@Mrwemt gammsnts” EUGENE GARFIELD INSTITUTE FOR SCIENTIFIC INFORMATION* 3501 MARKET ST, PHI LADE LPHIA. PA I9104 The 1985 NAS Award for Excellence h Scientific Reviewfng Goes to Ira Herskowitz for I-Ifs Reviews of Phage Biology

Number 16 Amil 22.1985

Ira Herskowitz, molecular biologist, ioral sciences. This year, Herskowitz has been awarded the 1985 National was selected from among a number of Academy of Sciences (NAS) Award for outstanding candidates in the biological Excellence in Scientific Reviewing. sciences. The last recipient of the NAS Editor of the Journal of Molecular Biol- Award for reviews in the biological sci- ogy, and professor in the Department of ences was Victor McKusick, Johns Hop- Biochemistry and Biophysics, University kins University School of Medicine. He of , , Herskowitz was recognized in 1982 for his reviews of will receive the award at the academy’s basic and clinical aspects of human 122nd annual meeting in Washington, genetics. 1 DC, on April 22. The NAS cited Herskowitz for his “in- He is the seventh scientist so honored, cisive reviews of phage biology, ” partic- and, at the age of 39, is the youngest ularly for his 1973 and 1980 reviewsz,s of among th~ group of outstanding authors bacteriophage lambda, His most-recent of scientific reviews. I hope this will en- review on lambda has just been pub- courage other young scientists to write lished.q Bacteriophage lambda is a bac- reviews. terial virus that has been used extensive- IS I@ and Annual Reviews Inc. have ly by geneticists to study how certain cosponsored this award and its $5,000 genes are turned on and off in the micro- honorarium since its establishment in organism Eschen”chia coli (E. coli). Un- 1979. The award honors James Murray like most viruses, which invariably Luck, who founded Annual f?evie ws and replicate themselves within cells and served as its editor-in-chief until his destroy the infected host cell, the bac- retirement in 1969. Luck remains on the teriophage lambda does not always kill edltonal committee of the Annual Re- the E. coli cells that it has entered. In vie w of Biochemistry, which he started fact, under some environmental condk in 1932, and on the board of directors of tions, infection of E. coli with bacterio- Annual Reviews Inc. phage lambda results in a “lysogenic The NAS Award recipient is selected response, ” in which the host cell survives by an independent committee appointed and stably acquires the genetic material by the NAS. Neither 1S1 nor Annual Re- of the bacteriophage. views is involved in the nomination of Herskowitz was cited by the NAS for, candidates or in the selection oi the re- among other things, hk discussions of cipient. The discipline from which re- gene regulation and cell physiology that viewers are chosen rotates annually govern whether infection with bacterio- among the biological sciences, the phys- phage lambda either kills the host cell ical sciences, including mathematics and (the lytic response) or becomes incorpo- engineering, and the social and behav- rated in the cell’s genetic material (the

