UNIVERSITAT BASEL UNIVERSITY OF BASEL

INSTITUT FOR HYGIENE UND BAKTERIOLOGIE INSTITUTE FOR HYGIENE AND BACTERIOLOGY

BASEL (switzerLanp) 25th August 1952

PETERSPLATZ 10

Dr, Joshua Lederberg
Associate Professor

The University of Wisconsin
Department of Genetics
Madison ,6

Dear Dr, lederberg,

I have sent you about 1 week ago two papers
summerizing my attempts on anthrax mutation and two others on
the complex structure of the capsule of the "mutant" or,as we
designated with an unbiased term, of Bac. M,

I started to work again on anthrax, because
I could not believe the possibility of a mutation of B. anthra-
cis, induced through the extracts of B. mesentericus, as reported
by Manninger and Nogradi in the Experientia, As you can see I
could not confirm their results. The only change I could observe
in my first paper was that the anthrax strain of Manninger, which
grow invariably in noncapsulated form on agar-medium under atmos-
pheric Oo tension, started to produce in the presence of mesen-
tericus extract, in a certain percentage of the experiments, smooth
colonies with typical capsulated bacilli, Since this strain‘was
still slightly virulent for mice and gave a typical picture of
anthrax infection and since at the time of its isolation showed
no sign of motility, I closed my first paper with more or less
negative results, The macoid strains, thus obtained, were put aside
in several subcultures in agar-plates during some months of the
summer period, At the first replating in September, the colonies
showed the same appearance, the capsulated bacilli revealed the
same morphology, but they were avirulent in mice and were distinct-
ly motile, These observations, published in the second paper could
inasmuch be recongiled with the anthrax derivation of the strain,
as the mucoid bacilli were agglutinated with an immune serum, pro-
duced with capsulated anthrax bacilli in rabbits to the same titer
as virulent B, anthracis cultured in the presence of CO, in mucoid
form, The fermentation reactions of this strain, differént from
any known type in the group Bacillus made it,however, necessary to
initiate a more profound immunological study of this group, before
further experiments on the "induced mutation" were reassumed, This
work, published partly in the subsequent two papers lead us to un-
expected observations regarding the complex nature of the bacterial
capsule in our strain as well as in B, megatherium, In our current
work we are clearing up the significance of the capsular transver-
sal septa in the structure of the bacterial cell with some really
surprising results,
Regerding the original problem, in which you are
interested, I can not give you without further work a definite
judgement, I acknowledge, that working with this group of bacteria,
fallacies might occur, specially since I started my work with the
original culture of Manninger without ’isolating single cells at
the time I wrote the two first papers, Still I have to assume
thet similarly carried out "induced mutations" might lead to un-
expected results, Presently we are mostly interested in & specl+ °
fic cell wall reaction, which we discovered in working with Bac.M,
This bacterium is very sensitive toward lysozyme, If we separate
through initial lysozyme activity the cell wall from the cytoplas-
mic membrane, we can demonstrate thst the former gives = reaction
with a certain polysaccharide antibody. In unstained preparations
in phase contrast microscope the cell wall shows up distinctly.

I hope ig continuing this study we can develop some more "markers"
which would make it worthwhile to reinvestigeate the original prob-
lem of induced mutation,

Your fundamental work on bacterial genetics will
certainly help us by planning this work, I thank you very much for
sending me your recent works. I am specially glad to pasess your
paper on "recombination analysis of bacterial heredity" since the
Cold Spring Harbor Symposia are not available in our Library,

Yours sincerely

fe weg
TY . a
Joseph Tomesik, M.D.

Professor of Hygiene
and Bacteriology