Copyright 0 1992 by the Genetics Society of America

Salvador Edward Luria (1912-1991)

'I'llC 511'1 S1u\~~uln

ALVADOR E. LURIA (SALVAto family and FRANCORASETT14 called LURIA'S attention to the ra- S friends) died on the 6th of February, 1991 at his diogenetic work on Drosophila5 by H. J. MULLERand Imme in Lexington, Massachusetts. He was one of the by N.W. TIMOF~EF-RESSOVSKY, and particularly to protagonists who, in the early 1940s brought bacte- DELRRUCK'Sexamination of the concept of the gene riophage into the limelight of genetics and helped to in physical terms." Also in Rome,LURIA met CEO develop this area of research into one of the roots of RITA,' a microbiologist, and was introduced by him molecular biology as we know it today. This was to bacteriophage. LURIAwas intrigued at thepossibil- recognized in 1969 with a Nobel Prize shared with itiesof bacteriophage for radiobiologicalwork and MAX DELRRUCKand ALFREDD. HERSHEY. started a series of experimentswith RITA'Shelp.8 His He was born SALVATORE LURIAin Turin, Italy, of resolve was further strengthenedby learning (presum- ;I Jewish family, and attended medical school there, ably through RASETTI)that DELRRUCK,who was by frequenting thehistology laboratory of professor GIU- then in the United States, had also started working SEPPE LEVI]as an intern. While specializing in radiol- on bacteriophage. ogy at Turin and, later, servingin the Italian army as Sadly, the Rome period was short lived. In July, ;I medical officer, LURIA began to considera career in 1938 the Fascist regime proclaimed the "racial mani- basic science as a more appealing alternativeto med- festo." Jewswere thrown out ofjobs.Many emigrated. icine. UCO FANO'was instrumental in this reappraisal. LURIAhad been awarded an Italianfellowship for LURIA started to studycalculus and physics and, in the study in the United States but it was suddenly with- fall of 1937, having moved to Rome to complete his specialization in radiology, was admitted as some kind FRANCORASP~I (b. 1901). close friend and colleague of FERMI.like of lowly trainee in ENRICO FERMI'S extended group at him professor of phvsics at Rome. author of one of the earliest textbooks of nuclear physics. He left Europe for Canada in 1938 andjoined JohnsHopkins the Physics Institute" of theUniversity of Rome. Here University in 1947. His broad scicntific interests included biology and pa- leontology. It seems likely that RASP~Iand I~ELRROCKhad known each I GIUSEPPELEVI (1872-1965). professor of human anatomy and one of other since the early 1930s. RASETTI spent partof 1931-1932 in LISE I he earliest tissue culture experts. had a large following of research students, MEITNER'S laboratory at Berlin-Dahlem. which DELRRWCKjoined in 1932. two other Nobel prize Gmers (KENATO I~ULRECCO andRITA LEVI-MONTAL- " LURIA.with a medical school hackground. had apparentlv no direct UNI) among them. A socialist. he was openly opposed to the Fascist regime. connection with the few Italian geneticists of the time. W:IS hrirfly jailed, ;Ind spent some time in hiding during the war. His strong "This was part of a classic 193.5 paper by N. W. TIMOF~EF-RE~SOVSKY, and colorful person;~lity emergesin N. GINZRURG'S Fami/? Sayings (translated K. ZIMMER and M. DELRRUCK(,Vachr. Ges. 12'iss. Gdtfingen 1: 189-24.5) hy I). M. Low from fmsiro Famig/iare; E. P. Dutton. Sew York. 1967) and "representing a cooperation between genetics and phvsics" (quoted from its passim in C. BARIGO~XI'S/.a Stanzadi Genefira (Francesco Nastro. Luino. preface), the impact of which is discussed at length by STENT(1982) and by 19NI). K. I)UI.RECCO'S Srienza, Vila e Avvenfura (Sperling & Kupfer. Milan. E. P. FISCHERand C. LIPSON(in Thinktng abouf Srience: Max De/bruck and fhe I W9). K. IXVI-SIOVIALCINI'SIn Praise o/Imper/Prtion:MyI-+ and Work (Basic Origins o/Afo/ecu/ar Biology. W. M'. Norton. New York. 1989). A shorter I%ooksI'uhlishers. Sew York. 1988). and LURIA (1984). version of this paper was prcsented bv TIMOF~EF-RF-WOVSKYat a conference Uco FANO(h. 1912), later professor