Popular Science Monthly/Volume 69/July 1906/The Relations of Embryology to Medical Progress
THE
POPULAR SCIENCE
MONTHLY
JULY, 1906
| THE RELATIONS OF EMBRYOLOGY TO MEDICAL PROGRESS[1] |
By CHARLES SEDGWICK MINOT, S.B., S.D., LL.D., D.Sc.,
JAMES STILLMAN PROFESSOR OF COMPARATIVE ANATOMY IN THE HARVARD MEDICAL SCHOOL, BOSTON
EMBRYOLOGY is the most complex subject in the domain of science. Living beings are the most complex objects which nature offers us for study, and of this great class the higher animals exceed all others in complexity. The anatomist who studies the structure of the adult has a finished apparatus to investigate; a machine which has been perfected, in which, to be sure, nature may still make repairs, but in the pattern of which she makes no radical changes. The physiologist deals with this machine at work. The embryologist, on the contrary, has for his theme the history of this machine and of its gradual production from a single cell and the progeny thereof. During the period of development the machine at every stage is a different machine from that which it was in the stage before and which it will become in the stage after, and yet in every stage it is actively at work performing its proper physiological functions. We have to deal not with a condition, but with a series of conditions, each of which is at once the consequence of that which went before and the cause of that which is to follow. The final problem of embryology is to determine the origin and cause of the structure of the living body, and incidentally it has to deal with the associated problems of teratology, growth, heredity and sex.
We acknowledge the immensity of the questions for which embryological science must seek answers, but it is far from my intention to imply that embryologists therefore are an order of scientists superior to all others. Embryology is so vast and varied that it offers problems adapted, I might almost say, to every size of mind, and persons of moderate capacity, as well as those of the highest gifts of genius, can find adequate opportunity to gratify successfully in the field of embryology any demon of research which may possess them.
Let us first consider some of the conditions upon which the progress of embryological science has depended. Of course the first and all-essential thing is the amount and quality of human ability which has gone into it. This is true of every science, as goes without saying. It may, however, be interesting to pause a moment, since contemporary events are directing so much of the interest of the world towards Russia, in order to point out that modern scientific embryology had its birth in that country, for the first step was the publication of the articles by C. F. Wolff on the 'Theory of Generation and the Development of the Intestine in the Chick'; and the second and more important step was the publication of the great work of Carl Ernst von Baer, which may be said without exaggeration to have created by itself a new science. Von Baer's treatise on the 'Entwicke-lungsgeschichte der Thiere' is one of the greatest works in the whole history of biological science, and established the author's reputation as a genius of research. By the aid of improved methods a tyro in embryology may now verify von Baer's discoveries, but there has been no one since von Baer, who could have approached with his scientific resources the magnitude of his achievement. Let us then honor his memory. Although Wolff and von Baer, both, were Russian subjects, they were of German descent, and we find indeed that throughout the greater part of the last century the advance of embryology was due chiefly to German investigations.
How recent this knowledge is we are apt to forget. From 1800 to 1840 the seminal animalcules were universally regarded as parasites. The fact that they are normal products of the testis and the true male sexual elements was first discovered in 1841 by the Swiss anatomist von Kölliker, who was a leader in microscopical research for sixty-five years, and whose death occurred last year. Of Kölliker it may be asserted safely that he knew more by direct personal observation of the microscopical structure of animals than any one else who has ever lived. He was much honored in Europe. The last time I met him was at the International Zoological Congress at Berne, in 1894. It was most impressive to see all the members of the congress spontaneously rise to their feet when the handsome old man unexpectedly entered the meeting. The fact that the spermatozoon enters the ovum and produces the so-called male pronucleus, the union of which with the female pronucleus completes the act of fertilization, was finally demonstrated only in 1875 by Oscar Hertwig. These two additions to our knowledge are so fundamental that we have become rapidly familiar with them, and easily forget how recently they have been added to our science. Many other illustrations of the newness of embryological knowledge might be given.
