LEDERTTL

BECKMAN CENTER FOR THE HISTORY OF CHEMISTRY

JOSHUA LEDERBERG

Transcript of an Interview
conducted by

lames 7. Bohning

at

Rockefeller University

on

25 June, 7 July, and 9 December 1992

(with subsequent Corrections and Additions)

Page 1


                                   LEDERCHR
JOSHUA LEDERBERG

192 5   Born in Montclai r, New Jersey on 23 May

Education

1944 B.A., bi ol ogy ! Co1 umbi a uni versi ty
1947   Ph.D., mi croblol ogy , Yale university

Professional Experience

1945-1946   Research assi stant , zoology, Co1 umbi a university
                (with F. I. Ryan)
1946-1947   Research fellow, Jane Coffin Childs Fund for Medical
Research, Yale University (with E. L. Tatum),
       University of Wisconsin,                Yale university

1947-1950      Assi Stant Professor of Genetics
1950-1954      Associate PrOfeSSOr of Geneti cs
1954-1959      Professor of Genetics
1957-1959     chai r, Department of Medi cal Genetics
    1950   Visiting PrOfeSSOr of Bacteriology, University of
California, Berkelev

   1957
Melbourne

1959-1978

1959-1978

1978-1990
1990-

HOnOrS

1957
1958
1960
1967
1967
1969
1970
1979
1979
1979
1980
1981
1981

    1982
Science
    1982
   1982
    1984
    1985
    1989

Visiting PrOfeSSOr of Bacteriology, University of

Stanford university school of Medi ci ne
  Professor of Genetics (al so Biolog Y , Computer
Science) , Stanford university schoo  of

  chai rman, Department of Genetics
The Rockefell er University
  President
University Professor

National Academy of Sciences
Nobel Prize for Physiology or Medicine
Sc.D. (honorary), Yale University
SC. D. (honorary) , University of Wisconsin
Sc.D. (honorary), Columbia University
M.D. (honorary), University of Turin
Sc.D. (honorary), Yeshiva Universit
Litt .D (honorary) Jewish Theolo 9- ica Y Semi nary
Foreign Member, Royal Academy o  Sciences
LL.D. (honorary), university of Pennsylvania
Honorary Life Member, New York Academy of Sciences
Sc.D. (honorary), Rutgers University
Honorary Fe1 1 ow, New York Academy of Medicine

Fellow, American Association for the Advancement of

Fellow, American Philosophical Society
Fe1 lOWI Ameri Can Academy of Arts and Sciences
Sc.D. (honorary), New York University
M.D.  (honorar >,
     7  Tufts University
National Meda  of Science

Medi ci ne

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                              LEDERDOl
INTERVIEWEE:   Joshua Lederberg

INTERVIEWER:   James 3. Bohning

LOCATION :     Rockefeller University

DATE:          25 June 1992

LEDERBERG:  Here is a more detailed chronological outline.  It will mostly not be
too meaningful to you, but it's sort of my first chronological sketch,  utting in
much more detail than will ever be written down in anything more compre ensive.
                           R       I'm
not transferring this to you; I'm letting you use it, but I'd like you not to copy
it and I'd like you to return it to me.  But it might be helpful to you in
structuring what you want to do.

BOHNING :  ~11 right.  That would be fine.

LEDERBERG:  If you prepare some rough outline of major themes  I'd like to see it
before it goes into any repository.

BOHNING:   Sure.

LEDERBERG:  ~11 right.  That applies to both of these documents.  YOU might want to
go home and study them in more detail.  what more do think you'd like to do today?
Do you want to take a minute or two to look at these documents, or do you have some
things that you already had in mind to get started with?

BOHNING:  I was not really prepared to start today.  I thought we would best spend
our time today just discussing where we're going to go and how we're going to do it,
so that you understood what I was looking for and vice versa.

LEDERBERG:   Sure.

BOHNING :  I think it was mainly these notes that I had indicated.  AS I said, I had
just put together a brief chronological outline and then added some notes on to that
to indicate the kinds of things that I was looking for.

LEDERBERG:  well, you'll see much more than you want to use on the chronological
agenda.  YOU can see here an answer to your question about dates.  NOW, I'd still
not like to waste the opportunity to visit.  Maybe there's some of this we could go
over together right now.  what's your feeling on the matter?

BOHNING :  well, if you want to spend some time, that would be fine.

LEDERBERG:  I have until 2:30; that's my only constraint, so that's an hour and a
half.

BOHNING :  okay.  one of the things we usually start with is parents and family
                         Page 1


background.

LEDERDOl

LEDERBERG:  okay.
notes].        As much as I know is down there [referring to bio
     what should I add that would come across orally but still 9 raphical
                                        c early?  I've
al ready highlighted to you the centrality of my dialectic with my father [zwi Hirsch
Lederberg].

     The central point is that he was an orthodox rabbi.
from what is now Israel, then Palestine.              He was an immigrant
                          He was quite fluent in English.   He was
we1 1 educated, having more of a seminary education than a university or a collegiate
one.  He had been viewed as a brilliant scholar and in fact had been sent to the
united states for studies here.
fifteen or he was eighteen.    There are conflicting accounts as to whether he was
                      I've tried to track down documentation on that without
much success,
University.   although he appears to have been enrolled in what is now the yeshiva
       That is at least one of the places that he was connected with, although
they can't find any records on him.

    That was fortunate for me in a number of ways, but for one thing he got the
equivalent of the Green Card at that time and the iron gates were slammed shut on
immigration not long thereafter.  on the strength of his prior residence, he was
able to immigrate here in 1924--a point I never investigated during my parent's
lifetimes.  In the few surviving records after my mother died some of how that
became possible became a little clearer.

    He had a religious vocation.  I would have liked to have probed more deeply
just where he stood on issues of modernity, and I suspect he was in some conflict.
He had a fairly orthodox background, and there is a family background and tradition
that goes back centuries in that direction.  I al so recall him as someone who was
very much interested in America and being a good American and in keeping u  with the
times in a wide variety of ways.  There was a certain ambivalence when he f: ad a
child who had no interest and certainly zero in the ritualistic aspect of the Jewish
faith, thoroughly involved and immersed in science, without that kind of
reconciliation.  That's what our debate was about.  cf. spinoza a model.

    I continue to regard science as a vocation and one I think he accepted as a

parallel to his, but the detail of that is something that I would have liked to work
out more clearly, especially in a dialectical axis, to some degree in my own mind.

     I'm not sure that there's more that I am able to dig out on that issue at
this point.

BOHNING:  what about other relatives?

LEDERBERG:  well, the nature of that family tradition was of some consequence. I
was very tardy about tr K ing to collect genealo ical  information.  There was no
developed interest in t is durin ? my parents' 7 ifetime, which was unfortunate, so I
never got information firsthand  rom them.  I ended up being the family historian,
although the record is mostly in Israel.

    There's a large Lederberg clone in Israel.  The
Throughout the world I think they are,and that's a puzz e in itself. what does it
                     Y 't-e all from one family.

mean?  I have no good evidence on that point.  But it comes from a town in Poland
called Plock, about 100 km west of warsaw on the vistula.  whether there's anything
left in the holocaust documentation that they've found, I just don't know.

    I've had one or two friends take a cursory look at those materials for a
more detailed investigation.  what's more important is the sense of tradition that
went along with that.  There was a strongly develo
scholarship on both sides of my family.   I now  7 ed tradition of Rabbinical
                                    rea ize it was more deeply ingrained
on my mother's side than on my father's.  MOSt of my father's relatives were
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                             LEDERDOI
busi ness people, with a sprinkling of rabbis among them, including especially the
progenitor, who is called the "Gaon," the Ayatollah of that part of Poland.   But
most of the descendants went into real estate or other businesses.  They were middle
class people in Jerusalem.

    Through the Turkish occupation, after the British advances, there is a story
about m  mother [Esther Goldenbaum Lederberg] at age fifteen, having been a nurse
and wor z i ng heroically for some of the wounded and helping to reassure the people in
Jerusalem at the time of the actual conflict.  what truth there is to that I just
don't know.  But that was sup osed
presented to my father's fami T   to have been one of the virtues that was

what I recall  b        y when they were negotiating their.marriage. That's
     Y way of background.
away from              This is in a way retroTZlonistlc, the movement
         Israe  and trying to represent the ideals of Judas sm 1 n the Diaspora.   I
guess I do stand for that ln my own way just as strong as my father did.  End of
report. [laughter]

BOHNING :  I be1 ieve you said he came here in 1924?

LEDERBERG:  He was here in 1921.  whether he had come here as early as 1918 seems
probl emati cal , but there are pieces of paper that I don't trust that say that. But
it was no later than 1921 that he was living here.  (He was born in 1904.)

    Then he went back to Israel and claimed his bride.  I'm sure it was a
negotiated marri age.  He brought his bride, my mother, with him back to the States
in 1924.  I was born in 1925.

BOHNING :  what are your earliest recollections?

LEDERBERG:  well, I wrote some of them down [referring to biographical notes]. They
may be screen memories, but here we go: Lindbergh, most traumatic events. My
brother [Seymour] was born when I was three and a half.  Then starting kindergarten
[in 19291.  I have vague recollections from when I was four or five years old.

BOHNING:  YOU were here in New York by that time?

LEDERBERG:  Yes,  I was.  I was born in Montclai r [New Jersey], and when I was six
months old we moved to New York.  I have what I'm sure is a false memory of the
train ride from Montclair to New York, but I don't believe it. [laughter]

    This is a piece of documentation my mother saved.  That's an interestin
fact, and that's literal [20 June 1932 essay on wanting to be a "scientistist" 7 ike

Ei nstei n] .  [1 aughter]



BOHNING :  YOU said you weren't inclined to follow the way
the family tradition, as it were, a religious tradition.

your father had followed

LEDERBERG:  I thought that was medieval, quite apart from the core of philosophical
validity that there might be in Judaic teachings.  Maybe I did know, and I would
have allied myself with a s inoza
faith, if you like.  But I c afed under the rituals.
          R    rather than my father. A heretic within the

Saturdays were the best days that I would have available to go to the
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                             LEDERDOl
library, and that was forbidden, so I evaded it.  I would walk a mile so that none
of my father's parishioners would see me,
the public library.               then get on the subway to go downtown to
            SO, I thought that was very old-fashioned, and I didn't
understand why they kept doing things.  I would hark back to my father,  askin
all these things were being done at the time of the Temple or are they ill -in B if
                                                           ormed

accretions through the experience of the stetl when the Jews were very tightly
segregated and were not part of the larger world.
fundamentalism. [laughter]                I was going back to

BOHNING:  How did your mother respond to this?

LEDERBERG:  Oh, very pragmatically.  She said, as my father did, "whatever you think
about the matter, your father's job depends on your not being seen as being in
vi 01 ation; they would be horrified that you're doing it.  We 11 talk about it
privately."  They didn't tell me I would be damned and go to hell on these points.
They had their own reservations about those deviations, but they were restrained.
They discouraged me,  but didn't condemn me for the deviations.

    And at other times they'd be very proud of what I represented.  We had role
models like [Albert] Einstein and chaim Weizmann who were very prominent ima es
                             9   in
Jewish life generally at that time, but also with scientists.             or-made
for m it view of the world.                        They were tai
                 I'm sure Albert Einstein did not observe the Sabbath; I'm
sure  e was regarded as a wonderful and great Jew,
father. [laughter]                     and I would throw that up to my
            It was not an unreasonable standard of behavior on my part.

BOHNING:  I was curious about your comment about your father's job, because I've
known Protestant minister's children who grew up in a small town and had that same
situation.  They were restricted in their behavior because of their father's
position as being the religious leader, and it created problems for a lot of them.

LEDERBERG:  well, there were also other expectations.  We had Hebrew school on
Sunday, and I was expected to follow that faithfully.  It was also expected that I
would be the paragon of achievement there as well; it was something that I really
didn't care much about.                        As I ve told many
7 eople,            I had to go to services unendingly.
    I had enough religious observation until I was thirteen to last me a
ifetime,  and I'll leave it at that.

BOHNING:  what about your brother?

LEDERBERG:  I have two brothers.  I haven't probed as deeply and as directly with
Seymour, who's close to me in age and has had a somewhat similar career.  I think he
feels much as I do about it.
reli ious fanatic,       we have a much younger brother [Bernard] who is a
&         and a dangerous person.  He's in the Lubavitcher movement and
thin s [Rebbe] Schneerson is the messiah.                  all the time.  He's
somewhat kooky.                  He is proselytizin
          He's reverted all the other way.  I sure my ! ather would be aghast
at his extremism.  Great surprises in family dynamics. [laughter]

BOHNING:  what's the age difference?

LEDERBERG:  Sixteen years.  He's a grandfather.  That really came home to me, that
my baby brother's a grandfather! [laughter]  He lives in Jerusalem now.

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LEDERDOl

BOHNING :  when did you start reading in earnest?  you've talked about setting your
goals very early in your life.

LEDERBERG:  well, I can't remember when they were otherwise.  This is the only
documentation I have, and it was a second grade class essay, "what do you want to be
when ii ou grow up?"  That was my statement at the time.  I don't know how seriously
to ta e it.  IS that something I invented at the moment, or did I just think it
might be a good idea? I don't know.  But within a few years of that I was very
actively reading al 1 the science I could.  when I was ten, I can remember the
headline when Stanley found the tobacco mosaic virus. when I went to look for it

   I could spot it instantly once I saw it on the page of the New York TimeS.
~iK$ter]
    I had teachers who were already nurturing me as a  recocious child.  I had a
contract with them--if I cooperated with them in he1 in
business, they'd leave me alone and I could sit in t e R %  t R e class move on with its
                                  ack of the room and study
all the things I wanted.  I remember confoundin  my algebra teacher with a phony
proof that two equals one,  and she couldn't wor ii her way out of it.  That's what
preci pi tated these contracts. [laughter]

BOHNING :  which is something you did purposely ?  At least you had the support of
these teachers.

LEDERBERG:  I did when I got to that stage.  There was a point where I was `ust so
bored and didn't think they were such great scholars, which was true, but t at's
                            i     not
the whole story, obviously, in teaching.  They were very wise people and very
compassi onate.  They would admit that to me and deal with me as an adult ,  sa i ng ,
"Look, we both have a problem to deal with.  I've got to bring the rest of t x is
class up to what it is that they need to know, and you've 4 ot to find some way to
use your time effectively, and don't do it by teasing me a 1  the time.  YOU probably
can catch me up on these things, but is that what you want to do the rest of your
life?"  They would have a hard talk with me in those terms.  SO we worked out a very
good agreement.  By the time I was eight to ten years old, I was certainly solidly
involved in self-study.

BOHNING :  while that self-study was directed in the scientific area, did it range
over other topics as well?

LEDERBERG:  YOU might say both.  It was largely concentrated in science, but I read
a lot of history, philosophy, political science, current events.  I was very much
involved in what was going on in Euro e, what the U.S. was going to do about it,
thin 7 s of that kind.  I tried to teat R myself everything I could.  I tried to teach
m se f music out of a book. [laughter]
tl                       Imagine that !  I knew what the notes meant,
w at the measures were and so on.  I did have a ver
librarians were very helpful and very nurturing.    good public library and the
                           T ey put no limit on the number of
                   i?
books I could check out and helped me find things I wanted. I had nothing but help
in that regard.

BOHNING :  Did you have any friends your age who were similarly inclined?

LEDERBERG:  NO, and that was a very troublesome point .  It wasn't until I got to
high school that I had peers, and I felt very lonely during that interval.

     I did have the luck to catch u

classmates, who remembers that interva f again with one of my grade school
                                           .  Through a strange series of circumstances,
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                              LEDERDOI
she's married to somebody I know pretty well,  but I didn't know the connection
between the two of them.  A common friend brought that out.  They 1 ived here in NW
York for some time.  They quite recently moved out to Cincinnati , and I had dinner
with them a couple of weeks ago when I had business there.
    she remembered me very we1 1 even though I hadn't. seen her in fifty-five
years.  she said that I was wi de1 y  reco nized as a phenomenon.
               ii                I said,  "You mean, a
freak?"  And she said, "No, it wasn't t at.  we just knew you were somebody pretty
special and we might have to make some allowances for you. "
detail about that.               she didn't go intos;;ch
           I thought I was pretty brash and rude and self-important.
minimized that and said, "we made a note of that, but we all understood."
    That's just amazing to me.  They must have been wonderful kids!  In other
observations I've seen exactly the opposite, how youngsters can gang up on somebody
that they're jealous of or something of that sort.  I think what she said to me was
genuine.  I don't recall much negative on the part of my  eers;
                      R     I just felt
isolated from them.  she gave me a different picture of t  at.  Isn't that something?
[1 aughter]



BOHNING :  was that isolation on an intellectual level , t:hat thei r interests were
just so totally different than yours?


LEDERBERG:  YE!;; :Lytd's,,what she said eventually when I said, "what -do you mean by
allowances?"        well, you just weren t 1 nterested 1 n the things that we
were, and we couldn't keep up with you, but we knew that what you were doing was
important , and that you would be something some day. "

   I had the same general nurture from my teachers and what only occurred to me
after my conversation with her is that I had viewed this as one at a time.  In the
relationship with my teachers, it occurred to me that they must have had some
collected discussion too about what to do about poor Joshua, because there was a
R retty consistent response.  It had just never occurred to me before that I would
ave been an object of di scussion.  some of the other things that Abby [Abigail
Levi n] mentioned made it pretty clear that I was.
    If you can believe this, they'd been doing some standardized tests on
standardizing the IQ test, and they actually announced the results.  I was supposed
to have had the highest score of anybody in the eastern united states, or som;ctElng
of that sort.  Abby was one of the  runners-u 7 ; that's why she remembers it.
recalls our being presented at a grade schoo  assembly, and Joshua was asked to
comment, and "It was supposed to have hurt my votes."  SO I was not invisible to the
faculty.



BOHNING :  Did you get skip grades?



LEDERBERG:  Yes, I skipped a couple of years.  I finished high school when I was
fifteen and a half, and I had to wait unti 1 that fall unti 1 I could enter co1 umbia
because they had an age limit.



BOHNING :  Let's discuss your se1 ection of Stuyvesant High School .  It wasn't
automatic that you would go there, was it?



LEDERBERG:  They had a corn eti tion for students interested in science.
          R                           They offered
a special curriculum and t ey had a special peer group.  so given the circumstances
it was automatic that I would apply, and I had no trouble getting admitted. So
that's where I went.  I think it was the peer group that made it very special.   For
                         page 6


LEDERDOI

the first time I began to have a bunch of youngsters that I could relate to and had
shared interests and were as bright as I was.  That did make a big difference.
    In some respects the teachers were not as experienced and wise as the ones I

had in grade school, but maybe that's because I was a little older and knew the
difference that makes. But the i: were fine.  A couple of them were really
super1 ati ve,  and others were a out what you'd expect.

BOHNING :  This was a time when it was not uncommon to have Ph.D. s teaching in a high
school.

LEDERBERG:  There were a few, but not man  .  The best known one was Dr. [Joseph]
Shipley in  En ? lish who had books on   Y
                          etymo ogy.  I barely knew him.  The pri nci pal ,
Dr. M.  Nardro f, had his Ph.D., but there weren't very many. There were no research
scholars among the high school teachers, and I was keenly aware of that.   It was not
until I got to college that I could meet people who really knew what science and
research was all about from their experience.

BOHNING :  How about the laboratory exposure?  You'd been doing all this reading,
even earlier on, in science.  when did you get your hands onto something?

LEDERBERG:  Like every other kid in those days, I had my own chemi stry 1 ab at home
and nearly blew myself up a few times.  I did al 1 the recipes and made al 1 the azo
dyes and discovered new reactions and all that kind of stuff. The school labs were
pretty dull .  we learned analytical and worked with hydrogen sulfide.  we had a few
advanced pl acement 1 abs .  we 1 earned how to use a bal ante and did quantitative
anal ysi s .  There was hardly any organic chemistry, and that's what excited me the
most.  I had to do that on my own, and taught myself.  I was able to get advanced
placement when I got to college,  and was in several advanced courses.

BOHNING :  How early did you acqui re this chemistry set?

LEDERBERG:  Twelve or thi rteen, something like that.  I was reading [Meyer]
Bodansky's textbook on R hysiological chemistry at that time (1). There was a little
disconnection between  t ese "great" chemical experiments and much more sophisticated
reading, but they were fun.

BOHNING :  How did your parents react to this?

LEDERBERG:  I don't think they fully understood the risks I was taking; I'm not sure
I did either. [laughter] I played with  otassi urn cyani de with aplomb.  There could
have been great mishaps; in fact, with t t: e exception of one or two fires and
explosions , the opportunity for poisoning would probably have been greater,  but  I
had a healthy respect for what they could do.

BOHNING :  HOW did you acquire your chemicals?

LEDERBERG:  There was no problem.  Eimer and Amend would sell them to anybody over
the counter.

BOHNING :  Real 1 y?

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LEDERDOl

LEDERBERG:  I shudder!  They sold me two hundred grams of sodium, and I was
experimenting with progressive increments to see what was the largest amount   ou
could throw into a pot of water and still only have an amusing pop.  [laughter Y

   There's a little thing in C&EN a week or two ago (2), when somebody
commented after reading about the woodward symposium that none of these things would
be possible today.

BOHNING:  FrOltl what  ou've said, a lot of your early experience in a laboratory
setting was chemical Y y-oriented.

LEDERBERG:  At school I was in the biology club and learned histology and how to
make sections.  I was doing a lot of that.
cytochemistry,               I got interested in micro-chemistry and
        and I thought that was what my career was goin I! to be--u;;;! ;t;anced
micro-chemical technology to explore the chemical nature of t e cell.
exactly the wording that I would use when I was fifteen, and so I was systematically
going through staining reactions and how they might be influenced by fixation.

    I got interested in the nucleolus, basophilic stained material that was
Feulgen [DNA] negative.  I would have been able to tell you that at fifteen.   so we
didn t know what it was and were tryin ? to figure out by micro-chemical procedures
by this point to determine its chemica  composition.  it was the appropriate scale
to be asking questions like that in those days.

   I didn't know it, but that was just about the time that [Jean Louis] Brachet
introduced the use of ribonucleases as a differential reagent.  The removal of
basophilia ribonuclease was his evidence of RNA.  I was still fumbling with the
issue.

[END OF TAPE, SIDE 11

24

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                             LEDERDOZ
LEDERBERG:  By the time I was sixteen,
could search out this kind of thing.   I had access to good enough libraries that I
                                  Coo er union allowed me to use its stacks when
I was a high school student,  and so I  `;
probably Bi 01 ogi cal Abstracts .      cou d go through Chemical Abstracts and
                        I could search out what I needed to know in most of
the literature.  The literature was one percent of what it is today.  Brachet's work
was done in Belgium, and those papers just didn't get out from behind the German
lines until after the war.

BOHNING :  Did anyone point you to things like Chemical Abstracts?
LEDERBERG:  I don't know who it was.  I think I just went to the library, and it
would have been the 1 i brarian that helped me if I wanted to look something up.   I
know I got interested in steroid chemistry while I was in high school. By a curious
coincidence, I got on to Russell Marker's papers about 1940 or 1941 (3). I read
them from beginning to end.
Carl Djerassl .  Of course,   what's amusing is that some years later, I met up with
                Syntex was founded on Marker's work.  Carl was astounded
that I knew all about that work. [laughter]

BOHNING:  That's fascinating.  He wrote some interesting papers.

LEDERBERG:  Did you ever meet him?

BOHNING: No.  we have an interview with him, but I didn't do it.

LEDERBERG:  I've met him once,  at some ccl ebrati on.  Carl's a great fan of his, of
course .  He's had a weird career. [laughter]

BOHNING:   Yes.

LEDERBERG:  SO, the libraries were my most important  resource.  I did some of this
laboratory work.  It was focused on cytochemistry.  In the spring of 1941, after I
finished high school and before going on to college, I had a chance to work for six
months in a reasonably equipped research laboratory [American Institute Science
Laboratory].  It was a predecessor of the westi nghouse science prizes.  They offered
a research experience, instead of the prize hullabaloo.  It was a much better idea.
They had a lab that IBM offered some space for and then documented.  They did a film
on it about four or five years ago.  It was quite a crew of people.  I kee `? running
into them all the time.  Charlie vanofsky and Barry Blumberg were in that  ab,  and
we all remember it very distinctly.  I continued working on this cytochemi stry
project.

BOHNING:  was i t se1 f -di rected?

LEDERBERG:  Pretty much.  I'd hoped to have some guidance, because that was part of
what was being offered.  But they didn't have anybody who knew anything about what I
wanted to do.

BOHNING :  Going back to high school for a moment, did the teachers 1 eave you pretty
much on your own?  were you in a structured curriculum or could you take what you
wanted?

LEDERBERG:  NO, there was more structure, but it was more advanced so I didn't feel
quite so bored.  Although most of the science I did,
before the course started, and if not,          I pretty much knew the material
                       it was pretty easy to catch up.  But there
are different grades to knowing something,  so there was a certain amount of drill
and knowing it inside out, which taking classes did help.  I didn't feel so bored at
that stage and also had some peers to talk things over with.

    AS an educational experi ence, high school was much more important in terms
of the social sciences and humanistic subjects.  There :I remember a civics course
that was absolutely superb.  It was a pretty advanced course in political science
                          Page 1


LEDERDOZ

and economics and rational policy making.  I've forgotten the name of the teacher,
but I have very powerful recollections of it.

BOHNING :  Are there an
          reco lections of some of your grade school teachers.
        Y other teachers that played a special role or influence?   YOU
seem to have fond                                         what about
hi gh school ?

LEDERBERG:                                                      I've
ke t     I got to know the biology teachers and I've known them ever since.
7  certain contact with them.
we 1,                They were professional teachers, they knew teaching
   and they knew their limitations.
me that there was in grade school.    They didn't have the personal rapport with

The fact that the           It wasn't quite that level of affection upon me.

Nurture is an awfu Y were men, not women,
            ly strong word,     made some difference in that regard.
                    but they were a positive influence with me. when
I think about it, they were reasonably di rect about thei r 1 imitations.  They just
weren't themselves research scientists and at their depth and intensity they were
not involved in doing research.
respect for their classes.     I had positive reactions to them, and I have great

BOHNING :  Do you think they were intimidated at al 1 by you?

LEDERBERG: No.  I think less in a way than m
1 ess singular phenomenon to have a high   Y grade school teachers were.   It was a
                              schoo  student readi ng co1 1 ege 1 eve1
material than to have a sixth grader doing that.  I don't know if I remember
anything that mi  ht  recall that.
their job to dea 7          They just considered it a more normal part of
          with bright kids and provide some channeling and disci
about thei r business.                     R line and go
&;EAyped it.       SO there was some professional pride in the way t ey
        I don't recall anything 1 i ke the personal touch that I had in grade

BOHNING :  YOU said that the six months before you could enter Co1 umbia was a uni  ue
way of doing things.  were there any special experiences during that time, or di 1
you just continued on with your own project?

LEDERBERG:  I was able to do it more or less full time, at least part of the
semester.  I think I worked durin  the summer.
ver g affluent .        %         My family was, to say the least, not
                                   een
ena led      Things must have    getting a 1 ittle bit better though, to have
     me to do that rather than have full -time work.  Al though,  I did work that
summer.  No, it was just the fact that it was the enjoyment of being able to
concentrate on one subject.  Then you have the kids there.
to talk things over with them.                   That was quite exciting

BOHNING:  why did you select Columbia, instead of, let's say, CCNY, which at that
time was also a very strong institution?

