PUBLIC HEALTH LABORATORY SERVICE
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Central Enteric Reference Laboratory and
zt, Bureau,

  

CENTRaE—-Poaric—-Heebt-LatenatoRy
COLINDALE AVENUE,
Lonpbon, N.W.9.

Telephone : COLINDALE 6044. & 4081.
Telegrams : DEFENDER, Hype, LONDON.

16th December, 1953.

Dear Dr. Lederberg,

Please forgive me for not having written before to thank you for
your letter of the 4th November, I heve been away for a short while and
heve had various preoccupations, and this was the reason for the delay in
writing to you.

(1) I very much appreciate the way in which you have replied to the
several questions raised in my previous letter. Paragraphs 1 to 6 of your
letter contain a wealth of evidence and I have to admit that the evidence
appears to be unassailable. That is to say, for the time being one hes to
accept the conclusion that bacteriophage particles are themselves transducing
particles, and watt to see whether or not the two will be separated in the
future,

What was quite new to me was the treatment with alcohol mentioned in
your paragraph 2. Has this been published already? And if so, would you
be good enough to give me the relevant reference?

The neutralization experiments referred to in your paragraph 5 are
also most interesting and important.

(2) I have no doubt whatsoever as to the correctness of the
serological typing of the various Salmonella strains employed in your
experiments, and I could see no point at all in re-examining the original
or the newly altered types.

(3) I had a talk with Dr. Spicer, as you suggested. He seemed to
be aware of the possible complications that might in the future arise fron
the use of the term "transduction" in respect of both, the homologous and
the heterologous antigens concerned in experiments with phage lysates.
However, he appeared to think of this risk as something of a remote
possibility, whereas I am looking upon it as a real danger that may very
soon confront workers engaged in enteric phage typing. Your recent paper
with Edwards in the Journal of Immunology, which you have mentioned but
which has not yet arrived here, and the paper with Stocker will certainly

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make a great impression not only on research workers but also on less
competent bacteriologists throughout the world. As you know, non-
motile variants, temporary O forms, are often found on primary isolation,
especially now that the modern enrichment media are employed, and the
thoughtless routine bacteriologist will immediately lock for help from
your transduction technique.

It seems to me to be highly desirable that you and your
collaborators take steps at an early stage to avoid confusion which
seems to be imminent. Whatever may be the fundamental theoretical
aspects that still await elucidation, from the practical point of view
I think it would be important to distinguish from the outset between the
two phenomena. If the unmasking of the inherent homologous antigens
were, for the time being, referred to by some distinctive term, for
instance, “induction”, in contrast to "transduction" of heterologous
antigens, that would be for practical purposes a sufficient safeguard
against possible confusion. I wonder what you think of this suggestion?

(4) I was delighted to read on page 4 of your letter (paragraph 4),
of the transducing genetic material being “inaccessibly embedded in the
phage particle." This reminded me of our earlier correspondence and I
looked up your letter of the 5th January, 1953, the last sentence of which
read as follows: “If all phages, and not merely lambda, prove to have
unique localizafions on bacterial chromosomes, I would have to admit
that they have not, in fact, evolved in this way."

I know you will say old Felix is always coming back to his hobby,
but I could not resist the temptation, Now that the endogenous origin of
phage is being gradually re-introduced, I may perhaps live long enough to
receive one day even some credit for having upheld my unorthodox views
almost single-handed.

As you see, I do derive genuine satisfaction from our correspondence.

With kind regards,

Yours very sincerely,

A

Pest en los x,

ofessor Joshua Lederberg,
epartment of Genetics,
University of Wisconsin,

p: fy
‘A Madison 6,
. I Wisconsin, U.S.A.

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