Edward Lawrie Tatum Biography (1909-1975)


Edward Lawrie Tatum's experiments with simple organisms demonstrated that cell processes can be studied as chemical reactions and that such reactions aregoverned by genes. With George Beadle, he offered conclusive proof in 1941 that each biochemical reaction in the cell is controlled via a catalyzing enzyme by a specific gene. The "one gene-one enzyme" theory changed the face of biology and gave it a new chemical expression. For the first time, the nature of life seemed within the grasp of science's quantitative methods. Tatum, collaborating with Joshua Lederberg, demonstrated in 1947 that bacteria reproducesexually, thus introducing a new experimental organism into the study of molecular genetics. Spurred by Tatum's discoveries, other scientists worked to understand the precise chemical nature of the unit of heredity called the gene. This study culminated in 1953 with the description by James Watson and Francis Crick of the structure of DNA. Tatum's use of microorganisms and laboratory mutations for the study of biochemical genetics led directly to the biotechnology revolution of the 1980s. Tatum and Beadle shared the 1958 Nobel Prizein physiology or medicine with Joshua Lederberg for ushering in the new eraof modern biology.

Tatum was born on December 14, 1909, in Boulder, Colorado, to Arthur Lawrie Tatum and Mabel Webb Tatum. He was the first of three children; a younger brother and sister would follow. Both of Edward's parents excelled academically.His father held two degrees, an M.D. and a Ph.D. in pharmacology. Edward's mother was one of the first women to graduate from the University of Colorado.Presumably an interest in science and medicine ran in the Tatum family: Edward would become a research scientist, his brother a physician, and his sistera nurse. As a boy, Edward played the French horn and trumpet; his interest inmusic lasted his whole life. He also enjoyed swimming and ice-skating.

In 1925, when Tatum was fifteen years old, his father accepted a position asa pharmacology professor at the University of Wisconsin. Tatum studied at theUniversity of Chicago Experimental School and for two years at the University of Chicago before transferring and completing his undergraduate work at theUniversity of Wisconsin. He almost became a geologist before deciding in hissenior year to major in chemistry.

Tatum earned his A.B. degree in chemistry from the University of Wisconsin in1931. In 1932 he earned his master's degree in microbiology. Two years later, in 1934, he received a Ph.D. in biochemistry for a dissertation on the cellular biochemistry and nutritional needs of a bacterium. Understanding the biochemistry of microorganisms such as bacteria, yeast, and molds would persistat the heart of Tatum's career.

After receiving his doctorate, Tatum remained at the University of Wisconsinfor one year as a research assistant in biochemistry. He married the same year he completed his Ph.D. In Livingston, Wisconsin, Tatum wed June Alton, thedaughter of a lumber dealer, on July 28, 1934. They eventually had two daughters, Margaret Carol and Barbara Ann.

From 1936 to 1937, Tatum studied bacteriological chemistry at the Universityof Utrecht in the Netherlands while on a General Education Board fellowship for postgraduate study. In Utrecht he worked in the laboratory of F. Kogl, whohad identified the vitamin biotin. In Kogl's lab Tatum investigated the nutritional needs of bacteria and fungi. While Tatum was in Holland, he was contacted by geneticist George Beadle. Beadle, seven years older than Tatum, had done genetic studies with the fruit fly Drosophila melanogaster Drosophila melanogaster while in the laboratory of Thomas Hunt Morgan at the California Institute of Technology. Beadle, newly arrived at Stanford University,was now looking for a biochemist who could collaborate with him as he continued his work in genetics. He hoped to identify the enzymes responsible for theinherited eye pigments of Drosophila.

Upon his return to the United States in the fall of 1937, Tatum was appointeda research associate at Stanford University in the department of biologicalsciences. There he embarked on the Drosophila project with Beadle for four years. The two men successfully determined that kynurenine was the enzyme responsible for the fly's eye color and that it was controlled by one ofthe eye-pigment genes. This and other observations led them to postulate several theories about the relationship between genes and biochemical reactions.Yet they realized that Drosophila was not an ideal experimental organism on which to continue their work.

