(b. Czernowitz, Austria-Hungary, 11 August 1905;
Chargaff is best known for his discovery of DNA “base ratios,” also known as “Chargaff’s rules,” in the late 1940s, while working at Columbia University in New York City. The discovery of base-ratios was later interpreted stereochemically by James Watson and Francis Crick in 1953 to also mean “base-pairings,” eventually becoming the most important feature of DNA structure, namely, the feature that explains DNA’s capacity for precise duplication. The base-ratios require that each base on one of DNA’s double helix’s two strands “pairs” with a complementary base only, as specified by Chargaff’s rules (see below, the chemical details of the various rules) from the other strand. Though DNA emerged since the mid-1960s as the best-known symbol of the new field of molecular biology, Chargaff preferred, even insisted, on calling himself a cell chemist, so as to emphasize the primacy of his chemical training and practices in his work on biological material. Indeed, Chargaff’s discoveries were both enabled and constrained by his training as a chemist who specialized in microanalytic studies of a wide variety of cellular components, including factors in blood coagulation, lipids and lipoproteins, the metabolism of amino acids and inositol, and the biosynthesis of enzyme phosphotransferases.
Early Years . Chargaff was born to Hermann Chargaff (1870–1934), owner of a small bank, and Rosa Silberstein Chargaff (1878–1943), in the multicultural town of Czernowitz, capital of the easternmost province of the Austro-Hungarian Empire, Bukovina. Famous as the Vienna of Eastern Europe, Czernowitz was the birth place of many cultural luminaries, most notably the foremost post–World War II poet in the German language, Paul Celan. To this day, former residents retain a distinct pride in their multicultural background and maintain their own Website. Czernowitz’s cultural diversity stemmed from a balance among several ethnic groups: the German-speaking Austrian bureaucracy at the top of the social hierarchy; Ruthenian peasants and landed gentry who spoke Romanian or Ukrainian; and Jews in various stages of emancipation, ranging from culturally assimilated, well-to-do German speakers, such as Chargaff’s parents, to poor shtetl dwellers who spoke Yiddish and bits of the local dialects of Romanian, Ukrainian, Polish, or Russian, and made up a quarter of the urban population, but a majority of its middle class. With the outbreak of World War I, Czernowitz was to change hands many times, having been occupied by the Russian Army in 1914, incorporated into Romania in 1919, ceded to the Soviet Union in 1939, occupied by Nazi Germany in 1941, and by the Soviet Union in 1945. Since 1991, it has been part of Ukraine, and called Chernivtsi. Chargaff relocated with his family to Vienna in 1914, and attended there a well-known humanistic gymnasium, the Maximilian, where his literary talents and ambitions could flourish. However, the great inflation of 1923, which ravaged the Central European middle classes, made it no longer possible for Chargaff to become a writer and he studied instead a profession that guaranteed a living: chemistry, famous for its employment opportunities in the chemical industry.
After his graduation with a PhD in analytical chemistry from the University of Vienna in 1928, Chargaff did two years of postdoctoral research at Yale University with R. Anderson, an editor of the Journal of Biological Chemistry, from whom he learned research methods in bacterial chemistry. Despite a productive experience and job offers in the United States, Chargaff chose to return to Europe, being apparently overwhelmed by “culture shock.” (He mentioned in his autobiography the endless commotion of New York City, especially during Prohibition and the Great Depression, as well as Yale’s “caste provincialism.”) Because he described his subsequent quest for a position in Berlin as doing “what desperate Viennese always threatened to do,” it is obvious that Chargaff, having arrived in the United States as a nonimmigrant, had been unprepared for his initial encounter with American culture.
Return to Europe . For the next two and a half years (1930–1933) Chargaff enjoyed “the best years of his life” as a privatdozent, or occupant of the first ladder in a professorial career at the University of Berlin’s Department of Public Health, where its head, Martin Hahn, appreciated Chargaff’s past experience at Vienna and Yale in bacterial and analytic chemistry. The admissions committee was particularly impressed with Chargaff’s cultivated manner and proficiency in central European literature. Rubbing shoulders in weekly colloquia with scientific luminaries such as the Nobel laureate chemists Fritz Haber and Otto Warburg, as well as other scientists, most notably Albert Einstein, Max von Laue, James Franck, Max Planck, Walther Nernst, and fellow Viennese Lise Meitner and Erwin Schrödinger, Chargaff also enjoyed the innovative and lively cultural life that became a hallmark of the Weimar Republic. He was convinced that he had found a suitable place for both his scientific and cultural aspirations, concluding reluctantly, like many before him, that Berlin surpassed even his native Vienna.
