AB
(v July 30, 1946.
Dear Dr. Luria-

I have spent the past two wecks on a wild goose chase: finally managing
to secure two Houble biochemical mutants in B/r (Y38-Y43 arginine;pethionine
and Y39-Y44 histidine;p-auinobenzoic ac.) Several experiments at attempting
to get prototrophs from their interaction, and from B/r and K=12 mutants,
have been entirely negative. I do not think,therefore,that you will have any
particular use for them, This is a fortunate occurrence, because it connects
very beautifully with the observation that you stated in your last letter
that your recent experiments indicate no recombinations of virus resistance
in B. It is clear then,I think, that we shall have to continue to work with
K-12 strains. If you have other strains of E. coli (preferably motile-just a
hunch of mine} which are susceptible to this series of viruses I might try
the same with them. I am looking very hard for a possible instance of ‘hetero~
thallism,'

Thank you very much for the informtion on the phage susceptibility pattern
of K~12. It does look kk like there may be a lot of material here. I would
suggest that it would be important for you to ascertain whether complex

OOOOCOL
resistance mutants occur in K-12; if so there 1s the chance of analysing
them. I have gotten what I think are some recombinations of biochemical
requirements and virus re.istance (aside from resistant and susc.ptible
prototrophs} but I'll have to look into that more carefully. Also, from
the ratios of resistant and susceptible prototrophs in various 'crosses!
there seems be be some sort of linkage (about 5@ %) between resistance to
T-L and sither proline or threonineless,. Since this will complicate con-
siderably any use of bicchemical factors as selectors, more work will have to
be done with a vraiety of these mutants to find sets that will allow a more

random distribution of resistance in the prototrophs.
I feel compe ent
to work with the segregation of single resistante factors,but I am very
anxious for your collaboration,or rather to collaborate with you, on the
complex mutation problem.(A word on terminology- I mean by complex a
phenotype different in several characters obtained by a ‘single mitational
step' as distinguished from maltiple mitations which are obtained in
iterated steps+)

I eatpect to be in New York in about two weeks, and will endeavour to
visit you, bringing the latest informtion, and possibly the most suitable
cultures. This is not certain,however; I would appreciate it if you could
let me know when you expect not to be at Cold Spring Harbour.

Very sincerely yours,

Joshua Lederberg.