Читать книгу The Organism as a Whole, from a Physicochemical Viewpoint - Jacques Loeb - Страница 8

by the addi­tion of the dried fat-free residue of the castor bean to a mixture of oleinic acid and glycerine. … No synthesis occurred with acetic, butyric, palmitic, and stearic acids with glycerine, mannite, and dulcite, and the experi­ments with the last two alcohols and oleinic acid likewise yielded no synthesis.

This suggests possibly a specific action of the enzyme. If this slight reversible action had any biological significance (which might be possible, since in the organism secondary favourable condi­tions might be at work which are lacking in vitro) there should be a parallelism between masses of lipase in different kinds of tissues and fat synthesis. Loevenhart indicated that this might be a fact, but a more extensive investiga­tion by H. C. Bradley has made this very dubious.21

Very little is known concerning the reversible action of the hydrolytic protein enzymes. A. E. Taylor digested protamine sulphate with trypsin and found that after adding trypsin to the products of diges­tion a precipitate was formed after long standing; and we may also refer to experi­ments of Robertson with pepsin on the products of caseinogen to which we shall return in the next chapter. It therefore looks at present as if van’t Hoff’s idea of reversible enzyme action might hold in the modifica­tion offered by Armstrong. It remains doubtful, however, whether this reversibility can explain all the synthetic processes in the cell. No objec­tion can be offered at present if any one makes the assump­tion that each cell has specific synthetic enzymes or some other synthetic mechanisms which are still unknown.

The mechanisms for the synthesis of proteins must have one other peculiarity: they must be specific in their action. We shall see in the next chapter that each species seems to possess one or more proteins not found in any other but closely related species. Each organism develops from a tiny microscopic germ and grows by synthetizing the non-specific building stones (amino acids) into the specific proteins of the species. This must be the work of the yet unknown synthetic enzymes or mechanisms. The elucida­tion of their character would seem one of the main problems of biology. Needless to say crystallography is not confronted with problems of such a nature.

The fact that the living cell grows after taking up food has given rise to curious misunderstandings. Traube has shown that drops of a liquid surrounded with a semipermeable membrane may increase in volume when put into a solu­tion of lower osmotic pressure. This has led and is possibly still leading to the statement that the process of growth by a living cell has been imitated artificially. Only one feature has been imitated, the increase in volume; but the essential feature of the process in the living cell, i.e., the forma­tion of the specific constituents of the living cell from non-specific products, has of course not been imitated.

4. The constant synthesis then of specific material from simple compounds of a non-specific character is the chief feature by which living matter differs from non-living matter. With this character is correlated another one; namely, when the mass of a cell reaches a certain limit the cell divides. This is perhaps most obvious in bacteria which on the proper nutritive medium take up food, grow, and divide into two bacteria, each of which takes up food, divides, and grows ad infinitum, as long as the food lasts, provided the harmful products of metabolism are removed. If it be true that specific synthetic ferments exist in each cell it follows that the cell must synthetize these also,22 as otherwise the synthesis of specific proteins would have to come to a standstill.

This problem of synthesis leads to the assump­tion of immortality of the living cell, since there is no a priori reason why this synthesis should ever come to a standstill of its own accord as long as enough food is available and the proper outside physical condi­tions are guaranteed. It is well known that Weismann has claimed immortality for all unicellular organisms and for the sex cells of metazoa, while he claimed the necessity of death for the body cells of the latter. Leo Loeb was led by his investiga­tions on the transplanta­tion of cancer to assume immortality not only for the cancer cell but also for the body cell of the organism. He had found in transplanting a malignant tumor from one individual to another that the tumor grew; that it was not the cells of the host but the transplanted tumor cells of the graft which grew and multiplied, and that this process could be repeated apparently indefinitely so that it was obvious that the transplanted tumor cells outlived the original animal. Such experi­ments have since been carried on so long that we may now say that an individual cancer cell taken from an animal and transplanted from time to time on a new host lives apparently indefinitely. Leo Loeb had found that these tumor cells are simply modified somatic cells. He therefore suggested that the somatic cells might be considered immortal with the same right as we speak of the immortality of the germ cells of such animals.23

This view receives its support first from the fact that certain trees like the Sequoia live several thousand years and may therefore be considered immortal and second, from the method of tissue culture. The method of cultivating tissue cells in a test tube, in the same way as is done for bacteria, was first proposed and carried out by Leo Loeb, in 1897,24 but his test-tube method did not permit the observa­tion of the transplanted cell under the microscope. This was made possible by a modifica­tion of the method by Harrison, who established the fact that the axis cylinder grows out from the ganglionic cell. Harrison and Burrows then perfected the method for the cultiva­tion of the cells of warm-blooded, animals, and with the aid of these methods Carrel succeeded in keeping connective-tissue cells of the heart of an early chick embryo alive more than four years, and these cells are still growing and dividing.25 Only very tiny masses of cells can be kept alive in this way since all the cells in the centre of a piece die on account of lack of oxygen; and every two days a few cells from the margin of the piece have to be transferred to a new culture medium.

