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Home , Gerhard Domagk, Hans Krebs (biochemist), Horace Freeland Judson, Stanford Moore

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I%e 102 Most-Cited Life-Sciences Pubkatims in the New 1945-1954 Science Citation Index. Part 2. Wonder Drugs, Ceil , 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, Biochemistry, $eparation Techniques Highlight Major TrerIds of Post-Worki War II Decade

Bernard Dixon 132 High Street Uxbridge, Middlesex UB8 lDP

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 , and pi- of Biological Chemistry by American bio- oneered the use of liver extracts to treat per- 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 (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 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, , 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 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 . 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 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 , 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 . 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 were 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- 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 . The (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 or medicine. Then fol- 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 . 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 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. Lipmann been invoived in the drawn-out and unpleas- left Germany in 1931 for The Rockefeller ant legal procedures. I reached the conclu- Institute, , and later went to Co- sion, not without great reluctance, that the penhagen before emigrating permanently to situation made a speedy disposition of the the US in 1939. When the two met in Stock- lawsuit essential.’”1 So Waksman agreed holm for the Nobel Prize ceremony in De- that Schatz should be legally recognized as cember 1953, Liprnann’s wife Freda dublxd co-inventor of streptomycin, and that he them ‘‘brothers-in-arms,”5

111 A paper co-authored by two more Nobel Another scientist who made a distinctive laureates in the 1945-1954 listing again con- series of contributions to the emergence of firms the often under-estimated importance a coherent picture of vitaf processes at the of experimental methods in science. Pub- molecular level was the Rumanian-born cy- lished by Stanford Moore and William H. tologist George E. Palade. Honoured with Stein in 1948, it received about 400 citations the 1974 Nobel Prize in physiology or med- over the lo-year period and described a pho- icine alongside the Belgian-born Albert tometric ninhydrin technique for use in chro- Claude and the Belgian (though English- matographing amino acids. Moore and bom) , Prdade was the dis- Stein, who began working together at The coverer of the ribosome, the nucleoprotein Rockefeller Institute in the early 1940s, particle on which proteins are assembled to shared the 1972 match sequencing instructions encoded on with Christian B. Anfinsen of the National messenger RNA. Co-authored with G. H. institutes of Heafth, Bethesda, Maryland, for Hogeboom and Walter C. Schneider, research which opened a new era in our un- Palade’s 1948 description of another cdl or- derstanding of the structure and function of ganelle, the , was cited on enzymes. over 325 occasions over the 1945-1954 de- Taking a different approach from that of cade. In this paper, as in all of his work, Sanger, Moore and Stein decided to produce Palade’s signal contribution was to correlate columns with which to separate the amino the structure of subcelhdar particles with acids releastd when proteins are hydrolyses. their functions. Palade settled in the US in By 1948, they had introduced a column, 1946 and became a naturalised US citizen packed with starch granules, that was capa- six years later. He worked in various capac- ble of resolving the amino acids from as lit- ities at The Rockefeller Institute untif tak- tle as one milligramme of hydrolyses pro- ing over the Department of Cell Biology at tein. By moditjing the existing ninhydrin re- Yafe University School of Medicine, New agent, which reacts with amino acids to give Haven, Comecticut, shortly before winning a purple color, they had also evolved a meth- the Nobel Prize. od of measuring the quantity of individual The final Nobel laureate in the 1945-1954 acids as they came off the column. Within listing is renowned more for his clinical 10 years, starch had been supplanted by ion- achievement than for a contribution to sci- exchange resins, and the technique had been ence per se. He is Andr6 Coumand, a automated to produce the earliest of the French physiologist who went to live in the modern generation of amino-acid autoana- US in 1930 and became naturalised in 1941. Iysers. Working with Dickinson Woodruff Richards These instruments reduced dramatically at the Columbia University Division of the amount of work involved in studying the Bellevue Hospital, New York, it was Cour- primary structures of proteins, which in the nand who was largely responsible for estab- case of some large molecules was so labo- lishing cardiac catheterisation as a safe, rou- rious as to be virtually impossible. Five tine technique. years after Sanger’s 1955 work on insulin, In 1929, a young intern at a small pro- Moore and Stein used their new technique vincial hospital near Berlin, Werner Forss- to determine the prima~ structure (the mam, inserted a catheter into a vein in his amino-acid sequence) of ribonuclease, an left arm and threaded it into his heart.b But enzyme that splits ribonucleic acid (RNA) such was the danger in this heroic procedure into its subunits. Ribonuclease was the first that Forssmann was thrown out of his hos- enzyme to be sequenced, and Ardinsen later pital by the distinguished surgem Ernst Fer- determined how the amino-acid chain of the dinand Sauerbmch, and the technique did enzyme folds into its characteristic three-di- not gain wide acceptance. Twelve years la- mensional structure. ter, however, Coumand and his colleague

