Erwin Chargaff

Ukrainian American biochemist

• Born: August 11, 1905; Czernowitz, Austria-Hungary (now Chernovtsy, Ukraine)
• Died: June 20, 2002; New York, New York

Twentieth-century Ukrainian American biochemist Erwin Chargaff was a pioneer in the field of genetics. The discoveries he made about the base ratios of DNA, which became known as Chargaff’s rules, led to the determination of the structure of DNA.

Primary field: Biology

Specialties: Biochemistry; molecular biology

Early Life

Erwin Chargaff was born on August 11, 1905, in Czernowitz, a provincial capital in what was then the Austro-Hungarian Empire. He was the son of Rosa Silberstein Chargaff and Hermann Chargaff, the owner of a small bank in Czernowitz. During the early part of World War I, Czernowitz and its surrounding region were occupied by the Russian army. The Chargaff family was forced to flee to Vienna, where they remained following the armistice in 1918.

Though the Chargaff family was relatively well-to-do prior to World War I, like much of former Austria-Hungary, they were financially ruined after the empire collapsed. Despite the family’s financial troubles, Chargaff was able to attend secondary school at the prestigious Maximilian Gymnasium in Vienna. The school gave Chargaff a solid grounding in the classics: Latin, Greek, mathematics, and history.

In 1924, Chargaff enrolled at the University of Vienna. Unsure of which program to study, he decided upon chemistry almost by default; he knew little of the subject, but nothing else seemed of interest. Chemistry also offered a better possibility of employment after graduation. Chargaff’s dissertation presented his work on organic silver complexes and the action of iodine on azides—compounds that form the conjugate base of the highly volatile hydrazoic acid—for which he was awarded a doctorate in 1928. He had produced two research publications prior to his dissertation, and he decided to remain in research following graduation. The same year Chargaff earned his doctorate, he married Vera Broido, a woman he had met at the university. They had one son, Thomas, born in 1938.

Life’s Work

There were few research positions available in Austria after Chargaff earned his PhD, so he decided to go to the United States. A colleague who had recently completed a lecture tour in the United States informed Chargaff that Rudolph Anderson, a researcher studying the tubercle bacillus (tuberculosis) at Yale University in New Haven, Connecticut, was interested in hiring a student to study lipids of the tubercle bacillus. Chargaff applied, and along with his acceptance he was awarded the Milton Campbell Research Fellowship in Organic Chemistry, which included a stipend for expenses. Chargaff spent two years in Anderson’s laboratory, publishing seven papers while there. Among his discoveries was the unusual branching of fatty acid chains on the surface of the tubercle bacillus, which accounted for scientists’ difficulty in staining the bacterium for identification.

Chargaff returned to Europe in 1930 and joined the bacteriology department at the University of Berlin. He considered the three years he spent there as a private lecturer among the happiest of his life. During his time in Berlin, Chargaff continued his research on tubercle bacilli. He also became involved in the Lübeck case, in which several physicians were accused of killing infants by giving them live tuberculosis bacilli instead of the Bacillus Calmette-Guérin (BCG) tuberculosis vaccine. Chargaff helped to prove that the vaccine preparations were not at fault.

In January 1933, Adolf Hitler assumed the government of Germany. Being Jewish and told he was no longer welcome at the university, Chargaff left Berlin for the Pasteur Institute in Paris, France. Despite his acceptance at the institute, Chargaff recognized that its lack of resources, money, and equipment would hamper his ability to carry out meaningful research. Remaining only until the end of 1934, Chargaff returned to the United States in 1935, where he was offered a position as research associate in the Department of Biochemistry at Columbia University in New York City. He remained at Columbia for the remainder of his professional career.

Chargaff’s initial research at Columbia dealt with plant proteins as well as the components of blood clotting. Two factors led Chargaff to move his research in a different direction. In 1944, Austrian physicist Erwin Schrödinger published a series of his lectures in a book, What Is Life?, in which he speculated that the source of genetic information in a cell was some form of a chemical crystal. While Schrödinger’s ideas were premature, their publication led a number of researchers, including Chargaff, to investigate the molecular basis for genetics. That same year, Canadian American physician and bacteriologist Oswald Avery and his colleagues demonstrated that deoxyribonucleic acid (DNA) was the genetic material in cells.

