The Use of Radioactive Tracers in Biology and Medicine

A very large share of investigative work in the biological sciences has been devoted to the study of the metabolism of organisms ranging in complexity from bacteria to man and embracing the more important members of the plant and animal kingdoms. Until the discovery of artificial radioactivity by Curie and Joliot in 1934 (1), the only method for studying the mechanisms whereby the various elements and compounds essential for life are assimilated, distributed throughout the tissues, converted into other compounds, and finally eliminated, was by a direct chemical approach to these problems. This mode of attack, although very productive of information, suffers from several serious limitations. First, in order to observe the manner by which a living organism metabolizes an element, as, for example, potassium, it is necessary to administer enough so that a detectable increase in the amount in the body will be produced. This axiom applies to most of the elements and compounds that are normal constituents of biological systems. Normally, the content of these substances is kept in most instances within relatively narrow limits by the body and for this reason it is necessary to administer a sufficient quantity of the element or compound to disturb this carefully regulated balance if fluctuations are to be produced that are large enough to be accurately determined by analytical chemical technics. It is obvious that such procedures will frequently disturb the normal chemical and physiological processes of the organism, and the experimental data thus obtained may not present a true picture of the normal metabolism of the substances that are being studied. Second, it is not possible by chemical procedures to differentiate between the atoms or molecules of the administered material and those that are already present in the tissues of the plant or animal. For example, the increase in excretion of phosphorus by an animal following the administration of this element is made up in part by the phosphorus atoms already in the body, which were displaced by the administered element, and in part by a portion of the phosphorus given to the animal. The classical procedures of chemistry and physics do not permit the investigator to determine what proportion of the phosphorus atoms in the excreta came from the administered material and the fraction that was displaced from the pre-existing phosphorus in the tissues. This limitation applies to all metabolic investigations in which the elements or compounds are constituents of the organism that is being studied. The first attempt to circumvent these limitations was made by Hevesy in 1923 (2), when he employed a radioactive isotope of lead (radium D) to investigate the metabolism of that element in plants. His procedure made it possible to measure quantitatively the uptake and distribution of the administered lead by determining the radioactivity of the different portions of the plant.