This effect of lack of oxygen explains also why the immortality of the somatic cells is not obvious. Death in a human being consists in the stopping of heart beat and respira­tion, which also terminates the action of the brain or at least of consciousness. Immediately after the cessa­tion of heart beat and respira­tion the cells of muscle and of the skin and probably many or most other organs are still alive and might continue to live if transferred to another body with circula­tion and respira­tion. As a consequence of the lack of oxygen supply in the dead body they will, however, die comparatively rapidly. It may be stated that hearts taken out of the body after a number of hours can still beat again when put into the proper solu­tions and upon receiving an adequate oxygen supply.

The idea that the body cells are naturally immortal and die only if exposed to extreme injuries such as prolonged lack of oxygen or too high a temperature helps to make one problem more intelligible. The medical student, who for the first time realizes that life depends upon that one organ, the heart, doing its duty incessantly for the seventy years or so allotted to man, is amazed at the precariousness of our existence. It seems indeed uncanny that so delicate a mechanism should func­tion so regularly for so many years. The mysticism connected with this and other phenomena of adapta­tion would disappear if we could be certain that all cells are really immortal and that the fact which demands an explana­tion is not the continued activity but the cessa­tion of activity in death. Thus we see that the idea of the immortality of the body cell if it can be generalized may be destined to become one of the main supports for a complete physico­chemical analysis of life phenomena since it makes the durability of organisms intelligible.

5. This generalized idea of the immortality of some or possibly most or all somatic cells has a bearing upon the problem of the origin of life on our planet. The experi­ments of Spallanzani, Schwann, Schroeder, Pasteur, Tyndall, and all those who have worked with pure cultures of micro-organisms, have proved that no spontaneous genera­tion of living from non-living matter can be demonstrated; and the statements to the contrary were due to experi­mental errors inasmuch as the new organisms formed were the offspring of others which had entered into the culture medium by mistake.

In the last chapter of that most fascinating book Worlds in the Making,26 Arrhenius discusses the possibility of life being eternal and of living germs of very small dimensions—e.g., the spores of micro-organisms—being carried through space from one planet to another or even from one solar system to another. If it be true that there is no spontaneous genera­tion; if it be true that all cells are potentially immortal, we may indeed seriously raise the ques­tion: May not life after all be eternal? Such ideas were advocated by Richter in a rather phantastic way and more definitely by Helmholtz as well as Kelvin. The latter authors assumed that in the collision of planets or worlds on which there is life, fragments containing living organisms will be torn off and these fragments will move as seed-bearing stones through space. “If at the present instant no life existed upon this earth, one such stone falling upon it might … lead to its becoming covered with vegeta­tion.” Arrhenius points out the difficulties which oppose such a view, as, e.g., the fact “that the meteorite in its fall towards the earth becomes incandescent all over its surface and any seeds on it would therefore be deprived of their germinating power.”

Arrhenius suggests another and much more ingenious idea based on the fact that for particles below a certain size the mechanical pressure produced by light waves—the radia­tion pressure—can overcome the attractive force of gravita­tion.

Bodies which according to Schwarzschild would undergo the strongest influence of solar radia­tion must have a diameter of 0.00016 mm. supposing them to be spherical. The first ques­tion is therefore: Are there any living seeds of such extraordinary minuteness? The reply of the botanist is that spores of many bacteria have a size of 0.0003 or 0.0002 mm., and there are no doubt much smaller germs which our microscopes fail to disclose.

This assumption is undoubtedly correct.

We will, in the first instance, make a rough calcula­tion of what would happen if such an organism were detached from the earth and pushed out into space by the radia­tion pressure of our sun. The organism would first of all have to cross the orbit of Mars; then the orbits of the smaller and of the outer planets. … The organisms would cross the orbit of Mars after twenty days, the Jupiter orbit after eighty days, and the orbit of Neptune after fourteen months. Our nearest solar system would be reached in nine thousand years.

For the assump­tion of eternity of life only the transference of germs from one solar system to another would have to be considered and the ques­tion arises whether or not germs can keep their vitality so many thousands of years. Arrhenius thinks that this is possible on account of the low temperature (which must be below −220° C.) at which no chemical reac­tion and hence no decomposi­tion and deteriora­tion are possible in the spores; and on account of the absence of water vapour.