The methods used by von Baer and by all his successors in embryology down to 1860, or even later, were exceedingly simple. They worked almost entirely with fresh material, hand lenses, and sometimes with acetic acid to render the objects a little more transparent. The embryologists of that period were few in number, but they made many fundamental discoveries. I fancy that if the researchlings of our present luxuriously installed laboratories were put back into that time of lean resources, their publications would cease. As you know, the fundamental procedures in modern microscopical technique are the making of sections and the staining of them. The introduction of section cutting came about so gradually that its history seems to be lost to us. Many persons in the middle of the last century appear to have made sections by hand of various tissues. This was especially a practise among botanists. At first only fresh material was used, but it was learned that preserved material, especially that which had been properly hardened in alcohol, could be cut to greater advantage, and gradually the process of 'hardening' before cutting became more and more common. So long as the cutting was done only by hand with that favorite unsuitable instrument of old days, the razor, no very fine sections were possible, save occasionally by some person of exceptional dexterity. The first microtome, so far as known to me, was that devised by Professor His and employed by him, about 1866,[2] for making serial sections of chicken embryos. Since then many inventors have contributed to the perfection of the instrument, and we now have the rather complex but very accurate and convenient automatic microtomes which are in such general use.
With the aid of microtomes, we can make perfect series of sections, and by mounting the entire series from a given object, it becomes possible to examine every part of it under the microscope. In the case of embryos serial sections are invaluable. We have been forming in my laboratory at the Harvard Medical School a collection of such series of sections of vertebrate embryos. The total number of series at the present writing is 1,106, of which forty-nine are from human embryos. The total number of sections is probably over 100,000. This collection has already served as the basis of forty-two embryological investigations and we trust that it will serve in the future for very many more. So far as I know the collection is unique in plan and extent. As soon as we are established in our superb new laboratory, into which we are about to move, we shall be glad to have you inspect our embryological museum. We value especially a fine human embryo which is in the youngest stage yet recorded by actual observation in America.
The history of staining is more definite. I have had the pleasure of hearing from Professor Leo Gerlach, Sr., himself the story of the introduction of coloring matters in microscopical technique. He was interested about 1857 in studying blood vessels, and wishing to trace them out by injection, applied to a local apothecary at Erlangen for a suggestion of some red coloring matter, and the apothecary proposed that he should use an ammoniacal solution of carmine, the pigment extracted from the cochineal insect. Professor Gerlach employed it, and in examining some of his preparations later found that the color had soaked through the blood vessels into the surrounding tissues, and had stained them so that they were much more distinct, and he also noticed that the stain had especially affected the nuclei. He at once recognized the importance of this coloration as a means of rendering more clear the character of cells and tissues, and to him we owe the introduction of carmine into histological technique, and it remains to-day the most important and valuable coloring agent for our purposes which we possess. The introduction of carmine marks an epoch in microscopical science. It was most fortunate that the accidental observation of the action of carmine was made by a man so thoroughly able to appreciate its great value. Since then many other staining reagents have been introduced by many different persons. I need not pause now to enumerate them, or hold up your attention in order to give a list of names and dates such as could be easily compiled. I will only recall to your minds that the introduction of chloride of gold, of osmic acid, of the aniline dyes, and of the Golgi method have each of them represented the beginning of a fresh advance, which without these added technical resources would undoubtedly have remained impossible for us.
Another class of methods are those by which we reconstruct from serial sections the anatomy of an embryo or an embryonic organ. To the late Professor His, of Leipzig, we owe practically the first recognition of the value and possibility of such reconstruction. He employed chiefly the method of drawing, by which many figures have been made. The process is laborious, for each section must be drawn and then the position of the parts measured and plotted off—but the labor is worth while as it results in accurate representations of the anatomy of parts which can not be dissected. I am in hopes that in our new Harvard laboratories that this method of reconstruction from sections will be applied to the adult, for I am sure that we can obtain by it representations of adult relations far superior to anything we now possess.
Doubtless to many of you the method of reconstruction from sections in wax models is also well known and its value appreciated as a means of giving us perfectly clear plastic conceptions of the arrangement of parts. The very ingenious wax-plate method was invented by the late Gustav Born, who conceived the happy idea of making wax models of single sections or parts of sections equally magnified in all three dimensions. It is only necessary to pile such wax plates in order, one on top of another, to get a correct model of the whole object. The method is very widely used and in my laboratory, for example, has been employed recently by Dr. John L. Bremer to model the anatomy of a human embryo and by Dr. John Warren to model the developing brain. Such models are truly revelations to one who has studied sections only.
