■■■ii I li'fi l!!t!;;li BOUGHT WITH THE INCOME FROM THE sage' ENDOWMENT FUND r- THE GIFT OF ' i' Henrg W. Sage 1891 A....z.A^7-i:j-.7- : z^..Ua/^2.S-..-:'^ 9963 B 3218.84 1908""""'"'^ ^'"^-'V The fipir ^ ^^2A 010 498 040 5^ if Si" The original of tliis book is in tlie Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924010498040 THE SCIENCE AND PHILOSOPHY OF THE ORGANISM Australasia Canada . . AGENTS The Macmillan Company 04 & 66 FitTH Avenue, New York The Oxford University Press, Melbourne The Macmillan Company of Canada, Ltd. 27 Richmond Street West, Toronto Macmillan & Company, Ltd. Macmillan Building, Bombay 309 Bow Bazaar Street, Calc cuw^ THE SCIENCE AND PHILOSOPHY OF THE ORGANISM THE GIFFOED LECTUEES DELIVEEED BEFOEE THE UNIVEESITY OF ABEEDEEN IN THE YEAE 1907 BY HANS DRIBSCH, Ph.D. "" HEIDELBERG LONDON ADAM AND CHAELES BLACK 1908 All rights reserved ^-^5.1€l-J PEEFACE This work is not a text-book of theoretical biology ; it is a systematic presentment of those biological topics which bear upon the true philosophy of nature. The book is written in a decidedly subjective manner, and it seems to me that this is just what " Gifford Lectures " ought to be. They ought never to lose, or even try to lose, their decidedly personal character. My appointment as Gifford Lecturer, the news of which reached me in February 1906, came just at the right moment in the progress of my theoretical studies. I had always tried to improve my previous books by adding notes or altering the arrangement ; I also had left a good deal ' of things unpublished, and thus I often hoped that I might have occasion to arrange for a new, improved, and enlarged edition of those books. This work then is the realisation of my hopes ; it is, in its way, a definitive statement of all that I have to say about the Organic. The first volume of this work, containing the lectures for 1907 — though the division into " lectures " has not been preserved — consists of Parts I. and IL of Section A, " The Chief Eesults of Analytical Biology." It gives in Part L a vi SCIENCE AND PHILOSOPHY OF THE ORGANISM shortened, revised, and, as I hope, improved account of what was published in my Analytische Thewie der organischen Entwichelung (1894), Die Localisation morphogenetiseher Vorgange ; ein Beweis Vitalistischen Geschehens (1899), and Die organischen Begulationen (1901), though for the pro- fessed biologist the two last-named books are by no means superseded by the new work. Part II. has never been published in any systematic form before, though there are many remarks on Systematics, Darwinism, etc., in my previous papers. The second volume — to be published in the autumn, after the delivery^of the 1908 lectures — will begin with the third and concluding part of the scientific section, which is a very carefully revised and rearranged second edition of my book. Die " Seele" als elementarer Naturf actor (1903). The greater part of this volume, however, will be devoted to the " Philosophy of the Organism," i.e. Section B, which, in my opinion, includes the most important parts of the work. Some apology is needed for my presuming to write in English. I was led to do so by the conviction, mistaken perhaps, that the process of translation would rob the lectures of that individual and personal character which, as I said before, seems to me so much to be desired. I wished nothing to come between me and my audience. I accord- ingly wrote my manuscript in English, and then submitted it to linguistic revision by such skilled aid as I was able to procure at Heidelberg. My reviser tells me that if the result of his labours leaves much to be desired, it is not to be wondered at, but that, being neither a biologist nor a PREFACE Vll philosopher, he has done his best to make me presentable to the English reader. If he has failed in his troublesome task, I know that it is not for want of care and attention, and I desire here to record my sense of indebtedness to him. He wishes to remain anonymous, but I am permitted to say that, though resident in a foreign university, he is of Scottish name and English birth. My gratitude to my friends at Aberdeen, in particular to Professor and Mrs. J. A. Thomson, for their hospitality and great kindness towards me cannot be expressed here ; they all know that they succeeded in making me feel quite at home with them. I am very much obliged to my publishers, Messrs. A. and C. Black, for their readiness to fulfil all my wishes with respect to publication. The lectures contained in this book were written in English by a German and delivered at a Scottish university. Almost all of the ideas discussed in it were first conceived during the author's long residence in Southern Italy. Thus this book may be witness to the truth which, I hope, will be universally recognised in the near future — that all culture, moral and intellectual and aesthetic, is not limited by the bounds of nationality. HANS DEIESCH. Heidelberq, 2nd Janucm/ 1908. CONTENTS OF THE FIRST VOLUME THE PROGRAMME On Lord Gifford's Conception of " Science " Natural Sciences and " Natural Theology " Our Philosophical Basis ..... On Certain Characteristics of Biology as a Science The Three Different Types of Knowledge about Nature General Plan of these Lectures .... General Character of the Organic Form . PAQB 1 3 5 9 13 15 19 SECTION A.— THE CHIEF RESULTS OF ANALYTICAL BIOLOGY PAET I.— THE INDIVIDUAL ORGANISM WITH REGARD TO FORM AND METABOLISM A. ELEMENTARY MORPHOGENESIS— Evolutio and Epigenesis in the old Sense The Cell The Egg : its Maturation and Fertilisation The First Developmental Processes of Echinus Comparative Embryology , The First Steps of Analytical Morphogenesis The Limits of Pure Description in Science £. EXPERIMENTAL AND THEORETICAL MORPHOGENESIS— 1. The Foundations of the Physiology of Development. "Evolutio" AND "Epigenesis" The Theory of Weismann Experimental Morphology 25 27 31 33 44 45 50 52 52 56 SCIENCE AND PHILOSOPHY OF THE ORGANISM The Work of Wilhelra Roux ... The Experiments on the Egg of the Sea-urchin On the Intimate Structure of the Protoplasm of the Germ On some Specificities of Organisation in Certain Germs General Results of the First Period of " Entwickelungs- mechanik " . Some New Results concerning Restitutions . 2. Analytical Theokt or Morphogenesis a. THE DISTKIBUTION OP MORPHOGENETIC POTENCIES Prospective Value and Prospective Potency . The Potencies of the Blastomeres The Potencies of Elementary Organs in General Explicit and Implicit Potencies : Primary and Secondary Potencies .... The Morphogenetic Function of Maturation in the Light of Recent Discoveries . The Intimate Structure of Protoplasm : Further Remarks ..... The Neutrality of the Concept of "Potency " PAOB 58 59 65 70 71 74 76 76 76 79 80 83 85 88 89 89 j3. THE "means" OF MORPHOGENESIS /3'. The Internal Elementary Means of Morphogenesis 90 Some Remarks on the Importance of Surface Tension in Morphogenesis On Growth .... On Cell-division .... j3". The External Means of Morphogenesis The Discoveries of Herbst THE FORMATIVE CAUSES OR STIMULI The Definition of Cause" Some Instances of Formative and Directive Stimuli THE MORPHOGENETIC HARMONIES ON RESTITUTIONS ..... A few Remarks on Secondary Potencies and on Second ary Morphogenetic Regulations in General . The Stimuli of Restitutions 99 99 102 107 110 110 113 The Problem of Morphogenetic Localisation : The Theory op the Harmonious -Equipotential system — First Proop of the Autonomy of Life . . us The General Problem . . . .118 The Morphogenetic " System " . . . 1x9 The " Harmonious-equipotential System " . 122 CONTENTS xi PAGE Instances of " Harmonious-equipotential Systems " . 126 The Problem of the Factor E . . . .132 No Explanation offered by "Means" or "Formative Stimuli" ...... 132 No Explanation offered by a Chemical Theory of Morphogenesis ..... 134 No Machine Possible Inside the Harmonious Systems 138 The Autonomy of Morphogenesis proved . . 142 "Entelechy" . . . . . .143 Some General Remarks on Vitalism . . . 145 The Logic of our First Proof of Vitalism . .146 4. On Cehtain othek Features of Moephogenesis Advo- cating ITS Autonomy . . . . . 150 Harmonious - equipotential Systems formed by Wander- ing Cells. " . . . . . .151 On Certain Combined Types of Morphogenetic Systems . 153 The " Morphaesthesia " of Noll . . ' . .157 Restitutions of the Secqiid Order .... 158 On the " Equifinality ", of Restitutions . . 159 Remarks on " Retro-Differentiation " . . . 163 C. ADAPTATION— Inteoductoky Remakks on Regulations in General . 165 1. Morphological Adaptation ..... 168 The Limits of the Concept of Adaptation . . . 168 Adaptations to Functional Changes from Without . . 172 True Functional Adaptation .... 176 Theoretical Conclusions ..... 179 2. Physiological Adaptation ..... 184 Specific Adaptedness moi " Adaptation " . . . 186 Primary and Secondary Adaptations in Physiology . 188 On Certain Pre-requisites of Adaptations in General . 189 On Certain Groups of Primary Physiological Adaptations . 190 General Remarks on Irritability .... 190 The Regulation of Heat Production . . . 193 Primai-y Regulations in the Transport of Materials and Certain Phenomena of Osmotic Pressure . . 194 Chromatic Regulations in Algae .... 197 Metabolic Regulations ..... 198 Immunity the only Type of a Secondary Physiological Adaptation ...... 204 No General Positive Result from this Chapter . . 209 A few Remarks on the Limits of Regulability . . 212 xii SCIENCE AND PHILOSOPHY OP THE ORGANISM D. INHERITANCE. SECOND PROOF OF THE AUTONOMY OF LIFE- PAGE Tlie Material Continuity in Inheritance .... 214 On Certain Theories which Seek to Compare Inheritance to Memory 216 The Complex-Equipotential System and its R81e in Inheritance . 219 The Second Proof of Life-Autonomy. Entelechy at the Bottom of Inheritance ....... 224 The Significance of the Material Continuity in Inheritance . 227 The Experimental Facts about Inheritance . . . 228 The R61e of the Nucleus in Inheritance .... 233 Variation and Mutation ...... 237 Conclusions from tbe First Main Part of these Lectures . 240 PART II.— SYSTEMATICS AND HISTORY A. THE PRINCIPLES OF SYSTEMATICS— Rational Systematica ...... 243 Biological Systematios ...... 246 S. THE THEORY OF DESCENT— 1. Gbneealities ....... 250 The Covert Presumption of all Theories of Descent . 253 The Small Value of Pure Phylogeny . . .255 History and Systematics ..... 257 2. The Pbinciplbs op Darwinism .... 260 Natural Selection ...... 261 Fluctuating Variation the Alleged Cause of Organic Diversity 264 Darwinism Fails all along the Line .... 269 3. The Principles of Lamakckism .... 271 Adaptation as the Starting- Point .... 272 The Active Storing of Contingent Variations as a Hypothetic Principle ..... 273 Criticism of the "Inheritance of Acquired Characters" assumed by Lamarckism ..... 275 Other Principles Wanted ..... 281 Criticism of the Hypothesis of Storing and Handing Down Contingent Variations ..... 282 4. The Real Results and the Unsolved Peoblems of Tkansfokmism . . . . . . 290 5. The Logical Value of the Organic Form according TO THE DIFFERENT TrANSFORMISTIO THEORIES . 293 The Organic Form and Entelechy .... 294 CONTENTS XIU PAOB C. THE LOGIC OF HISTORY 297 1. The Possible Aspects op History .... 299 2. Phylogenetic Possibilities ..... 304 3. The History of Mankind ..... 306 Cumulations in Human History .... 308 Human History not an " Evolution " . . .311 The Problem of the " Single " as such . . .315 Conclusions about Systehatics and History in General . 322 I. ;rHE PROGRAMME On Lord Giffoed's Conception of " Science " This is the first time that a biologist has occupied this place ; the first time that a biologist is to try to carry out the intentions of the noble and high-minded man to whom this lectureship owes its foundation. On such an occasion it seems to be not undesirable to inquire what Lord Gifford's own opinions about natural science may have been, what place in the whole scheme of human knowledge he may have attributed to those branches of it which have become almost the centre of men's intellectual interest. And, indeed, on studying Lord Gifford's bequest with the object of finding in it some reference to the natural sciences, one easily notes that he has assigned to them a very high place compared with the other sciences, at least in one respect : with regard to their methods. There is a highly interesting passage in his will which leaves no doubt about our question. After having formally declared the foundation of this lectureship " for Promoting, Advancing, Teaching and Diffusing the study of Natural Theology in the widest sense of that term," and after 2 SCIENCE AND PHILOSOPHY OF THE ORGANISM having arranged about the special features of the lectures, he continues : " I wish the lecturers to treat their subject as a strictly natural science, the greatest of all possible sciences, indeed, in one sense, the only science, that of Infinite Being. ... I wish it considered just as astronomy or chemistry is." Of course, it is not possible to understand these words of Lord Gifford's will in a quite literal sense. If, provision- ally, we call " natural theology " the ultimate conclusions which may be drawn from a study of nature in connection with all other results of human sciences, there cannot be any doubt that these. conclusions will be of a rather different character from the results obtained in, say, the special field of scientific chemistry. But, nevertheless, there are, I think, two points of contact between the wider and the narrower field of knowledge, and both of them relate to method. Lord Gifford's own phrase, "Infinite Being," shows us one of these meeting -points. In opposition to history of any form, natural sciences aim at discovering such truths as are independent of special time and of special space, such truths as are " ideas " in the sense of Plato ; and such eternal results, indeed, always stand in close relation to the ultimate results of human knowledge in general. But besides that there is still another feature which may be common both to "natural theology" and to the special natural sciences, and which is most fully developed in the latter : freedom from prepossessions. This, at least, is an ideal of all natural sciences; I may say it is the ideal of them. That it was this feature which Lord Gifford had in view in his comparison becomes clear when we read in his will that the lectures on natural theology are THE PROGRAMME 3 to be delivered "without reference to or reliance upon any supposed special exceptional or so-called miraculous revelation." So we might say that both in their logical and their moral methods, natural sciences are to be the prototype of "Natural Theology " in Lord Gifford's sense. Natural Sciences and " Natural Theology " But now let us study in a more systematic manner the possible relations of the natural sciences to natural theology as a science. How is it possible for a natural scientist to contribute to the science of the highest and ultimate subject of human knowledge ? Almost all natural sciences have a sort of naivete in their own spheres ; they all stand on the ground of what has been called a naive realism, as long as they are, so to say, at home. That in no way prejudices their own progress, but it seems to stand in the way of establishing contact with any higher form of human knowledge than themselves. One may be a first-rate organic chemist even when looking upon the atoms as small billiard balls, and one may make brilliant discoveries about the behaviour of animals even when regarding them in the most anthropo- morphic manner — granted that one is a good observer ; but it can hardly be admitted that our chemist would do much to advance the theory of matter, or our biologist to solve the problem of the relations between body and mind. It is only by the aid of philosophy, or I would rather say by keeping in constant touch with it, that natural 4 SCIENCE AND PHILOSOPHY OP THE ORGANISM sciences are able to acquire any significance for what might be called the science of nature in the most simple form. Unhappily the term " natural philosophy " is restricted in English to theoretical physics. This is not without a high degree of justification, for theoretical physics has indeed lost its naivete and become a philosophy of nature ; but it never- theless is very unfortunate that this use of the term " natural philosophy " is established in this country, as we now have no proper general term descriptive of a natural science that is in permanent relation to philosophy, a natural science which does not use a single concept without justifying it epistemologically, i.e. what in German, for instance, would simply be called " Naturphilosophie." Let us call it philosophy of nature; then we may say that only by becoming a true philosophy of nature are natural sciences of all sorts able to contribute to the highest questions which man's spirit of inquiry can suggest. These highest questions themselves are the outcome of the combination of the highest results of all branches of philosophy, just as our philosophy of nature originated in the discussion of the results of all the separate natural sciences. Are those highest questions not only to be asked, are they to be also solved ? To be solved in a way which does not exceed the limits of philosophy as the domain of actual understanding ? The beginning of a long series of studies is not the right place to decide this important question ; and so, for the present certainly, " natural theology " must remain a prob- lem. In other words : it must remain an open question at the beginning of our studies, whether after all there can be any final general answer, free from contradictions. THE PROGRAMME 5 applicable to the totality of questions asked by all the branches of philosophy. But let us not be disturbed by this problematic entrance to our studies. Let us foUow biology on its own path ; let us study its transition from a " naive " science to a real branch of the philosophy of nature. In this way we perhaps shall be able to understand what its part may be in solving what can be solved. That is to be our subject. OuK Philosophical Basis We call nature what is given to us in space. Of course we are not obliged in these lectures to discuss the psychological and epistemological problems of space with its three dimensions, nor are we obliged to develop a general theory of reality and its different aspects. A few epistemological points will be considered later at proper times, and always in connection with results of theoretical biology. At present it must suffice to say that our general philosophical point of view will be idealistic, in the critical meaning of the word. The universe, and within the universe nature, in the sense just defined, is my phenomenon. That is what I know. I know nothing more, either positively or negatively; that is to say, I do not know that the world is only my phenomenon, but, on the other hand, I know nothing about its "absolute reality." And more, I am not even able to describe in intelligible words what " absolute reality " might mean. I am fuUy entitled to state : the universe is as truly as I 6 SCIENCE AND PHILOSOPHY OF THE ORGANISM am — though in a somewhat different sense of "being" — and I am as truly as the universe is ; but I am not entitled to state anything beyond these two corresponding phrases. You know that, in the history of European philosophy at least, Bishop Berkeley was the first clearly to outline the field of idealism. But my phenomenon — the world, especially nature — consists of elements of two different kinds : some of them are merely passive, some of them contain a peculiar sort of activity in themselves. The first are generally called sensations, but perhaps would be better called elements or presentations ; the others are forms of construction, and, indeed, there is an active element embraced in them in this sense, that they allow, by their free combination, the discovery of principles which are not to be denied, which must be affirmed, whenever their meaning is understood. You know that I am speaking here of what are generally called categories and synthetic judgments a priori, and that it was Kant who, on the foundations laid by Locke, Hume, and Leibnitz, first gave the outlines of what may be called the real system of critical philosophy. Indeed, our method will be to a great exterit Kantian, though with certain exceptions ; it is to be strictly idealistic, and will not in the Kantian way operate with thii^gs in themselves ; and it regards the so-called " synthetic judg- ment a prim-i" and the problem of the relation between categorical principles and experience in a somewhat different manner. We think 'it best to define the much disputed concept "a priori " as " independent of the amount of experience " ; that is to say, all categories and categori- cal principles are brought to my consciousness by that THE PEOGRAMME 7 fundamental event which is called experience, and therefore are not independent of it, but they are not inferences from experience, as are so-called empirical laws. "We almost might say that we only have to be reminded of those principles by experience, and, indeed, we should not, I think, go very far wrong in saying that the Socratic doctrine, that all knowledge is recollection, holds good as far as categories and categorical principles are in question. But enough at present about our general philosophy. As to the philosophy of nature, there can be no doubt that, on the basis of principles like those we have shortly sketched, its ultimate aim must be to co-ordinate every- thing in nature with terms and principles of the categorical style. The philosophy of nature thus becomes a system ; a system of which the general type is afforded by the innate constructive power of the Ego. In this sense the Kantian dictum remains true, that the Ego prescribes its own laws to nature, though, of course, " nature," that is, what is given in space, must be such as to permit that sort of " prescription." One often hears that all sciences, including the science of sciences, philosophy, have to find out what is true. What, then, may be called " true " by an idealistic philosopher, for whom the old realistic formula of the conformity between knowledge and the object cannot have any meaning ? Besides its ordinary application to simple facts or to simple judgments, where the word truth only means absence of illusion or no false statement, truth can be claimed for a philosophical doctrine or for a system of such doctrines only in the sense that there are no contradictions amongst the parts of the doctrine or of the 8 SCIENCE AND PHILOSOPHY OF THE ORGANISM system themselves, and that there are no features in them which impel our categorical Ego to further analysis. Those of you who attended Professor Ward's lectures on "Naturalism and Agnosticism," or who have read his excellent book on that subject, will know what the aims of .a theory of matter are. You will also be aware that, at present, there does not exist any theory of matter which can claim to be " true " ; there are contradictions in every theory of matter, and, moreover, there are always some points where we are obliged to ask for further information and receive no answer. Experience here has not yet aroused all the categorical functions which are needed in order to form one unity out of what seem to be incom- patibilities at the present day. Why is that ? Maybe because experience is not yet complete in this field, but maybe also because the whole subject is so complicated that it takes much time to attach categorical functions to what is experienced. But it is not our object here to deal either with epistemology proper or with ontology : a full analysis of biological facts is our problem. Why, then, all these introductions ? why all these philosophical sketches in fields of knowledge which have quite another relation to philosophy than biology has? Biology, I hear some one say, is simply and solely an empirical science ; in some sense it is nothing ^ but applied physics and chemistry, perhaps applied mechanics. There are no fundamental principles in biology which could bring it in any close contact with philosophy. Even the one and only principle which might seem to be an innate principle of our experience about life, the principle of evolution, is only a THE PROGRAMME 9 combination of more simple factors of the physical and chemical type. It will be my essential endeavour to convince you, in the course of these lectures, that such an aspect of the science of biology is wrong ; that biology is an elemental natural science in the true sense of the word. But if biology is an elemental science, then, and only then, it stands in close relations to epistemology and ontology — in the same relations to them, indeed, as every natural science does which deals with true elements of nature, and which is willing to abandon naive realism and contribute its share to the whole of human knowledge. And, therefore, a philosophical sketch is not out of place at the beginning of lectures on the Philosophy of the Organism. We may be forced, we, indeed, shall be forced, to remain for some time on the ground of realistic empiricism, for biology has to deal with very complicated experiences ; but there will be a moment in our progress when we shall enter the realm of the elemental ontological concepts, and in that very moment our study of life will have become a part of real philosophy. It was not without good reasons, therefore, that I shortly sketched, as a sort of introduction to my lectures, the general point of view which we shall take with regard to philosophical questions, and to questions of the philosophy of nature in particular. On Certain Characteeistics of Biology as a Science Biology is the science of life. Practically, all of you know what a living being is, and therefore it is not necessary to formulate a definition of life, which, at the 10 SCIENCE AND PHILOSOPHY OP THE ORGANISM beginning of our studies, would be either provisional and incomplete, or else dogmatic. In some respects, indeed, a definition should rather be the end of a science than its opening. We shall study the phenomena of living organisms analytically, by the aid of experiment ; our principal object will be to find out laws in these phenomena; such laws will then be further analysed, and precisely at that point we. shall leave the realm of natural science proper. Our science is the highest of all natural sciences, for it embraces as its final object the actions of man, at least in so far as actions also are phenomena observable on living bodies. But biology is also the most difficult of all natural sciences, not only from the complexity of the phenomena, which it studies, but in particular for another reason which is seldom properly emphasised, and therefore will well repay us for a few words devoted to it. Except so far as the " elements " of chemistry come into account, the experimenter in the inorganic fields of nature is not hampered by the specificity of composite objects : he makes all the combinations he wants. He is always able to have at his disposal red rays of a desired wave length when and where he wants, or to have, at a given time and place, the precise amount of any organic compound which he wishes to examine. And he forces electricity and electromagnetism to obey his will, at least with regard to space, time, and intensity of their appearance. The biologist is not able to " make " life, as the physicist has made red rays or electromagnetism, or as the chemist has made a certain compound of carbon. The biologist is THE PROGRAMME 11 almost always in that strange plight in which the physicist would be if he always had to go to volcanoes in order to study the conductivity of heat, or if he had to wait for thunderstorms in order to study electricity. The biologist is dependent on the specificity of living objects as they occur in nature. A few instances may show you what great incon- veniences may hence arise to impede practical biological research. We later on shall have to deal with experiments on very young embryos : parts of the germ will have to be destroyed in order to study what will happen with the rest.^ N"ow almost all germs are surrounded by a membrane ; this membrane has to be detached before any operation is possible. But what are we to do if it is not possible to remove the membrane without killing the embryo ? Or what if, as for instance in many marine animals, the membrane may be removed but the germs are killed by contact with sea- water ? In both cases no experiments at all will be possible on a sort of germ which otherwise, for some special circumstances of its organisation, might have given results of importance. These results become impossible for only a practical, for a very secondary reason ; but enough : they are impossible, and they might have thrown light on problems which now must remain problems. Quite the same thing may occur in experiments on physiology proper or functional physiology : one kind of animals survives the operation, the other kind does not, and therefore, for merely extrinsic reasons, the investigations have to be restricted to the first, though the second might have given more im- portant results. And thus the biological experimenter always finds himself in a sort of dependence on his subjects, 12 SCIENCE AND PHILOSOPHY OF THE ORGANISM which can hardly be called pleasant. To a great extent the comparatively slow advance of biological sciences is due to this very fact : the unalterable specific nature of biological material. But there is still another feature of biology dependent on the same fact. If a science is tied down to specific objects in every path it takes, it first, of course, has to know all about those objects, and that requires nothing else but plain description. We now understand why pure description, in the most simple sense of the word, takes up such an enormous part of every text-book of biological science. It is not only morphology, the science of form, that is most actively concerned with description ; physiology also, in its present state, is pure description of what the functions of the different parts of the body of animals and plants actually are, at least for about nine-tenths of its range. It seems to me important to press this point very emphatically, since we often hear that physiology is from the very beginning a much higher sort of knowledge than morphology, inasmuch as it is rational. That is not at all true of the beginning of physiology : what the functions of the liver or of the root are has simply to be described just as the organisation of the brain or of the leaf, and it makes no difference logically that one species of description has to use the experimental method, while the other has not. The experiment which only discovers what happens here or what happens there, possesses no kind of logical superiority over pure description at aU. But there will be another occasion in our lectures to deal more fully with the logic of experiment and with the differences of descriptive knowledge and real rational science. THE PROGRAMME 13 The three Different Types of Knowledge about Nature Natural sciences cannot originate before the given phenomena of nature have been investigated in at least a superficial and provisional manner, by and for the practical needs of man. But as soon as true science begins in any limited field, dealing, let us say, with animals or with minerals, or with the properties of bodies, it at once finds itself confronted by two very different kinds of problems, both of them — like all " problems " — created in the last resort by the logical organisation of the human mind, or, to speak still more correctly, of the Ego. In any branch of knowledge which practical necessities have separated from others, and which science now tries to study methodically, there occur general sequences in phenomena, general orders of events. This uniformity is revealed only gradually, but as soon as it has shown itself, even in the least degree, the investigator seizes upon it. He now devotes himself chiefly, or even exclusively, to the generalities in the sequences of all changes. He is con- vinced that there must be a sort of most general and at the same time of most universal connection about all occurrences. This most universal connection has to be found out ; at least it will be the ideal that always will accompany the inquir- ing mind during its researches. The " law of nature " is the ideal I am speaking about, an ideal which is nothing less than one of the postulates of the possibility of science at all. Using for our purposes a word which has been already introduced into terminology by the philosopher Windelband, 14 SCIENCE AND PHILOSOPHY OF THE ORGANISM though in a somewhat different sense, we shall call that part of every branch of natural sciences which regards the establishment of a law of nature as its ideal, " nomothetic," i.e. " law -giving." But while every natural science has its nomothetic side, it also has another half of a very different kind. This second half of every natural science does not care for the same general, the same universal, which is shown to us in every event in a different and specified kind : it is diversity, it is specification, that constitutes the subject of its interest. Its aim is to find a sufficient reason for the types of diversities, for the types of specifications. So in chemistry there has been found a systematic order in the long series of the compounds and of the elements ; crystallography also has its different systems of crystals, and so on. We have already employed the word by which we shall designate this second half of every natural science : it is the " systematic " side of science. Nomothetic work on the one side and systematics on the other do, in fact, appear in every natural science, and besides them there are no other main parts. But " science " as a whole stands apart from another aspect of reality which is called " history." History deals with particulars, with particular events at such and such a place, whilst science always abstracts from the particular, even in its systematic half ^ ' Windelband {Geschichte wid Naturwisseiischaft, 3 Auflage, 1904) gives the name "nomothetic " to the whole of our " science " and calls the method of history " idiographic. " We thought it better to establish three funda- mental types of all possible branches of knowledge. THE PROGRAMME 15 G-ENEEAL Plan of these Lectures Turning now to a sort of short outline of what is to be discussed in the whole of our future lectures, this summer and next, it seems clear, without further analysis, that biology as a science has its nomothetic and its systematic part also ; respiration and assimilation, for instance, have proved to be types of natural laws among living phenomena, and that there is a " system " of animals and plants is too commonly known to require further explanation here. Therefore we might study first biological laws, and after that biological systematics, and in the third place perhaps biological history. But that would hardly correspond to the philosophical aims of our lectures : our chief object is not biology as a regular science, as treated in text-books and in ordinary university lectures ; our chief object is the Philosophy of the Organism, as aided and supported by scientific biology. Therefore a general acquaintance with biology must be assumed in these lectures, and the biological materials must be arranged according to their bearing on further, that is on philosophical, analysis. That will be done, not, of course, to the extent of my regarding every one of my audience as a competent biologist ; on the contrary, I shall explain most fully all points of biology proper, and even of the most simple and descriptive kind of biology, which serve as bases for philosophical analysis. But I shall do so only if they indeed do serve as such bases. All our biology will be not for its own sake, but for the sake of philosophy. Whilst regarding the whole of the biological material 16 SCIENCE AND PHILOSOPHY OF THE ORGANISM with such aims, it seems to me best to arrange the properly scientific material which is to be the basis of my discussions, not along the lines which biology as an independent science would select,^ but to start from the three different kinds of fundamental phenomena which living bodies offer to in- vestigation, and to attach all systematics exclusively to one of them. Tor there will not be very much for philosophy to learn from biological systematics at present. Life is unknown to us except in association with bodies : we only know living bodies and call them organisms. It is the final object of all biology to tell us what it ultimately means to say that a body is " living," and in what sorts of relation body and life stand one to the other. But at present it is enough to understand the terms " body " and " living " in the ordinary and popular sense. Eegarding living bodies in this unpretentious manner, and recollecting what the principal characters are of all bodies we know as living ones, we easily find that there are three features which are never wanting wherever life in bodies occurs. All living bodies are specific as to form — they " have " a specific form, as we are acaustomed to say. All living bodies also exhibit metabolism ; that is to say, they stand in a relation of interchange of materials with the surrounding medium, they take in and give out materials, but their form can remain unchanged during these processes. And, in the last place, we can say that all living bodies move ; though this faculty is more commonly known among animals only, even elementary science teaches the student that it also belongs to plants. Therefore we may ask for " laws of nature " in biology 1 See J. Arth. Thomson, The Science of Life, London, 1899. THE PROGRAMME 17 about form, atout metabolism, and about movements. In fact, it is according to this scheme that we shall arrange the materials of the biological part of our lectures, though, as we cannot regard the three divisions as equally impor- tant in their bearing on our ultimate purposes, we shall not treat them quite on equal terms. It will appear that, at least in the present state of science, the problems of organic form and of organic movement have come into much closer relation to philosophical analysis than have most of the empirical data on metabolism. It is /orm particularly which can be said to occupy the very centre of biological interest ; at least it furnishes the foundation of all biology. Therefore we shall begin our scientific studies with a full and thorough analysis of form. The science of living forms, later on, will afford us a key to study metabolism proper with the greatest advantage for our philosophical aims, and therefore the physiology of what is usually called the vegetative