UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON, D.C. 20460
November 10, 1986
THE PROCEEDINGS OF THE UNITED STATES
ENVIRONMENTAL PROTECTION AGENCY WORKSHOP ON
BIOTECHNOLOGY AND POLLUTION CONTROL
20, 21 March, 1986
Wimbledon Room
Linden Hill Hotel and Racquet Club
5400 Pooks Hill Road
Bethesda, Maryland 20814
THE OFFICE OF TOXIC SUBSTANCES
THE OFFICE OF POLICY, PLANNING, AND EVALUATION
The views, opinions, and/or findings contained in this document are those of
the Workshop's Panel members and should not be construed as an official U.S.
Environmental Protection Agency position, policy, or decision.
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THE PROCEEDINGS OF THE UNITED STATES
ENVIRONMENTAL PROTECTION AGENCY WORKSHOP ON
BIOTECHNOLOGY AND POLLUTION CONTROL
Zontract Mo. 63-02-3952
'/ork Assignment 2-16
November 10, 1986
Submitted to:
Office of Policy, Planning, and Evaluation
Office of Toxic substances
U.S. Environmental Protection Agency
401 N Street, S.V.
Washington, D.C. 20460
Submitted by:
The Dynamac Corporation
The- Dynamac Building
11140 Rockville Pike
Rockville, HD 20852
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MEMBERS OF THE PANEL
DR. GILBERT OMENN (CHAIRPERSON)
Dean
School of Public Health
University of Washington
Seattle, Washington 98195
MS. JODI BAKST
Environmental Protection Agency
(COCHAIRPESSON -and WORKSHOP COORDINATOR)
DR. DOUGLAS CALDWELL
Department of Applied Micro Food Sciences
University of Saskatchewan
Saskatoon, Saskatchewan, SIX, CVO, Canada
DR. ANAWDA CHAKRABARTY
University of Illinois Medical Canter
Microbiology Department
835 S. Wolcott Avenue
Chicago, Illinois 60637
DR. PETER CHAPMAN
Environmental Protection Agency
Environmental Research Laboratory
Sabine Island
Gulf Breeze, Florida 32561
THOMAS DAROAS, ESQUIRE
President and Chief Executive Officer
Detox Industries
4800 Sugar Grove Boulevard
Suite 210
Stafford, Texas 77477
DR. ALAN GOLDHAMMER
Industrial Biotechnology Association
2115 E. Jefferson Street
RocJcvllle, Maryland 20852
DR. BARRY KATZ
MYCOsearch
P.O. Box 941
Chapel Hill, North Carolina 53706
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MEMBERS OP THE EXPERT PANEL (continued)
DR. ANNE KOPECKY
Sybron Biochemical, Inc.
P.O. Box 808
Salem, Virginia 24153
DR. JOHN LOPER
Department of Microbiology and Molecular Genetics
University of Cincinnati Medical Center
Cincinnati, Ohio 452667-0524
DR. MARGARET MELLON
Environmental Law Institute
Suite 200
1516 "?" Street, M.V.
Washington, D.C. 20036
DR. ANDREW MIDDL2TON
Koppers Company, Inc.
440 College Park Drive
Monroeville, Pennsylvania 15146
DR. THOMAS PEYTON
AraTech consultants
Suite 517
Life Building
300 Main Street
Lafayette, Indiana 47902
DR. GEORGE PIERCE
Battelle Memorial Institute
505 King Avenue
Columbus, Ohio 43201
DR. GARY SAYLER
Graduate Program in Ecology
691 Old Dabney Hall
University of Tennessee
Knoxville, Tennessee 37996
DR. JOHN SMITH
Koppers Company, inc.
440 College Park Drive
Monroeville, Pennsylvania 15146
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CONTENTS
Page
I. EXECUTIVE SUMMARY 1-1
II. STATEMENT OF PURPOSE FOR THE WORKSHOP II-1
III. PROPOSED TOXIC SUBSTANCES CONTROL ACT (TSCA) REGULATOR*
POLICY FOR BIOTECHNOLOGY POLLUTION CONTROL PRODUCTS III-l
A. Proposed Policy [II-1
3. Categories of Concern III-2
1. Microorganisms produced by interger.eric transfer of
genetic informat ion ::i-2
2. Microorganisms containing genetic information
obtained from pathogenic microorganisms iLI-1
3. Microorganisms intended for deliberate release in the
environment • III-3
IV. BARRIERS TO AND INCENTIVES FOR FIELD TESTING MICROBIAL
POLLUTION CONTROL PRODUCTS IV-1
A. Field Testing Definitions IV-2
B. Conventional Versus Engineered Microorganisms IV-3
C. Barriers IV-6
1. Test site selection and requirements IV-7
2. Testing standards - design, performance, and
evaluation IV-10
3. Containment issues IV-12
a. Monitoring iv-13
b. Mitigation and emergency response IV-14
4. Assessment of'environmental Impact IV-15
5. Risk assessment criteria IV-15
6. Protection of proprietary rights and from litigation IV-17
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CONTENTS (continued)
Page
7. Regulation IV-18
a. Regulation under TSCA IV-19
b. Permitting and reporting IV-21
8. Public perceptions IV-21
D. Possible Incentives IV-22
1. Comparative evaluation of microbial and conventional
pollution control methods to assess "best demonstrated
available technology" IV-23
2. Consideration of biotechnology as an alternative to
conventional :'burn or bury" methods .:'/-.2 3
3. Use of existing contaminated sites 17-24
4. Development of Federal field testing programs under
RCRA/Superfund IV-27
V. BARRIERS TO AND INCENTIVES FOR THE COMMERCIALIZATION OF
MICROBIAL PRODUCTS FOR POLLUTION CONTROL V-l
A. Incentives For Commercialization V-l
1. Microbiological pollution control products -
historical and current uses V-l
2. Technological advantages presented by the development
of new biotechnology products V-2
3. Market opportunities and investment as a
function of existing regulatory statutes v-2
a. Air pollution control v-3
b. Water pollution control v-3
c. Solid waste management v-3
4. Basis for the expansion of the biotechnology
pollution control industry V-4
B. Barriers to Commercialization V-4
1. Technical barriers V-4
a. Need for basic, generic applied, and applied
research V-4
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CONTENTS (continued)
Page
b. Need for risk assessment methods and criteria . v-5
2. Economic barriers v-6
a. Research costs v-6
b. Development costs v-6
c. Commercialization costs v-6
3. Regulatory barriers ' • v-7
4. Public concerns and perceptions of risks v-3
C. Possible Solutions v-9
1. To address technical barriers . "-•)
2. To address regulatory barriers ':'—'»
a. Technical regulatory barriers V-9
b. Establish data on risk and expedite review process v-10
3. To address economic barriers V-ll
a. Government funding of generic applied and applied
research and the development of risk
assessment methods V-12
b. Use of Small Business Innovative Research (SBIR)
program to promote and support the development
and commercialization of biotechnology products v-12
c. use of low-interest-rate government loans to promote
and support development and commercialization V-14
d. Use of RCRA/Superfund Program to provide
characterized sites for field testing v-14 .
D. Suggested Regulatory Incentives V-15
VT. PUBLIC PERCEPTIONS OF RISKS AND BENEFITS OF BIOTECHNOLOGY
POLLUTION CONTROL PRODUCTS . VI-1
A. concerns about Risks Associated with the Use/Release
of Microbial Products ' Vl-3
1. Barriers to understanding biotechnology vi-4
a. Lack of information vi-4
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CONTENTS (continued)
Pace
b. Misconceptions vi-5
c. Lack of multidisciplinary communication vi-5
2. Perception of past industry priorities: Conflicts
between profit and safety issues VI-5
3. Prior overstated reassurances by agencies about
the extent of risks vi-7
4. Unclear sense of possible risks vi-3
a. Risks to environment and human health vr-3
b. Defining unreasonable risk vr-9
c. Ability of government agencies to evaluate risks • c-5
d. Risk analysis - baiancir.g costs and benefits '. :-LO
3. • Perception of Benefits of Biotechnology /:-!!
1. Use for pollution control vi-11
2. Use for emergency response VI-11
C. Initiatives Suggested To Address Concerns VI-11
1. Recognition of public perceptions by agencies
and industry VI-12
2. Education of public, academic, scientific,
and engineering communities and governmental
agencies vi-12
3. Maintenance of industry's and USEPA's credibility vi-13
4. Development and use of biotechnology-specific
tier testing and risk assessment methods VI-14
a. Database VI-14
b. Tier testing VI-14
c. Risk assessment Vl-15
VII. USEPA'S POLLUTION CONTROL-RELATED BIOTECHNOLOGY RESEARCH VII-1
A. Environmental Research Laboratories, Gulf Breeze, Florida vii-2
1. Detection of biodegradlng microorganisms vii-3
2. Cometabolism of organic compounds VII-3
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CONTENTS (continued)
Page
3. Degradation of chlorinated aromatic compounds by
anaerobic microorganisms vn-3
4. Degradation of halo-organic compounds - detection of
microorganisms and analysis of degradation pathways vil-3
5. Environmental impact - monitoring and assessment
methods and biological containment VII-4
a. Environmental ecology '7II-4
b. Methods for biological self-containment for
released microorganisms vir-5
3. Hazardous Vaste Engineering Research Laboratory,
Extramural Research, Cincinnati, Ohio
1. Chlorinated organic compounds - Jevelcpment of
.inaerobic blcdegraders
2. Microbial binding proteins - isolation and
characterization VII-6
3. Enhancement of microbial nitrification vil-7
4. Elucidation of the mechanisms of methanogenesis vil-7
C. Hazardous Waste Engineering Research Laboratory,
Intramural Research, Cincinnati, Ohio vil-8
1. Construction of blodegradative microorganisms vil-8
2. Microbial degradation of polychlorinated biphenyls vn-9
3. Plant uptake of hazardous wastes vii-9
4.: Degradation of chlorinated organic compounds by
white rot fungus vil-9
VIII. SUMMARY VIII-1
IX. APPENDICES
A. Dr. Omenn's Report on the Workshop A-l
B. Workshop Background Paper B-l
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CONTENTS (concluded)
Page
C. Workshop Program
C-l
D. Abbreviated Biographies of Panel Members
E. List of Workshop Observers
S-l
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I. EXECUTIVE SUMMARY
Consistent with its mission to protect the environment and human
health, the U.S. Environmental Protection Agency (USEPA) is exploring new
technologies that may have potential applications for the safe, effective,
and economical removal of hazardous substances from the environment.
Although microorganisms have been used for years in waste treatment, it is
conceivable that biotechnology products, consisting of both- jenetleally
engineered or nonengineered microorganisms and cheir cellular products, .T.ay
have broader applications for direct or complementary treatment of hazardous
substances in toxic dumps, chemical spills, and wastewaters. "M..- >c:
.nicrobiological treatment may decrease concentrations of hasar-icus
substances and thus eliminate che r.eed for secondary trsdcrr.er.-.3.
3iotechnology products may also be used as alternatives and/or complements
to existing pollution control technologies.
The development of biotechnology products (both genetically engineered
and nonengineered microorganisms and their cellular products) for pollution
control is lagging behind product development in other sectors of the
biotechnology industry. To identify and examine the factors that influence
the development of biotechnology pollution control products, the Office of
Toxic substances and .the Office of Policy, Planning, and Evaluation convened
the Biotechnology and Pollution control Workshop. The goals of this
Workshop . were to examine the barriers to and incentives for
commercialization; to develop recommendations for promoting, evaluating, and
regulating field testing; and to identify strategies to foster the
development and commercialization of biotechnology pollution control
products. The invited participants in the Workshop included academic,
industrial, and Agency biotechnology experts.
Several technological advantages of the application of biotechnology
products to pollution control were identified. Although these advantages
are conceivable for either engineered or nonengineered microorganisms, the
Panelists felt that genetic engineering would allow the development of
biotechnology products that can be specifically tailored. Included among
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the technological advantages of using biotechnology pollution control
products are the ability to:
1. Develop strains with enhanced activity in specific
degradative enzymes;
2. Develop strains whose functional activities are less
susceptible to environmental conditions;
3. Develop strains capable of withstanding highly toxic
environments;
4. Develop potentially controllable microorganisms;
5. Develop genetically marked strains that are intended cor
deliberate release in the environment (this would
facilitate the monitoring of survival and dispersal as
well as protect proprietary rights); and
6. Develop strains that ire safer than naturally cccurri~q
and nonengineersd strains.
In the Panelists' opinion, microbiological approaches to pollution
control may also become more cost effective than conventional methods once
the biotechnology pollution control industry is more fully developed.
In this Workshop, a variety of technical, economic, regulatory, and
public perception barriers to the commercialization of biotechnology
products were identified. Technical barriers were Identified as issues
associated with the field testing of biotechnology products, the need for
basic, generic applied, and applied research, and the need for the
development of risk assessment criteria and methodologies. Economic
barriers that were identified included the significant costs associated with
research, development, and commercialization of biotechnology products and
the industry's costs for indemnification and liability insurance. As
regulatory barriers, the regulatory policies and reporting and permitting
requirements of Federal, State and local governments were identified.
Finally, negative public response, which is based on the. public's concern
and perception of the risks presented by the applications of biotechnology,
was identified as an existing barrier.
Field testing is an important early step in the commercialization of
biotechnology pollution control products. Technical, economic, and
1-2 .
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regulatory barriers to field testing were identified. The technical
barriers included the lack of defined site selection criteria, testing
standards, environmental assessment methods, and. standardized methods for
containment, monitoring, and emergency response. The high costs associated
with research, field testing, indemnification, and liability insurance were
identified as economic barriers to field testing. As regulatory barriers,
the policies at Federal, State, and local levels were identified. These
barriers to field testing are all associated to some extent with a reed for
additional research. For example, research is needed to define and evaluate
the risk that may be associated with the environmental " release of
genetically engineered microorganisms. The results of such research could
be utilized to define criteria for selecting field test sites.
To reduce the barriers to field cestinq, the Panelists suggested :^.e
usci -f existing contaminated sites for field tests. r.^.ey -»pec ificjl ly
recommended that a federally designated/sponsored/managed field "sscing
program be developed under the Resource Conservation and Recovery Act (RCRA)
and/or the Comprehensive Emergency Response, Compensation and Liability Act
(CERCLA)/Superfund. They felt that the use of these already identified and
characterized sites could expedite field testing and perhaps reduce field
testing costs (monitoring, permitting, reporting, and liability) to
industry. Although, the multiplicity of contaminants that may be present in
existing landfills was identified as a major disadvantage of using such
sites, the Panelists felt that making sites available for field testing and
reducing the associated cost could act as incentives for field testing.
Technical, economic, and regulatory barriers to the development of the
biotechnology pollution control industry were also identified. Technical
barriers Included the need for additional basic, generic applied, and
applied research. However, industry representative pointed out that the
significant costs associated with conducting biotechnology research are
almost prohibitive. Although the government is committed to the funding of
basic research, government expenditures for generic applied research are
limited which may further retard biotechnology product development. The
point was also made that until the efficacy of microbiological pollution
control products is demonstrated, it is unlikely that industry would invest
large amounts of capital in applied/developmental biotechnology research.
Economic barriers that were identified were associated with product research
1-3
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and development costs, including field testing and indemnification and
insurance costs. Federal, State, and local governments' regulatory
requirements, the costs associated with meeting these requirements, and the
uncertain regulatory climate were also identified as barriers.
Several suggestions were made to eliminate technical and economic
barriers. It was suggested that government funding of generic applied
research be increased and that Federal funds be used to support comparative
evaluation studies of microbiological products and conventional waste
treatment methods. The Small Business Innovative Research Program and
lew-interest government loans were suggested -as a -neans of supporting
research chat is directed towards ass9ssing the "best 'Jemonstrated available
technology" and for demonstrating the efficacy of a microbiological apprcacn
to pollution control. These funding :7iechjnisms could also ce 'j^-j--: -3
promote and support generic applied and applied research. The ?3r.s:i3t5
felt "hat the government should partially offset che costs of
indemnification and liability insurance. Finally, the Panelists felt that
research currently underway in the USEPA's biotechnology research program is
critical for the development of evaluative and assessment criteria and
methods.
Suggestions were also made to reduce regulatory barriers. The
Panelists felt that legislative and regulatory incentives could be used to
provide guidance and to suggest the consideration of microbiological
approaches as alternatives to conventional waste treatment methods. In the
Panelists' opinion the full implementation of the existing RCRA/Superfund
statutes may produce greater interest in the development of effective,
economical techniques among waste generators and managers. It was pointed
out that the granting of variances from regulatory policies may also foster
the development of new technologies.
The public's concerns and perceptions of the risks associated with
biotechnology may influence the development of biotechnology products. For
example, public'concerns are most likely to be expressed by the population
near field testing sites. Thus, a negative public response may also present
a barrier.
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It was strongly urged that cooperative efforts by industry and the
Agency be undertaken to educate and inform the public with respect to the
scientific basis and potential beneficial applications of biotechnology to
pollution control. The Panelists felt that every attempt should be made by
industry and the Agency to maintain and build their credibility and
demonstrate their competence to the public. it was pointed out that field
tests would provide the Agency with excellent opportunities to educate,
inform, and involve the public and to demonstrate the potential benefits of
microbiological pollution control products. In addition to educating the
lay public thro.ugh the school systems, public hearings, and Involvement in
the Toxic Substance Control Act's Premanufacture Motif ication .-aview
process, it was suggested that information be made available to the
academic, scientific -and engineering communities at professional
conferences, seminars, ind via publications in professional journals.
The experts who participated In the USEPA's Workshop on Biotechnology
and Pollution Control identified and discussed various technical, economic,
and regulatory factors that they felt presented barriers to the development
of the biotechnology pollution control industry. Based on their
examination of these issues, the expert Panelists suggested specific actions
and initiatives that could facilitate field testing and demonstrate the
efficacy of biotechnology pollution control products. The Panelists
recommended strategies and initiatives that could provide economic support
and incentives and thus foster the development of the industry. These
experts also recommended initiatives and strategies for creating a positive
perception and for building the credibility of the biotechnology industry
and the Agency with the public.
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II. STATEMENT OF PURPOSE FOR THE WORKSHOP
The Nation has a need for safe and effective methods for pollution con-
trol. There are many priority pollutants in hazardous waste sites,
landfills, industrial effluents, groundwater, and other media. Conventional
methods of chemical pollution control include incineration, chemical de-
struction, and physical stabilization ("burn or bury" methods). New or
enhanced technologies are needed as alternatives and/or complements to the
conventional "burn or bury" methods. 7or example, microbiological methods
are currently being used to treat municipal and industrial wastewaters,
sewage, and toxic spills. The microorganisms that are employed cor these
purposes have not been genetically engineered. Improvements in the -:.< LJC ir.a
microbiological waste treatment methods c^n '.nerefore consist oc r jc ir.'.ng
nonengineered microbial products as well js the development of ^.enecicaliy
engineered microbial products.
. Consistent with its mission to protect the environment and human
health, the U.S. Environmental Protection Agency (USEPA) is exploring new
technologies that may contribute to the development of safe, effective
methods for the removal of hazardous substances from the environ- raent. The
Science Advisory Board Executive Committee, in its report1 to the
Honorable Lee Thomas, Administrator of the USEPA, in which the Agency's
capabilities to address several issues associated with the field application
of genetically altered organisms were evaluated, stated the following:
"The techniques of modern genetics and environmental
microbiology can aid substantially in reducing the
concentration or totally destroying chemical pollutants
In surface and groundwaters, Industrial and municipal
waste treatment systems and possibly in other
circumstances. Microorganisms have the advantage of
providing a low-cost, simple, and often highly effective
means for chemical destruction.'"
1 Science Advisory Board, Office of the Administrator. Assessing EPA's
Biotechnology Research and Information Needs. Report No.
SAB-EC-86-009. January 1986.
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The use of biotechnology products, either microorganisms or their
cellular products, may increase the Nation's capacity and capabilities for
pollution control. Biotechnology products, from either genetically
engineered or nonengineered organisms, may be used for direct or
complementary treatment of toxic dumps, chemical spills, and wastewaters.
Direct treatment may decrease the concentrations of the hazardous substances
and may eliminate the need for secondary treatments.
Biotechnology products have already -appeared in the pharmaceutical,
chemical, and agricultural .-narkets. 3y contrast, improvements in the
existing biotechnology products (r.cnengineered microorganisms) -and 'he
development of genetically engineered .nicrobial products for the pollution
control market has been slower. The Agency recognizes chat 3 variety jf
technical, economic, .and regulatory barriers co the commercial d^vei ^c.T.5-.:
of biotechnology products for pollution control -jxist and that these L.-..iLDit
the development of such products. The usEPA Workshop on 3iotechr.olc<:y snd
Pollution Control was held to identify and analyze the factors "hat
influence the development of safe biotechnology pollution control products.
In accordance with this purpose, it was requested that the Panelists
discuss three factors associated with the commercialization of
biotechnology. These were the identification and examination of the
technical, economic, and regulatory barriers to and incentives for the
commercial development of biotechnology pollution control products, the
development of recommendations for promoting, evaluating, and regulating
field testing, and the identification of strategies that would foster the
development and commercialization of biotechnology pollution control
products.
Field testing is one of the first steps in the commercialization
process. The Agency is anticipating having to evaluate and possibly
regulate the field testing of both engineered and nonengineered pollution
control microorganisms. Therefore, the Agency, sought information and
action- oriented recommendations from the Panelists on the design, site
selection, performance, and techniques for evaluating, regulating, and
promoting field tests. Specific suggestions were sought on how industry,
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academic, and Agency experts can cooperatively develop data that would
facilitate the evaluation of permit applications and expedite the review
process.
The Panelists were also requested to identify and explore existing and
potential incentives for commercial development of biotechnology pollution
control products and to develop strategies that would foster the development.
The invited participants included academic, industrial, and Agency
biotechnology experts, as well as individuals representative of public
interest groups. The views, opinions, suggestions, and recommendations of
the Panel members are reported in uhls proceedings of the Biotechnology -and
Pollution Control Workshop and do not represent an official uSEPA pcsitlsn
or policy.
