COLUMBIA LIBRARIES OFFSq'E HEALTH SCIENCES STANDARD HX641 35004 QP86 .M661 The problem oi age, RECAP Minot The problem of age, growth and death. '% Qilb iAkiftl Columbia ®nit)ers(ftp mtljeCitpofl^mtcrk Digitized by the Internet Archive in 2010 with funding from Columbia University Libraries http://www.archive.org/details/problemofagegroOOmino >T, THE PROBLEM OF AGE, GROWTH AND DEATH CHAELES SEDGWICK MINOT, LL.D., D.Sc. James Stilbman Pkopessoe of Comparative Anatomy in the Harvard Medical School [Reprinted from THE POPULAR SCIENCE MONTHLY, Vol. LXXI, June, August, September, October, November, December, 1907] Q? THE POPULAR SCIENCE MONTHLY JUNE, 1907 THE PEOBLEM OF AGE, GROWTH AND DEATH.^ By CHARLES SEDGWICK MINOT, LL.D., D.Sc. JAMES STILLMAN PROFESSOR OF COMPARATIVE ANATOMY IN THE HARVARD MEDICAL SCHOOL. I. The Condition of Old Age ^|"^HE subject of age has ever been one which has attracted human -*- thought. It leads us so near to the great mysteries that all thinkers have contemplated it, and many are the writers who from the literary point of view have presented us, sometimes with profound thought, often with beautiful images connected with the change from youth to old age. We need but to think of two books familiar more or less to us all — that ancient classic, Cicero's De Senectute, the great book on age, one might almost say, from the literary standpoint, and that of our own fellow-citizen, my former teacher and professor at the Medical School, Dr. Holmes, who in his delightful ' Autocrat ' offers to us some of his charming speculations upon age. From the time of Cicero to the time of Holmes numerous authors have written on old age, yet among them all we shall scarcely find any one who had title to be considered as a scientific writer upon the subject. Longevity is indeed a strange and difficult problem. Many of you doubtless have had your attention directed recently to the republished translation of Connaro's famous work and know how sensible that is, and as you read it you must have perceived how little in the practical fispect of the matter we have passed beyond the advice which old Connaro gave to us. And yet silently in the medical laboratories, and in the physiological and anatomical institutes of various univer- eities, we have been gathering more accurate information as to what is the condition of persons who are very old. ' Lectures delivered at the Lowell Institute, Boston, March, 1907. 482 POPULAR SCIENCE MONTHLY We know, first of all, from our common observation, that the very old grow shorter in stature. We see that they are not so tall as in the prime of life. The figures which have been compiled upon this sub- ject are instructive, for they show that at the age of some thirty years the average height of men — these figures refer to Germans — is 174 "" "'" 1 1 i i i 1 i 1 ^■H^Hhihhh, ^ I^^^L^I ■I 1 ^p "*' — - ''ifc.XSOHBl — giWniB aippM^SBK '. ""■'■?•■*•;,... ^_j||H|||i|Hi|| s Fig. 1. Photograph op Chevreul, taken oa his one hundredth birthday. He was asked to write in an album and replied "Que voulez vous que j'6crive sur votre album. Je vais 6crire mon premier priacipe philosophique, ce n'est par moi, qui I'ai formula, c'est Male- branche"On doit teadre avee effort a rinfallibilitS, sans y priStendre." Chevreul was born Aug. 31, 1786 and died Aug. 9, 1889. For the privilege of using this portrait I am indebted to Dr. Henry P. Bowditch, to whom the interesting original belongs. centimeters. It remains at that, however, only for a short period; then it decreases and at forty it is already less; at fifty decidedly less; and at sixty the change has become more marked; until at seventy years we find that the height has shrunk from 174 to 161. There it AGE, GROWTH AND DEATH 483 remains, or thereabouts, through the remainder of life, though there may be a small further diminution. This decrease in stature is due largely to the changes in the vertebral column. First of all there is a stoop. The vertebral column is, to be sure, never straight, but in old age it becomes more curved, and the result is a falling of the total stature. But this is not the chief cause, for in addition to this the Fig. 2. Photugkaph fkom a Ciiii-d at Birth. The original is owned by Dr. H. P. Bow - ditch, by whose courtesy tlie present reproduction is published. softer cartilages and elements of the spinal column become harder, change into bone, and as that change occurs they acquire a less extent and become smaller, and the result is that the vertebral column as a whole collapses somewhat and thus increases the diminution of height. We find, as we look at the old, a great change to have come over the face. The roundness of youth has departed; the cheeks are 484 POPULAR SCIENCE MONTHLY sunken; the eyes have fallen far back; the lips are drawn in. All of these changes indicate to us, when we think upon them, the fact that there has been a certain shrinkage and shrivelling of that which is within and beneath the skin. Expressed in technical terms, we should call this an atrophy, and to anatomists the mere sight of the face of a very old person reveals at once this fundamental fact of an atrophy of the parts, an actual loss of some of their bulk, which is one of the most characteristic and fundamental marks of old age. The gait becomes shuffling, the foot is no longer lifted free from the ground, as the old man walks along. He does not rise upon his toes, but the sole of the foot is kept nearly flat and as he drags it cumbrously for- ward it is apt to strike upon the sidewalk. This indicates to the physiologist a lessened power in the muscles, a lessened control over the action of these muscles, an inferior coordination of the movements, so that there has been in the old man, judged by his gait alone, a physio- logical deterioration as well as an anatomical atrophy. You notice too his slow speech, often difficult hearing, and imperfect sight. All of these qualities show a loss, and we commonly think of the old as those who have lost most, who have passed beyond the maximum of development and are now upon the path of decline, going down ever more rapidly. One of the chief objects at which I shall aim in this course of lectures will be to explain to you that that notion is erroneous, and that the period of old age, so far from being the period of true decline, is in reality essentially the period in which the actual decline going on in each of us will be least. Old age is the period of slowest decline — a strange, paradoxical statement, but one which I hope to justify fully by the facts I shall present to you in this course. In the old person you note that there is in the mind some failure and also loss of memory — less mental activity, greater difficulty in grasp- ing new thoughts, assimilating new ideas, and in adapting himself to unaccustomed situations. All this betokens again the characteristic loss of the old. And as we turn now from these outward investiga- tions to those which the anatomist opens up to us, we learn that in the interior of the body, and in every organ thereof, the species of change which I have referred to as characteristic of the very old, is going on and has become in each part well marked. Let us first examine the skeleton. In youth many parts of the skeleton are soft and flexible, like the gristles and cartilages, which join the ribs to the breastbone, but in the old man they are replaced by bone. Bone represents an advance in organization, in structure, as we say, over the cartilage. The old man has in that respect progressed be- yond the youthful stage; but that progress represents not a favorable change; the alteration in structure from elastic cartilage to rigid bone is physiologically disadvantageous, so that though the man has progressed in the organization or anatomy of his body, he has really AGE, GROWTH AND DEATH 485 thereby rather lost than gained ground. Indeed in the skeleton this principle of loss is already revealing itself. In the interior of the bones of the arms, of the legs, we find a spongy structure, bits of bone bound together in many different directions, as are the spicules or fibers in a sponge, and by being bound so together they unite lightness with strength. As you know a column of metal, if hollow, is stronger than the same amount of metal in the form of a rod. So with the bones. If they have this spongy structure, if their interiors are full of little cavities with intervening spicules acting as braces in every direction, then they acquire great strength with little material. ISTow in the old the internal spongy structure is dissolved away and there is left only a hard external shell. Partly on this condition depends the greater liability of the bones in the old person to break. If we ex- amine the muscles we see that they have become less in volume, and when we apply the microscope to them we see that the single fibers on which the strength of the muscles depends have become smaller in size and fewer in number.^ The muscle has actually lost; it is in- ferior, physiologically speaking, to what it was before. You remember how melancholy Jacques reminded us of this fact in speaking of the hose ' a world too wide for his shrunk shank.' His saying is justified by the loss of the muscles in volume and strength. The same phe- nomenon of atrophy shows itself in the digestive organs. Those minute structures in the wall of the stomach by which the digestive juice is produced, undergo a partial atrophy, in consequence of which they are less able to act; they are not so well organized, therefore, not so efficient as in earlier stages. The lungs become stiffened; the walls which divide off an air cavity from the neighboring air cavitiee do not remain so thin as in youth, but become thickened and hardened^ and the vital capacity of the lungs, that is to say the capacity of the lungs to take in and hold air, is by so much lessened. The heart — it seems curious at first — is in the old always enlarged; but this does not represent a gain in real power. On the contrary, if we study carefully the condition of the circulation of the blood in the old, we find that the walls of the large blood-vessels, which carry the blood from the heart and distribute it over all parts of the body — vesseU which we call arteries— have lost the elastic quality which is proper to them and by which they respond favorably to the pumping action of the heart. Instead they have become hard and stiff. We call this by a Greek term for hardening, sclerosis, and arterial sclerosis is one of the most marked and striking characteristics of old persons. Now when the arteries become thus stiffened, it requires a greater force ^ This statement is the one currently accepted — ^but I have found, as yet, no exact investigation upon the relative size and number of the muscle fibers in ol^ persons. Age 0-1 Mean Frequency 134 1-2 Ill 2-3 108 3-4 108 4-5 103 5-6 98 6- 7 ... . 93 7- 8 ... . 94 8- 9 89 9-10 . 91 10-11 . . . . 87 11-12 89 12-13 88 486 POPULAR SCIENCE MONTHLY and greater effort of the heart to drive the blood through them, and in response to this new necessity, the heart becomes enlarged in an effort of the organism to adapt itself to the new unfavorable condition of the circulation established by age. But the power of the heart be- comes inferior along with this hypertrophy or enlargement, and we see that in the old, in order to make up for the feebleness of the enlarged heart, it beats more frequently. In other words, the pulse rate in the old person increases.^ We find, for instance, that at the time of Mean Me>in Age Preqiienoy ^"^ Freqnenoy 13-14 87 25-30 72 14-15 82 30-35 70 15-16 83 35-40 72 16-17 80 40-45 72 17-18 76 45-50 72 18-19 77 50-55 72 19-20 74 55-60 75 20-21 71 60-65 73 21-22 71 65-70 75 22-23 70 70-75 75 23-24 71 75-80 72 24-25 72 80 and over 79 birth the pulse rate is at the rate of 13i beats to a minute. It rises slightly during the first three months of infancy until at the end of the third month it reaches some 140 beats a minute; it soon falls off, however, and at the end of the first 3^ear it has sunk to 111; at five or six years it becomes 98, and at twenty-one years it has sunk to 71 or 72. There are thereafter certain minor fluctuations in the rate of the heart-beat Avith advancing age, but generally it may be said that this value of 72 beats a minute is characteristic of adult life. But when a person becomes eighty years old, it has been found that upon the average the rate of the heart-beat rises and becomes 79 a minute. Hence it is clear that though the heart is larger, it has to make a greater effort, that is to say a more frequent beat, in order to main- tain the necessary circulation of the blood. We see also, as we go back to the anatomical examination of the body, that those important jitructures which we call the germ cells, upon which the propagation of the race depends, which present under the microscope certain clearly recognized characteristics by which they can be distinguished from all other cells of the body, that these germ-cells cease their activity alto- gether in the very old, and one of the great functions of life is thus blotted out altogether from the history of the individual. Turning now to the yet nobler organs, especially the brain, we see 'My friend, Professor W. T. Porter, has had the kindness to compile the following table for me, showing the pulse frequency from one to eighty years. For the first two months after birth, the rate is about 130, after the third month 140. The foetal rate is 135 to 140. AGE, GROWTH AND DEATH 487 a curious change going on, a change of which old age presents to us the culminating record. In order to study the weight of the brain, it is necessary to compare people of the same size, for the size and weight of the brain depend somewhat upon the size of the individual. Now it has been discovered by careful examination of persons of similar size that the brain begins relatively early to diminish its weight. Thus in persons of a height of 175 centimeters, and over, of the male sex, it is found that in a period of from twenty to forty years the brain weight is 1,409 grams. But from forty-one to seventy years it has sunk to 1,363, and in persons of from seventy-one to ninety it" has shrunk to 1,330. Women of corresponding size are not easily found, and a more average height for women is 165 centimeters; a woman of such a height is likely to have — among the white races, be it always understood — a weight of brain of 1,265 grams, at forty to seventy years a brain of 1,200, and at seventy-one to ninety years a brain of only 1,166 grams.* I give these figures because they show that there is no guessing, but a definite, positive knowledge, proving that soon after the maturity of life in the individual is reached, the shrinkage of the brain begins, and then continues almost steadily to the very end of life. It is not only the anatomist, but it is perhaps almost equally the physiologist who gives us insight into the changes, which go on in the old. I spoke a few moments ago of the pulse rate, and of the change which that offers. At first sight it seems as if a greater pulse rate indicated an improvement, but if you recall the explanation which I have given you, you will acknowledge that this is by no means an acceptable interpretation, but that on the contrary the change is a clear mark of enfeeblement. In the respiration, also, we observe a like change. Here the comparison is not quite so easy as we should at first imagine, because there is a relation between the size of the individual and the respiration. The respiration, as you all know, frees the body from the products of combustion, particularly from that product which we know as carbon dioxide. The result of the com- bustion going on in the body (which in its end term appears to us as carbon dioxide expelled from the lungs) is to produce heat, to de- velop the necessary warmth for the maintenance of the proper tem- * Ernst Handmann has recently published statistics on the growth of brain, based on measurements at the Leipzig Pathological Institute. See Archiv f. Anat. u. Entwickelungsges., 1906, p. 1. The following summarizes his results: Brain Weight in Grama Age Male Female 4-6 1215 1194 7-14 1376 1229 15-49 1.372 1249 50-84 (89) 1332 1196 488 POPULAR SCIENCE MONTHLY perature of the body. Now in the very young the bulk of the body is not great, but the loss of heat is very great, and this perhaps can be most readily explained to you if you imagine that you hold in one hand a very small potato and in the other a very large potato, both of which have come at the same moment from the same oven, and that you have just started out for a cold winter drive. You all know, of course, that in a little while the small potato, though it was as hot as the large one at first, will have lost its heat, will no longer serve to keep the hand warm, but the other hand, in which the bulkier potato is held, in which the volume of the heat — we might so express it, perhaps — is correspondingly great, benefits by the retained heat a long time. Es- sentially similar to this is the difference between the child and the adult. The child loses heat with comparatively great rapidity — ^the old person at a comparatively slow rate. Hence it is necessary for the child to produce more warmth in order to keep up the natural normal temperature of the body. When, therefore, we find that in the old person the respiration is diminished, and. that the production of carbon dioxide from the lungs is greatly lessened, we are not immedi- ately to jump at the conclusion that the quality of physiological action has been debased — that we see here a sign of decrepitude. On the contrary, the change is the result of physiological adaptation, of suit- ing the performance of the body to its needs. This is one of the great wonders, one of the mysteries of life, of which we here have a sample, the constant adaptation of the means to the end. That which the body needs is done by the body. A child needs more warmth, and its body produces more ; the old person needs less warmth, and his body produces less. How this is accomplished we are unable to say, but constantly we see evidence of this purposeful accommodation on the part of the body — what is called by the physiologists the teleological principle, the adaptation of the reaction of the body to its needs. There are innumerable illustrations of this, many of which are of course perfectly familiar to us, although perhaps we do not think of them as illustrations of this great law of nature. As, for instance, when we eat a meal, and the presence of food in the stomach calls into action the glands in the wall of the stomach by which the digestive juice is secreted. The juice is produced exactly at the time when it is needed. Innmuerable, indeed, are the illustrations of this fundamental principle. There is another class of phenomena characteristic of the very old which will perhaps seem a little surprising to you after the general tenor of my previous remarks. I refer to the power of repair. This, modern surgery especially has enabled us to recognize as being far greater in the old than we were wont to assume; and we know that there is a certain luxury, a certain excess reserve in the power of re- pair, and that we may go far beyond the ordinary necessities of our AGE, GROWTH AND DEATH 489 life in our demands upon our organism, and still find that our body is capable of making the necessary response. Ordinarily the amount of blood which we require is moderate in amount — moderate in the sense that the destruction of the blood continually going on in the body is not a very rapid process ; but if, through some accident, a person loses a large quantity of blood then by one of these teleological reac- tions of which I have spoken, the production of new blood is increased, the loss is soon made up, and we discover that the blood, so to speak, has been repaired. Or when a little of the skin is lost, it quickly heals over. That again is due to the power of repair. Ordinarily so long as the skin remains whole that power is not called into action, but if a wound comes, then the regenerative force resident always in the skin, but inactive, comes into play and produces the mending which is such a comfort. So in old people, some of this luxury of reparative power persists, so that they can recover from wounds in a far better way than we should imagine if we judged them only by the general physiological and anatomical decline exhibited throughout all parts of the body. Some of the luxury of repair comes in usefully in old age. Now if we consider all these changes in the most general manner, we perceive that they are clearly of one general character; they imply an alteration in the anatomical condition of the parts; but it is an al- teration which does not differ fundamentally in kind from the alterations which have gone on before, but it does differ in the extent and in part in the degree to which these alterations have taken place. When the elastic cartilaginous rib becomes bony, nothing different is happening from that which happened before, for there was a stage of development when the entire rib consisted of cartilage, and in the progress of development toward the adult condition that cartilage was changed gradually into bone, thus producing the characteristic, normal, effi- cient bony rib of the adult. When old age intervenes, the change of the cartilage into bone goes yet further, but it progresses in such a way that it is no longer favorable, but unfavorable. We have then in this case a clear illustration of a principle of change in the very old which is, I take it, perhaps sufficiently well expressed by saying that the change which is natural in the younger stage is in the old carried to excess. But there is in addition to this, something more, of which I have already spoken, namely the atrophy of parts, and by atrophy we mean the diminution, the lessening of the volume of the part. There is a partial atrophy of the brain in consequence of which that organ becomes smaller; there is an extensive atrophy of the muscles in consequence of which their volume is diminished, and their efficiency decreased. Atrophy is preeminently characteristic of the very old, and we see in very old persons that it becomes each year more and more pronounced. Indeed, it has l)een said recently by Professor Metchnikoff, a distinguished Russian zoologist, now connected with the 490' POPULAR SCIENCE MONTHLY Pasteur Institute in Paris, some of whose publications many of you have doubtless read, that his conception of the nature of senility, of old age, could best be expressed in a single word, atrophy. " On resume la senilite par un seul mot: atrophie."