functions will be to us a sort of appendix to our chapters on form ; only the theory of a problematic " living substance " and of assimilation in the most general meaning of the word will be reserved for the philosophical part ; for very good reasons, as I hope to show. But our chapters on the living forms will have yet another appendix besides the survey of the physiology of metabolism. Biological systematics almost wholly rests on form, on " morphology " ; and what hitherto has been done on the metabolical side of their problems, consists of a few fragments, which are far from being an equivalent to the morphological system ; though, of course it must be granted that, logically, systematics, in our general meaning of the word, as the sum of problems about the typically different 18 SCIENCE AND PHILOSOPHY OF THE ORGANISM and the specific, may be studied on the basis of each one of the principal characteristics of living bodies, not only on that of their forms. Therefore, systematics is to be the second appendix to the chief part of our studies in morpho- logy, and systematics, in its turn, will later on lead us to a short sketch of the historical side of biology, to the theory of evolution in its different forms, and to the logic of history in general. So far will our programme be carried out during this summer. Next year the theory of movements will con- clude our merely scientific analysis, and the remaining part of the course next summer will be devoted to the philosophy of living nature. I hope that nobody will be able to accuse our philosophy of resting on unsound founda- tions. But those of you, on the other hand, who would be apt to regard our scientific chapters as a little too long compared with their philosophical results, may be asked to consider that a small clock-tower of a village church is generally less pretentious but more durable than the campanile of San Marco has been. Indeed, these lectures will afford more " facts " to my bearers, than Gifford Lectures probably have done, as a rule. But how could that be otherwise on the part of a naturalist ? Scientific facts are the material that the philosophy of nature has to work with, but these facts, unfortunately, are not as commonly known as historical facts, for instance, generally are; and they must be known, in order that a philosophy of the organism may be of any value at all, that it may be more than a mere entertainment. Goethe once said, that even in so-called facts there is more " theory " than is usually granted ; he apparently was THE PROGRAMME 19 thinking of what might be called the ultimate or the typical facts in science. It is with such typical or ultimate facts, of course, that we must become acquainted if our future philosophy is to be of profit to us. Certainly, there would be nothing to prevent us from arranging our materials in a manner exactly the reverse of that which we shall adopt ; we could begin with a general principle about the organic, and could try to deduce all its special features from that principle, and such a way perhaps would seem to be the more fascinating method of argument. But though logical it would not be psychological, and therefore would be rather unnatural. And thus our most general principle about the organic will not come on the scene before the eighteenth of these twenty lectures, although it is not a mere inference or deduction from the former lectures : it will be a culmination of the whole, and we shall appreciate its value the better the more we know what that whole really is. Geneeal Chaeactek of the Oeganic Foem Our programme of this year, it was said, is to be ■devoted wholly to organic forms, though one of its appendixes, dealing with some characteristics of the physiology of metabolism, will lead us on to a few other phenomena. What then are the essentials of a living form, as commonly understood even without a special study of biology ? Living bodies are not simple geometrical forms, not, like crystals, merely a typical arrangement of surfaces in space, to be reduced theoretically, perhaps, to an arrange- ment of molecules. Living bodies are typically combined 20 SCIENCE AND PHILOSOPHY OF THE ORGANISM forms; that is to say, they consist of simpler parts of different chara,cters, which bave a special arrange- ment with regard to one another; these parts have a typical form of their own and may again be combiaa- tions of more simple different parts. But besides that, living bodies have not always the same typically com- bined form during the whole of their life : they become more complicated as they grow older; they all begin from one starting point, which has little form at all, viz., the egg. So the living form may be called a " genetic form," or a form considered as a process, and therefore morphogenesis is the proper and adequate term for the science which deals with the laws of organic forms in general ; or, if you prefer not to use the same word both for a science and for the subjects of that science, the physiology of morphogenesis. Now there are different branches of the physiology of morphogenesis or physiology of form. "We may study, and indeed we at first shall study, what are the laws of the morphogenetic processes leading from the egg to the adult : that may be properly called physiology of development. But living forms are not only able to originate in one unchange- able way : they may restore themselves, if disturbed, and thus we get the physiology of restoration or restitution as a second branch of the science of morphogenesis. We shall draw very important data, some of the foundations indeed of our philosophical discussions, from the study of such restitutions. Besides that, it is to them that our survey of the problems of the physiology of metabolism is to be appended. Living forms not only originate from the egg and are able to restore themselves, they also may give origin to other forms, guaranteeing in this way the continuity of life. THE PROGRAMME 21 The physiology of heredity therefore appears as the counter- part to those branches of the physiology of form which deal with individual form and its restitutions. And our dis- cussion on heredity riiay be followed by our second appendix to this chief section on form, an appendix regarding the outlines of systematics, evolution and history. Theoretical considerations on biology generally start, or at least, used to start, from the evolution theory, discussing all other problems of the physiology of form by the way only, as things of secondary importance. You see from our programme, that we shall go just the opposite way: evolution will come last of all, and will be treated shortly ; but the morphogenesis of the individual will be treated very fully, and very carefully indeed. Why then this deviation from what is the common practice ? Because we do not know very much aboi^t' evolution at all, because in this field we are just at the very beginning of what deserves the name of exact knowledge. But concerning individual morphogenesis we really know, even at present, if not very much, at least something, and that we know in a fairly exact form, aided by the results of experiments. And it will not be without its reward, if we restrict our aims in such a manner, if we prefer to deal more fully with a series of problems, which may seem at the first glance to be of less interest than others. After a few lectures we shall find already that we may decide one very important question about life merely by an analysis of individual form production, and without any regard to problematic and doubtful parts of biology: that we may decide the question, whether " life " is only a combination of chemical 22 SCIENCE AND PHILOSOPHY OF THE ORGANISM and physical events, or whether it has its elemental laws, laws of its own. But to prepare the road that is to lead to such results we first have to restrict our aims once more, and therefore the next lecture of this course, which eventually is to touch almost every concept of philosophy proper, will begin with the pure description of the individual development of the common sea-urchin. SECTION A THE CHIEF EESULTS OF ANALYTICAL BIOLOGY 23 PAET I THE INDIVIDUAL ORGANISM WITH REGARD TO FORM AND METABOLISM A. ELEMENTARY MORPHOGENESIS EVOLUTIO AND EPIGBNESIS IN THE OLD SENSE The organism is a specific body, built up by a typical com- bination of specific and different parts. It is implied in the words of this definition, that the organism is different, not only from crystals, as was mentioned in the last lecture, but also from all combinations of crystals, such as those called dendrites and others, which consist of a typical arrange- ment of identical units, the nature of their combination depending on the forces of every single one of their parts. For this reason dendrites, in spite of the typical features in their combination, must be called aggregates; but the organism is not an aggregate even from the ihost superficial point of view. We have said before, what must have been familiar to you already, that the organism is not always the same in its individual life,, that it has its development, leading from simpler to more complicated forms of combination of parts ; there is a " production of visible manifoldness " carried out during development, to describe the chief character of that 25 26 SCIENCE AND PHILOSOPHY OF THE ORGANISM process in the words of Wilhelni Eoux. We leave it an open question in our present merely descriptive analysis, whether there was already a " manifoldness," in an invisible state, before development, or whether the phrase "pro- duction of manifoldness " is to be understood in an absolute sense. It has not always been granted in the history of biology, and of embryology especially, that production of visible manifoldness is the chief feature of what is called an organism's embryology or ontogeny : the eighteenth century is full of determined scientific battles over the question. One school, with Albert von Haller and Bonnet as its leading men, maintained the view that there was no production of different parts at all in development, this process being a mere " evolutio," that is, a growth of parts already existing from the beginning, yes, from the very beginning of life ; whilst the other school, with C. F. Wolff and Blumenbach at its head, supported the opposite doctrine of so-called " epigenesis," which has been proved to be the right one. To some extent these differences of opinion were only the outcome of the rather imperfect state of the optical instruments of that period. But there were also deeper reasons beyond mere difficulties of description ; there were theoretical convictions underlying them. It is impossible, said the one party, that there is any real production of new parts ; there must be such a production, said the other. We ourselves shall have to deal with these questions of the theory of organic development ; but at present our objept is narrower, and merely descriptive. It certainly is of great importance to understand most clearly that there actually is a " production of visible manifoldness " during ELEMENTARY MORPHOGENESIS 27 ontogenesis in the descriptive sense ; the knowledge of the fact of this process must be the very foundation of all studies on the theory of development in any case, and therefore we shall devote this whole lecture to studies in merely descriptive embryology. But descriptive embryology, even if it is to serve merely as an instance of the universality of the fact of epigenesis, can only be studied successfully with reference to a concrete case. We select the development of the common sea-urchin (Echinus microtuberculatus) as such a case, and we are the more entitled to select this organism rather than another, because most of the analytical experimental work, carried out in the interests of a real theory of development, has been done on the germs of this animal. Therefore, to know at least the outlines of the individual embryology of the Echinus may indeed be called the conditio sine qua non for a real understanding of what is to follow. The Celli You are aware that all organisms consist of organs and that each of their organs has a different function : the brain, the liver, the eyes, the hands are types of organs in animals, as are the leaves and the pistils in plants. You are also aware that, except in the lowest organisms, the so-called Protista, all organs are built up of cells. That is. a simple fact of observation, and I therefore cannot agree with the common habit of giving to this plain fact the title of cell-" theory." There is nothing theoretical in it; and, ' E. B. Wilson, The Cell in Development and Inheritance, New York, Macmillan, 1896. 28 SCIENCE AND PHILOSOPHY OP THE ORGANISM on the other hand, all attempts to conceive the organism as a mere aggregate of cells have proved to be wrong. It is ths whole that uses the cells, as we shall see later on, or that may not use them : thus there is nothing like a " cell- theory," even in a deeper meaning of the word. The cell may have the most different forms : take a cell of the skin, of a muscle, of a gland, of the wood in plants as typical examples. But in every case two parts may be distinguished in a cell : an outside part, the protoplasm, and an inside part, the nucleus, to leave out of special account several others, which, by the way, may only be protoplasmatic modifications. Protoplasm is a mere name for what is not the nucleus ; in any case it is not a homogeneous chemical compound ; it consists of many such compounds and has a sort of architecture; aU organic functions are based upon its metabolism. The nucleus has a very typical structure, which stands in a close relation to its behaviour during the most characteristic morphological period of the cell : during its division. Let us devote a few words to a consideration of this division and the part the nucleus plays in it; it will directly bear on future theoretical considerations about development. There is a certain substance in every nucleus of a cell which stains most markedly, whenever cells are treated with pigments : the name of " chromatin " has been given to it. The chromatin always gives the reaction of an acid, while protoplasm is basic ; besides that it seems to be a centre of oxidation. Now, when a division of a cell is to occur, the chromatin, which had been diffusely distributed before, in the form of small grains, arranges itself into a long and ELEMENTARY MORPHOGENESIS 29 very much twisted thread. This thread breaks, as it were Fio. 1.— Diagram op Cell-Division (c^fter Boveri). a. Besting cell ; the chromatin distributed in the form of small granules inside the nucleus. Outside the nucleus is the "centrosome," not mentioned in the text. b. Beginning of division ; the chromatin arranged in the form of a long thread. Centro- some divided in two. c. The thread of chromatin cut into four parts, the " chromosomes." d. The four parts of the chromatin arranged symmetrically between the centrosomes and the star-like "spheres." e. Each of the chromosomes split at full length. /. Beginning of division of protoplasm ; the two parts of each chromosome separated. g. End of cell-division. by sections, into almost equal parts, typical in number for each species, and each of these parts is split at full length. 30 SCIENCE AND PHILOSOPHY OF THE ORGANISM A certain number of pairs of small threads, the so-called " chromosomes," are the ultimate result of this process, which intentionally has been described a little schematically, the breaking and the splitting in fact going on simul- taneously or occasionally even in reverse order. While what we have described is performing in the nucleus, there have happened some typical modifications in protoplasm, and then, by an interaction of protoplasmatic and nuclear factors, the first step in the actual division of the cell begins. Of each pair of the small threads of chromatin one constituent is moved to one side of the cell, one to the other ; two daughter-nuclei are formed in this way; the protoplasm itself at the same time forms a circular furrow between them ; the furrow gets deeper and deeper ; at last it cuts the cell in two, and the division of the cell is accomplished. Not only is the growth of the already typically formed organism carried out by a series of cell-divisions, but also development proper in our sense, as a " production of visible manifoldness," is realised to a great extent by the aid of such divisions, which therefore may indeed be said to be of very fundamental importance (Fig. 1). Each cell-division which promotes growth is followed by the enlargement of the two daughter-cells which result from it ; these two daughter-elements attain the exact size of the mother-cell before division, and as soon as this size is reached a new division begins : so the growth of the whole is in the main the result of the growth of the elements. Cell- divisions during real organ-formation may behave diflferently, as will be described at a proper occasion. elementary morphogenesis 31 The Egg : its Matueation and Fertilisation We know that all the organs of an animal or plant con- sist of cells, and we know what acts a cell can perform. Now there is one very important organ in all living beings, which is devoted to reproduction. This organ, the so-called ovary in animals, is also built up of cells, and its single cells are called the eggs ; the eggs originated by cell-division, and cell-division is to lead from them to the new adult. But, with a very few exceptions, the egg in the ovary is not able to accomplish its functions, unless certain typical events have occurred, some of which are of a merely pre- paratory kind, whilst the others are the actual stimulus for development. The preparatory ones are generally known under the name of "maturation." The egg must be "mature," in ■order that it may begin development, or even that it may be stimulated to it. Maturation consists of a rather com- plicated series of phenomena : later on we shall have -occasion to mention, at least shortly, what happens in the protoplasm during its course ; as to the nuclear changes •during maturation it may be enough for our purposes to say, that there occur certain processes among the chromosomes, which lead to an extension of half of them in the form of -two very small cells, the " directive cells " or " directive or polar bodies," as they have been somewhat cautiously ■called. The ripe or mature egg is capable of being fertilised. Before turning to this important fact, which, by the way, "will bring us to our specially chosen type, the Echinus, a few words may be devoted to the phenomenon of " partheno- 32 SCIENCE AND PHILOSOPHY OF THE ORGANISM genesis," that is to say, the possibility of development without fertilisation, since owing to the brilliant discoveries of the American physiologist, Jacques Loeb, this topic forms one of the centres of biological interest at present. It has long been known that the eggs of certain bees, lice, crayfishes, and other animals and also plants, are capable of develop- ment without fertilisation at all. Now Eichard Hertwig and T. H. Morgan already had shown, that at least nuclear division may occur in the eggs of other forms — ^in the egg of the sea-urchin for instance — when these eggs are exposed to some chemical injuries. But Loeb ^ succeeded in obtaining a full development by treating the eggs of echinoderms with chloride of magnesium ; thus artificial parthenogenesis had been discovered. Later researches have shown that artificial parthenogenesis may occur in all classes of the animal kingdom and may be provoked by all sorts of chemical or physical means. We do not know at present in what the proper stimulus consists that must be supposed here to take the place of fertilisation ; it seems, of course, highly probable that it is always the same in the last resort.^ But enough about processes, which at present are of a highly scientific, but hardly of any philosophic interest. By fertilisation proper we understand the joining of the male element, the spermatozoon or the spermia, with the female element, the egg. Like the egg, the spermatozoon is but a cell, though the two differ very much from one another ^ Amer. Journ. Physiol, vols. iii. and iv. 1900. ^ According to Delage (Arch. Zool. exp., 3 ser. 10, 1902), it is indifferent for the realisation of artificial parthenogenesis, whether but one, or both, or neither of the ' ' polar bodies "has been formed. But the egg must be in the first stages of maturation to the extent that the " nuclear membrane " must be already dissolved. ELEMENTARY MORPHOGENESIS 33 in the relation between their protoplasm and nucleus : in all eggs it is the protoplasm which is comparatively very large, if held together with somatic cells, in the spermatozoon it is the nucleus. A large amount of reserve material, destined for the growth of the future being, is the chief cause of the size of the egg-protoplasm. The egg is quite or almost devoid of the faculty of movement, whUe on the contrary, movement is the most typical feature of the spermia. Its whole organisation is adapted to movement in the most characteristic manner: indeed, most spermatozoa resemble a swimming infusorium, of the type of Flagellata, a so-called head and a moving tail are their two chief constituents ; the head is formed almost entirely of nuclear substance. It seems that in most cases the spermatozoa swim around at random and that their union with the eggs is assured only by their enormous number ; only in a few cases in plants have there been discovered special stimuli of a chemical nature, which attract the spermia to the egg. But we cannot enter here more fully into the physiology of fertilisation, and shall only remark that its real significance is by no means clear.^ The Fiest Development Peocess of Echinus Turning now definitively to the special kind of organism, chosen of our type, the common sea-urchin, we properly ^ The older theories, attributing to fertilisation (or to "conjugation," i.e. ita equivalent in Protozoa), some sort of ' ' renovation " or " rejuvenescence " of the race, have been almost completely given up. (See Calkins, Arch, fii/r Entwickelungsmechanik, xv. 1902). R. Hertwig recently has advocated the view, that abnormal relations between the amounts of nuclear and of proto- plasmatic material are rectified in some way by these processes. Teleologically, sexual reproduction has been considered as a means of variability (Weismann), but alao as a means of preserving the type ! 3 34 SCIENCE AND PHILOSOPHY OF THE ORGANISM begin with a few words about the absolute size of its eggs and spermatozoa. All of you are familiar with the eggs of birds and possibly of frogs; these are abnormally large eggs, on account of the very high amount of reserve material they contain. The almost spherical egg of our Echinus only measures about a tenth of a millimetre in diameter ; and the head of the spermatozoon has a volume which is only the four-hundred-thousandth part of the volume of the egg ! The egg is about on the extreme limit of what can be seen without optical instruments; it is visible as a small white point. But the number of eggs produced by a single female is enormous and may amount to hundreds of thousands ; this is one of the properties which render the eggs of Echinus so very suitable for experimental research ; you can obtain them whenever and in any quantity you like ; and, moreover, they happen to be very clear and transparent, even in later stages, and to bear all kinds of operations well. The spermia enters the egg, and it does so in the open water — another of the experimental advantages of our type. Only one spermia enters the egg in normal cases, and only its head goes in, the tail is left outside. The moment that the head has penetrated the protoplasm of the egg a thin membrane is formed by the latter. This membrane is very soft at first, becoming much stronger later on; it is very important for all experimental work, that by shaking the egg in the first minutes of its existence the membrane can easily be destroyed without any damage to the egg itself. And now occurs the chief phenomenon of fertilisation : the nucleus of the spermatozoon unites with the nucleus of the egg. "When speaking of maturation, we mentioned that ELEMENTARY MORPHOGENESIS 35 half of the chromatin was thrown out of the egg by that process : now this half is brought in again, but comes from another individual. It is from this phenomenon of nuclear union as the main character of fertilisation that almost all theories of heredity assume their right to regard the nuclei of the sexual cells as the true "seat" of inheritance. Later on we shall have occasion to discuss this hypothesis from the point of view of logic and fact. After the complete union of what are called the male and the female " pronuclei," the egg begins its development ; and this development, in its first steps, is simply pure cell- division. We know already the chief points of this process, and need only add to what has been described, that in the whole first series of the cell-divisions of the egg, or, to use . the technical term, in the whole process of the " cleavage " or " segmentation " of it, there is never any growth of the daughter-elements after each division, such as we know to occur after all cell-divisions of later embryological stages. So it happens, that during cleavage the embryonic cells become smaller and smaller, until a certain limit is reached ; the sum of the volumes of all the cleavage cells together is equal to the volume of the egg. But our future studies will require a more thorough knowledge of the cleavage of our Echinus ; the experimental data we shall have to describe later on could hardly be properly understood without such knowledge. The first division plane, or, as we shall say, the first cleavage plane, divides the eggs into equal parts ; the second lies at right angles to the first and again divides equally : we now have a ring of four cells. The third cleavage plane stands at 36 SCIENCE AND PHILOSOPHY OP THE ORGANISM right angles to the first two ; it may be called an equatorial plane, if we compare the egg with a globe ; it also divides equally, and so we now find two rings, each consisting of four cells, and one above the other. But now the cell- divisions cease to be equal, at least in one part of the egg : the next division, which leads from the eight- to the sixteen -cell stage of cleavage, forms four rings, of four cells each, out of the two rings of the eight-cell stage. Only in one half of the germ, which we shall call the upper one, or which we might call, in comparison with a globe, the northern hemisphere, are cells of equal size to be found ; in the lower half of the egg four very small cells have been formed at one " pole " of the whole germ. We call these cells the " micromeres," that is, the " small parts," on the analogy of the term " blastomeres," that is, parts of the germ, which is applied to all the cleavage cells in general. The place occupied by the micromeres is of great importance to the germ as a whole : the first formation of real organs will start from this point lat^r on. It is sufficient thus fully to have studied the cleavage of our Echinus up to this stage: the later cleavage stages may be mentioned more shortly. All the following divisions are into equal parts ; there are no other micromeres formed, though, of course, the cells derived from the micromeres of the sixteen- cell stage always remain smaller than the rest. All the divisions are tangential ; radial cleavages never occur, and therefore the process of cleavage ends at last in the forma- tion of one layer of cells, which forms the surface of a sphere ; it is especially by the rounding-up of each blasto- mere, after its individual appearance, that this real surface layer of cells is formed, but, of course, the condition, that ELEMENTARY MORPHOGENESIS 37 no radial divisions occur, is the most important one in its formation. When 808 blastomeres have come into existence the process of cleavage is finished; a sphere with a wall of cells and an empty interior is the result. That only 808 cells are formed, and not, as might be expected, 1024, is due to the fact that the micromeres divide less often than the other elements ; but speaking roughly, of course, we may say that there are ten steps of cleavage-divisions in our form; 1024 being equal to 2-^°. We have learned that the first process of development, the cleavage, is carried out by simple cell- division. A few cases are known, in which cell-division during cleavage is accompanied by a specific migration of parts of the protoplasm in the interior of the blastomeres, especially in the first two or first four; but in almost all instances cleavage is as simple a process of mere division as it is in our sea-urchin. Now the second step in development, at least in our form, is a typical histological performance : it gives a new histological feature to all of the blastomeres : they acquire small cilia on their outer side and with these cilia the young germ is able to swim about after it has left its membrane. The germ may be called a " blastula " at this stage, as it was first called by Haeck eL- whose useful denominations of the first embryonic stages may conveniently be applied, even if one does not agree with most, or perhaps almost all, of his speculations (Fig. 2). It is important to notice that the formation of the " blastula " from the last cleavage stage is certainly a process of organisation, and may also be called a differentiation with regard to that stage. But there is in the blastula no trace of one 'part of the germ becoming 38 SCIENCE AND PHILOSOPHY OF THE ORGANISM different with respect to others of its parts. If development were to go on in this direction alone, high organisatory complications might occur: but there would always be only one sort of cells, arranged in a sphere ; there would be only one kind of what is called " tissue." Fig. 2.— Early Development of Echinus, the Common SEA-nKoaiN. a. Two cells, b. Pour cells, e. Eight cells, arranged in two rings of four, above one another. d. Sixteen cells, four "microraeres" fonned at the "vegetative" pole. e. Optical section of the "blastula," a hollow sphere consisting of about one thousand cells, each of them with a small cilium. But in fact development very soon leads to true differences of the parts of the germ with respect to one another, and the next step of the process will enable us to apply different denominations to the different parts of the embryo. At one pole of the swimming blastula, exactly at the poiQt where the descendants of the micromeres are situated, ELEMENTARY MORPHOGENESIS 39 about fifty cells lose contact with their neighbours and leave the surface of the globe, being driven into the interior space of it. Not very much is known about the exact manner in which these changes of cellular arrangement are carried out, whether the cells are passively pressed by their neighbours, or whether, perhaps, in a more active manner, they change their surface conditions ; therefore, as in most ontogenetic processes, the description had best be made cautiously in fairly neutral or figurative words. The cells which in the above manner have entered the interior of the blastula are to be the foundation of important parts of the future organism ; they are to form its connective tissue, many of its muscles, and the skeleton. " Mesenchyme," i.e. " what has been infused into the other parts," is the technical name usually applied to these cells. We now have to learn their definite arrangement. At first they lie as a sort of heap inside the cell wall of the blastula, inside the "blastoderm," i.e. skin of the germ. But soon they move from one another, to form a ring round the pole at which they entered, and on this ring a process takes place which has a very important bearing upon the whole type of the organisation of the germ. You will have noticed that hitherto the germ with regard to its symmetry has been a monaxial or radial formation ; the cleavage stages and the blastula with its mesenchyme were forms with two different poles, lying at the ends of one single line, and round this line everything was arranged concentrically. But now what is called "bilateral symmetry" is established; the mesenchyme ring assumes a structure which can be symmetrically divided only by one plane, but divided in such a way, that one-half of it is the mirror image of the 40 SCIENCE AND PHILOSOPHY OF THE ORGANISM other. A figure shows best what has occurred, and you will notice (Fig. 3) two masses of cells in this figure, which have the forms of spherical triangles : it is in the midst of these triangles that the skeleton of the larva originates. The germ had an upper and a lower side before : it now has got an upper and lower, front and back, right wnd left half; it now has acquired that symmetry of organisation a, Q) o o c o o o o o o c> Fig. 3.— Formation of Mesenchyme in Echinus. a.) Outlines of blastula, side-view; mesenchyme forms a heap of cells at the "vegeta- tive " pole. oj. Heap of mesenchyme-ceils from above. 6. Mesenchyme-cells arranged in a ring round the vegetative pole. c. Mesenchyme-cells arranged in a bilateral-symmetrical figure ; primordia of skeleton in the midst of two spherical triangles. which our own body has ; at least it has got it as far as its mesenchyme is concerned. We leave the mesenchyme for a while and study another kind of organogenesis. At the very same pole of the germ where the mesenchyme cells originated there is a long and narrow tube of cells growing in, and this tube, getting longer and longer, after a, few hours of growth touches the opposite pole of the larva. The growth of this cellular tube marks ELEMENTARY MORPHOGENESIS 41 the beginning of the formation of the intestine, with all that is to be derived from it. The larva now is no longer a blastula, but receives the name of " gastrula " in Haeckel's ) terminology ; it is built up of the three " germ-layers " in this stage. The remaining part of the blastoderm is called "ectoderm," or outer layer; the newly -formed tube, " endoderm," or inner layer ; while the third layer is the " mesenchyme " already known to us. The endoderm itself is a radial structure at iirst, as was the whole germ in a former stage, but soon its free end bends and moves against one of the sides of the ectoderm, against that side of it where the two triangles of the mesenchyme are to be found also. Thus the endo- derm has acquired bilateral symmetry just as the mesen- chyme before, and as in this stage the ectoderm also assumes a bilateral symmetry in its form, corresponding with the symmetrical relations in the endoderm and the mesenchyme, we now may call the whole of our larva a bilateral-symmetrical organisation. It cannot be our task to follow all the points of organo- genesis of Echinus in detail. It must suffice to state briefly that ere long a second portion of the mesenchyme is formed in the larva, starting from the free end ' of its intestine tube ; that the formation of the so-called " coelum " occurs by a sort of splitting off from this same original organ ; and that the intestine itself is divided into three parts of different size and aspect by two circular sections. But we must not, I think, dismiss the formation of the skeleton so quickly. I told you already that the skeleton has its first origin in the midst of the two triangular 42 SCIENCE AND PHILOSOPHY OF THE ORGANISM cell-masses of the meseD chyme ; but what are the steps before it attains its typical and complicated structure ? At the beginning a very small tetrahedron, consisting of carbonate of calcium, is formed in each of the triangles ; the four edges of the tetrahedron are produced into thin rods, and by means of a different organogenesis along each of these rods the typical formation of the skeleton proceeds. But the manner in which it is carried out is very strange and peculiar. About thirty of the mesenchyme cells are occupied in the formation of skeleton substance on each fide of the larva. They wander through the interior space of he gastrula — which at this stage is not filled with sea water but with a sort of gelatinous material- — and wander in such a manner that they always come to the right places, where a part of the skeleton is to be formed ; they form it by a process of secretion, quite unknown in detail ; one of them forms one part, one the other, but what they form altogether, is one whole. When the formation of the skeleton is accomplished, the typical larva of our Echinus is built up ; it is called the " pluteus " (Fig. 4). Though it is far from being the perfect adult animal, it has an independent life of its own ; it feeds and moves about and does not go through any important changes of form for weeks. But after a certain period of this species of independent life as a " larva," the changes of form it undergoes again are most fundamental: it must be transformed into the adult sea-urchin, as all of you know. There are hundreds and hundreds of single operations of organogenesis to be accomplished before that end is reached; and perhaps the strangest of all these operations is a certain sort of growth, by which the symmetry ELEMENTARY MORPHOGENESIS 43 of the animal, at least in certain of its parts — not in all of them — is changed again from bilateral to radial, just the opposite of what happened in the very early stages ! But we cannot follow the embryology of our Echinus further here ; and indeed we are the less obliged to do so, since in all our experimental work we shall have to deal with it only as far as to the pluteus larva. It is impossible Fig. 4. — Larval Development of Echinus. A. The gastrula. B. Later stage, bilateral-symmetrical. Intestine begins to divide into three parts. C. Plutens larva. S=Skeleton. I = Intestine. under ordinary conditions to rear the germs up to the adult stages in captivity. You now, I hope, will have a general idea at least of the processes of which the individual development of an animal consists. Of course the specific features leading from the egg to the adult are different in each specific case, and, in 44 SCIENCE AND PHILOSOPHY OF THE ORGANISM order to make this point as clear as possible, I shall now add to our description a few words about what may be called a comparative descriptive embryology. Comparative Embeyology Even the cleavage may present rather different aspects. There may be a compact blastula, not one surrounded by only one layer of cells as in Echinus ; or bilateraUty may be established as early as the cleavage stage — as in many worms and in ascidians — and not so late as in Echinus. The formation of the germ layers may go on in a different order and under very different conditions : a rather close relative of our Echinus, for instance, the starfish, forms first the endoderm and afterwards the mesenchyme. In many cases there is no tube of cells forming the " endoderm," but a flat layer of cells is the first foundation of all the intestinal organs : so it is in all birds and in the cuttlefish. And, as all of you know, of course, there are very many animal forms which have no proper " larval " stage : there is one in the frog, the well-known " tadpole," but the birds and mammals have no larvae ; that is to say, there is no special stage in the ontogeny of these forms which leads an independent life for a certain time, as if it were a species by itself, but all the ontogenetical stages are properly " em- bryonic " — the germ is always an " embryo " until it becomes the perfect young organism. And you also know that not all skeletons consist of carbonate of calcium, but that there are skeletons of silicates, as in Eadiolaria, and of horny substance, as in many sponges. And, indeed, if we were to glance at the development of plants also, the differences ELEMENTARY MORPHOGENESIS 45 would seem to us probably so great that all the similarities would seem to disappear. But there are similarities, nevertheless, in all development, and we shall now proceed to examine what they are. As a matter of fact, it was especially for their sake that we studied the ontogeny of a special form in such detail ; one always sees generalities better if one knows the specific features of at least one case. What then are the features of most general and far-reaching importance, which may be abstracted from the individual history of our sea-urchin, checked always by the teachings of other ontogenies, includ- ing those of plants ? The Fiest Steps of Analytical Morphogenesis If we look back upon the long fight of the schools of embryologists in the eighteenth century about the question whether individual development was to be regarded as a real production of visible manifoldness or as a simple growth of visibly pre-existing manifoldness, whether it was "epi- genesis " or " evolutio," there can be no doubt, if we rely on all the investigations of the last hundred and fifty years, that, taken in the descriptive sense, the theory of epigenesis is right. Descriptively speaking there is a production of visible manifoldness in the course of embryology : that is our first and main result. Any one possessed of an average microscope may any day convince himself personally that it is true. In fact, true epigenesis, in the descriptive sense of the term, does exist. One thing is formed " after " the other ; there is not a mere " unfolding " of what existed already. 