Developers of genetically engineered organisms need to consider how biological techniques such as induced sterility can prevent transgenic animals and plants from escaping into natural ecosystems and breeding or competing with their wild relatives, or passing engineered traits to other species, says a new report from the US National Academies of Science's National Research Council. The committee that wrote the report used the term "bioconfinement" to describe such techniques.

"Deciding whether and how to confine a genetically engineered organism cannot be an afterthought," said committee chair T. Kent Kirk, professor emeritus, department of bacteriology, University of Wisconsin, Madison, and a former microbiologist with the U.S. Department of Agriculture. "Confinement won't be warranted in most cases, but when it is, worst-case scenarios and their probabilities should be considered. Also, progress in research aimed at developing new biological confinement methods will further minimize risks and boost the public's confidence in biotechnology."

Because no single bioconfinement method is likely to be 100 percent effective, the committee recommended that developers of genetically engineered organisms use more than one method to lower the chance of a failure. It was also clear to the committee that scientists need to do more research to understand how well specific methods work, and that planned combinations of confinement methods will need to be tested in organisms with representative genetic profiles and in a wide variety of field environments.

The report was requested by USDA, which is considering how to regulate a number of genetically engineered organisms that had not yet been developed when the federal government's original 1986 "Coordinated Framework" for regulation of biotechnology products was enacted. Ensuring confinement for some of these new organisms may become one of the requirements for regulatory approval, the committee noted.

Ecological studies have shown that some genetically engineered organisms are viable in natural ecosystems and can breed with wild relatives. The most publicized environmental danger is that invasive weeds could be created if transgenic crops engineered to tolerate herbicides or to resist diseases and pests pass these resistant genes to weedy relatives. Plants also can be engineered with traits that allow them to grow faster, reproduce more, and live in new types of habitats. An additional risk is that transgenic fish or shellfish could escape and mate with their wild counterparts or out-compete them for food. Another concern is that plants and animals engineered to produce pharmaceuticals could harm humans or other species who may accidentally consume them.

The efficacy of bioconfinement methods will vary depending on the organism and the environment in which it will be released. Other factors include how long confinement needs to last, and the size of the area affected. Confinement is expected to work best over short time scales and small geographic areas, the committee said, emphasizing that no one method can achieve complete confinement. Where confinement is deemed desirable, techniques are needed to monitor any escape of genetically engineered organisms or the flow of transgenes; mitigating a confinement failure will be far easier if it is discovered quickly.

The committee paid particular attention to transgenic fish, shellfish, trees, grasses, and microbes, because many of these organisms have been engineered successfully and currently are undergoing regulatory evaluation. Genetically engineered aquatic species can be confined by physical barriers, by disrupting sexual reproduction, or by methods that prevent their survival in the wild. For example, a technique called triploidization can sterilize some fish and shellfish by adding an extra set of chromosomes to the animal's cellular makeup, although the technique cannot guarantee 100 percent sterility. Fish also can be engineered to rely on a man-made substance for survival, so that they would die if they escaped into the wild. For plants, bioconfinement methods include inserting genes that induce sterility, or engineering plants not to produce pollen, which can help close this avenue of gene flow.

There are two major bioconfinement methods for microbes, the report says. One method involves engineering bacteria or fungi to use so much energy or nutrients that they do not compete well with native bacteria and fungi. Because of the rapid adaptability of microbes, the effectiveness of this bioconfinement method remains unclear, the committee cautioned. The second method is to use a chemical to trigger "suicide" genes in bacteria or fungi if they escape confinement and pose a risk, though this method has never been field tested. Little research has been done on bioconfinement of genetically engineered insects, the committee noted. Confining genetically engineered insects can be particularly challenging because the typically large number of insects in any population makes even a small confinement failure problematic.

The committee also said that when bioconfinement methods are needed, an "Integrated Confinement System," or ICS, should be used. ICS is a systematic approach that includes a commitment to confinement by senior decision-makers within the institutions developing genetically engineered organisms, written plans for confinement and for mitigation of failures, employee training, periodic outside review, and reporting to an appropriate regulatory body. The committee was not asked to evaluate current government practices or policy, but it said that "for ICS to work, it must be supported by a rigorous and comprehensive regulatory regime empowered with inspection and enforcement." Government regulators also need to consider the effects that a confinement failure could have on other nations.

The study was sponsored by the U.S. Department of Agriculture. The National Research Council is the principal operating arm of the National Academy of Sciences and the National Academy of Engineering. It is a private, nonprofit institution that provides science and technology advice under a congressional charter. A committee roster follows.

Copies of Biological Confinement of Genetically Engineered Organisms will be available later this winter from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at http://books.nap.edu/catalog/10880.html

NATIONAL RESEARCH COUNCIL
Division on Earth and Life Studies
Board on Agriculture and Natural Resources

Committee on the Biological Confinement of Genetically Engineered Organisms

T. Kent Kirk^* (chair)
Professor Emeritus
Department of Bacteriology
University of Wisconsin
Madison

John E. Carlson
Associate Professor of Molecular Genetics, and
Director
Schatz Center for Tree Molecular Genetics
School of Forest Resources
Pennsylvania State University
University Park

Norman Ellstrand
Professor of Genetics
Department of Botany and Plant Sciences
University of California
Riverside

Anne R. Kapuscinski
Professor
Department of Fisheries, Wildlife, and Conservation Biology, and
Founding Director
Institute for Social, Economic, and Ecological Sustainability
University of Minnesota
St. Paul

Thomas A. Lumpkin
Director General
Asian Vegetable Research and Development Center
Shanhua, Taiwan

David C. Magnus
Associate Professor,
Division of Medical Genetics, Department of Pediatrics,
and
Co-Director
Stanford Center for Biomedical Ethics
Stanford University
Palo Alto, Calif.

Daniel B. Magraw Jr.
President
Center for International Environmental Law
Washington, D.C.

Eugene W. Nester^*
Professor
Department of Microbiology
University of Washington
Seattle

John J. Peloquin
Group Leader for Protein Chemistry
American Protein Corporation Inc.
Ames, Iowa

Allison A. Snow
Professor of Evolution, Ecology, and Organismal Biology
Ohio State University
Columbus

Mariam B. Sticklen
Professor
Department of Crop and Soil Sciences
Michigan State University
East Lansing

Paul E. Turner
Assistant Professor
Department of Ecology and Evolutionary Biology
Yale University
New Haven, Conn.

RESEARCH COUNCIL STAFF

Kim Waddell
Study Director


^* Member, National Academy of Sciences