^ That is his estimate of old age. But that is not the only estimate of old age which has been made up to the present time. We find one, which is much more prevalent, is that which connects it with the condition of the arteries. Indeed, Professor Osier has written this sentence — "Longevity is a vascular question, and has been well expressed in the axiom that a man is only as old as his arteries." Now these are medical views, not biological, and you will find that there is a very extensive literature dealing with old age in man based upon the conception that old age is a kind of disease, a chronic disease, an incurable disease. Medical writers have put forward various conceptions giving a medical interpretation of this disease. That to which I just referred is the favorite one, the one you are most likely to hear from physicians to-day — namely, the theory of arterial sclerosis, that the hardening of the walls of the arteries is the primary thing; it interferes with the circulation, the bad circulation interferes with the proper working of every part of the body, and as the circulation becomes impeded, various accessory results are produced in the body in consequence. It is brought to a lower or more diseased condition than before. And so they interpret sclerosis of the arteries as the primary thing, because they can trace so many alterations in the old which resemble diseased alterations, to these natural changes in the arteries by which they acquire hardened and inelastic walls, which prevent the proper response of the artery to the heart beat, upon which the normal healthy circulation largely depends. Another interpretation, very curious and interesting, is that which has been recently offered by the same Professor Metchnikoff . whom I have just mentioned. He has written a book upon the ' Nature of Man,' translated in 1903, and published in this country. It is an interesting book. It gives a most attractive picture, incidentally, of Metchnikoff himself, a man of pleasantly optimistic temperament, but a man thoroughly imbued with the spirit which has so often been attributed to contemporary scientific men^ of cold, intellectual regard towards everything, towards life, towards man, towards mystery. For him mysteries of all sorts have little interest. Those things which are mysterious are beyond the sphere of what can hold his attention. He must reside in the clear atmosphere of definite, positive fact. This mental bias is shown in his book. He reviews in a happy way various past systems of philosophy; he describes various religions; and he points out his reasons for thinking that all of these are insufficient, that there is no satisfaction to be derived from any of the ancient ^UAnnee biologique, Tome III., p. 256, 1897. AGE, GROWTH AND DEATH 491 philosophies or from any of the great world religions. Nevertheless he is an optimist. He has noticed as a result of his meditations upon the arrangements within our bodies that we suffer very much from what he calls disharmonies, by which he means imperfect adaptations of structures within us to the performance of the body as a whole. He mentions various instances of such disharmonious parts. They do not seem to me quite so imposing as apparently they do to him, for many of his disharmonies are based upon the fact that we do not know that a certain structure or part has any useful role to play in the body. But I am inclined to suspect that in many cases it is only because we are ignorant; the list of useless structures in the human body was a few years ago very long; it has within recent years been greatly shortened, and we should learn from this experience a caution in regard to judging about these things, which, I think. Professor Metchnikoff has failed to exert duly in forming his opinions on these disharmonies. Xow among the disharmonies which he recognizes is that of the great size of the large intestine, which is of such a caliber that a considerable quantity of partially digested food can be retained in it at one time. When such food is retained in the intestine, it may undergo a process of fermentation. There are many sorts of fermentation, and some of them produce chemical bodies which are injurious to the human organism. Bacteria, which will cause fer- mentation of this sort, do actually occur in the human intestine. Metchnikoff thinks that, as we grow old, this tendency to fermentation increases. ISTow the bodies produced by fermentation, the chemical bodies, I mean, get into our system and poison us. The result of the poisoning is that the native capacities of the various tissues and organs of the body are lowered, as happens in a man ' intoxicated.' All parts of a man may be poisoned, not necessarily always with alcohol, but with many other things as well, and such a poisoning Professor Metchnikoff assumes to result from intestinal fermentation. More- over, he has further observations, which lead him to the idea that certain cells go to work upon the poisoned parts and do further damage. The cells in question are minute microscopic structures, so small that we can not at all see them with the naked eye, but which have a habit of feeding in the body upon the various parts thereof whenever they get a chance. Cells of this sort go by the scientific name of phagocytes, which is merely a Greek term for ' eating cells.' The phagocytes, for instance, devour pigment in the hair, and in old per- sons the production of white hair has resulted from the activity of phagocytes which have eaten the pigment which should have remained in the hair and kept its color. But the pigment of the hair is not the only thing they will attack; they will make their aggressive inroads upon any part of the body; and Professor Metchnikoff has advanced the theory that old age consists chiefly in the damage which is done 492 POPULAR SCIENCE MONTHLY by phagocytes to poisoned parts of the body, the poisoning being due to the fermentation in the large intestine. Now it has been observed by some of the German investigators of these matters that the presence of lactic acid interferes with this fermentative process as it goes on in the intestine. Lactic acid, as its name implies, is the characteristic acid which occurs in milk when it becomes sour. An Italian friend of Professor Metehnikoff tried drinking some sour milk with the idea of stopping the fermentation in the intestine, and so putting an end to the deleterious change, and he believes in the short time that he tried it that it did him good— quite, you see, in the way of a patent medicine. Professor Metchnikoff, on this basis, has recommended, in his book on the 'Nature of Man,' the regular drinking of sour milk, in the hope apparently that that will postpone senility, and will leave us our powers in maturity long beyond that period when we at present reach the fullness of our vigor, and advance the period of time when the changes of the years put us out of court. He regards this as an opti- mistic substitute for the various forms of philosophy and religion which many millions of people have found helpful in life, and cer- tainly it is the cheapest substitute which has ever been seriously proposed. There is another writer who, though having a German name, is in reality a Eussian, Professor Miihlmann. He has another theory in regard to the fundamental nature of senility. He takes such in- stances as that which I spoke of, of respiration in connection with the production of warmth in the child's body and in the body of the adult, and finds that the diminution of the surface in proportion to the bulk of the body is characteristic of the old, and he concludes that we become old because we do not have proportionately surface enough left. His view implies, apparently, that if we could keep ourselves more or less of the stature of pygmies we should be healthier and better off. I confess these theories, and many others which I might enumerate to you, seem to me to be somewhat fantastic — odd rather than valuable. Yet they all spring from this one common feeling, which is, I believe, a sinister influence upon the thought of the day, in regard to the problem of age — they spring from the medi- cal conception that age is a kind of disease, and that the problem is to explain the condition as it exists in man. Now that is precisely what I wish to protest against. What I hope to accomplish in these lec- tures is to build up gradually in your minds some acquaintance with the fundamental and essential changes, which are characteristic of age and in regard to which we have been learning something during the last few years — I might almost say only within recent years — and by means of this exposition to give you a broader view and a juster interpretation of the problem. I hope, before I finish, to convince you that we are already able to establish certain significant generaliza- AGE, GROWTH AND DEATH 493 tions as to what is essential in the change from youth to old age, and that in consequence of these generalizations, now possible to us, new problems present themselves to our minds, which we hope really to be able to solve, and that in the solving of them we shall gain a sort of knowledge, which is likely to be not only highly interesting to the scientific biologist, but also to prove, in the end, of great practical value. Surely we can not hope to obtain any power over age, any power over the changes which the years bring to each of us, unless we understand clearly, positively and certainly, what these changes really are. I think you will learn, if you do me the honor to follow the lectures further, that the changes are indeed very different from what we should expect when we start out on a study of age, and that the contributions of science in this direction are novel and to some degree startling. We can begin to approach this broader view of our subject if we pass beyond the consideration of man. If we turn from man to the animals which we are most familiar with, the common domestic quadrupeds, we see that they undergo a series of changes not very dissimilar to those which man himself must pass through. An old horse, an old dog, an old cat, shows pretty much the same sort of decrepitudes which characterize old men. But when we pass farther down in the scale to the fishes, or even to a frog, we dis- cover great differences. Do you think you could tell a frog when it is old by the way it walks — for it never walks — or a fish by the amount of hardening of the lungs, when it has none? Yet the lack of lungs is characteristic of the fish. And what becomes of the theory of arterial sclerosis when we go still lower in the animal kingdom, towards its lowermost members, and find creatures which live and thrive and have lived and thriven for countless generations, yet have no arteries at all? They, of course, do not grow old by any change of their arteries. But when we come to study these various animals more carefully, we learn that in them the anatomical and physiological features which I have indicated to you in my description of the changes in the human being, are paralleled, as it were, by similar changes; but only by similar, not by identical, changes. If we examine the insects, for instance, we see that in an old insect there is a hardening of the outer crust of the body which serves as a shell and a skeleton at once. That hardening increases with the age of the individual. We can see in the insect a lessening development of the digestive tract, and we can see — it has been demonstrated with particular nicety — a degradation of the brain. Insects have a very small brain, but wlien a bumblebee, or a honeybee, grows old, as he does in a few weeks after he acquires his wings, we see that the brain actually becomes smaller, and not only that, but as I shall be able to demonstrate to you with the lantern in the next lecture, the elements which build up the brain have each of them become smaller and the diminution in the size of 494 POPULAR SCIENCE MONTHLY the brain is due in part to the shrinkage of the single microscopic con- stituents. There is another point of resemblance. We find that when one of the better parts of the body undergoes an atrophy, it becomes not only smaller, but its place is to a certain extent taken by the in- ferior tissues — especially by those which we call comprehensively the connective tissues, which might perhaps be best described to a general audience as that which is the stuffing of the body and fills out all the gaps between the organs proper. In consequence of performing this general function, they are very properly called connective tissues, since they connect all the different organs and systems of organs in the body together. Now in every body there is a continual fighting of the parts. They battle together, they struggle, each one to get ahead, but the nobler organ, generally speaking, holds its own. There are early produced from the brain the fine bundles of fibers which we call the nerves, which run to the nose, to the tongue and to the various parts of the body. When these appear all the parts of the body are very soft. Afterwards comes in the hard, and, we should think, sturdy bone, but never, under normal conditions, does the bone grow where the nerve is. The nerve, soft and pulpy as it seems, resists absolutely the encroachment of the bone, and though the bone may grow else- where, and will grow elsewhere the moment it gets a free opportunity, it can not beat the soft delicate nerve.® Similarly we find that the substance which forms the liver is pulpy, very delicate. Those of you who have seen fresh liver in the butcher's shop know what a flabby organ it is, and yet though it is surrounded by the elements of con- nective tissue, which with great zest and eagerness produce tough fibers, it never gives way to them. The connective tissue is held back by the soft liver and kept in place by it. The liver is, so to speak, a nobler organ than the connective tissue and holds sway ordinarily; but in old age, when the nobler organs lose something of their power, then the connective tissue gets its chance, grows forward and fills up the desired place, and acquires more and more a dominating posi- tion. We can see this alike in the brain of man and in the brain of the bee. That which is the nervous material proper, microscopic ex- amination shows us to be diminished everywhere in the old bee and in the old man, and the tissue which supports it, which is of a coarser nature and can not perform any of the nobler functions, fills up all the space thus left, so that the actual composition of the brain is by this means changed. There is, you see, therefore, during the atrophy ' The nerve fibers of the olfactory membrane arise very early in the embryo and form numerous separate bundles. Later the bone arises between the bundles, for each of which a hole is left in the osseous tissue, so that the bone in the adult has a sieve-like structure, and hence is termed the cribriform plate. It offers a striking illustration of the inability of hard bone to disturb soft nerve fibers. AGE, GROWTH AND DEATH 495 of the brain, not only a diminution of the organ as a whole, but there is the further degradation which consists in the yielding of the nobler to the baser part, if I may so express myself. That, you recognize, necessarily implies a loss of function. The brain can not under senile conditions do the sort of fine and efficient work which it could do before. Now if we go on from insects to yet lower organisms, we see less and less appearing of an advance in organization, of correlated loss of parts, and when we get far enough down in the scale, senescence becomes very vague. The change from youth to old age in a coral or in a sponge is at best an indefinite matter. I should like, did the length of the course permit, to enlarge greatly upon this aspect of the question, and explain to you how it is that as the organism rises higher and higher in the scale, old age becomes more and more marked, and in no animal is old age perhaps so marked, certainly in no animal is it more marked, than in ourselves. The human species stands at the top of the scale and it also suffers most from old age. We shall learn, I hope, more clearly later on in the course of these lectures, that this fact has a deeper significance, that the connection between old age and advance in organization, ad- vance in anatomical structure, is indeed very close, and that they are related to one another somewhat in fashion of cause and effect; just how far each is a cause and how far each is an effect it would perhaps be premature to state very positively; but I shall show you, I think in a convincing way, that the development of the anatomical quality, or in other words of what we call organic structure, is the fundamental thing in the investigation of the processes of life in relation to age. We can see it illustrated again very clearly indeed when we turn to the study of plant life, for plants also grow old. Take a leaf in the spring. It is soft as the bud opens. The young leaf is delicate. It has a considerable power of growth. It expands freely, and soon becomes a leaf of full size. Then comes the further change by which the leaf gets a firmer texture; the production of anatomical quality in the leaf, so to speak, goes on through the summer, and the result of that advance in the anatomical quality is that the delicate, youthful softness and activity of the leaf is stopped. It can not grow any more; it can not function as a leaf properly any more. The develop- ment of its structure has gone too far and the leaf falls and is lost, and must be replaced by a new leaf the next year. When we examine the changes that go on in any flowering plant, we observe always that there is this production of structure, and then the decay, the end or death. At first structure comes as a helpful thing, increasing the usefulness of the part, and then it goes on too far and impairs the usefulness, and at last a stage is produced in which no use is possible any longer — the thing is worthless. It is cast away in the case of the plant life; and this casting away of the useless is a thing not by any 496 POPULAR SCIENCE MONTHLY means confined to plants; it occurs equally in ourselves all the time; at every period of our life we have been getting through with some por- tion of our body; that portion acquired a certain organization, it worked for us awhile, and then being done with it, we threw it away because it was dead. Very early in the history of every individual there was a production of blood, and then followed the destruction of some of the blood corpuscles and their remains were used for various purposes. The pigment which is in the liver comes from the destroyed blood corpuscles, and it is believed that the pigment which colors the hair is derived from the same source. The blood corpuscles contain a material which when