BM

611 Vest 113 th St
New York 25, N.Y.

September 18, 1949
Dear Josh:

I know I ought to have written to you long ago. You
and your wife did a lot more for me than most people do whan
for a house-guest, and I enjoyed the visit more than I ever
enjoyed a visit as a house guest. And the instruction and ideas
you gave me have been a tremendous help since I have returned.

Meningocodes grow on the synthetic medium, and as
you probably noticed in the recent JR, they don't even require
glucose, But 48 hour growth on solid simple medium is not so
heavy as 10 hour growth after the addition of 1% serum. The
first lot of medium I made up didn't show so much differ«nce,
or I didn't notice it, but Now I'm not satisfied with the syn-
thetic and I am trying to find out what the difference is.

Both crystalline albumin and thiamin improve growth slightly,
but not to compare with the serum,

At first I went akead on developing penicillin-resist-
ance, and increased it in two strains to four-fold, but then
the thermostat went bad and the incubator got too hot one niszht
and killed off allmm my strains. Since then I have been working
with the medium, and trying to develop a good differential for
fermentation. Most dyes inhibit growth in very low concentra-
tions, but I have just started to see if I can develop a strain
thet is xweskutantxke tolerant to EMB. Thet may be useless, be-
cause they produce acid only for ea short time, and then become
alkaline. I wonder if you could send me a very small sample of

tetrazolium, and tellme where you now get your supply.
In Miller's experiments on developing armumx peniciliin resist-
ance, he found that he could step it up faster bg taking growth
from the mexk second-highest concentration on which they grew at
each step. He assumed this was because of the size of the inocu-
lum, but didn't atkem report any attempt at measuring the inocu-
lum. That could be the explanation, but another possible explana
tion is that where many mutants grew, and were transferred, they
had a chance to recombine and get the benefit of several additive
mutations for the next stage. For the present, that is the thing
I have my sights set on rather than virulence.

while I was there you asked me for suggestions on whakxka
how to analyze your unexpected distribution phenomena, I haven't
been able to hit on any approach you are not already xx using.

I would expect the best results to come from the new HR strain
where there is no question of uniform bias, although I know you
have been using reciprocal crosses. And you say you have obtained
other heterozygote strains; of course they have biochemical defi-
ciencies, but I shall want to hear more about how they behave,

I'll write to you about any really interesting results I ob-
tain whenever I obtain them. Thanks again for all your help
and thoughtfulness,

Sincerely yours,

2
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TAM i Cte