(b. Wahoo, Nebraska, 22 October 1903; d. Pomona, California, 9 June 1989)
classical genetics, molecular genetics, plant biology, academic administration.
Beadle’s principal scientific discovery, for which he received the 1958 Nobel Prize in Physiology or Medicine, was the demonstration in 1941 that the primary role of genes is to specify the production of proteins. That insight, which was initially termed one gene–one enzyme (and came to be expressed as one gene–one polypeptide) transformed genetics from its classical mode, the abstract analysis of the patterns and mechanisms of inheritance, into a molecular science concerned with how genes act to create traits. He went on to become an effective science administrator, a university president, and a key science adviser to the federal government.
Early Life. A prominent sign posted on the road leading to Wahoo, a small town in the southeastern part of Nebraska, proclaims the names of five famous native sons: Darryl Zanuck of movie-making fame; Sam Crawford, elected to the Baseball Hall of Fame; C. W. Anderson, painter and children’s book author and illustrator; Howard Hanson, composer and orchestra conductor; and George W. Beadle, Nobel Prize–winning geneticist. While their accomplishments could not have been more different, each in his own way reflected the history, culture, and values of Wahoo in the early twentieth century. Wahoo’s citizens, and especially Beadle’s father, adhered to notions of independence, individual initiative, and hard work.
Beets (a nickname Beadle acquired as a boy and was used by his friends and family throughout his life) was born on a forty-acre family farm on the outskirts of Wahoo. He was the family’s second son and was followed by a sister. The death of his mother in 1908 and his brother in 1913 and the inadequate attention of surrogates imposed substantial responsibilities on Beets for helping his father work the farm and raising his younger sister. Throughout high school it was his and his father’s expectation that he would take over the family farm. But it did not take long for a young high school science teacher, Bess McDonald, to recognize Beadle’s intelligence and promise and to encourage him, against the wishes of his father, to continue his education at the University of Nebraska in nearby Lincoln.
Education. The Nebraska College of Agriculture had an outstanding reputation in plant sciences and Beadle thrived there, garnering academic honors and bachelor’s (1926) and master’s (1927) degrees. More important for his future, however, one of his professors, Franklin D. Keim, engaged Beadle in research and then convinced him to do graduate work at the College of Agriculture at Cornell University. Becoming a scientist supplanted his early aim to return to the family farm. Nevertheless, he never abandoned a lifetime interest in agriculture and no matter how busy his life he almost always had a garden.
Arriving in Ithaca in the fall of 1926, Beets soon demonstrated the independence and self-confidence that characterized his entire scientific career. He was dissatisfied with the arrangement Keim had made for him to work with a professor who was an ecologist and switched to the Department of Plant Breeding and Professor Rollins A. Emerson, one of the nation’s leading maize geneticists. The individuals that composed Emerson’s research group included brilliant young scientists such as Marcus Rhoades, Charles Burnham, and Barbara McClintock, and they were contributing to the steady advance of genetics in innovative ways. Using both classical genetic and novel cytogenetic techniques he learned from McClintock, Beadle investigated several sterile mutants of maize and demonstrated that mutations can affect chromosome behavior at different points during meiosis, the process that yields the sex cells, egg, and pollen. That work, embodied in fourteen published papers, was an original contribution showing that chromosomes themselves are under genetic control and formed the basis for his PhD degree (1930). In 1928, Beadle met and married Californian Marion Hill, a Cornell master’s student in botany. Marion and George Beadle’s son David was born in December 1931.
The Young Scientist. Beadle’s achievements as a PhD student won him a coveted National Research Council Fellowship for postdoctoral work at the California Institute of Technology (1930). At Caltech, Beadle completed his studies of maize mutants and collaborated with his Cornell professors Emerson and Allan Cameron Fraser in a major compendium of maize chromosome maps. Most significantly, he came under the tutelage of Thomas Hunt Morgan’s “fly group,” which included Alfred Sturtevant, Calvin Bridges, Theodosius Dobzhansky, and Jack Schultz. Beadle mastered the essentials of Drosophila (fruit fly) genetics, in the course of which he made seminal observations on the mechanism of crossing-over in meiosis. The lessons Beadle learned from his mentors remained with him, becoming the foundation of his own approach to research and teaching and his relationships with his students, postdoctoral fellows, and colleagues.