151 interest in yeast and lambda genes stems from the same “ultimate question . ... How do you turn genes on and off? Put another way, what molecular mecha- nisms are responsible for an undtiferen- tiated cell deciding to become, for ex- ample, a liver or brain cell?”T In 1972, Herskowitz joined the De- partment of Biology and Institute of Mo- lecular Biology at the University of Ore- gon, Eugene, where he eventually be- came a full professor. In 1981, he moved to the Department of Biochemistry and Biophysics, University of California, San Francisco, where he is professor and head of the Division of Genetics. In ad- dition to teaching and continuing his research, Herskowitz became vice chair- man of his department in 1982. In 1983, the American Society for Microbiology, the American Associa- lysogenic response). His own research tion of Immunologists, and the Ameri- has contributed to the understanding of can Society for Experimental Pathology this lysis-lysogeny decision. recognized Herskowitz’s contributions to lambda and yeast biology by awarding hlm the 1983 Eli Lilly Award in Blographkal Information Microbiology and Immunology. The Born in 1946 in Brooklyn, , award, which is accompanied by a Herskowitz was raised in the Midwest. $2,000 honorarium, is given annually to His decision to enter the field of genetics a researcher under 35 in the US or is fitting, since he is an identical twin (his Canada for fundamental research in mi- brother, Joel, is a pediatric neurologist crobiology or immunology. in Boston) and his father, Irwin H., is a Herskowitz is currently president of Drosophila geneticist and author of a the Genetics Society of America, editor widely used textbook on genetics. s of the Journal of Molecular Biology, and Herskowitz was introduced to bacte- associate editor of both the Annual riophage genetics at the California Insti- Review of Genetics and Genetics. He tute of Technology, Pasadena, where he also is on the editorial board of Mo[ecu - received his BS degree in 1%7. He did lar and Ce[lular Bioiogy. He has also his doctoral work on bacteriophage served as associate editor for Virology, lambda with Ethan R. Signer, in the De- and has lectured extensively throughout partment of Biology, Massachusetts In- the US, including special lectures at stitute of Technology (MIT), Cam- Notre Dame, Wkconsin, Harvard, and bridge. The 1970 papefi based on this re- Princeton. search was cited in at least 100 subse- quent publications. Herskowitz re- Why Write Reviews? mained at MIT for postdoctoral work with , in the Department Why does this obnously busy person of Biology, during which time he also take on the demanding task of writing served as an instructor in the same scientfilc reviews? The primary reason is department, During this period, he a desire to make bacteriophage lambda began to do research on yeast gene ex- understandable to as wide an audience pression. Herskowitz explains that his as possible. He explains: “I know that

152 the areas in which I’ve written reviews mal communication processes of science are considered arcane and incompre- are often crucial elements in the ad- hensible. So much is known about lamb- vances reported formally in the liter- da that unless you’re working in it, it’s in- ature. accessible. That’s where I hope I’ve been successful—in making it accessible to Research Front Data people.”7 Like several other winners of the NAS Herskowitz has published more than Award, Herskowitz perceives the signifi- 50 papers since 1970, which together cance of the relationship between re- have received more than 1,400 citations. view writing and teaching. In both, he These papers are divided between publi- tries to communicate the link between cations dealing with lambda genetics information and ideas. He explains: “A and publications on yeast genetics. nucleotide sequence or a mutant is just These latter papers deal largely with the raw data. The important step is to take mechanism by which yeast ceil type is this information and make logical and determined. This work centers around critical deductions based on it. I try to studying the regulatow genes coded by a stress that in teaching, in individual re- master regulatory locus. Herskowitz and search projects, and in review articles.”T hk colleagues have also extensively In addition to emphasizing the link be- studied the process by which a cell of tween ideas and information, Hersko- one sex will give rise to a cell of the op- witz tries, in his reviews, to create what posite sex, which, in turn, will produce a he terms “documents of record.. .a pic- cell of the same sex as the first cell, They ture of the state-of-the-field at a given have developed a “cassette” model for time.” He cites as examples of thk per- this process, which compares the activi- spective the “fabulous amount of prog- ty of the mating genes in the cell to a ress” made and recorded in hk reviews tape recorder with interchangeable between 1973 and 1980. He notes, cassettes. Briefly, they compare the site “There is an obvious progression from on the chromosome that regulates the one review to the next. The fwst review cell’s sex with the “playback” function of said that we know a lot but we still don’t a tape recorder, and the sex-determining know what we want to know about lamb- “jumping” genes that occupy that site in da. The second one said that we know a alternate generations with inter- lot more, and now we have a pretty clear changeable cassettes.g One of Hersk& idea of what we want to know. “TAppar- witz’s papers describing thk modello ently, these reviews have been more is a core document in research front than “hwtorical records.” The 1973 #82-2456, “Regulation of yeast mating paper has been his most-cited and per- type: transposition, chromatin struc- haps most-influential publication.z His ture, and control of transcription.” 1980 paper3 has already been cited at A list of Herskowitz’s review papers is least 70 times. included in the references cited at the Frank Stahl, who was Herskowitz’s end of this essay .z-d,11-13As mentioned colleague in the Department of Biology, earlier, his most-influential work is the , provides another 1973 paper in Annual Review of Genet- perspective on Herskowitz’s talent for ic~, The role this review has played in reviewing. He describes Herskowitz as phage lambda research is evidenced 6’...a walking encyclopedia in the areas from the fact that it is a core paper in two in which he works.” Stahl notes that of the 1S1 research fronts shown in “.. .if I need a review of anything about Figure 1. This historiograph, or string of lambda biology or yeast biology, I have annual research fronts, shows the evolu- only to telephone him and I will get an tion of phage lambda research from 1977 authoritative review on the spot.”g This to 1983. The map actually dates back to is a special gatekeeper talent. The infor- 1973, beginning with a front named