LEDERBERG:  well, I was headed to CCNY, but I knew a little bit about scientific
emi nence.  It was somewhat out of date, but I still associated Columbia with, if not
[Thomas H .] Morgan,  at least with E. B. Wilson.
Development and Heredi t                I had Wilson's book, The cell in
         iT (4) -
during my last year in      I still have my copy of it.  I 'd been reading that
             igh school. I was eager to go there.

    There were a couple of other possibilities.
'; robably didn't know that Wilson had died lon 9 since. c tology was the core of it. I
onger there, but it was the preeminent schoo   [raughter]   It certainly is no

special fi nanci al assi stance,        in biology. I knew that unless I had
                 I had to go somewhere where I could commute.  That
wasn't forthcoming.

    I did apply to Cornell. The botanist there, Leslie sharp, was in cytology,
and I knew thei r textbooks (5)) but I failed to get a Tell uride scholarship that
might have allowed it.  Robley Williams was on that committee, a fact that I
discovered a little later on, and I teased him a little bit about having turned me
down, but it was probabl a good thing for me. [laughter] Cornell was quite
discriminatory.  A farm ii
I couldn't.         oy could get to Cornell , and in the program I had in mind,
       As a matter of fact, there was Norman Krechner was a classmate of mine,
                         Page 2


LEDERDDZ

did get into Cornell and subsequently head of the pediatrics department at Stanford.
I'm having dinner with him tomorrow night.

      So a ver                                        That was the
only thing   i small sprinkling of New York City students made it.
        resem lin ? a state university.  city college was crowded,  ver Y few lab
facilities.  A lot o  brilliant people went there because there was no a ternative.
I did regard it as a last resort, and I was happy I could   et
at columbia.  I think that being able to go there was the 9  a tuition scholarship
                                              uckiest
happened to me.                                thing that ever

BOHNING:  YOU mentioned earlier you had been following events in Europe, and I know
that CCNY was a hotbed of communism. [laughter]
thinking politically.                 I was just wondering what you were

LEDERBERG:  I had some a e
and so on.          contemporaries who were very keen on it and anti-fascism
        I was very  s ;i eptical from the very beginning.  I didn't see that much
difference from one form of totalitarianism versus another, and I wasn't going to
buy that for one minute.

    My politics haven't changed much in all that time.
war in spain was a test of what democracy was able to do.   I had thought that the

dis                                  I thought it was a

wit 8 race that the west did nothing in those dimensions. But as far as taking sides
  the Soviets in fomenting revolution or whatever, I had no truck with that.

    It had its faults, but America was the best place in the world that anybody
could be.  I saw how the liberties of people had been achieved and yes that there
were many more things to do.
on my side,           Most of the scientific colleagues I had were sort of
       and the ones in the social sciences tended to be more leftist.

    I'll mention one more point.  The thin
Molotov-Ribbentrop Pact [1939].  That was real 7 that completely told us was the

on those matters.                  y the touchstone of where you stood
          I could sympathize with those who had had some pro-soviet

(because anti-fascist) leanings up to that time,  but when I saw drove after drove of
the kids that I knew then suddenly switched off their opposition to Hitler after the
Pact, I had nothing but contempt for them.

BOHNING:  You were only a few years old when the Depression started.  what effect
did it have in your life?

LEDERBERG:  I was born in 1925; that's a generational milestone.  I don't have
distinct recollections, but I think we were like the parson in the small town; while
our cash income was very limited, quite literally the butcher and the baker would
help out.

   I also remember guarding the telephone to make sure that if there were
special calls for religious officiation,
wedding or unveiling or something of that we wouldn't miss any o 7 portunity for a
                                     sort.           ho d of the minutes of
the synagogue that my father was the rabbi at,  I've gotten
this information, "No money, can't pay rabbi." and during that period that there is
                                  That's what's in the minutes.
[laughter]
the weddings SO it was the five dollar fee or fifteen dollar fee for officiating at
      and funerals that kept us going.

we were never very well off either,        we were never totally destitute, and
period.                 so we lived at that level throughout that

BOHNING:  Did they provide housing for your father?

LEDERBERG:  There must have been some deal.  I don't know what it was.   we were
living in what I can see now as a pretty comfortable apartment house. It was
incommensurate with the cash income, so there must have been some special deal. I
had to share a room with my brother most of the time.
own, but I didn't have to share with my parents,     Eventually I got a room of my

of the heap.                      so we were not at the very bottom

BOHNING:  where were you living in New York?
                         Page 3


LEDERDOZ

LEDERBERG:  washi ngton Heights .

BOHNING :  How would you classify washi ngton Heights at that time?

LEDERBERG:  It was just on the northern border of Harlem.  Thepublic school I
attended was right on the border and a lot of black kids attended the school.  There
was no great discrimination there.  There were kids who1 did pretty well ;  the
weren't at the top of the class,                  K
                   but they were good students. There was not ing
like the stratification that we have today,  and a minimum of racial strife.

    My problem was not the black kids but the Irish kids.  There were a number
of those, and the priest talking about chri St-killers, and so on.  There was
;;;;;Tnt strife straight off.  There were al lowed zones of traffic coming home from
     If you strayed one block from that, that was invading territory.  There
were 1 jttle pockets of Irish Catholics in a mostly Jewish community at that time,
and you'd get beaten up if you crossed the line.  Now, nobody ever pulled a knife or
a gun, so there were differences in that regard.

BOHNING :  As you were growing up, were you aware of anti-Semitism?

LEDERBERG:  It was pretty abstract for me.  I saw this event, but you could argue
that there were ethnic groups fighting one another all the time.  I would hear a lot
about the difficulties that other people had in getting1 jobs because they were Jews
and I'm sure there was some substance to that.   I  ersonally experienced very little
of that.  I think there may have been a considerab e 7  i niterval during which if   ou
super-excelled you could make it in almost any sphere, but that, other thin fl s i?i ei ng
equal, the non-Jew would be preferred over the Jew.  so it was a superable  andicap
in any event.

     I didn't realize how much of an issue it was in\ the world around me.   In a
way I was somewhat naive and `T rotected.  I knew it was an issue in college
admissions, but I got into co lege.  I knew it was an issue in medical school
admissions, and I got into medical school.  I'd hear complaints from others that
they had been left out because they were Jewish, and they were probably true. So
there was the external evidence, but my own experience was much more protected.
    when I was offered a job at Wisconsin in 1947, I had no idea until I got

this from later documentation.  one of the professors t:old me what a storm it caused
because I was the or one of the first Jews to be appointed to the college of
agriculture and that there was a lot of resentment about that.  The apparently
worked it out at the time; the people in my department worked  ver Y tl ard and I think
were quite furious at this kind of criterion.  There we!re other  e  ements in the
school that had made a fuss, but that was all dealt with before I got there. In
retrospect, I might have said that at a social level I was not as we1 come in some
places as I might have expected, I didn't have any standard and it was personally
dealt with.  I didn't have an inkling.  These storms could be going around my head,
and I wouldn't even know about it.  SO was I blinding myself to it?  Professor [R.
Alec] Brink was the chai rman of the department at the t:ime, and some years later
just before he died,  he shared this information.  I have every reason to have
gratitude for the part that he took in that.

BOHNING :  Jerome Karle has told me that when he came out of CCNY he desperately
wanted to get into medical school and he couldn't.

LEDERBERG:   Yes.


BOHNING :  And I think he went to Harvard and did a mast:er's degree in biology hoping
that would enhance his getting in, and that didn't help.

LEDERBERG: No.  [Arthur] KOrn wrote about his experience at Rochester and [
  ] whipple, who was deified in internal medicine, told him he was not going to
get the chief residency because he was Jewish.  He managed to make it, but there
                         Page 4


LEDERDOZ

were certainly those issue all the time.  At the university level, world war II made
an enormous difference.  The v-12 program, the ASTP [Army specialized Training
Program], those sorts of things that were based on examination scores only and
permitted no latitude for discrimination; the faculty did
had been five years younger,           stru gAfr:;;h
                 I think I might have been hit muc i4        that.  If I

BOHNING :  well, I know our time is up.

LEDERBERG:  okay.

BOHNING :  Thanks.

[END OF TAPE, SIDE 21
14

Page 5


                             LEDERD03
INTERVIEWEE:   Joshua Lederberg
INTERVIEWER:   James 7. Bohning
LOCATION :     Rockefell er University
DATE :        7 July 1992

LEDERBERG:  we could concentrate on some of the specific questions you asked, but
I'd also remark that I read through the transcript, and I asked what more was I
? etting out of that than I al read Y had down? The answer is, not a lot. There are a
ew things we went into in a li tt  e more detail, but I think it might be a more
efficient use of time--unless you have specific questions, and maybe there's no
other way to do the interview--to skip over this stuff that I've already written
extensively about and go on to other aspects of my career.

BOHNING :  1'11 leave that up to you.  In going through some of the notes that you
had given me, there were some things that about.

LEDERBERG:   Let me res ond to specific questions you have, but I won't go
discursively through t e things I've already written at length about. If they've
        R
raised questions you might as we1 1 ask and 1'11 respond to those.

BOHNING :  ~11 right.  Let me go back then through some of your early childhood just
to verify some things.  YOU had commented about some early traumatic events, but you
did not elaborate.  I don't whether you wanted to do that.

LEDERBERG:  I'm wondering what that was.  I thought I said I did not have any
traumatic experiences of the kind that others often refer to.  I didn't lose
anybody; I had parents that took good care of me.  I don't recall anything
t raumati c .


BOHNING :  YOU may have been referring to this one note here about the burn on the
left arm.  That kind of thing.

LEDERBERG:  Oh, yes.  That's kid's stuff; really it is.

BOHNING :  YOU tal ked about remembering Li ndbergh `s parade.  That's going back pretty
early to remember that.

LEDERBERG:  oh, okay.  Now I recall what it was.  I recall a few accidents, and
having it described as traumatic has some implications of li n ering consequence
which I didn't mean to imply.  SO technically it's correct. [?aughter] I had a'few
falls.  My parents used to quote this as an example of curiosity killing the cat. I
pulled the tablecloth that had a steam kettle on it,
doing things like that.                    and they said I was constantly
              I have a burn to this day along my arm.  It was a pretty
extensive burn, so yes, I do remember that.

BOHNING :  we talked about your grade school , but we didn't identify it.   You went to
P.S. 46.  we talked about your teachers and the contracts you had with them.   YOU
felt they were very compassionate and understanding teachers.

LEDERBERG:  Yes, I felt that was well-phrased in the transcript.

BOHNING :  Going back to those pretty early if rades, what kinds of things were you
doing while the other children were doing  t ei r regular work?

LEDERBERG:  I was studying my own textbooks which would be four, five, six years
ahead in grade of what they were looking at.

BOHNING :  were you drawing basically on the textbooks that the older children were
using or were your teachers helping you focus on other things?

LEDERBERG:  It was mostly out of the 1 i brary, and I did get some help from the
librarians.  There were books about chemistry, physics, mathematics, astronomy,
bi 01 ogy .  I remember reading Huxley's science of Life (5). It was a very good
                         Page 1


                            LEDERD03
snapshot of general biology at that time.  Do you know those books?

BOHNING:  I know of them; I don't know them specifically.  I was going to ask you
about [Paul] de Kruif's books, The Hunger Fighters and the Microbe Hunters (6).

LEDERBERG:  That's right.  I've mentioned those in my writings.  I don't know if
that's what I had in the classroom, but it was certainly contemporaneous. I
remember the picture Arrowsmith,
been about seven. I've seen that. somewhere around 1930, maybe 1932. I would have

    There were the inspirational works, such as [Bernard] Jaffe's crucibles (7).
I've dug out what I could, and I've already written it down.  I can't add much to
that.  But I also read adventure stories and fairy stories and things of that sort.
It was pretty eclectic, and I had the ambition to know everything! I sort of knew
that wasn't possible, but I was going to give it a hard try. [laughter]

BOHNING:  science fiction was starting as a genre at that time.

LEDERBERG:  I don't remember that per se.  H. G. Wells, yes,  but that's about as
much as I can recall of that particular kind of fiction.  I sort of looked down on
it.  I would criticize the science that they were attempting to portray. [laughter]

BOHNING:  Another thing I was curious about was the trip to Israel in 1933, which we
did not discuss.

LEDERBERG:  This was my mother's first return to her homeland.  she left in 1924,
had two children, and was bringin z them home to her sisters and nieces and nephews
and cousins.  I don't know where  er parents were; they were occasionally in the
States, occasionally in Israel.  They changed location,  so it wasn't for her own
parents.  It was her sister's family.  I have a picture that I can recall the taking
of it with them.

     This was under the mandate.  There had been some serious riots, but more was
yet to come after that point.  At that time it was pretty peaceful.  It was the
flowering of Zionism.  There were new settlements coming  u 7 everywhere and the
desert was being made the bloom.  There was that spirit we 1 in place at that time,
but already there were problems with limits on immigration into Israel. we wer-;dn;te
part of that; we had emigrated.  But it was already a fairly inspirin 9 place,
did see some of the historic sights.  we had free access to all of Pa estine,  which
took a long time and a war for that to be the case again.
    we did some traveling around, but mostly my brother and I were put away in a
camp for the summer.  we had to learn Hebrew to survive and did.  I'd learned some
of it in Hebrew school at home, and so that was somewhat circumscribed.  I remember
seeing a lot of citrus groves, the beginnings of some towns.  AS of that time, it
was obvious that things were just being brought out of the desert.

BOHNING:  YOU mention here something about Zionist meetings here in New York and
questioning whether you were introduced to [Albert] Einstein and [chaim] Weizmann.

LEDERBERG:  My father was involved in that.  Maybe that's a screen memory, but it's
not too im lausible.
    7       I know Einstein spoke at those meetings, and I have a very
vague  reco lection that's exactly what happened on one occasion.  He was Certainly
much talked about.

BOHNING:  Had you developed any role models at any point?

LEDERBERG:  well, he was one of them. [laughter]  I wasn't sure I was going to be a
physicist, but I generalized from that.  In that 1932 letter that I've mentioned,
the text is "I want to be a scientistist and study mathematics like Einstein."
[laughter]   He was somewhere between a role model and a folk hero.  It wasn't in
the sense that I could have any tangible expectation of matching his
accomplishments, but maybe some little bit of it might be imaginable.  I just want
                         Page 2


to clarify that.

LEDERD03

    on the trip back from Israel, I had a nasty scrape and ended up with in
retrospect what was rather          myelitis on my shins.  In retrospect I
shudder that I survived it; it was treated but we didn't have antibiotics in those
days.  I almost drowned on the voyage, but that was in the swimming  001 . [laughter]
The boat was rocked by a sudden wave, and I was dislodged; that's w at
                          R   I remember.

    We stopped in Naples, between ships.  For the best part of a week, I could
play in the streets around what must have been a lower second-class hotel. I got
some of the local co1 or, but there was fascism al 1 over the place.  It didn't have a
strong anti-Semitic tinge at that point  et, so it wasn't a matter of being
personal 1 y fearful ,  but nevertheless  Hit Y er had already made his start and there was
some image of that.

    when I came back and came off the pier, there were signs in al 1 the
storefronts.  It was the NRA [National Recovery Admini stration] ea le,
immediate reaction was, had fascism come to the states, too?  Pure y in terms of
                          ?   but my

that symbol.  I didn't know then that there were people of a different political
persuasion who could have said Roosevelt was a fascist , [1 aughter] but it was just
that symbology of the NRA.  I disabused myself of that pretty quickly.
   I'd been out of the country for three or four months and didn't know what

was happening.  I was perfectly capable and certainly from that age onwards, I
looked at the New `fork Times every day and kept abreast of what was ha pening
politically.  It was just being caught unawares, as I said, by the sym ology.
                           &


BOHNING :  Since you spent three or four months in Israel, did you have any sense
there of what was happening in Europe and what was the reaction of people there was
to what was happening in Europe?

LEDERBERG:  Oh, there was great, great fear about what Hitler was up to.  I remember
the headlines of the Reichstag fire and things of that sort.  There was a very good
radio commentator named H. V. Kaltenborne (?>.  That's where we got a lot of our
news from, and if you go through his broadcasts, you'll see just what we thought.
[laughter]

BOHNING :  we had tal ked last time about the Depression) but one thing we didn't
mention was K our father's illness, which evidently changed the situation within your
fami 1 y  somew  at.  That would have been around 1935 or so.

LEDERBERG:   Yes.  I think his first symptoms were about 1932.  He had a progressive
ulcerative colitis, which was quite debilitating.  He was barely able to continue
functioning through that time.  He sort of managed to get by; it was hard.

BOHNING :  Did this change the role your mother played in the family?

LEDERBERG:   Yes.  she just had to take a more managerial role in the family's
affai rs.  Towards the end of that decade, he was real 1 y only able to work  art time,
and she started working.  she did various things, teaching in Hebrew schoo 7 ,
catering, things of that sort.  she worked very, very hard.
BOHNING :  I have a note here about being reprimanded in school for notes about Lucky
Luci ano.

LEDERBERG:  [1 aughter]  That is just an incident I happened to remember.

BOHNING :  He must have certainly been in the news at that time.

LEDERBERG:   Yes.  He was the John Gotti of the time.  I don't remember what the note
was about, but it was some wisecrack.  He'd been running a prostitution ring, or
something of that sort,  so that was the context of it.  His name figured later in
that he did do some service to the oss [office of strategic Services] during world

Page 3


                             LEDERD03
war II.

BOHNING :   Yes.  That's right.

LEDERBERG:  But he was the most notorious Mafia type at the time.  I don't remember
any more than that.  I just recall I got in hot water.

BOHNING :  In 1936 you were in junior high school, and we've talked about your
reading, which 9 oes way back, and the types of reading you were doing.  Were you
trying to estab ish your own library or were these mostly books out of someone
else's library?

LEDERBERG:  I couldn't afford it.  It was the public library.  I did get Bodansky (
) as a Bar Mitzvah present.

BOHNING :  was that your request?

LEDERBERG:   Yes.  I got E. B. Wilson--that was the encyclopedia (8)--as a high
school graduation present.  I've still got those books.  I don't think I owned more
than two or three others.

BOHNING :  Did you start book collecting in any way later on, building your own
library when you were able to?

LEDERBERG:         As soon as I had some income.  They were so precious.   You see
the consequef2&yefiaughter]  Please, come in here and let me show you some things.
[break to examine books in adjoining room]
    of all the geneticists I ever knew at the time, I'd actually read about
[Ernest] G,rard (?) and Bodansky. [laughter]  I knew about them before Beadle (?)
did.

BOHNING :  That's interesting.  Did you take notes when you were doing this reading?

LEDERBERG:  I must have, but I have next to nothing from that date. I have a couple
of papers that I wrote when I was in high school.  That's about it in terms of my
own writing.  one of them was on the theory of fixation.  The other was at the
American Institute of science lab on the cytochemi stry of the nucleolus.  Those are
the only things I have of that vintage.

BOHNING :  what I was getting at was did you take notes as you were getting books out
of the 1 i brary or did you just commit it to memory?

LEDERBERG:  oh, no, no.  I took notes.  I'm confident of it.  In fact,  I used to
treasure paper to be able to do that,
like surveys.              and I'm sure I did things very systematically,
         I've forgot what I did it on, but I remember once I discovered my
mother had a roll of eleven-inch wide paper, used for lining drawers, and what a
wonderful thing that was for writing large schema on. [laughter]  That was my
blackboard.  I don't have any of that.  I wish I could have had it, too.

    I recall writing to Louis Fieser.  He had written about carcinogenic
polycyclic hydrocarbons, and I had some 9 uery about whether thei r carcino enic
action was related to their similarity o  structure to sterol s.  That wou ? d have
been the time I was reading Russell Marker and so on.  I know he responded in a not
totally perfunctory way, but a fai rly mechanical way.  He gave me some reference or
other.  I was interested in mechanisms of carcinogenesi s:  Any chemical that could
change life processes in the ccl 1 was something very exciting to me while I was in
high school.  I guess that's right up to the point of my research program now.

BOHNING :  How did you react to organic chemistry?  I've found most people have
either posi ti ve or negati ve react1 ons.

LEDERBERG: oh,  it was very positive.  I thought it was just wonderful, and I
                        Page 4


                              LEDERD03
wasn't daunted by the names.
I had a perfect memory at   There's a memory barrier, learning all the names, but
                that time,
    and it made total sense to me so that was no problem at all.
;Erl!i as; I could deal with them very systematically          I just gobbled
                      It wasn't something that was just a list of
                                        That was the
mental i ty al ready operating .
all out of books.      I actual 1 y 1 unged quite deep1
           I told you I did some 7             into it, but almost
                         ab experiments at 4: ome .

BOHNING :  Dyestuffs, things like that?

LEDERBERG:   Yes.  I remember I made a lot of different azo dyes, experimenting with
a variety of different coup1 i ng reagents.  I pla ed
what I had no idea of, though, and it's taken a Y  [Henry] Rerkin all over again.

YOU know,                        ong time, is the recentcy of that.
     anything that happens before you were born is all lumped together as
prehistoric.  I would have found it ver
still living at that time who had been i: hard to comprehend that there were many men
                                         orn before aniline dyes had been discovered.
I could see a date in the 186Os, 187Os, but that might as well have been B.C.
[laughter]

BOHNING :
1930s.   You mentioned Rerkin and Kipping; I think they were both alive yet in the
    Kipping was later one of the forerunners of silicone chemistry.

LEDERBERG:  That's reductionism taking hold.
understand physical                 I really felt that if I could
                    or ani c chemistr
reactions,  that would % e i ndi spensab Y ;! the underlying atomic theory of chemical
                      to try to understand biology as we1 1.  It's
partly true, partly not, and let's just skip over that detail for now.
x-ray diffraction of DNA is somewhere in between.               Doing an
                                      I worked hard to  et the mental
apparatus to be able to do that.  It's not a bad paradox; I still  re ate it to
                          7
students today to get as deep a ground as they can at that level.

BOHNING :  The idea that biological systems had a very important chemical nature is
really what I hear you're saying.  At that time was that a generally accepted view,
or were there still enough of the traditionalists around?

LEDERBERG:  In the books I read there was a lot of optimism that it might be an
infinite quest,  but that was the wa
it was sort of old-fashioned and si Y to go.  I never questioned it; I thought that
explain biolo ical phenomena.     ly to invoke anythi n
     i             I would have followed  Hux 7 outside of chemistry to

that.  I thin  that's pretty much their           ey-well s pretty closely on
anything to the contrary either in  schoo 7 erspective on it.  I was never taught
                                             .

fai rl y mechani sti c approach was adopted.   The question was either skirted or a

    There were the different levels of vitalism; there was de jure and de facto,
and there would have been people who would have scoffed at the idea that you in
practice could dissect the gene chemically.  That was so awesome that it could be
another five hundred years.  I may have been tinged with a little bit of that; just
a great  res
was that  am & ect for complexity as you've heard me articulate elsewhere.  SO there
        ivalence of an ultimate optimism but a fai r amount of humility on the
way.

[END 0~ TAPE, SIDE 31

45

Page 5


                             L EDERD04
LEDERBERG:  Then, as now, I was willing to put some questions as being operationally
inaccessible and therefore let's not argue about them.  The nature of mind or of
consciousness , things of that sort,
a chemi cal explanation,         I would have said that they will ultimately have
              but our detailed knowledge is just too dim. If you couldn't

think of an experiment--I was a Popperian before [
were--then there was no point in pressing the question.     1 Popper (?> as others
                                  The question would be

meaningless unless you could frame an experimental test for it.  I don't know where
I got that, but it may or may not have been what people like         would have
taught, but that's what I extracted from my readings like that.

BOHNING :  what about the taxonomic aspects of biology like botany and zoology?

LEDERBERG:  I thought they were pretty dull and detailed, but the  needed to be
known if you wanted a picture of all of life. This was the wa
it could be organized.  I thought morphology was a pretty shal T x
                                        t at one's image of
                                              ow basis for that

kind of description.  I wasn't thinking of DNA in those days as much as different
enzyme systems, the proteins that might be expressed.  I looked forward to more of a
chemical taxonomy coming along that might be somewhat more meaningful.   But I
respect it, and people had to do that.  I would never have scoffed at it.
not have felt it was my own cup of tea.                       I might

BOHNING :  The reaction of going to a natural hi story collection in a museum is one
of going on mental overload pretty quickly--a room full of bi rds, or a room full of
insects, or something of that kind.

LEDERBERG:  I tend to suppress detail.  I can skim a book.  I can skim an exhibit
and still not get turned off by it,  but extract what there could be of interest. I
would vi sit the American Museum of Natural Hi Story quite often and enjoyed those
displays without feeling drowned by them.

BOHNING :  what about the other cultural aspects of New York? were your
circumstances such to allow you to do more than just visit the museums that were
free?

LEDERBERG:  I might have gone to theater once in my young lifetime.  I'd go to the
movies.
York.   I don't think I ever visited the opera during my first residence in New
    They were financially inaccessible, if nothing else.  And I wasn't that
interested in going.  I did play around in the Metropolitan MUSeUm; in those days
kids were allowed to walk into the Egyptian tombs and things of that sort.
[1 aughter]  It was great fun!  And I enjoyed that a lot.

BOHNING :  I can imagine.

LEDERBERG:  TO tell a 1 i ttle story, and I wish I could document it more clearly, but
this was pretty early in high school.  A friend of mine and I got interested in
hypnosis, and we wanted to experiment with it .  we managed to nab a subject, and
boy, were we treading on thin ice. He felt very guilt  about masturbation, so we
said, "we'll see if we can help you with that if you'1 be our subject." we didn't
                   Y
intend to do anything to hurt him, but, my god, what an IRB (?> would think of that
kind of involvement.  I was maybe fourteen at the time.  This kid was probabl
fifteen or sixteen.  He was a Puerto Rican.1 think he was in the same junior K igh
school that we'd been in; maybe we were still in junior high.

    we'd read about hypnosis, post-hypnotic suggestion and all the rest of the

books, and we sort of went through the drill. He was a very willing, very
suggesti bl e subject, and we did manage to do this.  I remember that we got him to
the point that with the code was "oom, oom, sleep!" he would just go right under.
we had him conditioned to that.  I don't know what books we were looking into, but
we had read about regression under hy nosis;
little bit.  we had the shock of our 7     we just thought we'd explore this a
                             ives!

    we asked him to think back to when he was an infant and he gave appro  riate
responses.  we asked what was he before that, and what was he before that.  R
                                                                        T en we
                         Page 1


                              LEDERDO4
said, "we1 1 , okay.  were you ever reincarnated?"  He said,  "of course! "  we said,
"well, let's go back.  what are you now?"  Before long he was a scarab in Eg pt,  and
we were asking him to describe his envi ronment.  Here was a kid who was bare y Y
literate, and he started writing out hieroglyphics.  I've never been so astonished
in my life. [laughter]
    I can't give credit to this idea of how in the world am I
for this phenomenon.                   ? oing  to account
          we got a couple of pages of this kind of stu f, and w;h;Ere
trying to figure out if we could translate it, if we could figure it out.
could be the provenance of al 1 this?  when he was awake he confessed no knowledge of
anything about it.  And believe me, he would have been startled to think that he'd
ever heard of a hieroglyphic.
    We finally managed to see one of the Egyptologists at the museum.  I don't
know if we told him what we were up to or not, but we just asked him, "can you date
this material?  can you identify it?"  He looked at it for a while, and he said,
"This looks like some of the popularization of [Jean Fran$OiS] Champollin's work of
the mid-nineteenth century. "  There were mistakes in it, and they were not
compl etel y accurate1 y rendered, and that's how he was able to tag them.  He Wasn't
able to point to a book that this was copied out of, but he said it was of that
genre.
    To this day, I can't imagine where this kid had ever picked that up.
[1 aughter]  It's a totally unresolved mystery.  we were pretty scared when he first
started producing thi s.  we just didn't know what genie we'd let out of the bottle.

