TRANSCRIBED FROM RECORD RECLIVAD 4/2/58 FROM Da. LEDERBERG

Madison, wisconsin
March 31, 1558

Dr. Joseph Lein
Bristol Laboratories Inc.
Syracuse, New York

Dear Joet
Welcome home}

I can see that you were as much seduced by Japan as has been every
other one of my friends here who has been over there. we can't wait
for the experience ourselves.

i am really delighted to hear that you are moving, ahead on the
substitutional chemotherapy program. I fully understand your
position with ro,ard to the virus ap lication and will use my
discretion. iiowever, as 1 am sure you understand, you can hardly
hope to kvep a monopoly on a general idea for very long. Such
notions usually crop up in many places at about the same time,

On the wholc, 1 think it is a wiee thing to start the exploration of
this possibility with the systen that you can most conveniently handle,
namely, the antibacterials. If it should prove to be outstandingly
successful, which woulda be rather mush to hope for, then of course you
would use your ow judgment about the range of systems to apply it to,

A propos applications in tumor chemotuerapy, 1 can see at least as much
rationale in usin: the substituted products of b,. coli against tumors
as I can see the use of antibiotic broths. ihe time Hay come, however,
when you may wish to consider as the sources of the subatituted
products, the tumor cells themselves.

Would you not expect that most antitumor agents woula be likely to
be quite toxic to early developmental Stages; If so, then 1 wuld
think that a measure for use in the extraction of sone agents might
be, for example, toxicity to growing chick eggs. Ferhaps this is
already much more cumbersome a technique than you would prefer to
have,

The idea of using concentrated groupe of metabolites as sources of
substituted products is entirely sound, After all, from the broadest
point of view what you are trying to do both in the actinomycet
broth program and in this one is to get reasonable amounts of the
largest possible variety of hitherto untested organic molecules. So
it should hardly matter very much what your starting materials are.

The account of your progress in the delineation of antibiotics.
particularly active on synthetic medium sounds most exciting. tven

if some of the compounds prove not to be of trenendous chemotherapeutic
value, if nothing else, you may lateh on to a sericea of very useful
J. Lein 2 3/31/56

anti-metabolites of specific activity. This question of the unique
sensitivity of strain 112 does puzzle me, The only thing related to
it that I can think of at the moment is that it and strain C and to
& lesser extent strain B are among the most generally sensitive of

E. coli strains to various colicins. It is hard to imagine what
relationship they would have to the product you are now testing. K12
and C are, furthermore, both rather degraded from a serological
point of view having long since lost most of the typical somatic
antigens of E, coli group. If you will let me know how the results
of your current tests of strain specificity work out, it might give
me something a bit more definite to go on on what the unique sensitivity
of K12 might be correlated with.

i am a little surprised that you are having much trouble growing many
strains on the Davis medium. If you are serating the cultures by
bubbling, I would suggest that you supplement the trough=-put air with

a@ little carbon dioxide, for example, by passing the air over some
sodium bicarbonate before it enters the tubes. We have had some trouble
from this source in the past.

A propos vitamin C, it looks as if someone has beaten you to the punch
on this. While you were away in Japan, I sent Amel a sample of a
product called "Daily C" which is precisely what I was speaking for.
Whether this has any affect whatsoever on colds, who knows? Before
Bristol or any of its affiliates got into this particular game, I would
hope that there would be some laboratory experimentation, at least to
substantiate possible antibacterial activity of such a preparation.

Esther and I are leaving Tuesday to attend a meeting sponsored by the
Oak Ridge National Laboratory on Genetics of Somatic cells. Then
after coming back Saturday, beginning the following week, we have our
Symposium here on Genetics in Medical Research, I am afraid this is
going to be rather a chore, and that is one reason I hasten to

answer your record now.

For these reasons, I have not anticipated coming down to Chicazo, but
if you will be there, I will reconsider the possibility of coming
down for a day. If I do come down, I will look for you, but if you
want to tell me what hotel you're staying at, this might be helpful.
I will let you kmow if anything especially excitin, turns up at the
meetings.

A propos substitutional chemistry for tumor activity, I am sure that
one of the reasons you mentioned using groups of materials was the
prospect of getting analogues of nucleic acid components. Certainly
one would want to push that aspect of it at least as hard as any of
the others.

Dr. Cavallia-Sborza, with whom I had the luck to collaborate before, is
going to be in the lab for just a couple of months this Spring, and I am
hoping to do some concentrated research for a changes
Signing off for now, with all best regards.

Yours,

Joshua
JLeac
J». Lein 3 3/ 31/58

FP. S.As your secretary is going to tell you, there is some
dis-synchrony between our two machines, If you have too much
trouble reading this disk, do you want me to go to the service
agency here and adjust ours to your records, or Vice versa?

i was assured at the last occasion that this machine had been

adjusted to the universal standard of speed, whatever that
happens to be.

End.

Josh.