/ .# ; . + I I / RP:fit?KI; C?T-' T3.2. !~"K%YF? t:CC.~CW' &T AIEW WITS FXOIIIAL c <~ > ~~---~~~~;r'~~~~~~~~~~~~~ 1 <,: fj-2 `:.$ a ~::p" I, It fe not our purpose this afternoon to attempt a b, syetomatic analyola of r3voty's eclmtific contributiona and j their fmpzict on modern biological thought. No? %,e it feasible i b,, i i to draw a comprehensive p&trait of Peas and his extraordinary, anrlti-faceted poraanality. Rather, Sn thie eercleta of presenta- tlons, it 161 ens hope that, An an info-1 and leoo etructured I manner, tcb cetn convey the ctossntial sp%rit of the man, his i work, and its scientific conscquenco~4 There ia mch more of a central, unifying theme in Avery'~ career QD an investigator than the simple fact that ho was preoccupied for the greotcr part of it with a single group Of mfCrOOU$Uli~?DS, the ~I?C~~OC~CC~. Ris intuitive ability to ooloct significant prolkw for attack, the phlloeophy of hio approach to their oolution, and the strlngsnt demand8 he made on sclontific evidence before accepting UP experimental findings as final are among tho traits that give hir work a special f3tClmp. The SjuocticJnfI he poeed in dealing with the coq~lex hlologlcal oyete;ne with which he worked were character- iatically dircctpd tcnmrcl a fundamental understanding of tha subatancos responsible for specific$ty. When faced with the necefmity a ycnr or BO ago of preparing b papor with the rather EOrlAQc?I177 titlo "l!~loculnr E~iolov and M&icine*, it occurred to RO tl!at, as much ao he rnirrht ~ZWO disliked the doaignation, Fess was a nolecular biologist long before the term came into UBO. Thfa assertion in eriicquntsly sunported by the direction and development of each of his mafor Unos of inveotigotion, involving BB they did the laafatfon and characterization of biolog%eally active moloculcltir and efforts to establish the chemical bmisr for their specificity. Xt ie important to recognize that hie explorations of the !' .'A. ?' ', .p underlying biochemical basic, involved in the phenomena he ),,, .,-"A~; .! '. .: . . i ." ." dt,.f. ',b.I, I'$( :.! . . : ..I- , studied w0re motivated by a deep intereatin Uoad biological problems, including, as Colin I%&- will mphaoize, clfnfcal problems related to C(I~easm. One of the lmm well-known of ths Profossor@s major Intltaraeto wa8 hir concern with the host reepnse to disease procezimm~ Thio intorest findo itr;l most notable expreeraion ia his wrk on the human aorum ptotefn now known aa C-reactive protein. This substance, Mch 1s not present in the blood of normal individualr ktt maker lto apgearaace in reapon to a variety of inflamatory otimuli, was discovered in Mm laboratory by Tillett and Francis as a by-product of the pneumococcal work. The term *C-reactive* refere to the fact that the protein fortuitously reacts to fern a precipitate with tho eonatic C polysaccharide of the pneumo- C0Ccu8. His atudiere of thie substance with Abernathy and EIacLood lec_ to its ldsntlflcation as a protein and charnctari- ration of mazy of it8 propertlos, and fncidcntally one of thz first lsolntlono of a humanfirotein frl a highly purified, hcmogsneous form. Thucr, oven h2e exploration of the hczlt response to dimam davarlo~d along thG linec~ of molecu3x biokqy. A long succemlon of students and collaborators had tl:c intallectual atimulua of learning theos appraacheo to scientific -3- investigation from him by prscopt. At the sa11)3 time, there WWJ tho aooociatetd'enrichPng experience dorived from daily contact with a molat exceptional personality. These latter egerionceo are perhaps the most difficult to recapture because of their Bubjectfve nature and personal flavor. Certatnly, per:eonal remfnircences are natoxiously treacheroue, particularly with raspect to the accurate recollection of details and the temporal interrebationehipa of evento as the years recede. Zt Is my impression that all of Fesa~sr former associate8 have a rJimil&r picture of the major facetsr of hfar personallty.