ui CHEMICAL EMBRYOLOGY IN THREE VOLUMES VOL. I New Tork The Macmillan Co. London The Cambridge University Press Bombay, Calcutta and Madras Macmillan and Co., Ltd. Toronto The Macmillan Co. of Canada, Ltd. All rights reserved i" f) ^ 4' Vir PraecLarissinius GULIELMUS HARVEY. Mysterii Generationis Indaqator Diliqens. Q) r^^Lji(iJ<^i~^4^(tJ^^^i~^^L3(*J<^^>^L3(*^^ 0 CHEMICAL EMBRYOLOGY BY JOSEPH NEEDHAM M. A., Ph.D. Fellow ofGonville & Cains College, Cambridge, and University Demonstrator in Biochemistry VOLUME ONE NEW YORK: THE MACMILLAN COMPANY CAMBRIDGE, ENGLAND: AT THE UNIVERSITY PRESS 1931 3 'j>^t>r^^t>r^)(r>^t>f7)(j>^t>r^cp^^ ^ / PRINTED IN GREAT BRITAIN JOSEPHO NEEDHAM in Univ. Aberdon. Anat. olim Professori FREDERIGO GULIELMO SANDERSON Schol. Undel. olim Praeposito HUGONI KERR ANDERSON Coll. Gonv. et Caii olim Custodi FREDERIGO GOWLAND HOPKINS Artis chemicae ad animantia spectantis in Univ. Cantabrig. Professori et DOROTHEAE MOYLE hanc suam disquisitionem auctor sacram voluit For more, and abler operations are required to the Fabrick and erection of Living creatures, than to their dissolution, and plucking of them down : For those things that easily and nimbly perish, are slow and difficult in their rise and complement. William Harvey, Anatomical Exercitations concerning the generation of living creatures, London, 1653, Ex. XLi, p. 206. That discouraging Maxime, Nil dictum quod non dictum prius, hath little room in my estimation, nor can I tye up my belief to the Letter of Solomon ; I do not think, that all Science is Tautology; these last Ages have shown us, what Antiquity never saw; no, riot in a dream. Joseph Glanville, Scepsis Scientifica, an essay of the vanity of dogmatizing, and confident opinion, London, 1 66 1, Chap. XXII. CONTENTS VOLUW Prolegomena page 2 PART I The Theory of Chemical Embryology Philosophy, Embryology, and Chemistry 7 The Historical Perspective 10 Obstacles to Chemical Embryology 1 3 The Stumbling-block of Hormism 1 4 Finalism as a Rock of Offence 1 6 Organicism as an Occasion of Falling 25 Organicism and Emergence 3^ Neo-Mechanism as a Theory for Chemical Embryology 32 PART II The Origins of Chemical Embryology Preliminary Note 41 Section i . Embryology in Antiquity 44 I • I . Non-Hellenic Antiquity 44 1-2. Hellenic Antiquity; the Pre-Socratics 50 1-3. Hippocrates; the Beginning of Observation 53 1-4. Aristotle ^g 1-5. The Hellenistic Age 77 1-6. Galen 85 Section 2. Embryology from Galen to the Renaissance gi 2-1. Patristic, Talmudic, and Arabian Writers gi 2-2. St Hildegard; the Lowest Depth g^ 23. Albertus Magnus gy 2-4. The Scholastic Period 103 2-5. Leonardo da Vinci 1 07 2-6. The Sixteenth Century; the Macro-iconographers I lO NE h '> i / i\ '\ ^ , VUl CONTENTS Section 3. Embryology in the Seventeenth and Eighteenth Centuries page 125 3-1. The Opening Years of the Seventeenth Century 1 25 32. Kenelm Digby and Nathaniel Highmore 1 29 3-3. Thomas Browne and the Beginning of Chemical Embryology 135 3-4. William Harvey 138 35, Gassendi and Descartes; Atomistic Embryology 1 56 36. Walter Needham and Robert Boyle 1 60 3-7. Marcello Malpighi; Micro-iconography and Preformationism 166 3-8. Robert Boyle and John Mayow 169 3-9. The Theories of Foetal Nutrition 176 3-10. Boerhaave, Hamberger, Mazin 1 82 3-11. Albrecht v. Haller and his Contemporaries 1 88 3-12. Ovism and Animalculism 1 99 3- 1 3. Preformation and Epigenesis 205 3-14. The Close of the Eighteenth Century 215 3-15. The Beginning of the Nineteenth Century 220 PART III General Chemical Embryology Preliminary Note Section i. The UnfertiUsed Egg as a Physico-chemical System 1 . Introduction 2. General Characteristics of the Avian Egg 3. The Proportion of Parts in the Avian Egg 4. Chemical Constitution of the Avian Egg as a Whole 5. The Shell of the Avian Egg 6. The Avian Egg-white 7. The Avian Yolk 8. The Avian Yolk-proteins 9. The Fat and Carbohydrate of the Avian Yolk 10. The Ash of the Avian Egg 1 1 . General Characteristics of non-Avian Eggs 12. Egg-shells and Egg-membranes 13. Proteins and other Nitrogenous Compounds 14. Fats, Lipoids, and Sterols 15. Carbohydrates 16. Ash 231 232 232 232 236 242 255 265 280 287 294 302 306 321 331 346 355 357 CONTENTS IX Section 2. On Increase in Size and Weight page 368 368 2-1. Introduction 2-2. The Existing Data 369 2-3. The General Nature of Embryonic Growth 383 2-4. The Empirical Formulae 389 2-5. Percentage Growth-rate and the Mitotic Index 399 2-6. Yolk-absorption Rate 405 2 '7. The Autocatakinetic Formulae 408 2-8. Instantaneous Percentage Growth-rate 420 2-9. Growth Constants 434 2-10. The Growth of Parts 440 2-1 1. Variability and Correlation 455 2-12. Explantation and the Growth-promoting Factor 460 2-13. Incubation Time and Gestation Time 470 2-14. The Effect of Heat on Embryonic Growth 498 2-15. Temperature Coefficients 503 2 • 1 6. Temperature Characteristics 515 2-17. The Effect of Light on Embryonic Growth 533 2-i8. The Effect of X-rays and Electricity on Embryonic Growth 536 2-19. The Effect of Hormones on Embryonic Growth 538 Section 3. 3-1 3-2 33 3-4 3-5 3-6 37 3-8 3-9 On Increase in Complexity and Organisation The Independence of Growth and Differentiation Differentiation-rate Chemical Processes and Organic Form The Types of Morphogenetic Action Pluripotence and Totipotence Self-differentiation and Organiser Phenomena Functional Differentiation Axial Gradients Organised and Unorganised Growth 3-10. Chemical Embryology and Genetics 541 541 544 552 559 567 570 580 582 606 608 VOLUM] Section 4. The Respiration and Heat-production of the Embryo 615 4- 1 . Early Work on Embryonic Respiration 6 1 5 4-2. Respiration of Echinoderm Embryos in General 623 4-3. Rhythms in Respiratory Exchange 64 1 6-2 X CONTENTS Section 4-4. Heat Production and Calorific Quotients of Echinoderm page 649 Embryos 4-5. Respiration of Annelid, Nematode, Rotifer, and Mollusc 659 Embryos 46. Respiration of Fish Embryos 665 47. , Respiration of Amphibian Embryos 67 1 4-8. Heat-production of Amphibian Embryos 682 49. Respiration of Insect Embryos 687 4- 1 o. Respiration of Reptile Embryos 692 4-11. Respiration of Avian Embryos in General 693 4-12. Heat-production of Avian Embryos 7^4 4-13. Later Work on the Chick's Respiratory Exchange 7^8 4- 1 4. The Air-space and the Shell 7 1 9 4-15. Respiration of Mammalian Embryos 726 4" 1 6. Heat-production of Mammalian Embryos 732 4-17. Anaerobiosis in Embryonic Life 742 ^, 4" 1 8. Metabolic Rate in Embryonic Life 746 4-19. Respiratory Intensity of Embryonic Cells fn wVro 755 4-20. Embryonic Tissue-respiration and Glycolysis 758 4-21. The Genesis of Heat Regulation 772 4-22. Light-production in Embryonic Life 776 Section 5. Biophysical Phenomena in Ontogenesis 777 5-1. The Osmotic Pressure of Amphibian Eggs 777 5-2. The Genesis of Volume Regulation , 786 53. The Osmotic Pressure of Aquatic Arthropod Eggs 790 54. The Osmotic Pressure of Fish Eggs 793 5-5. Osmotic Pressure and