November 3, 1954

Dr. Clifford Grobstein
National Cancer Institute
Bethesda 14, Maryland

Dear Cliff:

The first thing that Father and I did when I got back to Yadison
was to set up some dry runs on experimnts to test the transfer of
"F+" through a menbrane filter. Some experimental trials are in the
mill now, using the standard thickness H filters. I will be quite
astonished if this works through 150 uw thickness [but I was also as-~
tonished when the first "contagion" experiment worked too}. We will
know about this in a few days.

The main point I wanted to tell you about is that the experimental
design is entirely feasible, and that with these filters it should be
possible to get clean results even with rather small pieces. The setup
ds such that I would prefe@ to use pieces about 3-4 om. in dhameter, but
that the actual critical dimensions are rather smaller, so that occasional
breaks ought not to be critical. The tnoculum that is planted on the
top surface forms small, well localized colonies whichd should be separable
without too mich trouble from any colonies that do come from breakthroughs.
As I told you before, there will not be the least difficulty telling when
such an event has happened: for example, the recipient culture is a strepto-
mycin-sensitive(S®) F-; the donor an ST F+. If any of the latter break
through as contaminants, they can be detected very readily by plating samples
of the recipient colonies on streptomysin medium.

If you can conveniently send us some of your special membranes, we should
be able to do some proper preliminary experiments to decide whether to pursue
this approachs Have you any suggestion about sterilizing theg? I would sooner
stay away from chemieals. If they won't take steam (stacked between blotters),
then a heavy dose of ultraviolet on both sides should do it, don't you think?

Under separate cover, I am sending a stack of reprints. Much of this stuff
may be somewhat obscure and of only marginal interest, but I would welcome any
comment you might have, especially on the F story, which has so far had a
remarkable similarity to your own. I need hardly add that many geneticists
have been groping for alternative formulations in addition to the siaplest
ideas of infective particles to account for examples of extrachromosomal deter—
mination.

Yours sincer: ly.

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K Joshyx Lederberg
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Yours sincerely.

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