Dept. Genetics, University of Wisconsin, Wadison 6, Wis., U.S.
Dec. 4, 1951

Dear Dr. Scholtens:

I should be very pleased to discuss the speculations on bacteriophage
mentioned in your letter and papers.

That a bacteriophage is a parcel of genetic material is, I think, beyond
doubt. The question is to what extent the host bacterium carries its own
genetic determinants (in a nucleus?) independently of the bacteriophage.

My own thinking on this question is that symbiosis adequately conveys the
concepts of the relationships between phage and bacterium. If one fdcusses
attention on the symbiotic complex, there are of course many traits that
are governed by the phage component.

To my mind, one can draw quite opposite conclusions than those expressed
by Doerr from the phenomenon of lysogenicity. The fact that a previously
sensitive bacterium can become lysogenic by infection with an exogenous
phage shows that the theory of phage as a viral parasite (or symbiont) is
adequate to explain the occurrense of lysogenic bacteria. The induction of
lysoggnicity is perhaps not so clearcut in the Salmonella group as, for example
in E. coli or in staphylococci, but so far as I can see, only because of the
prevalence of lysoggnicity in this group. I will admit the possibility that
the phage-bacterium complex may evelve in the direction of obligate symbiosis,
but there is no clearcut evidence that this has happened, and until this is
proven, I feel that the concept of the complex as an association of two organisms
remains more utilitarian. When this complex is as characteristic as it is
in the Salmohellae, there is considerable virtue in basing a practical classi-
fication (for epidemiological purposes) on it.

Although I could not honestly insist on a ftnal proof, I do not feel that
we should identify FA with the phage that provokes it. Most important by way
of evidence, the genetic capacities of FA are determined by the bacterium
from which it is produced, not the phage which elicited it. For example, a
phage from a streptomycin-sensitive lysogenic bacterium provokes FA for the
trait streptomycinOresistance when resistant bacteria are grown in the pre-
sence of such phage. On the other hand, phage from a resistant bacterium does
not provoke "resistance-FA" from bacteria sensitive to streptomycin. Of course,
you can argue if you wish that the properties of the phage are directly modi-
fied by the bacterium on which it is grown; I would say that if the phage plays
any direct role at all it is at most the vehicle of FA, not the immediate source
of its specificity,which comes from the bacterium, If the phage itself has
genetic properties usually associated with the bacterium these should be propa-
gated more consistently when the phage is grown on different hosts. This point
can be illustrated by other examples that will be familiar to you: for example,
the Lisbonmae- Varrere strdhn of E. coli produces a bacteriophage achive against
rough Shiga bacteria. Lysogenic Shiga can be secured by the action of the phhge
but these do not therefore show traits of the E. coli except for the phage itself

The behavior of FA is itself so surpkising that I would not wish to be dog-
matic about its relationships. But my own conclusions for the present are in
favor of the parasitic-virus theorg of bacteriophage, admitting that this type
of association may well evolve into something more subtle.

Yours sincerely,

Joshua Lederberg
Associate Professor of Genetics