UNITED STATES

ATOMIC ENERGY COMMISSION
WASHINGTON, D.C. 20545

 

October 3, 1966

Professor Joshua Lederberg
Department of Genetics
Stanford University

School of Medicine

Palo Alto, California

Dear Dr, Lederberg:

This is not exactly fan mail, although I do look forward to your pieces
in the Sunday Washington Post, You have a curiously detatched style
which invariably leaves me wanting to argue points; but no doubt that
is part of the game,

I believe your recent remarks on "Pill Heralds Biological Changes"--
that was the headline--do not engage the ultimate in what may be the
long-term aspects of the problem-hazard associated with its clinical
usage in the female. As presented in your column, it seems that you are
considering thrombosis to be a long-term effect in women using the pill.
Presumably it occurs while they are still on the drug, not years after
they have ceased taking it, and if this is true, a pharmacologist would
tend to classify thrombosis as a delayed drug reaction, Of course, one
recognizes that this classification is more descriptive than explanatory
and is not inherently discriminative,

Our work with radiation effects, which appears many years after an exposure,
may conform more closely with the usual definition or concept of "long-term
effects." The word "chronic" is rather too general to express the idea of
a lengthy, seeming disconnection between cause and response, Of course,
many of the biologic processes that appear as the clinical response are no
doubt building up during this "latent™ period.

Our concern with long-term effects has been condensed into the following
questions: Is employment in nuclear energy facilities and laboratories
associated with any discernable change in employee morbidity and/or
mortality patterns? This question must be raised despite the fact that
the typical exposure here is zero exposure or quite low-level continued or
repeated exposures above background,
Professor Joshua Lederberg -~2- October 3, 1966

This question must be dealt with by retrospective epidemiological procedures
and to that end we have contracted with Dr. Thomas Mancuso, Research
Professor, School of Public Health, University of Pittsburgh, to carry out
these studies if he finds usable for such an analysis the available data

on some millions of man-years at risk, He is presently in the early-middle
of this investigation, Not unexpectedly, he has had to invent many new
techniques as he has gone along, and these may turn out to be the most
important product, At the very least, we expect him to tell us how to

set up our occupational health services so as to accumulate proper pros-
pective data on this question,

Concurrently, Jim Neel is concerned with the genetic aspects of long-term
radiation effects and, of course, the Atomic Bomb Casualty Commission is
directly involved with learning what are the long-term effects in another
kind of irradiated population.

I have briefly described our problem in order to make the point that the
long-range hazard in the pill-takers should be sought perhaps 20 to 40 years
after they have stopped taking the pill. We have good experimental data in
animals to suggest what long-term radiation effects should be looked for,
but are there similar intimations from toxicologic studies of the pill?

Is it not reasonable to suppose that this chemical, which intrudes on the
ovulation-menstral cycle and feeds back to the pituitary, could also upset
other pituitary-endocrine gland cycles? This, if it were to happen, could
result in long-term effects in the context that we have been using the
word, Are there data from animal experiments to rule out such reactions?
Are there plans to search for such presumed reactions in women 10 or more
years in the future? We can testify to the difficulties in trying to
investigate such questions retrospectively.

If this letter causes you to ruminate
and philosophy that must be developed
it will have accomplished a purpose,

the problem, In any case, you may be

about the special problems, techniques,
in order to deal with long-range effects,
Perhaps you may choose to write about
assured that there are numbers of

medical, ethical, moral, social, financial, etc., considerations associated
with, or more likely dependent on, the logic to be evolved in this long-term

effects quandry, I am convinced that
tional sense are not possible,

Sincerely yours,

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H. D. Bruker, M.D.”

Assistant Director for

Medical and Health Research
Division of Biology and Medicine