UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

BEWELEY * DAVIS . IRVINE LOS ANCELES RIVERSIDE SAN DlECO SAN FRASCISCO SANTA BARBARA o SANTA CRUZ

SCHOOL OF MEDICINE

SAN FRANCISCO. CALIFORNIA 94143

October 19, 1977

Dr. John Z. Bowers
Josiah Macy, Jr. Foundation
One Rockefeller Plaza
New York, New York 10020

Dear Dr. Bowers:

Thank you for your letter of October 13.  Frankly, it was my first news of Michael
Stoker's new job,  and I have written to him, asking for the confirmation you re-
quested.

As I explained in the preamble to my peculiar research plan, my activities were
likely to be determined in part by circumstances.  Since I wrote the plan, the
writing on the wall seems clearer.
the necessary reagents for the hepatitis work, and my realistic assessment is that
little or no work will be done on this project until I return to San Francisco  in
mid-1979.
feasibility of initiating the molecular cloning experiments in Londor-.
cratic obstacles appear large and cannot be overcome from this distance.
moment, my plan is to ask after I arrive for permission to do one experiment---
cloning of mouse mammary tumor virus integration sites from mouse cells, using a
polyoma vector.
and the additional virtue of utilizing Mike Fried's expertise with the polyoma
system.
the newly-recommended guidelines for recombinant DNA research; these new guidelines
would allow us to proceed with most or all of the proposedaloning experiments,
using plasmid vectors,  in our local P3 facilities.  As a result of the abovediffi-
culties, I am planning to pursue most actively the plans to generate deletion mutants
of avian leukosis viruses.  This project has the advantage of integrating me most
fully into life at ICRF (both with Mike Fried as advisor in making deletion mutants
and with the RNA tumor virologists as consultants about the biology of leukosis viruses).
Moreover, I think the feasibility of these studies is very clear, and their potential
applicability to several aspects of my research program very appealing.

I have had considerable difficulty obtaining

Secondly, I have been corresponding with Mike Fried at  ICRF about the

The bureau-
For the

This experiment has many virtues from a biological point of view,

The rest of the cloning plans will presumably await NIH certification of

I hope this explanation helps to clear the muddy waters.

Yours truly ,

Harold E. Varmus, M.D.
Associate Professor
Depart ment o f Microb io logy

HEV/es