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III. PROPOSED TOXIC SUBSTANCES CONTROL ACT (TSCA) REGULATORY POLICY
FOR BIOTECHNOLOGY POLLUTION CONTROL PRODUCTS
A. Proposed Policy
Certain biotechnology products will be subject to review and reporting
requirements under the Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) and the Toxic Substances Control Act (TSCA). In its 1984 proposed
approach to regulating biotechnology products,2 the USSPA proposed to
subject all genetically engineered microorganisms to an equal level of
regulatory scrutiny. In response to this proposal, the Agency received and
analyzed comments from approximately 70 organizations and individuals. The
ccmmentors suggested that the Agency Identify categories of genetically
engineered microorganisms that present higher and lower levels oc r:.z.< -.r.-l
establish' a regulatory policy in accordance with these categories. c.n
consideration of the comments received in response to the 1984 proposed
regulatory policy and experience gained during its review of genetically
engineered microbial pesticides, the Agency proposed a modified regulatory
policy on microbial products.3
The modified USEPA policy on microbial products had not been released
at the time that this Workshop was held. Therefore, Ms. Anne Hollander/
Biotechnology Project Manager - OTS/USEPA, presented a keynote address,
describing the essential elements of the forthcoming policy. Thus, a
regulatory context was established in which Workshop discussions could be
framed.
Microbial products intended for use in waste degradation, chemical
production, conversion of biomass for energy, and other environmental and
industrial uses are subject to TSCA. However, the proposed policy for micro
USEPA. Proposal for a Coordinated Framework for Regulation of
Biotechnology. Federal Register 49:50880-50970 (December 31, 1984).
USEPA. Coordinated Framework for Regulation of Biotechnology;
Announcement of Policy and Notice for Public Comment. Federal Register
51:23301-23393 (June 26, 1986).
III-l
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bial products will be different from that for other chemical substances that
are subject to TSCA. Biotechnology products will have to be reported at an
earlier stage in their development. In addition, the Agency will have to be
notified before any environmental release, even on a small scale, can take
place.
Under the proposed policy, the Agency's resources will be focused on
those microorganisms whose behavior is most difficult to predict, those with
known inherent risks, and those with a potential for widespread -exposure.
The Agency proposes to initially give special consideration to three
categories of microorganisms. These categories ara discussed below.
3. Categories of Concern
1. Microorganisms produced by Inrargeneric transfer :>f j.j.ist !•:
Information
Microorganisms produced by deliberate human intervention that contain
genetic material from dissimilar source organisms (intergeneric micro-
organisms) are considered "new." Therefore, if they are to be manufactured
for TSCA purposes, the "new" microorganisms are subject to Premanufacture
Notification (PMN) requirements. This policy becomes effective when the
notice is published.
In addition, environmental testing of "new" (intergeneric) micro-
organisms will not be exempted from PMN requirements. Therefore, for "new"
microorganisms developed for commercial purposes, it will be required that
the USEPA be notified prior to environmental release. Ruleraaking will be
required to implement this policy. However, the Agency has requested
voluntary compliance with this policy until the rule is promulgated.
The Agency will consider an exemption from PMN requirements for those
"new" microorganisms that will be used solely in contained systems and that
are never intended for deliberate release in the environment.
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2. Microorganisms containing genetic information obtained from
pathogenic microorganisms
USEPA intends to complement its PMN policy with a prior notification
requirement for new environmental uses of genetically engineered micro-
organisms that are pathogens or contain genetic material that was obtained
from pathogens. This will be accomplished through a Significant Mew Use
Rule (SNUR) to be issued under Section 5(a)(2) of TSCA. The Agency expects
voluntary compliance until this rule is promulgated.
3. Microorganisms intended for deliberate release in the environment
The Agency intends to require that seme information (as yet undefined)
be reported prior to ail environmental uses of microorganisms that ira
subject to 7SCA but r.ot subject to .~MN or SNUR requirements. This -.-•ill '- =
accomplished through rulemafcing under the authority of Sect'.on 8(a) of rscA.
In addition to these three categories of concern, under TSCA,
manufacturers, processors, and distributors of microorganisms must
immediately notify the Agency if they become aware of new information that
suggests that the microorganisms present a substantial risk to human health
or the environment.
The Agency intends to require notification prior to all environ-
mental releases of microorganisms falling within categories 1 or 2. Almost
all other microorganisms subject to either the FIFRA or the' TSCA statute
will also have to be reported to the Agency prior to the first environmental
release (category 3). Information reporting requirements for microorganisms
in category 3 will be somewhat less detailed than that required for
categories 1 and 2, but will provide the US EPA with an important mechanism
to monitor environmental releases of microorganisms and to ensure that the
Agency is aware of any potential problems.
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IV. BARRIERS TO AND INCENTIVES FOR FIELD TESTING MICROBIAL
POLLUTION CONTROL PRODUCTS
Field testing is a necessary and critical step towards developing,
understanding, and commercializing microbial pollution control products.
The field testing step represents the first release of a candidate
commercial product from the laboratory to the environment. This testing
stage is designed to determine whether the potential product has value or
efficacy and is also designed to determine toxicity and environmental
effects posed by the release of the product.
Testing in the field represents ehe first point where the Agency nay
be required to implement regulatory policy, depending en the techniques -.ji--j
and the nature and quantity of che .-nicroorganisms. Currently, L.-.: a r L.TI
policy under FIFRA requires notification prior to all small-scale -field
studies involving microbial pesticides that contain naturally occurring
microorganisms for use in nonindigenous sites or microorganisms that have
been genetically altered or manipulated.4 Regulatory policy under TSCA
will also contain provisions and data requirements that pertain to field
testing studies.
Since field tests can be conducted in different ways and can be
designed to answer different questions, an attempt was made by the Panelists
to define field testing and to provide focus for more detailed examination.
Criteria relevant to genetically engineered and nonengineered microorganisms
were compared and contrasted, resulting in a discussion of the relevant
differences and their significance to field testing issues.
The risks and benefits presented by the deliberate release of gene-
tically engineered microorganisms into the environment are highly uncertain
when compared to more conventional pollution control technologies, and it is
these uncertainties that are major barriers to field testing. These barriers
Nicrobial Pesticides, Interim Policy on Small Scale Field Testing.
Federal Register 49(202) .-40659-40661 (October 14, 1984)
IV-1
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were discussed and examined at the Workshop and include site selection
criteria and test standard development, containment issues, risk and
environmental impact assessment procedures, protection of proprietary
rights, regulatory and permitting requirements, and public perceptions. The
purpose of the discussion was to promote the sharing of ideas among the
Panelists to develop ways of reducing or eliminating these barriers.
Although both risks and barriers are preser::, it was recognized that
there is both potential and a market for efficacious, genetically engineered
pollution control microorganisms. It was requested that che Panelists
examine possible incentives to encourage technology development.- The use of
existing contaminated sites, i.e., landfills, surface impoundments, and
waste dumps, for field otudies was discussed in detail. As another
incentive, the comparative evaluation of microbial Jegradaticn methods •i-.d
conventional pollution control methods could be .performed to assess ::-.-
"test demonstrated .available cachnology" for particular hazardous ••'•a-ic-i
sites. In addition, if government regulations and guidelines were :'3v«jio?ed
to encourage the use of more innovative biotechnology products as an
alternative to conventional pollution control methods, clear developmental
and marketing incentives could be provided to the biotechnology industry and
the research community. Finally, the development of a Federal field testing
program under RCRA and/or Superfund was perceived as a procedure that could
facilitate the field testing of experimental products by industry.
A. Field Testing Definitions
Field testing is an intermediate phase between research and product
development and is conducted after preliminary pilot studies and before
actual application or treatment of the product. The initial pilot or
feasibility studies are usually conducted in the laboratory. These
laboratory studies may be on a bench'scale, or may involve microcosm or
larger greenhouse studies, but they always take place in a controlled
setting. Pilot studies are designed to investigate the feasibility of the
product, but cannot effectively provide data for technical direction
(engineering applicability) or economic prediction. For these reasons and
others, field testing is an important stage of research and product
development. Field test designs draw on the results of laboratory
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feasibility studies and incorporate procedures to allow measurement and
understanding of the processes involved. Field tests are trials intended to
enhance assessments of feasibility, while examining the safety of the
product. These studies are. designed to determine the ability of the
microorganism to biodegrade the contaminant in a characterized environment,
on a limited scale, within a given time. They explore effects on target
species and more closely simulate weather and other variable conditions that
cannot be adequately investigated in a laboratory setting. Information
gathered from field studies allow for more accurate decision-making
concerning future capital investment and risk/benefit and cost/benefit
analyses.
Dr. Cmenn compared the development of biotechnology products -:o :>.e
development of medical products. He stated "hat :he approach to research :5
very much more cautious dnd regulated than cr.e approach to :reacmep.: . in
the medical realm, informed consent, review committees, institutional sacety
assessments, and elaborate procedures are required for research. Once
research findings are reviewed and procedures are developed into forms of
treatment, "almost anything goes with the broad domain of ethical
professional behavior and patient acquiesence." Dr. Omenn felt that
biotechnology field tests are likely to be considered as research endeavors
and will therefore be conducted with more caution and under more control
than the eventual applications.
Field studies are designed to generate data to guide the development
of appropriate treatment regimens. Risks must be elucidated and understood
from field testing before procedures can be expanded and extrapolated to the
much larger treatment scale.
B. Conventional Versus Engineered Microorganisms
Microorganisms and microbial products are not new to commerce. They
have been used for hundreds of years by the food and beverage industry, have
been registered for pesticidal use for approximately 20 years, and are used
in various systems for pollution control. Municipal and industrial waste-
water treatment generally rely on natural aerobic microorganisms for the
removal of dissolved organic compounds. Anaerobic fermentation processes
are commonly used to digest solid wastes in sewage treatment plants.
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Genetic engineering offers opportunities to enhance the capabilities
of naturally occurring microorganisms, providing the potential for increased
efficiency for current applications, as well as the opportunity for entirely
new applications. A broad range of techniques are available for modifying
microorganisms and the application of these techniques to create modified
microorganisms that will be deliberately released to the environment raises
questions as to possible risk.
From a field testing standpoint, criteria are being developed to be
used in selecting testing sites. .Vonengineered microorganisms have
undergone testing for pesticidal applications. Differences are perceived co
exist between genetically engineered and nonengineered organisms, and these
differences need co be examined with regard to selection of field -:is-: i.-.^
sites .and in design of measures co prevent migration from the site.
Genec ical I1' engineered organisms :iiay possess enhanced survivabilicy or
they may be less well equipped to survive than their naturally occurring
counterparts. In addition to having engineered to enhance a desired
function, engineered bacteria may differ with regard to proliferation, gene
transfer, dispersal, or migratory ability, but any difference can be an
increased or decreased potential, depending on the situation. Dr. Sayler
pointed out that engineered organisms may also possess "side benefits" that
were not present in the naturally occurring strains, such as traits to
promote better soil conditioning or biofertilization as ancillaries to
pesticidal functions.
Dr. Oraenn pointed out that distinguishing between genetically
engineered and conventional organisms is complicated since a genetically
engineered organism seems to be defined by its mode of generation rather
than its inherent characteristics. He added that ice nucleation bacteria
provide an example of this complication. No research or application
barriers are presented to discourage taking organisms directly from the
environment, where a certain percentage of the population have lost the ice
nucleation property. Similarly, no research or application barriers are
presented to discourage the production of uncharacterized mutations by
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treating ice nucleation bacteria with mutagenic agents to produce deletion
mutants for the ice nucleation property. On the other hand, in Or. Qmenn's
opinion, the production of an organism that has a deletion in a well
characterized gene through genetic engineering methods is subject to
research and application barriers. Therefore, Dr. Omenn stated "there is a
sort of awkwardness about the background for the focus on the genetically
engineered organisms."
The less specific "shot gun" approach, vhere mutagenic agents are
applied to a bacterial population to produce uncharacterized, untargeted,
nonspecific genetic changes, is commonly used by research and industrial
communities. In contrast, the very specific "surgical approach," where
recombinant deoxyribonucleic acid (rcr;A) techniques are used to n:ot!L5y i
characterized gerrome to perform a desired function, is subject to rigul-jcory
scrutiny. Awkwardness and inconsistency is created by scrutinizing Specific
changes while nonspecific genetic changes become routine.
Dr. Peyton added that many sectors .of the population, including
sanitary engineers, are not convinced that genetic engineering is necessary
to enhance microbial pollution control technology. Some feel that a
microorganism can be isolated from nature to perform almost any task and
that more effort should be expended on culturing and acclimatizing
techniques that yield these desired organisms.
In fact, identifying microorganisms present in specific sites, or even
those specific organisms that are working in major sludge treatment facility
processes, is very difficult to do. The microbial world is highly amorphic,
making determinations of the major number of species and the taxa they
actually represent difficult. Dr. Loper indicated that trivial genetic
phenomenon frequently occurs that change one species to another, as
determined by taxonomic criteria, among different microbial genera.
To further complicate matters, degradation processes in nature are not
carried out by a single type of organism. In the waste degradation process,
complete mineralization is achieved by the interaction of many micro-
organisms performing different steps along the pathway, and is dependent on
and dictated by chemical and physical aspects of the situation at hand.
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It was the general opinion of the Panel that one way to effectively
apply biotechnology to the waste degradation process is by promoting an
integrated approach. Physical and chemical technologies can be used
together with biological treatment to achieve more complete degradation.
Dr. Chapman suggested that bioavailability should be considered. Chemical
or physical pretreatment may serve to better solubilize the chemical to be
degraded, allowing organisms to attack the substance more effectively.
Dr. Loper added chat an integrated approach might also allow one to
rely on natural microorganisms co complete preliminary degradation '.vhile
more advanced physical, chemical, or biotechnological treatments could he
applied to recalcitrant substances to affect complete mineralization. Or,
Jurgen Sxner of International Technologies cited an example where Ince^r.it3d
treatment was used to claan up a formaldehyde spill along a railroad -'••.-.<.
in northern California. Physical treatment (excavation) was not •:'-:? i 31 i i i
along the rail line. lr\ situ chemical treatment reduced levels frcm '30,000
to 1,000 parts per million. Biological treatment further reduced the level
to the 1 part per million required by the state.
With regard to the selection of field testing sites and criteria and
the differences for engineered and nonengineered bacteria, we can only begin
to identify different sites by understanding the specific problems at hand.
Dr. Loper suggested that "(by) looking at the microbial species and the
heterogenicity of microorganisms in (various) environments—we can began to
identify different sites in the context of case-by-case problems."
C. Barriers
Although biotechnology applications in the pharmaceutical and
agricultural sectors are rapidly appearing, commercialization of
biotechnology for pollution control lags well behind. Many interrelated
factors give insight to understanding why such a potentially powerful
technology is not yet being vigorously developed for pollution control
applications. A variety of technical, commercial, and regulatory barriers
can be identified, including those that present problems to the development
of biotechnology as an industry and those that are specific barriers to
conducting field tests on developing products,
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This section will examine those barriers that are restricting field
testing. For example, appropriate field test study designs and protocols
have not been developed to the point where a standard exists. Test site
selection criteria and the design of testing standards, along with the cost
of testing, were discussed as barriers. Also, containment issues, including
the need for procedures required to monitor environmentally released bio-
technology products and plans for mitigation and emergency response, were
discussed. Assessments must be made by both industry and government con-
cerning the environmental impact and risk posed by genetically engineered
products. The lack of procedures for conducting and evaluating these
•assessments was identified as a barrier co field testing.
• 2eyond field testing and assessment hurdles, industry representatives
•discussed perceived barriers related co proprietary rights and liability
issues. .Regulatory barriers were discussed with regard to reporting
requirements (TSCA) and permitting (3C3A)/(CSRCLA). Public perceptions were
also examined as a barrier to technology development. The highlights of
these discussions are presented below.
1. Test site selection and requirements
Participants were asked to enumerate the criteria that industry and
academia have used in the past to select field testing sites for non-
engineered bacterial products. They were also asked to speculate on the
criteria that will be used in the future to select field testing sites for
both genetically engineered and nonengineered organisms. Recommendations
were solicited with regard to physical geographical characteristics;
technical parameters, such as complexity of contamination; commercial
considerations, such as cost effectiveness; and political/social factors,
including interaction with the public sector. Many suggestions were
contributed, which can be combined into suggestions for guidelines to
facilitate site selection.
These guidelines can be subdivided into physical characteristics,
ecological characteristics, accessibility, weather conditions, and
contamination features. Mr. Dardas pointed out the physical charac-
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teristics of soil that must be taken into account. These include the type
of soil, i.e., clay, sandy, loam, etc., soil, and whether a soil is going to
lend itself to the mixture and dispersement of the microorganisms. Dr.-
Smith also pointed out the importance of assessing the presence of rocks or
objects like drums that would impede test conduct. The geographical, layout
and topography, including slope, and relationship to aquifers will be
important factors. Dr. Smith stressed the importance of bedrock charac-
teristics to the prevention of groundwater contamination and pointed out
that "(fissures) or cracks in the bedrock (may result in) leaching to a
lower aquifer."
The prevailing environment within the proposed test site .nust be
assessed for suitability. A fcey feature identified by Dr. Chapman was -he
Itsvel of .aeration at the t^st site. Dr. Chakrabarty pointed >:-!Jt :r.a
importance of understanding -he availability of nutrients at the =>i:-2. cc .
Sayler stressed the need for a characterization of the organisms sxioci.-.g at
the site and their level of activity. He also expressed a need for a
controllable environment to work in, stating that "simplicity is a kind of
keynote; rather than working in organic sediments in streams, we'll try to
work in sandy or rocky systems where you don't have as much partitioning to
organic matrices."
The accessibility presented by the proposed test site will have impact
on site selection. Mr. Dardas of Detox Industries stressed the need for
adequate roads to allow transport of necessary equipment and research
staff. Utilities, such as electricity, should be readily available, as well
as resources, including water. Also the site must be easily accessible to
permit frequent reinoculation and monitoring as required. Proximity to
residential areas must be evaluated and avoided to prevent public outcry or
controversy. Access must be protected or restricted by fences or other
barriers to prevent entry of nonauthorized personnel. These factors should
be evaluated for each proposed test site, since they may have significant
effects on both safety and cost. ...
Prevailing weather conditions were considered important, since
temperature affects microbial degradation rate. Mr. Dardas gave an example
of the importance of weather conditions, stating, "We're targeting, in the
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winter months, the cleanup of sites in the southern parts of the United
States because...the weather is going to affect the microbial activity."
Also, he stressed consideration of the likelihood of storms and the dis-
persal of storm runoff based on natural slope.
Many features presented by the contamination at the proposed test site
were recommended for consideration. Mr. Dardas suggested chat contamination
should be minimal with clear characterization of the specific type(s) and
geographical extent of contamination. He also pointed out chat it is also
important to understand the distribution of contaminants within the test
site. for example, are the contaminants evenly dispersed or are they at
high concentrations in random pockets?
Complex or extensive contamination reduces the potential for
biodegradation since this could poison che organisms being uciiit=-J jf.d
interfere with microbial processes. Mr. Dardas stated that "some sicis have
a great deal of heavy metals that will Just inhibit the growth of
microorganisms...." He also pointed out that extensive contamination
presents containment problems such as the potential for runoff and
percolation.
The physical properties of the chemical contaminant, including water
solubility, soil absorption, and biodegradability should be well
understood. Mr. Dardas discussed the importance of water solubility to the
prevention of groundwater contamination. He stated, "If you're dealing with
a contaminant that isn't even water soluble to begin with, you have less
likelihood of dispersing that contaminant into the groundwater." Dr.
Chapman stressed the need for considering the potential of the contaminant
to adsorb to soil particles. Dr. Smith, with the Koppers Co., discussed the
importance of understanding the blodegradation pathway of the contaminant.
For example, "are you taking everything to CO, and water or...say in the
case of pentachlorophenol,.. .are you degrading -to one of the other
chlorinated phenols, which is more soluble in solution?...Are you
solubilizing them so they leach into groundwater, chlorinated phenols
(being) much more toxic than the material that stays (behind)?" In short,
the opinion of the Panel was that the contamination should be clearly
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defined with regard to type, extent, homogeneity, complexity, and physical
properties.
Several more generalized suggestions were made regarding site selec-
tion. The degree and duration of monitoring performed at the site should be
evaluated and may significantly contribute to appropriate or adequate site
selection. The degree to which the proposed test site resembles che
proposed treatment site is very important to site assessment. Simplicity
with regard to physical characteristics, environmental characteristics,
resident biological diversity, and chemical contamination was repeatedly
mentioned as a key factor. The Panelists felt that it is also important ;o
keep in mind the fact that one set of field testing data and results may not
be extrapolated to another; che approach must be case by case uncLi J.n
adequate database exists crcrri' -.vhich £o predict :rer.ds. Final':'/. -'-.ey
stressed the fact that chemical contamination is not the only . _.-.cjrn
associated with biotechnology; the dispersal of the :nicroor-j jnisms
themselves must also be taken into account.
2. Testing standards - design, performance, and evaluation
Feasibility testing, which has been the focus in the past, has centered
on the capacity of the organism to achieve the objective task. Dr. omenn
stated that little measurement of specific properties, such as growth,
survival, proliferation, transfer, or dispersal of the organism, has taken
place. He indicated the need for a stepwlse procedure where information on
the organism and the genetic manipulations are collected from the litera-
ture, followed by laboratory work, including both synthesized and natural
core-sample-type microcosms to establish feasibility. Then one must proceed
to the field with a clear purpose in mind. The purpose should define the
risk endpolnts that will be examined .and the functional objectives of the
test.
The test design should incorporate actual controls to verify that in.
situ application of organisms is valid and, furthermore, is responsible for
the observed, degradation. Dr. Sayler stressed the need for adequate repli-
cation of both nontreated control areas that may have different levels of
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contaminants and of areas treated with different levels of organisms. He
considered controls and replicability important to our ability to forecast
success from one application to another.
Another important test design factor is the microorganism selected.
The test organism should be well suited to both the chemical contaminant to
be degraded and the conditions at the test site. A good match is essential
to test success. The need and potential for adding nutritional supplements
should also be assessed in relation to test success and cost in eventual
application at treatment sites. Organisms may require the addition oc
proper nutrients, such -as carbon, nitrogen, phosphorous, or carbohydrate, or
even additional aeration via the introduction of hydrogen peroxide at
various depths. In addition to specific •.Tiicrobial and nutritional require-
ments, the size of the inoculijn co be used .Tiust be investisa:3d --:r.J
established to allow for adequate survival but minimal prolifarati.cn.
