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— * DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service
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National institutes of Health
Bethesda, Maryland 20892

Bidg. 7, Rm. 100
(301) 496-4205
FAX: (301) 496-8312

December 19, 1990

Dr. Barbara Rosenberg
Division of Natural Sciences
735 Anderson Hill Road
State University of NY
Purchase, NY 10577-1400

Dear Dr. Rosenberg,

There are many useful proposals in the FAS document of October 1990 but their
credibility is weakened by careless restrictions on mainstream biomedical research. The
whole system will collapse if reporting is cumbersome and hard to justify.

Specific comments:

Atticle IA - The phrase “altered properties that might enhance their usefulness as
weapons"...is extremely vague because who can know with certainty beforehand what
might increase stability, transmissibility, virulence or any other property that facilitates
the weaponization of a biological agent or toxin, It follows that the prohibition in 1A
could embrace any alteration. Such a flat prohibition could interfere with important
medical advances such as hyperexpression of a toxin for the purpose of elucidating its
mechanism of virulence or for production of a toxoid to be used for immunoprophylaxis.
It is our responsibility as scientists to assure that the benefits of such research are
realized, while at the same time precluding as effectively as possible the application of
this knowledge to weapons development. The latter can best be achieved by requiring
that (i) all military research on infectious agents and toxins be conducted openly, and (ii)
any research that has as its objective the enhancement of virulence, stability and/or
transmissibility of an infectious agent be performed under stringent regulation and
complete disclosure and only following the agreement of regulatory authorities, national
and perhaps international, that the prospective human benefits greatly exceed any
reasonable estimate of the risks. The framework for such oversight already exists in the
United States in the form of “recombinant DNA regulation" and is advocated globally in
Iy-C.

The phrase "is not justified under BWC for any military purpose, including
protection against possible hostile use"...can be interpreted in several ways and is thus
ambiguous. Some individuals do not distinguish between vaccines that are developed for
prevention of disease caused by a biological agent or toxin capable of being used as a
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military weapon and the potential weapon itself. These individuals, whom I regard as
misguided, hump an agent or toxin and its vaccine together and consider both to be
biological weapons. In their view, the preparation of an effective vaccine is considered
to be integral step, or at least an important contributory factor in the successful
development of a biological weapon and hence must be prohibited. This rigid, one-sided
view of immunoprophylaxs against agents or toxins that have military potential denies
the benefits of disease prevention to individuals at risk of naturally acquired infection or
attack by biological weapons. Article 1A as now written would be interpreted by these
individuals as directly prohibiting the use of contemporary techniques of molecular
biology to develop more effective and safer vaccines against agents and toxins that are
potential biological weapons, but which also continue to be important causes of disease
in elvillan populations worldwide. In most instances, the development of such needed
vaccines would include the construction of recombinants that express one or more of the
protective antigens of the potential weapons agent. These recombinants would qualify as
creations with altered properties under Article 1A and would be viewed by the
aforementioned individuals as subject to prohibition without regard to whether alteration
conferred beneficial (i.c., prophylactic) or deterimental properties.

We encounter a duality in vaccine development similar to that described above
for research on pathogenic organisms or toxins. Development of vaccines for pathogenic
agents or toxins can create a dangerous situation that might facilitate the use of these
agents or toxins as weapons. However, the same vaccines offer considerable benefits to
our global society. Again, we must realize the benefits, while precluding the dangers.
This can be accomplished most effectively by (i) conducting research on vaccines for
potential weapons agents openly and under conditions of regulation that now obtain for
all vaccines and (ii) disclosing in detail and at regular intervals the usage of these
vaccines and the populations immunized.

Atticle TIA, "relevant to permitted activities” is not well defined even if it was
used in other documents. Any research that advances our understanding of diseases or
prophylaxis is "relevant" to defense . Non-compliant states (under Geneva protocol and
BWC) should be added to non-signatories. Whether all medical research collaboration
with such states is proscribed should be clarified. Would the prohibition apply to citizens
and corporations as well as to States Parties (governments)?