BOHNING :  It's almost like the traditional speaking in tongues kind of thing, in
written form.

LEDERBERG:  Yes, but it ' s al so to1 d me to just never underestimate anybody's
i ntell ectual potenti al ; it can be overlain with all kinds of things, and if you only
get to root of it, you can get all kinds of fantastic productions.  I have no idea
what's happened since, and I have no idea whether we cured him of his habit. I'm
not even sure what our view on the matter was, but anyhow there you are.

BOHNING :  Did you try any more hypnotic experiments after that?
LEDERBERG: No.

BOHNING :  I'm amazed how easy it was for you to be able to do that.

LEDERBERG:  well , he was pretty suggestible and we were pretty confident. [laughter]

BOHNING :  That's a good combination.

LEDERBERG:  I have no doubt about the authenticity of it.  There was no way he could
have faked it.  we went through a lot of the routines, including sup ressing pain
reflexes where we would stick pins into him.  There were a few post- R y notic things.
we did nothing cruel ; we were not malicious.  we could have been  care ess.
                           `;


BOHNING :  SO your life was pretty much concentrated on your own self-study.

LEDERBERG:  That was the core of it.

BOHNING :  was there any interest in athletics?

LEDERBERG:  My mother would chase me out of the house every now and then and say,
"Joshie, you've really got to go out and play.  YOU can't stay indoors al 1 the
time."  I'd occasionally do it.  I might get into some gang or other that would
allow me to join in, but I guess our main sport would be stickball. we lived in a
very good location for that.  we lived right off a cul-de-sac, so there was no
traffic coming in or out.
   I enjoyed going through the woods and looking at the natural history of what
was there.  I remember bringing home a praying mantis and putting it in a bottle and
                        Page 2


                             LEDERDO4
keeping it as a little pet for a while.  My parents were somewhat horrified.   It was
a very formidable looking creature.

     There was a swimming 7 001 up at Hi ghbri dge park in the summer time.   It was
a great thing to go to, a pub ic pool.  But I was more likely to be at the library
than any other place.  And it was pretty well stocked.  I've been there since; it's
nothin  like it used to be in terms of just the range of texts, the range of
speci a i zed materi al .
  7          They had Bodansky there;  that's where I heard about it.

BOHNING :  I wanted to ask you abut that, because in Bodansky's introduction, he
mentions other books that you have said were very influential early on.   was
Bodansky the one that got you started in that sequence?

LEDERBERG:  I don't remember that.  I'd have to look at the introduction. It
wouldn't be unreasonable.  He had written on physiological chemi str  .
                          Y   If there was
such a thing as pathological chemistry I thought that would be real y exciting.
[laughter]  There's just not very much available on that.  There is a text by wells
called that (9), but it's quite disappointing.   1'11 have to see that to refresh my
memory .
    By the time I was in high school is the time we' re talking about here.
since the time I got the book, I certainly would have looked up some of the articles
he had in footnotes if the  were things I was special1 interested in. I don't
recall which ones they wou d have been,
          Y         al though the  a Y captonuria (?> story would be
a good candidate.  I wasn't reading German, and so many of these are in German.
Here is H. G. wells--that's a different one than the science fiction
writer--Chemical Pathology (9).  I do remember looking that up, and this is under
theories (?) of metaboli sm, so I was imbued with that young. [laughter]

BOHNING :  How old would you have been when you got your copy?

LEDERBERG:  I got my own copy when I was thirteen.  I was al ready very familiar with
it.  It was a Bar Mitzvah present, dated May 31st, 1938.  In this introduction, the
reference to [Joseph] Needham (10) would have excited me.  I know I'd read that, but
that was in college, very likely.  E. B. Wilson, The Physical Basis of Life (ll),
:;Alzid Fhemistry (12).  Boy, those are all very familiar.  I probably did look into
          ] chambers' The Nature of the Living Cell as Revealed by
Mi CrOiani pUlatiOn (13).
    I attended a lecture chambers gave; it had to have been about 1936. A
friend of mine, who's a little older than me, five or six years older than me tells
me that he'd been there too, and there was this young kid who got up and asked what
he felt was a very penetrating questi on. That was me. [laughter]  I was eleven. I
asked about the reality of spindle fibers (?) .  I must have al ready been reading
about that, and that is cross-referenced here, so it could have been a lead.   Just
as likely, I'd just go down the library shelves, and in that section I'd just look
at every book on the shelf and pick out things I thought I could understand.

BOHNING :  YOU got an unabridged dictionary at the New York Post office?

LEDERBERG:  It was an advertisement that you bring in the coupon, and you get it for
a dollar, or something like that.  I remember taking a trip down; it's just off the
East side Highway, right around here.  I got it and brought it home and it was one
of my books.  I don't have that one any more.  It had etymology in it, and I tried
to teach myself Greek and Latin roots by just compiling the roots of the words that
I looked up there.  I wrote my own concordance out of that.  I remember now--that's
what I used some of those big rolls of paper for. [laughter]

BOHNING :  At the same time you missed a word at the spell i ng bee at Radio City.  Did
you consider yourself a good speller?

LEDERBERG:  well , I was the champion in my school.  They had this competition, and I
won a chance to be on the radio.  I was struck out.  The announcer--and I could
                        Page 3


LEDERBERG:   Yes.  I guess that must have been when I graduated from junior hi
That was my first visit to Washington.   I 8 uite recently ran into m Y autograp book
                              z h.

from public school,  which sort of doubled  or that, and that had a  ittle record.
It had some sianatures of some of some of his colleaaues down there, so that's what
pinned that date down for me. I had         P-C        ] Kohl (?>, and

BOHNING :  Do you reca 11 anything specific?  The situation in Europe was certainly
ctl;;;;iorating by this time.  Did you attend any of the conference or were you just

L EDERD04

clearly hear it--said "emullient" and I was a little torn.  I knew the word
"emollient,"
struck out.  but he was pronouncing another word. I spelled it with a "u" and I was
       I looked it up in the dictionary; there was no work with a "u" and I

had no case. [laughter]

BOHNING :  That same year your father took you to Washington to the Palestine
Conference.

LEDERBERG:  I don't think so.  I think I `ust toured the sights in the city.   I was
deeply impressed--the Lincoln Memorial ,  t A e washi ngton Memorial , al 1 that wonderful
clean marble and the sense of power that there was in the white HOuSe, things of
that sort.

BOHNING :  I didn't realize you'd been a member of the boy scouts either.

LEDERBERG:  Yes, locally.

BOHNING :  It was the thing to do in those days, wasn't it?

LEDERBERG:   Yes.  There was one organized at the local Y, and it was a social
activity.  There were skills to learn, and there was some natural history.  we did a
few hikes.  I learned about knots and some things of that sort.  I didn't stay in
too long, but I was there.  I guess I made second class scout.  Some people
criticized it for being militaristic; I didn't see it that way at all.

BOHNING :  I was struck by your pile of New York Times here, because there's a note
here that says you saved the daily New York Times C?).

LEDERBERG:  [laughter]  you're absolutely right.  These I clean out every couple of
months, but I didn't do that at home.  I 'ust felt that here was history going by,
and how could you sort of 1 et it  o?  I t oroughly ingested and wanted to read
                A
things that might have been a wee ;i or a month old.  Just maybe I'd want to see it
again,  and sometimes I did.

    I was thrilled to learn that there were archives in the libraries where you

could get them, and subsequently was very disappointed that hard copy of old
newspapers doesn't exist any more.  That's a bitter blow. [laughter] They used to
have a rag paper edition that I would consult in the union Library.

    I don't know if I mentioned this before, but I felt that I ought to know
something about world war I, which I'd just read a very little about.  So I just
scanned the New York Times for the entire war just to get some sense of what it was
like to have lived through it.  That had to have been when I was in high school.
cooper union was a couple of blocks away.

BOHNING :  you've already talked about the tobacco mosaic virus that was the New York
Times, but I've forgotten what year that was.

LEDERBERG:  That was Wendell Stanley in 1935.

BOHNING :  That's much earlier.  In addition to the political scene, were you also
trying to watch the scientific scene?  was this one way of getting up to date on
                         Page 4


what ' s happeni ng?

LEDERD04

LEDERBERG:  well, the Times certainly included stories like that, but I didn't leave
it at that.  I didn't expect that to be my pri mar K source of information.  There was
something called Scientific Monthly.  I suspect t at I got it in the library
whatever.  That ' s probabl ti the thing I read regularly.  I didn't read science yet as
a routine,  but that's  pro ably the one.

BOHNING :   Nature?


LEDERBERG: No.  when I got to college, that would have been the journal that I
would have consul ted regul arl y for current developments .  There was one other one.
Science Digest.  I remember Watson was the editor.  It would have been in the
library at Stuyvesant; I would have gone for that.  I doubt if Science or Nature
would have been there.  Sci enti fi c American.  I'm trying to recall the format; it
did;n; look quite 1 i ke what it does today,  but it covered a somewhat similar kind of

The Sunday Times used to have a regular science feature; I remember that.

There was more there then than there was for a long time thereafter.  It woul
been the weekly equivalent of the Tuesday issues that they've had more recent

BOHNING :  Your high school yearbook said "CCNY Biochemist . "

LEDERBERG:   Yes.

BOHNING :  By this time you were al ready doing work in cytochemi stry and hi sto
and I just want to talk a little bit more about that.

have
Y-

LEDERBERG:  I still saw that as a branch of biochemistry, but I didn't know that
biochemists mostly did other things than that. [laughter]  But it was not
illegitimate.  It's just that cytochemistry would not have been mainstream for most
bi ochemi sts .  If I'd known better, I would have said cytochemi st.

BOHNING :  How were envisioning the work you were doing and what was happening in the
larger world, so to speak.  YOU say you were keeping up with it to a certain extent.
Did you feel that you were ready to make some original contributions at that point?

LEDERBERG:  The larger world you've just referred to is the political scene, and I
felt utterly powerless personally to do anything in that sphere. I thought if one
could marshal enough i ntell i gence, one might be able to figure out what to do
better, but I didn t feel very comfortable about my own world scheme. It wasn't
until the 1960s that I felt we1 1 enough educated pol i ti tally to be able to put in my
zoTdtwo cents in any reasoned way, other than parrot what other people might have

    Scientifically, I thought it would be quite a while before I would be making
original contributions.  I thought the quest was important, learning how to do
investigations.  one would come across interesting problems, and then somethin
would emerge.
would be making I didn't expect it in high school.  I didn't expect that in co1 9 ege I
         a significant contribution.  I did not accurately predict the future
in that regard.

[END 0F TAPE, SIDE 41

6

Page 5


                             LEDERD05
LEDERBERG:  I was intrigued by the fact that the crocus itself is not susce ti ble to
co1 chi ci ne , and there are species differences in it.  I never got into it t ough.
                             E       I
was 7 oing to use that as a clue about how to understand this a little bit more
deep y.  The next year I met Francis Ryan; he was away that first year. I'd heard
about him and  eopl e had spoken very admi ri ngl
     E             rl of him and that he'd be someone I'd
want to know w en he got back, as was indeed t e case.  He came back in the fall of
1942 with NeurOSpOra.  He learned that the previous year with Beadle and Tatum. I
camped on his doorstep.  He had no choice but to let me come and work in his
1 aborator z  and I was his disciple ever since.  I just put away my other work in
favor of earning what he had to offer and then started research on Neurospora.

BOHNING :  Pearl Harbor occurred at the end of your first semester.  How did you
react to that?  what was the reaction on the campus in general?

LEDERBERG:  There was a sense of inevitability and a mixture of gloom and optimism.
The  loom was that there was a pretty formidable opponent who had hit pretty hard at
Pear 9 Harbor.  It was not too soon to pitch in and rid the world of these pests. It
ended up being not unrealistic.  I think the level of sacrifice that Americans paid
was about what was anticipated.  I don't think we realize that it could have been a
lot worse.  In fact, eventual 1 y it was R retty harsh, I think.  I can count the names
of half a dozen people I knew who were  illed in action.  None of them was very
close to me.  when you consider we had probably in our own armed forces nearly as
many casualties in Vietnam as we did in world war II--I think that's right--we've
become inured.

    But the main thing was, my god, can we clear the world of that menace some
way or another?  I was very young, and I di dn `t see what personal role I could play.
In a couple of years I would be old enough to be drafted, and then I would do what
my country told me to do.  I didn't think it would be an efficient use of me to make
a combat infantryman out of me.  I doubt if they would have--just because of my own
combi nati on of  hysi cal and mental capabi 1 i ti es.
      `;                     But when the opportunity came
along,  I did en ist in the Nav z and let the Navy decide what to do, but had an
opportunity to continue my ski 1 s in education.  If the war was going to go on long
enough, I would be able to use those at a much higher 1 eve1 for what value I could
contribute.  what I saw was the national interest and my own converged, absolutely,
and I didn't hesitate for a second as soon as I heard about that program, a little
bit to my parents' consternation.  They thought I was rushing myself, getting signed
up 1 i terall y a year and maybe almost two years before I was vu1 nerable to be1 ng
drafted.

BOHNING :  You were still, sixteen, seventeen?

LEDERBERG:  YOU had to be seventeen to actually sign up, so I think it was on my
seventeenth birthday.  It worked out just as well by ever Y  account.  I still pay my
dues.  I'm spending this Friday at the CNO [         (?) , briefing them again
two weeks from now. [laughter]

BOHNING :  Let's just explore that a little more.  what were you thinking at that
time?

LEDERBERG:  I was a premed and thought I was going to go into medical research.
until I got deeply involved with Francis,  I would have thou  ht neurology was the
medical discipline that had the flavor and the tastes that  0th in practice and
                      %
research would be at the frontier of basic biology and would count the most. I
probably didn't understand that many specialists view it as the most futile or
dismal of specialties; it's probably the area where you can do the least with your
patients.  But that's still a challenge.

      SO I was si  ned up as a premed.
       F1            I was accepted into P & S fai rly earl  .
(1'11 have to get t e date on that.)  They had sort of an advanced acceptance z ist
and there was an accelerated program where most of the work got started.  I was in
the v-12 rogram as a
   R     7 respective medical officer, and I'm sure they even had the
name of t  e ship I wou d eventually be assigned to as part of their manpower
                         Page 1


                              LEDERD05
alignments.

    I got into uniform on 7~1~ 1, 1943, which was just past my eighteenth
birthday, but I had signed up when I was seventeen, before that. Life more or less
continued, except I was in uniform and now living on campus.  I didn't have to
commute any more.  I just lived in the dormitories and was actually gettin
9                             7 paid to
o to school; it was quite a bonanza.  I understood the necessity for dril  and a
ittle bit of military discipline and I didn't mind it.  some of my classmates would
bitch about it, but it didn't seem in any way unreasonable to me. They had very
objective standards.  You got into V-12 if you 7 assed your exams and maintained your
grade, and if you got down to a "c" you would f unk out and would just join the
ranks of other naval services.

    SO there were pretty high incentives for sustaining academic performance,
but it didn't bother me at all.  It probably meant a better academic morale among my
classmates.  If this had been peacetime there might have been the usual conflict
between the nerds and jocks which we were somewhat spared.

    The other consequence, though, was that I did not have an uninterrupted
college life, and every semester there was an issue--I had a fixed date for entering
medical school, but how was I to spend my time before then? optimizing my general
education was not the Navy's objective.  Their objective was the minimum amount of
time to meet the formal requirements, and any other time was to be spent on other
active service.  SO I did end up with everyone else spendin z the best part of a
year, but in blocks of four months at a time, working as a  ospital  car sman in the
naval hospital.  It was just interdigitated with my assignments to camp ete my
                            7
premed.

BOHNING:  was that here in New York?


LEDERBERG:  It ended up being at St. Albans.  It could have ended up being anywhere.
It was just the luck of the draw, but that's where they decided to assign me. I
was assigned, and it could have been anything.  A lot of the V-12's were put into
the clinical labs because they had some background for it.  I ended up in the
clinical pathology lab.

     Captain [        ] Jacobson had been a reserve medical officer. I
guess a would-be sailor, and for him it was something of a life's dream that he
actually had a command and call to active duty.  I had a very good relationship with
him; all of us did.  He used us, but at the same time he thought he would help us
continue our education in the lab.
    I got the parasitology assignment,
fecal floats and so on, looking for parasites.
                        so my job was to do the blood smears and
                                  we had most of the Third Division.
There were some other units back from Guadalcanal, and two-thirds of them had
malaria.  I had to do the slides that would monitor the course of their treatment
and whether they had             (3 -

    I got to learn a lot about malaria.  I've probably seen about as much of it
as anybody in that setting. [laughter]  Actually peering at it through the
microscope all day long, I became very familiar with its life cycle.  I thought
about its cytology, its cytochemistry.  I was probably the first person to try doing
Feulgen stains to see that they're active chromosomes that had DNA in them,
Plasmodium and so on.  so I really did get some intellectual benefit, and I was
imbued with the idea of a microbe having a sexual cycle, which certainly spilled
over to when I thought about bacteria later on.

BOHNING:  was that the first time that you had reached that point, that thinking?

LEDERBERG:  Not quite, because the same was true of NeurOSpOra, but this is
something that you think of being a little closer to bacteria than this fungus
that's got these macroscopic threads.  It's a microscopic microorganism.
Nevertheless, as tiny as it is, you can tell very directly it's got a sexual cycle.
                         Page 2


                             LEDERD05
But mostly by the accident of having followed it, both in the mosquito and the human
host.

    I had other 1 ife experiences.  I was on the morgue watch.  I knew that I'd
have to deal with cadavers in extenso when I got to medical school, and I had my
fi 11 of them at the hospital .  That meant if a patient died during the night and I
was on call, I had to get up and help with the movement of the remains and help a
little bit in setting it up for autopsy.  I was al ready eighteen by then.
    Also I was very impressed by the attitudes of the other sailors.  The other
sailors who were going to ship out were very resentful of us.
back were not at all . They said,                        The marines who came

but bless you."            "YOU guys are lucky you didn't have to face it,
          we took the best care we could of them, but it was a ver !I sharp
contrast.  we were really persecuted by the seamen second class [laughter  that we
had to deal with. well,  ou can understand it.
         -z              But the latter was unexpected, that
the returning marines wou d take that line, that view of it.  It was very generally
true.  I did get a very close sense of the war.  we heard lots of war stories about
what they'd been up to.

BOHNING :  That must have made quite an impression on you, hearing thei r experiences
at the front.


LEDERBERG:  well, it can't be anything like being there yourself, but I certainly
had a sense that they'd made a lot of sacrifices for my benefit. Not resenting it
made it al 1 the more poignant.  It may be a very sentimental attitude, but I've
never forgotten that.  I ve had assignments where I could be of some particular he1 p
to the Marines, and I've never forgotten it.
well; he was the commandant for a while.    I've gotten to know P. X. Kelly pretty



BOHNING :  Let's go back to Ryan.  YOU said that he'd been on leave and when he came
back you camped on his doorstep.  could you tell me a 1 i ttl e bit more about your
experi ence with him?  what kind of a person was he?

LEDERBERG:  I first have to say some things about age.
literally,                            I looked up to him, very
       as a father figure.  In retrospect, when I see
he looks more like an older brother.         R ictures of us together,
                       He may have been eig t or nine years older
than me, something like that.  Not much more.
fellow.                        He was al so a very bright, precocious

    He did his undergraduate work at Fordham and got his Ph.D. in pretty quick
time.  He was a year out of his Ph.D. when I met him.  He went to Stanford for his
immediate postdoctoral experience.  For someone as young as he was at that time--I'm
speaking now in retrospect--he had a very paternal attitude, R hi 1 osophi cal ,
nurturing .  He was remarkably uncompetitive and just one of t e most marvelous
teachers that I've ever encountered.  Everybody who knew him subscribed to that. He
would not instruct you, he would draw things out of you. He had a wonderful
Socratic method in how he dealt with that.

     I think I was an intellectual  challen e to him.
                 9       I may have been 7 retty
trying to him at times, but there was certain y a bond of affection as we 1.   I
adored hi m.  I en joyed very much any occasion for some kind of intellectual
sparring,  and those were numerous.  I think I gave him something, too, as young as I
was.  He understood one of the fi rst things I needed was some more di sci 1 ine in how
I organized my work, hand1 ed myself in my lab, kept my notebooks, a 1 i tt 7 e bit about
being more systematic in my thinking, more focused. He helped in defining a
strategic approach to deciding what you're going to work on.
    I owe all those things to him.  He was able to get a very small grant--I
think from the Rockefeller Foundation--for his Neurospora work, and he hired me as a
helper to do that.  I did everything.  I would recover used agar for him.  There
were great shortages in those days.  After he finished an experiment and it came out
of the autoclave, I would filter it and coagulate it and purify it, and
fresh batches of agar for him. [laughter] Pouring plates, inoculating t Le!zF&ies,
                            R
                         Page 3


                             LEDERD05
al 1 that kid of stuff.
into the genetics of it. I assisted him in his work, gradually getting more and more

    He was more of a physiologist than a geneticist and he was sort of veering
over a little further.  He did teach me what Beadle and Tatum had to offer.  I don't
know why I would say I came with a strong genetic impetus, but that's the way our
experiments went.  His own work was on factors that regulate the growth of
NeUrOSpOra and its nutrition and using it for setting up assays for different
vitamins and amino acids.

    I wanted to know more about mutation and things of that sort.  SO that's
where  it went.  I don't remember exactly which came first, and I'd have to check my
notes on this, but I first met him in September of 1942. I spent 1943 sort of half
at columbia, half at St. ~1 bans.  Ditto for the fi rst half of 1944.  I entered
medical school in either July or October of 1944; 1'11 check my notes on that.   But
I continued to live downtown.  I no longer had access to the barracks, but as a
medical student you could get a housing allowance, and I did get an apartment with a
graduate student, Kim Atwood, in the neighborhood, so I could spend a 1 arge part of
my time, even when I was in medical school, in his lab.

    In February of 1944, Avery's paper came out (18) and I got very excited

about that.   I  sug z ested to Francis to try and do the same experiment on Neurospora.
I'd been helping  im working a mutant which required leucine, so I said, "Let's try
to transform the leucine negative gene into a positive."  If we could get
transformation with DNA, or whatever it was in Neurospora, there would be no doubt
that we're talking about gene transfer.  we'd have big arguments about whether the
pneumococcus transformation was real 1 y defi nab1 e i n bi ol ogi cal terms.  But in the
course of those experiments, the controls showed reversions and so we were really
never able to use it very cleanly.  we did have some ex eriments where we had some
crude extracts, which we hoped included DNA.   But even & efore that got very far
along , it was plain that the controls reverted, and you couldn't really have a
reliable way to test for the transformation.

     Amazingly, that was the new finding and in retrospect it's hard to be1 ieve
that.  The idea of gene reversion was not the expected phenomenon.  So Francis said,
"Okay, why don't you study this phenomenon for now as your own special project."
And so I did, looking a 1 i ttle bit at the dynamics of where these reversions
occurred and then verifying that they really were reverse mutations that you could
localize where the gene was.  was it the same gene that had mutated? That meant a
lot of genetic crosses on the one hand.  A puzzle that still hasn't been solved, is
that if you apply a modest amount of leucine to the medium, you seem to suppress the
wild type and that obscured the dynamics of when the mutations would be observable.

     we were able to show it wasn't the initial mutation so much as what happened
in mixtures of leu+ and leu-.  These are in heterokaryons, these are
filaments that have mixtures of nuclei of the two kinds. They can move freely
throughout common cytoplasm.  It looks as if leut is at a disadvantage compared to
leu- as long as there's some leucine in the medium to allow the leu- to proliferate.

     I still don't understand why.  It's a real paradox because if  ou do a
growth tube to measure the greater progression as an estimate of growt rl down a long
tube, you inoculate one end of it and it grows through the agar.  If you have full
concentration of 1 euci ne and you start out with a mixed i nocul urn! it grows from
beginning to end.  If you have a minimal media without leucine, it starts somewhat
fitfully and then it grows from beginning to end, only what's at the end is only the
1 euci ne+.  If you have i ntermedi ate concent rations , it'll grow up to a certain point
and then stop and when you sample what's at the stop; it's all pure lucine-less.

    SO it's almost suicidal from the point of view of the complex; by killing
off the leu+--or diluting them out with nuclei, you end up with a final product
that's unable to grow further.  That's bizarre.  NO further progress has been made
                         Page 4


                             LEDERD05
on that since 1946.  That was the culmination of that experiment: but I still felt
WZJ frustrated That we had not been able to do more about Avery s finding.   so I
    If we can t transform Neurospora,
afteF all                     maybe we can do genetics with bacteria
      and in that way bring the Avery phenomenon and bacteria into the
mainstream."

     By this time,  havin  had a year of experience in using selective
methodologies to pull out w atever genotype you want,
          i!
idea arose about using a mixture of two auxotrophs,   that's when the germ of the
                               selecting for a prototroph and
using that as an index of whatever recombination could take place, and deciding to
apply that to bacteria.   I think I have some notes someplace.  The most tangible
note I can find is some scribbles in my class notes in bacteriology class which are
essentially the design of that experiment.  That would have been the summer of 1945.
So at Morningside Heights I started doing that kind of experiment with another
strain of E. coli, and the rest is history.  I've pretty well written all that down
(19) -

     I wish I could recall my discussions with FranCiS about doing this
experiment and going on further,
of it.                 but I'm afraid I just have no reliable recollection
    we certainly had intense dialogues about it.

BOHNING:  what kind of a group did he have working for him?  was it a big group?

LEDERBERG:  No, there were two, three, four other people in the lab.   Lillian
Schneider was his mainstay, a research technician who was with him for many,  man
years.  On and off his wife Elizabeth worked in the lab.  I just talked to her t x e
other day.  she still lives in the area.  There were one or two other students who
came in and out; I'd have to scratch to remember who they were.  There were some
very distinguished people who were there at some time after I left.  I don't recall
who they were just at the time I was there.

[END OF TAPE, SIDE 61

15

Page 5


                             LEDERDO6
LEDERBERG:  That was very formidable.  There were people 1 i ke E
with a hierarchy of contribution and accomplishment.

i nste in out there,

BOHNING :  Had you developed any new role models by the time you  were
high school?                                   getting through

LEDERBERG:  Not in the sense of an Einstein.  I'd seen these marvelous books that I
just quoted to you,  and I thou
them; I was still the student 9 ht they had a lot to teach.  I didn't identify with
                  ooking at what teachers had to say.  But the images
of people like [Louis] Pasteur and [Robert] Kokch and the others that de Kruif
talked about were there.  I guess I hoped I might someday be a person like some of
those without being too closely identified,
very diligent.                    but I'd have to work very hard and be

    There's a real paradox.  on the one hand I had pretensions about being the
smartest person I knew and I was going to learn everything, and I did know more
about most things than most of the people that I met in terms of my book learning,
certai nl y .  At the same time
objectively about that I can't I underestimated myself and if I 1 ook again fai rl
                  quite piece that out.           Y
but I didn't explore the full meaning of that term.   I did have a unique menta ity,
                                 I guess I felt there must be

somewhere hundreds of other kids like that, if I could only get to meet them and
find some day at the university some group of that sort. I did not have a clearly
formed picture of where I would stand in that hierarchy. To have ended up having
won a Nobel Prize by the time I was thirty-three for work I'd done at twenty-one--I
had no dream of anything like that. That might have been the end of a lifetime of
very hard work.  SO it's in that sense not totally accurate.

     But there's that paradox.  I'm still trying to resolve this in my own head
about where I would have placed myself.  I may have seen myself as being the big est
fish in a very small pond, but there must have been oceans around that I didn't I! now
anything about that I would have to think about.
metaphor I can think of.                 That's probably the closest

    I would have thought it would have been blasphemous for me to have compared
myself to Einstein, let's say. Maybe I still do,  but that isn't what I meant when I
said "to be like him."  A more accurate reflection of it would be to be some pale
image of that kind of personality.