46 SCIENCE AND PHILOSOPHY OF THE ORGANISM though in a smaller form ; there is no " evolutio " in the old meaning of the word. The word "evolution" in English usually serves to denote the theory of descent, that is of a real relationship of all organisms. Of course we are not thinking here of this modern and specifically English meaning of the Latin word evolutio. In its ancient sense it means to a certain degree just the opposite ; it says that there is no formation of any- thing new, no transformation, but simply growth, and this is promoted not for the race but for the individual. Keeping well in mind these historical differences in the meaning of the word " evolutio," no mistakes, it seems to me, can occur from its use. We now shall try to obtain a few more particular results from our descriptive study of morpho- genesis, which are nevertheless of a general bearing, being real characteristics of organic individual development, and which, though not calculated of themselves to further the problem, will in any case serve to prepare for a more profound study of it. The totality of the line of morphogenetic facts can easily be resolved into a great number of distinct processes. We propose to call these " elementary morphogenetic processes "; the turning in of the endoderm and its division into three typical parts are examples of them. If we give the name " elementary organs " to the distinct parts of every stage of ontogeny which are uniform in themselves and are each the result of one elementary process in our sense, we are entitled to say that each embryological stage consists of a certain number of elementary organs. The mesenchyme rinw, the coelum, the middle-intestine, are instances of such organs. It is important to notice well that the word elementary is ELEMENTAEY MORPHOGEKESIS 47 always understood here with regard to visible morphogenesis proper and does not apply to what may be called elementary in the physiological sense. An elementary process in our sense is a very distinct act of form-building, and an elementary organ is the result of every one of such acts. The elementary organs are typical with regard to their position and with regard to their histological properties. In many cases they are of a very clearly different histo- logical type, as for instance, the cells of the three so-called germ-layers ; and in other cases, though apparently almost identical histologically, they can be proved to be different by their different power of resisting injuries or by other means. But there are not as many different types of histological structure as there are typically placed organs : on the contrary there are many elementary organs of the same type in different typical parts of the organism, as all of you know to be the case with nerves and muscles. It wUl not be without importance for our future theory of development, carefully to notice this fact, that specialisa- tion in the position of embryonic parts is more strict than / in their histology. But elementary organs are not only typical in position and histology, they are typical also with regard to their form and their relative size. It agrees with what has been said about histology being independent of typical position, that there may be a number of organs in an embryonic stage, aU in their most typical positions, which though all possessing the same histology, may have different forms or different sizes or both : the single bones of the skeleton of vertebrates or of adult echinoderms are the very best instances of this most important feature of organogenesis. If we look 48 SCIENCE AND PHILOSOPHY OF THE ORGANISM back from elementary organs to elementary processes, the specialisation of the size of those organs may also be said to be the consequence of a typical duration of the elementary morphogenetic process leading to them.^ I hardly need to say, that the histology, form, and size of elementary organs are equally an expression of their present or future physiological function. At least they prepare for this function by a specific sort of metabolism which sets in very early. The whole sequence of individual morphogenesis has been divided by some embryologists into two different periods ; there is a first period, during which the foundations of the organisation of the " type " are laid down, and a second period, during which the histo-physiological specifica- tions are modelled out (von Baer, Gotte, Eoux). Such a discrimination is certainly justified, if not taken too strictly ; but its practical application would encounter certain difficulties in many larval forms, and also, of course, in all plants. Our mention of plants leads us to the last of our analytical results. If an animal germ proceeds in its development from a stage d to the stage g, passing through e and /, we may say that the whole of d has become the whole of/,, but we cannot say that there is a certain part of / which is d, we cannot say that /is d + a. But in plants we can : the stage / is indeed equal to a + 'b + c-\-d + e:\-a in vegetable organisms ; all earlier stages are actually visiblg as parts of the last one. The great embryologist, Carl Ernst ' The phrase " ceteris paribus" has to be added of course, as the duration of each single elementary morphogenetic process is liable to vary with the temperature and many other conditions of the medium. ELEMENTARY MORPHOGENESIS 49 von Baer, most clearly appreciated these analytical differences between animal and vegetable morphogenesis. They become a little less marked if we remember that plants, in a certain respect, are not simple individuals but colonies, and that among the corals, hydroids, bryozoa, and ascidia, we find analogies to plants in the animal kingdom; but never- theless the differences we have stated are not extinguished by such reasoning. It seems almost wholly due to the occurrence of so many foldings and bendings and migrations of cells and complexes of cells in animal morphogenesis, that an earlier stage of their development seems lost in the later one ; those processes are almost entirely wanting in plants, even if we study their very first ontogenetic stages. If we say that almost all production of surfaces goes on outside in plants, inside in animals, we shall have adequately described the difference. And this feature again leads to the further diversity between animals and plants which is best expressed by calling the former "closed," the latter " open " forms : animals reach a point where they are finished, plants never are finished, at least in most cases. I hope you will allow that I have tried to draw from descriptive and comparative embryology as many general analytical results as are possibly to be obtained. It is not my fault if there are not any more, nor is it my fault if the results reached are not of the most satisfactory character. You may say that these results perhaps enable you to see a little more clearly and markedly than before a few of the characters of development, but that you have not really learnt anything new. Your disappointment — my own disappointment — in our analysis is due to the use of pure description and comparison as scientific methods. 4 50 science and philosophy of the organism The Limits of Puke Description in Science We have analysed our descriptions as far as we could, and now we must confess that what we have found cannot be the last thing knowable about individual morphogenesis. There must be something deeper to be discovered : we only have been on the surface of the phenomena, we now want to get to the very bottom of them. Why then occurs all that folding, and bending, and histogenesis, and all the other processes we have described ? There must be something that drives them out, so to say. There is a very famous dictum in the Treatise on Mechanics by the late Gustav Kirchhoff, that it is the task of mechanics to describe completely and in the most simple manner all the motions that occur in nature. These words, which may appear problematic even in mechanics, have had a really pernicious influence on biology. People were extremely pleased with them. " ' Describing ' — that is just what we always have done," they said ; " now we see that we have done just what was right ; a famous physicist has told us so." They did not see that Kirchhoff had added the words " completely and in the most simple manner " ; and moreover, they did not consider that Kirchhoff never regarded it as the ultimate aim of physics to describe thunderstorms or volcanic eruptions or denudations ; yet it only is with such "descriptions" that biological descriptions of given bodies and processes are to be compared ! Physicists always have used both experiment and hypo- thetical construction — Kirchhoff himself did so in the most gifted manner. With these aids they have gone through the whole of the phenomena, and what they found to be ultimate ELEMENTARY MORPHOGENESIS 51 and truly elemental, that alone may they be said to have " described " ; but they have " explained " by the aid of elementalities what proved to be not elemental in itself.^ It is the method of the physicists — not their results — that morphogenesis has to apply in order to make progress ; and this method we shall begin to apply in our next lectures. Physiology proper has never been so short-sighted and self- satisfied as not to learn from other sciences, from which indeed there was very much to be learned ; but morphology has : the bare describing and comparing of descriptions has been its only aim for about forty years or more, and lines of descent of a very problematic character were its only general results. It was not seen that science had to begin, not with problematic events of the past, but with what actually happens before our eyes. But before saying any more about the exact rational and experimental method in morphology, which indeed may be regarded as a new method, since its prevalence in the eighteenth century had been really forgotten, we first shall have to analyse shortly some general attempts to understand morphogenesis by means of hypothetic construction ex- clusively. Such attempts have become very important as points of issue for really exact research, and, moreover, they deserve attention, because they prove that their authors at least had not quite forgotten that there were still other problems to be solved in morphology than only phylo- genetical ones. ' We shall not avoid in these lectures the word " explain " — so miieh out of fashion nowadays. To ' ' explain " means to subsume under known concepts, or rules, or laws, or principles, whether the laws or concepts themselves be "explained" or not. Explaining, therefore, is always relative: what is elemental, of course, is only to be described, or rather to be stated. B. EXPERIMENTAL AND THEOEETICAL MOEPHOGENESIS 1. The Foundations of the Physiology of Develop- ment. " EVOLUTIO " AND " EPIGENESIS " THE THEOKY of WEISMANN Of all the purely hypothetic theories on morphogenesis that of August Weismann^ can claim to have had the greatest influence, and to be at the same time the most logical and the most elaborated. The "germ-plasma" theory of the German author is generally considered as being a theory of heredity, and that is true inasmuch as problems of inheritance proper have been the starting-point of all his hypothetic speculations, and also form in some respect the most valuable part of them. But, rightly under- stood, Weismann's theory consists of two independent parts, which relate to morphogenesis and to heredity separately, and it is only the first which we shall have to take into consideration at present ; what is generally known as the doctrine of the " continuity of the germ-plasm " will be discussed in a later chapter. Weismann assumes that a very complicated organised /structure, below the limits of visibility even with the ^ Das Keiinplasma, Jena, 1892. 52 EXPERIMENTAL MORPHOGENESIS 53 highest optical powers, is the foundation of all morpho- genetic processes, in such a way that, whilst part of this structure is handed over from generation to generation as the basis of heredity, another part of it is disintegrated during the individual development, and directs development by being disintegrated. The expression, "part" of the structure, first calls for some explanation. Weismann supposes several examples, several copies, as it were, of his structure to be present in the germ cells, and it is to these copies that the word " part " has been applied by us : at least one copy has to be disintegrated during ontogeny. The morphogenetic structure is assumed to be present in the nucleus of the germ cells, and "Weismann supposes the disintegration of his hypothetic structure to be accom- plished by nuclear division. By the cleavage of the egg, the most fundamental parts of it are separated one from the other. The word " fundamental " must be understood as applying not to proper elements or complexes of elements of the organisation, but to the chief relations of symmetry ; the first cleavage, for instance, may separate the right and the left part of the structure, the second one its upper and lower parts, and after the third or equatorial ijleavage all the principal eighths of our minute organisa- tion are divided off : for the minute organisation, it must now be added, had been supposed to be built up differently in the three directions of space, just as the adult organism is. Weismann concedes it to be absolutely unknown in what manner the proper relation between the parts of the disintegrated fundamental morphogenetic structure and the real processes of morphogenesis is realised; enough that there may be imagined such a relation. 54 SCIENCE AND PHILOSOPHY OF THE ORGANISM At the end of organogenesis the structure is assumed to have been broken up into its elements, and these elements, which may be chemical compounds, determine the fate of the single cells of the adult organism. Here let us pause for a moment. There cannot be any doubt that Weismann's theory resembles to a very high degree the old " evolutio " doctrines of the eighteenth century, except that it is a little less crude. The chick itself is not supposed to be present in the hen's egg before develop- ment, and ontogeny is not regarded as a mere growth of that chick in miniature, but what really is sugposed__to_be present in the egg is nevertheless a somethingJJia.t_,iQ„alLits part3_ cgirrespqnds, to all the parts of. the chick^ only under a somewhat different aspect, while all the relations of the parts of the one correspond to the relations of the .parts of the other. Indeed, only on such an hypothesis of a fairly fixed and rigid relation between the parts of the morphogenetic structure could it be possible for the disintegration of the structure to go on, not by parts of organisation, but by parts of symmetry ; which, indeed, is a very strange, but not an illogical, feature of Weismann's doctrine. Weismann is absolutely convinced that there mmt be a theory of " evolutio," in the old sense of the word, to account for the ontogenetic facts ; that " epigenesis " has its place only in descriptive embryology, where, indeed, as we know, manifoldness in the visible sense is produced, but that epigenesis can never form the foundation of a real morphogenetic theory : theoretically one pre-existing mani- foldness is transformed into the other. An epigenetic theory would lead right beyond natural science, Weismann EXPERIMENTAL MORPHOGENESIS 55 thinks, as in fact, all such theories, if fully worked out, have carried their authors to vitalistic views. But vital- ism is regarded by him as dethroned for ever. Under these circumstances we have a good right, it seems to me, to speak of a dogmatic basis of Weismann's theory of development. But to complete the outlines of the theory itself : Weismann was well aware that there were some grave difficulties attaching to his statements : all the facts of so-called adventitious morphogenesis in plants, of regeneration in animals, proved that the morphogenetic organisation could I not be fully disintegrated during ontogeny. But these difficulties were not absolute : they could be overcome : indeed, Weismann assumes, that in certain specific cases — and he regarded all cases of restoration of a destroyed organisation as due to specific properties of the subjects, originated by roundabout variations and natural selection — that in specific cases, specific arrangements of minute parts were formed during the process of disintegration, and were surrendered to specific cells during development, from which regeneration or adventitious budding could originate if required. " Plasma of reserve " was the name bestowed/ on these hypothetic arrangements. Almost independently another German author, Wilhelm Eoux,^ has advocated a theoretical view of morphogenesis which very closely resembles the hypothesis of Weismann. According to Eoux a minute ultimate structure is present in the nucleus of the germ and directs development by being divided into its parts during the series of nuclear divisions. But in spite of this similarity of the outset, we enter an ^ Die Bedeutmtg der Kernteilungsfiguren, Leipzig, 1883. 56 SCIENCE AND PHILOSOPHY OF THE ORGANISM altogether different field of biological investigation on mentioning Eoux's name: we are leaving hypothetic con- struction, at least in its absoluteness, and are entering the realms of scientific experiment in morphology. EXPERIMENTAL MORPHOLOGY I have told you already in the last lecture that, while in the eighteenth century individual morphogenesis had formed the centre of biological interest and been studied experimentally in a thoroughly adequate manner, that interest gradually diminished, until at last the physiology of form as an exact separate science was almost whoUy forgotten. At least that was the state of affairs as regards zoological biology ; botanists, it must be granted, have never lost the historical continuity to such a degree ; botany has never ceased to be regarded as one science and never was broken up into parts as zoology was. Zoological physiology and zoological morphology indeed were for many years in a relationship to one another not very much closer than the relation between philology and chemistry. There were always a few men, of course, who strove against the current. The late Wilhelm His,^ for instance, described the embryology of the chick in an original manner, in order to find out the mechanical relations of embryonic parts, by which passive deformation, as an integrating part of morphogenesis, might be induced. He also most clearly stated the ultimate aim of embryology to be the mathematical derivation of the adult form from the distribution of growth in the germ. To Alexander Goette ^ ' Unsere Korperform, Leipzig, 1875. '■^ Die Entwidcelungsgeschichte der Unke, Leipzig, 1875. EXPERIMENTAL MORPHOGENESIS 57 we owe another set of analytical considerations about ontogeny. Newport, as early as 1850, and in later years Pfliiger and Eauber, carried out experiments on the eggs of the frog, which may truly be called anticipatory of what was to follow. But it was Wilhelm Eoux,^ now professor of anatomy at Halle, who entered the field with a thoroughly elaborated programme, who knew not only how to state the problem analytically, but also how to attack it, fully convinced of the importance of what he did. "Entwickelungs- mechanik," — mechanics of development — he called the " new branch of anatomical science " of which he tried to lay the foundations. I cannot let this occasion pass without emphasising in the most decided manner how highly in my opinion Eoux's services to the systematic exploration of morpho- genesis must be esteemed. I feel the more obliged to do so, because later on I shall have to contradict not only many of his positive statements but also most of his theoretical views. He himself has lately given up much of what he most strongly advocated only ten years ago. But Eoux's place in the history of biological science can never be altered, let science take what path it will. It is not the place here to develop the logic of experiment ; least of all is it necessary in the country of John Stuart Mill. All of you know that experiment, by its method of isolating the single constituents of complicated phenomena, is the principal aid in the discovery of so-called causal relations. Let us try then to see what causal ' Gesammelte Ahhandlungen, Leipzig, 1895. Most important theoretical papers: — Zeitschr. Biolog, 21, 1885 ; Die Entvnckelungsmechanih der Organis- men, Wien, 1890 ; Vortrage und Aufsatze iiber EntwichelungsTnechanik, Heft 1., Leipzig, 1905. 58 SCIENCE AND PHILOSOPHY OF THE ORGANISM relations Wilhelm Eoux established with the aid of morphogenetic experiment. THE WORK OF WILHELM ROUX We know already that an hypothesis about the founda- tion of individual development was his starting-point. Like Weismann he supposed that there exists a very complicated structure in the germ, and that nuclear division leads to the disintegration of that structure. He next tried to bring forward what might be called a number of indicia supporting his view. A close relation had been found to exist in many cases between the direction of the first cleavage furrows of the germ and the direction of the chief planes of symmetry in the adult : the first cleavage, for instance, very often corresponds to the median plane, or stands at right angles to it. And in other instances, such as have been worked out into the doctrine of so-called "cell-lineages," typical cleavage cells were found to correspond to typical organs. Was not that a strong support for a theory which regarded cellular division as the principal means of differentiation ? It is true, the close relations between cleavage and symmetry did not exist in every case, but then there had always happened some specific experimental disturbances, e.g. influences of an abnormal direction of gravity on account of a turning over of the egg, and it was easy to reconcile such cases with the generally accepted theory on the assumption of what was called "anachronism" of cleavage. But Eoux was not satisfied with mere indicia, he EXPERIMENTAL MORPHOGENESIS 59 wanted a proof, and with this intention he carried out an experiment which has become very celebrated.^ With a hot needle he killed one of the first two blastomeres of the frog's egg after the full accomplishment of its first cleavage, and then watched the development of the surviving cell. A typical half- embryo was seen to emerge — an organ- ism indeed, which was as much a half as if a fully formed embryo of a certain stage had been cut in two by a razor. It was especially in the anterior part of the embryo that its " halfness " could most clearly be demonstrated. That seemed to be a proof of Weismann's and Eoux's theory of development, a proof of the hypothesis that there is a very complicated structure which promotes ontogeny by its disintegration, carried out during the cell divisions of embryology by the aid of the process of nuclear division, the so-called " karyokinesis." To the dispassionate observer it will appear, I suppose, that the conclusions drawn by Eoux from his experiment go a little beyond their legitimate length. Certainly some sort of " evolutio " is proved by rearing half the frog from half the egg. But is anything proved, is there anything discovered at all about the nucleus? It was only on account of the common opinion about the part it played in morphogenesis that the nucleus had been taken into consideration. Things soon became still more ambiguous. THE EXPERIMENTS ON THE EGG OF THE SEA-URCHIN Eoux's results were published for the first time in 1888 ; three years later I tried to repeat his fundamental ^ Vvrchow's Archiv. 114, 1888. 60 SCIENCE AND PHILOSOPHY OF THE ORGANISM experiment on another subject and by a somewhat dififerent method. It was known from the cytological researches of the brothers Hertwig and Boveri that the eggs of the common sea-urchin {Echinus microtuherculatus) are able to stand well all sorts of rough treatment, and that, in particular, when broken into pieces by shaking, their frag- ments will survive and continue to segment. I took advantage of these facts for my purposes. I shook the germs rather violently during their two-cell stage, and in several instances I succeeded in killing one of the blasto- meres, while the other one was not damaged, or in separat- ing the two blastomeres from one another.^ Let us now follow the development of the isolated surviving cell. It went through cleavage just as it would have done in contact with its sister-cell, and there occurred cleavage stages which were just half of the normal ones. The stage, for instance, which corresponded to the normal sixteen-cell stage, and which, of course, in my subjects was built up of eight elements only, showed two micromeres, two macromeres and four cells of medium size, exactly as if a normal sixteen-cell stage had been cut in two ; and the form of the whole was that of a hemisphere. So far there was no divergence from Eoux's results. The development of our Echinus proceeds rather rapidly, the cleavage being accomplished in about fifteen hours. I now noticed on the evening of the first day of the experiment, when the half-germ was composed of about two hundred ele- ments, that the margin of the hemispherical germ benttogether a little, as if it were about to form a whole sphere of smaller size, and, indeed, the next morning a whole diminutive ' Zeitschr, wiss. Zool. 53, 1891. EXPERIMENTAL MORPHOGENESIS 61 blastula was swimming about. I was so much convinced that I should get Eoux's morphogenetical result in all its features that, even in spite of this whole blastula, I now expected that the next morning would reveal to me the half-organisation of my subject once more ; the intestine, I supposed, might come out quite on one side of it, as a half- tube, and the mesenchyme ring might be a half one also. But things turned out as they were bound to do and not as I had expected ; there was a typically wliole gastrula on my dish the next morning, differing only by its small size from a normal one ; and this small hut whole gastrula was followed by a whole and typical small pluteus-larva (Fig. 5). That was just the opposite of Eoux's result : one of the first two blastomeres had undergone a half-cleavage as in his case, but then it had become a whole organism by a simple process of rearrangement of its material, without anything that resembled regeneration, in the sense of a completion by budding from a wound. If one blastomere of the two-cell stage was thus capable of performing the morphogenetical process in its totality, it became, of course, impossible to allow that nuclear division had separated any sort of " germ-plasm " into two different halves, and not even the protoplasm of the egg could be said to have been divided by the first cleavage furrow into unequal parts, as the postulate of the strict theory of so-called " evolutio " had been. This was a very important result, sufficient alone to overthrow at once the theory of ontogenetical " evolutio," the " Mosaiktheorie " as it had been called — not by Eoux himself, but according to his views — in its exclusiveness. 62 SCIENCE AND PHILOSOPHY OP THE ORGANISM After first widening the circle of my observations by showing that one of the first four blastomeres is capable of performing a whole organogenesis, and that three of the first four blastomeres together result in an absolutely perfect organism, I went on to follow up separately one of the two fundamental problems which had been suggested by my first experiment : was there anything more to find FiQ. 5. — Illustration of Expbriments on Echinus. ai and b]. Normal gastrula and normal pluteus. og and 62- " Half "-gastrula and "half "-pluteus, that ought to result ftom one of the first two blastomeres, when isolated, according to the theory of " evolutio." as'aod b^. The small but whole gastrula and pluteus that actually do result. out about the importance or unimportance of the single nuclear divisions in morphogenesis 1 ^ By raising the temperature of the medium or by diluting the sea-water to a certain degree it proved at first to be possible to alter in a rather fundamental way the type of ' Zeitschr. wiss. Zool. 66, 1892. EXPERIMENTAL MORPHOGENESIS 63 the cleavage-stages without any damage to the resulting organism. There may be no micromeres at the sixteen-cell stage, or they may appear as early as in the stage of eight cells ; no matter, the larva is bound to be typical. So it certainly is not necessary for all the cleavages to occur just in their normal order. But of greater importance for our purposes was what followed. I succeeded in pressing the eggs of Echinus between two glass plates, rather tightly, but without killing them; the eggs became deformed to comparatively flat plates of a large diameter. Now in these eggs all nuclear division occurred at right angles to the direction of pressure, that is to say, in the direction of the plates, as long as the pressure lasted ; but the divisions began to occur at right angles to their former direction, as soon as the pressure ceased. By letting the pressure be at work for different times I therefore, of course, had it quite in my power to obtain cleavage types just as I wanted to get them. If, for instance, I kept the eggs under pressure until the eight-cell stage was complete, I got a plate of eight cells one beside the other, instead of two rings, of four cells each, one above the other, as in the normal case; but the next cell division occurred at right angles to the former ones, and a sixteen-cell stage, of two plates of eight cells each, one above the other, was the result. If the pressure continued until the sixteen-cell stage was reached, sixteen cells lay together in one plate, and two plates of sixteen cells each, one above the other, were the result of the next cleavage. "We are not, however, studying these things for cytological, but for morphogenetical purposes, and for these 64 SCIENCE AND PHILOSOPHY OF THE ORGANISM the cleavage phenomenon itself is less important than the organogenetic result of it: all our subjects resulted in absolutely normal organisms. Now, it is clear, that the spatial relations of the different nuclear divisions to each other are anything but normal, in the eggs subjected to the pressure experiments ; that, so to say, every nucleus has got quite different neighbours if compared with the " normal " case. If that makes no difference, then there cannot Fig. 6. — Pressure-experiments on Echinus. ai and bj. Two normal cleavage stages, consisting of eight and sixteen cells. 02 and hn. Corresponding stages modified by exerting pressure until the eight-cell stager was finished. See text. exist any close relation between the single nuclear divisions and organogenesis at all, and^ the conclusi£n_we_have_dTawn more pro visionally_ from the whole .development ^ofjsolj^ed blastpmeres_ has Jbeea- ext.ftnded-_aad-.prQved in the,^ most perfect manner. There ought to result a morphogenetic chaos according to the theory of real " evolutio " carried out by nuclear division, if the positions of the single nuclei were fundamentally changed with regard to one another EXPERIMENTAL MORPHOGENESIS 65 (Fig. 6). But now there resulted not chaos, but the normal organisation : therefore it was disproved in the strictest way that nuclear divisions have any bearing on the origin of organisation ; at least as far as the divisions during cleavage come into account. On the egg of the frog (0. Hertwig), and on the egg of annelids (E. B. Wilson), my pressure experiments have been carried out with the same result/ ON THE INTIMATE STRUCTUEE OF THE PROTOPLASM OF THE GERM Nuclear division, as we have seen, cannot be the basis of organogenesis, and all we know about the whole develop- ment of isolated blastomeres seems to show that there exists nothing responsible for differentiation in the protoplasm either. But would that be possible ? It cannot appear possible on a more profound consideration of the nature of morpho- genesis, it seems to me : as the untypical agents of the medium cannot be responsible in any way for the origin of a form combination which is most typical and specific, there mmt be somewhere in the egg itself a certain factor which is responsible at least for the general orientation and symmetry of it. Considerations of this kind led me, as early as 1893,^ to urge the hypothesis that there ■' In the pressure experiments I had altered the relative position of the nuclei in origine. In later years I succeeded in disturbing the arrangement of the fully formed cells of the eight-cell stage, and in getting normal larvae in spite of that in many cases. But as this series of experiments is not free from certain complications — which in part will be understood later on (see page 73) — it must suffice here to have mentioned them. (For further informa- tion see my paper in Archiv. f. EniwicTcelungsmechanik, xiv. , 1902, page 500. ) 2 Mitteil. Neapel. 11, 1893. S 66 SCIENCE AND PHILOSOPHY OF THE ORGANISM existed, that there must exist, a sort of intimate structure in the egg, including polarity and bilaterality as the chief features of its symmetry, a structure which belongs to every smallest element of the egg, and which might be imagined by analogy under the form of elementary magnets. This hypothetic structure could have its seat in the proto- plasm only. In the egg of eehinoderms it would be capable of such a quick rearrangement after being disturbed, that it could not be observed but only inferred logically ; there might, however, be cases in which its real discovery would be possible. Indeed Eoux's frog-experiment seems to be a case where it is found to be at work : at least it seems very probable to assume that Eoux obtained half of a frog's embryo because the protoplasm of the isolated blasto- mere had preserved the " halfness " of its intimate structure, and had not been able to form a small whole out of it. Of course it was my principal object to verify this hypothesis, and such verification became possible in a set of experiments which my friend T. H. Morgan and myself carried out together ,° in 1895, on the eggs of ctenophores, a sort of pelagic animals, somewhat resembling the jelly- fish, but of a rather different inner organisation. The zoologist Chun had found even before Eoux's analytical studies, that isolated blastomeres of the ctenophore egg behave like parts of the whole and result in a half-organisa- tion like the frog's germ does. Chun had not laid much stress on his discovery, which now, of course, from the new points of view, became a very important one. We first repeated Chun's experiment and obtained his results, with ' But the elementary magnets would have to be bilateral ! » Arch. Entw. Mech. 2, 1895. EXPERIMENTAL MORPHOGENESIS 67 the sole exception that there was a tendency of the endoderm of the half-larva of Beroe to become more than " half." But that was not what we chiefly wanted to study. We succeeded in cutting away a certain mass of the protoplasm of the ctenophore egg just before it began to cleave, without damaging its nuclear material in any way : in all cases, where the cut was performed at the side, there resulted a certain type of larvae from our experiments which showed exactly the same sort of defects as were present in j larvae developed from one of the first two blastomeres' alone. The hypothesis of the morphogenetic importance of ■protoplasm had thus been proved. In our experiments; there was all of the nuclear material, but there were defects on one side of the protoplasm of the egg ; and the defects in the adult were found to correspond to these defects in the protoplasm. And now 0. Schultze and Morgan succeeded in per- forming some experiments which directly proved the hypothesis of the part played by protoplasm in the subject employed by Eoux, viz., the frog's egg. The first of these investigators managed to rear two whole frog embryos of small size, if he slightly pressed the two-cell stage of that form between two plates of glass and turned it over ; and Morgan,^ after having kiUed one of the first two blastomeres, as was done in the original experiment of Eoux, was able to bring the surviving one to a half or to a whole develop- ment according as it was undisturbed or turned. There cannot be any dOubt that in both of these cases, it is the possibility of a rearrangement of protoplasm, offered by 1 Anat. Ann. 10, 1895. 