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During the early 1970s, as debate over the environmental and health risks of the new technology of gene recombination grew ever more heated, Maxine Singer was a leading voice of prudence, patience, and dedication to balancing scientific principles and public welfare. Recombinant DNA research promised to revolutionize the understanding of human genetics, development, and evolution by opening up new ways of studying the structure, expression, and regulation of genes. Yet because they involved manipulation of DNA, the chemical basis of heredity, scientists and laymen alike worried that these experiments might produce new pathogens that could endanger human health or irrevocably alter the environment and the course of evolution. Under Singer's leadership, a small group of prominent molecular biologists drew up restrictions governing recombinant DNA research, while petitioning the public and lawmakers for acceptance and continued funding of their work.

Singer first entered the nascent field of recombinant DNA research in 1967 with a review of the trailblazing experiments of Arthur Kornberg and Gobind Khorana in Science. Their successful syntheses of biologically active DNA in vitro, she predicted, "bring closer the day when the ability to manipulate genetic material can be used for improving the life of all humans." Doubts emerged, however, when Paul Berg and his research team at Stanford University used newly-discovered restriction enzymes to obtain a hybrid molecule containing the DNA of a gene from simian virus 40, a virus that causes cancer in rodents, and the DNA of a phage virus, which infects E. coli bacteria. The phage DNA had already been altered to include an E. coli gene, so that the new molecule had genetic elements from three different microorganisms: SV40, E. coli, and phage. Berg's experiment marked the beginning of genetic engineering. But because the novel molecule they had created appeared capable of replication once it was inserted into another E. coli bacterium, it raised the specter of a new hybrid, cancer-causing gene in a bacterium that naturally resides in human intestines.

In June 1973, Singer co-chaired with Werner Söll the Gordon Conference on Nucleic Acids, where conferees discussed, for the first time, the potential hazards of recombinant DNA research. After the conference, Singer and Söll drafted a letter to the president of the National Academy of Sciences (NAS), Philip Handler, warning that "new kinds of hybrid plasmids or viruses, with biological activity of unpredictable nature, may eventually be created," and calling for the creation of a committee to assess the dangers of genetic manipulation. Paul Berg headed the NAS committee, after he had halted his own genetic engineering experiments and had campaigned for a moratorium on such research pending the establishment of a framework for ensuring its safety. This moratorium on recombinant DNA research was the first such voluntary moratorium in the history of science.

The Berg committee recommended that scientists working in the new field convene a Conference on Recombinant DNA Molecules, which Singer helped organize for February 24-27, 1975, at the Asilomar Conference Center in Pacific Grove, California. Ninety American scientists, 60 scientists from 12 other countries, 16 members of the press, and a handful of lawyers, including Maxine Singer's husband, Daniel Singer, attended. Daniel Singer put together a small panel of lawyers which, on the evening of the final day of the conference, discussed legal ramifications of possible risk in recombinant DNA research, such as occupational safety, liability, and workmen's compensation issues.

While acknowledging that they could not predict or avert hazards with any certainty, the conferees categorized and assessed each type of recombinant DNA (rDNA) experiment according to its risk to laboratory and public safety. They determined that some low-risk experiments should proceed, while others required strict containment or even temporary prohibition. A summary statement, signed by Singer, Berg, and three others, called on scientists under the leadership of NIH to develop guidelines for minimizing the safety risks of rDNA research, and for lifting restrictions on research as knowledge of the new technology increased. The Asilomar Conference was a milestone in the development of social awareness and a sense of public responsibility among scientists. It also became synonymous with self regulation of scientific policy issues by scientists themselves, and therefore spurred controversy among environmental and health activists.

The task of issuing rDNA research guidelines fell to NIH Director Donald Fredrickson. Fredrickson was not a geneticist. He relied on a team of NIH staff scientists and administrators to help him draft the guidelines and evaluate the recommendations of the Recombinant Molecule Program Advisory Committee (RAC), chartered in 1974 "to evaluate hazards of recombinant DNA, develop procedures to minimize those risks, and devise guidelines for research with recombinant DNA." Maxine Singer proved to be an in-house confidante who was both independent-minded and deeply informed about the research--Fredrickson called her "an indispensable member of the kitchen RAC," his inner circle of advisers on rDNA.

