March 7, W72

Dr. Robert J. Huebner
Chief, Viral Carcinogenesis Branch
National Cancer Institute
Bethesda, Maryland 20014 RE: Your letter of 2-17-72, and

Proc. Net. Acad. Sci. 2:20-24 (1972)

Dear Dr. Huebaer,

The last paragraph of our paper vas intended to refer only to the
provirus hypothesis. The point is that we have to date been unable
to perform a definitive test of that hypothesis because of the presence
of virus-specific nucleotide sequences in DNA of the various nonnal
cells we have been using.  Because of the limitations in sensitivity
of the Gelb-Kohne-Martin technique, the presence of virus-specific
DNA in normal cells could obscure a mall but sufficient increase in
ouch ahuences as a consequence of transformation.
a system in which the nom1 cell is completely devoid of RSV-specific
DNA.
provide a good test of the provirus hypothesis. We now seem to have
our hands on such a system - nonual and RSV-trsnsfonwd 3T3 cells.
We should have definitive data shortly.
foregoing has little a0 nothinfgto do with the oncogene hypothesis.
We also recognize that although we have yet to obtain data which can
refute or confirm the provirus hypothesis, our present data provide a
physico-cheraical correlate to the biologicel data from which the onco-
gene hypothesis derives.

What we need is

$xaaination of such cells following transformation by RSV would

We recogniseothat all of the

We were certainly rcwaiss in omitting a reference  to the work of yourself
ahd 8, Sanaa, and apologirte for this overaight.

Thank you for your comments,
our work.

We appreciate your continuing interest in

Sincerely,

J. Wichaef Bishop, H.D.
Associa tc Professor
Depa r men t o f Xi c robi o logy

Harold E. Vamus, M.D.
Department of Microbiology