153 F@IW I: Hi.storiogrsph (cluster string) of gene expression and mapping, Numbers in parentheses represent the number of core/citing papers

82.3777 Mapping and Packaging of fla~m~~ge

(2/20) ‘

.90.0363 Leader RN As, Oper .“ i /

i 7R.WA5 I ~ ?,4’%4%!!%%%

6;’ii~T’’’”~--.(9/116)..,.- ~“ GiiiL” Y B2.0284 Local, zatmn and Regulatlcm of Genes Requm?d for Termm.a tmn and A.tfterm ma.

“?: %:%::;:1{;:

\ 830239 J t.lappmg and Gene Structure)n E COII and Other Bacteria and Plasmfds, m wtro 78.0820 790814 Transcription” RNA- 77.0944 Integrative Polymerase Isolat[on Nucleot4de Recombmant Recomb, nawm of 82-WY3 (1 OI471) Sequence of Identlfmatlon. DNA Cloning Bacieopl:ge / Transposcms Nucleot#de Se uence ( 12/245) Analys@. and ‘% NA- (4/85) (5/59) r .Po$yw!e@e Rf!cogn,- moters and

Reg @;’%~ Y \ 1

770872 79.1525 13actenophage Recomblnatlon 1“ Lam b::n:t;tor I. Bac;::b;:ge Recombmatao. (3/60) (6/103} ‘n “Bacteriophage lambda mutation.” and RNA-polymerase isolation. ” TO However, we have not reproduced the show the relationship of that front to entire map because it would occupy an other areas of molecular genetics re- inordinate amount of space. We are able search, we’ve also included a higher- to detect the linkages from year to year level map showing the more general re- by identifying the core documents that search area “cDNA cloning, gene struc- continue to be co-cited. As research in a ture, RNA activity expression and pro- particular field diversifies, the research tein structure. ” The multidimensional fronts themselves split, merge, or disap- scaling map in Figure 3 was created by pear, and new fronts appear. For exam- clustering research fronts, a process I’ve ple, Herskowitz’s 1973 review was fre- explained before, to illustrate the rela- quently cited in 1977 by researchers tionships ,between subspecialt y areas. working in an area appropriately named Research front #83-0239 is closely relat- “Regulation of gene expression in bac- ed to two other fronts on this map, Two teriophage lambda.” Then the review of these, represented by the points, emerged again as a core paper in re- #2825 and #8552, concern genetic stud- search front #82-0284, which we named ies of DNA sequences and #3810 deals “Localization and regulation of genes re- with the interaction of E, coii RNA-poly- quired for termination and antitermina- merase with DNA promoters in regulat- tion of transcription in bacteriophage ing transcription. For each of these, lambda, E. coli and other cells.” The there is another group of annual core eight core papers that identify thk 1982 papers, many of which can be observed front are shown in Table 1. in the ISI A tlas of Science: Biotechnolo- Citation curves for Herskowitz’s 1973 gy and Molecular Genetics. 14 To save and 1980 papers are shown in Figure 2. space on Figure 3, we have omitted four As you can see from one of the curves, research fronts linked to #5606. They are the 1973 review continues to be cited #3219, #4002, #5673, and #8040. even though it may not meet the two One of the “reviews” of which Hersko- criteria required to be included in the witz is particularly proud is unusual in core for each year, that is, citation fre- that it is a posterls that pictorially sum- quency and co-citation strength. For this marizes hk 1980 lambda review. De- reason, it was not included in the 1983 scribed as “whimsical and informative” core. Nevertheless, the appropriate 1982 in his NAS citation, the poster includes frent, #82-0284, mentioned above, was more than a dozen panels describing the linked to 1983 front #83-0239, “Mapping function of the lambda gene. Herskowitz and gene structure in E. coli, other bac- says that he created it at the prompting teria and plasmids; in vitro transcription of Stahl, who had originally asked hlm

Table 1: Core papers irr SCF’ research front #82-02E4, “Localization and regulation of genes required for termination and antitertnination of transcription in bacteriophage lambda, E, co/i and other cells.”

