The Fitness of the Environment

an enzyme possessing the power to select and catalyze any one of the reactions, the for- mation of any special one of the many possible products in comparative purity is an auto- matic result. Such processes are in nature carried out with a perfection which to the chemist is almost inconceivable, by means of organic structures of the highest intricacy; but in the last analysis they rest upon the native properties of the three elements. The important consideration, I repeat, is this : that reduction, the necessary first change of carbonic acid and water, can lead directly by a single continuous chemical transforma- tion, of which the exact control is no whit more remarkable than the accurate control of the other processes of chemical physiology,^ to the full intricacy of organic chemistry ; to the very most notable instance of number, variety, and activity of substances, all formed inevitably, in the nature of the case, which has yet come to light. It is of no consequence that most of the substances must be formed in mere traces by the spontaneous synthesis, for in highest degree the organism possesses the power, by enzymiatic catalysis, to select

1 Consult the work of Bayliss on Enzymes. London, Longmans, Green & Company. any one of a group of simultaneous reactions that may serve its needs, and make that one predominant. In short, the fitness is recip^ rocal," the unique chemical adaptability of the process and the unique chemical powers of the living organism interlock. Such, in brief, are the superlative advan- tages which the properties of the compounds of the three elements contribute to the organic mechanism. They include number of sub- stances, variety of substances, variety of properties, variety of reactions, facility of reactions (instability), and the remarkable relationship between carbon dioxide and water and the carbohydrates. And they insure that extreme variety of chemical relationship which especially fits organic substances, once created, to be, throughout the various forms of life, the source of still other bodies, and the source of energy, by means of far-reaching chemical changes rapidly accomplished.

In the course of digestion the principal foodstuffs, carbohydrates, fats, and proteins, undergo a series of changes which are substan- tially the same for all. Such processes are known as hydrolytic cleavage, or more loosely as hydrolysis. Essentially they amount to successive splittings of the large molecules of the native substances, each cleavage being •accompanied by the addition of a molecule of water, until finally from starches and like substances the simple sugars like glucose result; from the fats, fatty acids and glycerine; from the proteins, the so-called amino acids. The cleavage of fats closely resembles the hydrolysis of a simple ester; the cleavage of proteins and carbohydrates a little more remotely resembles the same process. Accord- ingly, the hydrolysis of the simplest ester, methyl formate, may serve as an illustration of the nature of the reaction: —

This process is nothing less than the typical reaction between water and organic sub- stances. Accordingly, it is not surprising that such reactions are by no means confined to the digestion of food. Once formed, the prod- ucts of digestion are absorbed, the more readily because of their simplicity, and, also because of their simplicity, they carry into the body no trace of the organism in which they previously existed. But, if they are to be built up into the tissues of the animal, they must now be turned back into such fats, carbohydrates, and proteins as are character- istic of his physical structure ; into glycogen, haemoglobin, fibrinogen, etc. Accordingly, they undergo a process which is the exact reverse of the digestive change, in the simple case: —

But this is by no means the end of the matter. For example, glycogen thus formed in the liver from the glucose of the portal blood is soon torn down to glucose again. More- over, there are a host of other special cases of the same hydrolytic cleavage, or the re- verse process, in mammalian physiology. For instance, the formation of hippuric acid frord benzoic acid and glycocoll, and the formation of urea itself from ammonium carbonate belong to this same class. In fact, such reactions make up a large part of all the chemical - changes which take place within the organism.

It must not be imagined, however, that hydrolytic cleavages are infrequent outside the organism, or that the types of processes which occur within the organism are the only ones of this class. There is no more common and universally important reaction in organic chemistry, and many compounds and classes of compounds which have nothing to do with the organism undergo hydrolysis. Moreover, generally speaking, all reactions of this class are very similar in their principal character- istics, resembling one another both dynami- cally and statically. Spontaneously they oc- cur not at all, or very slowly. Under the influence of enzymes, of acids, and of alkalies acting catalytically, that is to say, facilitating the process without in the end taking part in it, much as oil facilitates the action of a machine, they progress rather slowly and very smoothly. By-products are not formed ; the reactions are simple, uncomplicated, and reliable. Hence they enable the organism to make all sorts of rearrangements and recon- structions of chemical substances efficiently and without loss of material.

