Pebruary 15, 1950.

li. Ellis Engleaberg,
Dept/ Bacteriology,
‘University of California,
Berkeley 4, Calif.

Dear Englesberg:

Enclosed are your application forms with Dr. Brink's endorsement
asbrequested. ;

In general, your prospectus seems satisfactory. However, I think that
it might be worthwhile having it retyped more neatly by a professional
typist, as it is long enough to be somewhat tiring to read in its present
form. If you have time to revise, I would recommend that somewhat more
emphasis be put on the general problem, viz., the conditions of spon-
taneous mutation, and the possible role of normal metabolites. To the
list of substances with such functions, which should be investigated,
might be added peroxides and (in mammals, at any rate) cyanate [from urea).
After the generalized atatement would be the more appropriate point to
mention the more specific lines of approach -~ the correlation with growth,
and the particular work with formaldehyde. I think that 4t night be
advisable to stress that your predoctoral experience has been primarily
biochemical and bacteriological, and that the postdoctorate fellowship
might serve to widen your experience with genetic techniques and coneepts.
That is, a postdoctoral fellowship should have a broader function thah
the prolongation of a predoctoral research project. I think that it would
not be inappropriate to insfiauate this under section 9. The final paragraph
of this section as it stands 1s somawhat sophomoric, and the thought is
probabhy best put as the introductory statement of the problem.

To turn to a more scientific issue, I have lately been studying the
mechanism of bactericidal action of a number of compounds, including
feraaldeByde, on diploid strains of E. coli K-12. Formaldehyde seems to
kil in much the same way as UV and nitrogen mstard, by chromosomal or
nuclear inactivation [I leave to your imagination how this can be shown
with the help of heterozygous diploid stocks], and I am therefore a little
surprised at your conclusion that it is not mutagenic for coli B. Did you
allow for phenotypic lag in looking for induced phage-resistance mutants?
I would be interested to hear any details of your experiments that you
can conveniently transmit.

Yours with best wishes,

Joshua Lederberg