chemically elaborated reappears as the deposit which imparts to the hairs their coloration. You, of course, are all familiar with the loss of hair. It occurs to everybody, but did you ever think that it means that the hair which has lived has died, and that that hair which was a part of you has been cast off ? That is what the loss of hair means to the biologist — the death of a part and the throwing away of it, and it is typical of what is going on through the body all the time. It occurs in the intestines, where the elements which serve for purposes of digestion are continually dying and being cast off. The outer skin is constantly falling off and being renewed, and that which goes is dead. In every part of the body we can find something which is dying. Death is an accompaniment of develop- ment; parts of us are passing off from the limbo of the living all the time, and the maintenance of the life of each individual of us depends partially upon the continual death going on in minute fragments of our body here and there. Our next step in this course of lectures will carry us into the micro- scopic world, and with the aid of the lantern at the next lecture I shall hope to demonstrate to you a little of the microscopic structure of the body and of the general nature of the change, which exhibits itself in the body from its earliest to its latest condition. With such knowl- ege in our minds, we shall be able next to study some of the laws of growth. We shall gain from our microscopic information a deeper insight into some of the secrets of the changes, which age produces in the human body. THE POPULAR SCIENCE MONTHLY. AUGUST, 1907 THE PEOBLEM OF AGE, GEOWTH AND DEATH By CHARLES SEDGWICK MINOT, LL.D., D.Sc. JAMES STILLMAN PROFESSOR OF COMPARATIVE ANATOMY IN THE HARVARD MEDICAL SCHOOL II. Cytomorphosis. The Cellular Ciiaxges of Age Ladies and Gentlemen: 1 endeavored in my last lecture to picture to you, so far as words could suffice to make a picture, something of the anatomical condition of old age in man, and to indicate to you further that the study merely of those anatomical conditions is not enough to enable us to understand the problem we are tackling, but that we must in addition extend the scope of our inquiry so that it will include animals and plants, for since in all of these living beings the change from youth to old age goes on, it follows that we can hardly expect an adequate scientific solution of the problem of old age unless we base it on broad foundations. By such breadth we shall make our conclusion secure, and we shall know that our explanation is not of the character of those explanations which I indicated to you in the last lecture, which are so-called ' medical,' and are applicable only to man, but rather will have in our minds the character of a safe, soimd and trustworthy biological conclusion. The problem of age is indeed a biological problem in its broadest sense, and we can not study, as we now know, the problem of age without including in it also the con- sideration of the problems of growth and the problems of death. I hope to so entice you along in the consideration of the facts, which I have to present, as to lead you gently but perceptibly to the con- clusion that we can with the microscope now recognize in the living parts of the body some of those characteristics which result in old age. Old age has for its foundation a condition which we can actually make visible to the human eye. As a step towards tliis conclusion, I desire to show you this evening something in regard to the microscopic struc- ture of the human body. 98 POPULAR SCIENCE MONTHLY We now know that the bodies of all animals and plants are con- stituted of minute units so small that they can not be distinguished by the naked eye, although they can be readily demonstrated by the microscope These units have long been known to naturalists by the name of cells The discovery of the cellular constitution of living Fig. 3. Cells from the Mouth (Oral Epithelium) of the Salamander, to show the phases of cell division or mitosis. bodies marks one of the great epochs in science, and every teacher who has had occasion to deal in his lectures with the history of the bio- logical sciences finds it necessary to dwell upon this great discovery. It was first shown to be true of plants, and shortly after likewise of animals. The date of the latter discovery was 1839. We owe it to AGE, GEO]yTH AND DEATH 99 Theodor Schwann, whose name will therefore ever be honored by all investigators of vital phenomena. What the atom is to the chemist, the cell is to the naturalist. Every cell consists of two essential parts. There is an inner central kernel which is known by the technical name of nucleus, and a covering mass of living material which is termed the protoplasm and constitutes the body of the cell. I will now call for the first of our lantern slides to be thrown upon the screen. It presents to you pictures of the cells as they are found lining the mouth of the European salamander. The two figures at the top illustrate very clearly the elements of the cell. The protoplasm forms a mass, ofPer- ing in this view no very distinctive characteristics, and therefore offer- ing a somewhat marked contrast with the nucleus which presents in its interior a number of granules and threads. Every nucleus consists of a membrane by which it is separated from the protoplasm, and three internal constituents : First, a network of living material, more or less intermingled with which is a second special substance, chromatin, which owes its name to the very marked affinity which it displays for the various artificial coloring matters which are employed in micro- scopical research. The third of the internal nuclear constituents we m.ay call the sap, the fluid material which fills out the meshes of the network. Later on we shall have occasion to study somewhat more carefully the principal variations which nuclei of different kinds may present to us, and we shall learn from such study that we may derive some further insight into the rapidity of development and the nature of the changes which result in old age. While the picture is upon the screen, I wish to call your attention to the other figures which illus- trate the process of cell multiplication. As you regard them you will notice in the succession of illustrations that the nucleus has greatly changed its appearance. The substance of the nucleus has gathered into separate granules, each of which is termed a chromosome. These chromosomes are very conspicuous under the microscope, because they absorb artificial stains of many sorts with great avidity and stand out therefore conspicuously colored in our microscopic preparations. They are much more conspicuous than is the substance of the resting nucleus. And this fact, that we can readily distinguish the dividing from the resting nucleus under the microscope, we shall take advantage of later on, for it offers us a means of investigating the rate of growth in various parts of the body. I should like, therefore, to emphasize the fact at the present time sufficiently to be sure that it will remain in your minds until the later lecture in which we shall make practical use of our acquaintance with it. It is unnecessary for our purposes to enter into a detailed description of the complicated processes of cell division. But let me point out to you that the end result is that where we have one cell we get as the result of division — two; but the loo POPULAR SCIENCE MONTHLY two divided cells are smaller than the mother cell and have smaller nuclei. They will, however, presently grow up and attain the size of their parent. Every cell is a unit hoth anatomically and physiologically. It has a certain individuality of its own. In many cases cells are found to be isolated or separated completely from one another. But, on the other hand, we also find numerous instances in which the living sub- stance of one cell is directly continuous with that of another. When the cells are thus related, we speak of the union of cells as syncytium. Of this I offer you an illustration in the second picture upon the screen, which represents the embryonic connective tissue of man. In this you can see the prolongations of the protoplasm of a single cell body uniting with the similar prolongations from other cell bodies, the cells them- selves thus forming, as it were, a continuous network with broad meshes between the connecting threads of j)rotoplasm. The spaces or meshes are, however, not entirely vacant, but contain fine lines which corre- spond to the existence of fibrils, which are characteristic of connective tissue and at the stage of development represented in this picture, are beginning to appear. It is fibrils of this sort which we find as the main elements in the constitution of sinews and tendons, as, for in- stance, the tendon of Achilles, at the heel. In a very 3^oung body we find there are but few fibrils ; in the adult body an immense number. There is, in fact, as you projDably all know, a constant growth of cells; and this growth implies also, naturally, their multiplication. There has been in each of us an immense number of successive cell Fig. 4. Example OF A Syncytium. Embryonic connective tissue from the urn oilical cord of a human embryo of about three months, magnified about 400 diameters, c, c, cells ; /, inter- cellular fibrils. AGE, GROWTH AND DEATH loi generations, and at the present time a multiplication of cells is going on in every one of us. It never entirely ceases as long as life continues. The development of the bod}^, however, does not consist only of the growth and multiplication of cells, but also involves changes in the very nature of the cells, alterations in their structure. Cells in us are of many different sorts, but in early stages of development they are of few sorts. Moreover, in the early stages we find the cells all more or less alike. They do not differ from one another. Hence comes the technical term of differentiation, to designate the modifications which cells undergo with advancing age. At first cells are alike; in older individuals the cells have become of different sorts, they have been differentiated into various classes. This whole phenomenon of cell ■^ ri'i*j^-^~i«ii*-"=^-^-' i^ifi-r-ii... :.-g.,,^^.^.:\:. , ,' •"-'},'' D '""-lii.® ©.•'© Q© J3;^3^~^-^ ^ '^:m:^^. r ..■<€"0>- C m ■^~'pc^Zf&m^'& Fio. 5. Three Transverse Sections through a Rabbit embryo of seven and one HALF Days, from series 022 of the Harvard Embryological Collection. A, section 2J7 across the anterior part of the germinal area. B, section 200 across the middle region of the germinal area. C, section 381, through the posterior part of the germinal area. Magnified 300 diameters change is comprehensively designated by the single word, cytomorphosis, which is derived from two Greek words meaning cell and form, respect- ively. A correct understanding of the conception cytomorphosis is an indispensable preliminary to any comprehension of the phenomena of POPULAR SCIENCE MONTHLY development of animal or plant structure. I shall endeavor, therefore, now to give you some insight into the phenomena of cytomorphosis as regarded by the scientific biologist. The first cells which are produced are those which form the young embryo. We speak of them, therefore, as embryonic cells, or cells of the embryonic type. Our next picture illustrates the actual character of such cells as seen with the microscope, for it represents a series of sections through the body of a rabbit embryo, the development of which has lasted only seven and one half days. You will notice at once the simplicity of the structure. There are not yet present any of those parts which we can properly designate as organs. The cells have been produced by their own multiplication and are not yet so numerous but that they could be readily actually counted. They are spread out in somewhat definite layers or sheets, but beyond that they show no definite arrangement which is likely to attract your attention. That which I wish you particularly to observe is that in every part of each of these sections the cells appear very much alike. The nuclei are all similar in character, and for each of them there is more or less protoplasm; but the protoplasm in all parts of these young rabbits is found to be very similar; and indeed if we should pick out one of these cells and place it by itself under the micro- scope, it would be impossible to tell what part of the rabbit embryo it had been taken from, so much do all the cells of all the parts resemble one another. We learn from this picture that the embryonic cells are all very much alike, simple in character, have relatively large nuclei, and only a moderate amount of protoplasm for each nucleus to complete the cell. Very difi'erent is the condition of affairs which we find when we turn to the microscopic examination of the adult. Did time permit it would be possible to study a succession of stages and show you that the condition which we are about to study as existing actually in the adult is the result of a gradual progress and that in successive stages of the individual we can find successive stages of cell change; but it will suffice for our immediate purpose to consider the results of differentiation as they are shown to us by the study of the cells of Fig. 6. PoKTiON OF A Trans- verse Section of the Spinal Cord OF A Human Embryo of Four Mil- limeters. Harvard Embryological Collection, series 714. The spinal cord at this stage is a tubular struc- ture. The figure shows a portion of the wall of the tube ; the lefthand boundary of the figure corresponds to the inner surface of the tube. AGE, GROWTH AND DEATH 103 the adult. I will have thrown upon the screen for you a succession of pictures illustrating various adult structures. The first is, how- ever, a section of the embryonic spinal cord in Avhich you can see that much of the simple character of the embryonic cells is still kept. All parts of the spinal cord, as the picture shows, are very much alike, and the nuclei of the cells composing the spinal cord at this stage are all essentially similar in appearance. What a contrast this forms with our next picture, which shows us an isolated so-called motor nerve cell from the adult spinal cord. It owes its name motor to the fact that it produces a nerve fiber by which motor impulses are conveyed from the spinal cord to the mus- cles of the body. The j^ cell has numerous elon- gated branching proc- esses stretching out in various directions, but all leading back towards the cen- tral body in which the nucleus is situated. These are the processes which serve to carry in the nervous impulses from the periphery towards the center of the cell, impulses which in large part, if not ex- clusively, are gathered up from other nerve cells which act on the motor element. At one point there runs out a single process of a different char- acter. It is the true nerve filjer, and forms the axis, as it was formerly termed ; or axon, as it is at present more usually Fig. 7. Copy of the Okiginal Figure from THE Memoir of deiters, in which the proof of named, of the nerve fiber as the origin of the nerve fibers directly irom the nerve ceUs was first published. The raemoir is one of the classics of anatomy. It was issued posthu- mously, for the author died young to the great loss of science. The figure represents a single isolated motor nerve cell from the spinal cord of an ox. The -ingle unbrunched axon Ax, is readily distin- guished from the multiple branching dendrites. we encounter it in an ordinary nerve. This single thread- like prolongation of the nerve cell is likewise constituted by the living protoplasm and serves to carry the impulses away from the cell body and transmit them ultimately to the muscle fibers which are to be stimulated to contraction. In the embrj'onic I04 POPULAR SCIENCE MONTHLY Fig. 8 A Large Cell from the Small Brain (Cerebellum) of a Man. It is usually called a Puikinje's cell. It was stained black throughout by what is known as the Golgi silver method, hence shows nothing of its internal structure. After von Kollikt-r. spinal cord none of these processes existed, and the amount of the protoplasm in the nerve cell was very much smaller. As develop- ment progressed, not only did the protoplasm hody grow, but the processes gradually grew out. Some of them branched so as to better receive and collect the impulses; one of them remained single and very much elongated, and acquired a somewhat different structure in order to serve to carry the nervous impulses away. The third picture^ shows us a section through the spinal cord of an adult fish. It has been treated by a special stain in order to show how certain elements of the spinal cord acquire a modification of their organization by which • they are adapted to serve as supports for the nervous elements proper. They play in the microscopic structure the same supporting role which the skeleton performs in the gross anatomy of the body as a whole. They do not take an active part in the nervous functions proper. None of the appearances which this figure offers for our consideration can be recognized in any similar preparation of the embryonic cord. Obviously, then, from the embryonic to the adult state in the spinal cord there occurs a great differentiation. That which was alike in all its parts has been so changed that we can readily see that it consists of many different parts. A striking illustration of this is afforded by the next picture, which represents one of the large nerve cells which occur in the small brain, or cerebellum, that portion of the central nervous system which the physiologists have demon- ^ The illustration referred to is not reproduced in the text. AGE, GI10\\TH AND DEATH 105 strated to be particularly concerned in the regulation and coordination of movements. These large cells occur only in this portion of the Jus, yf. fVf/ y. jfj?*- ■.%1i ■\> & "^ ^ % 9 ^ ipr'^il^ \ hi/ (^ Fifl/L l-'i'l 'i Fif.}. J Fii;. y Vakiois Kinds of Human Nkkvk V,y.\.\.- Arier Sob"lla. DKSCKII'.KIi IN TliK TKXT. brain, and, as you see, differ greatly in appearance from the motor cells of the type which we were considering a few moments ago. And, again, io6 POPULAR SCIENCE MONTHLY another picture illustrates yet other peculiarities of the adult nerve cells. The upper figures in this plate are taken from cells which have been colored uniformly of a very dark hue, in consequence of which (T. (^> ©•I'^*® 'f»> -,. "'**^- ^ ^' /Sits I'lff.l. ^ Fiff.£. ^*>&& Ff (/..')'