A lot of progress towards combatting HIV/AIDS has been made possible by female scientists, but they’ve often been overshadowed. Yesterday I told you the story of one such woman, Flossie Wong-Staal who, among other achievements, was the first person to clone HIV & determine its genetic sequence. If you missed that story don’t worry, I recap it here. And I also tell you the story of 4 other female scientists who’ve been instrumental in the fight against Acquired ImmunoDefficiency Syndrome (AIDS) & the virus that causes it Human Immunodeficiency Virus (HIV): French virologist Françoise Barré-Sinoussi , who co-discovered HIV; Janet Lister Rideout, an organic chemist and one of the scientists who discovered that azidothymidine (AZT) could be used to treat HIV; Mathilde Krim, biologist and HIV/AIDS crusader who founded the nonprofit that became the Foundation for AIDS Research (amfAR); and Namandjé N. Bumpus, a pharmacologist who studies the effects of antiretroviral drugs. Note – there are a lot of other amazing women who have done/are doing HIV/AIDS research, but these are just a handful that I’ve covered in the past.
When the AIDS crisis struck, some tried to isolate themselves or ignore the problem – not this woman! French virologist Françoise Barré-Sinoussi co-discovered the cause of AIDS, HIV. Before this cause known, gay men and other populations hit hard by AIDS faced strong discrimination and stigma. Unfortunately many of those groups still face discrimination for other reasons…. but this discovery was a crucial step in understanding how AIDS spreads, helping to combat both the disease and the climate of fear that surrounded it.
Barré-Sinoussi made the discovery in 1983 while working at Paris’ Pasteur Institute (where she started as a volunteer). In recognition of her work, she and her former mentor Luc Montagnier were awarded the Nobel Prize in Physiology or Medicine in 2008. Barré-Sinoussi started her own lab at the Pasteur in 1988, where she continued research on HIV: basic research including factors that affect its transmission as well as more translational explorations into potential treatment and prevention measures. She has also been actively involved in international AIDS organizations including UNAIDS-HIV and the International Aids Society (where she served as president from 2012 to 2014) and has trained many of the “next generation” of AIDS researchers.
Additionally, Barré-Sinoussi has been a strong advocate for women in science. I was personally inspired by her when I had the great honor of hearing her speak at a special meeting at Cold Spring Harbor Laboratory: HIV/AIDS Research: Its History & Future.
photo credit: U. Montan
Virologist and molecular biologist Dr. Flossie Wong-Staal was the first person to clone and sequence a virus of the type that causes HIV (a pathogenic human retrovirus), and later she was the first to clone HIV itself, a breakthrough that helped her and her team figure out the function of the HIV virus’ different parts.
She was born Yee Ching Wong in China in 1947 and her family fled to Hong Kong in 1952. The first woman in her family to work outside the home or pursue an advanced education, she left Hong Kong as a teenager to attend UCLA, where she earned a BS in bacteriology followed by a PhD in molecular biology.
She moved to the NIH’s National Cancer Institute (NCI) in 1973 to work with Dr. Robert Gallo studying retroviruses, a type of virus that inserts itself into a host cell’s DNA. There, she was part of a team that co-discovered the retrovirus that causes AIDS, HIV (a second team, at the Pasteur Institute in Paris, including Françoise Barré-Sinoussi (another amazing female scientist we’ve profiled) also made this discovery). This breakthrough was only one (important) step in scientists’ contribution to the fight against AIDS. They still needed to figure out how this virus was able to cause the devastating disease, and in order to do that they needed to see what it contained.
Wong-Staal was able to clone and genetically map the HIV virus. Knowing the sequence helped in the development of blood tests for the virus and having the map helped them figure out the function of the HIV virus’ different parts, identifying several of its key components. Her team was also able to show that the virus depleted the immune system’s T cells, helping definitively pin down HIV as the cause of AIDS.
