ON HEREDITY AND REJUVENATION. BY CHARLES SEDGWICK MINOT. Reprinted from The American Naturalist, Jan. and Feb., 1896. THE AMERICAN NATURALIST Vol. XXX. . January, 1896. 349 ON HEREDITY AND REJUVENATION.1 Charles Sedgwick Minot.2 The subject of this article is presented under the following sections; I. The Formative Force of Organisms. 11. The Conception of Death. 111. A Comparison of Larva and Embryo. IV. Concluding Remarks, The first section is not new, but a reproduction without change, of an article published in Science, July 3d, 1885. As this article has not become generally known, and yet is an es- sential link in the chain of reasoning, I venture to repeat it- Though written in 1885, I consider that to-day it is still suffi- cient to disprove Weismann’s theory of germ plasm. Weis- mann has not considered this article, otherwise, from my point of view, he could not have maintained his theory. 1 This article is translated from one which appeared in the Biologisches Cen- tralblatt, Vol. XV, Page 571, August Ist, 1895. A few trifling changes have been made in the text. An abstract of the article was read before the Amer- ican Association for the Advancement of Science, at its recent Springfield meeting. 2 Professor in the Harvard Medical School. 2 The American Naturalist. [January, The views which I then defended have been recently brought forward in almost parallel form, and without essen- tial additions, by 0. Hertwig (Zeit-und Streitfragen der Biologie, I, Heft, D. 32-53) as arguments against the views of Weis- mann. The second section is also directed against Weismann, for it attempts to replace his conception of death by one more exact. The third section is intended to make the significance of re- juvenation clear, and at the same time, by a comparison of larvae and embryos, to demonstrate a law of heredity which has not been hitherto recognized. The Formative Force of Organisms. The assertion is safe, that the majority of biologists incline at present to explain the forming of an organism out of its germ upon mechanical principles. The prevalent conception is that the forces of the ovum are so disposed that the evolu- tion of the adult organism is the mechanical result of the pre- determined interplay of those forces. The object of the pres- ent article is to point out that this conception is inadequate, and must be at least supplemented, if not replaced, by another view, namely, that the formative force is a generally diffused tendency, so that all parts inherently tend to complete by their own growth and modification whole organism—a fact which finds a legitimate hypothetical expression in Dar- win’s Doctrine of pangenesis. The nature of the view here advanced will become clearer upon consideration of the evi- dence upon which it is based, and which is adduced below. The evidence that the formative force is diffused through all parts falls under three heads : 1. The process of regeneration in unicellular and multicellular bionts ; 2. The phenomena of of the duplication of parts ; 3. All forms of organic reproduc- tion. Let us briefly consider these categories. 1. Regeneration.—All living organisms have, to a greater or less degree, the ability to repair injuries; indeed, we must re- gard the power of regeneration as coextensive with life, but 1896.] On Heredity and Rejuvenation. 3 the capacity varies enormously in the different species. In man the power is very small, though more extensive than is generally realized. Among Annelids are species, the individ- uals of which may be divided in two, and each piece can re- generate all that is needed to render it a complete worm. We sometimes see a small fragment of a plant, a single switch of a willow, for instance, regenerate an entire tree, roots, trunk, branches, leaves, flowers, and all. In the last instance a few cells possess a latent formative force, which we recognize by its effects, but cannot explain. We perceive, therefore, that each individual has, as it were, a scheme or plan of its organ- ization to which it strives to conform. As long as it actually does so, the cells perform their routine functions ; but when an injury destroys or removes some portion, then the remain- ing cells strive to conform again to the complete scheme, and to add the missing fragment. The act of regeneration of lost parts strikes' the imagination almost as an intelligent pursuit by the tissues of an ideal purpose. Our knowledge of the regeneration power has recently re- ceived important extensions through the noteworthy experi- ments of Nussbaum3 and Gruber,4 who have demonstrated, in- dependently, the possibility of dividing unicellular animals so that each piece will regenerate the missing parts. In this manner the number of individuals can be artifically multi- plied. For example : Nussbaum divided a well-isolated Oxy- tricha into two equal parts, either transversely or longitudi- nally, and found that the edges of the cut became soon sur- rounded with new cilia. Although some of the substance of the body, or even a nucleus, was lost through the operation yet, by the following day, the two parts converted themselves into complete animals with four nuclei and nucleoli (Nebenkerne) and the characteristic ciliary apparatus. “ The head piece has formed a new hind end ; the right half, a new left half.” The 3M. Nussbaum, Ueber spontane und kunstliche Zellteilung, Sitzungsb. d. nei- derrh. Ges. f. Nat. u. Heilkunde, Bonn, 15, Dez., 1884. 