Flossie Wong-Staal (1946─2020)

Flossie Wong-Staal, a leader in HIV research at the onset of the AIDS epidemic, died on 8 July at the age of 73. A pioneer in the genetic structure and regulatory mechanisms of HIV, Wong-Staal played a key role in showing that HIV causes AIDS. She was also a trailblazer for female scientists. Born in Guangzhou, China, on 27 August 1946 as Yee Ching Wong, Wong-Staal moved to Hong Kong with her family when she was 7 years old. At the age of 18, she westernized her name (taking the name “Flossie” from a typhoon that had recently hit southern China) and emigrated to the United States. The first woman in her family to obtain a higher education, she graduated with a bachelor's degree in bacteriology in 1968 and a Ph.D. in molecular biology in 1972, both from the University of California, Los Angeles. In 1973, Wong-Staal began a postdoctoral position at the Laboratory of Tumor Cell Biology, led by biomedical researcher Robert C. Gallo, in the National Cancer Institute of the National Institutes of Health (NIH) in Bethesda, Maryland. She was promoted to section chief within a few years, and in the next decade she co-authored more than 100 journal articles. In 1990, Wong-Staal left the NIH to accept an appointment as the Florence Seeley Riford Chair in AIDS Research at the University of California, San Diego (UCSD). She was named director of the newly created UCSD Center for AIDS Research in 1994 and began pioneering the investigation of gene therapy approaches for HIV/AIDS. After her retirement from UCSD in 2002, she became vice president of Immusol, a biopharmaceutical company she cofounded, now known as iTherX Pharmaceuticals, where she pursued treatments for hepatitis C. Throughout her career, Wong-Staal trained a large number of postdoctoral fellows, many of whom went on to be leaders in their fields. When Gallo's team cultured the first human retrovirus in the late seventies, Wong-Staal was focused on retroviruses that caused leukemia in animals. She quickly pivoted to follow up on Gallo's work, and her section became the leading group working on the molecular biology of human retroviruses. In these early years of research on human retroviruses, the skepticism regarding their existence was widespread. Gallo later framed a letter from a reviewer who, citing the “fact” that there were no human retroviruses, rejected the initial human T cell leukemia virus (HTLV) paper. But Wong-Staal was among those who thought there was a connection between retroviruses and human diseases, and she was proved right. The molecular virology skills Wong-Staal brought to her laboratory were critical to her ability to apply state-of-the-art molecular biology techniques to quickly unravel the HIV genome organization and its replication strategies. In the early 1980s, Wong-Staal discovered molecular evidence of variations in HIV within and among infected individuals, which led to a fundamental realization: HIV is constantly mutating in response to immune pressures, so every isolation of the virus results in different virus clones. This understanding shaped the development of effective antiviral therapies to manage AIDS. Wong-Staal also provided the molecular biology necessary for the development of the second-generation blood test for HIV, one based on detection of the viral genome rather than antibodies to the virus. Her groundbreaking work on the molecular biology of HIV inspired scientists worldwide to join the field of human retrovirology, an entirely uncharted but increasingly exciting area of research in the 1980s and early 1990s. Wong-Staal's contributions were not limited to HIV. She had a keen interest in the molecular virology of HTLV-1, the retroviral causative agent of human adult T cell leukemia. Her work on nonstructural viral factors such as the HTLV-1 and HIV-1 transcriptional activators Tax and Tat and the posttranslational regulators Rex and Rev also had far-reaching implications in areas of basic biology, including transcription regulation and RNA transport. I joined Wong-Staal's lab in 1979 as a postdoctoral fellow. She was a very talented scientist who had an exceptional ability to sharply analyze data, focus, and move quickly to address the most essential research questions. She was willing to take risks and propose daring hypotheses, always expanding her knowledge and moving research forward. This mindset extended beyond her lab work. Decades ago, for a presentation at an AIDS meeting, she told the audience that instead of using the standard slides, she was going to give her presentation using a program called PowerPoint that she had learned about from her daughter. By the next meeting, there was not a slide presentation in sight; everyone was using PowerPoint. A stylish, elegant, and confident woman with a great sense of humor, Wong-Staal was competitive and tenacious. When she submitted her first grant application from UCSD after leaving the NIH, the reviewers did not give her a fundable score because they thought that, as a molecular biologist, she did not have the immunology experience required to carry out the proposed studies. In response, she conducted the study anyway, published the data, and sent the publication with her next grant application. In this way, Wong-Staal taught me persistence and resilience, skills that I have found to be invaluable in my career. Flossie Wong-Staal held her own and gained respect in a male-dominated scientific world through her strength, intelligence, kindness, and grace. She was a member of the National Academy of Medicine. In 2002, Discover magazine named her one of the 50 most important women in science. In 2019, she was inducted into the National Women's Hall of Fame, along with Angela Davis, Jane Fonda, and Sonia Sotomayor. It was a well-deserved honor for an influential researcher, who served as a role model to mentees and colleagues and will continue to inspire future generations of scientists.