However, by the time Chargaff was ready to submit his Habilitationschrift in 1933 (a formal condition for becoming a university professor), the scene had changed profoundly due to the Nazis’ rise to power. Despite his apolitical disposition and Austrian passport, Chargaff, who came from a family of Austrian Empire Jews who had assimilated into German culture as part of their upward mobility a generation earlier (his father Germanized the Spanish-Jewish last name of Chargaff’s paternal grandfather Don Isaak Chargaf by adding an “f”), realized that he had to leave Berlin immediately. He accepted an invitation to work at the Pasteur Institute in Paris, whose director, Albert Calmette, correctly realized that Chargaff’s expertise in bacterial chemistry could help exonerate him from accusations of responsibility for fatalities resulting from contaminated BCG (Bacille Calmette-Guerin) vaccines (Calmette was coinventor of that vaccine).
After two years at the Pasteur Institute, which Chargaff later described as “decadent,” he once again had to move when the increasing flow of refugees from Nazi Germany sparked displays of xenophobia (it was more of an antiforeigner than an anti-Semitic bias, though the two are often linked; France elected Leon Blum, a French Jew, as prime minister in 1936, a year after Chargaff had left; the derogatory term addressed at refugees that Chargaff recalled was “metheques” which means “foreign half-caste)” in France. Besides, research in France was not as well paid as in Germany, and careers for foreigners were next to impossible. After unsuccessfully scouting for job opportunities in the United Kingdom, with help from the Rockefeller Foundation’s European office in Paris, Chargaff returned to the United States, where he was eventually able to find a research position at Columbia University’s Department of Medicine at the College of Physicians and Surgeons, working on the chemistry of blood coagulation for a project run by surgeons. However, the chairman of the Department of Biochemistry, Hans Clarke, who knew German biochemistry from his own experience there before World War I, and who had already hired several refugees, most notably the department’s star, Rudolf Schoenheimer, in 1933, understood Chargaff’s potential and integrated him into the large Department of Biochemistry.
Move to Columbia . Chargaff was to remain at Columbia for the rest of his career, concluding as chairman of the Department of Biochemistry (1970–1974) and retiring as a recipient of the National Medal of Science (1975). However, his relationship to his department remained strained, in part because he inevitably compared it with his experiences in Vienna, Berlin, and Paris, as well as at Yale. During those early years, as a gifted and hardworking young man, Chargaff was spotted and appreciated by senior scientists, in the central European manner, according to which heads of research institutes invited promising young researchers to work with them, thus securing their future in a career that was supposed be based on excellence in research only.
By contrast, U.S. research departments were more decentralized, and opportunities for promotion often depended on a variety of extraneous factors, such as one’s negotiating position or networking position in the discipline at large, as well as in one’s department. Ironically, Chargaff turned out to be very capable of securing research grants, of interacting professionally with a wide range of scientists in other institutions and countries, lecturing well, and possessing all the ingredients for a successful career in the United States. But he could not avoid being trapped in the cultural values of another place and another time, of the Vienna of his serene childhood, prior to the demise of the Austro-Hungarian Empire, recalling the resulting social and political upheaval and the painful loss of his family’s former upper-middle-class status during the inflation of the early 1920s.
A major reason that Chargaff remained trapped by the values of his past was his experience in the 1920s as a follower of Vienna’s leading cultural critic, Karl Krauss. Young Chargaff naively absorbed Krauss’s apocalyptic vision, which dramatized the corruption of Vienna’s leaders, often contrasting it with earlier, more benign times. Krauss’s lamentations of the loss of Vienna’s former cultural glory resonated only too well with Chargaff’s own experience, and Chargaff, who referred to Krauss as “my only teacher,” hoped to emulate him as a writer and cultural critic at large. However, the social upheaval of post–World War I Vienna, when fascists and communists violently battled in the streets, and especially the Great Inflation of 1923, demanded that Chargaff choose a profession that would guarantee a living. He chose chemistry, a science that offered sure employment, especially in the large chemical industry, but he came to resent what he considered a betrayal of his initial, or more genuine, literary vocation, and thus he came to regard science as a “second best,” a mere profession.