4 A. Gruber, Ueber kunstliche Teilunq bei Infusorien, Biol. Centralblatt, Bd. IV, No. 23, 717-722. 4 The American Naturalist. [January, newformed duplicate Infusoria multiplied subsequently by spontaneous division. From one Oxytrachia cut in two, Nuss- baum succeeded in raising ten normal animalcules, which subsequent!y all encysted. After an unequal division, the parts are both still capable of regeneration, but parts without a nucleus did not survive, which suggests that the formative energy is in some way bound up with the nucleus. But nu- cleate pieces may break down. Thus, all attempts at artifi- cial multiplication of the multinucleate Opalina failed, al- though the division of Actinosphserium had been successfully made by Eichhorn as long ago as in the last century. Pelo- myxa palustris has been successfully divided by Greef, and Myastrunr radians by Haeckel. Gruber {I. c., p. 718) describes his experiments with Stentor : “ If one divides a Stentor transversely through the middle, and isolates the two parts, one finds on the cut surface of the hind part, after about twelve hours, a complete peristomial field with the large cilia and buccal spiral newly formed. On the other hand, the piece on which the old mouth is situated has elongated itself backwards, and attached itself in the manner peculiar to these Infusoria. If one has made a longitudinal section, so that the peristom is cut in two, then the peristoms both complete themselves and the lateral wounds heal over. I have repeatedly separated, by transection, pieces consider- ably less than half of the original Stentor, and these have also regenerated themselves to complete animals.” Gruber, too, observed that artificially divided Infusoria were capable of subsequent spontaneous multiplication. If the section is not very deep, there may arise double monsters; but here, just as in spontaneous divisions, as long as there remains an organic connecting band, the two parts act as one individual, showing that’the nervous actions are not restricted to determined paths. Gruber also adds that two divided pieces may be re- united if brought together quickly enough. The observation thus briefly announced is of such extreme interest and impor- tance that the publication of the full details of the experiment will be eagerly awaited. Gruber adds that at present we can- 1896.] On Heredity and Rejuvenation. 5 not go much beyond the proof of existence, to a high degree, of the regenerative capacity in unicellular organisms, He also makes the significant observation that in the Protozoa, we have to do foremost with changes of function ; in the Metazoa, with growth also. 2. Duplication of parts.—In these anomalies we find an or- gan which, although an extra member, yet still conforms to the type of the species. For example : a frog is found with three posterior limbs ; dissection proves the third leg to agree anatomically with the typical organization of the frog’s hind leg. In determining the importance to be attributed to this evidence, it should be remembered, on the one hand, that these instances are by no means unusual; on the other, that the agreement with the normal structure is not uniform. 3. Asexual reproduction.—When a species multiplies by fis- sion of any kind, we must assume that each part, after divis- ion, possesses the formative tendency, since we see it build up what is necessary so complete the typical organization of the individual. Again : a bud of a hydroid or polyzoon, although comprising only a small part of the body, is equally endowed with this uncomprehended faculty. In pseudova we reach the extreme limit; in aphis, for example, the parent gives off a single cell, the capacity of which, to produce a perfect and complicated individual, fully equals the like capacity of a hy- droid bud or of half a worm. The evidence forces us to the conclusion that the formative force or cause is not merely the original disposition of the forces and substances of the ovum, but that to each portion of the organism is given: 1. The pattern of the whole organism; 2. The partial or complete power to reproduce the pattern. The itali- cized formula is, of course, a very crude scientific statement, but it is the best which has occurred to me. The formative force, then, is a diffused tendency. The very vagueness of the ex- pression serves to emphasize our ignorance concerning the real nature of the force. In this connection, I venture to in- sist upon the fact that we know little or nothing concerning any of the fundamental properties of life, because I think the 6 The American Naturalist. [January, lesson of our ignorance has not been learned by biologists. We encounter, not infrequently, the assertion that life is nothing but a series of physical phenomena ; or, on the other hand, what is less fashionable science just now, that life is due to a special vital force. Such assertions are thoroughly unscientific ; most of them are entirely, the remainder nearly worthless. Of what seems to me the prerequisites to be fulfilled before a general theory of life is advanced, I have written elsewhere.5 11. Conception of Death. My thesis reads : There are two forms of death. These are first, the death of the single cells ; second, the death of multi- cellular organisms. Death in the one case is not homologous witli death in the other. Weismann assumed the complete homology of the two forms of death. Without this assumption, his hypothesis of the immortality of unicellular