November 26, 195)

Dr. Theedore 5. Hauschka

The Institute for Cancer Research
7701 Burholme Avenue

Boxchase

Philadelphia 11, Pennsylvania

Dear Ted:

Thank you for your provocative letter and note of the 18th, I hardly know
why you would predict that I "won't like it", I had discussed the matter in very
similar terms with both Paschkis and Klein but only by letter and I am looking
forward to an opportunity of meeting them personally. ‘George <lein's experinent
seems very well to show that whatever is carried over in the chromatin transfer
exceriments included not only the quality of tumor formation but also much or all
of the antigenic specificity of the donor tumor, Until one could nore directly
demonstrate that intact cells were present in the chromatin preparations one
cannot of course rely upon their participation. The methodology becomes very
mich like that involved in bacterial recombination experiments, and for this ob-
vious reason I have thought it advisable to include as many distinct genetic
markers as possible. That still will not settle the matter finally until one
can be sure whether there are or are not intact cells present,

I have wondered about still another approach, If intact cells are the
agent, they might be expected to be resistant to DNAase, while if chromatin
fragments are involved, this enzyme should inactivate them. It has been rebut-
ted that the tissue fluids already contain ample DNAase, but this is not a suf-
ficient argument in view of the success of Griffith's original experizents with
pneumococci,

I like the design of your crucial experiment E, Has anyone done the first
control experiment that you indicate, so that one coulc predict whether this test
would be feasible?

From the substance of my corr-spondence with Slein and your own remarks
under section D2 and 3, I would conclude that my most useful function at the
discussions would not be so much a concrete review or discussion of “lein's own
paper but rather a general presentation of the recent achievements of microbial
genetic work insofar as they seem to point to analogous experimental possibilie
ties with ascites tumor cells, Experiments on genetic transduction in a variety
of bacteria would lend very strong theoretical support to the possibilities en-
visaged in your paragraph D?, ‘Jhether that possibility has actually been realized
also in a tumor cell is of course the question that remains to be settled, By
analogy with genetic transduction elsewhere, I would have expected that the
chromatin-induced tumors would at least occasionally, if not invariably, show
antigenic equivalence with the recipient rather than the donor cells, Possibly
Klein's experimenss were simply not extensive enough to discover a second anti-
penic category.

Yours sincerely,

PRGBUE SERIA POPES tics

ay

Tr sn
Vid SYP