [him] that the three subjects who objected to 
being included in the study [could] be induced to change their minds." 93 Harris 
believed that the recalcitrant children could be "induced" to join in the study by 
emphasizing "the Fernald Science Club angle of our work." 94 

From the perspective of the science, it was considered important to 
conduct the research in an environment in which the diet of the children-subjects 
could be easily controlled. From this standpoint, the institutional setting of 
Fernald was ideal. The institutional settings of the boarding schools in the 
Boston area, however, would have offered much the same opportunity. Although 
the risks were small, the "children of the elite" were rarely if ever selected for 
such research. It is not likely that these children would have been willing to 
submit to blood tests for extra milk or the chance to go to the beach. 

The question of what is ethical in the context of unfair background 
conditions is always difficult. Perhaps the investigators, who were not 
responsible for the poor conditions at Fernald, believed that the opportunities 
provided to the members of the Science Club brightened the lives of these 
children, if only briefly. Reasoning of this sort, however, can all too easily lead to 
unjustifiable disregard of the equal worth of all people and to unfair treatment. 

Today, fifty years after the Fernald experiments, there are still no federal 
regulations protecting institutionalized children from unfair treatment in research 
involving human subjects. 95 The Committee strongly urges the federal 
government to fill this policy void by providing additional protections for 
institutionalized children. 96 

CONCLUSION 

If an ethical evaluation of human experiments depended solely upon an 
assessment of the risks to subjects as they could reasonably be anticipated at the 
time, the radiation experiments conducted on children reviewed in this chapter 
would be relatively unproblematic. 97 During this time, the association between 
radiation exposure and the subsequent development of cancer was not well 
understood, and in particular, little was known about iodine 131 and the risk of 
thyroid cancer. Both researchers and policymakers appear to have been alert to 
considerations of harm and concerned about exposing children to an unacceptable 
level of risk. 

At the same time, however, the scientific community's experience with 
radionuclides in humans was limited, and this approach to medical investigation 

346 



Chapter 7 

was new. Although the available data about human risk were encouraging and 
the biological susceptibility of children to the effects of radiation was not 
appreciated, we are left with the lingering question of whether investigators and 
agency officials were sufficiently cautious as they began their work with children. 
This is a difficult judgment to make at any point in the development of a field of 
human research; it is particularly difficult to make at forty or fifty years' remove. 
Investigators and officials had to make decisions under conditions of considerable 
uncertainty; this is commonplace in science and in medicine. Although the 
biological susceptibility of children was not then known, investigators and 
officials held the view that children should be accorded extra protection in the 
conduct of human research, and they made what they thought were appropriate 
adjustments when using children as subjects. If human research never proceeded 
in the face of uncertainty, there would be no such experiments. How little 
uncertainty is acceptable in research involving children is a question that remains 
unresolved. Today, we continue to debate what constitutes minimal risk to 
children, in radiation and in other areas of research. The regulations governing 
research on children offer little in the way of guidance, either with respect to 
conditions of uncertainty about risk or when risks are known. 

As best as we can determine, in eleven of the twenty-one experiments we 
reviewed, the risks were in a range that would today likely be considered as more 
than minimal, and thus as unacceptable in nontherapeutic research with children 
according to current federal regulations. It is possible, however, that four of the 
eleven might be considered acceptable by the "minor increase over minimal risk" 
standard. 98 In these four experiments, the average risk estimates were between 
one and two per thousand, the studies were directed at the subjects' medical 
conditions, and they may well have had the potential to obtain information of 
"vital importance." 

Physical risk to subjects is not the only ethically relevant consideration in 
evaluating human experiments. With the exception of the studies at Fernald, we 
know almost nothing about whether or how parental authorization for the 
remaining nineteen experiments we reviewed was obtained. And with the 
exception of the Fernald studies and the experiment at Wrentham, we know very 
little about the children who were selected to be the subjects of this research. 
Therefore, we cannot comment on the general ethics of these other experiments. 

The experiments at Fernald and at the Wrentham School unfairly burdened 
children who were already disadvantaged, children whose interests were less well 
protected than those children living with their parents or children who were 
socially privileged. At the Fernald School, where more is known, there was some 
attempt to solicit the permission of parents, but the information provided was 
incomplete and misleading. The investigators successfully secured the 
cooperation of the children with offers of extra milk and an occasional outing- 
incentives that would not likely have induced children who were less starved for 
attention to willingly submit to repeated blood tests. 

347 



Part II 

One researcher speaking almost thirty-five years ago set out the 
fundamental moral issue with particular frankness and clarity: 

... we are talking here about first and second class 
citizens. This is a concept none of our consciences 
will allow us to live with. . . . The thing we must all 
avoid is two types of citizenry." 

It might have been common for researchers to take advantage of the convenience 
of experimenting on institutionalized children, but the Committee does not 
believe that convenience offsets the moral problems associated with employing 
these vulnerable children as research subjects~now or decades ago. 



The Vanderbilt Study 

In an exceptionally large study" at Vanderbilt University in the 1940s, approximately 820 
poor, pregnant Caucasian women were administered tracer doses of radioactive iron. Vanderbilt 
worked with the Tennessee State Department of Health, and the research was partly funded by the 
Public Health Service. 11 Today, most women take iron supplements during pregnancy. This 
experiment provided the scientific data needed to determine the nutritional requirements for iron 
during pregnancy. 

The radioiron portion of the nutrition study, directed by Dr. Paul Hahn, was designed to 
study iron absorption during pregnancy.' The women, who were anywhere from less than ten 
weeks to more than thirty-five weeks pregnant, were administered a single oral dose of radioactive 



a. Most of the other tracer studies involving pregnant women and offering no prospect of benefit 
that were reviewed by the Committee involved fewer than twenty women as subjects. 

b. William J. Darby, Director of the Tennessee-Vanderbilt Project et al., Summary Report. Section 
B. Tennessee-Vanderbilt Nutrition Project. July 1. 1946 to December 31. 1946 (ACHRE No. CORP-020395- 
A), 97-1 10. This nutrition study summary report notes, "Considerable expansion of the program of study of 
maternal and infant nutrition has been made possible by a grant of $9,000 per year which was made by the 
U.S. Public Health Service. These funds were available beginning November 1, 1946." Ibid., 99. The 
summary observes that the grant was to be used for additional personnel, including the appointment of Dr. 
Richard Cannon, an obstetrics resident, to the staff of the Division of Nutrition beginning 1 January 1947. 
Dr. Cannon's name subsequently appears as an investigator in the medical report discussing the radioiron 
portion of the study, along with Dr. Paul Hahn's and others. 

c. P. Hahn et al., "Iron Metabolism in Human Pregnancy as Studied with the Radioactive Isotope, 
Fe-59," American Journal of Obstetrics and Gynecology 61 (March 1951): 477-486. The exact years of the 
radioiron portion of the nutrition study are uncertain. Minutes from a meeting of the nutrition study 
investigators indicate the study was to begin in September 1945. Tennessee-Vanderbilt Nutrition Project, 
Nutrition in Pregnancy Study, "Minutes of Meeting for Discussion of Nutrition in Pregnancy Study, August 
17, 1945" (ACHRE No. CORP-020395-A). 17A-C. The radioiron study probably began at approximately 
that time and appears to have continued until sometime in 1947, based on a review of periodic study 
summaries. 