~' It 18 not ourprioinq, howver, that there are difforcncso of opinion nncl of interprototion with respect to many OF his leoa familiar characterictice. These co-workera and frlar.28 concur in tti broad outlines, but each hao hie own privatevlw growing out of hire om pereonal rolationshlp with kvory. If them prcmloora nro correct, then it is clearly impossible for any one individual to advance a compreheneive analyeis of hlo character that will fully sntAafi/ all of Iris other former colleagues. In any event, I hnve no intention of attempting euch an analyei8. I ~uld like, hoWever, one of Avery's to touch upon one apieode which both dascribce trnito and illuotratos my point concorning the Inherent inaccuracy of personal racolloctlona. The 6ucco69 etory racorded in the eubsequont career8 of a long aerics of FCSQ~B boys eatabllohee beyond doubt hio prccmincnt talcnt for contributing to the molding and diracting of prornisgng yoiing acientlata. Ths techniques by which hs achieved thie - and inikcd whether apythlng qualifying as a tachnique was actually ir,vslved - hm long lm?n B eub)oct of debate. Sonto of the things tlmt Ixq.qxmd to al1 aapirlng invmtigatore on arrival in Awry*0 lebcmstory cm3 indisputable, bwever. The neophyt83 wm nwer under any circurmtancee given a rofesaor and put to worlc shortly after arrival on wxne arapect of pmumococ cal bmteriology which fittoe into tha ovorull interest6 of the laboratory. The gmcwe ww a niuch arlower and more gerinful one - mo8t especially for those w110 by trrxhlng and fnstSnct felt dependent upon direction from abtw- anCL wae baa04 on the firmly-held phi,loeoghy that every wxkar should eelect hie own problm. Thie end was achlsvad through c cmhination of subtly directed reading and a oetiea of discusesions that frequently took the form of mono1oquc6. Aa one gained a bettor lntoqrated improor;ion of t;ibo trend uf invssti;;ation in his dcpztrtmnt over the pare by reading - chi3fly from the collection of Copartmontal reprint6 - ones g;cnsp of the pattern and intsrrolatione of the research on t;Lo pneuraococcus WRB greatly onhancod by hlo oral dieacM.ation~ tIcit hava 'Lccn weLerrcd to am F3c30@0 Red Seal Record8. They I %PKO virtuoso performances tn which, with great logic anti clr?rity, hc wurlii duvclop h%io thcne, including historical Laclc- I gcund and tho riltiormlo of approscko umd. The oryonization ~mti p~lrc6colo~jy of theso vignettes had beon compor;cJ in his m5.33 at l-110 lciz~ro with grat care and WWQ ueed relatedly In rzeoenting tl;3 uubj3Ct t0 various tUaditOJ33. Tho young hopeful, inpatiant to got to work at the laboratory lxtxh, wxld at tha Qume tit90 be completely Caacinated a . by tlieoe 4!uocourees. Soon he would rafr;o pttestioaa abat certain aqpacts of the pneumococcue and ultfnstoly ~0~1~3 bo gently manauvered into sruggeeting hlg own groblcm by outlining his ideas for anowering one of the queetFona he had him&elf rMJUQ& In this way, the beginner selected hie own problem, an8 at the same time could be Qlverted through the medium of ~aliminary discussions from blind alleys and paths that had alraaQy bacon uneuccessfully followed. Xn my own caQ6i, it wars Roy recollection that this perciod of mixed frustration and intellectual stimulation want on for about two months. Thie grovea to be a b&utiful example of * tricko that can be played t;'~ a faulty rne~~~ry, and in thie cade ths correction is ouppliod by a *dinrp in tha fornp of 1abCatory notaa. I arrived at the IIockcfcAlcax Incstltuto on Scptcmber 1, 1941 and wall greeted by Frank Eorefall who La:! juot 1 that ciumrner returned to the Inatltuto etaff after hio sojourn I in the Rockcfallor Foundation laboratorier. Fess did not return ftom Wine until after the second week of September onU so ay fnkctrination (which had Men initiated with oo;;ro rsadfng matcrlal in the epring) ~8 not begun in earnest until tl;e nlidls of tha month, This wan the ertart of the pariod that 1 xmembor as haviny laataii many weeka, and yet the incontrovortiblo cvlc?ance of the lnboratory notebook reveals that 1 hGI carried out my fir% tentative exper~menta in p3eun3coccsl tranoLor3ation ~~fora the end of Septetintir. By mid-Octol=or f was engag& in the growth oflmasn cultttrcle of typo Iff gneumococci for extraction cf the crude transforming oubstnnce. My distorted manory of this period probably haa it8 basle in the rather special raituntion