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October 8, 191.

Dear Nick:

I'm quite glad to go along with your plan to give a narrafive account
of the histopy of E. coli recombination, although whether it will keep
your audience qwake is still an experimental question. At the outset, I
want to urge, very strongly, that you also consult Professor Tatum, mentioning
if you wish, that I thought it worthwhile to bother him about it.

Although his papers don't mention it, Tatum's purpose in going after
nutritional matants in E. coli was partly to test the possibility of recom-
bination. In 1945-46 I spent some time in Ryan's lab (while 1 was a medical
sgudent at Coluabia) working on reverse-mutation and heterokaryotic competi-
tions in Neurospora. The selection of prototroph reversions in Neurospora
suggested the possibility of similar selection for recombinants in bacterla.
Professor Tatum had a very similar notion, After he came to Yale, I wrote
to him asking for some di-auxctroph mitants. Both of us had gotten protobeophs
from monoauxotroph combinations, but could not, of course, be sure that
they were not merely reversions, His ultimate response to ay letter, facili-
tated by Ryan'a personal contact with him, was 4n invitation to work on this
problem at Yale (where Tatum was just organizing his lab.) whenever I could
get leave from medical school. An elective quarter, followed by a summer
vacation perlodg materialized starting in March 1946, partly as a result
of the abandonment of the Navy V-12 program, and the shift back to non-
accejerated echedules, after tims V-J day. I want to Yale with the help of
a fellowship from the Jane Coffin Ghilds Memorial Fund for Medical Research,
a cancer-research foundation administered at Yale, and as things turned out
took my Ph.D. at Yale, and my appointment here, rather than ever return to
medical school.

It would be difficult to say how or when the first prototroph occurred:
probably both Tatu and I had seen recombinants before either of us knew
of the other's interest, but the main problem was to establish the signifi-
cance of the prototrophs, and this meant learning how to use additional
markers. It was also necessary to learn the conditions under which syntrophism
operated. The project was started, on the Mambdumm one hand, on such a
long-chance basis, and on the other positive results were obtained so readily
(e.g. in the first critical combination of two diauxotrophs) that there was
o "lab opiniog” greatly different from our own. The first hint of the work
9 at a local bacteriology meeting. ("reprint enclosed). Wixkkmxmx The CSH
sosium was the firat real discussion of it (Evelyn can tell you about it).
‘e sent to Mature appeared prior to the publication of the 1946 symposium.
ve other anecdotal material is contained in my chapter in "Genetics in
th Century, and in gg our CSH 1951 ms. It happens that Esther worked
viginal isolation of the double auxterophs at Stanford (see PNAS 31:2193
relevant material ia enclosed.
Sincerely

J. Lederberg