Courtesy of the University of Chicago: Photograph by M. Weinstein.
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
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ANNUAL REVIEWS
Annu. Rev. Genet. 1990. 24;1-4 Copyright © 1990 by Annual Reviews
Inc. All
rights reserved
G. W. BEADLE
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
Adrian M. Srb Section of Genetics and Development, Cornell University, Ithaca, New York 14853
George Wells Beadle was born in 1903 and died in 1989. During his lifetime, the science of genetics changed dramatically. Beadle contributed definitively to that change. Perhaps more than that of any other investigator, his work prepared the way for the transition from neoclassical to molecular genetics. His contributions were recognized with a Nobel Prize and many other high honors. Beadle did his work with three among the relatively few organisms that offer well-developed facilities for genetic research, and learned these facilities in excellent environments for scientific accomplishment. His Ph.D. research was with maize. The studies were carried out under the direction of Professor R. A. Emerson, and in the company of some remarkable fellow students at Cornell, including Barbara McClintock, Marcus Rhoades, and Charles Burn ham. In postdoctoral work, Beadle turned to Drosophila-his major studies with that organism being carried out in collaboration with Boris Ephrussi. The evolution of Beadle's interests, which in part parallels the changing course of genetic science at that time, can be seen in the circumstance that Emerson was a magnificent formal geneticist, primarily interested in inheritance patterns, mapping and variations on the classical Mendelian ratios. Ephrussi, in con trast, while a highly competent geneticist, might better be described as a developmentalist who was adept at using genetic materials and techniques to address the problems that interested him. The third experimental organism with which Beadle worked, and the one with which he made his definitive contributions, was Neurospora. Indeed, largely due to Beadle and his coworkers, that organism has become one of the better established and most useful objects of genetic research. Until Beadle, Neurospora was relatively obscure in the scientific world. The mycologist B. O. Dodge had found Neurospora to have intriguing possibilities for fungal
0066-4197/90: 1215-0001$02.00
2
G. W. BEADLE
genetic studies but his vision of the possibilities was different than emerged in Beadle's work. When I first came to Stanford in 1941 to do graduate work with Beadle, who had come there from Harvard as a professor in 1937, the transition of his work with Drosophila to that with Neurospora was nearly complete. A refrigerator or two held bottles containing Drosophila pupae in storage, but in the laboratory Neurospora mutants were starting to emerge for study. In an informal seminar, or discussion with his students and coworkers, I re member Beadle saying, in words as nearly as I can recall, that he was "tired
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
of hearing other biologists say that geneticists only work with trivial attri butes of organisms, like kernel color in maize or eye color in Drosophila." Clearly Beadle felt challenged to do something about such a criticism, justified or not. Beadle had in mind to study genetic control of the steps in metabolic pathways. What was truly revolutionary in his plan was a practicable, although by modem standards not highly efficient, scheme for obtaining a large number of appropriate conditional mutants for study. The mutants that were sought, and in fact found, were nutritional mutants, each representing a genetically determined block at a particular step in a metabolic pathway. The standard, or Wild-type, Neurospora has simple nutritional requirements, little more than a few salts and sugar being needed. From this minimal m edium the organism makes all the biochemicals necessary for its existence-amino acids, nucleic acids, vitamins, complex structural components, and so on. By manipulating nutritional conditions, Beadle's scheme permitted detection, preservation, and study of mutant Neurosporas representing alteration of genes that control steps in essential biosyntheses. In essence, after treatment of experimental material with mutagens, appro priate mutants can be preserved on media supplemented with essential metabolites, and detected by transfer to the minimal medium for the un mutated organism. Systematic studies with particular nutritional substances, or the absence of them, refine the relationship of the mutant gene and its unmutated allele to particular biochemical reactions. One can view the Neurospora nutritional mutants as special instances of conditionallethals now so useful and widely employed in molecular genetics and other research on many organisms. Insight into Beadle's innovative research with Neurospora emerges from his immediately precedent work with Drosophila. Shortly after Beadle arrived at Stanford, E. L. Tatum, had come as a Research Associate to work on the biochemical genetics of eye pigmentation in Drosophila. The work was an extension of investigations carried out by Beadle and Ephrussi in Paris. Those studies had utilized different eye color mutants. Reciprocal trans plants of imaginal discs were made between larvae of different genotype. In
SRB
3
