The Organism as a Whole, from a Physicochemical Viewpoint

5. Dallinger stated that he succeeded in adapting certain protozoans to a temperature of 70° C. by gradually raising their temperature during several years. It is desirable that this statement be verified; until this is done doubts are justified. Schottelius found that colonies of Micrococcus prodigiosus when transferred from a temperature of 22° to that of 38° no longer formed pigment and trimethylamine. After the cocci had been cultivated for ten or fifteen generations at 38° they failed to form pigment even when transferred back to 22° C. Dieudonne1 used Bacillus fluorescens for similar purposes. At 22° it forms a fluorescing pigment and trimethylamine, but not at 35°. By constantly cultivating this bacillus at 35° Dieudonne found that after the fifteenth generation had been cultivated at 35° the bacillus produced

pigment and trimethylamine at 35°. Davenport and Castle1 found that tadpoles of a frog kept at 15° went into heat rigour at 40.3° C., while those kept for twentyeight days at 25° were not affected by this temperature but went into heat rigour at 43.5°. When the latter tadpoles were put back for seventeen days to a temperature of 15° they had lost their resistance to high temperature partially, but not completely, since they went into heat rigour at 41.6°. The authors suggest that this adaptation to a higher temperature is due to a loss of water on the part of protoplasm, whereby the latter becomes more resistant to an increase in temperature. This idea was put to a test by Kryz2, who found that the coagulation temperature of their muscle plasm is not altered by keeping cold-blooded animals at different temperatures.

Loeb and Wasteneys3 found that Fundulus taken from a low temperature of 10° C. die in less than two hours when suddenly transferred to sea water of 29° C. ; and in a few minutes if suddenly transferred to a temperature of 35° C. If, however, the fish were transferred to a temperature of 27° C. for forty hours they could live indefinitely in sea water of 35°. By exposing the fish each day two hours to a gradually rising temperature they could render them resistant to a temperature of 39°. The remarkable fact was that fish if once made resistant to a high temperature (35°) did not lose this resistance when kept for four weeks at from 10° to 14° C. Control fish taken from the same temperature died in from two to four minutes; immunized fish taken from 10° and put directly to 35° C. lived for many hours or indefinitely. They will even retain this immunity when kept for two weeks at a temperature of 0.4° C.

Why is it that an animal can in general resist a high temperature better if the latter is raised gradually than when it is raised suddenly? Physics offers us an analogy to this phenomenon in the experience that glass vessels which burst easily when their temperature is raised suddenly, remain intact when the temperature is raised gradually. Glass is a poor conductor of heat and when the temperature is raised suddenly inside a glass cylinder the inner layer of the cylinder expands while the outer layer on account of the slowness of conduction of heat does not expand equally and the cylinder may burst. We might assume that the sudden increase in temperature brings about certain changes in the cells (e. g., an increase in permeability or destruction of the surface layer?). If the rise of temperature occurs gradually the blood or lymph or the cell sap may have time to repair the damage, and this repair seems to be irreversible, at least for some time, as the

experiments on Fundulus seem to indicate. If the temperature rises too rapidly the damage cannot be repaired quickly enough by the cell or body liquids. It is also to be considered that substances might be formed in the body at a higher temperature which do not exist at a lower temperature, and vice versa, and this might explain results like those of Schottelius or Dieudonne and many others. 6. The theory of an adapting effect of the environment has often been linked with the assumption of the inheritance of acquired characters. The older claims of the hereditary transmission of acquired characters, such as Brown-Sequard's epilepsy in guinea pigs after the cutting of the sciatic nerve, have been shown to be unjustified or have found a different and more rational explanation. Recently P. Kammerer has claimed to have proven by new experiments that by environmental changes, hereditary changes can be produced.

It has been mentioned already that the mature male frogs and toads possess during the breeding season lumps on the thumbs or arms which are pigmented and which bear numerous minute horny black spines; these secondary sexual characters serve the male frog in holding the females in the water during copulation. There is one species which does not possess this sexual character, namely the male of the so-called midwife toad (Alytes obstetr leans). In this species the animals copulate on land, and it is natural to connect the lack of this secon-

dary sexual character in the male with its different breeding habit. Kammerer now forced such toads to copulate in water instead of on land (by keeping the animals in a terrarium with a high temperature). He makes the statement that by forcing the parents to lay their eggs during successive spawning periods in water he finally obtained offspring which under normal temperature conditions lay their eggs naturally in water; in other words, they have changed their habits. We will not discuss this part of his statement since the breeding habits of animals in captivity are liable to be abnormal. But Kammerer makes the further important statement1 that the male offspring of such couples will in the third generation produce the swelling on the thumb and the usual roughness, and in the fourth generation black pads and hypertrophy of the muscles of the forearm will appear. In other words, he reports having succeeded in producing an inheritance of an acquired morphological character which has never been known to occur in this species. Bateson, on account of the importance of the case, wished to examine it more closely and I will quote his report.

