United States Office of the Administrator EPft SAB-EC-86-009
Environmental Protection Science Advisory Board January 1986
Agency Washington, DC 20460
SERA Report of the
Study Group on
Biotechnology
Assessing EPA's
Biotechnology Research
and Information Needs
(
-------
UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D C 20460
February 7, 1986
OFFICE OF
THE AOMINISTR ATO*
Honorable Lee M. Thomas
Administrator
U.S. Envirorrental Protection
Agency
401 M Street, S.W.
Washington, D.C. 20460
Dear Mr. Thomas:
The Science Advisory Board's Study Group on Biotechnology has prepared
this report in response to the request to undertake a preliminary evaluation
of the Agency's existing research and risk assessment capabilities associated
with the field application of genetically engineered organisms. This report
also fulfills the request to conduct a Research Review of the Office ot
Research and Development's Research Program in Biotechnology.
Since the Agency has only recently begun its research and regulatory
activities, the Study Group felt that an intensive detailed report was
unnecessary at this time. In researching and preparing this report, the
Study Group was pleased with the cooperation and candor of Agency staff in
conducting briefings and answering questions.
In general, the Study Group believes that although the Agency has in-
creased its research staff and initiated a research program in biotechnology,
a larger and broader program than that envisioned is needed by EPA decision
makers. Dispersal of genetically engineered microorganisns, appropriate
remedial action in the event of release of such organisms, and possible
environmental effects of such a release, whether beneficial or detrimental,
are critical issues which should receive high priority by EPA. Research
on health effects, as presently planned, is limited in scope and should be
expanded with adequate resources made available for this purpose.
-------
-2-
The Study Group appreciates the opportunity to provide comments on this
critical issue. We look forward to the Agency's response to our report.
Sincerely,
i/i
Norton Nelson, Chairman
Executive Committee
Science Advisory Board
Martin Alexander, Chairman
Study Group on Biotechnology
Science Advisory Board
cc: A. James Barnes
Don Ehreth
Jack Moore
Terry Yosie
AUG 1 1986
?WVIRONM€NfAL
OTCCTION, AQ|N(
mat Fimoi
*
-------
SAB-EC-86-009
ASSESSING EPA'S BIOTECHNOLOGY RESEARCH AND INFORMATION NEEDS
REPORT OF THE STUDY GROUP
ON BIOTECHNOLOGY
U.S. Environmental Protection Agency
Science Advisory Board
Washington, D.C.
January 1986
-------
NOTICE
This report has been written as part of the activities of the
Environmental Protection Agency's Congressionally established Science
Advisory Board, a public group providing extramural advice on scientific
issues. The Board is structured to provide a balanced, independent,
expert assessment of scientific issues it reviews, and hence, the
contents of this report do not necessarily represent the views and
policies of the Environmental Protection Agency nor of other agencies
in the Executive Branch of the Federal Government.
-------
U.S. Environmental Protection Agency
Science Advisory Board
BIOTECHNOLOGY STUDY GROUP
Chairman
Dr. Martin Alexander, Department of Agronomy, Cornell University,
Ithaca, New York
Members
Dr. Ralph Baker, Plant Pathology and Weed Science, Colorado State
University, Fort Collins, Colorado
Dr. Rita Colwell, Department of Microbiology, University of Maryland,
College Park, Maryland
Dr. Stanley Falkow, Stanford University Medical School, Department of
Medical Microbiology, Stanford, California
Dr. Ralph Hardy, BioTechnica International, Cambridge, Massachusetts
Dr. Don Kaplan, ME Pruitt Research Center, DOW Chemical Corporation,
Midland, Michigan
Dr. Francis Macrina, Department of Microbiology and Immunology, Virginia
CCxiDiDnwealth University, Richmond, Virginia
Dr. James Moulder, Department of Molecular Genetics and Cell Biology,
University of Chicago, Chicago, Illinois
Dr. Gil Omenn, School of Public Health and Community Medicine, University
of Washington, Seattle, Washington
Dr. Robert P. Williams, Department of Microbiology and Immunology, Baylor
College of Medicine, Houston, Texas
Executive Secretary
Mr. Robert Flaak, U.S. Environmental Protection Agency, Science Advisory
Board, Washington, D.C.