particular instances, the occurrence of wild-type eye pigmentation in a de rivative adult Drosophila revealed the presence of diffusible precursor sub stances that had.accumulated behind genetic blocks in the mutants. In spite of the elegance of these sophisticated complementation experiments, the ex perimental system had clear limitations. The chemistry of the substances involved was extremely difficult to resolve. More importantly, the system as such could not be adapted to a broad attack on problems of gene action. At this point the association with Tatum, the biochemist in the team, was particularly fortunate. A microbiologist as well as biochemist, Tatum was
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
well aware of a growing body of literature that showed a remarkable diversity of growth requirements among microorganisms, some them quite closely related. A number of findings showed that in nature many of these organisms satisfied their growth factor requirements by some form of symbiotic relation ship between strains or species. The similarity between such a situation and that shown in the transplant experiments is fairly obvious-at least it was so to Beadle and Tatum. And out of such a background, the Nobel prize-winning work with Neurospora was generated. The various details of the Neurospora studies, and their extensions, have been often and well reviewed, and have become part of standard text book fare. They need not be summarized here. What needs to be said is that the volume and excellence of the work are in part due to Beadle's ability to attract outstanding associates. In the group that assembled early on at Stanford were, for example, Norman Horowitz, David Bonner, Herschel Mitchell. and Mary Houlahan Mitchell. Outstanding post doctorals like Francis Ryan were also drawn to Stanford, as was a full complement of graduate students. Beadle was well aware that in the long run his work with Neurospora would benefit from information about the organism in addition to that derived from experiments on the biochemical mutants per se. At one point he enticed Barbara McClintock to come to Stanford to have a look at the chromosomes of Neurospora. He fostered some detailed studies of heterocaryosis. And he persuaded his graduate students to do at least minimal mapping of the mutants with which they worked. Indeed, the fact that Neurospora became a major experimental object in the broad sense of the words is largely due to him and his generosity with strains of Neurospora that he had developed. The year 1946 was the beginning of the end of Beadle's experimental career. At that time he moved to Cal Tech as successor to T. H. Morgan as head of the Department of Biology. Highly successful in that position, he accepted the presidency of the University of Chicago in 1961, where he served with distinction until retirement in 1968. When Beadle retired from the presidency of the University of Chicago, he came full circle and began again to do experiments with maize. These had to do with the origin of com, a problem that had interested his first scientific
4
G. W. BEADLE
mentor, R. A. Emerson. Energetic and incisive as ever, Beadle attacked this problem. He became an enthusiastic proponent of the theory that the impor tant crop plant maize (com) derives from teosinte. At the last seminar he ever gave at Cornell, on a visit made after his retirement, he described how he had disposed of arguments that teosinte was too useless a food source to tempt primitive native peoples to take it through its first stages as a crop plant. Beadle told how he had shown that the very tough kernels of teosinte could be popped like popcorn, thus making them edible, and had shown in addition the possibility of gathering enough of the kernels to make them a feasible source
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
of food. Being Beadle, of course he had done genetic and cytogenetic studies, some in his graduate student days, some after retirement, that bore on the problem. He inevitably knew all the relevant studies by others, as reported in the literature, even to archaeological and cultural anthropological informa tion. Beadle was not only a great scientist and highly successful academic administrator. He was also an attractive and interesting human being. Born and raised on a farm near Wahoo. Nebraska, he was the kind of person whose fancy was tickled by his derivation from a community with an amusing name. He was also pleased to have come from a small place that in addition had nurtured such notables as Wahoo Sam Crawford, a famous old-time pro fessional baseball hero; Howard Hanson, American composer and Director of the Eastman School of Music; and Darryl Zanuck, a historic director of films. He often expressed gratitude to the local schoolteacher who had inspired and encouraged him to go to college at the University of Nebraska. He was similarly grateful to F. D. Keirn, a professor of agronomy at the university. Keirn, an unusually perceptive talent scout for young men of scientific promise, persuaded Beadle to go to Cornell for graduate study. Beadle's tastes were rather simple. He once told me that for pleasure reading his favorite author was H. H. Munro. Beadle liked activities that involved physical exertion. In all these activities he showed his basic com petiveness. He was a ferocious if not highly skilled tennis player. He invited his graduate students to compete with him in a now, and even then, outmoded athletic event called the standing broad jump. An enthusiastic gardener, he frequently wanted to place a small bet as to whether some other gardening friend could produce a larger pumpkin or grow earlier edible sweet com. The very few bets he lost were cheerfully paid.