The chief cause of such traits in hydrolysis is the fact that the energy transformation which accompanies the process is almost exactly nil. For it has been found in general that chemical reactions which liberate much energy are violent, hard to regulate, often complicated by intricate side reactions, and complete. In contrast, those which are with- out energy change generally proceed smoothly, slowly, and without complication to a state of equilibrium in which the reaction is very in- complete.^ Under the latter circumstances slight changes of conditions make possible a reversal of the delicately balanced process; the reaction can be made to run in either direction at will.

The absence of transformation of energy accompanying hydrolysis may be illustrated by a few typical cases chosen from the data of simple substances. Such measurements of heats of reaction fall well within the limits of error of the method of investigation, and there can be no doubt that in all such cases the heat of reaction is so small that it cannot be detected by the ordinary methods of measurement.^ 1 van't Hoff, "Acht Vortrage Uber Physikalische Chemie." Brunswick, 1902, Lecture 6.

''■ Stohmann, Zeitschrift fiir Physikalische Chemie, II, 29, 1888 (see also Ostwald's "Lekrbuch. der Allgemeinen Che- Thus it is evident that the process possesses another advantage. In the course of such rearrangements no energy is lost. This con- clusion is thoroughly confirmed by the studies of the energy transformations of metabolism. The body may carry on such processes as it will, in the greatest variety and complexity, rearranging and modifying its chemical struc- tures to any extent, and there will never be an appreciable wastage of precious material or of equally precious energy in the process.

This process, as we have seen, is the char- acteristic reaction between water and the organic compounds. As such it is necessarily one of our chief concerns ; its maximal fitness as a means of regulation, and otherwise, there- fore assumes real importance in the present discussion. With the survey of organic chemistry we have exhausted the compounds of carbon; mie"). These data are the most accurate now in existence which permit an estimate of the heat of hydrolysis of non- nitrogenous compounds. Numerous studies of protein deriv- atives from Fischer's laboratory prove that the facts are the same for these substances, and direct measurements confirm the measurements of heats of combustion.

not so those of hydrogen and oxygen. In ajmost equal frequency the latter elements take part in the reactions of inorganic chem- istry, and help to form its molecular struc- tures. As an illustration of their importance in this department of the science I have counted the compounds and the classes of compounds mentioned in the table of con- tents of the second edition of Erdmann's " Lehrbuch der Anorganischen Chemie." In all 435 substances are referred to; of these 259, approximately 60 per cent, contain oxygen; 130, or 30 per cent, contain hydrogen. There seems to be little doubt that this is a fair test, for the work is compendious, and all im- portant substances and classes of substances are mentioned. Even if the acids, and the small number of bodies which are referred to in connection with their water of crystalli- zation, be eliminated from the above count the great importance of the two elements remains clearly evident.

Only about one fourth of all the compounds mentioned contain neither hydrogen nor oxy- gen. A very large proportion of these con- sist of the chlorides, bromides, iodides, sul- phides, fluorides, and other similar binary compounds, whose importance certainly does not depend upon the variety of chemical reactions into which they may enter, while their formation unquestionably does depend upon the intervention of both hydrogen and oxygen. All told, the chemical substances which contain neither carbon, nor hydrogen, nor oxygen make up only a few per cent of known bodies.

It is also clear that an especially large pro- portion of the most active inorganic com- pounds contain either hydrogen or oxygen. All acids contain hydrogen; most of them oxygen as well. All bases contain oxygen. Moreover, the most important classes of re- actions of inorganic chemistry are probably oxidations and reductions, and the formation of salts from acids and bases. In such pro- cesses both oxygen and hydrogen are con- cerned. In addition to the oxides and resulting bases and acids, a few other important sub- stances which contain hydrogen or oxygen may be cited : ozone O3, hydrogen peroxide II2O2, ammonia NH3, hydrazine N2H4, hydrox- ylamine NH2OH, sulphuretted hydrogen H2S, hydrochloric acid HCl, nitrosyl chloride NOCl, thionyl chloride SOCI2, phosgene COCI2, phos- phine PH3, phosphorus oxychloride POCI3, arsine AsHs. Such compounds, and many other similar ones, are of great importance on

account of the variety of chemical processes into which they can enter. They make up the active agents of inorganic chemistry, and it is safe to assume that their activity depends in great part upon the properties of oxygen and hydrogen. The importance of oxygen and hydrogen in inorganic chemistry possesses a double significance in the present inquiry. In the first place it provides further confirmation of the view that the elements which make up water and carbon dioxide are unique. For the data of inorganic chemistry prove that hydrogen and oxygen are likely to confer great chemical activity wherever they are, and that they are quite unrivaled in this respect. Secondly, the occurrence of hydrogen and oxygen as primary factors of the metabolic process and as the chief constituents of the environment and of the living organism enables the latter to make use of other elements at * need. Without hydrogen and oxygen, op- portunities for the introduction of such other elements into the physiological processes would be necessarily much restricted, and in many cases the physiological utility of compounds containing the elements of inorganic chemistry is very great.