Electrical Conductivity in Worm and 799 Echinoderm Eggs 5-6. The Osmotic Pressure of Terrestrial Eggs 8l2 5-7. Specific Gravity 820 5-8. Potential Differences, Electrical Resistance, Blaze Currents 825 and Cataphoresis 5-9. Refractive Index, Surface Tension and Viscosity 833 Section 6. General Metabolism of the Embryo 839 6-1. The j&H of Aquatic Eggs 839 6-2. The j&H of Terrestrial Eggs 855 63. rH in Embryonic Life 865 6-4. Water-metabolism of the Avian Egg 870 CONTENTS xi Section 6-5. Water-content and Growth-rate page 883 6-6. Water-absorption and the Evolution of the Terrestrial Egg 889 6-7. Water-metabolism in Aquatic Eggs 906 6-8. The Chemical Constitution of the Embryonic Body in Birds 911 and Mammals 69. Absorption-mechanisms and Absorption-intensity 917 6- 10. Storage and Combustion; the Plastic Efficiency Coefficient 934 6-1 1. Metabolism of the Avian Spare Yolk 939 6-12. Maternal Diet and Embryonic Constitution 943 Section 7. The Energetics and Energy-sources of Embryonic Development 946 7-1. The Energy Lost from the Egg during Development 946 7-2. Energy of Growth and Energy of Differentiation 956 7-3. The Relation between Energy Lost and Energy Stored 962 7-4. Real Energetic Efficiency • 969 7-5. Apparent Energetic Efficiency 972 7*6. Synthetic Energetic Efficiency 98 1 7-7. The Sources of the Energy Lost from the Egg 986 Sections. Carbohydrate Metabolism 1000 8-1. General Observations on the Avian Egg lOOO 8-2. Total Carbohydrate, Free Glucose, and Glycogen lOOl 8-3. Ovomucoid and Combined Glucose 1 007 8-4. Carbohydrate and Fat 1014 8-5. The Metabolism of Glycogen and the Transitory Liver 1018 8-6. Free Glucose, Glycogen, and Insulin in the Embryonic Body IO29 8-7. General Scheme of Carbohydrate Metabolism in the Avian Egg 1035 8-8. Embryonic Tissue Glycogen 1 036 8'9. Embryonic Blood Sugar 1039 8- 10. Carbohydrate Metabolism in Amphibian Development 1043 8*i I. Carbohydrate Metabolism of Invertebrate Eggs I047 8-12. Pentoses 1 05 1 8-13. Lactic Acid 1 051 8-14. Fructose 1054 Section 9. Protein Metabolism 1055 9* I. The Structure of the Avian Egg-proteins before and after 1055 Development 9*2. Metabolism of the Individual Amino-Acids I059 9-3. The Relations between Protein and non-Protein Nitrogen 1065 9-4. The Accumulation of Nitrogenous Waste Products 10 76 xii CONTENTS Section 9-5. Protein Catabolism page 9-6. Nitrogen-excretion; Mesonephros, Allantois, and Amnios 9-7. The Origin of Protective Syntheses 9*8. Protein Metabolism of Reptilian Eggs 9-9. Protein Metabolism of Amphibian Eggs 9' 10. Protein Metabolism in Teleostean Ontogeny 9-11. Protein Metabolism in Selachian Ontogeny 9* 1 2. Protein Metabolism of Insect, Worm, and Echinoderm Eggs 9-13. Protein Utilisation in Mammalian Embryonic Life 9-14. Protein Utilisation of Explanted Embryonic Cells 9-15. Uricotelic Metabolism and the Evolution of the Terrestrial Egg Section 10. The Metabolism of Nucleins and Nitrogenous Extractives [O-i. Nuclein Metabolism of the Chick Embryo IO-2. The Nucleoplasmatic Ratio [0-3. Nuclein Synthesis in Developing Eggs [0-4. Creatinine, Creatine, and Guanidine Section 11. Fat Metabolism I • I . Fat Metabolism of Avian Eggs 1-2. Fat Metabolism of Reptilian Eggs I •2- Fat Metabolism of Amphibian Eggs I -4. Fat Metabolism of Selachian Eggs 1-5. Fat Metabolism of Teleostean Eggs 1-6. Fat Metabolism of Mollusc, Worm, and Echinoderm Eggs 1-7. Fat Metabolism of Insect Eggs 1-8. Combustion and Synthesis of Fatty Acids in Relation to Metabolic Water 1 1 -9. Fat Metabolism of Mammalian Embryos Section 12. The Metabolism ofLipoids, Sterols, Cycloses, Phosphorus and Sulphur 1 2- 1. Phosphorus Metabolism of the Avian Egg 12-2. Tissue Phosphorus Coefficients I2'3. Choline in Avian Development 12-4, The Metabolism of Sterols during Avian Development 1 2*5. The Relation between Lipoids and Sterols; the Lipocytic Coefficient 12-6. Cycloses and Alcohols in Avian Development 12-7. Sulphur Metabolism of the Avian Egg 12-8. Phosphorus, Sulphur, Choline, and Cholesterol in Reptile Eggs CONTENTS Section 12-9. Lipoids and Sterols in Amphibian Eggs page 1237 12-10. Lipoids, Sterols, and Cycloses in Fish Eggs 1239 i2'ii. Phosphorus, Lipoids and Sterols in Arthropod Eggs 1241 12-12. Phosphorus, Lipoids, and Sterols in Worm and Echinoderm 1243 Eggs 12-13. Lipoids and Sterols in Mammalian Development 1252 Section 13. Inorganic Metabolism 1255 [ 3- 1 . Changes in the Distribution of Ash during Avian Development 1 255 32. Calcium Metabolism of the Avian Egg 1260 33. Inorganic Metabolism of other Eggs 1 268 3-4. The Absorption of Ash from Sea-water by Marine Eggs 1 27 1 3-5. The Ani on/Cation Ratio 1 2 74 3-6. Inorganic Metabolism of Mammalian Embryos 1277 3-7. Calcium Metabolism of Mammalian Embryos 1285 Section 14. Enzymes in Ontogenesis 1289 4-1. Introduction 1 289 4-2. Enzymes in Arthropod Eggs 1290 4-3. Enzymes in Mollusc, Worm, and Echinoderm Eggs 1293 4-4. Enzymes in Fish Eggs 1 295 4-5. Enzymes in Amphibian Eggs 1300 4-6. Enzymes in Sauropsid Eggs 1303 4-7. Changes in Enzymic Activity during Development 1307 4-8. Enzymes of the Embryonic Body 1 3^0 4-9. Enzymes in Mammalian Embryos 13 12 4-10. The Genesis of Nucleases 1326 4-11. Foetal Autolysis 1 329 Section 15. Hormones in Ontogenesis 1335 5-1. Introduction 1335 5-2. Adrenalin ^337 53. Insulin 1342 5-4. The Parathyroid Hormone 134^ 5-5. The Hormones of the Pituitary 134^ 5-6. Secretin 134^ 5-7. Thyroxin 134^ 5-8. Oestrin and other Sex Hormones • 1353 VOLUM xiv CONTENTS Section i6. Vitamins in Ontogenesis page 1359 [6-1. Vitamin A 1359 [6-2. Vitamin B 1360 [6-3. Vitamin C 1 360 [6-4. Vitamin D 1 360 [6-5. Vitamins in Mammalian Development 1 363 [6-6. Vitamin E 1 365 Section 17. Pigments in Ontogenesis 1368 [7-1. The Formation of Blood Pigments 1 368 [7-2. The Formation of Bile Pigments 137^ [7-3. The Formation of Tissue Pigments 1 375 [7-4. The Pigments of the Avian Egg-shell 137^ [7-5. The Pigments of the Avian Yolk 1378 [7-6. Egg-pigments of Aquatic Animals 1380/ [7-7. Melanins in Ontogenesis 13^^ Section 18. Resistance and Susceptibility in Embryonic Life 1383 •I. Introduction 1 3^3 •2. Standard Mortality Curves 1 3^3 [8-3. Resistance to Mechanical Injury ^3^5 $-4. Resistance to Thermal Injury 1 388 5-5. Resistance to Electrical Injury ^392 [8-6. Resistance to Injury caused by Abnormal j&H 1 397 5-7. Resistance to Injury caused by Abnormal Gas Concentrations 1 399 (non-Avian Embryos) !-8. Critical Points in Development 1 409 !-g. Resistance to Injury caused by Abnormal Gas Concentrations 1 4 1 4 (Avian Embryos) >-io. Resistance to Injury caused by Toxic Substances 1420 ••I I. Resistance to Injury caused by X-rays, Radium Emanation, 1 43 1 and Ultra-violet Light Section 19. Serology and Immunology in Embryonic Life 1444 ig-i. Antigenic Properties of Eggs and Embryos ^444 19-2. The Formation of Natural Antibodies 1446 19-3. The Natural Immunity of Egg-white ^447 19-4. Inheritance of Immunity in Oviparous Animals HS^ 19-5. Serology and Pregnancy 1452 19-6. Resistance of the Avian Embryo to Foreign Neoplasms 1 454 CONTENTS XV Section 20. Biochemistry of the Placenta page 14.