The relevance of this seemingly peculiar fact for understanding Chargaff’s career in science pertains not only to his later emergence, since the 1960s, as a cultural critic of “Big Science,” a critique inspired by Krauss’s apocalyptic model. Rather, Chargaff’s perception of the loss of his true vocation led to his refusal to become fully absorbed by science. This moral distinction between vocation and profession, elaborated by Max Weber, led Chargaff to compensate for the abandoning of his “first love” or literary vocation by spending a great deal of his time on literary and cultural matters. This guilt-laden attitude also meant that, while Chargaff discharged his formal responsibilities in research and teaching in a dutiful manner, he refused to spend time on “career building” such as networking or cultivating mentors and peers. Though always busy with the responsibilities of a leading scientist, Char-gaff seemed to be waiting for an opportunity to become a full-time writer, which he accomplished in the 1960s, and
especially after his retirement in 1975. This conduct of letting cultural values override scientific priorities manifested itself in the two most important episodes of Char-gaff’s life, namely the discovery of DNA base ratios and his critique of molecular biology as Big Science.
Chargaff thus became one of very few scientists who immediately understood the implications of Oswald Avery’s seminal paper, published in 1944, on DNA’s ability to effect a genetic change in bacteria by itself, due to Chargaff’s extensive prior experience with diverse facets of cell chemistry, but also due to his research for the war effort, which required the study of tropical pathogens’ nucleic acids, starting in 1942. Placed at a great university in a great city, Chargaff had access to many graduate and postdoctoral students, to the effect that he was not only able to reorient his entire research program to focus on DNA, but could benefit from the work of many talented young scientists, many of whom became leaders in biochemistry and molecular biology (including, for example, those invited to speak at Chargaff’s retirement symposium: Aaron Benditch, George Brawerman, Seymour Cohen, David Elson, Boris Magasanik, David Shemin, and David Sprinson). The availability of research grants from both governmental agencies and private foundations and, after World War II, new equipment capable of measuring minute quantities were also key factors in enabling Chargaff to discover many structural features underlying DNA’s genetic function.
Research on DNA Bases . In a series of innovative experiments in the mid- and late 1940s, focused on measuring DNA’s base composition in a variety of species and organs, Chargaff established that the ratio of purines to pyrimidines (two- versus one-ring nitrogenous bases) was 1; that the ratios of adenine to thymine and guanine to cytosine, respectively, was also 1 (the former base in each pair is a purine and the latter is a pyrimidine); that DNA base ratios are similar across organs in the same organism; and that DNA composition or percentage of each base is species-specific. He further established such specificity for a wide range of species, ranging from bacteria to humans. These results refuted previous beliefs, according to which DNA structure was a repetition of the same four bases, and hence monotonous or unable to account for biological diversity. Prior to Chargaff’s work, scientists believed that the molecular basis of biological specificity resided in proteins, which were composed of twenty types of amino acids and thus possessed a structure more conducive to account for biological diversity, for example, the endless varieties of antibodies produced in immunological reactions.
At the time, Avery’s and Chargaff’s discoveries on DNA function and structure, respectively, were greeted with little interest because their transdisciplinary nature, combining biochemistry with genetics and microbiology, eluded the expertise of most scientists, who remained compartmentalized within disciplinary boundaries. Besides, most scientists still believed in the protein primacy of the genetic material, widely acknowledged to be a combination of protein and nucleic acids. Besides Char-gaff ’s laboratory, which focused on a microanalytic approach to DNA base composition, the only other laboratory to include DNA structure as a major research project was the Biophysics Unit of the Medical Research Council at King’s College, London, which had also begun in 1946, though work there on DNA intensified in 1950 with the arrival of Rosalind Franklin. Chargaff agreed to supply DNA samples to biophysicist Maurice Wilkins from King’s College, London, who wished to duplicate Franklin’s work. (The lab director, John T. Randall, transferred the study of DNA by x-ray diffraction to Franklin because Wilkins, who focused on optical studies, did not have such expertise.)