112 H. A. Ranges published a paper in which Mirsky may have intluencexithe Nobel Prize they described modifications making the commitsee.g At a Cold Spring Harhr Sym- procedure safer and demonstrated that the posium in 1947 Mirsky argued vociferous- pulmonary artery could be catheterised too. ly against the proposition that DNA had heen It was cited over 220 times between 1945 identified as the specific carrier of heredhary and 1954. Cournand developed an improved information. (Ironically, perhaps, a 1947 method of passing the tube into the vein, and paper on nucleoprotein co-authored by Mir- showed that a tube made of woven material sky and A. W. Pollister received about 235 strengthened with plastic was sufficiently citations in 1945-1954, just short of the stiff to transmit pressures accurately but not Avery paper.) so stiff that its introduction into the heart The official Nobel book Nobel: 7he Man would b dangerous. In 1956, Coumand, and His Pn”.zes states that Avery accom- Forssmann, and Richards shared the Nobel plished “one of the most important dis- Prize in physiology or medicine, and the coveries of modem biology” and that’ ‘the technique has now become a standard pro- discovery, because of its far-reaching im- cedure for investigating heart mrdfunctions, plications, aroused much interest. ” The text as well as being used in research. continues: “Avery was proposed for a No- bel prize. But doubts were rdso expressed, and the Nobel Committee found it desirable to postpone an award. Acturdly, Avery’s Other I-@Mighta of the Decade finding was not accepted in all quarters un- A “Nobel Prize that never was” is sym- til A.D. Hershey and M. Chase, in 1952, bolised by tie appearance in the 1945-1954 demonstrated that bacteriophage-DNA car- listing of the paper entitled “Studies on the ries the virrd genetic information from parent chemical nature of the substance inducing to progeny.”9 McCarty adds a significant transformation of pneumoeoccal types, ” rider: “They do not comment on the fact published by Oswrdd T. Avery, Colin M. that Avery lived for three years after MacLeod, and Maclyn McCarty in 1944. A 1952. ”8 core paper to one of ISI@’s research fronts With over 2S0 citations over the decade, for 1987, as mentioned in Part 1,1 this was the paper in which D. D. Woods revealed a key contribution which paved the way for the mode of action of the ‘‘stdpha drugs” the discovery of the DNA double helix and might also have led to a Nobel Prixe had it thus for the development of modern molec- initiated an era in which improved antimic- ular biology. Cited over 235 times over the robial agents could he designed for their decade, it showed for the first time that a specific actions against and other particular chemical substance, DNA, plays microorganisms. The sulphonarnides, intro- a role in altering the hereditary make-up of duced following work by German bacteri- an and that it is capable of repro- ologist in the mid- 1930s, ducing itself precisely “in amounts far in were the first worthwhile antimicrobial excess of that originally added.”7 The drugs, and it was Woods, together with Sir paper was doubly impressive for the vari- , who found out how they work. ety of experimental techniques which Avery Para-aminobenzoic acid (PABA) is an es- and his Rockefeller Institute colleagues sential nutrient for many bacteria, and the brought to bear on the problem. sulphonamides, whose structures closely re- Yet this primordial work was not recog- semble that of PABA, compete with it for nized by the Nobel accoiade. In his book 7he a site on the enzyme that normally handles Transforming Principle: Discovering tit the nutrient. Are Maa’eof DNA, McCarty suggests There were high hopes that pharmacolog- that strongly and publicly expressed skepti- ists could exploit this “competitive inhibi- cism from former collaborator Alfred E. tion” to block the uptake of other vital nu-