. Fi\g. 4 Pig. 10. Sections of Four Sokts of Epithelium. Alier Swbntta. they are rendered so opaque that the nucleus which they really contain is hidden from our view. But the deep artificial color makes it easy to follow out the form of the cells and the ramifications of their long processes. In the middle figures we have cells which have been stained by another method which brings out very clearly to the eye the fact AGE, GROMTH AND DEATH 107 that in the protoplasm of the cell there are scattered spots of substance of a special sort, is^o such spots can be demonstrated in the elements of the young embryonic nerve cells. To some fanciful observers the spots, thus microscopically demonstrable in the nerve cells, recall the spots which appear on the skin of leopards, and hence they have be- stowed upon these minute particles the term tigroid substance. The bottom figures represent the kind of nerve cells which occur upon the roots of the spinal nerves. It is unnecessary to dwell upon their ap- pearance, as the mere inspection of the figures shows at once that they differ very much indeed from the other nerve cells we have considered. We pass now to another group of structures, the tissues which are known by the technical name of epithelia. You can notice immediately in the figures from the skin that the appearances are very different from those we have encountered in contemplating the cells of the nervous system. And you can readily satisfy yourselves by the com- parison with the various figures now before you, of the fact that these epithelia are unlike one another. The figures represent epithelium, respectivel}^, first from the human ureter; second, from the respiratory division of the human nose; third, from the human ductus epidid3miidis, and fourth, from the pigment layer of the retina of the cat. We turn now to a representation of a section of one of the orbital glands. This is very instructive because we see not only that the cells which compose the gland have acquired a special character of their own, but also that they are not uniform in their appearances. This lack of uniformity is due chiefly to the fact that the cells change their appear- ance according to their functional state. We can actually see in these cells under the microscope the material imbedded in their protoplasmic A Ji Fig. 11. To snow tiik Okbitai, Glands, A, with the inrtterinl to form the secretion acfMJraulateU within the cells. /?, after loss of the material through prolonf^ed secretion. P'rorn R. Hei^lenbain after Lavdowsky. io8 POPULAR SCIENCE MONTHLY bodies out of which the secretion, which is to be poured forth by the cells, is to be manufactured. So long as that material for the secretion is contained in the cells, the cells appear large, and their protoplasmic bodies do not readily absorb certain of the staining matters, which the microscopist is likely to apply to them. When, however, the accumu- lated raw material has been changed into the secretion and discharged from the gland, the cell is correspondingly reduced in bulk, and as you see in this figure, it then takes up the stain with considerable avidity, as does also the nucleus which has likewise become reduced in size. These facts are very instructive for us, since they prove conclusively that with the microscope we can see at least part of the peculiarities in cells which are correlated with their functions. We can actually ob- serve that the cells of the salivary glands are able to produce their peculiar secretion because they contain a kind of substance which in the embryonic cell does not appear at all. There is a visible differen- tiation of these salivary cells from the simple stage of the embryonic cells. Something similar to this can be recognized in the next of our pictures representing a section of the gland properly known as the pancreas, but which is sometimes termed the abdominal salivary gland for the reason that it somewhat resembles the true salivary. In the cells of the pancreas also we can see the material, which is to produce the secretion, accumulated in the inner portion of the cell, and when it is so accumulated the cell appears enlarged in size and the nucleus is driven back towards the outer end of the cell where some unaltered protoplasm is also accumulated. When this raw material is turned Pig. 12. Two Sections of the Pancreatic Gland of a Dog. A, the cells are enlarged by the accumulation of material to form the secretion. B, the cells are shrunk because there has been prolonged secretion and part of their substance is lost. From R. Heidenhain. AGE, GRO}YTH AND DEATH 109 over into secretion by a chemical change, it is discharged from the cell, the cell loses in volume and in its shrunken state presents a very dif- ferent appearance, as is shown at B in the figure. It is necessary for the cells to again elaborate the material for secretion before they can a second time become functionally active. Here we have somethmg of the secret of the production of the various juices in the body revealed to us. Other excellent examples of the differentiated condition of the cells are afforded us bv the examination of hairs, of which I will show you two i^ictures. The first represents a section through the human Fig. 13. SiXTioN OF Tin-, IUman Skin, mai,k so that the Hairs akf. cut Lengthwise. skin taken in such a way that the hairs are themselves cut lengthwise and you can see not only that each hair consists of various parts, but also that the cells in these parts are unlike. The follicles within the skin in which the hair is lodged likewise have walls with cells of various 6orts. It may interest you also to point out in the figure the little muscle which runs from each hair to the overlying skin, so disposed that when the muscle contracts the " particular hair will stand up on no POPULAR SCIENCE MONTHLY end." Still more clearly does the variety of cells which actually exists in a hair show in the following picture, which represents a cross-section of a hair, and its follicle, hut more highly magnified than were the hairs in the previous figure. The adult body consists of numerous organs. These are joined together and kept in place by intervening ''//^/ '\,^ w ^•■5l.: ■■','••»'/'*' /^f/ Fig. 14. Ckoss Section of the Root of a Hair. substance. The organs themselves consist of many separate parts which are also joined by a substance which keeps them in place. This sub- stance has received the appropriate name of connective tissue. We find in the adult that it consists of a considerable number of structures- There are cells and fibers of more than one kind, which have been pro- duced by the cells themselves. There is more or less substance secreted by the cell which helps to give consistency to the tissue. In some cases this substance which is secreted by the cells becomes tougher and ac- quires a new chemical character. Such is the case, for instance, with cartilage. Or, again, you may see a still greater chemical meta- morphosis going on in the material secreted by the cells in the case of bone, where the substance is made tougher and stronger by the deposit AGE, GROWTH AXD DEATH of calcareous material. Nothing like cartilage, nothing like bone, exists in the early state of the embryo. They represent something different and new. The next of our illustrations shows us a muscle fiber of the sort which serves for our voluntary motions, which is connected typ- ically with some part of the skeleton. These muscle fibers are elon- gated structures. Each fiber contains a con- tractile substance different from protoplasm, and | •■ - ~- which exists in the form of delicate fibrils which run lengthwise in the muscle fibers, and is so disposed, further, that a series of fine lines are produced across the fiber itself, each line cor- responding with a special sort of material dif- ferent from the original protoplasm. These cross lines give to the voluntary muscle fibers a very characteristic appearance, in consequence of which they are commonly designated in scientific treatises by the term striated. A striated muscle fiber is that which is under the control of our will. It should perhaps be men- tioned that the muscle fibers of the heart are also striated, though they differ very much in other respects from the true voluntary muscles. And last of all for this series of demonstrations, I have chosen a representation of the retina. One can see at the top of the figure the peculiar cylindrical and developing projections, which are characteristic of a retina, projections which are of especial interest because they represent the apparatus by which the rays of light are transformed into an actual sensory perception. After this has been accomplished, the perception is transmitted into the interior substance of the retina, and by the complication of the figure you may judge a little of the complication of the arrangements by which the transmission through this sensory organ is achieved, until the perception is given off to a nerve fiber and carried to the brain. There is not time to analyze all I might present to you of our present knowledge concerning the structure of the retina. But it will, I think, suffice for purposes of illustration to call your attention to the com- plicated appearance of the section as a whole and to assure you that nothing of the sort exists in the early stage of the embryo. To re- capitulate, then, what we have learned from the consideration of these pictures, we may say that in place of uniformity we now have diversity. It should be added, to make the story complete, that the establishment of this diversity has been gradually brought about, and that that which Fig. 15. Part of a MU.SCLE Fiber of the Human ToNcrE to show THE Cross Striations. Two nuclei are included, one of which is shown at the edge of the fiber, the other in surface view. In the adult striated muscle fibers of mam- mals the nuclei are su- perficially placed. POPULAR SCIENCE MONTHLY Blood vessels. ment. ili-— Cone, outer seg- A^ ment. IP;""* Cone, inner seg- '^^l ruent. is^^'^v^ Rod, inner seg- O ment. ^' fg^yji."'^!^] Base of a cone Nucleus. Nucleus. Inner surface ot the retina (to- ward ttie light). Fibers which pass inio the optic nerve. Blood vessels Fig. 16. Section of a Human Retina, from Stohr's Histology, sixth American edition. Aithough the retina is very thin it comprises no le?s than twelve distinct layers ; the outermost layer is highly vascular. The pigment layer prevents the escape of light. The rods and cones convert the light waves into a sensory impulse, which is transmitted through the remaining layers of the retina to the optic nerve. The total structure is extremely complicated. we call develoiDiiient is in reality nothing more than the making of diversity out of uniformity. It is a process of differentiation. Dif- ferentiation is indeed the fundamental phenomenon of life; it is the central problem of all biological research, and if we understood fully the nature of differentiation and the cause of it, we should have probably got far along towards the solution of the final problem of the nature of life itself. The size of animals deserves a few moments of our time, for it is intimately connected with our problem of growth and differentiation. Cells do not differ greatly from one another in size. The range of their dimensions is very limited. This is particularly true of the cells of any given individual animal. Eecent careful investigations have been made upon the relation of the size of cells to the size of animals, and it has been found that animals are not larger, one than another, because their cells are larger, but because they have more of them. This statement must be understood with certain necessary reservations. There are some kinds of animals, like the star-fish, which have very small cells; others, like frogs and toads, which have large cells; so that a star-fish of the same bulk as a given frog would contain a great many more cells. Our statement is true of allied animals. For ex- ample, a large frog differs from a small 'frog, or a large dog from a small dog by the number of the cells. An important exception to this law is offered for our consideration by the cells of the central nervous AGE, GEO}yTH AND DEATH 113 system, the nerve cells properly so called. This is demonstrated by the slide now before ns, which shows us corresponding motor nerve cells of twelve different animals arranged in the order of their size — the elephant, the cow, the horse, man, the pig, the dog, the baboon, the cat, the rabbit, the rat. the mouse, and a small bat. You recognize im- El«^plum iiuli(Mi>s 84.1x71.5 lio.s laurii.H Evim.«< cnlHillii.*? 7L'.4xr,G.7 07.»>'."(;.7 > < y r Homo 07.r>x.^4.O 03.4x51. :j 3) - < ; (yiiocej»h(ilii.'< iMihiiiii Felix domestical Lepu.'^niniciilii.^ doiiH'slicii.s G().7xr>G.3 .5«.()x54.o 4'kr.x;i«;.4 ^ r Mils rnllus ulbus Miis inii.srnlu^ciibu.'^ AlSlapJio dnfrea 37.Hx:^:v.7 :i<-..ftxL»2.j) 31.5x28.0 FxG. 17. Motor Nerve Cells of Various Mammals, all from the cervical region of the spinal cord. The cells are represented, all unilormly magnified. After Irving Htudesty. mediately that there is a proportion l)etweon the size of these cells and the size of the respective species of animals. To a minor degree, but much less markedh^, there is a difference in the caliber and length of the muscle fibers. But with tliese exceptions our statement is very nearly exactly true, that llic diirci-cnce in size of animals docs not in- volve a difference in ilie size of tlicii' cells. For the ])ur|)osc of the study of devclopincnj, which we arc to make in these lectures, this uni- 114 POPULAR SCIENCE MONTHLY fcrmity in the size of cells is a great advantage, and enables us to speak in general terms in regard to the growth of cells, and renders it superfluous to stop and discuss for each part of the body the size of the cells which compose it, or to seek to establish different principles for different animals because their cells are not alike in size. ISTow we pass to a totally different aspect of cell development, that which is concerned with the degeneration of cells. For we find that, ../H,;^^^ t .. ... ,j ^^" '"v, '■::} -1. B Fig. 18. Changes in the Nerve Cells with Age. after the differentiation has been accomplished, there is a tendency to carry the change yet further and to make it so great that it goes beyond perfection of structure, so far that the deterioration of the cell comes as a consequence. Such cases of differentiation we speak of as a degeneration, and it may occur in a very great number of ways. Very frequently it conies about that the alteration in the structure of the cell goes so far in adapting it to a special function that it is unable to maintain itself in good physiological condition, and failing to keep up its own nourishment it undergoes a gradual shrinkage which we call atrophy. A very good illustration of this, and a most important one, is offered us by the changes which go on in the nerve cells in extreme old age. This is beautifully illustrated by the two pictures which are now before us, copied from investigations of Professor Hodge, of Clark University. The two figures represent human nerve cells taken from the root of a spinal nerve. The left-hand figure shows these cells as they exist in their full maturity; the right-hand figure, as they appear in a person of extreme old age. In the latter you will readily notice that the cells have shrunk and no longer fill AGE, GROWTH AND DEATH 115 the spaces allotted to them, the nuclei have hecome small, and the protoplasm has changed its appearance very strikingly because there have been deposited in it granules of the pigment which impart to these cells an appearance very different from that which they had in their maturity when their functional powers were at their maximum. You will notice also in other parts of the right-hand figure that the atrophy of the cells has led on to their disintegration, that they are breaking down, being destroyed, and that the result of their breaking down will ultimately be their disappearance. Thus the atrophy of a cell may lead to its death. The other two figures^ upon the screen show us the brain of the humljle bee. On the left is the brain of the bee in the condition in which we find it when the bee first emerges from the pupa or chrysalis. The cells are then in a fine physiological condition, but in a few weeks at most the bee becomes old and in the space which belongs to each cell we find only its shrunken and atrophied remnants, ' the nucleus greatly reduced in volume, and an irregular mass of proto- plasm shrunk together around it. These cells have likewise under- gone an atrophy and are on their way to death. In other cases we find that there is a change going on which we call necrobiosis, which means that the cells continue to live, but change their chemical organi- zation so that their substance passes from a living to a dead state. 'Ro more perfect illustration of this sort of change can be found than that which is afforded by the skin. In the deep layer of the outer skin are the living and growing parts, which we all know from experience are sensitive. As these multiply some of them move up towards the sur- face ; and they are continually shoved nearer and nearer the surface by the growth of the cells underneath. They finally become exposed at the surface by the loss of the superficial cells which preceded them. During this migration the protoplasm of each cell, which was alive, is changed chemically into a new substance which we call keratin, or in common language, horny substance. Ultimately the cell protoplasm becomes nothing but horny substance and is absolutely dead. Here life and death play together and go hand in hand. Hence the term necrobiosis, life and death in one. Another form of degeneration which occurs in many cases is of great interest because it seems as if the cells were making a last great effort; and their final performance is one of enlargement. They become greater in size than before; but there will follow a disintegration of these cells also; and they break down and are lost. This form of degeneration is termed hypertrophic, and represents a third type, as I have stated. In all parts of the body degenerative changes are going on, and they represent collectively a third phase in the cytomorphic cycle. But there is yet one more phase, which is needed to complete the story. That is the phase of the The two figures of the bee's brain are not reproduced in the text. ii6 POPULAR SCIENCE MONTHLY death and final removal of the cells. The degenerative change always results in the death of the cell. In many cases the dead material is removed merely by being cast off, as is the case with the skin. All the scales which peal off from the outer surface of our body represent little scraps or clusters of cells which are entirely dead ; and in the interior of the body, in the intestinal canal, and in the glands of the stomach, we find cells continually dying, dropping off from their place upon the walls, and being cast away. Or if we examine the saliva which comes from the mouth, we detect that that also is full of cells which have died and fallen off from their connection with the body and are thus removed. An even more important method of the removal of cells is by a chemical process in consequence of which the cells are dissolved and disappear before our eyes, very much as marble may disappear from sight under the corrosive action of an acid. Indeed, we know that all the parts of the body, so far as they are alive, produce within themselves a ferment which has a tendency to destroy the living sub- stance itself. The production of these destructive agents is going on at all times, apparently, in all parts of the body, which are alive. A striking illustration of this is offered in the stomach. The digestive juice which is produced in the stomach is capable of attacking and destroying living substance, and any organic material suitable for food which is placed in the stomach will, as we know, be attacked by the gastric juices, dissolved to a certain extent by them, and so destroyed. Why then does the gastric juice not attack the stomach itself? This is but one phase of the problem why the body does not continually destroy itself. It has lately been ascertained by some ingenious phys- iological investigations that the body not only produces the destructive agents, but also antagonists thereto, anti-compounds which tend to prevent the activity of the destroying factors. The whole problem is one of great interest and importance which calls for very much further investigation before we can be said to have arrived at a clear under- standing of it. But it helps us much in our conception of eytomor- phosis to know that all portions of the body are endowed with this faculty of destroying themselves, for it enables us to understand how it is possible that after the degeneration of a cell it will be dissolved away. It is merely that the agents of solution which are ordinarily held at bay are no longer restrained, and they at once do their Avork. There is another, but comparatively rare, mode of cell-destruction. The cells break up into separate fragments, which are then dissolved by chemical means and disappear, by the method of histolysis above described, or else are devoured by the cells, to which reference was made in the first lecture, and which are known by the name of phagocytes, and to which Metchnikoff has attributed so great an importance. It is un- questionable that phagocytes do eat up fragments of cells and of tissues, AGE, GROWTH AND DEATH 117 and may even attack whole cells. But to me it seems probable that their role is entirely secondary. They do not cause the death of cells, but they feed presumably only upon cells which are already dead or at least dying. Their activity is to be regarded, so far as the problem of the death of cells is concerned, not as indicating the cause of death, but as a phenomenon for the display of which the death of the cell offers an opportunity. The subject of the death and disintegration of cells i.- an exceedingly complex one, and might well occupy our attention for a long time. But it is not permissible to depart from the strict theme which we have before us, and I will content myself, therefore, with throwing upon the screen two tables^ which illustrate to us the varia- tions in the death of cells and in their modes of removal which are First. A. c. Second, A. B. Third. A. B. C. - 1. Death of Cells Causes of death. External to the organism : (1) Physical (mechanical, chemical, thermal, etc.). (2) Parasites. Changes in intercellular substances (probably primarily due to cells) : ( 1 ) Hypertrophy. (2) Induration. (3) Calcification. (4) Amyloid degeneration (infiltration). Changes inherent in cells : Morphological changes of dying cells. Direct death of cells : (1) Atrophy. (2) Disintegration and resorption. Indirect death of cells: (1) Necrobiosis (structural change precedes final death). (2) Hypertrophic aegeneration (growth and structural change often with nuclear proliferation precede final death). Removal of cells. By mechanical means (sloughing or shedding) By chemical means (solution). By phagocytes. II. Indirect Death of Cells Necrobiosis. ( 1 ) Cytoplasmic changes : (a) Granulation. (h) Hyaline transformation. (c) Imbibition. (d) Desiccation. (e) Blasmatosis. (2) Nuclear changes: (a) Karyorhe.