Adbya S & Gottesmmr M. Control of transcription termination. Armu, Rev, ffiochem. 47:%7-%, 1978. Das A, CoUrt D & Adhya S. Isolation and characterization of conditional lethal mutants of .?. co/i defective in transcription termination factor RHO. Proc. Nat. A cad. Sci. US 73:1959-63, 1976, Hemkowltz I & Hagen D. The Iysis-lysogeny decision of phage L: explicit programming and responsiveness. A mu, Rev, Genet. 14:399-445, 1980, Platt T. Termination of transcription and its regulation in the !ryptophan operon of E. co/i. Cc// 24: l@23, 1981. Roberts J W. Termination factor for RNA synthesis. Nature 224:1168-74, f%9. Rosenberg M, CourI D, Shfnmtake H, Brady C & Wrdff D L. Relationship between function and DNA sequence in an intercistronic regulatory region in phage-i. Nature 272:414-23, 1978. Saktrom J S & Szybatski W. Coliphage .brufL-: a unique class of mutants defective in the site of gene N product utilization for antitermirration of leftward transcription, J, Me/. Biol, 124:195-221, 1978, Shfmatake H & Rosenberg M. Purified A-regulatory protein cII positively activates promoters for Iysogenic development. Nature 292: [28-32, 1981,

155 FlmIm 2: Cbronoloeic distribution of citations to Hemkowitz’s 1973 (sotid line) and 1980 (dotted line) Dam’s. 7 m Annuaf Review of Genefics.

# A Pi :1 \ /’ \~, 1

0 I I I I I I r I I 1 I 1974 1975 1976 1977 1978 1979 1980 1981 :982 1983 1984

YEARS to write a review of bacteriophage lamb- award recipients have offered a variety da for the Cold Spring Harbor Labora- of explanations for their decisions to tory bookls that now includes the post- write scientific reviews. John S. Chip- er. Herskowitz said that in creating man, professor of economics, University the poster, he was trying to “conceptual- of Minnesota, Minneapolis, who won ize and demystify major messages the award in 1981, lb took special satis- learned from studies of lambda,” and faction in combhdng the synthesis of in- hopes that it is useful “for people at all formation with original thought in his different levels of familiarity with lamb- reviews. The 1983 recipient, Michael da.”7 He adds, “I would like people to Ellis Fisher, Horace White professor of stare at each panel of the poster and chemistry, physics, and mathematics, think about it. I tried to make the poster Cornell University, Ithaca, New York, like lambda itseff-further thought leads found that writing reviews contributed to deeper insights.”T to his own research by helping him “re- In these essays on the NAS Award for think current understanding and in- Excellence in Scientific Reviewing, the sight.”17whateverthereason,theim-

156 FlgrIre % Multidmenakmal scaling map of research fronts on “cDNA cloning, gene structure, RNA activity expression and protein structure.” A= 1983 research front number. B= research front title. For each named research area there is a group of two or more core documents identified in 1983.

A B

83-0239 Matrrrin~. ..- and gene structure in E. coli, other bacteti and plasmids; in vifm transcrintiOnr and RNA-polymerasx isolation 83-0514 Synthesis. chemical modiilcation and biochemical characterization of histone variants associated with cell differentiation and changes in cell growth 83-0664 Methods of biosynthesis of DNA and cDNA cloning into E. co/i in the production of human insulin 83-0692 Immunochemical identification of proteins after transfer blotting characterization of DNA bkdksg proteins 83-0693 Gene sequences and isolation of cDNA clones; characterization and transcription of messenger RNA

