Skip to main content

Full text of "Sickle disease research : an update : hearing before the Committee on Labor and Human Resources, United States Senate, One Hundred Third Congress, second session, on to award a grant to the Louisiana Department of Health and Hospitals to establish and construct the National Center for Sickle Cell Disease Research at Southern University in Baton Rouge, LA, and for related facilities and equipment at such center, July 28, 1994"

See other formats


S.  HRG.  103-694 

SICKLE  DISEASE  RESEARCH:  AN  UPDATE 


Y4.L  11/4:  S.  HRG.  103-694 


Sickle  Disease  Research:   An  Update, ...  RING 

OF  THE 

COMMITTEE  ON 

LABOR  AND  HUMAN  RESOURCES 

UNITED  STATES  SENATE 

ONE  HUNDRED  THIRD  CONGRESS 
SECOND  SESSION 

ON 

TO  AWARD  A  GRANT  TO  THE  LOUISIANA  DEPARTMENT  OF  HEALTH 
AND  HOSPITALS  TO  ESTABLISH  AND  CONSTRUCT  THE  NATIONAL 
CENTER  FOR  SICKLE  CELL  DISEASE  RESEARCH  AT  SOUTHERN  UNI- 
VERSITY IN  BATON  ROUGE,  LA,  AND  FOR  RELATED  FACILITIES  AND 
EQUIPMENT  AT  SUCH  CENTER 


JULY  28,  1994 


Printed  for  the  use  of  the  Committee  on  Labor  and  Human  Resources 


U.S.  GOVERNMENT  PRINTING  OFFICE 
82-663  CC  WASHINGTON  :  1994 


°"  26  1994 


For  sale  by  the  U.S.  Government  Printing  Office 
Superintendent  of  Documents,  Congressional  Sales  Office,  Washington,  DC  20402 
ISBN   0-16-044846-8 


S.  HRG.  103-694 

SICKLE  DISEASE  RESEARCH:  AN  UPDATE 


Y4.L  11/4:  S.  HRG.  103-694 


Sickle  Disease  Research:   An  Update, . . .  RING 

OF  THE 

COMMITTEE  ON 

LABOR  AND  HUMAN  RESOURCES 

UNITED  STATES  SENATE 

ONE  HUNDRED  THIRD  CONGRESS 
SECOND  SESSION 

ON 

TO  AWARD  A  GRANT  TO  THE  LOUISIANA  DEPARTMENT  OF  HEALTH 
AND  HOSPITALS  TO  ESTABLISH  AND  CONSTRUCT  THE  NATIONAL 
CENTER  FOR  SICKLE  CELL  DISEASE  RESEARCH  AT  SOUTHERN  UNI- 
VERSITY IN  BATON  ROUGE,  LA,  AND  FOR  RELATED  FACILITIES  AND 
EQUIPMENT  AT  SUCH  CENTER 


JULY  28,  1994 


Printed  for  the  use  of  the  Committee  on  Labor  and  Human  Resources 


U.S.  GOVERNMENT  PRINTING  OFFICE 
82-553  CC  WASHINGTON  :  1994 

For  sale  by  the  U.S.  Government  Printing  Office 
Superintendent  of  Documents,  Congressional  Sales  Office,  Washington,  DC  20402 
ISBN   0-16-044846-8 


0Cr26fi94 


COMMITTEE  ON  LABOR  AND  HUMAN  RESOURCES 


EDWARD  M.  KENNEDY,  Massachusetts,  Chairman 


CLAIBORNE  PELL,  Rhode  Island 
HOWARD  M.  METZENBAUM,  Ohio. 
CHRISTOPHER  J.  DODD,  Connecticut 
PAUL  SIMON,  Illinois 
TOM  HARKIN,  Iowa 
BARBARA  A.  MIKULSKI,  Maryland 
JEFF  BINGAMAN,  New  Mexico 
PAUL  D.  WELLSTONE,  Minnesota 
HARRIS  WOFFORD,  Pennsylvania 

NICK  LTTTLEHELD,  Staff  Director  and  Chief  Counsel 
SUSAN  K.  HattaN,  Minority  Staff  Director 


NANCY  LANDON  KASSEBAUM,  Kansas 

JAMES  M.  JEFFORDS,  Vermont 

DAN  COATS,  Indiana 

JUDD  GREGG,  New  Hampshire 

STROM  THURMOND,  South  Carolina 

ORRIN  G.  HATCH,  Utah 

DAVE  DURENBERGER,  Minnesota 


01) 


CONTENTS 


STATEMENTS 
Thursday,  July  28,  1994 


Page 


Johnston,  Hon.  J.  Bennett,  a  U.S.  Senator  from  the  State  of  Louisiana; 
and  Hon.  William  Jefferson,  a  Representative  in  Congress  from  the  State 

of  Louisiana  ■£ 

Prepared  statement  of  Senator  Johnston  <* 

Lenfant,  Claude,  M.D.,  Director,  National  Heart,  Lung,  and  Blood  Institute, 

National  Institutes  of  Health  ? 

Prepared  statement  ••■••• ••• ••••         9 

Kennedy,  Hon.  Edward  M.,  a  U.S.  Senator  from  the  State  of  Massachusetts, 

prepared  statement ■»•■ ■»•• •— •» •■•"•••'••••••:••"        *° 

Agnew,  Shawnita,  honor  student,  English  High  School  Boston,  MA;  Lillian 
McMahon,  M.D.,  Director,  Comprehensive  Sickle  Cell  Center,  Boston  City 
Hospital,  Boston,  MA;  Ernest  A.  Turner,  M.D.,  Director,  Comprehensive 
Sickle  Cell  Center,  Meharry  Medical  School,  Nashville,  TN;  William  E. 
Moore,  M.D.,  vice  chancellor  for  academic  affairs,  Southern  University, 
Baton  Rouge,  LA;  Kwaku  Ohene-Frempong,  M.D.,  Director,  Comprehensive 
Sickle  Cell  Center,  The  Children's  Hospital  of  Philadelphia,  Philadelphia, 

PA;  and  Hon.  Charles  D.  Jones,  Louisiana  State  Senator  17 

Prepared  statements  of: 

Ms.  Agnew j-° 

Dr.  McMahon  21 

Dr.  Turner 45 

Dr.  Moore  29 

Dr.  Ohene-Frempong 39 

Mr.  Jones  53 

an> 


SICKLE  DISEASE  RESEARCH:  AN  UPDATE 


THURSDAY,  JULY  28,  1994 

U.S.  Senate, 
Committee  on  Labor  and  Human  Resources, 

Washington,  DC. 

The  committee  met,  pursuant  to  notice,  at  1:34  p.m.,  in  room 
SD-430,  Dirksen  Senate  Office  Building,  Senator  Edward  M.  Ken- 
nedy (chairman  of  the  committee)  presiding. 

Present:  Senators  Kennedy,  Simon,  and  Wellstone. 

Opening  Statement  of  Senator  Simon 

Senator  Simon  [presiding].  The  hearing  will  come  to  order. 

This  is  a  hearing  requested  specifically  by  Senator  Bennett  John- 
ston, and  we  are  pleased  to  have  it.  I  am  pinch-hitting  temporarily 
for  Senator  Kennedy,  who  will  be  along  before  very  long  to  join  us 
for  the  hearing. 

The  hearing  is  about  sickle  cell  anemia,  a  very  major  problem  in 
our  country,  and  the  question  is  whether  we  are  doing  enough  re- 
search in  this  field.  In  the  whole  field  of  science,  there  is  no  one 
in  the  U.S.  Senate  who  is  as  knowledgeable  as  Senator  Bennett 
Johnston.  I  have  to  say  in  candor,  I  do  not  know  if  that  applies  to 
sickle  cell  anemia,  but  I  have  worked  with  him  on  a  variety  of 
other  scientific  projects  and  have  always  been  amazed  at  the  depth 
of  his  knowledge. 

One  of  the  questions  is  whether  we  should  be  earmarking  funds, 
and  how  do  we  make  sure  that  we  do  the  kind  of  research  job  that 
needs  to  be  done. 

So  we  are  pleased  to  call  on  you,  Senator  Johnston,  to  open  this 
up. 

STATEMENTS  OF  HON.  J.  BENNETT  JOHNSTON,  A  U.S.  SEN- 
ATOR FROM  THE  STATE  OF  LOUISIANA;  AND  HON.  WILLIAM 
JEFFERSON,  A  REPRESENTATIVE  IN  CONGRESS  FROM  THE 
STATE  OF  LOUISIANA 

Senator  Johnston.  Mr.  Chairman,  thank  you  very  much,  and 
thank  you  for  your  very  kind  comments,  which  I  appreciate. 

Mr.  Chairman,  this  bill  would  establish  a  sickle  cell  anemia  re- 
search center  at  Southern  University  in  Baton  Rouge. 

I  have  a  written  statement,  which  I  would  like  to  submit  for  the 
record. 

Senator  Simon.  It  will  be  entered  in  the  record. 

Senator  Johnston.  I  think  the  members  of  this  committee  gen- 
erally are  familiar  with  the  scourge  of  sickle  cell  anemia,  which  is 

(1) 


really  the  scourge  of  the  African  American  community  in  this  coun- 
try. 

The  trait  in  the  hemoglobin  affects  10  percent  of  the  African 
American  population.  Not  that  many  are  afflicted,  but  among  that 
10  percent,  you  never  know  where  it  is  going  to  strike  and  when 
it  is  going  to  strike,  and  when  it  does,  it  is  terribly  severe,  and  it 
has  just  been  a  terrible  thing  for  the  African  American  community 
and  one  that  cries  out  for  research;  there  is  not  enough  researcn 
being  done. 

The  real  focus,  I  think,  of  S.  1724  is  not  whether  or  not  sickle 
cell  anemia  is  serious  enough  to  warrant  the  kind  of  Federal  effort 
that  this  envisages.  I  think  that  question  answers  itself,  and  I 
think  it  is  overwhelmingly  in  favor  of  the  affirmative  answer.  Nor 
is  it  arguable  that  we  know  enough  about  it.  I  think  we  clearly 
need  to  do  that. 

The  question  is  why  Southern  University.  That,  I  think,  is  really 
the  crux  of  this,  and  that  was  the  question  that  submitted  itself  to 
the  President  who,  on  two  occasions,  endorsed  and  committed  him- 
self to  a  sickle  cell  anemia  research  center  at  Southern  University 
in  Baton  Rouge.  And  it  is  a  question  that  addressed  itself  to  the 
Black  Caucus  in  Congress,  and  the  Black  Caucus  addressed  the 
question,  and  every,  single  member  of  that  Caucus — and  I  would 
like  to  submit  for  the  record  letter  to  Donna  Shalala  endorsing  this 
research  center,  signed  by  each  and  every  member  of  the  Black 
Caucus,  some  of  whom  have  in  their  districts  institutions  that  do 
researcn. 

So  at  least  insofar  as  this  administration  and  all  of  the  members 
of  the  Black  Caucus,  they  have  made  the  determination  that 
Southern  is  the  appropriate  spot. 

So  the  question  for  this  committee  is  why  Southern.  Well,  we 
begin  with  the  fact  that  Southern  University  is  the  largest  histori- 
cally black  college  or  university  in  the  country.  It  has  16,000  stu- 
dents, among  whom  are  some  distinguished  graduates,  some  less 
distinguished — I  am  only  kidding — my  colleague,  Congressman 
William  Jefferson,  seated  beside  me,  is  a  graduate  of  Southern  Uni- 
versity undergrad  and  some  other,  mucn  less  distinguished,  law 
school — Harvard,  I  think  it  was. 

Thirty  percent  of  the  population  of  my  State  of  Louisiana  is  Afri- 
can American,  among  which  10  percent  have  this  sickle  cell  trait 
in  their  blood.  That  means  130,000  Louisianians  have  this  trait. 

More  to  the  point,  there  has  been  a  commitment  by  Southern 
University  to  fund  this  center.  You  will  be  hearing  later  from  the 
president  and  the  chancellor  from  Southern  University,  who  will 
tell  you  more  about  that  commitment,  but  suffice  it  to  say  that  the 
State  of  Louisiana,  through  our  Governor,  and  Southern  University 
have  committed  to  fund  this  institution,  to  keep  its  research  funded 
as  it  goes  on,  and  the  legislature  has  voted  $7  million  which  is  now 
available  in  a  fund  for  the  construction.  So  that  the  commitment 
of  the  State  of  Louisiana,  of  Southern  University,  and  of  the  legis- 
lature is  complete  and  is  not  matched  anywhere  else  in  the  coun- 
try. 

Now,  what  is  their  capability  of  doing  this?  Well,  the  legislation 
calls  for,  and  there  has  been  collaboration  with  Louisiana  State 
University  Medical  School  and  Tulane  University  Medical  School, 


along  with  the  other  sickle  cell  anemia  research  institutions  in  the 
country,  including  NIH,  Duke,  and  Children's  Hospital  of  Philadel- 
phia, which  have  all  given  resources  and  have,  in  the  case  of 
Tulane  and  LSU,  committed  to  enter  into  cooperative  agreements 
in  setting  up  this  institution,  which  in  turn  would  draw  upon  the 
very  best  in  research,  the  best  experts  in  the  country.  The  full-time 
faculty  would  be  given  tenure  status  at  Southern  University,  to 
which  Southern  has  committed. 

So  that  what  we  have  in  effect  is  a  total  commitment  from  the 
administration,  from  the  Black  Caucus,  from  Southern  University, 
from  our  Governor,  from  our  legislature,  and  from  the  State  of  Lou- 
isiana to  ensure  that  this  institution  would  be  the  best  and  do  the 
best  kind  of  research  that  is  possible  to  do. 

Mr.  Chairman,  I  do  not  think — I  know — that  there  is  no  other  in- 
stitution that  can  make  that  statement.  There  are  others  that  per- 
haps have,  along  with  a  lot  of  other  research — NIH,  for  example, 
does  very  good  research — but  the  African  American  community 
wants  a  place  that  they  can  identify  as  the  clearinghouse  where 
this  is  the  principle  endeavor,  the  principle  focus,  and  the  principal 
reason  and  raison  d'etre  is  sickle  cell  research — not  hundreds  of 
other  research  endeavors,  worthy  though  they  may  be,  but  one 
committed  to  sickle  cell  that  they  can  claim  as  their  own  and  that 
the  State  of  Louisiana  will  fully  support. 

Mr.  Chairman,  I  strongly  urge  this  committee  to  act  favorably 
upon  this  bill. 

Senator  Simon.  Thank  you  very  much. 

[The  prepared  statement  of  Senator  Johnston  follows:] 

Prepared  Statement  of  Senator  J.  Bennet  Johnston 

If  you  are  an  African  American,  and  particularly  if  you  are  an  African  American 
parent,  S.  1724  may  be  one  of  the  most  important  pieces  of  legislation  considered 
by  the  Congress  this  year. 

S.  1724  establishes  a  national  center  for  research  on  Sickle  Cell  Disease,  a  pain- 
ful, life-threatening,  inherited  illness  which  affects  African  Americans  almost  exclu- 
sively. Approximately  one  in  every  twelve  black  Americans  is  born  with  the  sickle 
cell  trait;  about  one  in  every  400  has  the  disease. 

Because  it  is  genetic  in  origin,  parents  pass  the  disease  to  their  children.  If  both 
parents  carry  the  trait,  one  in  four  of  their  children,  on  a  statistical  basis,  will  have 
the  disease.  For  thousands  of  African-American  parents,  the  joy  of  childbirth  is 
marred  by  fear,  because  in  our  present  condition  of  medical  ignorance,  doctors  do 
not  know  how  to  prevent  the  disease  or  cure  it.  The  best  they  can  do  is  treat  pa- 
tients for  the  excruciating  pain  which  accompanies  a  disease  crisis.  Children  af- 
flicted with  severe  forms  of  the  disease — about  one  case  in  four — do  not  usually  live 
through  adolescence. 

No  group  of  Americans  should  have  to  watch  its  children  live  and  die  in  pain  if 
there  is  anything  the  Congress  can  do  about  it.  In  this  case,  I  believe  that  we  can 
do  something  which  will  help  those  with  the  disease,  and  which  will  offer  hope  to 
those  carrying  the  trait.  We  can  establish  a  national  center  to  serve  as  a  resource 
for  those  affected  by  the  disease  and  those  trying  to  eliminate  it:  patients,  trait- 
bearers,  doctors,  psychologists,  counselors  and  researchers.  This  center  would  have 
three  missions. 

First,  it  would  perform,  or  collaborate  in  the  performance  of  research  into  the  na- 
ture of  the  disease:  a  hemoglobin  mutation  which  causes  the  distortion  of  red  blood 
cells.  Research  will  also  be  conducted  in  the  areas  of  molecular  biology  and  genetic 
engineering:  including  DNA  manipulation. 

The  tragedy  of  sickle  cell  disease  is  that  parents  suffer  as  much  as  their  afflicted 
children.  The  second  function  of  a  national  center  would  be  the  examination  of  the 
psychosocial  aspects  of  the  disease,  including  the  effectiveness  of  various  counseling 
and  education  methods.  Data  from  broad-based  studies  would  be  gathered  to  illu- 


minate  public  policy  issues  such  as  the  mandatory  genetic  testing  of  susceptible 
newborns. 

Finally,  a  national  center  would  function  as  a  clearinghouse  for  all  available  infor- 
mation, both  biomedical  and  psychosocial,  about  the  disease.  A  national  center  is  in 
a  position  to  track  ongoing  research  projects  at  universities  and  hospitals  across  the 
country,  to  organize  their  findings  and  disseminate  this  information,  in  an  acces- 
sible form,  to  research  scientists  worldwide. 

S.  1724  directs  that  this  national  center  be  located  at  Southern  University  in 
Baton  Rouge,  Louisiana.  Founded  112  years  ago,  Southern  is  a  land  grant  college 
with  a  distinguished  teaching  faculty.  Its  administration  is  committed  to  scholarship 
and  the  preparation  of  minority  students  for  the  professions,  including  medicine  and 
the  sciences.  Southern  is  the  largest  predominantly  African  American  university  in 
the  United  States  with  over  16,000  students  enrolled.  Because  its  administra- 
tion,faculty,  students  and  alumni  are  all  affected,  directly  or  indirectly,  by  sickle  cell 
disease,  research  performed  at  Southern  will  have  an  urgency  and  involvement  not 
necessarily  found  at  other  institutions. 

Location  of  the  Center  at  Southern  is  supported  by  the  State  of  Louisiana.  Sickle 
cell  disease  is  a  serious  public  health  problem  for  Louisiana's  30  96  minority  popu- 
lation: one  of  every  10  African  Americans  in  the  state — 130,000  people — carries  the 
sickle  cell  trait.  The  Louisiana  Legislature  has  indicated  the  strength  of  its  commit- 
ment by  appropriating  $7  million  for  the  project,  contingent  upon  a  three  to  one 
match  from  Federal  funds. 

Southern  University  is  prepared,  without  reservation,  to  commit  its  resources  and 
personnel  to  this  project.  The  University  will  offer  faculty  appointments  and  a  ten- 
ure track  in  order  to  attract  qualified  research  faculty  to  the  Center,  and  will  en- 
courage undergraduate  students  to  work  as  research  assistants.  Realizing  that  there 
might  be  concern  about  establishing  a  biomedical  research  center  at  what  is  pri- 
marily a  teaching  institution,  planners  for  the  Center  have  made  every  effort  to 
draw  upon  existing  medical  resources  in  Louisiana  and  in  the  sickle  cell  research 
community. 

A  team  of  eminent  scientists  with  expertise  in  sickle  cell  research  will  act  as  a 
Technical  Advisory  Council  to  the  director  of  the  Center.  A  number  of  these  experts 
including  representatives  of  Sickle  Cell  Centers  at  NIH,  Duke  University  and  the 
Childrens  Hospital  of  Philadelphia  have  already  participated  in  a  planning  session 
and  submitted  suggestions  for  projects  to  be  undertaken  by  the  Center. 

Louisiana  medical  centers,  including  the  Earl  R.  Long  Memorial  Hospital  in  Baton 
Rouge,  the  Louisiana  State  University  centers  at  New  Orleans  and  Shreveport  and 
the  Tulane  University  Medical  Center,  have  indicated  their  support  for  the  Center. 
They  are  willing  to  enter  into  collaborative  arrangements  to  conduct  clinical  trials 
of  the  Center's  research  findings.  Southern  University's  plan  for  a  National  Center 
is  fully  supported  by  the  Louisiana  community  and,  nationwide,  by  the  sickle  cell 
disease  research  community.  It  represents  a  systematic  and  well-thought-out  attack 
on  an  important  public  health  problem.  Its  research  offers  the  possibility  of  finding 
a  cure  or,  at  the  very  least,  a  more  effective  treatment  for  an  agonizing  disease 
which  targets  a  vulnerable  segment  of  our  population.  It  deserves  the  support  of  the 
Congress. 

Senator  Simon.  We  are  pleased  to  have  Congressman  Jefferson, 
who  by  now  is  a  veteran  in  the  House. 

Mr.  Jefferson.  Thank  you,  Mr.  Chairman.  Good  afternoon  to 
you  and  to  others  who  make  up  this  committee. 

I  reluctantly  admit  that  my  Senator  has  covered  just  about  ev- 
erything that  is  important  to  be  said  here  today  and  has  covered 
it,  I  think,  with  a  great  deal  of  compassion  and  sincerity,  which 
shows  his  strong  commitment  to  this  issue. 

Those  of  us  in  Louisiana  see  him  as  a  guy  who  works  a  lot  of 
mundane  little  things,  moving  around  the  issues,  and  putting  bills 
together.  He  exhibits  his  passion  very  carefully.  But  today,  Mr. 
Chairman,  I  think  we  saw  a  dose  of  it,  and  I  think  that  when  he 
shows  it,  he  really  means  it,  and  I  am  glad  that  he  is  working  hard 
on  this  bill,  which  I  think  is  worthy  of  all  of  our  best  efforts. 

So  I  do  appreciate  the  opportunity  to  appear  before  you  today  to 
give  a  brief  statement  in  support  of  his  bill,  S.  1724,  a  bill  to  estab- 
lish the  sickle  cell  disease  research  center  at  Southern  University. 


5 

I  am  in  strong  support  of  this  legislation,  and  I  hope  that  the  Sen- 
ate will  pass  this  bill  this  year. 

I  want  to  commend  you,  Mr.  Chairman,  for  your  leadership  in 
the  area  of  medical  research.  You  have  been  in  the  forefront  in  au- 
thorizing important  research  programs  that  will  1  day — and  some 
have  already  done  it — find" cures  for  many  of  the  diseases  that  are 
affecting  millions  of  people  around  the  world. 

As  a  graduate  of  Southern  University,  as  Senator  Johnston  has 
already  informed  you,  which  is  the  largest  predominantly  African 
American  university  in  the  country,  I  am  proud  that  this  center 
will  be  cited  if  this  legislation  passes — and  we  are  hopeful  that  it 
will — at  Southern  University.  Southern  University  has  committed 
itself,  its  resources,  and  its  personnel  to  seeing  that  this  project  is 
successful  and  that  it  produces  a  cure  for  this  dread  disease. 

As  Senator  Johnston  described  in  general,  the  sickle  cell  disease 
is  a  serious  illness  that  disproportionately  affects  African  Amer- 
ican. One  of  every  12  African  Americans  is  born  with  the  sickle  cell 
trait,  and  about  one  in  every  600  develop  the  sickle  cell  disease.  In 
my  State,  that  means  130,000  people  have  the  trait  out  of  1.3  mil- 
lion people,  and  approximately  4,000  people  currently  suffer  from 
the  disease  in  Louisiana. 

Although  the  impact  of  this  disease  has  been  greatest  in  the  Afri- 
can American  community,  it  also  occurs  in  other  populations,  in- 
cluding those  of  Puerto  Rican,  Cuban,  Southern  Italian  ancestry, 
and  more  recently,  other  population  groups. 

Despite  this  well-documented  data  on  this  disease,  despite  its 
high  incidence  of  occurrence  and  its  spread  to  broader  populations, 
there  is  no  national  research  center  seeking  a  cure  for  this  deadly 
disease. 

Mr.  Chairman,  sickle  cell  disease  is  a  very  painful  disease  caused 
by  inadequate  transportation  of  oxygen  due  to  an  abnormal  type  of 
hemoglobin  molecule  in  the  red  blood  cells.  Even  with  medication, 
this  disease  will  cause  long-term  suffering.  Until  recently,  a  person 
with  this  disease  usually  died  before  the  age  of  20.  Victims  of  this 
disease  have  strokes,  heart  attacks,  and  other  fatal  illness  due  to 
oxygen  loss. 

We  think  it  is  time  the  Congress  and  the  Nation  make  important 
steps  to  address  this  tragic  oversight.  The  legislation  before  us 
today  creates  an  excellent  partnership  between  the  Federal  Gov- 
ernment, State,  and  teaching  universities  in  Louisiana.  The  State 
of  Louisiana  has  already  appropriated  $7  million  to  match  our  re- 
quest for  a  $21  million  Federal  grant  from  the  Department  of 
Health  and  Human  Services. 

Southern  University  has  devoted  significant  resources  toward  the 
development  of  this  research  center,  as  Senator  Johnston  has 
talked  about,  and  there  will  be  a  collaborative  arrangement  for 
joint  research  programs  and  projects  between  LSU,  Tulane,  and 
other  medical  ana  research  institutions  in  our  State  and  in  our 
city. 

Mr.  Chairman,  today,  you  will  hear  from  a  number  of  people  in- 
volved in  this  project  who  are  committed  to  making  this  national 
research  center  the  best  research  facility  on  this  issue  in  the  world. 
I  hope  that  you  and  the  members  of  this  committee  will  support 
this  important  bill. 


6 

Thank  you  very  much  for  giving  me  this  chance  to  appear  before 
you. 

Senator  Simon.  I  thank  you  both. 

Let  me  just  ask  a  question,  and  I  am  speaking  for  myself  now 
and  not  for  the  chairman  of  the  committee.  How  did  you  arrive  at 
the  $21  million  figure?  Ordinarily,  in  NIH  grants,  we  have  the  peer 
review  process.  How  do  you  handle  that  aspect  of  it  to  make  sure 
that  we  really  are  spending  our  money  wisely? 

Senator  Johnston.  First  of  all,  they  have  formed  a  coordinating 
committee  made  up  of  researchers  from  all  around  the  country — 
NIH,  Children's  Hospital  of  Philadelphia,  LSU,  Tulane,  and  South- 
ern University  has  committed  personnel  to  this — who  have  done 
the  preliminary  design  upon  which  the  $21  million — actually,  it  is 
$28  million,  because  the  State  of  Louisiana  has  put  up  $5  million, 
and  I  think  they  have  just  appropriated  an  additional  $500,000 — 
so  that  comprises  the  $28  million  figure. 

Now,  this  will  be  a  national  canter,  drawing  on  the  finest  re- 
searchers from  around  the  country.  We  do  not  intend  to  have  this 
be  an  in-house  research  center,  but  rather  a  national  center,  fund- 
ed, to  be  sure,  by  the  State  of  Louisiana  through  the  Southern  Uni- 
versity budget.  But  the  researchers  who  are  available  from  around 
the  country  will  be  those  who  do  the  work  at  Southern  University. 

Now,  in  terms  of  the  peer  review,  Mr.  Chairman,  of  course,  it 
would  be  possible  to  say,  well,  let  us  do  this  research  at  NIH.  But 
the  legislature  of  NIH  has  not  put  up  $7  million;  the  President  has 
not  committed  to  build  this  at  NIH.  The  Black  Caucus  has  not  en- 
dorsed NIH.  And  I  think  it  is  because  there  is  a  particular  feeling 
of— is  the  word  "ownership"  of  this  disease.  I  mean,  this  is  a  dis- 
ease that  afflicts  African  Americans,  and  Southern  University  is 
their  institution,  and  there  is  that  proprietary  interest  at  Southern 
University.  It  is  not  just  a  Louisiana  deal  because  it  is  endorsed 
by  every,  single  member  of  the  Black  Caucus. 

So  I  think  that  is  the  reason,  rather  than  peer  review.  We  expect 
the  peers  to  be  those  who  run  the  institution. 

Mr.  Jefferson.  I  would  agree  with  what  Senator  Johnston  has 
said,  and  in  addition,  I  would  say  that  there  is  nothing  inconsistent 
about  what  we  are  doing  here  and  the  idea  of  peer  review.  There 
can  be  peer  review  of  this  proposal,  and  there  can  be  done  peer  dis- 
cussion about  the  funding  levels.  If  someone  wants  to  quibble  about 
whether  it  should  be  lower  or  higher.  So  this  does  not  prevent  a 
real  examination  of  whether  this  proposal  ought  to  go  forward  as 
it  is  presented  or  whether  it  ought  to  be  rearranged.  But  it  does 
set  a  framework  within  which  this  discussion  can  take  place,  and 
that  is  really  all  that  we  are  asking  to  have  done  here. 

Senator  Simon.  All  right.  I  was  not  suggesting  that  it  ought  to 
be  NIH,  but  simply  that  we  ought  to  have  some  mechanism  so  that 
we  make  sure — and  I  do  not  mean  this  disrespectfully  to  Southern 
University — that  we  are  really  putting  this  where  we  ought  to  be 
putting  the  money. 

Senator  Johnston.  Oh,  yes;  we  solicit  that,  we  seek  that,  be- 
cause indeed,  we  do  want  to  make  it  a  national  institute  of  the  very 
highest  quality.  So,  yes,  on  oversight,  during  the  construction,  dur- 
ing the  formulation  of  the  research  projects,  we  very  much  seek 


that,  and  if  the  legislation  should  more  explicitly  say  that,  we 
would  welcome  that. 

Senator  Simon.  And  real  candidly,  I  was  drafted  at  the  last 
minute  to  preside  here,  as  both  of  you  understand,  although  I  have 
been  interested  in  this  subject  for  a  long  time.  And  we  appreciate 
your  testimony.  It  is  a  worthy  cause,  and  it  sounds  like  something 
that  we  ought  to  be  looking  at  very,  very  carefully. 

I  appreciate  your  being  here.  Thank  you. 

Senator  Johnston.  Thank  you,  Mr.  Chairman. 

Mr.  Jefferson.  Thank  you,  Senator. 

Senator  Simon.  Our  next  witness  is  Dr.  Claude  Lenfant,  Director 
of  the  National  Heart,  Lung,  and  Blood  Institute  at  NIH.  We  are 
pleased  to  have  you  here,  Dr.  Lenfant,  speaking  in  behalf  of  your 
institute. 

Please  proceed. 

STATEMENT  OF  CLAUDE  LENFANT,  M.D„  DIRECTOR,  NA- 
TIONAL HEART,  LUNG,  AND  BLOOD  INSTITUTE,  NATIONAL 
INSTITUTES  OF  HEALTH 

Dr.  Lenfant.  Thank  you  very  much,  Mr.  Chairman. 

I  am  very  pleased  indeed  to  be  here.  As  you  just  noted,  I  am 
Claude  Lenfant,  and  I  am  director  of  the  National  Heart,  Lung, 
and  Blood  Institute,  which  is  one  of  the  institutes  at  the  NIH 
which  has  just  been  discussed. 

My  institute  is  responsible  for  the  sickle  cell  disease  program 
that  we  are  supporting,  and  the  invitation  which  I  received  from 
Senator  Kennedy  was  to  discuss  with  you  the  sickle  cell  disease 
center  that  the  National  Institutes  of  Health  supports. 

I  cannot  think  of  a  better  way  to  present  to  you  the  national  net- 
work of  sickle  cell  disease  centers  that  we  are  supporting  than  by 
telling  you  about  the  research  accomplishments  which  have  been 
realized  since  the  creation  of  this  network  in  1972. 

With  your  permission,  I  would  like  to  take  you  very  briefly 
through  two  charts  which  I  have  here.  I  hope  you  can  see  my  little 
pointer  here,  with  the  red  dots. 

Senator  Simon.  Yes. 

Dr.  Lenfant.  OK.  At  the  bottom,  we  have  a  span  of  three  dec- 
ades, from  1970  to  the  year  2000.  Here,  what  you  have  is  the  re- 
search progress  which  has  been  accomplished  during  that  period  of 
time  since  we  have  been  supporting  the  center  and  where  we  ex- 
pect to  go.  You  can  see  for  each  decade  some  very  significant 
achievements  which  have  been  accomplished  which  have  led  us  to 
where  we  are  today. 

Senator  Simon.  Is  the  red  line  dollars  spent? 

Dr.  Lenfant.  The  red  line  represents  the  progress  which  has 
been  made  and  the  accumulation  of  knowledge  which  is  going  to 
eventually  bring  us  to  a  cure  of  this  condition. 

