Fifty Years Of Biochemical Genetics: A Tribute

One milestone of the modern scientific era was the first publication by George W. Beadle (1903-1989) and Edward L. Tatum (1909-1975) on the biochemical genetics of Neurospora (PNAS, 27:499-506, 1941). Its 50th anniversary is being commemorated in several places this summer. Beadle and Tatum's work is worthy of fond celebration not only for its inherent scientific merit--its impact on biochemical research continues to resonate today--but also because it convincingly affirms the value of a kind of multi-disciplinary collaboration that, unfortunately, is insufficiently encouraged in the current research environment. Genetic research up to 1941 was dominated by work on the fruit fly, Drosophila melanogaster, and the efficiency of this research greatly relied on the ease with which thousands of these flies could be cultured and scanned. Much was learned studying mutations for visible morphological characteristics--bent wings, albino eyes, and so forth. But years of effort on the biochemical basis of these characteristics led only to frustration, and Beadle turned in desperation to a quest for other model organisms. It was the combination of Tatum's background in microbial biochemistry and Beadle's in genetic theory--a nearly unique convergence of disciplines at the time--that led them to consider, as an alternative to the fruit fly, the genetics and nutrition of the red bread mold, Neurospora. Within a few months in 1941, they (with help from B.O. Dodge of the New York Botanical Garden) converted their lab at Stanford University into the breeding site for this fungus, and, indeed, were successful at acquiring mutants with nutritional defects--blocks in the biosynthesis of vitamins like pyridoxine and thiamine. Where in the past, genetic research had depended on thousands of fruit flies, scientists now could study millions of mycelia--and these with well-marked biochemical pathways. Their paradigm soon yielded bacteria by the billions, and with still greater facility for chemical analysis. Of course, the biochemicalization of genetics was already in the air, manifested in the investigations of such notable researchers as Archibald Garrod, J.B.S. Haldane, Rose Scott-Moncreif, and others. But the Beadle-Tatum technique of exposing every metabolic pathway of an organism to options of mutational blocks, and using these experimentally derived strains for pathway analysis, is the very root of contemporary genetic analysis. Today we often witness collaborations, or even fusions, of genetic and biochemical skills among molecular biologists. In principle, such interdisciplinary collaborations are widely acknowledged to be a fruitful source of radical innovation. Nevertheless, the voices that might cheer them on are too often muted by academic turf jealousy and rigidities of funding channels. Worst of all is the establishment of new but enduring structures that are well-intentioned but likely to outlive their usefulness to the scientific enterprise: for example, the elaborate science and technology centers proposed by the National Science Foundation. Simply put, the best way to administer a creative research environment is to find people of great talent and reasonable ambition--whatever their specific disciplines--and leave them to their own devices. Had Beadle and Tatum been obliged to submit their ideas on Neurospora for project review before the fact, we know the most likely reaction would have been: "These able investigators are stepping out of their established expertise and have not proved the feasibility of what they propose to do." Joshua Lederberg is President Emeritus and University Professor at Rockefeller University, New York. In 1958, he, Beadle, and Tatum were all winners of a divided Nobel Prize in physiology or medicine: Lederberg for his discoveries in genetic recombination, Beadle and Tatum for their discovery that genes act by regulating definite chemical events.

Fifty Years Of Biochemical Genetics: A Tribute

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