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NATIONAL RESEARCH COUNCIL
CANADA

ATOMIC ENERGY PROJECT

CHALK RIVER. ONT.

October 31st, 1949.

Dr. Joshua Lederberg,
Department of Genetics,
University of Wisconsin,
Madison 6, Wisconsin.

Dear Joshua,

I was extremely glad to hear from you on the subject

or "delaved mutations", With regard to "segregation delay", I
had not realised that as many as half of your fermentation mutants
appeared as sectors (the proportion is not stated in your note on
the tetrazolium method of detecting mutants), and in the absence

of anything critical from my own data I had hesitated to do more
than indicate that a segregation delay had not been ruled out as a
contributory factor,

In this connection, have you any information relating
dose, killing, and ratio of "sector" to "non-sector" mutations,
since with increasing dose the proportion of survivors with two
viable nuclei should decline and together with it the proportion of
mutations which appear as sectors? I had thought of doing experiments
to see if this could be demonstrated, but gave them up as they
looked extremely time consuming. It it turned out that the proportion
of sector mutations did not decline with increasing dose one might
be forced to consider the possibility that the gene is effectively
double in some of the cells, although at the present time a nuclear
interpretation of sectoring certainly looks more likely,

I am grateful to you for having pointed out the
necessity of correcting for increase in C when obtaining average
rates. When this is done my ow data give approximately a five fold
difference between the two estimates of mutation rate tc phage
resistance.
Dr. Joshua Lederberg page 2 October 31/49

The model which you have used is easier to
visualise than one in which mutations may occur between fissions;
I had not realised however that this would sive estimates from 05
and from r which differ more widely than in the case of the Luria
and Delbruck model. It is diffucult at the moment to see how
the two models can be distinguished. If you eventually succeed
in getting heterozygotes which segregate for SR and SD, and thus
solve the dominance problem for this mutation it would eliminate
one of the unknowns, and perhaps enable dominant and recessive
mutations to be compared. Assuming dominance of SR, an estimate
of pure phenotypic lag could perhaps be got for this mutation from
irradiation experiments.

I am very much looking forward to discussing with you
the anomalous segregation phenomena in E. coli this Christmas. I
shall be going back to problems associated with induced mutation,
but my assistant will continue working on segregation effects using
the SR and SD mutants.

Thank you very much for letting me have yours and
Doudoroff's results. Is there any chance that SR introduced into
the other parent would yield a heterozygote which segregates? In
some of my experiments SD was introduced reciprogally into the two
parents, and the minority class was recovered in/orie out of the two
crosses. ‘

Sincerely,

Fi wih,

HBNibe Howard B, Newcombe