ofphvsics at the University of in Paris in 1937. TIMOF~XF-RFSSOVSKY'Slaboratory in Berlin-Ruch was a (:hicago, was ;I high schnol friend of LURIA'S. He emigrated to theUnited casualtv of the war. He, a Soviet citizen. was taken to the Soviet Union where Stxtcs in I9JH and collaborated with M. I~EMERECin the early 1940s at Cold he lived on in rather sxl circumst;mces and died in 1981. ZIMMER,the co- Spring Harbor on r;ldi;ltion-induced mutations in Drosophila. author ofthe 193.5 paper. followed ~'I~~OF~EF-RFSSOVSKYto the Soviet Union ' The Department of Phvsics at the Universitv of Rome was then at the but later wasable to return toWest Germany to continueworking in radiation pe~kof its hme. Its director. 0.M. CORRINO, eminent scientist. administrator hio!ogy at the Nuclear Research Center in Karlsruhe. near Heidelberg. ;md politician. had heen able to obtain extensive support for ENRICOFERMI ' (;EO RITA (b. 191 I). later professor of virology at the Univrrsitv of ;and his collaborators. CORRINO'S sudden death in 1937 probablv accelerated Rome. w.as working at the time on bacterial contamination of water and had the di;tspora of that group, already destahili7ed by the political situation (see isolated some phages in the course of this work. <:11;1pter9 of G. HotxoN's The Scientific Imagination: Case Studies, Cambridge *-rhese experiments, probahlv planned in consultation with RASETTI(see Universitv Press, 197H). For a sensitive although historically not quite correct I.. F~~~~'~I//usfriousImmigrants: The Intrllrcfual,Migrafion/rom Europe 1930- litcwrv recreation of the mood in the phvsics group BS the war approached. IY41. University of Chicago Press, 1968). reexamined the question of scc I.. SCIASCIA'SLa Sromparsa di Majorana (Einaudi. Turin. 1975: translated whether a single bacteriophage particle was sufficient for infection in liquid hv S. KARINOVICHas The Myste? o/,Wajorana, Carcanet Press, 1987). culture. They were published the following year in France.

Genetics 131: 1-4 (May, 1992) 2 G. Bertani drawn. Instead, he was able to move to Paris, where LURIA’Smost influential research contributions pre- FERNANDHOLWECK’ obtained a stipend for him at the ceded the “year of DNA” (1953). During this period Radium Institute. They collaborated with EUC~NE he continued radiobiological studies ofbacteriophage WOLLMAN”to measure the target size of a bacterio- (target size determination, the ”indirect effect” and phage exposed to different kinds of ionizingradiations “Luria-Latarjet curves”)(LURIA and EXNER194 1; Lu- (WOLLMAN,HOLWECK and LURIA1940). RIA and LATARJET1947), experimented with multiple But world events were pressing on. World War I1 and mixed infection as toolsfor probing the intracel- started in September, 1939. By late Spring of 1940 lular behavior of bacteriophage (DELBRUCKand LURIA the Germans were approaching Paris. LURIAleft by 1942; LURIAand DELBRUCK1942; LURIA1947; Lu- bicycle. In Marseilles he succeeded in obtaining an RIA and DULBECCO1949), discovered mutational American visa. He proceeded through Spain to Por- “jackpots” and invented the “fluctuation test” for tugal, where in September he boarded the ship that spontaneous mutation (LURIAand DELBRUCK1943), took him to New York.” was a key participant in the early electron microscopal In New York, with the help of FERMI(who had studies of the shapes and sizes of bacteriophage par- himself emigrated in 1938) and of LESLIEC. DUNN ticles (LURIAand ANDERSON1942; LURIA,DELBRUCK and the Rockefeller Foundation, LURIA was able and ANDERSON1943), examined a variety of bacterial withinweeks to again pursue radiobiologicalwork and bacteriophage mutation types (LURIA1945, 1946) with bacteriophage (in collaboration withthe physicist with implications for the mechanism of phage repro- FRANKM. EXNER)at Columbia University. He also duction based on the clone-size distributions of spon- verysoon sought contact withDELBRUCK, then at taneous mutants (LURIA,1951), and recognized the Vanderbilt University. Their first meeting led to a first case of whatwe now call “restriction and modifi- collaboration, both by correspondence and through cation” (LURIAand HUMAN1952; LURIA1953). bouts of joint experimental work at Nashville and Although the concept of mutation was already being Cold Spring Harbor, that was to last for more than a freely applied to bacteria and viruses by the few prac- decade. titioners, the fluctuation test for spontaneous muta- In 1943 LURIAobtained a faculty position at Indi- tions established a new and rigorous criterion and a ana Universityin Bloomington,” where he taught new technique for measuring mutation rates. Its math- bacteriology and started a course in virology. There ematical subtleties kept biostatisticians busy for years he met and married ZELLA HURWITZ, psychologist a afterward, while its technical simplicity obviated en- and now professor at Tufts University. DANIEL,their tanglements with the still extant experimental and only child and now an economist, was born in 1948. semantic problem of how a mutation becomes estab- In 1950 LURIAmoved to the University of Illinois in lished. Urbana.” Nineyears later he joined the Biology Restriction and modification was a different story. Department at the Massachusetts Institute of Tech- In this case the heightened confidence in the applica- nology, wherehe remained to the endof his days.For bility of basicgenetic principles tobacteria and viruses several years he also held administrative responsibili- brought out the apparent absurdity of very simple, ties as the first director of MIT’s Center for Cancer accidental observations and the recognition of a new, Research. Both at Illinois and at MIT, LURIAhad a quite general phenomenon. It then took years of hard lasting impacton their instructional and research pro- workin many laboratories to elucidate the diverse grams. enzymatic processes that modify DNA. The initial collaboration of DELBRUCKand LURIA ‘’ FERNAND HOLWECK(1890-1941), well known French radiation physi- cist. was later arrested by the German occupation troops and died in jail. established the foundation for a research movement ’I’ EUG~EWOLLMAN (1883-1943?) was then the leading bacteriophage focused on bacteriophage, a movement that grew specialist at the lnstitut Pasteur. He was engaged at the time in comparing bacteriophage radiobiological target sizeswith size determinations from beyond all expectations and recruited not only their ultrafiltration. He had earlier speculated about the possibility of a biological graduate students and close collaborators but also relationship between bacteriophage and genetic material (see PH. HADLEY’S 1926 review in]. Infect, Dis. 45: 263-434). Both WOLLMANand his wife, also attracted scientists from a variety of fields. It later a scientist, were deported by the Nazis in 1943 anddisappeared at Auschwitz merged with molecular biology. Much has been writ- (see P. NICOLLE.1946, Ann. Inst. Pasteur 72 855-858). ” I have told this part of LURIA’Slife in some detail, largely based on his ten about the “phage group” and this larger research autobiography (LURIA 1984). because it shows three historically interesting movement (e.g., CAIRNS,STENT and WATSON 1966) :Ispects of the beginnings of modern bacteriophage research: the troubled wartime background, the network of European emigris and, above all, the and need not be repeated here.14 In fact, the attraction “physics connection.” See D. FLEMING’S“Emigr; physicists and the biological of bacteriophage as experimental material remained revolution” (in The Intellectual Migration: Europe and America, 1930-1960, edited by D. FLEMINGand B. BAILYN,Harvard University Press, 1969) and 1.. FERMI’Sbook cited in footnote 8. z‘In an otherwise controversial article, F. M.BURNET wrote in the January Is lndiana was rather strong in biology, with T. M. SONNEBORN, R. E. 1, 1966,issue of The Lancet, “Almost the whole of the modern structure has CLELANDand, from 1945, H. J. MULLER,not to mention A. C. KINSEYof been built on thestandard strain of Escherichiu coli B and two phages T2 and wasps and sex fame. J. D. WATSONcame