Postmature Scientific Discovery and the Sexual Recombination of Bacteria
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INSTITUTE FOR SCIENTIFIC (N FORMATIONe 3501 MARKET ST PHILADELPHIA PA 19104 Postmature scientific Discovery and the SexuaI Recombination of Baeteria— The Shared Perspectives of a Scientist and a sociologist .,. ––1---- . .-,.,. Numr3er 3 January ID, IYUY Forty-three years ago Joshua Lederberg recognition, one aspect of prematurity, as and Edward L. Tatum, then at the Osbom in the cases of Peter D. Mitchel17,S and the Botanical Laboratory, Yafe University, New Higgs boson.g, 10Currently we are prepar- Haven, Connecticut, published a landmark ing an essay that deafs with the topic of de- paper in Nature reporting the discovery of layed recognition. It will appear in the next bacterial sex. 1Its importance convinced me few months. to reprint the piece here. Recently we have Some time ago sociologist Robert K. Mer- afso reprinted reminiscences by Lederherg, ton, Columbia University, honored me by now president, The Rockefeller Universi- writing the foreword to my book Citation ty, New York, on his work in genetics,z Indexing-Its Theory and Application in but as an aspiring swiologist of science I Science, Technology, and Humanities. 1I was even more attracted to the paper that There, he reflected on the possibility that the he coauthored with Harriet Zuckerman, De- Science Citation index@ was an ‘‘inevi~- partment of Sociology, Columbia Univer- ble” discovery. In a recent publication, he sity, New York, in the December 18, 1986, has also mentioned the reprint on posh-nature issue of Nature. In this paper, which we are scientific discovery that follows as an afso reprinting here, Zuckemmn and Letier- example of “sociological autobiogra- berg view this discovery from a sociologi- phy’’–combining the complementary ad- cal point of view. 3 In reading this remark- vantages of both Insider and Outsider per- able “case study” of the Lederberg-Tatum spectives, while minimizing the disadvan- discovery of bacteriaf sex, my thoughts res- tages of each. 12 Reading the Zucker- onated to their analysis of” postmature sci- man-Lederberg definition of postmature entific discovery. ” discovery made me realize the interesting Some Current Confer@ readers may not relationship between these: the inevitabili- be aware that Harriet and Josh coined this ty of discovery and postmaturity. Language term as a parallel to’ ‘premamre discovery, ” plays tricks on us—inevitability of discov- the phenomenon described by Gunther S. ery seems the right way to describe, for ex- Stent, professor of molecular biology, Uni- ample, simple techniques that are so ‘‘ob- versity of California, Berkeley, and vious” once they are invented. In patent others4,5 that we have discussed on many law, “inevitability” is often expressed by occasions. (A prototypical example is the the phrase “obvious to anyone versed in the case of botanist Gregor Mendel.G) Indeed, art. ” Many a patent application has Eeen de- we at ISI” have used citation anafysis to nied on that principle. study cases of premature discovery. These Both the inevitable “discovery” of cita- longitudinal studies have covered many tion indexing and the postmature discovery years of data and fmus especially on delayed of bacterial sex show the three attributes 16 specified by Zuckerman-LexJerberg. In ret- plication. While intuition tells us that this rospect, (1) it must be judged to have been has indeed been the case, this assertion is technically achievable at an earlier time with diftlcult to prove. Whether the ‘‘sociaf” en- methods then available; (2) it must be judged gineering of science through better under- to have been understandable, capable of be- standing of the discovery process (social sci- ing expressed in terms comprehensible to ence) can claim similar efficiencies remains working scientists at the time; and (3) its im- to be seen. But certainly the management plications must have been capable of hav- of the global science enterprise will pay a ing been appreciated. g smafl price for the continued investigation In an era of Big Science, with goals such of such processes that might accelerate both as the conquest of cancer, AIDS, and so on, research and technology transfer. Zucker- it is important to understand the limitations man and Lederberg have made an impor- of science, but also to understand how its tant contribution to that process. development may be accelerated. When I first entered the field of information science, ***** it was a tenet of our missionary zeal that in- formation technology could have a signifi- My thanks to Peter Pesavento for his help cant catalytic effect on discovery and its ap- in the preparation of this essay. ~1909IN REFERENCES 1. Lederberg J & TaturrrE L. Gene recombination in Ercherichia co[i, Nature 158:558, 1946. 2. Garfteld E. The impact of basic research in genetic recombination-a personal account by Joshua Lederberg. Parts l&2. Current Coruerm (24):3-17, 13 June 1988; (25):3-14, 20 June 1988. 