organisms falls to the ground and with it falls the entire superstructure of his speculations upon germ plasm. Oscar Hertwig (Zeit und Streitfragen, Heft 1) has already expounded, very clearly, the dependence of the theory of germ plasm upon the hypothesis of unicellular im- mortality ; it would, therefore, be superfluous to discuss it here. The conception of the biological problem of death, to which I still hold, was formed several years before Weismann’s first publication, which appeared in 1882, with the title, “ Ueber die Dauer des Lebens.” He has further defended his view in his article, “ Ueber Leben und Tod ” (1884), and has steadfastly ad- hered to it since. In the years 1877-1879 I published my theoretical interpretation of the problem.6 This interpretation became the starting point of elaborate special investigations, by which I endeavored to advance the solution of the problem and, in fact, observation and experiment have confirmed the SC. S. Minot, On the conditions to be filled by a theory of life, Proc. Amer. Assoc. Adv. Sc., XXVIII, 411. 6 Proc. Boston Soc. Nat. Hist., XIX, 167 ; XX, 190. 1896.] On Heredity and Rejuvenation. 7 original thesis.7 Moreover, in an especial short article I have directed attention to the fact that Weismann has not consid- ered the essential issue of the problem. The difficulties pointed out still remain, and, according to my conviction, can- not be removed. Weismann passes these difficulties by and carries out his speculations without first securing a basis for them. His method is illustrated by the following quotation ; “ I have, perhaps, not to regret that I cannot here discuss the article referred to (Minot’s Article in Science, Vol. IV, p. 398); nevertheless, almost all objections which are there made to my views are answered in the present paper.” (Weismann, Zur Frage nach der Unsterblichkeit der Einzelligen, Biol. Centralbl., IV, 690, Nachschrift). I have studied the paper with conscientious care and cannot admit that the objections have been answered. On the contrary, I maintain now, as formerly, the judgment: “He misses the real problem.” For this reason I hold it to be unnecessary to discuss the de- tails of Weisman’s exposition, because—if I am right—he has not considered the actual problem of death at all. “He misses the real problem.” The following reasoning leads to this decision ; Protozoa and Metazoa consist of successive gen- erations of cells ; in the former the cells separate ; in the lat- ter they remain united ; the death of a Protozoa is the anni- hilation of a cell, but the death of a Metazoon is the dissolu- tion of the union of cells. Such a dissolution is the result of time, that is to say, of the period necessary to the natural duration of life, and we call it, therefore, “ natural death.” Moreover, we know that natural death is brought about by gradual changes in the cells until, at last, certain cells, which are essential to the preservation of the whole, cease their func- tions. Death, therefore, is a consequence of changes which progress slowly through successive generations of cells. These changes cause senescence, the end of which is given by death. If we wish to know whether death, in the sense of natural death, properly so called, occurs in Protozoa or not, we must first pos- 7 Journal of Physiology, XII, and Proc. A. A. A. S., XXXIX, (1890). 8 The American Naturalist [January, sess some mark or sign, by which we can determine the occur- rence or absence of senescence in unicellular organisms. Around this point the whole discussion revolves. Certainly a simpler and more certain conclusion could hardly be drawn than that the death of a Metazoon is not identical, i. e., homol- ogous with the death of a single cell. Weismann tacitly as- sumed precisely this homology, and bases his whole argument on it. In all his writings upon this subject, he regards the death of a Protozoon as immediately comparable with the death of a Metazoon. If we seek from Weismann for the foundation of this view wre shall have only our labor for our pains. Starting from this view Weismann comes to the strictly logical conclusion that the Protozoa are immortal. This is a paradox ! In fact, if one compares death in the two cases, from Weismann’s standpoint, then we must assume a difference in the causes of death, and conclude that the cause in the case of the Protozoa is external only, while in the Metazoa it is internal only, for, of course, we may leave out of account the accidental deaths of Metazoa. If we ap- proach the problem from this side, we encounter the following principal question : Does death from inner causes occur in Protozoa? Weismann gives a negative answer to this ques- tion, with his assertion that unicellular organisms are immor- tal. The assertion remains, but the proof of the assertion is lacking. In order to justify the assertion, it must be demon- strated that there does not occur in Protozoa a true senescence, showing itself gradually through successive generations of cells. Has Weismann furnished this demonstration ? Cer- tainly not. He has, strictly speaking, not discussed the sub- ject. It is clear that we must first determine whether natural death from senesence occurs in Protozoa or not, before we can pass to a scientific discussion of the asserted immortality of unicellular beings. The problem cannot be otherwise appre- hended. Weismann has not thus conceived it, therefore the judgment stands against him : he misses the real 'problem. Senesence has been hitherto little investigated ; for many years I have been studying it experimentally and have tried 1896.] On Heredity and Rejuvenation. to determine its exact course. My paper, “ Senesence and Re- juvenation,” affords evidence of new facts proven by these ex- periments. I believe I have thus won the right to oppose my view to the pure speculations of Weismann. ( To he continued.) THE AMERICAN NATURALIST Vol. XXX. February, 1896. 