_
Dr. Joshua Lederberg 10/1/86
President, Rockefeller University

1230 York Ave.
New York NY 10021

Near Josh,

This iS A response to your request oF Writing rhe
history oF how J became interested in microbial genetics,
The beginnings go back tO 1948-41. I was a medical Student
and I spent the SuMmMer Holidays between the second and third
year of Medical school (total Six years) working with
Giovanni Magni an the microbiclogy-hygiene laboratory of the
Province of Como, north of Milan, At the beginning oF tha
third academic year the professor of Pathology, Emilisc
Veratti, gave us a@ book, "The Genetics OF Microorganisms", a
SYMPOSIUM Made in America shortly before the war, The book
belonged t9 Adriano Burzztati-Traverso; His Name was Written
inn Ais typical hand-writing on the First page, but I did
not KNOW him then, and Yeratti told us He had received thea
boak Fram Adriano, whe had suggested ta him ¢G give it ¢a
Students Who might bS8 interested, Veratti was an did man.
Sincerely interested in research, who gave us also on other
gccasions good advice, J] am saying "we" because Giovanni
Magni and J were working clesely tagether at the time,

Giovanni and J shared the translation into Italian of the
bGOkK GN MicTGbhial genetics, which was fairly naive bute had
SOme interesting ideas, J remember only a paper ty Mary
Bunting, on Prodigicsus COLlGT Mutcatkions; anyhow, we Later
Published in an Jta@lian scientific journal a summary oF the
bGOkK atid GF Whatever other literature we were ablie ¢a Find,

Adriano was in the army, in Lybia, but was dismissed
because of SiCKNESS- Probably an allergy, He returned ta his
university jOb in Pavia at the beginning of 1942 and started
giving a caurse in Genetics, When I heard about it, I
decided to Follow his Genetics course for Natural Science
Students, and in Fact prepared a detailed syllabus, on His
request, based on his lectures as Well as on the books on
Whith they were based, They were excellent books like
Sturtevant and Beadle, Waddington. and otmers, Through
Adrianc I Q@lso managed tao have the Firse books an
Btakistics, §nedecor, and Tippett, Which I had longed for,
but never had access tO, There were no books on Statistics
im TtaAlian of any Value At the time, QA book On Which I mad
Studied Mendel's laws in the First year of medical echool
had turned m@ off completely, DPuring the war there was oF
COuUTSE NO woy ¢G Ghtain English or American books and
journals,

Ponkacke with Adriano was very exciting, and I
Started thinking I might orient my choice towards genetics,
In the® Microbiological lab wheres Giovanni and I worked in
the summers we started a genetic problem: mucations induced
by ultraviolet in Bacillus anthracis, There was already some
evidence at the time, if [I remember correctly, that
leravioletr Might be mutagenic, There were of course no
germicidGl lamps, but plain mercury lamps, The chaice of the
Organism was Probably suggested by the director of the Como
laboratory, G@,Banezzi, whose main cancribution was the idea
bAQt ON cannot believe that a Variant Strain if a mutant
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caugGhs Us the FeCnnigqQue, and this was
B,AMERPr ALLS Wat Silly BSeCauUSsse it Forse
Brecaueians, &¢ the time chere were
MEOR Lf sometring went eroOne, We created
SOME LSEQLG&es, and rested their Ferme ’
Warulencs, We Found changes in both Bat Bu
NE an Tebtrospect, becaute we cested very Few colanies;
ROWEYET, WE did Publish thre Tesules, FOrrUuUNnatrely in Tealian
OMly., Jr is Nsarly impossible to fount on Plates
B.Onthracis, whith ordinarily Forms very long chains, a
kheres WS NG Simple way oF S@Sstimarting survisal Freaquancias,

a

& Consequence GF these investigations was an
inereased inktsrest in the measurement of virulence, mainiy
im response te the standard atticude oF bactericlagists oF
eRe btime, Who Claimed vitulence cannot be measured, We noted
GO Tegular ancrease iff time GF death oF Mice injected with
increasing dilutions of B,anthracis, and thought oF an
@xplanacion in carms oF logarithmic growth and the need tc
reach A Lethal concentration of Germs, independent of tha
injected dose,