113 trients by disease-causing microbes, and to Schneider confessed that his discovery interfere with other aspects of microbial me- rested in part on his misreading of one of tabolism. But such hopes were largely dis- Zacharias Dische’s papers in the Biochern- appointed. In practice, things have worked isches 22itschnj?. 10 the other way around. From penicillin on- Schneider’s paper appeared in the very wards, most have km dis- same issue of the Journal of Biological covered more pragmatically, by screening Chenu”stryas one on nucleic acid determina- likely producers. Only cg’?erwwrdshave they tion by Gerhard Schmidt and S.J. Thann- been used to reveal those metabolic pro- hauser-which also occurs in the 1945-1954 cesses that might have provided targets for listing, with about 415 citations. Schneider rational attack. spotted the strengths and wdmessea of both Aside from books and papers devoted to tdniques, combined the best features of methods, the remaining highly cited books each, and published a fhrther paper the fol- and papers of the decade range over the en- lowing year. tire landscape of biomedical science. The Three other research workers widely achievements recorded here include Leonor known for their scientific achievements but Michaelis and M.M. L. Menten’s descrip- emerging here as technical imovators are tion of the equation which explains the rate the US poliomyelitis vaccine pioneer Jonas of variation of enzyme-catalysed reactions E. Salk, French-born microbiologist Ren6 in relation to the concentrations of reacting 1. Dubos, and the Canadkn biochemist and substances (over 235 citations); and the iso- J.B. CoUip. Salk’s report on a lation of vitamin B12, used to treat perni- method of titrating the hemagglutinating ca- cious anaemia, by E.L. Rickes, Karl pacity of influenza virus was cited over 240 Folkers, and co-workers (about 225 cita- times. Dubos’s work with B.D. Davis on tions). Two papers under the name of Edwin the culture of tubercle bacilli was cited on Bemett Astwood (about 235 and 225 cita- about 240 occasions. tions) describe work which led to the use Collip is famed largely for his contribu- of thiouracil to treat exophthalmic goiter. tions to the discovery of ACTH and for iso- Fuller Albright’s Harvey hctwes on lating parathormone from the parathyroid Cushing’s syndrome attracted almut 220 ci- gland and introducing it in the treatment of tations, as did his review with E.C. Reifen- tetany. He also collaborated with Charles stein of the pa-athyroid glands and metabolic Best in purifying insulin. When the 1923 bone disease. Nobel Prize in physiology or medicine went solely to their colleagues Frederick G. Ban- ting and John J.R. MacLed (who had The Importance of Techniques played no active part in the work), Banting In addition to those already mentioned, 44 :xpressed his dissatisfaction by sharing his other papers are devoted solely or principal- half of the money with Best, whereupon ly to methods. American enzymologist Van MacLeod gave a corresponding part to Col- Rensselaer Potter of the University of Wis- Iip. In the 1945-1954listing, Collip received consin, Madison, received about 515 cita- about 245 citations for a paper (with E. P. tions for his paper with C.A. Elvehjem de- Clark as principal author) on the measure- scribing a new approach to tissue oxidations, ment of serum calcium. and over 250 citations for a paper on the as- In addition to Consden, A.H. Gordon, and say of respiratory enzymes, of which Martin, whose work was discussed earlier Schneider was principaJ author. A paper by md who were the joint authors of two papers Schneider on the estimation of nucleic acids {about240 and 885 citations), the names of (based on his doctoral dissertation under !hreeother innovators in laboratory methods Potter as his supervisor) also received about ippear twice in the listing. Particularly fa- 540 citations. Recalling this work in a miliar to biochemists is that of the Swedish Citation Classic essay 22 years later, >hemistOtto Folin. In 1912 he reported new

