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NATIONAL INSTITUTE OF ARTHRITIS AND METABOLIC DISEASES November 26 19 Sl
NATIONAL CANCER INSTITUTE ?

NATIONAL INSTITUTE OF DENTAL RESEARCH

NATIONAL HEART INSTITUTE

NATIONAL INSTITUTE OF MENTAL HEALTH

NATIONAL MICROBIOLOGICAL INSTITUTE

NATIONAL INSTITUTE OF NEUROLOGICAL DISEASES AND BLINDNESS
THE CLINICAL CENTER

DIVISION OF RESEARCH GRANTS

Dr. Joshua Lederberg
University of Wisconsin
College of Agriculture
Madison 6, Wisconsin

Dear Josh:

Many thanks for your most helpful letter of November 18th. Table 3
was deleted from the manuscript at the request of the editors of

the Journal, who suggested that the data be included in greater
detail in a following paper on the rate at which bacterial cultures
lose resistance, considered as a function of their preceding exposure
to the drug. The reference to the table was unfortunately not delet-
ed from the text in your copy of the manuscript.

Your point with respect to bacteriostatic vs. bactericidal action of
the drug is most pertinent. Actually, penicillin and streptomycin
are directly bactericidal, and when e.g. 103 organisms grow out to
form visible colonies in 5 days out of an inoculum of 108, the large
bulk of the bacteria have actually been killed by the drug, and the
clear areas of the plate are sterile on sub-culture. However, with
chloramphenicol (and terramycin) over a wide range of concentrations,
the drug is bacteriostatic rather than bactericidal, and "resistance"
should be expressed in terms of ratesof multiplication rather than
ability to grow at all.

The specific points you raise with respect to terminology and reference
citations are most helpful, and I will make those corrections in proof.

As you suspect, there will be more to come. I don't know that it will
be better, but I will certainly try to get your help and advice.

With kind regards,
C& dially,

Le

‘ Harry Hagle,
. Experimental Thefapeutics
Hiekm National Microbiological institute