Flossie Wong-Staal

KEYWORDS: Yee Ching Wong, Flossie Wong-Staal, AIDS, HIV

SHE THOUGHT IT

Flossie Wong-Staal is a Chinese-American scientist who holds a bachelor’s degree in Bacteriology (1968) and a PhD in Molecular Biology (1972) both from the University of California in Los Angeles. Her professional career in a laboratory started in the early 1970s when she joined the National Cancer Institute and began working with a pioneer scientist in the field of AIDS, Robert Gallo, with whom she researched retroviruses: “single-stranded RNA viruses that produce reverse transcriptase by means of which DNA is produced using their RNA as a template and incorporated into the genome of infected cells, that are often tumorigenic, and that include the lentiviruses (such as the HIVs) and the causative agent of Rous sarcoma”¹. Thanks to the many years of research, they were eventually able to identify HIV as the cause of AIDS.

Wong-Staal’s interest in this field did not cease and she kept on working until, in 1985, she became the first person to clone HIV and to generate a genetic mapping of the virus which would be used for the research and design of treatments for AIDS².

During the 1990s, her research focus turned to gene therapy and the use of ‘molecular knife’ ribosomes to represent HIV in stem cells, for which she oversaw what is considered to be the second research programme to be funded by the United States Government³. These studies were centred on Kaposi’s Sarcoma lesions (which are very common in AIDS patients) and led Wong-Staal to confirm the relationship between the quantity of Tat Proteins in HIV-1 infected cells and the amount of KS lesions in patients affected with HIV³.

Although she retired in 2002, she is still an important figure in the world of virology and molecular biology, having received several awards and substantial recognition for her contributions from many different entities such as The Asian American Heritage, the Discovery Magazine, and  The Daily Telegraph.

SHORT BIOGRAPHY

Flossie Wong-Staal was born in Guangzhou, China as the daughter of an import-export businessman and a housewife. Even though her mother never attended college, she claims: “my parents have been very supportive of my pursuing my education […] they never […] had the concept that girls should not […] have higher education, and, on the contrary, they were very happy and pleased and proud of my accomplishments”⁴ (p.1).

Flossie Wong-Staal

Wong-Staal attended an English-speaking school run by American nuns which followed the British education system back in China. The way such education is set up in Hong Kong, children must decide at a really early age if they want to go into science or non-sciencific area and, as she was a brilliant student, she went into science even though she was interested in many different fields⁴ (p.2).

In 1947, Flossie Wong-Staal travelled to America in order to attend university at the University of California in Los Angeles. In the 1940s, after the Communist Revolution, it was very common for promising Chinese students to fly to the States to pursue higher education⁷. In UCLA, she did a bachelor’s degree in Bacteriology, from which she graduated in 1968 magna cum laude; although she stated that no particular person or instance influenced her to study bacteriology; subjects such as microbiology and bacteriology were of particular interest to her⁴ (p.3).

In 1971, she married Steve Staal, whom she later divorced, and two years later they moved to Bethesda, in the state of Maryland. In 1972, she earned a PhD in Molecular Biology at the University of California, Los Angeles, and carried out a year of postdoctoral research at UC-San Diego. In 1973, she started working at the National Institute of Health (NIH) because Steve Staal also got a position at the institution.

Her postdoctoral work continued in 1974 when she left to work for Robert Gallo (1937) at the National Cancer Institute (NCI). His research centred on retroviruses, on “intracisternal A-particles, […] how they replicate, the biochemical analysis of intracisternal A particles”⁴ (p.7).

In 1982, she was named Chief of Section of Molecular Genetics of Hematopoietic Cells at NIH, a post she inherited from David Gillepsie after his retirement. The following year, her team at NCI identified “HIV as the cause of AIDS and […] two years later, Wong-Staal cloned HIV and then completed genetic mapping of the virus, […] [which] made it possible to develop HIV tests”³.

