Popular Science Monthly/Volume 54/April 1899/Iron in the Living Body



IRON occurs, in small and almost infinitesimal proportions, in numerous organic structures, in which its presence may usually be detected by the high color it imparts; and in the animal tissues is an important ingredient, though far from being a large one. It is essential, however, that the animal tissues, and particularly the liquids that circulate through them, should be of nearly even weight, else the equilibrium of the body would be too easily disturbed, and disaster arising therefrom would be always imminent. Hence the iron is always found combined and associated with a large accompaniment of other lighter elements which, reducing or neutralizing its superior specific gravity, hold it up and keep it afloat. Thus the molecule of the red matter of the blood contains, for each atom of iron, 712 atoms of carbon, 1,130 of hydrogen, 214 of nitrogen, 245 of oxygen, and 2 of sulphur, or 2,303 atoms in all. Existing in compounds of so complex composition, iron can be present only in very small proportions to the whole. Though an essential element, there is comparatively but little of it. The whole body of man does not contain more than one part in twenty thousand of it. The blood contains only five ten-thousandths; and an organ is rich in it if, like the liver, it contains one and a half ten-thousandths. When, then, we seek to represent to ourselves the changes undergone by organic iron, we shall have to modify materially the ideas we have formed respecting the largeness and the littleness of units of measure and as to the meaning of the words abundant and rare. We must get rid of the notion that a thousandth or even a ten-thousandth is a proportion that may be neglected. The humble ten-thousandth, which is usually supposed not to be of much consequence, becomes here a matter of value. Chemists working with iron in its ordinary compounds may consider that they are doing fairly well if they do not lose sight of more than a thousandth of it; but such looseness would be fatal in a biological investigation, where accuracy is necessary down to the infinitesimal fraction. The balances of the biologists must weigh the thousandth of a milligramme, as their microscopes measure the thousandth of a millimetre.

The great part performed by iron in organisms, what we may call its biological function, appertains to the chemical property it possesses of favoring combustion, of being an agent for promoting the oxidation of organic matters.

The chemistry of living bodies differs from that of the laboratory in a feature that is peculiar to it—that instead of performing its reactions directly it uses special agents. It employs intermediaries which, while they are not entirely unknown to mineral chemistry, yet rarely intervene in it. If it is desired, for example, to add a molecule of water to starch to form sugar, the chemist would do it by heating the starch with acidulated water. The organism, which is performing this process all the time, or after every meal, does it in a different way, without special heating and without the acid. A soluble ferment, a diastase or enzyme, serves as the oxidizing agent to produce the same result. Looking at the beginning and the end, the two operations are the same. The special agent gives up none of its substance. It withdraws after having accomplished its work, and not a trace of it is left. Here, in the mechanism of the action of these soluble ferments, resides the mystery, still complete, of vital chemistry. It may be conceived that these agents, which leave none of their substance behind their operations, which suffer no loss, do not have to be represented in considerable quantities, however great the need of them may be. They only require time to do their work. The most remarkable characteristic of the soluble ferments lies, in fact, here, in the magnitude of the action as contrasted with infinitesimal proportion of the agent, and the necessity of having time for the accomplishment of the operation.

Iron behaves in precisely the same way in the combustion of organic substances. These substances are incapable at ordinary temperatures of fixing oxygen directly, and will not burn till they are raised to a high temperature; but in the presence of iron they are capable of burning without extreme heat, and undergo slow combustion. And as iron gives up none of its substance in the operation, and acts, as a simple intermediary, only to draw oxygen from the inexhaustible atmosphere and present it to the organic substance, we see that it need not be abundant to perform its office, provided it have time enough. This action resembles that of the soluble ferments in that there is no mystery about it, and its innermost mechanism is perfectly known.

Iron readily combines with oxygen—too readily, we might say, if we regarded only the uses we make of it. It exists as an oxide in Nature; and the metallurgy of it has no other object than to revivify burned iron, remove the oxygen from it, and extract the metal. Of the two oxides of iron, the ferrous, or lower one, is an energetic base, readily combining with even the weakest acids, and forming with them ferrous or protosalts. Ferric oxide, on the other hand, is a feeble base, which combines only slowly with even strong acids to form ferric salts or persalts, and not at all with weak acids like carbonic acid and those of the tissues of living beings. It is these last, more highly oxidized ferric compounds that provide organic substances with the oxygen that consumes them, when, as a result of the operation, they themselves return to the ferrous state.