nesium, and it is thought that the process of reduction in the leaf may depend upon the characteristic properties of this element; at all events, in organic chemistry, magnesium, when employed in Grignard's reaction, is one of the most eflfective agents to accomplish reductions. In like manner, haemoglobin contains iron, and the capacity of haemoglobin to unite with oxygen, and as oxyhaemoglobin to carry it from the lungs to the tissues is unquestion- ably due to the chemical behavior of that metal. Other similar metallic elements, no- tably copper in the class of compounds known as haemocyanines, fulfill a similar function in lower animals.

Phosphorus in organic union is an essential constituent of a great variety of the chemical structures of living organisms, — the nucleic acids, which appear to be not less important than fats, carbohydrates, and proteids them- selves in both animal and plant cells, contain phosphorus as an essential constituent. Thus phosphorus follows close upon nitrogen, after carbon, oxygen, and hydrogen, as structural material in biological chemistry. This same element also occurs in many other compounds, the simplest derivative of such bodies being glycerophosphoric acid.

a compound of phosphorus, hydrogen, and oxygen with glycerine. Sulphur is a constituent of the proteins, and occurs in many other important com- pounds. In the metabolic process of the animal sulphur is converted from a derivative of hydrogen sulphide, HgS, by oxidation, into sulphuric acid, H2SO4, and in the plant the process is reversed. Iodine occurs in the thyroid and in many marine organisms. The availability of this element depends upon its existence in nature as iodides, that is to say, upon its capacity* to unite with hydrogen to form hydriodic acid, HI. Finally, it is the analogous com- pound of chlorine with hydrogen, hydro- chloric acid, which contributes acidity to the gastric juice.

This list might be much further extended, but I think that the nature of the case is now established. The conclusion seems inevitable that active, diverse, and important inorganic substances usually contain oxygen or hydro- gen, and that it is the union of other elements with these two which renders them available and useful to the organism. Every chemical change consists in simul- taneous rearrangements of matter and energy. The true nature of the chemical process is to be sought neither in the one nor in the other of these two phenomena, but in both together ; and properly energy is as much the chemist's concern as matter itself.

Thus far in the present investigation, con- siderations regarding energy have been avoided except in the case of hydrolytic cleavages, and these constitute a unique class of reactions. No other large and important class is char- acterized by inappreciable heat of reaction, for it is as heat that chemical energy commonly manifests itself when liberated. It is evident, however, in accordance with the fundamental postulates, that the organism must have energy to actuate as well as matter to form its mechanism. Therefore the nature of the energy transformations, which make up one

aspect of the chemical reactions into which carbon, hydrogen, and oxygen enter, must be now noticed. It has been shown above that the one pos- sible chemical process by means of which any- thing can be made out of the primary con- stituents of the environment is reduction, — the more or less complete tearing off of oxygen from carbon and hydrogen atoms in the mole- cules of carbon dioxide and water. As a function of the extent of the reduction the energy change involved in the process will vary. In all cases, however, the process is accompanied by large absorption of heat, as the following table of the energy absorbed per gram of the resulting substance, when reduction begins with water and carbonic acid, may indicate: —

Such new compounds hold their energy only so long as they persist unchanged, and upon oxidation they yield it all back again, just as water vapor on condensing yields back the latent heat which it has taken up during evaporation. In this manner, every gram of glucose or other monosaccharide is necessarily a temporary depository of solar energy amounting to about 3.74 calories, taking up just that amount of energy when synthesized by chlorophyll, yielding it back when burned in the muscle.

