International Dimensions of Biotechnology

Sue Ann Tolin, professor of plant pathology, Department of Plant Pathology, Physiology, and Weed Science, Virginia Polytechnic Institute and State University, Blacksburg.

Biotechnology knows no international boundaries, just as the potential applications of biotechnology to agriculture are boundless. The international dimensions discussed her( include U.S. competitiveness in biotechnology research and product development, the guidelines for biotechnology research, and efforts toward international harmonization of regulations.

Competition

The United States is the world leader in biotechnology. The Department of Commerce came to this conclusion in a 1984 report comparing the United States with Japan and five Western European countries West Germany, United Kingdom, Switzerland, Sweden, and France.

All countries have strong basic research and development programs in biotechnology that provide a substantial challenge to U.S. leadership in many biotechnological fields, particularly pharmaceutical and industrial applications.

Other countries, particularly the United Kingdom and Australia, have met the challenge in plant biotechnology research. Indeed, the science policymakers of most technologically developed countries have targeted biotechnology programs for special support.

Third World countries also have recognized biotechnology as a powerful tool for more rapid development o their agriculture and are anxious to use biotechnological approaches.

Marketable Products. Any assessment of a commercial competitive edge at this time must be recognized as largely speculative since few products of biotechnology are as yet being marketed. Furthermore, all early products were functional protein molecules purified as products of genetically engineered bacteria or other single cells growing in large fermentation vessels.

For example, human insulin, the first marketed product, was isolated from bacteria into which the DNA that directs insulin synthesis in human cells had been introduced.

Such products should not be fundamentally different from conventional products because they are produced by a more precise, efficient, and perhaps safer process.

Marketable Organisms. Fulfilling the predictions of the benefits of biotechnology for agriculture will require that at least some of the marketed products are living organisms.

The lead nation in the future for agricultural applications of biotechnology is likely to be the nation that is first to recognize that benefits from using genetically engineered organisms outweigh any potential disadvantages of untoward events encountered by introducing these organisms into the environment.

The early experimental field tests with engineered organisms as a part of the research process to demonstrate their safety and efficacy will be the key to establishing and maintaining a competitive position, in much the same way that field experimentation in agriculture and clinical trials in medicine have traditionally been used.

Research

Most of the major scientific discoveries that led to the beginning just over a decade ago of the new biotechnology era of science were made in this country, largely as a result of our long history of funding basic research.

U.S. scientists were the first to recognize and isolate enzymes from bacterial cells that had the power and specificity to cleave and rejoin bits of genetic information from different organisms. This technique became known as recombinant DNA (rDNA) since the DNA comprising the genes was "recombined" in a test tube from organisms not known to combine or otherwise interact genetically in nature.

Question of Safety. U.S. scientists also were the first to express concern over the safety of conducting certain rDNA experiments, since, in theory, a new organism with unpredictable properties could be created.

The National Institutes of Health (NIH) asked a group of eminent scientists, ultimately known as the RAC or Recombinant DNA Advisory Committee, to write a set of guidelines to be followed when conducting research with recombinant DNA molecules so that harm to laboratory workers and the environment could be avoided. The guidelines helped to allay concern and fears and allowed research with certain organisms to proceed in an orderly and safe manner under the continued purview of the RAC.

Although NIH could insist only that their own researchers or grantees comply with the guidelines, other Federal agencies including the U.S. Department of Agriculture were directed by executive order to follow the same guidelines for research that they funded.

Private institutions and industry also widely accepted the laboratory protocols set forth in the guidelines. After more than 10 years of widespread use of recombinant DNA techniques under the guidelines, no health or safety problems specifically associated with the techniques have arisen.

Research Under Guidelines.

With review and approval by either a local committee or from NIH for certain categories of experiments, countless academic, government, and industrial scientists proceeded to conduct research in which they discovered the many potential human, industrial, agricultural and environmental applications of this technology. They also found many unanticipated benefits from basic research discoveries.

Research also proceeded at a rapid rate in other nations. U.S. or similar guidelines for laboratory research were adopted by most nations, but few of them established a body equivalent to the RAC. They recognized that the RAC provided an internationally valid scientific forum for biotechnology and saw little need to duplicate it.

In its scientific and political wisdom, the United States had built flexibility into the guidelines, which permitted experiments to be recategorized as scientific knowledge about the organisms or the procedure accumulated instead of rigid regulations based on an, as yet, inadequate science base. This process helped to give U.S. scientists a competitive edge because approvals for certain types of research projects could be requested by them and quickly incorporated into research programs throughout the country. Other nations could adopt the changes in the U.S. guidelines after they were published in the Federal Register.

The evolution of guidelines for research into a de facto regulatory framework, nationally or internationally, could be viewed as either stimulatory, early on or inhibitory, later and currently, to biotechnology research and the development of agricultural applications.

Question of Release. Initially, the guidelines specifically prohibited deliberate release of any organism containing recombinant DNA into the environment. Thus, an Environmental Impact Statement written by NIH concluded that issuing guidelines for conducting research with recombinant DNA molecules would have no significant impact on the environment.

There was the underlying perception that less was known about these organisms than about other organisms in nature, and that because less was known they should not be released. Clearly, the only organisms in the minds of the early RAC members that would contain rDNA were bacterial pathogens of humans. The issues of transgenic plants and animals, of human gene therapy, and even of ice minus bacteria were scientific light-years away.

However, the safety of other techniques used in biology to produce genetically altered organisms, such as cell fusion, induced mutation, directed mutagenesis, somaclonal variation, and conventional plant and animal breeding, was not questioned at this time. Scientists and the public expressed no concern that use of these other techniques could result in any of the hazards initially conjectured for rDNA experiments. In addition, the long experiences with plants and animals in agriculture certainly demonstrated that field experimentation with organisms altered by these genetic engineering methods could be conducted safely.

Eventually, the RAC received requests to release rDNA-modified plants and micro-organisms in controlled field tests. Although the requests were approved because no untoward effects to humans or the environment could be envisioned, the legality of this RAC action was challenged because NIH was not a regulatory agency.

Regulation. When biotechnology moved from the laboratory to the marketplace, and living organism products were ready for testing, other agencies and statutory authorities became involved in the research process. The United States has essentially concluded that the existing framework for regulation of biological and chemical products is adequate to assure the safety of biotechnology. These laws are product specific, rather than process specific, to assure uniformity in product regulation. All research or all commercial products may not need safety regulation, provided the precision of the genetic modification is completely understood and the organism can be managed as it is introduced into the environment.

International Harmonization

The United States began thinking about both large-scale fermentations and release of organisms at an early stage of biotechnology research and regulation. Other countries have followed our lead, and some have now approved release of rDNA-containing plants in field tests. Many more will soon follow, particularly if the United States releases are blocked by litigation.

Nations have recognized the need, particularly in biotechnology applications, for uniform scientific principles on which to base their decisions. One of the most active international organizations in attempting to arrive at harmonization has been the Organization for Economic Cooperation and Development (OECD). Over the last 3 to 4 years, a special group of scientific experts, delegated by the more than 20-member nations, deliberated on a report entitled Recombinant DNA Safety Considerations. The report considers potential benefits and risks of rDNA organisms in industrial, environmental, and agricultural applications, and the extent to which risk assessment of these organisms differs from that applied to conventional organisms. It also identifies general scientific principles for achieving safety in the various applications, and makes recommendations to member countries for both general and specific issues that they can use in formulating their regulations.

The OECD report should provide the basis for an international consensus for the protection of health and the environment, the promotion of technological and economic development, and the reduction of international trade barriers.