Part 4

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.

_Isotopic Tracers in Biology_, M. D. Kamen, Academic Press Inc., New York, 3rd edition, 1957, 474 pp., $9.50.

_Autoradiography in Biology and Medicine_, G. A. Boyd, Academic Press Inc., New York, 1955, 399 pp., $10.00.

_A Tracer Experiment: Tracing Biochemical Reactions with Radioisotopes_, Martin D. Kamen, Holt, Rinehart & Winston, Inc., New York, 1964, 127 pp., $1.28.

_Molecular Biology: Genes and the Chemical Control of Living Cells_, J. M. Barry, Prentice-Hall, Inc., Englewood Cliffs, New Jersey, 1964, 139 pp., $3.35.

_Elementary Biophysics: Selected Topics_, Herman T. Epstein, Addison-Wesley Publishing Company, Inc., Reading, Massachusetts, 1963, 122 pp., $2.95 (hardback), $1.75 (paperback).

Articles

Autobiographies of Cells, R. Baserga and W. Kisieleski, _Scientific American_, 209: 103 (August 1963).

Electrons, Enzymes, and Energy, Michael G. Del Duca and John M. Fuscoe, _International Science and Technology_, 39: 56 (March 1965).

_Scientific American_, 205 (September 1961). This is a special issue on the living cell. The two articles cited below are of particular interest:

How Cells Divide, Daniel Mazia, 205: 101. The Living Cell, Jean Brachet, 205: 50.

Reports

_Liquid Scintillation Counting: Proceedings of a Conference Held at Northwestern University, August 20-22, 1957_, C. G. Bell, Jr. and F. N. Hayes (Eds.), Pergamon Press, Inc., New York, 1957, 292 pp., $10.00.

_Atomic Energy Research: Life and Physical Sciences; Reactor Development; and Waste Management_, A Special Report of the U. S. Atomic Energy Commission (December 1961), Superintendent of Documents, U. S. Government Printing Office, Washington, D. C. 20402, 333 pp., $2.25.

Booklets

_Radioisotopes in the Service of Man_, Fernand Lot, National Agency for International Publications, 317 East 34th Street, New York 10016, 1958, 82 pp., $1.00.

_Science and Cancer_, M. B. Shimkin, Public Health Service Publication No. 1162, Superintendent of Documents, U. S. Government Printing Office, Washington, D. C. 20402, 1964, 137 pp., $0.60.

Motion Pictures

_The Cell: Structural Unit of Life_, 10 minutes, sound, color or black and white, 1949, Coronet Films, Inc., 65 E. South Water Street, Chicago, Illinois 60601.

_Continuity of Life: Characteristics of Plants and Animals_, 11 minutes, sound, color or black and white, 1954, Audio-Visual Center, Indiana University, Bloomington, Indiana 47405.

_DNA: Molecule of Heredity_, 16 minutes, sound, color (No. 1825), black and white (No. 1826). 1960, Encyclopaedia Britannica Films, Inc., Wilmette, Illinois 60091.

_The Science of Genetics_, AIBS Secondary School Film Series, No. 13280, 25 minutes, sound, color, 1962, McGraw-Hill Book Company, Inc., 330 West 42nd Street, New York 10036.

Available for loan without charge from the AEC Headquarters Film Library, Division of Public Information, U. S. Atomic Energy Commission, Washington, D. C. 20545, and other AEC film libraries:

_Tracing Living Cells_, Challenge Film No. 11, 29 minutes, sound, black and white, 1962. Produced by Ross-McElroy Productions for the National Educational Television and Radio Center under a grant from Argonne National Laboratory. This nontechnical film demonstrates some of the uses of radioisotopes in the study of cell division and in medical therapy.

_The Eternal Cycle_, 12½ minutes, sound, black and white, 1954. Produced by the Handel Film Corporation. This nontechnical film illustrates the use of radioisotope tracers in biological research and is suitable for intermediate- through college-level audiences.