Compounds of carbon and hydrogen are especially well qualified to be reservoirs of energy which may be liberated by oxidation, as the following table shows: — Hydrogen, it will be seen, far exceeds any other element in the amount of heat that it yields upon oxidation; carbon is surpassed by but one other element, boron. Although necessarily a good deal of this heat cannot be stored in the compounds of the two elements which still contain some oxygen, yet enough remains to make the common constituents of the organism greater reservoirs of energy than most of the other elements themselves, far greater than compounds of any other elements. Thus the heat of combustion of carbohydrates ranges from about 3.7 calories to about 4.2 calories per gram, that of the proteins from about 5 calories to about 6 calories, that of the fats from about' 9.2 calo- ries to' about 9.5 calories. On account of the small quantity of oxygen and the large quan- tity of hydrogen which they contain, the fats are a richer source of energy than carbon itself, or than any other element except hydro- gen and boron.

There remains one other equally important consideration to be dealt with: the very great energy change which is involved in processes of oxidation and reduction compared with other chemical processes. The following table, showing the amount of heat liberated in the process of formation of certain binary compounds from their several elements, illus- trates the case: — Oxygen, as will be seen, far surpasses the other chemical elements (except fluorine) in the amount of energy liberated in the process of its chemical union with other substances.

Accordingly, it may be concluded that, on the whole, oxidations are the best chemical source of energy; reductions the best means of storing energy by chemical processes; and that among oxidations and reductions those of hydrogen especially, and then those of carbon, are associated with the largest energy transformations. This is the last argument which I have to present, but it is one of the most potent. The very chemical changes, which for so many other reasons seem to be best fitted to be- come the processes of physiology, turn out to be the very ones which can divert the greatest

flood of energy into the stream of life; and these are the reactions automatically provided for by the cosmic process. From the materialistic and the energetic standpoint alike, carbon, hydrogen, and oxy- gen, each by itself, and all taken together, possess unique and preeminent chemical fit- ness for the organic mechanism. They alone are best fitted to form it and to set it in motion; and their stable compounds, water and car- bonic acid, which make up the changeless environment, protect and renew it, forever drawing fresh energy from the sunshine.

THE statement of evidence for the bio- logical fitness of the environment is at length completed. Whatever favorable prop- erties of water, carbonic acid, and the com- pounds of the three elements, whatever results favorable to life, I have succeeded in finding, have been set forth. Now, therefore, we may return to the exam- ination of this evidence in the manner sug- gested in Chapter II. We may inquire into the exhaustiveness of the preceding treatment of important physical properties, seeking to discover what things have been overlooked. Thus it may be possible to decide the weighty question whether another group of elements can possess another group of equally impor- tant properties. Next, we may consider if there be other elements or compounds which rival carbon, hydrogen and oxygen, water and carbonic acid, in the qualities which make these fit for the organic mechanism, taking such properties as a whole. Unfortunately,

in adopting this somewhat rigid logical method, tedious and perhaps unnecessary repetition is involved, but the advantages of care at this stage of the inquiry seem to be very great, for it is not easy to survey so large a field, and at best certainty that impor- tant oversights have been avoided is obviously impossible. For example, peculiarities like the anomalous expansion of water, or the relation of carbonic acid and water to the carbohy- drates are not to be foreseen. On the other hand, the more general characteristics of matter are well known and, for the most part, must reveal themselves to diligent search.

First the natural phenomena which seem to be concerned in fitness may be brought to- gether analytically, and their effect briefly summarized. I. The occurrence of great quantities of water and carbon dioxide outside the solid crust of an astronomical body. /. (Thermal Conductivity.) g. Expansion before Freezing. h. (Expansion in Freezing.) i. Solvent Power. j. Dielectric Constant. k. Ionizing Power. I. Surface Tension. HI. Properties of Carbon Dioxide.

e. Constancy of Osmotic Pressure. /. Constancy of Alkalinity. g. Constancy of Composition. V. Chemical Properties of Carbon, Hydro- gen, and Oxygen. g. The Evenness and Lack of Energy Change of the Process of Hydro- lytic Cleavage. h. The Chemical Relationship of Car- bonic Acid and Water to the Sugars. I. The Number and Variety of Com- pounds and Reactions of Oxygen with Other Elements. m. The Number and Variety of Com- pounds and Reactions of Hydro- gen with Other Elements.

All the properties or other phenomena noted in the above table (except II /, and II h) are in character or in magnitude either unique or nearly so, and are in their effect favorable to the organism as defined in the fundamental postulates. Indeed, they constitute or bring about an extraordinary set of conditions favorable to life, — ubiquity, abundance, va- riety, stability, mobility, constancy of composi- tion, and in variance of physico-chemical con-