Popular Science Monthly/Volume 20/February 1882/The Fundamental Problems of Physiological Chemistry

From Wikisource
Jump to navigation Jump to search




WHEN the science which endeavors to determine the phenomena of life and their connection was enabled to employ more exact expedients for its observations, the influence which the chemical process exerts on that of life became known. The physical apparatus of the body are preserved in the aggregate state and form, which are necessary for the performance of their functions by a definite chemical composition of the organs and the fluids which saturate them; and the source of the power required by the living body for its movements is to be sought for in the destruction of the compounds of which it is composed. This statement is not only justified by the axioms of science, but it is also confirmed by experience. For, even where the best methods of chemistry are deficient, we meet with phenomena, the appearance of which can only be explained by chemical decomposition. The substances of which the muscle is formed and the manner in which they are arranged are still imperfectly known; of the chemical process which takes place in the sarcous elements, when a muscle passes from rest to the contracted state, we know scarcely anything; still, we can not doubt for a moment that the muscle owes its form to its composition, and its motion to a change of the latter. This is shown by the fact that even by a slight change, which we may produce in the chemical constitution, though it be only a change in the amount of water or salt in the muscle, its elasticity, its sensibility, its ability to raise weights, is affected. By comparing the composition of the muscle, recovered after long repose, with that of the muscle tired by exertion, we immediately see that a change has taken place in it. The same may be said of the nerve, which has hitherto offered almost insurmountable obstacles to chemical examination; for how can its tiring be explained except by a chemical change of its mass? All doubt must here be removed on considering the electric change which accompanies every excitation of the nerve, for the differences in the electric tension, which appear in this momentary phenomenon, give distinct evidence of a chemical change.

For a complete understanding of these phenomena, an exact knowledge of the chemical processes in the organism is essential. At present we do not possess this; nevertheless, it is well worth the trouble to examine how far we have advanced in this direction; what requirements are to be fulfilled for further investigations; and in what manner we are to proceed in order to arrive at the object to be accomplished.

For a series of the most important disclosures, we are indebted to those investigations which have been devoted to the life-processes of the lowest organisms, consisting of single cells. Not that we have here progressed any further than elsewhere, but we have attained the certainty that the most important processes take place in the cells themselves, and that substances are formed which are able to produce powerful chemical changes. The processes to be first considered are those included under the general name of fermentation.

The first known process of fermentation is that which cane-sugar undergoes. A fungus, the so-called yeast, converts the sugar into glucose, and then decomposes this into alcohol and carbonic acid, with the simultaneous formation of small quantities of other products, such as succinic acid, glycerine, etc. The amount of yeast is not increased unless other substances, particularly nitrogenous organic and certain inorganic salts required in building up the body of the cells, are present. From this it appears that various chemical processes take place within the cell, the most striking of which is the decomposition of the sugar. How this takes place is a question which has been largely discussed. From the circumstance that carbonic acid and alcohol are produced in such proportions that the quantities of carbon, hydrogen, and oxygen contained in them are just sufficient to form the sugar, one might suppose that the decomposition is very simple; but, notwithstanding all attempts, the same reaction has never been produced without the aid of yeast. Two hypotheses have been proposed to explain this phenomenon: the one assumes that the yeast-cell contains a ferment which splits the glucose directly into carbonic acid and alcohol, the same as invertin changes cane-sugar into dextrose and lævulose; the other, on the contrary, considers the decomposition of the grape-sugar as an effect of the vital action of the yeast-cells, comparable to the conversion of albumen into carbonic acid, water, and urea in the organism of mammals.

In order to form an opinion of the value of these hypotheses, we will briefly indicate the points of view whence they have been projected. In the first theory consideration is given chiefly to the similarity which the outward appearance of the yeast fermentation has with certain chemical processes, such as the decomposition of sugar by invertin. In both cases the presence of a small amount of yeast or invertin suffices to decompose a comparatively large quantity of sugar, without any apparent change being produced in the yeast or in the invertin. This has given rise to the supposition of the existence of an alcohol ferment in the yeast; a theory which will be verified, when the suspected ferment shall be separated from the yeast, as has already been done with the invertin. All experiments, however, which have been made in this direction have resulted negatively, and hence the supporters of this hypothesis have been obliged to resort to the theory that the ferment in question is so readily decomposed that it can not be isolated. The other hypothesis is based upon the failure of all attempts to prepare the alcoholic ferment, and therefore assumes that such a ferment does not exist in the yeast, but, that the sugar is decomposed in the yeast-cell in the same way as the albumen is decomposed in the organism of the mammalia. The fact that a small amount of yeast can by degrees decompose a large quantity of sugar is of no more account than that a dog, for instance, can by degrees decompose many times his own weight of albumen. The fundamental difference between the hypotheses, therefore, is, that one assumes the presence of a ferment, while the other denies it.