BOHNING :  you've had this interest in science virtually as far back as you can
remember.  Did you have any broad
rather than its just being an i nte 7 icture of science in terms of its usefulness
                           lectual  exercise?


LEDERBERG:  oh, sure.  They were all merged.  The scientific method would be the
salvation of our political and social problems, if we could only think that way. If
we could be dispassionate, we could end up being more effective and more
compassionate in the long run.  one had to distance oneself from a problem in order
to really effectively deal with it,
ambivalence.               so there again there was that kind of

    I had no thought about science for weapons, and a great deal of
indoctrination about all the advances in medical science, so Microbe Hunters ( >
would have been the paradigm.  Here many wonderful things, extraordinary things, had
come about, and yet the
be predicted.        were all based on very basic research, whose outcomes could
              It was a 1 Y  a seamless web, so the picture I have now I'm sure was
pretty close to what I had then.

    I had a little more faith that scientific accomplishment would more or less
automatically work out to human good, because I thought that its method, its focus
on long term goals would be part and parcel of how it would be used.  That was
obviously somewhat nacve.
one's thinking about that. TO that degree the bomb was certainly a turning point in

BOHNING :  YOU were al ready at Columbia when when Pearl Harbor occurred, is that
                         Page 1


right?

LEDERDQ6

LEDERBERG:   Yes.
    But while we're still at that epoch,
Fair and the MUSeUm of Science and Industry. I want to just recall about the world's
                            That was a great treat.
taped a film of a reminiscence about that.                I've just
                          It was on channel 13 the other night
(14) -  Those are very vivid images--the trialon and the perisphere and its
symbolism.  This was the new theology and that's the church steeple, but in the name
of science. [1 aughter]

    There was an optimism about the new technolog  , and then the paradox of all
this happenin
was, here's  t il just as the world was going to war.  T at wasn't lost. The image
                    K
        is wonderful opportunity if people would only think

scientificall
and human fol Y --that's a phrase I would have used in those days.  But they don't,
      y is going to result in the misuse of all that technology.  If we
would only somehow 1 nspi re a more--I would have then used the label --a more rational
use of those kinds of resources.  That was the basic paradox, and I haven't totally
resolved that yet.

      There was  `ust al 1 kinds of stuff.  I remember they had the transparent
woman.  They had a 1 the organs laid out in a wonderful way and this is a piece of
       1
natural hi story  nowhere better.  There was Polaroid, and I'd keep going in line
again and again to get the little free samples of these thin
stuff.  There was Bakelite, and I would a ain grab samples o
               4        7 s and play with this
                                     that and cook it up at

home. [laughter]  Now I know it's a forma dehyde  resin.  There's some chemistry
there that I'm still involved with in my current research.

    But there again, these were images of technological utopia.  I'd al ready
al so read Aldous Huxley and Brave New world (15).  I understood quite early what the
downside might be, about the potenti al i ti es for se1 f-destruction.  what was going on
in Germany was perfectly evident.  Here was a people who sort of allowed themselves
to be taken over and then become a menace to the rest of the world.  I didn't feel I
could understand those
That's our biggest cha lenge,
         7 henomena, and I sti 11 don `t on a social and political level .
                  to know how to keep ourselves from doing al 1 those

things.

    The MUSeUm of Science and Industry was somewhat earlier.  It was in Radio
City.

BOHNING :  This was in Chicago?

LEDERBERG: No, No.  There used to be one here.  It was not a bad match to the one
that still exists in Chicago.

BOHNING :  Real 1 y?  I didn't realize that.


LEDERBERG:  It was the same sorts of things I've mentioned at the world's Fair.
Half of it was sort of silly but straight out of Detroit--all the ways you can make
gears turn.  And the  had very funny looking gears--square ones and elliptical ones.
Machines that were x alls bouncing off of a steel plate but with perfect precision,
and it did give one a sense of determinism.  That even something that you think of,
flipping a coin as being a random event, you realize that's because you don't
corn letely control all the impulses that were put on the penny.
7                                     They had some very
ear y demonstrations of television.  I remember telautography (?I,
writing was there.  I was imbued with what communications were going to generate for
us as the of that time.  Those were the main messages.  But there again there was a
euphoria about how wonderful technology was.

     I did a poster in `unior high school,
          8            which was my own version of Better
Things for Better Living T rough chemistry.  I've just retrieved that from the du
Pant archives, and I'm going to send that in as one of the things for the oxford
Dictionary of Scientific Quotations.  Did I tell you about that?

BOHNING :   Yes.  Did you get my letter about Kekule?
                         Page 2


                             LEDERDO6

LEDERBERG:  oh, yes.  I just got it; it was in this morning's mail.

      SO I du  that out--at least it was one of my icons. [laughter].
     ?                                    It's just
so emblematic o  that sense of optimism.  They don't even dare use the word
chemistry these days.  what a difference.

BOHNING:  Dow Chemical is one of the few companies that purposely kept the name
"chemical" in its name, although they seriously considered removing it back about
twenty years ago.

LEDERBERG:  IS this when they were making napalm? [laughter]

BOHNING:  Among other things.  They had Agent Orange, they had mercury in Lake
Huron.  They had a number of problems they had to deal with.

LEDERBERG:  Anyhow, I just wanted to recreate that sense of optimism in that era.

BOHNING:  where was this museum located?

LEDERBERG:  In Radio City.  Quite recently, in the last six or eight years, I was
talking to Bess Meyerson, who was then the Deputy Mayor for Cultural Affairs.  There
was some rumor about getting a thing like that started again, and I begged her to
get it set up again in its old place or the AT&T building, but she got into some
political deal with [          ] Mannis (?) over in Queens and it got stuck
out in Flushing.  It's all right, but I think it would have been better in a more
central location.

BOHNING:  How long did that exist?  Did it have a long lifespan?

LEDERBERG: No.  It was folded up probably in 1942. The world war did knock out a
lot of things like that.

BOHNING:  YOU graduated from high school in  JanUar i: of 1941.  YOU spent the spring
semester at AISL [American Institute of Science La Oratory.  Maybe you could talk
some more about that, because ye sort of skipped over that lightly.  For example,
yo,otmentioned here about the first time you saw IBM punch cards, or something like
   I'm just wondering if you could tell me a little more about that whole
laboratory situation.

LEDERBERG:  It's been documented in this IMB Think story (16)' and in fact
somebody's done a film on it (17)' so you can get those ob'ective materials.
                       i:            They
had some sort of examination, qualification process,
kids were given this opportunity.                and  a out twenty-five or thirty

    A very fine, then very young, person, Henry Plant, who was a psychologist,
bumped into Tom Watson at the world s Fair, struck up a conversation, and the idea
for this was hatched right there.  BY late 1940, IBM sponsored a laboratory for high
school kids.  He was the administrator for it, and it was just that.  By design,
they would have mentors to guide people's research, but they never found anybody who
knew anything about what I was doing.
   SO I ended up doing histochemistry and cytochemistry.  I was going to study
the two things that I mentioned to you before--how the change in staining R roperties
of cellular materials under different fixation regimes might be clues to t eir
chemical composition, and the specific case, what was the chemistry of the
nucleolus.  I was in really deep water on that.  I could do experiments in which I
f~x;~r~;eparations, things like       different pH's and different solvents and
      . In retros ect,
       R   none of the reagents that I knew about would have told me
enough to reveal  muc  about what was there except lipid solubility.
    But [Jean Louis] Brachet did do the right experiment with enzymatic
extractions.  I didn't know enough to extend the reagents.  There are still a lot of
                        Page 3


LEDERDD6

aspects of staining that we don't understand and I was just trying to get some sort
of rational framework for why one dye works better than another one.  Is it the pK
and other binding pro erties?
        7      I was in quite over m  head, but I had the literature
and I had done a litt e work on staining of model  su i: stances under those conditions.

    I remember one paper that stuck with me for a long time, by [         1
Eister (?> (18), and this had to do with specific uptake of methylene blue by
charcoal.  what it boils down to is whether there are sites that are specific for
things like sulfonamides.  He thought he had evidence that he could use methylene
blue as a blanket reagent for adsorption, and he could display some of those sites
with more specific ligands.  And I tried to repeat the experiments, and I didn't
succeed in corroborating what he had described.  It's been something I've been
puzzling about to this day, whether this isn't something worth looking into.  Think
of charcoal as just a random ensemble of sites, and you could use competitive
cll;iiacement on it or much more  s
   . That would have been idea ogically connected with the issues of specificity
             7 ecific source of separations-than we're doing
and staining.

    That's what I was up to.  I think during that time I learned something about
colchicine, and I'm pretty sure I started that project there, and then continued it
when I entered college.  I was very interested in what the physiology of mitosis
would be, and here was a very specific reagent which seemed to do nothing else but
disrupt mitosis.
physiology.    I just wanted to see if I could understand more about its
       we didn t know zilch about what the receptor for colchicine was; it
wasn't until some time later that we knew about             , which it had
specifically absorbed with.

    It was a good idea, and how to make it applicable with the available
technology is another story, but I started looking at other metabolic poisons and
what they could do to mitosis.  I tried to see if by using cyanide and urethane and
fluoride and the range of metabolic inhibitors as was known u R to that time, would
you get some clue as to how this particular inhibitor was wor ing or what was the
dependence of mitosis on energy sources, things of that sort. There were a few very
reputable scientists, as I soon found out, doing not too distant kinds of things.
It never ended up being all that productive,  but that's because  ou're dealing with
very loosely coupled issues.  If you interrupt energy sources, o viously the
                         i:
tractile mechanisms in mitosis are just one of thousands of thin
be hit.  But it was a way to learn more about an interaction of ;i s that's  oing to
                                                                 nown meta olic
                            %
inhibitors with some unknown biological process that I was trying to get into.

BOHNING:  You've mentioned Brachet's paper.  SO he was doing the work essentially
the same time you were.

LEDERBERG:  Yes, but--

BOHNING:  unknown because of the war.

LEDERBERG:   Yes.  That's right.  I had some correspondence with him about that just
four or five years ago.  He died just about a year or so ago (?>.  I'm a little
puzzled he was able to continue to flourish and publish even though the work didn't
get out.  I--he was obviously not a member of the Resistance.  I don't know what
else was going on in BelgiUm.  But there was a lot of, to me, startling sort of
"life is normal" aspect about that during that occupation.  If his name had been
Lederberg, he wouldn't have been able to do that.

BOHNING:   Yes.  I think we've already talked about your--you wanted to go to Cornell
or you, at least, you also applied to Cornell.  CCNY was there really for you, and
then you--

LEDERBERG:  It was a last resort.

BOHNING:  --got the scholarship, you got a scholarship at Columbia.
                         Page 4


                            LEDERDO6

LEDERBERG:  It covered tuition, or most of tuition.

BOHNING :  You were still living at home and commuting from Washington Heights.
started at Columbia in September of `41.  Had you spent any time on the co1 umbia
campus before you arrived there as a student?

LEDERBERG:  I might have seen it and more or less been outside.  I knew it by
re utation, but, as I mentioned in the other transcri  t,  I was not aware that E. B.
wi 7 son was no longer there.  [laughs] But I'd known a out Thomas Hunt Morgan and
                    &
wi 1 son and be1 ieved, not totally inaccurately that it was a great center of
bi ol ogi cal  research.   But nobody advised me, nobody really knew zi 1 ch about the
scientific capabilities there.  schools had  re utations in those days that had much
more to do with thei r football teams than anyt R ing else.

BOHNING :  Sometimes they still do.

LEDERBERG:  well, at least there are other avenues of inquiry.  But anyhow I don't
know--yes, what I did not know was the feasibility of going to a E ood state
uni versi ty .  It would have meant traveling out of state, I would  ave had to work in
order to get money for board and room.  And it was an option nobody mentioned to me.
YOU know, maybe even out-of-state tuition even in those days would have been enough
to have hindered it, but the main point is the vacuum of advice on those points.
    Not every kid was going to college in those days although I suppose most
Stuyvesant graduates were expected to.  BUt I don't recall ever hearin z anything
sensible from any advisor.  when I compare that to what kids go throug  today, it's
astoni shi ng.

BOHNING :  So Stuyvesant sort of left you on your own.

LEDERBERG:   It seems so.  Now they--a complete blank on that.  They must have been
some help to me in contacting Co1 umbia to apply for the scholarship and so on.   But
I think they may have just decided that financial circumstances were such as--sort
of hope1 ess.  I was going to go to the City College and if something else came
along, well, okay.
    But what I resent is that nobody pointed out--I went to teach at a great
state university not too many years after that, and nobody ever mentioned that
possibilit   to me.
    Y        I mean, I may not have been able to make it, either.
     We 1, Columbia worked out just fine.  I'm very lucky to have gone there.

BOHNING :  It's surprising in a way because a school like Stuyvesant--Stuyvesant with
the  re utation it had, as you said most of the students were expected to be going on
to co1 `; ege--that they weren't more vigorous in student advising.

LEDERBERG:  well, I do find that difficult to understand.  I may be blocking out
some hi story, but it's not the kind of thing I would ex ect to have forgotten. But
there's--kids are nurtured more carefully today, genera ly.
                     7    I mean, when we talk
about these age issues and so on, the--it was less startling then than it would be
now.  I mean, kids were expected to be on their own a lot more than today. Go
through SUNY and so on (?I.

BOHNING :  YOU went to the Admissions office and you made the--took care of all that?

LEDERBERG:  well, it would have been by mail.  I don't remember doing it personally.
It was all--I just don't recall.  I could have had something to do.

BOHNING :  SO when  ou started in September of `41, were you gettin  an advice then
from Columbia facu ty, or were you just throwing in as a standard
       Y                   7 x
                                                      res man?


LEDERBERG:  No, no.  well, that--as soon as I was there, I was in a very different
milieu.  And I don't remember exactly whom I met first there.  But within a week or
two I'd met Barbara Mcclintock and talked to her about my paper on the nucleolus,
and could she, you know, he1 p me understand more deeply and so on. And this is one
                         Page 5


                            LEDERDO6
of many.  I very quickly located--I was very aggressive about it--but ingratiated
myself with al 1 the talent that was there.  I never lacked for sense (?). [laughter]

BOHNING :  This was the paper you wrote in high school .

LEDERBERG:   Yes.

BOHNING :  And I'm not clear, since we haven't been able to locate your pub1 i cation
list.
doing. was that published in a--it was just a paper you wrote based on what you were

LEDERBERG:  well, I'm trying to recall a little more.  oh, I know one of the first
people I met was my zoo 1 instructor, H. Bert (?) stei nbach, was one of the first
courses I took.  I'd started working on the nucleolus, but I wrote this paper during
my first semester there,  or at least another version of it.  And it was during, for
the preparation of that paper that I went to consult with Mcclintock (?).

     SO I would meet the professors in m  courses and I did have an advisor who
was,  I think, was ori ? inally a physicist ca led
                 Y   Banardroff, I think was brother of
the previous principa  at Stuyvesant, and then Keller the cytologi st (?> , who I've
kept in some contact with.  SO I started getting very good advice as well as easy
access to teachers and graduate assistants and thin ;i s of that sort.   So I more or
1 ess 1 ived in that department from that time on, I  ad a wonderful time.


BOHNING :  Did you--~ mean, you had already been so advanced in what you had been
doing up to this point.  Did they start you out in regular introductory courses, or
could you start much further down the line?

LEDERBERG:  well,  we discussed that.  I was able to place in quite a few of them. I
did get some list.  I think I have my curricul urn summarized there.  Yes,  these are
my fi rst courses.  well, I started right off.  I had--well, it was just as well; I
didn't know the comparative anatomy and morphology that was there. And then went
straight on to the next level course in embryology, morphogenesis and so on:  This
is the paper I just mentioned to you.  And then by the next semester or during that
year I was already into the graduate courses, these, the three digit courses were
al 1 graduate courses.

BOHNING :  As we--in my file I have copies of that correspondence with stadola (?).

LEDERBERG:   Yes.  well, he was just a wonderfully nurturing person.  And I placed to
an advance level in his course, and then completed it over that summer.  And, well,
you saw how encouraging he was.  He died just about six months ago.  I recently got
a notice of it.

BOHNING :  what about original research?

LEDERBERG:  well, I was playing around with colchicine during that first year, and
the only new finding I made was that there was a suscepti billty gradient down the
axis of the tip.  And that the most actively dividing ccl 1 s right at the tip of the
meristem (?) were less susceptible than the ones behind it.  And trying to make some
sense out of that.  But the phenomenon is real.  YOU could find critical
concentrations where you get the interrupted mitoses  u R to a certain level , and then
they'd be normal below it.  I never was able to straig  ten out whether that was
differential absorption, which could qualify as the kinetics of it (?> or the
intrinsic difference in the cells.  I still don't know.
[END OF TAPE, SIDE 53
19

Page 6


                             LEDERDD7
LEDERBERG:  He had a contract of OSRD [office of Scientific Research and
Development] to study the nutrition of clostridia--clostridium sp
of the other wound-infecting anaerobic bacteria.  And he had     rogenes and some
                                     some ody working for
                         g
him on that project. That was aimed at
i nfecti ons .                          therapeutic management of those

BOHNING :  You were sti 11 on the Hayden fellowship?

LEDERBERG:  Oh, no.  That was--that's, that was until I got to Bl2.

BOHNING :  Oh, I'm sorry.  So 812 was paying the way from there on.  was there--you
said you had intense discussions with him, or you're sure you did, but you don't
recall the nature of them.  was he there a lot?

LEDERBERG:  Oh, yes.

BOHNING :  was he in the lab all the time?
wandered through once in a while--      SO he was, he was not a person who

LEDERBERG:  Not at all.


BOHNING :  --but he was intensely involved.

LEDERBERG:  He had a great zest for himself doing the experiments and so on.   But I
suspect that about that time that,
experiments,              that I was doing most of the neurospora
       either ones on my own or at his behest.
mostly working on clostridia.                 And was with his own hands,
                  I didn't do any of that.

BOHNING :  YOU said it was a small--

LEDERBERG:  He had a full-time teaching load and so on,
the hours that he can (?).

and so he wasn't there all

BOHNING :  I guess in those days, financial support wasn

LEDERBERG:  I should say.  well, there were the particu
wasn't war work then what was your excuse for doing it,

`t all that great, was it.

                  l;;dcz;s;;aints that if it
                                                                        .  So I was sort of
smuggled in.  strangely enough,
Cl aughter] and recombi nati on,  the Navy was paying for work on neurospora
                 and OSRD was supporting this other stuff.

BOHNING :
the war.  Did your group interact--I'm just tryin
      I'm sure a lot of people were being  7 to get a feel for the middle of
                                  dra ted.  what was hap
other research groups within biology and what kind of interactions   ening with the
                                                                t Ii ere were.

LEDERBERG:  well,
fill in.       a lot of women came in as graduate students during that time to
     There was still a reduction in load that you had the whole (?). The
university was being turned to a variety of other projects.  I had a faint inkling
that the Manhattan Project was nuclear energy, and to my mind, it was confirmed when
I bumped into Harold urey going down the stai rs one day. [laughter] Couldn't be
anything else from my point of view.  But that was just a surmise.
the metallurgic project, I seem to recall (?) .               They called it

much,  And then training large numbers of--it was taken over by the Navy pretty
   B5, 87, midshipmen and so on.  And then there was sti 11 a trickle of
undergraduates.  It was sti 11 a boys' school,  so as far as  under ? raduates were
concerned, either it was the ~12's (?> in uniform or a very smal  number of kids who
could get deferments for one reason or another.
as premeds.                       A few were able to get deferments
       If they' re going to go straight to medical schools , then they could get
deferred to do that.  They weren't drafting anybody out of medical school at that
stage and apparently that was certainly wise (?).  They were then committed to a
term of service afterwards, which the services decided unilaterally to turn off.
They didn't even want the reserves.
`46, `45.                  Demobilization was pretty much complete in `44,

    Anyhow, these experiments began during that summer and it was pretty
                         Page 1


LEDERDD7

momentous as far as the way the war was going.
still going to continue,  and that there would  Then in November, I thought it was
have to continue with m  service obl i      be a post-war Navy, and I would still
rather suddenly, actual y Y i; with Ii ain ully short notice
              7 ations as everybody's expectations (?) . Then
decided to demobilize us                   the number of people--they
anything,         NOVem er and that they didn't
     and they weren't going to pay us anymore.     need us anymore for

and figure our where tuition was goin         Real 1 y had to scramble to try
there was some GI Bill availability, El to come from and so on.  For some students,
                                   ut it was quite limited if you hadn't--if your
only service was in training I think you had zero or very low eligibility for that,
reasonable.  SO it was quite a sudden turnaround.

BOHNING :  what kind of interactions did you have with the chemistry department?
you have any?                                                        Did

LEDERBERG:  well, I took a number of courses there.
and a few others.  I remember Professor Beckman.   I had just to do a little (?>
think, that's the way it was listed.         I had a minor in chemistry, I
hell of a guy I took my course with?  who was the physical organi c--he was quite a



BOHNING :   Hammett?

LEDERBERG: No.  who?

BOHNING :  Louis Hammett .

LEDERBERG:   Yes.  That's who it was, Louis Hammett.  I did some physics.  I had
Willis Lamb as my instructor, learning, studying radium, as a matter of fact,
electronics. [laughs]

BOHNING :
don't   well, I notice something here from the Institute of Radio Engineers, I
   know what the date on it is.

LEDERBERG:  oh, that's a different strand.  That's my NASA connection, Lloyd Berkner
was the president of what was then the IRE and asked me to sign up.

BOHNING :  That's the early '60s.

LEDERBERG:  I took a sort of beginning graduate courses in physics.  I had one
course in theoreti cal physics .

BOHNING :  Were you aware of the Manhattan Project,
urey and his group?                  the work that was going on by

LEDERBERG:  I only guessed that it was nuclear energy.
classified project called metallurgy.            There was this mysterious
it weren't just that.  That was my only I couldn't imagine what else he'd be doing if
                              ink1 in  of it.  I now realize Leo szilard
was on campus at the same time; I got to know ii
remember ever talking to him then.         im very well later, but I can't
   There were large blocks of several buildings that were sealed off.

BOHNING :  They were working in Havermeyer, I think.

LEDERBERG:  well, al so in ski rmerhorn and some in ~~.  There were several
areas that were closely guarded.

BOHNING :  I'm not familiar with where you, you would have been.

LEDERBERG:  Ski rmerhorn is where zoology was.

BOHNING :  okay.  where's that, just for my own information, where's that in
relationship to Havermeyer?

LEDERBERG:  Well, it's just across campus.  They have Havermeyer on the west side,
                        Page 2


                             LEDERD07
and skirmerhorn on the east side.

BOHNING :  okay.

LEDERBERG:  About the same level ;  it's about 119th street, I think.  Can you excuse
me just a minute?

BOHNING :  Oh, of course.  [Interruption]

LEDERBERG:  I think it was during that summer that I  su pose we were anticipating
some kind of leave or vacation period.  The school had & een going non-stop
throughout the war.  And Francis suggested that maybe I'd want to pursue this
experiment with Ed Tatum.  Ed was coming to Yale from Stanford.
     I was told later by Johnny Moore that one of Francis' motives was to find me
a patron who would be more potent in the establishment than he himself was. He
thought bei n i? an Irish catholic from New York was sort of next worse to being a Jew
from New Yor  and that we needed something more powerful to be listened to.   I was
not aware of ihat at the time, at the time it was a consideration, but it
was--Johnny was quite fi rm in saying that that was one of the things that Francis
had in mind about sending me to Ed.  And I realized--I didn't realize then how low
on the totem pole Francis was.  I mean, he was my god,  but he was an instructor and
then an assistant professor.  And I was at the point of announcing some
icon-breaking matters ; there's probably some merit that that might not come so
easily without a recognized sponsor, but I didn't know that.
   Anyhow, I, at Francis' suggestion, I wrote to Tatum, outlined the experiment
that I had in mind to do--and that s all on the record--asked if there would be an
occasion for me to visit his lab.  Francis had smoothed the way for that with him,
and Ed arranged a fellowship from the childe's Fund to do that.  SO I'd gotten up to
a certain point, but I needed a wider variety of mutant strains and I was starting
to make more, but Ed alread  had a library of mutants that he'd already derived.
And I was happy to have a c K ante to be in a different setting, and so it looked like
it would all be a good idea.   SO we did arrange it.  History permitted it, and I
was able to get there.  Was it March or April?--I've written it down--that I
actually arrived in New Haven and got started.  That's `46 now.

BOHNING :  somehow that  age--here we are.
     original 1 y you R ad--you were sti 11 planning to go to medical school .

LEDERBERG:  Yes, this was--I was actually still in medical school.  I was registered
for external research, and my standing at Yale was as a co1 umbia medical student, as
a guest at Tatum's laborator  .
          g  And the thought was I would do that for the spring
quarter or semester, presuma ly spend the summer there with m  vacation time as
well, and then reenter the regular annual cycle.  I wouldn't i ave slipped a class, I
mean, just my regular class, the following fall (?).  SO that was the game plan.
      Now, I don't know how I thought I was going to finance it , but I imagine I
had.some scholarships coming,  that were available at the school and had some
savings.  I think I had fifty dollars a month in the Navy, and somehow or another
was going to make it.  SO this job meantime al so had the advantage I could hope to
save a little bit from that and help out the following fall again, too.

BOHNING :  when did you realize you wouldn't be going back?

LEDERBERG:  we1 1, not for some time.  The experiments worked out very quickly that
spring,  and I recounted that in detai 1: I won't repeat it again.  And so durin  the
summer,  wrote and asked for an extension.  SO after the summer I was on leave B rom
Co1 umbi a and Ed arranged for an extension of my fellowship from the chi lde's Fund to
enable that.  And I thought after a year of that I would go back to medical school.
And was planning to pretty much to the end until Ed said, "Maybe you want to
consider an alternative."  And that was the job at Wisconsin that had opened up, and
he had come recently from wi sconsi n, so he felt pretty close to it.  And did look
into it, and with a lot of se1 f-exami nation decided that that probably was the
better thing to do--that since research was what I really wanted, I could pursue
that better by not interrupting the work that I was doing.  I still felt quite a
                         Page 3


                             LEDERDO-/
wrench about being disconnected from medicine.  Madison didn't offer that kind of an
o~p~;r-~~-i;y; it was in . the  a  school .
           Ii       That was an important negative consideration.
   R repai ring it--I  ad no anticipation that I would be able to--but in `55,
seven, eig t years later, I did start a department in the medical school at
Wisconsin.
    So that's how it worked out, and then I had to register retroactively as a
vale student for that year when I was really on leave and had to fork up tuition for
that--I remember that very vividly.  And the professors all signed up and said,
"Josh was at al 1 the seminars and lectures .`I  And I had already done the work for
the di ssertation, so we patched up a Yale Ph.D. out of the experience.

BOHNING :  what kind of a group did TatUm have, and did you interact with them very
much?