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
Further
Quick links to online content
ANNUAL REVIEWS
Annu. Rev. Genet. 1990. 24;1-4 Copyright © 1990 by Annual Reviews
Inc. All
rights reserved
G. W. BEADLE
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
Adrian M. Srb Section of Genetics and Development, Cornell University, Ithaca, New York 14853
George Wells Beadle was born in 1903 and died in 1989. During his lifetime, the science of genetics changed dramatically. Beadle contributed definitively to that change. Perhaps more than that of any other investigator, his work prepared the way for the transition from neoclassical to molecular genetics. His contributions were recognized with a Nobel Prize and many other high honors. Beadle did his work with three among the relatively few organisms that offer well-developed facilities for genetic research, and learned these facilities in excellent environments for scientific accomplishment. His Ph.D. research was with maize. The studies were carried out under the direction of Professor R. A. Emerson, and in the company of some remarkable fellow students at Cornell, including Barbara McClintock, Marcus Rhoades, and Charles Burn ham. In postdoctoral work, Beadle turned to Drosophila-his major studies with that organism being carried out in collaboration with Boris Ephrussi. The evolution of Beadle's interests, which in part parallels the changing course of genetic science at that time, can be seen in the circumstance that Emerson was a magnificent formal geneticist, primarily interested in inheritance patterns, mapping and variations on the classical Mendelian ratios. Ephrussi, in con trast, while a highly competent geneticist, might better be described as a developmentalist who was adept at using genetic materials and techniques to address the problems that interested him. The third experimental organism with which Beadle worked, and the one with which he made his definitive contributions, was Neurospora. Indeed, largely due to Beadle and his coworkers, that organism has become one of the better established and most useful objects of genetic research. Until Beadle, Neurospora was relatively obscure in the scientific world. The mycologist B. O. Dodge had found Neurospora to have intriguing possibilities for fungal
0066-4197/90: 1215-0001$02.00
2
G. W. BEADLE
genetic studies but his vision of the possibilities was different than emerged in Beadle's work. When I first came to Stanford in 1941 to do graduate work with Beadle, who had come there from Harvard as a professor in 1937, the transition of his work with Drosophila to that with Neurospora was nearly complete. A refrigerator or two held bottles containing Drosophila pupae in storage, but in the laboratory Neurospora mutants were starting to emerge for study. In an informal seminar, or discussion with his students and coworkers, I re member Beadle saying, in words as nearly as I can recall, that he was "tired
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
of hearing other biologists say that geneticists only work with trivial attri butes of organisms, like kernel color in maize or eye color in Drosophila." Clearly Beadle felt challenged to do something about such a criticism, justified or not. Beadle had in mind to study genetic control of the steps in metabolic pathways. What was truly revolutionary in his plan was a practicable, although by modem standards not highly efficient, scheme for obtaining a large number of appropriate conditional mutants for study. The mutants that were sought, and in fact found, were nutritional mutants, each representing a genetically determined block at a particular step in a metabolic pathway. The standard, or Wild-type, Neurospora has simple nutritional requirements, little more than a few salts and sugar being needed. From this minimal m edium the organism makes all the biochemicals necessary for its existence-amino acids, nucleic acids, vitamins, complex structural components, and so on. By manipulating nutritional conditions, Beadle's scheme permitted detection, preservation, and study of mutant Neurosporas representing alteration of genes that control steps in essential biosyntheses. In essence, after treatment of experimental material with mutagens, appro priate mutants can be preserved on media supplemented with essential metabolites, and detected by transfer to the minimal medium for the un mutated organism. Systematic studies with particular nutritional substances, or the absence of them, refine the relationship of the mutant gene and its unmutated allele to particular biochemical reactions. One can view the Neurospora nutritional mutants as special instances of conditionallethals now so useful and widely employed in molecular genetics and other research on many organisms. Insight into Beadle's innovative research with Neurospora emerges from his immediately precedent work with Drosophila. Shortly after Beadle arrived at Stanford, E. L. Tatum, had come as a Research Associate to work on the biochemical genetics of eye pigmentation in Drosophila. The work was an extension of investigations carried out by Beadle and Ephrussi in Paris. Those studies had utilized different eye color mutants. Reciprocal trans plants of imaginal discs were made between larvae of different genotype. In
SRB
3