^6 20-1. Introduction 1 45" 20-2. General Metabolism of the Placenta 145^ 20-3. Placental Respiration 1 46 1 20-4. Nitrogen Metabolism of the Placenta 1 462 20-5. Carbohydrate Metabolism of the Placenta 14^9 20-6. Fat and Lipoid Metabolism of the Placenta 1472 20-7. Placental Enzymes 1481 Section 21. Biochemistry of the Placental Barrier 1485 2 1 • I . The Autonomy of the Foetal Blood 1 4^5 21-2. Evolution of the Placenta -4^7 21-3. Histotrophe and Haemotrophe 149^ 21-4. Mesonephros and Placenta 1 493 21-5. Colostrum and Placenta ^497 21-6. Placental Transmission and Molecular Size 1497 21-7. QuaHtative Experiments on Placental Permeability 1 505 21-8. The Passage of Hormones 15^^ 2 1 -9. Factors Governing Placental Transmission 15^2 2I-IO. Quantitative Experiments on the Passage of Nitrogenous 15 14 Substances 2 1 -I I. Quantitative Experiments on the Passage of Phosphorus, Fats, 1520 and Sterols 2i'i2. Quantitative Experiments on the Passage of Carbohydrates 1525 2i*i3. Quantitative Experiments on the Passage of Ash 1 52 7 21-14. The Passage of Enzymes 15^9 2i*i5. The Unequal Balance of Blood Constituents 1530 Section 22. Biochemistry of the Amniotic and Allantoic Liquids 1534 22-1. Introduction 1 534 22-2. Evolution of the Liquids ^535 22-3. Avian Amniotic and Allantoic Liquids 1 537 22-4. Amount and Composition of Mammalian Amniotic and Allan- 1539 toic Liquids 22-5. Maternal Transudation and Foetal Secretion 154^ 22-6. Interchange between Amniotic and Allantoic Liquids 15^2 22-7. Vernix Caseosa 1 5^4 Section 23. Blood and Tissue Chemistry of the Embryo 1565 23-1. Blood 1565 23-2. Lung 1 57 1 23-3. Muscle 1574 xvi CONTENTS Section 23-4. Heart 23'5- Nervous Tissue 23-6. Connective Tissue 237. Lymph 23-8. Sense Organs 23-9- Intestinal Tract Section 24. Hatching and Birth 24-1. Introduction 24-2. Hatching Enzymes 24-3. Osmotic Hatching 24-4. Egg-breakers 24-5- Hatching of the Avian Egg 24-6. MammaUan Birth page 1577 1583 1592 1593 1594 1594 1595 1595 1595 1600 1602 1602 1605 Epilegomena The Two Problems of Embryology 1 6 1 3 The Cleidoic Egg and its Evolution 16 1 3 Chemical Synthesis as an Aspect of Ontogeny 1 623 Biochemistry and Morphogenesis 1 624 Transitory Functions in Embryonic Life 1627 The Theory of Recapitulation 1629 Recapitulation and Substitution ' 1632 Chemical Recapitulation 1638 Provisional Generalisations for Chemical Embryology 1 647 The Organisation of Development and the Development of Organisation 1659 The Future of Embryology 1 664 PART IV Appendices i. Normal Tables of Magnitudes in Embryonic Growth 1669 ii. A Chemical Account of the Maturation of the Egg-cell 1679 iii. The Chemical Changes during the Metamorphosis of Insects (by 1685 Dorothy Needham) iv. The Development of the Plant Embryo from a Physico-chemical View- 1 7 1 1 point (by Muriel Robinson) PART V Bibliography and Author-Index Subject-Index Index Animalium 1725 1971 2013 PLATES VOLUME I William Harvey frontispiece I. Primitive methods of incubation : (A) Egyptian, (B) Chinese facing page 46 II. The oldest known drawing of the Uterus (gth century) . „ „ 82 III. Illustration from the Liber Scivias of St Hildegard (ca. 1150A.D.) jj J3 96 IV. A page from Leonardo da Vinci's Anatomical Notebooks (ca. 1490 A.D.) ........„„ 108 V. Illustration from the De Formatione Ovi et Pulli of Fabricius (1604) „ „ 116 VI. Illustration {rom Highmore's History of Generation {16^1) . „ „ 134 VII. Illustrations from Malpighi: i)e Or;o in^M^a/o (1672) . ,, „ 168 VIII. Reaumur's Illustration of his Incubators (1749) . . „ „ 198 IX. Microphotograph of the yolk of the hen's egg at the time of laying, to show the vitelline globules . . . . ,, ,, 236 X. Microphotograph of the yolk of the hen's egg, not yet liberated from the ovary, to show the stratification . . „ ,, 288 VOLUME II The frontispiece of William Harvey's Generation of Ani- mals ( 1 65 1 ) ; Zeus liberating living beings from an egg . frontispiece XI. Microphotograph of the yolk of the hen's egg at the eleventh day of incubation, showing its heterogeneous state .......... facing page 836 XII. Microphotograph of the yolk of the hen's egg at the second day of incubation, showing the cholesterol esters . . „ ,,1218 VOLUME III An embryological investigation in the eighteenth century frontispiece TABLES 27. Ash of the avian egg .... 34. Distribution of amino-acids in egg-proteins 47. Ash content of egg . 195. Enzymes in the hen's egg 199. Enzymes in the human embryo 201. Enzymes in the pig embryo 220. Placental enzymes . 227, Passage of substances through the placenta Appendix 1, Table 3. Embryonic growth of the hen facing page 302 »5 55 330 .J 55 356 55 55 1304 55 55 I3I4 55 55 I316 55 55 1469 55 5' 1506 55 5? 1670 ACKNOWLEDGEMENTS OF INDEBTEDNESS THOSE who have assisted me in the preparation of this work are so numerous that it is impossible to mention them all by name. Its original impetus was derived from a discussion with Professor Sir F. G. Hopkins in 1923 on the observation of Klein that inositol, though absent from the undeveloped hen's egg, was present in considerable quantity at hatching; and throughout the period of preparation his encouragement, help, and advice were never-failing. I have derived great benefit from the discussion of various points with Miss Marjory Stephenson, M. Louis Rapkine, Dr R. A. Fisher, and my wife. Professor J. T. Wilson has been repeatedly helpful to me on anatomical points, and in the Zoological Laboratory I was always sure of obtaining expert advice from Mr James Gray, Mr J. T. Saunders, Mr C. F. A. Pantin and Dr Eastham. I have relied much upon the kindness and wide biological knowledge of Dr D. Keilin and Dr F. H. A. Marshall. As regards the historical chapters, I am most grateful to Dr Charles Singer, who annotated them with valuable comments, and to Professor R. C. Punnett who placed un- reservedly at my disposal his knowledge of the history of generation, and his library of old and rare biological books. To Dr Arthur Peck I am indebted for the correction of my Greek, and it was Professor A. B. Cook who guided me to the embryology of the ancients. Without the assiduous backing of Mr Powell, the Librarian of the Royal Society of Medicine, and his assistants, I should have dealt much more inadequately than I have with the papers which cannot be consulted in Cambridge. I have also to thank the administrators of the Thruston Fund of Gonville and Caius College for a grant which was devoted to incidental expenses. For the indexes I wish to thank Miss Helen Moyle, and for other services which have made the book possible, Mrs V. Townsend. My thanks are also due to the Editors of the following journals: Biochemical Journal, Journal XX ACKNOWLEDGEMENTS of Experimental Biology, Biological Reviews, Science