157 A B 83-0837 Applications of high-resohrtion two-dimensional protein electrophoresis to protein phospho@ation and other chemical modifications 83-1010 Prenatal diagnosis of @-thalassemia by DNA polymorph~m: restriction enzyme mapping and structure of globin gene fW1430 cDNA cloning from mexsenger RNA in E. cofi as probes of virus and eukaryote gene and protein stmcture 83-1501 Gene expression, regulation and cloning in E. coli K-12 and its mutants &3-1740 Oncogenes and the genetics of human cancerx; viral transforming genes and their DNA structure 83-1891 Role and arrangement of nucleosomes, histories and other proteins in the organization of the nuclear matrix and the structure of the chromatin DNA 83-2270 Isolation, expression, cloning and related studies of .$accharomyces cere visiae and other yeast genes and plasmids 83-2424 Nucleotide sequence of eukaryotic globin genes; characterization by messenger RNA analysis; use of viral gene expression and other in vifm modefa 83-2480 Transposable genes and TN5 insertion in Drnsop/ri/a melanogaster and E. coli; evolution of transposon DNA sequences in eukaryotes 83-2538 Gene transcription, expression and sequence including proteirr structure and RNA activity 83-2783 Transposable gene elements and hybrid dysgenesis in Drosophila mebrogaffen role in evolution 83-2808 DNA methylation; sequence structure and effect on gene activity 83-2825 Molecular cDNA cloning of genes in E. coii; rrucleotide sequence and protein structure fW24N2 Transcription of cfaxs Iff tranxfer RNA genes by RNA-polymeraw IfI in Xenopuf faevis and other eukmyotes 83-3142 Charactetiation of proteins via immunochemical and biochemical methods; rapid detection and modifications related to activity 83-3810 Characterization of E. cofi RNA-polymerase and its interaction with DNA promoters in the regulation of transcription 83-4037 Characterization of gene polymorphism in yeast, Saccharomyces cerevisiae; transcriptional and post-transcriptional regulation during development and differentiation in eukaryotex N-4111 Genetic analysis of gene expression in E. cofi and yeast by gene fusions: characterization of mutations of promoter regions E3-4840 Characterization of factorx affecting messenger RNA synthesis, activity and degradation; gene expression measurement by evaluation of in vitro translation products 83-5438 Transposable DNA sequences and satellite DNA in Drosophila; role of repetitive elements in evolution 83-5606 Processing of mex.senger RNA of murine immunoglobulin and hiatocompatibility genes: cDNA probes to study B cell regulation 83-5653 Nucleotide sequence of human and mouse genes as took to study evolution; cDNA for p-globin 83-5910 Analysis of mutagenesis and rrucleotide sequence of genes of E. coli. yeast and other eukaryotes; mutations by frame-shifting, ultraviolet radmtion, repeated sequences, hyper- variable sites and slipped mispairing 83-6017 DNA sequences, properties and mutants of simian virus-40 and polyoma virus 83-6485 Molecular cloning of human genes; enzymes, fibronectin and hiatocompatible antigen genes 83-6758 Avian virus oncogene products; characterization of trarrxforming proteins and induction of lymphoma in chickens ?$6764 Gene expression and relation to transformation in mammary tumor viruses, adenoviruses and mouse-human cell hybrids 83-7023 Cloning, isolation, and sequence analysis of cDNA and messenger RNA for genes from humans and other animals 83-7332 Repetitive DNA sequences in the organization of human genomic families 83-7918 Transposons of E. coli and Salmonella fyphimun”um: mutagenesis and construction of new gene elements 82-7997 Nucleotide sequence and gene structure of tumor and virus antigerr$ cap structures of messenger RNA 83-8138 Regulation of human globin genes; endonuclease and structural DNA studies in thalaxxemia 83-8418 RNA transcription in vitro; initiation and expression and charactcmkzation of RNA- polymerases 83-8546 Methods of protein pufllcation arrdcharacteriz.ation using silver-staining and twm dimensional polyacrylamide gel eleclrophoresis 83-8552 Genetic studies of DNAnucleotide sequerrces, protein acti~ation, messenger RNA structure and related topics

