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heads of comets shows a spectrum that is very similar to that of the incandescent electric light in gases containing hydrocarbon. But carbon is the characteristic element of the organic compounds, of which living bodies are composed. Who can say whether these bodies that swarm everywhere through space do not spread also the germs of life whenever a new world has become capable of affording a dwellingplace to organic creatures? And this life we might, perhaps, have reason to regard as even allied to our own in germ, however various may be the forms in which it might adapt itself to the conditions of its new dwelling-place."
Preyer objects to the cosmozoa theory that it only sets the question back to, How did life originate in the universe: and Helmholtz says: "The true alternative is evident; organic life has either begun to exist at some one time, or has existed from eternity."
Pflüger's theory of the origin of life is the most scientific yet proposed. He argues that living proteid differs from dead proteid by the existence in the former of a cyanogen radicle. He says: "In the formation of cell substance, that is, of living proteid out of food proteid, a change of the latter takes place, the atoms of nitrogen going into a cyanogen-like relation with the atoms of carbon, probably with the absorption of considerable heat." Pflüger calls attention to the resemblances between cyanic acid, HCNO, and living proteid. Both easily polymerise, the living proteid growing and the cyanic acid forming. the polymeric cynamelid HnOnNnOn. Both yield urea on dissociation; both are liquid and transparent at low temperature, and both coagulate at higher temperature. Pflüger concludes that the beginning of life depended upon the formation of cyanogen, and then he reminds us that cyanogen and its compounds are produced only at incandescent heat. He summarizes as follows: "Accordingly, I would say that the first proteid to arise was living matter, endowed in all its radicles with the property of vigorously attracting similar constituents, adding them chemically to its molecule, and thus growing ad infinitum. According to this idea, living proteid does not need to have a constant molecular weight; it is a huge molecule undergoing constant, neverending formation and constant decomposition, and probably behaves towards the living chemical molecules as the sun behaves towards small meteors."1
It will be seen that according to Pflüger life is a molecular phenomenon, and it seems to be that this must be true. Nonliving matter, whether it be inorganic or organic, is relatively stable intramolecularly, while living matter is never stable within its molecule, which is constantly casting out and as constantly absorbing atomic groups. It assimilates and it excretes, and these phenomena are its essentials. Deprive the living molecule of food, and it dies; prevent its excretion, and it dies. Reaction between the living molecule and outside matter is constant, and is necessary to the continuance of life. The fact that
1 The different theories of the origin of life are ably discussed by Verworm in his 'General Physiology."
life resides in the molecule is, as I have stated, taught in Pflüger's theory. It is also recognized by Allen, who, in speaking of living proteid, says: "It is a molecule of enormous size, and (so far as the dynamic elements are concerned) its various groups are linked together by many nitrogen atoms, but not in a chain. It is not a proteid, a cyan compound, an amid, an amine, nor an alkaloid, but something that can yield some of them during life and others at its death. Death consists in the relaxation of the strained relationship of the nitrogen to the rest of the molecule. When thus 'the silver cord is loosened,' the relaxed groups fall into a state of repose. Most of these groups are proteids in which the N is peripheral, triad and unoxidized, having yielded its O to some other element. If, however, such a proteid molecule be applied to a living cell, it can be linked on again by its N, which thus once more becomes central."
In his very interesting monograph on the "Biogen Hypothesis," Verworm objects to saying that a molecule lives. He states that it is illogical. "A living thing is only that which demonstrates the phenomenon of life-something that changes itself. A molecule of a given compound, so long as it remains unchanged, cannot be said to be living." Then, in order not to speak of living molecules, he introduces the term "biogen molecule," instead of the living molecule. Surely this is a distinction without a difference. I certainly agree that a molecule of a germ compound, so long as it remains unchanged, cannot be said to be living, but the point is that living molecules do not remain unchanged. When life is latent, as it is in seeds and spores, the molecules cannot be said to be alive; but when placed under suitable conditions, then the change between atomic groups in the molecule and the external food substance begins, and life first manifests itself. However, it matters but little, I suppose, whether we speak of living molecules or biogen molecules.
