United States
                    Environmental Protection
                    Agency
                              v* ^ '^
Industrial Environmental Research   - ," -c*7 '
Laboratory
Cincinnati OH 45268
                    Research and Development
EPA-600/S2-84-037  Sept. 1984
&ERA          Project Summary
                    Genetic Engineering and the
                    Development of  New Pollution
                    Control  Technologies

                    James B. Johnston and Susan G. Robinson
                      This report relates genetic engineer-
                    ing to biological waste treatment, so
                    that opportunities for its improvement
                    can be identified and evaluated. It
                    compares the present (mid-1983) state
                    of development of gene manipulation
                    and natural limits to biodegradation.
                      It identifies a number  of research
                    topics that are likely to contribute to
                    new pollution treatment  techniques.
                    These topics include the basic mechan-
                    isms underlying microbial co-metabo-
                    lism and oligotrophy; molecular genet-
                    ics in filamentous fungi,  in strict an-
                    aerobes and in archaebacteria; directed
                    evolution of enzymes and metabolic
                    pathways; and studies to advance under-
                    standing of dehalogenations by  mi-
                    crobes.
                      This Project Summary was developed
                    by EPA's Industrial Environmental Re-
                    search Laboratory, Cincinnati, OH. to
                    announce key findings of  the research
                    project  that is  fully documented in a
                    separate report of the same title (see
                    Project Report ordering information at
                    back).

                    Introduction
                      The objectives of this study were to
                    document the basis for developing new
                    pollution controls using genetic technol-
                    ogy, to describe the present state of such
                    development, and to recommend a re-
                    search policy for such an approach. The
                    study was performed by assembling three
                    review papers  dealing  with pollution
                    problems, gene manipulations, and natu-
                    ral limits to biodegradation. A panel of
                    experts representing disciplines that
                    might contribute to the development of
new treatment technologies assembled
in Urbana, Illinois, to discuss these pa-
pers.  Their recommendations were
merged with the information gathered in
the background papers to provide a sound
basis for recommending policy.
  It was generally concluded that the
spectacular recent advances in gene
manipulation afford a remarkable new
opportunity to design and create micro-
organisms with defined, desirable bio-
degradative capacities. But it was also
concluded that this ability represents only
one of the necessary conditions for the
creation of new and practical pollution
abatement processes. The other necessary
condition  is to bring a population of
microorganisms having a suitable amount
of a relevant catabolic potential into
contact with a pollutant. This involves
either  establishing a  new population of
microorganisms in a polluted environ-
ment or distributing the genes for a
biodegradative pathway among the mem-
bers of an existing microf lora at a polluted
site.
  Basic knowledge of these two process-
es is fragmentary compared to knowledge
of gene manipulation technologies. Con-
sequently, the primary recommendation
of the study is to support basic research
on organism establishment and gene
transmission in natural microbial popu-
lations. This recommendation states that
the establishment of  microbes, or their
genes, in polluted matrices is as important
to practical treatment processes as the
creation of microbes  with novel biode-
gradative capacities.
  Release  to the environment of engi-
neered microorganisms was identified as

-------
an issue of concern to the public and to
bodies such as the Recombinant  DNA
Advisory Committee (RAC) that is charged
with the oversight of some of the new
genetic technologies. To allay fears and to
ensure a prudent  and responsible de-
velopment  of  new biological pollution
treatments, it is recommended that exper-
iments involving the release of genetically
manipulated microorganisms be reviewed
and approved for environmental safety by
a scientifically qualified public body.
When possible, organisms destined for
release should be constructed without
the use of//? vitro recombinant DNA. This
should expedite approval of release, since
all techniques except the in vitro recombi-
nant DNA method are currently viewed as
essentially natural and innocuous.
  Two conventional treatment problems
that might benefit from exploration from a
genetic perspective were the  removal of
ammonia by low-aged wastewater sludg-
es and improvements in the flocculation
of these  sludges.  Unlike research on
organism establishment and gene trans-
mission in  indigenous populations,  no
priorities were assigned to these recom-
mendations.
  The study recognized that the advance-
ment of waste treatment through genetic
manipulations  will require the  involve-
ment of scientists in a very broad range of
disciplines. Even  in assembling the back-
ground papers for this study, communica-
tion  among scientists was impeded by
differences in disciplinary perspectives,
in terminology, and, most importantly, by
a poor understanding of the fundamental
capabilities and  limits of the essential
contributing disciplines. A number of
measures were recommended to improve
communication among the specialists in
the contributing sciences. These included
support for problem-focused symposia,
an occasional newsletter, the coordina-
tion of research support among govern-
ment agencies, and a listing of pollution
problems,  research needs, and current
developments.
Results
  There was general agreement among
the participants at the Urbana workshop
regarding some aspects of the develop-
ment of new biological pollution control
agents.  It  was generally held that this
approach offers a great deal of promise.
The following outline of conclusions and
recommendations provides a good sketch
of such promise and recommended re-
search.
Outline of Conclusions and
Recommendations