Senator  Simon.  How  do  you  measure  that?  When  you  put  it  on 
a  graph,  it  looks  very  precise. 

Dr.  Lenfant.  It  is  not  that  precise.  It  is  a  symbolic  representa- 
tion of  the  progress.  What  I  am  attempting  to  show  you  is  that  in 
the  early  1970  s,  when  the  center  network  program  was  created, 
our  knowledge  was  very  low,  very  rudimentary,  and  over  the  years, 
with  very  significant  support  from  the  Congress,  our  knowledge  has 


8 

increased  to  bring  us  close  to  what  we  believe  is  a  cure  for  this  dis- 
ease. It  is  in  sight.  I  cannot  tell  you  whether  it  is  going  to  be  in 
3  years  or  in  4  years,  but  I  can  tell  you  without  any  hesitation  that 
it  is  in  sight. 

And  basically,  what  you  see  on  these  charts  is  the  history  of  the 
basic  research  that  has  been  done — very  basic  research  at  the  cel- 
lular, at  the  molecular  level.  And  in  fact,  I  am  sure,  Senator,  you 
hear  in  Congress  and  elsewhere  the  term,  "molecular  medicine." 
Today,  medicine  is  seen  at  the  molecular  level.  And  it  may  be  of 
interest  to  you  that  the  term,  "molecular  medicine,"  was  invented 
in  relation  to  all  the  discoveries  and  the  advances  which  have 
taken  place  relative  to  sickle  cell  disease.  In  fact,  the  gene  which 
controls  this  disease  and  which  controls  the  hemoglobin,  which  we 
all  have  in  our  red  cells,  is  really  the  gene  about  which  we  have 
the  most  knowledge  today. 

The  second  chart  brings  you  the  clinical  research  and  the  ad- 
vances which  have  taken  place  during  that  period  of  time.  Here, 
during  the  first  decade,  you  can  see  great  advances  in  comprehen- 
sive care,  treatment  of  eye  abnormality — in  fact,  I  should  tell  you, 
Senator,  that  a  great  deal  of  the  work  concerning  the  eye  abnor- 
mality comes  from  investigators  from  Chicago,  from  your  State;  at 
this  point  in  time,  we  are  no  longer  supporting  them,  but  when 
they  were  supported  by  the  Institute,  we  were  extremely  proud  of 
the  very  remarkable  work  which  came  from  Chicago. 

I  would  like  to  underscore  susceptibility  to  infection.  So  many  of 
these  children  who  are  born  with  sickle  cell  disease  are  at  very 
high  risk  of  pneumococcal  infection,  which  is  a  respiratory  system 
infection,  and  would  die  from  that.  But  through  the  research  that 
has  been  done,  we  have  found  ways  to  prevent  this  complication, 
and  we  can  see,  as  we  move  along  from  the  1970's  to  now,  all  the 
advances  which  have  been  made  in  prenatal  diagnosis,  in  the  pre- 
vention of  stroke,  which  is  a  complication  of  this  condition,  the  de- 
velopment of  prophylactic  penicillin  to  treat  this  infection  that  I 
was  mentioning,  the  development  of  methods  for  newborn  screen- 
ing so  we  can  identify  babies  born  with  the  sickle  cell  trait  and  pre- 
vent occurrence  of  complications,  and  so  forth. 

Now,  to  finish  my  remarks,  I  would  like  to  return  to  the  first 
chart  and  tell  you  that  the  basic  research  that  is  ongoing  today  is 
bringing  us  to,  if  you  will,  the  eve  of  finding  a  cure  for  this  condi- 
tion. And  I  am  focusing  most  specifically  on  bone  marrow  trans- 
plantation and  gene  therapy,  two  therapies,  two  approaches,  that 
the  Congress  hears  a  lot  about  from  the  research  community. 

Bone  marrow  transplantation  is  not  yet  used  in  many  children. 
In  fact,  only  14  cases  have  been  completed  in  the  whole  world — I 
believe,  6  in  Europe  and  8  in  this  country — with  very,  very  inter- 
esting results.  Gene  therapy  is  also  something  which  is  getting  to 
be  in  our  possibilities,  and  n  fact,  within  a  couple  of  weeks,  the  Na- 
tional Heart,  Lung,  and  Blood  Institute  is  going  to  initiate  a  na- 
tional program  of  gene  therapy  research  for  the  cure  of  sickle  cell 
disease. 

We  think  that  the  prospects  from  these  two  therapeutic  ap- 
proaches are  just  enormous,  and  we  are  very  confident  that  within 
some  period  of  time— but  again,  I  have  to  tell  you  I  cannot  say 
whether  it  will  be  in  2  years,  5  years,  or  10  years — but  we  know 


where  to  go,  and  we  have  the  opportunity  to  do  it,  we  have  the 
basic  science  which  permits  us  to  reach  the  goals  that  we  want  to 
reach. 

So  when  I  was  asked  to  come  here  and  tell  you  about  this  na- 
tional network  of  sickle  cell  research  centers  that  has  been  sup- 
ported by  the  Congress  since  1972,  I  thought  the  best  way  to 
present  that  to  you  would  be  to  say  here  are  all  of  the  things  wnich 
nave  been  accomplished,  and  this  is  where  we  are  today  and  what 
we  expect  to  accomplish  within  an  attainable  period  of  time. 

I  would  be  glad  to  answer  questions,  Mr.  Chairman. 

[The  prepared  statement  of  Dr.  Lenfant  follows:] 

Prepared  Statement  of  Claude  Lenfant,  M.D. 

Mr.  Chairman  and  members  of  the  Committee,  I  am  Dr.  Claude  Lenfant,  Director 
of  the  National  Heart,  Lung,  and  Blood  Institute  (NHLBI),  a  component  of  the  Na- 
tional Institutes  of  Health  (Nffl).  I  am  pleased  to  appear  before  you  today  to  present 
testimony  about  our  research  program  in  sickle  cell  disease  and,  in  particular,  about 
the  Comprehensive  Sickle  Cell  Centers  grant  program. 

BACKGROUND 

To  place  my  testimony  in  context,  let  me  review  some  basic  facts  about  sickle  cell 
disease,  the  most  common  serious  inherited  blood  disorder  seen  in  this  country.  It 
is  characterized  by  recurrent  bouts  of  pain  called  "crises,"  chronic  anemia  related 
to  accelerated  destruction  of  red  blood  cells,  increased  susceptibility  to  certain  infec- 
tions, and  acute  or  chronic  damage  to  various  organs.  Sickle  cell  disease  results 
when  the  gene  for  defective  ("sickle  *0  hemoglobin  is  inherited  from  both  parents. 
In  the  United  States,  it  occurs  predominantly,  but  not  exclusively,  in  persons  of  Af- 
rican ancestry;  about  50,000  to  60,000  African  Americans  are  affected.  Medical  costs 
for  patients  with  sickle  cell  disease  can  be  extremely  high,  quality  of  life  is  im- 
paired, and  loss  of  time  from  school  or  employment  is  common.  Thus,  sickle  cell  dis- 
ease is  a  problem  of  significant  psychological,  social,  and  economic  importance. 

President  Nixon's  health  message  to  Congress  in  1972  identified  sickle  cell  ane- 
mia as  a  major  neglected  health  problem.  The  National  Sickle  Cell  Anemia  Control 
Act,  subsequently  passed  by  Congress,  provided  authorization  to  establish  programs 
of  research,  research  training,  and  demonstration  service  activities  related  to  the  di- 
agnosis, treatment,  and  control  of  sickle  cell  anemia.  The  NIH  was  designated  as 
the  lead  agency  for  the  National  Sickle  Cell  Disease  Program,  and  the  NHLBI  was 
assigned  responsibility  for  research  and  development  activities  and  for  coordination 
across  federal  agencies.  The  National  Sickle  Cell  Disease  Advisory  Committee  was 
appointed  by  the  Secretary,  Department  of  Health,  Education,  and  Welfare,  and 
charged  with  making  recommendations  on  program  direction  and  policy.  The  com- 
mittee articulated  the  overall  goals  of  the  program  as  reduction  of  the  frequency, 
morbidity,  and  mortality  of  sickle  cell  anemia  through  a  program  of  research  and 
development  and  demonstration  activities  in  education,  testing,  counseling,  patient 
referral,  and  rehabilitation. 

The  Comprehensive  Sickle  Cell  Centers  (CSCC)  Program 

HISTORY  AND  ACCOMPLISHMENTS 

Among  the  advisory  committee's  first  recommendations  was  a  program  of  com- 
prehensive centers  focusing  on  the  range  of  problems  associated  with  sickle  cell  dis- 
ease. The  Comprehensive  Sickle  Cell  Center  (CSCC)  program  was  established  in  fis- 
cal year  1972  as  a  direct  result  of  this  recommendation.  The  program  began  oper- 
ation with  a  total  of  10  centers  and  increased  to  15  centers  in  fiscal  year  1973.  The 
Institute  has  consistently  supported  10  centers  since  fiscal  year  1977,  each  for  a 
five-year  award  period.  Continued  funding  for  the  CSCC  program  was  ensured  in 
1983  by  the  passage  of  Public  Law  97-414,  which  directed  the  Secretary  of  Health 
and  Human  Services  to  "provide  for  the  development  and  support  of  not  less  than 
10  comprehensive  centers  for  sickle  cell  disease. 

The  goals  of  the  CSCC  program  are  to  conduct  basic  and  clinical  research  to  im- 
prove the  diagnosis  and  treatment  of  sickle  cell  disease  and  prevent  its  complica- 
tions. The  program  encompasses  both  scientific  investigation  and  service  so  that  ad- 
vances in  research  on  sickle  cell  disease  can  be  translated  readily  into  practice  and 


10 

incorporated  into  the  health-care  delivery  system.  Each  sickle  cell  center  is  com- 
prehensive in  that  it  integrates  and  coordinates  fundamental  and  applied  research 
with  clinical  applications  and  trials  to  assess  various  modes  of  therapy,  with  dem- 
onstration projects  that  address  methods  of  disease  diagnosis  and  approaches  to  pa- 
tient counseling  and  education,  and  with  training  programs  for  health-care  profes- 
sionals and  allied  personnel  that  focus  on  the  specific  problems  associated  with  sick- 
le cell  disease.  By  requiring  each  center  to  be  comprehensive,  the  NHLBI  ensures 
that  a  variety  of  models  based  on  this  approach  are  developed.  Furthermore,  by  al- 
lowing each  center  to  select  its  own  area  or  areas  of  primary  emphasis,  the  Institute 
encourages  development  of  specialized  expertise  in  individual  centers  that  can  serve 
as  a  shared  resource  for  the  entire  program. 

This  unique  program  concept  or  interrelated  investigational  and  service  compo- 
nents has  been  noteworthy  for  accomplishments  made  possible  by  the  synergistic 
interaction  of  scientific  investigators  and  a  well-informed  patient  population. 
Through  this  support  mechanism,  the  scope  and  quality  of  research  and  clinical 
studies  have  increased  markedly.  Highly  eflective,innovative  programs  in  education, 
diagnosis,  counseling,  and  patient  care  have  been  created  where  none  existed  before. 
The  program  has  proven  successful  in  attracting  talented  scientists  into  studies  re- 
lated to  sickle  cell  disease  by  providing  challenging  environments  conducive  to  cross- 
stimulation  and  synergism  between  specialties.  Collaborative  efforts  among  center 
projects-and  between  centers  enhance  research  productivity,  facilitate  technology 
transfer  between  research  and  clinical  components,  and  ensure  a  knowledgeable 
study  population  through  education  and  counseling. 

The  CSCC  program  has  contributed  to  many  important  advances  in  understand- 
ing molecular  mechanisms  and  the  pathogenesis  of  sickle  cell  disease.  Investigations 
conducted  in  the  centers  have  led  to:  progress  in  basic  sickle  cell  research  and  in 
management  of  sickle-cell-related  complications;  better  understanding  of  gene  ex- 
pression and  regulation  of  fetal  hemoglobin  synthesis;  a  scientific  foundation  for 
clinical  trials  of  hydroxyurea  as  a  therapeutic  approach;  modern  DNA  techniques  for 
prenatal  diagnosis  of  sickle  cell  disease;  identification  and  classification  of  over  300 
abnormal  hemoglobins;  and  guidelines  for  ocular  sequelae  of  sickle  cell  retinopathy. 
Clinical  investigations  have  shed  light  on  the  natural  history  of  sickle  cell  disease 
and  provided  a  basis  for  the  ongoing  collaborative  national  study  on  the  clinical 
course  of  sickle  cell  disease.  The  current  centers  have  implemented  additional  col- 
laborative clinical  research  protocols  in  preoperative  transfusion  therapy,  pain  man- 
agement, acute  chest  syndrome,  and  use  of  magnetic  resonance  imaging  to  diagnose 
and  follow  the  progression  of  cerebral  and  skeletal  events. 

REVIEW  PROCEDURES 

The  continued  quality  of  the  Institute's  CSCC  program  is  ensured  by  a  careful 
and  thorough  process  that  includes  review  and  approval  of  the  program  concept  by 
the  National  Heart,  Lung,  and  Blood  Advisory  Council,  peer  review  of  individual 
grant  applications,  and  internal  review  within  the  CSCCs.  Grant  applications  in  re- 
sponse to  announcements  for  CSCC  support  are  subjected  to  a  multistage  review 
process  that  parallels  that  for  review  of  other  large  program  grant  applications.  For 
example,  in  the  most  recent  competition  for  CSCC  grants  (for  funding  in  fiscal  years 
1993  through  1997),  20  applications  were  received  and  given  an  initial  review  by 
the  parent  peer  review  committee,  a  group  of  18  expert  scientists  and  clinicians  con- 
vened by  the  NHLBI.  Seventeen  applications  were  recommended  for  further  consid- 
eration. All  were  site  visited  by  teams  that  included  at  least  two  representatives 
from  the  parent  committee,  as  well  as  scientists,  clinicians,  educators,  and  other 
consultants  with  expertise  in  areas  proposed  by  the  applicants.  Reports  and  rec- 
ommendations of  the  site  visit  teams  were  then  referred  back  to  the  parent  commit- 
tee for  consideration  at  a  second  review  meeting.  Applications  were  evaluated  ac- 
cording to  a  number  of  criteria,  including  the  qualifications,  experience,  and  commit- 
ment of  the  center  director  and  senior  personnel;  the  scientific  merit  and  quality  of 
the  proposed  projects;  the  adequacy  of  laboratory  and  health-care  facilities  and  ac- 
cess to  patients;  the  overall  structure  and  management  of  the  center,  including  sci- 
entific and  fiscal  management,  integration  of  the  parts,  and  quality  control;  the  in- 
stitutional commitment  to  the  program;  and  the  appropriateness  of  the  budget.  The 
parent  committee  voted  a  numerical  priority  score  for  each  application,  reflecting  its 
overall  merit.  Reports  and  recommendations  of  the  parent  committee  were  then  con- 
veyed to  the  National  Heart,  Lung,  and  Blood  Advisory  Council  for  final  review  and 
consideration. 

As  with  all  NHLBI-supported  programs,  the  review  process  does  not  terminate 
with  award  of  the  grant.  Each  of  the  CSCCs  is  required  to  submit  an  annual 
progress  report  for  review  by  NHLBI  program  staff.  NHLBI  staff  members  also  visit 


11 

each  of  the  centers  during  the  middle  period  of  the  grant  cycle  to  provide  construc- 
tive guidance  and  work  with  center  staff  to  determine  what  improvements  might  be 
possible  in  their  programs. 

NHLBI  Research  in  Sickle  Cell  Disease:  Past,  Present,  and  Future 

The  CSCC  program  has  been  and  will  continue  to  be  an  important  element  in  our 
national  strategy  to  reduce  the  burden  of  sickle  cell  disease.  However,  I  want  to  em- 
phasize that  it  is  but  one  part  of  a  much  larger  effort.  For  the  past  22  years,  the 
NHLBI  has  initiated  and  supported  a  broad-based  program  of  basic  and  clinical  re- 
search in  sickle  cell  disease  with  the  goal  of  reducing  deaths  and  improving  the 
quality  of  life  for  patients  and  their  families.  We  believe  our  approach  to  achieving 
this  goal  has  been  logical  and  stepwise.  It  began  in  the  laboratory,  with  studies  at 
the  most  fundamental  level  of  the  red  blood  cell,  moved  to  research  on  globin  gene 
expression  and  regulation,  progressed  to  epidemiologic  studies  of  the  natural  history 
of  sickle  cell  disease  and,  today,  also  encompasses  clinical  trials  of  potential  thera- 
peutic agents. 

Let  me  give  you  a  brief  history  of  sickle  cell  disease  research  and  summarize  its 
most  important  advances.  This  information  provides  a  context  in  which  to  view  the 
contributions  of  the  CSCC  program,  and  offers  important  insights  into  where  we 
have  been,  where  we  are  now,  and  where  we  will  be  in  the  future  as  we  move  rap- 
idly toward  the  twenty-first  century. 

La  the  1970s,  basic  research  supported  in  scientific  laboratories  throughout  the 
country  brought  a  tremendous  revolution  in  our  understanding  of  sickle  cell  disease 
at  the  molecular  level.  One  of  our  earliest  Institute  initiatives  focused  on  research 
to  determine  the  mechanisms  that  regulate  the  'switch"  from  fetal  to  adult  hemo- 
globin during  infancy.  It  had  been  recognized  for  some  time  that  sickle  cell  patients 
who  were  fortunate  enough  to  have  inherited  a  tendency  to  continue  producing  fetal 
hemoglobin  beyond  the  first  year  of  life  had  relatively  benign  disease.  There  fore,  it 
seemed  logical  to  pursue  therapeutic  modalities  that  would  enable  patients  produc- 
ing adult  sickle  hemoglobin  to  "switch  back"  to  producing  normal  fetal  hemoglobin. 
This  research  catalyzed  the  field  of  molecular  biology,  and  became  the  cornerstone 
for  development  of  therapeutic  approaches  based  on  increasing  the  level  of  fetal  he- 
moglobin in  patients  with  sickle  cell  disease-  -work  that  continues  to  this  day. 

In  1977,  sickle  cell  anemia  became  the  first  human  disease  to  be  described  at  the 
level  of  DNA  and  RNA.  Breakthroughs  that  rapidly  followed  introduced  gene  map- 
ping into  prenatal  diagnosis,  and  made  it  possible  to  use  placental  tissue  rather 
than  fetal  Dlood  samples.  This  substantially  increased  the  safety  of  prenatal  diag- 
nosis for  sickle  cell  disease,  and  rapidly  led  to  the  application  of  molecular  genetics 
for  prenatal  diagnosis  of  other  inherited  diseases. 

Very  early  on,  it  became  apparent  that,  although  much  was  known  about  the  mo- 
lecular basis  of  sickle  cell  disease,  little  was  known  about  its  natural  history  or  clini- 
cal course.  Only  the  sickest  patients  were  described  in  the  medical  literature,  and 
most  clinical  reports  of  patient  outcomes  were  anecdotal  and  retrospective.  There 
was,  consequently,  a  poor  understanding  of  the  variable  severity  of  the  disease.  In 
1979,  the  NHLBI  responded  to  the  need  for  epidemiologic  and  clinical  information 
with  the  Cooperative  Study  of  Sickle  Cell  Disease  (CSSCD). 

The  CSSCD— a  large  scale,  multi-institutional  study — recruited  over  4,000  pa- 
tients of  all  ages,  from  newborns  to  people  in  their  sixth  decade.  The  study  clarified 
issues  of  growth  and  maturation  patterns  among  children  with  sickle  cell  disease; 
defined  causes  of  death  in  the  pediatric  population,  showing  longer  survival  rates 
than  had  been  reported  previously,  described  the  epidemiology  of  painful  episodes 
and  documented,  for  the  first  time,  that  the  frequency  with  which  such  crises" 
occur  is  a  predictor  of  premature  death  in  adult  patients;  and  pointed  out  the  risks 
of  alloimmunization  for  sickle  cell  patients  receiving  repeated  blood  transfusions. 
Most  recently,  exciting  new  data  from  this  study  showed  that  average  survival  of 

fiatients  with  sickle  cell  anemia  has  increased  to  48  years  of  age  for  women  and  42 
or  men.  Previously,  it  was  thought  that  the  average  patient  rarely  lived  beyond  20 
years  of  age.  These  findings,  recently  reported  in  the  New  England  Journal  of  Medi- 
cine dated  June  9,  have  provided  renewed  impetus  for  the  search  for  long-term 
therapeutic  agents  to  improve  the  quality  of  life  lor  sickle  cell  disease  patients. 

As  mentioned  earlier,  the  CSCC  program  has  had  a  major  impact  on  the  manage- 
ment of  sickle  cell  disease.  The  centers  have  served  as  models  for  a  revised  manage- 
ment approach  that  places  the  central  focus  on  the  patient.  Care  that  was  pre- 
viously fragmented,  impersonal,  and  episodic  has  been  replaced  with  a  team  ap- 
proach, involving  a  cadre  of  trained  personnel  that  include  not  only  the  clinician, 
but  the  nurse,  social  worker,  psychologist,  nutritionist,  counselors,  and  allied  health 
professionals. 


12 

In  the  mid-1980s,  an  NHLBI-supported  clinical  trial  demonstrated  the  value  of 

grophylactic  penicillin  in  preventing  major  infections  in  infants  and  young  children, 
efore  that  tune,  approximately  30  percent  of  sickle  cell  deaths  occurred  before  five 
years  of  age,  most  in  children  under  the  age  of  two.  Pneumococcal  infection  was  the 
major  cause  of  mortality  in  these  early  -years.  Prophylactic  penicillin  has  thus  been 
among  the  most  dramatic  contributions  to  saving  lives.  This  trial  also  provided  the 
impetus  for  recommending  that  all  newborns  be  screened  for  sickle  cell  disease.  In- 
fants at  risk  could  then  be  referred  for  comprehensive  care,  and  prophylactic  penicil- 
lin therapy  could  be  given  by  three  months  of  age.  Sickle  cell  disease  is  now  in- 
cluded in  the  screening  programs  of  more  than  40  states. 

Unfortunately,  many  children  with  sickle  cell  disease  are  faced  with  crippling 
central  nervous  system  (CNS)  complications,  including  strokes.  Chronic  transfusion 
therapy  to  maintain  the  level  of  sickle  hemoglobin  below  30  percent  is,  however,  ex- 
tremely effective  in  preventing  the  recurrence  of  strokes  in  such  children.  Current 
and  future  emphasis  is  on  preventing  the  initial  strokes  by  early  detection  of  nar- 
rowed cerebral  vessels  and  implementing  therapy  prior  to  CNS  damage. 

We  see  a  new  era  of  optimism  for  treating  sickle  cell  patients.  We  are  on  the 
threshold  of  moving  molecular  medicine  even  closer  to  the  bedside.  The  NHLBI  is 
currently  supporting  a  multicenter  clinical  trial  using  hydroxyurea  in  21  centers 
around  the  country.  Approximately  300  severely  affected  adult  patients  are  enrolled. 
Now  entering  its  thira  year,  this  trial  is  investigating  one  of  many  agents  identified 
as  able  to  "turn  on"  the  production  of  fetal  hemoglobin  in  patients  with  sickle  cell 
anemia.  If  efficacy  and  safety  are  proven,  hydroxyurea  will  be  the  first  agent  to  be- 
come available  as  an  effective  therapy  for  sickle  cell  disease.  Erythropoietin,  a  hor- 
mone, also  significantly  increases  fetal  hemoglobin  synthesis.  The  recent  availability 
of  recombinant  erythropoietin,  a  major  scientific  advance,  made  it  possible  to  use 
this  drug  in  combination  with  hydroxyurea.  This  combination  approach  offers  the 
possibility  that  lower  doses  of  hydroxyurea  can  be-used  to  achieve  the  required 
therapeutic  levels  of  fetal  hemoglobin. 

Because  we  recognize  that  this  approach  will  not  achieve  therapeutic  levels  of 
fetal  hemoglobin  in  all  patients,  parallel  research  efforts  to  seek  other  strategies  are 
continuing.  Looking  into  the  future,  gene  therapy  and  bone  marrow  transplantation 
appear  to  offer  the  best  hopes  for  a  cure  of  sickle  cell  disease.  Bone  marrow  trans- 
plantation has  been  successfully  used  by  several  investigators  in  Europe,  as  well  as 
a  small  number  in  the  United  States.  Although  early  reports  are  promising,  patient 
selection,  donor  availability,  and  complications  of  the  procedure  continue  to  be  po- 
tential problems  that  prevent  widespread  use  of  this  therapeutic  modality  today. 
Gene  therapy  research  is  advancing,  with  the  possibility  of  inserting  normal  genes 
for  hemoglobin  production  into  the  Done  marrow  precursor  or  stem  cells,  thus  lead- 
ing to  the  production  of  normal  hemoglobin.  This  approach  is  receiving  active  atten- 
tion by  many  researchers  around  the  country  ana  is  the  subject  of  a  targeted  re- 
search program  recently  initiated  by  the  NHLBI. 

A  number  of  opportunities  exist  for  further  advances  in  sickle  cell  disease  re- 
search. What  needs  to  be  done  was  best  stated  by  the  Sickle  Cell  Task  Force  on 
Investigator-Initiated  Research.  Its  report  defined  areas  of  research  that  currently 
hold  the  greatest  promise  for  achieving  a  cure  for  sickle  cell  disease,  including:  de- 
velopment of  mice  that  serve  as  models  of  sickle  cell  disease,  improved  understand- 
ing of  factors  important  in  the  switch  from  fetal  hemoglobin  to  adult  hemoglobin, 
targeted  studies  of  methods  for  gene  insertion  into  primitive  blood  cell  precursors, 
and  fundamental  studies  of  red  cell  structure  and  metabolism.  Also  recommended 
were  epidemiologic  investigations  of  the  role  of  clotting  and  clot  dissolution  in  sickle 
cell  crises  and  additional  studies  on  the  natural  history  of  sickle  cell  disease.  The 
NHLBI  is  strongly  committed  to  a  balanced  and  innovative  approach  to  achieve  our 
national  goal  of  reducing  the  personal  and  public  health  burden  of  sickle  cell  dis- 
ease. 

I  would  be  pleased  to  answer  any  questions  the  Committee  may  have. 


13 


History  of 
Basic  Sickle  Cell 


Research 


(0 
W 

O) 

o 


sz 
a> 

(A 

a> 


Membrane 
Proteins 


Rheology 


Polymer  Formation 
Cell  Sickling 
Kinetics  of  Delay 


Bone  Marrow 
Transplantation 


Hemoglobin 
"Switching"  Agents 


Gene  Therapy 


Globin  Gene 
Regulation 


'Haplotypes  and 
Population  Studies 


Sequence  of  the  (3-globin 

Gene 

Globin  Gene 
Expression 


1970  1980  1990  ? 

Enlightenment  Renaissance  Therapeutic 

Triumph 
Period 


2000     ? 
Cure? 


History  of 
Clinical  Sickle  Cell 


<n 
v 

O) 

o 


sz 
o 

ca 

0) 

in 

CD 

DC 


Comprehensive  Care 

Eye  Abnormalities 

Susceptibility  to 
Infections 


Prenatal  Diagnosis 


"Natural  History 

Study- 
Prevention 
of  Stroke 


Research 


Longer  Lifespan 


Painful  Episodes  - 
Influence  on  Mortality 


Leg  Ulcers 

Prophylactic 
Penicillin 

Aseptic  Necrosis 
Newborn  Screening 


CNS  -  Early  Detection 
and  Prevention 


Clinical  Severity  Index 


1970  1980  1990  ?  2000     ? 

Enlightenment  Renaissance  Therapeutic  Cure? 

Period 


Triumph 


82-553  0-94-2 


14 

Senator  Simon.  Thank  you. 

We  now  have  10  sickle  cell  centers. 

Dr.  Lenfant.  That  is  correct. 

Senator  Simon.  How  would  the  center  that  is  now  being  proposed 
for  Southern  University  differ  from  those  centers? 

Dr.  Lenfant.  Well,  I  should  say  to  you,  Mr.  Chairman,  that  we 
have  not  seen  a  detailed  description  of  the  proposal  that  would  be 
presented  by  the  university.  I  have  heard  the  two  previous  wit- 
nesses, and  many  of  the  things  which  they  have  discussed,  describ- 
ing research  that  would  span  from  very  basic  to  clinical,  describing 
supports  to  the  community  and  to  the  patients,  treatment,  care, 
counseling,  and  all  of  these  things,  there  is  a  very  remarkable  simi- 
larity between  what  I  think  I  have  heard  here  and  what  our  cen- 
ters are  now  supporting. 

Senator  Simon.  We  will  have  to  make  a  decision  on  this,  obvi- 
ously. If  you  were  a  member  of  the  U.S.  Senate,  would  you  vote  for 
it?  Is  this  a  wise  way  to  invest  the  money  in  terms  of  achieving 
the  breakthrough? 

Dr.  Lenfant.  That  is  a  very  difficult  question.  Let  me  answer  it 
this  way,  if  I  may.  The  more  research  we  support,  the  faster  we 
are  going  to  get  where  we  want  to  be.  Just  a  few  months  ago,  I 
testified  before  the  Appropriations  Committee  of  the  Senate  for  my 
budget,  and  Mr.  Harkin  asked  us,  if  you  had  so  much  more  money, 
what  would  you  do?  And  my  answer  is  basically  the  answer  that 
I  am  giving  you  today,  that  we  know  where  to  go,  and  we  know 
we  are  going  to  reach  it;  if  I  have  more  money,  I  will  reach  it  fast- 
er. I  think  that  is  a  decision  which  is  not  within  my  purview. 

Senator  Simon.  I  understand.  We  thank  you  very,  very  much. 
Senator  Kennedv  and  other  members  of  the  committee  may  have 
some  questions  for  you. 

Dr.  Lenfant.  I  will  be  here,  Senator,  for  the  duration  of  the 
hearing. 

Senator  Simon.  Thank  you.  And  they  may  be  submitting  some  in 
writing.  Senator  Kennedy  had  planned  to  be  here  by  now. 

My  difficulty  right  now,  frankly,  is  that  I  am  supposed  to  be  at 
another  meeting.  I  think  what  we  had  better  do  is  recess  tempo- 
rarily until  Senator  Kennedy  gets  here,  or  another  member  of  the 
committee  can  get  here.  So  we  will  take  a  temporary  recess  at  this 
point. 

[Recess.] 

Opening  Statement  of  Senator  Kennedy 

The  Chairman.  We  will  come  to  order. 

I  am  enormously  grateful  for  the  understanding  and  patience  of 
our  witnesses  this  afternoon  on  a  subject  which  is  of  enormous  im- 
portance to  all  of  us  on  this  committee  and  something  which  I  have 
been  involved  in  for  a  very  extensive  period  of  time. 

As  the  Senate  schedule  has  indicated,  we  are  caught  in  this  situ- 
ation of  advancing  the  hearing  and  sharing  the  leadership  in 
chairing  the  hearing,  so  we  are  very,  very  grateful  to  all  of  those 
who  have  testified  and  for  the  testimony  we  will  receive. 

I  will  put  my  full  and  complete  statement  in  the  record,  and  we 
will  utilize  the  time  we  do  have  to  hear  from  some  very  special  peo- 
ple. 


15 

[The  prepared  statement  of  Senator  Kennedy  follows:] 
Prepared  Statement  of  Senator  Kennedy 

Despite  the  unprecedented  growth  in  scientific  knowledge  and 
the  ability  of  medical  science  to  diagnose,  prevent,  treat,  and  cure 
many  illnesses,  sickle  cell  disease  continues  to  devastate  the  lives 
of  tens  of  thousands  of  Americans. 

Sickle  cell  disease  affects  an  estimated  50,000  African  Ameri- 
cans. It  is  a  hereditary  illness  that  occurs  in  1  out  of  every  625  Af- 
rican American  infants  born  in  the  United  States.  The  death  rate 
for  the  disease  during  infancy  can  be  as  high  as  30  to  35  percent 
if  treatment  is  delayed  or  inadequate.  Those  living  with  the  disease 
own  have  frequent  attacks  of  severe  pain.  They  suffer  strokes  at  an 
early  age  and  endure  debilitating  joint  and  bone  disease. 

The  severity  of  the  symptoms  and  life  expectancy  vary  consider- 
ably. Some  patients  survive  beyond  middle  age.  But  many  die  in 
childhood,  and  many  others  die  in  infancy.  Treatment  for  this 
chronic  illness  is  expensive  and  the  disease  places  a  heavy  psycho- 
logical burden  on  patients  and  caretakers  alike. 