to Indiana to study genetics and T4. . . For thirty years I have watched this structure develop around the became LURIA’Sfirst graduate student. central bacterium-phage theme, bringing in as needed contributions from “ Bacteriology at Illinois was being rejuvenated by H. ORINHALVORSON, the chemistry of the nucleic acids and proteins, from the genetics of higher xnd with 1. C. CUNSALUS,SOL SP~EGELMAN and LURIAunder the same roof, organisms, and from the pharmacology of antibiotics. It has been a magnifi- it made for a very lively department. cent achievement, to be ranked with the elucidation of subatomic structure Salvador Edward LuriaEdwardSalvador (19 12- 199 1) 3 unchallengeduntil powerful new biochemical tech- I was with LURIAfor almost five years as a research niques were developedwhich allowed effective manip- associate, initially at Bloomington and then at Urbana. ulation of more complex organisms. As STENT(1 982) His work at thattime was still centered on the growth correctly pointed out, the original innovations were cycleof bacteriophage T2. Even though he was at in the first place methodological (rigor of inference, first hesitant about my startinga new project, on quantitation, use of genetic concepts, careful limita- lysogeny, he obtained the needed strains for me and tions in the choice of material, strivingfor fundamen- supported my work in every possible way. Especially tals), for which DELBRUCKmore than LURIA was the at Urbana, he already was heavily engaged in teach- responsible ideologue. LURIA’Simpact derived from ing, writing and guidinggraduate students. He his numerous experimental contributions, his exten- worked on a regular schedule, always with intensity. sive teaching, his willingness to give talks and write He had a great capacity for taking in information, textbooks and reviews, the breadth of his interests in scanning papers and books. A fluent verbalizer, he microbiology and biochemistry, and his extensive con- often gave the impression of building ideas as he was tacts with the large constituency of professional bac- talking. He was always concerned about the welfare teriologists and virologists. of students and coworkers,yet he suffered alternating Inthe post-DNA era, LURIA’Sresearch activities moods and could be aggressive and irritable at some consisted mostly of guiding or advising graduate stu- times while buoyant, even whimsical, at others. I re- dents and postdoctoral fellows on a variety of topics member the reaction of the late PAT MCGRADY,sci- and experimental materials, usually concerning bac- ence editor for the American Cancer Society, after a teriophage behavior or effects. In the sixties his inter- long conversation with LURIA.MCGRADY had visited est shifted to colicins. He was intrigued by the fact our laboratory to gather material for an articleon the that a single colicin molecule, a protein, could kill a phage work. While 1 accompanied him out of the bacterial cell by suddenly and dramatically blocking a building, he checked with me some of the things he number of cell functions. With several collaborators hadlearned from LURIA. Aswe were partinghe he focused on this problem for more than a decade. paused a moment and then said, almost to himself, “He is so human!” Inparticular, they analyzed the impact ofcolicin adsorption on active transport across the cell mem- GIUSEPPEBERTANI brane (see LURIA 975a).151 Jet Propulsion Laboratory 1 25- 1 12 LURIAwas afluent, prolific writer. In1953 he California Institute of Technology published a textbook of virology that stressed general Pasadena, California 9 1109 biological principles and emphasized bacteriophage as a model. The outlines of his biology lecturesfor undergraduates at MIT (LURIA 1975b)make wonder- ful reading across the whole range of cellular proc- LITERATURE CITED esses. More literaryefforts were apopular science book (LURIA1973) and “a confessional account of CAIRNS,J., G. S. STENTand J. D. WATSON(Editors), 1966 Phage and the Origins of Molecular Biology. Cold Spring Harbor Lab- himself‘16 (LURIA 1984). oratory of Quantitative Biology, Cold Spring Harbor, N.Y. Throughout most of his life LURIAwas politically DELBRUCK,M., and S. E. LURIA, 1942 Interference between bac- engaged. He had strong sympathies for leftist move- terial viruses. I. Interferencebetween two bacterial viruses ments andcalled himself a socialist.” He was basically acting upon the same host, and themechanism of virus growth. Arch. Biochem. 