 I.  Release of Engineered  Organisms
    for Pollution Control
    A.  Concern  about  the  release of
        engineered organisms demands
        the experiments involving their
        release to the environment be
        reviewed and sanctioned by a
        scientifically qualified public
        body.
    B.  Current regulations governing
        the release of microbes altered
        by in vitro recombinant  DNA
        methods are not a barrier to the
        development of such organisms,
        although release to the environ-
        ment is regulated.
    C.  Development of new organisms
        by in vivo  recombination and
        other techniques not now regu-
        lated should be emphasized.
    D.  The possibility  of exceptional
        examples of potentially hazard-
        ous strains arising  during the
        development of pollution control
        agents by  purely unregulated
        manipulations cannot be ruled
        out at present.
 II.  General Conclusions
    A.  Genetic engineering offers prom-
        ise for new pollution treatments.
    B.  Single strains degrading a cate-
        gorical collection of pollutants
        (e.g., PCBs) will  not be found.
    C.  Compound-specif ic and site-spe-
        cif ic treatments must be empha-
        sized initially.
III.  Recommended Research
    A.  Fields
          i. Colonization of polluted
            environments by intro-
            duced microbes
         ii. Gene transmission in the
            environment
        iii. Co-metabolism
        iv. Oligotrophy
    B.  Areas
          i. The genetics of catabolism
            by archaebacteria
         ii. The genetics of catabolism
            by anaerobes
        iii. The genetics of catabolism
            by filamentous  fungi
        iv. The genetics of microbial
            dehalogenation
         v. Artificial evolution of en-
            zymes and metabolic path-
            ways
    C.  Projects
          i.  Flocculation in wastewater
            sludges
         ii.  Ammonia removal by low-
             age wastewater sludge
IV.   Implementation
     A.  Knowledge from relevant fields
        should be developed in parallel
        and integrated through a news-
        letter and problem-focused sym-
        posia.
     B.  Research undertaken by the
        USEPA and other government
        agencies and organizations
        should be coordinated.
     C.  A current listing of  relevant
        scientific developments,  pollu-
        tion problems,  and research
        needs should be compiled, dis-
        tributed, and updated regularly.

  Although  some aspects of this new
pollution technique appear  promising,
several cautionary notes were sounded.
An  obvious caution was that  pollution
problems must be clearly defined in terms
of their relevance to genetics  and bio-
degradation before potential solutions
can be discussed. Seemingly self-evident,
this  notion  is violated by  suggestions
such as the creation of "superbugs" to
reduce the  BOD of an effluent or the
volume of sludge from an aeration basin.
Genetic engineering most often involves
the specific alteration of individual bio-
chemical pathways in particular organ-
isms. Individual strains with specialized
pathways can have but little effect on the
uncharacterized and presumably hetero-
geneous organic matter measured by the
BOD test or on the organic matter present
in wastewater sludge.
  Similarly, a caution was expressed
about the prospects for developing single
organisms able to attack pollutants such
as PCBs or toxaphenes that are actually
collections of diverse substances. It was
pointed out that bacteria frequently attack
only specific members of a set of related
compounds. Thus, differences as small as
a single hydroxyl substitution, for example
in benzoic,p-hydroxybenzoic and salicylic
acids, are discerned by bacteria. Usually
such compounds are degraded by  sepa-
rate strains using wholly separate path-
ways. A single  bacterial strain will fre-
quently degrade compounds related as
intermediates in a catabolic pathway, for
example,  naphthalene,  salicylate, and
catechol,  more  readily than  a set  of
compounds with close chemical relation-
ships, for instance, the position isomers,
phthalic and terephthalic acid, or a set of
compounds with varying chemical substi-
tutions at one position, such as chloro-
benzene, phenol, aniline,  nitrobenzene,
and toluene. This apparently stems from

