September 20, 1950,

Dr. R. R. Mellon,

Western Pennsylvania Hospital,
Institute of Pathology,
Pittsburgh, Pa.

Dear Dr. Mellon:

I au sorry not to have answered your letter of August 7 sooner, but
I was spending the summer out of town and could not give it the attention
it deserved.

Lindegren is quite right in pointing out the existence of genetic
variations which can be shown not to be gene mitations, and his "red yeast"
case certainly provides such an example, although 7 do not quite apree
with his interpretations of it. Without crossing tests, it is of course
impossible to verify the genetic basis of a variation. However, fron my
own experience with “, coli, I doubt that such pseudo-mtations are very
common, although your own case of mucoid ~ t@= smooth in streptococci
may very well be such. In general, I think it safest to regard variations
as gene mutations, unless it cmbe shown otherwise. The role of acetate
in your system is the sort of thing that makes it very doubtful that the
i> change is an ordinary mutation, and it may very well be based upon the
loss of some cytoplasmic constituent, like kappa in Paramneciua.

A propos acetate, I would appreciate having 2 (another +?) copy of
your paper on the acetate effect which appeared a couple of years ago in
J. Bact. Do you have any further data on this system, in particular on
the population dynastes of the shift? I would be dolighted to hear about

Yours sincerely,

Joshua Lederberg,
Associate Professor of Genetics