Maxine Singer, Guiding Force at the Dawn of Biotechnology, Dies at 93

Maxine F. Singer, a biochemist and federal health official who in the 1970s was instrumental in developing guidelines that protected the then-nascent field of biotechnology while calming fears that this new science would give way to the spread of deadly lab-produced microbes, died on Tuesday at her home in Washington, D.C. She was 93.

Carnegie Science, a nonprofit research center in Washington, announced her death, saying Dr. Singer, a former 14-year president of the institute, had been treated for chronic obstructive pulmonary disease and emphysema.

The cracking of the genetic code in the 1960s had paved the way for new discoveries that allowed scientists to insert DNA from toads, fruit flies and viruses into bacteria to create organisms that would never exist in nature, a process known as gene splicing.

The experiments allowed scientists to study genes in living cells. But some of the new organisms contained cancer-causing genes, and no one understood the new science well enough to know if the lab-made microbes were safe.

Although discussed among scientists, the concerns did not come into public view until Dr. Singer, an administrator at the National Institutes of Health, and a colleague sounded an alarm in a letter published in 1973 in the journal Science, which was closely followed by academics and the news media.

The letter, sent on behalf of scientists who had attended a genetics conference, noted that while gene splicing held great promise for human health, it also enabled the creation of organisms “with biological activity of an unpredictable nature.”

“Certain such hybrid molecules may prove hazardous to laboratory workers and the public,” the letter continued. “Although no hazard has yet been established, prudence suggests the potential hazard should be seriously considered.”

The letter called on the National Academies of Science, a nonprofit adviser to the federal government on science policy, to address the problem.

“The train of events was thus set in motion,” Dr. Donald H. Fredrickson, who was then director of the N.I.H., wrote in a 1991 account of the gene-splicing controversy.

What ensued were five years of intense debate that would test the public’s confidence in science — a test that would be repeated in the decades to come as scientists learned to manipulate embryonic stem cells, clone whole organisms and edit genes.

Protests broke out in university towns, where residents and university employees saw themselves as guinea pigs in trials to assess the safety of the new technology. Sensational news accounts featured alarming graphics showing DNA double helixes ending in monster heads, evoking in some minds the epidemic imagined in the 1971 movie thriller “The Andromeda Strain.” The New York Legislature voted to ban the technology, but Gov. Hugh L. Carey, concerned about academic freedom, vetoed the bill.

Responding to the letter in Science, the National Academies assembled a small advisory committee of scientific luminaries, including James D. Watson, who, with Francis H.C. Crick, had discovered the double helix structure of DNA. The panel was led by Paul Berg, a Stanford molecular biologist who would go on to receive the 1980 Nobel Prize in Chemistry for his discoveries in gene splicing.

The committee agreed to a voluntary moratorium, the first in the history of science, on all gene-splicing experiments involving antibiotic-resistant strains or cancer-causing viruses, until federal guidelines were developed. Much of the gene-splicing research in the United States and around the globe was funded by the N.I.H.

Seeking recommendations from the broader scientific community, Dr. Singer helped lead what has become known as the Asilomar Conference on Recombinant DNA, named after the conference center in Pacific Grove, Calif., where it was held in January 1973. The meeting, attended by 150 scientists from 12 countries, was contentious.

At one point, according to Dr. Fredrickson’s account, Dr. Watson called for an abrupt end to the moratorium. “Maxine Singer was on her feet immediately to ask what had changed in the last six months to cause Watson to abandon the movement he helped launch,” Dr. Frederickson wrote.

Dr. Singer later recalled the moment. “Our motivation was to allow the research to continue with a minimal chance of hazards,” she told a 1997 symposium to mark the 20th anniversary of the guidelines. “Why not stop and wait awhile? Why was that so unacceptable?”

For much of the following year, Dr. Singer worked with N.I.H. colleagues and external advisers to mold the recommendations into federal guidelines. Issued in mid-1976, the guidelines established escalating levels of physical and biological containment, depending on the nature of the experiment. High-risk experiments were to be conducted in “hot zone”-type isolation rooms with separate ventilation and water systems. Researchers were limited to using only bacteria that could not survive outside the laboratory. And experiments with deadly pathogens were prohibited.

But the guidelines didn’t end the debate. Plain-spoken, direct and confident — sometimes, she admitted, to the point of arrogance — Dr. Singer became a formidable advocate for allowing gene splicing to continue with regulations in place. She testified against a municipal ban in Cambridge, Mass.; debated a humanities professor at a public forum at the University of Michigan; and appeared before Congress, which from 1976 to 1978 proposed more than a dozen bills regulating gene splicing.