35° ON HEREDITY AND REJUVENATION. Charles Sedgwick Minot. {Continuedfrom page 9.) 111. A Comparison of Larva and Embryo.B It has long been known that animals develop according to two types, appearing in their younger stages, either as larvse or as embryos. The larvse lead a free life and must obtain their own food. Embryos, on the contrary, do not lead a free life and are nourished by the yolk accumulated in the parent ovum. There is, of course, no absolute demarcation between the two classes; nevertheless, a general comparison between them establishes several conclusions which throw valuable light upon some recent biological hypothesis. First of all, it must be remarked that the larval develop- ment is primitive, and that the embryonic development has been evolved later. Geologists are able to present two princi- pal supports for this assertion: 1. In the lower animals we encounter only larvse, never embryos ; sponges, colenterates, echinoderms and worms, all pass through the early stages of 8 Read before the Amer. Soc. of Morphologists, December, 1893. 90 The American Naturalist. [February, their ontogeny as larva?. It would, therefore, be superfluous to linger for the defense of a view which is already accepted by all biologists. 2. The embryonic development depends on the presence of yolk. Now we have learned that the yolk has developed very gradually and in all the lower animals appears only in small quantities. It was not until the increase of yolk material had become enormous, as, for example, in the meroblastic vertebrates, that we find the development com- pletely embryonic in type. With the increase of the yolk comes the gradual transition from larval to embryonic devel- opment. Since the embryo is dependent on the yolk, and since the yolk exists only in the higher forms in sufficient quantity, it follows that fully typical embryos can occur ex- in the higher (later developed) animal types. The fact that larvae represent the primitive forms of de- velopment, obliges us to conclude that the correctnesss of Weismann’s theory of the continuity of germ plasm can be tested better in larvae than in embryos, since in embryos the rela- tions have undergone profound modifications by secondary changes, which in this connection might easily deceive us. I do not venture to assert that I know what the present form of Weismann’s continuity theory may be ; I hold, how- ever, the exact form of this much discussed theory to be non- essential, because, according to my conviction, the theory can in no form be brought into agreement with our present knowl- edge. Nussbaum founded the theory, and opened the way along which we certainly hope to make great advance. Let me acknowledge the great value and the strictly scientific character of Nussbaum’s work ; doing this not merely because I esteem it, but also because the unjust attempt has been made to diminish his claim. Nussbaum9 thought that the germ cells are direct decendents of the fertilized ovum, keeping the germinating power, while the rest of the cells developed from the egg are transformed into the tissue of the body. He brought forward several facts which could be interpreted in favor of his theory. By this theory the wdiole problem of her- 9M. Nussbaum, Zur Dlfferenzierung des Geschlechts im Tirreich, Arch. f. Mikrosk. Anatomic, XVIII, 1-121, (1880). 1896.] On Heredity and Rejuvenation. 91 edity and development was stated in an entirely new form. Since this publication of Nussbaum’s we are seeking for the explanation of the germinating power, and the propagation of this power ; formerly we sought for the causes of the inheri- tance of parental parts. The difference may be illustrated by the following example. Before Nussbaum we were ruled by Darwin’s conception of Pangenesis, and we investigated ac- cordingly for the agency by which the eye of the father re- produced itself in the child. Since Nussbaum we leave Pan- genesis behind—it belongs henceforth to the past—and try to determine how the germinal substance behaves, and especially in what way it is perpetuated from the ovum through the fol- lowing developmental stages, so that it is finally still present for the creation of the next generation. It is the conception of the continuity of the germinal substance which we prize so highly, and owe to Nussbaum. Larvae teach us that it cannot be special cells which affect this continuity. In fact, we find the organs of larval life fully differentiated before any sexual organs are recognizable, and indeed, in the majority of known larvae we cannot recognize even the rudiments of the sexual glands. On the contrary, we find in larvae unmistakably differentiated locomotive appa- ratus, such as cilia and often muscle fibres, a digestive canal, sensory organs, and, in many cases, also special excretory or- gans, and yet, only in a very few and exceptional cases can we distinguish the cells which belong to the future sexual glands. Thus, in regard to the primitive or larval type of