This is not a suitable occasion to review the history of the technical progress of embryological science. I wish only to so far indicate it as may suffice to direct your attention to the dominant importance of method in scientific problems. It seems to me that the greater part of the advance which is made from time to time in modern science is the direct result of either an improvement of old methods or the invention of novel methods. I can see in my own science clearly that this has been the case, and from what I learn about other sciences, infer that it is equally true of them. Viewed from the psychological standpoint, the vast majority of methods have a common purpose, namely, to present the results to the eye, so that we can see what the facts are with which we wish to become acquainted. When we make sections, it is in order to see the cells in their natural relative positions, and with all their various characteristics. When we stain sections, it is in order to make things visible which were before indistinct or perhaps invisible. When we make reconstruction or models it is to furnish again an image to the eye which we can not get from the actual object itself. The eye, indeed, is the chief agent in collecting information for us from the objects by which we are surrounded. It is because they help out the eye that the microscope and telescope have counted for so much. The eye is almost the monarch of research, and reigns even more supremely over our relations with our surroundings than does the ear over our intercourse with our fellow men.
The results of embryology for a long time remained rather meager, and when as a young man I went to pursue some of my scientific studies in Germany, the principal text-book of the science was a modest octavo volume by Professor Kölliker. Since that time (1873) the activity in this domain has increased by leaps, and is now enormous, and the latest handbook of the science, that which is in course of publication at this time under the editorship of Professor Hertwig of Berlin, will comprise eight volumes, each of which promises to exceed a thousand pages when complete; yet the work is only a digest of the researches upon the development of vertebrates and does not deal with the invertebrates at all. This bald statement may give you some impression of the present vast extent of the science.
What I wish to attempt on this occasion is to select out of this huge accumulation of discovery some illustrations of the way in which embryology has made contributions of practical value to medical science and medical practitioners. I have on another occasion spoken of the relations of science and the scientific spirit to medical education and practise, and on yet another occasion have discussed embryology as a basis of pathology, so that it seems unnecessary to deal again and before you with these more general aspects of the situation, but I shall ask your attention rather to certain more detailed and specific examples.
Every science has its larger aims and purposes. Those of embryology may be classed not unnaturally under five heads. First, I shall group together those researches that refer to the general topic of generation, the production of the new being, the conditions under which it first develops, including, of course, for man especially, the relations of the fruit to the womb. Under this head are comprised phenomena of impregnation, problems of heredity, the origin of sex, the conditions of gestation and pregnancy, and the physiological causes of birth.
Secondly, under the head of cytomorphosis we can put all the work which has been accomplished in tracing out the development of cells. The conception of cytomorphosis is one which has only recently become clear to us, but it is one of the most fundamental notions of biological science, and one which every student of morphology, pathology or physiology must clearly grasp and keep constantly in mind. Cytomorphosis has been defined as the comprehensive designation for all the structural modifications which cells or successive generations of cells may undergo from the earliest undifferentiated stage to their final destruction. It starts with the history of the undifferentiated cell, considers all phases of differentiation, and in those cases where the process goes to its end, it follows out the final steps of the degeneration and destruction of the cell. The law of cytomorphosis is indeed the chief foundation of all anatomical and pathological science. The possibilities of modification within a cell are determined by the stage of cytomorphosis which is reached, and as it goes forward from stage to stage the possibilities of further change become more and more limited in accordance with the recently established law of genetic restriction. I have expounded my views on the importance of the laws of cytomorphosis for pathology in the Middleton-Goldsmith lecture for 1901 and need not now dwell longer upon the subject.
Third, I should class the studies which refer to the germ layers, those laminæ of cells which, as it were, occupy an intermediate place between the single cell and the organ. They correspond to the first orderly arrangement of cells which we have in the organism, and from this tripartite arrangement the organs are fashioned. Of course, the fundamental morphological fact in regard even to the higher animals is the cell, but next to that we may place the existence of the germ layers, the complicated interrelations of which dominate the entire history of every individual alike in health and in disease. The comprehension of the morphological importance of the germ layers and their relation to the production of tissues and organs and abnormal growths of all kinds is absolutely indispensable to every medical man who wishes to have an intelligent mastery of his subject.
