The Organism as a Whole, from a Physicochemical Viewpoint

by Jacques Loeb

THE SPECIFIC DIFFERENCE BETWEEN LIVING AND DEAD MATTER AND THE QUESTION OF THE ORIGIN OF LIFE

1. Each organism is characterized by a definite form and we shall see in the next chapter that this form is determined by definite chemical substances. The same is true for crystals, where substance and form are definitely connected and there are further analogies between organisms and crystals. Crystals can grow in a proper solu­tion, and can regenerate their form in such a solu­tion when broken or injured; it is even possible to prevent or retard the forma­tion of crystals in a supersaturated solu­tion by preventing “germs” in the air from getting into the solu­tion, an observa­tion which was later utilized by Schroeder and Pasteur in their experi­ments on spontaneous genera­tion. However, the analogies between a living organism and a crystal are merely superficial and it is by pointing out the fundamental differences between the behaviour of crystals and that of living organisms that we can best understand the specific difference between non-living and living matter. It is true that a crystal can grow, but it will do so only in a supersaturated solu­tion of its own substance. Just the reverse is true for living organisms. In order to make bacteria or the cells of our body grow, solu­tions of the split products of the substances composing them and not the substances themselves must be available to the cells; second, these solu­tions must not be supersaturated, on the contrary, they must be dilute; and third, growth leads in living organisms to cell division as soon as the mass of the cell reaches a certain limit. This process of cell division cannot be claimed even metaphorically to exist in a crystal. A correct apprecia­tion of these facts will give us an insight into the specific difference between non-living and living matter. The forma­tion of living matter consists in the synthesis of the proteins, nucleins, fats, and carbohydrates of the cells, from the split products. To give an historical example, Pasteur showed that yeast cells and other fungi could be raised on the following sterilized solu­tion: water, 100 gm., crystallized sugar, 10 gm., ammonium tartrate, 0.2 gm. to 0.5 gm., and fused ash from yeast, 0.1 gm.[7] He undertook this experi­ment to disprove the idea that protein or organic matter in a state of decomposi­tion was needed for the origin of new organisms as the defenders of the idea of spontaneous genera­tion had maintained.

2. That such a solu­tion can serve for the synthesis of all the compounds of living yeast cells is due to the fact that it contains the sugars. From the sugars organic acids can be formed and these with ammonia (which was offered in the form of ammonium tartrate) may give rise to the forma­tion of amino acids, the “building stones” of the proteins. It is thus obvious that the synthesis of living matter centres around the sugar molecule. The phosphates are required for the forma­tion of the nucleins, and the work of Harden and Young suggests that they play also a rôle in the alcoholic fermenta­tion of sugar.

Chlorophyll, under the influence of the red rays of light, manufactures the sugars from the CO₂ of the air. This makes it appear as though life on our planet should have been preceded by the existence of chlorophyll, a fact difficult to understand since it seems more natural to conceive of chlorophyll as a part or a product of living organisms rather than the reverse. Where then should the sugar come from, which is a constituent of the majority of culture media and which seems a prerequisite for the synthesis of proteins in living organisms?

The investiga­tions of Winogradsky on nitrifying,[8] sulphur and perhaps also on iron bacteria have to all appearances pointed a way out of this difficulty. It seemed probable that there were specific micro-organisms which oxidized the ammonia formed in sewage or in the putrefac­tion of living matter, but the attempts to prove this assump­tion by raising such a nitrifying micro-organism on one of the usual culture media, all of which contained organic compounds, failed. Led by the results of his observa­tions on sulphur bacteria it occurred to Winogradsky that the presence of organic compounds stood in the way of raising these bacteria, and this idea proved correct. The bacteria oxidizing ammonia to nitrites were grown on the following medium; 1 gm. ammonium sulphate, 1 gm. potassium phosphate, 1 gm. magnesium carbonate, to 1 litre of water. From this medium, which is free from sugar and contains only constituents which could exist on the planet before the appearance of life, the nitrifying bacteria were able to form sugars, fatty acids, proteins, and the other specific constituents of living matter. Winogradsky proved, by quantitative determina­tion, that with the nitrifica­tion an increase in the amount of carbon compounds takes place. “Since this bound carbon in the cultures can have no other source than the CO₂ and since the process itself can have no other cause than the activity of the nitrifying organism, no other alternative was left but to ascribe to it the power of assimilating CO₂.”[9] “Since the oxida­tion of NH₃ is the only source of chemical energy which the nitrifying organism can use it was clear a priori that the yield in assimila­tion must correspond to the quantity of oxidized nitrogen. It turned out that an approximately constant ratio exists between the values of assimilated carbon and those of oxidized nitrogen.” This is illustrated by the results of various experi­ments as shown in Table I.