LEDERBERG:  oh, yes.  There were about half a dozen people there: Ed Adleberg; a
fellow called RayOUf?I; Mrs. FtWtOn--TOpSie; sophia Simmons was in the lab there with
him; poll Bunting.
   x       Her husband had died the year before, she was widowed quite
young.   s e went back to work; she'd been a microbiologist, done some work in
bacterial vari ati on.  SO she was in the lab then.  she later became the president at
Radcliffe, started the Bunting Center; I'm sure you've heard of her name in other
connections.  That was much later on.
     There were one or two other students.  They overlapped different parts of my
time there.  Charlie and ostie (?) came in I think the very end of my time or
shortly thereafter.  Ralph Llewen, likewise.  Those are the main names I remember.
Mrs. Tatum worked very actively in the lab then, June.  SO he was sort of just
getting underway--oh,  a fellow called Barrett was there.  It was almost enti rely a
neurospora 1 ab; I was the only one working on E. coli.
    Ed never really pushed very hard himself with that.  He'd been a
bacteriologist, and the way I reconstruct it he had two medical students at
Stanford, Gray and Anderson respectively that he sort of gave the job of looking for
mutants, and that was the beginning of that collection.  He didn't talk much about
it, didn't seem personally to be that deeply involved. He liked the idea that
bacteria might do some of the same things.  BUt he too--he was much more of a
biochemist than a enetici st,
       7       if you look at the detai 1 of the work he was doin  .
And he could do al the things he wanted to do very well with neurospora.  And e i!
really enjoyed it--he loved that organism.  so that was the division of labor.


BOHNING :  when did you know you had the final result? YOU had written all those
papers.

LEDERBERG:  I've documented that here.  I don't remember the dates; I looked them
up.  It was pretty early: I spent a lot of time on the controls.  I didn't dare do
an experiment until I was sure the controls were clean.  The last think in the world
I've ever wanted was to have an exciting, 7 rovocative result where I would then
still be uncertain.  SO I much prefer to c ean up first; I'm willing to wait.  Now,
there's probative kind of work. If it's not that important and you' re trying to
figure out what's the best way to do something, 1'11 do exactly the opposite--I'll
do quick and dirty.  But when I have what I believe is a critical experiment, I'm
sort of scared to do it until I know it's right.
    I don't want to be caught either with an unwonted disappointment because I
think it would--I don't like the disappointments,  but the unwonted is that I hadn't
thought of some variable that I should have had right at the very beginning and have
to scramble later in order to rescue the experiment.  And even worse is when it's
contaminated by a misleading result and have to be nagged by the idea ma be  it's
true,  ma be it isn't.      '    I find that intolerable, and I work very x
hand to eep it from haipil?kg.
   i:                                              ard before
                     well, I did that here.  I spent two months on the
controls and then, whammo, the ver Y fi rst experiment with mixed cultures, it was
such a cl ear result we didn't real  y need the controls.  BUt it's just as well.
    So that was in early June, I believe--late May or early June.   It was a
month or some weeks before the Cold spring Harbor symposium.  And it seemed like a
very short time, but I must have done a dozen repetitions with different strains and
different markers in that month.  so I had no doubt that there was a phenomenon, and
we al ready knew a lot about it by the time July rolled around.
                         Page 4


                             LEDERD07
    So Ed was already on the program.  A number of graduate students, including
myself, were welcome to attend.  And even after we were there it was problematical
whether we were going to say any more about it.  But when a number of other people
were either saying  cate ori call y how awful it was that there was no sex in bacteria,
or, well, we have some 8 ints that maybe there's this maybe there's that, we thought
we shouldn't hold back anymore.  And Ed asked Demeritz (?> if he could just assign a
special interval and we did find some time and presented it.  Had a long debate
afterwards.
    I've been trying to get some reconstruction of it without very much success.
I've circularized everybody        who was there, and just one or two replies.
Nobody kept any notes.  Nobody can even tell me exactly what day it was in that
meeting. [laughter]  And oddly enough I don't have that record.  So I can span it to
within an interval of four days.

BOHNING :  Susan [Lindee] was tellin ii me this morning,  she has cold  S ring Harbor
s mposia title pa ers going way bat  from something.
K      F:                      I don't know w ere she got
                           R
t  em from.  I oug t to find that out if it goes back that far.

LEDERBERG:  well , the Ameri Can philosophical society has Demeritz' records.  They do
not include the 1945--or `46 symposium.  SO maybe she's referring to that.

BOHNING :  well, let me check anyways, just to see.

LEDERBERG:  ~11 right.  once again, I'd be delighted.

BOHNING :   I mean, you know,  if she has it


LEDERBERG:  It's a mystery what happened to that particular file.  I've wanted it
for another reason, namely on the reception of Avery.  And it's been a tall point in
my argument on that that, far from being neglected, that, for example, he was
invited to present at this symposium.  And it--I liked to get documentation about
who suggested it, the wording for the letter of invitation and so on.
     I know that in the actual event, Mac Mccardy (?) came instead of Avery, but
there was a paper on the transformation.  YOU can't sensibly argue in my view
that nobody was paying any attention to it.  But I would have 1 i ked some deeper
documentation on that point.  That's another reason I lament the absence of that
particular file.

BOHNING :  what's your sense--since you have very little feedback--what's your sense
of the reaction and the discussion?


LEDERBERG:  Oh, it was a wonderful opportunity.  I mean, I recall the debate pretty
well. And there were-+kubov kept asking, "HOW do you know it isn't just a mixed
:;; ;u r: I , YOU         Because he had worked on centrophi c interactions.  And I
    I ve thought about that, and if it was a mixed culture, then it was a mixture
that'just didn't know how to separate.,,  And I had indicators like lactose
fermentations , so I could spot white and black colonies on EBM media; I didn't have
to pick them one at a time, and they were completely homogeneous.  I also had
selective markers, I had a phage resistant and a phage sensitive pair, and they
would segregate out.  some of the prototrophes (?> were all sensitive, no resistant
residuals from the supposed presence of one of the components; others would be pure
resi stant .
     I couldn't be as confident about that homogeneity.  I could certify those to
99.9%.  The ones that are total 1 y sensitive I could certify to five decimal places
because I could pick up tiny residuals of resistant organi sms .  I'd verified that by
making mixed cultures and so on.  so I felt a little put out that 1) that they'd
think that I hadn't thought of it, and 2) that even after I R resented what I thought
were very meticulous experiments to answer the point, that  t ey didn't seem to
listen. [laughs]
    But most people did accept it very promptly, but my view is it's been
informed by thinking about this with Harriet zuckerman, about the social dynamics of
that.  That it was a rare opportunity to be able to make that presentation to the
group of movers and shakers and within the discipline of an organized conference.
                         Page 5


                             LEDERD07
YOU know, they were really on their honor to complain or keep your peace, and you
don't always have that opportunity.
resistance unfocused,          I could have had all kind of sniping and
           if it hadn't been for the occasion to bring it all out.  So it
was a wonderful confrontation.
by the French academy.      It was like Pasteur's meetings that were organized
    I didn't appreciate the importance of that at the time.
to have the opportunity,                                I mean, I was glad
                but it never occurred to me what if that hadn't been there.
Maybe if I had just dropped this in the hopper and it had been published in one of
the routine journal s ,
not to believe in it, and a lot of peo le would have thought of al 1 kinds of reasons
              not to have the i nd of confrontation that this reflected.
              R
    SO I didn't get, Max Doberg (?) sort of didn't want to believe it and sort
of held out for a long time,
what's wrong with it,     but I repeatedly begged him to give some arguments,
something very wi se,  how could these experiments go wrong? And he actual 1 y said
      but it was done in a sufficiently abrasive way tha;eIs;p;ldn't
see through his resistance to where there was some good advice in it.
"Don't bother me with it.
anythi ng . "  A bio     unti 1 you've worked out the kinetics it doesn't mea;
    well, by R hysicist would do it those terms.
             inetics I thought he meant what's the yield as a function of the
concentration of the inputs,
bimolecular reaction.     and I had done those experiments and, yes, it's a
                      . I mean, kinetics could have meant to the time
course of a mixture in an interruption,
vollman (?) did. Of course,        and that's the experiment that Jacob and

it.               that was a very important contribution to understanding
    But it never got resolved on any intellectual ground.
significant resistance of which I'm aware.              That's the only
                          Most people who were there and were able
to experience the debate and the argument adopted it.
about it.                            Luria was very, very positive
      He was probably the main person who would have had reason to have an
opinion on the matter at the time.

BOHNING :  Did you realize the importance and the magnitude of the importance of what
you'd done and the effect it was going to have?

LEDERBERG:  Yes,  I think so.  I mean,
bring bacteria into the mainstream.   look, the purpose of the experiment was to
                     And behind that was to bring DNA into genetics.
Yes,  this was the master molecule that was
experimentation.            9 oi ng to be available for further
          I can say that without qua m.
[END 0~ TAPE, SIDE 71
107

Page 6


                            LEDERD08
LEDERBERG:  I was al so quite confident that it would have practical applications in
medi ci ne.  I didn't dream that there was going to be a biotechnology industry with
all these startups and the wall street involvement in it,  I thought it would be
incorporated into what the existing drug companies could do and become part of the
mainstream of their research and, yes, 1 t would be profi tab1 e and enhance what
pharmaceuticals could do, and so on.  I had no idea it would become the
entrepreneuri al game that it ' s become.  And it didn't need to; if the big firms had
been awake on thei r watch, they would have assimilated it twenty years earlier and
not necessitated the neoplasia that we've seen.

BOHNING :  why do you suppose they were asleep?

LEDERBERG:  well , it's the problem of organized large-scale research and getting so
caught up in the dynamics of what you've been doing that it's hard to make room for
anything that's more novel .  To some extent it's that your managers are the
scientists of twenty years earlier, and it's a little hard for them to wake up to
real i nnovati on.  Those are the two main factors.  There's a little bit of the
dynamics of doing research that requi res more than a nine-to-five mentality, and
there the incentive systems for what the entrepreneurs can make out of it does start
to play some role.  why should the people in a large organization exert themselves?

    So the usual problems of bureaucracy can be folded into it, and the
entrepreneurs are the counter-bureaucracy.  It wouldn't have to be that way, but you
take, I guess, more enlightenment than exists in those ranks to do a better job.
You know, they have their successes, as well as failures, but the development of
antibiotics could have--I mean, that's what I had as a paradigm, that this was a
major advance in medicine, was taken up by the big fi rms and you don't have a 1 ot of
entrepreneurial colonization as the way that that had happened.
differently.                                         It has worked out



BOHNING :  I don't know what your time constraints are.  It is three o'clock.

LEDERBERG:  well, if there's a natural ending point sometime soon, if it's not too
rigid.  I've just got a pile of paper on my desk that I've got to take care of.

BOHNING :  well, this might be a place--we've got you to cold spring Harbor and that
meeting and--

LEDERBERG:  well, why don't I finish up till I get to Wisconsin?  we could do that
in the next few minutes.


BOHNING :  okay.

LEDERBERG:  It's actually a fairly short story because the original discovery that
there was such a thing as recombination for both a set of next generation questions:
what would they be?  what are the interacting units?  well, they're cells.   YOU
don't get activity from filtrates.  Got nowhere trying to get transformation from
extracts.  Took a long time before E. co1 i would work that way.
    Boivin caused a whole flurry,  he talked about DNA transformation in E. co1 i ,
but that didn't pan out.  I guess Burt Davis did what he call ed a bundi ng board
experiment , where he had a filter separating the two cultures and they communicate
nothing through a filter, and in contrast to what you get with vi al transductions
which came out a couple years later on.  Adding deoxyri bonuclease to the medium does
not interfere with the process of genetic recombi nation.  so the presumption i s DNA
is being exchanged, but in a way that's protected from the external medium and
requires intact cells.
     Two, are there mating t pes?  And our first answer was no.
            K                                  Later on we
discovered there were mutants  t at showed that there could be, but a least our own
bank of cultures were promiscuous.  Three, how many markers could be involved?
well, an indefinite number--kept throwing (?> markers into the strains, 9 etti ng
mu1 ti pl e mutants and showing you could get al 1 the combi nations imagi nab  e,  but at
di fferenhkafCequenci es.
             , can you make a genetic map? And the answer is yes; there are a lot of
                         Page 1


LEDERD08

constraints because of the need to impose selection on the
an unbiased recovery of all the progeny, you can only get t ~"%~~'that already
                       R       YOU don't have
recombine on the markers that you're selecting on.  with that constraint map (?) it
seemed to work out pretty well; up to a certain point it didn't.  It's consistent
with what we got later on.

    SO those are the main findings for that year.  The first linkage maps and
the range of markers and then getting some excitement about what with genetic
analysis of those gray markers, so I glommed onto lactose ver  early.  I thought it
would be a very good paradigm for a z ene controlled enzyme;  t K at way we could do
detailed genetics with it. It's wor ed out that way. sort of use E. coli the way
one had done before with neurospora.

    write up those papers, used them for my doctoral dissertation, spend a
summer at woods Hole doing it and reading all of the antiquarian literature.  I had
seen some of it before then, mostly by Dubose, and getting a  ood sense of what the
history of the subject was at the same time. I've written a 9 ittle bit about that;
I don't know if you've seen that.  The last issue of ASN News I had a little paper
on that.  1'11 dig that out for you.

BOHNING:  we just got

LEDERBERG:  1'11
information.  we1 7 et it for you right now.  [Pause.] There's no biogra hical
                    ver

an interesting hisiory K little; I start out in the first paragra h.
                         7   T is paper has
                           R
            ecause I gave it at the Pasteur centennia  in '88.   It was
the keynote paper, and they were going to publish it in a book there.  But they ran
out of money and they only told me about six months ago they weren't goin   to
publish it after all.  And I sort of wanted it to go someplace, tried to 7 igure out
where it ought to go, and I think it ended up in 'ust the right  lace.  It's the
news bulletin of the ASN, but they truncated the 6 ibliography, w ich they didn't--
                        R

BOHNING:  oh, that's what the separate

LEDERBERG:   Yes.  If they'd looked at the page layout, they would have seen there
really was room to add quite a bit more, but they--anyhow I've had to restore my
original full bibliography to it.  And it reads a little bit awkwardly, but that's
because of the history. I few places are off.  But anyhow, that gives all the sort
of prehistory of that sub'ect.

     okay.   It was rea ly quite late that summer that the question of Madison
         1
came up.  [Interruption]  But we--that was really late in Au ust that I actually made
my first trip to the university.  My first airplane ride. [Laughs]

BOHNING:  YOU hadn't really traveled that much up to that point, had you?

LEDERBERG: No,  New York to New Haven.  well, Israel when I was a little kid.  And
that worked out, so we really quite hastily changed our plans.  oh, I'd gotten
married in the meantime--that's that "we." (?) okay?

BOHNING:   Yes.  I think that's a good point to break.

[END 0~ TAPE, SIDE 81
111

Page 2


INTERVIEWEE:


INTERVIEWER:

LOCATION :


DATE :

                LEDERDU9
Joshua Lederberg

James 7. Bohning
    Rockefell er University

9 December 1992

LEDERBERG:  If there is a definite historical structure you're trying to fit, that's
fine, but I sent you a little note about thematic issues.

BOHNING :  Yes, I have it right here.

LEDERBERG:  I had a couple of others that I've just been thinking about and was
talking to some of the people about other matters, but they sort of reflected back
on this.  This is not very carefully structured.  [laughter]
   I think I've seen this before, but in any biographical i nqui ry you have the

tension between looking at your subject in terms of his uniqueness and the other in
terms of how he's an example of the genre.  I guess those always fi 7 ht,  one versus
the other.  But I think it's an interesting question to ask about  a most any stage.

    Then I think we all live out some kind of a script.  we change it from time
to time, we look back and discover it didn't always work out the way we thought, or
we were working through a different script than we thought, but, what was the
script?  That's a life model kind of issue.  I think we ve al ready mentloned we' re
trying to focus on what were major decision points, which is sort of another way of
looking at the last previous question.  Then quite apart from my personal hi story,
there's the evolution of the science in which I was embedded, and how that was
moving and what was the perceptual framework.  NOt I'IeCeSSat? 1 fOCUSSiIIg to0
narrowly on what my own contributions were,  there was a lot  e Y se very interesting
going on that I was both an observer and a participant.

    The take home message is an issue of phi loso hy .
describing a life you're trying to communicate to ot R    what is it that in
                                                       ers
presentation or portraiture.                besides some matter of.ego
               I guess as much as anybody I've lived a life of, in,
and about science and then tried to apply that mentality in a wide variety of other
contexts as we1 1.  That's part of a life model in a sense, but how do the particular
things that you were doing or describing at any moment bear on that issue.

    Then there were a bunch of other sets of circumstances.  These sort of go
together, and they have to do with how to relate to others in the scientific
environment which is primarily your work life.  what was the laboratory environment?
Who you were dealing with?  I've talked a lot about my mentors.  I might want to
say a little bit more about those for whom I've played that role in turn.  Then
there are the various gates and the gatekeepers that you encountered at various
places--how they structure your interests and your opportunities, issues of
publication, granting, getting positions and so forth. There's another kind of
bottom line here, but the take home message there is to the world, and this is a
take home message about people in your own immediate arena, what can you draw from
your own life that could be of some use to them.

   The next is the philosophy of science, philosophy of discovery--a much more
abstract question than some of the others.  Then there are issues of styles of
scientific work and the 1 uestion of risk taking.  while that's not the on1 one
it's one that's dominate the kinds of polymorphous perverse enterprises t at I've
                            i?
%i iF  This is one aspect of a longitudinal enqui ry, but there is an evolution of
   in that starting as an undergraduate and as a graduate student, totally
immeksed, personally doing experiments that more and more you're at the first and
second and thi rd remove.  And I guess I've gone the who1 e way in going full time
into admi ni stration and then back again, but it's not a sharp demarcation. I think
                        Page 1


LEDERDg9

a lot of people don't understand the extent to which working scientists don't spend
a very large part of their time actually at the bench.

       Peo le ask me if am I now back in the laboratory, and my honest remark has
to be,  "NO 7 ess than any of my other colleagues as professors at the university."
But I have a little bit of a twinge that it s not a completely honest statement to
say I'm in the lab.  I'm in here talking to you. [laughter]  I do visit my lab from
time to time, but I spend most of my time interacting with what's  oing on actually
right here and of course relating to the 1 iterature, as well  e
there is an evolutionary developmental aspect of that detail  o 9 ual 7 y important.   But
                                            that work involved

as a scientist.

    I didn't know what other things like that you've encountered, in the long
experience that you have.

BOHNING :  you've actually outlined it very well, and I think this version is an
extension of what you sent to me early.  Those are exactly the kind of things that I
keep looking at when I'm talking to  eople.
we're now reaching a point where I R     we've touched on a little bit of that;
                                 t ink we want to explore some of those issues in
more depth.  I think it might be easier to do it chronologically.

LEDERBERG:  Episodically, at any rate.   It  `ust occurred to me as we were both
speaking at once that perhaps the point of 1 eaving New Haven is an episode of which
to just go through these themes and see if there anythin ? more you'd want to bring
out from that interval before we leave it that might ref ect on each of those
issues.  I suspect that one way or another they've been covered, but I think it's
not a bad heuristic to do that at different stages.  SO I agree with the
chronological framing of it.  what did you have in mind to go on with now?

BOHNING :  I had some pre-Wisconsin questions.

LEDERBERG:  Let's make sure we cover all that.

BOHNING :  As I said  unfortunate1 ii  for some reason my notes did make the trip with
me. At least I can't find them w ere they should be, so I'm going to have to rely
on my less than successful memory.
[blank section on tape]

LEDERBERG:  After I had done all the work, and it was in the context of an
alternative to my going back to medical school , which would have mooted the issue of
a Ph.D., that he thought I would have more fl exi bi 1 i ty, which was of course true.
So we arran ? ed for de facto retroactive registration and the big stumbllng point was
paying the  ees which I had to cou
and the paper that I was drafting 7 h  up.  It wasn't easy, but we managed to do that
                                      or  ubl i cation was accepted in fact as the
dissertation, plus another twenty or t irty pages of general commentary. That has
               R
become much more routine; in those days a dissertation used to be thought of-as
bei n i? a completely i ndependent manuscri pt.  I think vale was just then transitloning
to  t  e idea of accepting other pub1 i shed work as legi timate dl ssertatlon material.

BOHNING :  Tatum obviously was doing all of this for you.  DO you think there was any
objection on anybody's part?

LEDERBERG:  I don't think so, but the work stood for itself.  I think it was
recognized there quite promptly that it really was pretty important.  And it had
Tatum's imprimatur.

BOHNING :  I noticed in your        list that you indicate your Ph.D. thesis as
being some forty-five pages 7 ublication
                       ong.

LEDERBERG:  There is some additional commentary  most1 Y on some of the mathematical
aspects of calculating linkage maps.  But there's real y nothing substantial that
hadn't been published in the other papers.
                        Page 2


                            LEDERDgg

BOHNING:  We didn't say anything about that summer at woods Hole.  Basically you
were finishing writing up when you were down there.  That was the summer of 1947.

LEDERBERG:   Yes.  Entirely using the library.  That's where I dug a little deeper
into the background history of variation in bacteria.  I think I read everything
that anybody's ever written on the subject.  They had an excellent library,
twenty-four hour direct access to the stacks.  I may have given you a reprint of
that. I've revived some of the material I dug up at that time for this ASM News (
1.

BOHNING:  I wanted to pursue that because you had a very eloquent statement in
there, talking about today's students who are allergic to the dust in the library
stacks, as you put it, and that the recent journals are all they need.
by that comment.                                          I was struck
           I've had that same experience.  But I'm wondering whether in your
career that attitude has changed or is it more current now than it was when you
started?


LEDERBERG:  The distaste of students for antiquarian inquiry is a more recent
phenomenon.  I don't know how deep-seated it was at the time.  There was an
inclination to not bother much about historical stuff, as far back as I can
remember, on the part of other scientists.  But I had broader interdisciplinary
interests anyhow than most people did, so this fed into that strain.
    I can't really scold our youngsters today.  They've got more than the   can
handle in trying to keep up with the current literature; it's next to impossi  le to
                              i:
do that.  So it becomes an ever more obviously losing battle.  But there is stuff
there that can be quite informative and quite stimulating, and I mentioned a couple
of s ecific examples that were very clear.
stil  be pertinent.
I;                         I don't know how much of that would

   This is at a time of opening up not an undiscovered continent, but one in
which the existing inhabitants of microbiology barely had a few new biochemical
tools--that was rising discipline--but the role of genetic analysis was even more
closely coupled with issues of natural history.  There is an affinit  between
history and natural history, in part because  eople could make usefu  naturalistic
                  R         Y
observations with quite primitive tools,  so t  at literature goes back three hundred
years.  I'm sure there are still things that have been recorded a long, long time
ago that are going to be revived from time to time.
    But whether it's the most cost effective thing to do, it rather depends. If
Y ou're looking for major problem areas, it may be just as useful as the current
iterature.  If you try to solve an existing problematic challenge then it's
probably true you can't sample it all  and if you do nothing but last year's annual
reviews of the current literature, it's not perfect, but it s probably as good a use
of your time as anything.  YOU may have reason to feel badly if you find you've
already been anticipated, but it's hard to know what better heuristic to offer.
    I wasn't suggesting in my ASM NeWS article that students abandoned
everything they're doin 7 now, but just to have a little bit of sensitivity and
respect for that type o  inquiry.  since not many other peo le are doing it, I
thought I would exhume a number of old issues that are stil 7 sitting there. I'm
hoping that somebody will pick up some of the themes that I've mentloned.

BOHNING:  In that regard, it used to be very common to have a histor i: of chemistry
course in a chemistry department that was required for majors.  Did  iologists do
the same thing?

LEDERBERG:  No, there's very little history of biology offered. There may be four or
five chairs in the country that are doing this, and hardly at all for biologists.
SO there's a little bit of a specialty interest in it, but the general answer is no.
Now, a little bit of history is incorporated.  If you take a textbook of any of the
biological disciplines, you'll find some historical information. The better books
                         Page 3


                             LEDERDog
have more of it, in my opinion.
    And we' re beginning to see more reflection.  we've been through a stage of
such extraordinary dynamism in experimental biology in this century, and a number of
people are starting to take stock.  I have the fun of being able to do this within
my own lifetime.  The stuff I used to hear about and used to think about is now
hi story.  There's a series on developmental biology, for example, that [
    ] Gilbert has been editing (24) He's got some wonderful essays and
reflections.  There's beginning to be a school of hi story of recent biolog F; and of
course some of the stuff down in Philadelphia is an important element of t  at as
well.

BOHNING :  If I'm correct, there is no discipline center for hi story of biology as
there is for physics and chemistry, per se.  IS that true?

LEDERBERG: NO, nothing.  we're riding ragtail on your chemistry pro'ect, or a good
piece of it.  BiOlOgy'S such a diversified set of activities  it wou d be more
                          !
difficult to do it or know how to centralize it. And we don't have the societal
organization, which is again a reflection of the same matter to be that kind of a
focus.


BOHNING :  Do you think those people so inclined have more of an interest in the
hi story of medicine, in that aspect of biology?

LEDERBERG:  The hi story of medi tine is a more settled discipline than biology, and a
lot of physicians have turned to hi story, certainly in larger numbers and proportion
than biology.

BOHNING :  You've commented than the [Maclyn] McCarty paper of 1944, which was a
1 andmark paper, changed your life.

LEDERBERG:  It changed all of our lives, [laughter] but it did it in a very personal
and gripping way.

BOHNING :  I want to explore that a little bit. That's sort of in keeping with what
we were talking about here.  First of all, did you see that paper as a matter of
course in your reading, or were you aware of the results before the paper appeared?

LEDERBERG:  we heard a little bit of it before hand.  I can't give the precise
dates, but [Alfred E.] Mi rsky was a frequent traveler between Rockefeller and
co1 umbi a.  He was collaborating with Arthur Pollister, and so I'm sure we heard in
various seminars what was going on with nucleic acids.  Mi rsky had his own interest
in nuclear protein.  There was undoubtedly a certain amount of envy relationship,
between him and [Oswald] Avery.  That's been overplayed in later commentary; while
he and Avery were in dispute at a later stage, Mi rsky in fact was the principle
communicator of what was happening.
    I'm sorry I can't give more precise dates on that point, but I was going in
and out.  I was intermittently on campus.  I was being shuttled back and forth
between the naval  hos  ital where I was working as a corpsman when I was in the V-12
       and then  bat E to school   I know there had been some talk about it, but we
dPF~~T~m~et the journal in Morningside Heights.  I knew that Harri ett Taylor, later
Ephrussi , had a copy.  My guess 1 s she probably gave a journal club on it; she had
some cl ose connections .  she later went to work with Avery, a year or two after
that.  At that time she was a graduate student.  SO I asked to borrow her copy of
it, and that's when I fi rst actually read the detail of it.  I've actually written
in my diary about it.  I think  ou've seen the text quoted in one of my articles,
that kind of very gripping reco lection of it ( I.
            Y


BOHNING :  SO the response to that was, I won't say instantaneous, but very close to
it.


LEDERBERG:  oh, it was.  There was some prelude to it, but it was very fai rly
                          Page 4


                             LEDERD09
general talk.  Then I read the paper and was able to see in some detail the nature
of the experiments.  That told me this was solid  old.
                   %     while I didn't have to
believe everything about it, the paradox is that  ecause I thought it was so
important, I tried to keep an open mind about the details probably longer than most.
I would still be sympathetic to Mirsky's arguments that it had not yet really been
& roven that is was DNA alone and not DNA plus protein.   I was content  enou h to
elieve either one or the other, but I thought something as important as t at really
                             ii
ought to be nailed down very solidly before you take it as a matter of faith and go
on from there.  other people either ignored it or bought it and in a certain sense
didn't think any more deeply about it.  I just wanted to explain that paradox.

BOHNING :  In that somewhat lengthy argument about protein and DNA, did the people
who supported the protein argument finally give in, or was it a long drawn out
affair?