The ques­tion then arises: Have we any facts to warrant the assump­tion that spores may remain alive for thousands of years under such condi­tions and retain their power of germina­tion? We know that seeds have a very limited vitality, and the statement that grain found in the Egyptian tombs was still able to germinate has long been recognized as a myth. Miss White27 found that in wheat grains, there appeared a well-marked drop in their germinating power after about the fourth year, reaching zero in eleven to seventeen years. In a drier climate they last longer than in a moist climate. It is of importance that the hydrolyzing enzymes in the seeds, such as diastase, erepsin, remained unimpaired even after the germinating power of the seeds had disappeared. The seeds were able to resist for two days the temperature of liquid air, though the subsequent germina­tion was delayed by this treatment. Macfadyen28 exposed non-sporing bacteria, viz., B. typhosus, B. coli communis, Staphylococcus pyogenes aureus, and a Saccharomyces to liquid air.

The experi­ments showed that a prolonged exposure of six months to a temperature of about −190° has no appreciable effect on the vitality of micro-organisms. To judge by the results there appeared no reason to doubt that the experi­ment might have been successfully prolonged for a still longer period.

Paul Becquerel29 found that seeds which possess a very thick integument may live longer than the grain in Miss White’s experi­ments. The thickness of the integument prevents the exchange of gases between air and seed. Thus seeds of leguminoses (Cassia bicapsularis, Cytisus biflorus, Leucæna leucocephala, and Trifolium arvense) had retained their power of germina­tion for eighty-seven years. Becquerel has shown that the dryness of the membrane is very essential for such a dura­tion of life, since when dry it is impermeable for gases and the slow chemical reac­tions inside the grain become impossible.

In the cosmic space there is no water vapour, no atmosphere, and a low temperature, and there is hence no reason why spores should lose appreciably more of their germinating power in ten thousand years than in six months. We must therefore admit the possibility that spores may move for an almost infinite length of time through cosmic space and yet be ready for germina­tion when they fall upon a planet in which all the condi­tions for germina­tion and development exist, e.g., water, proper temperature, and the right nutritive substances dissolved in the water (inclusive of free oxygen).

While thus everything is favourable to Arrhenius’s hypothesis, Becquerel raises the objec­tion that the spores going through space would yet be destroyed by ultraviolet light. This danger would probably exist only as long as the germ is not too far from a sun. The difficulty is a real one since the ultraviolet rays have a destructive effect even in the absence of oxygen. It is possible, however, that there are spores which can resist this effect of ultraviolet light. Arrhenius’s theory can not of course be disproved and we must agree with him that it is consistent not only with the theories of cosmogony but also with the seeming potential immortality of certain or of all cells.

The alternative to Arrhenius’s theory is that living matter did originate and still originates from non-living matter. If this idea is correct it should one day be possible to discover synthetic enzymes which are capable of forming molecules of their own kind from a simple nutritive solu­tion. With such synthetic enzymes as a starting point the task might be undertaken of creating cells capable of growth and cell division, at least in the apparently simple form in which these phenomena occur in bacteria; viz., that after the mass has reached a certain (still microscopic) size it divides into two cells and so on. If Arrhenius is right that living matter has had no more beginning than matter in general, this hope of making living matter artificially appears at present as futile as the hope of making molecules out of electrons.

The problem of making living matter artificially has been compared to that of constructing a perpetuum mobile; this comparison is, however, not correct. The idea of a perpetuum mobile contradicts the first law of thermodynamics, while the making of living matter may be impossible though contradicting no natural law.

Pasteur’s proof that spontaneous genera­tion does not occur in the solu­tions used by him does not prove that a synthesis of living from dead matter is impossible under any condi­tions. It is at least not inconceivable that in an earlier period of the earth’s history radio-activity, electrical discharges, and possibly also the action of volcanoes might have furnished the combina­tion of circumstances under which living matter might have been formed. The staggering difficulties in imagining such a possibility are not merely on the chemical side—e.g., the produc­tion of proteins from CO₂, and N—but also on the physical side if the necessity of a definite cell structure is considered. We shall see in the sixth chapter that without a structure in the egg to begin with, no forma­tion of a complicated organism is imaginable; and while a bacterium may have a simple structure, such a structure as it possesses is as necessary for its existence as are its enzymes.

Attempts have repeatedly been made to imitate the structures in the cell and of living organisms by colloidal precipitates. It is needless to point out that such precipitates are of importance only for the study of the origin of structures in the living, but that they are not otherwise an imita­tion of the living since they are lacking the characteristic synthetic chemical processes.