The  disease  was  first  diagnosed  in  the  United  States  in  1910  by 
Dr.  James  Herrick.  The  discovery  was  made  on  a  dental  student 
from  Grenada,  rather  than  on  the  thousands  of  African  Americans 
with  the  disease.  It  was  called  sickle  cell  anemia  because  of  the 
characteristic  sickle  shape  of  the  red  blood  cells  in  patients  with 
the  disease. 

Ih  1949,  Dr.  Linus  Pauling  discovered  the  association  of  sickle 
cell  anemia  with  an  abnormal  form  of  hemoglobin,  and  later  won 
the  Nobel  prize  for  his  work  in  this  area.  Eight  years  later,  the  mo- 
lecular basis  of  the  disease  was  discovered  in  one  of  the  landmark 
breakthroughs  in  the  field  of  human  genetics.  Dr.  Vernon  at  Mas- 
sachusetts Institute  of  Technology  demonstrated  that  the  hemo- 
globin in  patients  with  sickle  cell  anemia  differed  from  normal  he- 
moglobin by  a  single  amino  acid  substitution  on  the  beta  chain  of 
the  protein.  In  1977,  Dr.  Bernard  Forget  identified  the  particular 
gene  responsible  for  the  disease. 

Patients  with  the  disease  inherit  a  sickle  cell  gene  from  both  par- 
ents. If  each  parent  has  a  sickle  cell  gene,  one-quarter  of  the  chil- 
dren on  the  average  will  inherit  both  genes  and  will  have  the  dis- 
ease. 

Half  of  the  children  will  inherit  one  of  the  genes.  They  will  be 
carriers  of  the  genes,  and  can  pass  it  on  to  their  own  children. 
Their  condition  is  called  sickle  cell  trait,  and  8  percent  of  African 
Americans  have  it.  The  sickle  cell  gene  has  persisted  in  operation 
even  though  a  double  dose  of  the  gene  is  so  lethal,  because  the  red 
cells  of  individuals  sickle  cell  trait  are  less  vulnerable  to  the  ma- 
laria parasite. 

In  spite  of  the  remarkable  knowledge  that  science  has  gained  as 
a  result  of  sickle  cell  research,  there  has  been  a  continuing  percep- 
tion over  many  decades  that  U.S  public  health  policy  has  not  given 
enough  priority  to  prevention  of  the  disease  and  treating  those  who 
suffer  from  it.  The  perception  is  especially  troubling  because  of  the 
racial  nature  of  the  disease. 

In  1971,  in  response  to  these  concerns,  I  joined  Senator  John 
Tunney,  Senator  Ed  Brooke,  and  other  Senators  in  sponsoring  the 


16 

National  Sickle  Cell  Anemia  Act,  which  was  signed  into  law  by 
President  Nixon  the  following  year.  I  still  regard  it  as  one  of  the 
most  important  health  bills  I  have  ever  introduced. 

The  Act  contained  numerous  provisions  on  screening,  counseling, 
research  and  training.  It  included  programs  to  educate  the  public 
about  the  disease  and  to  facilitate  early  diagnosis,  and  effective 
treatment. 

In  1972,  the  National  Institutes  of  Health  established  the  Sickle 
Cell  Disease  Branch  of  the  National  Heart,  Lung  and  Blood  Insti- 
tute. In  the  years  since  then,  Congress  has  enacted  legislation  to 
strengthen  basic  and  applied  research,  to  provide  more  extensive 
testing,  counseling,  and  treatment  and  to  expand  public  informa- 
tion and  education  programs. 

An  important  provision  in  the  Orphan  Drug  Act  of  1983  provided 
support  for  the  establishment  of  10  Comprehensive  Sickle  Cell  Cen- 
ters around  the  country.  These  national  centers  are  now  well-estab- 
lished. They  are  located  in  Alabama,  Georgia,  Massachusetts, 
North  Carolina,  Pennsylvania,  and  Tennessee,  and  two  centers  are 
located  in  New  York  and  California  these  centers  are  at  the  cutting 
edge  of  research  on  the  disease,  and  there  each  receive  Federal 
support  of  $1  to  $3  million  a  year.  Since  1972,  the  Federal  grant 
has  spent  $610  million  on  sickle  cell  research,  and  the  amount  for 
the  current  year  in  $46  million. 

The  developments  over  the  past  two  decades  have  seen  signifi- 
cant improvements  in  the  treatment  of  patients  with  the  disease. 
Thirty  years  ago,  50  percent  of  patients  with  the  disease  died  be- 
fore the  age  of  20.  Today,  50  percent  live  past  the  age  of  50.  Much 
of  the  recent  progress  has  come  from  research  conducted  by  the  ten 
Comprehensive  Sickle  Cell  Centers  around  the  country  and  from 
research  supported  by  the  Sickle  Cell  Disease  Branch  of  the  Na- 
tional Heart,  Lung  and  Blood  Institute.  These  Centers  have  suc- 
cessfully brought  together  experts  in  basic  science,  clinical  re- 
search, and  psychosocial  research  to  address  the  multitude  of  prob- 
lems faced  by  those  with  the  disease. 

In  the  important  effort  to  find  a  cure  for  the  disease,  promising 
research  is  Deing  carried  out  in  bone  marrow  transplantation  and 
gene  therapy.  In  addition,  promising  new  anti-sickling  drugs  are 
being  tested. 

In  spite  of  these  advances,  much  remains  to  be  done.  Our  hear- 
ing this  afternoon  will  assess  the  effectiveness  of  all  aspects  of  our 
current  efforts,  identify  unmet  needs,  and  try  to  develop  a  strategy 
to  achieve  more  rapid  progress  in  the  coming  years. 

I  look  forward  to  the  testimony  from  our  witnesses  today,  and  to 
working  closely  with  my  colleagues  on  the  committee  and  in  the 
Congress  to  achieve  this  goal. 

The  Chairman.  Shawnita  Agnew  is  an  honor  student  at  English 
High  School  in  Boston.  In  September,  she  will  be  a  freshman  at 
Fisner  College.  She  is  a  team  leader  in  sickle  cell  support  for  chil- 
dren, and  she  will  share  her  experience  with  sickle  cell  disease. 
Her  mother  is  here  as  well,  Ms.  Sharon  Agnew  Stewart,  who  is  a 
sickle  cell  counselor. 

We  also  welcome  Lillian  McMahon,  who  is  director  of  the  Com- 
prehensive Sickle  Cell  Center  at  Boston  City  Hospital  and  has  suc- 
cessfully brought  together  experts  in  basic  science  research,  clinical 


17 

research,  and  psychological  research,  to  address  the  many  problems 
faced  by  those  who  have  the  sickle  cell  disease. 

We  also  welcome  Dr.  Ernest  Turner,  who  is  director  of  the  Com- 
prehensive Sickle  Cell  Center  at  Meharry  Medical  School  in  Nash- 
ville, TN.  Clinical  studies  at  Meharry  have  vast  improved  the  un- 
derstanding of  sickle  cell  disease  and  its  treatment;  and  Dr.  Wil- 
liam Moore  is  vice  chancellor  for  Academic  Affairs  at  Southern  Uni- 
versity, and  is  the  principal  investigator  at  two  research  centers, 
minority  institution  projects  funded  by  NIH. 

Shawnita,  we  are  glad  to  hear  from  you.  We  know  that  you  have 
endured  a  good  deal  of  personal  discomfort  in  joining  us  here  today, 
and  we  are  also  very  mindful  that  it  is  difficult  to  share  one's 
health  experiences  and  needs  publicly,  so  we  are  certainly  grateful 
to  you  for  your  willingness  to  be  here  and  for  all  the  good  things 
that  you  do.  We  want  you  to  know  that  the  best  way  we  can  thank 
you  is  to  redouble  our  energy  and  commitment  in  terms  of  both  the 
research  and,  hopefully,  solutions,  to  some  of  these  challenges. 

We  are  thankful  to  you  for  being  here  today,  and  we  look  forward 
to  hearing  your  comments.  So  if  you  would  like  to  make  a  state- 
ment, we  would  be  glad  to  hear  from  you  now. 

STATEMENTS  OF  SHAWNITA  AGNEW,  HONOR  STUDENT,  ENG- 
LISH HIGH  SCHOOL,  BOSTON,  MA;  LILLIAN  McMAHON,  M.D., 
DIRECTOR,  COMPREHENSIVE  SICKLE  CELL  CENTER,  BOS- 
TON CITY  HOSPITAL,  BOSTON,  MA;  ERNEST  A.  TURNER,  M.D., 
DIRECTOR,  COMPREHENSIVE  SICKLE  CELL  CENTER, 
MEHARRY  MEDICAL  SCHOOL,  NASHVILLE,  TN;  WHXIAM  E. 
MOORE,  MX).,  VICE  CHANCELLOR  FOR  ACADEMIC  AFFAIRS, 
SOUTHERN  UNIVERSITY,  BATON  ROUGE,  LA;  KWAKU  OHENE- 
FREMPONG,  MJ).,  DIRECTOR,  COMPREHENSIVE  SICKLE 
CELL  CENTER,  THE  CHILDREN'S  HOSPITAL  OF  PHILADEL- 
PHIA, PHILADELPHIA,  PA;  AND  HON.  CHARLES  D.  JONES, 
LOUISIANA  STATE  SENATOR 

Ms.  agnew.  Hi.  My  name  is  Shawnita  Agnew,  and  I  am  a  young 
lady  who  lives  her  life  every  day  with  a  disease  called  sickle  cell 
anemia. 

As  a  child,  living  with  this  disease  was  very  hard  for  me.  I  really 
did  not  understand  it  as  much  as  I  do  now.  Many  times,  I  would 
have  to  be  admitted  to  the  hospital  with  terrible  pain  in  my  legs, 
my  back,  my  arms,  and  sometimes  my  chest.  I  would  need  to  stay 
many  days,  weeks,  sometimes  months,  with  i.v.  medication,  oxygen, 
and  sometimes,  blood  transfusions,  until  the  pain  was  bearable 
enough  to  go  home  and  later  return  to  school. 

As  a  child,  I  did  not  really  understand  why  I  could  not  partici- 
pate with  other  children  when  they  would  swim,  play  running 
games,  and  so  on.  I  could  not  get  too  hot  or  too  cold,  excited,  or 
sad.  It  really  confused  me. 

As  I  get  older,  I  started  to  understand  the  disease  more,  but  I 
still  did  not  participate  as  much.  But  I  started  to  learn  to  live  with 
it.  Together  with  other  kids  from  Boston  City  Hospital,  we  formed 
a  teen  group  for  support  with  each  other. 

I  will  be  working  with  this  teen  group  and  recruiting  younger 
kids  and  helping  them  to  understand  and  deal  with  the  disease. 


18 

Now,  being  18  years  of  age,  I  have  really  learned  how  to  take 
care  of  my  sickle  cell  anemia.  When  I  swim,  I  know  to  keep  warm. 
When  I  go  out  in  the  winter,  I  know  to  dress  warm.  When  it  is  hot, 
keep  cool,  and  drink  a  lot. 

In  September,  I  will  be  moving  on  to  Fisher  Junior  College  to 
study  early  childhood  education,  and  I  hope  to  become  a  teacher. 
I  think  I  have  improved  90  percent  from  what  I  used  to  be. 

The  model  for  our  teen  support  group  is  "A  Cure  in  My  Lifetime." 
Please  help  us  get  there. 

Thank  you. 

The  Chairman.  Thank  you  very  much.  We  will  come  back  to  you 

for  some  questions. 

[The  prepared  statement  of  Ms.  Agnew  follows:] 

Prepared  Statement  of  Shawn^a  Agnew 

Senator  Kennedy  and  members  of  the  committee,  hi,  my  name  is  Shawnita  Agnew 
and  I  am  a  young  lady  who  lives  her  life  every  day  with  sickle  cell  disease,  which 
doesn't  bother  me  any  more. 

As  a  child  living  with  this  disease  was  very  hard  for  me.  I  really  didn't  under- 
stand it  as  much  as  I  do  now.  Many  times  I  would  have  to  be  admitted  to  the  hos- 
pital with  terrible  pains  in  my  body  and  needed  to  stay  for  days  with  I.V.'s,  some- 
times blood  transfusions,  and  medications  until  the  pain  was  bearable  enough  for 
me  to  go  home  and  later  on  return  to  school. 

As  a  child  I  really  didn't  understand  why  I  couldn't  participate  with  the  other 
children  when  they  would  swim,  when  they  would  play  running  games,  and  etc.  I 
couldn't  get  cold  or  hot,  excited  or  sad,  it  really  confused  me.  Any  of  these  things 
could  bring  on  a  sickle  cell  crisis  and  I  would  end  up  in  the  hospital  again. 

As  I  got  older  I  started  to  understand  this  disease  more,  but  I  still  couldn't  par- 
ticipate as  much.  But  I  started  to  learn  to  live  with  it.  Together  with  other  kids 
from  Boston  City  Hospital  and  two  other  hospitals  we  formed  a  mutual  support 
team  for  teens  with  sickle  cell  disease  at  the  Boston  Sickle  Cell  Center.  Together 
we  shared  our  experiences  and  learned  more  about  the  disease.  Together  we  wrote 
a  booklet  for  teens  by  teens  on  what  it  is  like  to  have  sickle  cell  disease.  We  worked 
on  many  art  projects  and  Teens  for  Peace.  I  will  be  working  with  the  Teen  group 
this  year  in  recruiting  younger  kids  and  help  them  understand  and  deal  with  their 
disease. 

Now  as  me  being  18  years  of  age  I  have  really  learned  how  to  take  cars  of  my 
sickle  cell  disease  myself.  When  I  swim  I  know  to  keep  warm.  When  I  go  out  in 
the  winter  time  I  know  to  dress  warm.  When  it's  hot  I  know  to  keep  cool  and  drink 
too  much.  So  basically  living  with  sickle  cell  disease  doesn't  bother  me  now.  I  live 
my  life  as  a  regular  life.  It  seems  like  I'm  a  normal  person  now.  My  mind  has  ac- 
cepted the  fact. 

In  September  I  will  be  moving  on  to  Fisher  Junior  College  to  study  Early  Child- 
hood Education  and  I  hope  to  become  a  teacher.  I  myself  think  have  improved  90 
percent  of  what  I  used  to  be. 

The  motto  of  our  Teen  Group  is  "A  Cure  In  My  Lifetime".  Please  help  us  get 
there.  Thank  you. 

The  Chairman.  Dr.  McMahon. 

Dr.  McMahon.  Thank  you,  Senator  Kennedy. 

I  have  to  say  that  Shawnita  did  not  mention  that  she  is  right 
now  in  the  middle  of  a  painful  crisis.  I  offered  to  read  her  testi- 
mony here  before  the  committee,  but  she  was  determined  to  come 
in  spite  of  it  to  speak  to  groups  of  people  who  are  important  in 
maintaining  research  and  treatment  of  sickle  cell  disease.  Thanks, 

Shawnita. 

We  have  travelled  a  long  way  since  the  age  of  3,  when  she  was 
diagnosed  with  sickle  cell  disease,  and  there  have  been  many, 
many,  many  admissions  for  pain,  for  surgery,  for  infection,  and  a 
couple  of  near  misses.  So  she  has  come  a  long  way,  and  she  did  not 


19 

mention  that  she  did  receive  the  headmaster's  award  in  her  school, 
and  many  scholarships  which  will  allow  her  to  go  to  Fisher. 

I  want  to  thank  you,  Senator  Kennedy,  and  the  committee  for  in- 
viting me  here  to  speak  about  the  Boston  Comprehensive  Center. 
The  Boston  Center  is  one  of  10  national  comprehensive  centers  in 
the  United  States,  all  of  which  work  in  an  academic  environment 
within  a  university  and  medical  center,  which  is  actually  essential 
to  bring  both  researchers  and  clinicians  together  so  that  research 
does  not  happen  in  a  vacuum,  in  a  laboratory,  and  clinicians  are 
not  delayed  in  delivering  the  most  important  findings  of  research 
to  their  patients. 

So  Boston  Sickle  Cell  Center  is  particularly  important  that  it  has 
affiliated  four  medical  schools — Harvard,  Tufts,  and  Boston  Univer- 
sity— and  our  six  research  projects  take  place  in  six  university-af- 
filiated hospitals  and  one  graduate  school. 

The  Boston  Center  has  really  concentrated  their  research  in  red 
cell  membrane,  endothelial  adhesion  and  hemoglobin  switching.  It 
is  really  impossible  in  5  minutes  to  tell  you  the  accomplishments 
of  the  center,  but  I  will  try  to  highlight  them. 

In  red  cell  membrane,  our  investigators  have  focused  on  under- 
standing the  alterations  of  the  red  cell  membrane  which  contribute 
to  the  disease.  For  example,  one  group  of  our  researchers  under 
Jiri  Palek  has  discovered  sites  in  the  red  cell  membrane  where  the 
polymers  of  hemoglobin  will  penetrate,  disrupt  the  membrane, 
damage  it,  and  cause  cell  damage.  This  then  causes  sickling,  causes 
the  red  cells  to  stick  inside  the  lining  of  the  blood  vessels  and  occa- 
sions obstructions  to  blood  flow  and  produces  pain  or  organ  dam- 
age. This  is  vital  knowledge  that  has  increased  our  overall  under- 
standing of  the  disease. 

Another  group  of  our  researchers  under  Dr.  Carla  Brugnara  has 
developed  a  novel  approach  in  attempting  to  prevent  the  dehydra- 
tion of  the  red  blood  cell  which  occurs  in  sickle  cell  disease.  They 
began  with  the  premise  that  a  certain  channel  within  the  red  cell 
called  the  Gardos  channel,  which  is  calcium-dependent,  has  a  pri- 
mary role  in  the  potassium  loss  and  dehydration  of  the  red  cells. 
They  demonstrated  in  vitro  that  inhibitors  of  this  channel  actually 
would  block  the  water  loss  from  the  red  blood  cells.  And  one  such 
inhibitor,  a  drug  called  clotrimazole,  which  is  a  very  common  drug 
used  in  treating  fungal  infections  in  the  general  population  and  ac- 
tually had  concentrations  lower  than  what  is  routinely  used,  is  ac- 
tually effective  in  doing  this.  They  studied  this  in  transgenic  mouse 
model  of  sickle  cell  disease  and  demonstrated  that  indeed  it  is  ef- 
fective in  preventing  red  cell  damage.  And  on  the  basis  of  this  very 
exciting  and  promising  work,  we  are  now  embarking  on  phase  one 
trials  with  patients  with  sickle  cell  disease,  and  Shawnita  is  one 
that  is  looking  at  joining  one  of  these  trials. 

Another  approach  in  research  of  our  group  has  been  in  hemo- 
globin switching,  one  in  which  researchers  look  for  drugs  that  will 
promote  the  bone  marrow  to  increase  production  of  fetal  hemo- 
globin instead  of  sickle  in  patients  with  sickle  cell  disease.  This 
prevents  sickling. 

Well,  the  studv  of  hydroxyurea  originated  in  Boston  by  sickle  cell 
researchers,  and  this  drug  does  indeed  promote  the  bone  marrow 
to  produce  cells  with  a  greater  amount  of  fetal  hemoglobin  and,  in 


20 

selected  patients  who  have  been  put  on  clinical  trial,  it  decreases 
the  tendency  to  sickle  and  ameliorates  their  disease.  It  actually  di- 
minishes the  frequency  and  the  intensity  of  the  crisis. 

There  are  further  trials  that  are  now  taking  place  in  a 
multicenter  fashion. 

Another  drug  that  also  promotes  the  increase  of  fetal  hemoglobin 
is  butyrate.  Dr.  Perrine,  a  researcher  at  the  California  center,  has 
now  transferred  to  our  center  and  has  been  very  important  in  the 
investigation  of  this  drug,  and  clinical  trials  are  now  in  progress 
with  this  drug  in  sickle  cell  disease  and  thalassemia. 

Sickle  cell  disease  is  a  disease  that  affects  persons  from  birth  as 
long  as  they  will  live.  We  are  increasingly  happy  to  see  how  much 
longer  patients  are  living  as  a  result  of  better  medical  care  and 
translating  research  results  into  clinical  care. 

So  as  a  result  of  the  penicillin  prophylaxis  study  which  Dr. 
Lenfant  mentioned,  this  was  a  landmark,  multicenter  study  which 
demonstrated  that  administering  penicillin  twice  a  day  to  children 
prevents  the  mortality,  which  was  as  h;gh  as  30  percent,  in  the 
first  3  years  of  life  and  decreased  the  morbidity  of  infection.  As  a 
consequence  of  that,  newborn  screening  has  been  instituted  in  a 
majority  of  the  States  in  this  country,  so  that  our  center  was  in- 
strumental in  establishing  newborn  screening  in  Massachusetts. 

Babies,  as  soon  as  they  are  identified,  are  placed  on  penicillin, 
which  will  prevent  that  tremendous  human  loss  which  we  saw  be- 
fore this  study  was  published.  In  addition,  in  Massachusetts,  in 
conjunction  with  the  department  of  public  health,  we  have  ar- 
ranged so  that  any  family  that  does  not  have  insurance  or  a  way 
of  buying  penicillin  will  receive  free  penicillin  for  the  first  7  years 
of  life. 

The  Boston  Center  serves  also  as  a  resource  to  the  New  England 
area.  When  Rhode  Island  initiated  newborn  screening,  it  was  the 
Boston  Center  that  did  newborn  screening  for  Rhode  Island  until 
the  New  England  Regional  Newborn  Screening  Program  took  over 
this  task.  We  are  also  a  resource  to  New  England  States  for  test- 
ing, counseling  and  consultation. 

In  Rhode  Island,  we  helped  establish  a  sickle  cell  clinic  in 
Women  and  Infants  Hospital,  and  we  continue  to  do  testing  for 
Maine,  New  Hampshire  and  Vermont.  Outside  the  United  States, 
we  have  served  as  consultation  for  the  establishment  of  two  clinics 
in  England,  and  in  Brazil,  we  continue  to  share  our  experience  in 
basic  and  clinical  research  and  educational  materials,  which  I  have 
helped  to  translate  into  Portuguese,  in  their  efforts  to  establish 
screening  and  start  sickle  cell  clinics. 

The  physicians  of  the  Boston  Sickle  Cell  Center  are  responsible 
for  over  400  patients  in  the  greater  Boston  area  and  serve  as  con- 
sultants for  the  entire  State,  and  again,  for  the  region.  Our  popu- 
lation is  mostly  African  American,  African,  Haitian,  Cape  Verdean. 
Puerto  Rican,  and  other  countries  from  the  Caribbean,  Central 
America  and  South  America.  To  better  serve  this  population,  we 
try  to  hire  Spanish-speaking,  Haitian-Creole-speaking,  and  myself, 
as  both  Puerto  Rican  and  Portuguese,  also  help  to  address  many 
of  our  patients  needs  and  anxieties  in  their  own  language. 

Recently,  as  you  are  well  aware,  we  have  a  very  significant  num- 
ber of  refugees  from  Somalia,  wnich  are  increasing  in  numbers, 


21 

whom  we  are  now  testing  and  will  be  counseling  and  enrolling  any 
patient  that  we  discover  in  comprehensive  care. 

Finally,  because  the  ultimate  goal  of  the  combined  efforts  of  all 
researchers  in  the  10  national  centers  is  to  find  a  cure,  we  are  tre- 
mendously pleased  to  know  that  the  National  Institutes  of  Health 
will  be  funaing  three  projects  in  gene  therapy  this  year.  We,  along 
with  other  centers,  are  also  participating  in  bone  marrow  trans- 
plantation studies  for  young  patients  with  sickle  cell  disease. 

There  is  so  much  more  that  I  would  like  to  tell  you  about  my  cen- 
ter, but  I  know  there  are  other  colleagues  here  who  are  equally 
eager  to  tell  you  about  the  accomplishments  in  their  centers.  Again, 
I  thank  you  for  inviting  me  here  to  tell  you  about  this. 

The  Chairman.  Thank  you  very  much. 

[The  prepared  statement  of  Dr.  McMahon  follows:] 

Prepared  Statement  of  Lillian  Caldeira  McMahon,  M.D. 

Dear  Senator  Kennedy,  thank  you  for  inviting  me  to  testify  on  the  Senate  Com- 
mittee on  Labor  and  Human  Resources  hearing  on  Sickle  Cell  Research  next  Thurs- 
day^ July  28,  1994. 

The  Boston  Comprehensive  Sickle  Cell  Center  is  one  of  ten  national  comprehen- 
sive centers  funded  through  the  Sickle  Cell  Branch  of  the  National  Heart,  Lung  and 
Blood  Institute.  Each  of  the  ten  Sickle  Cell  Centers  operate  within  the  academic  en- 
vironment of  a  university  and  medical  center  which  allows  tar  a  productive  collabo- 
ration between  researchers  and  clinicians  and  for  continuity  of  care  of  patients. 

The  Boston  Sickle  Cell  Center  is  especially  fortunate  to  have  three  medical 
schools,  Tufts,  Harvard,  and  Boston  University,  affiliated  with  our  program.  Our  six 
research  projects  in  red  cell  membrane,  endothelial  adhesion  and  hemoglobin 
switching  are  conducted  in  six  university-affiliated  hospitals  and  a  graduate  school, 
Northeastern  University.  This  academic  and  clinical  environment  brings  together  a 
community  of  scholars,  researchers,  clinicians  and  other  health  professionals,  which 
are  vital  to  progress  of  sickle  cell  research  and  treatment  of  patients  with  sickle  cell 
disease. 

It  is  almost  an  impossibility  to  report  to  your  committee  the  accomplishments  of 
the  Boston  Sickle  Cell  Center  in  only  five  minutes  allowed  for  this  presentation. 
However  I  will  attempt  to  highlight  some  of  our  achievements. 

Investigators  in  the  Boston  Sickle  Cell  Center  have  focused  on  understanding  how 
alterations  in  the  red  cell  membrane  contribute  to  the  pathogenesis  of  sickle  cell  dis- 
ease. Such  knowledge  could  lead  to  the  development  of  therapeutic  strategies  that 
prevent  the  dehydration  that  is  such  a  critical  determinant  in  the  formation  of 
intracellular  sickle  hemoglobin  polymers.  Even  a  modest  reduction  of  the  hemo- 

f;lobin  concentration  inside  the  red  cell  could  have  a  marked  effect  in  inhibiting  sick- 
ing. 

Dr.  Carlo  Brugnara  and  co-investigators  in  the  Boston  Sickle  Cell  Center  have  de- 
veloped a  novel  approach  based  on  these  principles.  They  began  with  the  premise 
that  the  calcium  dependent  Gardos  channel  inside  the  red  cell  assumes  a  primary 
role  in  the  loss  of  potassium  and  cell  dehydration  that  accompanies  sickling.  They 
have  demonstrated  that,  in  vitro,  inhibitors  of  the  Gardos  channel  could  block  water 
loss  from  sickle  red  cells.  One  of  these  inhibitors,  clotrimazole,  a  commonly  used 
antifungal  agent,  was  fully  effective  on  sickle  red  cells  at  concentrations  lower  than 
that  used  in  patients  routinely  treated  with  the  drug.  They  then  tested  this  drug 
in  a  transgenic  mouse  model  of  sickle  cell  disease  and  demonstrated  the  efficacy  of 
the  drug  in  vivo  in  preventing  the  dehydration  of  sickle  red  cells.  On  the  basis  of 
these  exciting  and  promising  findings,  these  investigators,  in  collaboration  with  an- 
other Boston  Center  investigator,  Dr.  Orah  Piatt,  are  embarking  on  a  phase  I  clini- 
cal trial  in  patients  with  sickle  cell  disease. 

Also  in  red  cell  membrane  research  Dr.  Jiri  Palek  and  collaborators  discovered 
sites  in  the  red  cell  where  polymers  of  hemoglobin  penetrate  disrupting  the  mem- 
brane, causing  breakage  and  cell  damage,  which  in  turn  leads  to  stickiness  of  the 
cell  inside  the  blood  vessels  and  obstruction  of  blood  flow  all  this  resulting  in  pain 
to  the  patient  and  organ  damage.  This  important  work  was  published  in  the  journal 
Science. 

Research  using  the  drug  hydroxyurea  originated  in  Boston  by  sickle  cell  research- 
ers. Hydroxyurea  promotes  the  bone  marrow  to  produce  greater  quantity  of  red  cells 
containing  fetal  hemoglobin  and  decreases  the  tendency  of  the.  red  blood  cells  to 


22 

sickle.  The  use  of  hydroxyurea  in  selected  patients  with  sickle  cell  disease  resulted 
in  diminishing  the  frequency  and  intensity  of  their  sickle  cell  crises.  Further  clinical 
trials  continue  in  Boston  and  other  Centers  with  careful  monitoring  of  patients  by 
sickle  cell  researchers  and  clinicians. 

With  the  transfer  of  Dr.  Perrine  and  her  research  project  from  the  California  Sick- 
le Cell  Center  to  our  Center  in  Boston  we  are  continuing  the  investigation  of  other 
drugs,  such  as  butyrate,  which  also  promotes  the  bone  marrow  to  switch  from  pro- 
ducing sickle  hemoglobin  to  producing  more  fetal  hemoglobin.  Clinical  trials  are  now 
in  progress  with  patients  with  sickle  cell  disease  and  with  thalasseaia. 

The  Boston  Center  participated  in  the  landmark  multicenter  study  of  penicillin 
prophylaxis  in  children  with  sickle  cell  anemia  which  demonstrated  that  administer- 
ing penicillin  twice  daily  to  children  with  thin  disease  prevents  the  mortality  which 
was  as  high  as  30Q  in  the  first  3  years  of  life  and  diminishes  the  morbidity  caused 
by  certain  bacterial  infections  in  children. 

As  a  result  of  the  findings  of  this  study  screening  for  sickle  cell  disease  in 
newborns  was  instituted  in  most  states  in  the  U.S.  As  soon  as  babies  are  identified 
as  having  sickle  cell  disease  they  are  started  on  penicillin  prophylaxis,  preventing 
the  tremendous  human  loss  we  experienced  before  this  study.  The  Boston  Center 
was  responsible  for  establishing  universal  newborn  screening  for  sickle  cell  disease 
and  other  hemoglobinopathies  in  Massachusetts  in  1988  and  performed  sickle  cell 
screening  of  newborns  for  the  state  of  Rhode  Island  as  part  of  a  Special  Program 
of  National  and  Regional  Significance  grant.  We  now  serve  as  consultants  to  the 
Now  England  Regional  Newborn  Screening  Program  and  are  responsible  for  the 
medical  care  of  babies  identified  through  this  program  in  Massachusetts.  Once  iden- 
tified, newborns  with  Sickle  call  disease  are  started  on  penicillin  prophylaxis  and 
enrolled  in  a  comprehensive  medical  care  program.  We  continue  to  screen  for  the 
states  of  Vermont,  Maine,  and  New  Hampshire. 

We  serve  as  a  resource  for  the  New  England  states  for  testing,  education  and 
counseling,  and  for  consultation  concerning  sickle  cell  patients.  The  Boston  Sickle 
Cell  Center  participated  in  the  establishment  of  the  Sickle  Cell  Clinic  in  Women 
and  Infants' Hospital  in  Rhode  Island.  Outside  the  country  we  assisted  with  con- 
sultation in  the  creation  of  two  programs  for  screening  and  clinical  management  of 
patients  with  sickle  cell  disease  in  England,  and  share  our  experience  in  basic  and 
clinical  research,  as  well  as  educational  materials  with  our  colleagues  in  Brazil  in 
their  efforts  to  establish  screening  programs  and  start  sickle  cell  clinics. 

Boston  Sickle  Cell  Center  physicians  deliver  comprehensive  medical  care  to  over 
400  patients  with  sickle  cell  disease.  Our  population  is  diverse  and  comprised  of  Af- 
rican Americans,  Africans,  Cape  Verdeans,  Haitians,  Puerto  Ricans  and  persons 
from  other  Caribbean,  Central  and  South  American  countries.  To  best  meet  the 
needs  of  our  patients  the  Boston  Center  has  staff  who  speak  Spanish  and  Haitian 
Creole.  Myself,  as  being  both  Puerto  Rican  and  Portuguese,  am  able  to  address 
many  of  our  patients  in  their  native  language,  which  facilitates  communication  and 
helps  ease  patients'  anxieties.  There  is  presently  a  significant  and  increasing  num- 
ber of  refugees  from  Somalia  in'  Massachusetts  which  the  Boston  Center  will  test 
and  counsel  concerning  sickle  cell  disease,  and  enroll  in  comprehensive  medical  care. 