158 A B 83-8577 Transcription of ribosomal RNA genes in Xenopus Iaevis mice and E, coli 83-8788 Twmdimenxional gel electrophoresis in the characterization of protein synthesis and expression in ceiis 83-8889 DNA-mediated gene transfer and expression of herpes simplex virus thymidine kinaze gene in mammafian celfs 83-89(Y3 Expression of genes including the thymidkie kinase gene and the stability and inhibition of mammafian cell transf ornraiion

portance of critical reviews in making in- of the Home Secreta~, National Acade- formation accessible and meaningful my of Sciences, 2101 Constitution Ave- should not be underestimated. It is one nue, Washington, DC 20418. of our most valuable intellectual cre- ations in helping to overcome informa- ***** tion overload. Next year’s NAS Award will be pre- sented for reviews in the physical sci- My thanks to Joan Lipinsky Cochmn ences. Nominations should be submitted and Amy Stone for their help in the before September 16, 1985, to the Office prepamtion of this essay. Q19S5 ISI

REFERENCES

1. GmffeIsf E. The 1982 NAS fourth J.M. Luck Award for Excellence in ScientKlc Reviewing goes to Victor McKusick for his mapping of the literature in human genetics. Essays of an information scienjist. Pirifadelphla 1S1 Press, 1983. Vol. 5. p. 506-10. 2. JJerakowfts L Control of gene expression in bacteriophage lambda. Annu. Rev. Genet. 7:289-324, 1973. 3. Herekowitz 1 & Hagen D. The Iyaia-lysogeny decision of phage A: explicit programming and respnnsivenezz. A nnu, Rev. Genet. 14:399-445, 1980. 4. FrferfnsmI D 1, Ofscm E R, Georgoposks C, Tfffy K, Jkakowitz I & Banuett F. Interactions of bacteriophage and host macromolecules in the growth of bacteriophage k, Microbiol. Rev. 48299-325, 1984. 5. Hemkowltz L Genelic$. Bnstoru Little, Brown, 196S. 554 p. 6. EJerakowhs I & Sfgner E R. A site essential for expression of all late genes in bacteriophage A. 3. Mol. Biol. 47: S45-56, 1970. 7. Hemkowitz I. Telephone communication. 13 March 1985. 8. Stahf F. Telephone communication. 13 March 1985. 9, Jumping genes. UCSF Msg. 5(3):22-3, 1982. 10. Hfcks J B, Stsatbmri J N & Herakowltz L The ceaactte model of matin&lypeinterconversion. (Bukhari A I, Shapiro J A & Adhya S L, eda.) DNA insertion elements, plnsmids, and episomes. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1977. p. 457-62. 11. Herakowkz I, Bfafr L, Fork D, Hkka 1, KaaalI Y, Kushner P, Rime J, Sprague G & Strathesm J. Control of ceff type in the yeast Soccharomyces cerevisiae and a hypothesis for development in higher eukaryotes. (J.@hton T & Lnomis W F, eda. ) The molecular genetics of development. New York: Academic Preax, 1980. p. 79-118. f2. Herskowits I & Osbhtm Y. Control of celf type in .Saccharornyces cerevisiae mating type and mating type interconversion. (Strathem J N, Jones E W & Broach J R, eds.) The molecular biology of the yeasf Saccharomyces: life cycle and inheritance. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1981. p, f81-209. 13. Jlerakowitz 1, Roark S & Lynch E. k (Poster insert.) (Hendrix R W, Roberts J W, StahJ F W & Weisberg R A. eds.) L.umbda II. Cold Spring Harbnr, NY: Cold Spring Harbor Laboratory. 1983. 14. Garffeld E. Introducing the ISI Atlas of Science:Biotechnology and Molecular Genetics, 1981/82 and bibfiogmphic update ior 1983/84. Curren/ Conten/.r (41):3-15, 8 October 1984. 15. Hensb& R W, Roberta? W, Stabf F W & Wekherg R A, eda. ,!.ombdo II. Cold Spring Harbor, NY: Cold Spring Harbnr Laboratory, 1983.694 p. 16. Garffeld E. The 1981 NAS James Murray Luck Award for Excellence in Scientific Reviewing John S. Chlpman receives third award for hk reviews in economics. Essays of an inforrmfion scientist. Phdadelphla: 1S1 Press, 1983. Vol. 5. p. 96-9. 17. ------The 1983 NAS Award for Excellence in Scientific Reviewing goes to Michael Ellis Fuher for his reviews of the theory of equilibrium critical phenomena. Essays of an information scientist. Philadelphia: 1S1 Press, 1984. Vol. 6. p. 139-43.

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