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Biographical Memoirs: V.59 (1990)

Chapter: Edward Lawrie Tatum

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Suggested Citation:"Edward Lawrie Tatum." National Academy of Sciences. 1990. Biographical Memoirs: V.59. Washington, DC: The National Academies Press. doi: 10.17226/1652.
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EDWARD LAWRIE TATUM December 14, 1909-November 7, 1975 BY JOSHUA LEDERB ERG IN THE HISTORY OF BIOLOGY Edward Lawrie Tatum s name is linked with that of George Wells Beadle for their pioneering studies of biochemical mutations in Neurospora.~ First published in 1941, these studies have endures! as the prototype of the investigation of gene action to the present clay. A still more enduring legacy is their development of experimental techniques for the mutation analysis of bio- chemical pathways used claily by modern biologists. Though this sketch is written as a biography of Edward Tatum, these singular scientific accomplishments were in practice and attribution- intimately shared with BeacIle. Ta- tum brought to the work a background in microbiology and a passion for the concept of comparative biochemistry; Beadle, great sophistication in "classical genetics" and the leadership ant! drive to replace the underbrush of vitalistic thinking with a clear-cut, mechanistic view of the gene and the processes of life. Little more than the bare outlines of Edwarct Tatum's per- sonal history can be clocumentecl, because of his own aversion to accumulating paper and the fact that most of his corre- ~ George W. Beadle died on tune 9, 1989, when this essay was in press. His mem- oir, by Norman H. Horowitz, is also included in this volume. 357

358 BIOGRAPHICAL MEMOIRS sponclence was discarded cluring his various moves. His scientific achievements, however, were largely ant! appro- priately recognized. In 1952 he was elected to the National Academy of Sciences and in 1958, with George Beadle and Joshua Leclerberg, won the Nobel Prize in Physiology or Medicine. Tatum was also known for his commitment to nur- turing younger scientists, with whom he zestfully enjoyed every aspect of laboratory work. A still more enduring legacy of their work has been the everyday use of experimental mu- tation analysis of biochemical pathways in modern biology since then. EDUCATION AND EARLY LIFE Edwarc! Lawrie Tatum was born in BouIcler, Colorado, on December 14, 1909, the first surviving son of Arthur L. (~84-1955) and Mabel Webb Tatum. A twin, Elwood, died shortly after birth. At the time of Ec~ward's birth his father was an instructor in chemistry at the University of Coloraclo at Boulder, where Mabel Webb's father had been Superinten- dent of Schools. Arthur's own father, Lawrie Tatum, a Quaker who hac! settled in the Iowa Territory, hac! been an Indian agent after the Civil War and written a book, Our Red Brothers. In rapic} succession the Tatum family mover! to Madison, Wisconsin; Chicago, Illinois; Philadelphia, Pennsylvania; Vermillion, South Dakota; and, back in 1918 to Chicago. During this period the elcler Tatum helc! a succession of teaching positions while earning a Ph.D. in physiology and pharmacology from The University of Chicago and an M.D. from Rush Meclical College. By 1925 he was settled at the University of Wisconsin at Madison as professor of pharma- cology in a department that was a major center for the train- ing of professors of pharmacology. Among his research ac- complishments were the introduction of picrotoxin as an

EDWARD LAWRIE TATUM 359 antidote for barbiturate poisoning and the validation of ar- senoxide (mapharsen) for the chemotherapy of syphilis,2 the most effective drug for this purpose until the introduction of penicillin. Edward, having the double advantage of this remarkable family background and the Laboratory School at The Uni- versity of Chicago, continued his education at Wisconsin, earning a bachelor's degree in 1931. At Wisconsin he came upon the tradition of research in agricultural microbiology and chemistry that was then flourishing under the leadership of E. B. Fret! (later president of the University) and W. H. Peterson.3 Tatum's first research was a bachelor's thesis (published 1932) on the effect of associated growth of bacterial species Lactobacillus and Clostrt~ium septicum giving rise to racemic lactic acid. (In 1936 he clemonstratec! that the C. septicum racemized the d-lactic acid! produced by the lactic acid bac- teria.) He continuer! his graduate work at Wisconsin with fi- nancial support from the Wisconsin Alumni Research Foun- dation the beneficiary of royalties from Steenbock's patents on vitamin D milk. His Ph.D. dissertation (1935) concerned the stimulation of C. septicum by a factor isolated from potato, identified as a derivative of aspartic acid and later shown to be asparagine. This was follower! by collaborations with H. G. Wood and Esmond E. Snell in a series of pioneering studies 2.}ohn Patrick Swann, "Arthur Tatum, Parke-Davis, and the Discovery of Ma- pharsen as an Antisyphilitic Agent," Journal of the History of Medicine and Allied Sci- ences, 40(1985):167-87. F. E. Shideman, "A. L. Tatum, Practical Pharmacologist," Science, 123(1956) :449. Anonymous, "Profile of a Research Scientist," Bulletin of Med- ical Research, National Society for Medical Research, 8(1954):7-8. 3 The roots of their work can be traced to Koch, Tollens, and Kossel in Germany. See I. L. Baldwin, "Edwin Broun Fred, March 22, 1887-}anuary 16,1981," Biograph- ical Memoirs of the National Academy of Sciences, Vol. 55, pp. 247-290; and Conrad A. Elvehjem, "Edwin Bret Hart, 1874-1953," Biographical Memoirs, Vol. 28, pp. 117- 161. See also E. H. Beardsley, Harry L. Russell and Agricultural Science in Wisconsin (Madison, Wisconsin: University of Wisconsin Press, 1969).

