December a, 1953

Dr. Lawrence lee Weed
808 Nerth Broadway
Baltimore 5
Maryland

Dear Larry:

Z had just eat down to composes a letter to you when your own of
the 15th arrived, I am glad to hear that you have not been irrevocably
lost to sclense am! that your laboratory work remains your first lowe,

I had meant to write you that Miss Helen Byers, who has been take
ing the copper problem under hey wing for the time being, has finally
svocesded in sorting everything out so as to be able to reproduces your
principal findings, That is, she can consistently obtain very large
yields of the small colony variant by means of the copper treataent,

t seems now that the main reason for our former difficulties was the
fact that the culture of E, strain B was heterogeneous in ite con~
tent of types susceptible not susceptible to this copper effect.
The B straine that we had in the laboratory before consist primarily of
insuseeptible types, These are only very preliminary findings and may
perhaps not beer close future scrutiny but at any rate Miss Byers cox
has souething very tangible to go on by way of the extension of your
findings, Our immediate objectives are, of course, the difficult prob-
lem of deciding whether the effect of the copper is inductive or sel-
ective and as well genetic studies on the tyve of mutation that is ine -
volved, provided that we can get tbe emell colony variants in adequate
members in suitable strains,

Untdl this issue is decided I would not know how important a more
detailed biochemical analysis would be. If the copper bug is merely a
selected, spontaneous, resistant mtant the problem would not be nearly
so significant as it would be if the effect is inductive, We will, of
course, let you know of any substantial results at the earliest occasion,
but the problem is likely to be a tricky one,

Professor &, Rubbe, from the University of Melbourne, is visiting
ua for a period of a few months we have taken this occasion to do a
little bit of wrk with yeast, would suggest that, at least for a be«
ginning, a more profitable investigation of comparative maoleic acid con-
tent would be a studyof normal and “petite” colony yeast. We will be

very happy to provide you with relevant material if this project should
interest you.

Have you noticed, by the way, a series of papers in the J
Botanical magazine (volume 65, page 771, 1952) on "The Adaptation of
Page 2 « Letter to L. weed December 71, 1953

Yeast to Covper." The analysia seems highly confused but one possibly
pertinent conclusion was that the RNA extracted from copper-resistant
yeast was much more effected than that from sensitive yeast in counter-
acting the toxic effect of copper. You might be interested, also, to
note an old paper (1919) by Sturgess, Jour. of Bacteriology 1157, which
refers to the effect of copper in the sewage effluent from the Winchester
Arms work in causing a delayed development of colonies ont est plates,
There is not a small chance that he was observing your phenomenon,

Larry, I am really glad to hear that you are getting back to bio-
chemical work and I hope that this will give us an opportunity for a
closer collaboration than would otherwise have been possible,

With best wishes for the season,

Yours sincerely,

Joshua Lederberg