1: 11 1-141. a pacifist, more sensitive to inequalities of class and LURIA,S. E, 1945 Mutations of bacterial viruses affecting their social injustice than to the deadeningconsequences of host range. Genetics 30: 84-99. state socialism or the threatof world communism. He LURIA,S. E., 1946 Spontaneous bacterial mutations to resistance seems to have enjoyed the type of social intercourse to antibacterial agents. Cold Spring Harbor Symp. Quant. Biol. that goes with political activism, and this fulfilled an 11: 130-137. LURIA,S. E., 1947 Reactivation of inactivated bacteriophage by emotionalneed more than it reflecteda coherent transfer of self-reproducing units. Proc. Natl. Acad. Sci. USA philosophy. 33: 253-264. LURIA,S. E.,1951 The frequency distribution of spontaneous as one of the twomajor triumphsof twentieth century experimental science.” bacteriophage mutants as evidence for the exponential rate of Althoughbetter known for his later work in immunology and on animal phage reproduction. Cold Spring Harbor Symp. Quant. Biol. viruses, BURNEThad done outstanding work on bacteriophages in the 1930s 16463-470. using both virulent and lysogenic systems. Phage C16, used by WOLLMAN, LURIA,S. E.,1953 Host-induced modifications of viruses. Cold HOLWECKand LURIA (1940), had in fact been isolated by BURNET:it is a member of the same family as T2 and T4. Spring Harbor Symp. Quant. Biol. 18: 237-244. I” This work prepared the way for the major 1978 finding of S. J. SCHEIN, LURIA,S. E., 1973 Lije, the UnfinishedExperiment. Charles Scrib- U. L. KACAN and A. FINKELSTEIN(Nature 476 159-163), who showed that ner’s Sons, New York. :I colicincould establish a nonselective, ion-permeable channel in bilayer LURIA,S. E., 1975a Colicins and the energetics of cell membranes. membranes, leading to the collapse of the membrane proton motive force. ”’ The quoteis from the 1984 book review byS. BRENNER(Nature 308: 794). Sci. Am. 233(12): 30-37. I’ Because of his politics, LURIAwas for several years unable to travel abroad LURIA,S. E., 197513 36 Lectures in Biology. MIT Press, Cambridge, ;Ind was blacklisted by the National Institutes of Health. Mass. 4 G. Bertani

LURIA,S. E., 1984 A Slot Machine, a Broken TestTube. An Auto- leading to production of active bacteriophage from ultraviolet biography. Harper & Row, New York. inactivated bacteriophage particles. Genetics 34: 93- 122. LURIA,S. E., and T. F. ANDERSON,1942 The identification and LURIA,S. E., and F. N. EXNER,1941 The inactivation of bacteri- characterization of bacteriophages with the electron micro- ophages by X-rays: influence of the medium. Proc. Natl. Acad. scope. Proc. Natl. Acad. Sci. USA 28: 127-1 30. Sci. USA 27: 370-375. ILJRIA,S. E., and M. DELBRUCK,1942 Interference between bac- LURIA,S. E., and M. L. HUMAN,1952 A non-hereditary, host- terial viruses. 11. Interference between inactivated bacterial induced variation of bacterial viruses. J. Bacteriol. 64: 557- virus and active virus of the same strain and of a different 569. strain. Arch. Biochem. 1: 207-218. LURIA,S. E., and R. LATARJET,1947 Ultraviolet irradiation of LURIA,S. E., and M. DELBRUCK,1943 Mutations of bacteria from bacteriophage during intracellular growth. J. Bacteriol. 53: virus sensitivityto virus resistance. Genetics 28: 491-5 11. 149-163. INRIA,S. E., M. DELBRUCKand T. F. ANDERSON,1943 Electron STENT,G., 1982 Max Delbriick, 1906-1981. Genetics 101: 1-16. microscope studies of bacterial viruses. J. Bacteriol. 46: 57-76. WOLLMAN,E., F. HOLWECKand S. LURIA,1940 Effect of radia- LURIA,S. E., and R. DULBECCO,1949 Genetic recombination tions on bacteriophage C16. Nature 145: 935.