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:::..._..... oern7...orInUroX neiecvprer....raL1,:-.-,:._. EDEI.MAIY 1912, died in 1916 in Madrid at the age of eighty-fon'r. ADDmoNAL wOAICS IN SIiC3CIbti 711AId3t.M TTOW: Mtduw 1i93; Sbay, F. (ed.) Tw.pq-Lw SbW p1aY+. 1943. ?.BOL'T: Ctuad!u, F. W. ?.tedtm Ciradnatl.fi Pity- wsiyut,1931: Jiawwa, 5. Moaet n Dram L-v z•som 1929; Post Lott Msy-iuee 1910; Shaw. G. B. Dra.aaua 4Jpiuiemt aed F.Meys. :p06; Wurse. L. +ts. Modem SCraisii l.:u.w tun.1m. EDELMA,N: GERALD M. (July 1, 1929- ) Nobel Prize for Physiology or lviedicine, 1972 (sharad with -Kodz:ey R. i'arte: ) The Americsn biarktmst vera!d N:aEurice Edelman was bot•.tin *;Cw Yerk Girr; the son of Edward Edelrnan, x aaysicdan, -aA Mna (Frae3maa) Edelaasn. .a.tter att=ndirlg public- schools in tKew York, he easered tJraiaus Col- lege in Pearsyhrania, from which be received a B.S. in chemisty in i9S0. Edetmaa then matrictz2ared at the Unive:sity oi Pea,n3ylvsnis Medical Scho41, where be took his medical degree in 195a; fol3owed by a year as medical hovse ofscer at Massachusetts t3eneral Hos- pi'tal. In 1955 he joined tisa Unitsd States Araly. Medicsl Corps and prac-dced g,eneral mcdicine ' at a station hospitat in : aria. htues his disc3uge ia 195 <, Edeiman, who had decided to becomt a research biochensist ratiur thslt a physidz:, began gcaduate work at KockefaL'er Ur.ivesicy under Henry Kun., kel, a biothemist who xas investigating the structure of aa•sbodies. Discovered by Eurm vo-,r BfRxsrro in 11m, antibodies arc blood proteins known as immunoglobulias (Ig's). Beesnse they can bind to and inaativste bae- teria, viitses, and poisons, Ig molaoules ara a crsdal part of the body's chemical defenses. Antibodies have an unusual oombdmadon of biochemical properdes. ICAat. L.ArraV[strtU showed that the body can produce iltotally mil- Iivns of dif1treat andbodies, each of which binds b.a to one particular snbstasce, or sA- ti~en. A1l of theae aatibodtas ace w dmites ia ebsmical sttveatta, however, that it is virtnauy impciscible to isolate a singls antibody from notmal blood. Kunkel and his ¢o•arorkers wanted to determiae how Ig molecules could be at oaae structurally uniform and lhnction-' ally diverse. Research on antibody. strocture was him- is2 ' GERALD Twt. BDHL`dAl'R pered because Ig could not be purified and because Ige molacule are very large in. par3son to others, far too large to be stkbd--' using the chemical methods available fn tha ; late 1930:. Edslman believed that aatibodr struceture and frtnctfen could be e[tuidated bf-' brealrizg sn Ig molecule iato snnalles pieoea ia the hope that the individual fcagmeue: vould retain their ability to combine witb aatigens. In his doctotal distertuiou, he e:am{~d.vsl~ ious methods of splitting Ig moleenles. Afoer obtaining a Ph.D. In 1960, Edebaaa rtmaia.d R cltefeTter as a reseateber snd.facn~r a t o ~ ~ ~ L ~ ul~if7ci. Pravious reseatdters--'sacitiding Ra, R. Pow'ta, who fim split aatibodies into functional subeaits--had concluded that Igt~ molectw3es, the most important It, variat)r-ta' the blood, were toa,de up of a singk chs~of; 1,300 umino acids. Edelman tllought-thb .=--I likew, eveu iasnlia, Which has only 31 acids, is oompoted oi two amino Beanse the chemical bonds that linksa4iao add chains sn difderent from and mnalaa..lost' than tbose joiOtag the individnsi amdd~ within the chatas, they can be brnlsstr tri* Wattra ea:e. In 1961 EdelQUa and. a aol-' leagne, M. D. Ponlttc, reported tbutlrelt hrd . split IgC3 molecuWtato two aompooaat,, wMel are now aalled lisht and beavy ebdns.. ting Edelmam's experissssntt nodRcOe= fereat conditions, Porter combined ttle raa= with his own saadies of Ig(3 fincelonakafils, and, in 1962, annonaaed that the bssic•sttps,; ttare of the IgQ mo[eculs, had bess _dseae mined. altliougirPorcer's ntoael wes r

