April 15, 1969

Dr. Paul Kotin
P.G.Box 12233
Research Triangle Park, North Carolina

Dear Dr. Kotin,

TI have been trying te reach you by phone today but it maybe just
as well if I can get this letter to you before talking to you over the wire.

The question I want to raise with you concerns the biological effects of
Chloramine and its derivatives as are abundantly produced in water supplies
subjected to residual chlorination. There is, of course, an enormous

literature on the bactericidal efficacg of these procedures but I have been

able to Sh#adnebatdgially no information concerning the possible impact on

human health of chronic uptake of these materials. The problem is obviously
enormously compounded by the very wide range of substances with which chloramine
is expected to react in natural waterssupplies. It undoubtedly will become
greatly exacerbated as the pressures on available water call for the use of wore
and more chlorine for its decontamination.

The specific issue in which I am most deeply interested myself ccncerns
the possible Utichven ic effect of such materiala. I was startled to find that
amino acids and peptides as well as the nitrogenous bases of nucleic acids

all react readily with chlorine to form chloramines of varying degrees of
stability and further reactivity. I had, in fact, given some small thought to
this kind of issue many years ago and gone so far as to test fodine with a
vather negative result. However, I was not then aware of the prevelance of semi-
stable complexes of chlorine which could serve to carry this chemical re~-
activity far more deeply into tiddues and celle than would be possible for

the much more highly reactive free halogen.

I have also been startled to be unable to find any convincing literature
on the mechanism of action of chlorine as 4 bactericidal agent and on rather
general grounds would give priority of place to the likelihood that its target
is in fact DNA as is the case for ionizing radiation and for a range of other
toxic chemicals. The capacity of chlorine to inactivate a range of viruses
ie consistent with this view, although it is, of course, impossible without
specific experiments to disentangle the rele of proteins versus nucleic acica
as the target molecules.

I am in the course of starting some experiments on this question.
But I would be most grateful for on your part any further assistance in
scouring the literature for rel@v@nt publications which I have been notably
unsuccessful in finding for myself. What I have particularly in mind are
cellular toxicity tests of various forms of chlorine complexes, specific
evidence of reactions with well~defined target molecules, and in particular
any explicit test of the possibility of the production of genetic damage.

over.

 

 
I have also been unable to find any significant work on the transport of
chlorine from chlorination procedures into the animal or human body which would,
of coursee be most relevant to any practical concerns about the entire matter.

You will correctly suspect that I also have in mind sensitizing you to
the public policy implications of this speculation but I would, of course,

hasten back to the laboratory to find out whether there is real substance to
that.

Sincerely yours,

Joshua Lederberg
Professor of Genetics

JL/rr