_Chromosome Labeling by Tritium_, 15 minutes, sound, color, 1958. Produced by the Jam Handy Organization for the U. S. Atomic Energy Commission. This technical film discusses the advantages of tritium over other radioisotopes as labeling material in autoradiography.

_A is for Atom_, 15 minutes, sound, color, 1953. Produced by the General Electric Company. This nontechnical film explains the structure of the atom, natural and artificially produced elements, stable and unstable atoms, principles and applications of nuclear reactors, and the benefits of atomic radiation to biology, medicine, industry, and agriculture. It is suitable for elementary- through high-school audiences.

FOOTNOTES

[1]An organism is a complete living plant or animal.

[2]Metabolism is the sum of the life-sustaining activities in a living organism, including nutrition, production of energy, and synthesis (building) of new living material.

[3]Morphologists are biologists specializing in the structure of organisms or in the study of whole organisms. Biochemists, by contrast, study chemical reactions of biological materials.

[4]This is not to be confused with a cell nucleus. This word was borrowed from biology for atomic theory, however.

[5]An exception is the hydrogen atom, which has no neutron in its nucleus.

[6]Mev is the abbreviation for million electron volts.

[7]A concept for which James D. Watson of the United States and Francis H. C. Crick of England shared a Nobel Prize in 1962.

[8]The study of tissues.

[9]There are additional, more subtle metabolic events that lead to the synthesis of DNA, but they are not important in this discussion.

PHOTO CREDITS

Figure 1 Armed Forces Institute of Pathology Negative No. 4156 Figure 3 Dr. T. Tahmisian, Argonne National Laboratory Figure 4 Oak Ridge National Laboratory (photo on right) Figure 5 Oscar W. Richards, American Optical Company Figure 7 Brookhaven National Laboratory Figure 9 Battelle-Northwest Laboratory Figure 10 Oak Ridge National Laboratory Figure 19 Argonne National Laboratory Figure 23 Argonne National Laboratory Figure 24 Argonne National Laboratory Figure 28 Argonne National Laboratory Figure 29 Brookhaven National Laboratory

This booklet is one of the “Understanding the Atom” Series. Comments are invited on this booklet and others in the series; please send them to the Division of Technical Information, U. S. Atomic Energy Commission, Washington, D. C. 20545.

Published as part of the AEC’s educational assistance program, the series includes these titles:

_Accelerators_ _Animals in Atomic Research_ _Atomic Fuel_ _Atomic Power Safety_ _Atoms at the Science Fair_ _Atoms in Agriculture_ _Atoms, Nature, and Man_ _Books on Atomic Energy for Adults and Children_ _Careers in Atomic Energy_ _Computers_ _Controlled Nuclear Fusion_ _Cryogenics, The Uncommon Cold_ _Direct Conversion of Energy_ _Fallout From Nuclear Tests_ _Food Preservation by Irradiation_ _Genetic Effects of Radiation_ _Index to the UAS Series_ _Lasers_ _Microstructure of Matter_ _Neutron Activation Analysis_ _Nondestructive Testing_ _Nuclear Clocks_ _Nuclear Energy for Desalting_ _Nuclear Power and Merchant Shipping_ _Nuclear Power Plants_ _Nuclear Propulsion for Space_ _Nuclear Reactors_ _Nuclear Terms, A Brief Glossary_ _Our Atomic World_ _Plowshare_ _Plutonium_ _Power from Radioisotopes_ _Power Reactors in Small Packages_ _Radioactive Wastes_ _Radioisotopes and Life Processes_ _Radioisotopes in Industry_ _Radioisotopes in Medicine_ _Rare Earths_ _Research Reactors_ _SNAP, Nuclear Space Reactors_ _Sources of Nuclear Fuel_ _Space Radiation_ _Spectroscopy_ _Synthetic Transuranium Elements_ _The Atom and the Ocean_ _The Chemistry of the Noble Gases_ _The Elusive Neutrino_ _The First Reactor_ _The Natural Radiation Environment_ _Whole Body Counters_ _Your Body and Radiation_

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