The amount of iron contained in the body is small, but its functions are of the highest importance. As previously noted, the iron content of the adult man or woman is estimated at only 0.004 per cent, or 1 part in 25,000 parts of the body weight, or rather less than 3 grams (hardly one tenth of an ounce) in the entire body. Much the greater part of this iron exists as a constituent of the hemoglobin of red blood corpuscles and is constantly functioning in the general metabolism as the carrier of the oxygen upon which all of the oxidative (energy-yielding) processes of nutrition depend. There is no considerable reserve store of relatively inactive iron in the body corresponding to the store of calcium and phosphorus in the bones. Hence if the intake of iron fails to equal the output there must soon result a diminution of hemoglobin, which if continued must mean a greater or less degree of anemia. The investigation of iron metabolism has therefore been largely connected with the study of anemia and of hemoglobin formation.

Important changes of view in regard to the metabolism of iron have followed so closely and have depended so directly upon the progress of experimental methods that it seems desirable, in this case, to review in chronological order some of the more important steps in the development of our present knowledge.

Development Of Modern Views

It has long been known that iron is essential to the nutrition of both plants and animals, and that small amounts of the oxide or phosphate of iron occur in the ash of all natural food materials. A few decades ago it was assumed that the iron exists in the food as oxide or phosphate, and that hemoglobin is formed in the body by the combination of protein with inorganic iron. This view was hardly consistent with the ideas of animal metabolism taught by Liebig and generally held at the time, but appeared to be supported by the successful use of inorganic iron in the treatment of anemia.

The results obtained in a number of investigations published between 1854 and 1884 threw doubt upon the utilization of inorganic iron for the production of hemoglobin, since they indicated that iron salts when injected act as poisons and are quickly eliminated from the blood, and when given by the mouth reappear almost quantitatively in the feces, little, if any, evidence of absorption being obtained except when the doses were so large or long continued as to cause irritation of the intestine.

In the attempt to harmonize this result with clinical experience it was suggested that the inorganic iron might act by absorbing the hydrogen sulphide of the intestine, thus protecting the food iron from waste.

The view that medicinal iron acts by stimulation of the absorbing membrane was also advocated at about this time. It was held that the amount of iron in the ordinary food is always sufficient for the needs of the body, but that sometimes the intestinal mucous membrane becomes so bloodless that it cannot properly perform its functions of absorption. Under such conditions inorganic iron was believed to stimulate and tone up the membrane so that in a short time the increased absorption of food iron makes good the deficiency in the blood.

A very suggestive discussion of the metabolism of iron, the effects of a lack of iron in the food, and the amounts of iron required for the maintenance of the body in health was published by Von Hosslin in 1882, and long before this some attention had been given to the iron content of food materials by Boussingault. Boussingault's figures, however, are not sufficiently accurate to be of value at the present time, and little attention was given to the subject discussed by Von Hosslin until it was reopened by Bunge about two years later.

Bunge, in 1884, doubting the ability of the animal body to form hemoglobin from inorganic iron, undertook the study of the iron compounds of food materials in order to find in what form iron is normally absorbed and from what sort of iron compounds the growing organism ordinarily forms its hemoglobin. Practically all of the iron of eggs was found to be in the yolk. Yolk of egg does not contain any hemoglobin, but it must contain substances from which hemoglobin can be formed, since the incubation of the egg results in the development of hemoglobin without the introduction of anything from without. Bunge found no inorganic iron in egg yolk, but isolated considerable amounts of the precursor of hemoglobin, which he called "hematogen," and which exhibited the properties of a phosphoprotein containing about 0.3 per cent of iron in such firm "organic" combination that it gives none of the ordinary reactions of iron salts. In milk, cereals, and legumes similar organic compounds of iron and only traces of inorganic iron were found. At this time Bunge distinctly stated that iron occurs in food solely in the form of complicated organic com-pounds which have been built up by the life processes of plants. In this form, said Bunge, is the iron absorbed and assimilated, and from these compounds hemoglobin is produced.

In 1890 and subsequently, the absorption and assimilation of iron was studied by several experimenters, usually with particular reference to the question whether inorganic or synthetic organic compounds of iron are absorbed and assimilated, and especially whether such preparations contribute directly to the formation of hemoglobin. This question is, of course, extremely important, not only in connection with the therapeutic use of medicinal iron, but also in its bearing upon the iron requirements in health; for if inorganic iron could be utilized in the body in exactly the same way as the complex organic iron compounds of the food, it would follow that the iron of drinking water could replace that of food, and the supplying of food iron would be a matter of indifference to a man whose drinking water supplied a few milligrams of iron per day. In opposition to this view, Bunge held that little if any inorganic iron is assimilated, and that any effect of medicinal iron should be attributed to its action in protecting the food iron from loss in digestion, principally by absorbing the sulphur liberated as sulphide through intestinal putrefaction.