360 BIOGRAPHICAL MEMOIRS on the role of vitamins in bacterial nutrition. In 1936 they studier! the growth factor requirements of propionic acic! bacteria, fractionating one factor from an acetone extract of milk powder. Its ohvsical oronerties suggested that the factor might he thiamine, and indeed crystalline thiamine was fully 1 J 1 1- - __,=_. active as an essential growth factor. Vitamins hac! long been recognized to share a role in the nutrition of animals, man, and yeast. Tatum's work with Snell, Peterson, ant! Wood initiates! a genre of studies showing that many bacterial species tract diverse requirements for these identical substances. This was outstanding confirmation of the basic tenet of comparative biochemistry- the evolution- ary conservation of biochemical processes that produced common processes in morphologically diversified species. Tatum's education ant! ctoctoral research coincided with the culmination of understanding that all of the basic building blocks of life—amino acids, sugars, lipids, growth factors (anc! later nucleic acids) existed in fundamentally similar chemical structures among all forms of life. Hence the most fruitful way to stucly a problem in animal metabolism might be to begin with a microbe, which might well prove more convenient for experimental manipulation and bioassay and as the future would show genetic analysis anc! alter- ation. Tatum then won a General Education Boarcl postdoctoral fellowship that took him, his wife (the former June Alton, a fellow student at Wisconsin), and their infant daughter, Margaret, to Fritz Kog1's laboratory at Utrecht, The Nether- lancis, for a year. Kog] hadjust purified and crystallized biotin as a growth factor for yeast, and this enabled and inspirer! further studies on its nutritional role for other microorga- nisms. (Not until 1940 was the nutritional significance of bio- tin for animals recognizecl.) By Tatum's own account, his brief time at Utrecht, spent in efforts to isolate further growth factors for staphylococci,

EDWARD LAWRIE TATUM 361 never achieved a sharp research focus. More importantly, he befriended Nils Fries, another research fellow from Uppsala, Sweden, who was using the newly available biotin to define the specific nutritional requirements of an ever wicler range of fungi. Fries anc! Kog! were able to demonstrate striking examples of nutritional symbiosis—the compensation for complementary deficits in mixer! cultures of various fungi. Tatum's report to the General Education Board records his gratification at having been able to meet, as well, A. I. Kluyver at Delft, ant! B. C. I. G. Knight and P. Fildes in En- gland then aIreacly well known as leading investigators of bacterial chemistry and nutrition from a comparative per- spective. ~ I. H. Mueller at Harvarc! anc! A. Ewoff in Paris hac! also stresses} how microbial nutrition reflectec! evolutionary losses of biochemical synthetic competence—a concept that can be tracer! to Twort and Ingram in 94—though they hac} not as yet acloptec! the language or conceptual frame- work of genetics that would eventually describe such varia- tions as gene mutations affecting biosynthetic enzymes.) THE STANFORD YEARS ~ ~ 937—~ 945) That same year, 1937, Beadle was on the point of moving from Harvard to Stanford. His research program In pnys~- ological genetics was to continue the work on the genetics of Drosophila eye pigments that he tract initiated in colIabora- tion with Boris Ephrussi, first at Caltech, then in Paris. The Rockefeller Foundation's support of this enterprise was one of Warren Weaver's most foresighted initiatives in the gesta- tion of molecular biology.5 I.ooking out for a possible position for Tatum, his profes- 4 F. W. Twort and G. L. Y. Ingram, "A Method for Isolating and Cultivating the Mycobacterium enteritidis chronicae pseudotuberculosae fohne," and "Some Experiments on the Preparation of a Diagnostic Vaccine for Pseudo-tuberculous Enteritis of Bo- vines," Proceedings, Royal Society, London, Series B. 84(191 1-12):517-42. 5 See also Mina Rees, "Warren Weaver, July 17, 1894-November 24, 1978," Bio- graphical Memoirs, Vol. 57, pp. 493-530.

362 BIOGRAPHICAL MEMOIRS sors at Wisconsin forwarcled BeadIe's solicitation for a re- search associate "biochemist to work on hormone-like sub- stances that are concerned with eye pigments in Drosophila." But, practical-minclect, they recommencled that the young man undertake research on the chemical microbiology of butter, writing him that "this field is certainly getting hot." With jobs scarce, economic realities weighed as heavily as intellectual appeal in the choice between insect eyes and dairy microbiology. Arthur Tatum, Edward's father, was much con- cerned that, if his son undertook a hybrid role, he wouIc! Tic! himself an academic orphan, clisowned by each of the disci- plines of biochemistry, microbiology, and genetics. In the event, however, Tatum accepted] BeacIle's offered position, and the multiple challenges of comparative biochemistry that went with it. Though the economic importance of butter re- search was far more obvious at the time, it is certain that Edward! Tatum conic! not have chosen better than Drosophila as a means for contributing to the field of biotechnology. Joining Beadle at Stanford, Tatum was engaged between 1937 and 1941 with the arduous task of extracting pigment- precursors from Drosophila larvae. Ephrussi and BeadIe's earlier transplantation experiments had clemonstratec! that a diffusible substance or hormone produced by witcI-type flies was critically lacking in the mutant strain. Yet Tatum and BeacIle's own experience differed! significantly from the re- port published by Ephrussi and Chevais. According to this report, normal eye color could be restored in cultures sup- plementec! with tryptophane. Tatum, however, could confirm this only with cultures carrying a bacterial contaminant. Far from discarcling such a contaminant as an interfering vari- able, Tatum cultured the organism (a Bacillus species) to prove that it was a source of the elusive hormone. The inter- changeability of growth factors for bacteria and animals and the knowledge that many microbes synthesized vitamins re- quirecl by other species undoubtedly bolstered this theory.

EDWARD LAWRIE TATUM 363 A. I. Haagen-Smit, whom Beadle hack known at Harvard, was now at the California Institute of Technology, and Tatum visited him to learn microchemical techniques, then set out to isolate the "V + hormone" from the bacterial culture. He succeeded in doing this in 1941, only to be anticipated by Butenancit et at. in the identification of V+ as kynurenine. (Butenanclt, astutely noting from a Japanese publication— that kynurenine was a metabolite of tryptophane in clog urine, hac! tested the substance for eye color hormone activ- ity.) The jarring experience of having their painstaking work overtaken in so facile a way impellecl Beadle and Tatum to seek another organism more tractable than Drosophila for biochemical studies of gene action. Neurospora and the One Gene~ne Enzyme Theory In winter quarter 1941, Tatum (although a research associate without teaching responsibilities) volunteered to de- velop and teach a then unprecedented comparative biochem- istry course for both biology and chemistry graduate stu- clents. In the course of his lectures he described the nutrition of yeasts and fungi, some of which exhibited well-defined blocks in vitamin biosynthesis. Attending these lectures, BeacIle recalled B. O. Dodge's elegant work on the segrega- tion of morphological mutant factors in Neurospora that he hac! heart! in a seminar at Cornell in 1932,6 work that was followed up by C. C. Lindegren at Caltech. Neurospora, with its immediate manifestation of segre- gating genes in the string of ascospores, has an ideal life-cycle for genetic analysis. Fries's work suggested that Neurospora might also be cultured reaclily on a well definer! medium. It was soon established that Neurospora required only biotin as 6 See also W. J. Robbins, "Bernard Ogilvie Dodge, April 18, 1872-August 9, 1960," Biographical Memoirs, Vol. 36, pp. 85-124.

