Copy fer in /o
Joshua Lederberg.

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emetion

Fersonal and confidential

Gentral Enteric Reference Laboratory & Burear

6th February, 1953.
Dear Profesacr Dinger,

Thank you for your letter of the 31st January and for the reprint of
the paper "On the induction of Vi- antigen formation in a straia of palnonelia
Svebi free of Vi-antigen" by Hans L. Booy end Hendrik L. Wolff.

I remember very well the pleasant correspondence we had during 1949
on the work br, Lie Kian Joe did in your Institute and I would Like very much
to send you the phage preparations you have asked for. Unfortunately, I do
not feel justified in doing so for two reasons,

¥iretly, you may remember that the standardised phage preparations
for the typing of typhoid and peratyphoid-B becilld have been prepared for
the specific purposes of the International Schemes based on the suggeations
for the stendardisation of this procedure which I published jeintly with
J. Craigie in the Lancet, 1947, 1, 823. This Seheme is now operating in 26
countries and the demand fer these reagents is very considerable. The standard
phege preparations were made in quantities caloulated to satisfy the require-
nents of the National Reference Laboratories throughout the world for many
years, and it is necessary therefore to exercise the utzcet ecomomy in their
use. I see fron my files that I wrote to you on the 12th Jenuery, 1949, a8
follows: "However, you will see from the attached copy of the Recommendations
of the Comittee for interie Phage Typing adopted at Copenhagen in 1947, that
it was agrwed that, when necessary, the Hational Reference laboratory in each
country should act as the distributing centre for the standard phage preparations
and reference type strains. I am sure you will appreciate that I am bound by
this agreement and I would be departing fram it if I were to suntly typing
material direct to « laboratory situated in a country where « iational
Reference Leboratary 1s frnctioning.*

Nevertheless, I would perhera have made en exception and ssked Lr.
Schaltens to let you have the phages, if I were convinced of the real
necessity for using there reagenta in “greater quantity", se you heve atrted
in your letter, Heving read the pepar by Bogy and wolff very carefully I an
ort, say that these valuable reavents, which ere not eaay to make, would
not put to the best use if they were emplayed mm e lerge scale for the
testing of varianta of Salim typhi of the kind described in that paper. Anyone
acquainted with the past history of the variations that hove been observed in
etlmatyphd, particularly in strain 8 901, (see for example Journal of Hygiene,
1951, 42 on pages 94-95), will refuse to sccept the experiments by Booy and
Wolff as evidence of genetic transduction of Vi antigen.
4 few criticisms of the paper are a3 follows:

Qn page 186 Booy and Wolff state thet the agglutination tests were
carried out by slide agglutination; the pitfalls of this crude technique
are well knom. In Tables 1 and 2 there is no avidence to show that the
authors did in fact demonstrate the typhoid Vi antigen in the variants
4 and B, It is not stated how the sera or the suspensions were prepared;
there is no indication of the H, 0 and Vi antibody content of the sera
that were absorbed; there are no cantrols to show the relative sensitivity
of the suspensions to 0-agglutinins, or to solutions of NeCl, or to normal
serum proteins, It is evident fran the two tables that the authors are not
fanilier with the method of antigenie analysis.

I very much regret I have to be so critical, but the paper calis for
eriticiam, if only for the reason that it may lead astray other workers
who have little experience of the essential techniques required in sound
entigenic analysis of bseteris.

In these circumstances you will appreciate why I do not feel justified
in sending the sct of becteriophage preparations, if your sssistants sueceed
in isolating c mumber of variants that satisfy sll serological tests and, at
the finel stage, require testing by means of the stencerdized bacteriophage
preparations, I «m sure br. Scholtens will be willing to test such strains.
Bven if the number of such strains were a dozen or two br. Scholiens would
certainly not refuse to "type" them. In the worst case, the typing could be
cone in my department here.

With kind regards,

Yours sincerely,

(sed.) A, Felix

Professor ix. J.2. Dinger,
Instituut voor Tropische Geneeskunde
Rapenburg 33,

leiden,

Holland.