Part 7

The gene-action system actually is somewhat more elaborate than this. There are feedback mechanisms, genes that control the activity of other genes, either directly or through the production of specific proteins, and so on. However, the scheme just outlined gives a fair, if simplified, idea of how the genetic message is carried to the entire cell and how it is translated into actual life processes.

ISOTOPES IN RESEARCH: PROBING THE CANCER PROBLEM

... a riddle wrapped in a mystery inside an enigma.

Winston Churchill

The various procedures in which radioactive isotopes play a major role have been applied to many studies and investigations in the fields of biology and medicine. In fact, most of the concepts of modern biology that we have been discussing in this booklet owe their discovery to the judicious use of radioisotopes. To illustrate how radioisotopes can be used to solve a practical problem, we have chosen a typical example, the investigation, at a molecular level, of the effectiveness of an anti-cancer drug.

Several drugs that exert a beneficial effect, at least temporarily, on the course of certain cancers have been used by doctors for several years. Most of them were discovered empirically, that is, by accident, during routine trials against cancers. Doctors know they work but do not always know how. They would also like to know the mechanism of the drugs’ action at the molecular level so that the knowledge might open the way to the discovery of other drugs more effective against cancer and less toxic against normal cells. The following experiment shows how the molecular effect of an anti-cancer drug is studied.

Cells growing in tissue cultures are often used to test anti-cancer drugs (see Figure 28). These cells, derived from human cell lines, are grown in glass or plastic bottles as a suspension in a nutrient medium. To begin, a culture is divided into halves. To one half is added the anti-cancer drug Actinomycin D. The other half will continue to grow without addition of other substances and will serve as a control, or comparison. After a suitable time has elapsed for the drug to act on the cultured cells, similar portions of the drug-treated cells and the control cells will be tested in several ways. One portion of each kind of cells is incubated with ³H-thymidine to determine the effect of the drug on DNA synthesis. Two other portions are incubated with ³H-cytidine to study the effect on RNA synthesis. Another pair will be tested with ¹⁴C-leucine to investigate protein synthesis. The effect of the drug, of course, is determined by comparing the untreated control with the drug-treated culture.

The biochemical, autoradiographic, and counting techniques that we described previously are all used to determine the uptake of the radioisotopes into the cell’s components. Chromatography is used to ascertain if the drug has changed the concentration of precursors (thymidine, cytidine, or leucine) in the nutrient medium, since a change in these could produce misleading results. Finally, if the drug is found to have an effect on RNA, we can investigate the type of RNA that is affected by centrifuging phenol-purified RNA.

The results will disclose the primary site (DNA, RNA, or proteins) of the drug action on cell metabolism. More elaborate experiments can pinpoint more intimately the mechanism of action. By studying the life processes of cells, we can advance toward a common denominator in anti-cancer drugs that will lead to an effective anti-cancer treatment.

CONCLUSIONS

Thus, the task is, not so much to see what no one has seen yet; but to think what nobody has thought yet, about what everybody sees.

Arthur Schopenhauer

The use of radioactive isotopes in the study of life processes is of importance in understanding them. With the use of autoradiographic and radiochemical techniques, it is possible to obtain valuable information regarding the life of cells and the intimate mechanisms by which life processes determine the fate of the entire organism.

Our knowledge of the cell cycle and of the gene-action system has been useful in determining how organisms grow and how cancer cells behave. It has been determined that certain normal adult cells divide more frequently than some cancer cells and that the growth of cancers depends not so much on the speed of cellular proliferation as on the number of cells actually dividing.

Knowledge of the cell cycle has also brought new insight to the control of cell division, as in studies related to the therapy of cancer. The most important problem now is, not the control of cell division, but the control of the synthesis of DNA.

Our information on the gene-action system provides broad new opportunity for the investigation of many life processes. Hormone action, processes by which the body develops immunity to disease, and even cell division itself are apparently regulated through the gene-action system. This, in turn, offers possibilities for investigations meant to control these processes.

It is difficult to chart the future course of modern molecular biology, but it is not difficult to predict that the next few years will bring to biology the same kind of sweeping advances that revolutionized physics a few decades ago. The DNA molecule has been called the atom of life. When we have harnessed it, the harnessing of the uranium atom will seem, in comparison, a result of scientific adolescence. When man has mastered the genetic code, he’ll hold a vast power in his hands—power over the nature of coming generations.

SUGGESTED REFERENCES

Books

The Cell, Carl P. Swanson, Prentice-Hall, Inc., Englewood Cliffs, New Jersey, 1964, 114 pp., $1.75.

Inside the Living Cell, J. A. V. Butler, Basic Books, Inc., New York, 1959, 174 pp., $3.95.

Life and Energy, Isaac Asimov, Doubleday & Company, Inc., Garden City, New York, 1962, 380 pp., $4.95.

Applied Nuclear Physics, Ernest C. Pollard and William L. Davidson, John Wiley & Sons, Inc., New York, 1956, 352 pp., $6.00.

Adventures in Radioisotope Research, the collected works, with recent annotations, of George de Hevesy, Pergamon Press, Inc., New York, 1961, 1047 pp. (2 volumes), $30.00.

The Biochemistry of Nucleic Acids, J. N. Davidson, John Wiley & Sons, Inc., New York, 4th edition, 1960, 287 pp., $4.25.

The Machinery of the Body, A. J. Carlson and C. Johnson, The University of Chicago Press, Chicago, Illinois, 1961, 752 pp., $6.50.

Life: An Introduction to Biology, George G. Simpson and William S. Beck, Harcourt, Brace & World, Inc., New York, 2nd edition, 1965, 869 pp., $8.95.

From Cell to Test Tube, Robert W. Chambers and Alma Payne, Charles Scribner’s Sons, New York, 1962, 216 pp., $1.45.