LEDERBERG:  It was long and drawn out, and I guess giving in was more by exhaustion
than by any single event.  I'm writing a piece right now about the Watson-crick
paper in 1944 ( >, which coincided with the interval of "let's not make any more
fuss about it."  It is DNA and in some measure that was because the Watson-crick
model very beautifully correlated with the pure DNA model.  It wasn't that there was
any more experimental evidence on that point, but it did fit things together.
    There are people who will argue that the issue had to do with whether DNA
was capable of having the informational diversity needed for genetic activit  .
                             il   That
was certainly in there, but as soon as one kept an open mind about the [Phoe us
Aaron] Levene tetranucleotide model of DNA structure and could imagine any
irregularity in base sequence in the DNA, and you could do that without  oing all
the way to the double helix, then the possibility about the informationa 9  content
was there.  That was al ready tacit in Avery's first discussion of the matter.
    SO I would say it was rather a question of cleaning it up, both figuratively
and literally, to just be sure that protein wasn't sneaking in and playing some role
in the source of specificity.  curiously enough,  [Alfred] Hershey is often credited
in the Hershey- [Martha] chase experiment in 1952 with having given the final
experimental evidence that it was DNA alone that was sufficient in this case to
maintain the genetic propagation of bacteria phage.  YOU may remember he did a
double-label11 ng experiment where he labelled the DNA with p-32 and the protein with
sulphur, and found that after infection he could find the phosphorous in the
infected bacteria, but not the sulphur.  I've had arguments with people and I've
finally found the source that corroborated my recollection of the matter. In the
1953 cold Spring Harbor symposium, in the same meeting where there was an early
announcement by Watson and crick of the DNA structure and in the discussion of the
paper, Hershey was still expressing some reservations and was saying that if you
would ask him right now, he still thinks it is nuclear protein. His experiment
leans in the other direction, but he knew better than anybody that it was not that
concl usi ve.  YOU could still have had several percent contamination of the nucleic
acid and not have seen it.  what it did show was that most of the protein is shed
and most of the DNA gets into the cell.  so he was even at that stage still
reluctant to buy the pure DNA story.  But that was the last peep that I ever heard
in serious scientific vein.
      There were a  cou  le of other people.
         7             There was a paper by Barry Commoner
and there was one by Kar  Lindegren, still protesting--this was during 1953--that it
hadn't been proven that life is DNA.  There was no serious protest after that time.
The Watson-Crick model crystallized--figuratively, again, as well as literally--a
way to picture DNA structure that would be compatible with the rest of the
construct.


BOHNING :  was commoner attacking on scientific grounds?

LEDERBERG:  It's hard to say.  Barry's quite an ideolo  ue.
                     ;f    He's the same guy who's
stopped us from i nci nerati ng anything .  I don't know i  you've heard his name around
the country. [laughter]  I don't know why he dipped into that.  He had done a little
bit of work with plant viruses, but he was not really a geneticist or a DNA
                         Page 5


                            LEDERD09
bi ochemi st .  He just thought it was too simplistic.
   There were still some rumblings about this or some lack of realization that

this really has to be taken seriously as the chemical basis of genetics, and that it
was no longer just an interesting hypothesis but had to be regarded as the
foundation of any further work in the field.  AS I may have mentioned to you before,
I felt strongly enough about that when the time came for me to compose my Nobel
Prize lecture, I did something quite unorthodox.  I only referred incidental 1 y to my
own work and instead wrote a commentary on the field.  It's called "A View of
Genetics" and it was a manifesto that says DNA is the view of genetics ( > . I
refer to my work within that framework.  I thought it would have been folly
otherwi se.  I didn't think it would make too much sense just to talk about my own
experiments, which had been done in a way that was i nspi red by DNA models but did
not make direct use of them, much to my frustration (I would have very much liked to
do that) and then ignore thi s important revolution that was sti 11 going on.

[END OF TAPE, SIDE g]

??

Page 6


                              LEDERDIO
LEDERBERG:  That  aper was in a sense a protest in the Lutheran sense of nailing the
theses on the wal 7  that there was still something to protest about.   It was not so
much op osition as'sluggishness,
  &                that the main line of genetics really could no
     e diffident about it.  we weren't opposed to it, but it was a huge cultural
     to have to think this much biochemistry.  In effect I was saying, "Look, a
lot what we've been doing is now obsolete and we have to make a completely fresh
start and look at things in a new way. "  There were some folks who were not about to
do that overnight.

BOHNING :  was it a generational thing?

LEDERBERG:  In part.

BOHNING :  There's many examples in the hi story of science where it takes a
generation to disappear before something new is accepted. YOU were young, in your
early twenties.

LEDERBERG:   Yes.  But Avery himself was not.  Don't forget that. [laughter]   But
Avery was not a geneticist.   SO it's marginality as much as generational.

     But Certainly it is.  YOU have to have students who would then have been
trained from the outset to specialize in that direction and not be too encumbered
with too much else.  There were things lost as well as gained in that process. I
guess the image I had then as much as anybody was [Theodosius] Dobzhansky (?>, a
towering figure in the field who had no feel whatever for any kind of chemistry. He
did not do a lot to encourage it.  I know Francis Ryan had lots of problems trying
to sustain his place in that department while Dobzhansky was in charge of it.

BOHNING :  In that year between the 1946 cold Spring Harbor and the 1947 conference,
what kind of things were happening scientifically?  In other words, you had given
your results in 1946.  what was the status by 1947?

LEDERBERG:  By then [Salvador] Luria had tried the same experiments in E. coli B and
failed.  He made less of that failure than others.  I heard later that [Max]
Delbrock was touting this and saying he's not sure there's anything in it.  [Aaron]
Novick and [Leo] szilard wouldn't have repeated the experiments until after that.
There was no one else who asked for the strains, and I don't think they would have
wanted to.  I think there was a certain amount of a sense of latitude--don't jump on
somebody's back immediately because it is the first announcement.  Give them a
little bit of breathing room. YOU don't see that today. I would have had some
ambivalence about send1 ng the stuff out.  I think if an body had asked me point
blank I would have done 1 t, but I was sti 11 very, very g usy following up on the
first immediate observations.

    I must have had something started by 1946 with Max zelle because he
interceded in my debate with [Andr,] Lwoff as to whether the recombinant clones
really were clones,  really were derived from single cells.  He was pushing the idea
that they were simply continued mixtures of cultures and complementation. That's a
perfectly plausible hypothesis for the prototrophes and he had his own experience
with cross feeding of the nutritional requi rements.
    I resented a little bit the implication that I was not totally aware, both
of his work and of that hypothetical possibility, and I'd gone to great pains to
excl ude it .  This had to do with producing more than one kind of recombinant. It
was very difficult for me to see how you could invoke mixed cultures to account for
both a virus-resistant prototrophe on the one hand or a virus-sensitive prototrc$Ks
on the other.  vi rus-resistant segregating is a mark of that kind of a cross.
would have been a very sensitive 1 ndi cator.  If you have vi rus-sensi tivi ty, you know
there are zero virus-resistant cells in the culture.  That's easily demonstrated
with mixed cultures.

    SO there were a variety of ways that I was quite certain that had been
excluded.  Almost everybody else wasn't bothered to look at it, but Lwoff persisted
                         Page 1


                              LEDERDlg
and said, "until you've isolated single cells, you shouldn't call them clones.
Don't rely on ordinary bacteriological.plating methods.  YOU can't be sure,
etcetera, etcetera." I continued to give arguments why that was a needless
enterprise, but zelle said, "Look, it s not that hard.  1'11 show you how to isolate
single cells under the microscope and it isn't that hard."  SO he got involved
fairly early in some corroboration.  I think in the early experiments that I simply
sent him some of my prototrophe cultures and he re-i solated single cells, made
clones and they were still prototrophes.  That was his contribution.

    The fi rst repetition was done by Novi ck and szilard.  That must have been
after I got to Wisconsin, so it would have been in early 1948 before that was done.
They did and they circulated that news.  Luria was quite content with it.   It was
Luca Cavalli-Sforza who later on in 1948 wrote to me and said that R. A. Fisif?; ~II:
been very much impressed with this work.  I'd exchanged reprints with him.
him at Cold Spring Harbor in 1947 at the BiOmetriCS Society. Luca at that time was
a young postdoc at Cambridge.  Fisher was interested in crossing over and mapping,
and correctly thought that, with some complications, this might be very good
experimental material.  He suggested to Cavall i -Sforza that he look into 1 t.   So
Luca wrote to me and asked if I would send him the strains.  And of course, I did.
outside of m  own laboratory, he was the first
    z              I: erson who actually jumped
wholehearted  y into working on the system.  wit in a very short R eriod of time he
made a very important discovery and that was the so-called Hfr,  igh frequency of
recombi nati on.   It was i `ust a piece of 1 uck that a particular strain popped up that
had a thousand-fold hig er rate of recombination.  It just made the technology of
crossing very much simpler.  we began a collaboration at that time and it's gone on
ever si rice.  He wrote a 1 i ttle piece about that in Genetics (25).  Did you see that?

BOHNING:  No, I don't think so.

LEDERBERG:  1'11 have to get that out for you.  I think it's quite important.

     I was very bus 4: in my own lab.  other  peo le were doing other things.
                   R                       There
was more going on on  p age recombination during t  at 7 eriod.  Luria wrote a review
in which he referred to the E. coli work and positive y affirmed its significance
(261.  I guess you'd have to look at the 1947 sym osium to see what else was
happening scientifically.  The most interesting  t R ing relevant to our own work was
that Boivin popped up.  It was in 1947 that he published the paper.  He and Tatum
had some correspondence and he claimed to have some sort of DNA transforming system
in E. COli.  since that was exactly what I'd gone into bacteria to do in the fi rst
place, I was very excited about it.  But we were unable to corroborate it and after
a while he was as well.  There's no way of knowing what was happening there.   It was
another ten or fifteen years before we knew how to 7 et DNA into E. COli.  we've had
the legacy of K-12 as a by-product of that technica  glitch.

BOHNING :  You've used the term "messy" in terms of the laboratory work. I'm
wondering whether that was literal or figurative.

LEDERBERG:  You mean my own style?

BOHNING :  No, in general at this particular period.

LEDERBERG:  work in bacterial variation generally was very messy.  It was a little
bit of experimental technique, but mostly it was conceptual muddiness . If you
didn't even have to discuss.the concept of.thy gene, it's a little hard to see how
;;;-`,ca; cJyo;Ery crisp experiments if you did! t understand the difference between  a
         a population.  Likewise,  I think most of the microblolo  ists at that
time'were jus; not accustomed to thinking in those terms.  They saw cu 9 ture and they
thought it was an entity.  A tube of bacteria was 1 i ke one organi sm.   It seems
unimagi nab1 e that one could have that view, but it was quite prevalent at the time.
SO it became very difficult to understand exactly what it was that others had done,
or how a lot thin  s that were called transformations of cultures were very clearly
overgrowths of se ection,  sometimes contamination.
      9                     It was a little hard to pick the
wheat out of the chaff.           Page 2


LEDERDlO

     The other thin ;i that was often confused with genetic change was enz matic
adaptation.  If you  ta e  E. coli in the right conditions and provoke it wit -z
lactose, ten minutes later you have large quantities of the lactose-splitting enzyme
present in the cells.  That was very muddled with changes of genetic competence to
make the enzyme.  It was a totally different phenomenon.  That got mixed up in many
of the older people's writings.  It was a confusions at that time.

BOHNING:  one other thing that you've commented on in the same time period was the
importance of networking with other scientists and that you were actually developing
that network at this point, from 1946 on.

LEDERBERG:  Know it or not, I was, yes.

BOHNING :  From the cold spring Harbor meeting on, you certainly were thrust into the
forefront of being in contact with a huge number of people.

LEDERBERG:  I was very fortunate in the opportunity to do that, the happenstance of
being in the right place at the right time.  That cold Spring Harbor meeting was an
extraordinary op ortunity.  Since lt is simply what happened, I rather took it for
granted;  it's  on 7 y in retrospect that I can begin to imagine what would have been
the consequences if it simply hadn't existed.  Or even worse, if it had, but I for
one reason or another had not been admitted to it. [laughter]

   Did I tell you that Johnny Moore told me that one reason that Francis wanted
me to go to work with Tatum was that he thou ht Tatum would be much more useful for
me in Introducing me to those networks and t at was, as Johnny said, the special
                 z
disability of being a New Yorker, which I shared with FranCiS. Even more, I was a
Jewish New Yorker and FranCiS thought that those were prior impediments that would
need very special attention.  I was oblivious to that at the time, but just quote
that as something that a very dear and wise friend had mentioned.

BOHNING:  what was Tatum's status in that community at that time? was he
well-established by 1946?

LEDERBERG:  This is a very complicated story.  There's kind of a Beadle school and a
TatUm school.  They never had any public dispute on the matter, but a lot of this
was goin 7 on in the background on the part of their friends.  They had been very
close co laborators.  TatUm was much younger; he was at least junior. He had the
microbiological and the chemical  trainin ; he didn't know very much about genetics,
although he had the right instincts fair y early.
               9       The issue revolves around who
should have gotten the credit for the Nobel Prize on biochemical genetics of
neurospora.

    Ed was not a deep thinker.
do experiments,          He was a very pragmatic kind of person, loved to
         and had a very good intuition.  YOU might say if you judge by the
outcomes, Ed was a lot shrewder and insightful than he made out to be.  some of his
articulation of biological issues was fairly shallow, but he had wonderful
instincts, and what he really knew, whether he knew it or not, went deeper than
that.
sight. He had a lot of lore (?) that again didn't seem to be so obvious at first
   I'm sure he was thoroughly familiar with [Archibald] Garrod's work and that
Beadle was not; that was a ma'or anticipation of biochemical  enetics.  He knew
about fungi and how to
that.  He had a sense o !? row t i em;  I don't think Beadle ever i! new an thing about
              biochemical pathways.  He knew how to actua ly isolate and
                          z
crystallize and characterize something.  Beadle wouldn't have known how to do a
melting point, but Beadle did have the theoretical grasp, the oversight, the
strategic insights.

   I can't help but feel that he rather resented having to share the glory with
Ed, and he did very little to further Ed's career.  I don't know if he actually
obstructed it, but it's obvious at Stanford that he was either totally
incapable--which seems unlikely--or unwilling to go to bat for Ed in terms of
getting him a permanent faculty position. This was between 1941 and 1946. when
                         Page 3


LEDERDlg

;Tamdle went to caltech there was no hint that he was-going to ask Ed to go down with
. SO there are those tensions in that relationship.

    My own relationship with him was pretty clear-sighted.
wonderful thing and that was E.                     Ed gave me one
                 coli K-12, that specific strain that he had worked
on, without knowing that there was anything very special about it.
lucky, myself in R articular.                         We were all very

can't think that        He gave encouragement. He gave me a laboratory. I
                                                     I could be
wrong about that. e made a sin le conceptual contribution to the work.
             I've said o 7
of encouraging me,        Francis Ryan that he was very careful, in his mode
             to hold back on his own & art.
the detailed directions that he would have     He didn't immediately give me all
                                              een very capable of doing so.
   I don't think that was the case with Ed, but he was there, did all the right
things at the right time.  Every now and then something would come to the surface
that would tell you that there were things going on that were fairly deep, but you
didn't see them very often.  I have no doubt he brought a very special perspective
to that work, and he's certainly as deserving as Beadle.  In Jan Sapp's book (27)
he's gone through the [T. M.] Sonneborn papers and the correspondence between
sonneborn and  Ephrussi around 1958, when the Nobel Prize was awarded.  Their
consternation was about what was it for and what new thing had Beadle done?
had collaborated with Ephrussi.)                               (Beadle
                   Have you seen the [Richard M.] Burian and [Doris
T.] Zallen stuff about that (28)? They've gone into that in some detail.
quite challenging about that.                            They were

    Beadle was a very aggressive go-getter.
the presidency of the universit  of Chicago.    Nobody was surprised when he took

the kinds of ambitions that he rl         It was perfectly obvious those were
of biology at that level.    ad and he had a salutary effect on the development
               Lily Kay has written about his role at caltech as well
pulling biolo y together and making a big business out of it, since 1946 (29).  Ed
was none of t at.
     Ii    Ed loved workin
He loved the organism and did a 9 in the lab himself and puttering with neurospora.
                   ot of good things. He certain1 -l made much more of
a contribution in helping to develo R many people.  After his wor  for Beadle there
was nothing really very startling t at came out of his own experimental work.

BOHNING:  YOU have mentioned, and I quote,
transformation an irritant."         "Harriett Taylor's paper on pn.
                I was wondering what you were referring to.  This was
in March of 1947.

LEDERBERG:  Oh, that's the paper she gave at cold spring Harbor (30). Yes. she
didn't want to buy a straight Mendelian view. It was pretty mystical. Trying to
read that paper, I still can't figure out what she was after.  I saw what she was
getting at was a very nice story.  There were three or four subunits within the
polysaccharide gene in the pneumococcus and she was trying to make somethin  else
out of it;  I couldn't make head or tail out of it.           ? or
trying to force E.  coli into a Mendelian mold.    she was criticizing me
                           There are problems with that, but

they're not the problems that she was addressing;
structure that's held up very, very well.      even at the micro level of genetic

    she was six or seven years older than me,
woman.  I was a pretty young teenager when I first a very attractive and intelligent
you if I tell you I had a kind of a crush on her.  came to Columbia; I won't startle
                             I had not met many women like

that and I did not succeed in making very much of a personal  im
given the age issues.                 R ression on her,
                                                                   s
twenties.         I was a sixteen or seventeen year old,   e was in her early
     I knew that, and I had no unrealistic expectations, but that sort of
colors my relationship with her.
sparring partner.          After a time she got to recognize I was a peer
          I just have to record that as part of why I lamented that we
couldn't get to see eye to eye at a later time.
    At the same time, she was encouraging,                        careful
not to get her nervous in any way about m    but I really I had to be ver
                K personal attentions, because I t ought
                             K
that would be unable to relate to me in  t
do--talk about papers and so forth.    e ways that she would be willing to
                     I watched the progress of her romantic life
with some interest and it was pretty complicated.
Ephrussi, as you know.                  she ended up marrying Boris

                         Page 4


LEDERDIO

BOHNING :  I'm going to ask the next question and you can decide how  ou want to deal
with it because you've already indicated to me some feelings about  t K is.   You were
married at the end of 1946.  I don't know how you want to talk about that or not
talk about that; 1'11 leave that up to you.  But obviously that has to play a point
in some of the things that were happening in your 1 ife at that time.

LEDERBERG:
about it.  Let me just give you a few facts and then I won't go into much more
      Esther Zimmer was a graduate of Hunter High School and Hunter College.
she went to work for Alexander Hollaender at NIH in 1942 or 1943, more or less.   she
then applied for a position as graduate student at Stanford and went to work for
Beadle and TatUm as a master's student.  she was there in 1945-1946.  she did some
work on a mutant neurospora that requires paraminobenzoic acid.  I first heard her
name in connection with wanting to get hold of the mutant.  In those days Beadle was
farming out each biochemical mutant as somebody's personal province. Today we make
them by the hundreds of thousands, but that's the way it was then. He was a little
bit slow and wanted to give her a change to work it up.

    she was not encouraged to stay there and went looking for a job.  when TatUm
came east he agreed to give her a job as a technical assistant.  After COming t0 New
Haven, she went to work for Norman Giles; she was Giles'  research assistant in their
group.  I don't know whether TatUm had recruited Giles or Giles was there
beforehand, but there was a group of microbiologists in the botany department and
that's where I met her at that time.  we spent some time together during that time,
and in a rather short period of time we were married in December; we met in August.
The common thread of interest was in laboratory work and in genetics.   We went to
Wisconsin together, and she continued.   I encoura ed her to try to get a doctoral
degree, which she did in the department.  she wor ;;I ed in my own laboratory
thereafter, through the Wisconsin time, came with me to Stanford, and worked with me
up to the time of our divorce.  I've encouraged others to take the benefit of this
experi ence.  The romantic notion of working day and night in the laboratory next to
your significant other is fine and productive for a while, but it's not the best way
to pursue a long-term relationship.  Let me just leave it at that.

[END OF TAPE, SIDE lo]

??

Page 5


                               LEDERDII
BOHNING :  YOU had been planning to go back to P & s to get your M.D. degree.  unti 1
Tatum told you this,
going back to P & S? had you given any other thought to doing something other than

LEDERBERG: No.  I was hoping to find a way in which I could continue to do research
7 art time, as I had been doing before then.  R an would have accepted me into the
ab.  There was some serious questions about t e support, and I was not at all clear
                  K
about how I was going to manage it.  It might have ended up that Esther would have
been working to support us both while I was in medical school, a not unfamiliar
scenario in those days.  But that was unclear.

     I had applied for a Merck fellowship.   For worse,  Beadle was on the
selection board and I didn't get it.  I never had any more information on the
matter, but I have my continued suspicion that he was not particularly warm on the
matter.  I don't know who did: that would be a rather interesting, curious point to
try to find out.
[laughter]      If you have any way to do that, I'd be very curious about that.

BOHNING :  I think I do, as a matter of fact.

LEDERBERG:  A way to do it, or you know who it was?

BOHNING :  I don't know who it was, but I know the archivist at Merck who may have
access to that information.

LEDERBERG:  It should be pub1 i c information; it should have been announced.  That
would have been for the class of September, 1947.

     SO that was one issue, tryin
I would have qua1 ifi ed for the GI Bi 7 to figure out how to do it.  I don't know that
                             1  or not.  I did spend a year not just in
uniform, but actually in active duty.  I worked as a hospital corpsman; I might have
had some he1 p there.  Before I went to Yale, of course, I was in the V-12 program.
In November of 1946, after the war was over, that was just very abruptly canceled,
and they weren't even accepting applications for reserve commissions.  I looked into
it, and they weren't interested.  TWO years later they were desperately reversing
their policy. [laughter]  Times had changed a 1 i ttl e bit by then, or I might have
ended up in Korea.

    SO there was a financial issue, but I was still making that plan. I had no
other alternative plan.  I was going to have some sort of part-time job that would
help eke it out, and would help kee & me involved in the laborator
The alternative was a full-time jo , not the M.D., that would al z during that time.
                                                  ow me to devote
myself unremi tti ngl y to conti nui ng thi s research acti vi ty .  I think I made the right
deci sion and never real 1 y regretted it.  BUt I very much regretted loosening my
connection to medical affai rs .  when I was at Wisconsin I worked hard to restore
them and eventually did.  SO that was the trade off that was involved.

BOHNING :  HOW much did you debate about this in your own mind before you made that
deci si on?

LEDERBERG:  Quite a lot.

BOHNING :  It's a major turning point in your life.

LEDERBERG:           That's right.  I certainly discussed it with Esther, with
Francis,   That's right.
     with Ed, and in my own mind.  SO it was not an impetuous decision. It
wasn't clear at all whether I would like Madison.  I'd never lived in the midwest,
but I had a very warm reception from the people that I met there. I welcomed
7 etting away from urban hurry, which New Haven didn't do.  That was no different
rom New York in that regard.  It met my expectations.

BOHNING: when did you fi rst go out to Madi son?

Page 1


                             LEDERDll
LEDERBERG:  That would have been at the very end of August, or maybe even September.

BOHNING :  But you didn't accept it unti 1 you went out there fi rst.

LEDERBERG:  That's right.  oh, well, they didn't offer it to me either. [laughter]

BOHNING :  what I was after was your initial reaction to being there.
first plane trip.                                       It was your

LEDERBERG:  It was not very intense in a few moments.  I saw the town, saw a little
bit of the university.  The people especially impressed me.  There was an excellent
bacteriology department, folks 1 i ke Perry wi 1 son were very warm and we1 coming.   I
was very inexperienced on the issue,
a college of agriculture.       but I had to think through what I was doing in
                I al so knew the important scientifl c output that had come
from especially biochemistry, but also bacteriology.   Ed Tatum had been there
himself and it looked 1 i ke it was a good 1 iai son between the genetics and
bacteriology. The one thin
was nobody there I could  ? that was disappointing was the medical school.  There
                       re ate to.
a research establishment.       There was not much going on; it was not much of
                I don't remember exactly whom I visited during my first
trip out there, but I doubt if I saw anybody from the medical school. So I sort of
wrote that off as being on the loss side.

BOHNING :  It sounds like it was tailor-made for you.  why were they looking for a
person of that nature?

LEDERBERG:  That's a very interesting question.  I think A. R. Brink has some stuff
in the archives on that, so I don't really need to repeat it for documentary
pur oses
7     here.  But before him the just retired founder of the department was a man
cal ed L. J. [Leon] Cole.  He was an extraordinary man who had built the department
on the basis of important applications to agriculture and ani ma1 husbandry, and at
the same time felt that it needed to have a strong basic scientific foundation. He
had actual 1 y written a paper in 1918, in which he tal ked about bacterial variation
as an example of mutations (31).  (I found this out a little later on and I'm
curious to know when I did.)  It was the pure line concept (?> in bacteria, and it
was very clear minded.  SO he did have a lot to do with inspi ring the department to
go in that direction.  They decided they just wanted a basic scientist and that new
things were coming along; their instincts were exactly right.

    That was the right place to go for exciting new developments.   It was a
perfect match.  It was a very good thing for me, and me for them.  The fact that I
was not that narrow, that I could take an interest in what they were doing and
assimilate that into my own concerns, appealed to them.  It worked out very well on
all sides.

BOHNING :  YOU commented at the end of our fist session about what you found out
later regarding the problems that came up in the department about your own
background.  YOU said you had a warm welcome on that trip, and that you were unaware
of any of that going on behind the scenes, which is, I think, something in itself.
If it was of any magnitude, it's amazing that somewhere somebody didn't give you
that impression.

LEDERBERG:  well, I wasn't looking for trouble, so it may have been that element
too.

    It was something of the nature that this Hebrew (that would be the phrase
they would have used) may be pretty smart, but I don't want him in m K club.   But
they were also, in the best sense of the term, waspish enough that t ey would not be
discourteous or impolite, at the same time.  That's the way I can size it up.  Now,
I know there were people there who had opposed my appointment on those grounds (and
I only know this retrospectively) with whom I never had a warm relationshi   but
from whom I never heard a whisper.  They were not eager to become
friendly, but I think they respected my work. It would have been & ersonal $ 7
                                           eneath them, and
                         Page 2


LEDERDII

they wouldn't have wanted to think of themselves as anti -Semites or capable of
bi got ry .  It was sort of at an instinctive level.
the questi on.                      It didn't stop them from raising
                                          Brink did not share
with me what  But I've seen very little of the complaints.
         he had to face.  He did share with me what he wrote in res onse to it,
and the whole explicit statement was, "In spite of his race, Lederberg R as such
extraordinary intellectual accomplishments that I think we ou ht
anyhow. "  That was the way it was finally sold.  He told me t i?  to go for him
                                                         at had a touqh time

getting that across. [laughter]

BOHNING :  YOU were only twenty-two at the time, when that happened?   You weren
older than the graduate students.

`t any

LEDERBERG

I had one or two students who were older than me.

BOHNING :

Do you think age had anything to do with it?

LEDERBERG
objective i
of them.

It's hard to say.  It might have gone both ways.
y, while I was mature for my years,           It certainly meant
                    I nevertheless didn't have very many

 I'm sure I was brasher than they were accustomed to on that account,, plus
                    .I I               . -                     . -

whatever New YorK manners mignt nave developed along the way.   But it also made it
singular.  It said this is not the ordinary cut and dried kind of a thing; its a
very idiosyncratic kind of a situation.  In a way it might have made it easier.

BOHNING :  when they made you the offer, what was involved in that offer?