364 BIOGRAPHICAL MEMOIRS a supplement to an inorganic salt-sucrose medium and did indeed prove an ideal organism in which to seek mutations with biochemical effects demonstrated by nutritional require- ments. By February 1941,7 the team was X-raying Neuro- spora and seeking these mutants. ~ · . . · . . . ~ .arvestlng nutrltlona mutants in microorganisms in those days was painstaking hand labor; it meant examining single-spore cultures isolated from irradiated parents for their nutritional properties—one by one. No one could have predicted how many thousands of cultures would have to be tested to discover one that would have a biochemical defect marked by a nutritional deficiency. Isolate #299 proved to be the first recognizable mutant, requiring as it did pyridoxine. The trait, furthermore, seg- regated in crosses according to simple Mendelian principles, which foretold that it could in due course be mapped onto a specific chromosome of the fungus. Therewith, Neurospora moved to center stage as an object of genetic experimenta- tion. By May of the same year, Beadle and Tatum were ready to submit their first report of their revolutionary methods to the Proceedings of the National Academy of Sciences. In that report they noted "there must exist orders of di- rectness of gene control ranging from one-to-one relations to relations of great complexity." The characteristics of mu- tations affecting metabolic steps suggested a direct and simple role for genes in the control of enzymes. The authors 7 G. W. Beadle, "Recollections," Annual Revue of Biochemistry, 43 (1974):1-13. In his chapter, "Biochemical Genetics, Some Recollections," in Phage and the Origins of Molecular Biology, eds. J. Cairns, G. S. Stent, and J. D. Watson (Cold Spring Harbor, New York: C. S. H. Biol. Labs, 1966), Beadle confused the 1940-41 meeting of the Society of American Naturalists in Philadelphia, which made no reference to Neu- rospora, with that of the Genetics Society in Dallas in December 1941. The net effect is to date the Neurospora experiments to 1940 rather than to 1941. H. F. Hudson repeated the error in The Eighth Day of Creation (New York: Simon & Schuster, 1979), and it is bound to plague future historians.

EDWARD LAWRIE TATUM 365 hypothesized, therefore, that enzymes were primary prod- ucts of genes. Indeed, in some cases, genes themselves might be enzymes. This was what came to be labelled the one gene- one enzyme theory, the precursor of today's genetic dogma. We shall return to it later. In that same year Tatum was recruited as an assistant pro- fessor to the regular faculty of Stanford's Biology Depart- ment, where he developed an increasingly independent re- search program exploiting the use of Neurospora mutants for the exploration of biochemical pathways. Despite the ex- igencies of the war effort, an increasing number of talented graduate students and postdoctoral fellows flocked to Stan- ford to learn the new discipline. Their participation rapidly engendered a library of mutants blocked in almost any ana- bolite that could be replaced in the external nutrients. Today, that catalog embraces over 500 distinct genetic loci and well over a thousand publications from laboratories the world over.8 Anticipating the One Gene-One Enzyme Theory Would that contemporaries could anticipate what future historians will ask or what errors they will promulgate! How many simple questions we neglect to ask, or fad! to record the answers, that might have settled continuing controversies. Among these is the place of Archibald E. Garrod's work and thought in anticipation of the one gene-one enzyme hypoth- esis. The following discussion is offered in some detail in order to correct some prevalent misconstructions of that his- tory. In 190S, Garrod published his study of what was then called "inborn errors of metabolism," including alcaptonuria ~ D. D. Perkins, A. Radford, D. Newmeyer, and M. Bjorkman, "Chromosomal loci of Neurospora crassa," Microbiological Reviews, 46 (1982):426-570.

366 BIOGRAPHICAL MEMOIRS in many This work is sometimes portrayer! as a forgotten precursor of Beadle and Tatum's investigation of gene action. Indeed, many geneticists who specialized in maize or Dro- sophila, including Beadle himself, lamented not knowing of this pioneering work earlier—it having received remarkably little comment from geneticists until after Neurospora was launched in ~ 94 ~ . ~° Yet Garrocl's basic findings on alcaptonuria, which parallel the metabolic blocks in Neurospora mutants, were widely quoted in medical texts. I. B. S. Haldane cited them in a well- reac! essay in 1937. Tatum likewise referred to them in his course in comparative biochemistry before beginning his own experiments on Neurospora. BeacIle, in his Nobel Prize lec- ture in INS, was careful to acknowledge these antececlents, though widely quotes! reminiscences have blurred the cletaits of just when Beadle and Tatum became aware of Garrocl's work. Halclane, in his 1937 article, cited the (1ifficulty of exper- imentation on rare human anomalies as an important reason to seek other research paradigms- which Neurospora wouIc! eventually provide. But Garrod himself never quite made 9 "The Croonian Lectures of the Royal College of Physicians," Lancet 2(1908): 1- 7, 73-79, 142-148, 214-220. A H. Harris, ea., Garrod's Inborn Errors of Metabolism (Oxford: Oxford University Press, 1963); and B. Childs and C. R. Scriver, eds., Inborn Factors in Disease by A. E. Garrod (Oxford: Oxford University Press, 1989), include extensive discussion and bibliography on the history of his ideas. On the neglect of Garrod's work, see also R. Olby, The Path to the Double Helix (London, Macmillan Press, 1974). ~ ~ Though G. W. Beadle implies in PATOOMB (Phage and the Origins of Molecular Biology, see footnote 7 above), that he and Tatum were unaware of Garrod until perhaps 1945, they referred to Garrod in a paper on their Drosophila-pigment work delivered January 1, 1941 (see American Naturalist, 75[1941]: 107-16). Garrod's find- ings were also prominent in Tatum's winter 1941 course on comparative biochem- istry at Stanford. I first read about Garrod in Meyer Bodansky's Introduction to Phys- iological Chemistry (New York: Wiley & Sons, 1934), and the late Sewall Wright advised me that he had taught that material in Chicago since 1925. ]2~. B. S. Haldane, "The Biochemistry of the Individual," in Perspectives in Bio- chemistry, J. Needham and D. E. Green, eds. (Cambridge: Cambridge University