The former hypothesis was fully justified as long as the nature of yeast and the ferments of the present were unknown; but, since we know the latter as definite chemical compounds, which are also active without the cell, and do not require this for the development of their activity, we must strictly distinguish between their action and that which we see produced only by the living organism or cell. The latter is not at all to be considered the effect of fermentation, until actual evidence of the presence of a specific ferment is furnished. A simple consideration will show that the decomposition of the sugar, as the result of the vital action of the yeast-cell, may well be compared to the conversion of albumen into carbonic acid, water, and urea, in the higher organisms. If we assume the body of a mammal, a dog for instance, to be reduced to the size of a yeast-cell, without any change in its organization, we would manifestly obtain a microscopic organism, which would act on albumen in the same way that yeast acts on sugar. Its anatomy would be as inaccessible to us as that of the yeast-cell, for the organs would appear to us as dots and threads, similar to the grains which we find in the cells. The changes of the gases in the blood, together with the processes which take place in the intestines or in the liver, and which have so often been made the subject of the most thorough investigations, would be beyond the reach of our methods and we could only determine that these organisms have the power to convert comparatively large quantities of albumen into carbonic acid, water, and urea, with the absorption of oxygen—in short, the process would be similar to that of yeast fermentation. If we had chickens and snakes in the same diminutive state, we should find that they would produce uric acid instead of urea. It would be in vain to attempt to separate from these organisms a ferment which would convert albumen into carbonic acid, water, and urea, or uric acid, with the absorption of oxygen.

The fact that sufficiently reduced dogs and chickens would represent two different ferments shows clearly that the differences which are observed between yeast, the lactic ferment, and the butyric ferment, may be considered due to the inner organization of these most minute beings. The supposition that one variety of bacteria can produce lactic acid, another butyric acid, a third caproic acid, has recently been stigmatized as "superstition"; but it was forgotten that the cells of the hog's liver produce a different acid from that obtained from the liver of a goose, ox, or man a fact which evidently is of the same order as that given for the bacteria.

Another point deserves our special attention—the, inner organization of the single cells, and the organisms composed of them. Since our present means are insufficient to distinguish this with certainty, we consider the cell or living protoplasm as being without structure. This reasoning is untenable, as it is only supported by the imperfection of our apparatus and methods; on the contrary, other weighty facts are in favor of the presence of such an organization. Above all, it is to be emphasized that within each living cell a number of chemical processes are constantly taking place simultaneously, all of which are necessary for the existence and vitality of the cell. These processes are of so different a nature that it is difficult to believe that they take place within a perfectly homogeneous mass. It seems much more simple and natural to suppose that each of the reactions takes place separately, which could be most readily effected by an internal organization of the cell. The peculiar figures which have been noticed in the division of the cells also speak in favor of this, as do the differences in their exterior forms, which are always governed by the inner organization; the variations in the further development, and particularly the effect on the surroundings, are also in favor of this view. How can we perceive that the bacteria of ordinary putrefaction are comparatively harmless, while the bacteria of splenitis are so destructive, unless we seek the cause in the peculiar inner structure?

Hence the chemical processes within the living cell are of two kinds: those in which ferments take part, and those in which they do not. The ferments are definite chemical compounds, which are able to decompose large quantities of other substances without undergoing any apparent change themselves. The manner in which this takes place is not yet explained, but we have reasons for comparing these processes with others in which a small quantity of one body, e. g., sulphuric acid, gradually converts a large quantity of another, e. g., alcohol, into ether and water. In this case the sulphuric acid acts like a ferment on the alcohol, and the similarity is so striking that it has been attempted to explain both in the same way. Formerly it was supposed that the simple contact of one body with another was in many cases sufficient for complete decomposition, and contact action, produced by the so-called catalytic force, was spoken of. Later it was found that in the above example the sulphuric acid first combines with the alcohol to form ethyl sulphuric acid, which is afterward decomposed with a fresh quantity of alcohol into ether and sulphuric acid. Accordingly, the action of every ferment must be considered as consisting of at least two reactions, in the first of which the ferment forms with the substance to be decomposed a compound which is split up in the second with the regeneration of the ferment. This has not been experimentally proved for the real ferments, but it explains these processes so simply and completely that its correctness can not be doubted.

