Erwin Chargaff | Biography

In his own eyes, he was a natural philosopher, part of an extinct species of researcher. In the world of science, Erwin Chargaff was a pioneer in biochemistry whose demonstration that genes were comprised of deoxyribonucleic acid (DNA), was one of the most fundamental discoveries in the study of heredity. His accomplishments ranged over much of the field of biochemistry, including the study of lipids of microorganisms, blood coagulation, and the use of radioactive isotopes in the study of metabolism.

Chargaff was born in Czernowiz, Austria, which at the time was the provincial capital of the Austrian monarchy. Although he considered his education at Vienna's Maximilians Gymnasium excellent in quality, Chargaff found it limited in scope. Although his parents were not wealthy, having lost their money to an inflated economy, Chargaff successfully earned his doctoral degree in chemistry at the University of Vienna's Spath's Institute in 1928, working under the direction of Fritz Feigl.

His family's financial problems made a strong impression on Chargaff, who chose the field of chemistry because he believed it would be the most likely to offer employment. In fact, because students had to pay for their own chemicals and equipment, he chose to do his research with a particular chemistry professor whose work did not require much time or money.

Chargaff began his long, productive career in biochemistry at Yale University, where he worked under Rudolph J. Anderson from 1928 to 1930. From 1930 to 1933, he was an assistant at the University of Berlin before moving to Paris to work for nearly two years at the Pasteur Institute. In 1935, he settled into a permanent home at Columbia University, assuming the position of assistant professor of biochemistry. Chargaff became full professor in 1952, and was chairman of the department from 1970 until 1974, when be became professor emeritus. Chargaff was presented Columbia's Distinguished Service Award in 1982.

Chargaff's early work included studies of the complex lipids, the fats or fatty acids that occur in microorganisms. He helped to discover the unusual fatty acids and waxes in so-called acid-fast mycobacteria. This initial work led him to study the metabolism and biological role of lipids in the body, especially the lipoproteins, which are lipids attached to proteins.

Chargaff was a pioneer in the use of radioactive isotopes of phosphorus as a tool to study the synthesis and breakdown of phosphorus-containing lipid molecules (phospholipids) in living cells. As a result, he published the first paper on the synthesis of a radioactive organic compound called alpha-glycerophosphoric acid. Blood coagulation also caught his interest, and Chargaff studied the biochemistry of this important phenomenon, including the control of blood clotting by enzymes.

In 1944, while at Columbia, Chargaff's path veered sharply away from lipid metabolism and blood coagulation to the study of nucleic acids. Until then, most scientists believed that amino acids--the building blocks of proteins--carried genetic information. This seemed reasonable, since it was thought that the twenty amino acids that occur in cells could create enough combinations to form the complex code needed to make many thousands of different genes. DNA was also believed to be an unspecific aggregate of "tetranucleotides" made up of adenine, guanine, cytosine and thymine, that served as an attachment site for the amino acids that made up genes. But in 1944, Oswald T. Avery and his collaborators determined that DNA was a key element in property transfer between certain bacteria, and recognized that DNA could be the principle constituent of genes.

It was already known that a cell's nucleus is comprised in part by DNA, which is itself composed of sugar, phosphate and two types of complex molecules called purine bases (adenine and guanine) and pyrimidine bases (cytosine and thymine). Using two newly developed experimental techniques, Chargaff isolated DNA from cell nuclei and broke the giant, parent molecules down into constituent purines and pyrimidines. He first separated the bases from each other using a technique called paper chromatography. By then exposing these to ultraviolet light he identified the individual bases. Since different bases absorb ultraviolet light of specific wavelengths, he was able to determine how much of which bases were present by measuring the amount of light each quantity of base absorbed.

The results of this work represented a major contribution to the understanding of the structure of DNA. Chargaff and his colleagues showed that adenine and thymine occur in DNA in equal proportions in all organisms; likewise, cytosine and guanine are also found in equal quantities. However, the proportions of each pair of these nucleic acids differs among organisms. In other words, the presence of each pair of nucleotides is linked to the presence of the other.

Chargaff concluded that DNA, rather than protein, carries genetic information, and while there are only four different nucleic acids, the number of different combinations in which they can appear in DNA provides enough complexity to form the basis of heredity. In addition, he concluded that the identity of combinations differs from species to species; thus DNA strands differ from species to species.

These conclusions helped trigger a rush of new insights into DNA, the most important of which led James Watson and Francis Crick of the Cavendish Laboratory in Cambridge, England, to determine the exact structure of DNA. The Cavendish team showed that DNA consisted of two strands of sugar and phosphate connected by crosslinks of purines and pyrimidines. They concluded that the nucleic acids that make up each pair always occur in the same proportion because they always bond together, adenine to thymine, cytosine to guanine--known as the base-pairing rules. The entire molecule is stabilized by being twisted into a double helix structure. For their success in clarifying the structure of DNA, the Cavendish team won the Nobel Prize in 1962.

Chargaff continued to contribute to the understanding of how DNA and RNA (ribonucleic acid)work during the years after the double helix model was proposed. In 1962, Chargaff attended a symposium at Columbia University at which the nature of the genetic code was debated. He challenged a current concept of how the DNA code is translated into a precise sequence of amino acids. The theory held that each amino acid within a protein was coded by a specific series of three nucleic acids in the gene. But Chargaff's investigation of the genes for the protein bovine ribonuclease showed that the code, as then understood, could not be responsible for the specific amino acid sequences in this protein. Either the code was wrong, he suggested, or some amino acids may be coded by more than one sequence of nucleic acids. This theory, supported by the Spanish-American biochemist Severo Ochoa, turned out to be correct.

Despite his important contributions to the understanding of the biochemistry of nucleic acids, Chargaff was also very concerned with the state of the world at large. In his book, Heraclitean Fire: Sketches From a Life Before Nature, Chargaff wrote that society in general--manners, literature, music, and even science--had declined during his lifetime. He was particularly disillusioned with both his adopted country and the scientific community after the atom bomb was unleashed upon Hiroshima and Nagasaki at the close of World War II.

Chargaff also wrote longingly of the simpler days of science when research was not as influenced by money and politics. He summed up his disappointment with the way the world had turned out by saying that he had been "searching for a destiny that did not exist." His destiny, however, lead to important contributions in the field of biochemistry, including the addition of a key piece in the puzzle of the structure of DNA. In turn, this knowledge led to major developments in the field of medical genetics, and, ultimately helped pave the way for gene therapy and the birth of the biotechnology industry.

A visiting professor at Cornell University in 1967, Chargaff served that function in many countries around the world, including Sweden (1949), Japan (1958), and Brazil (1959). He also held the Einstein Chair at the College de France, Paris, in 1965. Among the many awards conferred upon him throughout his career, Chargaff received the Charles Leopold Mayer Prize in 1963, one of the highest awards granted by the French Academy of Sciences. The following year, he became the first recipient of the Heineken Prize in biochemistry from the Royal Netherlands Academy of Sciences. He received honorary degrees from both Columbia University and the University of Basel in 1976.