-------
CONTENTS
1. EXECUTIVE SUMMARY 1
2. INTRODUCTION 1
3. RESEARCH NEEDS 2
4. TESTING TOE PRODUCTS OF BIOTECHNOLOGY 5
5. RISK ASSESSMENT 6
6. INTERAGENCY COCRDINATICN 6
7. INTERNATIONAL ACTIVITIES 7
8. BIOTECHNOLOGY ADVISORY GROUP 7
9. APPENDIX
A. Charge to the Study Group A-l
-------
1. EXECUTIVE SUMMARY
Although the U.S. Environmental Protection Agency (EPA) has increased
its research staff and initiated a research program in biotechnology, a
larger and broader program than that envisioned is needed by EPA decision
makers. Dispersal of genetically engineered microorganisms, appropriate
remedial action in the event of release of such organisms, and possible
environmental effects of such a release, whether beneficial or detrimental,
are critical issues which should receive high priority by EPA. Research
on health effects, as presently planned is limited in scope and should be
expanded, with adequate resources made available for this purpose.
The Agency has published a preliminary policy statement for testing
genetically altered microorganisms that is adequate in light of the present
state of knowledge; however, attention needs to be given to developing
test protocols to ccmply with this policy statement and future policy and
regulatory requirements, while still allowing the evaluation of biotech-
nology products on a case-by-case basis.
The Study Group supports interagency coordination efforts to harmonize
test protocols, to minimize difficulties and delays in approving biotech-
nology products, and to facilitate evaluations of possible health effects.
International communication and cooperation in research and regulatory
activities are of great importance and are needed.
The Agency should establish an advisory panel to review the adequacy
and direction of research, testing procedures, and risk assessment approach
to biotechnology on a continuing basis.
2. INTRODUCTION
The EPA Administrator requested that the Science Advisory Board (SAB)
undertake a preliminary examination of EPA's existing research and risk
assessment capabilities associated with the field application of genetically
engineered organisms. The SAB's Executive Committee accepted this request
and authorized the formation of a Study Group on Biotechnology.
Both the Agency and the SAB Executive Committee asked the Study Group
to: (a) identify information gaps for performing risk assessments on the
products of biotechnology; (b) explore the direction of EPA's research
program in biotechnology; and (c) evaluate the availability of testing
procedures and EPA's assessment methods for genetically altered organisms.
The Study Group held meetings on March 19, July 22-23, and December 19,
1985, at which times it was briefed by John A. Moore, Assistant Administrator
for the Office of Pesticides and Toxic Substances (CPTS), and by the staff
of the Office of Pesticide Programs (CPP), Office of Toxic Substances (OTS),
-------
and Office of Research and Development (ORD). The Study Group also met
with scientists directing the newly initiated biotechnology programs at
the EPA's Gulf Breeze, Corvallis, and Research Triangle Park Laboratories
to review their research activities and plans. The Study Group received
extensive documentation frcm all Agency offices and laboratories currently
involved in biotechnology. In addition, QPP staff identified, without
revealing confidential business information (CBI), submissions for permits
to field test genetically engineered microorganisms.
The Study Group is pleased to note the completeness and frankness of
the staff presentations. The EPA staffs were forthright about information
gaps, problems and needs. Despite the restricted time available to meet
with them, the Study Group believes that it has a relatively clear under-
standing of what information is needed, the current status of the EPA's
research in biotechnology, and the availability of meaningful tests for
evaluating genetically engineered organisms. Because the EPA has only
recently begun its research and regulatory activities, an intensive
detailed report by the Study Group was not deemed necessary at this time.
3. RESEARCH NEEDS
A biotechnology research program adequate to meet the needs of the
Agency should include the following topics: (a) survival; (b) growth;
(c) genetic transfer in situ; (d) dispersal; (e) environmental effects;
(f) health effects; (g) remedial action; and (h) use of biotechnology for
destroying environmental pollutants.
• Survival - A genetically engineered microorganism may present a
problem only if it persists in natural environments, and organisms to be
used for pollution control must be able to endure. Nevertheless, it is
not new possible to predict survival for either regulatory purposes or
for the practical exploitation of microorganisms designed for biotechno-
logical uses.
• Growth - The few individual organisms that are released or persist
are not likely to have a detrimental or beneficial effect because of their
small populations, and an increase in numbers or bicmass is necessary for
these to have some ecological or health effect. However, the current data
base must be expanded to allow for accurate prediction of which types of
organisms will and which will not proliferate.