Like many other scientists who collaborated across disciplines at the time, Chargaff and Wilkins limited their exchange to correspondence and sample exchange, but did not seek to explore the ramifications of each other’s projects. Thus Wilkins was slow to conclude that Chargaff’s “base ratios” were the key to DNA structure, while sharing his view with Watson late in January 1953. But the question persists as to why Chargaff himself did not attempt to better establish how the biophysical structurists in London were using his discovery of base ratios, especially because he himself mentioned that their meaning must be essential to DNA function.
Chargaff’s base ratios were given a stereochemical interpretation as “base pairings” as part of the double-helix structure proposed by Watson and Crick in April 1953. Subsequently, after the mode of DNA replication was confirmed in the late 1950s and 1960s, DNA structure became an icon of the new biology, with base pairings its most salient feature, because it is the feature that explains DNA’s ability to duplicate correctly, by matching the correct base across its two strands, according to Char-gaff’s rules.
It is not obvious why the scientific community chose to highly value the base-pairing interpretation of Chargaff’s base ratios, while at the same time opting to devalue Chargaff’s results—results which made that interpretation possible in the first place. Many scientists thus strangely believe that Chargaff missed the greater discovery of the double helix, even though it is only too obvious that he had no intention to enter either crystallography or stereochemistry.
In any event, it is difficult to envisage the emergence and persistence of such a large disparity between base ratios and base pairings without myriad social processes such as discipline formation and social change in science after World War II. However, Chargaff’s own cultural constraints, such as his outlook of science as a “mere” profession and his perception of himself as a potential writer, sparing his better moments for literature—not for inquiring what others are doing or for forging alliances and opportunistic collaborations—go a long way to explain the differential reception of scientific discoveries related to DNA structure and function.
Chargaff took both Crick and Watson to task for providing inadequate and misleading citations to his work in their papers on DNA structure in 1953, to the effect that in the early twenty-first century readers do not understand its enormous importance for any DNA model. (Linus Pauling and Robert Corey’s model, also in 1953, and other preceding models of DNA failed, in part, because they ignored Chargaff’s rules.). Chargaff also attempted to comprehend the new style of doing science that developed after World War II, He commented that “molecular biology is the practise of biochemistry without a license,” (Chargaff, 1963, p. 176) with the obvious implication that the licensing system went bankrupt after the war, when the rapid rise in the number of scientists encouraged rapid mobility across disciplines, institutions, or techniques (Abir-Am, 1980). Chargaff’s critique of the rising field of molecular biology, an interdisciplinary field that came to focus on nucleic acids (DNA and several types of RNA) and their relationships with proteins, was first published in 1963 as a dialogue between an old biochemist and a young molecular biologist. It captured a generational transition between those trained prior to World War II, who retained loyalty to their formative disciplines (especially chemists such as Chargaff), and those trained after the war, often physical or medical scientists attracted to molecular biology by the availability of a wide range of new technical opportunities, such as artificial isotopes, ultracentrifuges, electrophoreses, several forms of chromatography, electron microscopes, and x-ray diffraction equipment. However, this change was also numeric, because the rapid growth of science in the 1950s—due to increased funding opportunities after the war, and again after the Sputnik launch in 1957—propelled large numbers of individuals into new fields, to the effect that scientists such as Chargaff, then fifty years of age, rapidly became a minority.
Chargaff’s witty reference to “DNA tycoons” or those who “made a killing in RNA,” captures the rising practice of scientific empire building, in which science had lost its earlier character as a search for truth and contemplation of nature via carefully designed experiments, having become immersed in slick and quick pursuits of power, money, and managerial control. Not only was science being destroyed by the invasion of numerous unlicensed practitioners, but the new allure of models in biology, artificial constructs that “legislate for nature,” was viewed by Char-gaff as having destroyed the very concept of the molecule—a concept at the heart of science, in his view. As the revolution of molecular biology destroyed Chargaff’s last refuge in science, both in terms of a science that became a mass occupation and in terms of molecules that no longer reflected nature but derived their reality from artificial models, he was propelled to fight back while recovering his long lost vocation as a cultural critic.