348 



Chapter 7 

iron, Fe-59, during their second prenatal visit, before receiving their routine dose of therapeutic 
iron.' 1 On their third prenatal visit, blood was drawn and tests performed to determine the 
percentage of iron absorbed by the mother. The infants' blood was then examined at birth to 
determine the percentage of radioiron absorbed by the fetus. The doses to the women were 
estimated in the study article, using crude dose-estimation methods available at the time, to be 
from 200,000 to 1,000,000 countable counts per minute." Although the investigators did not 
estimate doses to the fetuses in the original study. Dr. Hahn later estimated fetal doses to be 
between 5 and 15 rad. This estimate, however, has been questioned. 1 

There is at least some indication that the women neither gave their consent nor were 
aware they were participating in an experiment. Vanderbilt study subjects, expressing bitterness at 
the way they believed they had been treated, testified at an Advisory Committee meeting that the 
proffered drink, called a "cocktail" by the investigators, was offered with no mention of its 
contents. "1 remember taking a cocktail," one woman said simply. "I don't remember what it was, 
and I was not told what it was." B Although it is not clear what, if anything, the subjects were told, 
information about the Vanderbilt experiment was available to the general public. In late 1946 
news reports appeared in the Nashville press. 1 ' 

The actual risk to the fetuses in the Vanderbilt experiment has long been a matter of 
study. In 1963-1964, a group of researchers at Vanderbilt found no significant differences in 
malignancy rates between the exposed and nonexposed mothers. 1 However, they did identify a 
higher number of malignancies among the exposed offspring (four cases in the exposed group: 
acute lymphatic leukemia, synovial sarcoma, lymphosarcoma, and primary liver carcinoma, which 
was discounted as a rare, familial form of cancer). No cases were found in a control group of 
similar size, and approximately 0.65 cases would have been expected on Tennessee state rates, 
compared to which the three observed cases is a marginally significant excess. This led the 
researchers to conclude that the data suggested a causal relationship between the prenatal exposure 
to Fe-59 and the cancer. The investigators also concluded that Dr. Hahn's estimate of fetal 



d. The Advisory Committee has not been able to determine whether Dr. Hahn got the radioactive 
iron used in the study from a private or government source, or both. 

e. Counts per minute is a measure of the radioactivity detected by a specific counting instrument. 
The sensitivities of counting instruments vary; a specific instrument may not "see" and count all the radiation 
coming from a particular substance. Thus, the total amount of radiation emitted by a substance may be 
calculated by considering the sensitivity of the counter. 

f. Contemporary estimates of the fetal doses by the Committee and others suggest that the fetal 
effective dose was a few hundred millirems. 

g. Wilton McClure, transcript of audio testimony before the Advisory Committee on Human 
Radiation Experiments, Small Panel Meeting, Knoxville, Tennessee, 2 March 1995, 182. 

h. "Iron Doses with Radioactive Isotopes Aid to Pregnancy, Experiment Shows," Nashville 
Banner, 13 December 1946; "VU to Report on Isotopes," The Nashville Tennessean, 14 December 1946 
(ACHRE No. CORP-020395-A). 

i. The investigators identified the hospital records of 751 exposed mothers and 771 unexposed 
controls, as well as 719 exposed offspring and 734 unexposed offspring, and mailed them questionnaires. Of 
the exposed mothers, 90.4 percent responded, as did 91.45 percent of the unexposed mothers, 88.2 percent 
of the exposed offspring, and 89.2 percent of the unexposed. Ruth M. Hagstrom et al.,"Long Term Effects 
of Radioactive Iron Administered During Human Pregnancy," American Journal of Epidemiology 90 ( 1 969): 
1-8. 

349 



Part II 

exposure was an underestimation of the fetal-absorbed dose. 

A 1969 study, funded by the AEC and conducted by one of the investigators from the 
1963-1964 study, attempted to reconstruct the doses of Fe-59 to the fetuses in the original 
Vanderbilt study . J The investigators observed that the one case of leukemia might have been due 
to radiation damage, but that the doses in the other two cases were low; therefore, the relationship 
between the radiation exposure and the cancer in those cases might not have been causal. 
However, the researchers also noted that due to incomplete data, they could not estimate the dose 
absorbed by the fetus with confidence and that no definitive conclusions could be drawn from this 
study as to whether these exposures resulted in damage to the fetus. k 

The Vanderbilt study raises many of the same ethical issues as the experiments reviewed 
in this chapter. Like these experiments, the Vanderbilt study offered no prospect of medical 
benefit to the pregnant women or their offspring, raising the question of the conditions under 
which it is acceptable to put children at risk for the benefit of others, whether before or after birth. 
What could the investigators reasonably have been expected to know about the risks to which they 
put their subjects? Did they exercise appropriate caution in exposing fetuses to radiation? What 
were the pregnant women told, if anything, and was their permission sought? Who were these 
women, and how were they positioned relative to pregnant women, generally? 

The Committee did not have the resources to pursue these questions in both research in 
which children were the subjects and research in which children were exposed as fetuses. We did 
establish that the Vanderbilt study was not the only experiment during this period to expose 
fetuses in research that offered no prospect of medical benefit to them or their mothers. While the 
Committee did not conduct an exhaustive review of the scientific literature, we did find twenty- 
seven human radiation studies that included pregnant or nursing women as subjects between 1944 
and 1974.' Of these studies, eight were considered therapeutic, and nineteen offered no prospect of 
benefit to the subject. Most of the nineteen were tracer experiments. 

These studies were performed in order to examine human physiology during pregnancy 
or to study the uptake of radioactive substances by fetuses or nursing infants." 1 They generally 



j. Norman C. Dyer and A. Bertrand Brill, "Fetal Radiation Dose from Maternally Administered 
Fe-59 and 1-131," in Radiation Biology of the Fetal and Juvenile Mammal: Proceedings of the Ninth Annual 
Hanford Biology Symposium at Richland. Washington. May 5-8. 1969, eds. Melvin R. Sikov and D. Dennis 
Mahlum (Washington, D.C.: GPO, December 1969), 78-88. This study was reviewed in detail by the 
Committee. The study also investigated fetal absorption of radioiodine because that isotope was and is 
commonly used in diagnosis and therapy, including in pregnant women. 

k. Ibid., 85. 

1. All of the nineteen studies reviewed in detail by the Committee were conducted or at least 
partially funded by the federal government or were supplied with radioisotopes by the AEC. For the earlier 
years, the Committee relied on the ACHRE experiments database, AEC isotope distribution lists provided by 
DOE, and relevant biographies. The Committee also consulted relevant medical indexes and computer 
databases; the isotope distribution lists provided by DOE did not cover these years. While the computer 
search would have located nontherapeutic tracer experiments for this period as well, very few were 
identified. 

m. Of the nineteen tracer experiments (funded by the government) involving pregnant or nursing 
women identified by the Committee, only three administered tracer doses to nursing women that offered no 
prospect of benefit; in at least one of the studies the infants were exposed. In one case, six nursing women 
were given radioiodine to determine excretion in breast milk, the infants were not given the exposed milk. In 

350 



Chapter 7 

addressed valid scientific questions that could not be investigated in other populations. 
Knowledge of fetal exposure to radioiodine. for example, was relevant to issues such as potential 
harm to the fetus from maternal uptake of radioiodine in diagnostic tests or to estimate the 
potential effects of environmental exposure to radioiodine on the human fetus. In other studies, 
radioactive iron was administered to better understand the physiology of maternal and fetal intake 
of iron during pregnancy. 



another case, two infants were intentionally exposed to the breast milk of their mothers, who were given I- 
131. An I- 1 3 1 tracer study on the general population, incidentally included two nursing women. The report 
indicates that both had been nursing their children, and since there is no indication that the mothers were 
warned to avoid breastfeeding after the exposure, it is quite probable that the infants were exposed. 

351 



Part II 



Nasopharyngeal Irradiation 

Nasopharyngeal irradiation," introduced by S. J. Crowe and J. W. Baylor of the 
Otological Research Laboratory at the Johns Hopkins University, was employed from 1924 on as 
a means of shrinking lymphoid tissue at the entrance to the eustachian tubes to treat middle ear 
obstructions, infections, and deafness. For this treatment, intranasal radium applicators (sealed 
ampules containing radium salt) were inserted (at least three insertions per treatment cycle) into 
the nasopharyngeal area for twelve-minute periods. 11 The therapeutic effect of the treatments 
resulted from the penetrating radiation emitted from the radium source (gamma and beta rays), not 



a. Nasopharyngeal irradiation was studied in adults as well as children. In the early 1940s, 732 
submariners were subjects of a controlled experiment designed to test whether nasopharyngeal radium 
treatments could be used to shrink lymphoid tissue surrounding the eustachian tubes, thereby preventing and 
treating aerotitis media in submariners by equalizing external and middle ear pressure. This treatment was 
successful in 90 percent of the cases. H. L. Haines and J. D. Harris, "Aerotitis Media in Submariners," 
Annals of Otology. Rlrinology. and Laryngology 55 ( 1 946): 347-37 1 . In a 1 945 journal article, it was noted 
that a controlled study was considered by the Army Air Forces, but rejected because of the urgent need to 
treat fliers immediately and keep them flying. However, the published report describes differences between 
various dose groups, implying an uncontrolled experimental comparison was made. Captain John E. 
Hendricks et al., "The Use of Radium in the Aerotitis Control Program of the Army Air Forces: A Combined 
Report by the Officers Participating," Annals of Otology, Rlrinology. and Laryngology' 54 ( 1 945 ): 650-724. 
Tens of thousands of servicemen were subsequently given this nasopharyngeal radium treatment. 

