The Recombinant DNA Controversy: Twenty Years Later

February 24-26 of this year was the 20th anniversary of the Asilomar Conference that considered the public health implications of what was then a new genetic technologyrecombinant DNA. Looking back now, this unique conference marked the beginning of an exceptional era for science and for the public discussion of science policy-one that continues unabated to this day. This year alone saw a scientist turn back $614,000 in research grants, as a measure of what he perceives as the possible misdirections of current molecular genetics, and a call, by religious leaders representing 80 different faiths and denominations, opposing "the patenting of genetically engineered animals and human genes, cells, and organs." This 20th anniversary is then an important opportunity to reflect on the history of that occasion and its ramifications. What events led to the conference? Eight months earlier, in July 1974, a call for a voluntary moratorium on certain scientific experiments using the emerging recombinant DNA technology startled the world-wide scientific community (1). This unprecedented action by a group of American scientists echoed reservations expressed at a Gordon Conference on nucleic acids the summer before (2). Both groups acknowledged that the new technology created extraordinary novel avenues for genetics and could ultimately provide exceptional opportunities for medicine, agriculture, and industry. Nevertheless, the scientists were concerned that unfettered pursuit of this research might engender unforeseen and damaging consequences for human health and the Earth's ecosystems. In spite ofwidespread consternation among many scientists about the proscriptions, the validity of the concerns, and the manner in which they were announced, the moratorium was universally observed. One goal of the moratorium was to provide time for a conference that would evaluate the state of the new technology and the risks, if any, associated with it. That conference, held at the Asilomar Conference Center on California's Monterey peninsula, included scientists from throughout the world, lawyers, members of the press, and government officials. One aim of the meeting was to consider whether to lift the voluntary moratorium and, if so, under what conditions the research could proceed safely. Although there were few data on which to base a scientifically defensible judgment, the conference concluded, not without outspoken opposition from some of its more notable participants, that recombinant DNA research should proceed but under strict guidelines (3). Such guidelines were subsequently promulgated by the National Institutes of Health and comparable bodies in other countries (4). The primary motivation for the prompt actions taken by scientists and governments in the period 1973-1976 was to protect laboratory personnel, the general public, and the environment from any hazards that might be directly generated by the experiments. In particular, there were speculations that normally innocuous microbes could be changed into human pathogens by introducing genes that rendered them resistant to then-available antibiotics, or enabled them to produce dangerous toxins, or transformed them into cancercausing agents. The uncertainties stimulated a sometimes turbulent debate. Public fear was fanned by the popularity of "The Andromeda Strain" and the myriad "what ifs" floated by both serious and demagogic commentators. Also plaguing the debate over the necessity for or adequacy of the measures proposed to minimize imagined risks was the ignorance, even in the scientific community, about the properties of cells and viruses containing foreign genes, including whether such cells and viruses posed any risk at all. Some scientists, and public officials as well, were certain that recombinant DNA research was flirting with disaster and that lifting the moratorium was a blunder. Others, reflecting their intuition and expertise, argued that such cells, viruses, and recombinant DNAs posed no risk at all. The overwhelming assessment today is that the latter view was correct. Literally millions of experiments, many even inconceivable in 1975, have been carried out in the last 20 years without incident. No documented hazard to public health has been attributable to the applications of recombinant DNA technology. Moreover, the concern of some that moving DNA among species would breach customary breeding barriers and have profound effects on natural evolutionary processes has substantially disappeared as the science revealed that such exchanges occur in nature. The use of the recombinant DNA technology now dominates research in biology. It has altered both the way questions are formulated and the way solutions are sought. The isolation of genes from any organism on our planet, alive or dead, is now routine. Furthermore, the construction of new variants of genes, chromosomes, and viruses is standard practice in research laboratories, as is the introduction of genes into microbes, plants, and experimental animals. Equally profound is the influence it has had in many related fields. Even a brief look at journals in such diverse fields as chemistry, evolutionary biology, paleontology, anthropology, linguistics, psychology, medicine, plant science, and surprisingly enough, forensics, information theory, and computer science shows the pervasive influence of this new paradigm. But the most profound consequence of the recombinant DNA technology has been our increased knowledge of fundamental life processes. No longer is the gene an abstract notion, nor is it as enigmatic as interstellar dark matter or black holes. Genes, and chromosomes of which they are a part, are describable in precise chemical terms. Even more significantly, genes can be synthesized in test tubes, manipulated, and reintroduced into the cells of living organisms, enabling us to link genes with specific physiological functions. An even abbreviated enumeration of the extraordinary advances stemming from the recombinant and associated technologies is beyond the scope of this commentary, but a few brief examples can provide a sense of the breadth of the research's implications. (i) The ability to isolate genes readily and to determine their chemical structure unexpectedly revealed that genetic messages-the genes-of vertebrates, including humans are filled with interruptions, a feature that is largely missing from genes of "simpler" organisms. These interruptions must be edited out before the genetic messages make sense, and becausc the editing process can occur in a variety of ways, many genes encode multiple functions. Consequently, the amount of ge-