Personal memo from

JOSHUA LEDERBERG

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Lf Reply te HV, Lgetl” HLe Uh el89 19 Fed
THE ROCKEFELLER UNIVERSIT NEW YORK 1

 

 

DRAFT -- 1988

To return to Griffith: his was the successful, but it was not an isolated exemplar of
transmissible heredity in the Ist quarter of the century. Literature is rife with
“paragglutination" .... The principal marker available for bacteriological diagnosis was
agglutination by immune sera. These were imputed with a specificity that went far beyond
the reality, and great notice was given to a) natural occurrences of serolological cross-
reactions, and b) to modifications arising in mixed infections or in mixed culture in the
laboratory. Few reports offered a consistent, reproducible protocol. They are difficult,
therefore, to interpret even in hindsight. The majority were probably rough, non-specifically
agglutinating variants selected either by the metabolic milieu of the mixed cultures, or, in
some cases by smooth-specific, lysogenic bacterophages. In view of what we now know of
lysogenic conversion of somatic antigens in Salmonella, some of these mouldy papyri might
have been an authentic starting point of genetic enquiry, but with the exception of Griffith’s
transformation, none was systematically followed up. We have no indication whether
“paragglutination” was on Griffith’s mind when he did his experiment. He surely was aware
of that literature, and especially of the Weil-Felix reaction. This is a cross-reaction of the
somatic polysaccharide antigens of Proteus X strains with rickettsia. Originally, these Proteus
strains were isolated from the urine of typhus fever patients and were thought to have some
etiological significance. This was discounted, but agglutination of Proteus X by patient sera
was used for diagnosis. Some bacteriologists thought the cross-reaction was evidence of an
"exchange of receptors", we would now say a genetic homology between Proteus X and
rickettsia. This seems implausible, but I am not sure decisive tests of DNA homology have

been conducted to this day.
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