Relying on the risk estimate developed in the Sandler study, Stewart Farber, a radiation-monitoring 
specialist with a background in public health, has projected 5 1 .4 excess brain cancers over a fifty-year 
period in the 7,613 servicemen irradiated in the Navy and Army Air Forces studies noted above. Stewart 
Farber, Consulting Scientist of the Public Health Sciences, to Stephen Klaidman, ACHRE Staff. 8 March 
1995 ("Nasopharyngeal Radium Irradiation-Initial Radiation Experiments Performed by DODon 7,613 
Navy and Army Air Force Military Personnel during 1944-45"). Alan Ducatman, M.D.. of the University of 
West Virginia School of Medicine, who coauthored a letter with Farber to the New England Journal of 
Medicine regarding the radium exposure of military personnel, wrote that he found "no convincing evidence 
of excess cancer in the exposed population." He added, however, "there is also no good evidence for the null 
hypothesis." Alan Ducatman, West Virginia University School of Medicine, to Duncan Thomas, Member of 
the Advisory Committee on Human Radiation Experiments, 22 February 1995 ("I'm sorry I could not 
respond . . .") (ACHRE No. WVU-02 1 795-A). 

Han K. Rang, with the Environmental Epidemiology Service of the Veterans Health 
Administration, is currently conducting a study to assess the feasibility of an epidemiologic study of Navy 
veterans who received radium treatments. Han K. Rang. Environmental Epidemiology Service, Veterans 
Health Administration, "Feasibility of an Epidemiologic Study of a Cohort of Submariners Who Received 
Radium Irradiation Treatment," 23 August 1994. It is not clear, however, that sufficient numbers of 
treatment-documented personnel can be identified, as a group representing submariners has apparently been 
able to identify only six former Navy personnel from of a pool of twenty-seven whose records indicate they 
received radium treatment. (It is not clear whether the data being collected by the VFW with the support of 
Senator Joesph Lieberman of Connecticut will be from a representative sample of respondents. If, in fact, 
these data are from a highly nonrepresentative sample, the study may not be considered scientifically valid.) 
However, the Veterans of Foreign Wars organization apparently is now processing hundreds of surveys filled 
out by veterans who say they underwent nasopharyngeal radium treatment. Once this task is completed. 
Senator Lieberman plans to present the data to the Department of Veterans Affairs with a recommendation 
that an epidemiologic study be conducted. 

b. Samuel J. Crowe, "Irradiation of the Nasopharynx," Annals of Otology, Rhinology and 
Laryngology 55 (\9Ad): 31. 

352 



Chapter 7 

from the internal deposition of radium itself. Crowe and his colleagues reported that "under this 
treatment, the lymphoid tissue around the tubal orifices gradually disappeared, marked 
improvement or complete return of the hearing followed, and in many the bluish discoloration of 
the tympanic membrane also disappeared."" This method was used for more than a quarter century 
as a prophylaxis against deafness, for relieving children with recurrent adenoid tissue following 
tonsillectomy and adenoidectomy, and for children with chronic ear infections. Asthmatic 
children with frequent upper respiratory infections were also often considered for this type of 
irradiation. 

An average of 1 50 patients a month, mostly children, were given the treatment at the 
Johns Hopkins clinic over a period of several years.' 1 Many children received the treatment more 
than once as recurrent lymphoid tissue Was considered an indication for treatment. 

Crowe and his colleagues reported that the results following irradiation of the 
nasopharynx alone were not only as good as, but often better than, those following removal of 
tonsils and adenoids." In review articles, they noted that approximately 85 percent of treated 
patients responded with decreased numbers of infections and/or improved hearing when treated at 
young ages. They also concluded that "it is effective, safe, painless, inexpensive and has proved 
particularly valuable for prevention of certain ear, sinus and bronchial condition in children." 1 
Although early articles by Crowe and colleagues indicate that nasopharyngeal radium treatments 
were accepted as standard procedure for the prevention of childhood deafness, these treatments, 
like most standard interventions in medicine, had not been subjected to formal scientific 
evaluation. A controlled study was conducted from 1948 to 1953 by Crowe and his colleagues to 
determine "the feasibility of irradiation of the nasopharynx as a method for controlling hearing 
impairment in large groups of children associated with lymphoid hyperplasia in the nasopharynx; 
to draw conclusions concerning the per capita cost of such an undertaking as a public health 
measure." 6 Crowe et al. wrote in an NIH "Notice of Research" that "the procedure of treatment is 
not new, as an individual measure; this is the first adequately controlled experiment of sufficient 
size for accurate statistical analysis."' 1 

This work was funded by NIH for the entire period of study. As recorded in an NIH grant 
application, the study involved approximately 7,000 children screened for hearing impairment.' Of 
those screened, approximately 50 percent were selected for further study based on the chosen 
criteria for hearing loss. Half of this study group was irradiated with radium, while the other half 
served as a control group. Crowe and colleagues reportedly concluded from this study (published 
in 1955) that the radium treatments did shrink swelling of lymphoid tissue and improve hearing. 1 
This type of therapy was ultimately discontinued because of newly available antibiotics and the 



c. Ibid.. 30. 

d. Ibid., 33.; Dale P. Sandler et al., "Neoplasms Following Childhood Radium Irradiation of the 
Nasopharynx," Journal of the National Cancer Institute 68 ( 1982): 3-8. 

e. Ibid., 33. 

f. Ibid. 

g. S. J. Crowe et al.. The Johns Hopkins University School of Medicine and School of Hygiene 
and Public Health, to Federal Security Agency, Public Health Service, National Institutes of Health, July 
1948 ("The Efficiency of Nasopharyngeal Irradiation In the Prevention Of Deafness in Children, Notice of 
Research Project, Grant No. B-19") (ACHRE No. HHS No. 092694-A). 

h. Ibid, 
i. Ibid. 
j. Ibid. 

353 



Part II 

use of transtympanic drainage tubes, as well as awareness of the potential risks of radiation 
treatment. 

In addition to the targeted lymphoid tissue, the brain and other tissues in the head and 
neck region, including the paranasal sinuses, salivary glands, thyroid, and parathyroid glands are 
also exposed to significant doses of radiation during the radium treatments, prompting concern that 
these treated individuals might have been placed at increased risk for radiation-induced cancers at 
these sites. Dale P. Sandler et al., in their 1982 study of the effects of nasopharyngeal irradiation 
on excess cancer risk for children treated at the Johns Hopkins clinic, found "a statistically 
significant overall excess of malignant neoplasms of the head and neck among exposed subjects," 
based however on only four cases in comparison with 0.57 expected. 1 This excess was accounted 
for mainly by three brain tumors that occurred in the irradiation subjects. One other malignant 
tumor, a cancer of the soft palate, was also reported. The Department of Epidemiology at the 
Johns Hopkins University has undertaken a further follow-up study of the Crowe et al. cohort of 
children irradiated there, previously studied by Sandler et al. 1 Verduijn et al., in their 1989 study 
of cancer mortality risk for those individuals (mostly children) treated by nasopharyngeal 
irradiation with radium 226 in the Netherlands, reported that "the present study has found no 
excess of cancer mortality at any site associated with radium exposure by the Crowe and Baylor 
therapy. Specifically, 

the finding of Sandler et al. of an excess of head and neck cancer was not found in this study 
group.""' 

Among the Japanese atomic bomb survivors, no excess of brain tumors was found. 
However, several studies have noted an increased risk of both benign and malignant brain tumors 
following therapeutic doses of radiation to the head and neck region during childhood." From the 
Committee's own limited risk analysis of these experiments, we concluded that the brain and 
surrounding head and neck tissues would be put at highest risk and estimated the lifetime risk at 
approximately 4.35 per 1,000 and an increased relative risk of 62 percent." 



k. For the combination of benign and malignant neoplasms, there were 23 cases, for a relative risk 
of 2.08 with a 95 percent confidence interval of 1.12 to 3.91. Sandler, "Neoplasms Following Childhood 
Radium Irradiation," 5. 