• Genetic Transfer - A genetically engineered species that is harmful
might itself not survive or multiply, but the relevant genetic information
could be transferred in situ to other organisms. The latter might ultimate-
ly become harmful.. Although enormous progress has been made in recent years
in increasing our understanding of gene transfer under highly artificial
conditions, little information exists on gene transfer in nature.
2
-------
• Dispersal - The site of release of a genetically engineered or
nonindigenous organism is usually not the site where it can bring about
sane deleterious change because of the absence of suitable host animals
or plants, or the absence of suitable environmental conditions. Risk
assessment thus requires information on the mechanisms and likelihood of
dissemination by insects or other animal vectors, through air or soil,
by water transport, or by other means. Epidemiology and plant pathology
have developed good bases of knowledge on known pathogens, but little
attention has been given to the organisms of current or likely future
interest in biotechnology, and there is limited understanding of the
traits contributing to successful dispersal.
• Environmental Effects - Both the public sector and the scientific
community are concerned with effects on natural communities and natural
processes. Hie Agency has had a research program on measuring effects
of chemicals on such ccnimunities and processes and has considered the
influence of chemicals as part of its regulatory mission. Products of
biotechnology need to be evaluated in different ways from chemicals
because these organisms are highly specific for the plants, animals, and
microorganisms they may invade or harm, and the generalizations so useful
in toxicology probably have little meaning for potential communicable
agents.
o Health Effects - EPA needs information and expertise in public
health, communicable disease risks, and the relevant biomedical disci-
plines for its biotechnology program. Other Federal agencies, including
the National Institutes of Health (NIH) and the National Science Foundation
(NSF), are unlikely to fur id research that meets EPA's specific information
requirements in making regulatory decisions about any potential health
effects of genetic engineering applications. Also, in order to develop
scientifically defensible risk assessments, EPA must have in-house ex-
pertise.
Because of the large variety of possible organisms and applications,
it is not feasible at this state to develop a predictive model for health
effects. Instead, the Study Group recommends a case-by-case approach to
considering potential health hazards related to environmental releases of
genetically^altered organisms. Nevertheless, EPA must develop a biotech-
nology health effects research strategy and a critical mass of scientists
and address how the accumulation of experience from individual cases will
lead to more general guidelines in the future.
• Remedial Action - A means must be found to contain and possibly
destroy a geneticallyengineered organism in the unlikely event that,
despite the research conclusions and the testing before release, the
organism is found to be harmful. Some precedents exist on means for
remedial action from human and veterinary medicine and plant pathology,
3
-------
but the possible differences in environmental behavior of genetically
engineered microorganisms dictate that attention be given to containment
and rejnedial action.
• Biotechnology to Destroy Pollutants - The techniques of modern
genetics and environmental microbiology can aid substantially in reducing
the concentration or totally destroying chemical pollutants in surface
and ground waters, industrial and municipal waste-treatment systems, and
possibly in other circumstances. Microorganisms have the advantage of pro-
viding a low-cost, simple, and often highly effective means for chemical
destruction. The programs of the Agency could benefit greatly by increasing
financial and personnel resources in this area.
As part of its recently initiated research program, the Agency has
hired new personnel and initiated cooperative agreements. Research is
planned in methods development to detect genetically engineered micro-
organisms and measure the reliability and sensitivity of these methods.
Some research on survival, growth, genetic transfer in situ, and environ-
mental effects is also planned. Modest programs on health effects and
possible uses of biotechnology are also underway. However, the Study
Group believes that the magnitude of the program is, at present insuffi-
cient for the Agency's needs. In addition, as the products of biotechnology
move from the laboratory to ccanmercialization, the problems and processes
of scale-up need to be addressed.
EPA has already initiated work on survival, growth and genetic transfer.
However, the Study Group identifies the following areas as critical to the
Agency and needing additional attention:
• Dissemination - An adequate base of information needs to be
developed on the dispersal of genetically engineered micro-
organisms.
• Remedial Action - Research should be initiated to develop
methods for clean-up and containment in the event of the
dissemination of a harmful organism.
• Environmental Effects - The Agency has essentially no program
in this area. The EPA should mount a research effort to
assess possible perturbations in natural communities related
to genetically engineered microorganisms. Research also
should be conducted on the use of microcosms as models
for natural canmunities, using the microcosms to evaluate
effects of viable agents, as has been done for chemicals.
The feasibility of the testing protocols and the validity
of the risk assessment procedures might be tested using
naturally occurring or genetically engineered microorganisms
specifically selected or designed to bring about the in-
activation and degradation of environmental pollutants.
