Maxine F. Singer, a biochemist and federal health official who in the 1970s was instrumental in developing guidelines that protected the nascent field of biotechnology while allaying fears that the new science was giving way to the spread of deadly lab-grown microbes, died Tuesday at her home in Washington, D.C. She was 93.
Carnegie Science, a nonprofit research center in Washington, announced his death, saying that Dr. Singer, former president of the institute for 14 years, had been treated for chronic obstructive pulmonary disease and emphysema.
The cracking of the genetic code in the 1960s 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.
These experiments allowed scientists to study the genes of living cells. But some of the new organisms contained cancer-causing genes, and no one understood the new science well enough to know whether the microbes created in the lab were safe.
Although discussed among scientists, these concerns were not made public until Dr. Singer, administrator of the National Institutes of Health, and a colleague sounded the alarm in a 1973 letter in the journal Science, which was closely followed by academics and the media.
The letter, sent on behalf of scientists who had attended a genetics conference, stressed that while gene splicing held great promise for human health, it also allowed the creation of organisms “with biological activity of an unpredictable nature.”
“Some of these hybrid molecules may prove hazardous to laboratory workers and the public,” the letter continues. “Although no hazard has yet been established, prudence suggests that the potential hazard be seriously considered.”
The letter called on the National Academies of Science, a nonprofit that advises the federal government on science policy, to address the problem.
“The train of events was thus set in motion,” wrote Dr. Donald H. Fredrickson, then director of the NIH, in a 1991 account of the gene-splicing controversy.
What followed was five years of intense debate that would test public trust in science—a test that would be repeated in the decades to come, as scientists learned to manipulate embryonic stem cells, clone entire organisms, and edit genes.
Protests erupted in college towns, where residents and university employees saw themselves as guinea pigs in tests to assess the safety of the new technology. Sensationalized news reports ran alarming graphics showing double helices of DNA ending in monster heads, evoking in some minds the epidemic imagined in the 1971 thriller “The Andromeda Strain.” The New York Legislature voted to ban the technology, but Governor Hugh L. Carey, concerned about academic freedom, vetoed the bill.
In response to the letter in Science, the National Academies convened a small advisory committee of leading scientists, including James D. Watson, who, with Francis H. Crick, had discovered the double-helix structure of DNA. The committee was headed by Paul Berg, a Stanford molecular biologist who would receive the Nobel Prize in Chemistry in 1980 for his discoveries about gene splicing.
The committee agreed to a voluntary moratorium, a first in the history of science, on all gene-splicing experiments involving antibiotic-resistant strains or cancer-causing viruses until federal guidelines are developed. Much of the gene-splicing research in the United States and around the world has been funded by the NIH
Seeking recommendations from the broader scientific community, Dr. Singer helped lead what became the Asilomar Conference on Recombinant DNA, named after the conference center in Pacific Grove, California, where it was held in January 1973. The meeting, attended by 150 scientists from 12 countries, was controversial.
At one point, according to Dr. Fredrickson’s account, Dr. Watson called for an abrupt end to the moratorium. “Maxine Singer immediately stood up to ask what had changed in the last six months to cause Watson to abandon the movement he had helped start,” Dr. Frederickson wrote.
Dr. Singer later reflected on that moment. “Our motivation was to allow research to proceed with minimal risk of harm,” she said at a 1997 symposium marking the 20th anniversary of the guidelines. “Why not stop and wait a little bit? Why was that so unacceptable?”
For much of the next year, Dr. Singer worked with NIH colleagues and outside advisers to translate these recommendations into federal guidelines. Published in mid-1976, the guidelines established increasing levels of physical and biological containment, depending on the nature of the experiment. High-risk experiments were to be conducted in “hot zone” isolation rooms with separate ventilation and water systems. Researchers were to use only bacteria that could not survive outside the laboratory. And experiments with deadly pathogens were prohibited.
But the guidelines did not end the debate. Frank, direct, and self-assured—at times, she admitted, to the point of arrogance—Dr. Singer became a formidable advocate for continuing gene splicing subject to regulation. She testified against a municipal ban in Cambridge, Massachusetts; she debated a humanities professor at a public forum at the University of Michigan; and she appeared before Congress, which proposed more than a dozen bills regulating gene splicing from 1976 to 1978.
No ban was imposed, and the NIH restrictions were gradually relaxed as scientists understood the technology. Today, gene splicing is commonly used in laboratory experiments and in the creation of research tools, biotech 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 later champion. She believed that a science-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 that people see this little gray-haired Jewish grandmother, that I’m one of them. I’m not a crazy person, and few of my colleagues are.”
Maxine Frank was born in New York City on February 15, 1931, to Henrietta and Hyman Singer. Her father was a lawyer and her mother was a homemaker. Maxine attended public schools in Brooklyn, where, she later said, a “wonderful” chemistry teacher at Midwood High School sparked her interest in science.
She then attended Swarthmore College, where she majored in chemistry, and befriended five female students who also excelled in science. None of the men in her class, Dr. Singer said, “were better than those six women.”
“I tend to think that if, as an undergraduate, I had not been part of this group, I might not have had the drive and ambition to continue 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 friends, received a National Science Foundation fellowship to fund her graduate studies. (The fifth friend went on 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 and their four children, Amy, David, Ellen, and Stephanie, and their grandchildren.
Dr. Singer received his Ph.D. in biochemistry from Yale in 1957.
Although his dissertation focused on protein chemistry, his faculty advisor suggested that he focus his postdoctoral studies on a new, more promising field: DNA and RNA, nucleic acids that hold the keys to understanding heredity, evolution and disease.
Following that advice, Dr. Singer accepted a research fellowship at the National Institute of Arthritis, Metabolism and Digestive Diseases in Bethesda, Maryland. Working with Dr. Leon Heppel, one of the few scientists who studied nucleic acid chemistry, Dr. Singer used enzymes to create a library of RNA strands composed of various sequences of basic chemicals, such as UUU, for a uracil triplet. She shared her strands with Marshall W. Nirenberg, an NIH colleague, who used them to decipher the genetic code, a discovery for which he shared the Nobel Prize in Physiology or Medicine in 1968.
Although she rejected Dr. Nirenberg’s offer to collaborate formally with him (she valued her independence and did not want to be seen as “someone who worked for Marshall”), Dr. Singer counted her contributions to Nobel Prize-winning research among her greatest scientific achievements.
“At the time, not many people could have done that,” she said, referring to her ability to produce RNA, in an interview with writer Elga Wasserman for her book “The Door in the Dream: Conversations With Eminent Women in Science” (2000). “So it was a big deal to me.”
Dr. Singer was a research biochemist at the Bethesda Institute for 17 years. She joined the National Cancer Institute in 1975 as chief of the Nucleic Acids Section and in 1980 was promoted to chief of the NCI Laboratory of Biochemistry, where she supervised 15 research groups.
Dr. Singer served as the eighth president of the Carnegie Institution for Science (now Carnegie Science), from 1988 to 2002. There, she established a department of global ecology and established science education programs for students and faculty. 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 science. She published more than 100 scientific papers and co-authored several books with Dr. Berg.
An advocate for women in science, Dr. Singer has called for policy changes that would allow women to balance family and work lives. She said she encountered little gender discrimination at the NIH (she felt comfortable knitting sweaters for her children at journal club meetings, where colleagues discussed the latest research), but noted that her female scientist friends in academia struggled to compete with men for funding and tenure.
But she has few regrets about her career, she said. “I had a wonderful time in biology, and I was part of it,” she told a television reporter in 1988, “and there was never a day when I wanted to do anything else.”