de- velopment, we cannot say that the germ cells are constantly separated from the somatic cells during the segmentation of the ovum, but must rather draw precisely the opposite conclu- sion, namely, that the germ cells belong to the tissues which arise latest. We often meet many tissues in larvse at a time when there is still no indication of germ cells. We find the same relations in embryos also, since in them the principal tissues become recognizable before germ cells are present. This fact was well established for vertebrates many years ago. It is characteristic of Weismann that he long defended the continuity of germ cells, in defiance of the facts. He has since 92 The American Naturalist. [February, given up this wrong view and put in its place his hypothesis of the continuity of germ plasm. Of Nussbaum’s conceptions, Weismann has left out the fruitful part, and has sown broad- cast those ideas which were incapable of fruitful development. He has attempted to defend his notion of the difference be- tween the elements of the embryo destined for the construction of the body, on the one hand, and those elements destined for sexual propagation on the other. Now, since the sexual cells usually develop from somatic cells, he was forced to assume that there is a mysterious substance which he names “ Keim- plasma.” This substance is supposed to store itself in the body by some secret way, to separate itself at command from the histogenic plasm, to appear unchanged and ready to be the exclusive agent of hereditary transmission. Nussbaum furnished the conception of the continuity of germinal substance, which appears to be of immeasurable im- portance for tbe scientific investigation of the phenomena of heredity. But this continuity holds for all cells which arise from the fertilized ovum, as explained in the first section of this article. We must, therefore, seek for the causes of the differentiation of cells, that is to say, for the causes of the pro- duction of nerve cells, muscle cells, gland cells, etc, and of the production of germ cells. I will now try to make clear the significance of the compar- ison between larvae and embryos for the interpretation of germ cells. This calls for a short digression. In the course of my investigations on “ Senescence and Re- juvenation,” of which only the first part has been published (Journal of Physiology, xii, 97), I learned that as cells become older there occurs an increase of the protoplasm in proportion to the nucleus, and I further succeeded in proving, as an es- sential process in reproduction, the formation of cells with comparatively little protoplasm. Further, it was found prob- able that a rapid multiplication of cells is only then possible when the cells have small protoplasmatic bodies (Proc. A. A. A. S., XXXIX (1890). We, therefore, have learned that the power of development depends on a special condition of the cell. By these facts I have been led directly to the following hypothesis: 1896.] On Heredity and Rejuvenation. 93 The development of an organism does not depend on a substance stored in special cells, hut on a special condition {stage) of organi- zation. As a corollary of this hypothesis may be given this conclusion : Germ plasm, irt Weismann’s sense, does not exist. According to my view, every part inherits from the germ, and every part of the animal body, as well as its germ cells, possesses the multiplying morphogenetic force, the action of which, however, is inhibited to the condition of the parts themselves. What this condition may be is not yet exactly known, but this much we do know, that the morphogenetic force is found in full activity in cells with little protoplasm. It is in- deed highly probable that the slight development of proto- plasm in proportion to the nucleus is an unavoidable condi- tion of morphogenesis, or in other words, of the action of her- edity. In fact we see that the first processes of development —as I have elsewhere explained (Proc. A. A. A. S., XIX)— show in the most varied cases a remarkable uniformity, for they always accomplish the production of cells with little pro- toplasm. Compare, in this respect, the vegetation points of plants, the root buds of slips, the budding zones of Annelids, the germinal layers of vertebrates, etc. The condition which allows the morphogenetic or hereditary force to act, arises under differing conditions, of which the fertilization of the ovum is one only. Weismann tries to make comprehensible to us this one case, that of the fertilized ovum, by a special explanation which is available for no other case. Oscar Hertwig has recently (Zeit und Streitfragen, Heft I) clearly shown that Weismann’s ex- planation is a speculative assumption, which can only be saved from rejection by numerous and often selfcontradictory additional assumptions. As I fully agree with Hertwig’s crit- icism, I need only refer to his essay. We will return to our proper theme. The next point is to determine whether there is a difference in the condition of the cells, as, regards their capacity for development, between larvee, on the one hand, and embryos on the other. It can be proved that this is the case, by the following considerations- So far as we yet know, it is chiefly two factors which inhibit 94 The American Naturalist. [February, development: first, the increase of protoplasm ; second, the progress of organization, i. e., of differentiation. As I was about to close this article, I received through