EDWARD LAWRIE TATUM 367 the leap from the anomaly provoked by the mutant gene to the positive functioning of its normal allele. Nor clid he rec- ognize enzymes as the direct products of genes in their nor- mal function, but rather referred to mutational anomalies as freaks or aberrations to be compared with the effects of in- section or Intoxication. Theoretical biology in Garrod's time believer! in "proto- plasm" as an almost mystical, living colloid. When altered, genes might influence the workings of that protoplasm but were not yet thought to be the exclusive, or nearly exclusive, seat of hereditary information (to use an anachronistically modern expression).~3 In their 1941 paper, Beadle and Ta- tum cited the (now quaint) "rapidly disappearing belief that genes are concerned only with the control of 'superficial' characters." It would appear, then, that while Garrod uncler- stood how genetic anomalies could assist in the unravelling of metabolic pathways anct that biochemical individuality was a hallmark of human nature, he had no comprehensive theory of gene action. Any geneticist, however, would wish to give alcaptonuria a textbook example of a biochemical genetic defect full credit as a paradigm on par with the pigment mutation in flowers or in insect eyes. Before 1941, simple metabolic effects on gene mutation could be inferred in a hancifu! of cases like these, but the vast majority of mutants studies! in, say, Drosophila, were com- plex morphogenetic traits that clefied (anal still very nearly defy) simple analysis. The experimental material available made it impossible to arrive at any simple theory of gene action. Even more exasperatingly, it offered almost no avenue Press, 1937). Haldane remarked that "Garrod's pioneer work on congenital human metabolic abnormalities such as alcaptonuria and cystinuria had a very considerable influence both on biochemistry and genetics. But alcaptonuric men are not available by the dozen for research work...." \3 See J. Sapp, Beyond the Gene: Cytoplasmic Inheritance and the Struggle for Authority in Genetics (Oxford: Oxford University Press, 1987).

368 BIOGRAPHICAL MEMOIRS tor continued investigation. How frustrates! Tatum and Bea- c3le were between 1937 and 1941 in their efforts with Dro- sophila pigments! It was the conceptual and experimental methoclology they developed using nutritional mutants that provided the breakthrough. Today, four decades later, analyzing (levelopmental and physiological pathways by systematically cataloguing mutants that block them is standard procedure and Beadle and Tatum's papers are rarely cited. Taken for granted, this meth- oclology is yet central to sophisticated studies in physiology, development, and gene action and is of incalculable conse- quence to biotechnology. Tryptophane and E. cold K-12 The biosynthesis of tryptophane, possibly harking back to Drosophila eye color, remained one of Tatum's central inter- ests. At one point, Tatum and Bonner inquirer! whether the dismutation of tryptophane into indole + serine was a simple reversal of the synthetic reaction. Though this analogy has been complicated by further knowledge, we now know that there are indeed interesting similarities between the trypto- phane-cleaving enzyme and one subunit of the synthetase. In order to perform studies on tryptophanases, Tatum retrieved a stock strain of Eschertchia cold from the Stanford Bacteriology Department's long-standing routine strain col- lection. By this accident, E. cold K-12 came to be the object of further genetic experimentation. Its name will reappear shortly in our story. With Bea(lle's encouragement, Tatum used his familiarity with bacteria to recruit Acetobacter and E. cold as experimen- tal objects for biochemical analysis to parallel Neurospora. Despite the lack of any theoretical or experimental basis for expecting bacteria to have a genetic organization similar to that of higher organisms, Tatum intuitively favored a com-

EDWARD LAWRIE TATUM 369 monality of biological structure to match what comparative biochemistry tract revealer! in the realm of nutrition. Tatum's prompt demonstration that biochemical mutants like those in Neurospora conic! also be induced in E. cold was, in itself, strong provocation to apply some form of gene theory to bacteria. As their part in the wartime mobilization cluring ~ 944 and 1945, Tatum's laboratory was asked to use its expertise in fungal genetics in an OSRD-sponsorect, multi-laboratory search for better penicillin-yielding strains of Penicillium. Though Stanford macle significant improvements in yield, their efforts were outstripped by developments elsewhere. Tatum and [ederberg Genetic Recombination in Bacteria The team of Beadle and Tatum by this time hac! become world famous. But at Stanford, uncler President Tressider's troubled leaclership, the exigencies of finance adcled to the academic politicking in the Biology Department and left little promise for innovative scientific development. The role of a chemist in a department of biology as then understood was particularly controversial, and C. B. van Niel's unequivocal support for Tatum was of no avail. Despite Tatum's success, his father's foreboding premonition had materialized, anal, foreseeing a bleak academic future at Stanford, he sought a post where he could continue to work at the hybrid frontiers of microbiology, genetics, and biochemistry. in 1945, after a trial semester at Washington University in St. Louis, where Car! Lindegren hoped to find a niche for him, Tatum ac- ceptecl a position at Yale University. A year later Beadle and his formidable team left Stanford en bloc to reshape the biol- ogy program at Caltech. At Yale Tatum held a tenured chair and was charged with cleveloping a biochemically-orientecl microbiology program with the Department of Botany. His arrival prover! a seren-

370 BIOGRAPHICAL MEMOIRS dipitous break for this author, Joshua Lederberg, then a Columbia medical student studying Neurospora genetics with Francis J. Ryan an apprenticeship begun at Columbia College in 1942. In 1941 Ryan had gone to Stanford for a year's postdoc- toral fellowship, where he became one of the first disciples of Neurospora biochemical genetics. When he returned to Columbia, he brought back with him his enthusiasm for the new field. At Stanford, Ryan had established a warm friend- ship with Tatum, and hearing that he was moving to Yale- sent him Lederberg's proposals for studying genetic recom- bination in bacteria. On the strength of Ryan's commenda- tion Tatum invited Lederberg to join his laboratory at New Haven starting March 1946, where he was supported finan- cially by the Jane Coffin Childs Fund. What was to have been a few months' diversion from med- ical school exceeded Lederberg's wildest expectations. At the Cold Spring Harbor Symposium in July 1946, Tatum's labo- ratory could report a newly discovered genetic recombina- tion in E. cold K- ~ 2, vindicating Tatum's gamble that, indeed, E. cold had genes! ~4 Our use of E. cold strain K-12 for these studies derived from Tatum's prior development of single, then double, mu- tants blocked at different nutritional-biochemical steps. The use of such multiply-marked stocks averted a number of tech- nical artifacts in recombination experiments. Only later did we learn that K-12 itself was a remarkably lucky choice of experimental material: Only about one in twenty randomly chosen strains would have given positive results in experi- ments designed according to our protocols. In particular, strain B—which had become the standard material for work on bacteriophage would have been stubbornly unfruitful. |4 ]. Lederberg, "Genetic Recombination in Bacteria: A Discovery Account," An- nual Review of Genetics, 2 1 ( 1987):23-46.