There  is  so  much  more  that  I  would  like  to  relate  to  you  and  your  committee  but 
I  understand  that  my  colleagues  from  two  other  Sickle  Cell  Centers  are  equally  ex- 
cited and  eager  to  report  the  accomplishments  of  their  Centers. 

Finally,  because  the  ultimate  goal  of  our  combined  endeavors  is  to  find  a  cure, 
we  are  tremendously  pleased  to  hear  that  the  Sickle  Cell  Branch  will  fund  3  projects 
in  gene  therapy  this  year. 

Again  I  thank  you  for  this  opportunity  to  report  some  of  the  achievements  of  the 
Boston  Sickle  Cell  Center  to  your  Committee. 

The  Chairman.  Dr.  Turner. 

Dr.  Turner.  Thank  you,  Senator  Kennedy,  for  the  opportunity  to 
speak  before  you  and  your  committee  this  afternoon. 

We  have  given  you  some  written  information,  and  I  would  like 
to  focus  my  comments  around  three  of  the  slides  that  I  have  pre- 
pared for  you  to  try  to  give  you  an  overview  about  our  center.  This 
also,  I  think,  gives  a  better  overview  of  all  the  centers  in  the  Unit- 
ed States  that  are  currently  funded  by  the  NIH.  This  slide  is  the 
last  one  in  my  packet  that  gives  you  an  overview  of  the  program 
components  that  all  of  the  centers  currently  have. 

We  are  all  involved  in  research  activities,  which  includes  both 
basic  and  clinical  activities.  We  all  serve  as  resources  for  our  sur- 


23 

rounding  communities  and  catchment  areas.  I  am  at  Meharry  Med- 
ical College  in  Nashville,  TN,  and  I  serve  the  21  counties  as  my 
catchment  area  of  Tennessee,  and  in  addition  to  that,  I  serve  as  the 
consultant  for  the  State  of  Kentucky,  especially  southern  Kentucky, 
where  we  are  responsible  for  that  patient  population. 

In  addition,  all  the  centers  have  a  major  role  in  making  sure  that 
information  is  disseminated  to  the  lay  public  and  to  our  own  col- 
leagues, who  many  times  are  not  aware  of  new  developments  that 
may  happen  in  our  centers  and  other  research  activities. 

We  have  major  psychological  support  in  our  institution  in  terms 
of  research  activities.  We  have  a  joint  partnership  with  Vanderbilt 
University,  where  many  of  our  psychological  projects  are  conducted 
with  their  staff  at  Peabody  Institution,  which  is  a  major  institution 
that  has  been  involved  in  research  and  psychological  activities  in 
the  United  States  for  many,  many  years. 

We  are  involved  in  counseling,  and  we  also  have  the  State  con- 
tract for  making  sure  that  individuals  who  are  diagnosed  with  sick- 
le cell  trait  in  the  State  of  Tennessee  get  information  that  is  appro- 
priate for  the  type  of  hemoglobin  variant  that  they  have. 

We  have  not  talkea  about  yet  in  this  hearing  that  there  are  over 
700  known  hemoglobins  right  now  in  the  United  States  that  are 
documented,  recognized,  and  known.  Thus,  there  is  a  wealth  of  in- 
formation that  needs  to  be  translated  to  a  variety  of  individuals. 
As  was  mentioned  earlier,  we  have  State  newborn  screening  pro- 
grams, and  on  a  daily  basis  in  our  laboratory — I  am  the  reference 
laboratory  for  the  State  of  Tennessee — we  are  always  getting  this 
"alphabet  soup,"  as  I  call  it,  and  I  am  always  getting  calls  to  help 
someone  understand  what  hemoglobin-D  or  J  or  H,  or  hemoglobin- 
Bart  represents. 

So  we  have  a  tremendous  responsibility  to  make  sure  that  the  in- 
formation that  is  there  is  translated  to  other  individuals  who  may 
not  be  as  familiar  with  this  "alphabet  soup,"  that  I  call  the  700 
types  of  variants  that  may  be  available. 

What  I  would  like  to  do  in  the  next  few  minutes  is  talk  about 
some  of  the  accomplishments  that  have  occurred  at  our  center.  For 
the  past  20  years,  Meharry  Medical  College  has  been  involved  in 
sickle  cell  disease  research.  We  have  come  a  long  way.  We  started 
out  as  an  infant,  and  I  think  we  are  now  in  the  teenage  stage  of 
our  activities  at  Meharry  Medical  College  in  the  sense  that  we 
have  taken  our  time  to  develop  a  center.  There  needs  to  be  a  criti- 
cal mass  that  is  there  to  carry  on  these  kinds  of  activities,  these 
very  sophisticated  and  time-consuming  activities  that  occur  in  the 
center  itself.  So  we  have  a  critical  mass  that  has  allowed  us  to  de- 
velop basic  research. 

For  example,  many  of  us  in  this  room  know  we  now  believe  that 
the  reason  for  the  sickle  cell  gene  mutation  was  protection  against 
malaria.  And  we  have  been  working  with  one  of  the  membrane  re- 
ceptors, glycophorin,  over  the  past  10  years,  to  help  solidify  that 
concept  and  also  to  look  at  how  it  can  help  us  further  develop  strat- 
egies and  treatment  plans  for  individuals  who  have  sickle  cell  dis- 
ease. 

We  have  also  been  involved  in  looking  at  mechanisms  and  ma- 
nipulating systems  that  would  help  us  to  ultimately  get  closer  to 
gene  therapy — looking  at  the  viruses  that  may  possibly  serve  as 


24 

vectors  that  we  could  use  to  help  us  with  a  cure  for  sickle  cell  dis- 
ease. 

As  I  have  already  mentioned,  we  have  a  laboratory  that  is  the 
State  reference  laboratory.  We  are  a  recipient  and  participate  in 
the  cap  certification.  In  factx-  we  just  recently  sent  out  hemoglobin- 
Zurich  as  one  of  the  unknowns  to  all  the  State  laboratories;  that 
came  out  of  our  laboratory,  where  we  just  cloned  and  sequenced  the 
gene  that  was  responsible  for  that  hemoglobin-Zurich.  And  this  is 
a  very  interesting  hemoglobin  that  is  not  predominantly  found  in 
African  Americans,  but  is  found  in  individuals  from  Middle  Europe, 
and  individuals  who  may  get  exposed  to  certain  kinds  of  oxidants, 
specifically  sulphur  drugs,  may  have  occasion  to  become  severely 
ill.  So  the  family  that  we  described  is  not  an  African  American 
family;  it  is  a  Caucasian  family  from  middle  Kentucky,  where  we 
have  now  done  pedigree  studies  and  are  looking  at  the  extraction 
of  this  family  back  to  Central  Europe.  So  we  have  done  some  very 
interesting  work  in  that  area. 

We  are  involved  not  only  in  the  United  States — as  Dr.  McMahon 
has  said,  she  is  involved  in  Brazil — we  are  involved  in  Peru.  We 
have  an  ongoing  relationship  and  have  some  AID  grants  in  Peru. 
We  have  also  translated  with  my  help  into  Spanish  information 
that  is  now  being  used  in  Peru  from  our  center.  So  we  are  also  in- 
volved on  the  international  scene  and  have  been  involved  with  a 
number  of  other  centers  and  countries  in  sickle  cell  disease. 

I  would  really  like  for  us  to  think  of  this  as  a  global  issue  in 
many  ways.  As  I  mentioned,  there  are  700  different  types  of  hemo- 
globins. There  are  many  people  who  are  now  getting  involved  in 
this  arena.  And  as  the  world  gets  smaller,  we  are  starting  in  our 
area  to  see  other  kinds  of  hemoglobins  that  we  did  not  have  infor- 
mation on.  For  example,  hemoglobin-E  is  now  one  of  the  most  fre- 
quently diagnosed  hemoglobins  in  the  United  States.  This  is  a  he- 
moglobin that  has  its  predominance  in  Southeast  Asia,  and  in  mid- 
dle Tennessee,  we  have  a  fairly  large  Southeast  Asian  population — 
we  have  Cambodians  and  Vietnamese — and  in  our  center,  we  have 
an  individual  who  speaks  all  of  these  languages.  There  is  a  rural 
and  cultural  difference,  and  you  have  to  be  culturally  sensitive  to 
talk  about  taking  blood  from  those  individuals.  As  you  may  or  may 
not  know,  individuals  from  Southeast  Asia  view  blood  differently 
than  we  do.  So  we  have  a  person  in  our  center  who  is  aware  of 
that,  so  when  we  talk  about  taking  blood,  we  can  use  the  right  eth- 
nic-sensitive approach  in  helping  individuals  from  Southeast  Asia. 

So  we  are  involved  in  a  variety  of  things  that  I  think  have  ex- 
panded our  horizons,  and  those  systems  that  we  have  developed 
have  allowed  other  centers  to  use  them,  and  we  are  in  very  close 
collaboration  with  many  of  those  centers. 

So  the  support  that  we  have  received  has  been  very  important 
for  us  to  expand  our  horizons,  but  that  did  not  occur  overnight.  It 
took  us  a  while  to  get  to  that  point,  and  we  are  looking  forward 
to  continuing  to  be  able  to  do  that  with  adequate  support.  I  think 
that  is  one  of  the  issues  that  we  need  to  be  very  careful  about  in 
terms  of  recognizing  that  there  is  about  $60  million  to  $70  million 
coming  of  the  NIH,  but  hat  is  not  adequate  to  do  the  kinds  of 
things  that  we  need  to  do. 


25 

And  Dr.  Lenfant  did  not  get  into  it,  but  I  will  say  it — the  moneys 
that  have  been  coming  out  have  not  been  adequate.  They  have 
been  flat.  For  the  last  years,  we  have  taken  a  hit.  I  get  appro- 
priated a  line  item  from  NIH  in  terms  of  my  grant,  my  P-60,  and 
yet  I  have  had  to  take  from  5  to  8  to  10  percent  each  year  because 
of  the  lack  of  resources  that  the  NIH  has. 

So  I  think  one  of  the  things  that  I  would  like  to  see  come  out 
of  this  is  a  recognition  that  there  is  ongoing  quality,  adequate  re- 
search, but  despite  our  efforts,  we  are  handicapped  because  many 
times,  we  have  to  put  it  on  the  back  burner,  or  we  are  not  able  to 
follow  up  leads  we  have  in  terms  of  looking  at  those  leads  and 
helping  us  move  toward  curing  this  disease,  because  of  the  shortfall 
that  is  occurring  in  Congress. 

I  know  I  am  not  saying  anything  that  you  do  not  know,  but  what 
we  really  need  is  more  support,  in  a  variety  of  ways,  to  accomplish 
some  things  that  many  of  us  have  ideas  about  but  have  inadequate 
resources  for.  Out  State  institutions  many  times  are  not  available 
to  provide  adequate  resources.  So  it  would  be  very  nice  if  one  of  the 
things  that  happens  is  a  movement  to  put  more  money  in  the  pipe- 
line to  help  us  solve  some  of  the  problems  that  many  of  us  have 
on  our  burners. 

I  will  stop  here  and  let  my  other  colleagues  have  the  opportunity 
to  speak. 

Tnank  you. 

[The  prepared  statement  of  Dr.  Turner  appears  at  the  end  of  the 
hearing  record.] 

The  Chairman.  As  I  said,  I  am  managing  the  reauthorization  of 
the  Elementary  and  Secondary  Education  Act  on  the  floor,  which 
deals  with  disadvantaged  students,  and  I  am  going  to  have  to  go 
back  over  to  the  floor.  But  I  would  be  interested  if  the  researchers 
could  give  us  some  insight  as  to  the  similarities,  if  any,  in  terms 
of  sickle  cell,  Tay-Sachs  and  Cooley's  diseases.  Are  they  basically 
variations  on  a  theme,  or  are  they  pretty  disparate? 

Dr.  Turner.  The  biochemical  differences  are  totally  different. 
But  when  we  talk  about  a  chronic  illness,  whether  we  are  talking 
about  Tay-Sachs  or  sickle  cell  disease  or  hemophilia,  we  have  some 
common  elements  that  are  present.  A  chronic  illness  has  some 
things  that  need  to  be  dealt  with.  There  is  the  psychological  im- 
pact. There  needs  to  be  research  put  into  those  specific  diseases. 
So  there  are  similarities  in  that  respect.  But  in  terms  of  the  bio- 
chemistry, the  physiology,  there  are  some  differences. 

Did  I  understand  your 

The  Chairman.  Yes,  that  is  helpful. 

Dr.  Moore.  Both  diseases,  sickle  cell  and  Tay-Sachs,  are  genetic 
in  nature.  Both  seem  to  afflict  different  ethnic  groups,  have  a  pre- 
dominance of  influence  on  different  ethnic  groups.  The  incidence  of 
sickle  cell  disease  appears  to  be  much  higher  in  the  African  Amer- 
ican community  than  Tay-Sachs  is  in  the  Jewish  community. 

The  Chairman.  And  wouldn't  Cooley's  be  basically  ethnic  as 
well? 

Dr.  Turner.  If  you  are  referring  to  Cooley's  anemia,  we  are  talk- 
ing about  the  homozygous  condition,  and  the  predominance  of  that 
disease  would  be  in  Italian  descent.  But  we  have  beta-thalassemia, 
and  we  can  have  the  combination  beta-thalassemia  trait  in  the  Af- 


82-553  0-94-3 


26 

rican  American  population.  So  we  have  the  S-beta-thalassemia  syn- 
dromes that  we  have  to  address  also,  which  can  be  just  as  severe 
in  many  instances  as  the  homozygous  SS  condition  in  individuals 
with  sickle  cell  disease. 

Dr.  McMahon.  Putting  it  very  basically,  on  thalassemia  and 
sickle  cell,  in  sickle  cell,  hemoglobin  that  is  produced  is  abnormal, 
and  in  thalassemia,  there  is  not  sufficient  hemoglobin  being  pro- 
duced, although  biochemically,  it  is  normal. 

The  Chairman.  Thank  you. 

Just  before  calling  on  Dr.  Moore,  Shawnita,  if  I  could,  I  would 
just  like  to  ask  you  a  couple  of  questions.  As  far  as  your  greatest 
challenge  in  coping  with  the  disease,  what  is  the  most  difficult 
thing  about  coping  with  the  disease  itself  for  you? 

Ms.  agnew.  The  pain,  really. 

The  Chairman.  The  continuing  pain. 

Ms.  agnew.  Yes. 

The  Chairman.  And  that  iust  seems  to  go  on  and  on.  Has  the 
Boston  City  Hospital  Center  been  really  helpful  to  you? 

Ms.  agnew.  Yes,  a  lot. 

The  Chairman.  And  do  you  remember  which  programs  there 
have  been  the  most  helpful? 

Ms.  agnew.  The  teen  support  group. 

The  Chairman.  The  support  group.  And  have  you  thought  about 
the  research  a  little  bit  and  which  areas  you  would  like  to  see  re- 
searched, or  just  the  whole  thing? 

Ms.  AGNEW.  Everything,  the  whole  thing. 

The  Chairman.  Everything.  OK.  Thank  you. 

The  Chairman.  Dr.  Moore. 

Dr.  Moore.  Thank  you,  Mr.  Chairman. 

I  want  to  talk  about  Southern  University,  but  in  so  doing,  I  want 
to  allow  that  to  set  the  tone  for  what  I  believe  are  some  of  the  con- 
cerns that  have  been  raised,  especially  from  Senator  Simon,  a  con- 
cern that  was  raised  about  peer  review,  and  of  course,  the  degree 
of  medical  school  affiliation  and  whether  that  has  anything  to  do 
with  an  institution's  capability. 

I  am  William  E.  Moore,  vice  chancellor  for  academic  affairs  at 
Southern  University  in  Baton  Rouge.  I  am  pleased  to  have  the  op- 
portunity to  speak  in  behalf  of  our  institution  and  to  seek  commit- 
ted support  for  the  establishment  of  a  national  sickle  cell  research 
center  on  the  Baton  Rouge  campus,  a  major  constituent  of  the 
Southern  University  system. 

The  four  entities  that  constitute  the  Southern  University  system 
are  strategically  located  throughout  the  State  of  Louisiana.  They 
include  a  2-year  campus  in  Shreveport,  a  law  center  in  Baton 
Rouge,  an  urban  commuter  campus  in  New  Orleans,  and  a  Level- 
3  doctoral  institution  in  Baton  Rouge. 

The  Southern  University  system,  with  almost  17,000  students,  is 
the  only  system  of  higher  education  within  the  historically  black 
college  community  in  this  country,  or  in  the  world,  for  that  matter. 

Dr.  Delores  Spikes,  who  is  here  today,  is  president  of  the  South- 
ern University  system,  and  Dr.  Marvin  Yates,  who  is  also  here,  is 
chairman  of  the  Baton  Rouge  campus. 

I  am  also  joined  by  Dr.  Jonathan  Roberts,  who  is  the  director  of 
Charity  Hospitals  of  Louisiana.  Before  assuming  that  position,  Dr. 


27 

Roberts  served  as  coordinator  of  planning  of  our  national  sickle  cell 
disease  center. 

Our  appearance  here  today  provides  a  mechanism  for  us  to  share 
with  you,  Senator  Kennedy,  what  we  believe  to  be  indisputable  doc- 
umentation of  the  need  for  the  proposed  center  and  why  it  should 
be  at  Southern  University  in  Baton  Rouge — for  indeed,  despite  our 
best  efforts,  some  of  the  noteworthy  accomplishments  of  our  insti- 
tution remain  well-kept  secrets,  and  we  sense  the  tone  of  that 
today,  and  I  hope  in  your  allowing  me  to  tell  you  a  little  bit  about 
some  of  them,  we  will  also  address  the  issue  of  peer  review,  docu- 
mentation, and  of  course,  budgetary  needs. 

I  should  say  that  the  warm  hospitality  we  have  already  received 
has  enabled  me  to  dispel  the  belief  that  the  atmosphere  near  the 
Potomac  or  inside  the  beltway  would  be  intimidating  at  best.  We 
thank  you  for  this  reception. 

By  way  of  experience,  I  have  spent  my  entire  professional  career 
as  a  university  professor  and  administrator  having  had  the  privi- 
lege of  full-time  teaching  appointments  at  four  historically  black  in- 
stitutions. I  have  also  served  as  adjunct  professor  at  four  majority 
institutions,  the  latter  representing  some  of  the  finer  examples  of 
tradition,  elitism,  research  productivity,  and  academic  standards.  I 
have  been  a  visiting  lecturer  in  Italy,  Belgium  and  France,  the 
highlight  being  an  invited  lecturer  at  the  Pasteur  Institute  in  Paris 
in  1978. 

I  have  served  as  chairman  of  the  general  research  support  review 
committee  of  the  National  Institutes  of  Health,  and  I  am  currently 
serving  a  second  3-year  term  on  the  board  of  review  of  the  National 
League  of  Nursing. 

I  mention  these  affiliations  not  in  the  interest  of  self-indulgence, 
but  because  I  believe  these  experiences  have  given  me  an  oppor- 
tunity to  observe  and  participate  in  a  spectrum  of  scientific-related 
activities,  many  of  which  have  relevance  to  your  committee,  and 
some  of  which  I  will  refer  to  today  in  regard  to  sickle  cell  research 
and  the  appropriateness  at  our  university. 

Although  I  am  a  part  of  the  Southern  University  system,  I  will 
confine  my  remaining  comments  to  the  Baton  Rouge  campus,  the 
oldest  and  largest  unit  within  the  system.  Southern  University  at 
Baton  Rouge  is  an  1890  land  grant  institution,  with  enrollment  on 
the  Baton  Rouge  campus  in  excess  of  10,000  students,  the  history 
of  the  university  is  punctuated  with  the  achievements  of  its  grad- 
uates. 

For  example,  the  university  claims  among  its  graduates  eight 
generals  in  the  United  States  Army;  a  significant  percentage  of  the 
minority  lawyers  in  this  country — and  I  should  say  that  in  less 
than  10  years,  our  nursing  program  has  achieved  the  status  of 
being  one  of  the  leading  undergraduate  programs  in  the  United 
States.  Our  graduates  consistently  score  above  95  percent  on  board 
examinations,  and  our  recent  self-study  and  its  initial  accreditation 
was  selected  by  the  National  League  of  Nursing  as  a  model  for 
other  institutions  across  this  country  to  use  as  a  guide. 

Southern  University  has  a  long  history,  Mr.  Chairman,  and  this 
has  some  implications  of  peer  review,  as  one  of  the  leading  HBCUs 
to  produce   graduates   who  have   earned   the   Ph.D.   in   political 


28 

science.  In  fact,  we  rank  at  the  top  of  producing  black  political  sci- 
entists at  the  Ph.D.  level. 

What  is  little-known,  however — and  I  point  this  out  by  under- 
scoring it— is  that  between  1985  and  1989,  10  percent  of  all  of  the 
blacks  in  this  country  who  received  a  Ph.D.  in  physics  were  South- 
ern University  graduates.  This  is  indeed  a  major  accomplishment 
given  the  large  number  of  colleges  and  universities  in  this  country. 
Further,  Southern  University  provides  a  wholesome  intellectual 
and  cultural  environment  for  the  development  of  leaders  among  its 
graduates.  Three  former  Southern  University  student  government 
presidents  now  serve  in  the  Louisiana  legislature  or  have  served 
there,  and  as  I  speak  to  you  today,  I  should  remind  this  distin- 
guished committee  that  two  of  those  graduates,  William  Jefferson 
and  Cleo  Fields,  are  the  only  African  Americans  represented  in  the 
State  of  Louisiana  in  the  United  States  Congress.  And  a  third, 
State  Senator  Charles  Jones,  is  the  architect  of  the  sickle  cell  ane- 
mia bill  in  Louisiana,  and  is  also  present  today. 

My  point  in  mentioning  these  few  examples  is  to  underscore  the 
fact  that  our  general  university  environment  is  geared  to  support 
and  to  sustain  excellence  in  teaching,  research,  and  service. 

I  will  not  read  to  you  the  details  of  the  background  of  the  need 
for  tie  sickle  cell  center,  because  you  have  heard  about  that  from 
several  of  the  scientists  and  persons  who  have  testified  before  you 
today.  I  would  like  to  point  out,  though,  that  the  center  we  are  pro- 
posing will  include  a  section  which  will  focus  on  physical-chemical 
studies,  principally  on  in  vitro  studies  of  hemoglobin.  We  will  draw 
on  the  faculty  in  the  departments  of  physics,  chemistry,  and  biology 
to  investigate  the  effects  of  physical  stress  and  chemical  agents  on 
the  solution  properties  of  hemoglobin. 

We  will  also  have  a  division  which  will  focus  on  anti-sickhng 
agents,  which  are  still  important  despite  the  progress  that  is  being 
made.  This  division  will  be  devoted  to  the  isolation,  characteriza- 
tion, and  synthesis  of  anti-sickling  agents,  substances  which  enable 
patients  to  lead  a  normal  life  by  decreasing  the  chances  of  blood 
cells  to  become  sickled. 

We  will  have  a  clinical  division — and  this  is  extremely  important, 
because  we  have  heard  questions  raised  about  the  need  to  be  asso- 
ciated with  a  hospital.  We  will  devote  primary  attention  to  longitu- 
dinal studies  of  patients  who  have  sickle  cell  disease,  and  these  in- 
vestigations will  be  carried  out  in  conjunction  with  the  Earl  K. 
Long  Hospital  and  with  other  clinical  settings.  The  physicians  pro- 
viding immediate  supervision  for  these  studies  will  be  hospital  phy- 
sicians who  will  hold  adjunct  appointments  in  biomedical  sciences 
at  Southern  University. 

I  have  other  information  about  the  clinical  studies  in  the  written 

text. 

We  will  have  a  division  of  molecular  biology  and  genetic  engi- 
neering, where  we  hope  to  do  gene  therapy  research.  We  will  also 
have  a  laboratory  on  ultrastructural  studies,  in  which  we  will  en- 
gage in  electron  microscopy  as  a  major  tool  for  investigating  in 
vitro  and  in  vivo  sickling. 

Finally,  there  will  be  a  laboratory  on  behavioral  and  epidemiolog- 
ical studies.  This  division  of  the  sickle  cell  center  will  have  the  role 
of  investigating  disease  patterns  similar  to  what  you  have  already 


29 

raised.  Senator  Kennedy,  with  a  view  toward  using  the  knowledge 
gained  therefrom  for  education  and  prevention. 

The  Chairman.  Dr.  Moore.  I  am  going  to  have  to  interrupt  you 
here.  We  have  present  Dr.  Onene-Frempong,  who  will  be  testifying 
as  well.  I  have  keen  called  over  to  the  floor  Dy  the  Majority  Leader, 
and  Senator  Wellstone  will  be  here  momentarily  to  chair. 

Let  me  just  ask  you  this.  There  is  no  question  that  the  university 
has  been  an  extraordinary  educational  center.  I  suppose  the  ques- 
tion is  the  reason  why  it  is  necessary  to  have  a  new  center,  or 
whether  the  scarce  resources  should  not  be  further  targeted  on  the 
existing  research  centers  which  have  been  working  in  these  areas. 
How  would  you  respond  to  that? 

Dr.  Moore.  I  will  try  to  answer  that,  Senator,  by  giving  four  bul- 
lets, which  was  going  to  be  my  concluding  statement,  if  I  may,  be- 
cause I  think  that  shows  you  where  we  are  different  from 

The  Chairman.  If  you  can  do  it;  I  must  leave  in  a  couple  of  min- 
utes because  I  am  required  to  be  on  the  floor  of  the  Senate.  We 
could  make  it  part  of  the  record,  and  if  you  want  to  summarize  in 
a  couple  of  minutes,  I  would  be  glad  to  hear  you.  If  you  need  a 
longer  period  of  time,  we  can  put  it  in  the  record. 

Dr.  Moore.  Sure.  It  will  not  take  2  minutes  to  do  it. 

The  Chairman.  Fine.  Go  ahead. 

Dr.  Moore.  First  of  all,  the  State  of  Louisiana  has  already  com- 
mitted substantial  financial  support  to  this  effort.  The  proposal  has 
received  the  categorical  endorsement  of  both  State  and  Congres- 
sional Black  Caucuses. 

We  have  a  peer  review  at  the  Board  of  Regents  in  Louisiana,  and 
that  board  relies  heavily  on  outside  scientists  to  evaluate  what  we 
have  done. 

We  have  the  full  endorsement  of  the  hospital  systems  of  Louisi- 
ana, the  two  medical  schools,  Tulane  University  and  Louisiana 
State  University,  and  as  I  said,  we  have  the  director  of  Charity 
Hospital,  who  is  providing  support. 

So  when  you  look  at  the  track  record  combined  with  the  support 
that  has  emanated  from  within  our  State,  we  believe  that  it  is  un- 
matched in  any  State  in  this  Nation,  and  for  that  reason,  we  are 
seeking  your  support  for  the  momentum  that  we  have  already  gen- 
erated to  be  carried  out. 

The  Chairman.  Thank  you.  I  saw  some  references  to  those  points 
in  the  testimony,  which  I  will  study  further  at  another  time.  We 
appreciate  very  much  your  presence  nere. 

[The  prepared  statement  of  Dr.  Moore  follows:] 

Prepared  Statement  of  William  E.  Moore 

Mr.  Chairman  and  members  of  this  committee,  I  am  William  E.  Moore  ,  Vice 
Chancellor  for  Academic  Affairs  at  Southern  University  in  Baton  Rouge.  I  am 
pleased  to  have  the  opportunity  to  speak  in  behalf  of  our  institution  and  to  seek 
the  committee's  support  for  the  establishment  of  a  National  Sickle  Cell  Disease  Re- 
search Center  on  the  Baton  Rouge  Campus  a  major  constituent  of  the  Southern  Uni- 
versity System.  The  four  entities  which  constitute  the  Southern  University  System 
are  strategically  located  throughout  the  state  of  Louisiana.  They  include  a  two-year 
campus  in  Shreveport,  a  Law  Center  in  Baton  Rouge,  an  urban  commuter  campus 
in  New  Orleans,  and  a  Level  III  Doctoral  institution  in  Baton  Rouge.  The  Southern 
University  System,  with  almost  17,000  students,  is  the  only  system  of  higher  edu- 
cation within  the  Historically  Black  College  and  University  (HBCU)  Community. 

Dr.  Dolores  Spikes  is  President  of  the  Southern  University  System  and  Dr. 
Marvin  Yates  is  Chancellor  of  the  Baton  Rouge  campus.  I  am  joined  today  by  Chan- 


30 

cellor  Yates  and  by  Dr.  Jonathan  Roberts,  Director  of  Charity  Hospitals  of  Louisi- 
ana. Before  assuming  his  present  position  Dr.  Roberts  served  as  coordinator  of  plan- 
ning for  the  National  Sickle  Cell  Disease  Center. 

Our  appearance  here  today  provides  a  mechanism  for  us  to  share  with  you  what 
we  believe  to  be  indisputable  documentation  for  the  need  for  this  proposed  center 
and  why  it  should  be  at  Southern  University  at  Baton  Rouge.  For  indeed,  despite 
our  best  efforts,  some  of  the  noteworthy  accomplishments  of  our  university  have  re- 
mained well  kept  secrets,  and  it  is  through  a  hearing  such  as  this  that  we  are  able 
to  tell  you  why  this  modest  investment  would  serve  the  Nation  well  in  scientific  re- 
search and  improving  human  health. 

The  warm  hospitality  we  have  already  received  has  enabled  me  to  dispel  the  belief 
that  the  atmosphere  near  the  Potomac  or  inside  the  Beltway  would  be  intimidating 
at  best.  We  thank  you  for  this  reception. 

By  way  of  experience,  I  have  spent  my  entire  professional  career  as  a  university 
professor  and  administrator,  having  had  the  privilege  of  holding  full-time  teaching 
or  administrative  appointments  at  four  historically  black  institutions.  I  have  also 
served  as  visiting  or  adjunct  professor  at  four  other  majority  institutions — the  latter 
representing  some  of  the  finer  examples  of  tradition,  elitism,  research  productivity, 
and  academic  standards.  I  have  been  a  visiting  lecturer  in  Italy,  Belgium,  and 
France— the  highlight  being  an  invited  lecturer  to  The  Pasteur  Institute  in  Paris  in 
1978.  I  have  served  as  chairman  of  the  General  Research  Support  Review  Commit- 
tee of  the  National  Institutes  of  Health  and  I  am  current  serving  a  second  three- 
year  term  an  the  Board  of  Review  of  the  National  League  of  Nursing.  I  have  written 
for  The  New  York  Times,  Saturday  Review,  The  Houston  Chronicle  and  Change 
Magazine.  In  the  case  of  Change,  I  was  one  of  four  essayists  selected  in  1977  to  pub- 
lish articles  on  how  the  educational  needs  of  Blacks  are  being  met. 

I  mention  these  things,  not  in  the  interest  of  self  indulgence,  but  because  I  believe 
these  experiences  have  given  me  the  opportunity  to  observe  and  participate  in  a 
spectrum  of  scientific  and  health  related  programs,  many  of  which  have  relevance 
to  the  concerns  of  your  committee,  and  some  to  which  I  will  refer  today  in  regard 
to  Sickle  Cell  Disease  research  and  its  appropriateness  at  our  institution. 

Although  I  am  a  part  of  the  Southern  University  system  I  will  confine  most  of 
my  comments  to  the  Baton  Rouge  campus,  the  largest  and  oldest  unit  within  the 
system.  Southern  University  Baton  Rouge  is  an  1890  Land  Grant  institution  with 
an  enrollment  in  excess  of  10,000  students.  The  history  of  Southern  University  is 
punctuated  with  achievement  of  its  graduates.  For  example,  the  university  claims 
among  its  graduates  eight  generals  in  the  United  States  Army  which  is  more  than 
25  percent  of  all  generals  produced  by  1890  Land  Grant  institutions.  The  prominent 
role  the  University  has  played  in  graduating  a  significant  percentage  of  minority 
lawyers  is  no  doubt  well  known  to  this  committee.  In  less  than  ten  years,  we  have 
produced  one  of  the  leading  undergraduate  nursing  Programs  In  the  United  States. 
Our  graduates  consistently  score  above  the  95  percent  level  on  national  Board  ex- 
aminations, and  when  our  program  achieved  its  initial  accreditation,  our  self-study 
was  selected  by  the  National  League  of  Nursing  as  a  model  for  others  schools  across 
the  nation  to  use  as  a  guide. 

