January 27, 1949.
Dear Iurta,.

I will be very glad to submit a@ seotiorw on biochemical mutants
and genetic recombination in bacteria, for "Methods...." Can you
get for me information on a) style of references bd) reprints
o)length of art#oles d)as soon as possible, the other contri-
putors and the subjeots theywill cover? I expect I will need
not more than about 10 pages altogether. Professor Riker here
is very muoh interested in this project. Apparently, the AAAS
Committee on Genetivs of Pathogenic Mioroorganisms had oonsidered
sponsoring a cooperative book on methods, but they will probably
withdraw.

fhe problem that you suggested was taken up by Szilard a long
time ago, and there 1s no entirely satisfactory solution. I've tested
a considerable number of single colony isolsutes of the parents in
# crosses} there was no remarkable fluctuation in yield, but that
might be expected. Until the aberrant segregations in the hetero-
zygotes are cleared up, I don't think they coula be trusted for
the backeross experiments indicated. The fspontaneous" heterozygotes
(from cultures without "H") unfortunately show the same aberrant
behavior. I am beginning to wonder whether this aberration occurs
even in the "normal" formation of prototrophs, and that the hetero-
zygote behavior is just superimposed on this, and unmasks it. It
would probably have to come from the B-l- parent, so I have been

getting heterozygotes from other crosses. A biotin-histidineless
erossed with 4 TLB, "H" stock also gives aberrant heterozygotes
(abnormal segregation of Lac , etc), but the abnormality may
have come in with the biotinless. I've started crosses with
your tryptophane-adenineless, and find that it gives very satis-
factory yields of prototrophs (rather higher I think than in
comparable tests with BM « TLB,), but the weak fermentation of
lactose, maltose and glucose by this strain is a nuisance,

I would appreciate it very much if you could send me the single
mutant .from which you prepared the tryp-aden, and any other K-12
mutants that you might have which are not derived from wither
the biotinless or threonineless series that I have been using.

I hope that ML works out all right; it is the most mutabile strain
I have ever seen.

As I predicted during the seminar, Lao,- adapted on butyl-
galactoside does utilize lactose (although the enzyme is not main-
tained), while on lactose, the enzyme is not developed. Conversely,
the wild type which does not utilize lactobionate, responds to it
by forming the galactosidase. This should serve quite well to sepa-
rate the enzyme forming system from the enzyme itself.

See you in Chicago,

Sincerely,
Joshua Lederberg.

P.S. Could I ask you to send me your birthdate and not ask me
any questions about it? Thanks,