Fourth, we may place the strictly anatomical aspects of embryology, which give the morphological interpretations of organs and the explanation, as you know, of many anomalies of adult structure. The anatomy of the adult offers to us many riddles, for numerous are the arrangements and characteristics of the body which we can not understand or explain from the study of the adult alone. The language of adult structure we often can not read unless we have first studied the Rosetta Stone of embryology which affords us the key of translation. As a teacher in a medical school, I have again and again been profoundly impressed with the value of embryology to the student of anatomy. Things which are obscure are illuminated by a knowledge of the developmental changes. In an embryo we encounter simplified conditions; secondary modifications coming in later in the course of development not only add to the complication of parts, but often also produce so great changes as to mask the fundamental and original relations. What student of adult anatomy alone could possibly discover that the thymus gland is a modification of the lining epithelium of a gill pouch which exists as a pouch in the embryo and is homologous with the gill pouch of a fish? Or what pure anatomist could ever have discovered that the spermiduct is the modified duct of a kidney present in the embryo, but which in the adult has as such totally vanished? If we pass from mere human anatomy to the larger and more scientific subject of comparative anatomy, we feel again the value of embryology, which establishes the real homologies of structure, proving exact homologies from the study of the early stages of parts, which in different types become so unlike that their fundamental identity of origin is completely hidden. For example, without embryology we never should have known that the little bone of the ear which we call the malleus is homologous with the upper part of the lower jaw of a cartilaginous fish. Indeed, the stories which embryology has to tell are the most romantic known to us, and the wildest imaginative creations of Scott or Dumas are less startling than the innumerable and almost incredible shiftings of role and changes of character which embryology has to entertain us with in her histories. I have been tempted to exclaim sometimes while pursuing my science that in embryology only the unexpected happens.
Fifth and last, I should like to gather under the head of morphophysics a number of researches, nearly all of which are very recent, and which tackle the doctrine of the chemical and physical causes of development. These researches have been largely experimental in character, and though we are only at the beginning of this sort of work, yet the results already obtained are of the highest value and make us hope for far greater results to come.
There should be added logically a sixth heading for the physiology of the embryo, but so little has been done and so little is doing in this part of biology that only in the future can this logically correct sixth division correspond to a field of active research. Here poverty of achievement makes further present consideration by us superfluous.
It is unnecessary to argue in order to prove to you that the study of generation is of importance to the medical man. The results which embryologists have already offered in solving some of the problems of generation form part of the stock in trade of every practitioner, for every one must know something of the uterus and placenta, must know that there is no communication between the fœtal and maternal circulation—no passage of the blood from the mother to that of the child: that there is no machinery for the making of so-called maternal impressions; that conception depends primarily upon the fusion of two living elements, the ovum and spermatazoon, which arise as living and integral parts of the parental bodies, and must know thus that there is a continuity of life, an earthly immortality, and that from generation to generation life is uninterrupted. All these notions and many others derived from embryology are now-a-days part and parcel of every physician's information, and it is hard to realize that a short time ago many of these facts were unknown to us. I believe that in the course of the next few years many new discoveries concerning generation will be made which will in their turn become familiar to all. I expect especially in regard to the subject of heredity a great increase in our knowledge, because the subject has attracted many investigators and some notable results have already been achieved. I may instance the history of the germ cells in which I have been especially interested. Professor Moritz Nussbaum on the basis of certain observations which he had made, put forward in 1880 the theory of germinal continuity. He pointed out that there is noteworthy evidence in the development of various animals tending to show that the germinal cells from which the sexual products arise are separated off very early from the other cells of the embryo and undergo very little alteration until the time comes for them to be transformed into sexual elements, male or female, as the case may be. Dr. F. A. Woods, working in my laboratory upon the embryos of dog-fish brought the first conclusive demonstration that Nussbaum's theory is true for a vertebrate. He found that the germ cells are set apart, have a distinct history of their own throughout the embryonic period and do not contribute in any way to the formation of any of the organs of the body. Since then Mr. B. M. Allen has discovered that the history of the germ-cells in the turtle is strikingly similar, and Dr. Woods is now engaged in tracing out the history in birds. Every one present will, of course, immediately recognize the great importance of a discovery which tends to show that there is a permanent distinction between the reproductive cells and the somatic cells which belong to the body and do not serve for reproduction.