Progress, and the Monist, for permission to reprint passages from papers. I must record my gratitude to the following friends, who very kindly read through and criticised the proofs of the various sections: Part I Professor A. E. Boycott Dr J. H. Woodger Part II Professor R. C. Punnett Dr Charles Singer Dr Reuben Levy Dr Arthur Peck Sir William Dampier Professor A. B. Cook The Rev. W. Elmslie Professor F. M. Cornford Part III Section 1 Professor R. H. A. Plimmer Mr J. B. S. Haldane 2 Dr Samuel Brody Mr James Gray Dr E. N. Willmer 3 Mr G. R. de Beer Mr C. H. Waddington Mr J. B. S. Haldane 4 Dr D. Keilin Professor Munro Fox 5 Mr T. R. Parsons Dr Malcolm Dixon 6 M. Louis Rapkine Mr C. Forster Cooper 7 Miss Marjory Stephenson M. Louis Rapkine Dr D. Keilin 8 Dr Eric Holmes Dr Bruce Anderson & Mrs Margaret Whetham Anderson OF INDEBTEDNESS Section 9 Dr Dorothy Jordan Lloyd Professor J. Murray Luck Mr C. Forster Cooper lO Mile Eliane LeBreton II Professor J. B. Leathes 12 Dr Irvine Page 13 Dr Elsie Watchorn 14 Dr Barnet Woolf MrJ. B. S. Haldane 15 Dr Howard Florey 16 Dr Leslie J. Harris Dr A. L. Bacharach 18 Dr Howard Whittle 19 Mr C. F. A. Pantin Professor A. R. Moore & Mrs Moore 20 Dr John Hammond 21 Dr St G. Huggett 22 Dr Arthur Walton 23 Dr Barbara Holmes 24 Dr F. H. A. Marshall Epilegomena Professor L. G. M. B. Becking Dr D. Keilin Dr G. S. Carter Professor Lancelot Hogben Mr G. R. de Beer Professor A. R. Moore & Mrs Moore Appendix III Dr L. E. S. Eastham I am indebted to the Master of Gonville and Caius College for permission to reproduce the portrait of William Harvey (attributed to Rembrandt) in the Senior Combination Room. Finally, I am glad to record here my gratitude to the StafTof the Cambridge University Press for the unremitting care which they gave to my book during the course of its preparation. J. N. Note: The use of the shortened and (&) indicates collaboration between two or more authors. PROLEGOMENA The Sciences, unlike the Graces or the Eumenides, are not limited in number. Once born, they are immortal, but, as knowledge in- creases, they are ever multiplying, and so great is now the dominion of the scientific mind that every few years sees a new one brought into the world. Some spring, fully armed, from the brains of one or two men of genius, but most of them, perhaps, come only gradually to their full development through the labours of very many obscure and accurate observers. If the analogy may be permitted, physico-chemical embryology has so far been living an intra-uterine existence. Its facts have been buried in a wide range of scientific journals, and its theories have lain dormant or in potentia in reviews of modest scope. Physico- chemical embryology has, indeed, arrived at the stage immediately priox to birth, and all it needs is a skilful obstetrician, for, when once it has reached the light of day and has passed for ever out of the foetal stage, it will be well able to take care of itself. This obstetrical task is that which I have chosen and obviously enough it divides into three principal heads: first, to collect together out of all the original papers on the subject the facts which are known about the physico-chemical basis of embryonic development; second, to relate these facts to each other and to the facts derived from the labours of investigators in morphological embryology and " Entwicklungs- mechanik," and, third, to ascertain whether, from what is at present known, any generally valid principles emerge. I may as well say at the outset that in order to do this certain arbitrary boundary-lines are inevitable. The following arrangement has been adopted. Chronologically speaking, the prelude to all em- bryonic development is the maturation of the egg-cell, but this is not strictly embryology, and so has been relegated to an appendix. The egg-cell as a physico-chemical system is dealt with at the opening of Part III, and thereafter the physico-chemical aspects of develop- ment follow in order. No mention will be made of fertilisation, for this has been treated exhaustively by other writers (Lillie, Dalcq) and, after all, embryology presupposes fertiUsation whether natural or artificial. Nor in later chapters will any complete treatment be 2 PROLEGOMENA given of the events going on in the maternal organism during preg- nancy : for the present purpose the discussion will go as far into the mother as the placenta but no farther. Again, hatching or birth will put an end to the discourse as to the foetal state itself, save that, in the cases of animals which hatch before the yolk-sac is absorbed, their embryonic life is assumed to end when they first take food for themselves. Appendices are added dealing with the plant embryo and the insect pupa, which, in the later stages of metamorphosis, have points both of resemblance to and of difference from the growth of the embryo. It is natural to hope that the outcome of all this labour may be an increase of interest among biologists in this section of their domain, and a great accession to the number of those investigators who devote their energies to actual experiments in this new field. For it must be confessed that it is a new field. It has been opened up in very gradual stages: fitful and sporadic experiments on the constitution of embryonic tissues in the seventeenth century, a gradual growth of knowledge about the chemical composition of eggs in the eighteenth, a big increase of activity in the early nineteenth; d'lTxiug which appear the first observations on the physico-chemical changes taking place in the embryo during its development, and then in our own time a mass of very widely scattered work bringing the subject up to the "obstetrical" stage. Such a work as this, in my opinion, should not be compared with laboratory experiments in a derogatory sense, for, while it is true that facts are the ultimate court of appeal in any scientific discussion, yet at the same time the number of in- vestigators has grown to such extraordinary proportions in this century that some danger exists lest we should be so busily engaged in accu- mulating new facts as to be left with no time at all to devote any thought to those we have already. Classification, indexing, and maturer consideration about the facts we actually possess are at least as great a need at the present moment as the invention of new facts. "Everyone must realise", says Eugenio Rignano, "how much this theoretical elaboration, performed by means of analyses and com- parisons, of generalisations and hypotheses controlled and verified by the correspondence of facts with the results of the reasoning, is useful and necessary if one wishes to reach a progressive systematisation and an ever more synthetic vision of the confused mass of facts which experimentalists pour daily in a continuous stream into the scientific market." PROLEGOMENA 3 My predecessors in this work have been few in number. The