EDWARD LAWRIE TATUM 371 Subsequently K-~2 also proved to be a remarkably rich source of the plasmids F and lambda, which have become the objects of major experimental programs in their own right. The serendipity that so often marked Tatum's career cannot be attributed to any personal skill or insight on his part. But . his rece ?tivity to "far out" proposals from a medical student visiting his laboratory was typical of the man's unique com- bination of generosity of spirit ant! scientific vision. RETURN TO STANFORD (1948—1956) During his period at Yale, Tatum also recruited David Bonner to continue joint research on the biosynthesis of tryp- tophane and bolster the academic program in microbiology. But he was once again disappointed in the University's level of commitment to biochemically-oriented research in a department still heavily dominated by morphological-system- atic tradition. In 194S, when Douglas Whitaker took over the leadership of biological research at Stanford, Tatum was per- suaded to accept a full professorship in the department that had passer! him over just three years before. From this time forward! Tatum, with his particular brand of biochemical insights, pursued and supervised research projects that reconciled a variety of interests introduced by his students and colleagues. In early anticipation of the now famous Ames Screening Test, he became increasingly inter- ested in the analogy between mutagenesis and carcinogen- esis. If the induction of nutritionally dependent mutants in Neurospora was a rather laborious way to demonstrate mu- tagenicity of a chemical compound, it at least had the advan- tage of adding to the library of useful strains for biochemical pathway analysis. Many of us felt that E. cold was technically superior to Neurospora, both for biochemical and genetic studies (at least in the ease with which vast numbers of mu-

372 BIOGRAPHICAL MEMOIRS tents conic! be obtained and propagated; Tatum generally left the exploitation of this material to the students and while it was plain that Neurospora was Tatum's first love through- out his career, he leaned over backwards to give his intellec- tual heirs the utmost leeway for their own development. During the decade 1948 to 195S, Stanford macle a bicI to become a major center of scholarship, while California grew in economic, technological, clemographic, and political influ- ence. Stanforcl's then new president, the late I. E. Wallace Sterling, though himself a historian, warmly nurtured scien- tific ant] technical clevelopment. He supported an ambitious program to reconstruct the School of Medicine on the Stan- ford campus, transforming a hospital-based school in San Francisco with nominal connection to the University into a major center for medical ant! biological research. Uncler the leadership of Frec} Terman, similar institution- builcling was taking place in Stanforcl's School of Engineer- ing, nourished by vigorous federal support for science anct technology in the wake of World War IT. In short order the San Francisco Bay area was transformed into a center for high technology in the electronics and pharmaceuticals in- dustries a transformation that owed much to Sterling's and Terman's encouragement of University interaction with in- clustry. With regard! to academic policy at Stanford, Tatum proved an energetic spokesman for the rapidly emerging dis- cipline of biochemistry. As a member of the National Science Board he was an influential exponent of predoctoral and postcloctoral fellowship support for creative talent in the new fielcI. In this he no cloubt recalled that critical stage in his own career: his postdoctoral experience at Utrecht, that foreshact- owect his work with BeacIle. He was also a strong advocate of international cooperation among scientists and played an im- portant role in setting up a joint program with Japan.

EDWARD LAWRIE TATUM 373 At Stanforc! he gave strong encouragement to the devel- opment of a new, science-oriented curriculum in medical education ant! to the whole enterprise fraught with fiscal ant! managerial risks- of rebuilding the Medical School. In 1956 he was appointed to heat! a new Department of Bio- chemistry, an appointment that would take full effect in 1959 with the completion of the new medical center. Conflicts in his personal life, however, overshaclowect his other plans and he left Stanford, separating from his wife ant! two daughters. THE ROCKEFELEER INSTITUTE (1957—1975) In 1953 Detiev Bronk, president of the National Academy of Sciences, left Johns Hopkins to assume the presidency of The Rockefeller Institute in New York, marking the expan- sion of the Institute into a graduate university. In 1955, Whitaker was recruited from Stanford as vice-presiclent for administration. Between 1953 and 1957, Frank Brink, Keffer Hartline, Paul Weiss, and Fritz Lipmann joined the Institute faculty not to mention the elevation to full membership of Theodore ShedIovsky, George Palacle, ant! Keith Porter. Ta- tum was incluced to join this illustrious group in 1957, and he remained there until his death in 1975. In New York, Tatum married Viola Kantor, a staff em- ployee at the National Foundation/March of Dimes where he donated a great clear of time as scientific adviser. This re- builcling of his personal life was, however, to be scarred by Viola's illness and untimely death from cancer in 1974. As a professor at Rockefeller, Tatum concerned himself with institutional affairs just as he had at Stanford. He was also involves! with science policy on a national scale and served on the National Science Board. His special aim was to strengthen fellowship programs and other measures that wouIc} bolster support for young people entering scientific work. He was also chairman of the boars] of the Cold Spring

374 BIOGRAPHICAL MEMOIRS Harbor Biological Laboratory during a period of fiscal crisis and interpersonal turbulence that, according to one of his associates, was the most grievous episode of his professional life. THE NOBEL PRIZE (1958) The Nobel Prize came to Tatum in 195S, a year after his move to the Rockefeller Institute. In his Prize lecture, Tatum reviewed the history of biochemical genetics in his anct Bea- tile's hands. Comparing microbial cultures to populations of tissue cells, he saw cancer as a genetic change subject to nat- ural selection. From this vantage he looked forwarc! to "the complete conquering of many of man's ills, including herecI- itary defects in metabolism and the momentarily more ob- scure conditions such as cancer and the degenerative dis- eases.... Perhaps within the lifetime of some of us here, the cocle of life processes tier} up in the molecular structure of proteins and nucleic acids will be broken. This may permit the improvement of all living organisms by processes that we might call biological engineering." Tatum's prophecy erred mainly in its cliffidence; the breaking of the genetic cocle was well uncler way by 1961, with the reports of M. W. Nirenberg ant! I. H. Matthaei that matched specific triplets of RNA with individual amino acids in the assembly of polypepti(les. These rules of correspondence were the realization in ex- plicit chemical structural terms of the expectations of the one gene-one enzyme theory. In his own laboratory, Tatum was especially notable for nurturing inclependent-minclec! fellows in the pursuit of their own ideas. He was prouder of having cultivates! them as giftec! investigators than of his own contributions to their research. He strongly encouraged young faculty members at the Rockefeller, like Norton Zinder, and they have acknowI- eclgecl the debt.

