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3-10, 17 Aprij 1989 INSTITUTE FOR SCIENTIFIC lNFOfl MATION@ 3501 MARKET ST PHILADELPHIA PA 19104 I%e 102 Most-Cited Life-Sciences Pubkatims in the New 1945-1954 Science Citation Index. Part 2. Wonder Drugs, Ceil Biochemistry, Separation Techniques Highlight Major Trends of Post-WorM War II Decade Number 16 April 17, 1989 This essay concludes a two-part exami- niques. The contributions of Nobel laureates nation of 102 highly cited papers and books from this era are also examined. As in sev- in the life sciences, 1945-1954. In this patt, eral previous studies, this group of highly the five moat-cited works are featured, along cited papers demonstrates the criticrd itnpor- with some highlights and key developmen~ tance of methods and techniques in speed- of the decade-notably, work in endocrinol- ing scientific progress. ogy, protein structures, and wparation tech- Wonder Drugs, Cell Biochemistry, $eparation Techniques Highlight Major TrerIds of Post-Worki War II Decade Bernard Dixon 132 High Street Uxbridge, Middlesex UB8 lDP United Kingdom In the first partof this essay, the list of 102 most-citedpapers from the 1945-1954 Science Citation Indexm cumulationwas presentedand discussed. In this second part Bernard Dixon discusses the major developments of the decade as revealed by citation analysis. 1 The Top Five ments). Fiske joined the faculty of Harvard Medical School in 1918 and served as pro- fessor of biochemistry there from 1935 to By a considerable margin, the moat heavi- 1957, when he became professor emeritus. ly cited life-sciences pa~r between 1945 He discovered the cellular energy storage and 1954 was one published in the Journal compound adenosine triphosphate, and pi- of Biological Chemistry by American bio- oneered the use of liver extracts to treat per- chemist Cyrus Hartwell Fiske with his col- nicious anaemia long before the introduc- league Y. SubbaRow as far back as 1925. tion of vitamin B12(whose isolation is also Describing a coiorirnetric method for deter- recorded in the Bibliography that appeared mining the amount of phosphorus in solu- in Part 1l), But many biochemists and lab- tions, it was cited about 1,465 times (not to oratory technicians today will recall his mention the countless occasions when it has name largely as a result of the time-saving appeared in doctoral theses and other docu - , “Fiske and SubbaRow” assay. 109 Equally familiar to countless researchers “predictable Hungarian charm.’ ‘q But and students will be G.W. Snedecor’s Sta- Somogyi, too, had devised a solution to the tistical Method Applied to Experiments in same problem, which was included with per- Agriculture and Biology, the fourth edition mission in the Nelson paper. Somogyi later of which was published in 1946 and was cit- wrote up his work in more detail in two pa- ed about 1,110 times between 1945 and pers published together. These papers, too, 1954 (see W.G. Cochran’s Ciration Ckz.r- appear in the 1945-1954 listing (with about sic” 2 commentary on the fifth edition of 235 and 410 citations, respectively). 1956). It is followed by three.further meth- ods papers. These are: a description by R. Consden and colleagues (including Nobel NoM Latmatea laureate Archer J .P. Martin) of a paper- chromatographic technique for analysing In addition to Philip S. Hench and Edward proteins qualitatively (about 885 citations); C. Kendall, discussed in Part 1,1 there are L.J. Reed and H. Muench’s paper explain- 13 Nobel laureates in the list. One of them ing a simple method of estimating 50 per- is the English biochemist Fred Sanger, who cent endpoints (about 810 citations); and has won the chemistry prize on two occa- Norton Nelson’s 1944 report on a modifi- sions. In 1958, he was the sole recipient for cation of the Somogyi method for determin- his success in solving one of the greatest ing glucose (over 715 citations). problems of twentieth-century biology-the Nelson’s technique is especially note- structure of proteins, in particular, insulin. worthy because it originated in something His 1945 paper on free amino-acid groups of an emergency, when he and his brother of insulin attracted over 360 citations. In Waldo, together with Arthur E. Mirsky and 1980, nearly a quarter of a century after his Samuel Rappaport, were working together first telegram arrived from Stockholm, in Cincinnati at the end of the 1930s. Their Sanger shared the chemistry prize for work researches, on juvenile diabetes and other more properly described as molecular biol- conditions, involved a considerable amount ogy. He and Walter Gilbert were honoured of glucose analysis. But, as Nelson later re- for developing techniques which reduced c~l~ in Current Contents@, “Somewhere drastically the amount of toil required to de- along the line, perhaps about 1940, all re- code the sequences of nucleotide units along frigerators in all available institutes were stretches of DNA. Together with what are jammed with specimens awaiting anrdysis, now termed