\is. (h) Karyolysis. Hypertrophic degeneration. (1) Cytoplasmic: (a) Granular. (b) Cornifying. (c) Hyaline. (2) Paraplasmic: (a) Fatty. (5) Pigmentary. (c) Mucoid. id) Colloid, etc. (3) Nuclear (increase of chromatin). ii8 ■ POPULAR SCIENCE MONTHLY known at the present time. These tables are taken from a lecture which I delivered in New York a few years ago, which was subse- quently published. If any of you should care to make a closer ac- quaintance with them they are therefore readily accessible to you. How then, from the standpoint of cytomorphosis ought we to look upon old age? Cytomorphosis, the succession of cellular changes which goes on in the body, is always progressive. It begins with the earliest develop- ment, continues through youth, is still perpetually occurring at maturity and in old age. The role of the last stage of cytomorphosis, that is, of death in life, is very important, and its importance has only lately be- come clear to us. I doubt very much if the conception is at all familiar to the members of this audience. iSTevertheless the constant death of cells is one of the essential factors of development, and much of the progress which our bodies have made during the years we have lived, has been conditional upon the death of cells. As we have seen, cytomorphosis, when it goes through to the end, involves not only the differentiation but the degeneration and death of the parts. There are many illustrations of this which I might cite to you as examples of the great importance of the destruction of parts. Thus there is in the embryo before any spinal column is formed an actual structure which is termed the notochord. In the young mammalian embryo this structure is clearly present and plays an important part, but in the adult it has entirely disappeared, and its disappearance begins very early during embrj^onic life. There are numerous blood vessels which we find to occur in the embryo, both those which carry the blood away from the heart and those which bring blood to the heart, which during the progress of development are entirely destroyed, and disappear for- ever. Knowledge of these is to the practical anatomist and surgeon often of great importance. A'ast numbers of the smaller blood vessels which we- know commonly by the name of capillaries, exist only, for a time and are then destroyed. There is in the J-oung frog, while he is in the tadpole stage, a kidney-like organ, which on account of its posi- tion is called the head-kidney, but it exists only during the young stage of the tadpole. There is later produced another kidney which, from its position, is called the middle kidne}^ and which is the only renal organ found in the adult, for the head kidney entirely disap- pears in these animals long before the adult condition is reached. In the mammal there is yet a third kindey. We have during the em- bryonic stage of the mammal always a well-developed excretory organ which corresponds to the middle or permanent kidney of the frog, yet during embryonic life the greater part of this temporary structure is entirely destroyed. It is dissolved away and vanishes, leaving only a few remnants of comparatively little importance in the adult. The new structure, the permanent kidney which we have, takes its place AGE, GROWTH AND DEATH 119 functionally. Large portions of the tissues, which arise in the embryo, are destroyed at the time of birth, and take no share in the subsequent development of the child. If we follow out with the microscope the various changes which go on in the developing body we see revealed to us a very large number of cases of death of tissues, followed by their removal. Thus the cartilage which exists in the early stages dies and is dissolved away, and its place is taken by bone. Those things which we know as bony elements of the skeleton in the adult, in the embryo exist merely as cartilage, but the cartilage is not converted into bone but it is destroyed and its place taken by bone. There is overlying the heart of a child at birth a well-developed gland known as the thymus. After childhood this undergoes a retrograde development; it becomes gradually absorbed and persists only in a rudimentary condi- tion. With the loss of the teeth occurring during infancy, you are familiar, and know that the first set of teeth are but for a short period, and are to be replaced by the permanent set. In very old persons we see a great deal of the bony material absorbed, and this absorption of the bone is a phenomenon which occurs at almost every period of the development. Portions of the epidermis or outer skin are constantly shed, as is well known, and the loss of hair and the loss of portions of our nails are so familiar to us that we hardly heed them. Of the constant destruction of the cells, which are found in the lining of the intestine, I have already spoken. At all times in the body there is a vast amount of destruction of blood corpuscles going on, a destruction v/hich is physiologically indispensable, for the material which the blood corpuscles furnish is used in many ways. For instance, the pigment which occurs in the hair is supposed to be derived from the chemical substances the use of which the body obtains by destroying blood corpuscles. One of the most familiar instances of destruction is that of the tail of the tadpole. The young frog and the young toad during their larval stages live in the water and each of them is furnished with a nice tail for swimming purposes. As the time approaches for the metamorphosis of the tadpole into the adult, the tail is gradually dissolved away. It is not cast off, but it is literally dissolved, resorbed, and vanishes ultimately altogether. It is evident that such a vast amount of destruction of living cella could not be maintained in the body without the body going entirely to destruction itself, were there not some device for making good the losses which are thus l)rought al)Out. We find in fact that there is always a reserve of cells kept to make good the loss which it is essential should be made good. Some losses apparently do not have to be re- paired, but the majority of them must be compensated for, and thia is done by having in the body a reserve supply of cells which can produce new cells of the sort required. This leads us to considera- tion of the phenomenon of regeneration and of the repair of parts. I20 POPULAR SCIENCE MONTHLY These phenomena we can better take up later in onr course, when we have dealt with the general processes of development and growth. From the study of regeneration we shall be able to confirm the explana- tion of old age, which I want to lay before you. This confirmation is so important that it will be better taken up in a separate lecture, than slipped in now when the hour is nearly by. Old age, after what I have said, I think you will all recognize as merely the advanced and final stage of cytomorphosis. Old age differs but little in its cytomorphosis from maturity; maturity differs much from infancy ; infancy differs very much indeed from the embryo ; but the embryo differs enormously from the germ in its cytomorphic con- stitution. We know that in the early time comes the great change, and this fact we shall apply for purposes of interpretation later on. Cytomorphosis is then a fundamental notion. It gives us in a general law, a comprehensive statement of all the changes which occur in the body. None, in fact, are produced at any period in any of us except in accordance with this general cytomorphic law. There is, first, the undifferentiated stage, then the progressive difl'erentiation ; next there follows the degenerative change ending in death, and last of all the removal of the dead cells. Such we may conveniently designate as the four essential stages of cytomorphosis. This cytomorphosis is at first very rapid; afterwards it becomes slower. That is a significant thing. The young change fast ; the old change slowly. We shall be able, when we get a little farther along in our study, to see that in differentiation lies the explanation of a great deal of biological knowledge, lies the explanation of our conception of cell structures ; and in it also lies not only the explanation of the death of cells, but also, as it seems to me — and this is one of the points that I shall want particularly to bring forward before the close of the course — of general death, that which we mean by death in common parlance, when the continuation of the life of the individual ceases, and is thereafter bodily impossible. The explanation of death is one of the points at which we shall be aiming in the subsequent lectures of the course. Now we know that in con- nection with age there is always growth. I propose, therefore, in the next lecture, to take up the subject of growth. We shall arrive at some paradoxical conclusions, for it can be shown by merely statistical reckonings that our notion that man passes through a period of de- velopment and a period of decline is misleading, in that in reality we begin with a period of extremely rapid decline, and then end life with a decline which is very slow and very slight. The period of most rapid decline is youth; the period of slowest decline is old age, and that this statement is correct I shall hope to prove to 3^ou with the aid of tables and lantern illustrations at the next lecture. THE POPULAR SCIENCE MONTHLY. SEPTEMBER, 1907 THE PROBLEM OF AGE, GROWTH AND DEATH By CHARLES SEDGWICK MINOT, LL.D., D.Sc. JAMES STILLMAN PROFESSOR OF COMPARATIVE ANATOMY IN THE HARVARD MEDICAL SCHOOL III. The Rate of Growth Ladies and Gentlemen: In the first of the lectures, I described those grosser characteristics of old age, which we ourselves can readily dis- tinguish, or which an anatomical study of the body reveals to us. In the second lecture I spoke of the microscopic alterations which occur in the body as it changes from youth to old age. But besides the changes, which we have already reviewed, there are those others, very conspicuous and somewhat known to us all, which we gather together under the comprehensive term of growth. It is grt)wth which I shall ask you to study with me this evening, and I shall hope, by the aid of our study, to reinforce in your minds the conclusion which I have already indicated, that the early period of life is a period of rapid decline, and that the late period of life is one of slow decline. In order to study growth accurately, it is desirable, of course, to measure it, but since we are concerned with the general problem of growth, we wish no partial measure, such as that of the height alone would be. And indeed, if we take any such partial measure, how could we compare different forms with one another? The height of a horse is not comparable to that of a man; the height of a caterpillar is not comparable to that of any vertebrate. Katurally, therefore, we take to measuring the weight, which represents the total mass of the living body, and enables us at least with some degree of accuracy to compare animals of different sorts with one another. Now in studying this question of the increase of weight in animals, as their age in- creases, it is obviously desirable to eliminate from our experiments all disturbing factors which might affect the rate of growth or cause it to assume irregularities which are not inherent either in the organiza- 194 POPULAR SCIENCE MONTHLY tion of the animal or in the changes age produces. The animals which belong to the vertebrate sub-kingdom, of which we ourselves are mem- bers, can be grouped in two large divisions according to the natural temperature of their bodies. The lower vertebrates, the fishes, frogs and their kin, are animals which depend for their body temperature more or less on the medium in which they live. The other division of vertebrate animals, which includes all the higher forms, are so organized that they have within certain limits the power of regulating their own body temperature. Now it is easily to be observed — and any one who has made observations upon the growth of animals can confirm this — that animals otherwise alike will grow at different speeds at different temperatures. There are animals, like the frogs and salamanders, which will live at a very considerable range of tem- perature and thrive, ap- parently. No ultimate in- Jury is done to them by a change of their bodily tem- perature. Here we have a picture of four young tad- poles, all of which are ex- actly three days old. The first of these has been kept at a temperature not much above freezing. The fourth, at a temperature of about 24 degrees centigrade; the other two at temperatures Pig. 19. Four Tadpoles of the Eukopean Prog, , , rr>v, n A Rana fusca. After OskarHertwig. The four animals between. i hey are aii QC- are all of the same age (three days) and raised from the sCCndants from the Same same batch of eggs, but have been kept at different tern- , , n « ^ , -, peratares. oatch of frogs cggs, and yl at 11.5° Centigrade. £ at 15.0° Centigrade. you Can SCC readily that C " 20.0° " D " 24.0° " • . n , • ,-n the first one is still essentially nothing but an egg. The second one, which has had a little higher temperature, already shows some traces of organization, and those familiar with the development of these animals can see in the markings upon the surface the first indications of the differentia- tion of the nervous system. The third has been kept at a considerably warmer temperature, and is now obviously a young tadpole; here are the eyes, the rudimentary gills, the tail, etc. While the fourth tadpole, which was maintained at the best temperature for the growth of these animals, has advanced enormously in its development. Obviously, should we make .experiments upon animals of this class it would be AGE, GROWTH AND DEATH 195 necessary to keep them at a uniform temperature, if we wished to study their rate of development, and that is, for very practical reasons, extremely difficult and unsatisfactory. Far better it has seemed for our study of growth to turn to those animals which regulate their own temperature. This, accordingly, I have done, and the animal chosen for these studies was the guinea-pig, a creature which offers for such investigations certain definite advantages. It is easily kept; it is apt to remain, with proper care, in good health. Its food is obtainable at (/yi, 64 63 50 58 56 54 52 50 48 46 44 42 40 - ^,_H -^ VJlim Uo. 140 ISO 120 110 100 90 80 70 60 50 40 /Jc yy / Qvqi/i' ai W% Pe/ucvU 3'e/>-yi42l&-T~T J^eA^^jzCZ 4 5 6 7 8 9 10 II 12 13 14 15 16 l7 18 19 2Q 21 Zl 23 24 25 FlO. 24. CUUVE SHOWING THE LENGTH OF TiME RFXiUIRED TO MAKE EACH SUCCESSIVE INCKEAHE OF 10 PER CENT. IN WEIGHT BY FEMALE GUINEA-l'IGS. 200 POPULAR SCIENCE MONTHLY form of representation of this same phenomenon as it occurs in the human subject. Here is a diagram of growth, which represents, as accurately as I could determine it, the curve complete for man from the date of birth up to the age of forty years. It has been calculated by a simple mathematical process where these ten-per-cent. increments fall, and from each point in this curve where there has been such an increment, a vertical line has been drawn, as you see here. These lines are very close together at the start. One ten per cent, after another follows in a short interval of time, but gradually the time, as indicated by the space between two of these vertical lines, increases, and when the individual is three years old, you can see there has been a very great 2^'' ^^{''^ iiyrs 30 125.02 lbs. iZO / /i / lOO iZyrs / / BO 60 'r A / / 20 48.20 lbs. / / 40 '''' ^ y 15 / / 20 10 A x -A 11 Fig. 25. Curve showing the Growth of Man from Birth to^Maturity, with vertica Uaes added to mark the duration ot the periods, for each 10 per cent, addition to the weight. lengthening out of the period which is necessary for it to add ten per cent, to its weight. Then it comes at the age of twelve to a period of slightly more rapid growth, a fluctuation which is characteristic of man, but does not appear in the majority of animals. After that comes very rapidly the enormous lengthening of the period; and I have not added the last ten per cent, because the curve here at the top, you see, is not very regular, and it could not be calculated with certainty. Our diagram is merely another form of graphic representation of the fact that the older we are the longer it takes us to grow a definite proportional amount. The next slide carries us into another part of our study, away from the mammals which we have thus far considered, into the class of birds. The growth of chickens is represented here. Now a chicken is born in a less matured state than a guinea-pig, and has a good deal AGE, GROWTH AND DEATH 20I 03f8 13 i82i 283338 « S6 66 '7 90 '06 Fig. 26J Curve showing the Daily Percentage Increments in Weight BY Male Chickens. higher efficiency of growth at first. In a chicken, as in a guinea-pig, birth is a disturbing factor, and growth immediately after the hatching of the chicken is a little impeded, but the chick quickly recovers and, as we see, the first time when the rate can be distinctly measured we get a nine-per-cent. addition to the weight in a single day. In a chicken as in the guinea-pig, the rate gradually diminishes. The change from the rapid decline at first to the later slower decline is more gradual ; the curve is more distinctly marked in the chicken as a round curve. There is not in the bird so marked a separation of the preliminary rapid de- cline and the later slower decline as we find in the guinea-pig. The curve again is very irregular because I had only a very limited number of observations upon the weight of chicks. The other sex, as the next slide will show, presents similar phenomena, though the female chickens do not grow quite as fast as their brothers. Here we notice an increase ■^1 A PeAcsm^yt^ J-naU'rm/n/a CAccA^ •J'e'ryiaAd \ m \ \^ \ _ y / \ N -^ ^ ~~ ■ — r 1 OMa 1313222833^6 4« 56 66 '- 90 106 laUi^j^ Fig. 27. CuEVK showing the daily Percentage Increments in Weight BY Female Chickens. 