particular instances, the occurrence of wild-type eye pigmentation in a de rivative adult Drosophila revealed the presence of diffusible precursor sub stances that had.accumulated behind genetic blocks in the mutants. In spite of the elegance of these sophisticated complementation experiments, the ex perimental system had clear limitations. The chemistry of the substances involved was extremely difficult to resolve. More importantly, the system as such could not be adapted to a broad attack on problems of gene action. At this point the association with Tatum, the biochemist in the team, was particularly fortunate. A microbiologist as well as biochemist, Tatum was
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
well aware of a growing body of literature that showed a remarkable diversity of growth requirements among microorganisms, some them quite closely related. A number of findings showed that in nature many of these organisms satisfied their growth factor requirements by some form of symbiotic relation ship between strains or species. The similarity between such a situation and that shown in the transplant experiments is fairly obvious-at least it was so to Beadle and Tatum. And out of such a background, the Nobel prize-winning work with Neurospora was generated. The various details of the Neurospora studies, and their extensions, have been often and well reviewed, and have become part of standard text book fare. They need not be summarized here. What needs to be said is that the volume and excellence of the work are in part due to Beadle's ability to attract outstanding associates. In the group that assembled early on at Stanford were, for example, Norman Horowitz, David Bonner, Herschel Mitchell. and Mary Houlahan Mitchell. Outstanding post doctorals like Francis Ryan were also drawn to Stanford, as was a full complement of graduate students. Beadle was well aware that in the long run his work with Neurospora would benefit from information about the organism in addition to that derived from experiments on the biochemical mutants per se. At one point he enticed Barbara McClintock to come to Stanford to have a look at the chromosomes of Neurospora. He fostered some detailed studies of heterocaryosis. And he persuaded his graduate students to do at least minimal mapping of the mutants with which they worked. Indeed, the fact that Neurospora became a major experimental object in the broad sense of the words is largely due to him and his generosity with strains of Neurospora that he had developed. The year 1946 was the beginning of the end of Beadle's experimental career. At that time he moved to Cal Tech as successor to T. H. Morgan as head of the Department of Biology. Highly successful in that position, he accepted the presidency of the University of Chicago in 1961, where he served with distinction until retirement in 1968. When Beadle retired from the presidency of the University of Chicago, he came full circle and began again to do experiments with maize. These had to do with the origin of com, a problem that had interested his first scientific
4
G. W. BEADLE
mentor, R. A. Emerson. Energetic and incisive as ever, Beadle attacked this problem. He became an enthusiastic proponent of the theory that the impor tant crop plant maize (com) derives from teosinte. At the last seminar he ever gave at Cornell, on a visit made after his retirement, he described how he had disposed of arguments that teosinte was too useless a food source to tempt primitive native peoples to take it through its first stages as a crop plant. Beadle told how he had shown that the very tough kernels of teosinte could be popped like popcorn, thus making them edible, and had shown in addition the possibility of gathering enough of the kernels to make them a feasible source
Annu. Rev. Genet. 1990.24:1-6. Downloaded from www.annualreviews.org Access provided by 175.145.21.133 on 01/24/15. For personal use only.
of food. Being Beadle, of course he had done genetic and cytogenetic studies, some in his graduate student days, some after retirement, that bore on the problem. He inevitably knew all the relevant studies by others, as reported in the literature, even to archaeological and cultural anthropological informa tion. Beadle was not only a great scientist and highly successful academic administrator. He was also an attractive and interesting human being. Born and raised on a farm near Wahoo. Nebraska, he was the kind of person whose fancy was tickled by his derivation from a community with an amusing name. He was also pleased to have come from a small place that in addition had nurtured such notables as Wahoo Sam Crawford, a famous old-time pro fessional baseball hero; Howard Hanson, American composer and Director of the Eastman School of Music; and Darryl Zanuck, a historic director of films. He often expressed gratitude to the local schoolteacher who had inspired and encouraged him to go to college at the University of Nebraska. He was similarly grateful to F. D. Keirn, a professor of agronomy at the university. Keirn, an unusually perceptive talent scout for young men of scientific promise, persuaded Beadle to go to Cornell for graduate study. Beadle's tastes were rather simple. He once told me that for pleasure reading his favorite author was H. H. Munro. Beadle liked activities that involved physical exertion. In all these activities he showed his basic com petiveness. He was a ferocious if not highly skilled tennis player. He invited his graduate students to compete with him in a now, and even then, outmoded athletic event called the standing broad jump. An enthusiastic gardener, he frequently wanted to place a small bet as to whether some other gardening friend could produce a larger pumpkin or grow earlier edible sweet com. The very few bets he lost were cheerfully paid.
