June 30, 1953

Dr. S. Benzer
Biophysical Laboratory
Purdue Universi ty
Lafayette, Indiana

Dear Seymour:

It took ma three months, but I finally did get to read your ms.
It is a beautiful job, and I am sure that I have no reservations that
you have not already considered.

The most general assumption is tha proportionality of lysis time to
enzyme content. Have you been able to construct a plausible function of
time and lactase content that will fit the observed lysis/time curves?

In heterogeneous populations, I would imagine that the initial physio~
logical heterogeneity of the cells would imply a variable behavior both

of lactase and of phage formation, without these being necessarily directly
dependent cn one another. One could ask how the slopes of figure 8B and

of 6C and 7C compare on the basis of equivalent specific activity, or
rather how the lysis/time curves compared in your original protocols.

Has the change in optical density been related directly to the lysis
of cell populations? Doerrmann once described an independent variation
of these, based on some alteration of the optical properties of the in-
Bected bacteria.

Tam a little surprised that the cells grown without inducer are des-
cribed as completely devoid of lactase. This was not my experience with
K-12. What were your measurements on the specific activity of lactate~
grown cells? With NPG it should be possible to measure even 1/4000 of
the optimal activity, if a somewhat concentrated cell suspension is used
to make the extract.

I have never been entirely happy about the interpreta tion of "activation"
by cell lysis, though the most plausible explanation seemed to be the non~
permeationno£ sodium into the intact bacteria. Let us hope that it tamns
out to be so simple, or we may not have known what was being measured in
all these experiments. Boris Rotman has just started working here (and at
the Enzyme Institute) on a fellowship to study just this, and related
problems.

Yours sincerely,

Joshua Lederberg