the kindness of the author, Nussbaum’s address on differation, in which he has defended essentially the same views as those which I hold. Such an agreement is of great value to me. Now we know that larvae are animal forms which have to obtain their own food and to protect themselves against ene- mies, and therefore are provided with differentiated tissues. Embryos, on the contrary, take their nutriment simply from the ovum, and the cells continue for a long time, developing and multiplying, while the protoplasm of the single cells in- creases very slightly, and the beginning of the differentiation proper is correspondingly postponed. I believe that we here have to deal with causal relations. From the actual relations just described, I conclude that the most essential difference hitherto known between larvae and embryos, is to be found in the differing lengths of the period of multiplication of undif- ferentiated cells. In consequence of the shorter duration of the period in larvae they have a much smaller total num- ber of undifferentiated cells than embryos, or reversely ex- pressed, embryos are much better equipped with material for the construction of the adult body, than are larvae. As al- ready stated, embryos are produced by the higher animals. This fact finds its explanation in the relations just described, because the increased number of undifferentiated, or so called embryonic cells, is precisely the necessary preliminary condi- tion of the greater complexity of the differentiation by which the animal becomes more highly organized. For the sake of clearness I have put aside all complications which might come in to play. It goes without saying, that the relations, in many respects, are by no means simple, nev- ertheless, the main conclusion above given seems a secure gain. I therefore interpret the embryo as a device to render possi- ble the increase of undifferentiated cells, and consequently a higher ultimate organization. The origin of this device is conditioned by a supply of food independent of the embryo. 1896.] On Heredity and Rejuvenation. 95 From oar present standpoint it is a matter of indifference whether the independent food supply comes from the yolk or from the uterus, however important the difference may be from other points of view. It is to be further noted that our interpretation of the sig- nificance of the embryo is also opposed to Weismann’s theory of germ plasm, because it emphasizes the importance of the condition as opposed to the assumption of a germinal substance or plasm. This road also leads to the conclusion reached above by other ways, the conclusion, namely : Reproduction involves rejuvenation, and rejuvenation is characterized by the production of cells with little, and that little not differen- tiated, protoplasm. Since rejuvenated cells arise by asexual as well as by sexual reproduction, since they appear in much greater numbers in embryos than in larvae, and since they may be interpolated, as in the pupae of butterflies, in the midst of the development of an individual, we must admit that the hereditary impulse (vererbende Kraft) is distributed in very different cells and is probably distributed equally through all cells. Hertwig has reached the same conclusion, with which Weismann’s theory of germ plasm cannot be made to agree. As Weismann has neglected the problem of rejuvenation, he has necessarily often gone astray in his discussion of phe-r nomena in which rejuvenation plays the principal role. One is astonished at the slight attention bestowed on rejuvenation when one recalls that it is the central problem of all questions of heredity treated by him. Rejuvenation is one of the principal phenomena of life, and the rejuvenated condition of the cell is probably an unavoida- ble preliminary of heredity. We know that at least one ana- tomical sign of the rejuvenated condition is to be found in the preponderance of the nucleus in proportion to the protoplasm : a second anatomical sign is found in the structure of the pro- toplasm, which, in young cells always remains without differ- erentiation. The chief 'physiological sign of rejuvenation in cells which we as yet know is the power of rapid multiplica- tion. Thus, we see, in case of sexual rejuvenation, that the 96 The American Naturalist. [February, development of the fertilized ovum begins with an excessive proliferation of the nuclei, by which numerous cells are cre- ated, each with little protoplasm. Histogenetic differentiation begins later. The asexual rejuvenation has a similar course, but needs more thorough investigation. Now differentiation is the sign of inheritance, and this mor- phological inheritance cannot develop itself fully until the senescence of the cells becomes recognizable by the growth of their protoplasm. On the other hand, we see complete inher- itance develop itself, after preceeding rejuvenation. Accord- ingly we gain two conceptions: first, the hereditary impulse belongs to the inherent and constant properties of cells in gen- eral ; second, the activity of their impulse may be inhibited by the condition of the cells. My view may be expressed in the following way ; Somatic cells are simply cells in which the activity of the hereditary impulse is inhibited in consequence of their senescence, or, in other words, differentiation; but under suitable conditions the somatic cells may pass over into the rejuvenated stage, and thereupon develop the most com- plete hereditary