that o'btalnod at this time. Colin E&cUod had left the Rockefeller Institute that summer to &fmutm hia dutfos em PfoPewuor OP Micxobiology at New York University, 60 that Fese wa8 euddenly deprived of hisl cloeo colhboraator of the previouo 7 years. Although X had at the , ~j outset a latent interest in pzmamococcal transformation, and thie Gear1 Racorde on the subject, I was much too dLCfident to propooe to Foam that I join him on the problem, On hio part, he wad zrw3trafnecI from onlisting my aid as a collaborator not only by hia policy of lnsltetlng that the newcomer celect hio own problem but nleo, I am mre, by the unknown nature of my abilitieo ae a labo+atcxy worker. Eiow could he be mare that X would not be nsxo of a hindrance than a halp7 It was this impaaso that must have &on responrdido for the aberration of memory ti?ich czu5e.o ~33 to recall OS eevorol weeka what could not have bean rrioro thnn severer1 Caya. I have no cleat rocollaction of procF00ly how the inrpaaso was broken, and hera the laboratory notecr are CT no halp. There are rmny other respects in uhich thcca old lnboratory wA:elxx)ks prove their inndcquacy, nnd although they wxxn c;uitF t11cxou$1 anil s&quutely Ceocriptlve of experimental proce3iure tli:~y arc f10 'i wry useful in Qclineating tlm avolution of ifleon C,YT Vi0 0riQ:;in Oi: certain spilrOaClleQ* In particul.ar, f had l;opcQ t;o picco tcqether from them a clcnr rocoril of tho origin ani: gowth of tlrc i&x that the pncumococcal tranr+orming principle __-___ --._--~ .- -.... .._ -. .-._----___l- I r ' - -7. ie ccm_boblcff of Dia. Tars Ss ~me information on the goint, to be sum, hut not enough to reconstruct from thlo aourco alone an accurate pictmra of all atages In ths development of the idea. Mor ie there any reflection of the negative ZZactore ,' that werg6nttiuced on diacuesion with others, auah au tha prevailing biochemical dogma of the time that nucle:c aclda I from various m3urceb were monotonously alike la composltfon and thus unlikely candidates aa carrier6 of rrpealfic information. There are rewarde of a diffstsnt nature to be deriwd from a return to the old notebooko, howwet, ant3 thumbing through their pagee again aftor twenty-odd year8 tends to conjure up nemorlee of eplsodee and the daily laboratory routine of the perlob. One of the gratifying minor aapecte of the work with the pneumococcal tramforming syetom wae that each morning on r---- - - ------- - _-_. --I-- arrival in the laboratory the tesulte of tha experiment of the day before were waiting in the incubator.to be read. Thus, when thinge were going well, each day began nith a new bit of Information that provided the etimulus and direction for further experlmnta. reee and I had an unspoken agrecnent that prevented either of us from obtaining a cneak preview of the results before the other had arrived. 3 ( h lTe0 ld protocol8 -_ .- servo to recall the image of Fess as we converged on the 1 incubator each morning, and in particular X gee his cxpremsion, which Q.TM a curious nixturo of aaqer anticipation and of a~~pre- henoion for faar smcthfng hnd gone wrong with our complex biological teet ayatcm -- which, Alamo, was all too frequently the cake.) A multitude ofsuch picturoe remain in my memory aa I am .~.. ..-. ._ -.-.- __._ _~ ._ 1 e "- 8 sure they do in the memory of others. Derapits the fact that they may be d%otorted and blurred by tho paeaage of time, they remain aa teatfmony of the lasting lmpact of hia personality on hia aesoaietem. Thirr legacy tcr inextricably enmeehed in our minds with the t~olto durable and objective legacy of his scient=ific accomgliehmmita. In closing, I would like to expraro the peroonal plersursl that Z have darived from the tntenrrifierd reminiscences of Dr. Awry stimulated by this occasion and fram th@ opper- tunity to talk again with many of hio old friend6 and with hit brother and rietsr-in-law, Dr. and Mrs. Roy Avery. X must my, however, that the endless variety of there reminiscences hae renewed my convictfon that it Ati virtually impossible In a brief discourse to recapture more than a amall portion of his attrlbutoa as a ociantiot and 'as a friend. MMcCarty SoptemEsr 29, 1965