Southern  University  also  has  a  long  and  distinguished  history  as  one  of  the  lead- 
ing HBCU's  to  produce  graduates  who  have  earned  Ph.D.  degrees  in  political 
science,  chemistry,  and  biological  sciences.  In  fact  the  University  has  traditionally 
led  all  schools  in  producing  black  political  scientists  and  ranks  among  the  top  four 
HBCU's  in  producing  graduates  who  have  obtained  the  Ph.  D.  in  chemistry.  What 
is  little  known  is  that  during  the  period  of  1985  through  1989,  10  percent  of  all 
blacks  in  the  United  States  who  received  the  Ph.  D.  In  physics  were  Southern  Uni- 
versity graduates.  This  is  indeed  a  major  accomplishment,  given  the  large  number 
of  colleges  and  universities  in  this  country.  Further,  Southern  University  provides 
a  wholesome  intellectual  and  cultural  environment  for  the  development  of  leaders 
among  its  graduates.  In  1990,  three  former  student  government  presidents  from 
Southern  University  served  in  the  Louisiana  Legislature,  and  today  as  I  speak  to 
you,  I  should  remind  this  distinguished  committee  that  two  of  those  graduates  (Rep- 
resentatives William  Jefferson  and  Cleo  Fields)  are  the  only  African  Americans  rep- 
resenting the  State  of  Louisiana  in  the  the  United  States  Congress,  and  a  third 
former  SGA  president  (the  Honorable  State  Senator  Charles  Jones)  is  the  architect 
of  the  Bill  to  establish  a  Sickle  Cell  Disease  Center  at  Southern  university.  My  point 
for  mentioning  these  few  examples  is  to  underscore  the  fact  that  our  general  univer- 
sity environment  is  geared  to  support  and  sustain  excellence  in  teaching,  research 
and  service. 


31 

Background  and  Focus  of  The  Center 

Sickle  Cell  Disease  is  a  devastating,  multifaceted  blood  disorder  which  has  a  high 
incidence  in  African  Americans.  This  hereditary  disease  can  only  be  cured  by  a  com- 
plete bone  marrow  transplant  or  by  some  yet  to  be  discovered  method  of  DNA  ma- 
nipulation. The  former  approach  has  drawbacks  in  the  difficulty  of  the  procedure, 
the  problem  of  finding  suitable  marrow  for  transplantation,  and  the  inability  of  the 
patient  receiving  a  transplant  to  produce  non-sickle  cell  offspring.  The  genetic  solu- 
tion to  the  sickle  cell  problem  must  await  further  understanding  of  the  human 
gnome  and  the  development  of  DNA  procedures  which  can  shut  down  the  synthesis 
of  sickled  hemoglobin  and  activate  the  manufacture  of  normal  adult  hemoglobin. 

Because  sickled  blood  cells  do  not  bind  nor  transport  oxygen  effectively,  the  symp- 
toms of  the  disease  are  numerous.  These  may  include  stroke,  ulcers,  heart  attacks 
and  a  variety  of  internal  disorders.  Until  very  recently  most  patients  died  before  the 
age  of  25  and  those  who  managed  to  survive  experienced  intense  suffering.  Hence 
during  the  past  20  years  much  of  the  research  has  focused  on  developing  methods 
to  alleviate  pain,  to  minimize  crises,  and  to  enable  patients  to  function  without 
much  discomfort  or  suffering.  Success  in  this  area  has  come  through  the  synthesis 
and  isolation  of  a  variety  of  antisickling  agents — drugs  which  when  taken  properly 
will  cause  the  blood  cells  to  retain  a  normal  shape  and  will  minimize  the  likelihood 
of  a  patient  experiencing  a  crisis. 

Southern  University  at  Baton  Rouge  proposes  to  establish  a  comprehensive  sickle 
cell  research  center — one  which  will  offer  a  unique  opportunity  for  clinical  research 
affiliation  with  Earl  K.  Long  Hospital  and  other  medical  centers.  The  Southern  Uni- 
versity facility  will  focus  on  five  or  six  major  research  thrusts  which  will  include 
the  following: 

Physicochemical  Studies 

This  facet  of  the  program  will  focus  principally  on  in  vitro  studies  of  hemoglobins. 
Faculty  members  in  the  departments  of  physics,  chemistry  and  biology  will  inves- 
tigate the  effects  of  physical  stress  and  chemical  agents  on  the  solution  properties 
of  hemoglobins.  This  program  will  provide  further  knowledge  regarding  conditions 
under  which  sickling  is  most  likely  to  occur.  Such  information  will  have  national 
significance  and  will  prove  particularly  beneficial  to  other  investigators  in  the 
Southern  University  Center, 

Anti-Sickling  Agents 

This  division  will  be  devoted  to  the  isolation,  characterization,  and  synthesis  of 
antisickling  agents,  substances  which  enable  patients  to  lead  a  normal  life  by  de- 
creasing the  chances  for  blood  cells  to  become  deformed. 

Clinical  Studies  Division 

In  this  section  of  the  proposed  center,  We  will  devote  primary  attention  to  longitu- 
dinal studies  of  patients  who  have  sickle  cell  disease.  These  investigations  will  be 
carried  out  in  conjunction  with  the  Earl  K.  Long  Hospital  and  other  clinical  settings. 
The  physicians  providing  immediate  supervision  for  these  studies  will  be  hospital 

Ehysicians  who  will  hold  adjunct  appointments  in  biomedical  sciences  at  Southern 
Fniversity.  It  is  expected  that  some  members  of  the  nursing  faculty  at  Southern 
University  will  be  involved  in  this  program. 

The  clinical  studies  unit  will  have  a  strong  interdisciplinary  focus  which  will  bring 
together  chemists,  biologists,  biophysicist,  nurses  and  physicians.  Results  from  from 
the  basic  disciplines  wul  be  tested  within  the  boundaries  of  FDA  guidelines  and 
other  provisions  which  protect  human  subjects. 

Division  of  Molecular  Biology  and  Genetic  Engineering 

This  phase  of  the  program  will  focus  on  various  genetic  approaches  to  investigat- 
ing sickle  cell  disease.  In  this  regard  we  will  devote  particular  attention  to  DNA  ma- 
nipulation and  various  techniques  of  modern  biology  which  could  cause  a  patient  to 
begin  synthesizing  normal  adult  hemoglobin. 

Laboratory  of  Ultrastructural  Studies 

This  section  of  the  center  will  use  electron  microscopy  as  a  major  tool  for  inves- 
tigating in  vitro  and  in  vivo  sickling.  Although  many  research  studies  will  originate 
in  thislaboratory,  this  facility  will  provide  an  important  service  function  to  several 
other  parts  of  the  center.  This  use  of  the  electron  microscope  will  provide  an  impor- 


32 

tant  bridge  between  the  basic  physicochemical  and  biological  studies  and  hospital 
related  clinical  investigations. 

Laboratory  of  Behavioral  and  Epidemiological  Studies 

This  division  of  the  Sickle  Center  will  have  the  role  of  investigating  disease  pat- 
terns, with  a  view  toward  using  the  knowledge  gained  therefrom  for  education  and 
prevention.  This  facet  of  the  program  will  also  investigate  psychological  and  social 
manifestations  of  sickle  cell  disease.  In  this  regard,  the  new  knowledge  produced 
will  contribute  to  improved  counseling  approaches  and  better  behavioral  methods  for 
managing  the  disease. 

Summary 

By  way  of  summary  I  wish  to  call  the  committee's  attention  to  two  evaluative 
statements  recently  made  about  our  institution.  In  the  first  case  we  were  recently 
evaluated  by  two  different  panels  of  the  National  Institutes  of  Health  for  the  estab- 
lishment of  a  center  of  Cellular  and  Molecular  Biology  at  Southern  University.  At 
both  levels  of  review  the  panels  rated  our  scientific  leadership  and  administrative 
capability  as  outstanding.  For  this  review,  we  achieved  a  priority  score  of  the  high- 
est order. 

In  the  second  instance,  our  university  was  invited  to  be  featured  in  the  fall  1994 
Education,  a  118  year  old  scholarly  journal  of  which  I  have  the  privilege  to  be  guest 
editor.  We  were  recently  informed  by  the  publisher  that  the  Southern  University 
issue  promises  to  be  the  best  ever  produced.  And  this  is  in  the  face  of  some  of  the 
most  prestigious  universities  and  educational  agencies  in  the  country  having  been 
featured  in  previous  issues.  Mr.  Chairman,  That  is  the  standard  of  quality  we  con- 
tinuously set  at  Southern  University  and  that  same  spirit  of  competence  and 
achievement  would  carry  over  into  the  sickle  cell  disease  center. 

I  wish  to  further  summarize  further  by  reminding  the  committee  of  the  following 
elements  of  uniqueness  to  the  Southern  University  proposal: 

The  state  of  Louisiana  has  already  committed  substantial  financial  support  to  this 
effort. 

The  proposal  has  received  the  categorical  endorsement  of  both  the  state  and  con- 
gressional black  caucuses. 

The  university's  track  record  in  research  and  academic  excellence  are  well  docu- 
mented. 

Our  outreach  activities  are  well  established.  We  have  one  of  the  more  comprehen- 
sive wellness  programs  you  will  find  anywhere,  and  we  are  a  national  leader  in 
service  learning  at  public  institutions  in  the  United  States. 

The  uniqueness  of  the  Southern  University  System  makes  it  an  appropriate  set- 
ting for  the  sickle  cell  disease  research  center. 

Southern  University  is  prepared  to  establish  a  first  rate  National  Sickle  Cell  Dis- 
ease Research  Center.  The  disease  itself  is  one  that  afflicts  African  Americans,  and 
it  is  fitting  that  a  university  which  is  predominantly  African  American  has  the  vi- 
sion, track  record,  technical  capability  and  willingness  to  provide  leadership  in  this 
area.  Through  the  collective  efforts  of  the  Health  Research  Center,  the  School  of 
Nursing,  the  Center  for  Social  Research,  and  Center  for  Rehabilitation  Counseling, 
the  University  stands  poised  to  make  this  Center  become  a  reality— one  for  which 
the  Nation  will  be  proud. 

We  appreciate  this  opportunity  and  would  be  pleased  to  answer  any  questions  the 
committee  might  have. 

Southern  University  and  AaM  College 

INSnTUnUONAL  setting  and  research  capability 

During  the  past  thirty  years,  Southern  University  has  achieved  an  exemplary 
record  in  science  teaching  and  research — two  activities  which  compliment  one  an- 
other in  the  preparation  of  well  qualified  graduates.  The  following  examples  are  rep- 
resentative accomplishments  in  the  college  of  Sciences  and  health  related  areas. 

Student  Achevements 

-From  1967  through  1972  an  average  of  three  chemistry  graduates  per  year  ob- 
tained the  Ph.  D.  degree  in  chemistry. 

From  1972  to  1985  the  University  was  one  of  the  leading  producers  of  minority 
undergraduates  to  obtain  M.  D.  degrees. 


33 

From  1985  to  1989  the  university  produced  10  percent  of  all  African  Americans 
in  the  United  States  who  went  on  to  obtain  the  Ph.  D.  degree  in  physics. 

Although  the  School  of  Nursing  is  a  relatively  new  academic  unit  it  has  gained 
a  nation  reputation  for  the  quality  of  its  graduates  as  judged  by  performance  on 
board  examinations  and  overall  program  quality  revealed  through  the  accreditation 
process. 

Success  in  graduate  and  professional  school  is  matched  by  the  accomplishments 
of  other  science  graduates  who  have  risen  to  prominent  positions  in  government  and 
the  corporate  world. 

Faculty  Accomplishments 

In  addition  to  a  noteworthy  record  of  general  scholarship,  the  Southern  University 
Science  faculty  has  been  recognized  for  its  accomplishments  in  the  following  ways: 

In  1992-93,  Dr.  Fitzgerald  Spencer  of  the  Biology  department  was  appointed  a 
Fulbright  lecturer. 

Dr.  Gary  Ross,  a  long-time  biology  faculty  member  who  recently  retired  was  recog- 
nized as  a  world  authority  on  butterflies. 

During  the  past  ten  years  two  Southern  University  faculty  member  have  ap- 

Rointed  to  MH  Study  sections  at  the  National  Institutes  of  Health.  Dr.  William 
loore  chaired  the  General  Research  Support  Review  committee  in  1982  and  Dr. 
Earl  Doomes  is  presently  in  the  second  year  of  a  four  year  term. 

Faculty  in  the  computer  science  department  have  developed  software  that  is  used 
in  major  universities  in  the  United  States. 

Dr.  William  Moore  was  invited  lecturer  at  the  Pasteur  Institute  in  Paris,  France 
in  1978.  His  pioneering  work  on  plasma  albumins  is  closely  related  to  a  variety  of 
physicochemical  studies  of  sickle  cell  hemoglobin. 

In  1991  Dr.  William  Moore  was  elected  to  the  Board  of  Review  of  the  National 
League  of  Nursing.  He  is  one  of  two  public  members  serving  on  the  Board  which 
accredits  all  nursing  programs  in  the  United  States. 

In  the  applied  sciences,  Dr.  James  McNitt  has  become  a  leading  authority  on  rab- 
bitry  and  several  investigators  in  the  Center  for  Energy  and  environmental  Studies 
are  becoming  increasingly  recognized  for  their  work  on  pollution  of  the  Mississippi 
River. 

PERSONNEL 

The  basic  personnel  in  a  sickle  cell  disease  center  will  consist  of  a  director,  associ- 
ate director,  clerical  staff,  and  faculty  who  will  hold  tenure  or  tenure  track  appoint- 
ments in  an  appropriate  department.  A  second  level  of  personnel  would  include  re- 
search associates  and  assistants  who  may  be  employed  on  specific  funded  projects. 
Some  personnel  will  hold  adjunct  appointments  in  the  biomedical  sciences.  This 
group  will  consist  largely  of  physicians  (pediatricians  and  hematologists)  affiliated 
with  one  of  the  local  hospitals  or  health  care  agencies. 

Faculty  members  holding  joint  appointments  in  the  sickle  cell  research  center  will 
obtain  these  positions  through  released  time.  This  mechanism  will  enable  depart- 
ment chairs  to  find  suitable  replacements  to  meet  departmental  needs. 

Faculty  Research  investigators  will  be  hired  initially  through  support  from  exter- 
nal funding.  Each  investigator  employed  will  therefore  come  through  an  appropriate 
departmental  screening  process.  These  persons  would  move  into  funded  positions 
over  the  next  five  years  as  such  vacancies  become  available  through  anticipated  re- 
tirement or  other  forms  of  attrition.  Hence  by  1997,  there  should  be  at  least  one 
faculty  member  in  each  section  of  the  center. 

The  administrative  staff  and  other  core  personnel  would  be  supported  through 
special  funding.  However,  our  long-range  plan  would  call  for  the  raising  of  a  five 
million  dollar  endowment  which  would  cover  much  of  the  basic  operational  costs. 

Research  assistants  and  associates  would  be  employed  mainly  through  special 
grants.  It  is  projected  that  by  1998  there  would  be  at  least  one  funded  project  in 
each  division  of  the  center. 

Southern  University  and  A  a  M  College 

RESARCH  PROGRAMS  AND  CENTERS 

The  University's  demonstrated  ability  to  develop  and  sustain  research  centers 
over  a  long  period  of  time  provides  the  most  compelling  argument  that  Southern 
University  can  develop  and  implement  a  successful  sickle  cell  disease  center.  The 
following  three  examples  provide  evidence  of  that  success. 


34 

The  NASA  Industrial  Applications  Center 

In  1987  Southern  University  was  one  of  eleven  Universities  selected  by  the  Na- 
tional Aeronautics  and  Space  Administration  (NASA)  to  house  an  industrial  applica- 
tion center.  When  the  agency  discontinued  this  program,  Southern  University  main- 
tained its  industrial  applications  initiatives  through  funding  from  the  Department 
of  Defense  and  from  other  NASA  programs.  The  continuation  of  this  program  with- 
out State  support  underscores  the  University's  commitment  to  industrial  applica- 
tions and  to  identifying  funding  sources  to  sustain  this  effort. 

The  Health  Research  Center 

This  center  was  constructed  with  funds  form  the  Public  Health  Service  in  1961 
and  expanded  by  funding  from  the  National  Institutes  of  Health  in  1985.  Although 
the  center  has  attracted  limited  external  support  since  its  inception,  the  health  Re- 
search Center  as  been  an  area  of  pivotal  research  activity  at  Southern  University 
since  1972.  During  the  ensuing  20  years  the  University  has  attracted  Federal  sup- 

gort  from  the  National  Institutes  of  Health,  Eli  Lily  Foundation,  and  the  United 
tates  Department  of  Agriculture.  Only  nominal  state  support  has  been  required  for 
two  staff  positions  and  modest  supplies  and  travel. 

During  its  twenty-year  history  of  substantial  funding,  the  Health  Research  Center 
has  provided  salaries,  assistantships,  equipment  for  teaching  and  research,  and  in- 
direct costs.  Since  many  of  the  faculty  have  done  research  on  released  time,  the  cen- 
ter, through  grant  funding,  has  provided  a  mechanism  for  the  university  to  look  at 
a  long  list  of  temporary  faculty  and  determine  which  ones  were  suitable  for  proba- 
tionary appointments. 

On  numerous  occasions,  we  have  learned  that  the  large  number  of  graduates  who 
went  on  to  medical  school  and  graduate  school  gained  considerable  advantage  by 
having  had  positive  experiences  in  the  Health  Research  Center.  The  point  to  be  em- 
phasized is  that  for  more  than  20  years  the  health  research  center  has  become  an 
indispensable  component  of  scholarship  and  student  preparation  without  reliance  on 
State  funding.. 

The  Center  for  Energy  and  Environmental  Studies 

This  is  the  youngest  comprehensive  research  center  at  Southern  University.  After 
its  inception  in  1986  it  has  grown  to  become  a  thriving  unit  with  a  staff  of  more 
than  forty  persons  including  students  and  faculty  who  hold  part-time  appointments. 
The  center  has  been  designated  as  one  of  three  minority  centers  of  excellence  by 
the  Department  of  Energy.  Recently  it  completed  a  meritorious  policy  study  of  the 
Mississippi  River  Corridor  and  the  center  ranks  high  among  top  candidates  from  the 
McKnight  Foundation  to  conduct  a  more  comprehensive  study  of  the  integrity  of  the 
Mississippi  River.  At  present  the  center  receive  grants  and  contracts  in  excess  of 
two  million  dollars.  The  total  cost  of  state  funding  is  less  than  $100,000. 

There  are  other  examples  of  relatively  self  sufficient  research  centers  at  Southern 
University.  This  track  record  over  the  past  two  decades  indicates  that  with  suffi- 
cient start-up  funds  the  proposed  sickle  cell  disease  center,  within  a  six  year  period 
after  completion,  would  have  little  reliance  on  ongoing  state  support. 

William  E.  Moore  is  Vice  Chancellor  for  Academic  Affairs  at  Southern  University 
in  Baton  Rouge,  a  position  he  has  held  since  1989.  During  his  twenty-seven  years 
of  work  in  higher  education,  Dr.  Moore  has  held  a  series  of  professorial  and  admin- 
istrative positions  at  several  universities.  He  has  published,  more  than  35  articles 
as  a  research  chemist,  science  educator,  and  more  recently  in  the  broad  area  of  test- 
ing and  education  of  minorities.  In  1976,  he  served  as  a  NATO  Fellow  on  Computers 
in  Science  Education — a  conference  held  in  Brussels,  Belgium.  In  1977,  Dr.  Moore 
was  selected  by  Change  Magazine  as  one  of  four  essayists  nationally  to  write  on  the 
adequacy  of  education  of  minorities.  In  1978,  he  served  as  invited  lecturer  at  the 
Pasteur  Institute  in  Paris,  France.  There  he  gave  talks  on  his  work  on  the  chem- 
istry of  blood  proteins,  with  specific  reference  to  the  artificially  induced  aging  of 
glasma  albumins  and  in  1980  he  was  appointed  Chairman  of  the  General  Research 
upport  Review  Committee  of  the  National  Institutes  of  Health. 

During  the  1980's,  Dr.  Moore  assumed  several  administrative  positions  in  higher 
education  and  continued  to  publish  in  the  areas  of  science  education,  testing,  envi- 
ronmental science,  and  race  relations.  In  1985,  as  a  member  of  the  NAFEO  Science 
and  Technology  Advisory  Committee,  he  became  one  of  the  principal  contributors  to 
the  guidelines  for  the  Research  Centers  at  Minority  institutions,  known  as  the 
RCMI  program.  Since  that  time  he  has  been  principal  investigator  of  two  RCMI 
projects.  In  the  first  instance  he  led  a  $3.76  million  project  aimed  at  studying  dis- 
eases which  show  a  high  incidence  in  ethnic  minorities,  and  more  recently  he  as- 


35 

sumed  the  leadership  of  a  $4.8  million  NIH  project  to  establish  a  research  center 
in  cellular  and  molecular  biology  at  Southern  University.  At  the  time  of  this  award, 
Southern  was  one  of  two  such  non-Ph.  D.  programs  in  science  to  be  nationally 
awarded  a  center  by  NIH. 

In  1991  Dr.  Moore  was  elected  to  the  Board  of  Review  of  the  National  League  of 
Nursing  as  one  of  two  public  members  on  this  18  member  accrediting  council.  In 
1994,  he  was  reelected  to  a  three-year  term  on  this  body.  During  this  period,  he  also 
introduced  several  innovative  programs  aimed  at  improving  the  quality  of  under- 
graduate education  for  minorities.  These  included  a  wellness  program,  a  multimedia 
learning  environment,  a  mentoring  program,  a  precollege  enrichment  project,  and 
a  service  learning  requirement  for  all  undergraduates.  In  1991,  he  was  designated 
as  a  Commissioned  Research  Scholar  for  the  NABSE  Moody  Roundtable  and  that 
same  year  was  invited  by  the  NAACP  to  participate  in  the  Daisy  Bates  Educational 
Summit  at  Little  Rock,  Arkansas.  In  1994,  he  was  invited  to  serve  as  guest  editor 
of  Education  115  year  old  International  journal.  Recently  he  was  informed  by  the 

Eublisher  that  the  forthcoming  issue  which  will  feature  Southern  University  is  the 
est  issue  ever  produced.  Dr/Moore  holds  a  B.  S.  degree  in  Chemistry  from  South- 
ern University  and  was  the  first  African  American  to  earn  a  Ph.  O.  in  Chemistry 
from  Purdue  University.  He  is  married  to  the  former  Willa  Warren,  and  they  are 
the  parents  of  two  children,  Deirdra  and  Marcus. 

The  Chairman.  We  will  recess  just  very  briefly,  and  Senator 
Wellstone  will  be  here  for  the  completion  of  the  hearing.  I  want  to 
thank  all  of  you  very,  very  much.  Shawnita,  we  thank  you.  We 
know  you  have  made  a  special  effort  to  be  with  us.  You  are  a  very 
courageous  and  brave  individual  and  a  real  inspiration,  and  we 
thank  you  very,  very  much  for  your  presence. 

We  will  stand  in  recess. 

[Recess.] 

Senator  Wellstone  [presiding].  The  committee  will  come  to 
order. 

First  of  all,  let  me  apologize  to  the  panelists  for  the  delay.  We 
had  the  service  for  Hugh  Scott,  and  a  good  many  people  on  the 
committee  are  at  that  service;  and  in  addition,  the  Elementary  and 
Secondary  Education  Act  is  also  up  on  the  floor,  and  Senator  Ken- 
nedy had  to  go  to  manage  that.  So  I  really  apologize  from  all  of  us. 

Dr.  Ohene-Frempong,  would  you  proceed,  please,  and  thank  you 
very  much  for  being  here. 

Dr.  Ohene-Frempong.  And  thank  you  very  much,  Senator,  for 
the  opportunity. 

Earlier,  my  colleagues  at  Boston  Sickle  Cell  Center  and  at 
Meharry  Comprehensive  Sickle  Cell  Center  gave  overviews  that  I 
think  pretty  much  describe  what  the  comprehensive  sickle  cell  cen- 
ters are  about.  And  I  will  briefly  just  go  over  some  of  the  accom- 
plishments of  the  center  at  Philadelphia  where  I  am,  and  also  fin- 
ish with  some  recommendations  that  I  have  for  consideration. 

Our  center  serves  the  greater  Philadelphia-Delaware  Valley  area 
as  a  resource  for  families  affected  by  sickle  cell  disease.  Directly, 
we  care  for  520  children  up  to  19  years  of  age  who  are  affected  by 
this  disease.  We  also  serve  as  the  referral  center  for  all  of  Louisi- 
ana, for  the  southern  part  of  New  Jersey,  and  also  for  Delaware, 
for  children  with  sickle  cell  disease  who  suffer  very  serious  con- 
sequences. 

For  the  State  of  Pennsylvania,  we  also  serve  as  a  resource  in  de- 
veloping and  monitoring  the  State  sickle  cell  programs.  We  devel- 
oped the  newborn  screening  program  for  the  State  and  actually 
conducted  a  pilot  project  in  Philadelphia  for  2  years  before  the 
State  picked  up  the  program  and  went  statewide  with  it. 


36 

Our  sickle  cell  effort  started  in  1973,  and  we  have  had  some  sup- 
port from  the  State  to  care  for  sickle  cell  patients  continuously 
since  that  time. 

We  became  a  comprehensive  sickle  cell  center  in  the  1988-93 
cycle,  and  we  and  our  colleagues  here  went  through  the  competitive 
renewal  applications  in  1992  and  were  lucky  to  get  funded  from  the 
1993  to  1998  cycle. 

Our  research  addresses  all  the  major  areas  that  the  comprehen- 
sive sickle  cell  centers  deal  with.  We  have  basic  in  basic  laboratory 
areas,  in  clinical  areas,  in  psychosocial  areas,  and  in  education, 
counseling,  and  testing  areas. 

In  the  basic  research  arena,  our  attention  has  been  focused  on 
studies  that  would  lead  to  gene  therapy  and  other  treatment  for 
sickle  cell  disease.  A  team  of  our  investigators  studying  the  regula- 
tion of  the  synthesis  of  fetal  hemoglobin  at  the  DNA  level  found 
two  previously  undescribed  changes  in  the  DNA  from  Benin  and 
Bantu  haplotypes  of  sickle  cell  disease.  These  are  separate  origins 
of  the  sickle  cell  gene  in  Africa.  The  major  Benin  haplotype  was  as- 
sociated with  a  genetic  change  which  had  not  been  previously  de- 
scribed, and  another  change  was  also  found  in  the  Banto  haplotype. 

We  think  that  ultimately,  this  sort  of  knowledge  promises  to  be 
useful  in  developing  ways  to  modify  the  expression  of  these  fetal 
hemoglobin  genes,  and  hopefully,  this  will  lead  to  a  way  of  improv- 
ing sickle  cell  disease  as  patients  can  be  given  treatment  that  will 
increase  the  fetal  hemoglobin  production. 

As  we  all  know,  sickle  cells  are  abnormally  shaped  and  stiff  in 
comparison  with  normal  red  blood  cells.  Effective  treatment  or  cure 
for  sickle  cell  disease  will  have  to  alter  the  abnormal  morphology 
and  the  deformability  of  sickle  cells. 

Another  team  of  our  investigators  has  developed  an  accurate 
technique  to  analyze  the  morphology  of  sickle  cells,  using  a  comput- 
erized image  analysis  system.  This  technique  allows  the  accurate 
determination  of  morphological  differences  of  sickle  cells  numeri- 
cally, by  calculating  several  differentiated  factors.  This  system  fa- 
cilitates the  investigation  of  the  relationship  between  the  morphol- 
ogy of  sickle  cells  and  various  environmental  and  drug  conditions. 
This  technique  is  currently  being  applied  to  support  the  testing  of 
new  drugs  in  sickle  cell  disease  patients. 

One  of  the  drawbacks  of  the  development  of  new  treatments  for 
sickle  cell  disease  has  been  the  lack  of  animal  models  for  this  dis- 
ease. All  drug  tests  are  either  performed  in  vitro  in  the  laboratory 
or  directly  in  humans.  A  group  of  our  investigators  together  with 
others  in  the  country  have  developed  transgenic  sickle  cell  diseased 
mice  which  produce  sickle  cells  containing  human  sickle  hemo- 
globin. These  mice  offer  the  opportunity  to  study  sickle  cell  disease 
in  the  model  that  will  permit  the  testing  of  a  wide  range  of  agents 
and  also  for  trials  of  gene  therapy. 

In  clinical  research,  we  have  conducted  studies  aimed  at  under- 
standing some  of  the  most  difficult  problems  encountered  by  sickle 
cell  disease  patients,  as  well  as  to  test  new  drugs  for  potential  use 
in  treating  trie  disease.  Stroke  is  one  of  the  most  devastating  com- 
plications of  the  disease,  affecting  about  5  percent  of  all  patients, 
including  children  less  than  2  years  of  age.  Our  studies  of  the  blood 
circulation  of  the  brain  have  aimed  at  discovering  children  who 


37 

may  be  at  high  risk  for  stroke  so  that  preventive  therapy  can  be 
developed  for  them.  Using  magnetic  resonance  techniques,  we  and 
others  in  the  country  have  shown  that  as  many  as  20  percent  of 
children  with  sickle  cell  disease  suffer  silent  stroke,  and  that  these 
children  may  be  at  the  highest  risk  for  overt  strike.  We  are  cur- 
rently working  with  our  collaborators  at  the  national  level  to  de- 
velop methods  of  intervention  to  stop  the  occurrence  of  the  first 

stroke 

Stroke  and  sickle  cell  disease  again  have  a  nasty  tendency  to 
recur,  and  when  they  do  recur,  they  lead  to  more  severe  brain  dam- 
age. The  objective  of  current  treatment  of  stroke,  chronic  trans- 
fusion therapy,  is  to  prevent  this  recurrence.  One  of  the  major  haz- 
ards of  long-term  chronic  transfusion  therapy  is  iron  overload,  a 
problem  which  is  potentially  fatal  if  not  aggressively  treated.  Inves- 
tigators at  our  center  have  successful  demonstrated  that  iron  over- 
load in  chronically  transfused  patients  can  be  safely  reduced  in  two 
ways.  First,  they  demonstrated  that  in  stroke  patients  who  had 
been  transfused  aggressively  for  at  least  3  years  and  who  have  had 
no  neurological  setback,  the  intensity  of  the  transfusion  can  be 
safely  reduced  without  recurrence  of  stroke. 

In  addition,  they  have  shown  that  when  this  modified  trans- 
fusion program  is  coupled  with  a  red  cell  exchange  instead  of  sim- 
ple transfusion  regimen,  further  reduction  in  transfusional  iron 
loading  and  in  body  iron  stores  can  be  achieved.  These  findings  are 
expected  to  have  a  major  impact  on  management  of  the  problem  of 
iron  overload  in  sickle  cell  patients  who  are  on  chronic  transfusion 
therapy.  In  combination,  these  methods  have  the  potential  to  post- 
pone the  need  for  iron  chelation  therapy  for  a  number  of  years. 

Hydroxyurea  is  perhaps  the  most  promising  drug  ever  tested  in 
sickle  cell  disease.  This  drug,  as  we  heard  earlier,  is  currently  un- 
dergoing control  trials  in  adult  sickle  cell  patients  in  an  NIH-fund- 
ed  study.  In  anticipation  of  the  potential  impact  of  hydroxyurea  on 
sickle  cell  disease  treatment,  investigators  at  our  center  began  pre- 
liminary studies  of  hydroxyurea  in  children  with  sickle  cell  disease 
2  years  ago.  This  summer,  we  and  others  from  three  other  institu- 
tions are (beginning  a  limited  trial  of  hydroxyurea  in  a  larger  group 
of  children  in  an  NIH-funded  study. 

Have  we  made  any  progress  at  all  in  sickle  cell  disease?  The  an- 
swer is  a  qualified  yes.  Certainly,  sickle  cell  patients  today  are  liv- 
ing longer  than  they  lived  before.  Thirty  years  ago,  half  of  sickle 
cell  patients  did  not  live  beyond  20  years  of  age.  In  a  recent  publi- 
cation which  came  out  of  the  cooperative  study  of  sickle  cell  dis- 
ease, where  the  NIH  organized  a  large  group  of  centers  that  have 
been  collaborating  in  clinical  studies  since  1978,  we  have  been  able 
to  show  that  for  patients  at  least  living  in  the  1980's,  at  least  half 
of  them  lived  beyond  45  years  of  age.  This  is  a  tremendous  im- 
provement from  what  it  was  10  years  ago.  But  that  still  means 
that  about  half  of  these  patients  lose  at  least  30  years  of  useful  life, 
so  we  still  have  a  long  way  to  go,  and  sickle  cell  disease  research 
needs  to  be  supported. 