I. Jessica Yeh and Genevieve Matanowski, fax to Anna Mastroianni (ACHRE), 7 July 1995 
("Nasopharyngeal Power Analysis"), 1-3. 

in. Verduijn et al., "Mortality after Nasopharyngeal Irradiation," Annals of Otology. Rhinology, 
and Laiyngolog}- 98 ( 1 989): 843. 

n. S. Jablon and H. Kato, "Childhood Cancer in Relation to Prenatal Exposure to Atomic-Bomb 
Radiation," The Lancet, ii (1970): 1000-1003.; M. Colman, M. Kirsch, and M. Creditor, "Radiation Induced 
Tumors," in Late Biological Effects of Ionizing Radiation. Vol. I (Vienna: International Atomic Energy 
Agency, 1978), 167-180; R. E. Shore, R. E. Albert, and B. S. Pasternak, "Follow-up Study of Patients 
Treated by X ray Epilation for Tinea Capitis: Resurvey of Post-Treatment Illness and Mortality Experience," 
Archives of Environmental Health 31(1 976): 1 7-24; and C. E. Land.Xarcinogenic Effects of Radiation on 
the Human Digestive Tract and Other Organs." in Radiation Carcinogenesis, eds. A. C. Upton et al. (New 
York: Elsevier, 1986), 347-378. 

o. The radiation dose estimate to the head and neck region was calculated according to the 
following assumptions: ( I ) Source description: 50 ing of radium, active length 1 .5 cm, filtered by 0.3 mm of 
Monel metal. (2) Average treatment: 60 mg/hrs; based on three 12-minute treatments (radium applicators 
inserted through both nostrils)= ( 12x3x50x2 )/60 mins per hour= 60 mg-hrs. (3) Dose rate at points in a 
central orthogonal plane surrounding the source: for distances up to 5 centimeters dose estimated using 
published data (Quimby Tables, Otto Glasser et al.. Physical Foundations of Radiology, 3d ed. [New York: 
Paul Hoeber, Inc., 1961]) for linear radium sources with dose increased by 50% to allow for the reduced 

354 



Chapter 7 

The Hopkins nasopharyngeal study raises different ethical issues than those posed by the 
other experiments reviewed in this chapter, all of which offered no prospect of medical benefit to 
the children who served as subjects. By contrast, the nasopharyngeal irradiation experiment was 
designed to determine whether children at risk for hearing loss would be better off receiving 
radiation treatments or not receiving such treatments. A central issue here was whether it was 
permissible to withhold this intervention from "at risk" children. The application of radium was at 
this point a common, but scientifically unproven, treatment for children at risk of hearing loss; the 
risks of the treatment were not well characterized. If it was really unknown which was better for 
children-receiving radium or no intervention-then the medical interests of the children were best 
served by being subjects in the research because, as a consequence, they would have a 50 percent 
chance of receiving the better approach. The nasopharyngeal experiment thus belongs to a class of 
research the Committee did not investigate-therapeutic research with children. 



filtration provided by the applicator wall and converting roentgen to rad by a multiplication factor of 0.93. 
For distances greater than 5 centimeters, the dose rate is reduced in accordance with the inverse square law, 
with a proportionality constant of 690 rad-cnr. There was no dose correction for attenuation of the gamma 
rays by tissue absorbtion, which has been calculated to be about 2%/cm (yielding a dose reduction of about 
20% at 10 cm). 

The local gamma dose to the head and neck region was assumed to be distributed according to an 
inverse square law d(r) = 690/r rad. The Committee approximated the exposed region of the body by a 
sphere with radius 10 centimeters. This was felt to be a conservative assumption, because although the dose 
does not go to zero at the base of the neck, a 10-centimeter sphere would also extend outside the skull. 
Averaging this dose distribution over the exposed sphere, the average dose to the head was found to be 20.7 
rad. The exposed volume is about 4189 cm', or 29 percent of the total body, so the average whole body dose 
is about 6.0 rad. Multiplying this by the BEIR V risk coefficient for children exposed at age five. 1.4/1,000 
person-rad, produces a lifetime risk of about 8.4/1,000. This calculation assumes that the brain and other 
head tissues have average radiosensitivity. BEIR V also gives absolute-risk coefficients for brain cancer 
ranging from 1 to 9 per million person-year-rad, with 3 being a reasonable average. Applying this figure to 
an average head dose of 20.7 rad, the Committee estimates a lifetime risk of about 4.35/1,000. The 
corresponding relative risk coefficients average about 3 percent per rad, so this dose would correspond to an 
excess relative risk of 62 percent. 



355 





5 *« 




























•■^ .2 s — £ 


/^^ 






,^^, 


y-"V 




^^, 


^^^v 






CN 






— * 






<N 


00 




o 


rn 






00 






d 






d 


""J 




_' 


(N 






d 






m 


NO 


© 


VI 


o 


^f 


IT) 


TT 


d a, 


o 


tN 


tN 




o 
© 


o 
© 


o 
d 


d 


d 


Ss 


d 


d 


o 
d 


d 


o 

d 






73 


T3 


T3 


-a 


TD 


"O 


"O 


•a 


rs 




12 


2 




























<u 


O 


O 


O 


o 


o 


o 


o 


'3 


'3 




"5 


'o 


H 


H 


u 


u 


t- 


H 


>- 


u 


c 


"o3 

4-* 


c 


id 


0> 


>n 


>> 


>. 


>, 


>^ 


^ 


>. 


>, 


>! 


>> 


>, 


E 

£ 


X 


X 


J3 


J3 


J3 


X 


X 


X 


X 


o 


X 


X 


H 


H 


H 


H 


H 


H 


H 


P 


H 


H 


H 


H 


i- a 


























4) cy 














c 












o 


X t- 














w 2 












e 


3 IS 

z u 


o 






in 


m 


00 


•>*■ X 


r^ 


o 


r-~ 


ON 




"~ i 


On 


oo 


<N 


'O 


(N 


(N CD 


00 


t~- 


IT) 




NO 


i> 


4) 

o. 


























TS 


o 


• — i 


dd 


dd 


r-H 


p-H 


^>H 


^-l 


, — 1 


^H 


v^ 

<* 

1 


^d 


^d 


«< 


o 


<■<-> 


C"> 


m 


m 


r<"> 


m 


f^l 


c-i 


m 


m 


rn 


^d 


^d 


^d 


^^ 


»— « 


^— 


»— i 


^^ 


~— 


03 


dd 


^d 


o> 


i 


i 


i 


i 


i 


i 


l 


i 


i 


u 


1 


1 
























































i>> 






















CD 






£} 
















CO 


"3 




M 






-a 

S 














E 


o 

CD 


•a 


C4-H 


a 
a, 












"3 

s 




•3 

JO 
Cm 


o 

X 


x 1 




O 


D 






s 






CO 

a 
cd 




CD 


3 
CO 


X 

H 


'o 


03 

u 






OS 






J 


CO 
CD 




O 
CD 

03 


2 

Ct- 

O 


"2 

'o 

"o 


K 00 


H 

>> 

X 
H 


IT) 
•<* 

c 




03 


'■3 

s 

■M 

t/5 






1/3 

"o 
o 

co 

s 


> 

00 

c _ 
'co c"> 

CO 1> 


CO 

e 


D 

co 

CO 

CD 
i— 

& 


CO 

T3 
C 
c« 

o 

."2 


00 

c 
o 


1> — 

03 O 
^ CD 
— 00 

c < 


CD 
X 

>, 

X 


o 

CO 

CD 

■4— » 

03 

■*-^ 

X 


E 

CO 

"o 


CD 
X 

a. 

o 

Id 
■*-» 
CO 








is g 


a 


& 


'o 


s 


fc <U 


m 


PL, 


00 


Q 


la 


>3 




o 


-3 ^ 
^^ 

g <N 

id > — i 

2 £ 

3 .S 
U-o 

3 i— : 