Tatum and Beadle began searching for a suitable organism. After some discussion and a review of the literature, they settled on a pink mold that commonlygrows on bread known as neurospora crassa. The advantages to workingwith neurospora were many: it reproduced very quickly, its nutritional needs and biochemical pathways were already well known, and it had the useful capability of being able to reproduce both sexually and asexually. Thislast characteristic made it possible to grow cultures that were genetically identical and also to grow cultures that were the result of a cross between two different parent strains. With neurospora, Tatum and Beadle were ready to demonstrate the effect of genes on cellular biochemistry.

The two scientists began their neurospora experiments in March 1941.At that time, scientists spoke of "genes" as the units of heredity without fully understanding what a gene might look like or how it might act. Althoughthey realized that genes were located on the chromosomes, they didn't know what the chemical nature of such a substance might be. An understanding of DNA(deoxyribonucleic acid, the molecule of heredity) was still twelve years in the future. Nevertheless, geneticists in the 1940s had accepted Gregor Mendel's work with inheritance patterns in pea plants. Mendel's theory, rediscovered by three independent investigators in 1900, states that an inherited characteristic is determined by the combination of two hereditary units (genes), one each contributed by the parental cells. A dominant gene is expressed even when it is carried by only one of a pair of chromosomes, while a recessive gene must be carried by both chromosomes to be expressed. With Drosophila, Tatum and Beadle had taken genetic mutants--flies that inherited a variantform of eye color--and tried to work out the biochemical steps that led to the abnormal eye color. Their goal was to identify the variant enzyme, presumably governed by a single gene, that controlled the variant eye color. This proved technically very difficult, and as luck would have it, another lab announced the discovery of kynurenine's role before theirs did. With the neurospora experiments, they set out to prove their one gene-one enzyme theory anotherway.

The two investigators began with biochemical processes they understood well:the nutritional needs of neurospora. By exposing cultures of neurospora to X rays, they would cause genetic damage to some bread mold genes. If their theory was right, and genes did indeed control biochemical reactions, the genetically damaged strains of mold would show changes in their ability to produce nutrients. If supplied with some basic salts and sugars, normal neurospora can make all the amino acids and vitamins it needs to live except for one (biotin).

This is exactly what happened. In the course of their research, the men created, with X-ray bombardment, a number of mutated strains that each lacked theability to produce a particular amino acid or vitamin. The first strain theyidentified, after 299 attempts to determine its mutation, lacked the abilityto make vitamin B6. By crossing this strain with a normal strain,the offspring inherited the defect as a recessive gene according to the inheritance patterns described by Mendel. This proved that the mutation was a genetic defect, capable of being passed to successive generations and causing thesame nutritional mutation in those offspring. The X-ray bombardment had altered the gene governing the enzyme needed to promote the production of vitaminB6.

This simple experiment heralded the dawn of a new age in biology, one in which molecular genetics would soon dominate. Nearly forty years later, on Tatum's death, Joshua Lederberg told the New York Times that this experiment "gave impetus and morale" to scientists who strived to understand how genes directed the processes of life. For the first time, biologists believed that it might be possible to understand and quantify the living cell's processes.

Tatum and Beadle were not the first, as it turned out, to postulate the one gene-one enzyme theory. By 1942 the work of English physician Archibald Garrod, long ignored, had been rediscovered. In his study of people suffering froma particular inherited enzyme deficiency, Garrod had noticed the disease seemed to be inherited as a Mendelian recessive. This suggested a link between one gene and one enzyme. Yet Tatum and Beadle were the first to offer extensiveexperimental evidence for the theory. Their use of laboratory methods, likeX rays, to create genetic mutations also introduced a powerful tool for future experiments in biochemical genetics.

During World War II, the methods Tatum and Beadle had developed in their workwith pink bread mold were used to produce large amounts of penicillin, another mold. Their basic research, unwittingly, thus had a very important practical effect as well. In 1944 Tatum served as a civilian staff member of the U.S. Office of Scientific Research and Development at Stanford. Industry, too, used the methods the men developed to measure vitamins and amino acids in foods and tissues.