I  have  the  following  recommendations  to  make.  First,  that  the  10 
National  Institute  of  Health  approved  comprehensive  centers, 
which  have  not  had  a  real  increase  in  their  level  of  support  for  the 
last  15  years,  need  to  be  funded  at  least  at  their  approved  levels. 


38 

Last  year,  these  centers  suffered  an  average  of  about  8.5  percent 
reduction  in  their  funding,  and  this  year,  they  are  operating  at  5.6 
percent  below  their  recommended  and  approved  budgets.  We  ask 
that  Federal  funding  for  the  centers  be  increased  by  at  least  $4 
million  to  enable  the  approved  research  projects  to  be  conducted  as 
recommended  in  the  peer  review  process. 

The  centers  should  be  specifically  mentioned  in  the  language  of 
any  appropriation  for  increased  funding  for  the  National  Institutes 
of  Health. 

The  well-organized  cooperative  study  of  sickle  cell  disease,  a  net- 
work of  medical  centers  established  through  the  National  Heart, 
Lung,  and  Blood  Institute,  should  be  supported  as  the  ideal  set-up 
for  testing  of  new  treatments  in  sickle  cell  disease.  This  network 
demonstrated  its  value  in  the  1980's  by  the  rapid  conduct  of  the 
penicillin  prophylaxis  study  in  children  with  sickle  cell  disease,  and 
I  must  say  this  study  was  the  most  important  clinical  study  ever 
conducted  in  this  disease. 

Funding  for  centers  for  gene  therapy  for  sickle  cell  disease 
should  be  increased.  Many  brilliant  molecular  biologists  and  gene 
therapy  experts  whose  talents  could  be  recruited  into  this  area  of 
research  are  hesitant  to  join  the  effort  because  of  concerns  about 
long-term  commitment  of  support.  Congress  should  make  a  com- 
mitment to  finding  a  cure  for  this  genetic  disease  through  major 
funding  for  gene  therapy  for  sickle  cell  disease.  And  this  will  be  a 
fitting  response  to  the  contributions  made  to  medical  science  and 
the  understanding  of  genetic  diseases  in  general  by  those  affected 
by  sickle  cell  disease  and  its  related  disorders. 

My  final  recommendation  is  that  there  is  a  severe  under-rep- 
resentation  of  African  Americans  and  other  minority  groups  in  bio- 
medical research.  In  order  to  increase  the  number  of  African  Amer- 
icans and  members  of  other  minority  groups  in  biomedical  re- 
search, adequate  funding  should  be  provided  to  fully  fund  the  Mi- 
nority Supplement  Program  of  the  National  Heart,  Lung,  and 
Blood  Institute. 

In  addition,  in  accord  with  a  report  of  a  National  Heart,  Lung, 
and  Blood  Institute  task  for  on  the  declining  number  of  investiga- 
tor-initiated research  proposals  in  sickle  cell  disease,  a  Sickle  Cell 
Research  Scholars  Program  should  be  established  within  the  com- 
prehensive sickle  cell  centers.  Each  center  should  be  provided  suffi- 
cient resources  to  support  at  least  one  scholar  drawn  from  the 
ranks  of  young  investigators  on  the  medical  school  and  hospital  fac- 
ulties where  centers  are  funded. 

I  think  that  sickle  cell  centers  have  truly  been  much  more  than 
what  we  expected  from  them,  they  have  been  worth  much  more 
than  the  funding  that  they  have  received.  The  work  that  has  been 
done  through  the  Sickle  Cell  Disease  Branch  of  the  NIH  has  ad- 
vanced research  in  this  work  further  than  any  of  us  expected.  We 
are  very  close,  we  think — and  we  promise  this  to  our  patients — we 
are  very  close  to  a  cure  for  this  disease,  and  this  is  the  time  that 
I  think  we  should  pull  together  all  these  resources  to  support  the 
scientists  who  have  been  working  so  hard  in  this  area. 

Thank  you  very  much,  Senator. 

Senator  Wellstone.  Thank  you,  Doctor. 


39 

I  think  what  we  will  have  to  do,  since  I  will  have  to  leave  in  a 
short  period  of  time,  is  we  will  submit  written  questions  to  you. 

I  did  want  to  mention,  though — and  I  really  appreciate  your  tes- 
timony—I  was  a  little  saddened  by  what  you  said— not  by  what  you 
said,  because  I  was  actually  inspired  by  what  you  said — but  when 
you  talked  about  the  budgets,  I  think  back  to  when  my  father,  who 
suffered  from  Parkinson  s  disease,  was  in  the  original  L-DOPA 
pilot  group,  when  that  was  first  used  as  a  drug,  at  George  Wash- 
ington Hospital  here,  in  the  same  room  was  a  young  African  Amer- 
ican man  who  was  in  a  sickle  cell  crisis  period,  and  I  have  just 
never  seen  such  agony,  and  I  will  never  forget  it. 

The  reason  I  mention  that  is  I  work  with  people  who  come  here, 
unfortunately,  just  in  their  40's,  with  Parkinson  s,  and  they  too  are 
trying  to  see  some  expansion  of  the  budget,  and  there  is  all  sorts 
of  promise. 

On  the  NIH  budget,  there  is  the  Harkin-Hatfield  initiative  to  try 
to  have  a  set-aside  of  one  percent  increase  across-the-board.  I  just 
do  not  want  to  see  different  people  who  are  struggling  with  dif- 
ferent illnesses  pitted  against  one  another,  and  it  does  seem  to  me 
that  we  are  making  such  a  terrible  mistake  by  not  really  commit- 
ting the  resources  to  the  research,  to  save  money  in  the  short  run, 
we  end  up  spending  more  in  the  long  run.  It  is  not  just  a  question 
of  spending  less;  it  is  also  a  question  of  what  you  can  do  for  people. 
So  I  really  appreciate  what  you  say,  and  I  thank  you. 

Dr.  Ohene-Frempong.  Thank  you,  Senator. 

Senator  Wellstone.  And  if  it  is  okay,  I  would  like  to  get  some 
of  these  questions  to  you  to  get  a  response  in  writing. 

Dr.  Ohene-Frempong.  That  will  be  fine,  Senator. 

Senator  Wellstone.  Thank  you. 

[The  prepared  statement  of  Dr.  Ohene-Frempong  follows:] 

Prepared  Statement  of  Kwaku  Ohene-Frempong,  M.D. 

A.  GENERAL  COMMENTS 

Sickle  cell  disease  is  an  inherited  disease  of  red  blood  cells.  The  red  cells  of  people 
with  the  disease  have  a  tendency  to  become  rigid  ad  abnormally  shaped,  causing 
them  to  break  up  easily  and  lead  to  anemia,  and  also  block  the  flow  of  blood  through 
blood  vessels  and  lead  to  many  other  complications.  The  hallmark  of  the  disease  is 
the  episodic  attack  of  severe  pain  in  various  parts  of  the  body.  Most  people  with 
sickle  cell  disease  eventually  die  from  it.  In  the  best  circumstances,  half  of  all  sickle 
cell  patients  die  by  45  years  of  age,  about  30  years  earlier  than  expected  in  the  gen- 
eral population.  There  are  approximately  60,000  sickle  cell  disease  patients  in  the 
United  States  of  America  with  2.5  million  people  with  sickle  cell  trait,  the  healthy 
carrier  state  of  the  sickle  cell  condition.  Worldwide,  hundreds  of  thousands  of  babies 
are  born  each  year  with  this  disease,  about  150,000  in  Africa  alone.  Most  of  these 
babies  die  by  five  years  of  age  without  the  recognition  of  sickle  cell  disease  as  the 
underlying  cause  of  their  deaths  from  malaria,  respiratory  and  other  diseases.  Chil- 
dren with  sickle  cell  trait,  not  the  disease,  are  protected  from  severe  malaria.  While 
people  of  African  descent  are  predominantly  affected  by  sickle  cell  disease,  the  dis- 
ease is  also  found  in  all  the  countries  in  the  Mediteranean  basin,  especially  Italy, 
Turkey,  and  Greece,  all  the  Middle  Eastern  countries,  and  in  India.  Throughout 
these  areas  of  the  world  and  where  descendants  have  immigrated,  sickle  cell  condi- 
tions are  a  major  health  problem. 

Sickle  cell  disease  was  discovered  by  modern  medical  science  in  1907  in  Chicago. 
From  the  early  stages  of  research  into  the  nature  and  effects  of  this  disease,  it  was 
also  discovered  that  the  disease  in  the  United  States  of  America  affected  predomi- 
nantly Americans  of  African  origin.  The  fact  that  the  patient  through  whom  the  dis- 
ease was  revealed  to  medical  science  was  a  dental  student  from  Grenada  and  not 
one  of  the  hundreds  of  American  patients  who  must  have  suffered  the  pain  and 
other  complications  of  the  disease  may  reflect  another  facet  of  sickle  cell  disease. 


40 

Since  the  general  public  has  become  aware  of  the  disease,  there  has  been  the  im- 
pression that  the  disease  has  not  received  much  attention  because  it  affects  pri- 
marily a  minority  African-American  community. 

The  fact  is  that  sickle  cell  disease  has  received  plenty  of  attention  from  basic  lab- 
oratory research  scientists  in  the  U.S.  and  elsewhere.  Sickle  cell  disease  and  its  re- 
lated disorders  are  some  of  the  best  studied  and  best  understood  diseases  of  man. 
Sickle  cell  disease  was  the  first  "molecular  disease".  It  was  the  first  disease  whose 
cause  was  found  to  reside  in  dh  abnormality  in  a  molecule,  hemoglobin.  The  simple 
difference  between  "sickle"  hemoglobin  and  its  normal  version  was  determined  al- 
most 50  years  ago.  When  the  genetic  code  was  discovered,  the  genetic  basis  of  sickle 
cell  disease  was  easily  established  as  a  simple  singular  mutation  in  one  gene.  The 
gene  for  sickle  cell  disease  was  discovered  in  1977,  almost  twenty  years  ago!  With 
all  these  "firsts",  one  would  expect  that  research  would  have  made  dual  progress 
in  the  treatment  of  sickle  cell  disease.  Unfortunately,  medical  science  has  gained  a 
lot  more  from  the  study  of  the  blood  of  people  affected  by  sickle  cell  conditions  than 
the  people  have  received  from  medical  science. 

The  treatment  of  sickle  cell  disease  today  is  largely  symptomatic  and  does  not  ad- 
dress the  fundamental  cause  of  the  disease.  As  the  first  molecular  genetic  disease, 
it  has  always  been  expected  that  sickle  cell  disease  would  be  one  of  the  first  diseases 
for  which  gene  therapy  would  be  attempted.  To  date,  this  has  not  happened. 

However,  patients  with  sickle  cell  disease  are  better  off  today  than  they  were  20 
or  30  years  ago.  Thirty  years  ago,  only  half  of  children  with  sickle  cell  disease  were 
expected  to  live  beyond  20  years  of  age.  For  patients  living  in  the  1980's  this  had 
improved  to  about  45  years  of  age.  This  improvement  had  come  about  because  of 
on-going  research  to  understand  the  effects  of  sickle  cell  disease  and  to  develop 
treatment  methods  for  its  many  complications. 

Much  of  what  we  have  learnt  about  sickle  cell  disease  has  come  out  of  research 
sponsored  by  the  National  Institutes  of  Health  primarily  through  the  Sickle  Cell 
Disease  Branch  of  the  National  Heart,  Lung  and  Blood  Institute.  A  large  part  of 
this  NIH  effort  on  behalf  of  sickle  cell  disease  has  been  organized  through  the  Com- 

Erehensive  Sickle  Cell  Centers.  These  Centers,  funded  on  a  competitive  5-year  cycle, 
ave  provided  a  large  body  of  new  information  on  the  basic,  clinical  and 
psychosocial  aspects  ofsickle  cell  disease.  The  Centers  have  also  provided  opportuni- 
ties for  the  development  of  demonstration  projects  on  testing  and  counseling  of  indi- 
viduals for  sickle  cell  conditions.  The  lessons  learnt  from  the  testing  and  counseling 
of  large  numbers  of  people  for  sickle  cell  disease  are  currently  being  applied  to  other 
genetic  disorders  such  as  cystic  fibrosis,  as  the  discovery  of  the  genes  Tor  other  dis- 
eases make  such  testing  possible.  For  the  past  15  years,  there  nave  been  10  Com- 
prehensive Sickle  Centers.  Even  though  the  number  10  was  established  as  a  mini- 
mum there  have  not  been  more  than  10  Centers  since  that  minimum  was  estab- 
lished. The  Comprehensive  Sickle  Cell  Center  at  the  Children's  Hospital  of  Philadel- 
phia is  one  of  the  current  cycle  of  10  Centers.  Our  Center  and  some  22  other  Cen- 
ters have  participated  in  the  Cooperative  Study  of  Sickle  Cell  Disease  (CSSCD).  Per- 
haps the  greatest  achievement  of  the  CSSCD  is  the  studies  conducted  on  the  risks 
and  prevention  of  bacterial  infections  in  young  children  with  sickle  cell  disease.  The 
famous  Penicillin  Prophylaxis  Study  (PROPS)  conducted  in  the  mid-1980's  by  the 
CSSCD  showed  that  the  lives  of  young  children  with  sickle  cell  disease  could  be 
saved  by  giving  them  ordinary  penicillin  twice  a  day  every  day.  Infection  from 
strains  of  the  bacterium,  pneumococcus,  had  been  well  established  as  the  leading 
cause  of  death  in  these  children  and  the  first  3  vears  of  life  had  been  found  to  be 
their  riskiest  for  death.  The  eventual  outcome  of  PROPS  was  the  establishment  of 
newborn  screening  for  sickle  cell  disease.  Since  young  lives  could  be  saved  with  pen- 
icillin prophylaxis,  it  became  important  to  discover  babies  with  sickle  cell  disease 
early  so  that  the  penicillin  treatment  can  be  started  before  they  died  of  pneumo- 
coccal infection.  Today,  some  43  states  have  added  testing  for  sickle  cell  conditions 
to  their  newborn  screening  programs.  Many  young  lives  are  being  saved  and  the 
first  three  years  are  no  longer  the  most  dangerous  for  people  with  sickle  cell  disease. 
While  survival  beyond  childhood  may  not l>e  as  major  a  problem  as  it  used  to  and, 
while  their  overall  life  expectancy  has  improved,  the  lives  of  sickle  cell  disease  pa- 
tients are  not  without  tremendous  difficulty.  They  still  lead  lives  frequently  inter- 
rupted by  painful  attacks  ("crises  "),  paralyzing  strokes,  acute  chest  syndrome  (lung 
damage),  acute  splenic  sequestration  (lifethreatening  sudden  enlargement  of  the 
spleen),  aplastic  crisis  (transient  cessation  of  red  cell  production),  priapism  (painful 
sustained  erections),  and  other  acute  manifestations  of  the  disease.  Over  several 
years,  many  patients  suffer  chronic  damage  to  and  failure  of  organs  such  as  the 
spleen,  lungs,  kidneys,  liver,  and  heart.  In  the  absence  of  treatment  that  prevents 
the  production  of  sickle  cells,  much  of  our  efforts  has  been  directed  to  understanding 
and  management  of  these  acute  and  chronic  complications. 


41 

B.  RESEARCH  AT  THE  COMPREHENSIVE  SICKLE  CELL  CENTER,  THE  CHILDREN'S  HOSPITAL 

OF  PHILADELPHIA 

At  the  Comprehensive  Sickle  Cell  Center  at  The  Children's  Hospital  of  Philadel- 
phia, we  have  devoted  our  research  efforts  to  address  all  the  important  aspects  of 
sic  le  cell  disease,  basic,  clinical  and  psychosocial.  The  following  is  a  brief  summary 
of  our  recent  accomplishments,  placed  in  the  context  of  national  developments  in 
sickle  cell  disease  research. 

1.  Basic  Research 

Our  attention  has  been  focused  on  studies  that  will  lead  to  gene  therapy  and 
other  treatments  for  sickle  cell  disease.  A  team  of  our  investigators  studying  the 
regulation  of  the  synthesis  of  fetal  hemoglobin  at  the  DNA  level  found  two  pre- 
viously undescribed  changes  in  the  Benin  and  Bantu  haplotypes  of  the  sickle  gene. 
The  major  Benin  haplotype  was  associated  with  a  Gy-309  A  to  G  change  and  the 
Central  African  Republic  with  an  Ay-271  C  to  G  change.  Ultimately  this  knowledge 
promises  to  be  useful  in  developing  ways  to  modify  the  expression  of  fetal  genes  and 
therefore  ameliorating  the  severity  of  sickle  cell  disease. 

Sickle  cells  are  abnormally  shaped  and  stiff  in  comparison  with  normal  red  blood 
cells.  Effective  treatment  or  cure  for  sickle  cell  disease  will  have  to  alter  the  abnor- 
mal morphology  and  deformability  of  sickle  cells.  Another  team  of  our  investigators 
has  developed  an  accurate  technique  to  analyze  the  morphology  of  sickled  cells 
using  a  computed  image  analysis  system.  This  technique  allows  the  accurate  deter- 
mination of  morphological  differences  of  sickled  cells  numerically  by  calculating  sev- 
eral different  shape  factors.  This  system  facilitates  investigation  of  the  relationship 
between  the  morphology  of  sickled  cells  and  various  environmental  and  drug  condi- 
tions. It  is  currently  being  applied  to  support  the  testing  of  new  drugs  in  sickle  cell 
disease  patients. 

One  of  the  drawbacks  of  the  development  of  new  treatment  in  sickle  cell  disease 
has  been  the  lack  of  a  natural  animal  model  for  the  disease.  All  drug  tests  are  per- 
formed either  in  vitro  or  directly  in  humans.  A  group  of  our  investigators  and  others 
in  the  country  have  developed  transgenic  sickle  cell  disease  mice  which  produce 
sickle  cells  containing  the  human  sickle  hemoglobin.  These  mice  offer  the  oppor- 
tunity to  study  sickle  cell  disease  in  a  model  that  will  permit  the  testing  of  a  wide 
range  of  agents  and  also  for  trials  of  gene  therapy. 

2.  Clinical  Research 

In  clinical  research,  we  have  conducted  studies  aimed  at  understanding  some  of 
the  most  difficult  problems  encountered  by  sickle  cell  disease  patients  as  well  as  test 
new  drugs  for  potential  use  in  treating  the  disease. 

Stroke  is  one  of  the  most  devastating  complications  of  the  disease,  affecting  about 
5  percent  of  all  patients  including  children  less  than  2  years  of  age.  Our  studies  of 
the  blood  circulation  of  the  brain  have  aimed  at  discovering  children  who  may  be 
at  high  risk  for  stroke  so  that  preventive  therapy  can  be  developed  for  them  using 
magnetic  resonance  techniques,  we  and  others  in  the  country  have  shown  that  as 
many  as  20  percent  of  children  with  sickle  cell  disease  suffer  "silent"  stroke  and 
that  these  children  may  be  at  the  highest  risk  for  overt  stroke.  We  are  currently 
working  with  our  collaborators  at  the  national  level  to  develop  methods  of  interven- 
tion to  stop  the  occurrence  of  the  first  stroke. 

Strokes  in  sickle  cell  disease  have  a  tendency  to  recur  and  lead  to  more  severe 
brain  damage.  The  objective  of  current  treatment,  chronic  transfusion  therapy,  is  to 
prevent  this  recurrence.  One  of  the  major  hazards  of  long  term  chronic  transfusion 
therapy  is  iron  overload,  a  problem  which  is  potentially  fatal  if  not  aggressively 
treated.  Investigators  at  our  Center  have  successfully  demonstrated  that  iron  over- 
load in  chronically  transfused  patients  can  be  safely  reduced  in  two  ways.  First, 
they  demonstrated  that  in  stroke  patients  who  had  been  transfused  aggressively  for 
at  least  three  years,  without  any  neurological  set-back,  the  intensity  of  the  trans- 
fusion can  be  reduced  without  recurrence  of  stroke.  In  addition  they  have  shown 
that  when  this  modified  transfusion  program  is  coupled  with  a  red  cell  exchange  in- 
stead of  simple  transfusion  regimen,  further  reduction  in  transfusional  iron  loading 
and  in  body  iron  stores  can  be  seen.  These  findings  are  expected  to  have  a  major 
impact  on  the  management  of  the  problem  of  iron  overload  in  sickle  cell  patients 
on  chronic  transfusion  therapy.  In  combination  these  methods  have  the  potential  to 
postpone  the  need  for  iron  chelation  therapy  for  a  number  of  years. 

Hydroxyurea  is  perhaps  the  most  promising  drug  ever  tested  in  sickle  cell  disease. 
This  drug  is  currently  undergoing  a  controlled  trial  in  adult  sickle  cell  disease  pa- 
tients in  an  NIH-funded  study.  In  anticipation  of  the  potential  impact  of 
hydroxyurea  on  sickle  cell  disease  treatment,  investigators  at  our  Center  began  pre- 
liminary studies  of  hydroxyurea  in  children  with  sickle  cell  disease  two  years  ago. 


42 

This  summer,  we  and  investigators  at  three  other  institutions  are  beginning  a  lim- 
ited trial  of  hydroxyurea  in  a  larger  group  of  children  in  an  NIH -funded  study. 

C.  HAVE  WE  MADE  SIGNIFICANT  PROGRESS  IN  SICKLE  CELL  DISEASE  RESEARCH? 

The  importance  of  sickle  cell  disease  research  in  our  understanding  of  human  ge- 
netic disease  is  well  recognized.  Recent  developments  finally  are  bringing  some  hope 
of  effective  treatment  and  universal  cure  for  this  disease.  Some  of  these  important 
developments  are  summarized  below. 

1.  Treatment  to  increase  the  level  of  feted  hemoglobin  in  red  blood  cells 

Fetal  hemoglobin,  Hb  F,  is  the  predominant  hemoglobin  in  the  red  cells  of  babies 
during  pregnancy.  Normally,  we  switch  off  the  production  of  Hb  F  toward  the  end 
of  pregnancy  as  we  increase  the  production  of  Hb  A,  the  normal  "adult"  hemoglobin. 
Sickle  cell  disease  is  due  to  an  abnormal  form  (Hb  S)  of  Hb  A.  The  most  important 
fact  in  sickle  cell  disease  research  is  that  Hb  F  in  appreciable  amounts  can  block 
the  abnormal  behavior  of  Hb  S  and  prevent  the  formation  of  sickle  cells.  Much  re- 
search attention  has  been  devoted  to  understanding  the  natural  switch  for  Hb  F 
production  and  to  find  ways  to  stimulate  the  production  of  large  amounts  of  Hb  F 
beyond  birth.  Currently,  two  groups  of  medications  hold  promise  toward  this  goal. 
Hydroxyurea,  alluded  to  above,  has  been  the  most  tested,  and  Butyratess  are  begin- 
ning intensive  testing.  This  direction  of  research  promises  the  simplest  and  most 
cost  effective  way  in  which  sickle  cell  disease  can  be  treated  worldwide. 

2.  Bone  marrow  transplantation  for  sickle  cell  disease 

Sickle  cell  disease  can  be  cured  by  transplantation  of  normal  bone  marrow.  The 
application  of  this  treatment  to  sickle  cell  disease  was  first  attempted,  in  Belgium 
and  has  been  gaining  deliberately  slow  trial  in  the  U.S.  Because  of  the  risks  associ- 
ated with  marrow  transplantation  and  the  need  for  tissue  matched  donors,  it  is  not 
expected  that  large  numbers  of  sickle  cell  disease  patients  will  be  treated  with  this 
method  in  the  near  future.  Lessons  learnt  from  the  few  cases  being  performed  will 
be  very  useful  in  gene  therapy  for  sickle  cell  disease. 

3.  Newborn  testing  for  sickle  cell  disease 

In  the  public  health  arena,  the  addition  of  sickle  cell  testing  to  the  newborn 
screening  programs  of  most  (43)  states  is  the  most  important  development  in  the 

East  twenty-five  years.  In  1986,  the  Sickle  Cell  Disease  Branch  of  the  National 
[eart,  Lung,  and  Blood  Institute  with  the  CSSCD  published  the  results  of  the  Peni- 
cillin Prophylaxis  Study.  The  implementation  of  newborn  testing  and  penicillin  pro- 
phylaxis therapy  at  about  two  months  of  age  is  perhaps  the  most  significant  im- 
f>rovement  in  the  care  of  sickle  cell  disease  patients  to  date.  Implementation  of  simi- 
ar  programs  around  the  world  has  the  potential  to  save  over  a  hundred  thousand 
lives  a  year. 

4.  Gene  Therapy  for  sickle  cell  disease 

In  theory,  this  has  been  the  expected  cure  for  sickle  cell  disease  ever  since  the 
disease  was  found  to  be  caused  by  a  simple  mutation  in  a  single  gene.  Unfortu- 
nately, as  gene  therapy  was  being  aggressively  pursued  for  other  genetic  disorders, 
sickle  cell  disease,  the  prototypical  genetic  disease,  was  left  to  wait.  Encouraging  de- 
velopment came  this  year  as  the  NIH  accepted  applications  for  research  projects  in 
gene  therapy  of  sickle  cell  disease.  It  is  hoped  that  this  area  of  research  will  expand 
into  treatment  trials  in  the  not  too  distant  future. 

D.  RESEARCH  NEEDS  IN  SICKLE  CELL  DISEASE 

At  a  time  when  there  is  excitement  in  sickle  cell  disease  research  for  effective 
treatment  or  universal  cure,  scientists  are  being  discouraged  by  diminishing  funds 
for  research.  Since  1982,  investigator  initiated  applications  for  funds  for  sickle  cell 
disease  research  has  been  dwindling.  One  of  the  reasons  must  be  the  perception  of 
unavailability  of  funding  support.  Research  scientists  are  spending  half  of  their 
working  hours  writing  and  rewriting  grant  applications  as  they  search  for  support. 
On  the  patient  and  community  side,  there  is  increasing  concern  that  when  funds 
become  short  in  supply,  conditions  such  as  sickle  cell  disease,  which  affect  a  largely 
minority  population,  receive  even  less  attention. 

Sickle  cell  disease  has  been  a  "natural"  attraction  for  young  African  Americans 
and  members  of  other  minority  groups  seeking  careers  in  biomedical  research.  The 
Comprehensive  Sickle  Cell  Centers,  with  their  large  collection  of  senior  and  middle 
level  research  scientists,  have  served  as  fertile  breeding  grounds  for  such  budding 
scientists.  However,  the  Centers  are  no  longer  allowed  to  recruit  students  and  young 
physicians  as  part  of  the  Minority  Supplement  Program  of  the  NM.  Each  year,  we 
turn  down  several  applications  for  research  apprenticeship  from  students  because 
of  lack  of  support. 

I  would  like  to  make  the  following  specific  recommendations: 


43 

1.  Overall  the  funding  for  research  projects  dealing  directly  with  sickle  cell  dis- 
ease has  been  declining  in  relationship  to  other  conditions  supported  by  the  Na- 
tional Heart,  Lung,  and  Blood  Institute  of  the  National  Institutes  of  Health.  The 
10  National  Institutes  of  Health-approved  Comprehensive  Sickle  Cell  Centers  have 
not  had  a  real  increase  in  their  level  of  support  Tor  the  past  15  years.  These  Centers 
are  currently  funded  at  5.6  percent  below  their  recommended  and  approved  budgets; 
they  suffered  8.5  percent  reduction  in  funding  for  1993/94.  We  ask  that  federal  fund- 
ing for  the  Centers  be  increased  by  $4  million  to  enable  approved  research  projects 
tobe  conducted  as  recommended  in  the  peer  review  process.  The  success  of  the  Cen- 
ters concept  in  advancing  research  in  sickle  cell  disease  deserves  to  be  recognized 
by  adequate  funding.  The  Comprehensive  Sickle  Cell  Centers  should  be  specifically 
mentioned  in  the  language  of  any  appropriation  for  increased  funding  for  the  Nffl. 

2.  The  network  of  medical  centers  established  through  the  National  Heart,  Lung, 
and  Blood  Institute  of  the  National  Institutes  of  Health  for  clinical  investigations 
in  sickle  cell  disease  should  be  maintained  as  the  best  system  for  quickly  testing 
new  treatments  in  sickle  cell  disease.  In  this  regard,  the  well  organized  Cooperative 
Study  of  Sickle  Cell  Disease  should  be  supported  as  the  i  ideal  network  for  clinical 
trials  in  sickle  cell  disease.  This  network  demonstrated  its  value  in  the  rapid  con- 
duct of  the  Penicillin  Prophylaxis  Study.  ,„,,«. 

3.  Funding  for  Centers  for  Gene  Therapy  for  Sickle  Cell  Disease  and  Related  Dis- 
orders should  be  increased.  At  the  moment  only  two  such  Centers  are  expected  to 
be  established  through  the  National  Institutes  of  Health.  Many  brilliant  molecular 
biologists  and  gene  therapy  experts  whose  talents  can  be  recruited  into  this  area 
of  research  areliesitant  to  come  in  because  of  concerns  about  long  term  commitment 
of  support.  Congress  should  place  its  commitment  to  finding  a  cure  for  this  genetic 
disease  through  major  funding  for  gene  therapy  for  sickle  cell  disease.  This  will  be 
a  fitting  response  to  the  contributions  made  to  medical  science  and  the  understand- 
ing oogenetic  diseases  by  those  affected  by  sickle  cell  disease  and  related  disorders. 

4.  There  is  severe  underrepresentation  of  African-Americans  and  other  minority 
groups  in  biomedical  research.  In  order  to  increase  the  number  of  African  Americans 
and  members  of  other  minority  groups  in  biomedical  research,  adequate  funding 
should  be  provided  to  fully  fund  the  Minority  Supplement  Program  of  the  National 
Institutes  of  Health  particularly  in  relationship  with  the  Comprehensive  Sickle  Cell 
Centers.  In  addition,  in  accord  with  a  report  of  a  National  Heart,  Lung,  and  Blood 
Institute  Task  Force  on  the  declining  number  of  investigator-initiated  research  pro- 
posals, a  Sickle  Cell  Research  Scholars  Program  should  be  established  within  the 
Comprehensive  Sickle  Cell  Centers.  Each  Center  should  be  provided  sufficient  re- 
sources to  fund  at  least  one  such  Scholar  drawn  from  the  ranks  of  young  investiga- 
tors on  the  medical  school  and  hospital  faculties  where  Centers  are  funded. 

Senator  Wellstone.  Mr.  Jones. 

Mr.  Jones.  Thank  you,  Senator  Wellstone. 

It  is  indeed  an  honor  and  a  distinct  privilege  for  me  to  have  an 
opportunity  to  address  the  committee  this  afternoon  on  this  very 
important  issue. 

Southern  University  in  Baton  Rouge  has,  as  a  result  of  the  1992 
legislative  statute,  created  a  vehicle  for  a  national  research  center 
for  sickle  cell  anemia.  Southern  University  is  the  largest  predomi- 
nantly black,  historically  black  college  or  university  in  the  United 
States,  with  approximately  16,000  students  in  the  Southern  Uni- 
versity system. 

This  research  center  not  only  has  the  support  of  our  Governor 
and  our  legislature,  but  also  has  the  support  of  the  National  Bap- 
tist Convention  U.S.A.,  the  National  Rainbow  Coalition,  and  the  40 
members  of  the  Congressional  Black  Caucus.  So  this  research  cen- 
ter that  is  proposed  at  Southern  University,  as  a  national  research 
center,  because  there  is  no  national  research  center — there  are 
comprehensive  centers,  and  the  basic  difference  between  this  pro- 
posal and  the  comprehensive  centers  is  that  this  center  will  be 
dedicated  to  research  and  research  only. 

The  practical  effect  of  the  disease  was  summed  up  by  a  young 
woman  with  the  disease  who  made  this  statement  during  the  23rd 
Annual  Congressional  Black  Caucus  Week:  "I  have  sickle  cell  ane- 


44 

mia,  and  I  am  not  supposed  to  be  here  today.  I  usually  wish  that 
I  was  not.  I  wished  that  I  was  dead.  Sickle  cell  causes  me  a  lot  of 
pain.  The  pain  is  so  bad  I  cannot  stand  it.  Sometimes,  I  start 
breathing  fast  and  can  hardly  catch  my  breath.  I  get  weak.  I  start 
to  slur  my  speech  and  go  in  and  out  of  consciousness.  Sometimes, 
I  pass  out  in  the  street.  People  step  over  me  or  on  me.  They  think 
I  am  a  drug  addict.  If  I  get  to  the  hospital,  everybody  thinks  I  am 
on  drugs,  too,  and  they  treat  me  like  some  kind  of  criminal.  I  can- 
not hold  down  a  job  because  of  the  frequency  of  my  crises.  I  do  not 
have  no  money,  no  nothing,  because  of  sickle  cell." 