volumes of Haller's, Buffon's, and Milne-Edwards' great treatises, in which they deal with the phenomena of generation, contain as much in- formation as was available up to 1863, but this is purely of historical interest to us. In 1885, W. Preyer, Professor of Physiology at Jena, published his Spezielle Physiologie des Embryo, which still remains a most valuable review, and indeed, even to-day, is the only existing book specially devoted to embryonic physiology. The present century has produced only three books which even touch upon my subject, namely, T. B. Robertson's Chemical Basis of Growth and Senescence, F. H. A. Marshall's Physiology of Reproduction and E. Faure-Fremiet's La Cinetique du Developpement. The first of these was admittedly written to support a particular theory, and in any case says comparatively little about physico-chemical embryology. The second and the third deal with it only as a constituent part of a much wider field. In Marshall's case, the whole array of facts relating to oestrus and breeding, fertilisation and fertility, lactation and sex determination, have to be dealt with, and only three chapters out of sixteen are devoted to the subject of this book. The first of these is contributed by W. Cramer, and covers the biochemistry of the sexual organs, in- cluding the unfertiUsed egg ; the second, which deals with foetal nutrition and the placenta, is by J. Lochhead ; and the third, by these two investigators together, is concerned with changes in the maternal organism during pregnancy. Admirable as these chapters are, they are now rather out of date. Moreover, though one or two corners of the field I have before me were covered in Marshall's book, it was from a quite different standpoint. Faure-Fremiet's work is exactly analogous; it deals with physico- chemical embryology only, as it were, in passing. The relevant dis- cussion takes up only two chapters out of seven ; the rest are occupied with tissue culture, growth of protozoal populations, and general cytology. His book covers, it might be said, the third and fourth corners : all the main expanse of the field remains. Thus neither of these books deals with physico-chemical embryo- logy in an exhaustive and comprehensive fashion, treating it as, in my view, it ought to be treated, with the thoroughness which is deserved by a new branch of natural knowledge. Inseparable, how- ever, from thoroughness of treatment is the submergence of the parts of more general interest under a mass of detail, and it may be well. 4 PROLEGOMENA therefore, to mention now what sections of the book could be said to be most valuable to any student of general biology. Part i comes in this class, and of Part iii, the middle portion of Section i, all of Sections 2, 3, and 5, thelatter half of Section 7, Sections 8, 9 (especially the end), 11, possibly 18, and finally the Epilegomena. For my models in the preparation of this book, if it is permissible to name them, I have taken, Growth and Form by d'Arcy Thompson, surely the most scholarly work produced by a biologist in our time, and The Physiology of Reproduction by F. H. A. Marshall, already mentioned, which showed to all successors, in my opinion, how a colossal array of facts can be welded together into an absorbing and readable book, I am conscious that I shall not attain the level of these classics of modern biology, but then .... Pauci, quos aequus amavit Jupiter, aut ardens evexit ad aethera virtus. The progress of any branch of natural knowledge can be best described as a continual pilgrimage towards the quantitative. QuaUties can never be altogether left out of account and this is what makes it impossible for science to achieve its end with absolute finality. Yet an association with the probably unattainable is common to all the great types of man's activity. But "Fuyez toujours les a peu pres", as O. W. Holmes used to put it, is a proper maxim for the scientific mind, and whatever this book can do towards making embryology an exact science will be its final justification. PART I THE THEORY OF CHEMICAL EMBRYOLOGY . . . .to measure all things that can be measured, and to make measurable what cannot yet be measured. Galileo. THE THEORY OF ^^^-^S^aj^, CHEMICAL EMBRYOLOGY ^^' 0 ^'" Philosophy, Embryology, and Chemistry The penetration of physico-chemical concepts into embryology has not been entirely peaceful. "In experimental embryology", it has been said, "concepts borrowed from the physical sciences do not admit of calculations being made, and until they do they are not really playing the same role as they do in the sciences from which they have been borrowed and for which they were devised." "Nothing is more clear", says another writer, "in chemistry and physics than that identical results follow upon identical causes. Introduce a dis- turbing element, even a small one, into your experiment, and the experiment will fail. Such is not the case with the developing egg." W. McDougall, too, endows the egg with good intentions. "The embryo", he says, "seems to be resolved to acquire a certain form and structure, and to be capable of overcoming very great obstacles placed in its path. The development of the forms of organisms seems to be utterly refractory to explanation by mechanical or physico- chemical principles." Finally, J. A. Thomson goes farther than them all, and does not hesitate to say, "It is a mere impious opinion that development will one day be described in terms of mechanics". Chapter iv of his Gifford Lectures illustrates the antagonistic attitude to physico-chemical embryology in its most acute form. It can hardly be a coincidence that so many among the great embryologists of the past were men of strongly philosophic minds. It would be absurd to support this opinion by citing Aristotle, but it holds less obviously true of William Harvey, whose book on genera- tion is full of thoughts about causation, and in the cases of Ernst von Baer, Ernst Haeckel, Wilhelm Roux, Hans Driesch, dArcy Thompson and J. W. Jenkinson, there is no doubt about it. It is not really surprising, for of all the strange things in biology surely the most striking of all is the transmutation inside the developing egg, when in three weeks the white and the yolk give place to che animal with its tissues and organs, its batteries of enzymes and its dehcately regulated endocrine system. This coming-to-be can hardly have failed 8 THE THEORY OF [pt. to lead, in the minds of those most intimately acquainted with it, to thoughts of a metaphysical character. Nor, it seemed, did those who worked on it do much to diminish its wonder. "Neither the schools of physicians", as Harvey said, "nor Aristotle's discerning brain, have disclosed the manner how the Cock and its seed, doth mint and coine, the chicken out of the Ggg,'^ Or, in the words of Erycius Puteanus, "I will neglect gold, and will praise what is more precious than any metal, I will