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: OFFICE OF THE PRESIDENT
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February 14, 1990

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Dr. Robert E. Kohler

Department of History of Science
University of Pennsylvania
Philadelphia, Pennsylvania 19104

Dear Dr. Kohler:

Thank you for letting me have your manuscript on George
Beadle and Biochemical Genetics. I very much enjoyed the
approach that you took. (The copy you gave me was lacking
page 1 and I hope you can replace that.)

I was especially gratified to learn of Jack Schultz's
involvements which, as you say, were mainly unpublished. He
was quite a man!

You have a point about Drosophila nutrition having been
a precursor of the idea of moving to Neurospora. But I think
you may be highlighting it a bit more than the evidence would
demand. There is no indication that they had any expectation
of finding, and therefore of looking, for mutants with altered
nutritional status in Drosophila. They had to think about
synthetic media if they were going to use feeding as a much
more convenient method of introducing intermediates than by
transfusion. But you do have a point and certainly they be-
gan their work on fly nutrition a couple of years before
Neurospora was introduced.

To this day I just don't know whether anyone has gotten
a nutritional mutant in Drosophila. You might want to check:
the Drosophila catalogs on that point! It's rather difficult
to do, since one has to maintain strictly sterile conditions;
and that would have been multiply difficult beforé the advent
of antibiotics. I don't know whether Drosophila, as would be
the case for many other insects also have symbiotic bacteria
(as part of their "extended genome") and that would further
complicate nutritional studies.

A few little nitpicks: don't you want to say 1940s or
at least from 1946 when you refer. to K12? Also while neuros-
pora sitophila was used for the first one or two experiments,
it was very promptly replaced by Neurospora crassa.
Dr. Robert E. Kohler
February 14, 1990

-2-

Page 4: this is partly obliterated on my copy but do you
have "cystinuria" in Dalmatian hounds connected with the name
of Irwin Brand? I am just not acquainted with that connection.
Brand was of course a protein biochemist -- Francis Ryan col-
laborated with him on amino acid analyses -- but I usually
connect Dalmatian hounds with the excretion of uric acid; and
I am just not aware of Brand coming into that. (The dalmatian
uric acid excretion story was advertised for years as a likely
example of a genetic defect in uricase: it has turned out to
be much more -.complex and has to do with thresholds of renal
resorption of uric acid from the blood and is still not thor-
oughly understood.)

Page 39: “inspiration struck Beadle" that was probably in
January 1941; which is an astonishly short time before they |
actually consummated their experiments. The course was given
between January and March 1941. According to Carleton Schwerdt's
notes the references to fungal nutrition and in particular:
"biotin -- required by certain fungi" was on February 18, 1941..
(On February 27th he gives an account of the phenylketonuria
and alcaptinuria and the notes say "above reactions may be
blocked with incomplete metabolism due to presence of reces-
Sive genes". There is an account, beginning March 6th, or the
Drosophila pigment story; it then goes on to the plant pigments.
But there is no mention of Drosophila nutrition in Schwerdt's
notes for this particular course.

I rechecked the 1939 nutrition paper and of course he
really did not succeed in developing a defined medium, although
he had evidence that additional riboflavin, above what was in
yeast extract, was needed for rapid growth.

Page 46: the early methods of bioassay with Neurospora,
before the growth tube, simply involved filtering out the my-
celium either on glass filters or even on filter paper, wash-
ing them, rolling them up and wringing them between your
fingers, drying them out and weighing them. ‘The method of
growth tubes was really Ryan's contribution, of course in
Tatum's laboratory.

Where did you get #1090 as the strain number of the
thiamine mutant? (I don't have the strain catalogs handy.
If I don't remember, it may be that it was a sitophila mutant
and the stocks that I worked with were all a little later, and
in N. crassa. Or it may have been unstable to a troublesome
degree and was then superceded by mutants with later numbers.)

 

Again thank you, I very much enjoyed the article.

Yours/sincerely,

iY

Joéntia Lederberg

  

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