These processes of fermentation have an extraordinary distribution, for not only do the individual living cells produce ferments, but also those which form parts of complicated organisms. This is especially the case with those cells which are often united in enormous quantities to form a larger organ. I will recall the salivary gland, the peptic gland, and the pancreas, whose secretions are exceedingly rich in ferments. This is of the greatest importance for the economy of the animal organism, since it permits a considerable performance with a comparatively small expenditure of means.

I wish to call attention to another important peculiarity of the processes of fermentation—that is, to their sensibility to foreign influences. Some will only take place in a completely neutral or slightly alkaline solution, others only in a slightly acid solution; they all progress most rapidly at a certain temperature, and even slight deviations from the most favorable conditions are sufficient to sensibly retard the action of a ferment or to completely arrest it. The pepsin of the gastric juice acts exclusively in acid solution (best in hydrochloric acid); hence, if the gastric juice contains no free acid or only an organic acid, such as lactic acid, the pepsin will produce no effect on albumen, or only in a slight degree.

Although I have just described this sensibility as a peculiarity of the process of fermentation, it is not to be inferred that it is noticed here exclusively; on the contrary, we find it in all chemical processes, only in a less degree. How many reactions take place only at a given temperature, or at a given degree of concentration? Creatine, for instance, when boiled with baryta-water, is partly decomposed into urea and sarcosine, and partly into ammonia and methylhydantoin; and it is evident that the possibility of splitting up in different directions is increased with the size of the molecule. In the organism a large number of bodies are present which have a very complicated structure, and are therefore readily decomposed. They have an ephemeral existence only, but are, nevertheless, of the greatest importance in the economy of the whole. Most of them are unknown to us, but in some cases they have been successfully isolated. I will only mention glycogen, the discovery of which is several decades old, and the purple of the retina, which has only lately been recognized. All such complicated compounds, having a high molecular weight, are capable of furnishing very different products of decomposition under slightly modified conditions. If, therefore, the decompositions in the organism should always take place in the same manner, the governing conditions must be exceedingly constant. Every product of decomposition, which is not to be directly excreted, is further employed in the organism, and exerts an influence on the chemical processes taking place, and may therefore produce disturbances in them. An example will explain this: In a large number of mammals the glycocol formed in the organism is not separated by the kidneys under ordinary circumstances; but a quantity of benzoic acid taken with the food is sufficient to fix the glycocol with the formation of hippuric acid, and to separate it in this form. These and similar facts, which can be mentioned in large numbers, have a very important signification, for they give the strongest support to the assertion that the chemical process in the animal body may be considerably changed by apparently slight circumstances. If we accept this, and consider the occurrence of substances still unknown, and present, perhaps, only in very small quantity in the animal organism, we will obtain a hint as to the explanation of effects which many foreign substances produce, though in very small quantities, on the organism. Who does not know the action of strychnia, curarine, prussic acid, and similar poisons?

As our knowledge of these poisons has increased, we have found that they never act on the whole organism, but always on particular organs or groups of organs; these may be the nerves, the muscles, the glands, or only a portion of them. While the curarine paralyzes all voluntary muscles, the heart perceives nothing of its effects; on the other hand, the poison of the fly-agaric—muscarine—paralyzes the heart, but not the voluntary muscles. Strychnia acts only on certain portions of the spinal marrow, opium only on parts of the cerebrum; phenomena which remain completely unintelligible until we attempt to explain them from a chemical point of view, and assume that, at the points accessible to the action of these poisons, there occur, in very small quantities, substances which are of the highest importance to the vital action of the organism, and which are decomposed by them. Of course, chemistry has not yet shown us any essential difference between striped and unstriped muscles, between brain and the spinal marrow, or between the different parts of these organs; but, as the observation of certain lines in the spectrum has led to the discovery of new elements, so may the action of these poisons, at some future time, serve as a guide in searching for these suspected substances.