202 POPULAR SCIENCE MONTHLY of almost, but not quite nine per cent., rapidly falling down so that after the chick is two months old it never adds as much as three per cent, to its weight. It loses in the first two months from a capacity to add nine per cent., down to a capacity of adding less than three. It loses in two months two thirds of its total power of growth, for from nine to zero is divisible into two parts, of which the first, from nine down to three, would be two thirds, and the second, from three to zero, would be one third. Here then we learn that two thirds of the decline which occurs in the life of a chick takes place in two months, and for the rest of the life of the bird there is a decline of one third. That, you must acknowledge, is an extraordinary and most impressive difference. If it be true that the more rapid growth depends upon the youth of the individual, — its small distance in time from its procreation, then we may perhaps, by turning to other animals which are born in a more immature state, get some further insight into these changes; and that I have attempted to do by my observations upon the development of rabbits, Eabbits, as you know, are born in an exceedingly immature state. They are blind, they are naked, they are almost incapable of definite movements, quite incapable of locomotion, and are hardly more than little imperfect creatures lying in the nest and dependent utterly upon the care of the mother, quite unable to do anything for them- selves except take the milk which is their nourishment. They are in- deed animals born in a much less advanced stage than are the guinea- pigs. Upon the screen we see this interesting result demonstrated to us, that a male rabbit, the fourth day after its birth, is able to add over seventeen per cent, to its weight in one day. From that the curve drops down, as you see, with amazing rapidity, so that here at an age of twenty-three days the rabbit is no longer able to add nearly eighteen per cent, daily, but only a little over six. At the end of two months from its birth, the growth power of the rabbit has dropped to less than two per cent., and at two months and a half it has dropped to one. The drop in two and a half months has been from nearly eighteen per cent, down to one per cent., and the rest of the loss of one per cent, is extended over the remaining growing period of the rabbit. Could we have a more definite and certain demonstration of the fact that the decline is most rapid in the young, most slow in the old? It is not in this case any more than in the others the one sex that demonstrates this fact, for in the female we find exactly the same phenomena, as the next slide will show. The irregularities are not significant. The strange dip at thirty-eight days, for instance, corresponds to an illness of some of the rabbits which were measured, but they rapidly recovered from it and grew up to be fine, nice rabbits. If instead of measuring half a dozen rabbits, we had measured two hundred or five hundred, these irregularities would certainly have disappeared. The females in the case of the rabbits, as in the case of the guinea-pigs, are not able AGE, GROWTH AND DEATH 203 PcAce/nJcu^ Jnot^e^ne^o^ytj J2aMv^ rriaA^ 03 8 13 1833 ?8 33 38 55 77| 1O64 iSOoizy^ Fig. 28. CCRVE SHOWING THE DAILY PERCENTAGE INCKEMENTS IN WEIGHT BY Male Rabbits. to grow quite so fast at first. We see here sixteen instead of over seven- teen per cent, as the initial value, but the general character of the drop is the same, enormously rapid at first and very slow afterwards. All of our cases, then, show the same fundamental phenomena appearing with different values. Xow in regard to man, we do not possess any such adequate series of statistics of growth as is desirable. We have many records of tlie weight of babies, by which I mean children from the date of birth up to one year of age. We have also very numerous records of school children, which will extend perhaps from five and one half up to say seventeen, eighteen or even nineteen years. There are records of boys 2 04 POPULAR SCIENCE MONTHLY Fig. 29. Curve showing the Daily Peecentagk Increments in Weight BY Female Rabbits. at universities, and a still more limited number of weighings of girls at colleges. But all these statistics piled together do not give us one comprehensive set of data including all ages. This is very much to be regretted, and it would be an important addition to our scientific knowl- edge could statistics of the growth of man be gathered with due precau- tions. It would fill one of the gaps in our knowledge which is lament- able. We have, however, some rough, imperfect data which for our present purposes it seems to me are adequate, and the results of the study of these will be shown by the next series of pictures. But let us pause for a moment to consider this singular table. It shows in this column the number of days which it takes for each species ^ AGE, GROWTH AND DEATH 205 Table^ Days Needed to Double Weight 100 Parts Mother's Milk Contain Species Proteid Ash Lime Phosphoric Acid Man Horse Cow Goat Pig Sheep Cat Dog Eabbit 180 60 47 19 18 10 9^ 8 7 1.6 2.0 3.5 4.3 5.9 6.5 7.0 7.3 10.4 0.2 0.4 0.7 0.8 0.9 1.0 1.3 2.4 0.0328 0.124 0.160 0.210 0.272 0.453 0.8914 0.0473 0.131 0.197 0.322 0.412 0.493 0.9967 of animal indicated at the left to double its weight after birth. A man requires 180 days to double his weight; a horse, 60; a cow, 47; a goat, 19; a pig, 18; a sheep, 10; a cat, 9I/2; a dog, 8; a rabbit, 6 (or possibly 7 days). Now here are analyses of the milk. The main point of interest is to be found in the figures in this column, which represent the amount of albuminoid, or proteid material contained in the milk. You will observe that for man the proportion is lowest, 1.6 per hundred parts; the horse has a little more — 2; cattle — 3.5; and so the values run. In other words, it is obvious that the less the proteid in the milk, the longer does the species require to double its weight. This looks at first sight as if there were a relation between the composition of the milk and the period of growth of the animal; but you know very well that if you take the milk of a cow, which is very much richer in proteid material, and feed it to a baby, a human baby, that baby does not grow at the same rate as the young cow, but grows at the human rate. It is obvious, therefore, that it is somewhat more complicated than a mere question of food supply. We have in fact one of the beautiful illustrations of the teleological mechanism of the body. These various species have their characteristic rates of growth, and by an exquisite adaptation, the composition of the mother's milk has become such that it supplies the young of the species each with the proper quantum of proteid material which is needed for the rate of growth that the young offspring is capable of. It is a beautiful adjust- ment, but there is not a causal relation between proteid matter and this rate of growth. It is an example of correlation, not of causation. We pass now to the next of our slides, which carries us over into the study of our own species. It is not possible at the present time to represent in any form of curve which I have seen the daily percentages of increment for man covering the whole period of growth. In order to get the results together, I have confined myself here to the repre- sentation of the yearly percentages. Now from the age of zero to the age of one year, you see according to this table a child is able to in- crease its weight 200 per cent. But from the beginning of the first to * After Abdcrhalden, Zeitschrift fiir Physiologische Chemie, Band XXVI., p. 497. 2o6 POPULAR SCIENCE MONTHLY 200% [00% 20% 10% ^"^y_^^_^ / ^ \ 1 1 r ^tt>--^ YEfiRS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Fig. 30. 20p% 20% 10% \ Je •-^ - '^^^'ii 'W'"'-^ -'^'- ^"^ t-s^" € ^^kS^i^'^'^'"^ 13 Fig. 40. Three Sections through a Rabbit Embryo of Seven and One Half Days. each has its own nucleus, and each its own protoplasm. Xotice here that the two cells which finally result are smaller than the original cells from which they sprang. These are by no means imaginary pictures, but accurate microscopic drawings from real cells of the salamander skin. The two cells which are thus produced from one parent cell are characterized by their smaller size, and this smaller size applies not only to the cell as a whole, but likewise to its nucleus. After having been thus reduced in size, the nuclei and the cells will both expand, and soon the daughter cells will return to the mother dimension and be as large as the parent cell from the division of which 362 POPULAR SCIENCE MONTHLY Fig. 41. ^OTce6a ro/t, HIGHLY magnified. Drawn from a cover-glass preparation Irom a twenty-four hour culture. they arose. There is thus, we learn, the constant fluctuation in the size of cells, a fluctuation in their dimensions accompanying the process of cell division. Presently we shall have more to say in regard to this matter of the change in the cell in size. The next picture (Fig. 40) which I want to recall to you is one which we also had in an earlier lecture. These represent slices through a very young rabbit before any of the organs of the rabbit have begun to develop. We can see here clearly the nuclei, as I pointed out to you before, nearly uniform in structure, and you notice that the protoplasm around each nucleus is quite small in amount. If you will re- call the previous picture of the skin of the salamander, upon the screen a moment \ . Fig. 43. rrypanosoma Lewisi, from blood with two blood corpuscles alongside the same scale. KiG. 42. Tekttan Malarial Parasite. Two huiDfin blood corpuscles alongside and drawn on the same scale. ago, you will realize imme- diately, in comparing the two, that in these young cells the proportion of the proto- plasm to the nucleus is very small. That is again one of the fundamental facts to which we shall recur in a moment. I wanted to show you this picture in order to revive in your minds the con- ception which I endeavored to give you before of the undifferentiated tissue, where the cells have nuclei pretty the rat's drawn on AGE, GROWTH AND DEATH 363 uniform in appearance and in size, each with its little mass of proto- plasm about it, and this protoplasm appearing in all the cells under microscopic examination very much the same. We can not in this stage of development say of a given cell that it represents any special structure, by which, if we saw it isolated under the microscope, we could determine from what part of the young embryonic body it was derived. When we see a cell from the adult we can determine its origin with certainty by its microscopic appearance alone. As devel- opment progresses, the simple condition of the cells is gradually oblit- erated, but we find another condition arising which we call the differ- entiated one. Differentiation is a process which goes on in the body as a whole, but of course it is also a function of each individual cell. We can see something of the process of differentiation if we study the unicellular organisms, those creatures, each of which is complete in itself, although it consists of but a single cell, not of countless millions of cells as we do. The picture (Fig. 41) which I have chosen to throw upon the screen is one which I think might have an additional interest to you, for it is a photograph from the living cell known as the para- site producing dysentery. Its scientific name is amoeba coli. It is a photograph from life. Here vaguely in the center, marked with a finer granulation, and some of the darker spots in it, we can distin- guish the nucleus : here is the outline of the protoplasm of this cell, and in it are included some particles of food which this protoplasmic body has absorbed for purposes of digestion. This is a unicellular parasitic organism with scarcely any differentiation of its structure. The next of the slides shows us again another of these parasitic simple organisms. The figure here to the right of the field of view is the one which should especially attract your attention. The other two bodies near it are blood corpuscles, human blood corpuscles. The organism in this case is the one which causes malarial fever, and it is in a particular stage of its development; that which we distinguish as the tertian malarial parasite is the one here represented. You can see in this case also the outline of the nucleus, surrounded by the protoplasm — the whole thing only a little bigger than a single human blood corpuscle. Here also we note the absence of differentiation. Another stage of this same tertian malarial parasite is shown next. This I have projected upon the screen because it illustrates more clearly than the other the nucleus and the small amount of protoplasm about the nucleus. The malarial organism is one of great vitality, capable of enormously rapid multiplication, and it undoubtedly owes that faculty to its constitution, to the relation between the nucleus and the protoplasm. I will now show you another picture of parasites — one form of which, in a related species, occurs in man. This particular form is one which occurs in the rat and is called the Trypanosoma. You can see that the body, instead of being a small and sirnj)le struc- 364 POPULAR SCIENCE MONTHLY ture^ has elongated, acquired a peculiar form, and here in the interior are lighter and darker spots. These do not show very clearly in the picture, because it is from a photograph of a living specimen under the microscope. The lighter and darker spots correspond to the de- tails in the structure of the organism. Here is the tail of the organism, twisted, as you see, and in life capable of being bent. The movement of the animals in the natural fluid in which they are suspended is quite active. Alongside are some blood corpuscles, the figure, as you see, is magnified about the same as the one of the malarial parasite which I showed you a few moments ago. The next slide exhibits an B i Fig. ,44. Stenior coeruleus ^, cut into three pieces ; i?, regeneration of the first piece; C, of the middle piece ; D, of the posterior piece. After Gruber." organism which swims free in the water, and is pretty M^ell shown in this figure. It is called the Stenior. Here the chain of beads repre- sents the nucleus. Upon the surface of the body there are fine lines indicating superficial structure. At this point there occurs what we call the mouth. Over the rest of this minute organism there is a thin cuticle, but at the mouth the cuticle is absent, and the protoplasm is naked or uncovered so that food can be taken in. There are bands of hairs showing coarse and stiff in the figure but capable of movement, and with the aid of those vibratile hairs, or cilia, the organism can swim about in water. Here is another internal structure, the vacuole ; obviously in an animal like this we no longer have simple protoplasm AGE, GROWTH AND DEATH 365 alone, but the protoplasm in the interior of the cell has become in part changed into other things. Here then within the territory of a single cell Ave have differentiation. If now in these unicellular organisms we study both the protoplasm and the nucleus, we learn that most of these modifications which are so conspicuous upon microscopic observa- tion are due to changes in the protoplasm. It is the protoplasm which acquires a new structure. In the nucleus, on the contrary, we find perhaps a change of form, minor details of arrangement by which one sort of nucleus, or one stage of the nucleus, can be distinguished from another, but always the nucleus consists of the same fundamental constants. There is the membrane bounding it ; there is the sap or juice in the interior; the network of living threads stretching across it; and here and there imbedded in and connected with this network are the granules of special substance, which we call chromatin. These four things exist in the nuclei and are apparently always present, and there is usually not to be seen in the nucleus anything of change com- parable, in extent at least, with the change which goes on in the proto- plasm — on the other hand, the protoplasm acquires items of structure which were totally absent from it before. The nucleus rearranges its parts rather than changes them. This is a very important fact, and shows us, if we confine our attention even to these little organisms only, that the differentiation of the protoplasm is quant iiatively the more important of the two — the differentiation of the nucleus the less important. We can now turn from a consideration of these lowest organisms to the higher forms, among which we ourselves of course are counted, in which the body is formed by a very considerable number of cells. Again I should like to take advantage of your kindness and show you some of the pictures we have already reviewed, in order to utilize the features which they show as illustrations of the fundamental principle that the conspicuous change is in the protoplasm. Here we have nerve cells. In the first two photographs are represented two isolated nerve cells, to show their shape. They have been colored by a special process so dark that the nucleus which they contain in their interior is hidden from our view; it is of course none the less there. This dark stain- ing enables us to trace out the shape of these cells very clearly, and you can see that instead of being round and simple in form they have their elongated processes stretching out to a very considerable dis- tance; these processes serve to catch up from remote places nervous impulses and carry them into the body of the cell, and thus assist in the work of nervous transmission. The elongation of these threads is, as you see, adapted, like tlie elongation of a wire, to long-distance communication. Here are two other figures which represent nerve cells treated by a different process, and again artificially colored. But the color in this case has attacked certain spots in the protoplasm, z(>^ POPULAR SCIENCE MONTHLY consequent!}^ we see that the protoplasm around the nucleus in both of these tigures is no longer simple and uniform, but contains these deposits of dark-colored material. Here are other nerve cells; the one lig.l. pM^' mi '0 bif & © ^^l. p Fig. 4. %i Fig. Fig./J. Fig. 46. Various Kinds of Human Nerve Cells. After Sobotta. in the center shows you the accumulation of pigmented matter in the protoplasm; again an index of a change and lack of the previous uni- AGE, GROWTH AND DEATH 367 formity replaced by diversity in the composition of the various parts of the single cell. This' figure shows us more clearly the principle of structure of a nerve cell, for here we have the central body of the cell composed of protoplasm with its nucleus in the middle and a small spot in the center of the nucleus, and these long branching processes running out in all directions which can take up nerve im- pulses from other similar or dissimilar cells, as the case may be, and carry them to the central body. To carry the message out there is typically but one process, which is different in appearance from the other processes which carry the impulses in. The latter are branching and are therefore called the tree-like or dendritic processes. Here is a single process like a long thread to carry the impulses away, and which t*- — 'l^- MM».Mi;PARATIVE ANATOMY, HARVARD MEDICAL SCHOOI, VI. The Four Laws of Age Ladies and Gentlemen: I have referred in these lectures repeatedly to the cell and its two component parts, the nucleus and the proto- plasm. To-night I shall have only a few references to make directly to these, and shall pass on for the latter part of the hour to another class of considerations bearing upon the problem of age. Before we turn to these new considerations, however, I wish to say a few words by way of recapitulation concerning the changes in the cells as corre- sponding to age. Cells, as you know from what I have told you, undergo in the body for the greater part a progressive change which we call their differentiation. We may say that there are four kinds of cells for purposes of an elementary classification to be used in a simple exposition like the present. The first kind are those cells of the young type, in which the protoplasm is simple, and shows as yet no trace of differentiation. These cells are capable of rapid multipli- cation, and some of them are found still persisting in various parts of the adult body, and serve to maintain the growth of the body in its mature stage. Another class of cells presents to us the curious spectacle of a partial differentiation; such are the muscle fibers by which we accomplish our voluntary movements. These fibers consisted originally only of protoplasm with the appropriate nuclei, but, as they are differen- tiated, part of the protoplasm changes into contractile substance. Another part remains pure protoplasm unaltered. If now the mus- cular or contractile portion of the fiber be destroyed, the undifferen- tiated part of the protoplasm then shows that it has still the power of growth. It has only been held back by the condition of organization, and we see in the regeneration of these fibers evidence of the fact that so long as the protoplasm is undifferentiated it has the power of growth, which, however, does not reveal itself unless an opportunity is afforded. Third, we come to the cells which are moderately differen- tiated; such, for instance, are the cells of the liver, and, if for any reason a portion of the liver be injured by accident or disease, we find that these partially differentiated cells reveal at once that they have a limited power of growth still left. If we pass on to the fourth class, that in which differentiation is carried to the highest extreme, we find that the cells do not have the power of multiplication. Such aref the 5IO POPULAR SCIENCE MONTHLY ^ nerve cells by which the higher functions of the body are carried on. They represent the extreme of cellular differentiation, and almost never do we see these cells multiplying after the differentiation is accom- plished. Presented in this form, we then recognize, it seems to me clearly, the effect of differentiation upon the growth of cells. The facts are clear as to their meaning. We can, however, proceed a little farther than this, because we can actually determine, approximately at least, the rate at which cells mul- tiply, and that we can do by means of determining the mitotic index. The mitotic index is the number of cells to be found at any given moment in the active jDrocess of division out of a total of one thousand cells. May I pause a moment to recall this picture to you and ask you to notice at this point the curious darker spot which represents a nucleus in process of division ? You will see it would _^^ be easy in such a preparation as this to count the nuclei one by one until one had got up to a thousand, and to record, as one went along, how many of the nuclei are in process of divi- sion, for the nucleus in division is easily recog- nized. This process of division is named mitosis : the figure which the nucleus presents while it is undergoing division we call a mi- totic figure. Counting the dividing nuclei, we may