The systematists who have made a special study of Batrachia appear to be agreed that Alytes in nature does not have these structures; and when individuals possessing them can be produced for inspection it will, I think, be time to examine the evidence for the inheritance of acquired characters more seriously. I wrote to Dr. Kammerer in July, 1910, asking him for the loan of such a specimen and on visiting the Biologische Versuchsanstalt in September of the same year I made the same request, but hitherto none has been produced. In matters of this kind much generally depends on interpretations made at the time of observation; here, however, is an example which could readily be attested by preserved material.1

More recently the same author has reported another hereditary morphological change brought about by outside conditions.2 A certain salamander (Salamandra maculosa) has yellow spots on a generally dark* skin. Kammerer states that if such salamanders are kept on a yellow ground they become more yellow, not by an extension of the chromatophores (which would not be surprising) but by actual multiplication and growth of the yellow pigment cells; while the black skin is inhibited in its growth. The reverse is true if these salamanders are kept on black soil; in this case according to Kammerer the growth of the yellow cells of the skin is inhibited while the black part of the skin grows. Curiously enough, according to him, these induced changes are hereditary. Here again we are dealing with the inheritance of an acquired morphological character.

Megusar1 has repeated Kammerer's experiments on salamanders but contradicts him by stating that the colour of the soil has no influence on the colouration of salamanders. Of course, we know the phenomenon of colour adaptation in which the animal changes its colour pattern according to the environment. This is an effect of the retina image on the skin and has been interpreted by the writer as a case of colour telephotography, for which no physical explanation has yet been found.2 This phenomenon, however, does not lead to any hereditary change of colour. *, Kammerer makes many statements on the heredity of acquired modifications of instinct; indeed he claims that an interest in music on the part of parents produces offspring with musical talent. In such claims much depends upon the subjective interpretation of the observer.

The writer is not aware that there is at present on record a single adequate proof of the heredity of an acquired character. We have records of changes in the offspring by poisoning the germ plasm by alcohol given to parents — as in Stockard's well-known experiments— or by exposing butterflies to extreme temperatures, but in these cases the germ cells were poisoned or altered by the alcohol or by chemical compounds produced at very low or very high temperatures. This

2 Loeb, J., The Mechanistic Conception of Life. Chicago, 1912. is of course an entirely different thing from stating that by inducing the midwife toad to lay its eggs in the water the male offspring acquires the pads and horns of other species of frogs on its thumb; or that by keeping black salamanders on yellow paper the offspring is more yellow. Yet if there is an inheritance of acquired characters which can in any way throw light on the so-called phenomena of adaptation it must consist in results such as Kammerer claims to have obtained.

While the writer does not decline to accept Ehrlich's interpretation of the arsenic-fast strains of trypanosomes or Kammerer's statements in regard to the inheritance of acquired character, he feels that more work should be done before they can be used for our problem. 7. This attitude leaves us in a quandary. The whole animated world is seemingly a symphony of adaptation. We have mentioned already the eye with its refractive media so well curved and placed that a more or less perfect image of the outside objects is focussed exactly on the retina; and this in spite of the fact that lens and retina develop independently; we have mentioned and discussed the cases of instincts or automatic arrangements which are required to perpetuate life — the attraction of the two sexes and the automatic mechanisms by which sperm and egg are brought together; the maternal instincts by which the young are taken care of; and all those adaptations by

which animals get their food and the suitable conditions of preservation. Can we understand all these adaptations, without a belief in the heredity of acquired characters? As a matter of fact the tenacity with which some authors cling to such a belief is dictated by the idea that this is the only alternative to the supranaturalistic or vitalistic ideas. The writer is of the opinion that we do not need to depend upon the assumption of the heredity of acquired characters, but that physiological chemistry is adequate for this purpose.

The earlier writers explained the growth of the legs in the tadpole of the frog or toad as a case of an adaptation to life on land. We know through Gudernatsch that the growth of the legs can be produced at any time even in the youngest tadpole, which is unable to live on the land, by feeding the animal with the thyroid gland. As we have stated in Chapter VII, it is quite possible that in nature the legs of the tadpole begin to grow when enough of the thyroid or a similar compound has been formed or is circulating in the animal.

It might justly be claimed as a case of adaptation that the egg attaches itself to the wall of the uterus and calls forth the formation of the decidua. We have mentioned the observation of Leo Loeb that the corpus luteum of the ovary gives off a substance to the blood which alters the tissues in the uterus in such a way that contact with any foreign body (e. g., the egg) induces this decidua formation. Again what appeared as adaptation when unknown turns out to be a result of the action of a definite chemical substarice circulating in the body.

