APR 2 6 TR
STATE UNIVERSITY OF NEW YORK

AT STONY BROOK
(516) 246-5030

DIVISION OF BIOLOGICAL SCIENCES STONY BROOK, NEW YORK, 11790

DEPARTMENT OF CELLULAR
AND COMPARATIVE BIOLOGY

April 23, 1973

Professor Joshua Lederberg

Department of Genetics

Stanford University School of Medicine
Stanford, California 94305

Dear Dr. Lederberg:

Thank you for your comments about Gunther Stent's views on the history
of DNA and for the copy of your reply to Wyatt.

There are some half dozen letters, about 1945-47 which I read concerning
the transformation phenomenon. I will send xeroxes to you when I return to
the Lilly Library about May 1-10. The main points are these:

(1) Muller was aware of the importance of transformation as
genetic material, probably fragments, which paired and
recombined with the host chromosome.

(2) He considered the term 'transformation' unfortunate
because it implied directed mutation as the mechanism
involved.

(3) He accepted the identification of transforming principle
with DNA until Mirsky claimed it was actually nucleo-
protein.

(4) When Delbrick obtained recombinant-like "transformations"
in bacteriophage, about 1946, Muller equated these with
his own pneumococcus interpretation - the pairing and
erossing over of the introduced phage genetic material
resulting in progeny phage bearing new genotypic combina-
tions.

(5) Only in one aspect did Muller miss the boat. He thought
that replication and attraction of homologous genetic
material were related phenomena. He tried to use these
new phenomena as a way to study gene replication through
@ like-to-like rather than complementary mechanism (and
he relied heavily on Jehle's theories of gene "resonances"
and similar oscillation attractions by likes despite
Delbruck's insistence that Jehle's theories had little
merit).

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(6) Muller believed the genetic fragments in transforming
principle would be visible under electron microscopy and
he urged Martha Baylor (then at Illinois) to look for this.
~2.

I spoke at length to Hotchkiss at the Stadler Symposium this month. He
said Muller and Marshak did see the genetic implications correctly but neither
he nor any of the collaborators in the DNA identification at Rockefeller were
bold enough to commit themselves to this interpretation in the face of criti-
cisms by Sonneborn, Wndegren, Dobzhanky and others who espoused other genetic
interpretations. The important point, of course, is that the work was not
ignored, misunderstood, or delayed as Stent claims, but very vigorously inter-
preted by geneticists along different genetic lines.

Earlier Muller in 1938 to 1940 corresponded with Stadler and Delbruck
about the significance of ultraviolet absorption and mutation frequency. Muller,
Schultz, Stadler, Delbruck and others believed, erroneously, that the DNA served
a scaffolding function which, when broken by UV, caused proteins to alter their
position or shape and thereby result in mutation. I think they felt this way
because Stanley's TMV analysis a few years earlier had convinced them (especially
Muller) that genes were protein because TMV was nearly 95% protein. In one of
his letters about this time Muller emphasizes the importance of pursuing nucleic
acid research because it was so closely tied in to mutagenesis studies.

There are several references in Muller's letters about your work and the
importance he attributed to it (especially the sexuality in bacteria). I will
try to get copies of these for you, too.

I don't know if Robert Olby has corresponded with you. He has been working

- on a history of DNA and molecular biology. His knowledge of genetics is much

better now than it was a few years ago when he first began interviews for this
book. JI saw him in January in N. Y. C. and he had just come back from Rockefeller
University where he had discussed the transformation story in detail.

I hope you have copies of Muller's early papers on gene theory (Variation
o due to change in the individual gene; fhe gene as the basis of life; Physics in
the attack on the fundamental problems of genetics). If not, let me know and I

shall send xerox copies to you,

What you say about the paucity of source material from the participating

geneticists is very true in my own experience. Some scientists feel very insecure

2D about their reputations and they prune their correspondence of their errors and
controversies. This is true of Sturtevant's papers at Cal Tech and, from discus-
Sion I've had with him, of Sonneborn's which he will donate some day. Muller was
honest enough to save everything and it is possible to see how his ideas developed
and what influences dominated his thinking at different times in his life. The
only restrictions Mrs. Muller and I worked out were to put aside, for 25 years,
letters of recommendation, grant evaluations, and personal family health matters
that would embarass the careers of living and active individuals.

Sincerely yours,

Elof Axel Carlson

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