possibilities. The importance of rejuvenation must also be recognized when we consider the phylogenetic origin of single organs. Let us take a simple example. We may safely assume that the ancestors of mammals possessed a smooth skin, and that the covering of hairs is a new acquisition. Each hair is the product of a local growth. If we investigate the germ of a hair, we find that it consists of rejuvenated cells, that is to say, of cells with little protoplasm, or, as we are accustomed to say, of the embryonic type. Thus the formation of hairs depends on numerous centers of rejuvenation. In the multiplication of striped muscle fibres we find the agents to be the muscle buds, which are small, protoplasmatic structures, with rela- tively numerous nuclei. If we observe a developing gland, let us say a pancreas or a sweat gland, we find the rudiment to consist of rejuvenated cells; the cells multiply rapidly, and after the organ has its essential form, the histogenetic differenti- ation begins. It would be easy to multiply such examples a thousandfold. 1896.] On Heredity and Rejuvenation. 97 The consideration of the role of rejuvenation in the origin of organs leads us to the theory of Post-selection (Nach- auslese). The theory is by no means new, but I wish to em- phasize its far reaching importance. The preceding discus- sion teaches us to divide the origin of a new morphological part into two stages. The first stage is the development of the rudiment (anlage) by multiplication of the cells. The second stage is characterized by the gradual differentiation of the cells, by which they become capable of their ultimate functions. Especially in embryos is the difference in time very marked between the formation and the differentiation of the “ Anlage” Now it is evident that the undifferentiated “ Anlage ”is not useful, but becomes useful later. The forma- tion and conservation of the “ Anlage,” therefore, are due to se- lection, working, not directly upon the “ Anlage,” but indi- rectly through preservation of the fully developed organ. The conception advanced is very simple and appears to me a nec- essary consequence of our knowledge. For the conception itself there has been hitherto to no definite term, I propose, therefore, to call it “ Post-selection ” (in German, “ Nachaus- lese). To avoid possible misunderstanding, I give another ex- ample of post-selection. A parasitic wasp lays its egg in a certain caterpillar; the mother wasp gains no advantage, nat- ural selection does not touch her, but only her progeny, the wasp larva. Nevertheless, the survival of the fittest rules. In conclusion, I should like to direct the reader's attention to a problem which, so far as I am acquainted with the litera- ture of biology, has been left almost unconsidered. This pres- ent translation enables me to insert a qualification of the pre- ceding sentence, which ought to have been inserted in the original article, namely, that the problem has been the sub- ject of important discussions by Hyatt, Cope and a very few others among paleontologists. lam glad to be able to refer to the article b}r Professor Hyatt, (see Jan. Naturalist) and pre- sents the paleontological theory of the loss of ancestral charac- teristics. The problem above referred to is the 'problem of lost characteristics, which seems to me one of the fundamental problems of the doctrine of evolution, because we cannot un- 98 The American Naturalist. [February, derst&nd the development of the higher organisms until this problem is solved. Everybody is writing about the origin of new organs, and we take lively pleasure in discussions about acquired characteristics. But if we consider the circumstances closely, we recognize that the loss of ancestral characteristics almost equals in importance the acquisition of new character- istics for the formation of new species. We assume that man had fishlike ancestors, and we strengthen ourselves in this be- lief by the comparison so often made between the human em- bryo, on the one side, and the adult fish on the other. But if the comparison be impartial we are forced to admit that nearly everything which is most characteristic of the fish is conspicuously lacking in the human embryo. Taking the embryo at the stage when the gill clefts have their maximum development, we find the following relations: the body is not straight but coiled up, and this coiling up is indispensable, in order to bring about the proper distribution of the human nerves, blood vessels, and so forth ; the gill clefts are closed ; gills are wanting ; the digestive canal has no glands ; the epi- dermis has no scales; the chorda dorsalis does not form a large axis of the body, but is a minute string of cells. In short, the Biogenetisches Grundgesetz (Recapitulation theory or von Baer’s law, according to Adam Sedgwick) is scarcely half true. I have previously defended this conclusion at a meet- ing of the American Society of Morphologists, in December, 1893, Subsequently, but independently, Adam Sedgwick has reached a similar conclusion, see his paper “ On the Law of Development, etc.” (Quart, Jour. Micros. Sci., XXXVI, 35). Were it not, as above implied, that the departures from the fish type are in great excess, there would be no embryo at all, and consequently no man, for the adult form is a conse- quence of the embryonic. The embryo is the mechanical cause of the adult body. How has the disappearance of the ancestral fish characteristics been effected ? The question re- mains unanswered. It will, perhaps, be replied “ through dis- use ”or “ through panmixia.” But “disuse” is merely a name, not an explanation of the phenomena. Panmixia is an hypothesis erected on nothing. In fact, this hypothesis as- 1896.] On Heredity and Rejuvenation. 