The NIH Guidelines on Recombinant DNA Research, released on June 23, 1976, provided for both physical and biological containment protocols. Four levels of physical containment governed rDNA experiments, requiring protective measures from gloves to extractor hoods and, at the highest containment level, isolated rooms with separate ventilation and water systems, lower barometric pressure, and air-locks. They also provided for three levels of biological containment, meaning purposely modifying organisms so that they could not survive outside the laboratory. Experiments involving DNA from highly pathogenic bacteria or genes coding for toxins were prohibited outright. The NIH guidelines became an international standard of reference for researchers in academia and industry. Because they, and their subsequent revisions, were adopted only after lengthy public hearings, the guidelines also reflected unprecedented public input into scientific matters.

Nevertheless, public unease, heightened by perceptions of conflicts of interest on the part of scientists entrusted with regulating their own research, fueled media and political debates. The environmental activist Jeremy Rifkin called for a national referendum on recombinant DNA research. Science for the People, an activist organization, filed a lawsuit against NIH when the agency issued the guidelines without an Environmental Impact Statement, as required by federal regulations (although Singer helped draft one the following year). Municipal governments in Cambridge, Massachusetts, and Berkeley, California, sites of major laboratories in molecular biology at Harvard, MIT, and the University of California, proposed further restrictions on the new type of research. Congress debated more than a dozen bills to regulate recombinant DNA research through federal legislation between 1976 and 1978.

Singer defended self-regulation by scientists in the face of such growing public and congressional pressure. In January 1976, she debated Susan Wright, a historian at the University of Michigan and member of Science for the People who campaigned against the construction of a P3 containment facility at the university. She participated in hearings by the city of Cambridge, Massachusetts, about recombinant DNA research at MIT and Harvard in the summer of 1976, at which she defended the efficacy of the NIH guidelines. The council nonetheless imposed a three-months ban on such research, later extended to six, and created the Cambridge Experimental Review Board, a majority of its members non-scientists. Singer joined other prominent researchers in giving expert testimony in Congress opposing federal recombinant DNA bills. Donald Fredrickson later said that Singer's "role throughout a controversy, precipitated partly by her own sensitivity to the moral duties of science, had been enormous."

The NIH guidelines provided a mechanism for regular review and easing of restrictions on research as risks became better known. By 1978, most scientists believed that new evidence warranted revision of the guidelines, and Singer proposed downscaling risk and containment levels for many experiments. The process, however, became drawn out and contentious after the Secretary of Health, Education, and Welfare, Joseph Califano, assumed supervision of recombinant DNA policymaking. Singer complained in an editorial published in Science in January 1979 that Califano had adopted procedures "unsuitable to the complex problem of controlling creative activities . . . [and] the confidence of the scientific community in the wisdom behind these efforts is rapidly eroding."

Singer continued to press for simplification of the review, registration, and approval of experiments and argued successfully that NIH should end its review of the decisions of Institutional Biohazard Committees at research institutions, the committees that approved experiments for which containment levels were specified by the guidelines (as opposed to experiments not expressly mentioned in the guidelines, which had to be approved by NIH). Other key participants at Asilomar, namely David Baltimore and Norton Zinder, urged that the guidelines be converted into a code of recommended standard practices, except for prohibitions on certain types of experiments. Their proposals were not enacted, but in the absence of evidence that gene recombination and cloning experiments cause unexpected hazards, the NIH guidelines have been eased significantly since.

A quarter century after the Asilomar conference, Paul Berg acknowledged that "we overestimated the risks, but we had no data as a basis for deciding, and it was sensible to choose the prudent approach." He credited the voluntary moratorium and initially stringent guidelines with shoring up public confidence and defusing further controversy, allowing easing of restrictions as evidence permits. Singer has gone further, suggesting that this approach should be applied to the approval process for all new biological technologies, such as genetically modified crops. She has urged scientists to find new ways to explain the rapid advances in biology made possible by the recombinant DNA revolution to a skeptical public.