While Beadle was still a research fellow at Caltech, his interests took off in a totally new direction: how genes determine the processes of embryonic development. To pursue that problem, he teamed up with Boris Ephrussi, a visiting French embryologist. Together they decided to examine the development of Drosophila, specifically its eye pigments. They set out to determine whether embryonic eye buds (called imaginal discs) taken from one larva could develop into eyes if they were transplanted into another larva. Working together in Paris, they produced adult flies with three eyes, two in the normal head position and one in the abdomen. Transplanting eye buds
from mutants with various unusual eye colors into the abdomens of both mutant and normal flies, Beadle and Ephrussi then observed whether the transplanted eyes were of the normal or of the mutant color. These observations led them to conclude that each different mutation blocked a different step in the formation of eye pigment. Their experiments laid the groundwork for the idea that genes control the sequential order of chemical reactions within the cell.
The Professor. Beadle pursued the Drosophila eye color work for several years, first as an assistant professor at Harvard (1936–1937) and then as a tenured professor at Stanford. His hope was that this would lead to an understanding of how genes control particular metabolic reactions in a cell. But finally he concluded that Drosophila was not the optimal system for identifying the mechanisms through which genes exert their effect on a cell’s chemical reactions. Another approach was needed.
In a flash of brilliant insight early in 1941, Beadle realized that instead of trying to identify the metabolic reactions affected by known mutations, he should better turn the problem around and seek the genes that affect already-known metabolic reactions. It was a bold idea but it needed testing. To pursue that goal he teamed up with Edward Tatum, an American biochemist who had joined
his research group shortly after Beadle arrived at Stanford in 1937.
They decided that Neurospora crassa, a fungus that often covers rotting vegetation, was an ideal organism for testing the strategy. Its genetic system was well characterized, and it needed only minimal nutritional supplements to grow. The plan was to induce mutations in Neurospora spores and to determine if the sprouting cells were still able to grow in a minimal culture medium. Those isolates that were unable to grow were presumed to be deficient in their ability to make a required metabolite. To determine what function was affected, many normal metabolites were added first in groups and then singly to the minimal culture medium to determine if they were able to restore cell growth. Within only a few months, Beadle and Tatum discovered and isolated many Neurospora strains bearing mutations affecting a single gene; each of the mutants required a single identified nutritional supplement for growth.
Over the ensuing years, Beadle and Tatum and a large cast of undergraduate and graduate students and postdoctoral fellows isolated many different single mutants, some requiring one or another amino acid, or a vitamin, or one of the constituents of nucleic acids. Based on these experimental findings, they surmised that each mutation affected the organism’s ability to make the required amino acid, or the vitamin, or the nucleic acid precursor. Well aware that enzymes, protein catalysts, are responsible for the synthesis of all of these essential metabolites, Beadle and Tatum made the intellectual leap that each mutation affects the ability of a single enzyme to function as a catalyst, in their case to catalyze the formation of the required metabolite. This supposition came to be known as the one gene–one enzyme hypothesis, a truly transforming event in the field of genetics.
Initially, however, there was both skepticism and some serious criticism among biologists about the one gene–one enzyme concept. It was difficult for classical geneticists to accept that a mutation in a single gene affected only a single function. It took almost a decade to respond with additional experiments and, with the help of related and consistent observations, to convince the skeptics.
In time, Beadle and Tatum’s one gene–one enzyme formulation evolved into one gene–one polypeptide, because many proteins consist of several polypeptides, each the product of a single gene. Lamentably, those scientists who daily depend on Beadle’s one gene–one polypeptide formulation rarely know his name. Subsequently it became clear that genes are made of DNA and not proteins, as Beadle tended to believe. Also, it has become clear that many genes encode RNA as well as proteins.
Return to Caltech. In 1946, Beadle accepted the challenge of chairing the biology division at Caltech and abruptly ceased active research. The division needed rebuilding and Beadle’s vision was to promote a blending of genetics and biochemistry, the natural extension of his own discovery. That implied a new discipline, chemical genetics or what came to be called molecular genetics. He put his own interests aside in the interests of science and Caltech. Linus Pauling, who chaired Caltech’s chemistry division, shared this vision and supported Beadle’s recruitment of scientists who would advance these ideas. Beadle’s recruits would eventually garner five Nobel Prizes, in addition to his own. Outstanding students and postdoctoral fellows were trained at Caltech in the fifteen years of Beadle’s leadership and took the excitement of molecular biology to many institutions throughout the United States.
The Beadles’ marriage had grown increasingly troubled after their return to Caltech, and they were divorced in the summer of 1953. Soon after, he married widow Muriel McClure Barnett, the well-known editor of the Women’s Section of the Los Angeles Times, and adopted Muriel’s son, Redmond Barnett.