3. Zuckerrnan H & Lederherg J. Postmature scientific discovery? Nature 324:629-31, 1986. 4. Stent G S. Prematurity and uniqueness in scientific dkcovery, .Sci. Amer. 227(6):84-93, December 1972. 5. Barber B. Resistance by scientists to scientific discovery. Science 134:596-602, 1961. 6, Garfield E. Premature dkcovery or delayed recognition-why? Essays of an information scientist, Philadelphia: 1S1 Press, 19SI. Vnl, 4, p. 4S8-93. 7. ---——-. Tfre 1976 articles most cited in 1976 and 1977.2. Physical sciences. Jbid., p. 115-26. 8. Mitchell, Peter D. (Wasson T, cd.) Nobel Prize winners. New York Wilson, 1987. p. 713-5. 9. Veltman M J G. The Higgs boson. .Sci. Amer. 255(5):76-82, 1986. 10. Garfteld E. How to use citation analysis for faculty evaluations, and when is it relevant? Part 2. OP. cit., 1984. Vol. 6. p. 363-72. 11, Merton R K. Foreword. (Garfield E.) Citation indexing-ifs theory arrd application in science, technology, orrd humanities. New York: Wiley, 1979, p. v-ix. 12. ---------- Some thoughts on the concept of smiological autobiography. (Riley M W, cd.) Sociological lives. Vol. 2, socicd change and the lfe course, Newbury Park, CA: Sage, 19S8. p. 17-21. Reprmmd by permission from Nature Vol. 158, p. 558. Copyright (c) 1946 Macmillan MagazinesLtd. Gene Recombination in Escherichia coli Anatysis of mixed cultures of nutritional mu- ability to synthesize growth-factors. As a result tams has revealed the presence of new types which of these deficiencies they will onty grow in media strongly suggest the occurrence of a sexual pro- supplemented with their specific nutritional re- cess in the bacterium Escherichia coli. qttirementa. In these mutants single nutritional re- The mutants czmaiat of mains which differ from quirements are established at single mutational their parent wild type, strain K-12, in lacking the steps under the influence of X-ray or ultra-vio- 17 letl,2. By su-ive treatments, strains with sev- chemical requirements and phage resistance have eral requirements have beerr obtained. frequently been found. In the recombination studies herereported, two These types can most reasonably be interpreted triple mutants have been used: Y-10, requiring as instances of the assortment of genes in new threonine, Ieucirse and thiarnirr, and Y-24, requir- combinations. In order that various genes may ing biotin, phenylalanine and cystine. These have the opportunity to recombine, a cell fusion strains were grown in mixed crdtrrre in ‘Bacto’ would be required. The only apparent alternative yeast-beef broth. when filly grown, the cells were to this interpretation would be the occurrence in washed with sterile water and inoculated heavily the medium of transforming factors capable of in- into synthetic agar medium, to which various sup- ducing the mutation of genes, bilaterally, both to plements had been added to allow the growth of and from the wild condition. Attempts at the in- colonies of various nutritional types. This pro- duction of transformations in single cultures by cedure readily rdlows the detection of very small the use of sterile filtrates have been unsuccessfirl. numbers of celI types different from the parental The fusion presumably occurs only rarely, since forms in the cultures investigated only one celJ in a rr3il- The only new types found in ‘pure’ cultures of lion cars be classified as a recombination type. The the individual mutants were occasioned forms hypothetical zygote has not been detected cyto- which had reverted for a single factor, giving logically. strains which required only two of the onginrd These experiments imply the occurrence of a thrm substances. In mixed cultures, however, a sexual process in the bacterium ,flrchen’chiamfi; variety of types has been found. These include they will be reported in more detail elsewhere. wild-type strains with no growth-factor deficien- This work was supported in part by a grant from cies and single mutant types requiring ordy tbia- the Jane Coffin Childs Memorial Fund for Med- rnin or phenylalaoirw In addition, double require- icaJ Research. ment types have been obtained, including strains Joshua Lederberg* deficient in the syntheses of biotin and leucine, E. L. Tatum biotin and tfrreonine, and biotin and thiarnin re- spectively, The wild-type strains have been CJsbOm Botanical Laboratory, studied most intensively, and several independent Yale University, lines of evidence have indicated their stability and New Haven, Coon. homogeneity. Sept. 17. In other experiments, using the triple mutants mentioned, except that one was resistant to the ●FeUow of the Jane Coffin ChiJds MenmriaJ Fund for Medical Research. coli phage 11(obtained by the procedure of Luria and Delbriick3), nutritionally wild-type strains ‘Tatun, E. L , Pmc, Na. ,icad. .%i., 31, 215 (1945), lTatum, E. L., Cotd Spring Harbor, Symposia Quam. BIOI., were found both in sensitive and in resistant cat- “01 1 t (,” the press. 1946). egories. Similarly, recombination between bio- ‘Lure, S. E., and Detbriick, M.. Genetics, 2.S, 491 (1943), Reprinted by pmrussion from Nafure Vol.