The duration of the test must also be considered. Dr. Smith stated
that a test's duration should be specified based on organism performance in
feasibility studies and the desired degradation objective. He indicated
that degradation of an appreciable amount (90-95%) will take an average of
4-5 months in soil, as compared to 5 days of hydraulic retention time in an
aerobic tank or activated sludge system. The area of application must also
be specified. A large enough area must be utilized to give an adequate
prediction for engineering application and. scale-up, yet the transmission of
the organism must be controlled. Monitoring and containment procedures, In
addition to emergency response mechanisms, must be considered in the design
for testing.
Finally, Dr. Sayler stressed the need for documenting and under-
standing biological applications that are not successful. Tests that do not
produce desired results must be documented and evaluated to provide insight
for future studies. Only through the establishment of databases documenting
successes and failures can a predictive tool emerge.
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3. Containment Issues
The Panel was asked to discuss the parameters considered necessary to
provide a contained environment for field testing both genetically engineered
and nonengineered pollution control organisms. The characteristics that
might be used to describe appropriate containment levels may include physical
parameters, i.e., enclosure mechanisms; technical factors, e.g., a landfill
with a plastic (double) liner; financial features, e.g., cost effectiveness;
and political considerations, i.e., the social acceptability of the options
to be considered. Panelists were asked to consider different types of
contained environments, including greenhouses, lined or clay-capped land-
fills, sewage treatment facilities, and terrestrial oil wells, as potential
field testing sites. The Panelists were also asked co develop a : :.s'<
fjradient of possible containment levels.
Mr. Dardas of Detox Industries responded that containment praci'.c-^s are
currently in use, even though only naturally occurring microorganisms are
being used that are not perceived to pose risk. His company has controlled
the movement of microorganisms by installing berms that extend below the
level of contamination and are covered with plastic. Mr. Dardas pointed out
that these practices are, however, in place for the purpose of controlling
the migration of the chemical contaminant, as opposed the concern for the
dispersal of the microorganisms.
With conventional microorganisms, the escape or migration of organisms
from the site did not present a concern to the Panelists. They felt that
there are no existing criteria for governing the escape of conventional
organisms.
Dr. Smith described in situ treatment of pentachlorophenol-
contarainanted material in soil, stating that USEPA guidelines recommend a
5-foot buffer zone between the zone of incorporation (the area where soil
microorganisms are actively degrading the pentachlorophenol contaminant) and
the surrounding area. A 5-foot buffer zone is also recommended to protect
groundwater.
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The population density of the microorganisms is a factor to be
considered when considering containment, as pointed out by Dr. Caldwell.
Increased densities create problems in restricting distribution. High
densities increase the chance of contaminating key sites, such as drinking
water and recreational waters.
With regard to the criteria for containment, Dr. Loper indicated that
the recent Shackelton Conference addressed this subject in detail and
recommended that those proceedings be consulted. However, the need to design
containment measures to take the physical features of the site and extremes
of climate into account was stressed.
Others felt that attaining containment in an environmental setting :;23
an unrealistic expectation. Migratory birds -and insects cannot be r-r.-: j Lr.id
by plastic berms. Liners designed for landfills can leak, and if .:r.ey :on' ?.
leak new they can in the future. Dr. Sayler expressed the opinion chat
containment is an unrealistic consideration for organisms that are designed
to be released, survive and proliferate in the environment.
Dr. Loper added perspective to the containment issue as follows.
"We don't anticipate physical containment of any microbe
that's in use (as a biological agent), in an entity
sense. We expect to demonstrate that, the homeostasis of
the world, in most cases, is not going to lead to
biological escape of some organism because of Its own
biological containment with respect to all the other
organisms that are out there."
a. Monitoring
Attendees were asked to describe procedures currently used by industry
and academia to monitor experiments and/or commercial applications of
nonengineered organisms. Predictions were - also solicited with regard to
foreseeable changes that may be appropriate for monitoring genetically
engineered pollution control organisms in field test settings.
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Dr. Pierce explained that sites already defined in litigation, i.e.,
CERCLA or RCRA, usually have monitoring procedures in place and existing
data to characterize the site. Monitoring at different sampling sites is
required, as well as data from the endpoint site, that allows the area to be
certified as decontaminated. This monitoring is targeted towards assessment
of the pollutant, as opposed to microorganism levels. In addition to the
pollutant, intermediary and ultimate metabolites must be known and
monitored; biodegradative pathways do not always yield complete
mineralization.
Dr. Chakrabarty described "he -aed to monitor genetic traits when
genetically engineered microorganisms are released. When genetic traits are
incorporated on a broad spectrum plasmid, :he trait can be transmit cad '-.o a
large number of resident bacteria. As :hey acquire che capabi L :;•/ :o
degrade che contaminant, chey increase Ln number. Therefore, cha ;;-f ^c Lc
trait inust be monitored as opposed to, or in addition to, trte jeneticaiiy
engineered microorganism.
Monitoring becomes difficult and imprecise when the contamination
levels vary between sampling points, which is often the case at contaminated
sites. Heterogeneous concentrations are often present at DDT-polluted
sites, where pockets containing 1, 10,000, or 100,000 ppra can be inches away
from areas of extremely low concentration. Dr. Smith added that the cost of
analytical procedures required to assay monitoring samples may exceed
$100,000 and this was also cited as a barrier.
b. Mitigation and emergency response
The Panel was asked to describe emergency response methods presently
used for unexpected spills of nonengineered pollution control organisms and
to describe foreseeable changes required for genetically engineered
organisms.
Attendees .agreed that the concept of decontamination needs to be
introduced into the field testing picture. After the introduced organism
has done its job, and if it is perceived to present a problem by persisting.
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a decontamination phase should be initiated to kill off viable organisms.
Fumigation with methylene blue, irradiation, and physical removal methods
were discussed. Dr. Caldwell defined decontamination as a decrease of
organisms in the soil to a level that is present naturally in the
i
environment, since people regard soil as nontoxic and soil normally contains
microorganisms.
Achieving complete mitigation or decontamination cannot be dependent
on one system. Microbial-based technology must be integrated with chemical
and physical procedures. This is especially important in emergency response
situations, where a rapid response time is essential.
4. Assessment of environmental impact
Dr. Cmenn stated chat the progress in biotechnology and .'^necic
engineering over the last decade has been a pleasant surprise. The
technical progress has been much greater than most people expected. The
potential hazards, recognized very early in technology development by the
scientific community, have been reviewed with relative reassurance.
Progress in the environmental area will require a firm database,
comprised of data obtained and generated by accumulating appropriate field
test studies in contained environments and applications in a stepwise
fashion to ensure public confidence.
Field studies and monitoring data are important to environmental
assessments. .For example, if one knows something about the capability of an
organism to degrade pentachlorophenol to carbon dioxide, water, and inor-
ganic chloride, one has a basis for designing monitoring procedures to
follow the process in the environment. These types of data provide
reassurance about the potential for accumulation of partially chlorinated
phenols at the application site and are essential to adequate environmental
assessments.
5. Risk assessment criteria
Debate has arisen over the potential risk posed by field testing
genetically engineered organisms. The level of concern and the fact that
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accurate risk assessments of the potential damage to human health and the
environment are not available provide a barrier to field testing. Panelists
were asked to characterize a low risk testing situation and to provide a
rationale for this assessment.
Dr. Mellon, with the Environmental Law Institute, cited risk or safety
concerns as one of the primary reasons for conducting field tests. She
explained that from a regulatory point of view, we must presume that the
microorganisms to be tested are dangerous. Information on the degree of
danger must be gathered under contained, controlled conditions to .minimize
the risk posed to the environment by s imply performing the tast. Dr.
Caldwell expressed another point of view. He stated that "degrading 3 toxic
substance in the environment using microorganisms (involves) accsleratir.g j
natural process by using existing organisms tnat are already present :.•; -:he
environment. " To further tnis iJea, r.e sdded "people jrs '. i-sln1":
perspective" on the nature of che problem "(by) considering cha
microorganism itself as -a toxic substance...; While :!nere are xsnobiotic
compounds, I don't think we really have xenobiotic microorganisms (at this
point in time)
In testing genetically engineered microorganisms for pollution
control, Or. Peyton identified the need to define the risks. The danger may
come from exposure to genetically engineered organisms or from the pollutant
and its metabolic products.
Characteristics of survival, proliferation, dispersal on particles,
dispersal via insect carriers, migration through soil, movement in water,
and gene transfer from an engineered donor to environmentally occurring
recipients are all perceived to present additional risk. However, the
current use of nonengineered microorganisms requires environmental
perturbation, through mechanical disruption or nutrient addition to soil,
which also poses unevaluated environmental risk.
Field testing and monitoring are required to document benefit as well
as risk. Often acceptable risk levels cannot be defined unless benefits are
also considered. Cost is also a factor in defining acceptable risk.
Genetic engineering of pollution control microorganisms could conceivably
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reduce both the. cost and the risk created by hazardous substances. Most
conventional technologies create another hazardous waste rather than
achieving complete destruction. Biotechnological degradation has the
potential to alleviate this problem, alone or in combination with other
technologies. In order to assess risks, many factors must be balanced,
including benefits, costs, and risks of current technologies.
6. Protection of proprietary rights and from litigation
Mr. Dardas of Detox Industries expressed his company's posture
concerning demonstration of their developed technology. He explained chat
pilot or demonstration projects cannot be conducted without some assurance
that -follow-on contracting ifor site remediation will be awarded. Lie:'.2
protection is available to prevent clients crcm observing demonstrac icns ^-.d
chen applying 'he process themselves to their sites. This threat :o :he
proprietary nature and exclusive ownership of a company-demonstrated
technology presents a barrier both to the conduct of demonstration projects
and to field testing.
Dr. Peyton elaborated on this point, as follows:
"...Investing in genetic engineering is very expensive
and, if you do that, you want to make sure that you come
out with a product that can sell, that you have a viable
microorganism. As Tom (Dardas) was explaining...he has
clients who are willing to pay him $250,000 to do
something on a cubic yard so they have the rights to (use
the technology that his company developed) and he won't
do that. With an enzyme (the product can't be cultured
or grown) so you have some control over the market
penetration of your product. When you're investing a
significant amount into .equipping a genetic engineering
laboratory, you want to make sure that the product cannot
be stolen by a competitor."
It should be pointed out 'that based on the potential application of
one of projects underway in the USEPA's biotechnology research program (see
Chapter VII of this document), Mr. Dardas stated:
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"...while our company is not involved with genetic
engineering, I do believe that genetic engineering can
improve things we do. And so... I think we will
immediately begin working on genetic engineering in order
to give ourselves more protections of all of our
proprietary development as soon as we can afford to."
This comment was precipitated by the presentation of pollution
control-related project on methods for the biological self-containment for
released microorganisms chat is underway in the USEPA's biotechnology
research program. Under the direction of Dr. Cuskey, USEPA's ERL at Guif
Breeze, a plasmid-borne "suicide cassette" is being developed. The "suicide
cassette" would ensure the self-destruction of microorganisms harboring
*hese plasmids. Dr. CusJcey stated that
"...Mr. Dardas could start accepting chose .3250,000
contracts if they knew "hat the clients could sift
(through the) soil for a :ng time and not get the Detox
process."
Field testing is also important to the liability issue. Only through
preliminary studies can predictions be made on the likelihood of success.
If some guarantee of success can be predicted, companies are more willing to
withstand the possible cost of litigation.
Liability is a key issue. Indemnification is needed at field testing
sites. Insurance companies are reluctant to provide insurance for new,
unproven technology. Alternative sources of indemnification are needed to
surmount liability barriers. Time delays are created at litigious sites
because of indemnification reticence where new, innovative technologies are
concerned.
7. Regulation
Regulatory barriers are perceived to result from testing, development,
and reporting requirements under TSCA and permitting requirements under RCRA
and CERCLA.
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a. Regulation under TSCA
Regulatory requirements that may be Imposed on the biotechnology com-
munity are perceived as presenting a barrier to commercializing products or
applying techniques in the field. Genetic engineering has been confronted
with regulatory barriers from its inception, from research to application.
TSCA presents regulatory barriers in the testing and development stages.
The time required for the review process may present a barrier to
innovation. Dr. Goldhammer described the time lag that is perceived by
industry. He suggested that, after a company expends development time to
create an organism with significantly Improved capabilities, 90 days are
required cor -a ?remanuf3cture Notification (P^) -jr.der TSCA. This
requirement is not i.n I .self a burden, out aven if "you've Jcne /our
homework" additional materials may still be required. However, to obtain a
RCSA permit, the requirement for these "additional materials may take 1, 2,
3 years" for full compliance. This factor may be a significant impediment
to technology development.
Or. Caldwell expressed concern over the perspective posed by the
nature of the problem, specifically with regard to considering micro-
organisms as toxic substances. He stated that there are xenobiotic
compounds, but we don't have xenobiotic microorganisms yet. Using
microorganisms for degrading toxic substances represents an acceleration of
a natural process that already takes place in the environment. Genes that
already exist in those environments are merely recombined to alleviate a
particular problem more quickly than would normally occur.
Dr. Caldwell also pointed out that microbial ecologists have studied
the. behavior and capabilities of microorganisms in environmental settings
for some time and expressed concern that performing routine ecological
experiments in the environment would require reporting and be subject to
control under TSCA.
A substantial market currently exists that involves selling bacteria.
Highly concentrated microbiota from activated sludge plants or anaerobic
IV-19
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digesters that detoxify groundwater are currently transported considerable
distances to seed new facilities. This practice is common in sanitary and
environmental engineering and does not currently require notifying the USEPA.
The dangers presented by this practice, since viruses and human
pathogens may be present in the concentrated cultures, were discussed.
Materials that are heavily laden with uncharacterlzed microorganisms from
human excreta are known to be widespread in municipal treatment mixes. The
relative lack of regulatory control or scrutiny over this hazardous practice
is in contrast to the regulatory requirements for tasting microorganisms
developed for biotechnology applications that are not known to . be
hazardous. Dr. Omenn commented on ne "awkwardness (of)...che focus on
genetically engineered organisms." Dr. Cmenn noted that none of -.he
workshop's industry participants planned :o introduce improvement -.i::~.
•jenetic engineering techniques because of ;ra likelihood of ov.ervr.-3'. .vLr.g
regulatory procedures tied to the technique, rather than the prcduc: ic any
defined risk.
As will be discussed in Chapters V, VI, and VII, the Agency is making
efforts to reduce industry's concern about the PMN review process under
TSCA. To assess the risk of biotechnology products, specific risk
assessment criteria and methods are needed. The data and information
required to develop these may be obtained from projects that are underway in
the USEPA's biotechnology research program. In addition, the OTS is
developing a database of organisms, microbial products, strain development
techniques, and pollution control applications from the open literature.
These data may be of assistance in assessing PMN submissions in, identifying
the types of data the Agency would want in submissions and the classes of
products of concern to the Agency, and in developing tier testing criteria.
The development of risk assessment criteria and methods and the database may
facilitate technical evaluations of PMN submissions and expedite the review
process.
Mr. Ronald Evans, OTS/USEPA, and an observer at the Workshop, stated
the Agency felt that the review process could be expedited if the Agency
received information on biotechnology projects that were planned or underway
in industry prior to the PMN submission. He also stated that the Agency
IV-20
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consistently encourages potential PMN submitters to begin discussions with
the Agency early to determine what concerns the Agency has about a class of
chemicals and what type of data the Agency will require for its assessments.
b. Permitting and reporting
Mr. Dardas expressed concern over USELPA's emphasis on control and
reporting. He stated that reporting requirements make it very difficult cor
the industry to emerge. Small companies are significantly impacted since
they are without the financial resources to provide tasting and analysis
required for adequate reporting. :ie compared criminal law, where "a man
that's indicted is innocent until he'3 proven guilty" to biotechnology which
"has been proven guilty before it has even started."
Dr.. Smith expressed concern about regulatory permitting requirements.
He described the current permitting hurdles required for protection of
groundwater, air, etc., at both Federal and local levels, and questioned the
need for additional permitting requirements addressing genetically
engineered organisms. Ms. Franclne Jacoff, of USEPA's, Office of Solid
Waste, explained that
..."Each permit process is an individual process. RCRA
and CERCLA have been far apart, (but) they're not
anymore. (They) have to do the same things, except it
depends on whether it's an active site or an inactive
site and the whole thought that these two things are
separate is not working anymore. Management in RCRA and
CERCLA are realizing this but they are very, very slow to
pull it together There's never been a long-term look
(at) RCRA or CERCLA —because we're so busy with yester-
day's...and today's problems that we haven't looked to
tomorrow."
8. Public perceptions
The Panel felt that the use of existing landfills for field testing
may create negative impressions of biotechnology since landfills are already
perceived as hazardous. It would be advantageous to avoid guilt-by-
association inferences. Nonresident la1 areas should be sought for field
test sites to avoid publicity and controversy that may be damaging.
IV-21
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The selection of sites for field tests has and may elicit local
opposition. Dr. Mellon suggested that potentially useful sites are those
where the public has a vested interest in the success of the project. For
example, test sites for ice nucleation bacteria designed to protect
strawberry crops should be selected from areas where strawberry farming
contributes to the community economy. In this way, a supportive environment
can be created, contributing positively to test conduct and perceptions of
genetic engineering as a helpful technology.
While understanding seme of the advantages chat may come c"rcm
biotechnology applications, the public is also concerned with potential,
undefined risks. The public is also aware of the dangers presented by
hazardous waste. However, there has been relatively little political cr
community action over the technical choices presented by municipal -r
industrial waste management. Mo one wants -treatment facilities, ./xjsts
•Jumping, or landfills in their backyard. It is, therefore, common practice
to haul toxic chemicals somewhere else, thus creating the impression chat
the problem is solved.
Dr. Exner, from International Technologies, pointed out that by taking
"tremendous" precautions to control the risks that may be presented by
biotechnology, the risk, in turn, becomes greater in the public's perception.
D. Possible Incentives
Contributors were asked to develop ideas that could provide incentives
for research and commercialization of pollution control organisms,
especially .those that would encourage field testing. The use of existing
contaminated sites, comparative evaluation of microbial and conventional
technologies consideration of alternative versus conventional technologies,
and development of a Federal field testing program were introduced and
discussed.
Possibilities of reduced reporting requirements and associated fees,
tax incentives, and supported insurance policies were mentioned, but an
overriding theme was the need for a focus on existing regulations.
IV-22
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Regulations such as the Clean Water Act, RCRA, Superfund, and Safe Drinking
Water Act were mentioned as vehicles for implementing incentives to the
biotechnology community to allow demonstration of the applications of new
technologies and methods.
1. comparative evaluation of microbial and conventional pollution
control methods to assess "best demonstrated available technology"
TSCA is an unreasonable risk statute. To make this unreasonable risk
determination, OTS must consider the benefits associated with using
genetically engineered and nonengineered microbial products. Mew chemicals
are evaluated by comparing costs, physical-chemical properties, jnd ;jse
conditions to similar- parameters known for chemicals used for *!*.* -^rr.a
purpose. The benefits" presented by nicrobial (genetically engineer*•'. -.-
nonengineered) pollution control technology will .Tiost likely be ccmparjJ" :o
conventional pollution control methods; therefore, research is -aedad in
this area. The technologies must be compared with regard to .cost
effectiveness, and technical parameters, i.e., rates of degradation, unique
abilities, safety, and risks. once these parameters are documented, the
benefits of the technologies can be compared, providing a basis for
justifying or abandoning the further development and use of microbial
degradative technologies.
2. consideration of biotechnology as an alternative to conventional
"burn or bury" methods
Currently, the Agency relies on the "best demonstrated available
technology" for the treatment of hazardous wastes. To date, the existing
nonengineered microorganisms are not usually used in the open environment
and no genetically engineered microorganisms have been released for the
purpose of pollution degradation. Thus, the efficacy of biotechnological
procedures have not been demonstrated. In addition, the development of
genetically engineered biotechnology pollution control products has been
slow and this is due in part to. the high start up cost's and the fact, that
the Industry still finds it more cost-effective to use the conventional
"burn and bury" techniques.
IV-23
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It was the Panel's opinion that the shortcoming of current
technologies could be overcome by microbiological treatment. Integrated
methods, where wastes are pretreated microbiologically before incineration
or landfilling, could reduce both cost and toxicity. utilizing
microorganisms for a sizable percentage of the degradation helps to detoxify
sites and often makes the implementation of other technologies, which
complete the mineralization, more efficient. Currently the ash that is
generated by incinerators, if degradation of hazardous substances is
incomplete, must be transported to secure landfills. Techniques chat are
not totally destructive, or do not promote complete mineralization, result
in the creation of additional hazardous waste problems.
Dr. Cmenn noted that there has been relatively little use of specific
organisms as opposed to using naturally occurring mixtures of or-j-inis.T.s.
Inere is "tremendous dissatisfaction" with the state of the arr in :-?ii'.ncj
with landfills .-and other contaminated sices. The protocols :.-. ac jfe
recommended for pollution control measures under 3CRA, C51RCLA, Clean *ater,
Drinking Water, and Clean Air Acts should give attention to particular sites
where current methods are less than satisfactory and should introduce the
possibility for the evaluation of microbiological biodegradative treatment
options. The Panelists also agreed that Innovative technologies must be
evaluated seriously to try to overcome the rather dismal record produced by
conventional "burn and bury" techniques.
3. Use of existing contaminated sites
Some experts have suggested that existing disposal sites, such as
landfills, might be designated for field testing genetically engineered and
nonengineered pollution control organisms. The working group was asked to
discuss the advantages and disadvantages of this proposal from technical,
financial, legal, and political perspectives.
A discussion of potential sites took place first. Spills and leaking
storage tanks were considered less complex than landfills, since a single
chemical is usually involved. Industrial point sources may also be less
complex; some industrial sites contain noncomplex mixtures, such as lagoons.
IV-24
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wood preservative sites containing pentachlorophenol or creosote, and ponds
containing sludge. Advancing up a complexity continuum, sewage treatment
sidestreams, abandoned oil wells and oil sumps, and acid lakes were listed.
