CARNEGIE INSTITUTION OF WASHINGTON

.DEPARTMENT OF GENETICS

COLD SPRING HARBOR, LONG ISLAND, N. Y.
July 17, 1947.
Dear Lederberg,
a With regard to the experiments on delayed @ffect,
I dont think it is possible at this stage to déscriminate between
. the possibility that the end point mutants are the result of
delayed alteration of the genotype, and that they are the
. G@layed phenotypic expression gene mutations produced -earlier.
~ In the untreated material all that can be said with
certainty is that there ‘is an excess of mutations associated with
the lag and early logarithmic growth phases. These may be the result
of a genuine high mutation rate or they mey be the delayed expression
of gene changes ocourring in the resting stage. IT am sure that
they are not a mere accumulation of gene changes occurring at the
normal rate during the growth prior to the resting stage am which
~have failed to express themselves phenotypically, as it roula take
twenty generations at least to produce the observed numbers of

the excess. .

-The experiments done with irradiated’ material are not
terribly critical as the results seem to depend oh the design of the
experiment. They do however cast doubt on the concept of the
end voint mutants as the result of a finite number of changes.

In those exreriments which I have done there is a fixed or slightly
rising number of delayed mutations occurring as the result of

each generation. After a certain number of generations this
fixed increment is obscured by the spontaneoud mutations which become

more numerous as the ponulation increases. This imposes 4 practical

limit on the determination of the end point number, and true end point
number may be greater than estimateé cr may de infinite in which case the

concept is meaningless. A better description might be "induced mutation
ee

Livds ws

rate per clone per generation” since such a ficure seems to remain
pretty constant over the period of growth during which it cen be
measured, . ‘

‘© E would not like to be quoted on induced mutations es

‘the work I have done has not been sufficiently detailed: the

work on srontaneous mutations is now pretty conclusive, however,

and may be quoted “if ‘your review ccvers that aspeot of the

, Subject. It would naturally be better if we. could have a chat

about these thing, end I wish very much that you would have

a chance to visit us before you leave. i
_ & mumber of us have.been wondering. if it.would be

possible to induce you to come here for a few days: and. to

show us your techniques, aS we ought oe know. whether the induced

mutations we arte working with behave the same as pther genes.

, This would of course mean inducing “mutants in K-12 and doing

recombination studies to make sure that they ere not just sonie

€

. peculiar surface phenomenon.

However, you will probably hear further about this

from Mrs. Witkin if she is able to make the necessary arrangements
at this end,

All best wishes,

Sincerely,