.:....v"fa"i"•, r.F, V,.. I G"rGuV}ra'Y./..__.7:VL.J.._, _.L....f .J._._Vi_... 5ed and ia com- studied einthe aati dated by i would Latigeas. ined var- es. Afte: remained d faculty RODNEY ' dies Into I that 40 varlery in a chain of it this un- 51 amino 3t1 chaias. ink amino ch .veaher nino adda oken with ": Iad a col- ' i tbey had dns. Atter under dit- the results ional units .>asuc stnro- een deter- ua 1J •t one, it nonetheless provided a crucial frame of reference for specific biocbemical studies. In the flurry of antibody research that en- sued during the 1960s, Porter and Edelman encouraeed an etchanga of lufarmntion among scientists through a aeriea of infortnal "anti- body workshops." In their own work they studied protein of myelcmas, caacers of the Ig-producing cails. Gnsof the main difti•ciltias in studying antibodics had always ixen that natural Ig preoarations usually contain mix- ttuea of many tiightly different motscaliea. in the 2950s Kunk;.l bad realized that since ali of the myeloma ceUs in any given patient usually ara descended fromt a single ancestor, they produce naturslly homogeneous antibodies. (rhe monoclotui-antibody technology devzl- oped by GsoaGas K4ittLEa and CFsAa IVisL- srEiN in 1975 exploited this capability to produce homogeneous qualities of prMe:eeted antibodies, in addition to those that ot r-sr rac. domly in cancers.) During thG early 196Qa, Edelm3ai. Porter, and their colleagues studied the srqueC:ces ao amiao acids in subsrctlops of differem myc- lotaa proteins. In 1965 Edeltaan and his co- workers, "mad as we were," he lat;r said, "started'on the whole molecute, n gozstfy big job." In their effort to dttermina how all of the garts of an antibody fit together, they as- tablished the preciae amino ac:d sequance of an entire IgO tnoleatle from a myelonta. The completion of the project in 1969 elucidated tbe' order of all 1= amino acids in t3±a pro- tein, the longest aerino acid aequeaft identi. fied at that time. Porter's iQ modelwat pardcululy important because it predicted that both heavy and light After receiving tlu Nobel Prize, Edelman c6aias wose involved in the active site (the investigated other substsrces that, like anti- portion of the antibody that actaally binds tT.e bodies, can stimulate cells in the immune sys- antigen). This discovery led to a fundamental tem. He also proposed in 1975 a radically new reconaideration of the central question of an- theory of the brain suggested by his eaperi= tt'body diversity: how the different antibodies encas in imtutmology. In the body's immune are fosmed. "Ibis question had attracted in- t•espom, an invadittt vtrus or bacterium was creasing itusrest during the 1950s as taore be• fonnd not to tsach tbe JMM system how to came known about the relationship between construct an appropriate antibody, but rather genes and proteios. The humatt body may pro- to induce a selection of .ifect#vs antibodies duae at leat 10 osiUion dtlf~ent I~G proteins 4vtu among the available varieties, where- with as many as 10 million actlvre dtn. If anti= upon the body then cioaas the antibodies. bodiea, l3ka other proteins, wera produced ta Somewitat aoalosvnely, Edelman impHed, a oording to the "one sane, oaa protain" theory sensoty ~ ~ of brain eeli~s, but of Gaottos W. Buar.a and F.Dwwna L. Tw• tcoat a Ttst, the body would have to have 10 million rather leads to a$0iection from among com- IaCi gencs and would have no DNA left for pattng cell Roupa aad ioteroonttec.doas. The other purposes. -To resolve this dilemma, pritactpl: of selection is consistent with Dar- MACFAm_4rrn Btmtvsr had proposed In the wlniaa evolution. A primary requiement is late 19301 that antibodies are prodwxd from vstiety, to allow selection a range of action, aenes that mutate in the Ig~producaag eeifa. aa opposed to relatively fixed biolosic suuc- - nC ; .