Concerning cytomorphosis I need not add anything to what has been said concerning its general value in pathological study, but I should like to refer briefly to the good results which we may anticipate from direct application of the notions supplied by embryologists to the investigations which are yet to be made upon what we may call the morphological diseases, in distinction to those which are of parasitic origin. Morphological diseases arise through intrinsic causes, abnormal conditions due to the body itself and its reactions. Parasitic diseases have extrinsic causes. The dramatic—I might almost say melodramatic—growth of bacteriology and the kindred sciences has caused us to give most of our attention to diseases of the infectious type caused by some vegetable or animal parasite. This tendency is to be so far regretted that it has rendered investigation one-sided and lured it away from the class of diseases which may be attributed to pathological cytomorphosis. In regard to these the fundamental problem is identical for the pathologist and embryologist. It is the question of what and how the change in the structure of the single cell may be. Here is a central problem about which a vast number of lesser problems revolve like satellites. In the solution of this and of allied problems our greatest hopes for the future progress of medicine seem to lie. If we can find out what are the conditions which cause a cell to change its structure and advance in its cytomorphosis, we may hope that that discovery will include the explanation of why certain cells develop abnormally and become, as we commonly say, pathological, and we are to have precise knowledge of the cytomorphic causes we may dare, even now, to hope that we shall learn to regulate them, and that some, at least, of the diseases which are now beyond our reach will come under our control. It was not long ago that the idea of conquering diseases like malaria, yellow-fever, diphtheria and tuberculosis seemed a mere dream, a beautiful dream, yet control of them is now a reality, and is becoming almost daily more assured, complete and beneficent. So too in regard to the strictly morphological diseases, knowledge may bring mastery; and even sclerosis, that disease from which we are all assumed to be suffering in varying degrees, may, ere long, find itself subject to man.
Of the services which embryology has rendered to medical science within the last twenty-five years, the best known and probably the most important, certainly the most spectacular and unforeseen, is the revelation of the structure of the nervous system and of the relation of the nerve cells to one another. This wonderful achievement has been due chiefly to the introduction of a single new method, named after its inventor Golgi, one of those brilliant modern men who prove that genius is still the gift of the Italian race. He was born at Corteno on the ninth of July, 1843. The method was first described in 1875 in an article on the fine structure of the olfactory bulbs. The method was so radically different from anything known at that time that it was treated with scornful incredulity, and no attention was paid to the new invention which was destined to revolutionize our knowledge until it was introduced in Germany by Professor Kölliker in 1887. This marvelous method has been found to work best with embryos and has enabled us to trace out the form, including their ramifications, of the nerve cells and neuroglia cells of the brain and spinal cord throughout their whole period of development. As you know, all our contemporary teaching in regard to the structure and functions of the central nervous system, our conceptions of the nervous mechanism within the central nervous system and in the ganglia, are based upon the results obtained through the application of Golgi's method by embryologists. It is pleasant to note that in 1903 the completion of twenty-five years of teaching, and, by a happy coincidence, the anniversary of his silver wedding, were celebrated by Professor Golgi's pupils by the publication of his complete works, 'Opera Omnia,' in three magnificent quarto volumes. Copies of this publication ought to be in every pathological and histological laboratory in the world. Indeed, every text-book of anatomy, embryology or pathology published now-a-days is a memorial of Professor Golgi, for they are all abundantly supplied with figures of Golgi preparations. We may see in this history an illustration both of the value of the embryological data and also of the almost" creative power of a new method.
Degeneration has long been regarded as essentially a pathological process. This is the view which we have inherited. Nevertheless it is incorrect, as has been demonstrated by the more exact study of normal cytomorphosis during recent years. We now know that degeneration is to be looked upon as a normal end to a complete cytomorphic cycle. Instances of normal degeneration have long been familiar to us. Our mistake has been in overlooking their interpretation, their significance as part of the normal life. Thus the horny layer of the skin is made up of degenerated cells. Cartilage when it is replaced by bone undergoes a normal degeneration. In short, we must regard pathological degeneration very much as we regard those plants which we call weeds, things which are growing from our human point of view at the wrong time and in the wrong place, but which are not of themselves wrong or diseased, though they become so in man's nomenclature by their mode of occurrence. This broader conception of degeneration affords a new foundation for further investigation, and by the hearty cooperation of the embryologist and the pathologist we may expect new enlightenment.