EDWARD LAWRIE TATUM 375 His personal research interests during this phase centered on the use of Neurospora as a model for the genetic control of clevelopment. The effects of inositol deprivation or the addition of substances like verbose on the morphology of the fungus never failed to intrigue him. Features like mycelial branching, subsurface versus aerial hyphae, ant} the forma- tion of peritheciae and micro- and macro-conidia were thought to be models for the more complex cievelopmental patterns in animal embryogenesis. Such studies are only just · · ~ now coming into t near own. There is no doubt that mutational alteration of develop- mental patterns can throw a great clear of light on the inter- actions between genes and environment that lead to mor- phological elaboration. This type of material has yet to give us, however, those quasi-stable, epigenetic states expressed in higher plant and animal cells propagates! in tissue cul- ture whose biochemical genetic analysis would be extraor- clinarily helpful. IN CONCLUSION The ability to balance critical scientific objectivity, personal ambition, and interdependence on others" which some scientists take a lifetime to learn—was ingrained in Ed Tatum from the beginning. Despite misfortune in his personal life, he yet enjoyed the rare and well-earnec! pleasure of having so many of his fellow scientists look to him warmly as to a father or brother. At the time of Viola Tatum's cleath, Ed Tatum's health was already failing, and his friends could only watch with anguish the multiplying pains that attended a life to which he clung with the same cloggedness that made him a committed ciga- rette smoker. He cried on November 7, 1975, from heart fail- ure complicated by progressive, chronic emphysema. Edwarc! Lawrie Tatum was survived by two daughters

376 BIOGRAPHICAL MEMOIRS from his first marriage: Margaret (Mrs. John Easter) and Barbara. His brother Howarc} worked for many years with the Population Council cloing research on contraception. His late sister, Besse, was marries} to A. Frederick Rasmussen, professor of microbiology at UCLA. This memoir was completed more than a decade after Tatum's death forty-seven years after the climactic initia- tion of microbial genetics in 1941. Half a century may be almost enough time to see that work in historical perspective and yet allow for some brief overlap to call testimony from contemporaries. My own familiarity with Neurospora, dating to 1942 when Ryan returned from Stanford to Columbia, qualifies me only barely.~5 The one gene-one enzyme theory that a gene acts by con- trolling the formation of a specific enzyme in some fairly simple manner was implicit in earlier research on pigment biosynthesis. Before 1941 }. B. S. Haldane's speculative dis- cussion came close but neverjellect into a concrete theory that wouIcl lead to such effective lines of enquiry. Though the Neurospora work suggested that all biochemical traits couIct be studied in like fashion, it was Beadle and Tatum who extrapolates!—from diverse examples that all such traits would have an equally direct relationship to the correspond- ing genes. This fundamental observation is now stated as the DNA sequence providing the information for protein struc- ture (though the numerics are sometimes more complex). Many genes, ant! sometimes families of enzymes, can be in- volved in the quantitative regulation ant! environmental re- sponsiveness of enzyme synthesis. Enzymes are sometimes [5 Tatum's departure from Stanford in 1957 denied me the chance to be his col- league when I arrived there in 1959. His death in 1975 likewise predated my arrival at The Rockefeller in 1978. In sum, our academic careers ran in curiously parallel but dissynchronous tracks at Wisconsin, Stanford, and Rockefeller. Our sole con- gruence was at Yale for a year-and-a-half in 1946-47.

EDWARD LAWRIE TATUM 377 complex multi-chain ensembles ant! can contain nonprotein cofactors requiring the participation of many genes. Uncler- standing the role of RNA as a message intermediary between DNA and protein, the complexities of intervening sequences in RNA, RNA-processing, and post-translational processing came later and required more sophisticated biochemical anal- ysis—but all clerivec! from the concepts and the tools of the Neurospora studies. Beadle and Tatum's contribution, then, comprised the fol- lowing: 1) A methodology for the investigation of gene-enzyme relationships that exploited experimentally-acquired genetic mutations affecting specific biosynthetic steps. 2) A conceptual framework the one gene-one enzyme theory from which to search for and characterize these mutants. This framework was derived from the model that chromosomal genes contain (substantially) all of the blueprints for development and that enzymes (and other proteins) are the mediators of gene action. 3) The dethronement of Drosophila as the prime experimental ma- terial for physiological genetic research in favor of the fungus Neurospora. This further helped open the way to use of bacteria and viruses in genetic research and the culture of tissue cells as if they were microbes. These methods and concepts have been the central paradigm for experimental biology since 1941. Beadle ant! Tatum sharer! many awards in adclition to the 1958 Nobel Prize in recognition of these innovations. In 1952, Tatum was indiviclually honoree! by election to the Na- tional Academy of Sciences. In 1953 he received the Remsen Aware! of the American Chemical Society and was elected to the American Philosophical Society. He was president of the Harvey Society (1964-65) and the recipient of at least seven honorary clegrees. He served on the NAS Carty Fund Committee from 1956 to 1961. For the NRC, he took part in a number of panels

378 BIOGRAPHICAL MEMOIRS and committees having to do with genetics and biology and was a member of the Advisory Committee on the Biological Effects of Ionizing Radiations from 1970 to 1973. He also dice yeoman service on advisory committees for the National Institutes of Health, American Cancer Society, the National Foundation (March of Dimes), ant! other booties concerned with the award of fellowships and grants. He was chairman of the Scientists' Institute for Public Information and an advisor to the City of Hope Meclical Center, Rutgers University Institute of Microbiology, and SIoan-Kettering In- stitute for Cancer Research, and a consultant in microbiology for Merck and Co. He worked actively on many scientific publications, inclucling Annual Reviews, Science, Biochemica et Biophysica Acta, Genetics, and the Journal of Biological Chemistry. Testifying to a Congressional committee on behalf of the National Science Foundation in 1959, Tatum said: "The general philosophy [of the NSF] is concentration on excellence . . . making it possible for [the scientist] to use his capacities, both for research and for training the next generation . . . whether it is a particular research program in a given area, whether it may or may not be immediately prac- ticable in its application . . . freedom to develop the intellectual curiosity and abilities of the individual...." At this time Beadle and Tatum's legacy is embodied in published work that has influencer! biological research through several scientific generations. The original papers are "classics" ant! taken for granted. Personal recollections of Tatum are facling, and this re- port can hardly clo justice to his humor, his hobbies (includ- ing the French horn), his zest for experiments, his love of microbes, his attachment to students, friends, ant! family— the trauma of divorce notwithstanding the tragedy of his final year of bereavement and of an illness that left him gasp- ing for breath. He touched the lives of many young scientists.