-------
the generally high specificity of enzyme-
substrate interactions and from the need
to foster efficient degradation by integra-
ting the products of catabolism into the
central metabolism of an organism.
  Apparently exceptions to this specificity
do  exist.  Some oxygenases  occurring
early in a  degradative sequence show a
more universal appetite than is usual for
typical enzymes of intermediary metabo-
lism, for example, benzoate oxygenases
that can accept chlorobenzoates as sub-
strates or naphthalene oxygenases that
can utilize methyl naphthalenes. Further,
it has been pointed out that many cata-
bolic pathways tend to converge on a few
common metabolites, for example, aro-
matic degradations converging on cate-
chol or gentisate. Nevertheless, these
exceptions to absolute specificity are not
a sufficient basis for designing an orga-
nism to attack so broad a categorical set
of compounds as the PCBs; it must  be
anticipated that a large group of specifi-
cally developed bacterial  strains, each
attacking one or only a few members of
the set,  will be needed  to  achieve a
comprehensive attack  on  collections of
compounds like these.
  Another caution noted was that com-
pounds rarely  occur singly in nature.
Similarly, pollutants will most commonly
be found as components of a  mixture of
compounds. The other compounds occur-
ring in conjunction with a target pollutant
might be either beneficial or detrimental
to the organism degrading the pollutant.
In addition, the physical conditions pre-
sent at the polluted site will individually
and perhaps  synergistically  alter  the
functioning of  any given engineered
microbe. Thus,  a strain used at one site
would not necessarily work well at an-
other, even if both sites contain a common
target compound. This would be due to
the nature of the chemical  mixture or the
environmental conditions present at each
site. Thus, at least initially,  each pollution
problem should be  addressed site-by-
site, pollutant-by-pollutant. Ultimately, it
may be possible, after achieving improve-
ments in treatments of some specific
pollutants, to identify groups of sites with
sufficiently similar characteristics that a
particular manipulated organism can be
used at  all  similar sites.  The  initial
experimental work, however, should be
done with a narrow focus to  provide a
foundation for what will follow.
Conclusions and
Recommendations
  Presently, the strengthening  of re-
search in a few specific subjects appears
to offer the  most expeditious means to
promote the genetic engineering  ap-
proach to pollution control. The recom-
mended research outlined above varies in
scope  from  specific projects  to broad
fields of study.
  The establishment of introduced orga-
nisms in the environment and the trans-
mission of genetic material among indig-
enous  microflora are the two steps basic
to every suggested improvement in pollu-
tion control through genetic engineering.
The  current state of  understanding of
these processes does not permit predic-
tion of the success of either and does not
provide  the  molecular biologist  with
guides for the construction of successful
organisms. Study in these two fields was
assigned the highest priority.
    James B. Johnston and Susan G. Robinson are with the University of Illinois,
      Urbana, IL 61801.
    William A. Cawley is the EPA Project Officer (see below).
    The complete report, entitled "Genetic Engineering and the Development of Ne w
      Pollution  Control Technologies," (Order No. PB 84-148 972; Cost: $14.50,
      subject to change) will be available only from:
           National Technical Information Service
           5285 Port Royal Road
           Springfield,  VA 22161
            Telephone: 703-487-4650
    The EPA Project Officer can be contacted at:
           Industrial Environmental Research Laboratory
            U.S. Environmental Protection Agency
           Cincinnati, OH 45268
                                       S GOVERNMENT PRINTING OFFICE, 1984—759-016/7815

-------
United States
Environmental Protection
Agency
Center for Environmental Research
Information
Cincinnati OH 45268
Official Business
Penalty for Private Use S300


-------