68 SCIENCE AND PHILOSOPHY OF THE OEGANISM the turning over, which allows the isolated blastomere to develop as a whole. The regulation of the frog's egg, with regard to its becoming whole, may be called facultative, whilst the same regulation of the egg of Echinus is obligatory. It is not without interest to note that the first two blastomeres of the common newt, i.e. of a form which belongs to the other class of Amphibia, after a separation of any kind, always develop as wholes, their faculty of regulation being obligatory, like that of Echinus. Whole or partial development may thus be dependent on the power of regulation contained in the intimate polar- bilateral structure of the protoplasm. Where this is so, the regulation and the differences in development are both connected with the chief relations of symmetry. The development becomes a half or a quarter of the normal because there is only one-half or one-quarter of a certain structure present, one -half or one -quarter with regard to the very wholeness of this structure ; the develop- ment is whole, in spite of disturbances, if the intimate structure became whole first. We may describe the " wholeness," " halfness," or " quarterness " of our hypothetic structure in a mathematical way, by using three axes, at right angles to one another, as the base of orientation. To each of these, x, y, and z, a certain specific state with regard to the symmetrical relations corresponds ; thence it follows that, if there are wanting all those parts of the intimate structure which are determined, say, by a negative value of y, by minus y, then there is wanting half of the in- timate structure ; and this halfness of the intimate structure is followed by the halfness of organogenesis, the dependence of the latter on the intimate structure being established. EXPERIMENTAL MORPHOGENESIS 69 But if regulation has restored, on a smaller scale, the whole of the arrangement according to all values of x, y and z, development also can take place completely (Fig. 7). lY Fig. 7. — Diaokau illustrating the intimate Regulation of Protoplasm from " Half" to " Whole." The large circle represents the original structure of the egg. In all cases where cleavage- cells of the two-cell stage are isolated this original structure is only present as "half" in the beginning, say only on the right (+!/) side. Development then becomes "half," if the intimate structure remains half; but it becomes "whole" (on a smaller scale) if a new whole-structure (small circle 1) is formed by regulatory processes. I am quite aware that such a discussion is rather empty and purely formal, nevertheless it is by no means without value, for it shows most clearly the differences between what we have called the intimate structure of germs, responsible 70 SCIENCE AND PHILOSOPHY OF THE ORGANISM only for the general symmetry of themselves and of their isolated parts, and another sort of possible structure of the egg-protoplasm which we now shall have to consider, and which, at the first glance, seems to form a serious difficulty to our statements, as far at least as they claim to be of general importance. The study of this other sort of germinal structure at the same time will lead us a step farther in our historical sketch of the first years of " Entwickelungsmechanik " and will bring this sketch to its end. ON SOME SPECIFICITIES OF ORGANISATION IN CERTAIN GERMS It was known already about 1890, from the careful study of what has been called " cell-lineag6," that in the eggs of several families of the animal kingdom the origin of certain organs may be traced back to individual cells of cleavage, having a typical histological character of their own. In America especially such researches have been carried out with the utmost minuteness, E. B. Wilson's study of the cell-lineage of the Annelid Nereis being the first of them. If it were true that nuclear division is of no determining influence upon the ontogenetic fate of the blastomeres, only peculiarities of the different parts of the protoplasm could account for such relations of special cleavage cells to special organs. I advocated this view as early as in 1894, and it was proved two years later by Crampton, a pupil of Wilson's, in some very fine experi- ments performed on the germ of a certain mollusc.^ The egg of this form contains a special sort of protoplasm near 1 Arch. Entw. Meek. 3, 1896. EXPERIMENTAL MORPHOGENESIS VI its vegetative pole, and this part of it is separated at each of the first two segmentations by a sort of pseudo-cleavage, leading to stages of three and five separated masses instead of two and four, the supernumerary mass being the so- called " yolk-sac " and possessing no nuclear elements (Fig. 8). Crampton removed this yolk-sac at the two-cell stage, and he found that the cleavage of the germs thus operated upon was normal except with regard to the size and histological appearance of one cell, and that the larvae Fro. 8. — The Mollusc Dentalium (a/i!er E. B. Wilson). o. ThB egg, consisting of three different kinds of protoplasmatic material, fe. First cleavage-stage. There are two cells and one "pseudo-cell," the yolk-sac, which contains no nucleus. This was removed in Crampton's experiment. originating from these germs were complete in every respect except in their mesenchyme, which was wanting. A special part of the protoplasm of the egg had thus been brought into relation with quite a special part of organisation, and that special part of the protoplasm contained no 7iMclms,_ GENERAL KESULTS OF THE FIRST PERIOD OF " ENTWICKELUNGSMECHANIK " This experiment of Crampton's, afterwards confirmed by Wilson himself, may be said to have closed the first period 72 SCIENCE AND PHILOSOPHY OF THE ORGANISM of the new science of physiology of form, a period devoted almost exclusively to the problem whether the theory of nuclear division or, in a wider sense, whether the theory of a strict " evolutio " as the basis of organogenesis was true or not. It was shown, as we have seen, that the theory of the " qualitatively unequal nuclear division " (" qualitativ-un- gleiche Kernteilung" in German) certainly was not true, and that there also was no strict " evolutio " in protoplasm. Hence Weismann's theory was clearly disproved. There certainly is a good deal of real " epigenesis " in ontogeny, a good deal of " production of manifoldness," not only with regard to visibility but in a more profound meaning. But some sort of pre-formation had also been proved to exist, and this pre-formation, or, if you like, this restricted evolution, was found to be of two different kinds. First an intimate organisation of the protoplasm, spoken of as its polarity and bilaterality, was discovered, and this had to be postulated for every kind of germs, even when it was overshadowed by immediate obligatory regulation after disturbances. Besides that there were cases in which a real specificity of special parts of the germ existed, a relation of these special parts to special organs : but this sort of specification also was shown to belong to the protoplasm. It follows from all we have mentioned about the organisation of protoplasm and its bearing on morphogenesis, that the eggs of different animals may behave rather differently in this respect, and that the eggs indeed may be classified according to the degree of their organisation. Though we must leave a detailed discussion of these topics to morphology proper, we yet shall try shortly to summarise EXPERIMENTAL MORPHOGENESIS "73 what has been ascertained about them in the different classes of the animal kingdom. A full regulation of the intimate structure of isolated blastomeres to a new whole, has been proved to exist in the highest degree in the eggs of all echinoderms, medusae, nemertines, Amphioxus,i fishes, and in one class of the Amphibia (the Urodela); it' is facultative only among the other class of Amphibia, thej Anura, and seems to be only partly developed or to be wanting altogether among ctenophora, ascidia, annelids,! and moUusca. Peculiarities in the organisation of specijicl parts of protoplasm have been proved to occur in more cases j than at first had been assumed ; they exist even in the j echinoderm egg, as experiments of the last few years have shown ; even here a sort of specification exists at the ^ vegetative pole q£ the egg, though it is liable to a certain kind of regulation ; the same is true in medusae, nemertines, etc. ; but among molluscs, ascidians, and annelids no regulation about the specific organisation of the germ in cleavage has been found in any case. The differences in the degree of regulability , of the intimate germinal structure may' easily be reduced to simple differences in the physical consistency of their protoplasm.^ But all differences in specific organisation must remain as they are for the present ; it will be one of the aims of the future theory of development to trace these differences also to a common source. That such an endeavour will probably be not without success, is clear, I should think, from the mere fact that ^ It deserves notice iYi this connection, that in some cases the protoplasm of parts of a germ has been found to be more regulable in the earliest stages, when it is very fluid, than later, when it is more stiff. 74 SCIENCE AND PHILOSOPHY OF THE ORGANISM differences with regard to germinal specific pre-formation do not agree in any way with the systematic position of the animals exhibiting them ; for, strange as it would be if there were two utterly different kinds of morphogenesis, it would be still more strange if there were differences in morphogenesis which were totally unconnected with systematic relationship : the ctenophores behaving differently from the medusae, and Amphioxus differently from ascidians. SOME NEW RESULTS CONCERNING RESTITUTIONS We now might close this chapter, which has chiefly dealt with the disproof of a certain sort of ontogenetic theories, and therefore has been almost negative in its character, did it not seem desirable to add at least a few words about the later discoveries relating to morphogenetic restorations of the adult. We have learnt that Weismann I created his concept of " reserve plasma " to account for what little he knew about " restitutions " : that is, about the restoration of lost parts : he only knew regeneration proper in animals and the formation of adventitious buds in plants. It is common to both of these phenomena that they take their origin from typically localised points of the body in every case ; each time they occur a certain well-defined part of the body is charged with the restoration of the lost parts. To explain such eases Weismann's hypothesis was quite adequate, at least in a logical sense. But at present, as we shall discuss more fully in another chapter, we know of some very widespread forms of restitution, in which what is to be done for a replacement of the lost is not entrusted to one typical part of the body in every case, EXPERIMENTAL MORPHOGENESIS 75 but in which the whole of the morphogenetic action to be performed is transferred in its single parts to the siTigle parts of the body which is accomplishing restoration : each of its parts has to take an individual share in the process of restoration, effecting what is properly called a certain kind of " re-differentiation " (" Umdifferenzierung "), and this share varies according to the relative position of the part in each case. Later on these statements will appear in more correct form than at present, and then it will become clear that we are fully entitled to emphasise at the end of our criticism of Weismann's theory, that his hypothesis relating to restorations can be no more true than his theory of development proper was found to be. And now we shall pass on to our positive work. We shall try to sketch the outlines of what might properly be called an analytical theory of morphogenesis ; that is, to explain the sum of our knowledge about organic form-production, gained by experiment and by logical analysis, in the form of a real system, in which each part will be, or at least will try to be, in its proper place and in relation with every other part. Our analytical work will give us ample opportunity of mentioning many im- portant topics of so-called general physiology also, irrespective of morphogenesis as such. But morphogenesis is always to be the centre and starting-point of our analysis. As I myself approach the subject as a zoologist, animal morpho- genesis, as before, will be the principal subject of what is to follow. 2. Analytical Theory of Morphogenesis ' a. the distribution of morphogenetic potencies Prospective Value and Prospective Potency Wilhelm Eoux did not fail to see that the questions of I the locality and the time of all morphogenetic differentia- l tions had to be solved first, before any problem of causality proper could be attacked. From this point of view he carried out his fundamental experiments. It is only in terminology that we differ from his views, if we prefer to call our introductory chapter an analysis of the distribution of morphogenetic potencies. The result will be of course rather different from what Eoux expected it would be. Let us begin by laying down two fundamental concepts. Suppose we have here a definite embryo in a definite state of development, say a blastula, or a gastrula, or some sort of larva, then we are entitled to study any special element of any special elementary organ of this germ with respect to what is actually to develop out of this very element in the ^ Compare my Analytische Theorie der organischen Untwickelung, Leipzig, 1894, and my reviews in Srgebnisse der Anatomie und Enlwickelv/ngsges- chieMe, vols. viii. xi. xiv., 1899-1905. A shorter review is given in Ergebnisse der Physiologie, vol. v., 1906. The full literature will be found in these reviews. 76 EXPERIMENT AL MORPHOGENESIS 77 future actual course of this development, whether it be undisturbed or disturbed in any way ; it is, so to say, the actual, the real fate of our element, that we take in account. I have proposed to call this real fate of each embryonic part in this very definite line of morphogenesis its pro- spective value (" prospective Bedeutung " in German). The fundamental question of the first chapter of our analytical theory of development may now be stated as follows : Is the prospective value of each part of any state of the morpho- genetic line constant, i.e. is it unchangeable, can it be nothing but one ; or is it variable, may it change according to different circumstances ? We first introduce a second concept : the term prospective poterwy (" prospective Potenz " in German) of each embryonic element. The term " prospective morphogenetic potency " is to signify the possible fate of each of those elements. "With the aid of our two artificial concepts we are now able to formulate our introductory question thus : Is the prospective potency of each embryonic part fully given by its prospective value in a certain definite case ; is it, so to say, identical with it, or does the prospective potency contain more than the prospective value of an element in a certain case reveals ? "We know already from our historical sketch that the latter is true : that the actual fate of a part need not be identical with its possible fate, at least in many cases ; that the potency of the first four blastomeres of the egg of the sea-urchin, for instance, has a far wider range than is shown by what each of them actually performs in even this ontogeny. There are more morphogenetic possibilities con- tained in each embryonic part than are actually realised in a special morphogenetic case. V8 SCIENCE AND PHILOSOPHY OF THE OEGANISM As the most important special morphogenetic case is, of course, the so-called " normal " one, we can also express our formula in terms of special reference to it: there are more morphogenetic possibilities in each part than the observation of the normal development can reveal. Thus we have at once justified the application of analytical experiment to morphogenesis, and have stated its most important results. As the introductory experiments about " Entwickelungs- mechanik " have shown already that the prospective potency of embryonic parts, at least in certain cases, can exceed their prospective value — that, at least in certain cases, it can be different from it — the concept of prospective potency at the very beginning of our studies puts itseK in the centre of analytical interest, leaving to the concept of prospective value the second place only. For that each embryonic part actually has a certain prospective value, a specified actual fate in every single case of ontogeny, is clear from itself and does not affirm more than the reality of morphogenetic cases in general ; but that the prospective value of the elements may change, that there is a morphogenetic power in them, which contains more than actuality ; in other words, that the term " prospective potency " has not only a logical but a factual interest : all these points amount to a statement not only of the most fundamental introductory results but also of the actual problems of the physiology of form. If at each point of the germ something else can be formed than actually is formed, why then does there happen in each case just what happens and nothing else ? In these words indeed we may state the chief problem of our science, at least after the fundamental relation of the superiority of prospec- tive potency to prospective value has been generally shown. EXPERIMENTAL MORPHOGENESIS 79 We consequently may shortly formulate our first problem as the question of the distribution of the prospective morphogenetic potencies in the germ. Now this general question involves a number of particular ones. Up to what stage, if at all, is there an absolutely equal distribution of the potencies over all the elements of the germ ? When such an equal distribution has ceased to exist at a certain stage, what are then the relations between the parts of different potency ? How, on the other hand, does a newly arisen, more specialised sort of potency behave with regard to the original general potency, and what about the distribu- tion of the more restricted potency ? I know very well that all such questions will seem to you a little formal, and, so to say, academical at the outset. We shall not fail to attach to them very concrete meanings. The Potencies of the Elastomer es At first we turn back to our experiments on the egg of the sea-urchin as a type of the germ in the very earliest stages. We know already that each of the first two, or each of the first four, or three of the first four blastomeres together may produce a whole organism. We may add that the swimming blastula, consisting of about one thousand cells, when cut in two quite at random, in a plane coincident with, or at least passing near, its polar axis, may form two fully developed organisms out of its halves.'^ We may formulate this result in the words : the prospective potency of the 1 If the plane of section passes near the equator of the germ, two whole larvae may be formed also, but in the majority of cases the "animal" half does not go beyond the blastula. The specific features of the organisation of the protoplasm come into account here. See also page 65, note 1. 80 SCIENCE AND PHILOSOPHY OF THE ORGANISM single cells of a blastula of Echinus is the same for all of them; their prospective value is as far as possible from being constant. But we may say even a little more : what actually will happen in each of the blastula cells in any special case of development experimentally determined depends on the position of that cell in the whole, if the " whole " is put into relation with any fixed system of co-ordinates ; or more shortly, "the prospective value of any blastula cell is a function of its position in the whole." I know from former experience that this statement wants a few words of explanation. The word " function " is em- ployed here in the most general, mathematical sense, simply to express that the prospective value, the actual fate of a cell, will change, whenever its position in the whole is different.^ The " whole " may be related to any three axes drawn through the normal undisturbed egg, on the hypothesis that there exists a primary polarity and bUaterality of the germ ; the axes which determine this sort of symmetry may, of course, conveniently be taken as co-ordinates ; but that is not necessary. The Potencies of Elementary Organs in General Before dealing with other very young germs, I think it advisable to describe first an experiment which is carried out at a later stage of our well-known form. This experi- ment will easily lead to a few new concepts, which we shall want later on, and will serve, on the other hand, as a ' A change of the position of the cell is of course effected by each variation- of the direction of the cut, which is purely a matter of chance. EXPERIMENTAL MORPHOGENESIS 81 basis of explanation for some results, obtained from the youngest germs of some other animal species, which other- wise would seem to be rather irreconcilable with what our Echinus teaches us. You know, from the second lecture, what a gastrular of our sea-urchin is. If you bisect this gastrula, when it is completely formed, or still better, if you bisect the gastrula of the starfish, either along the axis or at right angles to it, you get complete little organisms developed from the parts : the ectoderm is formed in the typical manner in the parts, and so is the endoderm ; everything is proportionate and only smaller than in the normal case. So we have at once the important results, that, as in the blastula, so in the ectoderm and in the endoderm of our Echinus or of the starfish, the prospective potencies are the same for every single element : both in the ectoderm and in the endoderm the prospective value of each cell is a " function of its position " (Fig. 9). But a further experiment has been made on our gastrula. If at the moment when the material of the future intestine is most distinctly marked in the blastoderm, but not yet grown into a tube, if at this moment the upper half of the larva is separated from the lower by an equatorial section, you will get a complete larva only from that part which bears the " Anlage " of the endoderm„ while the other half wiU proceed in morphogenesis very well but will form only ectodermal organs. By another sort of experiment, which we cannot fully explain here, it has been shown that the endoderm if isolated is also only able to form such organs as are normally derived from it. And so we may summarise both our last results by a? Fig. 9.— The Starfish, Asterias. a^. Normal gastrula ; may be bisected along the main axis or at right angles to it (see dotted lines). a2. Normal larva, " Bipintiaria." &i. Small but whole gastrula that results by a process of regulation from the parts of a bisected gastrula. *2. Small but whole " BipvmiaHa" developed out of 6i. EXPERIMENTAL MORPHOGENESIS 83 ,:\ saying : though ectoderm and endoderm have their potencies equally distributed amongst their respective cells, they possess different potencies compared one with the other. And thi same relation is found to hold for all cases of what we call elementary organs : they are " equipotential," as we may say, in themselves, but of different potencies compared with each other. Explicit and Implicit Potencies : Primary and Secondary Potencies We shall first give to our concept of "prospective potency " a few words of further analytical explanation with the help of our newly obtained knowledge. It is clear from what we have stated that the prospective potencies of the ectoderm and of the endoderm, and we may add, of every elementary organ in relation to every other, differ between themselves and also in comparison with the blastoderm, from which they have originated. But the diversity of the endoderm with respect to the ectoderm is not of the same kind as its diversity in respect to the^ blastoderm. The potency of the endoderm and that of the ectoderm are both specialised in their typical manner, but compared with the potency of the blastoderm they may be said not only to be specialised but also to be re- stricted : the potency of the blastoderm embraces the whole, that of the so-called germ-layer embraces only part of the whole; and this Species of restriction becomes clearer and clearer the further ontogeny advances : at the end of it in the "ultimate elementary organs" there is no prospective potency whatever. 84 SCIENCE AND PHILOSOPHY OF THE ORGANISM A few new terms will serve to state a little more accurately what happens. Of course, with regard to all morphogenesis which goes on immediately from the blasto- derm, the potency of the blastoderm is restricted as much as are the potencies of the germ layers. We shall call thia sort of immediate potency explicit, and then we see at once that, with regard to their explicit potencies, there are only differences among the prospective potencies of the elementary organs ; but with respect to the implicit potency of any of these organs, that is with respect to their potency as em- bracing the faculties of all their derivations, there are also not only differences but true morphogenetic restrictions lying at the very foundations of all embryology. But now those of you who are familiar with morpho- genetic facts will object to me, that what we have stated about all sorts of restrictions in ontogeny is not true, and you will censure me for having overlooked regeneration, adventitious budding, and so on. To some extent the criticism would be right, but I am not going to recant; I shall only introduce another new concept. "We are dealing only with primary potencies in our present con- siderations, i.e. with potencies which lie at the root of true embryology, not with those serving to regulate disturbances of the organisation. It is true, we have in some way disturbed the development of our sea-urchin's egg in order to study it; more than that, it would have been impossible to study it at all without some sort of disturb- ance, without some sort of operation. But, nevertheless, no potencies of what may properly be called the secondary or restitutive type have been aroused by our operations ; nothing happened except on the usual lines of organogenesis. EXPERIMENTAL MORPHOGENESIS 85 It is true, some sort of regulation occurred, but that is included among the factors of ontogeny proper. We shall afterwards study more fully and from a more general point of view this very important feature of " primary regulation " in its contrast to " secondary regula- tion" phenomena. At present it must be enough to say that in speaking of the restriction of the implicit potencies in form-building we refer only to potencies of the primary type, which contain within themselves some properties of a (primary) regulative character. The Morphogenetic Function of Maturation in the Light of Recent Discoveries Turning again to more concrete matters, we shall first try, with the knowledge acquired of the potencies of the blastoderm and the so-called germ layers of Echinus, to understand certain rather complicated results which the experimental morphogenetic study of other animal forms has taught us. We know from our historical sketch that there are some very important aberrations from the tjrpe, to which the Echinus germ belongs,^ i.e. the type with an equal distribution of the potencies over all the blasto- meres. We know not only that in cases where a regulation of the intimate structure of the protoplasm fails to occur a partial development of isolated cells will take place, but that there may even be a typical disposition of typical cells ' The reader will remember (see page 65, note 1), that even the genn of Echinus is not quite equipotential along its main axis, but it is equi- potential in the strictest sense around this axis. The germs of certain medusae seem to be equipotential in every respect, even in their cleavage stages. 86 SCIENCE AND PHILOSOPHY OF THE ORGANISM for the formation of typical organs only, without any regulability. Let us first consider the last case, of which the egg of moUusca is a good type : here there is no equal distribution of potencies whatever, the cleavage-cells of this germ are a sort of real " mosaic " with regard to their morphogenetic potentialities. Is this difference between the germ of the echinoderms and the molluscs to remain where it is, and not to be elucidated any further? Then there would be rather important differences among the germs of different animals, at least with regard to the degree of the specifica- tion of their cleavage cells, or if we ascribe differences among the blastomeres to the organisation of the fertilised egg ready for cleavage, there would be differences in the morphogenetic organisation of the egg-protoplasm: some eggs would be more typically specialised at the very beginning of morphogenesis than others. In the first years of the study of " Entwickelungs- mechanik " I pointed out that it must never be forgotten that the egg itself is the result of organogenesis. If, therefore, there are real mosaic-like specifications in some eggs at the beginning of cleavage, or during it, there may perhaps have been an earlier stage in the individual history of the egg which did not show such specifications of the morpho- genetic structure. Two American authors share the merit of having proved this hypothesis. Conklin showed, several years ago, that certain intracellular migrations and re- arrangements of material do happen in the first stages of ovogenesis in certain cases, but it is to E. B. Wilson ^ that science owes a proper and definitive elucidation of the ' Journ. Exp. Zool. 1, 1904. EXPERIMENTAL MORPHOGENESIS 87 whole subject. Wilson's researches, pursued not only by descriptive methods/ but also by means of analytical ex- periment, led him to the highly important discovery that the eggs of several forms (nemertines, molluscs), which after maturation show the mosaic type of specification in their protoplasm to a more or less high degree, fail to show any kind of specification in the distribution of their potencies before maturation has occurred. In the mollusc egg a certain degree of specification is shown already before maturation, but nothing to be compared with what happens afterwards; in the egg of nemertines there is no specification at all in the unripe egg. Maturation thus becomes a part of ontogeny itself; it is not with fertilisation that morphogenesis begins, there is a sort of ontogeny anterior to fertilisation. These words constitute a summary of Wilson's researches. Taken together with the general results obtained about the potencies of the blastula and the gastrula of Echinus, they redxice what appeared to be differences of degree or even of kind in the specification of the egg-protoplasm to mere differences in the time of the beginning of real morphogenesis. What occurs in some eggs, as in those of Echinus, at the time of the definite formation of the germ layers, leading to a specification and restriction of their prospective potencies, may happen very much earlier in other eggs. But there exists in evert/ sort of egg an earliest stage, in which all parts of its protoplasm are ^ Great caution must be taken in attributing any specific morphogenetio part to diflFerently coloured or constructed materials, which may be observed in the egg-protoplasm in certain cases. They may play such a part, but in other- cases they certainly do not (see Lyon, Arch. Entw. Mech. 23, 1907). The final decision always depends on experiment. 88 SCIENCE AND PHILOSOPHY OF THE ORGANISM equal as to their prospectivity, and in which there are no potential diversities or restrictions of any kind. So much for differences in the real material organisation of the germ and their bearing on inequipotentialities of the cleavage cells. The Intimate Structure of Protoplasm : Further Remarks Where a typical half- or quarter -development from isolated blastomeres happens to occur, we know already that the impossibility of a regulation of the intimate polar- bilateral structure may account for it. As this impossibility of regulation probably rests on rather simple physical condi- tions^ it may properly be stated that equal distribution of potencies is not wanting but is only overshadowed here. In this respect there exists a logical difference of funda- mental importance between those cases of so-called " partial " or better, " fragmental " development of isolated blastomeres in which a certain embryonic organ is wanting on account of its specific morphogenetic material being absent, and those cases in which the " ^agmental " embryo lacks complete " halves " or " quarters " with regard to general symmetry on account of the symmetry of its intimate structure being irregularly disturbed. This logical difference has not always received the attention which it undoubtedly deserves. Our hypothetical intimate structure in itself is, of course, also a result of factors concerned in ovogenesis. Only in one case do we actually know anything about its ' It seems that these physical conditions also — besides the real specifica- tions in the organisation of the egg — may be different before and after maturation or (in other cases) fertilisation. (See Driesoh, Archivf. Entwicke- lungsmechanik, 7, p. 98 ; and Brachet, ibid. 22, p. 325.) EXPEEIMENTAL MORPHOGENESIS 89 origin : Eoux has shown that in the frog it is the accidental path of the fertilising spermatozoon in the egg which, together with the polar axis, normally determines the plane of bilateral symmetry ; but this symmetry may be overcome and replaced by another, if gravity is forced to act in an abnormal manner upon the protoplasm ; the latter showing parts of different specific gravity in the eggs of all Amphibia. The Neutrality of the Concept of " Potency " N"ow we may close our rather long chapter on the distribution of potencies in the germ ; it has been made long, because it will prove to be very important for further analytical discussion ; and its importance, in great measure, is due to its freedom from prepossessions. Indeed, the concept of prospective potency does not prejudice anything ; we have said, it is true, that limitations of potencies may be due to the presence of specific parts of organisation in some cases ; that, at least, they may be connected therewith ; but we have not determined at all what a prospective potency really is, what the term really is to signify. It may seem that such a state of things gives an air of emptiness to our discussions, that it leaves uncertain what is the most important. But, I think, our way of argument, which tries to reach the problems of greatest importance by degrees, though it may be slow, could hardly be called wrong and misleading. yS. THE "means " OF MOKPHOGENESIS We now proceed to an analysis of what may properly be called the means of morphogenesis, the word " means " 90 SCIENCE AND PHILOSOPHY OF THE ORGANISM being preferable to the more usual one " conditions " in this connection, as the latter would not cover the whole field. It is in quite an unpretentious and merely descriptive sense that the expression " means " should be understood at present ; what is usually called " conditions " is part of the morphogenetic means in our sense. yS'. The Internal Elementary Means of Morphogenesis We know that all morphogenesis, typical or atypical, primary or secondary, goes on by one morphogenetic elementary process following the other. Now the very foundation of these elementary processes themselves lies in the elementary functions of the organism as far as they result in the formation of stable visible products. Therefore the elementary functions of the organism may properly be | called the internal " means " of morphogenesis. Secretion and migration are among such functions ; the former happening by the aid of chemical change or by physical separation, the latter by the aid of changes in surface tension. But hardly anything more concrete has been made out about these or similar points at present. We therefore make no claim to offer a complete system of the internal elementary means of morphogenesis. We shall only select from the whole a few topics of remarkable morphogenetic interest, and say a few words about each. But, first of all, let us observe that the elementary means of morphogenesis are far from being morphogenesis them- selves. The word " means " itself implies as much. It would be possible to understand each of these single acts in morphogenesis as well as anything, and yet to be as far EXPERIMENTAL MORPHOGENESIS 91 from understanding the whole as ever. All means of morphogenesis are only to be considered as the most general frame of events within which morphogenesis occurs. Some Remarks on the Importance of Surface Tension in Morphogenesis. — There are a few purely physical phenomena which have a special importance in organic morphology, all of them connected with capillarity or surface tension. Soap- lather is a very familiar thing to all of you : you know that the soap-solution is arranged here in very thin planes separated by spaces containing air : it was first proved by Berthold ^ that the arrangement of cells in organic tissues follows the same type as does the arrangement of the single bubbles of a soap-lather, and Biitschli ^ added to this the discovery that the minute structure of the protoplasm itself is that of a foam also. Of course it is not one fluid and one gas which make up the constituents of the structure in the organisms, as is the case in the well-known inorganic foams, but two fluids, which do not mix with one another. One general law holds for all arrangements of this kind : the so-called law of least surfaces, expressed by the words that the sum of all surfaces existing is a minimum ; and it again is a consequence of this law, if discussed mathematically, that four lines will always meet in one point and three planes in one line. This feature, together with a certain law about the relation of the angles meeting in one line to the size of the bubbles, is realised most clearly in many structures of Organic tissues, and makes it highly probable, at least in some cases, that capillarity is at work here. In other cases, as for instance in many plants, a ' Studien iiber Protoplasmwmechanik, Leipzig, 1886. ° Unters. ub. mikroikopische Schdume und das Protoplasma, Leipzig, 1892. 