Oddly enough, the US. law is not in full compliance. Perhaps, this is because the
BWC omits "use" or perhaps because this was already forbidden under the Geneva
Protocol. The Kohl Bill likewise omits use and is therefore a poor prototype.

Page 7, Article V. D, - Same problem as IIIA. What does “jurisdiction or control"
mean? Does it mean any NYH grant?

"Permitted activity" is probably intended to mean suspect activity that is justified
because it is for defense against hostile biological attack. But almost all such research
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could also be justified as defense against existing disease or new forms of disease that
might evolve naturally. So, “permitted research” is either meaningless or all-embracing,
Such an ambiguity is mischievous and could be used to persecute legitimate civilian
research. So we need a better way to set the bounds of "forbidden" than by referring to
what is “permitted” under another treaty.

Page 7, V. D. should read that "all infectious disease research should be disclosed
if it is operated or contracted by the military establishment." It should also be disclosed
by all other individuals or institutions, unless they have an established Internal Review
Board (IRB) procedure and are subject to regulation by the national health and
environmental safety authorities. Most commercial research is so regulated, and unless it
was under military contract would not have to be reported via the national authority.
Certain egregiously suspect research, e.g. with variola, or with a very limited number of
very high risk agents should also be reportable. This also applies to a larger group of
projects if they involve larger levels of cultivation than are customary in biomedical
research.

Page 9, V. B - to plant pathogens add other forms of pest control, such as
myxomatosis virus which has been used to control rabbits in Australia.

Page 10 Y. C. - Add pedagogic to diagnostic and therapeutic - ¢.g., training of
medical and graduate students.

Appendix A, p. 1 - list of controlled agents:

A. Al and A.A2- “possessed in any quantity." This list is probably borrowed from
the history of weaponized agents, regardless of their plausibility. The toxins should have
& quantitative threshold. It is difficult to understand why the designated fungi are listed
as examples and not others. Puccinia is of very wide natural occurrence. So is Brucella.

A. 2 - should set a quantitative limit for declaration, perhaps another higher one
for prohibition.

Appendix A - page 2

Inclusion of Vibrio and Shigella and the plant pathogens, for example, as
requiring declaration taxes the credibility of the proposal. During the 1st 3 quarters of
1990, there were 200 papers published with "cholera" in their title; 62 with Brucella; 65
Shigella; 43 tetrodotoxin, 48 Ustilago + Puccinia, almost all from medically or
agriculturally beneficent work, Formally reporting all such work just dilutes the --
possibility of real surveillance. It means more administratively trivial red tape and will
generate many pseudo-infractions that lead to domestic as well as international
recriminations devoid of content. If there is to be formal reporting on such agents, there
should be an exemption for investigators who have published their work on these agents

in generally available books and journals during the previous 3 years. That will identify
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almost all of the mainstream work in the world, including commercial laboratories, and
this time interval will allow registration of intellectual property. There might be a case
for declaring research that has not been ventilated in that way, however, I hate to think
that anybody who has grown 10 ml. of bacteria from a stool culture with an investigative
purpose in mind will have to report to an international agency. Responsible scientists
should be eager to discuss their research or to respond to questions, if any, to explain
reasonable delays in publication related to protecting proprietary interests.

A very limited number of agents should by common agreement be declarable at
any level. Perhaps this should include risk group 4 subject to negotiated amendations,
and with an exemption for recently published work as indicated above.

Appendix A, page 3 - B B1 - These toxins are commercially available in much
larget quantities. Therefore, raise the threshold substantially.

General comment: Infectious disease research scientists are essentially not represented
in the core group, except for Dr. Alexis Shelokov, who shares some of my concerns about
the final draft. Incidentally, the contents of the final draft were shared with a delegation
of Soviet scientists who are members of the Soviet Academy of Sciences or Soviet
Academy of Medical Sciences. These scientists also voiced many of the concerns
enumerated above.

Sincerely,

Prem CLam cD

Robert M. Chanock, M.D.
Chief
Laboratory of Infectious Diseases
National Institute of Allergy

and Infectious Diseases
National Institutes of Health

co: dr. Robert Weinberg