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 ------- |