92 SCIENCE AND PHILOSOPHY OF THE ORGANISM kind of outside pressure, the so-called tissue tension, may- account for the arrangement in surfaces minimae areae. Cleavage stages are perhaps the very hest type in which our physical law is expressed : and here it may be said to have quite a simple application whenever all of the blastomeres are of the same physical kind, whilst some complications appear in germs with a specialised organisa- tion and, therefore, with differences in the protoplasm of their single blastomeres. In such instances we may say that the physical law holds as far as the conditions of the system permit, these conditions ordinarily consisting in a sort of non-homogeneity of the surfaces. It seems, from the researches of Dreyer,^ that the forma- tion of organic skeletons may also be governed by the physically conditioned arrangement of protoplasmatic or cellular elements, and some phenomena of migration and rearrangement among cleavage cells, as described by Eoux, probably also belong here. But let us never forget that the laws of surface tension only give us the most general type of an arrangement of elements in all these cases, nothing else. A physical law never accounts for the Specific ! Capillarity gives us not the least clue to it. As the organic substance, at least in many cases, is a fluid, it must of course follow the general laws of hydrostatics and hydrodynamics, but life itself is as little touched by its fluid-like or foam-like properties as it is by the fact that living bodies have a certain weight and mass. All indeed that has been described may be said to belong, in the broadest meaning of the word, to what is ' Jena. Zeitschr. 26, 1892. EXPERIMENTAL MORPHOGENESIS 93 called by Eoux " correlation- of masses," though this author originally intended to express by this term only some sorts of passive pressure and deformation amongst embryonic parts as discovered especially by His. We must be cautious in admitting that any organic feature has been explained, even in the most general way, by the action of physical forces. What at first seems to be the result of mechanical pressure may afterwards be found to be an active process of growth, and what at first seems to be a full effect of capillarity among homogeneous elements may afterwards be shown to depend on specialised metabolic conditions of the surfaces as its principal cause.^ There are other physical phenomena too, which assist morphogenesis ; osmotic pressure for instance, which is also well known to operate in many purely physiological processes. But all these processes are only means of the organism, and can never do more than furnish the general type of events. They do not constitute life ; they are used by life ; let it remain an open question, for the present, how the phenomenon of " life " is to be regarded in general.^ On Growth. — Among the internal morphogenetical means which are of a so-called physiological character, that is, which nobody claims to understand physically at present, ' According to Zur Strassen's results the early embryology of Ascaris proceeds almost exclusively by cellular surface-changes : the most typical morphogenetio processes are carried out by the aid of this "means." As a whole, the embryology of Ascaris stands quite apart and presents a great number of unsolved problems ; unfortunately, the germ of this form has not been accessible to experiment hitherto. ' Khumbler has recently published a general survey of all attempts to "explain" life, and morphogenesis in particular, in a physico-chemical way ("Aus dem Luckengebiet zwischen organismischer und anorganismisoher Natur," Ergeb. Anat. u. Entw.-gesch. 15, 1906). This very pessimistic survey is the more valuable as it is written by a convinced " mechanist." 94 SCIENCE AND PHILOSOPHY OF THE ORGANISM there is in the first place growth, which must be regarded as a very essential one. Analytically we must carefully discriminate between the increase in the size of the cavities of an organism by a passive extension of their surfaces and the proper growth of the individual cells, which again may be due either to mere extension or to real assimilation. Osmotic pressure, of course, plays an important part both in the growth of the body-cavities and in simple cellular extension. We repeat the caution against believing too much to be explained by this phenomenon : it is the organism which by the secretion of osmotic substances in the cavities or the protoplasm of the cells prepares the ground for growth even of this osmotic sort. The real cellular growth which proceeds on the basis of assimilation cannot, of course, be accounted for by osmotic events, not even in its most general type. Ontogenetical growth generally sets in, both in animals and in plants, after the chief lines of organisation are laid out ; it is only the formation of the definite histological structures which usually runs parallel to it. On Cell-division. — We have already said a good deal about the importance of cell -division in ontogeny: it accompanies very many of the processes of organisation in all living beings. But even then, there are the Protozoa, in the morphogenesis of which it does not occur at all, and there have also become known many cases of morphogenesis in higher animals, mostly of the type of regulation, in which cellular division is almost or wholly wanting. Therefore, cellular division cannot be the true reason of differentiation, but is only a process, which though necessary in some cases, cannot be essential to it. It must be conceded, I believe. EXPERIMENTAL MOEPHOGENESIS 95 that, the same conclusion can be drawn from all our experiments on very young stages of the germ. The investigations of the last few years have made it quite clear that even in organisms with a high power of morphogenetic regulation it is always the form of the whole, but not the individual cell, which is subjected to the regula- tion processes. Starting from certain results obtained by T. H. Morgan, I was able to show that in all the small but whole larvae, reared from isolated blastomeres, the size of the cells remains normal, only their number being reduced ; and Boveri has shown most clearly that it is always the size of the nucleus — more correctly, the mass of the chromatin — which determines how large a cell of a certain histological kind is to be. In this view, the cell appears even more as a sort of material used by the organism as supplied, just as workmen can build the most different buildings with stones of a given size. 0'. The External Means of Morphogenesis "We now know what internal means of morphogenesis are, and so we may glance at some of the most important " outer means " or " conditions " of organisation. Like the adult, the germ also requires a certain amount of heat, oxygen, and, when it grows up in the sea, salinity in the medium. For the germ, as for the adult, there exists not only a minimum but also a maximum limit of all the necessary factors of the medium ; the same factor which at a certain intensity promotes development, disturbs it from a certain other intensity upwards. Within the limits of this minimum and this maximum 96 SCIENCE AND PHILOSOPHY OP THE ORGANISM of every outside agent there generally is an increase in the rate of development corresponding to the increase of intensity of the agent. The acceleration of development by heat has been shown to follow the law of the acceleration of chemical processes by a rise of temperature; that seems to prove that certain chemical processes go on during the course of morphogenesis. Almost all that has been investigated of the part played by the external conditions of development has little bearing on specific morphogenesis proper, and therefore may be left out of account here : we must, however, lay great stress on the general fact that there is a very close dependence of morphogenesis on the outside factors, lest we should be accused afterwards of having overlooked it. Of course all " external " means or conditions of morpho- genesis can actually relate to morphogenetic processes only by becoming in some way " internal," but we unfortunately have no knowledge whatever how this happens. We at present are only able to ascertain what must necessarily be accomplished in the medium, in order that normal morpho- genesis may go on, and we can only suppose that there exist certain specific internal general states, indispensable for organogenesis but inaccessible to present modes of investigation.^ ITie Discoveries of Herhst. — There are but few points in the doctrine of the external means or conditions of organogenesis which have a more special bearing on the specification of proper form, and which therefore ' Compare the analytical discussions of Klebs, to whom we owe a great series of important discoveries in the field of morphogenetic "means" in botany. ( Willkurliche Entwickelungsanderungen bei Pflanzen, Jeua, 1903 ■ see also Biol. Centralblatt, vol. xxiv., 1904, and my reply to Klebs, ibid. 23, 1903.) EXPERIMENTAL MORPHOGENESIS 97 require to be described here a little more fully. All these researches, which have been carried out almost exclusively by Herbst/ relate to the effect of the chemical components of sea-water upon the development of the sea-urchin. If we select the most important of Herbst's results, we must in the first place say a few words on the part taken by lime or calcium, not_ only in establishing specific features of form, but in rendering individual morphogenesis possible at all. Herbst has found that in sea-water which is deprived of calcium the cleavage cells and many tissue cells also completely lose contact with each other : cleavage goes on quite well, but after each single division the elements are separated; at the end of the process you find the 80-8 cells of the germ together at the bottom of the dish, all swim- ming about like infusoria. There seems to be some influence of the calcium salts upon the physical state of the surfaces of the blastomeres. It is not without interest to note that this discovery has an important bearing on the technical side of all experi- ments dealing with the isolation of blastomeres. Since the separation of the single cleavage elements ceases as soon as the germs are brought back from the mixture without lime into normal sea- water, it of course is possible to separate them up to any stage which it is desired to study, and to keep them together afterwards. Thus, if for instance you want to study the development of isolated cells of the eight-cell stage, you will leave the egg in the artificial mixture containing no calcium until the third cleavage, which leads from the four- to the eight-cell stage, is finished. The single eight cells brought back to normal sea-water at ' Arch. Mill). Mech. 17, 1904. 7 98 SCIENCE AND PHILOSOPHY OF THE ORGANISM this point will give you the eight embryos you want. All researches upon the development of isolated blastomeres since the time of Herbst's discovery have been carried out by this method, and it would have been quite impossible by the old method of shaking to pursue the study into such minute detail as actually has been done. It may be added that calcium, besides its cell -uniting action, is also of primary importance in the formation of the skeleton. Among all the other very numerous studies of Herbst we need only mention that potassium is necessary for the typical growth of the intestine, just as this element has been found necessary for normal growth in plants, and that there must be the ion SO4, or in other terms, sulphur salts present in the water, in order that the germs may acquire their pigments and their bilateral symmetry. This is indeed a very important result, though it cannot be said to be properly understood. It is a fact that in water without sulphates the larvae of Echinus retain the radial symmetry they have had in the very earliest stages, and may even preserve that symmetry on being brought back to normal sea-water if they have spent about twenty-four hours in the artificial mixture. We may now leave the subject of Herbst's attempts to discover the morphogenetic function of the single con- stituents of normal sea-water, and may devote a few words to the other branch of his investigations, those dealing with the morphogenetic effects of substances which are not present in the water of the sea, but have been added to it artificially. Here, among many other achievements, Herbst has made the most important discovery that all EXPERIMENTAL MORPHOGENESIS 99 salts of lithium effect radical changes in development.^ I cannot describe fully here how the so-called " lithium larva " originates ; let me only mention that its endo- derm is formed outside instead of inside, that it is far too large, that there is a spherical mass between the ectodermal and the endodermal part of the germ, that a radial symmetry is established in place of the normal bilateralism, that no skeleton exists, and that the mesenchyme cells are placed in a quite abnormal position. All these features, though abnormal, are typical of the development in lithium. The larvae present no really pathological appearance at all, and, therefore, it may indeed be said that lithium salts are able to change fundamentally the whole course of morphogenesis. It detracts nothing from the importance of these discoveries that, at present, they stand quite isolated : only with lithium salts has Herbst obtained such strange results, and only upon the eggs of echinids, not even upon those of asterids, do lithium salts act in this way. 7. THE FORMATIVE CAUSES OR STIMULI The Definition of Cause We cannot begin the study of the " causes " of the differentiation of form without a few words of explanation about the terminology which we shall apply. Causality is the most disputed of all categories ; many modern scientists, particularly in physics, try to avoid the concept of cause altogether, and to replace it by mere functional dependence in the mathematical meaning of the term. ^ Zeitschr. wiss. Zool. 55, 1902 ; and Mitt. Neapel. 11, 1903. 100 SCIENCE AND PHILOSOPHY OF THE ORGANISM They claim to express completely by an equation all that is discoverable about any sort of phenomena constantly connected. I cannot convince myself that such a very restricted view is the right one : it is very cautious, no doubt, but it is incomplete, for we have the concept of the acting " cause " in our Ego and s.t:& forced to search for applications of it in Nature. On the other hand, it does not at all escape me that there are many difficulties, or rather ambiguities, in applying it. We may call the " cause " of any event, the sum total of all the constellations of facts which must be completed in order that the event may occur ; it is in this meaning, for instance, that the first principle of energetics applies the term in the words cmisa aequat effectum. But, by using the word only in this very general sense, we deprive ourselves of many conveniences in the further and more particular study of Nature. Would it be better to say that the " cause " of any event is the very last change which, after all the constellations necessary for its start are accomplished, must still take place in order that the event may actually occur ? Let us see what would follow from such a use of the word causality. We here have an animal germ in a certain stage, say a larva of Echinus, which is just about to form the intestine ; all the internal conditions are fulfilled, and there is also a certain temperature, a certain salinity, and so on, but there is no oxygen in the water : the intestine, of course, will not grow in such a state of things, but it soon will when oxygen is allowed to enter the dish. Is, therefore, oxygen the cause of the formation of the intestine of echinus ? Nobody, I think, would care to say EXPERIMENTAL MORPHOGENESIS 101 SO. By such reasoning, indeed, the temperature, or sodium, might be called the "cause" of any special process of morphogenesis. It, therefore, seems to be of little use to give the name of cause to that factor of any necessary constellation of events which accidentally happens to be the last that is realised. But what is to be done then ? Might we not say that the cause of any morphogenetic process is that typical property, or quality, or change, on which its specific character depends, on which depends for example, the fact that now it is the intestine which appears, while at another time it is the lens of the eye ? We might very well, but we already have our term for this sort of cause, which is nothing else than our prospective potency applied to that elementary organ from which the new process takes its origin. The prospective potency indeed is the truly immanent cause of every specification affecting single organogenetic processes. But we want something more than this. We may find what we want by considering that each single elementairy process or development not only has its specification, but also has its specific and typical place in the whole — its locality. Therefore we shall call the " cause " of a single morphogenetic process, that occurrence on which depends its localisation, whether its specific character also partly depends on this " cause " or not.' This definition of " cause " in morphology may be artificial ; in any case it is clear. And at the same time the concepts of the prospective potency and of the " means " of organogenesis now acquire a clear and definite meaning : ' In certain cases part of the specific feature of the process in question may also depend on the " cause " which is localising it, e.g. in the galls of plants. 102 SCIENCE AND PHILOSOPHY OF THE ORGANISM potency is the real basis of the specific character of every act in morphogenesis, and " means," including conditions, are the sum of all external and internal general circumstances which must be present in order that morphogenetic processes may go on, without being responsible for their specificity or localisation. It is implied in these definitions of cause and potency, that the former almost always will be of that general type which usually is called a stimulus or "Auslosung," to use the untranslatable German word. There is no quantitative correspondence between our " cause " and the morphogenetic effect. Some Instances of Formative and Directive Stim,uli Again it is to Herbst that we owe not only a very thorough logical analysis of what he calls "formative and directive stimuli " ^ but also some important discoveries on this subject. We cannot do more here than barely mention some of the most characteristic facts. Amongst plants it has long been known that the direction of light or of gravity may determine where roots or branches or other morphogenetic formations are to arise ; in hydroids also we know that these factors of the medium may be at work ^ as morphogenetic causes, though ' Herbst, " Ueber die Bedeutung die Reizphysiologie fiir die kausale Auffassung von Vorgiingen in der tierisohen Ontogenese " {Biol. Centralblait, vols, xiv., 1894, and xv., 1895); Formative Meize in der tierisohen Ontogenese, Leipzig, 1901. These important papers must be studied by every one who wishes to become familiar with the subject. Tlie present state of science is reviewed in my articles in the Ergebnisse der Anatomie und Entwicke- lungsgeschichte, vols. xi. and xiv., 1^02 and 1905. ^ Compare the important papers by J. Loeb, Untersiichuiigen zur physiologischen Morphologie der Tiere, Wiirzburg, 1891-2. EXPERIMENTAL MORPHOGENESIS 103 most of the typical architecture of hydroid colonies certainly is due to internal causes, as is also much of the organisation in plants. Light and gravity are external formative causes ; beside that they are merely " localisers." But there also are some external formative stimuli, on which depends not only the place of the effect, but also part of its specification. The galls of plants are the most typical organogenetic results of such stimuli. The potencies of the plant and the specific kind of the stimulus equally contribute to their specification ; for several kinds of galls may originate on one sort of leaves. Scarcely any exterior formative stimuli are responsible for animal organisation ; and one would hardly be wrong in saying that this morphogenetic independence in animals is due to their comparatively far-reaching functional inde- pendence of those external agents which have any sort of direction. But many organogenetic relations are known to exist between the single parts of animal germs, each of these parts being in some respect external to every other ; and, indeed, it might have been expected already a priori, that such formative relations between the parts of an animal embryo must exist, after all we have learned about the chief lines of early embryology. If differentiation does not go on after the scheme of Weismann, that is, if it is not carried out by true " evolutio " from within, how could it be effected except from without ? Indeed, every embryonic part may in some respect be a possible cause for morpho- genetic events, which are to occur on every other part : it is here that the very roots of epigenesis are to be found. Heliotropism and geotropism are among the well-known 104 SCIENCE AND PHILOSOPHY OF THE ORGANISM physiological functions of plants : the roots are seen to bend away from the light and towards the ground ; the branches behave just in the opposite way. It now has been supposed by Herbst that such "directive stimuli" may also be at work among the growing or wandering parts of the embryo, that their growth or their migration may be determined by the typical character of other parts, and that real morpho- genetic characters can be the result of some such relation ; a sort of " chemotropism " or " chemotaxis " may be at work here. Herbst himself has discussed theoretically several cases of organogenesis in which the action of directive stimuli is very probable. What has become actually known by experiment is not very much at present : the mesenchyme cells of Echinus are directed in their migration by specified places in the ectoderm, the pigment cells of the yolk-sac of the fish fundulus are attracted by its blood vessels, and nerv es may be foiiced to turn into little tubes containing_brain substance ; but of course only the first two instances have any bearing on typical morphogenesis. The first case of an " internal formative stimulus " in the proper sense, that is, of one embryonic part causing another to appear, was discovered by Herbst himself The arms of the so-called pluteus of the sea-urchin are in formative dependence on the skeleton — no skeleton, no arms ; so many skeleton primordia,^ in abnormal eases, so many arms; abnormal position of the skeleton, abnormal position of the arms : these three experimental observa- tions form the proof of this morphogenetic relation. ' I use the word "primordia" for the German "Anlage" ; it is better than the word "rudiment," as the latter may also serve to signify the very last stai^e of a certain formation that is disappearing (phylogenetically). EXPERIMENTAL MORPHOGENESIS 105 It may be simple mechanical contact, or it may be some chemical influence that really constitutes the " stimulus " in this case ; certainly, there exists a close and very specific relation of the localisation of one part of the embryo to another. Things are much the same in another case, which, after having been hypothetically stated by Herbst on the basis of pathological data, was proved experimentally by Spemann. The lens of the eye of certain Amphibia is formed of their skin in response to a formative stimulus proceeding from the so-called primary optic vesicle. If this vesicle fails to touch the skin, no lens appears ; and, on the other hand, the lens may appear in quite abnormal parts of the skin if they come into contact with the optic vesicle after transplantation. But formative dependence of parts may also be of different types. We owe to Herbst the important discovery that the eyes of crayfishes, after being cut off, will be regenerated in the proper way, if the optic ganglion is present, but that an antenna will arise in their place if this ganglion has also been removed. There must in this case be some unknown influence of the formative kind on which depends, if not regeneration itself, at least its special character. In other cases there seems to be an influence of the central nervous system on the regenerative power in general. Amphibia, for instance, are said to regenerate neither their legs (Wolff ), nor their tail (Godlewski), if the nervous com- munications have been disturbed. But in other animals there is no such influence ; and in yet others, as for instance, in Planarians, it must seem doubtful at present whether the 106 SCIENCE AND PHILOSOPHY OF THE ORGANISM morphogenetic influence of the nervous system upon processes of restoration is more than indirect ; the movements of the animal, which become very much reduced by the extirpation of the ganglia, being one of the main conditions of a good regeneration. Of course, all we have said about the importance of special materials in the ripe germ, as bearing on specifically localised organisations, might be discussed again in our present chapter, and our intimate polar-bilateral structure of germs may also be regarded as embracing formative stimuli, at any rate as far as the actual poles of this structure are concerned. This again would bring us to the problem of so-called "polarity" in general, and to the "inversion" of polarity, that is to a phenomenon well known in plants and in many hydroids and worms, viz., that morphogenetic processes, especially of the type of restitutions, occur differently, according as their point of origin represents, so to speak, the positive or the negative, the terminal or the basal end of an axis, but that under certain conditions the reverse may also be the case. But a fuller discussion of these important facts would lead us deeper and deeper into the science of morphogenesis proper, without being of much use for our future considerations. And so we may close this section ^ on formative stimuli 1 A full analysis of the subject would not only have to deal with formative stimuli as inaugurating movphogenetio processes, 'but also with those stimuli which terminate or stop the single acts of morphogenesis. But little is actually known about this topic, and therefore the reader must refer to my other publications. I will only say here, that the end of each single morpho- genetic act may either be determined at the very beginning or occur as an actual stopping of a process which otherwise would go on for ever and ever ; in the first case some terminating factors are included in the very nature of the morphogenetic act itself. EXPERIMENTAL MORPHOGENESIS 107 or " causes " of morphogenesis by shortly adding, more on account of its factual than of its'logical interest, that the phenomenon of the determination of sex,^ according to the latest researches, seems to depend on cytological events occurring in the very earliest embryonic stages, say even before ontogeny, and not on formative stimuli proper ^ : it seems, indeed, as if the sexual products themselves would account for the sex of the individual produced by them, particularly if there were differences in their chromatin.* 8. THE MOEPHOGENETIO HARMONIES ^ Let us now turn again to considerations of a more abstract kind : we have become acquainted with some morphogenetic interactions among the parts of a developing embryo ; and, indeed, we can be sure that there exist far more of such interactions than we know at present. But it is far from being true that the development of each embryonic part depends on the existence or develop- ment of every other one. On the contrary, it is a very important and fundamental feature of organogenesis that it occurs in separate lines, ' A full account of the present state of the subject will be found in Morgan's Experimental Zoology, New York, 1907. ' But there certainly exist many formative relations between the real sexual organs and the so-called secondary sexual characters. Herbst has given a full analytical discussion of all that is known on this subject ; but the facts are much more complicated than is generally supposed, and do not lend themselves therefore to short description. See also Foges, Pflilger's Arch. 93, 1902. " It seems that in some cases {Dinophilus, certain Arthropods) the sexual products are invariably determined as " arrenogennetic " or as "thelygen- netic" (Wilson, Journ. Exp. Zool. ii. and iii. 1905-6), whilst in others (Amphibia) the state of maturation or "super "-maturation determines the sex of the future organism (R. Hertwig, Verh. D. Zool. Ges. 1905-7). 108 SCIENCE AND PHILOSOPHY OF THE ORGANISM that is to say, in lines of processes which may start from a common root, but which are absolutely independent of one another in their manner of differentiation. Eoux has coined the term " self-differentiation " to denote this pheno- menon, and we admit that this term may be conveniently used for the purpose, if only it can be kept in mind that I its sense is always relative, and that it is also negative.^ Suppose a part. A, shows the phenomenon of self-differ- entiation : this means that the further development of A is not dependent on certain other parts, £, C, and D ; it does not mean at all that A has not been formatively dependent on some other parts, ^ or -f at the time of its first appear- ance, nor does it imply that there might not be many formative actions among the constituents of A itself We indeed are entitled to say that the ectoderm of Echinus shows " self-differentiation " with regard to the endoderm ; it acquires its mouth, for instance, as has been shown by experiment, even in cases where no intestine is present at all (Fig. 1 0) ; but ectoderm and endoderm both are formatively dependent on the intimate and the material organisation of the blastoderm. It further seems from the most recent experiments that the nerves and the muscles of the vertebrates are independent of each other in their differentiation, but that their fate is probably determined by formative processes in the very earliest stages of ontogeny. The phenomenon of self- differentiation, properly under- stood, now may help to the discovery of one most general character of all development. If the phenomenon of self- differentiation really occurs iu ontogeny in its most different aspects, and if, on the other hand, in spite of this relative morphogenetic independence of embryonic parts, the result- EXPERIMENTAL MORPHOGENESIS 109 ing organism is one whole in organisation and in function, some sort of harmony j)f^constellaMon, as it may properly be styled, must be said to be one of the most fundamental characters of all production of individual form. In establish- ing this harmony we do nothing more than describe exactly what happens : the harmony is shown by the fact that there is a whole organism at the end, in spite of the relative independence of the single events leading to it. But still another sort of harmony is revealed in morpho- PiQ. 10.— Pluteus-larva of Sphaerechinus. The Intestine (i) is developed outside instead of inside (by means of raising the tempera- ture) ; but the mouth (r) is formed in its normal place. S=Skeleton. genesis, by an analysis of the general conditions of the formative actions themselves. In order that these actions may go on properly the possibility must be guaranteed that the formative causes may always find something upon which to act, and that those parts which contain the potencies for the next ontogenetic stage may properly receive the stimuli awaking these potencies : otherwise there would be no typical production of form at all. This, the second species of harmonious relations to be described in ontogeny, may be called causal J^armony; the term simply expresses the 110 SCIENCE AND PHILOSOPHY OF THE ORGANISM unfailing relative condition of formative causes and cause- recipients. Finally, in functional harmony we have an expression descriptive of the unity of organic function, and so we may state, as the latest result of our analytical theory of development up to this point, that individual morphogenesis is marked by a threefold harmony among its parts. 6. ON RESTITUTIONS^ At this stage we leave for a while our analytical studies of ontogeny proper. We must not forget that typical ontogenesis is not the only form in which morpho- genesis can occur: the organic form is able to restore disturbances of its organisation, and it certainly is to be regarded as one of the chief problems of analytical morpho- genesis to discover the specific and real stimulus which calls forth the restoring processes. For simply to say that the disturbance is the cause of the restoration would be to evade the problem instead of attacking it. But there are still some other problems peculiar to the doctrine of restitutions. A few Bemarhs on Secondary Potencies and on Secondary Morphogenetic Regulations in General We have only briefly mentioned in a previous chapter that there exist many kinds of potencies of what we call the secondary or truly restitutive type, and that their distribution may be most various and quite independent ^ Driesoh, Die organischen Begulottionen, Leipzig, 1901 ; Morgan, Eegenera- tion, New York, 1901. EXPERIMENTAL MORPHOGENESIS 111 of all the potencies for the primary processes of ontogeny proper. Let us first add a few words about the concept of "secondary restitution" and about the distribution of secondary potencies in general. Primary ontogenetic processes founded upon primary potencies may imply regulation, or more correctly, restitu- tion in many cases : so it is, when fragments of the blastula form the whole organism, or when the mesenchyme cells of Echinus reach their normal final position by an attraction on the part of specific localities of the ectoderm in spite of a very abnormal original position enforced upon them by experiment. In these cases we speak of primary regulations or restitutions ; disturbances are neutralised by the very nature of the process in question. We speak of secondary restitution whenever a disturbance of organ- isation is rectified by processes foreign to the realm of normality ; and these abnormal lines of events are revealed to us in the first place by the activity of potencies which remain latent in ontogeny proper. We know already that a certain kind of secondary restitution has been discovered lately, very contradictory to the theoretical views of Weismann ; the process of restoration being carried out not by any definite part of the disturbed organisation, but by all the single elements of it. The problem of the distribution of secondary potencies in these cases of so-called " re-dififerentiation " is to form our special study in the next chapter. In all other cases restoration processes start from specific localities ; if they occur on the site of the wound which caused the disturbance, we speak of regeneration ; if they occur at some distance from the wound, we call them adventitious 112 SCIENCE AND PHILOSOPHY OF THE ORGANISM processes. Besides these three types of processes of restitu- tion there may be mentioned a fourth one, consisting in what is generally called compensatory hypertrophy; the most simple case of such a compensatory process is when one of a pair of organs, say a kidney, becomes larger after the other has been removed.^ Finally, at least in plants, a change of the directive irritability, of so-called " geotropism " for instance, in certain parts may serve to restore other more important parts. In two of these general types of restitution, in regenera- tion proper and in the production of adventitious organs, the potencies which underlie these processes may be said to be " complex." It is a complicated series of events, a proper morphogenesis in itself, for which the potency has to account, if, for instance, a worm newly forms its head by regeneration, or if a plant restores a whole branch in the form of an adventitious bud. Such generalisations as are possible about the distribu- tion of complex potencies are reserved for a special part of our future discussion. Secondary restitution is always, like ontogeny, a process of morphogenesis, and therefore all the questions about single formative stimuli, and about internal and external conditions or means, occur again. But of course we cannot enter into these problems a second time, and may only ' But real compensatory differentiation occurs in the oases of so-called "hypertypy" as first discovered by Przibram and afterwards studied by Zeleny : here the two organs of a pair show a different degree of differentia- tion. Whenever the more specialised organ is removed the less developed one assumes its form. Similar cases, which might simply be called "com- pensatory heterotypy," are known in plants, though only relating to the actual fate of undifferentiated " Anlagen" in these organisms. A leaf may be formed out of the Anlage of a scale, if all the leaves are cut off, and so on. EXPERIMENTAL MORPHOGENESIS 113 say that, especially in regeneration proper, the specific type of the regenerative formation of any part may differ very much from the ontogenetic type of its origin : the end of both is the same, but the way can be even fundamentally different in every respect. Tlie Stimuli of Restitutions^ But now we turn to the important question : what is the precise stimulus ^ that calls forth processes of restitution ; or, in other words, what must have happened in order that restitution may occur ? That the operation in itself, by its removing of mechanical obstacles, cannot be the true stimulus of any restitutions, is simply shown by all those restitutions that do not happen at the place of the wound. If we took a narrower point of view, and if we only considered regeneration proper from the wound itself, we might probably at first be inclined to advocate the doctrine that the removing of some obstacles might in fact be the stimulus to the process of restoration ; but, even then, why is it that just what is wanted grows out? Why is there not only growth, but specific growth, growth followed by specification ? The removing of an obstacle could hardly account for that. But, of course, taking account of all the adventitious ^ For a fuller analysis compare my opening address delivered before the section of " Experimental Zoology " at the Seventh Zoological Congress, Boston, 1907: "The Stimuli of Restitutions" (see Proceedings of that Congress). ^ The problem of the stimulus of a secondary restitution as a whole must not be confused with the very different question, what the single ' ' formative stimiili" concerned in the performance of a certain restitutive act may be. With regard to restitution as a whole these single "formative stimuli" might properly be said to belong to its "internal means" — in the widest sense of the word. 114 SCIENCE AND PHILOSOPHY OP THE ORGANISM restitutions — that is, all restorations not beginning at the wound itself — the theory that the removing of obstacles is the stimulus to restoration becomes, as we have said, quite impossible.