December 14, 1952

Dr. Lawrence L. Weed
Army Medical Center
Waahington 12, D.C.

Dear Dr. Weed:

Thank you for your kindness in letting me see your manmicriptdon B/Cu.
I am returning it herewith. e

You asked for ay critical comments. The only serious criticism that
occurs to me is the discrepancy between the introductory paragraph, with its
emphasis on the unelucidated role of environment in heredity, and the actual
content of the paper which makes only a passing reference to the genetic aa-
pects of the phenomenon. In tioular, as you say yourself, it is very diffi-
cult to prove whether the B/Cu form is actually induced, or simply selected,
by the Cu but this is the orux of the general introduction. It might be added
that gost bacterial geneticists are more optimistic about their understanding
of the "environment-heredity" question, and that, to me, at least your paper's
greatest interest would be in exposing a possible exception opposed to the bulk
of serious experimental findings on environmentally "induced" heredisary changes.
As, again, you have pointed out yourself EphRusei's work on petites-colonies
matations in yeast provides a very sound precedent. But 1t would be a mistake
to confuse the intense interest in this exceptional phenomenon with its role
in yeast inheritance, the preponderant mass of which is fairly ordinary mendeliem,
and therefore not so exciting. Dr. Spicer has the impression that you have a
rather more explicit case for specific inductioh of B/Cu than is presented in
this ms. ‘

I have some additional notes which are questions rather than criticisms.

pe 2: B/Cu can hardly be related to L-forms if their misrospopic morphology
is typically bacilliform. [I have been culturing some of Dienes!' Proteus L-type
growth, and its micrdscopic appearance is unmistakable. ] The L~forms present

such a confusing story that such a correlation does noone any benefit unless there
is some substantial basis for it. [I've fallen into this trap myself, cf. Cold
Spring Harbor Symposium, 16:438-439, 1951].

p+4 Inoculmm 5x10? B, in what volume? Presumably 10 al from the size tube
used.

ps Spicer and I were both surprised at your serology: I had thought that
B was ag rough as could be, and would be most interested to see a verified O and K
diagnosis. The lactose story is confusing. Does B/Cu grow any better in glucose?
Apparently not, if "a similar inoculum...would have remained small", Does it appear
more likely that reversion occurs more promptly on lactose medium. Could the small
colony form be due to a growth factor deficiency, inefficiently provided by the
usual complete media? If there is a specific lactese effect, it should be easy
to test for the formation of lactase using nitrophenyl galactosdé@e--I will send
you some if warranted.
p-7 foot. I could not understand just what you meant. Which correlations abe
erratic-—and there must be some explanation.

Bibliography:
4. LiInstitut 14. Not "Gleerupska University,"

But Gleerupska University-Bokhandeln,
5, Klieneberger—Nobel (I.E. Gleerupska, University Bookstore)
12. Kelner Probably a more intelligble reference

would be Acta pathologica, Suppl. 62.
for the identiehl publication.
20. 639-7007?

7? Where's Colwell, C?7A. 1946 Small colony vardanta of EB. coli.
J. Bact. 52:417-422. Her atory is almost as certainly related
to yours, as L-forms are not.

I will see what I can do now with Cu and with naphthaquinone on crossable strains
of E. coli, and will let know what goes from there. We should wait for this before
any serious discussions, I think.

Yogr suggestion of a visit to this lab. is appealing. However, we are very
cramped for space in the immediate future. Some remodelling is planned for this
Spring which may relieve this situation to some extent. I would much prefer a
longer visit that would permit some real progress on a problem, over a shorter
one. Do you think you could arrange an extended assignment? (10-15 weeks).

Of course we did run into sach other at P&S. But as younknow, I never did
return $o P&S after taking a research leave at Yale for what was to have been
a few months. Instead, I came here in 1947 after getting my Ph.D. at Yale.

a

Sincerely,

+

Joshua Lederberg =.
TOA CR! ]

 

FS.) MT LA MS ra
“a lf he ary tebe ng a ae
7 ,

f . - .
fp fff
f°? GABA AA OHI AT