Activated lagoons, where water Is pumped In, aeration is installed,
microorganisms are applied, and degradation is monitored, were considered as
potential field testing sites.
Landfills were identified as the most complex sites, yet these are Che
most prevalent and are in need of advanced degradative technology. Several
types of lane' "'.11s were identified, including "old" landfills chat contain
mixtures of compounds that may be easier to degrade since microorganisms are
already present. Mutritional activation and environmental adjustment
(addition of water or air) :Tiay allow degradation to take place.
Other types of Landfills discussed included uncontrolled 1 ar.d ?-i L L 3 or
open dumps. These were defined as being uncharacterized with respect to
contaminant content, not monitored, and are perhaps not useful as test
sites. RCRA landfills are better characterized and can be of several
types. Subtitle D landfills are classified as sanitary landfills, while
Subtitle C designates hazardous waste landfills. Subtitle C~ landfills can
fall under interim status when the landfill is being retrofitted or expanded
to meet regulatory requirements or may be classified as having final permit
status. RCRA-perraitted landfills may have groundwater monitors in place,
may have single or double liners, and may also have leachate collection
systems. Some may be clay capped. Since RCRA-perraitted landfills have the
greatest degree of containment and monitoring equipment in place, they are
considered as the best candidates for field testing sites.
Dr. Chu of the General Motors Corporation provided some points for
consideration with regard to using landfills as field testing sites. He
stressed the need for testing the total site, rather than a corner or core,
since the leachate collection system serves the total site. Segregation by
slurry wall construction may be- possible- but the cost would be prohibitive.
Clay caps may present problems for field testing applications, since the cap
must be removed before the organism can be applied, percolated, or its
activities assessed. He added that the depth and compaction of the fill
must be taken into account.
IV-25
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Advantages and disadvantages of using RCRA landfills as field testing
sites were discussed. The advantages included some theoretical points as
well as more technical and political aspects. Utilizing landfills would
provide for testing of capabilities in a defined environment, a relevant and
potentially useful approach. 'Mr. Dardas pointing out that such testing
could serve to remove or mitigate known chemical hazards, help to develop a
better understanding of testing conditions, and for the development of new
and better microorganisms for pollution control.' Appropriate sites will
already be lined, providing for containment. Monitoring data will be
available for historical evaluation and site characterization, as well as to
provide for future sampling. Both legal and commercial aspects will be
served, since many landfill 3ites have been targeted for cleanup by
regulatory .mandate or Legal action. significant expenditure may '-lave
already -:aken place co bring landfills Into 3CSA compliance, so :na: :he
•jdcJad cost of microbiological rreatmenc could be relat ively. modest .
Although landfills present many advantages as test sites, disadvantages
are also presented. As stated by Dr. Mellon, landfills may not be
theoretically relevant for basic research since they represent one of the
ultimate intended applications. More precisely, using landfills may require
the substitution of the research and development objective with an objective
of application before the preliminary data are gathered.
in the Panelists' opinion, the major disadvantage of landfills is the
complexity of the environment. There is likely to be a nonhomogeneous
conglomeration of chemical constituents whose interactive behavior is not
well known, and the component chemicals may be toxic to the microorganisms,
making survival uncertain. A landfill's environment is often extreme and
far from optimal for encouraging the growth of microorganisms. Not only are
different parts of the landfill variable with regard to composition, but
each landfill .can be a vastly different environment. Testing results may be
so site specific that data cannot be extrapolated to make predictions of
feasibility or safety at other sites. Costs may also be elevated as a
result of environmental complexity, since more contaminants will be degraded
than those targeted for eradication. In addition. Dr. Smith pointed out
that the presence of components such as drums and plastic containers in
IV-26
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landfills may impede physical actions, such as digging or turning that are
necessary to enhance raicrobial growth.
Although containment measures may have already been taken at landfill
sites, the integrity of containment by liners is suspect. Groundwater
contamination may have already taken place, compromising any assessment or
evaluation of the test treatment potential for groundwater contamination.
The Panelists recognized the fact that landfills represent contentious
settings, and their use -as field testing site could meet with resistance
from local communities and/or Stata and federal agencies. Publicity and
public controversy may arise addina to a negative view of landfills, which
nay be carried over to .nicrobial treatment and use of Motechnoloqy. C.n
•addition, .nicrobial treatment /nay worsen the si-tuacion, .?.obi 11-l.-q ;•.-
.Tie caboli zing che pollutants -and increasing risk to r.uman health ir.d ~'r\e
environment.
4. Development of Federal field testing programs under RCRA/Superfund
Panelists expressed the need for federally designated and federally
managed or sponsored field testing sites. In their opinion, the Panelists
thought that the innovators of mlcrobial degradation technology need
assistance in matching microorganisms, with existing, we11-contained and
monitored, contaminated sites where the results will be most credible and
the regulatory barriers minimal.
Several.types of sites were mentioned as candidates for consideration.
These included military sites, national laboratories such as oak Ridge
National Laboratory, sites in Florida mentioned by Dr. Al Bourquin, General
Motors Corporate sites in New York as described by Dr. Joe Chu, and known
contaminated sites such as Love canal or Times Beach. Dr. Pierce
recommended the generation of a list, similar to the U.S. Food and Drug
Administration's GRAS (generally- recommended as safe) -list, of potential
field testing sites.
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V. BARRIERS TO AND INCENTIVES FOR THE COMMERCIALIZATION
OP MICROBIAL PRODUCTS FOR POLLUTION CONTROL .
The development of microbiological products for pollution control has
been slow when compared with product development in other sectors of the
biotechnology industry. In an effort to understand this phenomenon, the
Panelists were requested to provide information on some of the rate-
determining steps for the introduction of genetically engineered pollution
control organisms. Vhile economical incentives on'd regulatory
considerations are important factors, the Panelists were also asked to
discuss che !
-------
2. Technological advantages presented by the development of new
biotechnology products
The directed development of microorganisms for the degradation of
chemical pollutants could be beneficial for pollution control. AS will be
discussed in Chapter VII of this document, it is possible to develop
microbial strains that are targeted for specific pollutants, capable of
surviving in highly toxic environments, and that present novel pollution
control capabilities. Dr. Pierce pointed out that these new pollution
control products could be used to augment conventional methods, provide
safer microbial products, and stabilize che results achieved with existing,
nonengineered microorganisms. For example, products could be developed chat
have enhanced degradative enzyme levels, enzymatic activities or in which
new degradative pathways have been constructed, or chat are less susceptible
to environmental conditions. In addition, oocsntially con:rolLdble
.•nicroorganisms could bs developed chat will self Jestruct or wncsa jrowth
can be specifically regulated by directed changes in the environmenc, '..3.,
the "suicide cassette" regulatory control mechanism. Microbial strains chat
produce specific compound- or ligand-binding proteins may also be
developed. Or. Kopecky felt that the development of such products for use
in the management of chemical spills would be useful. Finally,
microorganisms developed for pollution control can be "marked" genetically.
Genetically marked strains can be used to monitor the microorganisms'
dispersal and migration and provide one method for the protection of
proprietary rights. The Panelists seemed to be of the opinion that most of
these technological advantages could, and should, be first achieved with
nonengineered microorganisms.
/
3. Market opportunities and Investment as a function of existing
regulatory statutes
Dr. Thomas Peyton presented an update on market investment
opportunities for the manufacture and application of biotechnology pollution
control products. According to Dr. Peyton, the total cost .of pollution in
the United states is $70 billion in today's, dollars while the total market
for biotechnology products for toxics was estimated to be $2.6 billion. He
also pointed out that the amount that the government spends on generic applied
v-2
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and applied research is minor, but that government spending "...is important
for guiding and stimulating the environmental market "
Dr. Peyton summarized market opportunities for biotechnology pollution
control products under existing regulatory statutes. These opportunities
are described below.
a. Air pollution control
Under the Clean Air Act, $30 billion was spent in 1985 for the control
of air pollution. It is conceivable that a biotechnology product such as
i.Tjnobilized enzymes could be used to rjeqrade toxic organic substances "nat
jre present in flue or stack fjases.
b. 'Vater pollution control
Under the Clean Water Act and the Safe Drinking Water Act (SDVA), 325
billion was spent in 1985 for the control of water pollution. Most of this
expenditure is for biological treatment facilities, e.g., public sewer
systems. Under SDWA, the focus is the protection of potable drinking water
sources, aquifiers, and surface reservoirs. Expenditures are also made to
meet effluent guidelines. Funding from Congress for the biological
treatment of acid lakes is anticipated shortly.
c. Solid waste management
under CERCLA and RCRA, $12 billion was spent in 1985 for solid waste
management. Biotechnology products may be more applicable to chemical
spills than to "abandoned dumps" that contain unknown materials.
While the development of the biotechnology pollution control industry
may provide an economical and effective alternative to conventional waste
management methods, Dr. Pierce pointed out that the cost-effectiveness of
these products cannot be evaluated in the absence of field test results.
V-3
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4. Basis for the expansion of the biotechnology pollution control
industry
According to Dr. Peyton, it is possible that biotechnology products
can capture a significant portion of the existing pollution control market,
perhaps up to $18 of the $70 billion total.
In addition. Dr. Peyton identified new potential applications for
biotechnology pollution control products. These included the break down of
toxic substances; the maintenance and cleaning of containers, drums, storage
tanks, piping systems, and underground tanks; 'use as biological barriers and
underliners; and use for environmental diagnostics.
3. Barriers to Commercialization
1. Technical barriers
a. Meed for basic, generic applied, and applied research
The need for additional research was identified as one of the
technical barriers to the development of biotechnology products for
pollution control. Basic research is critical for maintaining the
scientific base on which new technologies rest. It stimulates advances in
technologies, and focuses on the discovery and understanding of phenomena.
The goal of applied research is to obtain information necessary for the
development of products and processes to fulfill recognized, specific
needs. Applied generic research bridges the gap between basic and applied
research.9 It has more specific goals and is of longer duration than
basic research and has higher economic risks than applied research. Basic
and generic applied research have historically been performed under
government sponsorship, while research involved in commercialization of
products (applied research, e.g., developmental and scale-up research, and
field testing) has been the traditional role of industry. The costs
associated with biotechnology research are significant,
U.S. Congress, Office of Technology Assessment. JH Gibbons (Director).
Commercial Biotechnology: An International Analysis. 1984.
V-4
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and this tends to discourage the performance of relevant research. During
the discussion, it was pointed out that the lack of such research hinders
the development of methodologies needed to design, monitor, and evaluate
field tests and for assessing risks (Chapter VII). Although the government
is committed to funding basic research, government expeditures for generic
applied research are limited and this may retard biotechnology product
development.6 Moreover, the Panelists felt that until the efficacy of
biotechnology pollution control products has been demonstrated, it is
unlikely that industry will invest significant amounts of capital in generic
applied or applied research.
.Research is also needed to ccnipare the safety and effectiveness of
genetically engineered and nonengineered biotechnology pollution cor.tcol
products. This is because genetic engineering and its presumed 1 i.rrlc le^s
potential seems to be the basis for many of 'he concerns for bic'ecr.r.oic-jy
products that are held by che regulatory agencies, industry, ir.d the
public. By comparison, fewer concerns have been expressed about
nonengineered microorganisms. Mr. Dardas described one of Industry's
concerns about genetically engineered pollution control products:
"...one of the problems with dealing with genetically
engineered microorganisms is that it may actually
stigmatize work done with naturally occurring
microorganisms, especially if there is a problem created
with genetically engineered microorganisms."
b. Need for risk assessment methods and criteria
As was. pointed out in Chapter IV of this document, raicrobial products
may survive, proliferate, and migrate in the environment. This produces a
need for microbiological-specific risk assessment criteria and methods.
However, the data required to develop these criteria and methods are not
readily available. Because the needs for these data and methods are
pressing, the Panel recommended that the USEPA continue to conduct research
relevant to the development of standards for field testing and to develop
risk assessment 'criteria and methods. It was also pointed out that only the
USEPA may be able to do research on methods for monitoring.
Ibid.
V-5
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2. Economic barriers
a. Research costs
The costs associated with conducting biotechnology research are
significant. Because of this, little generic applied or applied
biotechnology research is being conducted in academia or in industry.
b. Development costs
Unless the prospective economic benefits are significant, industry is
reluctant to -allocate funds for biotechnology product development. At this
point in time, it seems that industry, especially larger ccrr^nies, -Jo r.ot
perceive aither -a r.eed or a :n.ar:<5t Sec Biotechnology poliucion ccncr^i
products. Thus, seemingly little -Javelopmental research is underway.
c. Commercialization costs
At present, a few of the smaller biotechnology companies are
interested or engaged in the commercialization of biotechnology pollution
control products. However, it was pointed out that the costs of
commercialization are also significant, especially the costs involved in
field testing. The cost for field testing alone poses a significant
economic barrier to smaller companies. Moreover, additional costs that may
be incurred as a result of regulatory testing requirements or as part of the
permit application review process further enhances the economic barrier to
the development of biotechnology products for pollution control.
To cover commercialization costs, small businesses frequently have to
raise capital. Mr. Dardas described the difficulty that small companies
have in raising capital:
"It's very, very difficult to raise money in this area
because you're dealing with an area that is new. Any
time something is new it's very difficult to get
capital. It's very hard to get new companies and
emerging companies to try to develop an industry "
v-6
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Thus, for businesses chat engage in the commercialization of
biotechnology pollution control products, the availability of capital poses
a barrier.
3. Regulatory barriers
The biotechnology industry's perception of an uncertain regulatory
climate and the prospect of burdensome regulatory requirements currently is
hindering improvements in existing nonengineered microorganisms and the
development of genetically engineered biotechnology products' for pollution
control. Federal, State, and local regulatory policies and their reporting
and permitting' requirements for environmental testing of products present
additional regulatory barriers to commercialization.
The policies and requirements of che various regulatory acenc'ies .r.ay
be duplicative, differing, or unformulated. Dr. Smith described current
permitting hurdles required by the Agency for protection of groundwater,
air, etc., at both Federal and local levels and questioned the need for
additional permitting requirements addressing genetically engineered
organisms. In response to Dr. Smith's query, Ms. Jacoff, osw/USEPA, and an
observer at the Workshop, explained that "each permit process is an
individual process." She pointed out that at the Federal level, RCRA and
CERCLA have been separated, historically, but that this separation seems to
be lessening. One incident Involving Advance Genetic Sciences (ACS)
provides an example of differing permitting requirements. Experimental use
permits were granted to ACS for field testing an ice nucleation mutant by
the USEPA's - Office of Pesticides Programs and the state of California but
not by the Monterey County Board of supervisors.
It was also pointed out that the length of time involved in the
regulatory review process may pose a barrier. Dr. Goldhammer commented that
even though the PMN review takes 90 days, the RCRA permit requirements and
the possible need to provide additional' data "may take'l, 2 or 3 years."
Thus, the regulatory review process can retard technology development.
V-7
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Finally, the unevenness of the Agency's regulation of microbiological
products was discussed. The Agency's relative lack of regulatory control or
scrutiny over existing hazardous practices was discussed. These practices
include the transportation of highly concentrated samples of microorganisms
used by activated sludge plants or anaerobic digesters to seed new
facilities. It was also pointed out that high concentrations of
uncharacterized microorganisms from human excreta are present in municipal
treatment mixes. By contrast, regulatory testing requirements are being
formulated for microorganisms that are developed for pollution control
applications and chat are not known to be hazardous.
The apparent unevenness Ln regulation and the fact that .iiost of che
regulations focus on the developmental technique rather than -the product or
any Jecir.ed risk inhibit ihs expansion of the industry. :t was Dr. •"--.-in1;
impression chat none of ths Industry participants in the workshop :• l-in-._>• j •:•;>
use genetic engineering techniques to introduce improvements because jc :he
likelihood of overwhelming regulatory procedures that are tied :o che
techniques.
4. Public concerns and perception of risks
As will be discussed in Chapter VI of this document, the public has
concerns and vague perceptions about the risks that may be presented by
biotechnology. The Panelists felt that the public's concerns are centered
around genetic engineering technology and are based in part on the public's
lack of understanding of the scientific basis and applications of the
technology. If these concerns are not addressed, the public's response to
biotechnology may present a barrier to the commercialization of
biotechnology products. This effect may be most apparent in the response of
the local population near field testing sites.
in addition to the public. Dr. Peyton noted that, in general, sanitary
engineers also have an inadequate understanding of genetic engineering
technology. Dr. Sayler noted a similar lack of understanding in the
academic, science, and engineering communities as well as misconceptions
held by some government agencies' personnel.
V-8
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C. Possible Solutions
1. To address technical barriers
As will be discussed in Chapter VII of this document, it was the
opinion of the Panel that the government should continue to sponsor basic
and generic applied research. Thev also felt that generic applied research
should be emphasized and that the USEPA should continue to conduct
biotechnology-related research that is not underway in academia or industry,
especially in the areas of basic and scale-up research, environmental
survival/persistence and impact, field tasting, and risk assessment
methodologies.
2. To address regulatory barriers
a. Technical regulatory barriers
Because the need for data and methods for risk assessment and criteria
is pressing, the Panel recommended that the USEPA continue to conduct
research relevant to the development of standards for field testing and of
risk assessment criteria and methods that is currently underway in the
Agency's biotechnology research program. The rationale for this opinion was
summarized by Dr. Mellon, who stated:
"No one in industry nor in academia is going to have any
incentive to do the kind of research that is necessary to
assess the ecological effects of release of these
organisms nor are they going to do the kind of work
that's going to be necessary to develop the battery of
tests that the applicants are going to have to do to
provide EPA (with) Information on which it can make a
decision as to whether or not the technology is safe."
It was further stressed that, at. this point in time, only, the USEPA may be
able to conduct.research on monitoring methods. This is the case because
the costs associated with field tests pose an economic barrier, especially
for small companies. Dr. Smith noted that the costs of the analytical
procedures that are required for monitoring may exceed $100,000.
V-9
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b. Establish data on risk and expedite review process
One way of expediting the commercialization of biotechnology pollution
control products is through cooperative efforts by the USEPA, industry, and
academia to identify regulatory concerns early in the development of
potential projects. Therefore, the Agency requested the Panelists to
determine if incentives could be identified that would encourage industry to
notify the USEPA of research and development progress for genetically
engineered products in advance of PMN submissions.
Mr. Sonald Evans, OTS/USEPA, and an observer at the Workshop, briafly
explained the background for :his topic. According to Mr. Evans, the Agency
felt that the review process could be expedited if the Agency received
information on biotechnology projects that were planned or underway '..-:
industry prior to the PMN .submission. This would allcw the Agency ;o 02
nonintrusively involved in project design such that the Agency would rscaive
the data/inrormation needed for its assessments during the PMN review
process. He also pointed out that through such cooperative efforts, a
positive impression of industry and the Agency can be made with the public.
Mr. Evans stated that the Agency consistently encourages potential PMN
submitters to begin discussions with the Agency early to determine what
concerns the Agency has about a class of chemicals and what type of data the
Agency will require for its assessments.
Under TSCA, the opportunity exists for exempting or reducing reporting
requirements for categories of chemical substances under Section 5(h)(4).
The Agency, therefore, expressed an interest in obtaining information on
potentially exemptible categories of biotechnology products. The Panelists
were asked to suggest categories of biotechnology products that presented
inherently low risk. The Agency was particularly interested in information
that would justify why a category of products would meet the unreasonable
risk standard. To stimulate the discussion, the following categories of
products were suggested: attenuated species, pathogens versus nonpathogens,
mobile versus nonraobile, indigenous versus nonindigenous, plasmid-borne
products, and microbial enzymes.
v-10
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The Panelists discussed the issues that were raised by this topic and
the perceived associated risks. The Panelists did not agree on the nature
of the distinctions between pathogenicity, opportunistic pathogenic!ty, and
nonpathogenicity. It was suggested that the Agency consult the National
Institutes of Health, for their list of pathogens. In addition, the
definitions of indigenous and nonindigenous strains could not be agreed
upon. Mobility, more specifically, containment, was also discussed but no
conclusion was made. It was, however, pointed out chat a conference7 on
containment had been recently held, the proceedings of which are expected to
be available shortly.
Dr. Omenn summarized the discussion on 3xemptible categories of
biotechnology products by saying, "we are making (the) recommendat i~n ^'nac
the Agency Resist in trying to develop the category (of -vxei-or :::•: e
biotechnology products)."
3. To address economic barriers
The Panelists were asked to discuss current and future sources of
financing for the commercialization of genetically engineered pollution
control organisms. It was specifically requested that the Panelists respond
to and discuss the following questions. What innovative financing tech-
niques exist to aid in the development of genetically engineered organisms
for pollution control? For example, what is venture capital's role? How
can the Small Business Innovative Research program be used more
effectively? Are collaborative research ventures within industry a viable
option? What other avenues are available? OTS was hoping to gain an
understanding of some of the dynamics of the industry's financial segment.
The Schakleton Point workshop: Prospects for Physical and Biological
Containment of Genetically Engineered Microorganisms. 1-4 October,
1985, Schakleton Point, N.Y. Sponsored by the Cornell University
Ecotoxicology Program in conjunction with several Federal agencies and
private companies.
V-ll
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a. Government funding of generic applied and applied research and
the development of risk assessment methods
Dr. Goldhararaer suggested that the biggest potential source of money to
support research and technology development is the Superfund program. If it
could be worked out legislatively, research and development funds could be
generated to fund feasibility studies by either the private or public
sector. In these studies microbial biotechnology products (both engineered
and nonengineered organisms) would be compared with conventional pollution
control methods.
Following up on Dr. Goldhammer's remarks, Dr, Middletown suggested
that there is a need...
"...to fund 5c^<* demonstrative 3f:dies -:o get data
shewing that i.nd-id there is potential here that can be
realized. . .and. . .maybe comparacive studies. . .where -.he
nonengineered organisms are compared with the engineered
organisms and...with the incineration alternative in
terms of cost. Once these comparative studies have been
conducted (and information is generated) then ... people
might start pouring money into biotechnology research..."
b. Use of Small Business Innovative Research (SBIR) program to promote
and support the development and commercialization of
biotechnology products
The SBIR program was discussed as a possible source of funding for
biotechnology developmental research and commercialization by small
businesses. Dr. Barry Kat2, who had received SBIR support, summarized the
program and its funding mechanism. Because the SBIR funding cycle is on an
annual basis and projects are funded in three phases, there are time elapses
during and between each phase. Therefore, it would take three and. a half
years to get to the upper scale of funding under the SBIR program.