Intrigued by the role of DNA, Chargaff began an investigation into the chemical composition of the molecule. The components of DNA had been established earlier by Lithuanian American biochemist Phoebus Levene in 1929. Levene determined that DNA is composed of four different nucleotides. Each nucleotide contains a five-carbon deoxyribose sugar and a phosphate group, but they differ in the nitrogen base attached—adenine, guanine, thymine, and cytosine. Levene had proposed that the bases were present in equal amounts, which was the foundation for his 1929 hypothesis regarding tetranucleotide.

To determine the quantities of nucleotide bases in DNA, Chargaff used biochemical techniques that became available in the late 1940s, including the separation and quantification of molecules through paper chromatography and spectrophotometry. He discovered that contrary to the tetranucleotide hypothesis, the bases were not present in equal amounts, but varied depending on any given species. Furthermore, the quantity of adenine always equaled that of thymine, and the quantity of guanine always equaled that of cytosine. This equality of DNA base ratios became part of what is known as Chargaff’s rules.

In 1950, Chargaff published his findings in a paper entitled, “Chemical Specificity of Nucleic Acids and Mechanism of Their Enzymatic Degradation.” The significance of the ratios was missed by Chargaff at the time, since the actual structure of DNA was still unknown. However, his discovery played a key role two years later in enabling American molecular biologist James D. Watson and British molecular biologist Francis Crick to produce their model for the structure of DNA.

Chargaff spent many of his later years mired in controversy. Despite being one of the pioneers in the field of genetics, he objected to genetic engineering, considering it a greater threat to the world than nuclear technology. Still, he was the recipient of numerous honors, including election to the National Academy of Sciences in 1965 and being awarded the National Medal of Science in 1975. Chargaff served as chair of Biochemistry at Columbia University from 1970 to1974, after which he retired as professor emeritus. He died on June 20, 2002, at the age of ninety-six.

Impact

Chargaff is recognized for his contributions to several areas of biochemistry, and he published numerous papers; it was his discovery of the base ratios of DNA, Chargaff’s rules, for which he is most remembered. The significance of his observation was largely overlooked until Watson and Crick began building models of prospective structures of DNA in 1952. The ratios provided a clue toward that structure when Watson and Crick realized that not only did adenine bond with thymine (AT), and guanine with cytosine (GC), but that the space of the AT base pair was exactly the same as with the GC pair. Once they determined the relative positions of the components of DNA, with the phosphate-sugar backbones held together by the AT or GC pairings, the structure of DNA became apparent.

In their 1953 paper describing the structure of DNA, Watson and Crick acknowledged the role Chargaff’s discovery played in their work. While Chargaff was recognized for his discovery by Watson, Crick, and others, he was never awarded a Nobel Prize. When the 1962 Nobel Prize in Physiology or Medicine was awarded to Watson, Crick, and British biochemist Maurice Wilkins for their work on DNA, Chargaff responded with critical letters sent to scientists worldwide. He considered his contribution to the study of DNA equal to theirs, arguing that it was he who provided the critical information necessary for determining the molecular structure of DNA. Although the Nobel Prize committee overlooked Chargaff’s work, his contributions to the fields of biochemistry and genetics are still recognized.

Bibliography

Chargaff, Erwin. Heraclitean Fire: Sketches from a Life Before Nature. New York: Rockefeller UP, 1978. Print. Offers an autobiography of Chargaff’s life and philosophical approach to science, featuring anecdotes and stories that provide insight into the field of science and the behaviors of scientists.

Hausmann, Rudolf. To Grasp the Essence of Life: A History of Molecular Biology. Norwell: Kluwer Academic, 2010. Print. Includes the history of DNA, covering its discovery, function, and determination of structure. The contributions of Chargaff are described.

Olby, Robert C. Francis Crick: Hunter of Life’s Secrets. Cold Spring Harbor: Cold Spring Harbor Laboratory P, 2009. Print. Presents a biography of Francis Crick, covering the work he did with James D. Watson leading to the determination of the structure of DNA. Includes the confrontation between Chargaff and Crick.

Witkowski, Jan A., ed. Inside Story: DNA to RNA to Protein. Cold Spring Harbor: Cold Spring Harbor Laboratory P, 2005. Print. Collected perspectives on major figures in molecular biology and their work, including Chargaff.