99 sumes that the majority of variations fall below the value maintained by natural selection, and consequently that when the influence of natural selection is eliminated (as in disuse), the mere variation will bring the traits concerned to disap- pearance. It marks Weismann’s style of thought to find that he has entirely omitted to determine whether his assumption was correct, and nevertheless in his book, “ The Germ Plasm,” presents panmixia as an established law. As a matter of fact, the statistics of variations which we already have, show that his assumption is erroneous, and that it is equally probable that mere variation will magnify a characteristic as it is that it will diminish it. Let us return to the embryo. The following hypothesis may be advanced : The loss of ancestral characteristics in the embryo is due to post- selection, the cells being kept in a rejuvenated stage, in order that they may afterwards accomplish new differentiations. This conclusion follows directly from the preceding consid- erations, and, therefore, needs no further defense. IV. Concluding Remarks. The views presented in the preceeding sections are inti- mately connected one with another and collectively determine our conception of the process of heredity. The conception concerns only the process and not the essential character or cause of heredity. According to my view, heredity exists in all cells, but its display is inhibited by organization of the liv- ing substance, and can be complete only in embryonic cells ; embryonic cells arise under very various conditions. That which is novel in this theory is the significance attributed to embryonic cells. Embryonic cells I prefer to designate as re- juvenated cells. The theory above presented is an unavoidable consequence of the facts known, and stands in absolute contradiction with Weismann’s theory of the germ plasm. I have read with the greatest conscientiousness every article hitherto published by Weismann, which deals with his theo- ries of heredity. My final impression from this study is that 100 The American Naturalist. [February, the “ Theory of Germ Plasm ” corresponds to the personal in- clinations of its author and is in no sense a logical deduction won by the collation of facts. The assumption of a difference between germ plasm and histogenic plasm explains nothing. Even according to Weismann’s own exposition it explains nothing, for the supposed phenomena which the assumption is said to explain, according to Weismann, do not exist. Ac- cording to him, the circumstances are the following ; The phe- nomena due to the germ plasm do not occur in somatic cells, therefore they have a different plasm, namely, histogenic ; further, these phenomena do occur in somatic cells, there- fore, they have germ plasm. Attention must he directed also, and explicitly, to the fact that Weismann oilers no obser- vations to support his fundamental assumption. His theory is mystical to an extreme degree. In Weismann’s book, “ Germ plasm ” one finds one hypothesis after another in order to support his tottering first hypothesis—germ plasm and his- togenic plasm are special and separate substances. I demand of Weismann that he lay aside all his hypotheses, and present to us solely the facts, which support his theory of germ plasm. Then he will learn, as other investigators have already learned, that his hypothesis has been built up without suffi- cient foundation. Let an investigator enquire for a possibility of testing the existence of the “Ids,” “ Biophors,” “ Determinants,” etc., as- serted by Weismann, and he will discover that the whole fabric is woven by speculative imagination. Confirmation of his ideas has, strictly speaking, not been attempted by Weis- mann. Indeed, confirmation is altogether impossible, for his conceptions are far beyond the limits of present human means of investigation. It is time to finally discard a theory which leads astray and which, although it arose without scientific justification, is again and again pushed to the front by its promulgator. It is a scientific duty to take an unhesitating stand against Weismann’s theory, for only so can it become known that those who have specially occupied themselves with the problem of heredity reject Weismann’s theory of germ plasm unconditionally. 1896.] The Formulation of the Natural Sciences. 101 APPENDIX. The Theory of Panplasm. It appears desirable that the modern theory of heredity should be designated by a brief and appropriate name, and accordingly I propose the term “ Panplasm,” and that the the- ory be called “ The Theory of PanplasAi.” By panplasm will be understood the physical basis of hereditary transmission, which is supposed to be distributed through all cells, and which accounts for the phenomena of sexual reproduction, re- generation and asexual reproduction. Panplasm is not a col- lection of gemmules or biophors. The term “ panplasm ” was first used by me at a meeting of the Society of Arts, in Boston, November 14, 1895. On another occasion I hope to discuss the theories of pan- genesis and panplasm in their historical aspects. Reprinted from The American Naturalist, Jan., and Feb., 1896.