Facts of this sort are too nearly universal not to have been observed very long ago, but they were not fully understood till about the middle of this century. The chemists of the time—Liebig, Dumas, and especially Schönbein, Wöhler, Stenhouse, and many others—established the fact that ferric oxide provokes at ordinary temperatures a rapid action of combustion on a large number of substances: grass, sawdust, peat, charcoal, humus, arable land, and animal matter. A very common example is the destruction of linen by rust spots; the substance of the fiber is slowly burned up by the oxygen yielded by the oxide. About the same time, Claude Bernard inquired whether the process took place within the tissues, in contact with living matter in the same way as we have just seen it did with dead matter—the remains of organisms that had long since submitted to the action of physical laws—and received an affirmative answer. Injecting a ferric salt into the jugular vein of an animal, he found it excreted, deprived of a part of its oxygen, as a ferrous salt.

This slow combustion of organic matter, living or dead, accomplished in the cold by iron, represents only one of the aspects of its biological function. A counterpart to it is necessary in order to complete the picture. It is easy to perceive that the phenomenon would have no bearing or consequence if it was limited to this first action. With the small provision of oxygen in the iron salt used up, and, if reduced to the minimum of oxidation, the source of oxygen being exhausted, the combustion of organic matter would stop. The oxidation obtained would be insignificant, while the oxidation should be indefinite and unlimited, and it is really so.

There is a counterpart. The iron salt, which has gone back to the minimum of oxidation and become a ferrous salt, can not remain long in that state in contact with the air and with other sources of the gas to which it is exposed. It has always been known that ferrous compounds absorb oxygen from the air and pass into the ferric state; we might say that we have seen it done, for the transformation is accompanied by a characteristic change of color, by a transition from the pale green tint of ferrous bases to the ochery or red color of ferric compounds.

We can understand now what should happen when the ferruginous compound is placed in contact alternately with organic matter and oxygen. In the former phase the iron will yield oxygen to the organic matter; in the second phase it will take again from the atmosphere the combustible which it has lost, and will be again where it started. The same series of operations may be continued a second time and a third time, and indefinitely, as long as the alternations of contact with organic matter and exposure to atmospheric oxygen are kept up, the iron simply performing the part of a broker. The same result will occur if atmospheric air and organic matter are constantly together; the consumption will continue indefinitely, and the iron will perform the part of an intermediary till one of the elements of the process is exhausted.

This explanation was necessary to make clear the solution of the mystery of slow or cool combustion, the existence of which has been known since Lavoisier, without its mechanism being understood. That illustrious student gave out the theory that animal heat and the energy developed by vital action originated in the chemical reactions of the organism, and that, on the other hand, the reactions that produce heat consisted of simple combustions, slow combustions, that differed only in intensity from that of the burning torch. The development of chemistry has shown that this figure was too much simplified from the reality, and that most of these phenomena, while they are in the end equivalent to a combustion, differ greatly from it in mechanism and mode of execution. By this we do not mean to say that all the combustions are of this character, and that there do not exist in the organism a large number of such as Lavoisier understood, and of such as the combustions effected by the intervention of iron furnish the type of. Lavoisier's successors, Liebig among them, tried to find reactions conformed to this type. Their attempts were unsuccessful, but they had the happy result of revealing, if not the real function of iron in the blood, at least that of the red matter in which it is fixed.

The question of the presence of iron in the coloring matter of the blood gave rise to long discussions. Vauquelin denied it. He made the mistake of looking for iron in the form of a known compound, in direct combination with the blood, while later researches have shown that it is found almost exclusively in the red matter that tinges the globules, in a complicated combination that escapes the ordinary tests; or, according to a usual method of expression, it is dissimulated. Liebig also failed to find this combination, and it was not till 1864 that Hoppe-Seyler succeded in obtaining it pure and crystallized. But Liebig had already perceived its essential properties, and was able to point out approximately its functions as early as 1845; yet the single fact that there was no assimilation possible between this substance and the salts of iron, cut this question off into a kind of negative suspense. Different from these compounds, it could not behave like them, and accomplish slow combustions of the same type. It is a remarkable fact, and one that illustrates well how iron preserves through all its vicissitudes some trace of its fundamental property of favoring the action of oxygen on substances, that this composition, so special and so different from the salts of iron, behaves nearly as they do. While it is not of itself an energetic combustible, it is, according to Liebig's expression, "a transporter of oxygen"—a luminous view, which the future was destined to confirm. Although the transportation is not produced by the mechanism supposed by Liebig, but by another, the general result is very much the same from the point of view of the physiology of the blood. The coloring matter of the blood conveyed by the globules fixes oxygen in contact with the pulmonary air, and distributes it as it passes through the capillaries upon the tissues. The globule of blood brings nothing else and distributes nothing else, contrary to the opinion that had been held before. The theory of slow combustion effected through iron, while not absolutely contradicted in principle, was not entirely confirmed in detail, so far as concerned iron, or the more prominently ferruginous tissue.

