July 3, 1959

Or. J. Letn
Bristol Laboratorles
Syracuse, New York

Dear Joe:

| just wanted to bring to your attention this enclosed note
by Schwartz and Dameshek which relates very closely to aur previous
discussions of screening for substances to modify the immunological
response.

1 might say that the selection theory of immunity, which by
the way reached print in SCIENCE for June 19th, did receive a
Sympathetic reception wherever Burnet and ! talked about it in Europe.
| mention this because the theory gives so much more stralght forward
an explanation of Schwartz's results than the one he proposes in
this note.

This report does substantiate our general feeling that we might
very well find such effects among agents otherwise suitable for cancer
chemotherapy. It Is even possIble that 6-mercapto purine wi!! have
some advantageous use in this way although one would certainly want
to look for additional compounds of lower general toxicity, that is
compounds with a more selective effect on the antibody-forming system.
| would take this report as a strong encouragement to continue with
this type of work. As an early step, it might well be worthwhile
to see whether 6-mercapto purine will give a positive result in the
screening methods that we had discussed earlier. Those methods might
be much cheaper and more convenlant than the ones used by Schwartz.
There is one contro! missing [n Schwart's results that Is the effect
of mercaptopurine without the antigen at the same time. It is conceivable
that he has induced not so much tolerance as a more generalized loss
of the capacity to respond to a certain class of antigens without the
antigen itself having played any role in the development of this
nonreactivity. This is a little less likely In view of the distintive
results with globulin antigen but he still does not have as clean an
experiment as one would like. 1! have heard by the grapevine that
Ben Rubin has followed thés experiment by successful skin transplantation
but more work certainly has to be done In this area. It Is quite likely
that Nossal and | will be doing some experiments along these lines.
However, these will be from the point of view of elucidating the
mechanism of tolerance rather than screening for Interesting reagents.
If you do enlarge a screening program {| think it Is quite poss!lbéeé we
might have some interesting possibilities for collaboration.

1 don't have anything to add to the telephone conversation that
we just completed and | am very much looking forward to seeing you again
on your way through this fall.

AS ever,