determine that in a thousand cells there are a given number which have nuclei in proc- ess of division, and such a number I propose to call " the mitotic index." I wish now only to call to you attention this picture because it enables me to illustrate before 5^ou the method of measuring the mitotic index. In the rabbit embryo at seven and one half days, I have found by actual count that there are in the outer layer of cells, known techni- cally as the ectoderm, 18 of these divisions per thousand. In the middle layer, technically the mesoderm, 17, and in the inner layer, the ento- derm, 18. At ten days we find the number al- ready reduced, and the figures are, respectively, 14, 13 and 15, and for the cells of the blood only 10. There has already been a great reduction. In the next phase of development (rabbit embryo of thirteen daysj, we find, however, that the parts are growing irregularly, some faster, some slower. We note that wherever a trace of differentiation has occurred, the rate of growth is diminished : where that differentiation does, not show itself, the Fig. 61. Portion of the Outer Wall of a Primitive Muscular Segment of a Cat Embryo op 4.6 mm. Harvard Embryological Collection Series 398, section 115. Ttie resting nuclei are oval, pale and granular. The dividing or mitotic nuclei, of which there are three, are dark, ir- regular in outline and show the chromosomes. In this case the dividing nuclei all lie near the inner surface of the wall. The picture illu- strates the ease with which mitotic figures may be recog- nized. AGE, GROWTH AND DEATH 511 rate of growth may even increase in order to acquire a certain special de- velopment of a particular part. So that instead of uniformity of values for the mitotic index, we get a great variety. But, nevertheless, the general decline can be demonstrated by the figures. In the spinal cord the index is 11, in the general connective tissue of the body 10; for the cells of the liver 11 ; in the outside layer of the skin 10; in the excretory organ 6 ; in the tissue which forms the center of the limb also 6. There has, then, been a rapid decline in the rate of cell multiplication just in this period when differentiation is going on. This is, so far as I know, an entirely new line of research. The counting of a thousand cells is not a thing to be done very rapidly ; it must be undertaken with patience, care, and requires time. It has not, I regret to say, been possible for me yet to extend the number of these counts beyond those I have given you, but it is easy to say that in the yet more differentiated state, the number of cells in division is constantly lessened, and it is only a ques- tion of counting to determine the mitotic index accurately. That there is a further diminution beyond that which the mitotic indices I have demonstrated to you represent is perfectly certain. I only regret that I am not able to give you exact numerical values. I wish very much that my time permitted me to branch off into certain topics intimately associated with the general theme we have been considering together on these successive evenings, but we can only allude to a few of these. The first collateral subject on which I wish to speak to you briefly is that which we call the law of genetic restric- tion, which means that after a cell has progressed and is differentiated a certain distance, its fate is by so much determined. It may from that pass on, turn in one direction or another, always progressing, going onward in its cytomorphosis ; but the general direction has been pre- scribed, and the possibilities of that cell as it progresses in its develop- ment become more and more restricted. For instance, the cells which are set apart to form the central nervous system after they are so set apart can not form any other kind of tissue. After the nervous system is separated in the progress of development from the rest of the body, its cells may become either nerve cells proper or supporting cells (neuroglia), which latter never acquire the nervous character proper, but serve to uphold and keep in place the true nervous elements. They represent the skeleton of the central nervous system. After the cells of the nervous system are separated into these two fundamental classes they can not change. A cell forming a part of the supporting frame- work of the brain can not become a nerve cell ; and a nerve cell can not become a supporting cell. The destiny of them becomes more and more fixed, their future possibilities more and more limited, as their cytomorphosis goes on. The law of genetic restriction has a very important bearing upon questions of disease. When disease occurs, the cells of the body offer 512 POPULAR SCIENCE MONTHLY to us two kinds of spectacles. Sometimes we see that the cells causing the diseased condition are more or less of the sort which naturally be- long in the body; that they are present where they do not belong, or they are present where they ought to be, but in excessive quantity. There is a kind of tumor which we call a bony tumor. It consists of bone cells such as are naturally present in the body, but that which makes this growth of bone a tumor is its abnormal dimensions, or per- haps its being altogether in the wrong place. The second sort of pathological alteration, which I had in mind, is that in which the cells really change their character. ISTow, the young cells are those which can change most; in which the genetic restriction has least come into play ; and accordingly we find that a large number of dangerous, morbid growths, tumors, arise from cells of the young type, and these cells, having an extreme power of multiplication, grow rapidly, and they may assume a special character of their own; their genetic restriction has not gone so far that all their possibilities of change in the way of differ- entiation have been fixed; there is a certain range of possibilities still open to them, and they may turn in one direction or the other. Hence there may be pathological growths of a character not normally present in the body. It seems to me, so far as my knowledge of this subject enables me to judge, to be true that all such pathological growths de- pend ujDon the presence of comparatively young and undifferentiated cells being turned into a new direction. The problem of normal development and of abnormal structure is one and the same. Both the embryologist and the anatomist, on the one hand, and the pathologist and the clinician on the other, deal ever with these questions of differ- entiation, and practically with no others. All that occurs in the body is the result of various differentiations, and whether we call the state of that body normal or pathological matters little; still the cause of it is the differentiation of the parts. The second of the collateral topics which I should like briefly to allude to is another branch of the study of senescence. The fact was first emphasized by the late Professor Alpheus Hyatt that in many animals there exist parts formed in an early stage and thereafter never lost. The chambered nautilus is an animal of this kind. The inner- most chamber represents the youngest shell of the nautilus, and as its age increases, it forms a new chamber in its shell, and so yet more and more until the coil is complete. When we examine a shell of that kind we see permanently before us the various stages, both young and old, as recorded in shell formation. And so too in the sea-urchin, and in many of the common shell-fish, we find the double record, of youth and old age, preserved permanently. This has made it possible for Pro- fessor Hyatt and for Professor Eobert T. Jackson, who has adopted a similar guiding principle, to bring a great deal of new light into the study of animal changes, and to attack the solution of problems which AGE, GROWTH AND DEATH 513 without the aid of this senescent interpretation, if I may so term it, would be utterly impossible. This is an enticing subject, and I wish I had both time and competency to dwell upon it. But it is aside, as you see, from the main inquiries with which we have been occupied, for our inquiries concern chiefly the effect of cell-change upon the properties of the body, and the correlation of cell-change with age. A natural branch of our topic is, however, that of longevity, the duration of life. Concerning this, we have very little that is scien- tifically satisfactory that we can present. We know, of course, as a fundamental principle, that every animal must live long enough to reproduce its kind. Did that not occur, the species would of course become extinct, and the mere fact that the species is existing proves, of course, this simple fact — that life has lasted long enough for the parents to produce offspring. The consideration of this fact has led certain naturalists to the supposition that reproduction is the cause of their termination of life; but it is not, it seems to me, at all to be so interpreted. We know, in a general way, that large animals live longer than small ones. The elephant is longer lived than the horse, the horse than the mouse, the whale than the fish, the fish than the insect, and so on through innumerable other instances. At first this seems a promising clue, but if we think a moment longer we recognize quickly the fact that a parrot, which is much smaller than a dog, may live one hundred years, whereas a dog is very old at twenty. There are insects which live for many years, like the seventeen-year locusts, and others which live but a single year or a fraction even of one year, and yet the long-lived and the short-lived may be of the same size. It is evident, therefore, that size is not in itself properly a measure of the length of life. Another supposition, which at first sounds very attract- ive, is that which explains the duration of life by the rate of wear, of the using up, of the wearing out, of the body. This theory has been particularly put forward by Professor Weismann, who in his writings calls it the AhnutzungstJieorie — the theory of the wearing out of the body. But the body does not really wear out in that sense. It goes on performing the functions for a long time, and after each function is performed the body is restored, and we do not find at death that the parts have worn out. But, as we have seen, we do find at death that there has been an extensive cytomorphosis, cell-change, and that the living material, after having acquired its differentiation, passes now in one part, now in another, then in a third, to a yet further stage, that of degeneration, and the result of degeneration, or atrophy, as the case may be, is that the living protoplasm lofees its living quality and be- comes dead material, and necessarily the functional activity ceases. We must, it seems to me, conclude that longevity, the duration of life, depends upon the rate of cytomorphosis. If that cytomorphosis ia 514 POPULAR SCIENCE MONTHLY rapid, the fatal condition is reached soon; if it is slow, the fatal condi- tion is postponed. And cytoniorphosis in various species and kinds of animals must proceed at different rates and at different speeds at different ages. Birds grow up rapidly during their period of develop- ment; the cell change occurs at a high speed, far higher than that which occurs in man, probably, during his period of development. But after the bird has acquired its mature development, it goes on almost upon a level for a long time ; the bird which becomes mature in a single year may live for a hundred or even more. There can be during these hundred years but a very slow rate of change. But in a mammal, a dog or a cat, creatures of about the same bulk as some large birds, we find that the early development is at a slower rate. The animals take a much longer period to pass through their infancy and reach their maturity, but after they have reached their maturity they do not sustain themselves so long. Their later cytomorphosis occurs at a higher speed than the bird's. This is a field of study which we can only recognize the existence of at present, and which needs to be ex- plored before, to any general, or even to a special scientific, audience, any promising hypotheses can be presented. Definite conclusions are of course still more remote. Next as regards death. The body begins its development from a single cell, the number of cells rapidly increase, and they go on and on increasing through many years. Their whole succession we may appropriately call a cycle. Each of our bodies represents a cell cycle. When we die, the cycle of cells gives out, and, as I have explained to you in a previous lecture, the death which occurs at the end of the natural period of life is the death which comes from the breaking down of some essential thing — some essential group of members of this cell cycle; and then the cycle is broken up. But the death is the result of changes which have been going on through the successive generations of cells making up this cycle. There are unicellular organ- isms; these also die; many of them, so far as we can now determine, never have any natural death, but there are probably others in which natural death may occur. It is evident that the death of a unicel- lular organism is comparable to the death of one cell in our own bodies. It is not properly comparable to the death of the whole body, to the ending-up of the cell cycle. Is there anything like a cell cycle among the lower organisms? among the protozoa, as the lowest animals are called ? It has been maintained by a French investigator, by the name of Maupas, that such a cycle does exist, that even in these low organisms there is a cell which begins the development, and that gradually the loss in the power of cell multiplication goes on until the cycle gives out and has to be renewed by a rejuvenescent process, and this rejuvenating process he thinks he has found in the so-called conjugating act of these animals, in which there occurs a curious migration of the nucleus of AGE, GROWTH AND DEATH 515 one individual into the cell body of another. Whether he is right or not remains still to be determined. You will recognize, I hope, from what I have said, that we have now some kind of measure of what con- stitutes old and young. We can observe the difference in the propor- tion of protoplasm and nucleus, the increase or diminution, as the case may be, of one or the other. If it be true that there is among protozoa, among unicellular animals, anything comparable to the gradual decline in the growth power which occurs in us, we shall expect it to be revealed in the condition of the cells — to see in those cells which are old an increase in the proportion of protoplasm, and consequently a diminution in the relative amount of nucleus. That subject is now being investigated, and we shall probably know, within a few years at least, something positive in this direction. At present we are reduced to posing our question. We must wait patiently for the answer. The scientific man has many occasions for patience. He has to make his investigations rather where he can than where he would like to. Certain things are accessible to our instruments and methods of research at the present time, but other things are entirely hidden from us and inaccessible at the present. We are indeed, more perhaps than people in any other profession of life, the slaves of opportunity. We must do what we can in the way of research, not always that which we should like most to do. Perhaps a time will come when many of the questions connected with the problems of growing old, which we can now put, will be answered, because opportunities, which we have not now, will exist then. Scientific research offers to its devotees some of the purest delights which life can bring. The investigator is a creator. Where there was nothing he brings forth something. Out of the void and the dark, he creates knowledge, and the knowledge which he gathers is not a precious thing for himself alone, but rather a treasure which by being shared grows; if it is given away it loses noth- ing of its value to the first discoverer, but acquires a different value and a greater usefulness that it adds to the total resources of the world. The time will come, I hope, when it will be generally understood that the investigators and thinkers of the world are those upon whom the world chiefly depends. I should like, indeed, to live to a time when it will be universally recognized that the military man and the govern- ment-maker are types, which have survived from a previous condition of civilization, not ours ; and when they will no longer be looked upon as the heroes of mankind. In that future time those persons who have really created our civilization will receive the recognition which is their due. Let these thoughts dwell long in your meditation, because it is a serious problem in all our civilization to-day how to secure due recognition of the value of thought and how to encourage it. I believe every word spoken in support of that great recognition which is due 5i6 POPULAR SCIENCE MONTHLY to the power of thought is a good word and will help forward toward good results. In all that I have said;, you will recognize that I have spoken con- stantly of the condition of the living material. If it is in the young state it has one set of capacities. If it is differentiated, it has, accord- ing to the nature of its differentiation, other kinds of capacities. We can follow the changing structure with the microscope. We can gain some knowledge of it by our present chemical methods. Fragmentary as that knowledge is, nevertheless, it suffices to show to us that the con- dition of the living material is essential and determines what the living material can do. I should like to insist for a moment upon this conception, because it is directly contrary to a conception of living material which has been widely prevalent in recent years, much de- fended and popularly presented on many different occasions. The other theory, the one to which I can not subscribe, may perhaps be most conveniently designated by the term — the theory of life units. It is held by the defenders of this faith that the living substance contains particles, very small in size, to which the vital properties are especially attached. They look at a cell and find that it has water, or water con- taining a small amount of salts in solution, filling up spaces between the threads of protoplasm. Water is not alive. They see in the protoplasm granules of one sort and another, in plants chlorophyll, in animals perhaps fat or some other material. That is not living sub- stance, and so they go striking out from their conception of the living material in the cell one after another of these component parts until they get down to something very small, which they regard as the life unit. I do not believe these life units exist. It seems to me that all these dead parts, as this theory terms them, are parts of the living cell. They are factors which enable the functions of life to go on. Other conditions are also there, and to no one of them does the quality of life properly attach itself. Of life units there is an appalling array. The most respectable of them, in my opinion, are the life units which were hypothetically created by Charles Darwin in his theory of pan- genesis. He assumed that there were small particles thrown off from different portions of the body circulating throughout the body, gather- ing sometimes in the germ cells. These particles he assumed to take up the qualities of the different parts of the body from which they emanated, and by gathering together in immense numbers in the germ cells they accomplished the hereditary transmission. We know now that this theory is not necessary, that it is not the correct theory. But at the time that Darwin promulgated it, it was a perfectly sound defensible theory, a theory which no one considering fairly the history of biological knowledge ought to criticize unfavorably. It was a fine mental achievement, but I should like also to add that of all the many theories of life units, this of Darwin's is the only one which seems to AGE, GROWTH AND DEATH 517 me intellectually entirely respectable. Of supposed structural life units there is a great variety. Besides the gemmules of Darwin, there were the physiological units of Herbert Spencer. Professor Haeckel, the famous German writer, has special structural life units of his own which he terms plastidules; he gave them the charming alliterative title of perigenesis of the plastidules; the rhythm of it must appeal to you all, though the hypothesis had better be forgotten. Then came Nageli, the great botanist, who spoke of the Idioplasma-Theilchen. Then Weisner, also a botanist, who spoke of the Plassomes. Our own Pro- fessor Whitman attributed to his life units