The chemistry of the animal body is not simply confined to the formation and decomposition of definite chemical compounds; the organism also makes use of certain physical phenomena which are inseparably connected with the chemical, namely, the electric and the thermic. The former take part in the excitation of the nerves, perhaps also in some of the chemical processes; the latter are to be considered as the source of heat in warm-blooded animals as well as of the mechanical force developed by the different muscles. These important facts throw light on the total character of the chemical processes; for, if the organism is able by their use to keep its own temperature at a higher point than that of its immediate surroundings, and also to develop mechanical force, then, if not all, at least a majority of these processes, are accompanied by a rise of temperature. As is well known, however, the highest temperatures are obtained by combustion—that is, by the combination of other bodies with oxygen. Since oxygen is continually inhaled and consumed by animals during life, we are obliged to consider this as the source of heat and force. We have here a problem which is open to discussion, namely, whether the energy liberated by the combustion was originally contained in the oxygen or in the other substances. It appears as if the latter assumption was generally accepted; at least, statements are often met with, such as, for instance, that coal contains the heat of the sun which has been stored up during thousands of years. Although we can not, at present, with the means at our disposal, definitely solve this problem, it can at least be shown that the statement has little in its favor. The decomposition of carbonic acid by the influence of the light and heat of the sun is effected in such a manner that the carbon is employed in the formation of the compounds of which the plant is built up, while the oxygen escapes into the atmosphere., Now, we know that solids contain the least energy, because it must be supplied to them in the form of heat in order to convert them into the liquid or gaseous state, while, on the contrary, heat must be withdrawn from gases to condense them to liquids or solids. Oxygen is one of the most permanent gases, and must therefore possess an enormous amount of energy, while carbon, on the other hand, being one of the most difficultly diffusible and volatile bodies, can only contain a little energy. This makes it extremely probable that the force of the sun, taken up by the plants, is not stored in their bodies, but in the free oxygen of the atmosphere. Hence the latter is to be considered as the inexhaustible source of power on which man and animals draw, and in the carbon we possess a valuable aid for making this energy, contained in the oxygen, available.

After this digression, let us return to the chemical processes in the animal body. The production of heat and mechanical force, as well as the large quantity of oxygen consumed, indicates that the greater part of these processes must consist of oxidations, and accordingly we find that, among the products of excretion, carbonic acid and water form the principal parts, two bodies which can not be further oxidized. Besides these (to which sulphuric acid and phosphoric acid may be added), other substances are excreted in small quantity, which admit of further oxidation, but which have not suffered it in the organism. I will only mention urea, uric acid, and creatinine. All these compounds are products of chemical action, and the question is raised, How are they produced in the body? to what reactions do they owe their origin? to a single one, or to a whole series? Here we must confess we have no answer, save in exceptional cases. Wherever matter is found definitely arranged, it is also accompanied by effects dependent upon the arrangement; platinum, zinc, and sulphuric acid, when connected in a proper manner, form a galvanic element and give rise to a galvanic current. Similar relations exist in the animal body; here we also find the constituents in a definite arrangement which we term organization, and by means of which the body has control over such peculiar conditions that we can not, or at best only in rare cases, imitate them in the laboratory, and produce the same reactions as are produced by the body. Although we have been taught, by the celebrated discovery of the artificial production of urea by Wöhler, that the compounds occurring in the organism may also be produced out of the body, this and similar experiments have given no explanation of the manner in which the reaction takes place in the organism. Neither have those experiments been explained in which, after the introduction of certain substances into the body, new compounds, not ordinarily present, are found in the excretions. These investigations have, however, considerably increased our knowledge, by showing beyond a doubt that intermediate products are formed in the body, which are generally directly decomposed, and therefore withdrawn from observation, but which can be fixed by the introduction of foreign material, and so protected from further decomposition. How they are produced or fixed is not explained by these experiments; even if we assume, for instance, that the two components unite, with the elimination of the elements of water, we have not the slightest idea how it is effected. Numerous experiments, in which the amount of substances taken up and excreted by the organism were determined, have given valuable results, but not in regard to the reactions taking place in the body. The chemistry of the living body shows the peculiarity that all reactions take place at the temperature of the body, which is quite low, without the intervention of strong reagents in the ordinary sense. If we wish to produce similar reactions outside of the organism, we generally employ a high temperature and substances which would destroy the organism itself. For instance, to prepare hippuric acid from benzoic acid and glycocol, in the laboratory, it is necessary to heat both for some time to 160°, while in the body it is only necessary to dissolve them in blood, and pass the solution through a kidney, when a combination is effected. A problem is here presented, the solution of which is of the greatest importance to physiological chemistry, and which must, therefore, be attempted with all perseverance. It is no longer sufficient to show that certain substances are changed in the animal body, and give rise to the formation of others, nor does it suffice to make the synthesis which the cell produces, by any means whatever, but we must endeavor to work under similar conditions and with the same means as the body itself. We must make our experiments at the temperature of the body, we must employ no reagents whose presence would be injurious to the organism, we must also take into consideration that we may not he able to attain our object by a single process, but by a whole series of altogether different processes—only by a most careful observation of all these points can we arrive at results which will allow us to draw conclusions with reference to the corresponding processes in the body.

