November 18, 1951

Dr. Harry Eagle,
Microblological Institute
National Inst&tutes of Health
Bethesda 14, Md.

Dear Harry:
Thanks for letting me see your ms., which I return herewith.
Unfortunately, Table 3 seems to be missing! I hope you have it.

I think that the factual content is se clear as to obviate any
discussion, and I was pleased by the rather clear statement of alterna-
tive interpretations. I might wonder at the extensiveness of the general
discussion in this clearly preliminary paper, but 1t is obvious that you
are preparing your readers for more and better to come. I had not seer
Gibson and Gibson's note: their suggestion seems to be very plausible.
As you point out yourself, however, the data of the present paper offers
no basia for a decision as to different hypotheses.

Without Table 3, my critical machinery is somewhat impaired, but TI
take it that the main conclusion is that the reelstance of selected types
is related to the concentration at which selection was exercised. But it
4s only at moderately low survivorships that the experiments can give any
definite information. It would be of interest to mow just how precise
the generalization can be made, Oeg., with comparisons of replicates of
the sase isolate, of different teclates from the same concentration, and
of isolates from slightly different concentrations, to determine just how
sricoth the "stepless" distribhtion of reaistance increment really is.

The one point that confuses my thinking the most ia a lack of apprehensior:
of what is being measured when a cell suspension is plated with an antibiotic.
The interplay of bacteriostatic and bacééricidal effects will have to be clari-

fied before I gan pretend tounidetatand auch experiments.

Since I cannot be very useful with reapect to content, I wonder if you
would be interested in some poor suggeations on form, offered for whatever
you care to do withbthen.

1. Lederberg '52 should be Lederberg,J. and Lederberg, E.'i. 1952 (Renlica

plating and indirect selection of bacterial mutants. J. Sacte In Press.;

The editor wouldprobably complete the reference from page proof, #e returhed
the galleys a week ago.

2. Do you pré@er or distinguish “adaptative” from “adaptive"-~ the latter
fe in more general use.

3. (peG line 10) ‘that are "several logs"? Do you mean decades, e-kades |
How about proportional for linearly related.
A. Annale (de l'Institut Pasteur) should be Annales, or Ann.

5. May I suggest some references that may illustrate your points as well
and perhaps be more accessible or us-to-date than some that you
cite, especially with regard to induced genetic effects:

Sonneborn 1943 is not apropos. May I suggest instead a compre-
hensive review article:

Someborn, T.M.e 1950 The cytoplasm in heredity. Heredity,
4g 11-36. or

1951 The role of the genes in cytoplasmic
inheritance. In, Genetics in the 20th Century, MacMillan.

For Ephrusei's work: .
EphruseiyB.e. 1951 Remarks an Cell Heredity. Loc. Cit.

In connection with both of these, you might be intereeted in
Provasoli, ot. als, 1948 Streptomycin~induced chlorophylless races
of Buglenae Proce Soce Expt. Biol. Meade, (MeYe) Gi 279-282

Brown, CH. 1950 Elimination of kappa particles from "Idlier"
strains of Paramecium aurelia by treatment with chloromycetin.
Nature, 166, 527. (9/23/50).«

The one other promising case I know @f is the induction ofsparabasal
forms of trypanosomes with various dyes. You must know this litera-

ture better then I do. If you know of a modern treatment of the prob-
lem would you let me know about it?

Yours sincersly,

Joshua Lederberg