Decenber 17, 1954

Bear Syd: cn

It was a pleasure to hear from you agaih. Originally, I had only
wanted to walt a decent intervak before replying to yours of the 15th July,
but in time, it became a question of finding a few minutes.... I am happy
to have this reminder. > ee cS

' We spent the best part of the summer at Woods Hole, and had a splen-
did time, including many discussions with Ephrussi. I happened to see him
again last Saturday in Chicago; he is just about ready to go back to Paris, and
would like very much to keep in touch with you on your yeast experiments. I
promised to send that word on to you.

This fall semester, I have been rather prececupied, what with an
expansion of my lecture course in microbialgenetics, and a wonderful visit by
the Cavallis, who came in midSeptember and left about two weeks ago. What time
I've had has been at the conjugal E. colis.

The lab has not changed very much in demeanour, The hoped-for remodelling
is stilléfalled in the planning offices. I do my manipaulations at the accustomed
place; the Cavallis sat where you had worked. On the opposite side of that bench,
facing the window, Bob Wright and a new man, Dr. S. G. Bradley are working. There's
no one else new in the lab. Tom's off to the Institute of Microbiclogy at Rutgers
University (with W. Szybalski; this is Waksman's automemorial). Aleck and Helen are
getting married (tomorrow?) They're die to return to England together this summer;
she will presumably continue ler graduate work someplace there. The research pro-
gram is what you already know about; Bradley is a postdoctcral fellow trying to do
some genetics with actinomycetes.

Bob Wright is doing splendidly! I am really terribly grateful to you for
helping to smooth the way for him to come here. As you know, he is tackling the
genetic analysis of cytoplasmic effects in terms of the presumptive dikaryons that
Fowell and others have described as incidents of copulation. He has some highly
fertile haploids that seem to show this effect with high frequency, and during
the past months has been trying to build up mutant markers. And guess what! All
the auxotrophs(after UV irradiaticn) have been petites! ive were just discussing
what to do about this when your letter arrived. Ephrussi had also commented on
the same observation, and clearly someyione (namely SDR) ought to look inte this effech.
T'll wager you though that it turns out to be an effect of the UV, independent of
auxotrophy, and that the petites are cytoplasmic rather than segregational. This is
just an intuition. Ephrussi has been working lately on "suppressive! petites. These
differ from the "neutral" pebites previously described in that crosses of suvpressive
by normal give petite hybrid diploids. These generally cannct sporulate sc the analysis
ends there (dikaryons would be very helpful indeed for thts situation!) It will be im-
pertant to look out for this and use a verified “neutral" as the recipient in any
restoration experiments. Our main concern, like yours, is tc find methods of obtaining
auxotrophic markers sans petite, and I hope we shall not have to resort to backcrosses
to wild type for it. But the basic nhenomenca should be carefully studied itself, an
I hope your ketter is an indication that you are¢ going into it.

I am sorry that I simply overlooked your earlier request for Caroline's
strains (but I received your letter on holiday). We'll send them off promptly.

Have you worked out a sati&sfactcry method for selectively isolating infrequent
normals from a petite background? Lindegren has a paper in the 9/54 J. Bact.
which may help: namely, a peptone acetate phencl red broth. This works very
well indeed to discritinate petites from normals (the latter cxidtize the acet.
ani accumulate OH~) and may be a better basis than alcohcl. Ye haven't tested
its use for selecticn; it may need some modification.

Your syllabus fcr the lab. course was quite impressive, I haven't had
the facilities for such a course, so can't comment from personal experience.
It ‘looks an exeellent job. _ Your last letter also asked for comment
on your scheme for restoration. Until we learn how to dd it, anything's worth
trying, and if a proper selective method is available, it is certainly sound.
Ephrussi (in litt.) -had once speculated along similar lines, but I don't know
whether he did any experiments/ with conjugating cells. Another possibility
might be to learn to inject budding cells. The injected cell will doubtless
be killed, but perhaps nct without some chance cf contaminating its bud.
Bob, maqumxknmy and Mari Lind were married, as you know, last summer.
I think Mari ie becoming somewhat more accustomed to being a scientist's wife
than ycu might have guessed. At any rate, she is coming to work in the lab 2s
a general assistant starting the first of the yeab, and I am sure «ill de ac
excellent. job of it. To continye. about Australians, I have also been very
well impressed with Nency Millis. I see her in class, and at our seminars.
. Considering. the handicap of having had practically. no formal training in
genetics, she has been doing very well in class,. and asks cheracteristically
_ intelligent questions. I haven't had any chance to discuss her swan work with
. her. . Log . .

Syd, the very best wishes to you: for the new year.

Joshua Lederberg

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