certain other essential quali- ties and called them idiosomes. A German zoologist, Haacke, has called them gemmules. Another German writer, a Leipzig anatomist, Altmann, calls them granuli. Now these different life units, of which I have read you briefly the names, are not identical according to these authors. Everybody else's life units are wrong, falsely conceived, and endued with qualities which they do not combine. There is a curious assemblage here of doxies, and each writer is orthodox and all the others are heterodox; and I find myself viewing them all from the standpoint of my doxy, that of the structural quality of the living matter, and, therefore, interpreting every one of these conceptions as heterodox, not sound doctrine, but something to be rejected, condemned and fought against. These theories of life units have filled up many books. Among the most ardent defenders of the theory of life units is Professor Weismann, whose theories of heredity many of you have heard discussed ; though I doubt if many of you, imless you recall what I said previously, are aware of the fact that the essential part of Weismann's doctrine was the discovery of the theory of germinal con- tinuity by Professor Nussbaum, whose name is seldom heard in these discussions. Weismann has gone much farther in the elaboration of the conception of life units than any of the other writers. He thinks the smallest of the life units are biophores. A group of biophores brought together constitutes another order of life units which he calls determinants; the determinants are again grouped and form ids; and the ids are again grouped and form idants. If you want to accept any theory of life units, I advise you to accept that of Weismann, for it offers a large range for the imagination, and has a much more formidable number of terms than any other. I want to pass now to an utterly different line of study, the question of psychological development. If it be true that the development is most rapid at first, slower later, we should expect to find proof of that rate in the progress of mental development. In other words, wo should expect to find that the baby developed faster than the child mentally, that the child developed faster than the young man, and the young man faster than the old. And do you not all instinctively feel immediately that the general assertion is true? In order, however, that 5i8 POPULAR SCIENCE MONTHLY you may more fully appreciate what I believe to be the fact of mental development going on with diminishing rapidity, I should like to pic- ture to you briefly some of the things which the child achieves during the first year of its life. When the child is born, it is undoubtedly sup- plied with a series of the indispensable physiological functions, all those which are concerned with the taking in and utilising of food. The organs of digestion, assimilation, circulation and excretion are all functionally active at birth. The sense organs are also able to work. Sense of taste and of smell are doubtfully present. It is maintained that they are already active, but they do not show themselves except in response to very strong stimulation. Almost the only additional faculty which the child has is that of motion, but the motions of the new-born baby are perfectly irregular, accidental, purposeless, except the motions which are connected with the function of sucking, upon which the child depends for its nourishment. The instinct of sucking, the baby does have at birth. It might be described as almost the only equip- ment beyond the mere physiological working of its various organs. But at one month we find that this uninformed baby has made a series of important discoveries. It has learned that there are sensations, that they are interesting; it will attend to them. You all know how a baby of one month wall stare; the eyes will be fastened upon some bright and interesting object. At the end of a month the baby shows evidences of having ideas and bringing them into correlation, associa- tion, as one more correctly expresses it, because already after one month, when held in the proper position in the arms, it shows that it expects to be fed. There is, then, already evidence and trace of memory. At two months much more has been achieved. The baby evidently learns to expect things. It expects to be fed at certain times; it has made the great discovery of the existence of time. And it has made the discovery of the existence of space, for it will follow, to some extent, the bright light ; it will hold its head in a certain position to catch a sound appar- ently from one side; or to see in a certain direction. The sense of space and time in the baby's mind is, of course, very imperfect, doubt- less, at this time, but those two non-stuff realities about which the metaphysicians discuss so much, the two realities of existence which are not material, the baby at this time has discovered. Perhaps, had some great and wonderfully endowed person existed who preserved the memory of his own psychological history, of his development during babyhood, we should have been spared the gigantic efforts of the meta- physicians to explain how the notions of space and time arose. With- out knowing how, the baby has acquired them, and has already become a rudimentary metaphysician. We see, also, at the end of the third month, that the baby has made another remarkable discovery. It has found not merely that its muscles will contract and jerk and throw its parts about, which is doubtless earlier a great delight to it; but that AGE, GROWTH AND DEATH 519 the muscles can contract in such a way that the movement will be directed ; there is a coordination of the muscular movements. I should like to read to you just these three or four lines from Miss Shinn, who has given perhaps the best story of the development of a baby which has yet been written. This is not merely my opinion, but also the opinion of my psychological colleagues at Cambridge whom I consulted before venturing to express the idea before you, and I find that they take the view that Miss Shinn's book, which is charmingly written, is really done with such precision and understanding of the psychological problems involved that it may fairly be called the best of the books treating of the mental development of a baby. Miss Shinn says, re- ferring to the condition of the child at the end of two months — " Such is the mere life of vegetation the baby lived during the first two months ; no grown person ever experienced such an expansion of life — such a progress from power to power in that length of time." She is not thinking of senescence, as we have been thinking of it, but she makes precisely the assertion, which seems to me to be true, that the baby in two months has accomplished an amount of development which no adult is capable of. And now at three months we find another great discovery is made by the baby, that it is possible to bring the sensations which it receives into combination with the movements which it makes. It learns to coordinate its sensory impressions and its motor responses. We hardly realize what a great role this adjustment, between what our muscles can do and what our senses tell us, plays in our daily life. It is the fundamental thing in all our daily actions, and though by habit we perform it almost unconsciously, it is a thing most difficult to learn. Yet the baby has acquired the art, though he only gradually gets to be perfect in it. Again we see, at the end of the fourth month, that the baby begins to show some idea of another great principle — the idea that it can do something. It shows evidence of having purpose in what it does. Its movements are no longer purely accidental. At four months we find yet another equally astonishing addition to the achievements of this marvelous baby. He makes the amazing discovery that the two sides of an object are not separate things, but are parts of the same. When a face, for instance, disappears by a person's turning around, that face, to a baby of one month, probably simply vanishes, ceases to exist : but the baby at four months realizes that the face and the back of the head belong to the same object. He has acquired the idea of objects existing in the world around him. That is an enormous achievement, for this little baby has no instructor; he is finding out these things by his own unaided efforts. Then at five months begins the age of handling, when the baby feels of everything. It feels urgently of all the objects which it can get hold of and perhaps most of all of its own body. It is finding that it can touch its various parts and that when its hands and parts of its own body come in contact it has the double 520 POPULAR SCIENCE MONTHLY sensation, and learns to bring those together and thereby is manufactur- ing in its consciousness the conception of the ego, personal, individual existence, another great metaphysical notion. Descartes has said — Cogito, ergo sum — I think, therefore I am. The baby, if he had written in Descartes's place, would have said — " I feel, therefore I am." The first five months constitute the first period of the baby's development. Its powers are formed, and the foundations of knowledge have been laid. The second period is a period of amazing research, constant, uninter- rupted, untiring; renewed the instant the baby wakes up, and kept up until sleep again overtakes it. In the six months' baby we find already the notion of cause and effect. You see he is dealing mostly in meta- physical things, getting the fundamental concepts. That there is such an idea as cause and effect in the baby's mind is clearly shown by the progress of its adaptive intelligence. It evidently has now distinct purposes of its own. It shows clearly at this age also another thing which plays a constant and important role in our daily life. It has the consciousness of the possibilities of human intercourse ; it wants human companionship. And with that the baby's equipment to start upon life is pretty well established. It has discovered the material universe in which it lives, the succession of time, the nature of space, cause and effect, its own existence, its ego and its relationship with other in- dividuals of its own species. Do we get at any time in our life much beyond this? Not very much; we always use these things, which we learn in the first six months, as the foundation of all our thought. By eight months baby is upon the full career of experiment and ob- servation. Everything with which the baby comes in contact interests him. He looks at it, he seizes hold of it, tries to pull it to pieces, studies its texture, its tensile strength, and every other quality it pos- sesses. ISTot satisfied with that, he will turn and apply his tongue ^to it, putting it in his mouth for the purpose of finding out if it has any taste. In doing this, hour after hour, with unceasing zeal, never inter- rupted diligence, he rapidly gets acquainted with the world in which he is placed. At the same time he is making further experiments with his own body. He begins to tumble about; perhaps learns that it is possible to get from one place to another by rolling or creeping, and slowly he discovers the possibility of locomotion, which you know by the end of the year will have so far perfected itself that usually at twelve months the baby can walk. During this period of from five months to twelve the baby is engaged upon a career of original research, unaided much by anybody else, getting doubtless a little help and, of course, a great deal of protection, but really working chiefly by himself. How wonderful it all is ! Is any one of us capable of beginning at the moment we wake to carry on a new line of thought, a new series of studies, and to keep it up full swing, with unabated pace, all day long till we drop asleep ? Every baby does that every day. AGE, GROWTH AND DEATH 521 When we turn to the child who goes to school, behold how much that child has lost. It has difficulties with learning the alphabet. It struggles slowly through the Latin grammar, painfully with the subject of geometry, and the older it gets, the more difficult becomes the achievement of its study. The power of rapid learning, which the baby has, is clearly already lessened. The introduction of athletics affords a striking illustration of the decline of the learning power with the progressing years. When golf first came in it was considered an excellent game for the middle-aged; and you have all watched the middle-aged man play. He was so awk- ward, he could not do it. Day after day the man of forty, fifty, or even older, would go to the golf field, hoping each time to acquire a sure stroke, but never really acquiring it. The young man learned better, but the good golf players are those who begin as children, twelve and fourteen years of age, who in a few months become as expert and sure as their fathers wished to become, but could not. In bicycling it was the same. Eight lessons was considered the number necessary to teach the intelligent adult to ride a wheel. Three for a child of eight. And an indefinite number of lessons, ending in failure, for a person at seventy. It would have been scientifically interesting to have kept an exact record of the period of time which it took at each age to learn bicycling, but I think enough has been said to convince you that if we could acquire such a measure of psychological development as would enable us to express its rate in figures, we should be able to construct a curve like the curve which I showed you in the third lecture illustrating the decline in the rate of growth, and we should see that during the early years of life, the decline in the power of learning was extremely rapid, during childhood less rapid, during old age very slow. But the great part of the decline would occur during early years. Here we see the principle of stability, in maturity, which we see also illustrated in structure and growth. The mind acquires its devel- opment; it retains that development in the adult a long time. But surely there comes a period when the exercise of the mind is difficult. It requires a great effort to do something new and unaccustomed. A sense of fatigue overwhelms us. I believe that this principle of ps)'- chological development, paralleling the career of physical development, needs to be more considered in arranging our educational plans. For if it be true that the decline in the power of learning is most rapid at first, it is evident that we want to make as much use of the early years as possible — that the tendency, for instance, which has existed in many of our universities, to postpone the period of entrance into college, is biologically an erroneous tendency. It would be better to have the young man get to college earlier, graduate earlier, get into practical life or into the professional schools earlier, while the power of learning is greater. 522 POPULAR SCIENCE MONTHLY Do we not see^ in fact, that the new ideas are indeed for the most part the ideas of young people. As Dr. Osier, in that much-discussed remark of his, has said, the man of forty years is seldom the productive man. Dr. Osier also mentioned the amiable suggestion of Trollope in regard to men of sixty, which has been so extremely misrepresented in the newspaper discussions throughout the country, causing biologists much amusement. But I think that Dr. Osier probably took a far too amiable view of mankind, and that in reality the period when the learn- ing power is nearly obliterated is reached in most individuals very much earlier. As in every class of biological facts, there is here the principle of variation to be kept in mind. Men are not alike. The great majority of men lose the power of learning, doubtless some more and some less, we will say, at twenty-five years. Few men after twenty- five are able to learn much. They become day laborers, mechanics, clerks of a mechanical order. Others probably can go on somewhat longer, and obtain higher positions; and there are men who, with ex- treme variations in endowment, preserve the power of active and orig- inal thought far on into life. These of course are the exceptional men, the great men. We have lingered so long together studying phenomena of growth, that it is natural to allude to one more, which is as singular as it is interesting, namely, the increase in size of Americans. It was first demonstrated by Dr. Benjamin A. Gould in his volume of statistics derived from the records of the Sanitary Commission — a volume which still remains the classic and model of anthropometric research. Any one, however, can observe that the younger generation of to-day tends conspicuously to surpass its parents in stature and physical develop- ment. How to explain the remarkable improvement we do not know. Our discovery of the fact that the very earliest growth is so enormously rapid, makes that earliest period especially important. If the initial growth can be favored a better subsequent development presumably would result. In brief, I find myself led to the hypothesis that the better health of the mothers secures improved nourishment in the early stages of the offspring, and that the maternal vigor is at least one important immediate cause of the physical betterment of the children. Much is said about the degeneracy of the American race, but the con- trary is true — ^the American race surpasses its European congeners in physical development. You will naturally wish to ask, before I close the series of lectures, two questions. One, how can rejuvenation be improved ; the other, how can senescence be delayed. These questions will strike every one as very practical. But the first, I fear, is not an immediately practical question, but rather of scientific interest, for we must admit that the production of young individuals is, on the whole, very well accom- plished and much to our satisfaction. But in regard to growing old. AGE, GROWTH AND DEATH 523 in regard to senescence, the matter is very different. There we should, indeed, like to have some principle given to us which would delay the rate of senescence and leave us for a longer period the enjoyment of our mature faculties. I can, as you have readily surmised by what I have said to you, present to you no new rule by which this can be ac- complished, but I can venture to suggest to you that in the future deeper insight into these mysteries probably awaits us, and that there may indeed come a time when we can somewhat regulate these matters. If it be true that the growing old depends upon the increase of the protoplasm, and the proportional diminution of the nucleus, we can perhaps in the future find some means by which the activity of the nuclei can be increased and the younger system of organization thereby pro- longed. That is only a dream of the possible future. It would not be safe even to call it a prophecy. But stranger things and more unexpected have happened, and perhaps this will also. I do not wish to close without one added word. The views which I have presented before you in this series of lectures I am personally chiefly responsible for. Science consists in the discovery made by indi- viduals, afterwards confirmed and correlated by others, so that they lose their personal character. The views which I have presented to you, you ought to know are still largely in the personal stage. Whether my colleagues will think that the body of conceptions which I have presented are fully justified or not, I can not venture to say. I have to thank you much, because between the lecturer and his audience there is established a personal relation, and I feel very much the compliment of your presence throughout this series of lectures, and of the very courteous attention which you have given me. To recapitulate — for we have now arrived at the end of our hour — we may say that we have established, if my arguments before you be correct, the following four laws of age. First, rejuvenation depends on the increase of the nuclei. Second, senescence depends on the increase of the protoplasm, and on the differentiation of the cells. Third, the rate of growth depends on the degree of senescence. Fourth, senescence is at its maximum in the very young stages, and the rate of senescence diminishes with age. As the corollary from these, we have this — natural death is the con- sequence of cellular differentiation. COLUMBIA UNIVERSITY LIBRARIES This book is due on the date indicated below, or at the expiration of a definite period after the date of borrowing, as provided by the library rules or by special arrangement with the Librarian in chaj-ge. DATE BORROWED DATE DUE DATE BORROWED DATE DUE i)L )JTj . L . •iUFlLKT ( C2S(S42)M iO SOUTH P^OPPRTY QP86 -+- ' ^ "««1 I-.iinot The pr oblem of ase, grovrbh and "Seatlu ' ^^y-j C. U. EliSIDSRY r.^.