June 19, 1952

Dear Dr, Inoki:

Thank you for your letter and the papers which arrived a day or
two ago. Your account of antigenic variation in Trypanesoma was
very interesting indeed. You certainly should seek to present it
at the International Congresses next year, if you can find funds
to travel to Europe. I do not see just how I can assist you in this
respect. If you travel via the U.S. I hope you will have an opportunity
to visit Madison, and to discuss the possibility of working here for a
time. I am doubtful that this laboratory would be the most suitable, as
we are mainly interested in bacterla, but I trust you are also in correspon—
dence with Professor Sonneborn.

On the face of it, your interpretation of the antiserum-induced variation
seems entirely correct, although it seems incredible that such changes could
occur so rapidly in a medium that will not support growth of the trypanosomes.
It should be noted that some of the Paramecium transformations will occur in
a few hours, before any fission has occurred, but you should consult Sonneborn
for the details.

Your note on Trichomonas was most interesting, but I regret that I am not
competent to evaluate it. For your trypanosome work, I think that it would be
desirable to report some more experimental details, especially the controls
which show that , in vitro, the induced return to the original serotype
gives trypanosomes which react specifically with serum for the O- and none
of the others, I appregiate the limitations of using mouse—serum for the
reagents. Would it not be feasible to vaccinate rabbits to obtain larger

quantities of antiserum for each of the serotypes, especially
for the in-vitro experiments?

It is indeed surprising that, in your vaccthnation experiments, trypano-
somes which respond in a few minutes to antiserum in vitro remained unchanged
for many days in vivo!Have you tested freshly smwarxx drawn blood mixed with
trypanosomes} mmx Can you inoculate a heavy dose of O- trypanosomes in an
O-immune mouse, and then remove blood samples, keeping them in vitro for
various length of time to look for the change?

Metallagy 1s as good a word as any. Before introducing it into the litera-
ture, itb might be better to wait until the mechanism fs more thoroughly
understood.

Are you acquainted with other work on antigenic variation in
trypanosome pelapses (and with the comparable studies on Borrelia)?
They are reviewed by Harrison in the Ann. Rev. Microbiol. 1947. I
did not understand the reference 15. in your paper from the Osaka Un.
Med. J.

Sincerely,