IN REPLYING. ADDRESS THE
PUBLIC HEALTH SER"lCE

FEDERALSECURITY AGENCY

  PUBLIC HEALTH SERVICE
     WASHINGTON 25, D. C.

REFER TO:

Tbc. Research Laboratory,
l+ll E. 69th St., New York Zl, h1. Y,

March 9, 1949.

Dr. Jo&da Isderberg,
Department of GenetLcs,
The University of Wisconsin,
College of Agriculture,
Madison 6, Vfisconsin.

Dear Josh:

     Thanks an awful lot for sending the stock of mutants;
you certainly do have a talent for translating thoughts i.nto action!
It is very difficult to interrupt the chain of ex,periments which
flow so naturally from one to the next, but Kerner or I will definitely
be starting on K-l.2 very shortly.

     Some spurious excitement fflled the lab this Past week.
WC just got a mutant which responds to alpha-amino-butyric acid, and
also grows very well on casein hydrolysate,  I had visions of iden%i-
fying a new amino acid in animal protein but the spot tests, which at
one day showed growth only on this compound, showed .respohse to
isoleucine on further incubation.  This still is an interesting problem
because the bug requires about three tiaes as much Ssoler;cine as it
does alpha-amino-butyric, and it is very hard to explain these findings
in terms of possible impurities.  I am going to try to track this down
a little farther but certainly don't hsve any evidence with several
protein hydrolysates that cannot be accounted for at present by their
contents of isoleuci;le,

     I have been continuing with the phenomlc barrier to back
mutetlon, switching to a more quantitative type of experiment on pour
plates, and have obtafned even more dramatic results with the trypto-
phane-requiring mutant than with the pantothenic one that I showed in
ChIcago.  Pantothenic seenv to be a poor one to work :vith since in some
experiments it grows 2 bit in minimal medium, and in others not. I
pmsu.me the amount of ava?.lable stored material varies with the
physiological state.  The tryptophane mutant, however, seems to be
absolute and well suited to this kind of analysis.

My best regards to Esther,

Bernard D. Davis

BDD,'hl


-2-

Dr. Joshua Lederberg

  P.S. - Incidentally, the back mutation of the tryptophane mutant was
not promoted, either in streaks or on pour plates, by the presence
of a purine requiring mutant growing on a limited amount of adenine.
w@&-waa promoted only by tryptophane itself, This strengthens my
  canbidbnum in the original interpretation.  I don't thir& thia
  necessarily should discourage one from ctte  ting m quantitative
  frequency studies with revertse mutations. -8 number of W induced
mtiations to tryptophane independence 80 far exceeds the spontaneous
ones that one shodd not have to worry about the correction for plate
mutants that might be produced by adding a little tryptophane to the
  medium.  I do wonder, however, how much validity there would be to
  measurement of back mutation rate on minimal agar.  I no&e that Guthrie
  has been carrying out such studie8.

B.D.D.