•" C+-I 

6 ^ 

C^ CO 

•— <u 

II 

C3 P 

■*— » 

s-S 

3 3 

o o 

5- C 
>^ cd 

•^ IZ 


^^ 


3 


1- 




O XI 


i—i 


**h ti 


c 




EM 

S 


■a 

3 

co 

<*■ 
o 

at 

H 


E 

CO 

"o 


-o 

c 

03 

£ 

O 

C 
O 


E 
o 
x> 

(U 

2 

c 

CO 


o 
-a 

CD 

i-i 

'3 

a* 

CD 


X 

H 

_c 

n 
_o 


c 

-4—* 

tU CD 

I— ( 

T3 03 
O ^ 


? I 

g §■ 

u 3 
"O co 

x 1 


■ 

CD 

•3 
o 

CD 
C 

o 


° c5 

CD ^ 

,0) 03 

W CQ 
E | 

"o 5 


o 

X 

'1 

a 

CD 

Id 

2 


03 

'3 

O 

o 

a 


1/9 

e 

►>> 

s 
s 

3 

in 




00 

c 
o 

_c 

a 
_o 

-4— » 

o 

c 

3 

"2 
'S 

In 
>> 

X 

H 


f 

o 

CO 

X 

< 

CO 

fc 

<+d 
O 

c 
_o 

CO 

J 

CO 

w 


a 

en 
<u 

03 

a. 
D 

<u 
c 

"3 

_o 

'o 

03 


CD 

g 

•3 "^ 
^ '3 

O XI 
CD H 
00 — 

03 « 
co C 

o E 
Q o 

■a* 

,§^ 

§2 


c 

CD 
CD 

C 

o 
U 

CD 

a 

•3 

_o 

i 

CD 

_> 
■*— > 

CD 

c3 co 

.2 | 


O o 
-a ca 

3 £ 

CD X 

§•0 

co .~ 

S " 


1 5 

"3 j 

3 CQ 

CO Dh 

c -a 

o c 

•^3 03 

S M 
P 03 

2 D 

o _ 

!h ' — ' 

>>fN 

[S2 


o 

CD 
-^ 
03 

CU co 

2 c2 

•S c 

o g 

5 I 

CO cD 

< a. 


Q 03 

« u 

O CD 

1-3 

.3 o 

.S o 

co E^ 
CD >n 

X ° 
^ CQ 

CO .S 


X 

u 

CD 

03 

a. 
D 

CD 
C 

■3 

_o 

'o 
•3 

03 

06 


_o 

'■*d 

CD 

c 

3 
Pd 

"2 
'o 

id 

X 

H 

(4-1 

o 

CO 

1) 

-3 
3 

00 


2 


4> — • 

15 "- -C 
« © 3 

Q a, 


in 


^ 


r*l 


m 


<N 


o 


r~~ 


r- 


MD 


M3 


in 


"* 


vo 


no 


VO 


VO 


>0 


NO 


IT) 


>o 


<o 


in 


in 


in 


93 

H 


On 


ON 


ON 


On 


ON 


On 


ON 


On 


C3N 


ON 


On 


ON 










iS 


C 










1— 

CD 

E 

t: 

03 










il 

1 3 


CS 

c 
u 
X 
03 
CO 


"3 

00 

o 


i5 

c 

03 

> 


O 

CO 

O 


03 
C 
CD 
X 
03 
CO 


E 

o 

X 
00 

O 


'"O 

c 

3 


CD 
C 


Id 

CD 

C 

c 


C 
03 

£ 

•a 

.2 


03 

-o 

3 
CD 

CQ 




S 


Q 
o 


< 


H 


s 


W 


CO 


o 


w 


o 

CQ 




u 






M 


S 


s 


CBJ 


M 


cd 


d 


J 


w 


u- 


< 


u ' 





fN 


3" 








m 








fN 






O 


O 








o 








fN 






























o 


C) 


m 


00 


m 


«* 


fN 




^, © 


NO 








o 


o 


© 


o 


O 




(N 








O 


O 


o 


o 


o 


o 


© 




O w 


d 






T3 


■a 








T3 






-o 


T3 






O 


o 






_ 


O 


__ 




2 


O 






<- 

>> 

H 


X 
H 


2 
o 


B 

O 

H 


c3 
O 

H 


X 

H 


ca 

o 
H 




X 

H 


X 

H 


















































^ 
























*** 




r- 




in 


o 

fN 


t— 


VO 


■* 




NO 

(N 


in 


> 
























K 
























53 












ITl OS 










^ 


"« 




m 


ro 


m 


fN 


m in 
i i 


f> 


m 
i 




m 


m 




i 


1 


i 


ft. 


u. u. 




00 




^^ 


-H 


















a 






T3 










s 


cn 






<u 






O 

X 

H 










o u 

ao o 


3 
O 
CD 

c 
ca 


s 
_2 


ca 
c 


X 

r ) 




c 






en 
C 

tS 

3 

e 

o 

X 

2 

"ca 

o 
2 


<*- 
o 

1) 

Q, 
>> 

H 

S3 

u 

S 
c+- 

o 


Dtein in the Study of Protein Di 
ith and without Cystic Fibrosis 


Blood Volume in Congenital Cyanotic Heart Disease: Simull 
Measurements with Evans Blue and Radioactive Phosphorus 


o 

1/3 

X) 

< 

c 

o 

c 

o 

en 

o 

o 

ca 

-a 

o 
o 

PL, 

1— 

u 
X! 


ne-13 1 Thyroid Uptake and Ur 
othyroid Children 


s 
_o 

ca 

o 

u- 

e 

-— 

o 

u 
C_ 

o 
o 

ea 

CJ 




CD 
X 

U 

g 

en 
CD 

•3 

3 
oo 

en 

C 

ca 

i 

X 


T3 

CD 
u. 

CD 

■a 

o 

en 

5 

-a 

c 
ca 

la 

o 
2 

CD 
X 

X 


5 
a 
g 

'1 
S 

c 
5 

1 




<*- 
o 

<u 

J^ 

ea 
■*— • 
a. 

D 

g 

■a 

o 


Uptake in the Stu 
ism in Childhood 


s-131 Labeled Pr 
on in Children w 


O 

-o 

c 
ca 

C/3 
CD 
■4— » 

ca 
■«-j 

>. 

X! 

Cu 

(+- 


Radioactive lodi 
Normal and Hyp 


T3 
CJ 

c 
ca 

CA 

ca 

u 

g 

'8 
o 

X 


en 
'en 

O 

— 
X 

D, 

CD 

2 


_g 
CD 

£ 

3 
U 
CD 

ca 
D 


CD 
g 

'•3 

CD 
_> 

■4—* 

i-i 
« S 

.2 2 

-Q T3 

ca ~ 


-s: 
u 
a 

> 




_> 

■*— » 

o 

ca 

o 
■3 

ca 

Pi 


<d 12 

S o 
.2 o 

-73 O. 


Use of lodin 
and Absorpti 
Pancreas 


O 

W 
u 

X 

H 


£.5 

£ S 

i o 

t- ■« 

<D «J 

C u 

ca x 

U W 


13 

"33 

X 

ca 
-J 


'o 

g, 
X 


<D 

g 

•o 
2 
'o 

-3 

ca 

Pi 


(V X 

O 3 
<D """ 
^ T3 

ca s 
S.i2 
D O 


ca 

en 

"a 
53 




■^j- 


m 


(N 




o 


o 


o 




ON 


r~- 


o 






i/~> 


>/~> 


»/■> 


>T) 


IT) 


in 




■^r 


"*■ 


SI 




ON 


on 


ON 


ON 


ON 


O 


On 




ON 


ON 






s 


















en 




43 

o 

5 


CS 














>^ 


>. 


a 




CD 
> 




+-i 

o 

CD 


e- 

ca 

X 


'5 

Pi 

< 


4) 




CD 

O 


X 

s 

3 


•1 

en 
ca 




C/3 
U 

> T3 


OO 


ca 

00 


00 


00 

2 


U 






a 

X 


5 




JS 


00 


Cu 


S 


J 


£ 


> 




a 


ui 


* 



ENDNOTES 



1 . As noted in the report of the Massachusetts Task Force, "many of the people 
who became residents of the Walter E. Fernald School . . . were not admitted with a 
diagnosis of mental retardation. Societal and cultural norms of the day permitted persons 
to be admitted to state-operated institutions for a number of reasons. All were labeled 
mentally retarded just by virtue of having lived within the facility." Task Force on 
Human Subject Research, to Philip Campbell, Commissioner, Commonwealth of 
Massachusetts Executive Office of Health and Human Services, Department of Mental 
Retardation, April 1994, "A Report on the Use of Radioactive Materials in Human 
Subject Research that Involved Residents of State-Operated Facilities within the 
Commonwealth of Massachusetts from 1943 to 1973" (ACHRE No. MASS-072194-A), 
1. 

