RADIOACTIVE ISOTOPES: THE BIOLOGICAL DETECTIVES

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Man ... has found ways to amplify his senses ... and, with a variety of instruments and techniques, has added kinds of perception that were missing from his original endowment.

Glenn T. Seaborg

Atomic Structure

Practically everyone nowadays is to some extent familiar with the atomic structure of matter. Atomic energy, nuclear reactors, and radioisotopes are terms in everyday usage. However, to appreciate how radioisotopes can be applied to the study of life processes, we must have at least a working knowledge of their properties, their preparation, and their limitations. It is therefore appropriate to examine them in detail so that the succeeding chapters will be more easily understood.

According to present-day theory, an atom consists of a nucleus[4] that is made up of protons and neutrons[5] and is surrounded by electrons. In each atom there is an equal number of protons (positively charged) in the nucleus and electrons (negatively charged) moving concentrically around the nucleus; since neutrons have no electrical charge and since protons and electrons cancel each other’s charges, the whole atom is electrically neutral, or uncharged. Each atom is identified by an atomic number and an atomic weight. The atomic number of an element (for example, carbon, nitrogen, oxygen) is determined by the number of protons, or positive charges, carried by the nucleus (or by the number of electrons surrounding the nucleus, which is the same). The atomic weight is the weight of an atom as compared with that of the atom of carbon, which is taken as a standard. The weight, or mass, of an atom is due chiefly to its protons and neutrons because the mass of its electrons is negligible.

Isotopes

Atoms of the same element, that is, atoms with the same number of protons and electrons, may vary slightly in mass because of having different numbers of neutrons. Since the chemical behavior of an element depends upon its electrons’ electrical charges, extra neutrons (which do not have an electrical charge) may affect the mass of an atom without disturbing its chemical properties. Atoms having the same atomic number but different atomic weights are called isotopes. For example, as shown in Figure 8, the isotope ¹H, or ordinary hydrogen, consists of a nucleus containing a proton (charge: +1; mass: 1) around which revolves an electron (charge: -1; mass: negligible); ²H, known as deuterium, contains an additional nuclear particle, a neutron (charge: 0; mass: 1); ³H, or tritium, contains two neutrons. Since the chemical behavior of an element depends upon the number of its electrons, these three atoms, although differing in weight, behave identically in chemical reactions. For convenience, the atomic weight is written as a superscript to the left of the element’s symbol. For instance ¹4C is the isotope of carbon with an atomic weight of 14 (ordinary carbon is the isotope with an atomic weight of 12, and it is written ¹²C).

Figure 8 Isotopes of hydrogen.

Practically all elements have more than one isotope. There are two general classes of isotopes, stable and radioactive. Stable isotopes have no distinguishing characteristic other than their mass; radioactive isotopes not only differ from their brothers in mass but also are characterized by unstable nuclei. When the nucleus of an atom is unstable, because of an unbalanced number of protons and neutrons, a redistribution occurs sooner or later, and the atom decomposes spontaneously and emits one of several kinds of radiations. Because of their common mode of action and effects on living organisms, these different kinds of radiations are known collectively as ionizing radiations.

All radioactive elements emit one or more of three types of penetrating (ionizing) rays. Alpha rays or particles are double-charged helium nuclei, 4He (atomic number: 2; mass: 4). They are emitted by many heavy radioactive elements, such as radium, uranium, and plutonium. Beta rays or particles can be either positive or negative. Negative beta particles are high-speed electrons and are emitted by many radioactive elements. Positive beta particles are positively charged electrons (positrons), have only a transitory existence, and are less common. Gamma rays are electromagnetic radiations, a term that also describes radiowaves, infrared rays, visible light, ultraviolet light, and X rays. Gamma rays are usually emitted after the emission of alpha or beta particles. In our studies of life processes, we are interested only in the radioactive isotopes that emit gamma rays or beta particles.

Radioactive Isotopes

Radioactive isotopes occur as minor constituents in many natural materials, from which they can be concentrated by fractionation procedures. In a very limited number of cases, more significant amounts of a radioactive isotope, for example, radium or radioactive lead, can be found in nature. Most radioactive isotopes in use today, however, are prepared artificially by nuclear reactions. When a high-energy particle, such as a proton, a deuteron, an alpha particle, or a neutron, collides with an atom, a reaction takes place, leading to the formation of a new, unstable compound—a man-made radioactive isotope.

The great usefulness of radioactive isotopes, as we shall see later, is that they can be detected and identified by proper instruments. Biochemists have long recognized the desirability of “tagging” or “labeling” a molecule to permit tracing or keeping track of the “label” and consequently of the molecule as it moves through a reaction or process. Since the radiations emitted by radioactive isotopes can be detected and measured, we can readily follow a molecule tagged with a radioactive atom.

Figure 9 A laboratory technologist preparing dissolved biological materials as part of a study of the uptake of radioactive substances in living organisms. Note the radiation-detection instrument at right.

The earliest biochemical studies employing radioactive isotopes go back to 1924, when George de Hevesy used natural radioactive lead to investigate a biological process. It was only after World War II, however, when artificially made radioactive isotopes were readily available, that the technique of using isotopic tracers became popular.

In our investigations of life processes, we are especially interested in three radioactive isotopes: ³H, the hydrogen atom of mass 3; ¹4C, the atom of carbon with atomic weight 14; and ³²P, the atom of phosphorus with atomic weight 32. These radioactive isotopes are important because the corresponding stable isotopes of hydrogen, carbon, and phosphorus are present in practically all cellular components that are important in maintaining life. With the three radioactive isotopes, therefore, we can tag or label the molecules that participate in life processes.

Figure 10 A visiting scientist at an AEC laboratory uses radioactive tritium (³H) to study the effect of radiation on bean chromosomes. The famous scientist, George de Hevesy, also used beans in conducting the first biological studies ever made with radioisotopes.

Hydrogen-3 is a weak beta emitter; that is, it emits beta particles with a very low energy (0.018 Mev[6]) and therefore with a very short range. Carbon-14 is also a weak beta emitter (0.154 Mev), although the beta particles emitted by ¹4C have a higher energy and therefore a longer range than those emitted by ³H. The beta particles emitted by phosphorus-32 are quite energetic (1.69 Mev) and have a longer range.

Radioactive Isotopes’ Value in Biological Studies

To biologists, then, the essential feature in the use of radioactive isotopes is the possibility of preparing “labeled” samples of any organic molecule involved in biological processes. With labeled samples it is possible to distinguish the behavior and keep track of the course of molecules involved in a particular biological function.

In this capacity the isotope may be likened to a dynamic and revolutionary type of “atomic microscope”, which can actually be incorporated into a living process or a specific cell. Just as a real microscope permits examination of the structural details of cells, isotopes permit examination of the chemical activities of molecules, atoms, and ions as they react within cells. (Neither optical nor electron microscopes are powerful enough for us to see anything as small as a molecule clearly.)

                                                                                                                                                                                                                                                                                                           

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