In order ¢0 b@ able tO discuss this @xplanation with
G& biologist who was mot completely put GOFF by G& Mathematicai
Formula, Giovanni and I went in the summer °‘427 to Frankfure,
With G Shore ¢cerm SchoOlarBsHiP, tO work with Richard Prigge,
The Suggestion had comes From Verattri, and proved excellent,
Priggée was very mice £6 us and let us use Kundreds oF mice ¢
all of the Same weight and s@x, Plus minus half & gram) ana
Save us help co carry Our exXperimentcs on varulence, this
ciMe ON PNeuMmococeci, Results were dutifully Published on
Zeneralblace Fur Bakteericlagie, Griginally the intention was
£0 do genetics OF Virulence, but We Never came to it.
because after we ert Prigge’s loboratary the chance of
WOrKING SO well neaver occurred again, Adriano
Suggested that we Should, during cur stay in Germany, joint
him Gn Berlin, where he Was working with Timofeerfr-Ressovaeky
on radiation atid GlEG GM PoOPUlatiOon genecics oF Drosophila,
and $0 We did, That Stay WAS caoMmpletelely determining for my
research career, The brilliant personality oF Timoreerr had
A deep impact on me, He convinced me complately that
BENEetics was the best Choice I could make, and on my return
tO Pavia J became a regular *intern* in Qdriano’s lab. I did
SOME TESEGT CH Work GF na greac interest in cytogenetics,
Padiogenstics, and Finally {with greater satisfaction:
Populacion genecics oF Orasophila, I chose to do a theeis an
tre Killing of bacteria by M-rays, hoOWevar., in the hope oF
understanding something of the bacterial nucleus of F.eali,
For this @im, J Want to Rome State [Institute of Health For
& Few MONthsS, where I Found goGd Suppor’: in cerms oF
SUPP1LLi8s. BSle@crron microscopy, and ¥ ray, An MLD, thesis was
SUPOOCSed tG be & miner effort’, atid IT certainly made no

iscoveries, MOSt OF My lab time between °“43 and *45 was
Brent if OTrcsGcehilad work with Gdrianc ae & temporary
Lgeation (Pallanza, On Lake@® Maggiors) chosen by him to avoid
deetecruccion of che lab by bombs, Getugily, neither this
Place, mor, to Say the truth, Pavia were touched by bombs,
Im this period ~I alsa tried my patcential interest Far a
Medical career by serving a5 M.D. in the Local hospital, I
Was Complecely turned of F,

TR ere North Of Tbraly the war anded on April 264,
L945, with Che arraval of allied troops, The Ttalian
UNLVOPSTtiss Ware inf foMPLEtSs disarray, anid there was no
Crening in Sight, The First came in i949, an cesistane
*professor" job With Adriano; at the time I was in England
and not interested, but Liaovannhni €oock it. Thus aot the ena or
 

IM Suguser $745 7] Found & FPoOsition at a
PRaThHGCeuciogl Farm, © AON-PrOoOFic Making aerganizacian, where
T WAS SUPPOSed £5 WOPK in the Yesearch department wath «a
bright ammungiaogis¢c, E,cariinranti, TRE Qenerail directcar af
gre Place (the Tsrtiktutrs Jgr_erarerarics Milanese) was a1509 the

COPBSBSOr OF Mifrobiolsagy art the Liniversity OF MHiian, He was
am antcelirigen’t but unbalanced perean and e007n laGset Ais joo
AS director, I was asked, Saontrary €£5 ifiriaAl praomisas, +5

Spend marnings bleeding bload donors; I developed skilis [
MSGed Later in field work, bur eartainiy I did not eanisy this
use OF My tCime, In the aFternacans I did Same experimental
and Stakistical work on immunology. but soon was abie +a
have Enaugh independence ¢a come back ba botteria, Niccalia’
Visconti cama 45 & Guest +O the lab, and together we tasted
eragse-Tesistance GF E,¢ali B and ByYr €6 X-rays and nitragen
Mustard, I was A1sd anterestad if understanding tha
PRySiGicogy oF the sensitivity to radiation of the B strain,
At QO time when Tfadiations seemed to offer thea anlY approach
tc the Study aF the Bacterial nucleus, the behavicur OF B
Sounded Ourragescus,

I hod been very active trying to get a Fellawship
tO QO abroad: I managed +9 get one From the Ttalian National
Research council, anid Gbhtained it while I was in the army
For conseription duty, I managed +9 get Sut OF Fhe army in
G@erii L488. The FellaowsShip was meane ¢G last G year , bBuUE it
COuld barely Poy For threes or Four months OF cheap
A°OCGMHMadaeION in England, Fartunately I got & Paid leave
From my Place in Milan,and the family coOUld survive, We had
One child, Matteo, Ge the time; Alba and Matteo Seaid it
Milan, JI still Rad a Strong attraction For statistics, ana
For the genetics of Quantitaeive characters; it Seemed to me
they were very important For evolution, K,Marher, then at
the John Innes Horciculcural [Inseicucian, at Mereon near
LOndon was working On it; he WOS AlSO 4 Strong
Seatrigcician,o J asked to spend my FEeELlILOWShip there, TI
WOrked in Drosophikla Gquantitative inheritance and isarned
Multivariate analysis in Mather’s lab, between April and
August 1948,