2. Task Force on Human Subject Research, April 1994 ("A Report on the Use 
of Radioactive Materials in Human Subject Research that Involved Residents of State- 
Operated Facilities within the Commonwealth of Massachusetts from 1943 to 1973"); 
and the Working Group on Human Subject Research to Philip Campbell, June 1994 
("The Thyroid Studies: A Follow-up Report on the Use of Radioactive Materials in 
Human Subject Research that Involved Residents of State-Operated Facilities within the 
Commonwealth of Massachusetts from 1943 through 1973") (ACHRE No. MASS- 
072194-B). 

3. Unfortunately, the published reports of the twenty-one research projects we 
review in this chapter often provide little or no information that could be used to identify 
the individual children. Many published reports provide information only about the 
child's age, weight, and diagnosis. Other reports provide only the child's initials and 
diagnosis. In either case, it would be difficult or impossible to identify specific 
individuals from this limited information. An existing chart may or may not confirm a 
child's involvement in a research project. If the investigators maintained records, those 
could serve as a key to identify the individuals. Even if the hospital records do exist, 
however, records for a period of several years prior to publication of the research would 
have to be reviewed in order to match a set of initials with a diagnosis. However, it is 
unlikely that research records have been maintained for many of these projects for the 
past three to five decades. Finally, the identification of an individual would be only the 
first step in tracking him to his current location. 

Many of the children at the Wrentham and Fernald Schools have been located 
through extensive local efforts. The existence of the research records, as well as the 
records of these long-term residential institutions, have made these identifications 
possible. 

4. There are a few exceptions to the usual involvement of parents in decisions 
concerning their minor children. Children who are considered either "emancipated 
minors" or "mature minors" are generally able to receive routine medical care without 
any need for parental involvement. Emancipated minors are minor children who have 
taken on adult responsibilities, such as maintaining financial independence and/or living 
away from the parents' home. A mature minor, on the other hand, is considered to be 
decisionally capable under special circumstances because he or she has demonstrated the 
maturity and ability to decide treatment decisions for himself or herself. Adolescents can 
be considered emancipated or mature minors and are thereby exempted from parental 
consent. In addition, if a minor is close to the age of majority (at least fifteen), the 
treatment clearly benefits the minor and is medically necessary, there is good justification 
for not obtaining parental consent, and if the procedure is not extraordinary or one 

358 



involving substantial risk to the child, then practitioners are usually able to deliver 
medical care without parental permission. A number of states permit minors to give 
consent to the diagnosis or treatment of venereal disease, drug addiction, alcoholism, 
pregnancy, or for purposes of giving blood. For more information on this subject, please 
see: A. R. Holder, Legal Issues in Pediatrics and Adolescent Medicine (New Haven, Yale 
University Press, 1985), 123; and Robert H. Mnookin and D. Kelly Weisberg, Child, 
Family, and State: Problems and Materials on Children and the Law (Little Brown and 
Company, New York, 1995). 

5. Mnookin and Weisburg, Child, Family, and State, 536. In addition, parents 
are considered to be "legally responsible for the care and support of their children," and 
"the parental consent requirement protects parents from having to pay for unwanted or 
unnecessary medical care and from the possible financial consequences of supporting the 
child if unwanted treatment is unsuccessful." 

6. In addition to the exceptions given in endnote 4, there are other standard 
common law and statutory limitations and exceptions to the general parental consent 
requirement. "These relate to mandatory immunizations and screening procedures 
(applicable to all children), the neglect limitation (where a court may override a parental 
decision for an individual child), the emergency treatment of children (where no parental 
consent is required if the parent is unavailable)." Ibid. 

7. "Some medical procedures are required of all children and in this sense 
represent generally applicable limitations on parental prerogatives. The Supreme Court 
has held, for example, that a state could impose a compulsory smallpox vaccination law 
as a 'reasonable and proper exercise of police power.' Jacobsen v. Massachusetts, 197 
U.S. 1 1, 35 (1905) quoting Viemeister v. White, 72 N.E. 97 (1904). A vaccination 
requirement may act to protect society from various public health hazards created by 
communicable diseases where a parental decision may endanger not only a particular 
child but society at large." Mnookin and Weisburg, Child, Family, and State, 55 1 . 

8. The National Commission for the Protection of Human Subjects of 
Biomedical and Behavioral Research, Research Involving Children: Report and 
Recommendations (Washington, D.C.: GPO, 1977), and Protection of Human Subjects, 
45 C.F.R. § 46, subpart D. 

9. Protection of Human Subjects, 45 C.F.R. § 46.408. 

10. Ibid., § 46.404. 

11. Ibid., § 46.406. 

12. Ibid., § 46.407. 

13. Susan E. Lederer and Michael A. Grodin. "Historical Overview: Pediatric 
Experimentation," in Children as Research Subjects: Science, Ethics, and Law, eds. 
Michael A. Grodin and Leonard H. Glantz (New York: Oxford University Press, 1994), 
4. 

14. Ibid., 5. 

15. Ibid., 6. 

16. "Orphans and Dietetics," American Medicine 27 (1921): 394-396. 

1 7. Lederer and Grodin, Children as Research Subjects, 11-12. 

18. Ibid., 14. 

19. Ibid., 12. 

20. Ibid., 15. 

2 1 . This ruling is summarized in Jay Katz, Experimentation with Human 
Beings, the Authority of the Investigator, Subject, Professions, and State in the Human 
Experimentation Process (New York: Russell Sage Foundation, 1972), 972-974. 

22. Ibid. 

23. Ibid. 



359 



24. Ibid. 

25. This case is also discussed in "Use of Fifteen Year Old Boy as Skin Donor 
Without Consent of Parents as Constituting Assault and Battery: Bureau of Legal 
Medicine and Legislation Society Proceedings," Journal of the American Medical 
Association 1 20 ( 1 7 October 1942): 562-563. 

26. For more information on the Nuremberg Code, please see United States v. 
Karl Brandt, et ai, "The Medical Case," Trials of War Criminals before the Nuremberg 
Military Tribunals under Control Council Law No. 10 (Washington, D.C.: GPO, 1949), 
2; Jay Katz, "Human Experimentation and Human Rights," St. Louis University Law- 
Journal 38 (1993); and George J. Annas and Michael A. Grodin, eds., The Nazi Doctors 
and the Nuremberg Code: Human Rights in Human Experimentation (New York: 
Oxford University Press, 1992). 

27. Irving Ladimer, "Legal and Ethical Implications of Medical Research on 
Human Beings," (S.J.D. diss., George Washington University, 1958), appendix II, 202- 
208. 

28. Ibid., 207. 

29. Ibid., 206. 

30. Ibid., 208. 

3 1 . Henry Seidel, interview by Gail Javitt ( ACHRE), transcript of audio 
recording, 20 March 1995 (Research Project Series, Oral History Project), 67-68. 

32. Ibid. 

33. William Silverman, interview by Gail Javitt (ACHRE), transcript of audio 
recording, 14 February 1995 (Research Project Series, Oral History Project), 26. 

34. Ibid. 

35. Boston University, Law-Medicine Research Institute, 1 May 1961 
("Conference on Social Responsibility in Pediatric Research")(ACHRE No. BU-062394- 
A). This was part of a larger LMRI project (which was funded by NIH) to investigate 
actual practices in clinical research. The project began in early 1960 and continued until 
1963, resulting in a lengthy final report, which was never published. 

36. Ibid., 5. In this document, speakers are identified by initials. A list of 
participants found in these same records generally makes identifying particular speakers 
in the transcripts quite straightforward. In this case, however, a complexity arises 
because the speaker is identified as "WF." The list of participants reveals no one with 
these initials, and "WF" appears only once in the transcripts. It is almost certain that 
"WF" is a typographical error, and given the flow of the transcripts, it is also almost 
certain that "WF" should have been "WS"--William Silverman. 