TABLE I

	No. 5	No. 6	No. 7	No. 8
	mg.	mg.	mg.	mg.
Oxidized N	722.0	506.1	928.3	815.4
Assimilated C	019.7	015.2	026.4	022.4
Ratio N : C	036.6	033.3	035.2	036.4

It is obvious that 1 part of assimilated carbon corresponds to about 35.4 parts oxidized nitrogen or 96 parts of nitrous acid.

These results of Winogradsky were confirmed in very careful experi­ments by E. Godlewski, Sr.[10]

The nitrites are further oxidized by another kind of micro-organisms into nitrates and they also can be raised without organic material.

Winogradsky had already previously discovered that the hydrogen sulphide which is formed as a reduc­tion product from CaSO₄ or in putrefac­tion by the activity of certain bacteria can be oxidized by certain groups of bacteria, the sulphur bacteria. Such bacteria, e. g., Beggiatoa, are also commonly found at the outlet of sulphur springs. They utilize the hydrogen sulphide which they oxidize to sulphur and afterwards to sulphates, according to the scheme:

(1) 2H₂S + O₂ = 2H₂O + S₂

(2) S₂ + 3O₂ + 2H₂O = 2H₂SO₄

The sulphuric acid is at once neutralized by carbonates.

Winogradsky assumes that the oxida­tion of H₂S by the sulphur bacteria is the source of energy which plays the same rôle as the oxida­tion of NH₃ plays in the nitrifying bacteria, or the oxida­tion of carbon compounds—sugar and others—in the case of the other lower and higher organisms. Winogradsky has made it very probable that sulphur bacteria do not need any organic compounds and that their nutri­tion may be accomplished with a purely mineral culture medium, like that of the nitrite bacteria. On the basis of this assump­tion they should also be able to form sugars from the CO₂ of the air.

Nathanson[11] discovered in the sea water the existence of bacteria which oxidize thiosulphate to sulphuric acid. They will develop if some Na₂S₂O₃, is added to sea water. These bacteria can only develop if CO₂ from the air is admitted or when carbonates are present. For these organisms the CO₂ cannot be replaced by glucose, urea, or other organic substances. Such bacteria must therefore possess the power of producing sugar and starch from CO₂ without the aid of chlorophyll. Similar observa­tions were made by Beijerinck on a species of fresh-water bacteria.[12]

Finally the case of iron bacteria may briefly be mentioned though Winogradsky’s views are not accepted by Molisch.

We may, therefore, consider it an established fact that there are a number of organisms which could have lived on this planet at a time when only mineral constituents, such as phosphates, K, Mg, SO₄, CO₂, and O₂ besides NH₃, or SH₂, existed. This would lead us to consider it possible that the first organisms on this planet may have belonged to that world of micro-organisms which was discovered by Winogradsky.

If we can conceive of this group of organisms as producing sugar, which in fact they do, they could have served as a basis for the development of other forms which require organic material for their development.

In 1883 the small island of Krakatau was destroyed by the most violent volcanic erup­tion on record. A visit to the islands two months after the erup­tion showed that “the three islands were covered with pumice and layers of ash reaching on an average a thickness of thirty metres and frequently sixty metres.”[13] Of course all life on the islands was extinct. When Treub in 1886 first visited the island, he found that blue-green algæ were the first colonists on the pumice and on the exposed blocks of rock in the ravines on the mountain slopes. Investiga­tions made during subsequent expedi­tions demonstrated the associa­tion of diatoms and bacteria. All of these were probably carried by the wind. The algæ referred to were according to Euler of the nostoc type. Nostoc does not require sugar, since it can produce that compound from the CO₂ of the air by the activity of its chlorophyll. This organism possesses also the power of assimilating the free nitrogen of the air. From these observa­tions and because the Nostocaceæ generally appear as the first settlers on sand the conclusion has been drawn that they or the group of Schizophyceæ to which they belong formed the first settlers of our planet.[14] This conclusion is not quite safe since in the settlement of Krakatau as well as in the first colonizing of sand areas the nature of the first settler is determined chiefly by the carrying power of wind (or waves and birds).

We may now return from this digression to the real object of our discussion, namely that the nutritive solu­tions of organisms must be very dilute and consist of the split products of the complicated compounds of which the organisms consist. The examples given sufficiently illustrate this statement.

The nutritive medium of our body cells is the blood, and while we take up as food the complicated compounds of plants or animals, these substances undergo a diges­tion, i. e., a splitting up into small constituents before they can diffuse from the intestine into the blood. Thus the proteins are digested down to the amino acids and these diffuse into the blood as demonstrated by Folin and by Van Slyke. From here the cells take them up. The different proteins differ in regard to the different types of amino acids which they contain. While the bacteria and fungi and apparently the higher plants can build up all their different amino acids from ammonia, this power is no longer found in the mammals which can form only certain amino acids in their body and must receive the others through their food. As a consequence it is usually necessary to feed young animals on more than one protein in order to make them grow, since one protein, as a rule, does not contain all the amino acids needed for the manufacture of all the proteins required for the forma­tion of the material of a growing animal.[15]

3. The essential difference between living and non-living matter consists then in this: the living cell synthetizes its own complicated specific material from indifferent or non-specific simple compounds of the surrounding medium, while the crystal simply adds the molecules found in its supersaturated solu­tion. This synthetic power of trans­forming small “building stones” into the complicated compounds specific for each organism is the “secret of life” or rather one of the secrets of life.