Qs you fan s@e@. JT had been on and oFfF bacterial
genecics For ix years, mostly GFF, atid yGu May Find my
Story a Little irrelevant sofar, But now comes the turning
pointe, G&S you know, there was no bacterial genetics until
1945, and J was Teally waiting For it +o be founded, {I
believe my Fairse chance ¢ca read yaur CSH Paper muse have
been when JT Was at Marton With Mather, because it took much
time after che war For English and American journals ¢€6
Starke coming again, To my best recollection. J] must have
read your i947 arcicie at Merton, when I wos with Mather. I
ramember J had Some difficulties understanding how the
selection of BM Gand Th markers affected che Lac Ui
segregation,

In August 1948 there was an international Gongress
GF Genetics at Stackholm, and I decided tc go and give a
paper On the cross resistance work tO NHitrogen mustard and xX
TayYS with Yiscanti, Gisa Yernan Bryson gave & Similar paper,
2NdsPpeaendaentiy, AN Almost ianecredibis rhing happenad ar
Steackhaim, FJ introduced myselFr to R.A, Fisher, I sremember
gaistinetrtly, on the steps of the Lecture hall oF the
CONnQGress, and afcer I said the First ten words he affered me
Q gOb at Cambridge to Work on bacterial generics, MY
immediate reacrion was divided, Naturally, I was extremely
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Zone’ s Lae, and had chasen Mather inscesd,
her and Haldane seamed like unapproachabla
imply ancredible ¢G be offered a job in F
J AlSO had a fONcerNs POW fOuld Ke offer
id na more than cen wards ¢G Him? How could
OUSly¥? J never asked Him tren or Later, but
have Heard of me From Mather, with whom I had by
+ Several months, Anyhow, J accepted on the spor,

OM My arrival ca Cambridge, on the fFirse Getaber aF
J had $09 Order averythinag $5 start a bacterial
@cics& lab, [J wat able ¢c begin doing sameching in Feb,
I got one Fourth of the room ordinarily used For tea i
yOu KNGW, AT important ceremony in England) ¢o mare my
amid another Fourth for the kitchen, The Lniversity gave
me G& §GGb Leese good than Origanakiy BSromised, whith should
have been that of ASSistant Director of Pesearch, In pare,
chey enjoyed playing tricks ta Fisher; in addition, they
certainly were unhappy giving a job t9 an Italian, of ali
People, You may remember when the F stary came cut, gndersan
WEOte JoOkingly {TJ hope): hOW can you believe in bacterial
SOH, GN wHeredibie story told by an Irishman, an Tealian and
a (@W7 JT have Forgottan which Was the order in Which ha
faced us, bul ie Might Say Something about the order af
wNacceeptability +o British eyes of these Sthnic groups,

I started by repeating your K-12 segregations,

Fisher Was very interested: his Teal desire was to have an
erganism for studying recombination and interference if
Larg® samples . Most if not all of His research was at the
cime Of PFecombinatiaon and interference an mice and plants,
H@® had immediately understood the effacts oF the sagregation
conseraines aon the recombination pateern in E,eali., When I
Qdd@d azide resistance, it was Norman Bailey who developed
the mam, likelihood estimatiom For it, None OF US 4tE Che time
WUOdARaTShoaid hha GRagrecdeakinn gpoakkarn Af sgugears daertrihnsad hy
Newcombe (Amer. Naturalise 1949, I] believer; it became clear
tO MB Only Much later. and I] developed their analysis ina
L954 paper with Jinks,

J decided +9 start Studying the genetics oF
PAGIOFeSIiStaNnce and Sensitivity, bute it turned cut that K-13
WAS NOt Lika B , J Selected For nitrogen mustard resistance,
and goo HEE (Cas well as an F- inf §8-idgt, if I temember
correctly; at least I presume it was}, I immediately
started working ¢G make Sure HFr was really a frequency oF
recombinstion mutant and not something 8158, The person who
WOS MOS SCePCICGL when I spoke at G meeting in Cambridge in
Spring *4%7 was Pontecorvo;: he later invited ma to repeat the
K-12 experiments in Glasgow, in the presence of sScEepticgi
bacteriologists. which I did, Some bacteriologists of the
Cimé, @SPeciaglly From medical labaratraries, Said apenly that
bacterial ganericists were crazy, At fambridge the
biochemist E,F., Gale was cold; BD, G.Cantcheside locked at
bacteria with suspicion, Perhaps because He was used to the
Tegular mendelian behavior of Fungi, Fisher was the only
Parson WhO WAS Sympathetic and supportive,