Chargaff eventually expanded his critique of molecular biology as Big Science to its recombinant-DNA phase. He published articles such as “Triviality in Science: A Brief Meditation on Fashions” (1976) and “In Praise of Smallness: How Can We Return to Small Science?” (1980), promoting the notion that “small is beautiful” with the rare voice of an “outsider on the inside.” Whether denouncing big, slick, industrial, artificial, genetically centered outlooks that prevailed in the United States since the 1960s, or lamenting the passing of the small, noble, empirical, and biochemically centered outlook of pre–World War II science, Chargaff’s experience of cultural displacement and loss of vocation, in the interwar period, led him full circle to find and lose again his refuge in twentieth-century DNA science.
In the last two decades of his life Chargaff began writing books in German, and became a frequent radio and TV interviewee in central Europe. A documentary was made of his life in 1996 by an Austrian filmmaker. A literary archive was established for his writings in Marbach, Germany. Chargaff died in 2002 at age ninety-six at his home in Central Park West in New York City, where he had lived for almost seven decades, always dreaming of his lost life in interwar Europe.
Chargaff’s scientific archive is at the American Philosophical Library in Philadelphia.
WORKS BY CHARGAFF
“On the Nucleoproteins and Nucleic Acids of Microorganisms.” Cold Spring Harbor Symposium on Quantitative Biology 12 (1947): 28–34.
“Chemical Specificity of Nucleic Acids and Mechanism of Their Enzymatic Degradation.” Experentia 6 (1950): 201–209.
Essays on Nucleic Acids. Amsterdam: Elsevier, 1963. See especially chapter 11, which includes the composite dialogue between an old chemist and a young molecular biologist.
“A Quick Climb up Mount Olympus.” Science 159 (1968): 1448–1449. Review of James D. Watson’s The Double Helix, 1968.
“The Paradox of Biochemistry.” Columbia Forum (Summer 1969): 15–18.
“Preface to a Grammar of Biology.” Science172 (1971): 637–642.
“Bitter Fruits from the Tree of Knowledge: Remarks on the Current Revulsion from Science.” Perspectives in Biology and Medicine 16 (Summer 1973): 486–502.
“Voices in the Labyrinth: Dialogues around the Study of Nature.” Perspectives in Biology and Medicine 18 (Winter 1973): 251–285.
“A Fever of Reason: The Early Way.” Annual Review of Biochemistry 44 (1975): 1–18.
“Profitable Wonders: A Few Thoughts on Nucleic Acid Research.” Sciences (August–September 1975): 21–26.
“Triviality in Science: A Brief Meditation on Fashions.” Perspectives in Biology and Medicine 19 (Spring 1976): 325–333.
“Experimenta Lucifera.” Nature 266 (1977): 780–781.
Heraclitean Fire: Sketches of a Life before Nature. New York: Rockefeller University Press, 1978.
“Strands of the Double Helix.” New Scientist (17 August 1978): 484.
“In Praise of Smallness: How Can We Return to Small Science?”Perspectives in Biology and Medicine 23 (Spring 1980): 370–385.
“Swindle: Scientific and Otherwise.” Science and Society BioEssays 2, no. 3 (1985): 132–135.
“A Dialogue and a Monologue on the Manufacture of Souls.” Perspectives in Biology and Medicine 31 (Autumn 1987): 81–93.
“In Retrospect: A Commentary by Erwin Chargaff.” Biochemica et Biophysica Acta 1000 (1989): 15–16. Ein Zweites Leben. Stuttgart, Germany: Klett-Cotta, 1990.
———. “Noblesse Oblige: Lives of Molecular Biologists.” Isis 82 (1991): 326–343.
———. “The Molecular Transformation of Twentieth-Century Biology.” In Science in the Twentieth Century, edited by John Krige and Dominique Pestre, 495–524. London: Harwood, 1997.
Appelfeld, Aharon. “Buried Homeland.” New Yorker (23 November 1998): 48–57.