despise feasts, and will set forth praises of something better than any food or drink. If you would know of what it is that I intend to speak, it is the egg; men marvel at the sun, at meteors flung from heaven, at stars swimming therein, but this is the greatest of all wonders". Here, however, there is one significant thing. It is that the very chapter of Harvey's book in which the preceding remark is found has as its heading "The Efficient Cause of the Chicken, is hard to be found out". It certainly was, but the right clue was in the heading to that exercitation. This close association of embryology with philosophy, then, made it necessary to discuss at the outset of this book certain points in the more theoretical regions of biology, and, as it were, to defend from a theoretical angle the extension of the domain of physics and chemistry over embryology. I might have entitled this part of the book "The philosophy of embryology", but, in deference to those metaphysicians who rightly insist that the word philosophy should only be used of a definite system of experience which looks at the universe as a corporate whole, I adopted the present heading. Under it I propose to discuss the exact status of the chemical aspect of embryology. For many biologists, having perhaps insufficiently con- sidered the nature of the scientific method, think it likely that the discoveries of modern times may allow of some other basis for biology than mathematical physics and that the scientific niethod may rightly be different in biology from what it is in chemistry. It is this factor in our present intellectual climate which makes it neces- sary to preface by a philosophical discussion a book in which the concepts of physics and chemistry are extended to a field of biology where they have never before received more than a conventional and formal reverence. The aim of all studies in physico-chemical embryology must be that expressed by T. H. Huxley when he said, " Zoological Physiology is the doctrine of the functions or actions of animals. It regards I] CHEMICAL EMBRYOLOGY 9 animal bodies as machines impelled by certain forces and perform- ing an amount of work which can be measured and expressed in terms of the ordinary forces of nature. The final object of physiology is to deduce the facts of morphology on the one hand and those of oecology on the other hand from the laws of the mole- cular forces of matter". It may be regarded as very noteworthy that Huxley here puts morphology as secondary to physiology and as it were derivable from it; he does not place morphology and physiology on two high places, "neither afore or after other", as has so often been done, but he plainly states his view that the anatomical aspect of animals, their external and internal forms, could be deduced from the interplay of physico-chemical forces within them, if we only knew enough about those forces. This is the idea of the primacy of function. It seems always to have two meanings, firstly, the Epicurean-Lucretian one which Huxley adopts here and Roux so brilliantly developed, in which shape is regarded as the outward and visible sign of the properties of matter itself, and, secondly, the Aristotelian one emphasised by J. B. de Lamarck's writings in the eighteenth century, and in our time by E. S. Russell's great work Form and Function, in which psychical factors are intro- duced as the essential elements in the ultimate analysis of shape. In both these interpretations, function has the priority over form, but the meaning of function is the point of difference. Some biologists, however, seem to think that physiology and morphology are cate- gorical, and the latter is emphatically not reducible to or derivable from the former. The two spheres of study represent, for them, correlative and immiscible disciplines, morphology aiming ultimately at solid geometry, physiology at causation, and "rerum cognoscere causas" is not the basic desire of the scientific mind. They object to the view which regards "the ovum as a kind of chemical device wound up and ready to go off on receipt of a stimulus, the task of the causal morphologist being to disentangle the complex of events which constitute the unwinding process" (Woodger), complaining that in this view no account is taken of the past history of the race, which is left to genetics, again a causal discipHne. To some extent these opinions spring from a conviction that the analytical method is inapplicable to a living being because it is an organism, and of that there is more to be said. But they also arise from a profound unwillingness to subsume biology under physics and a desire to uphold 10 THE THEORY OF [pt. "the autonomy of biology". This precludes the promise of an ever- increasing homogeneity in the structure of science, and hence an ever-increasing simplicity. The Historical Perspective That the older embryologists awaited the extension of physico- chemical conceptions to embryology is no mere matter of conjecture. Until the mechanical theory of the universe had been consolidated by the " corpuscularian philosophy" of the seventeenth century it would be useless to look for illustration of this, but by 1674 John Mayow was tracing the part played by the " nitro-aerial particles" in the development of the embryo, and in 1732 Hermann Boerhaave was discussing chemical problems with explicit reference to embryonic development. Many other examples of this point of view in the eighteenth century will be given later. Then, when the second decade of the nineteenth century had nearly gone, von Baer, perhaps the greatest of all embryologists, was careful to preface his Entwicklungs- geschichte by a careful account of all that was known about the chemical constitution of the Qgg, and that, although his philosophical inclinations were deeply vitalistic, and even his practical interests morphological. In Roux, of course, this future reference came out explicitly, and the extension of biochemistry into embryology was allowed for and foreseen. An early instance was the association be- tween Wilhelm His and Hans Miescher. Miescher, writing to Hoppe- Seyler in 1872 said, "I am now collecting material from fishes, birds, and amphibia to lead to a chemical statics of development. With this end in view I shall do analyses of ash, nuclein, and lecithin". Embryology before Harvey, however, was rigidly Aristotelian, a statement the meaning of which George Santayana has lucidly ex- plained. "Aristotle", said he, "distinguished four principles in the understanding of Nature. The ignorant think that these are all, equally, forces producing change, and the cooperative sources of all natural things. Thus, if a chicken is hatched, they say that the Efficient Cause is the warmth of the brooding hen, yet this heat would not have hatched a chicken out of a stone, so that a second condition, which they call the Material Cause, must be invoked as well, namely, the