The fourth head under which we classed the work of embryologist corresponded to the field of anatomical research. We all know that the embryological explanation of the anatomical disposition in the adult is a real and clarifying explanation. Certainly no teacher of anatomy to-day, competent to his work, will undertake to teach the structure of the brain, of the urogenital system or of the heart, except on an embryological basis. But there are a great many other anatomical conceptions which may best be made clear if we start with an examination of the conditions in the embryo. My experience as a teacher has afforded me many examples of this. Let me mention a few. The arrangement of the great cephalic nerves is a subject of peculiar difficulty to the student, but by the examination of a few properly chosen sections through the head of mammalian embryos all the essential topographical relations can be made easily understandable, and these essential relations are never obliterated by any further development. The disposition of the peritoneum is one of the greatest bugbears to the first-year medical student. But let him study the peritoneum in its relation to the viscera in the young embryo and he easily overcomes his difficulties and gets a clear and correct conception of the topographical relations of the peritoneal membrane and is able thereafter to comprehend the secondary modifications by which the adult topography is so much complicated. So too in regard to the thorax, a few sections from embryos give definite and exact conceptions of the fundamental relations of the heart and lungs, the mediastinum, and of the pleural and pericardial membranes. A good student may obtain from such a section a visual image which he will carry with him throughout life and which will always serve to make clear in his mind all these anatomical relations. One more similar instance may suffice. Students are always perplexed by the nature and mutual connections of the three membranes of the spinal cord and brain. Here also experience convinces us that sections of embryos reveal the facts so perfectly that they are readily comprehended and not easily forgotten. But I think I need not argue further to convince you that embryology as an aid to anatomical study is of incalculable value, and ought, if we are to do our anatomical teaching conscientiously, to be included in every medical curriculum.
Not infrequently the study of embryos establishes entirely new anatomical conceptions. An instance of this is offered by the study of blood vessels. We have learned in recent years that in addition to the long recognized arteries, veins and capillaries, there is another class of blood vessels of great importance. These vessels are called sinusoids and to a certain extent resemble capillaries, but their development and their relation to the parts of the organs in which they occur are entirely different from those of true capillaries. A sinusoid is developed by the subdivision of a single large vessel. It consists of endothelium, but that endothelium rests directly, or almost directly, upon the cells of the organ in which this type of vessel occurs. Capillaries, on the other hand, are developed as small buds from preexisting vessels and are always found in connective tissue. The most important organ in which sinusoids occur is the liver, and the peculiar circulatory arrangements in that organ, which have so long seemed singular and puzzling, have become comprehensible, and have acquired greater significance since the conception 'sinusoid' was established. This newly formed conception has unlocked the mystery of the portal circulation, and has explained the supply of venous blood to the liver. A morphological explanation of the portal vein had previously remained impossible.
To the fact that embryology explains many anomalies of the adult structure, we have already referred. Let us leave out of consideration the true monstrosities and confine our attention for the present to the anomalies, which are due to arrest of development. These are comparatively frequent, and many of them are so definite we may fairly call them typical. Such, for instance, is the preservation in the adult of the foramen ovale between the auricles of the heart, or of the open ductus arteriosus by which blood of the pulmonary and body circulation may mingle. In case of the veins also an arrangement of vessels is often found in the adult which is due to the persistence of a truly embryonic condition. The urogenital system seems to be peculiarly subject to arrests of development. When it starts the rudiments for both sexes are complete and the two sexes become differentiated largely by the obliteration in the individual of one sex of those structures which are characteristic of the other, but not infrequently it happens that this law of suppression is disturbed, and we then get very interesting and significant anomalies with which the physician often has practically to deal. Such cases do not produce a true hermaphroditism. That is a condition which apparently may occur in the human species, but is of the utmost rarity. Among other of the most frequent and familiar illustrations of arrested development I will mention cleft palate and hair lip. It is quite unnecessary to prolong this list, for it is evident that the anomalies we are considering are of a definite prescribed nature. They are all of practical importance to the physician, and unless he knows something of embryology he can not know what these probable anomalies are. If he does know something of embryology he can understand much of what may be expected in this class of variations of structure.