Dr. Katz also shared some of his insights and opinions on the SBIR
program. He noted that:
v-12
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"...The SBIR program is designed to take academic type
work that has potential commercial application and
convert it into real application ---- "
"Another area which is relevant. . .is. . .phase 3 follow-on
funding. If you have a project that they feel is good
enough to be commercialized, they also feel it important
to document that (fact)... and the way they feel chat you
can document this is to get a contractual commitment from
the private sector for at least a matching amount of
funds
"...The main problem (with follow-on, funding is)... the
fact that investors are not interested in investing in
projects (in che dollar range of) $50,000 to $500,000;
5500,000 is really tco little for most investors to be
concerned with.... The minimal matching funds or minimal
investment for rnost venture capital sources is $2
million."
"Venture capitalists will risk money on a . . ,
high value-added product, patentabla product... But it's
very hard for them to imagine in an area like hazardous
waste, partly because if you're dealing with genetically
engineered organisms, you have to be able to establish
without a shadow of a doubt that the benefits of this
kind of work far outweigh the use of nonengineered
organisms."
"Another problem with venture capital (for) follow-on
(funding) is that venture capital Is concerned about a
time line. Venture capital is concerned about seeing the
time horizon that's in the 2- to 4-year range..."
"...On the constructive side, EPA has to reassure the
private investors that the private investors will have an
ownership, secure ownership position in anything that's
developed, and that they're willing to fund this for a
period of time that will enable the venture capitalists
to step in on a time horizon that's suitable to them.
In response to Dr. Katz remarks on venture capital investments. Dr.
Niddleton pointed out that:
"...In the area of hazardous waste, a high premium is put
upon permitted facilities. If you look at wall Street
and the venture . capitalists, if you have a permitted,
secure hazardous waste • landfill, you have a permitted
hazardous waste Incinerator, then you can probably get
all the money you want."
V-13
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In the absence of access to such facilities, Dr. Middleton stated that
it's hard to get money. He continued:
"In looking at the area of the genetically engineered microorganism'
in pollution control (and)...evaluating it as a potential
investment, the key issue will be are there any data available that
show...that this approach will offer a competitive economic
advantage over the use of conventional organisms or the other
alternatives...such as the landfilling or incineration...."
Based on this discussion, it seems that under the SBIR program, small
companies can get government funding without losing their proprietary
rights. A need for venture capital sources that are interested In and
willing to fund projects at the levels needed by small businesses was
identified.
c. 'jse of Icw-interest-rata government loans to promote and s
development and commercialization
As a means of encouraging venture capitalists to invest in the
development and commercialization of biotechnology pollution control
products, Or. Peyton suggested tru:
"...many venture capitalists get money that originally
comes from the Government. They get cut rate
loans....And...if cleaning up pollution is in the public
interest, not only for profit, (then) something could be
written in the...legislation so that maybe a point or two
off the percentage rates could be provided to venture
capitalists for investing in that type of biotechnology
for pollution control...."
d. Use of RCRA/Superfund Program to provide characterized sites for
field testing
As discussed previously (see chapter IV), there are technical,
economic, and regulatory barriers to field testing. In the Panel's opinion,
the use of federally designated/sponsored/managed sites would be an
incentive to conduct field tests. The use of sites that are already
characterized and contained, and that are being monitored could reduce the
costs associated with field testing, would facilitate the selection of
appropriate site-specific microorganisms, and may be more likely to produce
V-14
-------
credible results. Towards this end, Superfund sites were suggested for use
in field tests. The use of federally-designated sites may also address the
concern regarding the maintenance of proprietary rights by developers.
D. Suggested Regulatory Incentives
The Panelists suggested that the full implementation of existing
Superfund and RCRA statutes could foster the development of the
oiotechnology industry. Enforcement of these statutes would promote and,
perhaps, expedite waste "cleanups." Under lax enforcement-, it is more
economical for polluters to pay the fines than clean up the wastes.
Legislative i.ncencives •-era suggested that would foster the
development of biotechnology pollution control, products. These :..-.ci'jde
funding to support comparative studies to evaluate microbial (engineered and
nonengineered) and conventional pollution control methods ("burn or bury")
to assess the "best demonstrated available technology"; providing guidance
by suggesting the consideration of biotechnology as an alternative to
conventional methods; granting variances to foster the development of new
technologies; and establishing Federal field testing programs.
The Panelists also pointed out that the opportunities provided by
field tests should be used by the Agency to educate, involve, inform, and
demonstrate to the public the potential benefits of biotechnology pollution
control products.
v-15
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VI. PUBLIC PERCEPTIONS OF RISKS AND BENEFITS OF BIOTECHNOLOGY
POLLUTION CONTROL PRODUCTS
Public perceptions of genetic engineering can influence the rate at
which biotechnology pollution control products are commercialized.B/9 The
general public has -latent apprehensions about the actual and perceived risks
genetic engineering, and, by association, applications of biotechnology may
present to human health and the environment. Genetic engineering or bio-
technology also elicits public concerns because, In the public's perception,
the distinction between human and industrial applications are not always
clearly distinguished. Therefore, the association of an accident or the
perception of an adverse consequence with genetic engineering or biotsc'nr-.oloay
can incite public fears, and the .ensuing public response can nave on Impact on
the future development of biotechnology.
Concern for potential risks has long been associated with the directed
genetic alteration of microorganisms. Initially, the scientists themselves
raised issues regarding potential hazards posed by genetic alterations. As
far back as the 1940's, the potential for the creation of uncontrollable
chemically induced mutations in microorganisms was raised as an issue.10 In
the 1960's, the concern centered around potential hazards that might be
presented by possible indiscriminant genetic transformation of microbial
cells. Limited public concern was expressed with respect to these early
hazard issues that were associated with genetic alterations in laboratory
settings.
8 U.S. Congress, Office of Technology Assessment, JH Gibbons (Director).
Commercial Biotechnology: An International Analysis-. 1984.
9 U.S. Congress, Office of Technology Assessment. Genetic Engineering.
1982. Research and Education Association, New York, NY.
10 Hotchkiss RD. Recombinant DNA Research, vol. 5, NIH publication No.
80-2130, March 1980, p. 484.
VI-1
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In the 1970's, greater public apprehension was expressed for the
potential risks presented by genetic alterations accomplished by rDNA
technology.11/12 Again, the issue of potential biohazards was raised by
the scientists themselves. Open debates and numerous conferences and study
groups were convened to address the issues of the risks that might be posed
by rDNA technology to laboratory workers and society at large. These forums
made information on rDNA technology accessible, were covered by the media,
and tended to support the public's subliminal concerns about potential risks
presented by rDNA technology.
While the Initial conjectured hazards of rDNA technology at the
laboratory level appear to have been overstated, different types of
potential hazards may be presented by the .-ieveicpment of the .biotechr.olo:;y
industry. Public interest In the future Jevelopment of biotechnology '.^
»:
-------
and academla. To initiate the discussion, the following methods for
information dissemination were suggested: directed use of the media, e.g.,
feature articles, news releases, documentaries; allowing public interest
groups, industry, and academia to more frequently comment on Agency policy
via Science Advisory Board meetings; Congressional hearings; and development
of a forum of public meeting.
At the request of the Chairpersons, Dr. Margaret Mellon presented an
overview of and lad the discussion on- public perceptions of the
biotechnology industry. Dr. Mellon began the session by pointing out 'hat
the actual risks that are presented by biotechnology are distinct from
perceptions of risks...
"...chat 'hose perceptions are an independent factor that
:TiUst be considered by policy makers and by the industry
in this field....It's very important that the two be kept
separate."
To illustrate the importance of the public's perception, Dr. Mellon
mentioned the fact that it was local public opposition that stopped Advanced
Genetic Sciences' (ACS) experiment1* in Monterey County, California, and
that Congressional hearings were instigated within days after the public
learned that ACS had conducted "an unauthorized release" of the micro-
biological product. She advised policy makers that "...it is certainly
prudent... .not to underestimate the public perception factor."
A. Concerns about Risks Associated with the Use/Release of Microbial
Products
Dr. Mellon identified several concerns about biotechnology that she
felt are held by the public. The main public concern about genetic
engineering and, thus biotechnology, is that uncontrollable and/or
unpredictable organisms may be created. Dr. Oraenn elaborated on this point
using the ice nucleation bacteria as an example. He stated that little ap-
19 On 14 November 1985, the USEPA under FIFRA Section 5 approved an
experimental use permit to test ice nucleating, bacteria (Pseudomonas
fluorescens and syringae, INA-, deletion mutants on a test plot (0.2
acre) of 2,400 strawberry plants near Castrovllle in Monterey County,
California.
VI-3
-------
parent concern seemed to be associated with either the isolation of ice
nucleation mutants from the environment or by the development of ice nucle-
ation mutants using conventional genetic methods, i.e., chemical mutation
induction. He also noted that by contrast, the removal of a well-character-
ized ice nucleation gene from microorganisms using rDNA techniques did raise
concerns. In Dr. MelIon's opinion this somewhat vague concern is deeply
rooted and appears to be based in part on a lack of understanding of the
scientific basis and applications of biotechnology.
The public's distrust of industry was identified as another concern.
This distrust seems to be based en the public's recollection of past
incidents involving conflicts between the industrial profit motive and
public safety issues. A final concern "hat was identified by Dr. Mellon Is
the uncertainty about what possible risks .Tiay be presented by aopl I-VJE icr.3
of biotechnology. In the public's perception, irhese potential r:^'.<3 :-.jv»
yet to be- identified or evaluated.
The highlights of the discussions on public concerns are presented
below.
1. Barriers to understanding biotechnology
Several factors that appear to act as barriers to understanding
biotechnology for the general public and for the academic, scientific, and
engineering communities were identified and discussed by the Panelists. The
highlights of the discussion of each "barrier" are summarized and presented
below.
a. Lack of information
The public's concern about genetic engineering probably stems from an
inadequate understanding of this technology's scientific basis. The public
is not generally aware of the facts that the transfer of genetic information
between microorganisms occurs in nature and that genetically altered
microorganisms, albeit constructed by conventional genetic, techniques, have
been used for years to provide goods and services on which the public
depends and which serve the public benefit. For example, nonengineered
Vl-4
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genetic alteration techniques have been employed to develop microorganisms
used in the production of foodstuffs, beverages, and Pharmaceuticals, con-
ventional methods for genetic alteration have also been used to develop/
improve strains of plants and animals in agriculture. Moreover, genetically
selected/altered microorganisms have been used and are currently used for
municipal and wastewater treatments, septic tanks, land waste treatment
systems, and as microbial pesticides. Currently, microorganisms are being
employed in the cleanup of chemical spills.
b. Misconceptions
In addition to the 'jeneral public, some individuals with various
governmental agencies have misconceptions about genetic engineering ar.d, ;y
association, about biotechnology. Sr. Sayler reported that during a jemlr.-ir
he recently attended, an individual who identified himself as a .uicrc'o'.al
ecologist with one of the Federal agencies cited an outlandish example thac
associated "very unacceptable risks" with the environmental release of
genetically engineered organisms. In this instance, a representative of the
Federal government was "misinforming" the academic community. As another
relevant example of misconceptions about genetic engineering, Dr. Goldhamraer
alluded to the questions and concerns expressed by some of the members of
the Monterey County Board of Supervisors and local residents and statements
made by some of the Supervisors during hearings on the ACS field test.16
c. Lack of multidisciplinarv communication
During the discussion of public perceptions, Dr. Gary Sayler pointed
out that in the academic, science, and engineering communities...
16 Public Hearing before the Monterey County Board of Supervisors on 27
January 1986. The Board of Supervisors, P.O. Box 1728, Salinas,
California 93902. This was an information-gathering and fact-finding
hearing to determine whether .to allow a microbial pesticide
experimental field test to proceed. In this case, the microorganism to
be employed was ice nucleating, deletion mutants of Pseudomonas
fluorescens and syringae. It should be pointed out these mutants were
developed without using rDNA techniques.
Vl-5
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"in terms of their real, fundamental understanding of the
approaches and the molecular basis for the genetic
engineering technique the actual knowledge and
understanding in the science and academic community is
very scattered."
In addition, Dr. Peyton pointed out that some sanitary engineers do
not perceive a need for the use of genetic engineering techniques to enhance
microbiological pollution control capabilities. They apparently feel that
microorganisms that are capable of performing these tasfcs already exist in
nature. 3ased on this opinion, the sanitary engineers believe that the main
thrust in the development of the biotechnology pollution control industry
should be directed towards the isolation and development of culturinq ir.d
.acclimatizing techniques to harness these existing na'tural processes. T.'-.-JS,
"there's a real perception problem (regarding jsnatic -engineer-l.-.^ i.-vJ
thereby with the biotechnology industry) in the science and engineering and
academic" communities and in governmental agencies.
2. Perception of past industry priorities: Conflicts between profit
and safety issues
The public's perception of the biotechnology industry is influenced by
the recollection of prior instances in which other industries appeared to
place a higher priority on profits than on health and safety. To illustrate
this point, Dr. Mellon mentioned two notable examples where
"...when the profit motive conflicted with the health and
safety obligations, the companies didn't come forward.
(For example) — the tobacco industry (still insists) that
the evidence proving that cigarettes are harmful to your
health is not all that strong, and the asbestos industry,
which has certifiably ... withheld ... information that
the exposures to the product that they were making are
(detrimental to human health). These (incidents) are not
directly relevant to this new industry...but...this
distrust of industry statements, ... is something that
(the biotechnology industry Is-)-not going to be able to
get around at least right away."
Dr. Mellon went on to point out that the ACS incidents are the first
instances in which the biotechnology industry "revealed itself to be some-
Vl-6
-------
what disingenuous about a health issue or an environmental issue." However,
in her opinion, the public perception of the credibility for this new
industry is "very high," and it is important that existing credibility of
the industry, the Agency, and public interest groups be maintained and
nurtured.
3. Prior overstated reassurances by agencies about the extent of risks
The issues of the public's distrust of- regulatory agencies' risk
assessment capabilities and of the agencies' and industry -proponents'
reassurances regarding the safety of biotechnology were discussed. Or.
Robert Nicholas, an observer at the Workshop, pointed cut that...
"One of the problems 33 far -33 public perceptions is
concerned is what I call the noncredible risk expressions
of proponents of the technology...."
"We occasionally hear proponents saying well there's no
credible risk. We all know that nothing can happen.
We've seen this for a hundred years or what have you,
we're not worried about it."
"It may very well be that that's absolutely true. But
the public is seeing Three Mile Island and it's seeing
the Space Shuttle and it's saying these people told us
that this couldn't possibly happen and it did happen.
How can we trust you now?"
Dr. Oraenn pointed out that with it's small biotechnology database, the
Agency had no basis on which to reassure the public without overstating the
facts.
Following up on the point made by Dr. Nicholas, Dr. Mellon elaborated
on the Space Shuttle incident involving the Challenger explosion:
"I think NASA is a very good example. I think...the
problem that they're having right, now (is) because they
were revealed upon investigation to have lied. ' Now, the
immediate public reaction to that disaster among everyone
I know was that it was just a tragedy, that everybody
knows that NASA has been working as hard as humanly
possible to prevent these accidents. That Agency had
more credibility than any one in Washington. And had
their credibility stood up, they would have withstood this
VI-7
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accident beautifully, without pretending that this (was)
anything other than a terrible human disaster."
"What we need to do in this enterprise is to set
ourselves up to be like NASA was a short 4 weeks ago so
that ... when the equivalent of a disaster occurs, there
is a credible Agency (which) on examination will be
proved not to have lied, not to have dissembled, not to
have cut corners, and will be able to (acknowledge that)
this happened, it means this, but for the future of the
technology (the Agency is) going to take it into account,
not shoving it under the rug, and going to go forward. I
think that the public is very able to handle the notion
of 'we don't know.'"
4. Unclear sense of possible risks
Dr. Peyton- Identified :he need to define the potential r'\ .-;xs
associated with ^eneticaliy engineered .-nicroorganisms. While .id cur a ILy
occurring, conventionally developed, and genetically ^ncir.eared
microorganisms are all candidates for use, the public's concern is the risks
that may be presented by the use of genetically engineered biotechnology
pollution control products. Dr. Peyton also pointed out that the risks
associated with exposure to hazardous substances, to genetically engineered
microorganisms, and/or to the degradative products of hazardous substances
should be identified and information used in the development of risk
assessment criteria.
a. Risks to environment and human health
In Dr.. MelIon's opinion, the public's concern is for the undefined
potential for risks that may be presented by biotechnology products in
general and by genetically engineered microorganisms in particular. Dr.
Mellon described the public's apprehension as follows: " — The root concern
is with the technology which is widely preceived to have great
potential...." And in the public's perception, this technology provides an
unlimited potential for..."manipulating- the form and .the shape and the
properties of organisms "
vi-8
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During the Monterey County Board of Supervisors' public hearing on the
ACS experiment, it was revealed that regulatory agencies do not have
standardized methods and criteria with which to assess identified risks.
This fact tends to reinforce Dr. MelIon's assessment of the public's
perception that perhaps even serendipitously...
"...we really will somehow create something (primarily
microorganisms, although genetic engineering of humans is
an associated concern) whose properties we cannot
predict, that we will not be able, to control and is
somehow going to hurt us...."
Since the concern about risks i3 not based on factual information, Dr.
Mellon postulated that the public's apprehension could be addrass^J .i.-.d
"...challenged with case-by-case information about what biotechnolocy cii'Ay
means and how it relates to this general concern."
b. Defining unreasonable risk
Under TSCA's PMN review process, unreasonable risk is the standard
used to decide whether or not regulatory action will be taken for a
particular chemical. In its review process, the Agency identifies and
analytically evaluates the risks and takes both benefits and risks into
account in judging whether the risk may be unreasonable. Given the fact
that the possible risks associated with the use of genetically engineered
microorganisms have yet to be determined, the public may be at a loss for
understanding how unreasonable risks are determined. It should be pointed
out that there is an incongruence between the scientific assessment and
public's intuitive perception of risk. This can lead to contradictory
evaluations of unreasonable risk by the Agency and the public. Dr. Mellon
felt that the differences in these evaluations should be recognized,
addressed, and resolved.
c. Ability of government agencies to evaluate risks
Concern about the ability of the USEPA to evaluate the risks presented
by biotechnology products may have, been raised in the public's mind by the
ACS incident. The injunction by the Monterey County Board of Supervisors
VI-9
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and suits filed by public interest groups expressed concerns about the
identification and evaluation of risks to human health that might have been
presented by the ACS field test and about the methods and criteria by which
the Agency evaluated the ACS application.
Dr. Alan Goldhammer pointed out chat site inspections by the Agency
are not required for the issuance of experimental use permits...
"...SPA did give them an experimental use permit. They
(SPA) did not go out and look at the site and find (as)
it was revealed that the site was (near residences). 3ut
you look at the regulations -and every time SPA issues an
experimental use permit they don't look at sites...."
.-.1. .?isk analysis - balancing costs and benefits
To assess risk, TSCA requires that the Agency take both the risks and
benefits -of genetically engineered pollution control microorganisms into
account. Due to the lack of standardized assessment criteria and methods,
the Panelists felt that risk should be determined and evaluated on a
case-by-case basis. The Panelists also felt that the cost effectiveness of
genetically engineered microorganisms should be compared with naturally
occurring and nonengineered microorganisms as well as with conventional
pollution control methods.
The public is uncertain about how the Agency's assessments of risks,
benefits, and cost effectiveness are utilized in the decisionmaking
process. To inform the public on the issues, to address public concerns,
and to educate and increase the public's understanding of the risk
assessment process for biotechnology products, the Agency has proposed to
make some information about submissions accessible to the public, invite
comments from interested members of the public, and to include
representatives of the lay public on the Biotechnology science Advisory
Board.*7
17 USEPA. "Coordinated Framework for Regulation of Biotechnology:
Announcement of Policy and Notice1 for Public comment. Federal Register
51:23301-23392 (June 26, 1986}
VI-10
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B. Perception of Benefits of Biotechnology
1. Use for pollution control
As was brought out during the discussions on field testing and related
research (see Chapters IV and viz in this document), the application of
biotechnology products, to pollution control may increase the Nation's
capabilities for safe and effective waste treatment methods. In the opinion
of the Panel, the public is generally aware of the benefits that may be
presented by the development and use of biotechnology products for the
control of hazardous and nonhazardous wastes in the environment.
2. Use for emergency response
Indigenous and selected indigenous microorganisms have been used for
the cleanup of chemical spills. Dr. J. Exner, Technical Director at
International Technologies and observer at the Workshop, reported that his
company has used biological treatment for chemical spills. He stated that
microorganisms in conjunction with chemical treatment had been used in situ
for a formaldehyde spill in northern California. The biodegradation of a
marine oil spill18 has been reported in the open literature, ' and
Pseudomonas indigenous to the Nevada Test Site has been shown to absorb
plutoniura.19 New biotechnology products may enhance existing emergency
response capabilities for hazardous substance spills.
C. Initiatives Suggested to Address Concerns
Based on the discussion by the Panelists, several initiatives were
suggested to educate and inform the public and to address and alleviate the
public concerns. These are summarized below.
18 Murakami A et al. Hakkogaku Kaishi 63(2) :145-152 (1985).
19 Hersman LE. Abstr. KN-100, American Society for Microbiology Meeting,
Washington, D.C., March 23-28, 1986.
VI-11
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1. Recognition of public perceptions by agencies and industry
The public's perception of genetic engineering and the biotechnology
industry and public concern for the potential risks that may be presented by
these technologies should be recognized and addressed by Federal regulatory
agencies and industry. It was the general opinion of the expert Panel that
the issues surrounding the use of biotechnology products for pollution
control should be discussed openly and honestly.