114 micromethods of determining urea, total ni- sarcoma usually affecting the shafts of long trogen, and ammoniacal nitrogen, but ap- bones, received over 290 citations. One of pears here for his work on amino acids and the books, by D.H. 13ergeyand R.S. Breed, blood SOS@SiS./dthOU@ FolitIdiedin 1934, Manual of Determinative Bacteriology, is his two papers (the fwst co-authored with the bacteriologist’s’ ‘bible,” successive edi- V. Ciocaheu and the second with I+. Wu) tions of which present the currently accepted received about 290 and 260 citations, re- classification of bacteria into orders, fami- spectively, in 1945-1954. G. Gomori reg- lies, genera, and species. The sixth edition, istered over 260 and 330 citations for papers published in 1948, rated about 255 citations. on the determination and distrihtion of Only one of the listed books is in a language phosphatase, while S.M. Partridge received other than English—L. Lison’s Histochimie about 225 and 550 citations for imovations Animale, which was published in in in partition chromatography. Another nota- 1936 and received about 220 citations. ble name is that of the English geneticist and pioneer statistician Sir Ronald A. Fisher, Conclusion who rated over 230 citations for a contri- In terms of overall trends, ISI’s scrutiny bution on statistical methods for research of citations in the life-sciences literature of workers. 1945-1954 has thrown up some unexpected findings and underlined a crucial but often Books underestimated aspect of research. One sur- As well as those discussed previously, 12 prise is the fact that of the 102 items in the books appear in the list. Especially signifi- list, is the subject of only 2–the cant is Hans Selye’s Stress: Zhe Physiology books by Ewing and R.A. Willis. Thk is and of Exposure to Stress, which a reminder, perhaps, of how litie was sets out hk pioneering work on the ‘‘gen- known about cancer and carcinogenesis in eral adaptation syndrome. ” Selye unified the first half of this century. Real scientific our understanding of this condition, which understanding of malignant disease (whether is mediated by the hormones of the adrenal through molecular biological research into cortex, orchestrated by the pituitary gland, oncogenes or epidemiological studies such and includes energy mobilisation, shrinkage as those linking smoking with carcinoma of of the lymphatic organs, and inhibition of the lung) has developed much more recent- allergies. Although published only in 1950, ly. Somewhat surprising toois the small the book had registered over 250 citations number of papers— 10 at most—which are by the end of the decade up to 1954. Selye concerned with communicable diseases. Yet was born in Vienna and educated in Hun- the listing does include key papers on three gary, Czechoslovakia, France, and Italy be- of the major highlights (arguably the major fore settling at McGill University, Montre- highlights) of antimicrobial warfare-the al (where he was for a while a research stu- successive introduction of sulphonamides, dent under Collip). He also received about penicillin, and streptomycin. 665 citations for a paper on adaptation pub- The major themes emerging from the lished in 1946, which became the tirst paper study are the maturing of endocrinology as ever subjected to citation analysis. 1I a scientific discipline and the laying of the Of the remaining books, the largest num- foundations of . No less ber of citations (over 480) was to C.L. than 21 of the highly cited items, including Hull’s Principles of Behavior: An Introduc- those by Selye and by Hench and his tion to Behavior Zheory, wldle Joseph Need- co-workers, concern various aspects of hor- ham’s classic Biochemistry and Morphogen- mones, their mtural functions, and their esis was cited about 260 times. Neoplastic therapeutic potentird. It was in 1936 that the Diseases: A Treatise on Tumors by the American biochemist Edward Doisy pro- American pathologist James Ewing, who pi- posed the criteria by which endocrinology oneered radhun treatment and described a could become an established area for scien-