The  role  of  the  National  Sickle  Cell  Research  Center  at  Southern 
University,  again  unlike  the  10  comprehensive  sickle  cell  service 
and  counseling  centers  which  presently  exist,  this  center  will  en- 
gage exclusively  in  research,  basic  biomedical  research  and 
psychosocial  research. 

Why  establish  the  National  Sickle  Cell  Research  Center  at 
Southern  University,  some  have  asked.  Even  if  Congress  opts  to 
support  a  National  Sickle  Cell  Research  Center,  why  should  it  be 
located  at  Southern  University,  and  not  in  some  other  State  or  at 
another  institution? 

The  answer  is  three-fold.  One,  Southern  University's  location  in 
the  State  of  greatest  need,  in  a  State  that  is  approximately  one- 
third  African  American,  with  3,248  persons  with  the  disease,  25 
percent  of  whom  will  have  the  acute  form  of  the  disease  which  is 
usually  fatal. 

The  second  point  is  that  Southern  University  is  in  the  State  of 
Louisiana,  and  the  State  of  Louisiana  has  made  a  commitment  to 
this  project  as  evidenced  by  a  $7  million  appropriation  to  the  na- 
tional center  for  its  establishment.  No  other  State  in  the  United 
States  has  made  such  a  commitment.  In  fact,  in  furtherance  of  the 
State's  effort,  this  year,  just  2  months  ago,  the  State  of  Louisiana 
put  an  additional  $700,000  into  the  State  budget  to  create  clinics 
for  sickle  cell  patients  throughout  the  State  of  Louisiana.  There  is 
not  one  urban  area  in  the  State  of  Louisiana  that  will  not  have  a 
sickle  cell  clinic  where  these  patients  will  be  able  to  receive  treat- 
ment, with  a  hematologist  on  staff. 

Senator  Wellstone,  as  I  sit  here  today,  a  little  more  than  1  year 
after  the  national  center's  launching  meeting  at  Southern  Univer- 
sity, in  addition  to  the  $7  million  committed  to  the  effort  by  the 
State  of  Louisiana,  Southern  is  obtaining  financial  commitments 
for  the  center  from  alumni,  corporations  and  foundations.  Southern 
has  faculty,  research  staff  commitments,  and  collaboration  between 
LSU  and  the  Earl  K.  Long  Hospital,  which  are  located  less  than 
5  miles  from  Southern. 

I  am  here  today  to  a:k  the  Federal  Government  to  join  us  in  this 
collaborative  public-private  venture,  to  help  us  turn  the  lives  of 
tens  of  thousands  of  Americans  who  are  impacted  by  sickle  cell 
anemia.  Join  in  our  partnership  to  find  a  cure  for  sickle  cell  anemia 
tomorrow  by  investing  the  3-to-l  match  of  $21  million  today. 

The  investment  will  help  the  State  of  Louisiana  and  the  region 
to  develop  a  cure  for  the  United  States  and  for  all  persons  who  are 
affected  by  sickle  cell  anemia. 

I  would  like  to  again  thank  you  for  this  opportunity  of  addressing 
the  committee  and  to  say  that  we  are  committed  to  finding  a  cure 


45 

for  sickle  cell  anemia.  We  need  your  help,  and  we  would  ask  you 
to  vote  favorably  and  support  this  support  this  initiative. 

[The  prepared  statement  of  Mr.  Jones  appears  at  the  end  of  the 
hearing  record.] 

Senator  Wellstone.  Thank  you,  Mr.  Jones. 

Certainly,  there  is  no  question  about  the  reputation  of  Southern 
University,  and  I  think  we  will  probably  want  to  put  some  ques- 
tions to  you  as  to  what  the  State  commitment  might  be,  not  just 
this  year,  but  the  following  year  and  the  year  after  that,  what  kind 
of  annual  appropriation  would  it  be  over  a  period  of  time.  But  let 
us  put  those  questions  to  you  and  get  a  written  response. 

I  thank  botn  of  you,  and  I  do  apologize  for  the  committee.  It  is 
very,  very  unusual  the  way  this  happened  today.  It  is  the  worst 
possible  timing  for  everyone.  I  personally  think  that  all  too  often, 
sickle  cell  and  those  who  suffer  and  struggle  with  it  are  out  of 
sight,  out  of  mind,  put  in  parentheses  and  put  into  brackets.  There 
should  be,  must  be,  has  to  be  more  of  a  commitment. 

I  only  came  in  at  the  very  end  because  of  other  commitments  I 
made  a  long  time  ago,  but  I  think  your  testimony  is  very  impor- 
tant, and  I  thank  everybody  who  was  here  today,  and  I  apologize 
for  my  colleagues  for  the  conflicts  that  they  had. 

[Additional  statements  and  material  submitted  for  the  record  fol- 
low:] 


THE      ACCOMPLISHMENTS       OF       THE      COMPREHENSIVE      SICKLE       CELL 
CENTER  AT  MEHARRY   MEDICAL   COLLEGE 


JULY    26,    1994 
rpwryr  x  turner.   M.S..  „„,-«-, 

HTBttCTOR.     ttlMPREHENSiyg    STCXL2    CKT.l    CSUTSR 
^thxbry    HrpTr*T-   rnT.T.T.RP. 
NftSHVILLS,    TT*   37209 


INTRODUCTION 

Sickle  cell  disease  (3CD)  refers  to  a  group  of  chronic, 
hereditary  blood  disorders  that  primarily  affects  African- 
Americans.  One  in  every  400  black  babies  born  in  the  United 
States  is  affected  by  SCD.  The  disease  is  characterized  by 
diverse  symptoms ,  and  numerous  complications ;  throughout  their 
lives  affected  individuals  are  plagued  by  recurrent  bouts  of 
pain  secondary  to  vaso-occlusion  which  is  the  hallmark  of  the 
disease.  These  recurrent  episodes  of  pain  and  vaso-occlusion 
often  result  in  incapacitation.  Other  problems  include 
increased  risk  of  infections  aseptic  necrosis,  increased  risk 
of  infections,  and  delays  in  growth  and  development  just  to 
name  a  few  of  its  associated  complications. 

The  Physical  Aspects  of.  SC3 

Sickle  Cell  Disease  is  an  autosomal  recessive  red  blood  cell 
disorder  characterized  by  sickling  of  erythrocytes, 
obstruction  of  the  microcirculation  and  a  chronic  hemolytic 
anemia.  The  disease  is  seen  predominantly  among  the  Afericain- 


46 

American  population  in  the  United  States,  but  is  also 
prevalent  among  populations  of  Africa,  the  Mediterranean, 
Caribbean,  Middle  East,  and  southern  India.  Thus  because  the 
United  States  is  composed  of  many  individuals  from  all  parts 
of  the  world  its  is  also  diagnosed  in  other  ethnic  groups 
within  the  US.  On  the  African  continent  SCD  is  thought  to 
provide  a  natural  immunity  to  malaria,  but  it  has  no  such 
usefulness  to  its  carriers  in  the  rest  of  the  world. 

Pathogenesis 

The  first  documentation  of  SCD  was  made  in  1910,  by  a 
Chicago  cardiologist,  James  Herrick  who  discovered  it  in  the 
bloodstream  of  a  west  Indian  student.  Almost  four  decades 
later,  Pauling  and  colleagues  demonstrated  that  the  sickling 
phenomenon  was  due  to  a  structural  defect  in  the  hemoglobin 
molecules  and  this  work  resulted  in  reward  of  the  Nobel  prize 
for  medicine. 

Hemoglobin  is  composed  of  heme,  the  red-colored 
substance,  and  globin,  a  protein  component.  The  function  of 
hemoglobin  is  to  transport  oxygen  from  the  lungs  to  the 
tissues.  The  abnormality  in  siclcle  cell  disease  lies  in  the 
globin  portion  of  hemoglobin.  Globin  consists  of  two  pairs  of 
polypeptide  chains  which  include  alpha  chains  and  non-alpha 
chains.  The  alpha  chain  consists  of  141  amino  acids,  while  the 
non-alpha  chains  consist  of  146  amino  acids. 

A  decade  after  Pauling's  discovery,  Ingram  demonstrated 
that  the  abnormality  in  the  hemoglobin  molecule  was  due  to  a 
biochemical  alteration,  which  was  the  resuit  of  the 
substitution  of  a  single  amino  acid  by  another.  With  classic 
sickle  cell  disease,  sickle  cell  anemia,  (HbSS),  valine  has 
be*n  substituted  Cor  glutamic  aeid  at  the  sixth  position  or 
the  beta  chain.  Currently  over  700  abnormal  hemoglobin  are 
Known.  Some  of  the  more  common  variants  are  describe  are  found 
in  Table  1. 

Table  1 


syndrome 

HbS 

Substitution 

Site 

Glu->  Valine 

36 

HOC 

Glu->  Lysine 

fl6 

HbD 

Glu->  Glna 

3121 

HbE 

Glu->  Lysine 

326 

Ordinarily,  red  blood  cells  with  normal  hemoglobin  are  able 
to  maneuver  through  the  microcirculatory  system  with  relative 
ease.  In  sickle  cell  anemia,  because  of  the  single  amino  acid 
substitution  the  hemoglobin  takes  on  different  properties.  It 
continues  to  have  normal  oxygen  carrying  capacity.  Upon 
deoxygenation,  however,  there  i3  a  change  in  the  solubility  of 
the  protein  so  that  the  HbS  molecules  clump  together  to  form 
tactoid.  The  cell  membrane  becomes  distorted,  and  assumes  a 
sickle  shape,  these  cells  are  inflexible,  sticky,  and  survive 
about  7-20  days.  Sickled  cells  are  often  described  as  having 
a  "log- jamming  effect"  in  the  smaller  passage  ways,  which 
result  in  a  broad  range  of  clinical  manifestations,  sickled 
cells  can  resume  their  rounded  shape  upon  re-oxygenation  but 
only  for  a  limited  number  of  times.  After  a  period  of  time, 
they  become  irreversibly  3ickled  and  are  removed  from 
circulation  via  the  reticuloendothelial  system. 

Hfoqloftjn  Variants 

Currently  more  than  700  abnormal  types  of  hemoglobin  have 
been  identified  in  man.  Three  hemoglobin  form  our  total 
hemoglobin  picture:  Ha,  Ha,,  and  HbF.  Hemoglobin  A  is  the  most 
abundant  of  the  three.  It  is  composed  of  two  alpha  chains  and 
two  beta  chains.  The  other  two  hemoglobin  are  found  in  lesser 
amounts,  but  must  be  oresent  for  a  normal  hemoglobin  pattern. 
Ha,  is  composed  of  two  alpha  chains  and  two  delta  chains.  HbF 
is  composed  of  two  alpha  chains  and  two  gamma  chains.  HbF  is 


47 

also  known  as  fecal  hemoglobin  and  is  the  major  type  of 
Hemoglobin  produced  before  birth.  After  birth,  production  of 
gamma  chains  decreases  as  production  of  beta  chains  begin, 
thus  one  would  see  a  decreased  amount  of  HbP  and  an  increased 
amount  of  Ha.  Host  abnormal  hemoglobin  result  from  point 
mutations  in  the  structural  genes  that  code  for  the  amino 
acid  3eguence  of  the  globin  chains  of  the  molecule. 

Hemoglobin  AS  is  sickle  cell  trait.  Sickle  cell  trait 
occurs  in  one  out  of  every  10  Black  Americans.  In  fact,  there 
are  over  two  million  Black  Americans  with  sickle  cell  trait. 
Sickle  cell  trait  is  not  a  disease,  it  is  a  benign  carrier 
state  that  rarely  produces  health  problems.  The  concern  of  the 
3ickle  cell  trait  carrier  is  that  of  prospective  parenthood. 
If  both  partners  have  the  trait,  there  is  a  2S  p«r  cant  chanco 
that  with  each  pregnancy  the  couple  will  have  a  child  with 
sickle  cell  anemia.  Except  in  a  few  unusual  circumstances, 
individuals  with  sickle  cell  trait  are  asymptomatic. 

The  carrier  state  AS  is  benign  because  there  is  a 
preponderance  of  hemoglobin  A  in  each  red  blood  cell  of  the 
hemoglobin  AS  type.  Usual  proportions  in  each  cell  are 
approximately  60  per  cent  hemoglobin  A  and  40  per  cent 
hemoglobin  S.  There  is  therefore  not  enough  hemoglobin  S  to 
cause  the  symptoms  of  the  homozygous  condition,  HESS. 

Vai-^ntB  at    SCD 

After  sickle  cell  anemia,  the  most  common  forms  of  sickle 
cell  disease  in  decreasing  order  of  frequency  are  sickle 
hemoglobin  C  disease  (HbSC),  and  sickle-beta  thalassemia  of 
which  there  are  two  subtypes  ( S-6°  and  S-fl*  disease ) .  In  each 
form  of  sickle  cell  disease,  at  least  one  3-globin  structural 
gene  B*  codes  for  the  synthesis  of  a  sickle  hemoglobin.  The 
allelic  fl-globin  gene  may  code  also  for  a  sickle  hemoglobin 
(HbSS) ,  another  structural  abnormal  hemoglobin  (HbSC),  or  may 
produce  either  a  partial  defect  in  hemoglobin  A  synthesis  (S- 
B*  thalassemia),  or  a  complete  defect  in  hemoglobin  A 
synthesis  (S-B° thalassemia) . 

sickle  Hemoglobin  C  Disease 

It  has  been  estimated  that  2  per  cent  of  the  Black 
population  carry  the  gene  for  hemoglobin  C.  The  incidence  is 
1  per  1000  live  births.  The  carrier  state  as  in  the  case  of 
sickle  cell  trait  is  asymptomatic. 

Sickle  hemoglobin  C  disease  has  been  described  as  a 
milder  form  of  classic  sickle  cell  disease, that  is  sickle  cell 
anemia.  Individuals  with  the  disease  have  a  higher  hemoglobin 
level  and  less  frequent  episodes  of  pain.  Growth  and 
development  may  not  be  affected  to  the  same  degree  as  in 
hemoglobin  ss  disease.  As  in  the  case  of  sickle  cell  anemia, 
HbSC  patients  have  an  increased  risk  of  developing  certain 
complications  that  are  related  to  their  disease.  For  example, 
retinopathy  can  result  in  retinal  detachment,  and  necrosis  of 
the  femoral  head  can  be  seen  (Lin-Fu,  1979).  Individuals  with 
HbSC  have  bouts  of  transient  functional  hyposplenia.  This  puts 
them  at  risk  for  not  being  able  to  combat  infections 
adequately.  Many  individuals  with  the  disease  are  Less 
symptomatic  than  the  homozygous  HbSS  patient  and  may  not 
obtain  adequate  medical  supervision. 

TTgnoglobin  Sickle  3>f»-f hn1w«5«wi>i 
Sickle  beta-thalassemia  occurs  in  about  0.4  per  cent  of 
the  Black  population  in  the  United  States.  Individuals  with 
sickle  beta-thalassemia  have  symptoms  that  vary  from  mild  to 
those  as  marked  as  hemoglobin  SS.  Clinically,  there  is  less 
anemia,  and  less  sickling  was  found  in  vivo.  The  vaso- 
occiusive  phenomenon  that  causes  painful  episodes  still 
occurs . 


48 

As  was  mentioned  earlier,  there  are  two  types  of  beta- 
thalassemia,  3*  and  3*.  In  sicXia  beta"-tnalassen\ia  some  normal 
hemoglobin  A  is  produced,  but  far  more  of  the  abnormal 
hemoglobin  S  is  produced.  In  sickle  beta" -thalassemia ,  only 
abnormal  beta  chains  are  made,  producing  hemoglobin  s,  and  no 
hemoglobin  A  is  found.  Often  different  clinical  pictures  are 
seen  with  these  two  hemoglobinopathies.  Variability  is  an 
important  factor,  some  experts  report  that  Sickle  beta- 
"thalassemia  produces  milder  clinical  symptoms  than  sicXle 
beta'-thalassemia.  Nevertheless,  sicXle  beta-thalassemia  is  a 
sickling  disorder  and  must  be  managed  in  the  same  way  as  other 
sickling  syndromes. 


Table  2 


Incidence  of  SicXle  Cell  Disease 
in  the  United  States 


Condition 


Hb  Types 


%  of  BlacXs 


SicXle  Cell  Trait  AS 

SicXle  Cell  Anemia  SS 

Hemoglobin  C  Trait  AC 

Homozygous  C  Disease  CC 

SicXle  Hemoglobin 

C  Disease  SC 

Hemoglobin  D  Trait  AD 

Homozygous  D  Trait  DD 

Hemoglobin  £  Trait  AZ 

SicXle  Call  Thalassemia  S-Thal 

Beta-Thalassemia  Trait  Thai  Minor 


8-14% 
0.3-1.3% 
2.3% 
.016% 

0. 1-0. 25% 

0.08-0.4% 

MA 

HA 

0.04% 

1% 


*  KA  =»  Hot  Available 


Diagnosis 

The  diagnosis  of  sickle  cell  disease  is  aade  by 
performing  a  hemoglobin  electrophoresis.  The  basic  concept  of 

electrophoresis  is  that  protein  molecules  are  electrically 
charged  and  will  migrate  in  an  electric  field.  The  way  a 
particular  hemoglobin  migrates  depends  upon  the  pH  and  allows 
for  identification  of  different  proteins. 

Clinical  Manifestations 

The  complications  of  sickle  cell  disease  are  quite 
varied.  In  some  cases  individuals  are  entirely  asymptomatic 
and  are  detected  only  during  population  screening,  wneraas 
others  are  constantly  plagued  by  painful  episodes. 

The  major  complications  of  sickle  cell  disease  can  be 
placed  into  three  categories:  acute  events,  chronic  events,  or 
health  related  events  that  require  added  medical  attention. 
Acute  events  include  painful  episodes,  acute  chest  syndrome, 
right  upper  quadrant  syndrome,  skeletal  and  joint  events, 
hand-foot  syndrome,  cerebrovascular  accidents,  aplastic 
episodes,  sequestration  crisis,  acute  febrile  event,  and 
priapism.   Chronic   events   include   leg   ulcers,   renal 


49 

complications,  aseptic  necrosis,  and  ocular  complications. 
Health  related  events  include  delayed  growth  and  development, 
delayed  sexual  maturation,  pregnancy,  surgery,  and  anesthesia 
(Walters,  1983). 

For  the  first  few  months  of  life  there  ia  usually  no 
indication  of  the  disease  upon  physical  examination.  Because 
there  is  more  production  of  sickle  hemoglobin  and  less  HbF,  by 
six  months  of  age,  more  symptoms  begin  to  develop.  These 
include  dactylitis,  hepatomegaly,  and  splenomegaly.  In  the 
older  child,  during  non-acute  phases  varying  degrees  of 
pallor,  scleral  icterus,  hepatomegaly  and  cardiomegaly  can  be 
seen.  In  homozygous  HbSS  disease,  the  spleen  is  enlarged  in 
early  childhood  as  a  result  of  its  function  in  removing 
sickled  cells  from  circulation.  Functional  activity  is  lost, 
however,  in  the  first  few  years  of  life.  After  about  6-3  years 
of  age,  autosplenectomy  or  the  self-destruction  of  the  spleen 
occurs  as  a  result  of  repeated  splenic  infarcts.  Delayed 
growth  and  delayed  sexual  maturation,  frontal  bossing,  and 
sometimes  gnatopathy  are  characteristic  of  sickle  cell 
disease. 

The  physical  aspects  of  sickle  cell  disease  constitutes 
only  one  facet  of  the  health  problem.  A  number  of  psychosocial 
issues,  including  the  psychological  concomitant  of  extended 
hospitalization  and  isolation,  long  tern  adjustment  to 
survival,  and  an  uncertain  disease  course  have  also  surfaced. 
Mary  care-givers  feel  that  addressing  these  problems  is 
equally  as  important  as  addressing  the  physical  problems  that 
arise  as  a  result  of  the  disease. 

Despite  the  complexities  of  SCO,  the  health  prognosis  has 
improved  over  the  past  decade.  Prior  to  1974,  SCD  was 
considered  a  terminal  illness.  Although  still  considered  a 
chronic  disease,  SCD  is  no  longer  considered  a  fatal  disease 
prior  to  adulthood.  In  fact,  individuals  with  33  have  been 
reported  as  living  well  into  their  70s.  Deaths  occurring 
before  adulthood  were  largely  related  to  severe  infections, 
e.g.,  pneumonia  and  organ  failure.  Fortunately,  treatment  and 

management,  which  include  early  detection,  proper  medication, 
and  counseling,  have  improved  the  overall  physical  status. 

In  summary,  SCD  is  a  non-contagious,  inherited  blood 
disorder.  There  are  many  variants  of  SCD,  the  S3,  and  the  SC 
states  are  the  most  prominent  in  the  United  States.  Although 
many  physical  discomforts  are  associated  with  the  disease, 
affected  individuals  can  lead  useful  and  productive  lives , 
given  proper  medical  treatment  and  management. 

The  improvement  in  the  overall  survival  of  individuals 
with  SCD  has  occurred  since  1972  when  President  Nixon  in  1972 
enacted  the  National  Sickle  Call  Disease  Act.  This  is  directly 
related  to  the  establishment  of  Comprehensive  Sickle  Cell 
Centers  which  have  provided  for: 

1.  an  environment  for  research 

a.  basic 

b.  clinical 

2.  Laboratory  diagnosis 

3 .  genetic  counseling 

4.  universal  slckla  cell  education 

At  the  Meharry  Comprehensive  Sickle  Cell  Center  the 
development  of  our  center  has  in  addition  to  the  above 
activities  being  accomplished  the  following  have  also  bean 
achieved : 

1.  the  achievement  of  a  referral  Center  status 

2.  Stimulation  of  Research 

a.  intramural 

b.  extramural 

3 .  becoming  a  resource  center  locally  and  especially  for 
region  IV 

4 .  the  development  of  a  strong  community  outreach 

program 


50 


STIHUIATIOK  OF  RESEARCH 

without  the  support  of  the  NIH  and  tha  sickle  cell  disease 
branch  it  would  have  been  difficult  to  establish  the 
environment  where  limited  resources,  facilities  and  manpower 
existed  to  coordinated  and  stimulate  research.  The  actual 
development  process  took  a  number  of  years  to  develop. This 
support  has  also  allowed  us  interact  with  vanderbilt 
University  School  of  Medicine  to  further  develop  and  apply 
application  of  new  knowledge  in  the  diagnosis  and  treatment 
of  sickle  call  disease.  In  the  development  of  these  overall 
activities  a  multidiscipline  team  approach  from  many 
individuals  involved  with  health  care  delivery  was  required. 
And  to  maintained  the  activities  requires  that  this  team 
approach  be  maintained. 


EDUCATION 

TESTING 

COUNSELING 

PATIENT  CARE 

RESEARCH 


51 


COMPREHENSIVE  SICKLE  CELL  CENTERS 


Program  Components 


EDUCATION 

Pallenl 
Famly 

General  Pubttc 
Professionals1 


PSYCHOSOCIAL 
SERVICES 


RESEARCH 
Basic 
CCm'cai 
Appled 


PATIENT 


COUNSELNG 

Carriers 

Disease 

Oilier 

Abnormal 

I  leinogloblns 


DIAGNOSIS 

Pallenl 

Family 

Prenalal 

Newborn 


COMPREHENSIVE  SICKLE  CELL  CENTER 

COMPONENTS 


PATIENT  CARE 


COUNSELING    - 


RESEARCH 


COMMUNITY 
-   OUTREACH 


DIAGNOSIS 


EDUCATION 


52 


COMPREHENSIVE  SICKLE  CELL  CENTER 

COMPONENTS 


INFANTS 


MTiENT 
DARE"  m 


ADULTS 


ADOLESCENTS 


COMPREHENSIVE  SICKLE  CELL  CENTER 
CASE  MANAGEMENT 

Genetics, 


Science     Emergency  Medicine 
^-—  * — ^       JJursing 

X.  Legal  Services 


Health  Education* 


X 


Radiology* ►/  —*.-—■--  ^  --^T ,  Social  Services 

PA  II  E  N  llY^»  Pharmaceutics 
PATI  £  ^^  [^Ophthalmology 

J ►  Hematology 

/— ♦Ob/Gyn 
/■-*.  Family  Medicine 


Surgery 

Vocational  Rehab 
Pediatrics, — 


Home  Health  Services 


/ 
/  ■ 

\ 


Private   NIH 
Agencies        DePt- of 


Family  Support  Systems 

TN. 


Health  and  Environment 


53 


TESTIMONY  OF  CHARLES  D.  JONES 
LOUISiANA  STATE  LEGISLATOR 
CHAIRMAN, {LAW  &  JUSTICE  COMMITTEE, 
NATIONAL  BLACK  CAUCUS  OF  STATE  LEGISLATORS 

& 

CONVENOR.  CHAIRMAN,  DELfTA  PILOT  ECONOMIC  DEVELOPMENT  PROJECT 

DELTA  ECONOMIC  ENERGY  DISTRICT 

BEFORE  THE  UNITED  STATE  SENATE 

COMMITTEE  Ot\  LABOR  AND  HUMAN  RESOURCES 

JULY 28,  1994 


INTRODUCTION 

Chairman  Kennedy ,  Senator  i  assenbaum,  other  distinguished  members  of  the  Committee, 
I  am  Louisiana  State  Senator  Charges  Dean  Jones,  representing  Louisiana's  34th  Senatorial 
District.  I  also  appear  before  you  ttlis  morning  as  Chairman  of  the  Law  &  Justice  Commiaee 
of  the  National  Blade  Caucus  of  Stale  Legislators  (NBCSL)  and  as  the  Convener  and  Chairman 
of  the  Delta  Pilot  Economic  Deyeioj  ment  Project  and  its  Delta  Economic  Energy  District,  Inc. , 
(DEED).  My  remarks  before  this  body  today  are  also  embraced  by  the  National  Baptist 
Convention,  USA,  Inc.,  and  the  Naional  Rainbow  Coalition.1 

Before  discussing  the  background  of.  the  need  for  and  the  utility  of  federal  support  for 
the  National  Sickle  Cell  Research  'Center  at  Southern  University,  I  want  to  thank  Senator  J. 
Bennett  Johnston  for  his  unstinting  support  and  his  championship  in  the  United  States  Senate  of 
legislation  authorizing  the  Secretary  bf  the  Health  and  Human  Services  to  award  a  grant  for  me 
establishment  of  the  National  Center)  for  Sickle  Cell  Disease  Research  and  Southern.  I  want  to 
thank  Senator  Johnston  also  for  his  iresence  here  today. 

I  take  this  opportunity  to  eitend  my  gratitude  to  my  long-time  friend  Congressman 
William  Jefferson  (D-2-LA)  who  is  >roviding  the  leadership  necessary  to  advance  the  measure 
through  the  United  States  House  of  R  spresentanyes.  Congressman  Jefferson  also  joins  us  today. 
Finally,  I  take  this  opportunity  to  ack  xrwledge  the  efforts  of  Congressman  Clco  Fields  (D-4-LA) 
to  gamer  support  for  House  legisation  that  wILL  establish  on  the  campus  of  Southern 
University-  located  in  Congressman  Field's  District-  the  National  Sickle  Cell  Research  Center. 
The  establishment  of  this  Center  is  ; ,  matter  of  paramount  concern  not  only  to  the  residents  of 
Congressman  Fields'  District  and  to  others  in  the  State  of  Louisiana  and  the  Delta  Region,  but 
to  African  Americans  across  the  nation. 

As  evidence  of  the  broad  national  support  for  the  National  Sickle  Cell  Research  Center, 
I  note  that  the  unanimous  40-membc  Congressional  Black  Caucus  of  the  United  States  Congress 
is  in  support  of  the  National  Center.  In  March  of  1993,  every  member  of  the  Congressional 
Black  Caucus  joined  in  sending  a  later  to  Secretary  of  Health  and  Human  Services.  Donna 
Shalala,  urging  her  support  for  tbe  Rational  Research  Center  at  Southern.  (Letter  attached.) 


1  The  National  Baptist  Convention,  USA,  Inc.,  (NBC,  USA)  is  the  nation's  oldest  and 
largest  association  of  Black  Baptis,  rninisters,  representing  tens  of  thousands  of  active  and 
involved  registered  voters  across  A  merica,  as  well  as  residents  of  Africa  and  the  Caribbean. 
The  national  president  of  NBC,  US  \  is  Reverend  Dr.  T.J.  Jemison,  who  hati«  from  the  State 
of  Louisiana.  Last  year  at  its  annuil  convention  in  New  York  City,  NBC,  USA,  adopted  by 
unanimous  consent  "A  Concurrent  Resolution"  urging  and  requesting  that  its  members  support 
in  any  manner  of  means,  the  establishment  of  a  national  Sickle  Cell  Disease  Research  Center 
at  Southern  University.  (Resolution! attached.) 

The  National  Rainbow  Coalition  is  a  national  multi-racial,  multi-cultural  political  and 
economic  empowerment  association,  founded  and  chaired  by  The  Reverend  Jesse  L.  Jackson. 
Earlier  this  year.  The  Rainbow  Coalition's  Health  Task  Force  recommended  to  Congressman 
Louis  Stokes  (D-OH),  Chairman  of  the  Congressional  Black  Caucus  Health  Braintrost  and 
Convener  of  the  African  American  Leadership  Health  Care  Reform  Work  Group,  that  the  CBC 
and  the  Work  Group  support  and  urge  the  appropriation  of  adequate  federal  funds  to  compliment 
(in  a  three  to  one  match)  the  state  ftnds  appropriated  by  the  State  of  Louisiana  to  establish  and 
rnainiain  at  Southern  University,  this  nation's  only  Sickle  Ceil  Research  Center. 


54 


The  National  Blade  Caucus  <k  State  Legislators,  too,  is  in  support  of  the  Center.  During 
its  17th  Annual  Conference  in  Deiver  Colorado  last  year,  NBCSL  adopted  a  resolution  in 
support  of  the  National  Centex  for  Sickle  Cell  Research ,  by  unanimous  consent.  NBCSL  is  the 
educational,  research  and  training  association  of  the  nation's  540  African  American  state 


legislators  who  primarily  represent 
and/or  work  in  rural  communities, 
many  who  exist  in  poor  America 
Americans,  NBCSL  members  are 
social  empowerment  of  African 
institutions,  is  central  to  the  coi 
too.  are  united  in  the  belief  that 


icons  Americans  across  the  country— some  of  whom  reside 
in  urban  areas.  Some  who  exist  in  affluent  America, 
Whether  representing  urban  or  rural,  affluent  or  poor 
.ted  in  their  belief  that  the  continued  political,  economic  and 
and  the  enhancement  of  their  communities  and 
growth  and  development  of  this  nation.  NBCSL  members, 
equality  in  this  country  can  only  be  achieved  when  each 
American  is  guaranteed  equality  or  life  chances;  and  that  a  crucial  prerequisite  for  likely 
achievement  of  equal  life  chancre  e  accessibility  of  affordable,  quality  health  care  beginning 
before  birth.  This  access  must  include  necessary  research  to  find  cures  for  diseases  peculiar  to 
either  gender;  diseases  peculiar  to  ijfants,  children,  and  seniors;  and  people  of  every  race  and 
ethnicity,  including  African  Americans.  Access  must  also  include  necessary  research  to  find 
cures  for  those  whose  diseases  are  behavioral  in  origin  and  those  whose  diseases  are  hereditary. 

