Popular Science Monthly/Volume 71/December 1907/The Problem of Age, Growth and Death VI

1538214Popular Science Monthly Volume 71 December 1907 — The Problem of Age, Growth and Death VI1907Charles Sedgwick Minot

THE PROBLEM OF AGE, GROWTH AND DEATH

By CHARLES SEDGWICK MINOT, LL.D., D. Sc.

JAMES STILLMAN PROFESSOR OF COMPARATIVE ANATOMY, HARVARD MEDICAL SCHOOL

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 protoplasm. 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 corresponding 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 multiplication, 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 differentiated, part of the protoplasm changes into contractile substance. Another part remains pure protoplasm unaltered. If now the muscular or contractile portion of the fiber be destroyed, the undifferentiated 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 differentiated; 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 are the 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 accomplished. 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 multiply, 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 process 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 Fig. 61. Portion of the Outer Wall of a Primitive Muscular Segment of a Cat Embryo of 4.6 mm. Harvard Embryological Collection Series 398, section 115. The resting nuclei are oval, pale and granular. The dividing or mitotic nuclei, of which there are three, are dark, irregular in outline and show the chromosomes. In this case the dividing nuclei all lie near the inner surface of the wall. The picture illustrates the ease with which mitotic figures may be recognized. 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 division, for the nucleus in division is easily recognized. This process of division is named mitosis: the figure which the nucleus presents while it is undergoing division we call a mitotic figure. Counting the dividing nuclei, we may determine that in a thousand cells there are a given number which have nuclei in process 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 you 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 technically as the ectoderm, 18 of these divisions per thousand. In the middle layer, technically the mesoderm, 17, and in the inner layer, the entoderm, 18. At ten days we find the number already 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 days), 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 rate of growth may even increase in order to acquire a certain special development 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 question 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 restriction, 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 prescribed, and the possibilities of that cell as it progresses in its development 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 framework 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 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 belong 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 perhaps 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. Now, 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 differentiation 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 depend upon 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 differentiation, 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 innermost 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 Professor Hyatt and for Professor Robert 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 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 scientifically satisfactory that we can present. Ye 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 attractive, 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 Abnutzungstheorie—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 loses its living quality and becomes 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 is rapid, the fatal condition is reached soon; if it is slow, the fatal condition is postponed. And cytomorphosis 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 development; 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 explored 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 organisms; 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 unicellular 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 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 constitutes old and young. We can observe the difference in the proportion 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 nothing 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 government-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 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 constantly 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, according 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 condition 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 defended 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 containing 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 substance, 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 pangenesis. He assumed that there were small particles thrown off from different portions of the body circulating throughout the body, gathering 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 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 Nägeli, the great botanist, who spoke of the Idioplasma-Theilchen. Then Weisner, also a botanist, who spoke of the Plassomes. Our own Professor Whitman attributed to his life units certain other essential qualities 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, unless 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 continuity 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, we 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 you may more fully appreciate what I believe to be the fact of mental development going on with diminishing rapidity, I should like to picture 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 supplied with a series of the indispensable physiological functions, all those which are concerned with the taking in and utilizing 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 equipment 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 will 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, association, 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 apparently 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, doubtless, 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 metaphysicians to explain how the notions of space and time arose. Without 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 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, referring 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 rôle 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 sensation, and learns to bring those together and thereby is manufacturing 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, uninterrupted, 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 metaphysical 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 rôle 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 individuals 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 observation. 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 possesses. Not 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 interrupted 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.

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 awkward, 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 development; 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 psychological 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.

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 learning 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 extreme variations in endowment, preserve the power of active and original 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 development. 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 contrary 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 vriW 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 accomplished and much to our satisfaction. But in regard to growing old. 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 accomplished, 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 prolonged. 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 individuals, 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 consequence of cellular differentiation.