National Leadership. The 1950s generated many public issues concerning science and scientists. Scientists were sought out for advice and leadership on national policies for science, radioactive fallout, health, and technology.
COURTESY OF THE ARCHIVES, CALIFORNIA INSTIUTE OF TECHNOLOGY.
Beadle, who had a reputation for being thoughtful, non-political, and wise, accepted a full load of these responsibilities. As an individual he also worked, in the early days of the Cold War, to counter the national paranoia concerning scientists who might sympathize with the U.S.S.R. Publicly and privately, he defended those he believed to be falsely accused of disloyalty to the nation, with special attention to close colleagues. When, in the face of such false accusations including a campaign by Senator Joseph McCarthy, the Caltech trustees called for Linus Pauling’s dismissal, Beadle spoke up for his colleague. When the U.S. Public Health Service began to rescind grants to suspected communists without a hearing or other elements of due process, he led, with the support of Caltech’s trustees, the faculty’s successful challenge to the Public Health Service.
In 1955, as president of the American Association for the Advancement of Science, he urged the scientific community, in a strong editorial in Science magazine, to protect the integrity of science against government interference and unscientific propaganda. Beadle did believe that the nation’s nuclear secrets required protection. However, he objected to government procedures for rooting out security risks and to restrictions on researchers doing unclassified work.
The academic pursuit of genetic research became of immediate public interest in the 1950s because of widespread concern regarding radioactive fallout from atmospheric testing of nuclear weapons. American geneticists were themselves worried when the official statements of the U.S. Atomic Energy Commission tried to calm public fear by claiming that the radiation from fallout was safe. The commission had disregarded or was ignorant of extensive work on the genetic effects of radiation.
Beadle joined a National Research Council study panel, funded by the Rockefeller Foundation, that was charged with explaining the genetic hazards. For five years, eventually as chairman, Beadle participated in this challenging task. The panel members, a who’s who of genetics, included Alfred Sturtevant, Sewell Wright, Milislav Demerec, and Herman J. Muller, who had won a Nobel Prize for the discovery of the mutagenic effects of ionizing radiation. The panel’s job was made more difficult by deep disagreements between Muller and Wright and by official secrecy concerning essential data.
Beadle’s pragmatic and judicious views helped the group reach consensus over its final reports. The committee concluded, “that from a genetic point of view there appears to be no threshold level of exposure below which genetic damage does not occur” (“Genetic Effects,” 1960). It recommended establishing a lifetime limit on the amount of radiation exposure to individuals, including medical x-rays, and proposed such a limit. It also described a research agenda that predicted the shape of biological research over the next decades.
With the Division of Biology now strong, Beadle was able to take a year’s sabbatical and accept appointment as the George Eastman Visiting Professor at Oxford during the 1958–1959 academic year. Muriel Beadle’s quaint and humorous account of that year’s stay in Oxford appears in her book These Ruins Are Inhabited. While in England, he learned that he and Ed Tatum would share, with Joshua Lederberg, the 1958 Nobel Prize in Physiology or Medicine.
Later Years. Upon returning to Caltech in late summer of 1959, Beadle was appointed dean of the faculty. He had always traveled a great deal and was now often invited to speak on matters of science policy. Improving the relations between science and society was a major theme in these presentations. In 1961, Beadle accepted the presidency of the University of Chicago. The university had experienced a tumultuous and disruptive period since the end of World War II, and the trustees hoped he would restore the institution’s former academic eminence as well as its finances. He succeeded on both scores and reestablished civility and confidence between the faculty and administration. During the disruptive period of the 1960s, he coped judiciously, firmly, and fairly with the student opposition to the way the university responded to local civil rights issues and the encroachment of the war in Vietnam and the draft on the students’ futures.
Beadle retired at the mandatory age of sixty-five and, after twenty years away from research, returned to experimental work. As a graduate student, he and Emerson had investigated the origin of maize, alone among common crop plants in having no obvious wild parent. As far as he was concerned, his last paper on the topic (in 1939) put the matter to rest: teosinte, a Mexican wild grass, was of the same species as maize and its immediate progenitor. In the intervening years, a competing concept was widely accepted. For more than a decade after his retirement, Beadle labored to prove his original conclusion. With the help of amateurs and professionals, he carried out classical genetic experiments on maize-teosinte hybrids, planting tens of thousand of plants in Mexico. These experiments confirmed that the two plants differed by no more than four to five genes. Finally, all the battling scientists had to agree that Beadle’s forty-year-old proposal was correct.
