September 1, 1946.

Dear Dr. Lindegren,

Thank you for your letter, and for the collection of reprints which you
sent. The data, in the Yeast Genetics paper in Bact. eve, on the inheritance
of vitamin recuirements in interspecific crosses in Saccharamyces ure of very
great interest,to me, in relation to what I have been finding in bacterial
crosses. In addition to the prototrophs which were described at Cold »sring Harbour,
a number of multiple-requirement recombination types have been isolated; in ud
dition ax a large variety of biochemical-virus resistances recombinations. He wever
there is a large departure from random segregations, resulting in a preponderance
of prototrophs, nd of types with only a single re:uirevent, in 6 or 7 fictor
crosses. It will be very difficult to study the basis of this deviation in the
material now uvailable; were that ve could do tetrad analyses, ts cun be done
in yeast! For that reason, I um very anxious to contribute whet I can to the
story there, anc the progr.m you suggested seems very sitisfuctory. is far’ as the
bucteria go, the discrepancies from rendomness may rest on any or all of the vol-
lowing buses: selective interactions; linkages: Hsays dosage effects (i. . cvto-
genes; or, pebheps 'Konversion' or intruceiiular trinsformition or, us you have
put it, absofption of cytogenes on ho recessive chrovopenes. e@ have Lhe sichimma
dilemma of explaining how relitively stable mutants can be gotten if the litter
consiucrations apcly. attempts at 'tronséorg-tiom'with filtrates hive beer uniformly
unsuccegsful, und the occurrence of multiple-requirement types his convinced me that
we have been hybridizing bacteria.

Sith best reggrds,

Joshua Lederberg