October 25, 1951.

Dr. Klaus H. Rothfels
Department of Botany
University of Toronto
Toronto 5, Canada.

Dear Rothfels:

Your ms. (private copy) arrived a few days ago, not long after the
original was received by the Editors of Genetics, which is now located
in this Department. It will not surprise you that the Editors asked
me to review it, but there does not seem to be mich point in pretending
anonymity. I have asked them, therefore, to return the original for
your use in any revisions, while my annotations are madé in red on the
draft copy you sent me.

Most of the comments should be self-explanatory; a few are of a more
general nature, as follows:

You have, of course, formal permission to refer to any of our unpublished
work. Howeverg rather than cite it ea such, I suggest a citation to
the CSH manuscript: Lederberg,J., Lederberg,E.M., Zinder, N.D., and Lively,
E.R., 1951 Recombination analysis of bacterial heredity. Cold Spr. Harb.
Symp. 16: In Press. The reference may be completed in proof if the pagina-
tion is learned in time. There are very few if dny places where this
would not be preferable. The reference to Cavalli (p.2) is: Cavalli, L.L.
1950 La sessualita nei batteri. Boll. Ist. Sieroterap. Milano 29:21-29.
The same thing might be done for Delamater: mitnme his CSH paper, A new
cytological basis for bacterial geneticsyyete. Finally, some points of
our unpublished work may be covered in ay chapter in Genetics in the 20th
Century (MacMillan 1951), for which I regret there are no reprints.

I hope you will note my suggested amendation of your acknowledgment,
for which I thank you.

Was your abbreviation of "N. & N."* intentional? If so, it should be
explicit: e.g., Newcombe and Nyholm (N.&N.). If the editors accept this,
the same might be done for L. or L. et al.,

The usage of Het 4s, I think, quesaionable. It was an unfortunate ab-
breviation for a hypothetical factor leading to nondisjunction or restttution.
The resulting exceptions should, I think, be called heterozygotes, persistent
diploids, or unreduced exceptions. Het and the crossover regdons a, b, ¢ etc.
should be underlined.

Four points of gontent rather than form:
The discussion of L, is still somewhat obscure, both as to the hypothesis
for its origin and the experimentak justification for it. p/8 mehtions
Leucine-inhibited prototrophs, but suggests they are elaborated upon later,
which I cannot find. Their occurrenge might be emphasised more clearly.
Also, what account is taken of L-Lm as a possible missing class? Do you
have any direct evidmaee (e.g. from TL crosses) of its ocuurence? If you
happen to have saved an L+Lm- culture, I should appreciate the opportunity
of handling it.

I think there may be some hedging on the revertibijity of M@. I have never
gotten 2 protottroph from 58-161: Have you? If not, it might be worthwhile
saying so.

This may be picayune (except for some of our data), but linearity is
really well established by this work only for Lac-V,-L-T, and the inclusion
of Min the series is more inferential. Miss Fried has been repeating some
of the S° x TL crosses in Mesupplemented medium that I wrote you about
earlier, and can find no evidence that M and Lew are linked.The frequency
of "a 0.0." is detergined by something else (segregation anomaly?)4 I don't
mean to insist on this point which is based on work largely suggested by
your paper, but I thought the comment would interest you whether or not
you wished to amend the ms.

The latter also applies to the next point of information which relates
to the qgestion of p.16. T-L- mugeagatiomexfs segregants from your TL-
eross give markedly abnormal or rather novel linkage behavior, in my one
experience. If you can confirm this, I would be delighted. The alteration
appears, however, to influence the relative frequency of “a C.0.", rather
than the other relationships along the arm. Would you be interested to
do a comparable study of TL-sgoplemented crosses using such a parent? -
perhaps this is what you meant by the backeross studies you were tempted
to do,

This is about all. To turn to less officious matters, I hope that you
did submit a discussicn based on this work for the CSH volume. I had con-
flicting reports from Newcombe and Mrs. Warren, both of whom should have known.
Thanks for pointing out that slip about interference. I remember our
talking about it, but am not sure whether itcwas finally corrected.

We've gotten onjo a curious byway on streptomycin resistance. Did you
notive that many S recombinants in your cresses were unusually mutable to ,
s’ ? This sees to be the case and suggests that the mitation from S° to S
may occur normally in two steps, the first stage being the highly mutable s§,

Sincerely,

Joshua Lederberg