In 1990, she moved to the University of California, San Diego (UCSD), where she continued to study HIV as the Florence Riford Chair in AIDS Research. In 1994, she was chosen to lead UCSD’s Center for AIDS Research, the same year she was elected to the National Academies’’ Institute of Medicine. She retired in 2002 as Professor Emerita but continued a career in biotechnology, co-founding and serving as the Chief Scientific Officer of iTherX Pharmaceuticals, which researches treatments for another deadly virus, hepatitis C. Sadly, Flossie did July 8, 2020. more: https://bit.ly/flossiewongstaal
Mathilde Krim (1926-2018)
Among her other accomplishments, biologist and HIV/AIDS crusader Mathilde Krim founded the nonprofit that became the Foundation for AIDS Research (amfAR). Krim was born in Italy in 1926 and raised in Switzerland, where she received degrees in genetics from the University of Geneva. She worked for a time at the Weizmann Institute of Science in Israel before moving to New York, where she took a position at Cornell University Medical School and, later, Memorial Sloan Kettering Cancer Center.
She was deeply involved in research on the use of the drug interferon to treat leukemia when a physician friend drew her attention to mysterious disease clusters we now know to be caused by HIV/AIDS. Showing her characteristic flexibility in techniques and pathways, but never morals, she switched her research focus to HIV. Quickly becoming deeply involved in the HIV/AIDS community, she was deeply troubled by the stigma surrounding the disease, stigma she began to work tirelessly to dispel, in part through helping explain the science behind it.
Krim knew that she was in a unique position to address the AIDS crisis – she had a strong scientific background as well as connections to people in power (and sources of money) through her movie mogul husband, Arthur Krim. Utilizing these resources, she co-founded what would become amfAR in 1983. She served as amfAR’s chairman for over a decade, helping introduce legislation for increased research into AIDS as well as improved access to AIDS treatment. In addition to working through scientific and political channels, she recruited prominent celebrities to her cause – through fundraisers and events they raised millions of dollars while also helping with destigmatization.
Mathilde Krim has been described as a “scientist turned activist,” but these roles are not mutually exclusive – Krim was a scientist AND activist. After decades of research, she eventually left academia to focus on advocacy; but when she left the lab, she didn’t leave science, she merely contributed from new angles. Furthermore, Krim was an advocate all her life, active in numerous civil and human rights movements around the world. No, Krim was not a scientist TURNED activist, she was a scientist AND activist who was able to unite these two roles to great effect.
Photo credit: amfAR
Janet Rideout is an organic chemist and one of the scientists who discovered that azidothymidine (AZT) could be used to treat Human Immunodeficiency Virus (HIV). She also played a key role in the development of acyclovir, the first effective treatment for herpes viruses.
Rideout was born Janet Litster January 6, 1939 in Bennington, Vermont. She received bachelor’s and master’s degrees in chemistry from Mount Holyoke College followed by a PhD in organic chemistry from State University of New York, Buffalo (UB) in 1968. Shortly before graduating from UB, Rideout was hired by chemist and future Nobel laureate Gertrude Elion to work at a small US subsidiary of the British pharmaceutical company Burroughs Wellcome Company (now GlaxoSmithKline).
In June 1984, Burroughs Wellcome initiated a program to identify chemical compounds that might be effective against HIV, and they put Rideout in charge of choosing which compounds to test. There was limited knowledge about HIV at the time, but Rider’s search was aided by the finding that HIV was a retrovirus, a type of virus that transfers between cells with its genome encoded in RNA but, once it infects a host cell, reverse transcribes its RNA genome into a DNA copy which it then inserts into the host cell’s DNA, so that the cell and all its progeny are perpetually infected. Knowing that HIV was a retrovirus, Rideout searched for compounds with antiretroviral activity.
One of the compounds she chose to test was azidothymidine (AZT), a structural mimic (analog) of the canonical nucleoside thymidine, one of the building blocks of DNA. Unlike thymidine, AZT doesn’t have the chemical group needed to link nucleotides together, so it could potentially act as a chain terminator (when the virus tried to reverse transcribe its RNA, it would incorporate the analog and get stuck since additional nucleotides couldn’t link to it).
Colleague Marty St. Clair tested it against two animal retroviruses, and found it to be highly effective. To see if it was also active against HIV, they collaborated with scientists at the National Cancer Institute (NCI), including Samuel Broder and Hiroaka Mitsuya, who found AZT to be highly effective against HIV in human cells, and it went on to become the first FDA-approved treatment for HIV. Rideout is listed as the first co-inventor on the patent for the use of AZT to treat HIV (one of more than 40 U.S. patents she now holds).
