Frank H. Dickey

Department of Chemistry
California Institute of Technology
Pasadena, California

November 29, 1949

Professor Joshua Lederberg
Department of Genetics

The University of Wisconsin

College of Agriculture

Madison 6, Wisconsin

Dear Professor Lederberg,

I was glad to hear from you again. It had been my intention to send
you a note about our genetics work but I never got around to it. Your
surmise that the article in Heredity had excaped my notice was fully justi-
fied. Indeed, I have not read it yet and I will have to defer an extensive
comment until I have done so. However, two points occur to me on reading
the derivation given in your letter.

First, Neurospora conidiospores are multinucleate and one might sus-
pect that a spore would remain viable as long as a single nucleus had
survived the treatment whereas the appropriate mutation in a single nucleus
would lead to a counted mitant. It has been shown, for example, by hester-
gaard et al in the latest issue of Hereditas and in our om work, that the
mutant colonies are heterocaryotic for the reversion to wild type. This
problem is further complicated by the fact that mutations preventing the
independent survival of a nucleus may be compensated in some measure by
the presence of nuclei not affected in the same way. Accordingly, I am

not sure that a 63% mortality should be expected to give the greatest num-

ber of mutants although I would certainly like to think so.
Secondly, we have been concerned with an idea that is moreor less of
an obvious corollary to the one that you mention. If it is assumed thet
all mutations arise through the same mechanism and that the poverful muta-
gens kill only by the induction of lethal mutations, then all such mutagens
should lead to the same maximum mutation rate based on the number of
treated individuals. Our most recent datasuggest that a number of chemical
agents produce the same mutation rete under optimum conditions but ultra
violet light clearly prodvces a rate about three times higher. I have
tried, vainly so far, to relate this d&screpancy to the fact that there are
several nuclei per spore. If you have any ideas about this problem ve
should certainly like to hear then.

Finally, I would point out that all of this stuff breaks down if it
develops that genes do not show the same relative response to different
agents. We have been collecting unstable, biochemically deficient Neur-
ospora strains and are just starting to measure their back-mutation rates
after various treatments. This work is only barelyunder way but we have
been astonished to find in our preliminary experiments evidence that the

relative
/potencies of different mutagenic agents are not the same vhen they are
applied to different genes.

I also am still hoping that you can find time to repeat the specific
adsorption experiments. If you do get a chance to try it , though, it
would be a good idea to write for the latest receipt since some progress
is being made in improving the technicues.

Regarding water elution of the gels there is no experimental evidence

to show thet this would be harmful. I have always used mehthanol. Obviously,
though, water might accelerate a deterioration of specific configurations

of the surf ace. Moreover, if water were to be used as the eluent it is
likely that a special technique would be required. I am working on a

paper (for presentation at the Houston ACS meeting) that will contain

some information that it would be important to take into account before
applying these procedures to lactose. I will send a digest of this material
as soon as it is in reasonable order.

All of my completed experiments have empioyed a Simple Soxhlet extractor
for removing dye from the gels. However, there is reason to believe that
the gels lose their properties with aging and hence it is possible that
cold extraction would give much better results. Samples prepared by
extraction with cold methanol in a colum have just been finished and
their characteristics will be determined in the next week or so,

The study of the catalytic action of specific adsorbents is still
entirely inconclusive. Gels have been prepared that were intended to
simlate the action of invertase, catalase, and carbonic anhydrase but
no definite results have been obtained. The first named, simply a gel
prepared in the presence of sucrose, showed a spectacular positive :»esult
but a careful analysis of the experiments shows that the controls were
inadequate and the work will have to be repeated.

I will have more to say «bout all of these things a fer weeks hence,

| Sincerely yours,

Cah Leeds

Prank H. Dickey