We will turn now to the fifth and last of our headings, that of morpho-physics. It is only of recent years that methods of experimentation, as distinguished from methods of observation only, have been applied to embryological problems. Naturally under the circumstances many crude experiments have been undertaken, many of doubtful validity; but there have also been many others, soundly planned, rightly executed and fruitful in results. Already the new conclusions constitute an increment both large and precious to our stock of embryological knowledge. One important class of these experiments has been based upon the discovery of the possibility of grafting parts of amphibian embryos on to one another; or to get two large pieces of two distinct embryos, or even two halves of two embryos, to grow together. The grafting experiments which have already been made are very numerous. Let me present one or two examples of the sort of results that these experiments yield. If the halves of two species of frog in a very early stage are grafted together, they will unite perfectly, but it is found that the epidermis of the species which forms the anterior half of the graft will spread to a certain extent over the posterior half, thus showing that the skin can actually crawl over the underlying tissues. It is probable, indeed, that the migration of epithelial cells along the surfaces upon which they rest is a very general phenomenon, and plays a very important part in the animal economy. In another series of experiments the embryonic optic vesicle has been removed and grafted on to a new part of the larva. Where the optic vesicle comes in contact with the epidermis it causes the epidermis to form a typical lens for the eye. Thus it is proved that the formation of the lens is not a specific function of that part of the epidermis from which it is normally produced, but is a potential function of the entire embryonic epidermis which may be called forth into activity by contact with the growing optic vesicle. I believe that we have in this an illustration of one of the fundamental principles of the establishment of structure and that much depends upon the interaction and mutual stimulation of parts.
Another class of experiments has been conducted by those who have been somewhat jocosely named the 'egg shakers.' An egg during an early stage of segmentation is divided artificially into its natural segments, or into groups of such segments, as the case may be. In many cases this division can be accomplished by shaking the eggs somewhat violently so as to break the segmentation spheres apart; hence the name above quoted. Now it has been demonstrated that in some cases fragments of a single egg will develop into an embryo perfect apparently in structure, though only of say half the normal size, whereas in other cases half an egg will develop only into half an embryo. Investigators are still busy studying out these results, the final interpretation of which has as yet by no means been reached. The experiments have opened to us a new realm of inquiry full of astonishing surprises.
Experiments on artificial parthenogenesis have been much written about in the daily press, and many absurd things concerning this topic have been printed in the newspapers. Ordinarily the ovum requires to be fertilized in order to develop, but it has long been known that certain ova, of bees, of plant lice, of some Crustacea and of other animals will develop without being fertilized. To this process the term parthenogenesis has been applied. Artificial parthenogenesis designates the development of unfertilized ova which normally would not develop at all and which are stimulated to development by placing them under artificial chemical conditions. Doubtless many of you have seen in the newspapers these experiments referred to as if they gave the actual creation of life. Of course that is nonsense. The life is there in the ovum. What artificial parthenogenesis accomplishes is to supply a stimulus, chemical in nature and capable of replacing the fertilization by the spermatozoon, which would otherwise be necessary. The possibility of artificial parthenogenesis was first partially demonstrated by Richard Hertwig, but has been perhaps more studied by Professor Loeb, now at the University of California, than by any one else. Hertwig produced artificially only a development of very limited degree, but Loeb by treating the eggs of a sea-urchin for about two hours with a weak solution of magnesium chloride succeeded in 1899 in producing larval sea-urchins (so-called plutei) from unfertilized ova. He concludes from this that fertilization is a chemical process, and that it is distinct and separate from hereditary transmission. No words of mine are needed to emphasize the importance of such investigations, for they are basic.