In 1990, she moved to the University of California, San Diego, where she became the director of its AIDS research centre “to develop possible treatments, including inserting gene coding to prevent growth and reproduction of AIDS cells”⁶. In that same decade, she became chief scientific officer and executive vice president of research for Immusol (San Diego), a company which “discovers, develops and commercialises products based on ribozyme gene therapy and ribozyme-mediated gene functional analysis”⁷.

In 2002, Wong-Staal retired from UCSD and now holds the title of Professor Emerita, where she keeps on working as a Research Professor. She is considered to be one of the most important scientists of our times and her main contributions have helped to the development of the field of biotechnology⁸.

SCIENTIFIC COLLABORATION AND RECOGNITION

Flossie Wong-Staal has developed all her work in a laboratory environment working side by side with other scientists and researchers. In the 1970s, she started collaborating with Robert Gallo because he was working on retroviruses, a field which was of interest for her⁴ (p.6); additionally, David Gillespie, the person who actually innovated the hybridisation procedure with Sol Spiegelman, was section chief within the lab, so she wanted to train with him in order to gain knowledge on the molecular techniques of hybridisation⁴ (p.7).

In 1981, Wong-Staal and Gallo were investigating the possibility of viruses linked to cancer and ended up discovering the Human T-Cell Leukaemia Virus (HTLV), which came to be the first virus proven to cause human cancer⁴ (p. 18). During the next two years, they also found a virus named HTLV-2 and the HTLV-3; the latter, is now known as HIV or Human Immunodeficiency Virus and was simultaneously discovered by the Pasteur Institute in France ⁶.

After being named Chief of section of Molecular Genetics of Hematopoietic Cells at NIH in 1982, her “goals were to understand the HIV virus at a molecular level; as it turned out to be a very complicated virus, [they] identified each of its genes and tried to prove the existence and function of the novel genes which were not found in other retroviruses”⁴ (p.10). 1982 turned out to be a very good year for her and her team as they attained several important advances in the field⁴ (p.11), which, in fact, allowed her to collaborate with important figures such as Ricardo Dalafaber, who was the first person to “show mic gene amplification in leukaemia cells in primate leukaemia”⁶.

1985 was the year of Wong-Staal’s main breakthrough or, as she stated, “the highlight of [her] career […] that period of intense discovery”⁴ (p.20). After she, Gallo and their team of NCI scientists had identified HIV as the cause of AIDS in 1983, a team of researchers led by Wong-Staal cloned HIV and completed the genetic mapping of the virus in order to develop HIV tests; for such research, she collaborated with other researchers such as Jennifer Fontini (she worked along with Wong-Staal in the mapping of the fas gene from the feline sarcoma virus)⁴ (p.12). This breakthrough is very important for the history of biotechnology and “her work is seen as a major step in understanding the way the virus worked, which, in turn, led to the antiretroviral drugs used today”⁹. In fact, all through the 1980s, in “ISI’s annual list of most-cited papers, published by Eugene Garfield in Current Contents, AIDS-related papers […] made up approximately a quarter of each year’s list”¹⁰. In fact, between 1981 and 1988, her work received “almost 7,800 citations from her peers, an impressive number for such a short period”⁹. Additionally, the UCSD chose Wong-Staal to be “the first recipient of the Florence Seeley Riford Chair for AIDS Research” in the University’s Department of Biology and Medicine¹¹.