My Getemptes at Seeing the PTGCeSS GF Mating with HFr
Ware totally negative, J became more interested in
GUECTOSEING E,COli atid, lacer,ae Studying quantitative
whreritance tO ohlagramphenicol, My Position at Cambridge was
mae $c Secure; -T was originally given a three years
eontract, and J Felt pretty isolated scientifically, 30 when
I was OFFETed & BgOGd POSition back at che Sieraterapicea

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MLLOANSES. Where os mew director gaye MQ ALS £5
gevelapr Che Place intG a Teasonabi Byaitucsion, f[
gaCiced +o return +o YTtaly, FT had 5s 3.37
amar idge, and Lert chere GZivulia Ma I $8ad catied
From Pavia and trained For a Year, Re WOPK,
This if the etary OF my beginnings feericgi
Generics, To was back in Milan in Get YEN wikh &
mew dairectar Fram the £i,5., the Sier maitied, the
MGdigcra place it Always was, I kas and more

technicians buc Gleo more Tetpansabilities, It wos here,
however, that J develope the story of F; IT was trying to
ercecses TLBLi- ¢G itsSelF and déveloped new markers Far this
Purpose, Untransformed TLAL- derived strains never ersssed
eG each other, bute Gli recombinanes crossed Freely, Sa I
ried G Menage 4 trois Bxkperiment and than direct infection,
Ge che Same cime you did, The best visitor I hod was gon
JENKS, Wath Whom We Found HF was Linksd t9 GAL; this was
mode Public at Che Genetics Congress af Bellagio in @uguse
1953 But Nobody noticed except Bertani, Somehow. Hayes
managed €G get much Attention and Fublicity For the same
Soservations on inheritance af HFr done Later: his
getreptomycin and UY experimencs had got the limelightcs Far
him, ANd Paris Circles advertised them widely,

I Came ¢Go Madison if 1954, and we worked an Sib
selection in liquid medium, J a21s0 saw then your
MICTOMANIPULACION experimencs with Slim HFr and Fae Fe
felis, and was unable +o Bae motinas with the EM, My work
Back if Milan was not very praductive, My interest’ secarted
turning more and mare Heavily towards HuMan genetics, after
“& Slow beginning Sometime during the early Fifties, In early
IVS? JT leafe the Sieroterapico and started helping Adriana
S@ececcing up PRG, like courses in Pavia which were che
Prelude to the constitution of LIGH at Naples,

On My second Visic ¢G Madison, iff 1958, we spent ali
the tame trying to disprove the chromosome insertion theory
OF WOllmann atid jacGb, We were not successful and yee it
Looked SO improbablis, Somehow, all the bacterial generics
work aif; Pavid between L958 and if48 was unsuccessful and che
Last work JT did was With you and Esther, putting trogethar
JGiNe GHServaktiane on Gal Suppression by strepcomycin,

These reminiscences are probably much more than you
OSked; iff retrospect, My worst mistake was to return ta
Italy, Had I spent one more year in Cambridge, I probably
WOUld RaVEe had the job promised by Che University Gt the
beginning, and would not have returned to a Hopeless
Scientific desert, There was mo way ¢G Stay competitive in
th@2 Papidly developing field of ‘microbial genetics working
a% 280 1aGbtian in G& Plnce like the Sieraterapiceo, where I had
LimitO’d MObility, increasing loss of Scientific Freedom and
Jatctie ar na chances of discussion, Had I stayed in
Cambridge, a year or two later there would have been big
iseal developmencs, OFT I Should have moved to the States, [
l@Ft bact@rial genetics too early £0 do anything Substantive
Geher than For Che work done with you on F, and the HFr
WOrK, Which are often credited to Hayes only, The way things
wernt, However, T did mot dG ¢oG badly in human genetics, The
move to Stanford gave mé@ a chance +o gd back +o some
experimental work, develop many mew things, and be in the
Paght pPlac® when the DNA revalution was rips, J kKeap a
Lecter from you it the earity sixties in which you offered me
Q chair at Stanford, I accepted your invitation some tran
yeare later, [t is Fubile ta sSperUulate what IT could have
done if I] had come to Stanford earlier, What I did in the
Sixeies in Tealy was limited ¢& Starting the work on
Pragmies, and developing the Pavia lab and department which
WOULld GthREerwite HaVeE Heer destroyed. “A2drians did noe wank ea
 

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aGne €& this rule, No meed ¢& feli you this =
Bly confidential; J wOuULd Or KBP ah fanFi
id change things, bute FT dG mot x#nGwW What Saul
it,

JT PRBALISS bis Letter is Much roo Long ana
WOU @nxpectations, Bur your Question was pro
aang abauc at “occupied pleasantly my ime an
ko, and back From Europe,

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