It may appear remarkable that, in the syntheses which have been made, these conditions were not considered; but it must not be forgotten that a chemist makes a synthesis for its own sake, unconcerned whether he attains his result in the same manner as the organism. He can only attempt the solution of this question when he knows the steps by which the structure is built up. But in this respect we are still far behind, for our knowledge of the chemical properties of the bodies which we find in the organism is still very incomplete. The substances which are most important in the economy of the organism, the albuminoids, notwithstanding the labor and time employed, are very little known, and the same may be said of other substances, such as the bile, the nerve-substance, etc. We do not even know whether the albuminoids and similar compounds have ever been obtained in a pure state; their composition is, therefore, only approximately known; the question, whether the ash which they leave on burning is an essential constituent or an impurity, still remains undecided, and a good method for separating the different members of larger groups is a pious wish. The changes and decompositions of these substances are only known in general; in many cases we know the final but not the intermediate products, which are of the highest importance, as, without doubt, the organism operates with these. Here, above all, it is necessary to throw some light on the obscurity which surrounds this problem, and the necessity will best be shown by an example. If albuminoids are treated with digestive ferments, or with dilute acids, there is at first produced a series of peculiar compounds still similar to the albuminoids, called peptones. If the latter are exposed to the action of strong acids or alkalies, they are finally decomposed into amido acids; at the same time carbonic acid, ammonia, oxalic acid, and other simple compounds, are formed in small quantities. Although completely justified in assuming that the elements of water have been taken up in these processes, it is not positively known in what relation the peptones stand toward the albuminoids; whether the peptones produced from various albuminoids are different or identical, or whether only one or several peptones are produced from each albuminoid; whether they are crystallizable or not; whether the peptones are directly decomposed into amido acids, or whether further intermediate products are formed—in short, we are only beginning those investigations which promise to give the most important results.