From that moment on, Wong-Staal did not cease to research the complicated world of HIV and, starting in 1990, her research focused on gene therapy and used a ribozyme ‘molecular knife’ to represent HIV in stem cells³. The protocol she developed for her research was “the second one to be funded by the United States Government”³. In this period, a team of researchers led by Wong-Staal studied the effects of the Tat Protein within the viral strain HIV-1-which has a pivotal role in HIV-1 replication because it stimulates transcription from the viral long terminal repeat (LTR) promoter by binding to the TAR hairpin in the nascent RNA transcript¹² (p.2) found in Kaposi’s Sarcoma lesions, which are commonly found in AIDS³. The team performed a series of test on different cells infected by HIV-1 and in control (a culture of healthy human endothelial cells) for which Wong-Staal used a type of cellular analysis entitled Radioimmunoprecipitation³, an “inmunoprecipitation using antibodies or antigens labelled with a radioisotope”¹³. The results of these tests enabled to show that the amount of Tat protein present within HVI-1 infected cells is directly correlated to the amount of KS lesions an AIDS patient shows and, consequently, to develop new treatments for HIV/AIDS patients suffering from such lesions³.

Also, in the 1990s, Wong-Staal moved from NCI to UCSD, where she continued her research on HIV and, in 1994, she was named as chairwoman of UCSD’s Center for AIDS Research and elected to the Institute of Medicine of the US National Academies. Additionally, she started working at a San Diego-based company, Immusol, which she co-founded while still at UCSD,  where she turned the focus of the research into HCV therapeutics and renamed it iTherX Pharmaceuticals so that the name would reflect the activities developed⁴ (p.48).

An article published by The Scientist in May 1990, which focused on the citation records of relevant contemporary women scientists under the age of 45¹⁰, ranked her fourth on the list and “identified her as a researcher whose work in the 1990s [was] likely to be worthy of particular notice”¹⁰.

Recognition for Wong-Staal’s job in the field of biotechnology continued after the turn of the century and, following her retirement from UCSD in 2002, she was appointed Professor Emerita at the aforementioned university. In addition, the magazine Discovery named her one of the fifty most extraordinary women scientists in 2002³ and, in 2007, The Daily Telegraph heralded Dr Wong-Staal as number 32 out of the 100 top living geniuses in the “Top 100 Living Geniuses”¹⁴.

SHE SAID IT

For me, as for most researchers, the main motivation is simply the satisfaction of making discoveries, finding out things that no one knew before.

cited in Hellar, A.E. (28 Aug. 2013) “Flossie Wong-Staal”, Hellar Reviews: Science Fiction and Fantasy by Women,  https://hellarreviews.wordpress.com/women-in-science/flossie-wong-staal/   (last accessed 28 Feb. 2017)

It adds to the joy of discovery to know that your work may make a difference in people’s lives.

cited in “Meet Flossie Wong-Staal, pioneer in HIV research”, Scientista: Women in Science and Engineering, The Scientista Foundation Inc,

http://www.scientistafoundation.com/brain-break/meet-flossie-wong-staal-pioneer-in-hiv-research (last accessed 28 Feb. 2017)

Actually, I personally, throughout my career, have not experienced any overt discrimination on the basis of being a female or on the basis of being a foreigner. I mean, sometimes it’s hard to dissociate these two minority standings. But, obviously, I see it happening, and sometimes it’s real subtle. It could be at the higher level, you know, high-level decisionmaking, and that’s when the old boys’ club operates. But when you’re young and starting, I think I don’t see too much discrimination.

Wong-Staal, Flossie, interviewed by Victoria Harden and Caroline Hannaway (10 Dec. 1997), National Institutes of Health, https://history.nih.gov/archives/downloads/wongstaaltranscript.pdf (last accessed 28 Feb. 2017)

You need to have a passion for making discoveries because this is the most rewarding aspect of a scientific career. Eureka moments are few and far between. It’s important to go into a research lab, both to get some experience with the scientific process and see the kind of work that’s required. It’s also helpful to expose yourself to the passion and enthusiasm of outstanding scientist. In this way, you can get a glimpse of the dedication that science requires and also the satisfaction it can provide.