BACKGROUND  AND  NEED  FOR  THE  NATIONAL  SICKLE  CELL  RESEARCH  CENTER 

It  is  axiomatic  that  acccssibi  ity  of  affordable,  quality  health  care,  proper  nutrition,  safe 
and  sanitary  home  and  cmploynent  conditions  and  a  clean  environment  are  necessary 
components  of  an  overall  quality  health  care  system.  It  is  a  fact  that  quality  health  care,  proper 
nutrition,  safe  and  sanitary  home  and  employment  conditions,  and  a  clean  environment  are 
necessary  to  begin  to  equalize  life  chances  among  the  haves  and  the  have-nots.  As  a  child  who 
grew  up  m  the  poorest  region  in  -unerica.  in  the  nation's  poorest  city,  Lake  Providence, 
Louisiana,  where  82%  of  the  population  is  on  public  assistance;  and  as  a  state  legislator  for 
nearly  two  decades,  representing  ax  only  Lake  Providence,  but  also  the  city  of  Monroe. 
Louisiana,  where  I  presently  reside--  which  is  the  nation's  third  poorest  city-  I  see  daily  and 
have  witnessed  firsthand  for  more  han  four  decades,  the  fact  that  children  cannot  study  to 
capacity  and  cannot  grow  to  be  sturc  y,  productive  members  of  our  communities  without  sound 
nutrition,  safe  housing  and  health  maintenance  based  on  prevention.  I  have  seen  firsthand  the 
deleterious  and  debilitating  effect  uit  poverty  and  the  concomitant  lack  of  health  and  human 
needs  services;  absence  of  proper  nutjrition;  lack  of  safe  and  sanitary  and  employment  conditions; 
and  a  hazardous  environment  have, 
entire  region. 


not  only  on  a  people,  a  dry,  parish  or  a  state,  but  on  an 


It  was  in  part  my  witnessing  these  things,  that  lead  me  in  1993,  to  organize  the  Delta 
Pilot  Economic  Development  Project,  and  to  launch  as  its  initial  project  the  Rural  Community 
Health  Service  Project.  The  Delu|  Pilot  Economic  Development  Project  is  an  Arkansas/ 
Louisiana/ Mississippi  Tri-State  rtgiobal  economic  and  human  development  corporation  launched 
at  my  urging  with  broad  and  diversfe  support  from  the  Tn-State  region,  including  that  of  the 
governors  of  the  three  states;  many  members  of  the  congressional  delegations  of  the  three 
states;  state  and  local  elected  officials  from  the  Tri-state  Region:  business  persons,  labor, 
religious  leaders,  community  leaders]  and  with  the  support  of  thousands  of  the  suffering  residents 
of  this  beleaguered  region.  Our  goal  is  to  formulate  and  implement  collaborative  regional 
solutions  to  the  myriad  problems  wrfich  plague  this  region,  not  the  least  of  which  are  that  it  has 
the  nation's  highest  illiteracy  rate,  highest  poverty  rate,  rural  poverty  and  minonty  poverty  rate, 
highest  infant  mortality  rate,  highestjmfinnity  rate,  and  lowest  educational  attainment  rate  in  the 
nation.  The  group  set  as  goals,  Inz'tr  alia,  the  establishment  of  an  economic  development  and 
heaith  corridor  defined  by  the  Mississippi  River.  In  so  doing,  we  were  building  upon  and 
organizing  to  implement  the  recoramendations  of  the  Lower  Mississippi  Delta  Commission, 
chaired  by  then  Governor  Bill  Clini  an. 

With  regard  to  the  cstabllsl  ment  of  the  Health  Corridor,  the  Delta  Pilot  Economic 
Development  Project  noted  that  the  ArkLaMlss  Region  has  the  highest  percentage  of  medically 
under-served  residents  in  the  nation ,  the  highest  infant  mortality  rate  in  the  nation,  the  highest 
low  birth  weight  births,  the  highest  inridwm  of  births  to  teen  mothers,  among  the  lowest 
primary  care  physician-to-patient  arid  registered  nurse-to-patient  ratio  in  the  nation.  Collective 
remedial  goals  were  established  to  iring  the  Tri -State  region  at  least  up  to  par  with  the  rest  of 
the  nation.  Each  of  yon  has  been  provided  with  a  copy  of  the  Delta  Pilot  Economic 
Development  health  care  findings  and  goals. 


55 


The  Sate  of  Louisiana  took  the  lead  in  following  up  on  the  Tri-State  Health  Care 
recommendations.  The  Northeast  Louisiana  Council  on  Black  Economic  Development  conducted 
a  surrey  of  the  rural  health  care  pmblems  in  all  45  rural  parishes  in  the  state.  A  copy  of  the 
survey  and  a  copy  of  the  recommendations  and  actions  taken  pursuant  to  the  survey—including 
the  passage  of  state  legislation  to  address  some  of  the  findings—  have  been  provided  to  each  of 
you  this  morning.  While  all  of  the  findings  are  troubling,  most  were  anticipated.  We  were 
alarmed,  however,  by  the  »w»rfingi  y  high  number  of  African  Americans  across  the  state  with 
the  Sickle  Cell  Anemia  disease  or  Q  ait.  We  found  that  Louisiana  has  the  highest  number  of 
citizens  per  capita  afflicted  with  die  £  ickle  Cell  disease  in  the  moon.  Of  Louisiana's  1,299,281 
minorities.  3,248  have  Sickle  Cell  .'mania  and  129.928  have  the  trait.  In  the  rural  parishes 
alone,  990  residents  have  the  disease  while  37,838  possess  the  trait.  Nationally,  the  sickle  cell 
disease  is  estimated  to  affect  more  tr.  in  50,000  Americans.  Approximately  one  in  every  twelve 
(12)  black  Americans  is  born  with  th :  Sickle  Ceil  trait,  and  about  one  in  four  hundred  (400)  has 
Sickle  Cell  Anemia. 

For  those  of  you  who  are  "nfamiliar  with  the  disease,  it  is  not  a  silent  killer,  like  high 
blood  pressure,  it  takes  its  victims  lacking  and  screaming.  It  causes  excruciating  pain.  It  causes 
diseases,  infections,  mal-functioning  of  crucial  organs  like  the  spleen,  then  it  kills!  It  is  an 
inherited  disorder  of  the  red  blood  cells,  that  disproportionately  affects  persons  of  African 
ancestry.  To  a  far  lesser  degree,  pei  sons  of  Arabian,  Caribbean,  Centrai  and  South  American, 
East  Indian  and  Mediterranean  ancestries  are  affected  by  the  disease,  also.  As  you  know,  red 
blood  ceils  carry  oxygen  to  all  parts  of  the  body  through  a  protein  called  hemoglobin.  Normal 
red  blood  cells  contain  normal  hemoglobin  and  are  donut  shaped.  They  move  easily  through 
blood  vessels.  For  those  with  sickle  cell  disease,  the  red  blood  ceils  contain  sickle  hemoglobin 
which  causes  them  to  have  a  curved  or  sickle  shape—  much  like  the  end  of  a  tuning  fork—  after 
oxygen  is  released.  Sickied  cells  become  stuck  in  blood  vessels,  thus  blocking  the  blood  flow 
and  causing  damage  to  the  tissue.  A  major  effect  of  the  disease  is  the  sickle  cell  "crisis"  which 
occurs  when  sickle  cells  plug  blood  vessels  and  block  the  flow  of  blood.  The  blockage  typically 
lasts  several  days,  usually  affecting  ihe  arms,  legs,  hands,  feet,  abdomen  or  another  local  part 
of  the  body.  Tissue  damage,  often  i  tvolymg  major  organs,  occurs  with  each  successive  episode 
of  oxygen  deprivation.  The  cumulative  effects  of  the  disease  are  debilitating  and  life 
threatening.  Those  affljrtrd  with  severe  forms  of  the  disease  usually  do  not  live  through  their 
teens. 

The  practical  effect  of  the  Usease  was  summed  up  by  a  young  woman  in  her  early 
twenties,  from  Senator  Mikulski's  sate,  who  appeared  on  a  panel  Congressman  Louis  Stokes 
convened  on  this  deadly  disease,  last  September  during  the  23rd  annual  Congressional  Black 
Caucus  Week.   Said  the  woman: 


"I  have  Sickle  Cell 

today 

dead. 


taemia  and  I  am  not  supposed  to  be  here 
1  usually  wist  that  I  wasn't  [sic]  here.  I  wish  that  I  was 
sickle  cell  cstses  me  a  lot  of  pain.  The  pain  is  so  bad 


[sic]  catch  my  breath 


I  can't  stand  it....  Sometime  I  start  breathing  fast  and  can't  hardly 


...  I  get  weak,  start  to  slur  my  speech  and  go 


in  and  out  of  consciousness.  Sometime  I  pass  out  In  die  street. 
People  step  over  me  or  on  me.  They  think  I'm  a  drug  addict.  If 
I  get  to  the  hospital,  ( Yerybody  there  think  [sic]  I'm  on  drugs,  too, 

and  they  treat  me  like  some  kind  of  criminal I  can't  hold  down 

a  job  for  long  because  of  the  frequency  of  my  crises.  I  don't  have 
oo  [sic]  money,  no  nothing  [sic]  because  of  Sickle  Cell." 


Despite  the  fact  that  the  cause 
very  rninor  structural  variation  in  tte 
toward  developing  a  cure  or  suitable 
ncatmem  for  the  painful  crisis  is  med  can 
symptoms.  It  does  not  cure  the  malady 
sickle  cell. 


of  the  sickle  cell  disease  has  been  known  for  years— the 

mutant  hemoglobin-very  little  progress  has  been  made 

treatment  for  the  disease.   At  the  present  dine,  the  major 

ion  for  relief  of  pain,  which  simply  treats  the  immediate 

or  enhance  the  quality  of  the  lives  of  those  who  have 


In  recent  yean,  the  federal  government  has  been  responsive  to  this  situation.  The 
Department  of  Health  and  Human  Services  has  a  nanonal  program  to  reduce  the  morbidity  and 
mortality  from  sickle  cell  disease.  The  Department's  National  Heart,  Lung  and  Blood  Institute 
(NHLBI)  of  the  National  Institutes  ojf  Health  (NIH)  has  the  lead  responsibility  for  carrying  cut 


56 


gfffm  ?nf 


the  government's  sickle  ceil  ah 
Sickle  Cell  centers  across   'he 
screening,  diagnosis,  management, 
center  dedicated  exclusively  to 
discovery  of  a  cure  for  this  deadly 
federal  authorization  legislation 
ihe-art  Sickle  Cell  Research  Center 
There  is  a  need  for  such  a  center, 
that  affects  more  than  50,000 


program.  There  are  currently  ten  (10)  Comprehensive 

nation  which  engage   in  demonstration  education  projects, 

c  muscling  and  clinical  studies.  No  where  is  there  a  national 

cot  ducting  multi-disciplinary  research  that  will  lead  to  the 

disease.  And,  neither  the  current  NIH  appropriations  nor 

ide  for  the  expenditure  of  federal  funds  to  erect  a  stete-of- 

No  present  monies  can  be  used  for  structural  development. 

foster  the  expeditious  discovery  of  a  cure  for  this  disease 


provide 


tc 


Amercans 


THE  ROLE  OF  THE  NATIONAL 


SICKLE  CELL  RESEARCH  CENTER  AT  SOUTHERN 


Unlike  the  ten  (10) 
presently  exist,  the  National  Sickle 
basic  biomedical  research,  and 


comprehensive 


Sickle  Cell  service  and  counseling  centers  which 
Cell  Research  Center  will  engage  exclusively  in  research: 
research. 


BASIC  BIOMEDICAL  RESEARCH 


The  Center  will  undertake 
formation  of  sickle  ceils,  the  behavior 
the  characteristics  of  sickle  cells  al  Der 
isolation,  characterization,  and  synthesis 
of  the  disease  to  lead  more  normal 
deformed.  These  areas  of  investigation 
prevent,  inhibit,  or  reverse  the  sickl  jog 
is  an  area  of  basic  investigation  tha : 


Collaborative  arrangements 
have  the  interest  in  and  expertise  to 


psychosocial 


i  lvestigations  such  as  gaining  a  better  understanding  of  the 

of  sickle  ceils  when  they  flow  through  blood  vessels,  and 

they  sickle.  Considerable  study  will  be  devoted  to  the 

of  anti-sickling  agents-  substances  that  enable  victims 

'.  ives  by  decreasing  the  '•frrr**  of  red  blood  ceils  becoming 

are  required  in  order  to  determine  the  types  of  drugs  that 

process.  A  search  of  current  literature  suggests  that  this 

leaves  many  questions  unanswered. 


will  be  undertaken  with  other  universities  In  the  state  that 
do  basic  biomedical  research  related  to  anti-sickling  agents 
as  well  as  sickle  cell  disease  and  oha  hemoglobin  abnormalities. 

The  Center  will  conduct  studies  as  the  ultrastructural  levels  in  the  areas  of  molecular 
biology  and  genetic  engineering.  These  investigations  will  focus  on  various  generic  approaches 
to  the  sickling  process.  Specific  ittention  will  be  given  to  DNA  manipulation  and  other 
techniques  of  modern  biology  which  could  cause  panents  to  begin  synthesizing  normal  adult  or 
fetal  hemoglobin.  Electron  microscopy  is  one  of  the  tools  that  will  be  used  in  investigating  in 
varo  and  in  vivo  sickling.  The  cor  wpt  of  genetic  engineering  is  one  of  the  new  and  rapidly 
developing  disciplines  io  science.  S  Miches  of  the  literature  suggest  that  not  enough  attention 
is  being  given  genetic  engineering  with  sickle  cell  disease  at  the  target. 

PSYCHOSOCIAL  RESEARCH 

The  Center  will  conduct  a  wide  variety  of  human  behavioral  studies  designed  to  shed  new 
knowledge  on  such  issues  as  the  effectiveness  of  various  counseling  and  education  methods, 
coping  drills  on  the  part  of  patiems  and  families,  and  counselor  education  and  evaluation. 
Qualification  standards  do  not  currently  exist  for  sickle  cell  generics  counselors.  Research 
questions  need  to  be  answered  as  to  What  rnimmum  body  of  knowledge  needs  to  be  mastered  in 
order  to  become  effective  in  the  rol« 


A  broad  range  of  national 
related  to  Sickle  Ceil  Anemia  will 
of  which  some  will  be  descriptive  w 
types  of  research  questions  they 
studies  on  questions  related  to  ma 
testing  for  the  presence  of  S  (si< 
registries  are  all  areas  of  public  po 


es  intended  to  shed  new  light  on  public  policy  issues 
undertaken.  Many  of  these  will  be  observational  studies 
e  others  will  be  analytical  in  approach,  depending  on  the 
Cross-sectional,  group  comparison,  and  longitudinal 
atory  genetic  testing  of  susceptible  newborns,  premarital 
;)  genes  and  the  need  for  state  and  national  sickle  cell 
that  lack  hard  data. 


Clinical  Research  Collaborative  arrangements  win  be  made  with  other  Louisiana  higher 
education  institutions,  such  as  the  sireYeport  and  Tulane  University  Medical  Center  to  conduct 
clinical  trials  on  anti-sickling  agents,  some  of  which  may  have  been  discovered  during  basic 
laboratory  investigations  at  this  CerJcer  and  elsewhere.  Because  of  the  close  proximity  of  Earl 
K.  Long  Memorial  Hospital  to  Southern  University,  basic  biomedical  investigators  at  the  Center 
and  LSU  faculty  at  Earl  X.  Long,  yul  be  able  to  conduct  a  number  of  joint  studies. 


57 


The  Center  will  not  engage  ib 
of  its  research  objectives.  Howevei 
Sickle  Oil  Foundadoo  ind  other 
these  organizations  to  do  so. 


Sfckle 


WHY  ESTABLISH  THE 
AT 


sickl*  cell  services  to  patients  except  as  negrirrl  in  support 

,  die  Center  will  work  cooperatively  with  the  Baton  Rouge 

Cell  service  organizations  in  the  state,  when  asked  by 


NATIONAL  SICKLE  CELL  RESEARCH  CENTER 
SOUTHERN  UNIVERSITY 


:ven  if  Congress  opts  to  support  a  National  Sickle  Cell 
located  at  Southern  University  and  not  in  another  state  or 


Some  of  you  have  aslced, 
Research  Center,  why  should  it  be 
at  another  institution.  The  answer  tj>  this  question  is  twofold 

Southern's  Location  in  the  State  of  Greatest  Need, 

Its  Capability  and  Its  '  Commitment  to  the  National  Center;  and 

The  State's  Cornmrcmmt  to  the  Project  as  Evidenced  by  its 
S7  million  Appropnat  on  for  the  National  Center. 

SOUTHERN'S  LOCATION  IN  TIE  STATE  OF  GREATEST  NEED,  ITS  CAPABILITY 
&  ITS  COMMITMENT  TO  THE  JNATIONAL  CENTER 

Southern  University  is  located  in  Baton  Rouge,  Louisiana.  As  noted  previously,  the 
state  of  Louisiana  has  the  highest  mimber  of  citizens  per  capita  afflicted  with  the  Sickle  Cell 
disease  in  the  nation.  Of  Louisianais  nearly  1.3  million  minorities,  more  than  133,000 
have  either  the  disease  or  the  trait.  NCore  than  10%  of  the  state's  minority  populauon  is  direcdy 
affected  by  this  killer  disease.  Nationally,  approximately  one  of  every  twelve  (12)  persons  of 
African  descent  is  affected.  Southern  University,  one  of  the  state's  premier  institutions  of  higher 
education,  and  the  nation's  largest  1  istorically  and  predominantly  black  land  grant  insotunon, 
wants  to  do  something  immediately  to  find  a  cure  for  this  disease.  Southern  has  begun  taking 
steps  to  identify  a  remedy  for  this  nalady. 


Located  in  Baton  Rouge, 
has  been  graduating  scholars  and 
for  113  years.  It  has  a  long  track 
some  of  whom  go  on  to  attend 
the  sciences,  including  chemistry 


morfe  than  16.663  students  attend  Southern  University.  Southern 

sen  ling  them  out  into  the  national  and  international  workforces 

re  cord  of  graduating  students  with  degrees  in  basic  sciences, 

medic  al  school.  Others  receive  advanced  degrees  in  research  and 

aqd  biology. 


aid 


The  National  Aeronautics 
acknowledged  Southern's  research 
American  scholars.  Senator  Mikulfcki 
Administration  and  the  Department 
grant  to  develop   an  aerospace  eh] 
Engineering.  This  is  just  one  examal 
and,  the  type  of  federal  recognition]the 


Space  Administration  and  Department  of  Energy  have 
capability  and  its  important  role  in  educating  African 

just  last  year,  the  National  Aerospace  and  Science 

of  Energy  awarded  the  institution  a  five-year,  S5  million 

>gineering  undergraduate  option  in  the  Department  of 

e  of  the  type  of  federal  support  the  institution  has  received 

institution  receives  for  academic  excellence. 


As  the  nation's  largest  HBCTJ  and  one  that  is  located  in  the  state  with  the  largest 
percentage  of  sickle  cell  victims,  5  outbern  has  •^tr"nittr*i  its  resources  to  finding  a  cure  for 
Sickle  Cell  disease.  Toward  this  « ad,  the  University  assembled  on  its  campus  for  a  two-day 
work  session,  the  foremost  experts  n  the  fields  of  biomedical  research,  psychosocial  research, 
pediatric  hematology,  oncology,  ar  d  related  fields.  (The  attendees  and  notes  from  the  work 
sessions  are  contained  in  the  back  c  f  the  Rural  Community  Health  Service  Project,  which  you 
have  been  provided.)  The  group  de  reloped  a  proposed  curriculum  for  the  Center,  a  set  of  goals 
and  a  timetable  for  launching  the  N  ational  Research  Center.  It  was  resolved  that  the  National 
Sickle  Cell  Research  Center  at  Sjuthern  would  conduct  collaborative  research  with  other 
Louisiana  universities,  agencies  am  I  medical  schools.  The  group  resolved  that  the  Center  will 
later  collaborate  with  other  universities  and  agencies  in  the  region,  and  across  the  nation.  The 
work  group  also  discussed  the  ways  at*  means  of  budding  a  state-of-the-art  Sickle  Cell  Research 
center.  Southern  alumnae,  loundadons,  corporanons,  state  and  federal  funds  were  targeted  for 
support  of  the  project. 

Southern  is  taking  affirmative  steps  to  prepare  its  faculty  for  the  coming  of  the  Center 
Faculty  internships  have  been  conducted  on  Southern's  campus  in  the  area  of  Sickle  Ceil 


58 


Anemia.  For  one  week,  faculty 
the  sickle  cell  disease. 


attend 


i  lectures  conducted  by  the  nation's  foremost  experts  on 


Evidencing  its  support  for  th*  National  Cenicr,  the  Louisiana  State  Legislature  passed  a 
bill  which  I  authored,  committing  S{1  million  to  the  effort:  an  initial  SI. 5  million  in  start  up 
funds;  and  S5.5  million  for  capitol  butlay  to  be  used  toward  building  a  research  center.  This 
latter  appropriation  is  contingent  upoi  1  Southern' s  receiving  a  three-to-one  match  from  the  federal 
government. 

CONCLUSION 

Mr.  Chairman,  as  I  sit  here  tpday,  a  little  more  than  one  year  after  the  National  Center's 
launching  meeting  at  Southern,  in  addition  to  the  S7  million  committed  to  the  effort  by  the  state 


of  Louisiana,     Southern  is  obtaini 
corporations  and  foundations, 
collaboration  agreements  with  LSU 
miles  from  Southern.     I'm  here 
collaborative  public/private  venture 
of  Americans  who  are  impacted  by 


.ig  financial  commitments  for  the  Center  from  alumnae. 
Southern  has  faculty,  research  staff  commitments  and 
ind  Earl  K.  Long  Hospital,  which  are  located  less  than  five 
loday  to  ask  the  federal  government  to  join  us  in  the 
:o  help  us  turn  the  lives  around  of  the  tens  of  thousands 
Sickle  Ceil  Anemia.  Join  in  our  partnership  to  find  a  cure 


for  Sickle  Cell  Anemia  tomorrow,  >y  investing  $21  million  today 

This  investment  will  help  the  State  of  Louisiana  and.  the  Delta  Region  take  the  first  step 
toward  launching  its  regional  health  ind  economic  development  corridor-both  of  which  are  sorely 
oeeded  to  bring  relief  to  this  beleaguered  region.  For,  as  long  as  the  Delta  is  suffering,  America 
will  suffer.  As  long  as  there  is  poverty  in  the  Delta,  the  region  of  New  Pngiand  won't  be  rich. 
As  long  as  disease  is  rampant  and  thousands  of  people  in  the  Delta  cannot  expect  to  live  to  be 
twenty  or  thirty  years,  the  people  cf  Minneapolis  can  never  be  totally  healthy  even  if  they  get 
a  good  check  up  at  the  Mayo  Clinic  Senator  Durenburger.  For  we  can  never  be  what  we  ought 
to  be  until  the  "least  of  these"  are  'that  they  ought  to  be.  We  are  interdependent  No  man  or 
woman  stands  alone.  Senator  Kennedy,  Members  of  this  Commioee,  please  stand  with  Southern 
University,  the  State  of  Louisiana,  the  Delta  Economic  Energy  District,  the  Congressional  Black 
Caucus,  the  National  Black  Caucus  of  State  Legislators,  the  National  Baptist  Convention,  USA, 
the  National  Rainbow  Coalition  an|l  the  50,000  Americans  whose  lives  are  adversely  affected 
by  Sickle  cell  Anemia,  on  the  isaic  of  funding  a  National  Sickle  Cell  Research  Center  at 
Southern  University. 


I  thank  you;   and  I  will  be  nappy  to  entertain  any  questions  you  may  have. 


59 


2^m.mii'a*  a—  Kunmn  — ui  ^.ttCAt  -v~-^ui 


JON  0.  JOHNSON 

CAo/rmon 
MA«TY  J.  CHAiHT 

Gr*oon>  J.  Sorro 

Jim  Cax 
Willi*  C.-oin 
Oswald  0*cvir 
Marc  H.  Mortal 
CkiI  Pieoro1 
John  Saunaan 

77m  Honorable  Donna  Shahia 
Secretary,  Department  of  Hearth 
and  Human  Services 
200  Independence  Avenue,  SW 
Washington,  D.C.  20201 


Dear  Secretary  Shaiata: 


:i0*t  U2-:o*i 


LAJi  i.  arvjcm 


MfeVC/l  JO,  1993 


J*N<2  MUCHt5 


During  the  1992  Louisiana  Legisiative  Regular  Session,  7.5  million  was 
appropriated  lor  start-up  funding,  planning  and  designing  the  first  National 
Research  Center  for  SickleiCell  Anemia  in  the  United  States, 

As  Chairman  of  the  Revenue  and  Fiscal  Affairs  Committee  for  the  Louisiana  State 
Senate,  please  know  mat  m  plan  to  amend  the  Capital  Outlay  bill  this  session  to 
Include  5  J  million  dollars  tor  the  First  National  Sickle  Cell  Anemia  Research  Center 
at  Southern  University  •  Baton  Rouge,  Louisiana. 


is  natidr, 


As  you  know,  there  Is  national  support  for  the  Research  Center  and  Its  purpose, 
which  is  to  research,  to  develop  and  to  conduct  a  nationally  recognized  short  and 
long  range  program  that  will  delve  into  the  causes  of  Sickle  cell  disease  and  its 
cure.  The  Research  Center  will  be  domiciled  at  Southern  University  In  Baton 
Rouge  and  establish  a  cooperative  relationship  with  the  Department  of  Health  and 
Hospitals,  other  Universities,  National  and  International  Associations  and  Agencies 
interested  In  the  Research  center. 

Thank  you  tor  your  conspiration  of  this  matter. 


Very  Truly  Yours, 


Jon  D.  Johnson 
Chairman 


60 


3ouc-n«m    ■JnJ.v«rsity,     latan    .i.ouq«,     Ju.Uirj 
Maclaaal    sicx_L«   Call   An—la    iueirc".  Cantar 


JOtn   District, /Taxas 

V1U1M  Clay       / 

lac  an  triers,    Ulsaouxi    j 


rXon*\ld  7.   3»lluasT 
3«n  District,   Caliiorala 


5th   District,   itissouri 
Sth   3l»erlct.    laor^l* 


Craig  a.    waaninetan. 
L8tn  District.  ?«u« 


/Luclsn   31actw«il 
Sad  district,   Pennsylvania 

I 

carol  :^o»«iaY/6fc*un 
U.S.    Sanata,  fliiaoia 

;arriao  3rswn/ 

3rd  District y  Tlorida 

Smrl  Milliard 

7th  District,  Alabama 


ilcs«  Hasting"  y 

lara^Dlstrict.    ?lprtda 


/Sax&ara-Ross  Coilins^"^ 


■^i  <«y  c.  Dixon 
j5Btf"Diatrirt,    Calixorai* 


ai-pftaj   Towns 
.Ota  District,   *«v  Tor* 


Donald  M.   ?ayn« 

icth  District,   Maw  jaravy 


5tS  ilstrict. 


lonnsctirut 


tlaanor  Holaaa-Horton 
Siatrict   ai   Caluaoia 

Sva  X.    Clayton     y 

1st   District,   .ions  Carolina 

?  & 

a     r>  >  ;?■  ,.     i 

Sanxoro  D.    3i*aop     I  /  / 
2aflF-oifctrict,  SsorgU  / 


»s   S.   Cly&nm  / 

5th  District,    south-  C*roli.T* 


Carrie  ?.   xm* 

17ts«»3istrict.   riojjios 


xsirta 

2nd  District,  'Illinois 


61 


waller  ?ocJe»r,   1X2 


AU»rt  '<*ym»  " 

*«»  Otstzicc,   Maryland 


Rob*^*^— Scott 

3rd  3i«*rict,  vtrtjiaia 

.lelvin  w«tc 

:2th  Di*tricc,   NortA  Carolina 


(SENATE 

STA71E    OF    LOUISIANA 


CHARLES  0.  JONES 
MarwiM 

FandMtal- 
!  «Uand.  Em,  Coral.  TcnMl. 


Ul  DCSIMO  STREET  JUITtlli 
MONROt.  lOUBUNA  71 201 


COMMITTEES: 

S*noM> aW  Gi'ihiipwhj  AHam. 
vk»  ChaMinm 
MfM 
r  t 


A  CONCURRENT   RESOLUTION 


r  M  I' 

:o w  Ouaor 
Hid 


To  urge  and  reguestj  the  members  or  the  National  Baptist 
Convention,  U.S.A.,  Inc.  to  take  the  necessary  steps  to  support  the 
National  Sickle  Call  Disease  Research  Center  located  at  Southern 
University  and  Agricultural  and  Mechanical  College  in  Baton  Rouge, 
Louisiana . 

FURTHER,  to  set  aside  one  Sunday  annually  for  ail  churches 
belonging  to  the  National  Baptist  Convention,  U.S.A.,  Inc.  to 
recognize  and  financially  contribute  to  the  research  program  of  the 
"National  Sickle  Ceil  Disiease  Research  Center."  On  this  Sunday, 
member  churches  will  take  part  in  a  "One  Great  Hour  of  Sharing" 
special  offering  to  be  donated  to  the  Research  Center  in  its  vorfc 
toward  eradicating  3icklej  cell  disease. 

WHEREAS,  there  is  no  national  center  exclusively  devoted  to 
sickle  cell  disease  research  currently  existing  in  the  United 
States;  and 

WHEREAS,  the  Congressional  Black  Caucus,  consisting  of  4a 
members  of  the  United  States  Congress  unanimously  is  in  support  of 
•etablishing  a  national  sickle  cell  disease  research  center  on  the 
campus  of  Southern  Univerjsity;  and 

WHEREAS,  during  its f 1992  Legislative  Session,  the  Louisiana 
Legislature  created  a  National  Sickle  Cell  Anemia  Research  Center 
under  the  leadership  of  Senator  Charles  D.  Jones,  and  funded  it 
with  $1.5  million  for  planning  and  development  and  a  $5 . 5  million 
outlay. commitment  to  begin  construction;  and 


jia 


WHEREAS,  President-elect  Bill  Clinton  has  committed  his 
support  for  the  establishment  of  a  national  sickle  cell  research 
center  on  the  campus  of  southern  University  and  has  committed  to 
appropriate  a  three  to  dne  match  of  the  State  of  Louisiana's  $7 
million,    in  the  amount  o±   $21  million;   and 

WHEREAS,  the  National  Black  Caucus  of  State  Legislators  has 
commended  the  Louisiana  Legislative  31ack  Caucus,  the  State  of 
Louisiana  and  Senator  Charles  D.  Jones,  lead  author,  for  passing 
legislation  and  for  funding  the  creation  of  the  nation's  first 
National    Sickle   Cell    Aneaia  Research  Center;    and 


BOSTON  PUBLIC  LIBRARY 


62     3  9999  05982  600  6 


WHEREAS,  the  National  31ack  Caucus  of  Stare  Legislators 
supports  the  efforts  of  the  Louisiana  State  Black  Caucus  to 
establish  thia  research  center  at  Southern  University  at  3aton 
Rouge,  Louisiana;  and 

WHEREAS,  only  the  sra^ll  amount  of  $15  million  is  contributed 
annually  by  the  federal  government  to  research  sickle  cell  disease; 
and 

WHEREAS,  one  in  ten  African  Americans  carries  a  gene  for 
sickle  hemoglobin,  and  one  in  every  five  hundred  black  nevroorns  in 
the  United  States   has  sickle  cell;  and 

WHEREAS,  all  newborns  at  risk  should  be  screened  for  3ickle 
cell  disease  to  permit  iarlier  diagnosis  and  treatment  and  to 
significantly  reduce  illness  and  the  death  rate  among  those 
children  with,  the  disease t  .and 

WHEREAS,  there  existjs  a  need  to  emphasize  the  importance  of 
early  detection  and  educate  the  primary  medical  care  providers , 
parents  and  community  jsn  the  importance  of  timely  medical 
management  of  those  patients  with  this  inherited  diseaoe;  and 

WHEREAS,  sickle  celij  disease  is  one  of  the  least  understood 
diseases  of  our  time,  vhLch  presently  has  no  cure  and  continued 
research  into  its  causes  and  cure  is  vital;  and 

I 

WHEREAS,  the  establishment  of  a  research  center  for  such 
purposes  would  certainly  enhance  the  programs  currently  in  place  by 


broadening  the  resource 


committed  to  finding  relisf  for  the  unfortunate  victims  who  suffer 


base  for  research  using  those  experts 


serious  and  life- threatening  disease. 

resolved   that   the   National   Baptist 
hereby  urges  and  requests  its  members  to 


the  consequences  of  this 

THEREFORE ,   BE   IT 
Convention,  U.S.A.,  Inc.  nereoy  urges  ana  requests  its  meraoers  to 
take  the  necessary  steps  to  support  the  national  sickle  cell 
disease  research  center  at  Southern  University  and  Agricultural  and 
Mechanical  College  in  Bation  Rouge,  Louisiana. 

BE  IT  RESOLVED  that  a  copy  of  this  Resolution  be  transmitted 

_to  sach_  member  church,  leach  member  of  the  Congressional  31ack 

"Caucus"  of  the  United  Stages  Congress ,  each  member  of  the  National 

Association  of  Black  State  Legislators   and  the  President  of  the 

United  States . 


LtbtK)    £>  tf/iZrusr^ 


Senator  Wellstone.  Thank  you  very  much.  The  committee  is  ad- 
journed. 

[Whereupon,  at  3:36  p.m.,  the  committee  was  adjourned.] 


82-553    (68) 


ISBN   0-16-044846-8 


9  780160"448461 


90000