January 9, 1951.

Dr. Maria Umberto Dianzini,
Institute of General Pathology,
University of Genoa,

Italy.

Dear Dr. Dianzint:

Thank you very much for your kindness in sending your E. coli strains
and your tao reprints.

I am especially glad that you sent the paper "Matdzioni indotte...",
for 1t brings out certain details which are obscure in your note in Experi-
entia. May I take the liberty of discussing them with you?

The most important of these concerns the technique and interpretation
of your manometric tests. I interpret the phrase‘ "I geraig prelevati dalle
colture su agar con solusione fisiologica..." to mean that the bacteria were
grown on pladn nutrient agar, without sugar or perhaps with just glucose.
This is extremly important because of the phenomenon of enzymatic adaptation,
i.e., that bacteria frequently are unable to assimilate certain carbohydrates
unless they have been grown in their presence. This has to be distinguished
from the parallel phenomenon of mtation and selection for the ability to
use substrates previously non-utilizable (v., e.g., Monod & Audureau, Ahn.
Institut Pasteur, 72:868, 1946, or Monod, Growth, 11:223~289 1947). Your data
therefore refer not to the potential ability of the organism to attack the
sugars, but to the rathey low and variable activities which they may have in
the absence of adaptation.

I was particularly interested in your work because I had the impression
that you were dealing with characteristics like those in my work on recombi-
nation., and that you had, for example, been able to transform a nonsucrose—
fermenter into a sucrose fermenter. A simple streaking on Eosin-methylene blue
sucrose medium shows, however, that while your UQ strain is a powerful sucrose-
fermenter, the other three strains (I, SG, and I (SQ-16)) are essentially non-
fermenters. At least in terms of the cultural characteristics which I have been
studying, there is no difference between I and I(sG-16). I venture to predict
that you will find, if the cells are grown on nutrient sucrose agar, that UQ
will give a mich higher rate of sucrose-oxidation than any of the other three
strains.

I do not mean to imply that you have not achieved an interesting transfor-
mation, the proof of which will require further careful and thoughtful investi-
gation, but it does appear that your report is likely to be misunderst in its
present form, for I am sure that most readers will have thought that your
determinations were carried out on adapted cells. May I presume to SUZE st
that a further research in this dissection on your part might be most
fruitful?

A second question has also arisen in my mind, but largely obscured by
the first. You have seen yourself that the metabolic characteristics of
your straihs, as measured by your own technique, have not been entirely
constant and reliable even in the absence of any treatment (e.g., on p.
164; 2) "41 germe, dopo 22 passagi su afar saccarosio al 2%, hasattacato
il substrato." This raises the question whether the variations you find
with nucleoprotein treatment may not be induced by the NP, but rather
that the NP provides the most favorable conditions for the overgrowth
of the farlant cells.

One final point: you refer in your papers to Boivin's transformation
of E. coli. Unfortunately, his strains have been lost, so that it is
impossible to reproduce his experiments on serological transformations.
However, it should be pointed out that he has retracted the claim to have
induced a change in pflenzymatic properties of E. coli, for moh the same
reasons as raised in the previous paragraph. (Cold Spring Harbor Symp.,
volume 12, Pe; 1947.)

£ shall look forward to hearing from you again, and with ay sincere
appreciations for your cordiality,

Yours truly,

Joshua Lederberg,
Associate Professor of Genetics.

P.S. I shall be hapsy to send you mmy all reprints which are still available.