That life resides within the molecule and that metabolic processes are intramolecular, are shown by numerous investigations, some of the most important of which may be briefly stated as follows:
(1) As long ago as 1867 it was shown by Hermann, in his studies. on the metabolism of isolated muscle, that the carbonic acid and lactic acid that are formed by muscular contraction result from the action of intramolecular or combined oxygen. This was demonstrated by the fact that when a muscle was freed from all its uncombined oxygen under an air pump and then caused to contract in an oxygen-free medium, it gives off carbonic and lactic acids. Contraction, a vital muscle phenomenon, is thus shown to result from intramolecular changes.
(2) In 1875. Pflüger kept a frog at a temperature of a few degrees above zero in an atmosphere free from oxygen for twenty-five hours, and found that during that time the animal continued to give off carbonic acid. From this Pflüger concluded that the living content of the organism consists of proteid, which he designates "living proteid," in
contradistinction to dead proteid, and that the carbonic acid gas results from the decomposition of a labile proteid molecule, the nitrogenous constituents of which are capable, with the help of the fats and carbohydrates of the food, to regenerate "the living proteid molecule."
(3) It has been shown by recent research in my own laboratory that both the toxin and the carbohydrate of the cell of the colon bacillus are held in chemical combination with other constituents of the cell. This microorganism will grow in a medium which contains organic nitrogen, as amino compound only, and with this nitrogen and inorganic salts as its sole food, it builds up by synthetical process a complex glyco-nucleo-proteid, forming a large molecule which contains as atomic groups, pentose, nuclein bases, amino and diamino compounds. These constituents are held chemically in the cell. They cannot be washed out by physical solvents, and can be isolated only by chemically breaking down the cell molecule.
Besides the above-mentioned experimental data showing that life manifests itself by intramolecular reaction, the following general considerations indicate the same thing:
(a) In taking its food the cell, whether it be vegetable or animal, whether it be that of a unicellular or that of a multicellular organism, manifests a selective action which can be best explained-indeed, I might say, can only be explained-on the ground that it is due to chemical affinity. Mass and molecular attractions are not specific, while atomic attraction, or chemical affinity, as it is usually designated, is specific, or at least selective. This fact, as is well known, is the basis of the side chain theory of Ehrlich, who, upon this principle, explains the nutrition of cells, the action of many therapeutical agents. and the production and action of antitoxins. It is well known that certain poisons have a selective action for certain tissues, and this means that the chemical affinity between the poison and the constituents of certain cells is greater than that between this poison and other cells. If pharmacology and toxicology ever become exact sciences it will be, most probably, through investigations directed along this line.
(b) The fact that the secretions of cells are specific is a strong argument for the theory that action on the pabulum upon which they feed is intramolecular. The liver cells produce bile pigments and acids, each of the digestive fluids elaborates its specific products, the specific secretions of the adrenals and the thyroid gland have been. studied and are now largely and successfully employed therapeutically. And still all these organs are supplied with the same blood and lymph. Certainly the only possible explanation for these well-established facts is that of a chemical reaction, or an intramolecular reaction, between the cells and the constituents of the substances with which they are brought into contact.
While other arguments might be adduced to show that metabolic processes, the only phenomena with which we are acquainted, that are characteristic of all living matter and which do not occur in dead mat
ter, are due to intramolecular reactions, it seems to me that those already given are sufficient to establish my thesis, that is, life is molecular.
If I have made good my contention so far, it follows that life begins with the first molecule that is endowed with the capability of growth and reproduction. The life of such a molecule would depend upon its continued reaction with matter outside of itself, or, in other words, it must feed; and reproduction in its simplest form would depend upon polymerization. In this way the wonderful experiments of Loeb upon the artificial fertilization of certain ova are easily explained. The ovum is not alive; it possesses only latent life, and when acted upon by certain stimuli it begins active life. This stimulus may be a spermatazoon or some inorganic salt in a certain definite strength of solution.
If life be molecular, it is possible that its lowest manifestations are without form. They may be infinitely small, and it is not beyond the range of possibility that they may exist as solids, liquids, or gases.