LEDERBERG:  It was as assistant 7 rofessor.  I would teach the courses in microbial
genetics .   Not an onerous schedu e,
it meant one course each semester.  but more than one sees these days.  Basi call y ,
                   I would collaborate with the bacteriology

department.and set up a research program.  The teachin
less than in A &.s, because.we were part of the agricu tural
                     9 loads in the ag schools were
part of the fund1 ng for agr1 cultural research.          experiment station,
di rector of the agricultural experiment station, I d write reports ever Ii year for the

not have much of a 1 ab.             describing what I wor ed on. I-did

under the eaves.      I had a room about this size [ten by twenty feet],
          It was very hot in the summer.

in the summer time.                      It was pretty tou ii! h workin upt;;;kt
                                                                           .  The 7
would never congeal . I essentially gave up trying to do serious wor
            No air conditioning.                         p ates

done under those conditions.          But we got a lot of very exciting work

rooms together.         I think I eventually got as much space as these two

BOHNING :  This was the genetics department in the ag school?

LEDERBERG:  That's right.

BOHNING :  Why it was in the ag school and not in the med school?

LEDERBERG:  The med school didn't have anything research-wise.  Genetics had been an
outgrowth of plant breeding and it had practical agricultural applications.   It was
one of the first departments to be called genetics, not the other.  That was L. J.
`faked who was tryi n
   . We had peop e like E.
       9 to enhance the scientific foundations of the school and of the

resident of the university.  B. Fred was first the dean of agriculture, then the
E nown nutritional biochemist. Connie [Conrad A.] Elvehjem was his successor, a well
                      And Fred's 7 redecessors were much of the same.  Much
as was happening with medicine some years  ater on, they saw that for agriculture to
prosper they needed some sort of important fundamental scientific base and this was
just one example.of it.  you saw the same in bacteriology.  It covered the gamut
rf;;iEEtter stral ns for making cheese to nitrogen fixation to very fundamental

BOHNING :  How many people were in that genetics department?

LEDERBERG:  It must have been between eight and ten faculty at that time.  we had
Bob [M. Robert] Irwin.  Irwin was a very di sti ngui shed immunogeneti ci st .  He did
very practical work on getting genetic markers 1 n cattle, which helped to raise

Page 3


                              LEDERDII
pedigrees.  He and Ray Owen laid the groundwork for what we know today as the
histocompatibility system in mice and in other animals. It's a very good example
again of covering the gamut.

BOHNING :  You mentioned Ray Owen.  wasn't he at cal tech when you arrived?

on leave at Caltech and then

at Cal tech?

nation--again I only found
icy CneCKed me out wltn Ray
     . , .           . I

asking what about this tellow Lederberg?  Ray
Delbrock, a diffident one from Beadle, but sai 1 uoted a fai rly  ne
                             everybody else  t z ative report f t-Am
                                              inks  his work was
just great and he didn't think there was any substance to the other two. They were
not that deep-seated and there was no content to them, so he was willing to give his
own vote and that was the decisive one in terms of getting me into the department.

LEDERBERG:  I think the first year I was there he was
he decided to stay there.

BOHNING :  wasn't there some question about references

LEDERBERG:   Yes.  when my credentials were under exam
this out much later through Brink's, correspondence--t
  .                                       -

BOHNING :  You've made the comment that you looked forward to interacting with these
people in the ag school ! eventual 1 y in what one might call biotechnology.  what
kinds of interactions did you have with them on a practical sense?

LEDERBERG:  It ended up being less than I antici pated.  Basical 1 there would have
been a good opportunity to go into genetic analysis on any and a 1 Y
issues.  There were a few starts.                  of these kinds of
of nitrogen fixation,     Perry Wilson was interested in the bio;L;m;;;ry
            and I was eager to collaborate with him in workin
genetic basis of it.  That ended up bein  later on a very, very fruitfu 9 area of
inquiry.  There was al so Rhi zobial (?>  p 7 ant interactions.  But to do it would have
meant trying to locate a  raduate student who was willin  to work in a joint
pro ram,
wou ?    and I don't thin I! that ever eventuated.  we wou d have joint seminars. I
                     9
   d teach some of their students.  I picked up a little bit of the technique and
the lingo, but my efforts at transplantation were only part1 successful, so I can't
really say that anything fi rmer actually came out of it.   I Y earned about antibiotic
fermentation,
improvement .  and was eager to have them use mutational approaches for strain
        (This was 1 n the 1 ate 1940s that we' re talking about .>  There was a
little bit of it.  Ken [Kenneth B.] Raper was working on that; he'd done penicillin
improvement during world war II.  They were already doing some of the cut and dried
things, but it never really caught on anything beyond that.

BOHNING :  what kind of an agenda did you set for yourself in taking that position?

LEDERBERG:  It was a comprehensive research program, and I think I've outlined to
you the different themes that I thought I would get into.  I don't know whether that
was all worked out in advance.  some things couldn't have been because there were
fortuitous discoveries after we got there, 1 i ke the F system and the special lambda.
But I did write a proposal , which was the basis of what we were working on, for the
Rockefell er Foundation.  I asked for sup ort
Al Umni Research Foundation] , which is t e patent licensing intermediary for the
               R   from them and from the WARF [Wisconsin
[Harry] steenbock patents and later the Warfarin patents. They were very lucrative
sources of income to help support research there.

    That work was the genetic basis of control of enzyme formation.  The lac
system is what we worked on there, and I think we did make some significant
contributions to that.  A lot of other things just fell in--transduction in
salmonella, specialized transduction with lambda, more on the mapping, the Hfr,  the
heterozygotes.  That's on the list I've given you, and we can go into those in some
detail one at a time.  But the core theme, the over-arching one of genetic systems
in bacteria, was what were the mechanisms of genetic exchange and then the
application area for genetic analysis which was genetic control of enz me
Those were good deci si ons and with al 1 we know today, wouldn't have  a Y   formation.
                                                     tered it a
bit.  They were right on the button of what E. co1 i was good for and did have
important consequences.           Page 4


LEDERDII

    Starting around 1949 and 1950, we began to see very intense activity at the
Pasteur Institute.  They had the wonderful advantage of bein  in Paris and
attracting a lot of Americans postwar to spend sabbaticals  t ii ere.  They had a lar e
stream of American scientists going there and they fertilized the place wonderful ? y.
It's just a lot of hands.  It was very, very difficult to compete with my tiny
laboratory with what they were churning out.  They had some very good minds there,
too, with people like Fran*ois Jacob.

BOHNING :  Norton zinder started with you very early on.

LEDERBERG:  He was my first graduate student.  The year after I arrived he came the
following fall .  He's told the story of his youth (32). I'd been intrigued with the
idea of recombination in salmonella, even before I did the E. coli experiments, just
to get the natural history of seroty es.
              &    It seemed to me to make it a foregone
conclusions that there was going to   e some kind of recombi national mechanism.
using Occam's razor, I thought, "why invent new ones.  Let's look for what we
already know is in E. coli.  E. coli is a pretty close neighbor to salmonella.
    So when Nort came to the lab, I said, "Go to town.  Here's some salmonella
strains and go to it."  I sort of left him alone at that point.  It kept not
working.  Then he got some flickers of things, and some single mutants seemed to
give some prototrophes.  It looked 1 i ke it was more than you got from the parent
cultures alone, but I was very worried those could all be artifacts. we didn't know
how much continued growth there was on the plates, so I refused to acknowledge it
ti 11 he had a double mutant that would work.  He then found with a particular double
mutant strain that he could get prototrophes.  Finally there was a phenomenon that
could be investigated further.

    He did ninety percent of the actual lab work on the matter.  He was in
constant consul tation with me on the matter, very, very di rectly.  He thought to
repeat some of the experiments with a bundling board that Bernie Davis had done to
show it took cell contact to get recombination in E. coli.  The idea here was that
you put your two cultures that putatively could cross with one another in a u-tube
that was separated with a sintered glass filter that did not allow cells to go
through, but would allow soluble products of the cells to be exchanged freely. That
experiment showed that whatever was responsible for crossing in salmonell a did get
across this filter, whereas if you did the same experiment in E. coli you could not
get it.  SO we knew there was a different phenomenon now.

     This now became the hunt for the filterable activit i:  and this eventually
turned out to be a bacteriophage.  The story gets a 1 ittle 4 t compl i cated because
you have two salmonella strains.  They' re not of identical clonal origin.  we always
did experiments with that design, among others,  because we were never sure whether
they mi
one of ? ht be mating types.  we would maximize the chance if you had one of male,
    emale if they were of different origin.  If you have an identical origin
they might be the same mating type.

[END OF TAPE, SIDE 111

??

Page 5


                             LEDERDIZ
LEDERBERG:  The story finally got itself worked out.  Strain A
some double nutritional mutants, was carrying a bacteriophage,
PLT-22, phage of Lillingham (?) type twenty-two. [
was the guy who gave us the strains; he had a collection of sa
other strain might be LT-7 and was susceptible to the phage PL
              starts from the PLT-22 strain grows on
                                                                  

I


1
T

in which we'd made
which we called
    ] Lillingham
monel 1 a st rai ns .  The
-22.  SO the
the LT-7 strain.   Now
              --

you have a            pha e.
might be a fresh batch or a di ?   That phage can be reabsorbed back onto cells. It
                  ferent genotype of PLT-22 strain origin.  when it
does so it also carries genetic markers from the LT-7. Those are the recombinants
that we'd seen.                 is quite different.  It's not cell to cell
contact, it's phage particles carrying tiny bits of genetic information from the
host in which they've just been qrown,  to the new host that they're going to enter

i

and I
s now
into

into.  SO it was a new-phenomenon and I wanted to give it a distinctive name,
called it viral transduction.  This has had very important repercussions and
the basis of gene therapy; when people are using retrovi ruses to import genes
human cells, it's essentially the same phenomenon.

    It also opened up doing I! enetics in salmonella.  There are rather
far-reaching imp1 ications from  t  e view that a-vi rus could have genetic funct

ions;

you couldn't think of it only as a pathological entity. As soon as it was possible
to do this, I differentiated my own interest in the salmonella story, the pursuit of
the  serolo 7 i cal types.  I went to visit P. R. [Philip] Edwards, who was the honcho
of salmone la serology in this country at that time down in chamblee, Georgia.  That
was the unit that's now the Centers for Disease Control in Atlanta; it was in a
suburb at that time.  I spent three weeks there picking up his lore, getting him
interested in it.  we had a very effective and extensive collaboration and very
& romptly corroborated that indeed you could % enerate a wide variety of new seroty es
y transducti onal recombi nation.   NO one dou  ts that that's the natural hi storica 7
source of this kind of diversification.  There is sti 11 a lot of unanswered
questions about sal monel 1 a vi rul ence and serol ogy,  but those fundamentals have stood
up very well.

      In retrospect, NOrtOn thought I was very dense about not seeing that phage
was the mediating factor.  I don't recall the detailed incident, but in his write-up
he says it was Harri ett Ephrussi who said, "That's what it must be, " when he
described this general pattern of events.  At one stage we knew it was associated
with phage; we could get the filterable activity defined as that which transforms
cells of the nutritionally negative phenotype to the nutritionally positive one.
That was by bioassay.  They were present in phage lysates, but my not yet being
prepared to insist on the view that the phage itself was a genetic vehicle, I
thought that this was a way of liberating, solubilizing genetic constituents in the
cell, which is certainly true, without necessarily have ng to be packaged within the
phage parti cl es.  when the issue was put that way we then continued to fractionate
the activit Y and showed that it sedimented with the pha e.
                     9    That was the evidence
that it rea ly is in the phage itself and not some anti lary material connected with
it.

    with specialized transduction, which came up a little bit later on, another
one of my graduate students was working on the genetics of the galactose genes in E.
coli ;  this is an extension of the work on the lactase loci .  These are enzymes in
gal actose metabol i sm.  He ran into somewhat similar kinds of observations, and
qui ckl K on the basis of what had gone on before was able to come to the conclusion
that t e phage lambda, which is present in E. coli K-12, could pick up the gal gene.
This was with salmonella, and not a lot of the others.  It was quite specialized,
so it would be just that one factor,  and that would remain associated with the
lambda durinq further propaqation.  There the association of the genetic activity
                                            out it s a defective

with the phage was clearer right from the start.   It turns
phage in that case; you can generate lambda particles conta
those particular particles then do not convey a full -blown
have to rep1 ace a vital gene of the 1 ambda with a gene from
the phage defective as far as further infection's concerned
little bit more complicated.

ni ng the gal gene, but
ambda infection.   YOU
the host, and that makes
SO it got to be a

Page 1


                             LEDERDIZ
    But here were now two systems of viral transduction going on side by side,
and enough difference between them to suggest that we're into a whole new family of
phenomena.  We ourselves didn't push for many more but others have and it's now
known that there's a wide variety of interactions of which these are special
examples.  That in turn supported the more general philosophical concept of the
pl asmi d.  It's just a way of looking at genetic particles that  sa  s,  let's not waste
a lot of time deciding whether something is a vi rus or a gene.   T at
                         iJ4   has to do with
just what impact they have on the further development of the cell.  In either case,
this is genetic information; it can be used either way.  That's been an important
unifying concept.  It's removed all the quarrels about whether something was a
? enetic phenomenon or an infectious phenomenon; it says it really can be both
ittle bit of a wave-particle dualism that one can resolve in that way.
8                                     Thatls been
uite important in straightening out a major source of confusion in biological
eve1 opment .

    sonneborn got to be impaled on that.  He was very excited about  c to lasmi c
heredity in paramecium, as he should have been. Then he came under attac t R
                                                                           w en
peopl e,, sai d , "oh, these kappa parti cl es are merely symbiotic bacteria, they are not
genes.   I tried to say it is not a contradiction between those two statements.
sonneborn himself never completely bought it, but I think that's the way most people
would view it today.
    Jan sapp was here 1 ast year; he's written hi s thi rd book.  This one is on
the history of symbiosis, and he's done a very good job of inte rating that part of
the story into his writing.  He knows much more about the Sonne orn archives and
                        El
correspondence than I do.  It's really a pleasure to hear from him about that.  That
book will be coming out pretty soon.

     The plasmid conce t was fired up by what I just told you--the ambiguities of
what is lambda.   Here we R ave a bacteri urn, which every now and then gives rise to a
bacteriophage.  we were able to even localize the map location of the
lambda-generating factor on the chromosome;
factor, which is not a coincidence.     it happens to be right next to the gal
                     so you could again have this dualism of
something that was in the chromosome coming out and being a vi rus.
    Then there was the other phenomenon which again `ust fell into our laps,
both the case of the original discovery of lambda as a p age in resident in E. co1 i
                      i
and the discovery of the F factor, which is the factor necessary for fertility in E.
co1 i crosses, which turns out to be another cytoplasmi c particle.  In fact, it
doesn't make a phage;  it's a little like lambda.  It can live either in the
cytoplasm as a pl asmid, or it can become integrated into the chromosome and then it
becomes         Hfr, when it's so integrated.  But in this case it cannot
package an externally viable particle, which is what a virus can do.  SO it has an
incomplete cycle as a vi rus and it can only get from cell to cell by cell
con j u ati on.
  ii     In normal life history the bacteria doesn't have a preliving state of
a pat aged virus particle: it wouldn't last very long as free DNA, if it ever got
out of the cell.

    Those observations led to the formulation of the plasmid conce t, so they
were a re-integration of this variety of ex erimental  observations.
                R                        T ey were not
                           R
part of my original research program.  In t ose da  s you could walk down a path and
stumble on a stone and pick it up and there would i: e a golden newt under it almost
every time you went anywhere.  I was about to say that the initial observations,
both of lambda and of F, came from Esther's very astute abilities to observe what
was happening in the course of other ver Y routine work.  There were two very similar
occasions when she would show me these p ates and there was this curious anomaly;
she had just noticed that things weren't going the way they were supposed to in
certain combinations of crosses.  she does certainly deserve very great credit for
her observational ski 11 s.  It took more than that to go through the experimental
analysis and I won't say any more than that.

BOHNING :  I'm looking at the time frame from startin ? at wi sconsin to when you went
to Berkeley in the summer of 1950.  HOW easy was it  or you to get graduate
                         Page 2


students?

LEDERDIZ

LEDERBERG:  I got them, but it wasn't easy.

BOHNING :  HOW did you attract Norton zi nder?

LEDERBERG:  I can't remember.  I suspect mostly by writing letters in the informal
network.  we didn't do much advertising in those days, but I don't recall if we did.
1'11 have to look up my [M. L . ] MOrSe (?) car respondence.  In NOrtOn'S case he was
recommended to me by Francis Ryan.  So it was also word of mouth. E. R. Lively and
Miriam Fried (?) were word of mouth associations.

BOHNING :  YOU said Norton didn't start your second year, so were you doing much of
your own work that first year, or were you just getting things set up?

LEDERBERG:  Setting up.  we did get along,  and here's where Ester worked like a
Trojan in the laboratory.  I had a research assistant.  It would have been probably
three people and maybe a part-time dishwasher.  That was the lab that first year,
and it didn't get to be much 1 arger than that.  There might have been two or three
others.

BOHNING :  YOU received offers of other positions at least twice in this time frame,
once from Chicago in 1949 and once at oak Ridge in 1950.

LEDERBERG:  well, there were more than that.  But up to 1950, yes, that's right. I
didn't take oak Ridge too seriously.

    I'd always admi red Chicago for its intellectual richness, and its
preoccupation with academic matters.  BUt it came a little too soon; we'd just moved
and the idea of living in Chicago on the South Side was not very appealing.  I think
that was what it hinged on.  we did have contacts there that we visited fai rl y
frequently, so we were not totally bereft.

BOHNING :  Your notes talk about the fi rst press notice in May of 1949 in a Madi son
newspaper about bacteria having sex 1 ife.

LEDERBERG:  I'd run into this somewhere, and I just thought I'd catalogue it that
way.

BOHNING :  This is something you've done retros ectively,  rather than at the time. I
was after how you reacted to seeing something 7 ike that in print at that time.

LEDERBERG:  I wasn't too interested.  In fact, a few years later, there was a
well-known Wisconsin painter, Eri n Borag (?) who told me Time magazine had
commissioned him to do a portrait;  I was going to be a cover personality on Time,
and I said I didn't want to do it.

BOHNING :  why?

LEDERBERG:  I didn't think that public hoopla would be of any particular use to me
or to the public.  I didn't think the press would handle things in a particularly
;;;;;ate or graceful *way, and I didn't like being a subject at somebody else's
  . I guess I still have some feeling about that.  I've refused to be sculpted
and refused to be subject to some great photographic artists.  For them to pursue
thei r profession is fine, but I have something else to do than to be thei r clay.

BOHNING :   Let's `ump ahead a little bit then since you're talking about that.
couldn't avoid  t iA                                                            YOU
                  e media when you won the Nobel .  How did you handle that?

LEDERBERG:  I tried the best I could.  I don't think I went out of my way to attract
attention, but it was not really in my hands.  SO I began to think a little bit more
careful 1
obtainab e,
   z about what use to make of it.  It was both unavoidable and easi 1
        and there's a fine line between the two.  Maybe I developed a z ittle
                         Page 3


LEDERDI2

further confidence that I could control what would be a very difficult interaction,
and that I'd better get into it.  so I began to start thinkin  of being a voice for
something.  It was a question of what?  It eventually materia ized
                        4    that not that
many years later I decided I wasn't going to entrust my interactions with the press
to the press:  I was aoina to write on mv own.  Startina in 1966 I had my own column

in the hashington PO; t. -That's flipping from one extreme to the other,-but I
avoiding what was my
over-sensationalized, real fear and bane, that of being misrepresented,
            and dealt with in a shallow or Inaccurate manner by the
I guess I still feel that way. [laughter]  I much prefer to speak for myself
have somebody else do it for me.

BOHNING:  That headline from the Madison paper is typical of what the press w
with something like that.

was

press.
than

11 do

LEDERBERG:   Yes.  I remember being offended by it, but it was what I knew would be
the fate of any press mangling.  I didn't know any Walter Sullivans or Larry AltmanS
in those days.  If I had, I think I might have been more than happy to confide in
how they would deal with it.  I was really quite inexperienced in this matter. I
started out with certain prejudices and then had the feeling that I wasn't sure that
this couldn't get out of control, and I had better shy away from it.   I was not
interested in public publicity.  I didn't see what it had to do with my scientific
work.  I was never adverse to trying to teach others, but it didn't seem to me that
this press coverage was going to do that, either.

BOHNING:  Maybe I could pursue that a little more, because what is the
responsibility of the scientist towards educating the public?

LEDERBERG:  I don't lay a trip on individuals.  I think it's very important that the
FEyAic be educated.  I think that scientists who have the knack don't need to be
   I will say that it's a responsibility in the sense that we shouldn't chide or

down'rade people who exercise it.
i?                 I think Carl Sagan has got some inappropriate
knot s for that reason.  I wince a little a bit when I see some of what he's had to
do or wanted to do, but after that instant reaction I go back and congratulate him.
I'm glad he's a headline hound because it helps motivate him to do something that
somebody really ought to do. [laughter]  But it doesn't mean I want to operate in
that mode.  I speak to a little different level of audience than he does, and I
think they're both important roles.  I don't think I wrote anything for public
interest or consumption before the early 1960s.  The first place can recall that is
the ciba symposium, The Future of Man, that was held in London in 1962 (33).

BOHNING:  HOW did this column in the Post get started?

LEDERBERG:  I was sitting on the airplane from Nice to London with Ni ;1 el calder, and
then I was going to on go back to New York.  we were both attending  t e meeting of
COSPAR (?).  He was reporting on it for either the New Statesman or the New
Scientist, if the latter was in being by that time.  He asked me if I would be
willing to write a regular column for it.  I said I didn't think so, but I would
give it some thought, and I found that I was giving it some thought.  AS is my Wont
ln those cases, I say "well, don't just jump.  Try to understand the context of this
interest, and if you're going to do it, ask yourself is this the optimum of that
genre that you want to do?"  I thought, for the effort given, there would be a
rather modest audience in the New Scientist, especially at that time.  If it were
the New York Times, I might think that the effort would be worthwhile.  I tried that
and didn't get very far.  I did have some contacts with the Graham family, and also
with Howard Simons, (?) who is the science editor of the Washington Post, and that
materialized.  SO that's how it happened.

BOHNING:  How long did that run?

LEDERBERG:  Five years and then some.  It kind of petered out during the sixth year.
I stopped doing it primarily because I could not turn myself into a reporter in the
sense of writing a column or doing a piece and then putting it out of mind and doing
something else.  I ended up continuing to research the columns that I did, often by
                         Page 4


LEDERDl2

a factor of ten or a hundred times more. [laughter]  once a sub'ect had opened up I
couldn't let it go.  I decided, that's oka z , you may pull all t at material together
                         i
in various ways, but you-can't keep multip ying it. I was too much of a scholar to
-jE;ze;round from one topic to another and then give it the depth that I felt lt

[END OF TAPE, SIDE 121

??

Page 5


                              LEDERDI3
LEDERBERG:  It was also a drain on time.  A year or two into that, I'd been through
a divorce and married again.  I know it was quite a strain on my new family
relationships to have this on top of everything else;
difference. [1 aughter]                   a very sharp deadline makes a
                week after week after week.

BOHNING :  SO it was weekly then?

LEDERBERG:  oh, yes.  without remit .  SO that was part of it.  But mostly it's what
I `ust said.
iA      I've sti 11 got forty or fifty 1 inear feet of files that pertain to the
su jects I was researching in that vein.  SO that was my education in pub1 i c
affairs; basically, the research that I started and then continued to do around this
newspaper co1 umn.

BOHNING :  what kind of topics did you se1 ect?

LEDERBERG:  They were not organized a priori with a particular reflection.  About
half of them had to do with what we would now call environmental issues of one sort
or another  or of related matters concerning to health and the world we 1 ive in.
There wasn't much envi ronmental news in the press in those days, which is hard to
remember as well , so today there would be much 1 ess need for it, or else it would be
countercommentary,  rather than commentary.  If that's half, maybe a   uarter was
devoted to nati onal security, mi 1 i tary, arms control related kinds o  issues. SALT,
                          9
nuclear weapons bans, things of that kind.  The stuff that would appear in the
Bulletin of the Atomic Scientists, which is one of the sources of impetus to be
i nvol ved i n thi s way; Leo Szilard is somebody who kept urging me to do more.  And
the other was just miscellaneous scientific topics that might usually be of some
interest about human nature.  It was call ed "Science and Man, " and today it would
have to be -Sci ence and Humankind . "

BOHNING :  you've mentioned Leo Szilard a number of times.  I picture Leo Szilard in
a totally different vein.  How did he become involved in this kind of work?

LEDERBERG:  Richard Rhodes has a beautiful account of his role in the making of the
bomb (34).  After the war Szilard wanted to have nothing more directly to do with it
and decided to go into biophysics.  He got an ap ointment at Chicago and recruited a
then-young fellow called Aaron Novi ck to be his 7 ieutenant to be his laboratory
implementer.  Novick hade al so worked at Los Al amOS.  They were a very interesting
team.  Aaron was interested in doing experiments and bringi n 9 things to an
interesting conclusion, and Leo was wandering all over the p ace and theorizing
about the nature of life in all kinds of dimensions,  buttonholin  people and using
that very special physics mentality that he had for pursuing bio ogi cal questions.
                         ?
He al so very shrewdly organized what he called a phage seminar.  phage is a buzz
word for the general area.  There was a lot going on in the midwest 1 n those days,
and we'd meet once a month, usually in Chicago,  but sometimes in Madi son or Urbana
or Bloomington.  Those are the main centers that we'd get together in and just talk
about what was happening in this new area.  This was ostensibly for hi s education
but it got us together and al so had the benefit of his kind of probing.
    SO he was actively involved in related areas.  His lab did the fi rst repeats
on crossing; that was not published.  Their research got onto the uses of the
chemostat.  This was a method of regulating the
flow of a nutrient.            7 rowth of bacteria by a continuous
            you'd set up a bacterial  cu ture, inoculate it and then you'd
have a drip that one drop every minute there would be fresh culture medium and one
drop every minute the culture as a whole would be withdrawn, so it was a constant
volume system and it would come to a steady state.  It could be set up in ways that
was nutrient 1 imi ted, so you had bacteria in a physiological steady state, but of
various degrees of nutrient limitation.  HOW fast would a bug grow if it had
concentration of six mi cromolar tryptophan compared to ten ml cromolar and so on.
They were able to do a lot of very quantitative studies on bacterial growth using
that apparatus, and it suited them just fine as physicists to operate in that mode.
They did some very interesting things with it.  That was the main content of their
biophysi cal investigations , the growth of bacteria under various kinds of nutrient
1 imitations in the chemostat and looking at genetic phenomena, accumulation of
                         Page 1


                             LEDERDI3
mutants, changes in mutation rates.  using that system, they discovered
anti-mutagens, things that would lower the spontaneous mutation rate.  They had some
interesting things come out of it.

     At the same time, Leo was very active in arms control matters and certainly
inspired me to try to pick up those same themes.

BOHNING:  That was in the height of the cold war days, wasn't it?

LEDERBERG:   Yes.


BOHNING:  If I read your notes correctly, you were consulting with someone at Fort
Dietrich.  I was wondering whether there was a biological warfare aspect to any of
that?

LEDERBERG:  I didn't know how much of an offensive program they had going on, and I
had no relationship to it.  Werner Brawn was my main contact and he had a research
program on the genetics of brucella.  From what I knew of it, it was for the
development of vaccines.  I was vaguely aware that we were developing offensive
weapons.  I was very much interested in arms control arrangements that would abolish
it.  I understood the need to do that bilaterally.  At least at that time, I felt
that we couldn't just unilaterally drop our interest in the matter and have the
Russians continue with unhindered and unlimited programs and that was something
ought to be bargained about.