“Best of Public Health: Dr Flossie Wong-Staal” (2014), Asian Heritage Awards, The Asian Heritage Awards, http://www.asianheritageawards.com/best-of-public-health.html (last accessed 28 Feb. 2017)

THEY SAID IT

We are delighted that the biotechnology community has recognized Dr. Wong-Staal for her contributions to biotechnology, and moreover, in the field of functional genomics. The Innovator of the Year selection is a testimonial to Flossie’s pioneering work in drug target discovery here at Immuso,”commented Dr. Tsvi Goldenberg, Chairman and CEO of Immusol.

“Dr Flossie Wong-Staal of Immusol Receives Biotech Innovator of the Year Award” (10 Jul. 2001), Evaluate, Evaluate Ltd, http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=11826 (last accessed 28 Feb. 2017)

PRIZES, ACHIEVEMENTS AND HONOURS

1990:  Florence Seeley Riford Chair for AIDS Research (University of California San Diego)
1990: Fourth position in the ISI’s Science Citation Index files by Waksman Inst., Inst. for Advanced Study, Princeton, N. J.
2002: Asian American Heritage Award for the Best of Public Health (Asian American Heritage)
2002: One of the 50 most extraordinary women scientists (Discovery)
2007: Number 32 out of the Top 100 Living Geniuses (The Daily Telegraph)

WORKS BY FLOSSIE WONG-STAAL

 The following is a selection of publications by Flossie Wong-Staal made by WorldCat Identities depending of how widely held each work is:

with Gallo, Robert C. (1990), Retrovirus biology and human disease, New York, Dekker

with Franza, Robert / Bryan Cullen (1988), The Control of HUman Retrovirus Gene Expression, Cold Spring Harbor (NY), Cold Spring Harbor Laboratory.

with Haseltine, William A. (1988), The Molecular Biology of the AIDS Virus, Emmitsburg (MD), National Emergency Training Center.

with Ensoli, Barbara / Giovanni Barillari / S. Zaki Salahuddin / Robert C. Gallo (May 1990), “Tat protein of HIV-1 stimulates growth of cells derived from Kaposi’s sarcoma lesions of AIDS patients”, Nature, 344 (6270), pp. 84-86.

with Haseltine, William A. / Harvard AIDS Institute (1991), “Genetic Structure and Regulation of HIV” in Harvard AIDS Institute Series on Gene Regulation of Human Retroviruses volume 1, New York, Raven Press.

with Koff, Wayne C. / Ronald C. Kennedy (1991), AIDS Research Reviews, New York, Marcel Dekker.

with Koff, Wayne C. / Ronald C. Kennedy (1992), AIDS Research Reviews Volume 2, New York, Marcel Dekker.

with California University San Diego  School of Medicine / United States Army Medical Research and Development Command (1992), “Transdominant rev and proteased mutant proteins of HIV/SIV as potential antiviral agents in vitro and in vivo: annual report” in Archives of Human Sexuality and Identity: LGBTQ History and Culture since 1940, Washington D.C., Army Medical Research and Development Command.

with Koff, Wayne C. / Ronald C. Kennedy (1993), AIDS Research Reviews Volume 3, New York, Marcel Dekker.

with National Institutes of Health (U.S.) (1993), Gene therapy for AIDS: fantasy or feasibility?, Bethesda (MD), National Institutes of Health.

with California University San Diego Department of Medicine (30 Oct. 1993), Transdominant Rev and Protease Mutant Proteins of HIV-SIV as Potential Antiviral Agents in VItro and in Vivo (AIDS), San Diego, Ft. Belvoir Defense Technical Information Centre.

Wong-Staal, Flossie, “Flossie Wong-Staal’s Speech”, (Jun. 1994), International Conference on AIDS, Berlin, Germany.

Wong-Staal, Flossie, “Gene Therapy”, (10 Aug. 1994), International Conference on AIDS,  Yokohama, Japan.

with Gallo, Robert C. (2002), AIDS Vaccine Research, New York, Marcel Dekker.

National Institutes of Health (2011), “NIH 30th Annual Asian American Pacific Islander Heritage Month Observance”, The National Institutes of Health.