2. Education of public, academic, scientific, and engineering
communities and governmental agencies
Since the public's concerns about biotechnology are due, in part, to a
lack of understanding of both scientific basis -and applications -DC "."•<*
technology, the Panelists celt chat a significant effort should te /.ads to
enhance the lay public's understanding of basic biology. Dr. Chakr -ib^r ;y
suggested the effort be extended to include ensuring that the curriculum of
the present generation of students includes courses to expose the students
to biology, especially microbiology and genetics. In addition to
7\
scientific fundamentals, it was suggested that the following information
also be conveyed to the public:
o The transfer of genetic information occurs in nature.
PIasmids can be exchanged between different genera of
microorganisms existing in close proximity;
o With respect to the reproduction of microorganisms, the
fact that soil and waste treatment plants are analogous
to chemostats; large numbers of microorganisms are
generated in all three; and
o Currently, society benefits from the use of
microorganisms developed by conventional genetic
techniques. Microorganisms are used to treat wastes and
sewage, thus microorganisms are already being used for
pollution control. The use of genetically engineered
microorganisms may enhance and expand existing microbial
vi-12
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waste treatment capabilities and complement nonmicrobial
pollution control methodologies.
Dr. Mellon suggested that field tests and demonstration projects
involving biotechnology products should be used to acquaint the public with
the potential and specific benefits of the applications of biotechnology for
pollution control. "...Each...application represents an opportunity to
educate an interested segment of the public...."
Dr. Mellon also suggested that field testing sites, be carefully
selected. She advised against the selection of sites that are already
perceived as hazardous. She pointed out that the selection of sites where
the local public has a vested interest in the success of the project would
be .advantageous. This would foster a supportive environment and contribute
positively to the perception of genetically engineered microorganisms for
pollution control.
The Panel also suggested that information on the scientific basis and
potential applications of biotechnology be disseminated to academic,
scientific, and engineering communities, to Federal, State, and government
staffs, and to environmental public interest groups. These are the groups
to whom the public might turn for information and judgements about
biotechnology. For these groups, it was suggested that information be made
accessible at professional conferences, seminars, and via presentations in
technical journals.
3. Maintenance of industry's and USEPA's credibility
It was the opinion of the Panel members that the biotechnology
industry and USEPA should make efforts to maintain and build their
credibility with the public. Specific suggestions that were made include:
o Agency statements should be factual*;
o Applications and proposed applications should be
reviewed on a case-by-case basis and discussed with the
interested public, especially potentially affected local
groups; and
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o Care should be taken In making statements regarding
potential risks and assurances of safety.
4. Development and use of biotechnology-specific tier testing and
risk assessment methods
A cooperative effort by the industry, USEPA, and academia to develop
specific methods for the tier testing criteria and risk assessment of
biotechnology products could help build public confidence in the industry.
The Agency, therefore, requested from industry and academia relevant
information and/or data co supplement chat which it is
developing/collecting. The status of the USEPA's database, tier testing,
•and risk assessment -are outlined below.
a. Database
There is little information available for use by the Agency during Its
PMN review process. To alleviate this deficiency, the Agency (OTS) is
developing a database of organisms, microbial products, strain development
techniques (both conventional genetic and rDNA techniques), and pollution
control applications from the open literature. These data may be of
assistance in assessing PMN submissions and permit applications, in
identifying the types of data the Agency would want in applications and the
classes of products of concern to the Agency, and in developing tier testing
criteria. The development of this database may facilitate technical
evaluations as well as expedite the review process.
b. Tier testing
Under TSCA, test data on chemicals can be required for assessing risk
during PMN review process. Several research projects that are relevant -for
the development of tier testing criteria are being conducted by the Agency
in its biotechnology research program. . The results of. these studies may
assist the Agency in identifying the kinds of tests that it will require for
biotechnology products intended for deliberate release in the environment.
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c. Risk assessment
in its biotechnology research program, the USEPA is conducting
research directed towards the development of risk assessment criteria and
methods for biotechnology products. These are needed in order for the
Agency to review PMN submissions.
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VII. USEPA's POLLUTION CONTROL-RELATED BIOTECHNOLOGY RESEARCH
Basic, generic applied, and applied research are essential for the
commercialization of new technologies.20 These kinds of research provide
information needed during the various phases of the product
commercialization process. Historically, the Federal government has funded
basic and, to a limited extent, applied generic research while industry has
sponsored applied research.
The USEPA recently initiated -a biotechnology research program.
Although genetically engineered microorganisms are the primary fscus, seme
of the projects in the -program involve .nonengineered microorgan is-.s.
Research projects that are underway or planned Ln this program include basi...-
and generic applied research in the areas of .nicrobial survival, grcwth. L^
situ transfer of genetic information, dispersal, biological containment, jnd
environmental and health effects. Those research projects that are related
to the application of biotechnology to pollution control were briefly
described to the Panelists by USEPA personnel who are conducting/managing
these projects.
The goal of this session of the Workshop was to develop ideas on both
basic and applied research projects that could enhance the study of
genetically engineered organisms for pollution control. The Panelists were
asked to suggest the kinds of research and development projects that the
USEPA and industry should undertake that would be the most useful for
pollution control purposes. In addition, the Panelists were also requested
to develop a rank ordered list of projects that would be best suited for
funding by the government.
20 U.S. Congress, Office of Technology Assessment, JH Gibbons (Director)
Commercial Biotechnology: An International Analysis. 1984.
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A. Environmental Research Laboratories, Gulf Breeze, Florida
Dr. Al Bourquin described the philosophy and Che research orientation
at the Gulf Breeze Laboratories. Dr. Bourquin stated that at Gulf Breeze,
the emphasis is on understanding...
"...the physiological and genetic mechanisms involved in
biodegradation in both engineered and nonengineered microorganisms and
how the rnicrobial community functions in order to promote :he
facilitation of degradation, both genetically and physiologically."
He also pointed out that the Gulf Breeze biotechnology research program
recently expanded its capabilities in genetics and physiology to i-cr.cucc
••nore investigations of genetic mechanisms with an emphasis :-n risk:
assessment and on the risks associated with the environmental release of
genetically altered microorganisms.
Dr. Bourquin briefly described some of the pollution control-related
research projects that are currently underway. These include -the catabolism
of chlorinated aliphatic and aromatic hydrocarbons and the development of
methodologies to determine survival, genetic stability, stress on the
ecosystem, and other factors that may be associated with the assessment of
risks for biotechnology.
In the studies on waste degradation, a number of different approaches
have been used. These include the use of nutrient supplementation of
resident raicroflora; field testing to calibrate biodegradation systems for
laboratory-developed jet fuel components, with an emphasis on the
biodegradation rates; and physical alterations of the environment to
facilitate anaerobic versus aerobic biodegradation, e.g., flooding, creating
slurries, and agitation.
Other ongoing research projects at Gulf Breeze that are relevant to
biotechnological approaches to pollution control were also briefly described
and are summarized below.
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1. Detection of biodegrading microorganisms
Dr. Ananda Chakrabarty directs a project on the detection of
biodegradative microorganisms in the environment. Further details about
this project were not provided.
2. Cometabolism of organic compounds
Dr. Peter Chapman presented a brief review of the ccmetabolism project
he directs. In cometabolism, the transformation of organic compounds Ls
dependent upon the presence of a second compound. The underlying basis of
the cometabolic process is not currently understood. Dr. Chapman Is
investigating the rp.echanis.-ns of .aromatic hydrocarbon degradation. ::-.-!
.aerobic biodegradat ion of t;- .chloroethy lene (TCS) has been shown to '.-.• i
ccmetabolic process requiring the presence of oher.ol. The ultimate ;c.3i3 of
this project are to determine whether and/or what ccmetabolic processes
occur in environmental organisms and to determine how these processes may be
manipulated.
3. Degradation of chlorinated aromatic compounds by anaerobic micro-
organisms
Dr. Barbara Sharak-Genther is investigating the mechanisms by which
anaerobes degrade chlorinated aromatic compounds. She is currently
developing laboratory methods to enumerate and isolate dehalogenating
microorganisms from anaerobic sediments. The genetic and physiological
analysis of such microorganisms may be useful for advancing the development
of anaerobic chlorinated aromatic compound blodegraders.
4. Degradation of halo-organic compounds - detection of
microorganisms and analysis of degradation pathways
Dr. Deb Chatterjee, in Dr. Chakrabarty's laboratory, is using genetics
to-elucidate the degradation pathways for 2,4,S-T.
Dr. Michael Nelson has isolated a gram-negative, aerobic microorganism
that mineralizes TCE. This organism was isolated from an environmental
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sample. Characterization of the organism has shown that its biodegradation
of TCE is coraetabolic since the presence of phenol is required. Phenol was
present in the sample from which the TCE biodegrader was isolated. Further
characterization of the requirements for and mechanisms of TCE cometabolism
and a field test of the TCE biodegrader are anticipated.
5. Environmental impact - monitoring and assessment methods and
biological containment
a. Environmental ecology
Several projects are underway that are relevant to the development of
methods for monitoring ecosystems and for assessing environmental impact.
The group conducting ecosystem studies at Gulf Breeze has i!ev= •.-;-oed
laboratory microcosms and has begun fiald .tasting and/or field cai Ibr i: Ion
studies of these systems.
Or. Tamar Barkay is investigating the adaptation of microbial
communities to stress. As a model, Dr. Barkay is developing methods for the
detection of mercury-resistant genes and their movement through microbial
communities in aquatic ecosystems.
Or. Fred Genthner is investigating the frequency of the conjugal
transfer of genetic information between aquatic microorganisms in laboratory
microcosms.
Dr. Hap Pritchard and Dr. Ellen O'Neil are developing laboratory
microcosms for use in predictive studies on biodegradation rates in natural
environments.
It was also mentioned that efforts are underway to adapt the
sequencing of 16S ribosoraal RNA for studying and defining ecological
microbial communities.
vn-4
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b. Methods for biological self-containment for released microorganisms
Dr. Stephen Cuskey is directing several projects on microbial
degradation of hazardous wastes. In these projects, an emphasis is placed
on the development of methods that may be useful for the containment of
environmentally released biotechnology products. Several potential
containment methods have been developed.
One method involves the use of a temperature-sensitive mutation in an
ultraviolet-irradiation-resistant gene. The presence of this mutation in
microbial cells would confer sensitivity to sunlight at the restrictive
temperature. For example, the inclusion of a cold-sensitive mutation in the
ACG3 strain (ice nucleation strain developed by Advanced Genetic Sciences)
would make these cells more sensitive to sunlight at colder temperatures
than at warmer temperatures.
Another method that is under development is the cloning (genetically
engineered placement of) the genes for the uptake of mercury on a plasmid.
For biodegradative microorganisms harboring this plasmid, the addition of
sublethal concentrations of mercury can be coordinated with the elimination
of targeted hazardous substances from the environment. Thus, in the
presence of mercury, biodegradative microorganisms bearing this plasmid
would be selectively killed.
A third method involves the construction and use of a plasmid-borne
"suicide cassette" which would ensure the self-destruction of microorganisms
harboring these plasmids. A "suicide cassette" would encode genetic
information for the constitutive production of a killing factor and genetic
information for a protecting factor. Expression of the gene(s) for the
protecting factor is regulated by a predetermined promoter. When the
promoter that controls the production of the protecting factor is specific
for a particular pollutant, microorganisms harboring "suicide cassettes" are
protected for as long as the pollutant is present in their environment. In
the absence of the pollutant, i.e., through biodegradation, the gene for the
protecting factor is not expressed and the constitutively produced killing
factor is lethal for microorganisms harboring a "suicide cassette." A
"suicide cassette" specific for the pollutant 3-chlorobenzoate is being
VlI-5
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developed using the plasmid pEPA22 and a promoter specific for 3-chloro-
benzoate.
Based on the specificity of the promoter that is employed, the
"suicide cassette" method has potentially wide applicability. In addition
to promoters specific for a variety of pollutants, promoters that respond to
light or to the presence or absence of oxygen may be used.
The "suicide cassette" may also be used by biotechnology companies for
the protection of their proprietary rights. Dr. Cuskey stated that "people
like Mr. Dardas could start accepting those $250,000 contracts if they knew
that the clients could sift (through the) soil for a long time and not get
the Detox process."
B. Hazardous Waste Engineering Research Laboratory, Extramural .Research,
Cincinnati, Ohio
Mr. Venosa briefly reviewed four extramural genetic engineering
projects that are being funded by the Hazardous Waste Engineering Research
Laboratory and that are currently underway. One of the four projects
involves biodegradation while the other three are basic research.
1. Chlorinated organic compounds - development of anaerobic
biodegraders
Dr. George Pierce at Battelle in Columbus, Ohio, is directing this
project to develop strains of anaerobic microorganisms that biodegrade
chlorinated organic compounds. This project has been underway for 2 years.
One such anaerobic microorganism that dechlorinates 3-chlorobenzoate has
been isolated. Efforts are currently underway to identify, clone, and
sequence the genes involved in 3-chlorobenzoate dechlorination.
2. Microbial-binding proteins - isolation and characterization
Dr. Clem Furlong at the University of Washington at Seattle is
directing this project. Microbial-binding proteins reversibly conjugate
VII-6
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ligands for which they are specific. These proteins may, therefore, have
applications for the selective removal of pollutant ligands from waste-
waters and sludges.
The pollutant phosphate causes putrification in lakes and streams.
The gene for an Escherichia coli (E. coli) protein that binds phosphate has
been cloned onto a multicopy plasmid and introduced into an E. coli double
mutant. One mutation involves the cell wall and allows the binding protein
to leak out of the cells. The second mutation confers a phosphate require-
ment and causes the cells to constitutively overproduce the phosphate-
binding protein, e.g., 70 percent of the cells' protein is phosphate-binding
protein. Cells bearing both of these mutations constitutively produce and
release the phosphate-binding protein. This protein can then be extracted
from the culture medium, immobilized, and used to remove pollutant phosphate
from wastewater.
Cadmium-binding proteins have been detected in E. coli and other
organisms. Efforts are currently underway to develop methods for the use of
the cadmium-binding protein to remove cadmium from wastewaters and sludges.
3. Enhancement of microbial nitrification
Dr. Michael Carciotes at the university of Cincinnati is directing a
project that focuses on enhancing the nitrification process in micro-
organisms by either increasing the nitrifier's intrinsic growth rate or
increasing the rate of nitrification. The latter may be achieved by
stimulating or enhancing the enzymes responsible for the oxidation of
nitrite to nitrate. As a first step, the genetics of nitrifiers is being
studied. To date, the leucine B gene from a nitrobacterium has been cloned
and expressed in E. coli. Efforts are underway to reintroduce and
characterize the expression of this gene in the nitrobacterium.
4. Elucidation of the mechanisms of methanogenesls
Dr. John Reeve at Ohio State University is directing a project to
elucidate the mechanism by which microorganisms produce methane from carbon
dioxide and hydrogen. Efforts are being directed towards the cloning of the
VII-7
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gene for the terminal enzyme in methanogenesis, methyl coenzyme, and methyl
reductase activity in E_._ coli. Efforts are also being directed towards
characterizing the enzyme with respect to its activity at different
dissolved oxygen concentrations, pH levels, and other environmental
stresses. Once the mechanism of methanogenesis is understood and the
pertinent genes are identified and cloned, it may be possible to alter the
genes, introduce the altered genes and into methanogens that are already
adapted to particular environments; this may result in the development of
more useful methanogens.
In response to questions from the Panelists, Mr. Venosa pointed out
several possible technological advances and benefits that may also result
from the latter two research projects:
1. The enhancement of nitrification could reduce the
costs associated with nitrification, e.g., smaller
and/or less expensive reactors may become feasible.
2. The insights gained from work on nitrification may
be transferable/exploitable for the enhancement of
oxidation of ammonia by heterotrophs.
3. The elucidation of the mechanisms of nitrification
and methanogenesis may facilitate the development of
these traits in other more tractable microorganisms.
4. Information gained during the tailoring of
methanogenesis genes may allow the stabilization of
this process with respect to environmental
conditions, e.g., fluctuations in oxygen and pH.
C. Hazardous Waste Engineering Research Laboratory. Intramural Research,
Cincinnati. Ohio
Mr. Pat Sferra, Project Officer, briefly described projects involving
microbial degradation of pollutants that are underway at or funded by the
Hazardous Waste Engineering Research Laboratory.
1. Construction of biodegradative microorganisms
Dr. Chakrabarty will head a project to construct microorganisms that
will biodegrade targeted chemical pollutants. Dr. Chakrabarty will also
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direct a project at Gulf Breeze Laboratory aimed at detecting biodegrading
microorganisms.
2. Microbial degradation of polychlorinated biphenyls
In a collaborative effort. Dr. David Gibson at the University of Texas
has been funded to study one aspect of microbial degradation of
polychlorinated biphenyls (PCBs) mediated by strain LB-400, a microorganism
developed by General Electric (GE). GE will study another aspect of PCB
degradation.
3. Plant uptake of hazardous wastes
As a visiting scientist, Dr. Robert Bell, who is affiliated with the
University of Liverpool, will investigate the uptake of hazardous wastes by
plants. In this study, the ability of plants to remove and/or detoxify
pollutants from the environment will be assessed.
4. Degradation of chlorinated organic compounds by white rot fungus
Dr. Steven Aust of Michigan State University is being funded to study
the degradation of organic compounds by the white rot fungus, Phanerochaete
chrvsosporium. To date, the compounds degraded by this microorganism include
these chlorinated hydrocarbons: dichlorodiphenyltrichloroethane; tetrachloro-
biphenyl; hexachlorobiphenyl; p-chlorobenzoic acid; poly-chlorinated
biphenyls; and 2,3,7,8-tetrachlorodibenzo-p-dioxin. This microorganism has
also degraded benzoic acid, cyclohexane, biphenyl, and benzo(a)pyrene. The
white rot fungus degrades most of these compounds slowly and at different
rates. This microorganism has been proposed for field testing, originally
on private property, but now at a military site. It seems that the
permitting process is posing a barrier to the field testing of the white rot
fungus.
Through an Interagency agreement. Dr. E. Kent Kirk at the Forests
Research Laboratory, United States Department of Agriculture, Wisconsin, has
been funded to conduct survivability tests with the white rot fungus.
VII-9
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In summarizing the potential applications for genetically engineered
microorganisms (GENS), Dr. Cuskey pointed out several of their technological
advantages. GEMS can be constructed that have increased efficiency and/or
rate of the degradative process. This can be accomplished by increasing
enzyme production. Using genetic engineering technology, the regulatory
controls of degradative enzyme production can be manipulated, and altered
degradative enzymes and new degradative pathways can be designed and
constructed. Genetic engineering may also be used for the biological
containment of microorganisms released in the environment.
Finally, Dr. Bourquin pointed out that the development of genetically
engineered microbial products for pollution control would not be immediate,
and that microorganisms developed with traditional genetic techniques, those
not involving the transfer of genetic information, could be available sooner
for pollution control applications.
In response to the presentations of these projects, Dr. Caldwell
commended
" — the EPA for working on genetic techniques for
containing organisms and genes as opposed to physical
techniques, also for developing genetic methods—to
monitor the dispersal of microorganisms in the
environment. Given all the ecological complexities, I
just don't think it's possible to physically contain a
gene or microorganism that might result in harm—but you
can greatly decrease the probability if you have some
genetic safety mechanisms and if you've done your best to
develop them."
The role of USEPA's research in the development of biotechnology
products for pollution control was discussed briefly by the Panelists. The
general opinion of the Panelists was that USEPA should continue to conduct
the kinds of biotechnology-related research that are not underway in
academia or industry, especially in the areas of basic and scale-up
research, environmental survival/persistence and impact, field testing, and
in health risk assessment methodologies.
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This opinion was best summarized by Dr. MelIon's comment:
"EPA ought not do anything that anybody else is doing.
Resources are limited EPA ... ought to be filling in
the research gap .... It seems to me that there is a gap
... (in) the research phase of R&D, (of) particularly
desirable technologies, and there is also a very large
and agonizing gap in (the) development of risk assessment
methodologies."
Moreover, in Dr. MelIon's opinion, the projects that are underway in
the USEPA biotechnology research program could help to fill several of the
existing research gaps. She suggested that...
"...much of the basic and applied research that has been
presented'is at a stage that you (the USEPA researchers)
could move into the microcosm testing, especially in the
soil degradation systems, without going to the field; and
at that time the experiments should be designed with the
appropriate controls to begin to delineate the
(potential) improvements that (the use of) a genetically
engineered organism could make over conventional or
indigenous organisms.. .No one in industry nor in academia
is going to have any incentive to do the kind of research
that is necessary to assess the ecological effects * of
release of these organisms nor are they going to do the
kind of work that's going to be necessary to develop the
battery of tests that the applicants are going to have to
do to provide EPA (with) information on which it can make
a decision as to whether or not the technology is safe."
It should be pointed out that these kinds of studies are needed for
the development of testing criteria and for demonstrating and comparing the
effectiveness of biotechnology products (engineered and nonengineered
microorganisms) for pollution control.
The relevance of the projects that is underway in the USEPA's
biotechnology research program and the potential for its application to the
protection of pollution control industry's proprietary rights prompted Mr.
Dardas to state that his company
"...will immediately begin working on genetic engineering
in order to give ourselves more protections of all of our
proprietary development....as soon as we can afford to."
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Dr. Omenn summarized the discussion on the role of USEPA's
biotechnology research program in the development of biotechnology products
for pollution control as follows:
"It is clear that there is a role for EPA here, that the
companies have hot and by all counts will not, exploit
genetically engineered modifications until someone else
demonstrates that the organisms are ready, and the
techniques are easy, and the need is there."
As discussed in Chapter V of this document, the need for research, the
lack of risk assessment methodologies and testing criteria, and the
significant costs of research pose technical and economic barriers to
commercialization of biotechnology pollution control products. Moreover,
the continuation of limited expenditures for generic applied research by the
government may widen the gap between basic and applied biotechnology
research, and this may also retard the commercialization of biotechnology
products. Since basic and generic applied research are critical for the
development of this industry, the Panelists felt that USEPA's research is
critical for fostering and facilitating the development of biotechnology
products for pollution control.
The Panel decided against developing a rank order list of research
projects that are best suitable for governmental funding.