Cohen, Seymour S. “Presentation of Academy Medal to Erwin Chargaff.” Bulletin of the New York Academy of Medicine 56, no. 7 (1980): 601–606.
Crick, Francis. What MAD Pursuit: A Personal View of Scientific Discovery. New York: Basic Books, 1988.
Deichmann, Ute. Biologists under Hitler. Cambridge, MA: Harvard University Press, 1996.
Dubos, Rene J. The Professor, the Institute, and DNA. New York: Rockefeller University Press, 1976.
Eisenberg, Henryk. “Never a Dull Moment: Peripatetics through the Gardens of Science and Life.” Comprehensive Biochemistry37 (1990) 265–348.
Forsdyke, Donald R., and James R. Mortimer. “Chargaff’s Legacy.” GENE 261 (2000): 127–137.
Judson, Horace Freeland. The Eighth Day of Creation: Makers of the Revolution in Biology. Expanded ed. Plainview, NY: CSHL Press, 1996. See especially the appendix on Chargaff.
Maddox, Brenda. Rosalind Franklin, the Dark Lady of DNA. London: Harper Collins, 2002.
Magasanik, Boris. “A Midcentury Watershed: The Transition from Microbial Biochemistry to Molecular Biology.” Journal of Bacteriology 181, no. 2 (1999): 357–358.
McCarty, MacLyn. The Transforming Principle: Discovering That Genes Are Made of DNA. New York: W.W. Norton, 1985.
Rezzori, Gregor von. “Memoirs of an Antisemite.” New Yorker (26 April 1969): 42–83.
Sayre, Anne. Rosalind Franklin and DNA. New York: W.W.Norton, 1985.
Srinivasan, Parithychery R., Joseph S. Fruton, and John T.Edsall, eds.The Origins of Modern Biochemistry: A Retrospect on Proteins. Special Issue of Annals of the New York Academyof Sciences 325 (1979): 1‒373.
Watson, James D.A Passion for DNA: Genes, Genomes, and Society. Oxford: Oxford University Press, 2000.
Wilkins, Maurice. The Third Man of the Double Helix. Oxford:Oxford University Press, 2003.
Pnina G. Abir-Am
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.
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. □
Erwin Chargaff has been a pioneer in the study of the chemical nature of nucleic acids. Chargaff's work proved that, contrary to the prevailing views about nucleic acids in the 1940s, DNA was actually a complex and highly variable molecule that could serve as the genetic material. He also established the relationships, now known as "Chargaff's rules," among the four bases found in DNA.
Chargaff was born in 1905 in Czernowitz, which at the time was a provincial capital of the Austrian monarchy. His parents, Hermann Chargaff and Rosa Silberstein Chargaff, had been moderately well off, but they were financially ruined during the Great Inflation after World War I. As a child, Chargaff was a voracious and eclectic reader. In 1914, at the outbreak of World War I, his family was forced to move to Vienna to avoid the Russian occupation of Czernowitz. Chargaff received most of his education at the Maximiliansgymnasium in Vienna. He enjoyed school and excelled in literature and the classical languages. Chargaff, who is well known for his literary style, remembers having a special relationship to language ever since his childhood.
At the University of Vienna, Chargaff decided to major in chemistry. His dissertation dealt with organic silver complexes and the action of iodine on azides. Eventually, he was able to utilize some aspects of his thesis research in identifying the presence of sulfur-containing amino acids on paper chromatographs. While at the university, he met his future wife, Vera Broido. After Chargaff received his doctoral degree in 1928, he obtained a research fellowship at Yale University, where he worked with Rudolph J. Anderson on the lipids of tubercle bacilli. Chargaff and Vera Broido were married in New York in 1929 and returned to Europe in 1930. Their son was born in 1938.