~ .7U '!` ~ JJMM,M,I V C,YEa.WL.1. However, it Ig active sites aro made from parts of two dzfferent amino acid cbaina, as Porter's mod.lindicated.lG) million antibody Se:ies are not needed A sufltdent number could be made from all possible combinations of some 3,000 heavy- and 3,000 llght-+chaiti genes. Through. out the 1960s and the 1970s, a debate raged between those scientists who subscribed to a theory of separate genes for each heavy chain and each light diain and tt>ose who thought that only a few heavy- and light-cbain aeries r..utated to produce the difterent proteins. Edelman disagreed with both theories, and in 1967 lsa and an asaociate, Joseph Gaily, aropoaed a new solution. By that tiau, it was ~wown that each ckaio, whether heavy or light. is the product of two genes that move around and raeombine while antibody-produwng cells ar_ daveloping. Edelmaa and Gally suggested that much antibody diversity arises from small eTors that Occnr during the psocass of recom- bfnation. Although esseneially correct, their theory was too far ahead of its time to win Aaneral acaptsuce until the late 1970s, when genetic-eagiaeeriag techniques aUoxed anti. +~ody genes to be eaattrined dtrecelp. Edeltnan and Porter were awarded the 1972 Nobel Prize for Physiologyr or Mediciae "for their diseoveries concerninf tlse ebes.zical strsrcttiue of antibodies." In his Nobel lectstre,. Edelman asserted that the field of immuno'•ogy is a particularly tniitfttl one for the scientist became "it provokes tmusual' Ideas, some of which ara not easily come upon through other yelda of study." and predicted that "for this reasoa, immunology will have a great impact on other braao6ee of biology and medicine." F~K

%~Y F/ 1 G r._.. VV.- ~ ----- f._.:' ._`f~.'_ J:Y... ~:. K 0 0 0 0 0 ~. ~ .~ ~. ~. 0 EMMICH tures limited to intleidble responses to chang-g ins conditions. Edelman found the source of variety in the brain in embryoa"sc d'eve?op- utent. According to tWs view, genes aveisee the formation of body tissues in the crnbryo but do not dictate every detrsl. Patr;ct:lar cei* aca not predestined for pr,rtic:aar orf,aac. rZather. certain genes direct the prod'stction of varioos types of cell cement (severul of which were discovered by 8delman end his colkagues in the late I9'IOa), and cells carrying like cemer,t adbere in groups. Celi groups send signals ~hat turn eement-pradttcing genes on and off, c.=- eler0i6iIIg some control over t?3.iT own G;•s- tiay. Different cell groups (with di:.-cerea: ce- tnenta) form bordera b*twee- ;?:em, r.nd Edelmaa and nis coileaguas hah:: sacwn .na: group: on opposite sides.of a border specialize into different kinds of csilit. This process was dramaticalty demonstrated in Edrr.msn'n lab- oratory in espe:iments that toi!owed the toc- matton of a single fc :the: on a cyiclcen. Since a oe31's future deflend: on whcre it happens to be, its past bistory, its present acigttbors, Bad possibly other factoss. no two embryos can be Identical, even twins with apparently identical geneuc endowments_ Edalmma then showed ~ow en intrinsically ve:satsL atrnctnre and organizadcn of brain eelk could, r,itcr birth *ad thc ccssat:on of embryonic developmect. fi=iaa as a system for lsaraiag by seleceion. His theory had three llYndamental ekmentr. in the eabryo, the brain develops a highly variabta and individual pat tern of connections between brain cells: the pattern of connections is fsx.ed after birth and dillereat for each individual, but a stimulus can evoke a responre involving certain cotu- bioatioas-of connections; attd groups of calls us connected in sheets pika road maps), which commt;n3este wntli each other in tlu pertoras- aaca of varioua high•level brain activities. His theory accounts for much of tbe brain's enor- %tionmly ffexible capabtlitims to cope with ttn- famt'lar scenes and events, as well as the many iantaa of researahers to pidpoint specific atn of soch brein functions, as memory. Fdelman served as aaociate dean of @r'ad- v.te stndies at Roclcefelist University from 1963 to 1966, when he became a fWi professor there. Slnce 1974 be has been Vincent Astor Dist-guisbed Professor at RockeLaIIer. He is on the board of governors of the Weizmann Iastitnts of Science and Is a unsts of the Salk Institute for Biologieal' Studirs. Fdeln+on married Maxine Morrison in 1950. they hsve one daughter and two sont. ?54 In addition to the Nobel Priae, he has re- ceived the Speneer ibtorrle Award of the Utti- 'a vetsity of Pennsylvania (1954), the Eli Lilly '.~ Prize of the American Chemical Society (1965), .:Lm the Albert Einstein Commemorative Award ' of Yeshiva University (1974), and the Buch• ..t man Memorial Award of the Califoinia ln<ti- _~w tt:te of Technology (19?S). He is a member of : the New York Academy of Sciences, the ..~ American Academy of Arts and Sciences, the :d National Academy of Scieaces, the American .. ~ Society of Cel1 Biologists, and the eienettct ; Society. He holds honorary degrees from the University of Pennsylvania, jJrsintts Gollege, A Williarr.s College, the University of Siena, and a Gustavus Adolphus College. ; Sr.'.ECIPd) WORxS:'Iaalrlindut Bcdn, i9s3. wWwp. nva MounrcatiK: How We Kaow, i4ef. aith othees. _.-" ~s ABOUT: Nrr Yo.lt 23mN Oootrer 1D.19Tf; Diaw Yodcer Jaasury 1o.1ms'•leiem+s (>atobar 1?.19'll. ,.,'. 12MICH, PAUL (Msrr.h 14,1834-Angnat T•0,1915) Nobel Prize for Physiology or Medicine, 1908 (shared with Ilya Metchndroff) The German pharmacologist and im:auaol-A ogist Pau1 Ehrlich was born in Strehien (no+v x Suzefin, Poland), tb. son of ILmar Ehrlich, a: prosperous Jewish innlceeper; and Rcw•'& (Weigert) Eh rheb, both of whom came from •; tamilies.vith a acieatiIIc baclt;round. Bhritcit'i I paternal erandfather, who lsetured to hds , neighbors on pltysics and botaay, was an early ~ infiuenca, but his career was decisively stiut- ; uiated by bis cotnia, Gri Weigert. ... : i Weigert, a bacteriologist, was among tbe a luat scientists to use ant'lis:r dyes (diseovar.d micros~pao PnW~rsttc~ In 1853)forstataft Zbese dyes malce selectiw s:amlag po:s~b: that ih one ekas.at of a tissne ie ate~d others ara stained onCy lightly or not at Under his coatin's nto.iags, Ehrilch learaed' the bindipg properties of variom dyes. In 1S16 ; he read a book on the distribution of lead !n , the organs of poisoped animals, which ssito-4 ulated what was to be a, lifelong interest in i what he lsur described ar "the manner and', the method of the distribt;tion of substanas'; within the body and its cells.•• .. 's•' Elutich entered the University of Bresl~ (now Wroclaw, Poland) in 187Z. Fiowever. one semester he t:anderred to the U m