4
-------
• Health Effects - The scientific staff should, at a minimum,
be involved in the following health effects activities:
(a) development of test protocols, building upon and revising
the existing protocols in Subdivision-M of the Pesticide Assess-
ment Guidelines; (b) technical assistance on current information
and emerging trends in health effects and biomedical mechanisms.
Staff must draw upon the relevant reference materials, published
literature, computerized data bases, regular contacts with out-
side scientists, scientific societies, and their own research.
One objective of this function is to facilitate both industrial
and in-house selection of microorganims least likely to present
health risks—based upon an ongoing analysis of the features of
pathogenicity, including propensity for exchange of genetic
material; and (c) an expanding program of well-focussed, peer-
reviewed intramural research, supported in order to attract
and retain able scientists who can meet the regulatory science
needs and interact with extramurally-supported scientists.
The scientific staff concerned with all of these topics should serve
as resource personnel to respond to technical issues raised by program
officials. The staff should influence the kinds of generic questions that
the program offices address to the research agenda.
4. TESTING TOE PRODUCTS OF BIOTECHNOLOGY
Both CPP and OTS have developed a logical framework for obtaining
information from developers of biotechnology products. The types of data
sought by the staff should provide a scientifically improved basis for
appropriate regulatory decisions. Despite the absence of a substantial
base of information concerning environmental fate and possible environmen-
tal effects of introduced organisms, OPP and OTS staff have developed
preliminary guidance addressing, on a case-by-case basis, the issues of
possible consequences of biotechnology products. We encourage the inter-
action between EPA and industry to continue to gain information.
Hie absence of generally accepted tests and test methods, however,
is cause for concern. Some tests do now exist in Subpart M of the Pesticide
Guidelines in certain areas of risk assessment. Although EPA requires
results of tests of survival, multiplication, dispersal and possible
ecological effects of genetically engineered organisms, generally accepted
test protocols for providing such data do not exist. This absence creates
problems both for industry in the attempts to satisfy requests for inform
mat ion from the Agency and for EPA and the public in evaluating the
potential risk.
The Study Group recommends that EPA initiate research to develop
appropriate tests for evaluating survival, multiplication, dispersal and
possible deleterious effects of genetically engineered organisms. We
believe that certain of these tests will need to be conducted using micro-
cosms specifically designed for biotechnology products; hence, appropriate
protocols will need to bo Revised with a view to applying EPA's experience
with microcosms to biotechnology products. These laboratory and microcosm
testing methods will also need to be validated by field trials with engi-
5
-------
neered organisms whose safety is known or by using surrogate species.
Publicly owned, professionally managed "contained sites" should be identi-
fied for this testing.
The Study Group believes that the availability of generally accepted
testing procedures does not minimize the importance of, or the need for,
considering each organism submitted for approval on a case-by-case basis.
The development of biotechnology for practical purposes is too new an
endeavor to warrant a generic approach to product evaluation at this time.
5. RISK ASSESSMENT
The EPA's fundamental mission, as defined in the various statutes
through which it establishes and administers environmental programs, is
to identify, assess, and abate the risks of pollution to human health and
the environment. The risks or perceived risks that accompany the develop-
ment and introduction of chemicals into the environment create the need
for research on environmental fate and effects and human health impacts of
chemicals and the development of regulatory programs. Fran this research,
scientific investigators and regulatory personnel hope to gain the knowledge
to estimate the risks of chemicals to the environment and to human health.
Previous research on the fate and persistence of chemicals in the environ-
ment has been used to determine appropriate test protocols and to assign
risks to the chemicals developed by industry.
With the evolution of biotechnology, a new and exciting challenge has
arisen to discover the principles that govern the dispersal and persistence
of genetically engineered microorganisms in the environment, as well as to
determine their ability to multiply? the latter issue does not pertain to
chemicals. However, scientists recognize that there have been few problems
because of the release into the environment of organisms produced by tradi-
tional genetic means. As with chemicals in the environment, scientists
hope that after these principles are discovered, predictive models can be
developed for use in preparing reliable risk assessments. Innovative
research over an extended period of time by EPA, other Federal agencies,
the private sector, universities, and others will be required before
scientists discover these principles. Only then will definitive test
protocols gain general acceptance and predictive models for health and
environmental risk assessment have real relevance to private and public
sector decision making.
