| Dono GeuRee

‘ ole es Wis.

( Vm disn, | Wis )

March 15. 1950.

Dr. H. J. Muller,
Dept. Zoology,
Indiana University,
Bloomington, Indiana.

Dear Dr. Muller:

I am seeking your counsel on an issue that is somewhat related to
"mtational prophylaxis", and té which, therefore,-I suppose you have
given some thought.

Lately, we have been dtudying the mechanism of radiation killing of
bacteria, by examining the effects of X-ray and UV on heterozygous diploid
E,. cold. It may not surprise you that recessive lethals do not play a detec-
table role in killing, but that there is a very striking degree of "haploidi-
gation" of the treated diploid cells, which I assume to reflect grosser
chromosome damage and loss.

I next thought that this might be a useful mathod for classifying bacteri-

_ Gidal compounds and agents into those with predominantly "nuclear", and

predominantly "cellular" modes of killing. Nitrogen mstard, as expected,
gave the same results as radiations. However, we wore surprised to find
that quite a considerable number of other organic reagents gave comparable
results too, including: formaldehyde, dimtBhyl sulfate, acetio anhydride,
and hydrogen peroxide. Killing by heat, basic dyes, Lodoacetamide or iodine,
urethane, and some others, had no detectable genetic correlate.

These results raise a number of questions, some of first theoretical
interest. In view of the homologies, I think 4t ie likely that radiogenttio
effects are mediated by reactive compoundsy free radieaas, or tons which share
the capacity to bring about substitution reactions, like those mediated by
alkyl peroxides, cyclic ethenammoniun, formal, alkylating anhydrides, etc.

The results do not bear on the problem of the immediacy of the effects on
genes. But aside from this important theoretical question, I am led to wonder
whether the potential mutagenic effects [speaking very broadly) of such a

wide variaty of organic reagents does not create a hazard broader even than
those of Jonjzing radiations. Clearly, we do not know whether such agents

are likely to induce mitations in mammals, considering problems of penetration,
but it seems to me that this ignorance is potentially dangerous, for the same
reason that personal ignorance of X-ray effects is dangerous to the species.
I wonder whether this whole problem should not be brougtt before’ some
such body as the National Researoh Couhcil. Ordinarily, I Wold not be
very enthusiastic for programmatic research, but it ig obvicug that any
undertaking to investigate mutagenic effects of industrial Chemleals in
mammals would have to be organized on a large scale, and receaivs very
broad support, presumably from the Public Health Service or soke other
governmental agancy. I do not know of any existing institution that would \
be capable of absorbing such a program. But I think that you will agree
that no study of the toxleology of industrial compounds would be complete
if it left unrelieved any suspicion of potential mutagenic effects,

Pr

 

My own experience with such matters is so limited that I feek that any
comments you might make would be very valuable. Perhkps the problem is
exaggerated, but I have the feeling that, in our ignorance, chemical mta-
genesis poses a problem of the same magnitude as the indiscriminate use
of radiations. On the other hand, 4t would be unfortunate if these notions
were improperly publicised — I should not like to see many repititions
of the "Blastophthorie lead poisdning", which appeared in Eapedournal of
Heredity a year or so ago.

Yours sincerely,

Poy .
/ doshua Lederberg 4

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