In 1945, at the end of the war, Tatum accepted an appointment at Yale University as an associate professor of botany with the promise of establishing a program of biochemical microbiology within that department. Apparently the movewas due to Stanford's lack of encouragement of Tatum, who failed to fit intothe tidy category of biochemist or biologist or geneticist but instead mastered all three fields. In 1946 Tatum did indeed create a new program at Yale and became a professor of microbiology. In work begun at Stanford and continued at Yale, he demonstrated that the one gene-one enzyme theory applied to yeast and bacteria as well as molds.

In a second extremely fruitful collaboration, Tatum began working with JoshuaLederberg in March 1946. Lederberg, a Columbia University medical student fifteen years younger than Tatum, was at Yale during a break in the medical school curriculum. Tatum and Lederberg began studying the bacterium Escherichia coli . At that time, it was believed that E. coli reproducedasexually. The two scientists proved otherwise. When cultures of two different mutant bacteria were mixed, a third strain, one showing characteristics taken from each parent, resulted. This discovery of biparental inheritance in bacteria, which Tatum called genetic recombination, provided geneticists with anew experimental organism. Again, Tatum's methods had altered the practicesof experimental biology. Lederberg never returned to medical school, earninginstead a Ph.D. from Yale.

In 1948 Tatum returned to Stanford as professor of biology. A new administration at Stanford and its department of biology had invited him to return in aposition suited to his expertise and ability. While in this second residenceat Stanford, Tatum helped establish the department of biochemistry. In 1956 he became a professor of biochemistry and head of the department. Increasingly, Tatum's talents were devoted to promoting science at an administrative level. He was instrumental in relocating the Stanford Medical School from San Francisco to the university campus in Palo Alto. In that year Tatum also was divorced from his wife June. On December 16, 1956, he married Viola Kantor in New York City. Kantor was the daughter of a dentist in Brooklyn. Owing in partto these complications in his personal affairs, Tatum left the West Coast andtook a position at the Rockefeller Institute for Medical Research (now Rockefeller University) in January 1957. There he continued to work through institutional channels to support young scientists, and served on various nationalcommittees. Unlike some other administrators, he emphasized nurturing individual investigators rather than specific kinds of projects. His own research continued in efforts to understand the genetics of neurospora and the nucleic acid metabolism of mammalian cells in culture.

In 1958, together with Beadle and Lederberg, Tatum received the Nobel Prize in physiology or medicine. The Nobel Committee awarded the prize to the threeinvestigators for their work demonstrating that genes regulate the chemical processes of the cell. Tatum and Beadle shared one-half the prize and Lederberg received the other half for work done separately from Tatum. Lederberg later paid tribute to Tatum for his role in Lederberg's decision to study the effects of X-ray-induced mutation. In his Nobel lecture, Tatum predicted that "with real understanding of the roles of heredity and environment, together with the consequent improvement in man's physical capacities and greater freedomfrom physical disease, will come an improvement in his approach to, and understanding of, sociological and economic problems."

Tatum had a marked interest in social issues, including population control. In 1965 and 1966 Tatum organized other Nobel laureates in science to make public endorsements of family planning and birth control. These included statements to Pope Paul VI, whose encyclical against birth control for Catholics wasissued at this time.

Tatum's second wife, Viola, died on April 21, 1974. Tatum married Elsie Bergland later in 1974 and she survived his death the following year, on November5, 1975. Tatum died at his home on East Sixty-third Street in New York City after an extended illness. In a memoir written for the Annual Review of Genetics, Lederberg recalled that Tatum's last years were "marred by ill health, substantially self-inflicted by a notorious smoking habit." Lederbergnoted, too, that Tatum's "mental outlook" was scarred by the painful death ofhis second wife.

In addition to the Nobel Prize, Tatum received the Remsen Award of the American Chemical Society in 1953 for his work in biparental inheritance and sexualreproduction in bacteria. In 1952 he was elected to the National Academy ofSciences. He was a founding member of the Annual Review of Genetics and joined the editorial board of Science in 1957. Tatum's collected papers occupy twenty-five feet of space in the Rockefeller University Archivesand span the years from 1930 to 1975.

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