January 7 , 1950.

Dr. L. Cavalli,

Devt. Genetics, .
University of Cambridge
England.

Dear Cavalli:

Thank you for your "123" cultures, wyich arrived some time ago in
excellent condition. I can't recall whether I've mentioned the unlixeli-
hood that the second culture is “Lac3-", owing to ita glut phenotype.
However, I will be glad to try to chassify in temms of the arbitrary
designations given to our Lac- mutants. .

I have tried two crosses with the "123" strain (which I shall record
as N-1258). X 677 and X 1178 (the latter is a Mal- mtant froma TLBI-
Lacl-Vl" segregant from H-1). The $lelds were very poor on the first cross,
and“the backgppund rather heavy. The second came out very well, with good
ylelds of prototrochs, some of which may be dinloid, but doubtfully.
There were about 1% Lac-, 99% Lac+. Of 100 Lact, 98 were Mal+vi> (parental),
1 Mai-V35, and 1 Mal+Vl", Of 9 Lac-, 5 were Mal+V1i5, 3 Mal+Vi", and
1 Mal-7," (par.) There seems to be Little question of the validity of
recombination between these strains. Some colonies show peculiar mottled
aopearance on ExB Lac, with a very variable colony size and fermentation
intensity on restreaking, and theae may conceivably have been diploid,
but not yet proven to be.

2 most important point that I would like to convey is that 7-1258
4s very susceptible to the lysogenic phage, lambda, carried by X-12,gtccks.
Considerable plaquing was observed in the background growth of the cross
1258 x 677, which led to our check on this point. Thd virus aay be an in-
portant barrier to hybridization, and may also play some part in the very
peculiar segregation ratios observed in these crosses. I am working to

secure Lambda-resistant or lysogenic 1258 cultures, and will send these
promptly if successful.

We have been trying our own hand at determining the nutritional require— |
ments of this culture, and they are very complaex indeed. Excellent growth
can ba obtained on complete media to which a bit of yeast extract is added
(.3%). The requirement seems to be for a balanced combination of at least
three aminomacids--I hope to have more definite information soon.
I hope you will not think it impertinent if I raise some suggestions
concerning your personal plans. Do you have a permament staif appointment
now at Cambridge? I think that I would enjoy very mich the opportainity of
discussions with you at closer range than across the Atlantic, and I won-
der if you have given any thought to the desirability of visiting or working
at some of the many microbial-genetics laboratories in this country, per-
haps oh a fellowship basis. Owing to space limitations, we could not accomo—
date you satisfactorily here for perhaps another 12 or 15 months, but even
go, it would not be too early to explore the possibilities, as well as the
interest that you might have in such arrangements. In addition, I have been
asked for suggestions for potential importations of scientific talent in
this field, for fellowships or staff appointments at other universities in
this country. Your name has been mentioned, but I have not known whether
to press it, because I could not tell whether you would have the slightest
interest, on the one hand, nor did I have the most elemantary information
[vis., your age, marital status, academic history, present position, etc. ]}
on the other. If you could give me your reactions to thees particular points,
and to your interest in working in this country, I am sure that something
eminently satisfactory might be worked out. Possibly, I aa overreaching my-
self in raising this question, but please be assured that there is no matter
of patronisation, but only my hope for a closer convergence of our related
intergsts.

To close on a scientific note, we have been doing some UV experiments
on heterozygous diploids. The only prominent effect is the apparent "conversion™
of diploid to haploid (i.e. eells which would form mosaic colonies to cells
which form only pure colontes). No balanced lethal diploids have been
found, nor have partial losses (i.e., pure for one factor; segregating for
others). The analgsis will be very complex, owing to the multinucleate
character of diploid and haploid eells]; we are concentrating now on the
genetic effects of very low doses (with negligible killing), to determine
whether the shoulder or threshold region of the UV sterilization curve
has genetic effects, which is ta say, whether it is actually due to genetic
(nuclear?) reduplication. I have been toid that the reported linear kinetics
of UV killing even in B may be fallacious; it certainly does not hold with
K-12 or with the diploids. Since segregations occur uncontrollably (arguing
from the absence of balanced heterozygotes on complete medium), the model
may be a multinucleate cell the sterilization of which requires a lethal
hit (not necesaarily homologous) in each nucleus. Fven if the lethal mutations
are recessive, and the cell is not "killed" thereby, it will be sterilized
since the heterokarybtic (or hetercgenic) conditions is not maintained
(ag it is e.g. in Neurospora). This may mean that minimal medium, on which
the equivalent of lethals (viz. nutritional requireg nts) are maintained
balanced, actually maintains the diplophase by more than merely selecting
for it, or to state the converse, that compkete medium actually induces
segregation. This is being tested. This conclusion assumes that lethal mutations
should have been induced in diploids with U¥ dosages which induce substantial
killigg.

Sancerely,

Joshua Lederberg