-' But where then is the stimulus to be found ? There is another rather simple theory of the " Auslosung " of restitutions,^ which starts from the phenomena of com- pensatory hypertrophy and some occurrences among plants. The removal of some parts of the organism, it is said, will bring its other parts into better conditions of nutrition, and therefore these parts, particularly if they are of the same kind, will become larger. Granted for the moment that such a view may hold in cases when one of a pair of glands becomes larger after the other has been removed, or when pruning of almost all the leaves of a tree leads to the rest becoming larger, it certainly must fail to explain the fact that in other cases true new formations may arise in order to restore a damaged part, or that the latter may be regenerated in its proper way. For merely quantitative differences in the mixture of the blood or of the nourishing sap in plants can never be a sufficient reason for the highly typical and qualitative structure of newly-formed restitutions. And even in the most simple cases of a mere increase in the size of some parts, that is, in the simplest cases of so-called compensatory hypertrophy,^ it is at least doubtful, 1 T. H. Morgan is very right in stating that, in regeneration, the " obstacle " itself is newly formed by the mere process of healing, previous to all restitution, and that true restitution happens all the same. ^ I merely mention here the still "simpler" one— applicable of course to regeneration proper exclusively— that for the simple reason of being "wounded," i.e. being a surface open to the medium, the "wound" brings forth all that is necessary to complete the organism. » That compensatory hypertrophy cannot be due to "functional adapta- tion " — to be analysed later on — was proved by an experiment of Ribbert's. EXPERIMENTAL MORPHOGENESIS 115 if not very improbable, that the compensation is accomplished in such a purely passive way, because we know that in other cases it is usually the growth of the young parts that actively attracts the nourishment : there is first differentiation and growth, and afterwards there is a change in the direction of the nourishing fluids. The process of true regeneration, beginning at the locality of the wound itself, has been shown by Morgan, even as regards its rate, to occur quite irrespectively of the animal being fed or not.^ There could hardly be a better demonstration of the fundamental fact that food assists restitution, but does not " cause " it in any way. But in spite of all we have said, there seems to be some truth in regarding the nutritive juices of animals and plants as somehow connected with the stimulus of restitutions : only in this very cautious form, however, may we make the hypothesis. It has been shown for both animals and plants, that morphogenesis of the restitutive type may be called forth even if the parts, now to be " regenerated " have not been actually removed; e.g. in the so-called super-regeneration of legs and tails in Amphibia, of the head in Planarians, of the root-tip in plants and in some other cases. Here it has always been a disturbance of the Compensation may occur before the function has made its appearance, as was shown to he the case in the testicles and mammae of rabbits. (Arch. JEntw. Meeh. 1, 1894, p. 69.) ^ At any given time only the absolute size of the regenerated part is greater in animals which are well fed ; the degree of differentiation is the same in all. Zeleny has found that, if all five arms of a starfish are removed, each one of them will regenerate more material in a given time than it would have done if it alone had been removed. But these differences also only relate to absolute size and not to the degree of differentiation. They possibly may be due in fact to conditions of nourishment, but even here other explanations seems possible (Zeleny, Journ. exp. Zool. 2, 1905). 116 SCIENCE AND PHILOSOPHY OF THE ORGANISM normal connection of some parts with the rest of the organism which proved to be the reason of the new formation. This shows that something to do with the communication among parts is at least connected with restitution, and this communication may go on either by. the unknftwn action of specific tissues or by th,eaM, oO.be blood pr^sap^* But in what this change or break of specific communication consists, is absolutely unknown. One might suppose that each part of the organisation constantly adds some sort of ferment to the body fluids outside or inside the cells, that the removing of any part will change the composition of these fluids in this particular respect, and that this change acts as a sort of communication to summon the restituting parts of the whole to do their duty.^ But I see quite well that such a theory is very little ' For a good discussion of " super-regeneration " in the roots of plants see Nemec, Studien iiber die Regeneration, Berlin, 1905. Goebel and Winkler have succeeded in provoking the "restitution" of parts which were not removed at all by simply stopping their functions (leaves of certain plants were covered with plaster, etc.). {Biol. Cewtralbl. 22, 1902, p. 385; Ber. Sot. Ges. 20, 1902, p. 81.) A fine experiment is due to Miehe. The alga Oladophora was subjected to " plasmolysis, " each cell then formed a new membrane of its own around the smaller volume of its protoplasm ; after that the plants were brought back to a medium of normal osmotic pressure, aud then each single cell grew up into a little plant (all of them being of the same polarity!). Two questions seem to be answered by this fact: loss of communication is of fundamental importance to restitution, and the removal of mechanical obstacles plays no part in it, for the mechanical resistances were the same at the end of the experiment as they had been at the beginning. {Ber. Bot. Ges. 23, 1905, p. 257.) For fuller analysis of all the problems of this chapter see my OrganiscJie RegidcUimicn, my reviews in the Ergelmisse der Anatomie und JEntwickelungsgesdiichte, vols. viii. xi. xiv., and my Boston address mentioned above. Compare also Fitting, Ergehn. d. Physiol, vols. iv. and v. ^ The so-called "inner secretion" in physiology proper would offer a certain analogy to the facts assumed by such an hypothesis. Compare the excellent summary given by E. Starling at the seventy-eighth meeting of the German " Naturforscherversammlung, " Stuttgart, 1906. EXPERIMENTAL MORPHOGENESIS 117 satisfactory ; for what has to be done in restitution in each case is not a simple homogeneous act, for which one special material might account, but is a very complicated work in itself. It was the defect of the theory of " organ- forming substances" as advocated by Sachs, that it over- looked this point. So all we know about the proper stimuli of restitutions is far from resting on any valid grounds at all ; let us not forget that we are here on the uncertain ground of what may be called the newest and most up-to-date branch of the physiology of form. ¥o doubt, there will be something discovered some day, and the idea of the " whole " in organisation will probably play some part in it. But in what manner that will happen we are quite unable to predict. This is the first time that, hypothetically at least, the idea of the whole has entered into our discussion. The same idea may be said to have entered it already in a more implicit form in the statement of the threefold harmony in ontogeny. Let us now see whether we can find the same problem of the " whole " elsewhere, and perhaps in more explicit and less hypothetical form. Let us see whether our analytical theory of development is in fact as complete as it seemed to be, whether there are no gaps left in it which will have to be filled up. 3. The Problem of Mokphogenetic Localisation a. the theoey of the harmonious-equipotential system fikst proof of the autonomy of life "We have come to the central point of the first part of these lectures ; we shall try in this chapter to decide a question which is to give life its place in Nature, and biology its place in the system of sciences. One of the foundation stones is to be laid upon which our future philosophy of the organism will rest. The General Problem Our analytical theory of morphogenesis has been founded upon three elementary concepts : the prospective potency, the means, and the formative stimulus. Its principal object has been to show that all morphogenesis may be resolved into the three phenomena expressed by those concepts ; in other terms, that morphogenesis may be proved to consist simply and solely of what is expressed by them. Have we indeed succeeded in attaining this object? Has nothing been left out ? Is it really possible to explain every morphogenetic event, at least in the most general way, by the aid of the terms potency, means, and stimulus ? All of these questions are apt to lead us to further 118 EXPERIMENTAL MORPHOGENESIS 119 considerations. Perhaps these considerations will give us a very clear and simple result by convincing us that it is indeed possible to analyse morphogenesis in our schematic way. But if the answer were a negative one ? What would that suggest ? The full analysis of morphogenesis into a series of single formative occurrences, brought about by the use of given means and on the basis of given potencies, might assure us, perhaps, that, though not yet, still at some future time, a further sort of analysis will be possible : the analysis into the elemental facts studied by the sciences of inorganic nature. The organism might prove to be a machine, not only in its functions but also in its very origin. But what are we to say if even the preliminary analysis, which possibly might lead to such an ultimate result, fails ? Let us then set to work. Let us try to consider most carefully the topic in which our concept of the formative cause or stimulus may be said to be centred, the localisa- tion of all morphogenetic effects. Is it always possible in fact to account for the typical localisation of every morphogenetic effect by the discovery of a single specific formative stimulus ? You will answer me, that such an analysis certainly is not possible at present. But I ask you again, are there any criteria that it is possible, at least in principle ; or are there any criteria which will render such an aim of science impossible for all future time ? The Morphogenetic " System " "We know from our experimental work that many, if not all, of the elementary organs in ontogeny show one 120 SCIENCE ANB PHILOSOPHY OF THE ORGANISM and the same prospective potency distributed equally over their elements. If we now borrow a very convenient term from mechanics, and call any part of the organism which is considered as a unit from any morphogenetic point of view, a morphogenetic "system," we may sum up what we have learnt by saying that both the blastoderm of the echinoderms, at least around its polar axis, and also the germ-layers of these animals, are " systems " possessing an equal potentiality in all of their elements, or, in short, that they are equipotential systems. But such a term would not altogether indicate the real character of these systems. Later on we shall analyse more carefully than before the distribution of potencies which are the foundation both of regeneration proper and of adventitious growth, and then we shall see that, in higher plants for instance, there is a certain " system " which may be called the organ proper of restitutions, and which also in each of its elements possesses the same restoring potency ; I refer to the well- known cambium. This cambium, therefore, also deserves the name of an " equipotential system." But we know already that its potencies are of the complex type, that they consist in the faculty of producing the whole of such a complicated organisation as a branch or a root, that the term " equipotential system " is here only to signify that such a complicated unit may arise out of each of the cells of the cambium. The potencies we have been studying in the blastula or gastrula of echinoderms are not of the complex type : our systems are equipotential to the extent that each of their elements may play every single part in the totality of what EXPERIMENTAL MORPHOGENESIS 121 will occur in the whole system ; it is to this single part that the term "function of the position" relates. We therefore might call our systems equipotential systems with single potencies ; or, more shortly, singular-equipotential systems. But even this terminology would fail to touch precisely the very centre of facts: it is not only the simplicity or singularity of their potencies which characterises the r61e of our systems in morphogenesis,^ hut far more im- portant with respect to the production of form are two other leading results of the experimental researches. The proper act to be performed by every element in each actual case is in fact a single one, but the potency of any element as such consists in the possibility of many, nay of indefinitely many, single acts : that then might justify us in speaking of our systems as " indefinite equipotential," were it not that another reason makes another title seem still more prefer- able. There are indeed indefinite singular potencies at work in all of our systems during ontogeny : but the sum of what happens to arise in every case out of the sum of the single acts performed by all of the single equipotential cells is not merely a sum but a unit ; that is to say, there exists a sort of harmony in every case among the real products of our systems. The term harmonious-equipotential system therefore seems to be the right one to denote them. We now shall try first to analyse to its very extremes the meaning of the statement that a morphogenetic system is harmonious-equipotential. ' The name of singular-equipotential systems might also be applied to elementary organs, the single potencies of which are awaked to organogenesis by specific formativb stimuli from without ; but that is not the case in the systems studied in this chapter. 122 SCIENCE AND PHILOSOPHY OF THE ORGANISM The " Harmonious -Equipotential System," We have an ectoderm of the gastrula of a starfish here before us ; we know that we may cut off any part of it in any direction, and that nevertheless the differentiation of the ectoderm may go on perfectly well and result in a . typical little embryo, which is only smaller in its size than it would normally be. It is by studying the formation of the highly complicated ciliary band, that these phenomena can be most clearly unders);ood. Now let us imagine our ectoderm to be a cylinder instead of being approximately a sphere, and let us imagine the surface of this cylinder unrolled. It will give us a plane of two definite dimensions, a and h. And now we have all the means necessary for the analytical study of the differentia- tion of an harmonious-equipotential system. Our plane of the dimensions a and 6 is the basis of the normal, undisturbed development ; taking the sides of the plane as fixed localities for orientation, we can say that the actual fate, the " prospective value " of every element of the plane stands in a fixed and definite correlation to the length of two lines, drawn at right angles to the bordering lines of the plane ; or, to speak analytically, there is a definite actual fate corresponding to each possible value of X and of y. Now, we have been able to state by our experi- mental work, that the prospective value of the elements of our embryonic organ is not identical with their " prospective potency," or their possible fate, this potency being very much richer in content than is shown by a single case of ontogeny. What will be the analytical expression of such a relation ? EXPERIMENTAL MORPHOGENESIS 123 Let us put the question in the following way : on what factors does the fate of any element of our system depend, in aU possible cases of development obtainable by means of operations ? We may express our results in the form of an equation :— TP.v. (2r)=/(...) i.e. " the prospective value of the element JT is a function of. . ."—of what? We know that we may take off any part of the whole, as to quantity, and that a proportionate embryo will result, unless the part removed is of a very large size. This means that the prospective value of any element certainly depends on, certainly is a function of, the absolute size of the actually existing part of our system in the particular case. Let s be the absolute size of the system in any actual experimental case of morphogenesis : then we may write p.v. (X) =/ (s . . . ). But we shall have to add still some other letter to this s. The operation of section was without restriction either as to the amount of the material removed from the germ, or as to the direction of the cut. Of course, in almost every actual case there will be both a definite size of the actual system and a definite direction of the cut going hand-in- hand. But in order to study independently the importance of the variable direction alone, let us imagine that we have isolated at one time that part of our system which is bounded by the lines a^ b^, and at another time an equal amount of it which has the lines a^ b^ as its boundaries. Now since in both cases a typical small organism may result on development, we see that, in spite of their equal size 124 SCIENCE AND PHILOSOPHY OF THE ORGANISM the prospective value of every element of the two pieces cut out of the germ may vary even in relation to the direction of the cut itself. Our element, X, may belong to both of these pieces of the same size : its actual fate nevertheless will be different. Analytically, it may be said to change in correspondence to the actual position of the actual boundary lines of the piece itself with regard to the fundamental lines of orientation, a and 6 ; let this actual position be expressed by the letter I, I marking the distance of one^ of the actual boundary lines of our piece from aox h: then we are entitled to improve our formula by writing p.v. {X) =f (s, I . . . ) (Fig. 11). But the formula is not yet complete : s and I are what the mathematicians call variables : they may have any actual value and there will always be a definite value of p.v., i.e. of the actual fate which is being considered ; to every value of s and I, which as we know are independent of each other, there corresponds a definite value of the actual prospectivity. Now, of course, there is also a certain factor at work in every actual case of experimental or normal development, which is not a variable, but which is the same in all cases. This factor is a something embraced in the prospective potency of our system, though not properly identical with it. The prospective potency of our system, that is to say of each of its elements, is the sum total of what can be done by all ; but the fact that a typically proportionate develop- ment occurs in every possible case, proves that this sum comes into account, not merely as a sum, but as a sort of > The distance of the other boundary line from a or b would he given by the value of s. EXPERIMENTAL MORPHOGENESIS 125 order : we may call this order the " relation of localities in the absolutely normal case." If we keep in mind that the term "prospective potency" is always to contain this order, or, as we may also call it, this "relative proportionality,'' which, indeed, was the reason for calling our systems " harmonious," then we may apply it without further ex- planation in order to signify the non-variable factor on Fig. 11.— Diagram to show the Chaba€teristics of an " Harmonious-equipotential System." The element X forms part of the systems a b or ai &i or a^ 62 1 its prospective value is diflferent in each case. which the prospective value of any element of our systems depends, and, if we denote the prospective potency, embrac- ing order, by the letter E, we are now able to complete our formula by saying p.v. (X) =/ (s, I, E). So far the merely analytical study of the differentiation of harmonious-equipotential systems.^ ^ A far more thorough analysis of this differentiation has been attempted in ray paper, "Die Localisation morphogenetisoher Vorgange. Ein Beweis vitalistisohen Geschehens," Leipzig, 1899. 126 SCIENCE AND PHILOSOPHY OF THE ORGANISM Instances of " ffarmonious-JEquipotential Systems " We must try at first to learn a few more positive facts about our systems, in order that we may know how im- portant is the part which they play in the whole animal kingdom, and in order that our rather abstract analysis may become a little more familiar to us. We know already that many of the elementary morphogenetic organs have been really proved to be harmonious-equipotential systems, and that the same probably is true of many others ; we also know that the immature egg of almost all animals belongs to this type, even if a fixed determination of its parts may be established just after maturation. Moreover, we said, when speaking about some new discoveries on form-restitution, that there are many cases in which the processes of restitution do not proceed from single localities, the seat of complex potencies in the organism, but in which each single part of the truncated organism left by the operation has to perform one single act of restoration, the full restitution being the result of the totality of all. These cases must now be submitted to a full analysis. All of you have seen common sea-anemones or sea-roses, and many of you will also be familiar with the so-called hydroid polyps. Tubularia is one genus of them : it looks like a sea-anemone in miniature placed on the top of a stem like a flower. It was known already to Allman that Tubularia is able to restore its flower-like head when that is lost, but this process was taken to be an ordinary re- generation, until an American zoologist. Miss Bickford, succeeded in showing that there was no regeneration process at all, in the proper sense of the word, no budding of the EXPERIMENTAL MORPHOGENESIS 127 missing part from the wound, but that the new tubularian head was restored by the combined work of many parts of the stem. Further analysis then taught us that Tuhularia indeed is to be regarded as the perfect type of an harmonious-equipotential system : you may cut the stem at whatever level you like : a certain length of the stem will always restore the new head by the co-operation of its parts. As the point of section is of course absolutely at our choice, it is clear, without any further discussion, that the pro- spective value of each part of the restoring stem is a "function of its position," that it varies with its distance from the end of the stem; and so at once we discover one of the chief characteristics of our systems. But also the second point which enters into our formula can be demonstrated in Tuhularia : the dependence of the fate of every element on the actual size of the system. You would not be able to demonstrate this on very long stems, but if you cut out of a Tuhularia stem pieces which are less than ten millimetres in length, you will find the absolute size of the head restored to be in close relation to the length of the stem piece, and this dependence, of course, includes the second sort of dependence expressed in our formula. The figures will serve to show you a little more con- cretely what has been described. The head of Tuhularia consists of a sort of broad base with a thin proboscis upon it, both bearing a large number of tentacles ; these tentacles are the first things to be seen as primordia (" Anlagen ") in the process of restitution. You notice two rings of longitudinal lines inside the stem ; the lines will become walls and then will separate from the stem until they are only connected with it at their basal ends ; the new tentacles are ready as 128 SCIENCE AND PHILOSOPHY OF THE ORGANISM soon as that has happened, and a process of growth at the end will serve to drive the new head out of the so-called perisarc or horny skeleton, which surrounds the stem. By comparing the two figures, 1 2 e, and g, you easily find out FlO. 12.— TUBULARIA. a. Diagram of the " Hydranth," with its short and long tentacles. 6. Eestitution of a new hydranth inside the perisarc (p). c. The same— later stage ; the tentacles are complete ; the whole hydranth will be driven out of the perisarc by a process of growth that occurs at the locality marked ^. d. A stem of Tubularia cut either at ax 61 or at 03 &2, or at ttj c. e. Position of tentacles in the piece cut at ni &i. /. ,, ,, „ 02 &2) which is equal in length to Oi 61. ff. ,, „ ,, aj c, which is half as long as Oi 61. that the absolute lengths of the two tentacle rings are very different, and that both are in proportion^ to the actual size of the stem (Fig. 12). ' This statement is not strictly correct for Tuhularia. I found {Archiv /, Eiiiwickdungsmechanik, ix. 1899), that a reduction of the length of the stem is always followed by a reduction of the size of the hydranth-primor- dium, but there is no real proportionality between them. It is only for theoretical simplification that a strict proportionality is assumed here, both in the text and the diagram. But there is an almost strict proportionality in all eases of " closed forms." EXPERIMENTAL MORPHOGENESIS 129 So we find our formula 'ig.v. {X) =f (s, I, E) very well illustrated in Tubularia. The formula indeed may help us to predict, in any case, where a certain part of the polyp's organisation is to originate, at least if we know all that is included under our letter U, i.e. the normal proportion of our form. Of course such prediction would not have much practical importance in all our cases of morphogenesis, hut nevertheless I should like to state here that it is possible ; for many scientific authors of recent times have urged the opinion that prediction of, and domination over, what will happen, can be the only true aims of sciences at all. 1 myself judge these aims to be of second or third-rate im- portance only, but, if they may be reached by what our purely theoretical study teaches, so much the better. Another very typical case of a morphogenetic system of the harmonious type is supplied by the phenomena of restoration in the ascidian Clavellina. I cannot fully describe the organisation of this form (Fig. 13 a), and it must suffice to say that it is very complicated, consisting of two very different chief parts, the branchial apparatus and the so-called intestinal sac; if these two parts of the body of Clavellina are separated one from the other, each may regenerate the other in the typical way, by budding processes from the wound. But, as to the branchial apparatus, there may happen something very different : it may lose almost all of its organisation and become a small white sphere, consisting only of epithelia correspond- ing to the germ-layers, and of mesenchyme between them, and then, after a certain period of rest, a new organisation will appear. Wow this new organisation is not that of a branchial apparatus but represents a very small but com- 130 SCIENCE AND PHILOSOPHY OF THE ORGANISM ; plete ascidian (Kg. 13). Such a fact certainly seems to j be very important, not to say very surprising ; but still ( another phenomena may be demonstrated on the animal which seems to be even more important. You first isolate the branchial apparatus from the other part of the body, and then you cut it in two, in whatever direction you please. Provided they survive and do not die, as indeed many of them do, the pieces obtained by this operation will each lose their organisation, as did the whole branchial apparatus, and then will each acquire another one, and this new organisation is also that of a complete little Glavellina. So we see that not only is the branchial apparatus of our animal capable of being transformed into a whole animal by the co-operative work of all its parts, but even each part of it may be transformed into a small whole, and it is quite at our disposal how large this part shall be, and what sort of a fragment of the original branchial apparatus it shall represent. We could hardly imagine a better instance of an harmonious-equipotential system. I cannot give you a description of all the other types of our systems subservient to restitution, and I can only mention here that the common hydra and the flatworm Planaria are very fine examples of them. But to one special case of harmonious equipotentiality you must allow me to direct your further attention. It has been known for many years that the Protozoa are also capable of a restoration of their form and organisa- tion after disturbances, if at least they contain a certain amount of their nuclear substance. This process of restora- tion used to be regarded as belonging to the common type EXPERIMENTAL MORPHOGENESIS 131 of regeneration proper, until T. H. Morgan succeeded in showing that in the genus Stentor it follows just the very lines which we know already from our study of embryonic organs or from Tuhdaria ; that an harmonious-equipotential system is at the basis of what goes on. Now, you know a. FiQ. 13.— Clavellika. a. Diagram of the normal animal; E and /= openings ; iir= branchial apparatus; D= intestine ; Ar=stomach ; if =heart, b. The isolated branchial apparatus. c-e. Diflferent stages of reduction of the branchial apparatus. /. The new w?ioZe little ascidian. that all Protozoa are but one highly organised cell: we have therefore here an instance where the so-called " elements " of our harmonious-morphogenetic system are not cells, but something inside of cells ; and this feature must appear to be of very great moment, for it first shows, as we have already pointed out on another occasion, that morphogenesis is not dependent on cell-division, and it states at the same time that our concept of the harmonious- 132 SCIENCE AND PHILOSOPHY OF THE ORGANISM equipotential system may cover a very great area — that, in fact, it is a scheme of a very wide extent. The FroUem of the Factor E We turn back again to considerations of a more abstract form. We left our analysis of the differentiation of the harmonious-equipotential systems, and particularly of the phenomena of localisation during this differentiation, at the point where we had succeeded in obtaining an equation as the expression of all those factors on which the pro- spective value, the actual fate, of any element of our systems depends, p.v, (X)=/ (s, I, E) was the short ex- pression of all the relations involved ; s and I, the absolute size of the system and the relative position of the element with respect to some fixed points, were independent variables ; E was a constant, namely, the prospective potency, with special regard to the proportions embraced by it. We shall now study the significance of the factor E. What does this E mean ? Is it a short expression merely for an actual sum of elemental agents having a common resultant? And, if so, of what kind are these agents ? Or what may E mean, if it can be shown Twt to be a short sign for a mere sum ? No Explanation Offered hy " Means " or " Formative Stimuli " For practical purposes it seems better if we modify the statement of our question. Let us put it thus : E is one of the factors responsible, among variables, for the localisa- tion of organic differentiation ; what then do we actually know about the causal factors which play a localising part EXPERIMENTAL MORPHOGENESIS 133 ill organogenesis ? "We, of course, have to look back to our well-studied "formative stimuli." These stimuli, be they " external " or " internal," come from without with respect to the elementary organ in which any sort of differentiation, and therefore of localisation, occurs : but in our harmonious systems no localising stimulus comes from without, as was the case, for instance, in the formation of the lens of the eye in response to the optical vesicle touching the skin. We know absolutely that it is so, not to speak of the self- evident fact that the general " means " of organogenesis have no localising value at all.' So we see there is nothing to be done, either with the means or with the formative stimuli ; both are entirely unable to account for those kinds of localisation during differentiation which appear in our harmonious systems. But is there no possibility of explaining the phenomena of organogenetic localisation by any other sort of interaction of parts ? Two such possibilities may at the first glance seem to exist. ' One might object here that in a piece of a Tubularia stem, for instance, the tissues are in direct contact with the sea-water at the two points of the wounds only, and that at these very points a stimulus might be set up — say by a process of diflfusion — which gradually decreases in intensity on its way inward. And a similar argument might apply to the small but whole blastula of Echinus, and to all other cases. But, in the first place, stimuli which only differ in intensity could hardly call forth the typical and typically localised single features realised in differentiation. On the other hand — and this will overthrow such an hypothesis completely — the dependence of the single localised effects in every case on the absolute size of the frag- ment or piece chosen for restoration renders quite impossible the assumption that all the singularities in the differentiation of the harmonious systems might be called forth by single stimuli originating in two fixed places in an independent way. These would never result in any "harmonious," any proportionate structure, but a structure of the "normal" proportionality and size at its two ends and non-existent in the middle ! 134 SCIENCE AND PHILOSOPHY OF THE ORGANISM No Explanation Offered hy a Chemical Theory of Morphogenesis Though never set forth in the form of a properly worked- out theory, the view has sometimes been advocated by biologists, that a chemical compound of a very high degree of complication might be the very basis of both development and inheritance, and that such a chemical compound by its disintegration might direct morphogenesis. Let us first examine if such a view may hold for the most general features of organic morphogenesis. It seems to me that from the very beginning there exists one very serious objection to every chemical theory of form-building, in the mere fact of the possibility of the restoration of form starting from atypical localities. The mere fact, indeed, that there is such a thing as the regeneration of a leg of a newt — to say nothing about restitution of the harmonious type — simply contradicts,^ it seems to me, the hypothesis, that chemical disintegration of one compound may govern the course of morphogenetic events : for whence comes the re-existence of the hypothetical compound, newly to be disintegrated, after disintegration has been completed once already? And we even know that regeneration may go on several times running from the same locality ! ' See my article in Biolog. Centralblatt, 27, 1907, p. 69. The question is rendered still more complicated by the fact that in the case of the regenera- tion, say, of a leg it is not the original "morphogenetic compoimd" which is again required for disintegration, after it has become disintegrated once already, but only a specific part of it : just that part of it which is necessary for producing the leg ! On the other hand, it would be impossible to under- stand, on the basis of physical chemistry, how the isolated branchial apparatus of Clavellina could be transformed, by chemical processes exclusively, into a system of which only a certain part consists of that substance of which the starting-point had been composed in its completeness. EXPERIMENTAL MORPHOGENESIS 135 But, if we intentionally disregard this difficulty, in spite of its fundamental character, how could the hypothesis of chemical disintegration give the reason for the differentia- tion of our harmonious-equipotential systems, with special regard to the localisation of it ; how could it account, in other words, for the appearance of typically localised speci- fications in an organ for which no external localising causes can be predicated ? Let us remember that a few original intimate differences exist in our harmonious systems : the main directions of the intimate protoplasmic structure including polarity and bilaterality. There are therefore three times two specified poles in each of these systems, at least in bilateral organisms, but no other differences are present in them. A few very simple cases of harmonious differentiation might indeed be understood on the theory of a disintegrating chemical com- pound in connection with these few differences. Imagine that the original compound, of the quantity a, is disintegrated to the amount of a^ ; from a-^ are formed the two more simple compounds, 6 and c, both of them in definite quantities ; then we have the three chemical individuals, a — Oj, & and c, as the constituents of our harmonious system ; and it now might be assumed, without any serious difficulty, though with the introduction of some new hypotheses, that the two poles of one of the fundamental axes of symmetry attract 6 and c respectively, a — aj remaining unattracted between them. "We thus should have the three elementary constituents of the system separated into three parts, and as they all three are of a definite quantity, their separation would mean that the system had been divided into three parts, a — «!, & and c, also with regard to its proper form. 136 SCIENCE AND PHILOSOPHY OF THE ORGANISM It is clear, that by taking away any part of the original system, by means of operations, there would be taken away a a certain amount of the original compound ; say that - 'Th is left; then, of course, the three constituents after the partial disintegration would be J, - and -, and so it n n n follows that the proportionality of localisation would really be preserved in any case. But these considerations, evident as they seem to be in the most simple case, fail to satisfy in a really general sense : for two different reasons. First, they could never account for the fact that the differentiated organism by no means consists of so many different compounds as it shows single parts of its differentiation, but that, on the contrary, it only consists, as we know, of a certain rather limited number of true different morphogenetic elements, these elements occurring again and again — as for instance, nervous or muscular elements — but typical each time in locality, quantity, and form. And in the second place, the very form of elementary organs, their form as such, does not at all go hand-in-hand with chemical differences ; this feature alone would absolutely overthrow any sort of a chemical morphogenetic theory to account for the problem of localisation. Take the typically arranged ring of the mesenchyme cells in our Echinus-gastrula, with its two spherical triangles, so typically localised; look at any sort of skeleton, in Radiolaria, or in starfishes, or in vertebrates : here you have form, real form, but form consisting of only one material. Not only is the arrangement of the elements of form typical here, e.g. the arrangement of the single EXPERIMENTAL MORPHOGENESIS 137 parts of the skeleton of the hand or foot, but also the special form of each element is typical, e.g. the form of each single bone of the foot; and, on a purely chemical theory of morphogenesis the sufficient reason for the production of typical form in such a sense would be want- ing. For atoms or molecules by themselves can only account for form which is arranged, so to speak, according to spatial geometry— as in fact they do in crystallography ; but they can never account for form such as the skeleton of the nose, or hand, or foot. You will answer me perhaps, that there may be non-chemical agents in the germ,^ re- sponsible for typical form-localisation, but by such reasoning you would be departing from a purely chemical theory. Our next paragraph will be devoted to this side of the question. That is the principal reason for rejecting all sorts of chemical morphogenetic theories put forward to explain the problem of localisation; it is more explicit, and therefore, I suppose, still more convincing than the more general con- sideration that the very fact of restitutions in itself must contradict the hypothesis that a disintegration of compounds might be the directive agency in morphogenesis. To sum up : Specificity of organic form does not go hand-in-hand with specificity of chemical composition, and therefore cannot depend on it; and besides that, specific organic form is such that it can never be explained by atomic or molecular arrangement in the chemical sense ; for, to state it in a short but expressive manner, the " form " of an atom or molecule can never be that of a lion or a monkey. To ' Besides the specified poles determined by the polar-bilateral structure of the protoplasm. 