Jamary 18, 1954

Dear Ed:

To deal with constructive matters first, yes I'm happy to send you
W~-1305.funder—eeparate—cover). We have not mamfactured as ST derivative,
but you should have no trouble in it. If you'd care to send such back,
we might have some future use of it.

From the tone of your letter, I suppose you are already acquainted
(whence?) with my reluctance to send out cultures that are the subject
of instant study here. For some time, we had a comletely unreserved
policy, but the results worked out so badly that I am now adopting the
alternative policy, though one which (as in the present case) it is
sometimes rather enbarrassing to uphold. To be consistent, I would have
either to withhold a culture, or distribute it unreservedly. If you re-
ceived material with strings attached, it would simply transfer to your
own conselence the embarrassment of withholding it against forceful pree—
sures. But if we can be of any other help to you, please let ms know. Per-
haps we could construct the diploids you were interested in? They are
rather tricky beasts anyhow, whose behavior is full of pitfalls, so there
might be some advantage to our keeping an eye on the genetic end of it.
Or it may be that there are (not improbably) som: inherent limitatdons tht
may not be immediately obvious but that would make a diploid analysis im-
practical. If I can consult with you on this, or assist in any other way,
please let me know, as you can be sure that the notion of withholding
materials, especially from my friends, is deeply distasteful to m and
I would be looking for any alternative way of making it up.

Tom Nelson and I have been using the diploids to explore the details of
elimination. In the first place it 1s clearly post-sygotic, (not pre-gamtic),
for the diploids in an F+ x F- cross are invariably hemizygous in the Mal-S
region, but not always for the contribution of the F~ parent. I.f., in about
85% of the diploids, the F+ segment is missing; in about 12%, the F+ segment
is present and the F~ missing, and about 2% are crossovers, part F-type, part
F+type. This fits in very well with some data we have on segregational anomalies
from an exceptional diploid once picked up which is in fact heterozygous for
Mal and S, but appears to undergo elimination during segregation, so as to
disturb the segregation ratios very markedly. These data were on numbers of
haploid clones in single call progenies, so relative growth does not com in.
Finally, I've been pulling out the early hybrids as single cells by micromanipu-
lation. In many instances, single cells have split out the full genetypes of
the two parents, though the same cells show a restricted range of recombinants,
4.e., with Mal-S elimination usually of the F+ (Hfr) contribution. Thus again
the timing of the defect can be narrowed to an event subsequent to the formation
of the hybrid, but dur or before segregation. The Het—diploids are clearly
not the primary hybrids (if only becanse they can often be homozygous for some
markers) but must be non—disjunctions of segregated meiotic products. The
mating itself is probably a conjugation, with the F+ parent transferring a
nucleus to the F— partner, but the cell studies are not yet absolutely conclusive
on this. As you see, we are at a point of tying together a lot of loose ends

to make a comprehensive picture, but I have not been moved to make too many
explicit, public dicta on it until we are certain of our ground.

With best wishes to everyone,

| Yours,

|
oo‘ Joshua Lederberg