Tatum, Edward Lawrie (1909-1975)

Tatum, Edward Lawrie (1909-1975)

American biochemist

Edward Lawrie Tatum's experiments with simple organisms demonstrated that cell processes can be studied as chemical reactions and that such reactions are governed 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. Tatum, collaborating with Joshua Lederberg , demonstrated in 1947 that bacteria reproduce sexually, 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 Prize in physiology or medicine with Joshua Lederberg for ushering in the new era of modern biology.

Tatum was born in Boulder, Colorado, to Arthur Lawrie Tatum and Mabel Webb Tatum. He was the first of three children. Tatum's 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. As a boy, Edward played the French horn and trumpet; his interest in music lasted his whole life.

Tatum earned his A.B. degree in chemistry from the University of Wisconsin in 1931, where his father had moved the family in order to accept as position as professor in 1931. In 1932, Tatum 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 persist at the heart of Tatum's career.

In 1937, Tatum was appointed a research associate at Stanford University in the department of biological sciences. There he embarked on the Drosophila (fruit fly) project with geneticist George Beadle, successfully determining that kynurenine was the enzyme responsible for the fly's eye color, and that it was controlled by one of the eye-pigment genes. This and other observations led them to postulate several theories about the relationship between genes and biochemical reactions. Yet, the scientists 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 commonly grows on bread known as Neurospora crassa. The advantages of working with 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. This last 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. Although they 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 12 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 variant form 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 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 another way.

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 the ability to produce a particular amino acid or vitamin. The first strain they identified, after 299 attempts to determine its mutation, lacked the ability to 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 the same nutritional mutation in those offspring. The x-ray bombardment had altered the gene governing the enzyme needed to promote the production of vitamin B₆.

This simple experiment heralded the dawn of a new age in biology, one in which molecular genetics would soon dominate. Nearly 40 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 from a 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 extensive experimental evidence for the theory. Their use of laboratory methods, like x 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 work with pink bread mold were used to produce large amounts of penicillin , another mold. 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. 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 fruitful collaboration, Tatum began working with Joshua Lederberg in March 1946. Lederberg, a Columbia University medical student 15 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 reproduced asexually. 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 a new experimental organism. Again, Tatum's methods had altered the practices of experimental biology. Lederberg never returned to medical school, earning instead 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 a position suited to his expertise and ability. While in this second residence at 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, then remarried in New York City. Tatum left the West coast and took 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 national committees. 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 three investigators 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-rayinduced 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 freedom from physical disease, will come an improvement in his approach to, and understanding of, sociological and economic problems."

Tatum's second wife, Viola, died in 1974. Tatum married Elsie Bergland later in 1974 and she survived his death the following year, in 1975. Tatum died at his home on East Sixty-third Street in New York City after an extended illness, at age 65.

See also Fungal genetics; Microbial genetics; Molecular biology and molecular genetics; Molecular biology, central dogma of