EDWARD LAWRIE TATUM 379 The enduring appreciation of his role in their clevelopment is the memorial he would have cherished most. THE TANTALIZINGLY FEW personal papers of Edward Tatum now extant are on deposit at the Rockefeller University Archive Center. I am particularly indebted to Professor Carlton Schwerdt for hav- ing preserved and made available his lecture notes on Tatum's 1941 course on comparative biochemistry, to June Alton Tatum for making available to me materials regarding Tatum's life before 1946, and to the staff of the Rockefeller University Archive Center. I am also indebted to the following important studies for infor- mation that appears in this account: R. M. Burian, lean Gayon, and Doris Zallen, "The Singular Fate of Genetics in the History of French Biology," Journal of the History of Biology, 21~19881:357-402, on the Beadle-Ephrussi collaboration that led directly to Beadle and Tatum's work on Drosophila eye color "hormones" and dis- cusses the use of that terminology for what would later be termed "precursors." Lily E. Kay, "Selling Pure Science in Wartime: The Biochemical Genetics of G. W. Beadle," journal of the History of Biology, 22~1989~:73-101, reviews the Beadle-Tatum work on pen- icillin improvement during World War II.

380 BIOGRAPHICAL MEMOIRS SELECTED BIBLIOGRAPHYl6 1932 With W. H. Peterson and E. B. Fred. Effect of associated growth on forms of lactic acid produced by certain bacteria. Biochem. J., 26:846-52. 1934 Studies in the biochemistry of microorganisms. Ph.D. Dissertation, University of Wisconsin, Madison. 1936 With H. G. Wood and W. H. Peterson. Essential growth factors for propionic acid bacteria. II. Nature of the Neuberg precipitate fraction of potato: Replacement by ammonium sulphate or by certain amino acids. I. Bacteriol., 32: 167-74. With H. G. Wood and W. H. Peterson. Growth factors for bacteria. V. Vitamin Be, a growth stimulant for propionic acid bacteria. Biochem. }, 30: 1 898-1 904. 1937 With E. E. Snell and W. H. Peterson. Growth factors for bacteria. III. Some nutritive requirements of Lactobacillus delbruckii. ]. Bacteriol., 33:207-25. With W. H. Peterson and E. B. Fred. Enzymatic racemization of optically active lactic acid. Biochem. l., 30:1892-97. 1938 With G. W. Beadle. Development of eye colors in Drosophila: Some properties of the hormones concerned. l. Gen. Physiol., 22:239-53. 1939 Development of eye colors in Drosophila: Bacterial synthesis of v+ hormone. Proc. Natl. Acad. Sci. USA, 25:486-90. Nutritional requirements of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA, 25:490-97. }6 A complete bibliography can be found in the Archives of the National Academy of Sciences and in the Rockefeller University Archive Center.

EDWARD LAWRIE TATUM 1940 381 With G. W. Beadle. Crystalline Drosophila eye color hormone. Sci- ence, 91:458. 1941 With G. W. Beadle. Experimental control of development and dif- ferentiation. Am. Nat., 75: 107-16. Vitamin B requirements of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA, 27:193-97. With A. I. Haagen-Smit. Identification of Drosophila v+ hormone of bacterial origin. I Biol. Chem., 140: 575 -80. With G. W. Beadle. Genetic control of biochemical reactions in Neurospora. Proc. Natl. Acad. Sci. USA, 27:499-506. 1942 With G. W. Beadle. Genetic control of biochemical reactions in Neurospora: An "aminobenzoicless" mutant. Proc. Natl. Acad. Sci. USA, 28: 234-43. 1943 With L. Garnjobst and C. V. Taylor. Further studies on the nutri- tional requirements of Colpoda duodenar?a. ]. Cell. Comp. Phys- iol., 21: 199-212. With F. I. Ryan and G. W. Beadle. The tube method of measuring the growth rate of Neurospora. Am. J. Bot., 30:784-99. With D. Bonner and G. W. Beadle. The genetic control of biochem- ical reactions in Neurospora: A mutant strain requiring isoleu- cine and valine. Arch. Biochem., 3:71-91. With D. M. Bonner. Synthesis of tryptophan from indole and serine by Neurospora. I. Biol. Chem., 151 :349. 1944 With D. Bonner. Indole and serine in the biosynthesis and break- down of tryptophan. Proc. Natl. Acad. Sci. USA, 30:30-37. Biochemistry of fungi. Annul Rev. Biochem., 13:667-704. With C. H. Gray. X-ray induced growth factor requirements in bacteria. Proc. Natl. Acad. Sci. USA, 30:404-10.

382 BIOGRAPHICAL MEMOIRS 1945 With N. H. Horowitz, D. Bonner, H. K. Mitchell, and G. W. Beadle. Genic control of biochemical reactions in Neurospora. Ann. Nat., 79:304-17. With G. W. Beadle. Biochemical genetics of Neurospora. Ann. Mo. Bot. Garden, 32:125-29. X-ray induced mutant strains of E. coli. Proc. Natl. Acad. Sci. USA, 31 :215-19. With G. W. Beadle. Neurospora II. Methods of producing and de- tecting mutations concerned with nutritional requirements. Am. I. Bot., 32:678-86. 1946 With T. T. Bell. Neurospora III. Biosynthesis of thiamin. Am. J. Bot., 33:15-20. With I. Lederberg. Novel genotypes in mixed cultures of biochem- ical mutants of bacteria. Cold Spring Harbor Symp. Quant. Biol., 11:113-14. Induced biochemical mutations in bacteria. Cold Spring Harbor Symp. Quant. Biol., 11:278-84. 1947 Chemically induced mutations and their bearing on carcinogene- sis. Ann. N.Y. Acad. Sci., 49:87-97. With I. Lederberg. Gene recombination in the bacterium Esche- r~chia coli. ]. Bacteriol., 53:673-84. 1950 With R. W. Barratt, N. Fries, and D. Bonner. Biochemical mutant strains of Neurospora produced by physical and chemical treat- ment. Am. I. Bot., 37:38-46. With R. C. Ottke and S. Simmonds. Deuteroacetate in the biosyn- thesis of ergosterol by Neurospora. l. Biol. Chem., 186:581-89. With D. D. Perkins. Genetics of microorganisms. Annul Rev. Mi- crobiol., 4:129-50. With E. A. Adelberg. Characterization of a valine analog accumu- lated by a mutant strain of Neurospora crassa. Arch. Biochem., 29:235-36.