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VIII. SUMMARY
Consistent with its mission to protect the environment and human
health, the USEPA is exploring new technologies that may have potential
applications for the safe, effective, and economical removal of hazardous
substances from the environment. In addition to chemical production,
conversion of biomass for energy, and agricultural and pharmaceutical
applications, biotechnology products (either engineered and nonengineered
microorganisms or their cellular products) may have pollution control
applications. Potential technological advantages that may be achieved by
the development of biotechnology pollution control products include the
direct treatment of hazardous substances in waste sites, landfills,
effluents, groundwater; as alternatives and complements to existing waste
treatment methods; and the expansion of the Nation's toxic waste treatment
capabilities.
The commercialization of genetically engineered biotechnology
products for pollution control is slow when compared to the development of
biotechnology products for other markets. To address this issue, the
Offices of Toxic Substances and Policy, Planning, and Evaluation (USEPA)
convened the Workshop on Biotechnology and Pollution Control to identify
and examine factors that influence the development of biotechnology
products for pollution control. The major findings and recommendations of
the expert Panelists who participated in this Workshop are summarized below.
During this Workshop, technical, economic, and regulatory barriers to
the commercialization of biotechnology products were identified. Technical
barriers include field testing issues, the need for field tests and basic,
generic applied, and applied research, and the need for the development of
risk assessment criteria and methodologies. Economic barriers that were
identified include the significant costs associated with research,
development, and commercialization of biotechnology pollution control
products and the industry's costs for indemnification and liability
insurance. The Panelists identified the barriers that are presented by
regulatory policies and reporting and permitting requirements at the
Federal, State, and local levels. Finally, adverse public response, which
is based on the public's concerns and perceptions of the risks presented by
VIII-1
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the applications of biotechnology, was also identified as an existing
barrier.
Field testing is a necessary early step In the commercialization of
biotechnology products for pollution control. Technical barriers to field
testing include the lack of defined site selection criteria, testing and
evaluation standards, and environmental impact and risk assessment
criteria. In addition, standardized methods for containment, monitoring,
emergency response, and risk assessments have not been developed. These
barriers are all associated to some extent with a need for. additional
research. For example, research is needed to define and evaluate the risk
that may be associated with the environmental release of genetically
engineered microorganisms. The results of such research could be utilized
to define criteria for selecting field test sites.
Basic, generic applied, and applied research are needed. The costs
associated with conducting biotechnology research are significant, and this
tends to discourage the performance of relevant research and hinders the
development of methodologies needed to design, monitor, and evaluate field
tests and for assessing risks. Traditionally, basic and generic applied
research have been sponsored by the government, while the research involved
in the commercialization of products has been performed by industry.
Although the government is committed to funding basic research, government
expenditures for generic applied research have been limited. A need for
generic applied research has resulted, and this need for research retards
the development of biotechnology products. Finally, the Panelists felt
that until the efficacy of biotechnology pollution control products has
been demonstrated, the biotechnology industry will probably not invest
large amounts of capital in applied/developmental biotechnology research.
Federal, State, and local regulatory policies pose barriers to field
testing and thereby to the development of commercial genetically engineered
biotechnology products. Permitting and reporting requirements and the
uncertain regulatory climate were identified as additional barriers to the
development of the biotechnology pollution control industry.
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The public has vague concerns about the risks that may be presented
by the use of biotechnology products. The Panelists felt that the public
does not usually perceive a distinction between engineered and
nonengineered microorganisms and that the public does not understand the
scientific basis or applications of biotechnology. These deficiencies pose
a barrier to the public's ability to evaluate the issues raised by and the
risks associated with biotechnology. In addition,- the expert Panel
identified other public concerns. These concerns involve the credibility
and capabilities of industry and regulatory agencies to identify and assess
potential risks presented by biotechnology and how risks and benefits are
balanced in the decision-making process, if the concerns of the public are
not addressed, this can lead to adverse public response that may pose a
barrier to commercialization. The public's response is most likely to be
expressed by the local population near field testing sites.
Finally, members of the biotechnology industry identified concerns
that they perceived as barriers to the development and use of biotechnology
pollution control products. These concerns were for the protection of
their proprietary rights and for the costs of indemnification and liability
insurance for field testing and use. These perceived barriers may lead to
a reluctance on the part of the industry to conduct field tests and pilot,
demonstration, and/or cleanup biotechnology projects. The industry's
concerns, therefore, may pose barriers to the commercialization of
pollution control products.
Several advantages for applying microbiological products to pollution
control were identified by the Panelists. These advantages include the
ability to:
1. Develop strains with enhanced activity in specific
degradative enzymes
2. Develop strains whose functional activities are less
susceptible to environmental conditions;
3. Develop strains capable of withstanding highly toxic
environments;
4. Develop potentially controllable microorganisms;
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5. Develop genetically marked strains that are intended for
deliberate release in the environment (this would
facilitate the monitoring of survival and dispersal as
well as protect proprietary rights); and
6. Develop strains that are safer than naturally occurring
and nonengineered strains.
Although these benefits may be achieved by the use of either
nonengineered or engineered strains of microorganisms, the Panelists felt
that they could be more directly achieved with genetically engineered
microorganisms. In the Panelists' opinion, microbiological approaches to
waste treatment may become more cost effective than conventional methods
once the biotechnology pollution control industry is more fully developed.
During discussions in this Workshop, strategies/incentives to reduce
the various barriers and possible incentives for the commercialization of
biotechnology products for pollution control were identified by the Panel
members.
The recommendations that were made to reduce the barriers and provide
incentives for field testing included:
o Use of existing contaminated sites for field tests. Many.
such sites have been identified and characterized to some
extent with respect to contaminant identity and
concentration and are presently being monitored. Use of
existing sites may facilitate the selection of appropriate
microorganisms, reduce industry's costs, and expedite
field testing;
o Performance of demonstration projects to compare and
evaluate biodegradation by microbiological and
conventional methods. Such studies can help to assess the
"best demonstrated available technology" and demonstrate .
the efficacy of microbiological pollution control
technology;
o Use of nonengineered microorganisms in Initial field
tests, e.g., microorganisms developed for enhanced
production of degradative enzymes. This would demonstrate
the efficacy of microbiological pollution control products
without regard to the concerns that are associated with
genetic engineered microorganisms; and
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o Development of a Federal field testing program under
RCRA/Superfund. This may reduce industry's cost and
expedite field testing, thus promoting the
commercialization of biotechnology pollution control
products.
To reduce technical and economic barriers and to provide economic
support mechanisms and incentives that are directed towards the alleviation
of technological deficiencies, the following Initiatives were suggested:
o Increase the government's funding of generic applied
research, to use government funding to promote applied
research to develop risk assessment methods, and to
continue research underway in the USEPA's biotechnology
research program. These actions may alleviate some of
research needs and address, in part, the costs of such
research;
o Use of Small Business Innovative Research Program funding
to promote and support applied research and
commercialization;
o Use of low-interest government loans to promote and
support developmental research and commercialization;
o Government funding of comparative evaluation laboratory
and field studies to assess the "best demonstrated
available technology" and demonstrate the efficacy of
microbiological pollution control technology; and
o Government supplementing/underwriting or otherwise
partially offsetting the industry's costs for
indemnification and liability insurance.
Recommendations that were made to reduce regulatory barriers and
provide incentives for technology development included:
Guidance from the regulatory agencies suggesting that
waste generators and waste management organizations
consider biotechnology as an alternative to conventional
treatment methods;
Full implementation of the existing Superfund and RCRA
statutes regarding waste management. This may induce more
interest in effective and economical waste management
methodologies by industry;
Use of legislative incentives to promote microbiological
alternatives to conventional waste management methods and
to provide economic disincentives for inadequate waste
management; and
VIII-5
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o Granting of variances in regulatory policies in order to
foster the development of new technologies.
Finally, to address the issue of public perceptions that pose
barriers to the development of biotechnology pollution control
methods, the Panelists suggested that:
o Efforts be undertaken by the Agency and industry to build
and maintain their credibility with the public;
o Cooperative efforts be made to educate, inform, and
involve the public, the academic, scientific, and
engineering communities, and regulatory, agencies
personnel with respect to the scientific basis of and
applications for biotechnology, i.e., developing a Center
for Environmental Biotechnology; and
o Field tests be used by the Agency to educate, involve, and
inform the public about the potential benefits of
biotechnology products.
In the opinion of the expert Panelists, the implementation of these
suggestions may overcome existing barriers and/or act as incentives for the
development and commercialization of biotechnology products for pollution
control.
Dr. Omenn's summary of the major findings of this Workshop is provided
in Appendix A.
Vlll-6
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APPENDIX A
DR. OMMEN'S REPORT ON THE WORKSHOP
A-l
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university of Washington
Seattle. Washington 98195
school of public health and community medicine
March 25, 1986
office of the dean, sc-30
(206)543-1144
The Honorable Lee M. Thomas
Administrator
U.S. Environmental Protection
Agency
401 M Street, S.W.
Washington, D.C. 20460
Dear Lee:
1 had the pleasure of chairing EPA's Workshop on Biotechnology and
Pollution Control this past week (20-21 March, 1986, in Bethesda). EPA staff,
led r>/ Jodi Bakst, prepared very well for the meeting and gathered a strong
pc?.nel. There was a good group of obsecvers, including a contingent from EPA.
And Don Clay offered the Panel a helpf.;! informal question and answer session
during the first evening.
Jodi Bakst, Ron Evans, and other IvIPA staff will draft a report from the
Workshop. In the meantime, however, 1 thought it might be useful to you and
such colleagues as Jack Moore, Henry Ix>ngest, Marcia Williams, Don Clay, and
Jim Barnes to have a brief report directly from me.
The following are our main conclusions:
1. The Nation needs alternative technologies to complement present "burn or
bury" approaches to chemical pollutants. There are many high priority pol-
lutant targets in landfills, hazardous waste- sites, industrial effluents,
groundwater, and other media for which microbial techniques could be, or
already are, helpful. The approach must respect particular properties of
specific sites.
2. within the microbiological treatment arena, improvements are needed, some
of which might draw upon genetic engineering methods. We should be alert to
the risk that reporting requirements or regulatory approvals beyond what are
definitely necessary to build public confidence may inhibit desirable techni-
cal developments. At present, none of the industry participants in our
Workshop plans to introduce improvements with genetic engineering techniques,
because of the likelihood of overwhelming regulatory procedures tied to the
technique, rather than the product or any defined risk.
Emblem: "Soul Catcher"... a Northwest Coast Indian implement used by shamans or spiritual healers to ward off spirits that brought physical
or mental illness. These instruments were usually carved from the long bones of large animals and handed down from generation to generation.
A-2
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The Honorable Lee M. Thomas
March 25, 1986
Page 2
3. EPA's regulatory scheme and stimulation of innovation should encourage
stepwise testing, first in laboratory scale experiments, including- various
kinds of microcosms, and then in well-selected field sites. Our Panel sug-
gested an array of criteria that should be applied to the assessment of pro-
posed field tests. Landfills received special attention, with advantages and
disadvantages clearly outlined.
4. Federally-designated field sites are considered essential. Innovators
need assistance in matching microorganisms with potential for pollution con-
trol to well-contained and monitored sites where the results may be most
credible.
5. Cooperation between EPA and developers of the technology and the public at
large should be fostered in a variety of aspects:
o Balancing regulator/ objectives with pollution control objectives.
o Building the Research and Development agenda and identifying sites for
field tests.
o Identifying organisms and test- sites that would be the. equivalent of
FDA's "generally regarded as safe (GRAS)" and identifying chemicals
that rank high on RCRA, CERCLA, and other EPA media-specific lists of
problem pollutants.
o Communicating what is known and what is sought to be learned to the
public, especially the interested public in the local areas where any
test or field application would be undertaken.
o Providing incentives via requirements to evaluate microbiological
approaches to clean up site«? or prevent contamination of media.
Superfund RI/FS protocols should require detailed evaluation of micro-
biological approaches, whether assisted by genetically-engineered
modifications or not. Too often potentially attractive alternative
technologies are dismissed out of hand by contractors and consultants
who simply are not familiar with the possibilities. Likewise, EPA
regional reviewers of proposed technological options must be informed
about the prospects and encouraged to look out for sites where such
applictions might prove attractive.
A-3
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The Honorable Lee M. Thomas
March 25, 1986
Page 3
I hope that this brief summary whets your appetite for the full report and
that some initiatives may be considered in the interim. I would be pleased to
meet with you or your colleagues if that would be helpful. Copies of this
letter will be sent to the individuals named below.
Best wishes.
Sincerely yours,
Gilbert S. Omenn, M.D., Ph.D.
Dean, School of Public Health
and Community Medicine
GSO:lc
cc: James Sarnes
John Moore
Henry Longest
Don Clay
Marcia Williams
Tbdi Bakst
'Ron Evans
A-4
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APPENDIX B
WORKSHOP BACKGROUND PAPER
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EPA WORKSHOP
Oil
BIOTECHNOLOGY AMD POLLUTION CONTROL
Hire* 20, 21, 1986
The Office of Toxic Substances
The Office of Policy, Planning,.and Evaluation
B-2.
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BACKGROUND PAPER TO THE WORKSHOP
The Office of Toxic Substances (OTS), in cooperation with the Office of
Policy, Planning, and Evaluation, has designed a workshop entitled Bio-
technology and Pollution Control to examine specific regulatory, commer-
cial, and technical barriers to the commercialization of biotechnology pol-
lution control products. OTS, which is responsible for regulating various
types of genetically engineered and non-engineered organisms,.including
those for pollution control, plans to use the workshop to obtain necessary
information to aid the Agency in implementing its regulations. Further-
more, the workshop is to be a forum where industry and academic experts
explore existing and potential incentives to promote product development.
The Office of Toxic Substances will soon be publishing its policy statement
on biotechnology as part of an overall Federal strategy. (We will be
sending a copy of the policy statement when it is published.) One of the
major obstacles to effectively Implementing the Agency's policy is the lack
of information on how to evaluate the field testing of pollution control
organisms. Field testing Is usually a necessary and critical step towards
commercializing pollution control products. Field testing Is also the
first point in the commercialization process where, depending on the tech-
nique used and the type and amount of the organism to be field tested, the
Agency may have to evaluate and potentially regulate the field testing of
the pollution control organism. (As such, the Agency wishes to gather
information on criteria for selecting field testing sites, containment
techniques, monitoring and emergency response methods and incentives for
field testing.
OTS nas designed the second day of the workshop to focus more broadly on
the barriers to the commercialization of biotechnology pollution control
products. The Agency recognizes that there are regulatory, commercial, and
technical factors inhibiting the growth of this area of the biotechnology
industry. As such, the goals of this section are: for OTS to gather addi-
tional information to aid the regulatory decisionmaking process; for the
B-3
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Agency, Industry, and academic experts to discuss how they can work
together to develop better data and to expedite reviews; and for industry
and academic experts to explore existing and potential incentives to
promote product development.
Since the mid-1970's there have been varying degrees .of opposition to tne
development of biotechnology. Recently, a major ongoing dispute is witn
the release of genetically engineered organisms into the environment.
Because biotechnology pollution control organisms will, in many cases, be
released into the environment, public opposition is likely to arise. To
help ensure there is an ongoing exchange of information, the latter part: of
the second day will be spent discussing the most effective ways industry,
academia, and the Agency can best inform the public of the risks and bene-
fits associated with this technology for pollution control.
The specific issues to be discussed can be found in the section titled
Questions for the Expert Panel.
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QUESTIONS FOR THE EXPERT PANEL
Purpose: To compare and devise strategies and incentives for field testing
genetically engineered and non-engineered pollution control
organisms, and to discuss how to evaluate and promote the product
development of these organisms.
Field Testing
1. What criteria have industry and academia used in the past to select:
field testing sites for non-engineered organisms? What criteria
Mill be used in the future to select field testing sites for both
genetically engineered and non-engineered organisms? If differ-
ences exist, why have they come about?
2. Some experts have suggested that existing disposal sites, land-
fills, etc., be designated for field testing genetically engineered
and non-engineered pollution control organisms. What would be the
advantages and disadvantages?
3. What does Industry and academia consider to be characteristics of
containment with respect to the field testing of engineered and
non-engineered pollution control organisms?
Could greenhouses, sewage treatment facilities, lined landfills,
and land oil wells be considered:
a) contained environments, or
b) field testing sites?
Why or why not?
B-5
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4. Is it possible to develop a "risk gradient" of containment levels?
What factors must be considered? Can industry characterize a "low
risk" testing site? Why or why not?
5. What monitoring and emergency response methods are presently used
for unexpected spills of non-engineered pollution control
organisms? What monitoring and emergency response methods do
industry and academia plan or foresee using with the field testiny
of genetically engineered pollution control organisms?
6. What would give industry an incentive to field test?
Product Development
1. How can the benefits of genetically engineered pollution control
organisms be evaluated? Are the benefits significantly different
from those associated with current pollution control technologies?
If yes, in what ways are they different?
2. How can EPA, Industry,, and academia work together to establish data
on risk and to expedite reviews? For example, can Incentives be
provided to encourage Industry to notify the EPA of research and
development progress for genetically engineered products in advance
of PMN submissions? Similarly, can Industry suggest categories of
products they consider to Inherently present a low risk? What
other Ideas could be developed?
3. What Innovative financing techniques exist to aid in the develop-
ment of genetically engineered organisms for pollution control?
For example, what is venture capital's role? How can the SBIR
(Small Business Innovation Research) program be used more effec-
tively? Are collaborative research ventures within industry a
viable option? What other avenues are available?
B-6
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4. What kinds of research and development should the EPA and Industry
undertake which would be the most useful for pollution control pur-
poses?
5. What are the key technical barriers to developing pollution control
organisms?
Public Perceptions
1. What are the most effective ways industry and the Agency can best
inform the public of the risks and benefits associated with usiny
genetically engineered organisms for pollution control?
B-7
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APPENDIX C
WORKSHOP PROGRAM
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UNITED STATES ENVIRONMENTAL PROTECTION AGENCY
WASHINGTON. D.C. 20460
EPA WORKSHOP
ON
BIOTECHNOLOGY AND POLLUTION CONTROL
MARCH 20, 21, 1986
The Office of Toxic Substances
The Office of Policy, Planning, and Evaluation
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ANNOTATED AGENDA
BIOTECHNOLOGY AND POLLUTION CONTROL EXPERT GROUP
MARCH 20 AND 21
Thursday, March 20
8:30 a.m. Coffee
9:00 a.m. Welcome: Jodi Bakst
Opening remarks
Introduction of Dr. Gilbert Omenn as Chairperson and
Jodi Bakst as co-chair.
9:05 a.m. Introductory remarks: Dr. Gilbert Oraenn
Participants introduce themselves
Explain agenda - There will be approximately 55
minutes for each question. The workshop
chairperson, at the close of each question, will
summarize the major points discussed. The
proceedings from the workshop will later be
summarized into a formal paper and distributed to
the participants and observers. An effort will also
be made to make the paper available to the public.
Role of participants - The participants were not
asked to prepare formal papers, but rather succinct
answers for a practical discussion of the major
issues associated with each question. '
Role of observers - Observers will be recognized by
the chair for 30 minutes at the end of each day to
make comments or ask questions for clarification.
9:15 a.m. Status of policy statement - Anne Hollander
Update of the product development of pollution
control organisms - Dr. Thomas Peyton
Questions from experts: Clarification of technical
issues
C-3
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9:35 a.m. Criteria to select field testing sites
What criteria have industry and acadesnia used in the
past to select field testing sites for.non-
engineered organisms? What criteria will be used in
the future to select field testing sites for both
genetically engineered and non-engineered
organisms? If differences exist, why have they come
about?
OTS" is looking to understand what is considered in
selecting field testing sites. Specifically, are technical
factors the overwhelming criteria? Also, are changes in the
selection criteria expected just because a microorganism is
genetically engineered?
The following types of characteristics are what we are
looking for:
0 Physical — geographic characteristics
0 Technical -- limited exposure, single contaminant
0 Commercial -- cost effectiveness
0 Political/Social -- interactions with constituency
10:25 a.m. Coffee
10:40 a.m. Osing existing landfills etc.
Some experts have suggested that existing disposal
sites, landfills, etc., be designated for field
testing genetically engineered and non-engineered
pollution control organisms. What would be the
advantages and disadvantages?
This is clearly a topic many people will have strong
feelings for. OTS wants to hear a discussion of the various
viewpoints. A few of the disadvantages are that whil'e the
potential exists to reduce various public health hazards, there
is some chance that, in the case of an error or accident/ the
public health problem could be made worse off. Political and
social opposition may also exist due to the fear that these
health problems could be compounded. Other examples may be:
0 Legal concerns — e.g. liability
0 Jurisdictional problems —.e.g. State vs. Federal
0 Financial
0 Technical
04
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11:35 a.m. Characteristics of containment
What do industry and academia consider to be
characteristics of containment with respect to the
field testing engineered and non-engineered
pollution control organisms? Could greenhouses,
sewage treatment facilities, lined landfills, and
land oil wells be considered contained environments
or field testing sites? Why or why not?
OTS has a few goals with this question. Overall, we are
looking for a definition of containment (release, minimal
release, or that which is technically feasible). Is there a
consensus on what is a "contained" environment?. What "questions
should be considered in developing a definition of containment
with respect to field testing genetically engineered and non-
engineered pollution control organisms?
We are looking for the following type of characteristics:
0 Physical — enclosed vs. not enclosed (what does
enclosed mean?)
0 Technical — a landfill having a plastic liner
0 Financial -- cost effectiveness
0 Political — are the options socially viable
0 Differences in treating engineered and non-
engineered organisms
12:30 p.m. Lunch
1:30 p.m. Risk gradient of containment levels
Is it possible to develop a "risk gradient" of
containment levels? What factors must be
considered? Can industry characterize a "low risk"
testing site? Why or why not?
It has been argued that field testing genetically
engineered organisms would not present significant concerns of
damage to human health and the environment. OTS would like
information on the factors which need to be considered in
determining if. there are "low risk" field testing sites. The
ultimate challenge would be to get the group to characterize a
"low risk" testing site, and provide a rationale as to why it
would be considered "low risk". We would also like the experts
to rank order their choices. Factors which may be considered
are:
0 Physical — are liners better than clay caps?
0 Financial — cost effectiveness of the
possibilities
0 Technical — water releases, worker exposure, and
the organisms used
c-5
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2:25 p.m. . Monitoring and emergency response
What monitoring and emergency response methods are
presently used for unexpected spills of non-
engineered pollution control organisms? what
monitoring and emergency response methods do
industry and academia plan or forsee using with the
field testing of genetically engineered pollution
control organisms?
