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   STOCKHOLM 60
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INST. FOR CELL RESEARCH AND GENETICS
     KAROLINSKA INSTITUTET
        STOCKHOLM 60

Dr.Joshua Lederberg
The University of Wisconsin
Madison 6,Wisconsin

Dear Dr.Lederberg:

          Many thanks for your kind letter. We are sending
you our reprints under separate cover.

          I Was readinG with great interest some of your
ingenious papers. Recently we started to apply so:ne methods used
in Lnicntobial genetics to some problems that concern tumor cell
populations. Our experience with 42  mouse tumors has shown that
only some oI +J them (12, on the whole) would grow as typical "asci-
tes tumors". All 12 ascitcs tumors belong to the very rapidly
growing and highly anaplastic category. The rest of the tumors
that grew only in the solid form, comprises both rapidly growing
and anaplastic and, to the greater part, more slowly growing
and comparatively better differentiated forms. We are trying
to learn more about the conditions that enable a tumor to grow
in a fluid as dissociated free cells. It seems that such a capacity,
if once. obtained,is a characteristic that is permanent to the tumor
cell lineage and is independent of the actual form in which the
tumor is maintained r&utinely (solid or ascites). Jack Schultz
suggested to me some years ago that we may be dealing with mutants.
We try to follow Law in applying the fluctuation test of Luria
and DelbrUck for tumor c-e11 populations for deciding this question,
At the same time we try to make independent comgrarisons on the
different cell populations involved with respect to other characters
than capacity for growth as ascites tumors, to establish possible
other correlations.

         As to the problem concerning the effect of chromatin
fractions a your suggestion to use DNAse may prove to be very valuable
indeed. We are doing some experiments presently where, we treat
established tumors with various, definitely noncellular fractions
that have been isolated from other tumors whEch differ from the
tumor-on which the fractions am tested in var&ous quantitative
respects. If there could exist something analogous to the bacterial
transforming principles 3.n case of tumors, the probability of
demonstrating it might be higher if we look for small but definite
changes than if we *try to transform a normal to a tumor oell -a
process that may involve a great numb&= of steps.

paper about   I was very much interested in the abstract of your
      the filterable agent with transforming activity, I should

very much appreciate a reprint of the full paper when available, as
well as any other reprints of your previous work that you could
spare,

  Most sincerely yours,
A    G-m u