Fortunately, the organism also contains more simple compounds, which are well known, and the formation of which can be discovered more readily. One of the most important of these is urea, and by this we can show that the problem is capable of solution. The high physiological importance of this body is due to the fact that it contains the greatest part of the nitrogen introduced with the food, and removes it from the body. Its composition is very simple, its synthesis has been effected in many ways, and there appears to be no difficulty in explaining its formation in the animal organism. At first it was supposed that it is formed by direct oxidation of the albuminoids, but all attempts to prove this experimentally have failed. Later it was found that nitrogenous bodies, other than albuminoids, particularly the products of decomposition of the same, such as glycocol, asparagin, even ammonia, were converted into urea in the organism; and, as glycocol and ammonia each contain only one atom of nitrogen, while urea contains two, evidently by synthesis. Accordingly, two hypotheses were proposed to explain the formation of urea in the organism: the one assumed that by the oxidation of the nitrogenous bodies cyanic acid is first formed, which, combining with ammonia, forms ammonium cyanate, and is transformed into urea; the other, which is principally based on the experiments in which ammonium carbonate is introduced into the organism, assumed a separation of water from this salt, which would of course give m-ea. But neither of these hypotheses is tenable: for, on the one hand, no chemist has ever obtained cyanic acid by the oxidation of nitrogenous substances under the conditions which are found, or may at any rate be assumed, in the organism; on the other hand, the ammonium carbonate which is introduced with the food can not be resorbed as such, for it is decomposed by the acid juices of the stomach, neither can this substance be formed in the organism from carbonic acid and ammonia. From the facts which have been observed, however, a third hypothesis may be deduced which is more probable than either of the former. It has been shown that by the oxidation of nitrogenous organic bodies, particularly glycocol, leucine, and tyrosine, in alkaline solution and at a blood-heat, carbonic acid is always formed; also that, by the union of carbonic acid and ammonia in aqueous solution and in presence of the strongest bases, carbonic acid is produced. We must therefore assume that in the blood or in other parts of the body, wherever nitrogenous compounds are oxidized, carbonic acid is constantly formed. From this salt the formation of urea must take place by the elimination of water, a reaction which has long ago been effected by heating the salt to 140° with absolute alcohol. In the organism this elimination of water must evidently take place in a different manner, and especially at the temperature of the body. This may be effected in two ways: either the water is eliminated as such, or its elements are removed one after another by two different reactions. The latter assumption is the most probable, for it will make it readily perceptible that the reaction takes place in an aqueous solution. If it is asked in what manner the oxygen and the hydrogen may be removed from the ammonium carbonate, the simplest answer will be that the hydrogen is removed by oxidation and the oxygen by reduction. Experiment has confirmed my expectations. If an aqueous solution of ammonium carbonate is submitted to electrolysis, reversing the current and employing platinum or graphite electrodes, small quantities of urea are formed, which may be isolated and identified as such with certainty. By the evolution of hydrogen and oxygen, alternately at short intervals, the hydrogen is removed by oxygen, and the oxygen is eliminated by hydrogen, and urea remains.

Since both oxidation and reduction are continually taking place in the body, the solution of the question how urea is formed is given, viz., from the ammonium carbonate which is first formed it is produced by further oxidation and reduction.

Here we have urea produced without the body, under conditions which may be assumed to exist within; above all, the temperatures were such as are noted in animals. For this reason this synthesis is particularly adapted to show an acceptable process of the formation of urea in the organism. The question, by what means the organism effects the oxidations and reductions, whether electrolytically or chemically, of course, remains unanswered, but this will also be solved as soon as the processes taking place in the animal system are better known.

This synthesis also distinctly shows what developments physiology is to expect from pure chemistry. The experiments made on animals, by which the conversion of ammonia into urea in the organism was first established, did not teach a single fact which would have indicated that this conversion is the result of two directly opposite processes. This supposition was arrived at, independently of the experiments with animals, by purely chemical considerations, and it was simply necessary to furnish the experimental evidence of their correctness. In this, as in all similar cases, the physiological experiment will disclose the occurrence of synthesis and decompositions; and it will be the province of pure chemistry to discover the ways and means by which the organism produces the results. Both physiological and chemical experiments will have to be jointly and yet independently made, if the chemistry of the living organism is to be established.

Though we must confess that our knowledge of the chemical processes in the animal body is still very incomplete, we must recognize that the investigations made in this direction have given us much information. Though the substances which react on each other are known in the fewest cases, we have obtained hints regarding the manner in which they react. It has been shown why we are obliged to assume that oxidation takes place. We are also acquainted with processes which indicate reduction, others in which decomposition takes place with the assimilation of water, or synthesis with the elimination of water. Indigo blue is reduced to indigo white, potassium ferri-cyanide is reduced to the ferrocyanide, potassium bromate and iodate are reduced to bromide and iodide; glycogen is converted into sugar with the assimilation of water, albumen into peptone, and then into amido acids and other products. Hippuric acid is formed, with the elimination of water, from benzoic acid and glycocol.

But we ask in vain: What is it that effects these reductions? how does the pepsin act? how do benzoic acid and glycocol combine? Here is a field in which chemistry must cultivate independently, not as the servant of physiology, for the fruits of the labor will be of equal value to both sciences. Whatever difficulties this problem may produce, we are certain that its solution is within our reach. It was different when, where now we see groups of atoms acting upon each other in a definite manner, irritability or an incomprehensible life-force was permitted to rule. Then the future was without prospect; no vulnerable point seemed exposed for the attack of genius. At present we may say, that which is ponderable can be weighed, and that which proves to be an individual can be isolated. After, however, the analysis is once completed, synthesis will be close at hand.

  1. Translated for "The Popular Science Monthly" by William Rupp, F.C.S.