nature of an egg; the essence of eggness being precisely a capacity to be hatched when warmed gently — because, as they wisely observe, boiling would drive away all potentiality of hatching. Yet, as they I] CHEMICAL EMBRYOLOGY ii further remark, gentle heat-in-general joined with the essence-of- eggness would produce only hatching-as-such and not the hatching of a chicken, so that a third influence, which they call the Final Cause, or the End-in-view, must operate as well, and this guiding influence is the divine idea of a perfect cock or a perfect hen presiding over the incubation and causing the mere eggness in the egg to assume the likeness of the animals from which it came. Nor, finally, do they find that these three influences are sufficient to produce here and now this particular chicken, but are compelled to add a fourth, a Formal Cause, namely, a particular yolk, a particular shell, and a particular farmyard, on which and in which the other three causes may work, and laboriously hatch an individual chicken, probably lame and ridiculous despite so many sponsors." The Aristotelian account of causation could not be better expressed. Santayana puts this description of it into the mouth of Avicenna in his imaginary dialogue, and makes him go on to say, "Thus these learned babblers would put nature together out of words, and would regard the four principles of interpretation as forces mutually supplementary com- bining to produce material things ; as if perfection could be one of the sources of imperfection or as if the form which things happen to have could be one of the causes of their having it. Far differently do these four principles clarify the world when discretion conceives them as four rays shed by the light of an observing spirit". In this last observation we may perhaps trace the germ of the Copernican revolution in philosophy effected by Kant, if we may take it to enclose the idea of the activity of the experient subject in all perception. In science generally, however, the x\ristotelian conceptions went without serious contradiction, and thus formed the framework for all the embryological work that was done, as, for instance, by Albertus Magnus. Owing to its association with the idea of the plan of a divine being, the final cause tended in the Middle Ages to eclipse the others. In the seventeenth century this feeling is well shown in a remarkable passage, which occurs in the Religio Medici of Sir Thomas Browne: "There is but one first cause, and four second causes of all things; some are without Efficient, as God; others without Matter, as Angels; some without Form, as the first matter; but every Essence created or uncreated, hath its Final cause, and some positive End both of its Essence and Operation ; this is the cause I grope after in the works of Nature ; on this hangs the providence of God ; to raise so 12 THE THEORY OF [pt. beauteous a structure as the World and the Creatures thereof, was but his Art; but their sundry and divided operations, with their predestinated ends, are from the Treasure of his Wisdom. In the causes, nature, and affections of the EcHpses of the Sun and Moon there is most excellent speculation, but to profound farther, and to contemplate a reason why his providence hath so disposed and ordered their motions in that vast circle as to conjoyn and obscure each other, is a sweeter piece of Reason and a diviner point of Philosophy; therefore sometimes, and in some things, there appears to me as much Divinity in Galen his books De Usu Partium, as in Suarez' Metaphysicks: Had Aristotle been as curious in the enquiry of this cause as he was of the other, he had not left behind him an imperfect piece of Philosophy but an absolute tract of Divinity". This was written in Harvey's time, and in Harvey's thought the four causes were still supreme ; his De Generatione Animalium is deeply con- cerned with the unravelling of the causes which must collaborate in producing the finished embryo. But the end of their domination was at hand, and the exsuccous Lord Chancellor, whose writings Harvey thought so little of, was making an attack on one of Aristotle's causes which was destined to be peculiarly successful. There is no need to quote his immortal passages about the "impertinence", or ir- relevance, of final causes in science, for they cannot but be familiar to all scientific men. Bacon demonstrated that from a scientific point of view the final cause was a useless conception; recourse to it as an explanation of any phenomenon might be of value in metaphysics, but was pernicious in science, since it closed the way at once for further experiments. To say that embryonic development took the course it did because the process was drawn on by a pulling force, by the idea of the perfect adult animal, might be an explanation of interest to the metaphysician, but as it could lead to no fresh experi- ments, it was nothing but a nuisance to the man of science. Later on, it became clear also that the final cause was irrelevant in science owing to its inexpressibility in terms of measurable entities. From these blows the final cause never recovered. In England the seven- teenth century was the time of transition in these aflfairs, and in such books as Josfeph Glanville's Plus Ultra and Scepsis Scientifica, for in- stance, and Thomas Sprat's Defence of the Royal Society, the stormy conflict between the "new or experimental philosophy" and the Aristotelian "school-philosophy" can be easily followed. Francis I] CHEMICAL EMBRYOLOGY 13 Gotch has given a delightful account of the evening of AristoteUanism, but it involved a stormy sunset, and the older ideas did not give way without a struggle. Harvey's work is perfectly representative of the period of transition, for, in his preface under the heading "Of the Method to be observed in the knowledge of Generation", he says, "Every inquisition is to be derived from its Causes, and chiefly from the Material and Efficient". As for the formal cause. Bacon expressly excluded it from Physic, and it quietly disappeared as men saw that scientific laws depended on the repeatableness of phenomena, and that anything unique or individual stood outside the scope of science. Thus in the case of the developing egg, the formal (the particular farmyard, etc.) and the final causes are scientifically meaningless, and if it were desired to express modern scientific explanation in Aristotelian terminology, the material and efficient causes would alone be spoken of, essence-of-eggness being a "chymical matter" as well as the heat of the brooding hen. Obstacles to Chemical Embryology The complexity of living systems, however, is such that many minds find it difficult to accept this physico-chemical account as the most truly scientific way of looking at it. This is doubtless due in part to an erroneous notion, which is yet very tenacious of existence, that the mechanical theory of the