recombinant DNA procedures with which our staff, even with weekend evolved by the third recipient, Paul Berg, work, were unable to keep abnmst. Obvious- this was the work that first made genetic en- ly something neaied to be done and that was gineering a practical possibility. to improve the efficiency of glucose analy- Sanger’s research on insulin was greatly sis, without losing the advantages of the facilitated by a technique developed by the Somogyi procedure.”3 1952 Nobel Prize winners in chemistry, the The answer proved to be a new arseno- English chemist Martin and a fellow coun- molybdate reagent. This allowed M. Som- tryman, biochemist Richard L.M. Synge, ogyi’s existing copper reagents, then used while working together at the Wool Indus- for estimating glucose by a lengthy and te- tries Research Association in Leeds in north- dious titration procedure, to be adapted and ern England. Their 1941 paper describing updated in a quick and reliable coloritnet- a new form of chromatography attracted ric method. “Within a few weeks our re- over 235 citations. Partition chromatogra- frigerators, though not precisely empty, phy appears to be disarmingly simple—as were clearly ready to receive more speci- seen when a piece of filter paper is spotted mens, ” wrote Nelson, who later met Dr. with a solution containing several different Somogyi in St. Louis and was taken by his substances, which are then separated as a 110 liquid soaks through the paper and carries should receive $125,000 for the assignment them different distances forward. Yet this of all foreign patent rights, and 3 percent technique transformed biomedical science, of the royalties. allowing new substances to be traced and Another Nobelist in the list, the Swedish isolated, new metabolic pathways to be biochemist Ame Tiselius, received the 1948 charted, and fragments of large molezules chemistty prize “for his researches on elec- such as proteins to be separated. Sanger’s trophoresis and adsorption analysis, espe- use of paper chromatography in 1955 to sep cially for his discoveries concerning the arate the amino acids from insulin-the first complex nature of the serum proteins. ” A protein to be sequenced-was the first ma- pupil of The Svedberg, inventor of the ul- jor demonstration of its immense power. tracentrifige, Tiselius brought electropho- Next to penicillin, the most famed anti- resis to a considerable degree of perfection microbial “magic bullet” must be strepto- as a means of purifying colloids and high mycin, whose inception virtually ended the molecular weight substances. His primor- terrors and miseries of tuberculosis. It was dial 1937 paper (which was cited about 235 described in a 1944 paper co-authored by times in 1945-1954) describes a new appa- Albert Schatz, Elizabeth Bugie, and Selrnan ratus for achieving this. A. Waksman, then working at Rutgers Uni- Sharing the 1953 Nobel Prize in physiol- versity, New Jersey. The paper was cited ogy or medicine were Hans Krebs and Fritz over 275 times in the period 1945-1954. The Lipmann-Krebs for discovering the citric Russian-born Waksman, who became a nat- acid cycle (which followed his work on the uralised American in 1916, had been study- urea cycle mentioned in Part 11) and Ger- ing antagonisms between different soil mi- man-born biochemist Lipmann for discov- croorganisms for many years. Spurred by ering coenzyme A and its importance in in- the early results with penicillin, he turned termediary metabolism. The citric acid (or with his collaborators to a fungus, Sfrepto- Krebs) cycle is a sequence of reactions myces grisew, which he had isolated 28 through which energy is released from car- years earlier and which proved to produce bohydrates. It was disentangled by Krebs an extremely powerful antitubercular sub- and his co-workers at the University of stance, which he named streptomycin. Sheffield, UK, principally in the years In 1952, Waksman received the Nobel 1936-1937, Krebs having fled from Nazi Prize in physiology or medicine. Then fol- Germany in 1933 when Hitler seized power. lowed an unseemly dispute when Schatz In June 1937, incidentally, Nature rejected filed a complaint demanding an order re- Krebs’s letter describing the citric acid cy- straining Waksman from representing him- cle, and a full paper appeared less than two self as the sale discoverer of streptomycin months later in En.zymologia. and demanding a share of royalties on the Coenzyme A plays a key role in both the antibiotic. At this point, Waksman recalled Krebs cycle and many other vital prrwesses. a few years later (though without mention- Between 1927 and 1930 its discoverer, Lip- ing Schatz by name), ‘‘1felt a moral obliga- mann, had worked in the same building as tion to my associates, to my university and Krebs in Berlin at the Kaiser Wilhelm In- to all others who had supported my work stitute for Biology-he under Otto Meyerhof throughout many years, who would have and Krebs under Otto Warburg.
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