EDWARD LAWRIE TATUM 383 1951 With E. A. Adelberg and D. M. Bonner. A precursor of isoleucine obtained from a mutant strain of Neurospora crassa. ]. Biol. Chew., 190:837-41. With E. A. Adelberg. Origin of the carbon skeletons of isoleucine and valine. I. Biol. Chem., 190:843-52. 1954 With S. R. Gross, G. Ehrensvard, and L. Garnjobst. Synthesis of aromatic compounds by Neurospora. Proc. Natl. Acad. Sci. USA, 40:271-76. With D. Shemin. Mechanism of tryptophan synthesis in Neuro- spora. I. Biol. Chem., 209:671-675. 1956 With S. R. Gross and R. D. Gaylord. The metabolism of proto- catechuic acid in Neurospora. I. Biol. Chem., 219: 781-96. With S. R. Gross. Physiological aspects of genetics. Ann. Rev. Phys- iology, 18:53-68. With R. A. Eversole. Chemical alteration of crossing-over fre- quency in Chlamydomonas. Proc. Nat. Acad. Sci. USA, 42:68- 73. With L. Garnjobst. A temperature independent riboflavin requir- ing mutant of Neurospora crassa. Am. I. Bot., 43: 149-57. With R. C. Fuller. Inositol-phospholipid in Neurospora and its re- lationship to morphology. Am. J. Bot., 43:361-65. 1958 With R. W. Barratt. Carcinogenic mutagens. Ann. N.Y. Acad. Sci., 71: 1072-84. Molecular basis of the cause and expression of somatic cell varia- tion. J. Cell Comp. Physiol., 52:313-36. 1959 A case history in biological research. Science, 129:1711-15. Also in: Les prix Nobel en 1958, Stockholm, pp. 160-9. With A. J. Shatkin. Electron microscopy of Neurospora crassa my- celia. I. Biophys. Biochem. Cytol., 6:423-26.

384 BIOGRAPHICAL MEMOIRS 1961 With James F. Wilson and Laura Garnjobst. Heterocaryon incom- patibility in Neurospora crassa Micro-injection studies. Am. i. Bot., 48:299-305. With Noel de Terra. Colonial growth of Neurospora. Science, 134: 1066-68. With E. Reich, R. M. Franklin, and A. I. Shatkin. Effect of actino- mycin D on cellular nucleic acid synthesis and virus production. Science, 134:556-57. 1962 Biochemical genetics and evolution. Comp. Biochem. Physiol., 4:241-48. With A. {. Shatkin, E. Reich, and R. M. Franklin. Effect of mito- mycin C on mammalian cells in culture. Biochem. Biophys. Acta, 55:277-89. With E. Reich, R. M. Franklin, and A. J. Shatkin. Action of acti- nomycin D on animal cells and viruses. Proc. Nat. Acad. Sci. USA, 48:1238-45. 1963 With Noel de Terra. A relationship between cell wall structure and colonial growth in Neurospora crassa. Am. l. Bot., 50:669-77. With B. Mach and E. Reich. Separation of the biosynthesis of the antibiotic polypeptide tyrocidine from protein biosynthesis. Proc. Nat. Acad. Sci. USA, 50:175-81. 1965 Perspectives from physiological genetics. In: The Control of Human Heredity and Evolution, ed. E. Sonneborn, New York: Macmillan, pp. 20-34. With E. G. Diacumakos and L. Garnjobst. A cytoplasmic character in Neurospora crassa. The role of nuclei and mitochondria. I. Cell Biol., 26:427-43. With C. W. Slayman. Potassium transport in Neurospora. III. Iso- lation of a transport mutant. Biochem. Biophys. Acta, 109: 184- 93.

EDWARD LAWRIE TATUM 1966 385 With Z. K. Borowska. Biosynthesis of edeine by Bacillus brevis Vm4: In viva and in vitro. Biochem. Biophys. Acta, 114:206-9. The possibility of manipulating genetic change. In: Genetics and the Future of Man, First Nobel Conference, Gustavus Adolphus Col- lege.. Ed., J. D. Roslansky, New York: Appleton-Century-Crofts, pp. 51-61. With B. Mach. The biosynthesis of antibiotic polypeptides. In: Ninth International Congress for Microbiology, Moscow, London: Pergamon Press, pp. 57-63. With S. Brody. The primary biochemical effect of a morpholog- ical mutation in Neurospora crassa. Proc. Nat. Acad. Sci. USA, 56: 1290-7. Molecular biology, nucleic acids, and the future of medicine. Per- spec. Biol. Med., 10: 19-32. 1967 With B. Crocken. Sorbose transport in Neurospora crassa. Biochem. Biophys. Acta, 135: 100-5. With E. Pina. Inositol biosynthesis in Neurospora crassa. Biochem. Biophys. Acta, 136:265-71. With S. Brody. Phosphoglucomutase mutants and morphological changes in Neurospora crassa. Proc. Nat. Acad. Sci. USA, 68:923-30. With L. Garnjobst. A survey of new morphological mutants in Neu- rospora crassa. Genet., 57:579-604. With M. P. Morgan and L. Garnjobst. Linkage relations of new morphological mutants in linkage group V of Neurospora crassa. Genet., 57:605-12. With P. R. Mahadevan. Localization of structural polymers in the cell wall of Neurospora crassa. ]. Cell Biol., 35:295-302. 1970 With N. C. Mishra. Phosphoglucomutase mutants of Neurospora sitophila and their relation to morphology. Proc. Nat. Acad. Sci. USA, 66:638-45. With L. Garnjobst. New crisp genes and crisp modifiers in Neuro- spora crassa. Genetics, 66:281-90.

386 BIOGRAPHICAL MEMOIRS 1971 With W. A. Scott. Purification and partial characterization of glucose-6-phosphate dehydrogenase from Neurospora crassa. ]. Biol. Chem., 246:6347-52. 1972 With E. G. Diacumakos. Fusion of mammalian somatic cells by mi- crosurgery. Proc. Nat. Acad. Sci. USA, 69:2959-62. 1973 With N. C. Mishra. Non-Mendelian inheritance of DNA-induced inositol independence in Neurospora. Proc. Nat. Acad. Sci. USA, 70:3875-79. 1974 With C. R. Wrathall. Hyphal wall peptides and colonial morphol- ogy in Neurospora crassa. Biochem. Genet., 12:59-68.

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