How does industry and academia currently monitor their
experiments and/or commercial applications of non-engineered
organisms? What methods are used to determine microbial •
movement? Regarding existing field tests, if a person has
concerns about microorganisms moving beyond the test site, what
measures are taken to prevent migration? OTS also wants
information on how, if at all, these techniques would change in
the case of genetically engineered organisms. -This will
hopefully aid the staff in understanding what control measures
are currently used and what may be desirable for work with
genetically engineered organisms.
3:20 p.m. Break
3:35 p.m. Incentives to field test
What would give industry and academia an incentive
to field test?
0 Free for all - brainstorm
The key here is to develop ideas that could provide
incentives for research and commercialization of pollution
control organisms. While there are numerous reasons (financial,
technical/ etc) for areas other than pollution control to be the
focus of research, OTS would like to use this time to focus on
those issues (if any) that are unique to field testing. For
example, would Federally designated test sites provide an
incentive to field test? Or is industry leaning more towards
wanting incentives such as reduced reporting fees, a tax break or
less expensive insurance policies? If no unique issues present
themselves it would still be useful to discuss some of the
broader issues.
4:05 p.m. Questions and answers
4:40 p.m. Objectives for tommorrow's session
4:45 p.m. Adjourn until tomorrow
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Friday, March 21
8:30 a.m. Coffee
9:00 a.m. Goals for rest of meeting
9:10 a.m. Benefits
How can the benefits of genetically engineered
pollution control organisms be evaluated? Are the
benefits significantly different from those
associated with current pollution control
technologies? If yes, in what ways are they
different?
TSCA is an unreasonable risk statute. To make this
unreasonable risk determination, OTS must consider the benefits
associated with chemical substances, which includes genetically
engineered and non-engineered organisms. OTS now uses a
relatively simple method of benefits analysis (comparing price,
physical-chemical properties and use conditions versus chemicals
already used for the same purpose) for evaluation of new
chemicals. OTS wants to learn if there are additional benefits
from this technology which should be incorporated into the
Agency's benefits analysis. Specifically, some benefits may be:
Cost effectiveness
Technical e.g. increased rate of degradation
Scientific - research/innovation
Uniqueness - nothing else will do the job
Toxicity
10:05 a.m. Coffee
10:20 a.m. Public Perceptions
Introduce Dr. Margaret Mellon from the 'Environmental
Law Institute
What are the most effective ways industry and the
Agency can best inform the public of the risks and
benefits associated with using genetically
engineered organisms for pollution control?
One of the key issues in getting genetically engineered
pollution control organisms onto the market will be public
perceptions. OTS wishes to use this session to develop ideas on
cooperative methods of informing the public of the risks and
benefits associated with genetically engineered organisms.
The key is to develop methods which present the information in
the most unbiased manner. Possible ways the Agency can better
inform the public are: better use of the press, documentaries,
and allowing public interest groups,. industry and academia to
more frequently comment on Agency policy via Science Advisory
c-7
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Bjroa'd meetings, congressional hearings or Dy ceveloping a'new
form of public meeting.
11:15 a.m. Establish data and expedite reviews
How can EPA, industry, and academia work together co
establish data on risk ana to expedite reviews? For
example, can incentives be provided to encourage
industry to notify the EPA of researcn ana
development progress for genetically engineerea
products in advance of PMN submissions? Similarly,
can industry suggest categories of products tney
consider to inherently present a low risk? What
other ideas could be developed?
ODviously, the easiest way to get genetically engineerea
organisms for pollution control to market in a safe, efficient
manner is for EPA, industry and academia to work together. OTS
is looking for information on incentives to get these groups
working together so regulatory issues can be identified early in
the development of potential projects. For example, perhaps the
EPA could aid in finding an appropriate testing site, or have
industry forward its data to the Agency in advance of submission
to lengthen the review period.
Similarily, TSCA presents the opportunity for exempting or
reducing reporting requirements for categories of chemical
substances under section 5(h)(4). However, a finding of "will
not present an unresonable risk" must be made by EPA before this
category can be exempt. OTS is looking for information on
possible candidate categories. The most important information
will be the justifications for why a category would fit the
unreasonable risk standard. Categories of products may oe:
attenuated species
pathogen/non-pathogeh
mobile/non-mobile
indigenous/non-indigenous
plasmid encoded
enzymes
OTS is also interested in hearing it products should be, it
at all, differentiated by the technique used?
C-8
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11:45 a.m. Innovative financing techniques
What innovative financing techniques exist to aid in
the development of genetically engineered organisms
for pollution control? For example, what is venture
capital's role? How can the 5BIR (Small Business
Innovative Research) program be used more
effectively? Are collaborative research ventures
within industry a viable option? What other avenues
are available?
For this session, OTS is interested in getting information
on where the financing for genetically engineered pollution
control organisms is coming from and where it will come from in
the future. OTS is hoping to gain an understanding of some of
the dynamics of the industry's financial segment.
0 Brainstorm on innovative financing techniques. We
want industry and acaderaia to exchange information
among themselves. Specifically, Dr. Barry Katz of
MYCOsearch has received a Phase I and II S8IR from
NSF, and Dr. Middleton of Koppers has practical
experience dealing with venture capital.
12:10 p.m. Lunch
1:15 p.m. Introduce Dr. Al Bourquin from Gulf Breeze
Laboratory, and
Dr. Cuskie; Dr. Peter Chapman; Dr. P. Hap Pritchard;
Dr. Tamar Barkay; Dr. Fred Genthner; Dr. Michael
Nelson; Dr. Ellen O'Neil; Dr. Barbara Sharak-Genthner
These 9 Gulf Breeze scientists are here to present;
SPA'S RESEARCH ON THE APPLICATION OF BIOTECHNOLOGY
TO WASTE DEGRADATION
2:00 p.m. Research and Development (Also led by Dr. Bourquin)
What kinds of research and development should the
EPA and industry undertake which would be the most
useful for pollution control purposes?.
EMPHASIZE FOR POLLUTION CONTROL ORGANISMS
In general, R & D has been discussed to death by
government, industry and academia. However, this session is
designed to focus on R & D for pollution control purposes only.
The goal of this session is to develop ideas on both basic and
applied research projects which could enhance the study of
genetically engineered organisms for pollution control. OTS
would like to come away with a rank ordered list of projects
which are best suited to be funded by a government agency.
09
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2:45 p.m. Break
3:00 p.m. Technical Barriers
What are the key technics! barriers to developing
pollution control organisms?
0 Free for all
OTS is looking to gather information on some of the rate
determining steps for the introduction of genetically engineered
pollution control organisms. While financial and regulatory
considerations play a key role, OTS is looking for a discussion
of the technical factors keeping this technology in its infant
stage. For example, is lack of knowledge of the basic biology of
likely-candidates crucial to the development of the industry? Is
the fact that most lagoons, dumps etc., contain multiple
chemicals of different natures a crucial aspect? What could be'
done to address these issues?
3:45 p.m. .Questions and answers
4:20 p.m. Concluding statements
Meeting Adjourned
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APPENDIX D
ABBREVIATED BIOGRAPHIES OF
EXPERT PANEL MEMBERS
D-l
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Dr. Douglas Caldwell
Dr. Caldwell received his Ph.D. in Microbiology from Michigan State
University in 1974. He was a research associate at the University of Wis-
consin from 1974 to 1975, an Assistant Professor of Biology at the Uni-
versity of New Mexico from 1975 to 1982, and is presently an Associate
Professor in the Department of Applied Microbiology at the University of
Saskatchewan, where he teaches undergraduate and graduate courses in
Microbiology and Microbial Ecology. He has published numerous papers and
reviewed articles which concern the ecology of sulfur bacteria, discovery of
the genus Thermothix, derivation of microbial colonization kinetics,
computer-enhanced microscopy, and the study of microbial growth kinetics
with the hydrodynamic boundary layers of surface microenvironments. . He has
evaluated local fecal coliform standards as a consultant to the State of New
Mexico, and participated in the. development of microbiological criteria for
the disposal of nuclear waste as a consultant to Los Alamos National
Laboratories.
Dr. Ananda Chakrabarty
Dr. Chakrabarty received his Ph.D. in Biochemistry from the University
of Calcutta in 1965. He has been a Professor of Microbiology at the
University of Illinois since 1979. His major research interests are
Pseudomonas infection in Cystic Fibrosis; plasmids and biodegradation of
synthetic toxic chemicals; and hydrocarbon microbiology and microbial oil
recovery. In 1980, Dr. Chakrabarty received the first patent for a living
microorganism designed to degrade petroleum fractions. He received the
Selected Industrial Research Scientist Award in 1975, and the Inventor of
the Year Award in 1982. Dr. Chakrabarty participated in the Asllomar and La
Jolla Recombinant DNA Conferences, is a consultant to the United Nations
Committee on the Application of Genetic Engineering in Developing Nations,
and is a member of both the NIH Study Section on Microbial Genetics, and the
Advisory Committee of the International Center for Genetic Engineering and
Biotechnology (Trieste, Italy and New Delhi, India).
Dr. Peter J. Chapman
Dr. Peter J. Chapman, an EPA-Distinguished Visiting Scientist
(1985-1987), is a Professor of Microbiology and Biochemistry with the
University of Minnesota, St. Paul. He received his Ph.D. in 1961 from the
University of Leeds. He was the recipient of a Fulbright scholarship and
has authored or co-authored over 70 scientific publications on microbial
degradation of alicylic and aromatic compounds. Dr. Chapman's research
interests include the study of the biochemical mechanisms of biodegradation
of chlorinated compounds and understanding the molecular basis of
biodegradation mechanisms. He is currently investigating co-metabolic
processes in work that bridges microbial ecology and microbial physiology,
using multi-substrate systems under controlled conditions.
Thomas Dardas. Esquire
Mr. Dardas is the President and Chief Executive Officer of Detox
Industries, Inc., a Texas Corporation. Detox Industries, Inc. is a service
D-2
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company which is active in biological degradation of hazardous and toxic
wastes. At this time. Detox Industries is the only company in the U.S. with
regional EPA approval of its PCB biodegradation process which can be applied
in situ to any matrix. Mr. Dardas received his J.D. degree from Suffolk
University Law School in 1970, his M.S. degree from the University of
Pittsburgh in 1971 and his B.S. from Lowell Technological Institute in
1967. Mr. Oardas is currently a member of the American Bar Association,
Texas Bar Association and Massachusetts Bar Association, and is licensed to
practice law in both Texas and Massachusetts.
Dr. Alan Goldhammer
Dr. Goldhammer is the Director of Regulatory Affairs at Industrial
Biotechnology Association. After receiving a.B.A'. in Chemistry from the
University of California at Santa Barbara and his Ph.D. in Biochemistry from
Indiana University, he was a Postdoctoral fellow at Cornell University. He
worked at the National Institute of Health for five years before going to
work for the Industrial Biotechnology Association.
Dr. Barry Xatz
Dr. Katz has received his Ph.D. and M.S., in Botany from the Univer-
sity of North Carolina in 1979 and 1973, respectively. His predominant
interest is .focused on understanding fungus habitats and the isolation of
persistent vegetative fungi from decomposing plant matter contaminated with
bacteria and the spores of common fungi. In 1979, Dr. Katz founded
MYCOsearch where he collects rare and potentially useful fungi from plant
communities worldwide. He has traveled to or received material from Brazil,
Costa Rica, Thailand, India and the U.S. His research collecting program is
currently plans to study plant communities in Western Africa, China, Mexico
and Chile. MYCOsearch's collection, numbering approximately 15,000
isolates, is offered to natural product screening programs for commercial
applications including hazardous waste detoxification. Recently, MYCOsearch
was awarded a Phase II SBIR grant from NSF to screen for PCB, DDT and
cellulose degrading fungi. MYCOsearch is also investigating the microbial
flora of human-altered and hazardous waste sites. Dr. Katz has authored
over 15 publications, and often presents symposiums to corporations and
academic institutions around the world.
Dr. Ann Kopecky
Dr. Kopecky received her Ph.D. in Microbiology/Biochemistry from the
University of Texas Medical Branch, Galveston, Texas, where she also per-
formed her Postdoctoral research in Biochemistry and Genetic Engineering.
In 1981 she became a Senior Research Microbiologist for Sybron Chemicals,
Inc., Biochemical Division in Salem, Virginia. Sybron Chemicals is a major
manufacturer of adapted bacteria for treatment of industrial and municipal
waste. Sybron owns patents on four of their bacterial systems, and has been
supplying bacterial cultures for wastewater treatment for over forty years.
Dr. Kopecky is specifically involved with new product development,
production quality management, and application technical services.
D-3
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Dr. John Loper
Dr. Loper received his Ph.D. in Biology/Genetics from John Hopkins
University in 1960. He received his M.S. degree in Biology/Cytology from
Emory University in 1953, and his B.A. in Biology from Western Maryland
College in 1952. Dr. Loper spent most of his career teaching Microbiology.
Since 1974 he has been a Professor of Microbiology and Molecular Genetics at
the University of Cincinnati College of Medicine. His research interests
are environmental mutagenesis, isolation and identification of mutagens in
drinking water, and the use of microbial and molecular genetics in the
control of chemical mutagens and carcinogens in the environment. The EPA
has funded his current research on gene engineering of yeasts for the
degradation of hazardous waste, specifically, cytochromes P-450 genes in
yeasts and fungi. Dr. Loper is a member of numerous associations and
committees, and he has authored over 35 publications.
Dr. Margaret Mellon
Dr. Mellon brings both a scientific (Ph.D., Biology, University of
Virginia; M.S. and B.S., Biology, Purdue) and a legal (J.D., University of
Virginia Law School) background into her current role as Program Director of
the Environmental Law Institute. Her present efforts are directed at
research and public education in toxic substances control and related
areas. She previously conducted research in Molecular Virology. She has
been admitted to the Bar of the District of Columbia and the Bar of the
Court of International Trade.
Dr. Andrew Middleton
Dr. Middleton received his Ph.D. in Environmental Engineering from
Cornell University in 1974. He received his M.S. in Sanitary Engineering in
1971 and his B.S. in Civil Engineering in 1970 from Virginia Polytechnic
Institute. He worked as a Civil Engineer from 1974 - 1978. Since 1978 he
has held various positions with Koppers Company, specifically, Senior
Research Engineer in the Research Department, Manager of the Water Quality
Engineering Section of the Environmental Resources & Occupational Health
Department, and Vice President & General Manager of the Environmental
Resources Section. Since 1984 he has been Vice President & General Manager
of the Pioneering Technologies and Environmental Resources Section. His
overall responsibility is to manage Koppers Environmental Affairs Section.
Included in Koppers Operations are over 50 chemical & allied product plants
including 17 wood preserving plants, as well as other facilities producing
metal products and road materials. Dr. Middleton has authored over 20
publications.
Dr. Gilbert Omenn
Dr. Omenn received his Ph.D. in Genetics from the university of
Washington in 1972, his M.D. from Harvard in 1965 and his A.B. from
Princeton in 1961. His internship and residency in Internal Medicine were
at the Massachusetts General Hospital in Boston. .He was research fellow at
the Woods Hole Oceanographic Institution, the Brookhaven National
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Laboratory, the Veizmann Institute of Science in Israel, and the National
Institutes of Health in Bethesda, Maryland. He was a White House Fellow at
the Atomic Energy Commission in 1973-1974. Dr. Omenn also served as a
Deputy to Frank Press, President carter's Science and Technology Adviser and
Director of White House Office of Science and Technology Policy, and then as
Associate Director for Human Resources in the Office of Management and
Budget. Dr. Omenn, in 1982, became Professor of Medicine and Environmental
Health and Dean of the School of Public Health and Community Medicine at the
University of Washington, Seattle. His research and public policy interests
lie in areas of genetic predisposition to environmental and occupational
health hazards, chemoprevention of cancers, the improvement of science-based
risk analysis, and applications of genetic engineering.
Dr. Thomas Peyton
Dr. Peyton formed AmTech Consultants in 1981 in Vienna, Virginia as a
private consulting practice in the fields of biotechnology and the
environment. Through AmTech he provides research and consultative services
to government and industry in areas ranging from techno-economic analyses of
new; product developments to field operations and services in environmental
control. Dr. Peyton received his Ph.D. in Bionucleonics from Purdue
University's School of Pharmacy and Pharmacal Sciences in 1974 and majored
in Molecular Biology during his undergraduate studies at Purdue. His
experience includes the areas of environmental and radiological health,
environmental biotechnology research and applications, and risk assessment!
He is the author of over 60 publications and reports, including the
biotechnology section of the 1983 US Congress, Office of Technology
Assessment report on "Technologies and Management Strategies for Hazardous
Waste Control," and the 1985 book "Hazardous Waste Treatment: Impact of
Biotechnology." Dr. Peyton has published several review articles in
biotechnology journals on biotechnology and environmental protection,
including economic, technical, and regulatory aspects.
Dr. George Pierce
Dr. Pierce received his Ph.D. in Microbiology in 1976 and his B.S. in
Biology in 1969 from Rensselaer Polytechnic Institute. As a Postdoctoral
Associate at Rensselaer, Dr. Pierce applied his knowledge of petroleum
biodegradation to the degradation of pesticides and related toxic compounds
in aqueous environments. Since 1977 he has worked as the Task Leader of the
Microbial Genetic Engineering Program at Battelle Laboratory in Columbus,
Ohio. His work began with the isolation and characterization of a plasmid
to degrade halo-organic compounds. Genetic manipulative technologies are
also being used to stabilize and optimize 2,4-D degradative ability.
Battelle labs also is working to develop improved microbial strains to
degrade chlorinated hydrocarbons. Additionally, his experience ranges from
developing and/or researching: alcohol fermentation; cellular-immobilization
and entrapment; the use of microorganisms to degrade petroleum and DDT and
its analogs; and developing cloning vectors and host systems suitable for
work with genes from environmental strains of Pseudomonas.
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Dr. Gary Savler
Gary S. Sayler, received a B.S. in Bacteriology from North Dakota
State University, and a Ph.D., 1974, in Microbial Ecology from the
Department of Bacteriology and Biochemistry at the University of Idaho,
which was followed by Postdoctoral research in Marine Microbiology at the
University of Maryland. He has been conducting research on bacterial
biodegradatlon of PBC and related contaminants since 1976 at the University
of Tennessee, Knoxville. There he is presently Professor of Microbiology
and Ecology with additional faculty appointments in the Environmental
Toxicology and Biotechnology Graduate Programs. With EPA funding and an NIH
Research Career Development Award his work led to the discovery of a novel
PCB degrading plasmid. His laboratory is active in investigating microbial
community response to contaminant stress, and the evaluation and role of
catabolic plasmids in accommodating environmental contamination, currently,
his laboratory is developing and using molecular approaches, such as gene
probe technology and DMA reassociation kinetics, to study the maintenance
and impact of genetically engineered microcosms in the environment. He is
an editorial board member for Appl. Environ. Microbial., J. Microbial.
Methods, and Indust. Microbial. and serves on the Applied and Environmental
Microbiology Subcommittee of the ASM Public and Scientific Affairs Board.
He has authored over 50 papers, and has directed approximately 2 million
dollars in corporate and Federally-sponsored research.
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APPENDIX E
LIST OP WORKSHOP OBSERVERS
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WORKSHOP OBSERVERS
JODI BAKST, EPA - WORKSHOP COORDINATOR
STAN ABRAMSON, OGC
DR. JANET ANDERSON, OPP
DR. ANGELA AULETTA, OTS
DR. TAMAR BARKAY, ERL - Gulf Breeze
DAVID BASSART, OSW
JUDY BELLIN, OSW
JAMES BERLOW, OSW
DR. AL W. BOURQUIN, ERL - Gulf Breeze
"JOHN BURCKLE, ERL - Cincinnati
DR. CAMELE, OPPE
JOSEPH P. CHU, Ph.D., P.E.
Assistant Director, Plant Environment
Environmental Activities Staff
General Motors Corporation
General Motors Technical Center
30400 Mound Road
Warren, Michigan 48090-9015
DR. NANCY CHIU, EPA
DR. CORNETT, Tyndall Air Force Base
DR. STEPHEN CUSKEY, ERL - Gulf Breeze
KATE DEVINE, OTS
RON EVANS, OTS
JURGEN H. EXNER, Ph.D.
International Technologies
Technical Director
Regional Office
1815 Arnold Drive
Martinez, California 94553
DR. ERNEST FALKE, OTS
CAROL FARRIS, OTS
DR. FLANAGAN, NSF, Ecology Program
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WORKSHOP OBSERVERS (Continued)
BOB FREDERICK, OTS
ELAINE FRIEBELLE, Versar, Inc.
DR. FRED GENTHNER, ERL - Gulf Breeze
DR. BARBARA SHARAK-GENTHNER, ERL - Gulf Breeze
VAL GIDDINGS, OTA
STEVEN HASSUR, OTS
ANNE HOLLANDER, OTS
FRANCINE JACOFF, OStf
DR. DAPHNE KAMELY, ORD
JAN KURTZ, Dynaraac
MORRIS LEVIN, ORD
ELLIOT LOMNITZ, OSW
LARRY LONGANECKER, OTS
STEVE LYONS, Biogen
GREG MACEK, OTS
DOUGLAS McCORMICK, Bio/Technology Magazine
JOB MONTGOMERY, ORD
DR. MICHAEL NELSON, ERL - Gulf Breeze
ROBERT NICHOLAS, Blum, Nash, and Railsbach
DR. ELLEN O'NBIL, ERL - Gulf Breeze
DR. HAP PRITCHARD, ERL - Gulf Breeze
JULIA SCHWARTZ, Versar, inc.
DR. MARK SEGAL, OTS
DR. P. R. SFERRA, ERL - Cincinnati
MICHAEL SHAPIRO, OTS
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WORKSHOP OBSERVERS (Continued)
JOHN STERLING, Genetic Engineering News
ART STERN, OTS
GREG THIES, OPPB
AL VENOSA, ERL - Cincinnati
LAJUANA VILCHER, OA
THOMAS WILSON, Department of State
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