138 SCIENCE AND PHILOSOPHY OF THE ORGANISM assume that would be to go beyond the limits of chemistry in chemistry itself. No Machine Possible Inside tlie Harmonious Systems And now we turn to the last possibility which is left to us in our endeavour to " understand " the localisation of the differentiation in our harmonious-equipotential systems by the means of physics and chemistry. Outside causes have failed to account for it, chemical disintegration of a compound has failed too. But could there not exist some sort of complicated interactions amongst the parts of the harmonious system themselves ? Could there not exist some kind of a real machine in the system, which, if once set going, would result in the differentiations that are to take place ? Then we might say that the " prospective potency " of the system is in fact that machine ; we should know what the letter E of our equation stood for : viz., a resultant action of many complicated elemental inter- actions, and nothing more. Weismann, we know already, had assumed that a sort of machine was the prime mover of morphogenesis. We have seen that his theory cannot be true ; the results of experiments most strongly contradict it. But, of course, the experiments only showed us that such a machine as he had imagined to exist could not be there, that development could not be governed by the disintegration of a given complicated structure into its simplest parts. But might not some other machine be imaginable ? We shall understand the word " machine " in a most general sense. A machine is a typical configuration of EXPERIMENTAL MORPHOGENESIS 139 physical and of chemical constituents, by the acting of which a typical effect is attained. We, in fact, lay much stress upon embracing in our definition of a machine the existence of chemical constituents also ; we therefore understand by the word " machine " a configuration of a much higher degree of complication than for instance a steam-engine is. Of course a machine, whose acting is to be typical with regard to the three dimensions in space, has to be typically con- structed with regard to these three dimensions itself; a machine that was an arrangement of elements in a strict plane could never have typical effects at right angles to that plane. This is a point which must well be kept in mind in all hypothetical considerations about machines that claim to explain morphogenesis. It must be granted that a machine, as we understand the word, might very well be the motive force of organo- genesis in general, if oidy normal, that is to say, if only undisturbed development existed, and if a taking away of parts of our systems led to fragmental development. But we know that, at least in our harmonious- equipotential systems, quite another process occurs after parts have been taken away : the development that occurs is not fragmental but whole, only on a smaller scale. And we know, further, that this truly whole develop- ment sets in irrespective of the amount and direction of the separation. Let us first consider the second of these points. There may be a whole development out of each portion of the system — above certain limits — which is, say, of the volume V. Good ! Then there ought to exist a machine, like that which exists in the whole undisturbed system, in this portion V also, only of smaller dimensions; but it also 140 SCIENCE AND PHILOSOPHY OF THE ORGANISM ought to exist in the portion Fj which is equal to V in amount, and also in V^, in Fg, V^ and so on. Indeed, there do exist almost indefinitely many F„, all of which can perform the whole morphogenesis, and all of which therefore ought to possess the machine. But these different portions F^ are only partly different from each other in spatial relation. Many parts of Fg are also parts of Fj and of Fg and of F4, and so on ; that is to say, the different volumes F„ overlap each other successively and in such a manner that each following one exceeds the preceding one in the line by a very small amount only. But what then about our machines ? Every volume which may perform morphogenesis completely must possess the machine in its totality. As now every element of one volume may play any possible elemental role in every other, it follows that each part of the whole harmonious system possesses any possible elemental part of the machine equally well, all parts of the system at the same time being constituents of different machines. A very strange sort of machine indeed, which is the same in all its parts (Fig. 14) ! But we have forgotten, I see, that in our operation the absolute amount of substance taken away from the system was also left to our choice. From this feature it follows that not only all the different F^, all of the same size, must possess the hypothetic machine in its completeness, but that all amounts of the values V^ — n, n being variable, must possess the totality of the machine also : and all values V^ — n, with their variable n, may again overlap each other. Here we are led to real absurdities ! EXPERIMENTAL MORPHOGENESIS 141 But what is the conclusion of our rather wild considera- tions ? It seems to me that there is only one conclusion possible. If we are going to explain what happens in our harmonious-equipotential systems by the aid of causality based upon the constellation of single physical or chemical factors and events, there must be some such thing as a machine. Now the assumption of the existence of a machine proves to be absolutely absurd in the light of the experimental V? - ^\ ' ^ \' — ^ X Fio. 14. — Aif " Habmonious-equipotential System " of whatever kind. According to the " machine-theory " ot life this system ought to possess a certain unknown very complicated machine in its aompleteness : (a) in its total length, and (&) in each of the equal volumes v, vj, v^, U3 and so on, and (c) in each of the unequal volumes w, x, y, and so on, and (d) in every imaginable volume, no matter of what size. Therefore the *' machine-theory" of life is absurd. facts. Therefore there can be neither any sort of a machine nor any sort of causality hosed upon constellation underlying the differentiation of harmonious-equipotential systems. For a machine, typical with regard to the three chief dimensions of space, cannot remain itself if you remove parts of it or if you rearrange ^ its parts at will. Here we see that our long and careful study of morpho- genesis has been worth while : it has afforded us a result of the very first importance. ' The pressure experiments and the dislocation experiments come into account here ; for the sake of simplicity they have not been alluded to in the main line of our argument. 142 SCIENCE AND PHILOSOPHY OF THE ORGANISM Tlu Autonomy of Morphogenesis Proved No kind of causality based upon the constellations of single physical and chemical acts can account for organic individual development ; this development is not to be explained by any hypothesis about configuration of physical and chemical agents. Therefore there must be something else which is to be regarded as the sufficient reason of individual form-production. We now have got the answer to our question, what our constant E consists in. It is not the resulting action of a constellation. It is not only a short expression for a more complicated state of affairs, it expresses a true element of nat ure. Life, at least morpho- genesis, is not a specialised arrangement of inorganic events ; biology, therefore, is not applied physics and chemistry : life is something apart, and biology is an independent science. All our results at present, indeed, are negative in their form; our evidence was throughout what is called per exclusionem, or indirect or apagogic. There were excluded from a certain number of possibilities all except one ; a disjunctive proposition was stated in the form : H is either this, or that, or the other, and it was shown that it could not be any of all these except one, therefore it was proved to be that one. Indeed, I do not see how natural science could argue otherwise; no science dealing with inorganic phenomena does ; something new and elemental must always be introduced whenever what is known of other elemental facts is proved to be unable to explain the facts in a new field of investigation. We shall not hesitate to call by its proper name what we believe we have proved about morphogenetic phenomena. EXPERIMENTAL MORPHOGENESIS 143 What we have proved to be true has always been called vitalism, and so it may be called in our days again. But if you think a new and less ambitious term to be better for it, let us style it the doctrine of the autonomy of life, as proved at least in the field of morphogenesis. I know very well that the word " autonomy " usually means the faculty of giving laws to oneself, and that in this sense it is applied with regard to a community of men ; but in our phrase autonomy is to signify the being subjected to laws peculiar to the phenomena in question. This meaning is etymologically defensible, and besides that I perhaps may remind you of a certain chapter of Professor Ward's Gifford Lectures, in which he holds the view that, psychologically and epistemologically, there is more than a mere verbal relation between the civil and the natural " law." Vitalism then, or the autonomy of life, has been proved by us indirectly, and cannot be proved otherwise so long as we follow the lines of ordinary scientific reasoning. There can indeed be a sort of direct proof of vitalism, but now is not the time to develop this proof, for it is not of the purely scientific character, not so naive as our present arguments are, if you choose to say so. An important part of our lectures next summer will be devoted to this direct proof. " Entelechy " But shall we not give a name to our vitalistic or autonomous factor E, concerned in morphogenesis ? Indeed we will, and it was not without design that we chose the letter E to represent it provisionally. The great father of systematic philosophy, Aristotle, as many of you will 144 SCIENCE AND PHILOSOPHY OF THE ORGANISM know, is also to be regarded as the founder of theoretical biology. Moreover, he is the first vitalist in history, for his theoretical biology is throughout vitalism ; and a very conscious vitalism indeed, for it grew up in permanent opposition to the dogmatic mechanism maintained by the school of Democritus. Let us then borrow our terminology from Aristotle, and let that factor in life phenomena which we have shown to be a factor of true autonomy be called Entelechy, though without identifying our doctrine with what Aristotle meant by the word ivTeKs'^eia. We shall use this word only as a sign of our admiration for his great genius ; his word is to be a mould which we have filled and shall fill with new contents. The etymology of the word evreXe'xeia allows us such liberties, for indeed we have shown that there is at work a something in life phenomena " which bears the end in itself," o e^et ev eavTw to TeXo<;. Our concept of entelechy marks the end of our analysis of individual morphogenesis. Morphogenesis, we have learned, is " epigenesis " not only in the descriptive but also in the theoretical sense : manifoldness in space is produced where no manifoldness was, real " evolutio " is limited to rather insignificant topics. But was there nothing "manifold" previous to morphogenesis? Nothing certainly of an extensive character, but there was something else : there was entelechy, and thus we may provisionally call entelechy an "intensive manifoldness." That then is our result: not evolutio, but epigenesis — " epigenesis vitalistica." EXPERIMENTAL MORPHOGENESIS 145 Some General Remarks on Vitalism "We now shall leave entelechy where it stands : next summer we shall turn back to it and shall make its full logical and ontological analysis our chief study. At present we are satisfied with having proved its existence in nature, with having laid some of the foundations of a doctrine to be based upon it. I hope that these foundations will evince themselves strong : that is all-important.^ It indeed has been the fault of all vitalism in the past that it rested on weak foundations. Therefore the discussion of the basis underlying our doctrine of the autonomy of life is to occupy us still a considerable time. We shall devote to it two more of this year's lectures and three of the next ; we shall examine all sorts of phenomena of life in order to find out if there are any further proofs of vitalism, independent perhaps, of what we way call our first proof, which is based upon the analysis of the differentiation of harmonious-equi- potential systems. We shall find some more independent proofs ; and besides that we shall find many kinds of phenomena upon which future times perhaps may erect more of such independent proofs. For we shall be chary of bestowing the name "proof" except on what is a proof indeed, of course according to our critical conviction. Vitalistic views in biology have arisen ' Mj' "first proof of vitalism" was first developed in the paper, "Die Localisation morphogenetischer Vorgange," Leipzig, 1899. (See additional remarks in Organische Eegulationem, Leipzig, 1901, and in Archiv fur Sntunckelungsmechanik, 14, 1902.) I cannot admit that any really serious objection has been brought forward against it. (See my articles in Biologisches Oentralhlatt, 22, 23, 27, and in Ergebnisse d. Anat. u. JSfnttmckelungsgesch. 11, 14.) An historical sketch of vitalism will be found in my book, Der Vitalismus als Geschichte und als Lehre, Leipzig, 1905. 10 146 SCIENCE AND PHILOSOPHY OF THE ORGANISM in rather numerous forms during the last fifteen years, especially in Germany — though in very strong contrast to the so-called official German biology — but I can only admit that one of all the arguments of " neo-vitalism " has proved its statements. I refer to the theory of " morphaesthesia " as developed by Noll, which we shall study briefly in the next lecture. I cannot concede that Eeinke or Schneider or Pauly have really proved what they believe, and I can- not even allow to the most original thinker in this field, Gustav Wolff, that he has given a real demonstration of his views. He states that the existence of so-called " primary purposefulness," that is, the existence of adaptive processes, which cannot be imagined to have arisen on Darwinian principles, is able to prove vitalism ; but I say that it only proves teleology, which is a broader concept than vitalism. The possibility of a machine at the root of the phenomena in question always has to be excluded in order that vitalism may be proved, and I cannot grant that the necessity of such an exclusion has been actually shown by any of my fellow-combatants against so-called mechanism, except NoU.^ The Logic of our First Proof of Vitalism Let us devote the end of our present lecture to an account of the logical means by which it has been possible to develop what we hope will be regarded as a true proof of life autonomy. Firstly, we have looked upon the phenomena of 1 We are dealing here with morphogenesis and .so-called vegetative physiology only ; to certain psychologists, who have refuted the theory of psycho -physical parallelism, I must grant that they also have proved -vitalism. (See Volume II.) EXPEEIMENTAL MORPHOGENESIS 147 morphogenesis without any prepossessions ; we may say that we have fully surrendered ourselves to them; we have not attacked them with any sort of dogmatism except the inherent dogmatism of all reasoning. But this dogmatism, if it may be called so, does not postulate that the results of the inorganic doctrines must hold for the organic world, but only that both the inorganic and the organic must be subject to certain most general principles. By studying life as a given phenomenon, by fully devoting ourselves to our problem, we not only have analysed into its last elements what was given to us as our subject, but we also, more actively, have created new combinations out of those elements : and it was from the discussion of these positive constructions that our argument for vitalism was derived. We have analysed morphogenesis into elementary pro- cesses, means, potency, formative stimulus, just as the physicist analyses mechanics into time, velocity, mass, and force ; we have then rearranged our elements into " systems " — the equipotential systems, the harmonious - equi - potential system in particular, just as the physicist composes his elements into the concepts of momentum or of kinetic energy or of work. And finally, we have discussed our compositions and have obtained our result, just as the physicist gets his ultimate results by discussing work and kinetic energy and momentum. Of course the comparison is by no means intended to show that mechanics and biology are sciences of the same kind. In my opinion, they are not so at all ; but neverthe- less there do exist similarities of a logical kind between them. And it is not the formal, logical character alone which 148 SCIENCE AND PHILOSOPHY OF THE ORGANISM allows us to compare biology with other natural sciences : there is still something more, there is one kind of assump- tion or postulate, or whatever you may choose to call it, without which all science whatever would be altogether impossible. I refer to the concept of universality. All concepts about nature which are gained by positive con- struction out of elements resulting from analysis, claim to be of universal validity; without that claim there could indeed be no science. Of course this is no place for a lecture on methodology, and it therefore must suffice to make one remark with special regard to our purpose, which we should like to emphasise. Our concept of the harmonious -equipotential system — say rather, our concept of the prospective potency itself — presumes the understanding that indeed all blastomeres and all stems of Tuhularia, including those upon which we have not carried out our experiments, will behave like those we have experimented with ; and those concepts also presume that a certain germ of Echinus, A, the blastomeres of which were not separated, would have given two whole larvae, if separation had taken place, while another germ, B, which actually gave us two larvae after separation, would only have given one without it. Without this presumption the concept of " potency " is meaningless, and, indeed, every assumption of a " faculty " or a " possibility " would be meaningless in the whole area of science. But this presumption can never be proved ; it can only be postulated. It therefore is only with this postulate that our first proof of vitalism holds ; but this restriction applies to every law of nature. EXPERIMENTAL MORPHOGENESIS 149 I cannot force you to agree with this postulate : but if you decline you are practically saying that there exists a sort of pre-established harmony between the scientific object and the scientist, the scientist always getting into his hands such objects only as have been predestinated from the very beginning to develop two larvae instead of one, and so on. Of course, if . that is so, no proof of natural laws is possible at all ; but nature under such views would seem to be really dasmonic. And so, I hope, you will grant me the postulate of the universality of scientific concepts — the only "hypothesis" which we need for our argument. 4. On Certain other Features of Morphogenesis Advocating its Autonomy Our next studies on the physiology of form will be devoted in the first place to some additional remarks about our harmonious-equipotential systems themselves, and about some other kinds of morphogenetic " systems " which show a certain sort of relationship with them. For it is of the greatest importance that we should become as familiar as possible with all those facts in the physiology of form upon the analysis of which are to be based almost all of the future theories that we shaU have to develop in biology proper and philosophical. Our discussions, so far as they relate to questions of actual fact, will contain only one other topic of the same importance. But though it is designed to complete and to deepen our analysis, the present considerations may yet be said to mark a point of rest in the whole of our discussions : we have followed one single line of argumentation from the beginning until now ; this line or this stream of thought, as you might call it, is now to break into different branches for a while, as if it had entered from a rocky defile into a plain. It seems to me that such a short rest will be not uncon- ducive to a right understanding of all we have made out ; and such a full and real conceiving again, such a realising 150 EXPERIMENTAL MORPHOGENESIS 151 of our problems of morphogenesis and their solutions, will be the best preparation for the philosophical part of these lectures. HARMONIOUS-EQUIPOTENTIAL SYSTEMS FORMED BY WANDERING CELLS All of the harmonious-equipotential systems which we have studied so far were the bases of histological differentiation ; that is to say, the processes of their differentiation, consisted in specifically localised elements of theirs becoming different in situ. ISTow we know at least one type of systems which also may be called harmonious-equipotential, but the differentiation of which does not simply relate to elements at a fixed place. An additional phenomenon enters here into the sphere of the others. The elements not only become different where they are, but a specific changing of locality, a specific kind of wandering, goes hand-in-hand with differences relating to the prospective value to be attained. I am speaking of the formation of the larval skeleton of our well-known Echinus. We know that the mesenchyme cells, which have left the blastoderm and are arranged in a sort of ring of bilateral structure, are the starting-point of this skeleton ; it indeed originates in a sort of secretive process on the part of the cells ; the cells are moving about and are secreting carbonate of lime during their wandering. The experiments now have shown, as we know, that a whole, though smaller, skeleton may also be formed, if only a half or a quarter of the mesenchyme cells are present, as happens to be the case in all experiments with isolated 152 SCIENCE AND PHILOSOPHY OF THE ORGANISM blastomeres of the two or four-cell stage of cleavage. It is clear that in these cases the performance of each single cell must be different from what it is in the normal case, and that the same sort of differences in the morphogenetic performances appears again, if the two- and the four-cell stage are compared with each other. And there are still some other phenomena showing the possibility of different performances being carried out by the individual cells. Peter has shown that the number of mesenchyme cells may vary enormously under certain conditions ; but, in spite of that, the skeleton always will be complete. It may be said that this line of research is only of a relative value to our own questions, as, of course, variability relates to different individuals : but it seems to me that it adds a very good supplementary instance to what the experiment on the individual itself has established. We should only be repeating ourselves if we were to analyse again what happens here as the expression of the harmonious-equipotentiality itself. But indeed there occurs something new in this instance : the single mesen- chyme cell not only has to perform in each case that single act of specific secretion which the case requires, but it also has to wander to the right place in order to perform it ; there must be some order, not only about the acts of secretion after wandering, but also in the migrations them- selves. If undisturbed ontogeny alone were possible, and if therefore a theory like that of Weismann were in place, we might say perhaps that each mesenchyme-cell is specified not only as to its performance in secretion, but also with regard to its chemotactical irritability, the latter being typically localised, so that its effect becomes typical, thanks EXPERIMENTAL MORPHOGENESIS 153 to the typical arrangement of all the cells with respect to each other. But that is certainly not the case. Now, you may ask yourselves if you could imagine any sort of a machine, which consists of many parts, but not even of an absolutely fixed number, all of which are equal in their faculties, but all of which in each single case, in spite of their potential equality, not only produce together a certain typical totality, but also arrange themselves typically in order to produce this totality. We are indeed familiar with certain occurrences in nature where such curious facts are observed, but I doubt if you would speak of " machines " in these cases. The mesenchyme-cells, in fact, behave just as a number of workmen would do who are to construct, say, a bridge. All of them can do every single act, all of them also can assume every single position : the result always is to be a perfect bridge; and it is to be a perfect bridge even if some of the workmen become sick or are killed by an accident. The " prospective values " of the single workman change in such a case. I well know that it is only an analogy which I am offering to you. The mesenchyme-cells have not " learned," have no " experience." All that is to occupy us next summer. But in spite of it, there is truth in the analogy ; and perhaps you will prefer it to the merely abstract consideration. ON CERTAIN COMBINED TYPES OF MOKPHOGENETIC SYSTEMS For the sake of completeness it may be remarked, only by the way, that the type of the proper harmonious- equipotential system may go hand in hand with another 154 SCIENCE AND PHILOSOPHY OF THE ORGANISM type of " systems " which play a part in morphogenesis ; a type which we have shortly mentioned already and which will be studied fully a few chapters later. "We know that there are equipotential systems with complex potencies : that is to say, systems which may produce a whole organism equally well from any one of their elements ; we know the cambium of Phanerogams to be such a system. Now it is easily understood that the germ of our Echinus, say in the stage of two or four or eight cleavage cells, is not only an harmonious-equipotential system, but a complex-equipotential system too. Not only may there arise a whole organism out of |- or 1^ or f , ^, -f, f , ■§■ of its elements, in which cases the harmonious role of the single element with regard to its single performance in a totality is variable, but there may also arise four whole single larvae out of the four cells of the four-cell stage, or eight single whole larvae out of the eight-cell stage.^ Ixi these cases, of course, each of the four or eight elements has performed not a part of the totality, changing with its "position," but the totality itself. With respect to these possible performances the " systems " present in the four or eight-cell stages of cleavage must be called complex-equipotential ones. We propose to give the name of mixed-equijootential systems to all those equipotential systems which, at the same time, may be regarded as belonging to the harmonious or to the complex type. It is not only among cleavage- stages that they are to be found; you may also find 'them very clearly exhibited in our ascidian Clavellina for instance. ' The eight laivae would be incomplete in some respect, but not with regard to symmetry. They would be "whole "ones, only showing certain defects in their organisation. See page 65 note 1, and page 73. EXPERIMENTAL MORPHOGENESIS 155 We know already that the branchial apparatus of this form is typically harmonious-equipotential, but it is complex- equipotential too, for it also may regenerate what is wanting in the proper way, by a budding from the wound ; and the same is true of many other cases, the flatworm Planaria for instance. Another type of systems, which might be said to be of a higher degree, is exhibited in some very strange phenomena of regeneration. It was first shown most clearly by some experiments of Godlewski's that a whole tail may be regenerated from a wound inflicted on the body of a newt, even if this wound involves section of only a portion of the body-diameter. Section of the whole of the body-diameter of course would cause the formation of the whole tail also ; but it was found that even an incomplete cross-section of the body is capable of performing the whole on a smaller scale. The series of possible cross-sections which are all capable of regeneration would have to be called a system of the complex type in this case ; but, now we learn that every single cross-section is of the harmonious type, we must speak of complex-harmonious systems. What we have described is not the only in- stance of our new type of morphogenetic systems. Some other instances had been discovered a few years earlier, though nobody had pointed out their true significance. In the flatworm Flanaria a partial cross-section is also capable of forming a whole structure, say a head, and all cases of so-called " super -regeneration " after the infliction of a complicated wound probably belong here also. You may say that our two additions to the theory of 156 SCIENCE AND PHILOSOPHY OF THE ORGANISM systems are merely formal, and indeed I am prepared to concede that we shall not learn anything altogether new from their discussion : their analysis would lead either to what was our " first proof " of the autonomy of life- phenomena or to what will be our " second " one. But the mere descriptions of the facts discovered here will interest you, I think, and will fill your minds with more vivid pictures of the various aspects of form-autonomy. While dealing with our harmonious-equipotential systems as the starting-points of processes of restitution, e.g. in Tubularia, Glavellina, the flatworms, and other instances, we always have regarded cross-sections of the body as constituting the elements of equipotentiality. Now cross- sections, of course, are by no means simple in themselves, but are made up of very different tissues, which are derivates of all three of the original germ layers — ectoderm, mesoderm, and endoderm. Owing to this com- posite character of the cross-sections, taken as elements of harmonious systems, a special phenomenon of morpho- genesis is presented to us, which teaches somewhat more than the mere concept of harmonious-equipotentiality can express. If composite elements concerned in morpho- genesis result in one whole organisation in spite of the development of the single tissues of these elements going on independently, then there must be a sort of corre- spondence or reciprocity of the harmonious development among these tissue constituents themselves ; otherwise a proportionate form could not be the final result. We may conveniently speak of a reciprocity of harmony as existing between the single tissues or germ layers which constitute many harmonious-equipotential systems, and there can be EXPERIMENTAL MORPHOGENESIS 157 little doubt that we have here an important feature with regard to general morphogenesis.^ A few other groups of morphogenetic facts may find their proper place here, though they are not properly to be regarded as additions to the theory of harmonious systems but as forming a sort of appendix to it. THE " MOEPHAESTHESIA " OF NOLL ^ We may briefly mention that group of botanical phenomena, by which the botanist Noll has been led to the concept of what he calls " morphaesthesia," or the " feeling " for form ; a concept, the full discussion of which would lead to almost the same conclusions as our analysis of the harmonious systems has done. In the Siphoneae, a well-known order of marine algae with a very complicated organisation as to their exterior form, the protoplasm which contains the nuclei is in a constant state of circulation round the whole body, the latter not being divided by proper cell-walls. On account of this constant movement it is certainly impossible to refer morphogenetic localisation to definite performances of the nuclei. Nor can any sort ' Keciprocal harmony may be reduced in some cases to the given pro- portions of one original harmonious system, from which the single constituents of the complicated system, showing reciprocal harmony, are derived. Then we have only an instance of "harmony of constellation " (see p. 109). But reciprocal harmony seems to become a problem itself, if it occurs in restitutions starting from quite a typical point, selected by the experimenter. It will be a problem of future research to give an exact formula of what happens here. Keciprocal harmony also occurs in regeneration proper. It is known that the formation of the regenerative bud and the differentiation of this bud follow each other. As the bud is composed of different elementary systems, it follows that these different systems, of which every single one is harmonious, also have to work in reciprocity to each other, in order that one whole proportionate formation may result. 2 Biol. Centralblatt. 23, 1903. 158 SCIENCE AND PHILOSOPHY OF THE ORGANISM of structure in the outer protoplasmic layer, which is fixed, be responsible for it, for there is no such structure there : hence there must be a sort of feeling on the part of the plant for its relative body localities, and on account of this feeling morphogenesis occurs. This " feeling " is styled " morphaesthesia " by Noll, and to it he tries to refer all sorts of different botanical form-phenomena,^ for instance what is called " autotropism," that is, the fact that branches of plants always try to reassume their proper angle with regard to their orientation on the main axis, if this orienta- tion has been disturbed. It may be an open question if this particular application of the theory is right : certainly there seems to be much truth in the establishment of the concept of morphaesthesia, and we only have to object to its psychological name. But that may be done in a more general form on a later occasion. KESTITUTIONS OF THE SECOND OEDEE In the hydroid polyp Tiubularia, already familiar to us as being a most typical representative of the harmonious- equipotential systems, a very interesting phenomenon has been discovered ^, almost unparalleled at present but never- theless of a general importance, a phenomenon that we may call a restitution of a restitution, or a restitution of the second order. You know that the first appearance of the new head of Tubularia, after an operation, consists in the * Certain phenomena of the physiology of growth of Geranium Robertianum, recently discussed by France from a vitalistic point of view {Zeitschr. Eniw. lehre. 1, 1907, Heft iv.), might also belong here. I cannot see an independent proof of vitalism in these facts if taken by themselves ; a pre-existing "machine " cannot be absolutely excluded here. 2 Driesch, Arch. Enlw. Mech. 5, 1897. EXPERIMENTAL MORPHOGENESIS 159 formation of two rings of red lines, inside the stem, these rings being the primordia of the new tentacles. I removed the terminal ring by a second operation soon after it had arisen, disturbing in this way the process of restitution itself: and then the process of restitution itself became regulated. The organism indeed changed its course of morphogenesis, which was serving the purposes of a restitution, in order to attain its purpose in spite of the new disturbance which had occurred. For instance, it some- times formed two rings out of the one that was left to it, or it behaved in a different way. As this difference of morphogenetic procedure is a problem by itself, to be discussed farther on, we shall postpone a fuller description of this case of a restitution of the second degree. At present I do not see any way of proving independently the autonomy of life by a discussion of these phenomena ; their analysis, I think, would again lead us to our problem ■of localisation and to nothing else ; at least in such an «xact form of reasoning as we demand. ON THE " EQUIFINALITY " OF EESTITUTIONS ^ I have told you already that Tubularia in the pheno- mena of the regulation of restitutions offers us a second problem of a great general importance, the problem of the Eqidfinality of Bestitutions. There indeed may occur restitutions, starting from one and the same initial state and leading to one and the same end, but using very different means, following very different ways in the different individuals of one and the same species, taken from the same locality, or even colony. 1 Driesch, Arch. Entw. Mech. 14, 1902. 