Between 1930 and 1933 Chargaff carried out further research on tubercle bacilli at the University of Berlin's Institute of Hygiene. Chargaff was involved in the investigation of the "Lübeck scandal," which involved the prosecution of several physicians who had caused the deaths of several babies by using cultures of virulent tubercle bacilli instead of BCG vaccine. Chargaff's work helped to prove that BCG itself had not been responsible for the disaster. In 1933 Albert Calmette (1863-1933) invited Chargaff to work at the Pasteur Institute. One year later, Chargaff returned to the United States to work at the Mount Sinai Hospital in New York, before accepting a research position in the department of biochemistry at Columbia University, where he carried out research on the biochemistry of blood coagulation. He also studied lipids, lipoproteins, phospholipids, inositols, hydroxy amino acids, and conducted the first synthesis of a radioactive organic compound. Chargaff remained at Columbia for the rest of his professional career. He became an assistant professor at 33, an associate professor at 41, and a professor at 47. He retired in 1974 and is currently Professor Emeritus and Special Lecturer in Biochemistry and Molecular Biophysics.
In 1944 Chargaff read Oswald T. Avery's (1877-1955) famous paper on the transforming principle and became convinced that DNA was the "hereditary code-script." He had recently read Erwin Schrödinger's (1887-1961) What Is Life? and was already thinking about the biochemical nature of genes. The combined impact of Avery's paper and Schrödinger's book convinced Chargaff to study nucleic acids. Work previously carried out by Phoebus Aaron Levene (1869-1940) suggested that DNA was a repetitious polymer, but Chargaff disproved that assumption by conducting precise analyses of nucleic acids from many sources, such as beef thymus, spleen, liver, human sperm, yeast, and tubercle bacilli. Using methods that first became available after World War II—paper chromatography, UV spectrophotometry, and ion-exchange chromatography—he proved that the four bases were not present in equal amounts, contrary to Levene's "tetranucleotide hypothesis." Chargaff called attention to the noteworthy fact that in all DNA molecules the molar ratios of total purines to total pyrimidines, and, more specifically, the ratios of adenine to thymine and of guanine to cytosine, were about one. The meaning of this "regularity" could not be determined at the time, but it was later explained in terms of the complementarity rules of the DNA double helix.
Chargaff was elected to the National Academy of Science in 1965. His voluminous writings include a two-volume work called The Nucleic Acids (1955, 1960), Essays on Nucleic Acids (1963), Voices in the Labyrinth (1977), and the autobiographical Heraclitean Fire (1978). Although the Nobel Committee has failed to acknowledge his crucial work on the biochemistry of DNA, he was awarded the National Medal of Science in 1975. At the end of the twentieth century, Chargaff was still actively thinking about science and the meaning of life, as indicated in his essay "In Dispraise of Reductionism," which was published in the journal Bioscience in 1997. Here, he analyzed issues related to the term "reductionism" and their implications for science.
LOIS N. MAGNER
CHARGAFF, ERWIN (1905–2002), U.S. biochemist. Chargaff was born in Czernowitz, then Austro-Hungary, and gained a doctorate in chemistry from the University of Vienna (1928). He held postdoctoral research posts consecutively at the Universities of Yale, Vienna, and Berlin, and at the Institut Pasteur in Paris before awareness of the Nazi menace led him to immigrate to the U.S. (1934). He joined the Department of Biochemistry of Columbia University's College of Physicians and Surgeons, where he became professor, department chairman, and professor emeritus before retiring in 1992. Early in his research career Chargaff made major contributions to characterizing the proteins involved in blood clotting. In 1944 he accepted Avery's evidence that dna in a bacterium determined its hereditary characteristics. He reasoned that genetic differences in dnas must be attributable to chemical differences in these molecules. He established that in all species of dna tested the molar ratios of purines to pyrimidines, of adenine to thymine, and of guanine to cytosine is virtually 1.0. These "Chargaff rules" were a vital contribution to the elucidation of the structure of dna by Watson, Crick, and Wilkins and the role of base pairing in gene copying. Subsequently Chargaff was embittered that his contributions to solving arguably the most important problem in biology received inadequate recognition, not least from the proponents of the double helix model. As his skills as an analytical chemist became increasingly irrelevant to the development of molecular biology, he turned instead to his great literary skills, which he used to express prophetic warnings on the evils of unbridled biotechnology. Nevertheless his contributions are now recognized and his many honors included election to the U.S. National Academy of Sciences (1965) and the National Medal of Science (1974).
[Michael Denman (2nd ed.)]