No search was made for other tissues or organs presenting more favorable conditions, for no others were known that had iron in themselves. The liver and the spleen were supposed to receive it from the blood under the complicated form in which it exists there, or under some equivalent form. It was not, therefore, supposed till within a very few years that the two conditions were realized in any organ that were required to secure a slow combustion by iron—that is, combinations resembling ferrous and ferric salts with a weak acid and a source of oxygen. The doubt has been resolved by recent studies. The liver fulfils the requirement. It contains iron existing under forms precisely comparable to the ferrous and ferric compounds, and is washed by the blood which carries oxygen in a state of simple solution in its plasma and of loose combination in its globules. Thus all the conditions necessary for the production of slow combustion are gathered here, and we can not doubt that it takes place. A new function is therefore assigned to the liver, and it becomes one of the great furnaces of the organism.

Compounds of iron are so abundant in the ground and the water that we need not be surprised when we find them in various parts of plants, and particularly in the green parts. Their habitual presence does not, however, authorize the conclusion that this metal is necessary to the support and development of vegetable life. Some substances, evidently indifferent, foreign, and even injurious, if they exist abundantly in a soil, may be drawn into roots through the movement of the sap, and fix themselves in various organs. This occurs with copper in certain exceptional circumstances when the soil is saturated with its compounds, and if such a condition should be found to be repeated over a large extent of country, we might be led, by analysis alone of its vegetable productions, to the false conclusion that copper was an essential or even necessary constituent of them. But the value of the part performed by an element can not be determined by analysis alone. Direct proofs are necessary for that, methodical and comparative experiments in cultivation in mediums artificially deprived or furnished with the element the importance of which we wish to estimate. This has been done for combinations of iron, and the utility of that metal, especially to the higher plants, has been made thereby to appear.

If iron is absent from the nutritive medium the plant will wither. If we sprout seeds in a solution from which this metal has been carefully excluded, the development will follow its regular course as long as the plant is in the condition properly called that of germination, or while it does not have to draw anything from the soil. The stem rises and the first leaves are formed as usual. But all these parts will continue pale, and the green matter, the granulation of chlorophyll, will not appear. Now, if we add a small quantity of salt of iron to the ground in which the roots are planted, or a much-diluted solution is sprinkled on the leaves and the stem, the chlorotic plant will recover its health and take on its normal-coloration. Experiments of this sort make well manifest that iron is necessary to green plants, and they show, besides, the bearing of its action, and that what is most special and most characteristic in the phenomena of vegetable life may be traced exactly to the organization of that green matter. It was long thought that if iron was necessary for the formation of chlorophyll, it was because it had a part in its constitution. We know now that this is not so. The metal does nothing but accompany the chlorophyll in the granulation in which it is found.

The influence which iron exerts in the development of the lower plants, like the muscidenes, was illustrated with great precision in a study made about thirty years ago by M. Raulin, who experimented with the common mold (Aspergillus niger), to determine the coefficient of importance of all the elements that have a part in its vegetation. When the iron was removed from a medium that had been shown capable of giving a maximum crop of that mold, the plants languished, and the return fell off immediately to one third. Estimating the quantity of metal that produces this effect, it was found that the addition of one part of iron was sufficient to determine the production of a weight of plant nearly nine hundred times as great. The suppression of the iron further caused an irreparable loss, for when it was sought to remedy the wilting of the plants by restoring the iron which had been taken from the medium—an experiment which had been successful with higher plants—the attempt was a failure, and the plants could not be prevented from perishing.

These facts are full of interest in themselves, and they further show well the necessity or utility of iron in plant life, but they teach us no more. They reveal nothing of the mechanism of the action, and if we wish to penetrate further in the matter we always have to turn to animal physiology.—Translated for the Popular Science Monthly from the Revue des Deux Mondes.