universe must, if accepted at all, be accepted as an ultimate ontological doctrine, and so involve its sup- porter in one of the classical varieties of metaphysical materialism. It cannot be too strongly asserted that this is not the case. To imagine that it is, is to take no account of the great space that separates us from the last century. "When the first mathematical, logical, and natural uniformities", said WilHam James, "the first Laws, were discovered, men were so carried away by the clearness, beauty, and simplification that resulted that they believed themselves to have deciphered authentically the eternal thoughts of the Almighty. His mind also thundered and reverberated in syllogisms. He also thought in conic sections, squares, and roots and ratios, and geometrised like Euclid. He made Kepler's laws for the planets to follow, he made velocity increase proportionately to the time in falhng bodies; he made the laws of the sines for light to obey when refracted; he established the classes, orders, families, and genera of plants and animals, and fixed the distances between them." 14 THE THEORY OF [pt. Far different is the account of itself which science has since learned to give. But this change of attitude is not a revolt against thought as such, or against reason as such ; it is only a loss of belief in the literal inspiration of the formulae proper to science. It would be just as extravagant to claim that the scientific investigator of the twentieth century sets down absolute truths in his laboratory notebook, and, armed with an infallible method, explores the real structure of an objective world, as it would be fantastic to claim that Jehovah dictated an absolute code of the good to Moses on Mount Sinai. To say that the development of a living being can best be described in a metrical or mechanical way is not to say that it is metrical or me- chanical and nothing else. The physico-chemical embryologist is not committed to any opinion on what his material really is, but he is committed to the opinion that the scientific method is one way of describing it, and that it is best to apply that method in its full rigour if it is to be applied at all. In other words, following the train of thought of William James, he does not assert that the courts of Heaven as well as those of our laboratories resound with expressions such as "organisers of the second grade," and "so many milHgrams per cent." The mechanical theory of the world, which is, as many beHeve, bound up indissolubly with one of the ultimate types of human experience, can no longer be considered as necessarily involving the exclusion of other theories of the world. Or, put in another way, it is a theory of the world, and not a pocket edition of the world itself But before bringing forward any arguments in support of this attitude and in defence of physico-chemical embryology, it will be well to consider briefly those theoretical tendencies in modern biology which go together under the inexact adjective "neo-vitalistic", for their influence in scientific thought has been far-reaching. To deal critically with them is not a waste of time, for, were we to adopt any one of them, we should find that the notion of embryology as complicated biophysics and biochemistry would have to be abandoned, and quite other means of approach (never, indeed, very well defined) would have to be used. The Stumbling-block of Hormism Hormism, or "Psychobiology," may be dealt with in a few words. Chiefly supported by A. Wagner in Germany, and by E. S. Russell and L. T. Hobhouse in this country, it holds that — to I] CHEMICAL EMBRYOLOGY 15 use Lloyd Morgan's terminology — a physiological tale cannot be told separately from a psychological tale. Instead of expressing living processes in terms of physical causes and effects, the hormists wish to regard unconscious striving as the essential urge in life, and such conceptions as food, rest, fatigue, etc., as irreducible biological cate- gories. These thinkers do not often acknowledge their debt to Galen of Pergamos, who put forward, as early as a.d. 170, an essentially similar conception as the basis of his biology. In the treatise On the Natural Faculties he says, "The cause of an activity I term a faculty.... Thus we say that there exists in the veins a blood-making faculty, as also a digestive faculty in the stomach, a pulsatile faculty in the heart, and in each of the other parts a special faculty corresponding to the function or activity of that part". He also said, "We call it a faculty so long as we are ignorant of the cause which is operating", but he never actually suggested any such underlying cause, and seems to have thought it impossible to ascertain. So do the hormists. According to them the actions of protozoa are to be described in terms of avoiding responses, seeking responses and the like, language which, as they claim, is much simpler than the complex terminology of surface tension and molecular orientation. Everything, of course, depends on what is meant by simple. To say that a protozoon seeks the light is evidently more naive than to say that a dimolecular photochemical reaction takes place in its protoplasm leading to an increase of lactic acid or what not on the stimulated side, but since the latter explanation fits into the body of scientific fact known already it is open to the biochemist to say that, for his part, he. con- siders the latter explanation the simpler. It is, in fact, simpler in the long run. Psychobiology or hormism differs from the other forms of neo-vitalism because it insists on retaining " commonsense " explanations in biology as categories of biological thought beneath which it is impossible to go. It dismisses the entelechy of dynamic Teleology, on the ground that it acts, as it were, in addition to the mechanistic schema, accepting the latter fully but interfering in it. It resembles much more finaUsm and organicism, but lays stress rather on the unconscious striving force which seems to animate colloidal solutions of carbohydrates, fats, and proteins. It resembles the Behaviourism of J. B. Watson superficially by emphasising animal behaviour, but it fundamentally differs, for it asks the question — Does an animal see the green light and the red light in this experiment i6 THE THEORY OF [pt. as we do, or does it see them as two shades of grey as colour-blind people do? while the behaviourist asks — Does it respond according to difference of light-intensity or difference of wave-lengths ? Hormism, in fact, recurs continually to psychical factors. Samuel Butler, for instance, one of its principal exponents, wrote, "I want to connect the actual manufacture of the things a chicken makes inside an egg with the desire and memory of the chicken so as to show that one and the same set of vibrations at once change the universal sub- stratum into the particular phase of it required" (cf. ^ rov hwdixei, 6vTo