By the age of eighty, Beadle had been diagnosed as suffering from Alzheimer’s disease. The Beadles had moved to a retirement community in Pomona, California. As the disease took its toll, even the life-long pleasure he obtained from working in the garden was lost. Until his death, he was increasingly divorced from reality.
Beadle’s Legacy. Beadle was an early articulate spokesman for the integration of biochemistry and genetics. Although not a biochemist, he assailed the barriers between biochemists and geneticists. He was prophetic in believing that the biochemist could not understand what goes on chemically in the organism without considering genes any more than the geneticist could fully appreciate the gene without taking account of what it is and what it does. He coined and consistently used the term biochemical genetics, seemingly preferring it to molecular biology, although the latter won out in the end.
Equally significant, his work on Drosophila eye pigments and on Neurospora established an experimental paradigm for analysis of complex biological processes such as the cell cycle, embryonic development, and memory. In the first step of this approach, a large number of mutant organisms affecting various stages of a particular biological process are isolated. Then, from the phenotypes of the mutants, the order of the various steps in the process can be determined. In the early twenty-first century, the affected genes can be identified and isolated and the corresponding gene products and their functions identified.
Beadle and his generation also demonstrated to future scientific generations the relevance of genetics to societal issues and the importance of an active role for scientists in fostering sound national policy. Altogether, this Nebraska farm boy left a profound scientific legacy.
BIBLIOGRAPHY
WORKS BY BEADLE
With Boris Ephrussi. “Transplantation in Drosophila.” Proceedings of the National Academy of Sciences of the United States of America21 (1935): 642–646.
With Rollins A. Emerson and Allan Cameron Fraser. ASummary of Linkage Studies in Maize. Cornell University Agricultural Experiment Station Memoir 180. Ithaca, NY: Cornell University, 1935. This paper was referred to in Nature in volume 436 (25 August 2005): 1119–1126.
With Boris Ephrussi. “The Differentiation of Eye Pigments in Drosophila as Studied by Transplantation.” Genetics21 (1936): 225–247.
“Teosinte and the Origin of Maize.” Journal of Heredity30 (1939): 245–247.
With Edward L. Tatum. “Genetic Control of Biochemical Reactions in Neurospora.” Proceedings of the National Academy of Sciences of the United States of America 27 (1941): 499–505.
“Biochemical Genetics.” Chemical Reviews 37 (1945): 15–96.
“The Genetic Control of Biochemical Reactions.” HarveyLectures Series 40 (1945): 179–194.
“H. J. Muller and the Geneva Conference.” Science 122 (1955): 813.
“Genes and Chemical Reactions in Neurospora.” 1958 Nobel Prize Lecture. In Nobel Lectures, Physiology or Medicine 1942–1962. Amsterdam: Elsevier Publishing Company, 1964. Also available from http://nobelprize.org/nobel_prizes/medicine/laureates/1958/beadle-lecture.html
With others. “Genetic Effects.” In The Biological Effects ofRadiation, Summary Reports. Washington, DC: National Academy of Sciences–National Research Council, 1960. The report of the genetics panel regarding the effects of radiation fallout.
“Biochemical Genetics: Some Recollections.” In Phage and theOrigins of Molecular Biology, edited by John Cairns, Gunther S. Stent, and James D. Watson. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1966.
“Recollections.” Annual Review of Biochemistry 43 (1974): 1–13.
OTHER SOURCES
Beadle, Muriel. These Ruins Are Inhabited. New York: Doubleday, 1961. A memoir of the Beadles’ experiences at Oxford.
Berg, Paul, and Maxine Singer. George Beadle, An UncommonFarmer: The Emergence of Genetics in the 20th Century. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 2003. A full biography of Beadle.
Crow, James F. “Quarreling Geneticists and a Diplomat.” Genetics 140 (1995): 421–426. A description, by a participant, of the genetics panel investigating the genetic effects of radiation fallout.
Doebley, John. “George Beadle’s Other Hypothesis: One-Gene, One-Trait.” Genetics158 (2001): 487–493. The story of the determination of the relation between teosinte and maize
Horowitz, Norman. H. “George Wells Beadle.” In NationalAcademy of Sciences: Biographical Memoirs. Vol. 59. Washington, DC: National Academy Press, 1990, pp. 26–53.
———, Paul Berg, Maxine Singer, et al. “A Centennial: George W. Beadle, 1903–1989.” Genetics 166 (2004): 1–10.
Singer, Maxine, and Paul Berg. “George Beadle: From Genes to Proteins.” Nature Reviews Genetics5 (2004): 949–954. The present article is a modified version of this publication.
Maxine Singer
Paul Berg