37. Ibid., 7. 

38. Ibid,, 3. 

39. Ibid. 

40. Ibid., 2. 

41. Ibid., 6. 

42. Ibid., 17. 

43. Ibid., 15. 

44. Ibid. 

45. The Declaration of Helsinki can be found in many sources, but its earliest 
published appearance was perhaps "Human Experimentation: Code of Ethics of the 
World Medical Association," British Medical Journal 2 (1964): 177. 

46. Ibid. 

47. Ibid. 

48. Ibid. 

49. Ibid. 



360 



50. Much has been written on the Willowbrook studies; for a short summary of 
this episode see Ruth R. Faden and Tom L. Beauchamp, A Histoiy and Theoiy of 
Informed Consent (New York: Oxford University Press, 1986), 5, 163-164. 

5 1 . Henry Beecher, Research and the Individual: Human Studies (Boston: 
Little, Brown, and Company, 1970), 122-127. 

52. There were many exchanges in the medical literature over the hepatitis 
studies conducted by Saul Krugman at the Willowbrook State School. Stephen Goldby 
wrote an editorial to The Lancet, expressing his outrage over The Lancet's position on 
Krugman's research, saying that the research was "quite unjustifiable, whatever the aims, 
and however academically or therapeutically important are the results. ... Is it right to 
perform an experiment on a normal or mentally retarded child when no benefit can result 
to that individual?" The editors of The Lancet responded to Goldby's letter, expressing 
agreement with his position, stating, "The Willowbrook experiments have always carried 
a hope that hepatitis might one day be prevented there and in other situations where 
infection seems almost inevitable; but that could not justify the giving of infected 
material to children who would not directly benefit." Krugman responded to these 
editorials by arguing, 

Our proposal to expose a small number of newly 
admitted children to the Willowbrook strains of hepatitis 
virus was justified in our opinion for the following 
reasons: 1 ) they were bound to be exposed to the same 
strains under the natural conditions existing in the 
institution, 2) they would be admitted to a special, well- 
staffed unit where they would be isolated from exposure 
to other infectious diseases which were prevalent in the 
institution. . . . Thus, their exposure in the hepatitis unit 
would be associated with less risk than the type of 
institutional exposure where multiple infections could 
occur; 3) they were likely to have a subclinical infection 
followed by immunity to the particular hepatitis virus; 
and 4) only children with parents who gave informed 
consent would be included. 

The debate over these experiments continued, as evidenced by editorials by Geoffrey 
Edsall, Edward Willey, and Benjamin Pasamanick in The Lancet and through an editorial 
in JAMA as well. Jay Katz, Experimentation with Human Beings, 1007-1010; Geoffrey 
Edsall, "Experiments at Willowbrook," The Lancet ( 1 July 1971): 95; Edward N. Willey 
and Benjamin Pasamanick, "Experiments at Willowbrook," The Lancet (22 May 1971): 
1 078- 1 079; and "A Shedding of Light," Journal of the American Medical Association 
212(11 May 1970): 1057-1058. 

53. S. Allan Lough, Chief of the Radioisotopes Branch, AEC Isotopes Division, 
to Drs. Hymer L. Friedell, G. Failla, Joesph G. Hamilton, A. H. Holland, Members of 
AEC Subcommittee on Human Applications, 19 July 1949 ("Revised Tentative Minutes 
of March 13, 1949 Meeting of Subcommittee on Human Applications of Committee on 
Isotope Distribution of U.S. Atomic Energy Commission, AEC Building, Washington, 
D.C.") (ACHRE No. NARA-082294-A-24). For price list and isotope catalogue, see 
AEC Isotopes Division, Supplement No. 1 to Catalogue and Price List No. 3, September 
1949 (ACHRE No. DOD-122794-A), 3-4. 

54. S. Allan Lough, 19 July 1949 ("Revised Tentative Minutes of March 13, 
1949 Meeting..."), 10. 



361 



55. AEC General Manager Carroll Wilson's two 1947 letters that address the 
consent issue (see chapter 1) did not specifically mention children. The second letter, 
dated November 1947, required that "the patient give his complete and informed consent 
in writing, and (c) that the responsible nearest of kin give in writing a similarly complete 
and informed consent. . . ." It is not clear, however, that Wilson's phrase, "responsible 
nearest of kin," was written out of concern for children and other patients not capable of 
giving "complete and informed consent," as opposed, for example, to adult patients who 
were too sick to give such consent. Moreover, it is not even clear whether the letter was 
intended to apply to experiments with healthy subjects, as opposed to sick patients, or to 
experiments using tracer amounts of radioactive substances. The second letter is 
specifically focused on "substances known to be, or suspected of being, poisonous or 
harmful." It is plausible, for example, that tracer amounts of radionuclides were 
considered "harmless," especially since the Wilson letter expressly prohibited the 
administration of "harmful" substances unless there was a reasonable hope that "such a 
substance will improve the condition of the patient." Carroll L. Wilson, General Manager 
of the AEC, to Stafford Warren, the University of California, Los Angeles, 30 April 1947 
("This is to inform you that the Commission is going ahead with its plans . . .") (ACHRE 
No. DOE-051094-A-439), 1. Also C. Wilson, General Manager, AEC, to Robert Stone, 
University of California, 5 November 1947 ("Your letter of September 1 8 regarding the 
declassification of biological and medical papers was read at the October 1 1 meeting of 
the Advisory Committee on Biology and Medicine.") (ACHRE No. DOE-052295-A). 

56. J. H. Lawrence, "Early Experiences in Nuclear Medicine," The Journal of 
Nuclear Medicine 20 (1979): 561 . (Publication of speech given in 1955). Dr. Lawrence 
concludes, however, that "as a matter of fact, in the 20 years since we first used 
artificially produced radioisotopes in humans, we have not run into delayed effects or 
complications as some of the skeptics predicted we would." Ibid., 562. 

57. This correspondence can be found in Task Force on Human Subject 
Research, A Report on the Use of Radioactive Materials, appendix B, documents 16-18. 

58. Citations for the studies for which the Committee performed detailed risk 
analysis can be found in the supplemental volumes. 

59. S. H. Silverman and L. Wilkins, "Radioiodine Uptake in the Study of 
Different Types of Hypothyroidism in Childhood," Pediatrics 12 (1953): 288-299. 

60. V. C. Kelley et al., "Labeled Methionine as an Indicator of Protein 
Formation in Children with Lipoid Nephrosis," Proceedings of the Society for 
Experimental Biology and Medicine 76 ( 1 950): 1 53- 1 55. 

61 . M. A. Van Dilla and M. J. Fulwyler, "Thyroid Metabolism in Children and 
Adults Using Very Small (Nanocurie) Doses of Iodine- 125 and Iodine- 131," Health 
Physics 9 (\963): 1325-1331. 

62. For more information, please see the "Introduction: The Atomic Century," 
sections entitled "How Do We Measure the Biological Effects of Internal Emitters?" and 
"How Do Scientists Determine the Long-Term Risks From Radiation?" 

63. International Commission on Radiological Protection, Publication 53: Data 
for Protection Against Ionizing Radiation from External Sources (New York: Pergamon 
Press, 1973); see also National Council on Radiation Protection and Measurements, 
Report 80: Induction of Thyroid Cancer by Ionizing Radiation— Recommendations of the 
National Council on Radiation Protection and Measurements (New York: The Council, 
1985). 

64. R. E. Shore et al., "Thyroid Tumors Following Thymus Irradiation," Journal 
of the National Cancer Institute 74 ( 1 985): 1 1 77- 1 1 84. 

65. E. Ron and B. Modan, "Thyroid and Other Neoplasms Following Childhood 
Scalp Irradiation," in J. D. Boice, Jr., and J. F. Fraumeni, Jr., eds., Radiation 



362 



Carcinogenesis: Epidemiology and Biological Significance (New York: Raven, 1 984), 
139-151. 

66. R. L. Prentice et al., "Radiation Exposure and Thyroid Cancer Incidence 
among Hiroshima and Nagasaki Residents," National Cancer Institute Monographs 62 
(1982): 207-212. 