The rollout of AZT, given the chemical name zidovudine and the proprietary name Retrovir, was contentious, as the product was rushed to market and approved at doses later shown to be toxic. Additionally, many protested the high price of the treatment. Today, AZT is given at lower doses and as part of a combined antiretroviral therapy for AIDS. It is also important for preventing the transmission of HIV from mother to unborn child. It is on the WHO list of essential medicines.
After over 26 years at BW, she moved to Inspire Pharmaceuticals (now part of Merck) where she studied nucleoside-based signaling molecules. She retired in 2001.
Namandjé N. Bumpus
Many life-saving drugs, including those used to treat HIV & hepatitis, can have side effects that themselves can be life-threatening. Often these side effects come from breakdown of the drug into toxic compounds. Pharmacologist Namandjé N. Bumpus uses mass spectrometry and molecular pharmacology to figure out what toxic compounds are produced from these drugs, why they’re toxic, and how their toxic effects can be prevented.
In addition to carrying out this critical research as a Professor of Medicine and Pharmacology at John Hopkins University, she was recently named Director of the Department of Pharmacology and Molecular Sciences! This makes her the first Black woman to become a department director at Hopkins Medicine and – currently – the ONLY Black woman chairing a pharmacology department at any medical school – in the entire United States.
Bumpus studies anti-HIV drug metabolism – metabowhatta? Metabolism is just a term we use to describe the chemical changes our body makes to molecules, and metabolite’s what we call the changed version. When you ingest a chemical that’s in one form, that’s not necessarily the form it stays in as it travels throughout your body and “does its thing.” You take some drug, your liver does something to it and, bam – it’s a metabolite.
Just like the food you eat gets processed, the pharmaceutical drugs you take do too. They’re already pretty small (much smaller than that bite of sandwich) but they can still get broken down further. And they don’t just get broken down, they can also get added onto or just tweaked a bit. All of these changes fall under “metabolism” and it’s a big focus for pharmacologists, because these changes can affect the drugs’ activity – either positively or negatively. Different people can have different variants of the the proteins that do this metabolism stuff (including the cytochromes, aka CYP proteins), so different people sometimes metabolize drugs differently.
Bumpus researches what metabolites form when patients take anti-HIV drugs, how they form, where they go, how they cause problems, how we can tell they’re causing problems before things get too bad, and whether we can keep them from causing problems.
Among other accomplishments, Bumpus worked out the pathway of metabolism of several anti-HIV drugs including tenofivir & Riplivirine (RPV). She found that genetic variants in CYPs can make them more or less active at metabolizing some of these drugs. So some patients might have drugs buildup while others need higher doses. This sort of thing is the realm of “pharmacogenetics” – the idea is that, for drugs where there is a known difference based on what version of a specific gene you have (the genotype) doctors should take that into account when prescribing a dosage – or maybe they need to prescribe a different drug altogether.
But often the dosages are set based on studies done just white people, which means that people of color, who are more likely to inherit certain genetic variants, can end up receiving ineffective doses. Bumpus found that one such variant, CYP3A5*1, which is rare among white people, but common among African Americans (almost 1/2 of African Americans have 2 copies of it), makes their bodies better at “detoxing” an HIV treatment & pre-exposure prophylaxis drug called maraviroc (trade name Selzentry). https://bit.ly/2VpoM06
This might sound good, but “detoxing” the drug means their livers chemically modify the maraviroc into a form which, instead of preventing or treating HIV infection by blocking HIV from getting into cells, just gets removed from the body. Basically, their cells are “too good” at getting rid of the drug, so they can end up being underdosed. Bumpus published her findings and pushed the drug makers into doing follow-up studies. And she continues to advocate for diversity in medical research.
Bumpus earned a bachelor’s degree in biology from Los Angeles’ Occidental College, followed by a Ph.D. in pharmacology from the University of Michigan-Ann Arbor. She then did a postdoctoral fellowship at the Scripps Research Institute. Her many honors include one from a president himself – President Obama awarded her a Presidential Early Career Award for Scientists and Engineers. She also received 2014 Tanabe Young Investigator Award from the American College of Clinical Pharmacology and ASPET’s 2015 Drug Metabolism Early Career Achievement Award.⠀
Bumpus is one of far too few Black female professors in the biomedical field and she’s working to change this. She served as Hopkins’ first associate dean of institutional and student equity and instituted mentoring programs to expand access to resources and opportunities. more: https://bit.ly/diversitybumpus
Photo credit: John Hopkins University