No bans were imposed, and the N.I.H. restrictions were gradually eased as scientists came to understand the technology. Today, gene splicing is routinely used in laboratory experiments and in creating research tools, biotechnology drugs and disease-resistant crops.

For Dr. Singer, the gene-splicing controversy was a lesson in the need for science education, a cause she would go on to advance. She believed that a scientifically literate public was essential to scientific progress, a product of human curiosity to be encouraged, not feared.

“I’ve given talks where it was really important for me to say, ‘Yes, I’m a nerd and I’m proud of it,’” she said in a 2002 interview with The New York Times. “It’s important for people to see this small, gray-haired Jewish grandma, that I’m one of them. I’m not some crazy person, and few of my colleagues are.”

Maxine Frank was born in New York City on Feb. 15, 1931, to Henrietta and Hyman Frank. Her father was a lawyer, and her mother oversaw the household. Maxine attended public schools in Brooklyn, where, she later said, a “terrific” chemistry teacher at Midwood High School sparked her interest in science.

She went on to Swarthmore College, where she majored in chemistry, becoming good friends with five female students who also excelled in science. None of the men in her classes, Dr. Singer said, “were any better than these six women.”

“I tend to think that, if as an undergraduate, I had not been in that group, I might not have had the will and the ambition to keep going in science,” she said in an interview with Magdolna Hargittai, an author and chemistry professor based in Hungary.

Dr. Singer earned her bachelor’s degree in 1952 and, along with four of her friends, received a National Science Foundation fellowship to support graduate studies. (The fifth friend went to medical school.) Of the 600 predoctoral fellowships awarded by the foundation that year, only 32 went to women.

Immediately after graduation, she married Daniel Singer, a Swarthmore classmate and political science major. He survives her along with their four children, Amy, David, Ellen and Stephanie, and their grandchildren.

Dr. Singer received her doctorate in biochemistry from Yale in 1957.

Though her dissertation was in protein chemistry, her faculty adviser suggested that she shift her postdoctoral studies to a new, more promising area: DNA and RNA, nucleic acids that hold the keys to understanding heredity, evolution and disease.

Following that advice, Dr. Singer accepted a fellowship at the National Institute of Arthritis, Metabolism and Digestive Diseases, in Bethesda, Md. Working with Dr. Leon Heppel, one of the few scientists studying nucleic acid chemistry, Dr. Singer used enzymes to build a library of RNA strands composed of varying sequences of base chemicals, such as UUU, for a triplet of uracil. She shared her strands with Marshall W. Nirenberg, an N.I.H. colleague, who used them to crack the genetic code, a discovery for which he shared the 1968 Nobel Prize in Physiology or Medicine.

Though she rejected Dr. Nirenberg’s offer to formally collaborate with him — she valued her independence and did not want to be seen as “somebody who worked for Marshall,” she said — Dr. Singer counted her contributions to the Nobel Prize-winning research among her biggest scientific achievements.

“There weren’t many people at the time who could have done that,” she said, referring to her ability to make RNA, in an interview with the writer Elga Wasserman for her book “The Door in the Dream: Conversations With Eminent Women in Science” (2000). “So that was a big thing for me.”

Dr. Singer was a research biochemist at the Bethesda institute for 17 years. She moved to the National Cancer Institute in 1975 as chief of its nucleic acid section and in 1980 was promoted to chief of the N.C.I.’s biochemistry laboratory, where she oversaw 15 research groups.

Dr. Singer was the eighth president of the Carnegie Institution for Science (now called Carnegie Science), serving from 1988 to 2002. She created a department of global ecology there and established science education programs for students and teachers. She was also a member of the National Academy of Sciences and a recipient of the National Medal of Science, the nation’s highest honor in the field. She published more than 100 scientific papers and wrote several books with Dr. Berg.

An advocate for women in science, Dr. Singer called for policy changes that would allow women to balance family and work. She said she had experienced little gender bias at the N.I.H. — she was comfortable enough to knit sweaters for her children at “journal club” meetings, during which colleagues discussed the latest research — but noted that female scientist friends in academia struggled to compete with men for funding and tenure.

But she had few regrets about her career, she said. “I’ve lived through an extraordinary time in biology, and I’ve been part of it,” she told a television interviewer in 1988, “and there hasn’t been a day when I’ve wanted to do anything else.”