WORKS CITED

1.  The Editors of Merriam-Webster Dictionary, “Retrovirus”, Merriam-Webster Dictionary, https://www.merriam-webster.com/medical/radioimmunoprecipitation (last accessed 28 Feb. 2017)
2. Thomson, Gale (2006), “Flossie Wong-Staal Biography”, BookRags, BookRags Inc, http://www.bookrags.com/biography/flossie-wong-staal-wmi/#gsc.tab=0 (last accessed 28 Feb. 2017)
3. “Flossie Wong-Staal”, Revolvy, CC-BY-SA, https://www.revolvy.com/main/index.php?s=Flossie%20Wong-Staal&item_type=topic (last accessed 28 Feb. 2017)
4. Wong-Staal, Flossie, interviewed by Victoria Harden and Caroline Hannaway (10 Dec. 1997), National Institutes of Health, https://history.nih.gov/archives/downloads/wongstaaltranscript.pdf (last accessed 28 Feb. 2017)
5. “Chinese Immigration and the Chinese in the United States” (15 Aug. 2016), National Archives, The U.S. National Archives and Records Administration, https://www.archives.gov/research/chinese-americans/guide.html (last accessed 28 Feb. 2017)
6. Wong-Staal, Flossie (1946-)”, Dictionary of Women Worldwide: 25,000 Women Throught the Ages, Encyclopedia.com, http://www.encyclopedia.com/women/dictionaries-thesauruses-pictures-and-press-releases/wong-staal-flossie-1946 (last accessed 28 Feb. 2017)
7. “Immusol Inc: Company Profile”, Bloomberg, https://www.bloomberg.com/profiles/companies/IMSL:US-immusol-inc (last accessed 28 Feb. 2017)
8. “Dr Flossie Wong-Staal of Immusol Receives Biotech Innovator of the Year Award” (10 Jul. 2001), Evaluate, Evaluate Ltd, http://www.evaluategroup.com/Universal/View.aspx?type=Story&id=11826 (last accessed 28 Feb. 2017)
9. Robbins, Gary, Paul Sisson (4 Mar. 2013), “UCSD researchers help confirm HIV cure”, The San Diego Union-Tribune, The San Diego Union-Tribune, http://www.sandiegouniontribune.com/news/health/sdut-ucsd-hiv-richman-cure-2013mar04-story.html (last accessed 28 Feb. 2017)
10. The Scientist (19 Feb. 1990), Leading AIDS Researcher Chosen For New Chair At UC-San Diego, The Scientist: Exploring Life, Inspiring Innovation, webpage http://www.the-scientist.com/?articles.view/articleNo/10936/title/Leading-AIDS-Researcher-Chosen-For-New-Chair-At-UC-San-Diego/ (last accessed 28 Feb. 2017)
11. Grissom, Abigail (15 Oct. 1990), “Research: Top 10 Women Scientist of the ‘80s: Making a Difference”, The Scientist: Exploring Life, Inspiring Innovation, The Scientist, http://www.the-scientist.com/?articles.view/articleNo/11393/title/Research–Top-10-Women-Scientists-Of-The–80s–Making-A-Difference/
12. Das, Atze T., Alex Harwing, Ben Berkhout, (Sept. 2011) “The HIV-1 Tat Protein Has a Versatile Role in Activating Viral Transcription”, Journal of Virology, 85(18), pp. 9506.16, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165771/ (last accessed 28 Feb. 2017)
13. The Editors of Merriam-Webster Dictionary, “Radioimmunoprecipitation”, Merriam-Webster Dictionary, https://www.merriam-webster.com/medical/radioimmunoprecipitation (last accessed 28 Feb. 2017)
14. “Top 100 living geniuses” (30 Oct. 2007), The Telegraph, Telegraph Media Group Limited, http://www.telegraph.co.uk/news/uknews/1567544/Top-100-living-geniuses.html (last accessed 28 Feb. 2017)