The American biochemist Erwin Chargaff (born 1905) discovered that DNA is the primary constituent of the gene, thereby helping to create a new approach to the study of the biology of heredity.
Erwin Chargaff was born in Austria on August 11, 1905. He graduated from high school at the Maximiliangynasium in Vienna and proceeded to the University of Vienna. In 1928 he obtained a doctoral degree in chemistry after having written a thesis under the supervision of Fritz Feigl at Spath's Institute. He went to the United States in 1928 as a Milton Campbell research fellow at Yale University. He stayed until 1930, when he went to the University of Berlin as an assistant in the public health department. In 1933 he transferred to the Pasteur Institute in Paris, and in 1935 he returned to the United States to become an assistant professor of biochemistry at Columbia University. He became a full professor 17 years later and was chairman of the department from 1970 to 1974, when he became an emeritus professor of biochemistry.
Chargaff's most important contribution to biochemistry was his work with deoxyribonucleic acid, more commonly known as DNA. At the time he was working it was not known that genes were composed of DNA. Instead, it was generally accepted that the 20 amino acids which compose the protein in the cell were the carriers of genetic information. Scientists reasoned that because there were so many different kinds of amino acids in the cell, they could combine in enough different ways to form a sufficiently complex basis for the gene. It was only in 1944 when O. T. Avery and his co-workers showed that DNA was a key agent in biological transformations that Chargaff realized that DNA could in fact be a major constituent of the gene.
Two major facts were already known about DNA. The first was that it is contained in the nucleus of every living cell. The second was that, in addition to sugar (2-deoxyribose) and phosphate, DNA is composed of two bases: pyrimidines, of which there are two types (cytosine and thymine), and purines, of which there are also two types (adenine and guanine). In addition, two important experimental methods involving paper chromatography and ultraviolet light absorption had recently been developed.
To test the idea that DNA might be a primary constituent of the gene, Chargaff performed a series of experiments. He fractionated out nuclei from cells. He then isolated the DNA from the nuclei and broke it down into its constituent nucleic acids. Then, using paper chromatography, he separated the purines and the pyrimidines. This was done on the basis of the solubility of the substances being analyzed (a piece of chromatography paper is dipped into the solution and the different components of the solution travel different distances up the paper: the most soluble component travels the farthest up, to the driest section of the paper, and so on). He next exposed the separate components of the solution to ultraviolet light. Because each base absorbs light of a different, "characteristic" wavelength, he was able to determine how much of which bases are present in DNA.
What Chargaff discovered was that adenine and thymine exist in equal proportions in all organisms, as do cytosine and guanine, but that the proportions between the two pairs differ depending on the organism. These relationships are usually expressed as follows: purines (adenine + guanine) equal pyrimidines (cytosine + thymine); adenine equals thymine; and guanine equals cytosine. Chargaff drew the conclusion that it is in fact the DNA in the nucleus of the cell that carries genetic information rather than the protein. His argument was that, while there were only four different nucleic acids, as opposed to 20 proteins, the number of different proportions in which they could exist and the many different orders in which they could be present on the DNA strand provided a basis of complexity sufficient for the formation of genes. He also realized that there must be as many different types of DNA molecules as there are species.
Chargaff's conclusions revolutionized the biological sciences. One extremely important result of his discovery was that it helped James D. Watson and Francis Crick of the Cavendish Laboratory in Cambridge, England, in their determination of the structure of DNA. They reasoned that because adenine and thymine always exist in the same proportion, they must always bond together, and similarly for cytosine and guanine. This conclusion led them to propose a double helix structure for DNA, for which they won the Nobel Prize in 1952. Their model showed DNA as consisting of two strands of sugar and phosphate (alternating on each strand) with the pyrimidine and purine bases attached to each sugar component and bonding the two strands together.
Though his main interest lay in the living cell and he liked to think of himself as a naturalist philosopher, Chargaff did research in many areas of biochemistry. He did a lot of work with lipids, the molecules that form fats, and in particular studied the role of lipid-protein complexes in the metabolism. He also did work with thromboplastic protein, the enzyme (biological catalyst) that initiates blood coagulation.
Chargaff received honorary degrees from Columbia University and the University of Basel in 1976. A member of many scientific societies including the National Academy of Science, he was a visiting professor in numerous universities around the world. He also won many awards, including the Pasteur medal in 1949, the Charles Leopold Mayer Prize from the Academy of Science in Paris in 1963, and the Gregor Mendel medal in 1973.
In his later years Chargaff eschewed scientific research and turned to writing. He gained popularity in Europe for his prize-winning essays and "doomsday" lectures. He mourns most emphatically the loss of "excellent science" in modern society. In a 1985 interview for Omni Magazine Chargaff emphasized his dismay at the contemporary evolution of scientific research into a modern commercial commodity. He repeatedly denied any bitterness in being overlooked for the Nobel Prize, despite the fact that his discoveries laid the cornerstone for the work of Watson and Crick. He rejects further any comparison between their work and his own.
Further Reading
A concise description of the function of DNA in the cell can be found in Maya Pines's Inside the Cell (1975), published by the U.S. Department of Health, Education and Welfare. In The Double Helix (1969) James Watson gives a lively and exciting account of his discovery of the structure of DNA with Francis Crick. General information on DNA can be found in A View of Life (1981), co-written by Singer, Luria, and Gould. Also see Omni, November 1982; June 1985.