A line of work combining experimental and observational methods in which I have been especially interested deals with the problem of growth. It can be shown statistically that the growth of the embryo in early stages goes on at an enormous rate, and also that during the period of fœtal development that rate is constantly declining, so that something over 98 per cent, of the growth power is lost by the time of birth. After birth decline in the growth power continues, but gradually the decline becomes slower and slower, so that though growth is slight in rate, the growth power is long continued. A study of the condition of cells while this decline of the growth power is going on reveals to us that while the growth power is rapid the nucleus of the cell is active and well developed, and that the protoplasm of the cell is but slightly developed. As the proportion of protoplasm in the cells increases the power of growth diminishes, and as differentiation of protoplasm goes on the power of growth diminishes. I consider it probable that the growth and differentiation of protoplasm is the direct cause of the diminution of the growth power. The observations on growth bring out clearly to our minds the conception that the decline is by far the most rapid in the very early periods of embryonic development or, better expressed, that the rate of decline is at its maximum during the earliest periods. The older the individual becomes the less is the power of growth, but also the less rapid is the decline in that power. Thus we reach the paradoxical conception that the period of most rapid development is also the period of most rapid decline. This view, it seems to me, applies to all development, at least in the higher animals. As I have spoken on this subject more fully elsewhere, I will not pursue it longer now, but it seemed to me desirable to refer to it as an illustration of the far-reaching character and wide scope of embryological investigation, which inevitably allies itself with every other biological science.
It would be no difficult task to extend my discourse by multiplying illustrations of the beneficial influence of embryology upon other departments of medical science. It is one of the institutes of medicine—a part of the foundation of knowledge upon which medical practise is erected.
Embryology supplies facts which are directly valuable to the practitioner. It supplies explanations and interpretations of many anatomical structures and relations which would otherwise remain incomprehensible. It supplies the clues to many common and rare anomalies, and it supplies to pathology a series of fundamental conceptions, without which our actual present pathological knowledge could not have been upbuilt. These claims of embryology to recognition are very great, but nevertheless they do not include her greatest claim to a preeminent place among the medical sciences. That greatest claim is established in my opinion by the contributions of embryology to the solution of the problem of organic structure.
Structure is the only distinctive mark of living bodies, by which we know them to differ from inanimate objects. In the final discrimination between living and dead all other distinctions fail us or at best are utterly uncertain. In the higher forms we see differences of function always correlated with visible differences of structure. From such evidence, together with much other, we have established the hypothesis or theory—for at best it is only a theory—that all living functions are dependent upon organic structure. It is quaint, we may remark in passing, to read in recent essays by a learned German botanist the announcement of this theory, which the vast majority of biologists have long adopted, as a new foundation for biological philosophy, because he terms the ultimate unknown facts of structure 'Determinanten.' How often has science been impeded by the intrusion of a pedantry which mistakes the invention of a new term for the introduction of a new idea!
To find out what structure really is is the goal of all biological science. When we discover this secret, we may hope to discover also how structure functions and why it exists. The problem of structure—of organization—is double; there is first the question, what are the essential qualities of the structure of living matter as such, and there is, second, the question of the variations and specializations, which structure may undergo. With both of these questions embryology is confronted and both of them it is seeking to answer. The first is the riddle of life. Embryologists are bravely attacking it and have, I believe, already made a little real progress towards its solution. To them it presents itself as a series of queries concerning the germ-cells and the fertilized ovum. Searching analyses of the details with the highest powers of the microscope and the most refined technique coupled with experiments have indeed increased our knowledge of the organization of the germ cells. America, thanks to the brilliant work of E. B. Wilson and E. G. Conklin, and of their associates and followers, occupies a leading position in this difficult exploration. The importance of knowledge of the fundament of organic structure can hardly be exaggerated, and when it is obtained it will, I may prophecy, have profound far-reaching and enduring effects upon all medical science.
Even more intimately is embryology occupied with the second part of the problem of structure, namely, the question of differentiation, i. e., of the gradual production of the varied organization of the adult with almost innumerable unlike parts. To-day the central problem of biology is that of differentiation, and the main purpose of cotemporary embryological research is to attack that problem. The problem is three-fold, for we must learn what differentiation is, how it is produced, and why it is produced. Embryology might almost be termed the science of organic differentiation. Now all that you do, as practising physicians, is to deal with differentiated organs and tissues. You deal with a function, normal or diseased, which is rendered possible by the differentiation of cells. You deal with pathological states, every one of which has its special differentiation. Every phenomenon which you encounter in your professional work is conditioned by the differentiation of the organic living substance. To regulate that differentiation, to set it right when it has gone wrong, is the brightest vision of future human power which I can conceive, and I can not but think of embryology, which strives unceasingly to discover the laws of differentiation, as that Institute of Medicine which is to be the foundation of a greater practical medical progress than any yet achieved. The physician's knowledge is the mother of mercy.