160 SCIENCE AND PHILOSOPHY OF THE ORGANISM Imagine that you have a piece of paper before you and wish to sketch a landscape. After drawing for some time you notice that you have miscalculated the scale with regard to the size of the paper, and that it will not be possible to bring upon the paper the whole of the landscape you want. What then can you do? You either may finish what you have begun to draw, and may afterwards carefully join a new piece of paper to the original one and use that for the rest of the drawing ; or you may rub out all you have drawn and begin drawing to a new scale ; or lastly, instead of continuing as you began, or erasing altogether, you may compromise as best you can by draw- ing here, and erasing there, and so you may complete the sketch by changing a little, according to your fancy, the proportions as they exist in nature. This is precisely analogous to the behaviour of our Tuhularia. Tvhularia also may behave in three different ways, if, as I described to you, the terminal one of its two newly arisen rings of tentacle primordia is removed again. It may complete what is left, say the basal tentacle ring, then put forth from the horny skeleton (the " perisarc ") the new head as far as it is ready, and finally complete this head by a regular process of budding regeneration. But it also may behave differently. It may " erase " by a process of retro-differentiation all that has been left of what had already been formed, and then may form d& novo the totality of the primordia of a new head. Or, lastly, it may remove a part of the middle of the one ring of tentacle rudiments which was left, and may use this one ring for the formation of two, which, of course, will not be quite in the normal relations of place with regard to each other and EXPERIMENTAL MORPHOGENESIS 161 to the whole, but will be regulated afterwards by processes of growth. Thus, indeed, there is a sort of equifinality of restitution : one starting-point, one end, but three different means and ways. It would, of course, contradict the principle of uni- vocality, as we shall see more fully later on, to assume that there actually are different ways of regulation whilst all the conditions and stimuli are the same. We are obliged to assume, on the contrary, that this is not the case, that there are certain differences in the constellation, say of the general conditions of age or of metabolism, which are responsible for any given individual choosing one process of restitution instead of another ; but even then the phenomenon of equifinality remains very striking. It has long been known that restitution in general does not always follow the same lines of morphogenesis as are taken by ontogeny, and it was this feature that once led Eoux to point out that the adult forms of organisms seem to be more constant than their modes of origin. But, comparing ontogeny with restitution in general, we see that only the ends are the same, not the points of starting; the latter are normal or non-typical in ontogeny, atypical in restitution. In the new discoveries of an equifinality of restitutions we have the same starting-point, which is decidedly non- typical but atypical, i.e. dependent on our arbitrary choice, leading by different ways always to the same end. There may be many who will regard the fact of equifinality as a proof of vitalism. I should not like to argue in this easy way; I indeed prefer to include part of the phenomena of equifinality in our first proof 162 SCIENCE AND PHILOSOPHY OF THE ORGANISM of autonomy, and part in the second one, which is to follow. Another important phenomenon of the equifinality of regulation was discovered by Morgan. A species of the flatworm Planaria was found to restore its totality out of small pieces either by regeneration proper, if the pieces were fed, or by a sort of rearrangement of material, on the i basis of its harmonious-equipotentiality, if they were kept f fasting. It is important to note that here we see one of the conditions determining the choice of the way to restoration, as we also do in the well-known equifinal restitutions of the root in plants, where the behaviour of the organism depends on the distance of the operation-wound from the tip.^ In Tubularia the actual stage of restitution that has been already reached by the stem when the second operation takes place, may account for the specification of its future organogenesis, but this is not at all clearly ascertained at present. Clavellina also shows equifinality in its restitution, as has already been shortly mentioned. The isolated branchial (•apparatus may restitute itself by retro-dififerentiation to an indifferent stage followed by renovation ; or it may regenerate the intestine-sac in the proper way. Nothing is known here about the conditions, except perhaps that young in- dividuals seem more apt to follow the first of these two ways, older ones the second; but there are exceptions to this rule. The discussion of other instances of equifinality, though ' The root may be restored by regeneration proper, or by the production of adventitious roots, or by one of the side-roots changing its geotropism from horizontal to positive, according to the smaller or greater distance of the wound from the tip. EXPERIMENTAL MORPHOGENESIS 163 important in themselves, would not disclose anything fundamentally new, and so we may close the subject with the remark that nothing can show better than the fact of the equifinality of restitutions how absolutely inadequate all our scientific conceptions are when confronted with the actual phenomena of life itself. By analysis we have found differences of potencies, according as they are simple or complex ; by analysis we have found differences of " systems," differences of means, and indeed we were glad to be able to formulate these differences as strictly as possible : but now we see how, in defiance of our discriminations, one and the same species of animals behaves now like one sort of our " systems," and now like the other ; how it uses now one sort of " potencies," now another. But even if it is granted that, in the presence of such phenomena of life, our endeavour seems to be like a child's play on the shores of the ocean, I do not see any other way for us to go, so long, at least, as our goal is human science — that is, a study of facts as demanded by our mental organisation. EEMAEKS ON " EETEO-DIFFERENTIATION " We shall finish this part of our studies by mentioning a little more explicitly one fundamental fact which has already entered incidentally into our considerations, viz. retro- or hack-differentiation} We know that it occurs in Clavellina and in Tvhularia; we may add that it also happens in Hydra, and that in the flatworm Planaria the pharynx, if it is too large for a piece that is cut out, ' " Retro "-differentiation, of course, is not "Re "-differentiation (" Um- differenzierung," see p. Ill), though it may help it to occur. 164 SCIENCE AND PHILOSOPHY OF THE ORGANISM may be differentiated back and be replaced by a new pharynx, which is smaller. It is not death and sloughing of parts that occurs in these cases/ but a real process of active morphogenesis ; not, however, a process consisting in the production of visible manifoldness, but the opposite. Loeb was the first to lay much stress upon this topic, and indeed, there may appear a very strange problem in its wake : the problem, whether all morphogenesis might be capable perhaps of going backwards under certain conditions. It is important to note that in most ^ cases retro- differentiation occurs in the service of restitution : it goes on wherever restitution requires it. This fact alone would show that not very much could be explained here by the discovery of modern chemistry, important as it is, that one and the same " ferment " or " enzyme " may affect both the composition and the decomposition of the same compound. We could regard what is called " catalysis " solely as an agent in the service of entelechy. But this point also will become clearer in another part of the work. ^ Of course such a real decay of parts may happen in other oases. ^ Certain cases of retro-differentiation occurring under conditions of strict fasting will be described in a later chapter. C. ADAPTATION Intkoductoey Eemakks on Eegulations in General We have finished our long account of individual morpho- genesis proper. If we look back upon the way we have traversed, and upon those topics in particular which have yielded us the most important general results, the material for the higher analysis which is to follow, it must strike us, I think, that all these results relate to regulations. In fact, it is " secondary " form-regulations, according to our terminology, that we have been study- ing under the names of equifinality, back-differentiation, restitution of the second order, and so on, and our harmonious- equipotential systems have figured most largely in processes of secondary form-regulations also. But even where that has not been the case, as in the analysis of the potencies of the germ in development proper, form-regulations of the other type have been our subject, regulations of the primary or immanent kind, the connection of normal morphogenetic events being regulatory in itself It was not the pheno- menon of organic regulation as such that afforded us the possibility of establishing our proof of the autonomy of morphogenesis : that possibility was afforded us by the analysis of the distribution of potencies; but upon this 165 166 SCIENCE AND PHILOSOPHY OF THE ORGANISM distribution regulation is based, and thus we may be said to have studied some types of regulation more or less indirectly when analysing potencies. It therefore seems to me that we shall have hopes of a successful issue to our inquiries, if we now, on passing to what is called the physiology of the vegetative functions, proceed to focus our attention on the concept of regulation as such. And that 'is what we shall do : on our way through the whole field of physiology, we shall always stop at any occurrence that has any sort of regulatory aspect, and shall always ask ourselves what this feature has to teach us. But let us first try to give a proper definition of our concept. We shall understand by "regulation" any occurrence or group of occurrences on a living organism which takes place after any disturbance of its organisation or normal functional state, and which leads to a reappearance of this organisation or this state, or at least to a certain approach thereto. Organisation is disturbed by any actual removal of parts ; the functional state may be altered by any change among the parts of the organism on the one hand, by any change of the conditions of the medium on the other ; for physiological functioning is in permanent interaction with the medium. It is a consequence of what we have said that any removal of parts also changes the functional state of the organism, but nevertheless organisation is more than a mere sum of reactions in functional life. All regulations of disturbances of organisation may be yjalled restitutions, while to regulations of functional disturbances we shall apply the name adaptations. It is with adaptations that we have to deal in the following. ADAPTATION 167 Let us begin our studies of adaptations in a field which may justly be called a connecting link between morphogenesis and physiology proper, not yet wholly separated from the science of the organic form, morphology. 1. Morphological Adaptation Morphological adaptation is a well-established fact, and I need only mention the striking differences between the land and water form of amphibious plants, or the differences between the same species of plants in the Alps and in the plains, or the very different aspect of the arms of an athlete and of an ascetic, to recall to your memory what is meant by this term. Morphological adaptation is no part of individual morphogenesis proper, but occurs at the end of it ; at least it never occurs previous to the full individual life of an organism, previous to its true functional life ; for it relates to the functions of the complete organism. THE LIMITS of THE CONCEPT OF ADAPTATION It is especially, though by no means exclusively, among plants that morphological adaptation assumes its most marked forms ; and this topic, indeed, may very easily be understood if we remember that plant-life is in the very closest permanent dependence on the medium, and that this medium is liable to many changes and variations of all kinds. In order to elucidate our problem, it therefore seems convenient to restrict our considerations for a while 168 ADAPTATION 169 to the study of plants. There exist very many external formative stimuli in the morphogenesis of vegetation : would it then be possible to regard every effect of such an external formative stimulus as a real morphological adaptation ? No ; for that would not meet the point. The general harmony of form is indeed concerned if gravity forces roots to shoot forth below at a spot where they can enter the ground, or if light induces branches and leaves to originate at places where they can obtain it for assimila- tion ; but gravity and light themselves are mere formative stimuli — of the localising type — in these instances, for they relate only to the individual production of form, not to the functioning of already existing form. We therefore are warned not to confuse the effects of formative stimuli from without with real adaptive effects until we have fully analysed the particular case. We have drawn a sharp line between causes and means of morphogenesis, applying the term " means " to those con- ditions of the morphogenetic process which relate neither to the specificity nor to the localisation of its constituents, though they are necessary for the accomplishment of the pro- cess in the most thorough manner. Would it be possible to connect our new concept of an adaptation with our well- established concept of a means of morphogenesis in such a way that we might speak of a morphological " adaptation " whenever any specific feature about morphogenesis proves to be immediately dependent for its success on some specific means, though it does not owe its localisation to that means as its " cause " ? It seems to me that such a view would also fall wide of the mark. It is well known, for instance, that the flowers of many plants never fully develop in the 170 SCIENCE AND PHILOSOPHY OP THE ORGANISM dark ; light is necessary for their morphogenesis. Is, there- fore, their growth in the presence of light to be called a morphological " adaptation " to light ? Certainly not : they simply cawmo^ originate without light, because they require it for some reason. It is precisely here that our conception of light as a " means " of morphogenesis is most fully justi- fied. There are many^ such cases; and there are stiU others of an apparently different type, but proving the same. All pathological forms produced in plants by animal parasites or by parasitic fungi could hardly be called adapta- tions, but must be attributed to some abnormality of means or of stimuli. It may be that the organism reacts as well as possible in these cases, and that if it reacted otherwise it would die — we know absolutely nothing about this ques- tion. But even then there would only be some sort of regulation in the process of pathological morphogenesis, but the process itself could hardly be called adaptive. So far we have only learned what is not to be regarded as morphological adaptation. No response to external forma- tive stimuli is in itself an example of adaptation, nor are processes dependent for their existence on any kind of condition or means to be called, simply because they are dependent on them, adaptations to those agents. What then, after all, is a morphological adaptation ? Let us remember what the word adaptation is really to mean in our discussions : a state of functioning is adapted — ' Klebs has suppressed the reproductive phase of organisation altogether, in fungi as well as in flowering plants, or has made it occur abnormally early, merely by changing the " external conditions " and by altering the " internal " ones correspondingly. There is hardly anything like an adaptation in these cases, which, by the way, offer certain difiieulties to analysis, as the boundaries between "cause" and "means" are not very sharp hero. ADAPTATION 171 a state of functioning must therefore have been disturbed ; but as functioning itself, at least in plants, certainly stands in close relations to the medium, it follows that all adapta- tions are in the last resort connected with those factors of the medium which affect functioning. In being correctives to the disturbances of functioning they become correctives to the disturbing factors themselves. 4 But again, the question seemS to arise whether these factors of the medium, when they provoke an adaptation by some change that is followed by functional disturbance, do so in the capacity of " causes " or of " means," and so it might seem that we have not gained very much so far by our analysis. The reproach, however, would not be quite justified, it seems to me : we indeed have gained a new sort of analytical concept, in the realm of causal concepts I in general, by clearly stating the point that adaptations are jrelated directly to functionality, and only indirectly, through functionality, to external changes. By the aid of this logical formulation we now are entitled to apply the term " cause," in our restricted sense of the word, to every change of the medium which is followed by any sort of adaptation in regard to itself. Our definition stated that a " cause " is any one of the sum of necessary factors from without that accounts either for the localisation or for the specification of the effect, and the definition holds very well in this case. Indeed, the specification of the effect is determined by the outside factor in every case of an adaptation to it, by the mere fact of its being a specific adaptation to this specific factor. We must not forget that in this chapter we are not studying real individual morphogenesis as the reahsation 172 SCIENCE AND PHILOSOPHY OF THE ORGANISM of what has been inherited, but that at present we regard morphogenesis proper as an accomplished fact. Morpho- genesis proper has laid the general lines of organisation ; and now adaptation during the functional life, so to speak, imposes a second kind of organisation upon the first. It is for that reason that the meaning of the word " cause " is now becoming a little different from what it was before. In order to study a little more in detail what has been discovered about morphological adaptation in animals and plants, let us separate our materials into two groups, one of them embracing adaptations with regard to functional changes from without, the other adaptations to those functional changes which come from the very nature of functioning. Almost all of our previous general con- siderations have applied to the former group, with which we shall now proceed to deal. ADAPTATIONS TO FUNCTIONAL CHANGES FROM WITHOUT^ The differences between plants grown in very dry air, very moist air, and water, respectively, are most distinctly seen in all the tissues that assist in what is called transpiration, that is, the exchange of water-vapour between the plant and the medium, but especially in the epidermis and the conductive fibres, both of which are much stronger in plants grown in the dry. Indeed, it seems from ex- periments that transpiration is the most essential factor to which " adaptation " occurs in amphibious plants, though • Compare Herbst, Biol. Gentralbl. 15, 1895 ; and Detto, Die Theorie der direkten Anpassung, Jena, 1904. A full account of the literature will be found in these papers. ADAPTATION 173 the changes of the mechanical conditions according to the medium also seem to have some sort of structural effect. If plants stand very deeply in water, the conditions of illumination, so important for assimilation in plants, may have been altered, and therefore much of the structural change can be attributed also to them. It is unimportant in our general question what is due to one of these factors and what to the other. That there is a real sort of adaptation cannot be doubtful; and the same is true, as experimental observations of the last few years have shown, with regard to the structural differences between so-called sun-leaves and shade-leaves of plants grown in the air : it has been actually shown here that the functional life of the former goes on better in the sun, of the latter better in the shade. It is very important to emphasise this point, as the adaptive character of all sorts of structural differences in plants dependent on light and on moisture has lately been denied, on the supposition that there is only a stopping of organogenesis in the case of the more simple, a continuance in the case of the more complicated modification, but nothing else. Indeed, all morphological adaptation has been conceived as only consisting in differences dependent upon the absence or the presence of necessary means or causes of development, and as offering no problem of its own. We have gained the right position from which to- oppose this argument, it seems to me, in our formula that all adaptations do relate Tiot directly to the agents of the medium, but to changes of functional states induced 6y those agents ; that adaptations only are " adaptations " by being correctives to the functional state. 174 SCIENCE AND PHILOSOPHY OF THE ORGANISM There simply is an " adaptation " of structure in such a sense in all the cases we have mentioned. We can say neither more nor less. Granted that one of the outside factors which comes into account is merely a necessary " means " : then why is the histological consequence of the presence of the means an actual adaptation to it as far as its relation to functioning is concerned — why is the consequence of its absence also an adaptation to this absence in its relation to functioning ? Why, to complete the series, is the degree of the consequence of its presence an adapta- tion to the degree of its presence ? All these relationships, which are so many facts, have been absolutely overlooked by those who have been pleased to deny morphological adaptation to functional changes from without. To do full justice to them we may speak of " primary " regulative adaptations in all the cases mentioned above, applying the word " primary," just as was done with regard to restitutions, to the fact that there is some sort of regulation in the normal connection of processes. We reserve the title of " secondary adaptations " for cases such as those described, for instance, by Vochting,^ where not merely one and the same tissue originates adaptively with regard to the degree of its normal functioning, but where * Vbchting (Jahrb. wiss. Bot. 34, 1899) forced the bulbs of plants to become parts of the stem, and parts of the stem to form bulbs ; in both cases the most characteiistic changes in histology could be observed, being in part adajitations, but in part restitutions of the proper type. (See also my Organische Regulationen, 1901, p. 84.) A true and simple instance of a "secondary adaptation" seems to be furnished in a case described by Boirivant. In Robinia all the leaflets of a leaf-stalk were cut off : the leaf- stalk itself then changed its structure in order to assist assimilation, and also formed real stomata. ADAPTATION 175 a profound disturbance of all functioning connections, due to the removal of portions of the organisation, is followed by histological changes at absolutely abnormal localities ; that is, where a real change of the hivd of functioning is the consequence of the adaptation. It, of course, will be found very difficult to discriminate such phenomena from real restitutions, though logically there exists a very sharp line between them. A few more concrete instances may now close this account of adaptation to functional changes coming from without. Though almost all the adaptive characters in the aquatic forms of amphibious plants represent a less complicated state of organisation than the corresponding structures in their terrestrial forms, and therefore have wrongly been regarded as simply due to a stopping of morphogenesis for want of necessary means, yet there are a few of them that are positive complications in comparison with the land-forms : the so-called aerenchyme, especially well developed in the water-form of Jussiaea is such an instance. This tissue stands in the direct service of respiration, which is more difficult to be accomplished under water than ordinarily, and represents a true adaptation to the altered function. Among animals there is only one well-studied instance of our first type of adaptive morphological characters. Salamandra atra, the blacl^ salamander, a species which only inhabits regions at least two thousand feet above sea-level, does not bring forth its young until metamorphosis has taken place. The larvae, however, may be removed from the mother's body at an earlier stage and forced to complete their development in water. Under these circumstances. 176 SCIENCE AND PHILOSOPHr OF THE ORGANISM as was shown in an excellent memoir by Kammerer,^ they will change the whole histological type of their gills and skin in order to meet the new functional conditions. The change of the conditions of functioning is very severe here, for whereas the gills had served for nutrition and respiration in the uterus — by a process of endosmosis — they now serve for respiration only, and, of course, are surrounded by quite an abnormal chemical medium. But all other cases of morphological adaptation among animals, and several in the vegetable kingdom too, belong to our second group of these phenomena, which in our analytical discussion we have called adaptations to functional changes that result from the very nature of functioning, and which we shall now call by their ordinary name, " functional adaptation." It was Eoux who first saw the importance of this kind of organic regulation and thought it well to give it a dis- . tinguishing name. By functioning the organisation of organic tissues becomes better adapted for functioning. These words describe better than any others what happens. It is well known that the muscles get stronger and stronger the more they are used, and that the same holds for glands, for connective tissue, etc. But in these cases only quantitative changes come into account. We meet with functional adaptations of a much more complicated and important ' Arch. Eniw. Mech. 17, 1904. ^ Eoux, Gesammelte Abhandlungen, vol. i. 1895 ; in particular, Der Kampf der Teile im Organismus, Leipzig, 1881. ADAPTATION 177 kind, when for instance, as shown by Babak,'' the intestine of tadpoles changes enormously in length and thickness according as they receive animal or vegetable food, being nearly twice as long in the second case. Besides this the so-called mechanical adaptations are of the greatest interest. It has long been known, especially from the discoveries of Schwendener, Julius Wolff, and Koux, that all tissues whose function it is to resist mechanical pressure or mechanical tension possess a minute histological structure specially suitable to their requirements. This is most markedly exhibited in the stem of plants, in the tail of the dolphin, in the arrangements of the lime lamellae in all bones of vertebrates. All these structures, indeed, are such as an engineer would have made them who knew the sort of mechanical conditions they would be called upon to encounter. Of course all these sorts of mechanically adapted structures are far from being "mechanically ex- plained," as the verbal expression might perhaps be taken to indicate, and as indeed has sometimes been the opinion of uncritical authors. The structures exist for mechanics, not hy it. And, on the other hand, all these structures, which we have called mechanically " adapted " ones, are far from being mechanical " adaptations," in our meaning of the word, simply because they are " adapted," Many of them indeed exist previous to any functioning, they are for the most part truly inherited, if for once we may make use of that ambiguous word. But, the merely descriptive facts of mechanical adapted- ^ Arch. Entw. Meek, 21, 1906. By a very detailed comparative study Babak was able to prove that it is the plant proteids to which the effect of vegetable food is chiefly due ; thus we have an adaptation to digestibility. Mechanical circumstances are only of secondary importance. (See also Yung.) 178 SCIENCE AND PHILOSOPHY OF THE ORGANISM ness having been ascertained, there have now been discovered real mechanical processes of adaptations also. They occur among the statical tissues of plants, though not in that very high degree which sometimes has been assumed to exist ; they also occur in a very high perfection in the connective tissue, in the muscles and in the bone tissue of vertebrates. Here indeed it has proved possible to change the specific structure of the tissue by changing the mechanical condi- tions which were to be withstood, and it is in cases of heal- ing of broken bones that these phenomena have acquired a very great importance, both theoretically and practically : the new joints also, which may arise by force of circumstances, correspond mechanically to their newly created mechanical function. So far a short review of the facts of " functionelle Anpassung." They seem to prove that there does exist a morphological adaptation to functional changes which result from the very nature of functioning. In fact, the actual state of all functioning tissue, the intensity of its state of existence, if you care to say so, may be said to be due to the functioning itself: the so-called atrophy by in- activity being only one extreme of a very long line of correspondences.' We now, of course, have to ask ourselves if any more intimate analysis of these facts is possible, and indeed we easily discover that here also, as in the first of our groups of morphological adaptations, there are always single definite agents of the medium, which might be called " causes " or " means " of the adaptive effects, the word " medium " being 1 Atrophy of muscles by inactivity is not to be confused with atrophy by cutting the motor nerve ; the latter is very much more complete. ADAPTATION 179 taken as embracing everything that is external to the reacting cells. But of course also here the demonstration of single formative agents does not detract in the least from the adaptive character of the reaction itself. So we may say, perhaps, that localised pressure is the formative stimulus for the secretion of skeleton substance at a particular point of the bone tissue, or of the fibres of the connective tissue ; the merely quantitative adaptations of muscles might even allow of a still more simple explanation.'^ But adaptations remain adaptations in spite of that ; even if they only deserve the name of " primary " regulations. THEORETICAL CONCLUSIONS We have stated in the analytical introduction to this chapter and elsewhere, that functional changes, which lead to morphological adaptations of both of our groups, may arise not only from changes of factors in the medium, but also from a removal of parts. As such removal is generally followed by restitution also, it is clear that restitutions and adaptations very often may go hand in hand, as is most strikingly shown in a fine series of experiments carried out by Vochting, which we have already alluded to. Here again I should like to lay the greatest stress upon the fact that, in spite of such actual connections, restitutions and adapta- tions always have been separated from another theoretically, and that the forms are never to be resolved into sums of the latter. Such a view has been advocated by some recent 1 Loeb has advocated the view that the ' ' adaptive " growth of working muscles is simply due to the presence of a greater number of molecules in their protoplasm, muscular activity being generated by a process of chemical decomposition. 180 SCIENCE AND PHILOSOPHY OF THE OBGANISM authors, especially by Klebs, Holmes, and Child : ^ it is refuted I think by the simple fact that the first phase of every process of restitution, be it regeneration proper or be it a sort of harmonious differentiation, goes on without functionmg at all, and only for future functioning.^ And there has been advocated still another view in order to amplify the sphere of adaptation : all individual morphogenesis, not only restitution, is adaptation, it has been said. In its strictest form such an opinion of course would simply be nonsense : even specific adaptive structures, such as those of bones, we have seen to originate in ontogeny previous to all specific functions, though for the help of them, to say nothing of the processes of the mere outlining of organisation during cleavage and gastrulation. But they are " inherited " adaptations, it has been answered to such objections. To this remark we shall reply in another chapter. It is enough to state at present that there is a certain kind of, so to speak, architectonic morphogenesis, both typical and restitutive, previous to specific functioning altogether. If now we try to resume the most general results from the whole field of morphological adaptations, with the special purpose of obtaining new material for our further ^ What has been really ■proved, to exist by the very careful studies carried out by Child, is only certain cases of functional adaptation to mechanical conditions of the strictest kind, and relating to the general mobility only, but nothing more ; such adaptations can be said to accompany restitution. See, for instance, Jouni. exp. Zool. 3, 1906, where Child has given a summary of his theory. '^ Even in Voohting's experiments (see page 174, note 1), in which adapta- tions are mixed with true restitutions in the closest possible manner, a few phenomena of the latter type could most clearly be separated. The stimulus. which called them forth must have been one of the hypothetic sort alluded to in a former chapter (see page 113). The best instances of true restitutions were offered in those cases, where, after the removal of all the bulbs, typical starch-storing cells were formed without the presence of any starch. ADAPTATION 181 philosophical analysis, we have reluctantly to confess that, at present at least, it does not seem possible to gather any new real proof of life-autonomy, of "vitalism," from these facts, though of course also no proof against it. We have stated that there is in every case of both our types of adaptive events a correspondence between the degree of the factor to which adaptation occurs, and the degree of the adaptive effect. We here may speak of an answering between cause and effect with regard to adapta- tion, and so perhaps it may seem as if the concept of an " answering reaction " (" Antwortsreaktion "), which was introduced into science by Goltz^ and which is to play a great part in our discussions of next summer, may come into account : but in our present cases " answering " only exists between a simple cause and a simple effect and relates almost only to quantity and locality. There is therefore lacking the most important feature, which, as will be seen, would have made the new concept of value. We only, I believe, can state the fact that there are relations between morphogenetic causes and effects which are adaptations, that functional disturbances or changes are followed by single histogenetic reactions from the organism, which are compensations of its disturbed or changed functional state. We are speaking of facts here, of very strange ones indeed. But I feel unable to formulate a real proof against all sorts of mechanism out of these facts : there might be a machine, to which all is due in a pre- established way. Of course we should hardly regard such a machine as very probable, after we have seen that it ■ 1 Beitrage zur Lehre von den Functionen der Nermncenlren des Frosches, Berlin, 1869. 182 SCIENCE AND PHILOSOPHY OF THE ORGANISM cannot exist in other fields of morphogenesis. But we are searching for a new and independent proof; and that is indeed not to be found here/ At present it must be taken as one of the funda- mental facts of the organogenetic harmony, that the cells of functioning tissues do possess the faculty of reacting to factors which have changed the state of functioning, in a way which normalises this state histologically. And it is a fact also that even cells, which are not yet functioning but are in the so-called embryonic or indifferent condition contributing to the physiological completion of the tissue, react to factors embracing new functional conditions of the whole in a manner which leads to an adaptation of that whole to those conditions. , This is a very important point in almost all morphologi- cal adaptation, whether corresponding to functional changes from without or resulting from the very nature of function- ing. In fact, such cells as have already finished their histogenesis are, as a rule, only capable of changing their size adaptively, but are not able to divide into daughter- cells or to change their histological qualities fundamentally ; in technical terms, they can only assist " hypertrophy " but not " hyperplasia." Any adaptive change of a tissue there- fore, that implies an increase in the number of cellular elements or a real process of histogenesis, has to start from "indifferent" cells, that is to say, cells that are not yet functioning in the form that is typical of the tissue in question ; and, strange to say, these " embryonic " cells — ' The " secondary adaptations " observed by Vbchting are too complicated and too much raingled with restitutions to allow any deiinite analysis of the fact of the " secondary adaptation " as such. ADAPTATION 183 i.e. the " cambium " in higher plants and many kinds of cells in animals — can do what the functional state requires. It is to be hoped that future investigations will lay a greater stress upon this very important feature of all adaptation. 2. Physiological Adaptation ^ It is but a step from morphological adaptations to adaptations in physiology proper. The only difference between regulations of the first type and those which occur in mere functioning is, that the resulting products of the regulation are of definite shape and therefore distinctly visible in the first case, while they are not distinctly visible as formed materials but are merely marked by changes in chemical or physical composition in the latter. Metabolism, it must never be forgotten, is the general scheme within which all the processes of life in a given living organism go on ; but metabolism means nothing else, at least if we use the word in its descriptive and unpretentious meaning, than change in the physical or chemical characteristics of the single constituents of that organism. In saying this, we affirm nothing about the physical or chemical nature of the actual processes leading to those physical or chemical characteristics, and by no means ^ General literature : Frohlioh, Das naiurliche ZwedcinSssiglceitsprincip ill seiner Bedeutung fur Kranhheit mid Heilung, 1894. Driesch, Die organiscJien Megulatimwn, 1901. A. Tschermak, "Das Anpassungsproblem in