    But I didn't get involved in the politics of that particular issue in any
significant way until much later.  I informed myself about it and saw BW [biological
warfare] as a horrible threat that had to be stopped.  But the focus of that would
have been arms control  arran ements.
          4      It was hard to see how that was ever going to
be negotiated and how it wou d be verified.  until we had overhead inspection, we
had nothing that would have been of any benefit, and as we know from our experience
with Iraq, even with it and with a treaty, it's of limited utility.  so that was my
connection with that.

    My main consulting then was commercial, starting with the Bristol
Laboratories in 1950.  They were in Syracuse, New York.  It was a little bit of a
nuisance getting there from Madison to,  two towns that don't have direct air
service.  [laughter] Joe Lean (?) was the person in charge of microbiolo ical
antibody development.  He wanted some input on how to use genetic techno ogies.
                            ?
They listened with great interest and they paid we what seemed like a great stipend.
I don't know, it might have been a hundred dollars a month, or something of that
sort; maybe it was fifty.  But they never did anything with it. [laughter]  But it
7 ave me some early introduction to how R & D works in that industry and left me with
ess than a upmost opinion of how far sighted it was.  They were themselves the
world leaders.  They were bettin 9k on a different horse.  They had [John C.] Sheehan
doing the chemistry and they wor ed out all kinds of semi-synthetic penicillin.
They had great success; it made them less desperate to try to look to what would
today be called biotechnology as a route to improvement. He would attend some of
our consultants meetings.

BOHNING:  Sheehan?


LEDERBERG:   Yes.  He's written a wonderful book about that ex erience
that's how I got my first familiarity with how that kind of t R     (35): So
                                    ing went on in the
world.  That was a long time ago.

BOHNING:  YOU said flying was difficult.  It was difficult under any circumstances
in 1950.

LEDERBERG:  If you had a direct connection, it was great.  Those DC3'S were
wonderful airplanes.  [lau hter]
         ?     It just took a little while.  It was more the
schedules than the aircra t themselves.  If you were going across the country it
took a little longer.

Page 2


LEDERDI3

BOHNING:  During that three year period before you went to Berkeley . . .

LEDERBERG:  Berkeley was just a summer, you know.  It's an interesting turning
point.

BOHNING:   Yes.

LEDERBERG:  okay.

BOHNING :
position?    were you feeling more and more comfortable with a university
    `vou'started out at Wisconsin and had wanted to do lots of research.   Now
yo;,ve got three years and you've got graduate.students and you're.getting the work
  . Are you feeling more comfortable being in a university setting?

LEDERBERG:  I was never uncomfortable with it, never have been, never was, never
will be. [laughter]  But I was becoming ingrained with it, and I think feeling that
I was well-integrated into Wisconsin.  I think whatever might have been in the
back round before I got there on anti-Semitism, it was never an issue. I don't
thin i! it was even an issue underground after the first introductions.  First of all
the world was changing,
important.         and then as you get to know people it becomes less
       It was also notable that a number of other new appointments were Jewish
people.  There had always been some in the H & S, but I may have been the very first
one, or if not, very close to it, in the school of agriculture.  But then the school
as an academic unit was upgrading, taking itself much more seriously, settingIbi:E;;
and higher admissions standards until  the ii were just as rigorous a program.
to be a little bit demeaning that it was  ind of the easy degree for dumb farm kids.
That's crazy on all sides.  They're not dumb, they don't get an easy degree, and I
think it was doing them a disservice to set less than the highest standards for
them.  They've done just fine in a more integrated basis.

BOHNING :  SO at this point you were pretty well convinced that you would stay in the
academic track?

LEDERBERG:  oh, I never doubted it.  I'd been on the academic track since I entered
columbia.

BOHNING :  But the M. D. thoughts disappeared very rapidly?

LEDERBERG:  oh, M. D. versus the rest?

BOHNING :  In your writings you seem to hang on to that little bit of "what if I had
stayed in medicine?"

LEDERBERG:  I saw the medical school as part of the university and I would not have
been interested in the medical school if it wasn't. That was roughly the case for
the one at Madison until about 1955.  I met John Bowers probably in 1950 (it might
have been in 1952; it might have been both) at Curt stern's house in Berkeley.
Stern was a  rofessor           a real wonderful elder statesman in the field.
His life wor R      of genetics,
        had been in Drosophila genetics,  but he wrote a textbook in human
genetics and he taught that at Berkeley.  It's a wonderful text (36). He'd gotten
to know Bowers, who was the director of one of the major  pro ? rams  in the AEC on
biological effects of radiation,  which included a fair bit o  genetics, genetic
damage and that kind of stuff.  He was an experimentalist, what I would call
contract big science these days,  but I didn't make those distinctions at that time.
I didn't know when I met him that he was being considered to be the new dean at
Madison.  I'd gone on at some time about what I thought was right and wrong with
medical education, that it didn't have an adequate scientific base and so on. He
turned up as dean and asked me to come and see him.  was I serious about my interest
in the matter?  I said I sure was.  what would I want to do about it?  I said,
"well, how about starting a department of genetics in the medical school." And he
said,  "Sure." [laughter]  so, that happened. [laughter]

                         Page 3


                             LEDERD13
BOHNING :  Just that easy.

LEDERBERG:  He wanted to make a splash and wanted to do something distinctive. It
was something he. could have some feel for himself, and it was very rational thing
f$ y;rn to do, given al 1 those preml ses.  There were some issues about how to pay
    . when push came to shove, it wasn't always as easy to get the appointments
through that I thought he had promised in that direction.   But his heart was in the
right place.

BOHNING :  where was biochemistry?

LEDERBERG:  In the ag school.

BOHNING :  In the ag school, too?

LEDERBERG:   Yes.  He set up something called the enzyme institute, which had some
autonomy but at least grew out of the ag school.  It may have been biochemistry's
answer to this question about having an acknowledgement of its roots in basic
science.  It was the same cast of characters.  A couple new people were recruited.
David Green came in.  I had high expectations of it , but I couldn't get any of them
interested either in DNA chemistry or in protein synthesis.  They thought it was too
hard.  It really wasn't until I left that they recruited [Har Gobind] Khorana to the
enzyme institute.  I might not have gone if he'd been there. [laughter]

BOHNING :  what happened to genetics in the ag school? Are they still there?

LEDERBERG:  what eventually happened, and it's sensible, is that the two departments
have merged,  and the  have a rather unique situation.
       z                     It's a department which is
both in the ag schoo  and in the medical school.  It has a unified admini stration
and gets some of its budget slots on each side.  I think the medical side of it is
the predominant one today in terms of where the action is.

BOHNING :  The Berkeley summer.  Your notes are filled with all kinds of things about
Berkeley .

LEDERBERG:  That was an exciting experience.  I had met Mike Doudoroff and Roger
Stanier at Cold Spring Harbor a couple of times.  I think Esther had known one or
the other of them, too.  She'd spent a summer in [C. B.] van Neil's course at
Paci fi c Grove,  the Ho kins marine station at Stanford.
        7                     Stanier was very much van
Neil's protege and co laborator over the course of that.  I think that was the
immediate instigation, but, yes, they were not segregated departments.  There was a
big department of life sciences, and they just invited me to be a visiting professor
for the summer and sort of bring bacterial ? enetics to that campus in that way. It
was exciting.  It was my first trip to Cali  ornia. The Berkeley campus was a rather
richer envi ronment, especially the depth that was going on there.  with the virus
laboratory and the microbiolo ists that I just mentioned, it seemed like it would be
a somewhat more stimulating  p ace.
           9    And you could work there in the summertime,
which you couldn't do in Madison. [laughter]

    SO I really first developed a yen that I might want to move west sometime.
I visited again more briefly in 1953; this was to receive the Lilly award
1 ectureshi R  and that reinforced it.  At that time Stanford was still pretty slee y.
Ed Tatum ad gone back there, but not much else was going on. The medical  schoo 7
was Still at San Francisco, so I didn't give much thought to Stanford as a place. I
think we began talking about possibly some day I might come to Berkeley.  SO that
started in the summer of 1950.


BOHNING :  The Korean war started then, too.

LEDERBERG:   Yes.  whi 1 e we were en route.  we drove across the country, and I
remember getting the news on the way.

BOHNING :  That was also the [Joseph R.] McCarthy era.
                         Page 4


                            LEDERD13

LEDERBERG:  That's right.

BOHNING:  were you caught up in that at all?  Did you have discussion with the
people there about that?

LEDERBERG:  The discussions were more in California than Wisconsin.  until he became
indiscreet, and it was his downfall, McCarthy was very careful not to bring this
stuff home where his own constituents could look more closely at it and know what
bullshit he was peddling.  There was a ver  limited degree of that kind of red
baiting in Wisconsin.  There was a little i: it of it, but nothing compared to what
you saw in Washington and elsewhere.  They did make a big fuss about the loyal oath.
My view was that I didn't see any problem with the substance of it, but I thought
it was egregious that the regents felt it necessary to impose it.   It was
humiliating and insulting and it has done exactly the opposite.
innocence until proven guilty and there's no reason in the world to t ink t ere s
                     The RresumEtio? of
any problem.  I don't think there was; I don't think any security risk has ever come
out of Berkeley in that regard.  But to this day I still have mixed feelings about
that whole episode.  I think there was a core of pro-stalinism in this country.
Anybody who could survive the Ribentroff-Molotov Pact in 1939 and not see Russia as
the autarchy that it was was being pretty much of a dupe.  I took u;;; s~;ously
the issue of the defections.  oh, who were the spies who were trie El
convicted?


BOHNING:  The Rosenbergs [Ethel and Julius Rosenberg]?

LEDERBERG:  The Rosenbergs, yes.  I thought and still do think that there's a pretty
good case that they were traitors and that there was some level of serious
revolutionary activity that was a conspiracy to overthrow the government.   It was
supported from Moscow.  But Mccarth  just amplified it way out of any kind of
reasonable proportions.  I didn't t ink then and still don't now, that any of the
             ii
people he himself fingered were guilty of what he was claiming.  He was drawing on a
current of fear and concern that had some tiny core of merit involving anybody. I
also felt that we were being victimized by the communists as well as by the right.
They kind of needed one another, and this notion of covering up on whether you d
ever been a member of the party and the rest of it was something that the hard core
communists were eager to inculcate, not primarily to protect themselves, because the
most evident of them were quite visible, but in order to divide and weaken the
country.
   I guess I would have favored a view of the matter that would have said,
"Yes,  I was a communist.  I didn't do anything wrong.  I was complying with the law.
I'm going to stand by that."  If more people had done that, and eighty percent of
the ones who took the fifth amendment would have been in that category, it would
have disarmed McCarthy in the first place.  McCarthy was a tool of the hard core
communists as much as vice versus.  I really felt we were being done in by
extremists on both sides.  I had a lot of sympathy for what was then authentically
the liberal element view of the matter.  I thought there were civil liberties
~IA;s;~~;s involved in those kinds of inquiries.  so I supported the op osition  to
     But I thought it was a bad strategy to oppose it and it wou d have been a
                           7
better one to say, "yes, I was a communist and I had good reasons for it at the
time, and if I'm not today I have repudiated.  Maybe some others don't share that
and maybe they have undertaken some activities that ought to have further inquiry,
but there's no reason for me to be involved in that." It's a very unpopular view,
and I don't espouse it too loudly anywhere.  people mi  ht misunderstand it and it
would come under attack from both the right and the le t today.
                     ?

BOHNING:  It's a very plausible one.  certainly for people who joined the party in
the 1930s in the midst of the Depression, there was a rationale.

LEDERBERG:  Thousands of people did, and they had no reason to hide it.  They began
to, it because if it became something that you were ashamed of, people would think
that where there's smoke there's fire.  I really think it could have been disarmed.
                         Page 5


                             LEDERD13
That would have taken some courage.  I don't know if I would have had the courage
m self to do it, but it was not a very good defense.
-i                                People got fired anyhow, and
t  e notion that you could somehow escape because you wouldn't be found out because
somebody didn't tell on you, I thought was pretty foolish.  So it fed into McCarthy.
He's one of the vilest people we ever had and I've never had any hesitation in
saying that.

BOHNING:  Towards to end of the McCarthy era, was the university affected at all?

LEDERBERG:  Hardly at all.  There were one or two minor skirmishes.  when he started
going after a couple of Wisconsinites, all the local press who had been sort of
divided about him started denouncing him too.  It was crazy; when he started going
out after Eisenhower he was finished absolutely.  I can't swear that there was no
sin le person at the universit
not I! ing like as big an issue t ere
           x who was somehow singled out or injured, but it was
                         as it was in California.  I don't think the
regents took much attention in terms of the symbolic acts of genuflection.

[END OF TAPE, SIDE 131

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                               LEDERD14
LEDERBERG:  Generally I was really very much & reoccupied with my own research. I
took seriously these questions of academic li erties, but they were not in any way
at the top of my mind.  I was not engaged in consulting in Washington during that
era.


BOHNING :  I'm not sure if there's anything else about the Wisconsin period.  we've
talked about getting genetics in the med school final 1 y.  But you had some
frustrations with that, didn't you?

LEDERBERG:   Yes.  we got started and there was some ambiguity about what scale it
was going to be and what the funding was.  That slowed me up in terms of recruiting.
we didn  t really get very far during that time I was there.  I think it really
didn't go operational until 1957, so it was about 1955 when it was formally
established.  we probably did get to where I taught at least one year's medical
class.  The teaching was the thing that was the operational 1 y unique step.  The med
school as a whole was undergoi n 8 a lot of changes at the time.  Thi ngs hadn ' t shaken
down very far during the time t at I was still there.

    It did mean that starting from 1955,  I did end up being busier and busier
with administrative detail, just trying to get things moving.  I don't have a clear
image of it, but I must have been spending twenty to twenty-five percent of my time
just trying to pull all the pieces together, get the funding and that kind of thing.
So that was my evolution in that di recti on.  I think up to that point I would have
been either in the classroom or the library or the lab. I had no reason to be
anywhere el se.
BOHNING :  Did your graduate student level stay pretty much the same?

LEDERBERG:   Yes.  I would have two, three at the most, maybe one postdoc at any
given time.  It was a pretty small lab.  I didn't squawk very loudly about it. I
didn't realize what influence I might have had.  It wouldn't have been easy, but I
think I could have swung more space.  There must have been some of that getting
ready in the medical school,  which I don't think I ever  ot to occupy; there was
some new building going on and that was part of what  cou d have eventually have
                      4
been.

    Funding was adequate for what I was looking for.  NIH was COmi ng i nt0 play.
My first grant was for three thousand dollars.  It started growing after that. I
did end up havin 7 most of my support eventually from NIH ;f rants.  It started out
with the Rockefe ler Foundation Awards and a 1 ittle bit o  department money, which I
mentioned to you.
    Let's review Wisconsin from the perspective of the thematic issues that I've
mentioned to you.  First of all, uniqueness.  I was a very young fellow, pushing
right along, pulling the department together.  The issue of precocity becomes less
and less as I eventually did get to be twenty-five. [laughter]  It became less of an
issue.  I'd say b  that time,
      z       if there was anything unique it would have been not a
qualitative singu arity, just having a very active, intense research program in an
area of major interest.  But there might have been fifteen or twenty others more or
less like that at that point.
    In the generic aspects, I think I was the model of an active research
sci enti st .  That was my 1 i fe model at the time.  I felt very excited about what was
happening from day to day, and I think fairly content.  I felt a little bit restless
about the sort of the larger philosophical frame;  the medical involvement was an
issue.  we could have done more about other elements of culture.  I don't want to
depreciate them.  Wisconsin was not totally bereft of them, by any means.  It wasn't
quite the excitement that one experienced either at Berkeley or Stanford. I guess
that's true today, too.  It's a good school .  I certainly don't want to depreciate
it, but it might not be at the very top of the list.  There were a few outstanding
i ndi vi dual s .  I was probably as close then to 1 ivi ng out my 1 i fe model as at any
time.  That was the very core of how I would have viewed myself.  I was probabl
itching for more application.  Here I was making an important contribution to t K e
substratum of biol ogi cal investigation.  I think that a pretty both large and
                         Page 1


                               LEDERD14
realistic view of how important it was.  I don't think I underestimated it in any
way.  It was wonderful fun being in the middle of the action.  I always wanted to
keep an eye out for how you can make something useful out of what you're doing, and
that wasn't eventuating.  It wasn't happening at Bristol .  I didn't see too many
other avenues for doin f! too much about it, so I just thought, "okay, publish your
work.  Others will pit  it up and it will come to mean something someday."

    Decision points I think we've covered.  The main ones--going to Wisconsin in
the first place, not being more ambitious about growing and space and funding and so
forth, although I al so wonder if I might not have overplayed my hand if I pushed it
any further.   In  retros ect I think not;
         R           I had more potential power and influence
than I understood or ac nowledged at the time.  It was only when the issue came
about my leaving, that I realized that people really would care to that degree. I
don't mean that they were careless but there might have been a wa  to get the deans
to try to undertake some special measures.  The Enzyme Institute K ad far better
laboratory facilities than I did, and one thing I might have done would have been to
try to press for membership in that.
like that.                  It just never occurred to me to ask for things
       It may seem a strange thing to say, but I was unduly modest on that
score.  Decisions about trying to set up a medical school --that was getting on the
slippery slope, but I can't see how I would have or could have done otherwise. Then
eventually deciding to leave there.  SO I think we've covered the major issues.
    what else was going on in biology during that decade? That's a lot of
homework.  There's not much in my oral history, in my recollection, that would add
to trying to do a piece of scholarship.  But in fact, let *me get somethin  out for
`;;;o,and s(ou take a look.at it and bring it back.  1'11 give it to you be ore you
                            ii
    I ve written a hi story of what I call the vi cennl urn (?> , the period of 1930
to 19!iO, which I see as the crucial flowering of microbiology, bringing it into the
modern era.  It's not quite the right interval for this one.

    Certainly the playing out of the DNA story is the big thing that was
happening during that time.  There was a lot of activity in Paris.  There were the
beginnin  s of the messenger RNA,
   i!                enzymatic induction and so on.  That was the real
center 0  the action, at that oi nt, for the details on DNA structure,
corroboration, bol steri n ,
         ?   not ing as nearly as  revolutionar
           R            iT  as DNA.  You sort of
have to get to the end o  that decade before you in a sense  ave the RNA story
starting to emerge with the genetic code and so on.

     But that is relevant to my own situation, because here I was still doing
experiments with the technology of 1946 when the field was becoming increasingly
more domi nated with biochemical i nputs.   I was 7 icking up some of them.   I wrote a
paper on beta-D-gal actosidase (37).  But I real y wasn't adequately equipped to do
serious molecular biology.  That was harder then than it is now, because you needed
ultracentrifuges.  we didn't have gel electrophoresi s and things of that sort;
they're just wonderful further assistance.  That is one of the reasons I left
Wisconsin;  I wanted to be in an environment at least where work of that level and
that kind was going on and I had some better chance of participating in it.  Arthur
Kornberg at Stanford was my attractive magnet from that point of view.

    I wasn't much involved in popular culture at that time.   I would have to
look around.  I think I did have a letter to the Bulletin of Atomic Scientists, in
which I said, "You're making a big fuss about radiation dama e and let's measure it,
and that's okay.  But nobody has said anything about chemi ca 4 mutagenesi s . "  I think
that was the first public mention of it, and that was in 1955.  I remember some
c;;;espondence with H. G. Muller asking him what he thou ht.about that.
                      gk           He said,
   that is an important 1 ssue and should we try to  ta  e 1 t to the Academy?" He
was member of that and I wasn't.  Nothing came of it; there was no receptivity.
That seems crazy toda . [laughter]
        x         There are environmental mutagens everywhere. So
I do think that was  t  e introduction to that subject.  A couple of people had done
experiments with chemicals, as I had done, but not make that extrapolated leap to
where these are a public health hazard,  no less and no more than radiation is, for
comparable reasons.

                         Page 2


                              LEDERD14
    I can't think of any other public issue I came in on that is special to my
own science.  I had some loose affiliation with progressive politics in Wisconsin.
It was an extraordinary state from that point of view.  It had the [Robert] La
~ollette kind of tradition.  In civil liberties I've forgotten what the hot
challenges were, but I did belong to the ACLU at that time. But those were
second-order matters.  The lab was really the main focus of interest.

     Social relations and lab environment.  I think I've described that to you as
fair1  stable in the cast of characters.
  i:                       The names are in the record; I don't
remem er them nearly as well as I can find the detail.  Gatekeepers were pretty
friendly.  I wasn't asking for very much, so I got all I asked for--  rants,  papers
were published with any problem.  NOW and then, I started getting a ? ew papers for
review.  I should look up when I started going on NIH study sections; that would
have been my first connections with Washington.  It was during that period, probably
the early 1950s.  I was starting to sit on some of the sections.
    oh, I should bring up something, and that's Gene [Eugene] Garfield. He
published a paper in 1955 about the concept of citation indexing, referring to
Shepard's Citations (38).  YOU know I was already interested in scientific
literature quite dee ly at that time.
        R           The paper made an important impression on me
because it was somet ing to worry about following. Two or three years later, I
asked myself whatever happened to Gene Garfield's idea?  I had not met him.  I knew
about Current contents.  Then it hit me that that was a self-exemplifying question.
If there were a citation index I would know how to answer the question and then that
sort of thing would come up over and over again. [laughter]
    SO I wrote to him and said, "what's happened to it? what are you going to
do about it?"  I think I started my relationship with him in early 1958; it might
have been slightly earlier than that.  He said he didn't know quite where to go.
I'm not sure who brought up what first, but the idea eventuated about applying to
the NIH for a grant to do a demonstration.  I told him I'd be agreeable to being an
advisor to his project, so it was submitted to the genetic stud x section.  Since
geneticists have an instant reflex about generational relations ip of parent and
descendent, which is analogous to paper and bibliography, they can understand the
idea of citational networking instant1 .
               Y  It's amazingly difficult to explain this
to others sometimes.  They very prompt y supported the concept and ordered a small
grant to just demonstrate it and produce a sample genetics citation index.

      That was done.  I was an advisor to it, and it looked like the thing could
work.  There was a sufficient bulk of exem lary material to give you a sense of just
how useful it would be.  It was still fair y primitive.
                7         It had very abbreviated
citations and everything was on punch cards.  A little bit of mainframe computing
was what was available in those days.  It inspired Gene to say, "This thing looks
like it might work.  There is enough interest in it out in the community; I'm going
to see if I can make a business of it."  I remember saying, "Gene, don't' do that.
You're going to lose your shirt. [laughter]  vou'll never break even on it."
[laughter]
    It also reflects a fairly early interest I had in using computers for some
useful purposes in science.  But that was the beginnings of the citation index and
my relationship with Gene.  I think he  ot started on it and then in the very early
196Os, maybe 1961, he asked me if I wou d join his board and offered to allow me to
               ?
make a small investment in the company at that time.  AS a matter of fact, I think I
was his first shareholder.   That was the best investment I ever made.  Gene did
make a profit out of ISI [Institute for Scientific Information]

BOHNING:  In spite of your predictions.

LEDERBERG:   Yes.  That's something I feel pretty proud about, having had some part
in this.  Then also exobiology started during that interval.  we haven't said
anything about that yet.  sputnik was the incident of that.  I've already done some
oral history on that.  Steve [Steven I.] Dick is an historian at the U.S. Naval
observatory, and he did an interview with me just a couple of weeks ago focused on
just that episode.  SO I think I won't repeat that here.  we'll get the text of it
                        Page 3


                               LEDERD14
and share it.  There's not too much overlap with the other stuff I have here. It
relates to how I met Carl Sagan and got him introduced to NASA.  It began with
sputnik, which sort of made things
question of whether there could be 7 ossible.  I've had a background interest in the
                     ife elsewhere than on earth, but never saw any

way to do anything about it.  SO it was left in the realm of pure speculation, and
Sputnik seemed to open an era where than might possibly eventuate.  I got to be
quite active on that at that point.

    I haven't said anything about theories of antibody formation.  That was also
still during my Wisconsin days.  I've written a memoir on that (39), titled "the
Ontogeny of the Clonal Selection Theory of Antibody Formation."
thoroughly written down,               That's been pr;;;y
                 and I can't think of too much that would add to that.
background on that was a Fulbri B ht Fellowship which I took to go to Australia for a
few months, just a little bit o  wanderlust.  I'd never had a sabbatical up to that
point.  I was going to work with Mac [Macfarlane] Burnet in Melbourne, ostensibly on
genetic recombination of bacteria in the influenza virus.  He had discovered a
system of genetic exchange there.  He was a wizard at flu and knew nothing whatever
about genetics.  I thought there might be a useful reciprocity in that.  when I got
there he told me he had dropped working on that subject and he was working on
theories of antibody formation.  I have written about this in another memoir in  some
detail (40).  This was while I was still at Wisconsin.  I did some experiments with
Fritz (?) Nossal, who is now BUtVet'S heir as the director of the
               institute in Melbourne.  He's been there for some time now.

    They did support the view that  sin
antibody and that an animal making a lot o 7 le cells produce only one species of
                      different antibodies is segregated cell

by cell, which is part of the clonal selection theory, which is now universally
accepted.  Ken shafner (?) has written a little bit.  Just recently I got a paper
from him on the acceptance of the theory,
filling in that detail (41).        and I think he's done a pretty good job of
                 That's still something I feel I want to go into in a
little more detail some day, of the resistance to it.  Both BUtWet and I faltered
for a while.
we were trying It looked like it was damning evidence and we believed in evidence.
        to find some way to rescue it.  It still seemed like a very good
idea, fundamentally. The evidence, the negative evidence turned out to be an
artifact; it was as good as gold all the way, and is now the common dogma.  That was
a tiny experiment.  It was centered on a distractional ex erience,  but it had
wonderful proofs.  It may have been the first time I real 7
with purely theoretical speculation,        y saw how far on;h;;r;lsgo
                     if you have a good firm background.
without doing much experimentation.  I had done that before, but I'd always done my
;XV; T;&erimentation after that.  There was a limit to how much one could do in one's

    I had my first brush with computers at Wisconsin in the early 195Os, 1953 I
would guess.  I took a course on the plugboard program, card machines, and then
decided that although you could do standard deviations with a whole pack of cards,
it wasn't worth it and there didn't seem much more to do at that stage.   I was
keeping an eye out for what computers might be useful for some day and sort of i ust
                                                         ept
it in reserve.  My first contact with those machines was in 1941, when I was a high
school student and attending American Institute Science Laboratory.

[END OF TAPE, SIDE 141

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                              LEDERDI5
LEDERBERG:  The American Institute Science Laboratory was a predecessor to the
science fai r programs.  This was then sponsored by Westinghouse and IBM.  IBM lent
some space that we used as a lab, and we could tinker with what we wanted to do with
some very remote supervision.  They had one of thei r advanced card calculators on
display at that time.  I didn't do very much with it,  but I was able to see what the
best of the electronic art was as of 1941, and thinking, "we1 1, that's a machine
that's going to be interesting to biologists someday.  It sort of emulates what
organisms can do in some very, very crude way, but it's not worth investing as yet."
when I got to Stanford, that changed that.

    I can't think of any other themes for that particular decade, so maybe that
does wrap that up.

BOHNING :  That's a good point to close in the day.

LEDERBERG:  okay.

BOHNING :  Again, I appreciate the time you spent with me.

[END OF TAPE, SIDE 151

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                                  LEDERNOT
NOTES

    M. Bodansky,
S&IS, 3rd. ed.,    Introduction to Physiological chemistry (New York: John Wiley &
          1934).

N&s, 70 Richard A. Balford, "Remembering Early them Labs," chemical and Engineering
     , No. 23 (8 June 1992): 3.

    See Russell E. Marker interview by Jeffrey L
B&kman Center for the HiStOry of Chemistry,        Sturchio, 17 April 1987; The
                    Transcribt #0068.

E. B. Wilson, The Cell in Development and Heredity (New York: MacMillan,

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