It appears as a case of adaptation that the eggs of the majority of animals cannot develop without a spermatozoon, and yet we can imitate the activating effect of a spermatozoon on the egg by definite chemical compounds, which leads to the suggestion that the activating effect of the spermatozoon on the egg might be due to the fact that it carries such a compound. The wonderful adaptations exhibited in the mating instincts seem to be due to definite substances secreted by the sex glands, as was shown by Steinach (Chapter VII). Here, again, the process as popularly conceived, is the reverse of the truth; those survive that have the equipment, — they did not acquire the equipment under the influence of environment.

It is absolutely imperative for green plants that their stems and leaves be exposed to the light since only in this way are they able to form carbohydrates; and it is equally essential that the roots should grow into the soil so that the plant may get the nitrates and phosphates required to build up its proteins and nucleins. This result is, in the language of adaptationists, brought about by an adaptive response of the plant to the light. In reality this adaptive response is due (Chapter X) to the presence of a photosensitive substance present in almost all green plants.

Lewis has shown that if the optic cup is transplanted under the skin of a young larva into any part of the body the skin in contact with the optic cup will form a lens; it looks as if a chemical substance from the optic cup were responsible for the formation of the lens. These examples might be multiplied indefinitely. They all indicate that apparent morphological and instinctive adaptations are merely caused by chemical substances formed in the organism and that there is no reason for postulating the inheritance of acquired characters. We must not forget that there are just as many cases where chemical substances circulating in the body lead to indifferent or harmful results. As an example of the first type, we may mention the existence of heliotropism in animals living in the dark, of the latter type, the inheritance of deficiencies like colour-blindness or glaucoma.

While it is possible for forms with moderate disharmonies to survive, those with gross disharmonies cannot exist and we are not reminded of their possible existence. As a consequence the cases of apparent adaptation prevail in nature. The following observation may serve to give an idea how small is the number of existing or durable forms compared with the number of forms incapable of existence. We have mentioned the fact observed by Moenkhouse, the writer, and Newman, that it is possible to fertilize the eggs of each marine bony fish with the

sperm of practically every other marine bony fish. The number of teleosts at present in existence is about ten thousand. If we accomplish all possible hybridizations, one hundred million different crosses will result. Of these only a small fraction of one per cent, can live (see Chapter I), and it is generally the lack of a proper circulation which inhibits them from reaching maturity. It is, therefore, no exaggeration to state that the number of species existing today is only an extremely small fraction of those which can and possibly do originate, but which escape our notice and disappear because they cannot live or reproduce. If we consider these facts wre realize that the mere laws of chance are adequate to account for the fact of the apparently purposeful adaptations; as they are adequate to account for the Mendelian numbers.

DARWIN'S work has been compared to that of Copernicus and Galileo inasmuch as all these men freed the mind from the incubus of Aristotelian philosophy which, with the efficient co-operation of the church and the predatory system of economics, caused the stagnation, squalor, immorality, and misery of the Middle Ages. Copernicus and Galileo were the first to deliver the intellect from the idea of a universe created for the purpose of man; and Darwin rendered a similar service by his insistence that accidental and not purposeful variations gave rise to the variety of organisms. In this struggle for intellectual freedom the names of Huxley and Haeckel must be gratefully remembered, since without them Darwin's idea would not have conquered humanity.

Darwin assumed that the small fluctuating variations could accumulate to larger variations and thus cause It was the merit of de Vries1 to have pointed out that fluctuating variations are not hereditary and hence could not have played the r61e assigned to them by Darwin, while discontinuous variations as they appear in the so-called " sports" or mutations are inherited. This was an important step in the history of the theory of evolution. It did not touch the foundation of Darwin's work, namely the substitution of the idea of an accidental evolution for that of a purposeful creation; it only modified the conception of the possible mechanism of evolution. According to de Vries, there are special species or groups of species which are in a state of mutation. He considers the evening primrose on which he made his observations as one of these forms. Morgan and his pupils have observed over 130 mutations in a fly Drosophila. From our present limited knowledge we must admit the possibility that the tendency toward the production of mutants is not equally strong in different forms. Whether this part of de Vries' s idea is or is not correct there can be no doubt that variations occur which consist in the loss and apparently, though in rarer cases, in the gain or a modification of a Mendelian factor. If we wish to visualize the basis of such a change we may do so by imagining well-defined chemical constituents in one or more of the chromomeres undergoing a chemical change.