6. INTERAGENCY COORDINATION
At least four agencies (EPA, FDA, NIH and USDA) have direct concerns
related to developments in biotechnology, while others, such as the Depart-
ment of Defense, will also be impacted by this technology. The Office of
Science and Technology Policy has proposed a formal mechanism, the
Biotechnology Science Coordinating Committee, to establish a coordinated ¦
framework for the regulation of biotechnology. 1
1 "Coordinated Framework for Regulation of Biotechnology; Establishment of
the Biotechnology Science Coordinating Committee," Federal Register,
November 14, 1985.
6
-------
Among the benefits frcm such coordination is the identification of a
lead agency for defined products and processes of biotechnology; that
lead agency will be available to industry or research scientists for
advice on field testing and/or registration of these systems. Related to
this is the need for harmonizing minimum test protocols. The Study Group
believes that a single lead agency is necessary for individual products
and processes. This lead agency should use any major experience base of
other agencies.
The EPA does not currently have financial resources adequate to develop
protocols on the health effects of biotechnological agents. Because the
need exists, however, EPA should seek to involve other agencies to parti-
cipate in the necessary research and help establish the requisite test
protocols.
7. INTERNATIONAL ACTIVITIES
The impact of biotechnology applications obviously has worldwide
significance. Since biotechnological developments do not have geographi-
cal boundaries, international communication and cooperation is of great
importance. The Study Group recognizes and commends the efforts made by
EPA and other Federal agencies to emphasize cooperative research with
foreign investigators and to attempt to harmonize international regulatory
activities.
8. BIOTECHNOLOGY ADVISORY GROUP
We are impressed with what the EPA staff has done in the brief time of
its involvement with biotechnology, and we believe that the value of the
programs will be augmented by input frcm experienced technical personnel.
We believe that the scientific basis of biotechnology, regulatory as
well as research activities of EPA, would profit greatly frcm advice
and review by specialists with knowledge and experience in the relevant
scientific disciplines.
Thus, we reccmmend that EPA establish one advisory panel to review
the intramural and extramural research programs, the adequacy of the
testing procedures, and the Agency's risk assessment approach to
biotechnology. The specific charge to the committee should include:
a) review of selected individual risk assessments; b) review of cross
media and cross program scientific issues; c) comparison of specific risk
assessments to ascertain the degree of internal consistency including
unnecessary duplication of effort among EPA programs; d) evaluation of
trends arising frcm the consideration of groups of individual risk assess-
ments and regulatory applications; e) consider the environmental and
health consequences of the likely growth of the biotechnology industry;
and f) recommendation of needed research.
7
-------
Among the benefits anticipated from an external advisory process are
enhancement of EPA's credibility with the scientific community, providing
a forum for developing scientific consensus, and providing peer review of
EPA's risk assessments. Hie panel might be an independent committee that
contains representatives of both the Science Advisory Board and the Science
Advisory Panel (SAP) of OPP, or it might be part of SAB or SAP. This
advisory panel should include members with expertise in microbial ecology,
population genetics of microorganisms, ecosystem ecology, communicable
diseases of animals and plants (especially of natural populations), pest
management, molecular genetics, microcosms, chemical and environmental
engineering and risk assessment, as well as other disciplines that the
Agency deems necessary. Such a panel should have the flexibility to
recruit more specialized expertise, when needed, and establish sub-
committees to carry out its review responsibilities. The advisory panel
should report directly to the Administrator.
8
-------
CHARGE TO THE SCIENCE ADVISORY BOARD STUDY GROUP ON BIOTECHNOLOGY
Administrator William D. Ruckelshaus requested that the Science
Advisory Board (SAB) Executive Committee take a preliminary look at
EPA's current capabilities in addressing several issues associated with
the field application of genetically altered organisms. The Committee
accepted this request and authorized the formation of a Study Group on
Biotechnology. The Executive Committee chose to form a study group at
this juncture based upon its belief that it would be premature to carry
out any formal SAB review until the many inter-Agency jurisdictional and
policy questions related to biotechnology are resolved within the Federal
government.
The information to be gathered by the Study Group includes:
• Identification of information gaps for performing risk
assessment;
• Exploring the direction of EPA's research program in
biotechnology; and
• Assessing the availability of testing procedures for
genetically altered organisms and EPA's assessment methods.
Hie Study Group will present its findings, options, and recommendations
to the SAB Executive Committee.
A-l
-------
|