June 19, 1954

Dre William Cherry
Communicable Disease Center
Dadagnostic Bacteriology Lab.
Box 185, Chamblee, Ga.

Dear Bill:

I was very happy to hear from you about your work with Bacillus. I
had seen the Manninger-Tomseclik contributions, but found ther: rather un-
convincing. There was a hint of your new stuff on a reprint postcard
from Brown (I think), and I had been waiting to hear sone details of
it.

I will tryT&o answer your questions about the Salmonella system.
Some of the points are taken up rather obliquely in the various papers
(see also Zinder, Cold Spr Harb Symp. Vol 18), but some of the findings
have not been published in detail.

Ge Inactivation by DNAse? A. No effect of the enzyme. The idea that the
phage particle carries "DNA" 1s hypothetical, by analogy with the pnew:o-
coceus story. To my mind "DNA" is another term for "chromosome fraguent™;
whether DNA is absolugély all that is relevant hae not, to my mind, been
finally settled.

q. Phage or something else in lysate. A. The genetic activity is carried

by particles( sedimentable at high speed) which are indistinguishable fron
Phage in the following respects: seize (filtration)¢ sedimentation); tolerance
to heat; tolerance to certain disinfectants; tolerance to ultrasonic disruption:
neutralization by anti-phage serum; abeorption by live or killed susceptible
bacteria (and non~absorption by rough or other serotypes). The ratio of
activity to phage count is constant Por different lyekkes. All this would
show that the active particle 1s superficlallysinilar to phage, but does not
exclude that the internal contents of the particle might be different. However,
Under conditénns of low multiplicity of infection, thore is a definite cor-
relation between transduction and lysogenization, so that the particle carrying
the activity must also carry phage activity. (Of course -ost phage particles
are tranaductively inactavey.

Ge Separathén of phage from genetic activity. A. Of course, not every
enetic effect of phage is transduétion. Most phage -articies are inactive
distinction from the diphtheria toxigenicity effect, esz.). Also, the

activity of a given lysé&e depends completely on the »vacterial host. We

hae not found any method of depriving a phage prep'n of ite traneducing con-
petence (except of course by growing it on a new host) without impagring
its lytic activity at the same time. With ultra-violet light, however, the
lytic activity is destroyed (preswably by lethal rutathonsin the phage)
much more rapidly than traneductive competence. With UV'd phage, therefore,
one can get traneduction without lysogenization. This also havend fairly

offen with maladaptive phage-bacterium combinations , ee. typhimurium phage +
paratyphiB.

I would like to hear more of your findsiggs/ I am afraid I did not fully

assimilate your letter. Do I understand that you propagate phage on a non-

motile B. anthracis and get lysates that will confer motility on the sane

or related anthrax strains? This does notsugzest transduction in the dane

sense as in Salmonella. (The DNAse effect might mean that the genetic material

is more accessible, perhaps nearer the outside of the phage particle). It might
BS, st

be closer to the diphtheria story.

Of course your confidences on this story will be fully respected-~ I trust you
will let me know when they can be relaxed.

With best regards,

Yours sincere ly,
4 é
fn OE Fearn a

- doshua Lederberg
Professor of Genetics