This way of looking at the origin of variation has had the effect of putting an end to the vague speculations concerning the evolution of one form from another. We demand today the experimental test when such a statement is made and as a consequence the amount of mere speculation in this field has diminished considerably. It is possible that any further progress concerning evolution must come by experimental attempts to bring about at will definite mutations. Such attempts have been reported but they are not all beyond the possibility of error.1 The most remarkable among them are those by Tower who by a very complicated combination of effects of temperature and moisture claims to have produced definite mutations in the potato beetle. The conditions for these experiments are so expensive and complicated that a repetition by other investigators has not yet been possible.

It is, however, still uncertain whether the mere addition or loss of Mendelian characters can lead to the origin of new species. Species specificity is determined by specific proteins (Chapter III.), while some Mendelian characters at least seem to be determined by hormones or substances which need neither be proteins nor specific for the species. 1 For a critical discussion of the details, see Bateson, W., Problems of Genetics, New Haven, 1913, Chapter X.

I. It is an old saying that we cannot understand life unless we understand death. The dead body, if its temperature is not too low and if it contains enough water, undergoes rapid disintegration. It was natural to argue that life is that which resists this tendency to disintegration. The older observers thought that the forces of nature determined the decay, while the vital force resisted it. This idea found its tersest expression in the definition of Bichat, that "life is the sum total of the forces which resist death." Science is not the field of definitions, but of prediction and control. The problem is: first, how does it happen that as soon as respiration has ceased only for a few minutes the human body is dead, that is to say, will commence to undergo disintegration, and second, what protects the body against this decay while the respiration goes on, although temperature and moisture are such as to favour decay?

why it was that the stomach and intestine did not digest themselves. The hydrochloric acid and the pepsin in the stomach and the trypsin in the intestine digest proteins taken in in the form of food; why do they not digest the proteins of the cells of the stomach and the intestine? They will promptly digest the stomach as soon as the individual is dead, but not during life. A self -digestion may also be caused if the arteries of the stomach are ligatured. Claude Bernard and others suggested that the layer of mucus protected the cells of the stomach and of the intestine from the digestive enzymes; or that the epithelial layer had a protective effect. Pavy suggested that the alkali of the blood had a protective action. All these theories became untenable when Fermi showed that all kinds of living organisms, protozoans, worms, arthropods, are not digested in solutions of trypsin as long as they are alive, while they are promptly digested in the same solution when dead.1 This is in harmony with the fact that many parasites live in the intestine without being digested as long as they are alive. Fermi concluded that the living cell cannot be attacked by the digestive ferments, while with death a change occurs by which they can be attacked. But what is this change? Fermi seems to be inclined to think that the "living molecule" of protein is not hydrolysable (perhaps because the enzyme cannot attach itself to it?),

while a change in the constitution or configuration of the proteins takes place after respiration has ceased. The fact that the living cell resists the digestive action of trypsin and pepsin has found two other modes of explanation, first, that the cells are surrounded by a membrane or envelope through which the enzyme cannot diffuse, and second, that the living cells possess antiferments. But the so-called antiferments are also said to exist after the death of the cell, whereas after death the cell is promptly digested. Fredericq, as well as Klug, has shown that worms which are not attacked by trypsin are digested by this enzyme when they are cut into small pieces; although the pieces of course contain the antienzyme. . The other suggestion that a membrane impermeable for trypsin protects the cells would explain why living protozoa are not digested by trypsin, but it leaves another fact unexplained, namely, the autodigestion of all the cells after death by enzymes contained in the cells themselves.

2. The disintegration of the body after death is not caused exclusively or even chiefly by the digestive enzymes of the intestinal tract or the micro-organisms entering the dead body from the outside, but by the enzymes contained in the cells themselves. This phenomenon of autolysis1 was first characterized by Hoppe-Seyler.2 All organs suffering death within the organism, in the absence of oxygen, undergo softening and dissolution in a manner resembling that of putrefaction. In the course of that process, albuminous matter gives rise to leucin and tyrosin, fat to free acids and soaps. This maceration, identical with the pathological conception of softening, is accomplished without giving rise to ill odour and is a process similar to the one resulting from the action of water, acids, and digestive enzymes.

In work of this kind, rigid asepsis is required to exclude the possibility of bacterial infection and this was first done by Salkowski, who showed that in aseptically kept tissues like liver and muscle the amount of substances that can be extracted with hot water jHaftef^aS1*^ By £h£,work of .Qthers, especially Martin Jacoby and Levepg,».it was established that the power of self-digestion is shared by all organs. Analysis of the products of the autodigestion of tissues shows that, e. g., the amino acids, which constitute the proteins, are produced. Dakin, Jones, and Levene demonstrated the hydrolytic products of the nucleins, in the case of the self-digestion of tissues. x