67. National Council on Radiation Protection and Measurements, Report 80: 
Induction of Thyroid Cancer by Ionizing Radiation. The BIER V report recommends a 
figure of 0.66 but with a broad confidence interval of (0.14-3.15). National Research 
Council, Board on Radiation Effects Research, Committee on the Biological Effects of 
Ionizing Radiation, Health Effects of Exposure to Low Levels of Ionizing Radiation: 
BIER V{ Washington, D.C.: National Academy Press, 1990), 5, 298. 

68. Task Force on Human Subject Research, "A Report on the Use of 
Radioactive Materials in Human Subject Research that Involved Residents of State- 
Operated Facilities within the Commonwealth of Massachusetts from 1943 to 1973." 

69. Protection of Human Subjects, 45 C.F.R. § 46. 1 02. 

70. Ibid., § 46.406. 

71 . F. P. Castronovo, "An Attempt to Standardize the Radiodiagnostic Risk 
Statement in an Institutional Review Board Consent Form," Investigative Radiology 28 
(1993): 533-538. 

72. W. L. Freeman, "Research with Radiation and Healthy Children: Greater 
than Minimal Risk," IRB: A Review of Human Subjects Research 5, no. 16 (1994): 1-5. 

73. B. J. Duffy and P. J. Fitzgerald, "Thyroid Cancer in Childhood and 
Adolescence: A Report of Twenty-eight Cases," Cancer 3 (November 1950): 1018-1032. 

74. R. Murray, P. Heckel, and L. H. Hempelmann, "Leukemia in Children 
Exposed to Ionizing Radiation," New England Journal of Medicine 261(1 959): 585-597. 

75. Eugene L. Saenger et al., " Neoplasia Following Therapeutic Irradiation for 
Benign Conditions in Childhood," Radiology 74 (1960): 889-904. For more information 
on the work of Eugene Saenger, please see chapter 8, "Total-Body Irradiation: Problems 
When Research and Treatment Are Intertwined." 

76. Ibid., 889. 

77. Ibid., 901. 

78. S. A. Beach and G. W. Dolphin, "A Study of the Relationship Between X- 
Ray Dose Delivered to the Thyroids of Children and the Subsequent Development of 
Malignant Tumors," Physics in Medicine and Biology 6 ( 1 962): 583-598. 

79. Ibid., 583.' 

80. One rep (roentgen equivalent physical), a unit that is no longer used, is 
approximately equivalent to one rem (roentgen equivalent man). 

81. J. C. Aub, A. K. Solomon, and Shields Warren, Harvard Medical School, 7 
May 1949 ("Tracer Doses of Radioactive Isotopes in Man") (ACHRE No. HAR- 100395- 
A). It appears that at least one physician-researcher of the time determined to avoid an 
unknown risk by not administering radioisotopes in studies with pregnant women and 
children. In his recent autobiography, Dr. Francis Moore, an eminent Boston-based 
surgeon, recalled that "in pregnancy, even very small doses of radiation are dangerous to 
the unborn child, so we did not use radioactive isotopes in studying the body composition 
in pregnant women or in young children." Presumably Dr. Moore is referring to the 
1940s when he began his pioneering research employing radioisotopes to determine the 
composition of the body, although this is not clear. Whether Dr. Moore's view was 
informed by dialogue with the relevant pediatric perspectives reviewed here also is 
unclear. Francis D. Moore, M.D., A Miracle and a Privilege: Recounting a Half Century 
of Surgical Advance (Washington, D.C.: Joseph Henry Press, 1995), 109, 111. 



363 



82. L. Van Middlesworth, "Radioactive Iodide Uptake of Normal Newborn 
Infants," American Journal of Diseases of Children 88(1 954): 44 1 . 

83. Malcom J. Farrell, Superintendent, Walter E. Fernald State School, to 
Parent, 2 November 1949 ("The Massachusetts Institute of Technology and this 
institution are very much interested . . ."), as cited in the Task Force for Human Subject 
Research, "A Report on the Use of Radioactive Materials," appendix B, document 19. 

84. This form states, 

To the Superintendent of the Walter E. Fernald State 
School: 

This is to state that I give my permission for the 

participation of in the project mentioned in your 

letter of 

Witnessed by: 



Signature 
Date: 



Relationship 

Permission form from Parent to the Superintendent of the Walter E. Fernald State School, 
2 November 1949 ("This is to state that I give my permission . . ."), as cited by the Task 
Force on Human Subject Research, in "A Report on the Use of Radioactive Materials," 
appendix B, document 19. 

85. Clemens E. Benda, Director of Research, the Walter E. Fernald State 
School, to Parent, 28 May 1953, as cited by the Task Force on Human Subject Research, 
in "A Report on the Use of Radioactive Materials," appendix B, document 23. 

86. As stated in the Massachusetts Task Force report, the purpose of the 
nutritional research studies was to "understand how the body obtained the minerals iron 
and calcium from dietary sources and to find out whether compounds in cereals affected 
their absorption ... the immediate goal of the research was to understand if either of 
these cereals was preferable from a nutritional point of view." Ibid., 16. 

87. Ibid., 43. 

88. Fred Boyce, transcript of audio testimony before the Advisory Committee 
on Human Radiation Experiments, 16 December 1994, 38. 

89. Task Force on Human Subject Research, in "A Report on the Use of 
Radioactive Materials," 33. 

90. Susan E. Lederer and Michael A. Grodin, "Historical Overview: Pediatric 
Experimentation," 12-13. 

91. Boston University, Law-Medicine Research Institute, 1 January 1960 to 31 
March, 1963, /J Study of the Legal, Ethical, and Administrative Aspects of Clinical 
Research Involving Human Subjects: Final Report of Administrative Practices in Clinical 
Research, Research Grant No. 7039 (ACHRE No. BU-053194-A), 34. 

92. Fred Boyce, 16 December 1994, 38. 

93. Robert S. Harris, Professor of Biochemistry and Nutrition, Massachusetts 
Institute of Technology, to Clemens E. Benda, 1 May 1953, as cited by the Task Force 
on Human Subject Research, in "A Report on the Use of Radioactive Materials," 
appendix B, document 21,1. 



364 



94. Ibid. 

95. Children who are considered "wards of the State or any other agency, 
institution, or entity" can become subjects of research if the research is related to their 
status as wards and conducted in a setting in which the majority of children involved in 
the research are not wards. If the research meets these conditions, the IRB must then 
appoint a special advocate not associated in any way with the research, who will act in 
the best interests of the child. Protection of Human Subjects, 45 C.F.R. § 46.409. 

96. There are also no special regulations protecting institutionalized adults. The 
Committee believes that the federal government should inplement public policies to fill 
this regulatory gap. 

97. This conclusion does not hold for people who believe that it is never 
acceptable to use children as subjects in nontherapeutic research, even if the research is 
risk-free. 

98. G. S. Kurland et al., "Radioisotope Study of Thyroid Function in 21 
Mongoloid Subjects, including Observations in 7 Parents," Journal of Clinical 
Endocrinology and Metabolism 17 (1957): 552-60; A. Friedman, "Radioactive Uptake in 
Children with Mongolism," Pediatrics 16 (1955): 55; S. H. Silverman and L. Wilkins, 
"Radioiodine Uptake in the Study of Different Types of Hypothyroidism in Childhood," 
288-299; and E. H. Quimby and D. J. McCune, "Uptake of Radioactive Iodine by the 
Normal and Disordered Thyroid Gland in Children," Radiology 49 (1947): 201-205. 

99. Boston University Law-Medicine Research Institute, Final Report of 
Administrative Practices in Clinical Research, 34. 



365 



8 

Total-Body Irradiation: 

Problems when Treatment and 

Research Are Intertwined 



In the fall of 1971, a public controversy erupted about the ethics of a 
research project at the University of Cincinnati College of Medicine funded for 
more than a decade by the Department of Defense (DOD). In this research, the 
subjects were cancer patients who underwent external total-body irradiation (TBI); 
the DOD was funding postirradiation research on the biological effects of this type 
of exposure to radiation. Critics of the research charged that the physician- 
investigators were exposing unknowing patients to potentially lethal doses of TBI- 
-not to treat their cancer, but to collect data on the effects of nuclear war f