115 tific investigation. The items in the 1945-1954 citation study clearly reflect that process of authentication and maturation. The second largest group of items(13 in all) describe various aspects of investigations into proteins and nucleic acids—the macro- molemdes upon which life depends and whose study is the centrepitxe of molecular biology. Particularly noteworthy are the high scores recorded by Moore and Stein and by Martin and Synge (and Consden, Gordon, and Martin) for their innovations in chromatography. As confirmed by this ci- tation study, the work of the 1952 Nobel lau- reates Martin and Synge and the 1972 lau- reates Moore and Stein was enormously in- fluential. It was crucial to the later achieve- ments of Sanger and others in determining Bernard Dixon the structures of key enzymes and other macromolecules. AUthe more strange, then, 1945-1954, science is by no means all about that Horace Freeland Judson’s monumen- theories, speculation, and purely intellectual tal and otherwise highly impressive history revolution. of molecular biology, published in 1979, faifs to mention any one of those four imo- ***** vators in technique. 1z As vividly demon- strated by those individuals, and by the My thanks to Maria Luisa De Gu.unan and emergence of methods as the basis of about Eric i’?wrschwell for their help in the half of the most heavily cited papers in preparation of this essay. o:W7m

REFERENCES 1. Dixon B. The 102 moat-cited life-sciences publications in the new 1945-1954 Science Cikzrion Index. Part 1. Titles, jnurnals, and research fronts, Current Content$ (15):4-10, 10 April 1989. 2. Cdmmr W G. Citation Clrtssic. Commentary on Statistical methods applied to experiments in agriculture ond biology. Ames, IA: Iowa State University Press, 1956, (Barrett J T, ed. ) Contemporary clarsics in the Ife sciences. Volume 2: the molecules of lye. Philadelphia: 1S1 Press, 1986. p. 251. 3. Nefmn N. Citation Classic. Commentary on J. BioL Chem. 153:375-80, 1944. (Barrett J T, cd.) Contemporary classics in the li~e sciences, Volume 2: the molecules of lfe. Philadelphia: 1S1 Press, 1986. p, 3. 4. Wakssnan S A. My life with the microbes. Lxmdon: Hale, 1958. p. 284. 5. Kreba H. Ham Krebs: reminiscences and ref7ectimhr. , UK: Cfarendon Press, 1981. p. 168. 6. Forasrmmn W. Experiments on myself memoirs of a surgeon in Germany. New York: St. Martin’s fkss, 1974.352 p. 7 Avery O T, Ma&eod C M & McCarty M. Studies on the chemical nature of tfte substance inducing transformation of pneumacnccal types: induction of transformation by a desoxyriknmcleic acid fraction isolated from pneunwccccus Type III. J, Erp. Med. 79:137-58, 1944. 8. McCarty M. Jle transforming principle: discovering that genes are made of DNA. New York: Nofion, 1985, p. 219. 9. Nobel Fourtdatinn & Odelberg W, eds. Nobel: the man and his prizes. New York: American Elsevier, 1972. p. 201. 10. Schneider W C. Citation Classic, Commentary on J. BioL Chem. 161:293-303, 1945. (Barrett J T, cd.) Contemporary classics in the life sciences. Volume 2: fhe molecules of life. PhiLade@biw 1S1 Press, 1986. p, 60. 11. Garfield E. Citation indexes for science. A new dimension in dmuncntation through association of ideas. Science 122:108-11, 1955. (Reprinted in: Ersays of an information $cientist. Philadelphia: 1S1 kSS, 1984. Vol. 6. p. 468-71,) 12. Judams H F. 7he eighth &y of creation: rrmkers of the revolution in biology. New York: Simon & Schuster, 1979.686 p.

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