Spontaneous generation has never been proved to be impossible; indeed, it will not be easy to disprove spontaneous generation. I agree with Naegele in the following statement: "One fact-that in organisms inorganic substance becomes organic substance, and that the organic returns completely to the inorganic-is sufficient to enable us to deduce by means of the law of causation the spontaneous origin of organic nature from inorganic. . . If in the physical world all things stand in causal connection with one another, if all phenomena proceed along natural paths, then organisms, which build themselves up from and finally disintegrate into the substances of which inorganic nature consists, must have originated primitively from inorganic compounds. To deny spontaneous generation is to proclaim a miracle.”
The experiments of Tindall, Pasteur, and others, which were supposed to completely and forever overthrow the doctrine of spontaneous generation, in my humble opinion, did no such thing. They simply demonstrated that bacteria do not spontaneously generate in meat infusions and similar media, nothing more. Now, it seems to me that bacteria, which we frequently call the lowest forms of life, are by no means certainly entitled to this distinction. They may be the lowest forms with which we are acquainted, the smallest living things that we can see with our best microscopes. But chemically they are composed of extremely complex molecules, as has been shown by recent research in my laboratory. As I have already stated, the cell of the colon bacillus consists of a highly complex glyco-nucleo-proteid, yielding, on chemical disintegration, a carbohydrate, pentose, the nuclein bases, the monamino and diamino bodies, as tyrosin, leucin, lysin and arginin. In other words, chemically the colon molecule is quite as complex as that of the lower grade tissues in man. Now, if there has been a chemical, as well as a morphological, evolution, the colon bacillus is not the lowest form of life; indeed, it must be far removed from the first molecule that manifested metabolic activity.
The following quotation from Nussbaum, as given by Loeb, shows that the biologist recognizes that the cell is not the unit of life: "The cell is not the ultimate physiologic unit, even though it must remain such for the morphologist. We are, however, not able to tell how far the divisibility of a cell goes, and how we can determine the limit theoretically. Yet for the present it will be well not to apply to living matter the conceptions of atoms and molecules, which are well defined in physical chemistry. The notion, micella, introduced by Naegele, might also lead to difficulties, as the properties of living matter are based upon both nuclein and protoplasm. The cell, consequently, represents a multiple of individuals."
Pflüger has shown that the egg, which has been thought to be a unit, can give rise to many individuals, and Loeb states that his own experiments, as well as those of Driesch, confirm this finding.
It is highly probable that the lowest forms of life cannot feed upon proteids. This is true of the yeast cell. These cells grow rapidly when placed in a solution of sugar and nitrates, but proteids must be broken up by putrefactive bacteria before the yeast germs can feed upon them. Indeed, many of the cells of the body of man cannot feed upon proteids, which must be split up by the digestive enzymes into much. smaller and simpler groups before the cell molecules can assimilate them. Even the carbohydrate, starch, must be hydrated before it can become a source of energy in muscle. Proteid solutions injected into the blood of man are poisonous, but the same substance, after being properly split up, is an essential cell food. There are weighty reasons. for believing that proteid is not produced by the lowest forms of life. However, as proteid, or cellular life, is the only form of life that we know, it would be quite useless to attempt to go further along this. line.
I have probably said enough concerning spontaneous generation to bring down upon myself the anathemas of the orthodox in science, and since my opinion on this subject does not have any essential relation to the important thesis of this paper, I will leave this point without further discussion.
If the characteristic phenomena of life are due to intramolecular reactions, we must conceive the living cell, whether it belong high or low in the scale of development, as consisting in its essential or vital part of a chemical compound made up of complex molecules, composed of atoms, each surrounded by its electrons, all in motion, and with a constant absorption of atomic groups from other molecules, and with a like constant casting off of atomic groups.
This molecule feeds by splitting off such groups as it may need from the pabulum within its reach, or it may absorb whole molecules, at the same time rearranging the atoms and making them a part of itself.
When, in ordinary physiological function, a portion of this molecule, which we may designate its chemical nucleus, remains undisturbed and