Roscoe B. Jackson Memorial Laboratory

BAR HARBOR, MAINE

June 4, 1956 Cable Address
“JAXLAB’

Dr. Joshua Lederberg
Department of Genetics
University of Wisconsin
College of Agriculture
Madison 6, Wisconsin

Dear Dr. Lederberg:

Thanks very much for the reprints which I am much pleased indeed to
receive.

Over the past four or five years Nate and I have dreamed up ourselves
or had suggested to us an extraordinary variety of hypothesis to account for
the enhancing effect. Recent experiments have narrowed these down very con-
siderably and we now begin to get a real picture of the basis of the phenomenon.
It is probably a rather specialized situation. One of many original ideas con-
cerning it, suggested by a knowledge of Ray Owen*s work,but before Medawar's
demonstration of tolerance induced by treatment of the’ embryo,was that it might
be a tolerance phenomenon in what is now the accepted sense of this word.
This explanation now appears to be ruled out however. Evidently, contrary to
the first guess of both Medawar and myself, there are several types of immune
blockage or tolerance. In the forthcoming issue of Transplantation Bulletin
there are notes by both Billingham, Brent and Medawar and myself in which we
arrive at similar conclusions about the enhancing effect. As Nate Kaliss has
shown an antibody is essential to the phenomenon. It is surprising to find a
reversal of immunity due to an antibody although apparently the professional
immunologist accepts this a little more readily than a novice in this field
such as I am. The exact way in which the antibody works is still a matter of
speculation but the guess which both Medawar and I have advanced is that it
in some way blocks the passage of antigens from the tumor to the regional
lymph nodes thus preventing the development of the cellular immunity which is
most potent in blocking the growth of homografts.

Whether tolerance in the sense in which Medawar uses this term can be

induced in the adult is still an open question. There is some evidence that
it can.

If I remember correctly you recently suggested that the isogenic resist-
ant lines of mice could be used for a study of mutations in tumor by working
with tumors of the F) hybrid. I have just got a letter from Avrion Mitchison
in which he describes exactly this experiment. The results promised to be of
great interest; he seems to get sharp transformation to tumor types that will .
grow in the parental types. He speculates that this may be due to systemic somatic
crossing over. It looks as if he were going to have something very fascina-
ting here. . om . , 4 oy
ny, lai. rome , A w+ ween deny K; hh, , nmi nee Lert P- ~ ttn AS

With regards and best wishes, I am

Sincerely yours,

Ge D. Snell