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Figures indicate fractional mortalities after tumor inoculation
29th May,1956

Dear Lederburg,

It was a great pleasure for me to read your clear and concise
note in the symposium a few weeks ago, and I was tickled pink then to
read your proposed experiment on the heterozygous tumors. Now that I
have got your kind letter, I shall perhaps frame it and stick if on
the wall.

After that stimulating talk we had in your lab, I went off to
Snell's lab full of good intentions about selecting antigenic variant-
However quite a large series on tumour inoculations from one isogenic
strain into another gave negative results, with and without irradiation
of the tumor cells, and other treatments designed to enhance somatic
“mtation™. But the preliminary runs with Fl tumoms seem to be doing
much better. Here is a pedigree of an anaplastic squamous carcinoma,
4nduced in an Fl mouse by methylcholanthrene injected last October.
It's more or less self-explanttory: you can see that sub-lines were
established in the two parental strains, which killed 100% of the
parental strain. The sub-lines retained their modified character after
passage through the Fl, indicating that the change is long-lasting.
And, though the figures are too small to be statistically significant,
the modification appears to be irreversible.

The tekes (25%) of the original tumor line in the parental
strain seem to me to be selective rather than adaptive for this reason:
in all mice, whether or not the tumor will grow progressivély later,
their is an initial period of tumor growth during the first 5-10 days.
In the Fl, or in the parental strins with "adapted" tumon lines, the
tumor then rapidly increases in size; in mice which eventually reject
the tumor,the lump: then regresses; while in the parental hosts which
eventually grow the Fl line, thete is a more-or-less prolonged latent
period while the tumor mass remains constant or even declines temporarily

Conditioning of the changes by the hosts is certainly not
excluded in this experiment. In fact I have quite an open mind about
the mechanism of the change. I'm looking forward to hearing what
Ford has to say about the chromosome counts, though the material
is not as well adapted for this as an ascites tumor (which I am
trying to produce).

You will be interested to hear that the= way now seems to be open
for a decisive test of the old question, whether continued presence
of antigen is needed in the antibody-producing cell. I have very
strong evidence that there is extensive multiplication of antibody-
producing cells which have been transplanted into irradiated mice.
So I'm hoping to have a shot at this - and possibly try serial
trensfer and multiplication - quite soon.

By the way, thank you for the reprints, which I always read with
great interest.

When are you coming to Europe?

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