Flossie Wong-Staal, a molecular biologist who helped establish H.I.V. as the cause of AIDS, revealed the virus’s inner-workings by cloning it and then laid the foundation for treatments, died on July 8 in San Diego. She was 73.
Her death, at Jacobs Medical Center in the La Jolla section of the city, was caused by complications of pneumonia not related to Covid-19, her husband, Jeffrey McKelvy, said.
Her former colleague Robert C. Gallo said Dr. Wong-Staal was a “whiz kid” in molecular biology when she went to work for the National Institutes of Health in the 1970s, adept at manipulating the components of living things like DNA and proteins.
Calm and collected, she produced dozens of groundbreaking papers amid personal and professional turmoil in the lab at a time when Dr. Gallo, its leader, was caught up in investigations over his disputed claim to have discovered H.I.V.
Dr. Wong-Staal was a member of the National Academy of Medicine and was inducted into the National Women’s Hall of Fame last year. Her work was so prolific and influential that the magazine The Scientist named her the most cited female scientist of the 1980s.
“Flossie was the best of the best,” Dr. Gallo said in an interview.
Dr. Wong-Staal joined Dr. Gallo after he had started studying what was then considered an obscure class of viruses known as retroviruses. Unlike ordinary viruses, retroviruses invade the cellular nucleus and insert their genes into the DNA of their hosts. Retroviruses had been observed in birds and mice but not humans, and Dr. Gallo’s research was ridiculed at first.
He soon discovered the first human retrovirus, called HTLV-1, which caused a kind of leukemia in humans. Dr. Wong-Staal went to work studying its various parts and how the virus interfered with human DNA to activate certain cancer-causing genes called oncogenes. Her work contributed to the broader understanding of the role of oncogenes in cancers not associated with viruses.
In a strange coincidence, a year after HTLV-1 was discovered, Dr. Gallo and Dr. Wong-Staal suspected that another human retrovirus might be the cause of a new disease that was spreading in the gay community and elsewhere. Eventually called AIDS, the mysterious disease had many traits in common with HTLV-1: Both were transmitted sexually, through blood or from mother to child, and both infected T-cells, a type of white blood cell.
Dr. Gallo and Dr. Wong-Staal turned out to be right, but they were not alone. While Dr. Gallo and a French group led by Luc Montagnier were locked into a protracted fight over who got credit for discovering H.I.V., Dr. Wong-Staal moved the science forward by figuring out how the virus worked.
She took the virus apart, probing its genes and proteins to see what each component did. One protein became the target of the drug AZT; another became the target of a class of drugs known as protease inhibitors.
In Dr. Gallo’s 1991 book, “Virus Hunting,” Dr. Wong-Staal was quoted as saying: “Working with this virus is like putting your hand in a treasure chest. Every time you put your hand in, you pull out a gem.”
Her virology work is now being deployed in the fight against the novel coronavirus.
“H.I.V. research built a strong foundation for Covid-19 research,” said David Ho, a Columbia University virologist, who directs the Aaron Diamond AIDS Research Center there. “It’s why things are moving so fast on the vaccine front and the antibody front, as well as the development of drugs.”
Yee Ching Wong was born on Aug. 27, 1946, in Guangzhou, China, to Sueh-Fung Wong, who was in the import-export business, and Wei-Chung (Chor), a homemaker. The family moved to Hong Kong in 1952.
She attended a Roman Catholic girls school, where her teachers noticed her academic talents and encouraged her to adopt an English name. She asked her father for help. “She said, ‘I don’t want to be another Teresa or Mary,’” Mr. McKelvy, her husband, said.
Her father came up with Flossie, taking it from a hurricane by that name. “He said, ‘That’s you, you’re a Flossie,’” Mr. McKelvy said.
Dr. Wong-Staal moved to the United States to study bacteriology at the University of California, Los Angeles, graduating magna cum laude in 1968. She earned a doctorate in molecular biology from U.C.L.A. in 1972. While attending graduate school she married Stephen Staal and had a daughter with him. The marriage ended in divorce in 1986.
Dr. Wong-Staal went to work with Dr. Gallo at the National Institutes of Health in 1973 and was quickly promoted to lead a group of molecular biologists. When the lab turned its attention to AIDS, she was the first to transform H.I.V. from tissue and blood samples into something that could be studied using a labor-intensive process known as cloning.
Cloning allowed researchers to study each part of the virus, and in doing so it revealed a critical facet that made H.I.V. so challenging to fight: its genetic diversity.
“We now know this diversity is enormous, and is a big obstacle to vaccine development,” said Prof. Beatrice Hahn of the University of Pennsylvania, who worked with Dr. Wong-Staal.
That diversity — a surprise to the researchers, since other retroviruses did not have this feature — allowed H.I.V. to evade the immune system. But once they figured out the role of the individual genes and proteins, they could target them. “It was a logical next step in characterizing a completely new pathogen,” Professor Hahn said. “It was an exciting time, and Flossie was in charge.”
In 1990, Dr. Wong-Staal took a job at the University of California, San Diego, where she continued to study H.I.V., looking for new treatments and a vaccine. In 2002 she became the chief scientific officer of Immusol, a biotech company she co-founded. She later renamed it iTherX Pharmaceuticals, after its had mission shifted from AIDS to hepatitis C. (The company is no longer active.)
Dr. Wong-Staal had a longstanding romantic relationship with Dr. Gallo, which was well known in the virology community, and she was open about the fact that he had fathered her second child.
In interviews, she called him a polarizing figure. Dr. Gallo had originally claimed that a variant of his original human retrovirus, which he called HTLV-3, was the cause of AIDS. The French lab led by Dr. Montagnier proposed a different virus, called L.A.V., which proved to be the right one and was later named H.I.V.
Dr. Gallo would himself propose L.A.V. as the virus that causes AIDS, but the French researchers accused him of using samples obtained from their lab. That led to federal investigations, a patent dispute and, in 2002, a 670-page book by the journalist John Crewdson, though the fight was never completely resolved.
Through it all, Dr. Wong-Staal was known for navigating this brutally competitive, male-dominated research world with quiet confidence, while supporting the many younger researchers in her lab who went on to have extraordinary careers.
“She was strong and resilient,” Dr. Gallo said. “We could be like bulldogs, but I think she was able to get up easier.”
In addition her husband, Ms. Wong-Staal is survived by her daughters Stephanie Staal and Caroline Vega; a sister Nancy Yao; two brothers, Raymond Wong and Patrick Wong; and four grandchildren.
Mr. McKelvy said that he and Ms. Wong-Staal had taken up ballroom dancing in her last decade for recreation, but that even there her competitive nature eventually came through. “It became a passion, and she took it really seriously, as she did most things,” he said. It wasn’t long before they were entering competitions.