What clew have we in regard to the nature of this synthetic power? We know that the comparatively great velocity of chemical reac­tions in a living organism is due to the presence of enzymes (ferments) or to catalytic agencies in general. Some of these catalytic agencies are specific in the sense that a given catalyzer can accelerate the reac­tion of only one step in a complicated chemical reac­tion. While these enzymes are formed by the action of the body they can be separated from the body without losing their catalytic efficiency. It was a long time before scientists succeeded in isolating the enzyme of the yeast cell which causes the alcoholic fermenta­tion of sugar; and this gave rise to the premature statement that it was not possible to isolate this enzyme since it was bound up with the life of the yeast cell. Such a statement was even made by a man like Pasteur, who was usually a model of restraint in his utterances, and yet the work of Buchner proved him to be wrong.

The general mechanism of the action of the hydrolyzing enzymes is known. The old idea of de la Rive, that a molecule of enzyme combines transitorily with a molecule of substrate; the further idea, which may possibly go back to Engler, that the molecule of substrate is disrupted in the “strain” of the new combina­tion and that the broken fragments fall off or are easily knocked off by collision from the ferment molecule which is now ready to repeat the process, seems to be correct. On the assump­tion that the velocity of enzyme reac­tion is propor­tional to the mass of the enzyme and that de la Rive’s idea was correct, Van Slyke and Cullen were able to calculate the coefficients of the velocity of enzyme reac­tions for the fermenta­tion of urea and other substances, and the agreement between calculated and observed values was remarkable.[16]

While the hydrolytic action of enzymes is thus clear the synthesis in the cell is still a riddle. An interesting sugges­tion was made by van’t Hoff, who in 1898 expressed the idea that the hydrolytic enzymes should also act in the opposite direc­tion, namely synthetically. Thus it should not only be possible to digest proteins with pepsin but also to synthetize them from the products of diges­tion with the aid of the same enzyme. This expecta­tion was based on the idea that the enzyme did not alter the equilibrium between the hydrolyzed and non-hydrolyzed part of the substrate but only accelerated the rate with which the equilibrium was reached. Van’t Hoff’s idea omitted, however, the possibility that in the transitory combina­tion between enzyme molecule and substrate a change in the molecular configura­tion of the substrate or in the distribu­tion of intramolecular strain may take place. The first apparently complete confirma­tion of van’t Hoff’s sugges­tion appeared in the form of the synthesis of maltose from grape sugar by the enzyme maltase, which decomposes maltose into grape sugar. By adding the enzyme maltase from yeast to a forty per cent. solu­tion of glucose Croft Hill[17] obtained a good yield of maltose. It turned out, however, that what he took for maltose was not this compound but an isomer, namely isomaltose, which has a different molecular configura­tion and cannot be hydrolyzed by the enzyme maltase.

Lactose is hydrolyzed from kephyr by an enzyme lactase into galactose and glucose; by adding this enzyme to galactose and glucose a synthesis was obtained not of lactose but of isolactose; the latter, however, is not decomposed by the enzyme lactase.

E. F. Armstrong has worked out a theory which tries to account for this striking phenomenon by assuming “that the enzyme has a specific influence in promoting the forma­tion of the biose which it cannot hydrolyze.”[18] The theory is very ingenious and seems supported by fact. This then would lead to the result that certain hydrolytic enzymes may have a synthetic action but not in the manner suggested by van’t Hoff.

The principle enunciated by Armstrong, that in the synthetic action of hydrolytic enzymes not the original compound but an isomer is formed which can not be hydrolyzed by the enzyme, may possibly be of great importance in the understanding of life phenomena. It shows us how the cell can grow in the presence of hydrolytic enzymes and why in hunger the disintegra­tion of the cell material is so slow. It was at first thought that the forma­tion of isomers contradicted the idea of the reversible action of enzymes, but this is not the case; on the contrary, it supports it but makes an addi­tion which may solve the riddle of what Claude Bernard called the creative action of living matter. We shall come back to this problem in the last chapter.

Kastle and Loevenhart demonstrated the synthesis of a trace of ethylbutyrate by lipase if the latter enzyme was added to the products of the hydrolysis of ethylbutyrate, ethyl alcohol, and butyric acid by the same enzyme.[19] Taylor[20] obtained the synthesis of a slight amount of triolein

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 White[27] 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. Macfadyen[28] 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 Becquerel[29] 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.

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