M. Katharine Holloway and Chen Zhao

Ten years after AZT was developed (see Janet Rideout), the tide truly changed for AIDS. In the 1990s a new class of drugs called protease inhibitors came on the scene. M. Katharine Holloway and Chen Zhao are two of the chemists who worked on teams that developed these important drugs. Protease inhibitors squash a type of enzyme (called protease) in the HIV virus, making new copies of the virus harmless. When combined with other drugs, like AZT, protease inhibitors can greatly extend the lifespan of HIV patients. By the late 1990s this “combination therapy” turned HIV infection from a death sentence into a disease that can be managed for long periods, though it is still incurable. Protease inhibitors have helped cut the U.S. death rate from AIDS by roughly 70 percent.

About M. Katharine Holloway

M. Katharine Holloway (born 1957) is a native of Tupelo, Mississippi. When she was six years old her family moved to Laurel, at the opposite end of the state. She remembers being jealous of the chemistry set her older brothers got for Christmas one year. (This seems to be a common story among girls who grew up to be chemists.)

Holloway stayed close to home for college, studying at the University of Southern Mississippi in nearby Hattiesburg. Having a talent for languages, she first majored in French. But she also loved science, so she eventually decided to double major, studying environmental science along with French. Environmental science involves both chemistry and biology, but when Holloway realized she was better at chemistry than biology, she changed her second major to chemistry. She attended graduate school at the University of Texas at Austin, studying computational chemistry.

Computational chemistry uses computers to make models of molecules before they are synthesized (made by a series of chemical reactions) in the laboratory. Since drugs, which are essentially molecules, work by interacting with other molecules in the human body, computational chemists make models both of the potential drug molecules and the molecules they want the drug to interact with in the body. Then they put the model molecules together in a computer simulation to see how they interact. Using computer simulations, scientists can predict which molecules might make good drugs. Then scientists have only to synthesize and test the molecules that seem to work well in the computer simulation, saving lots of time and money.

After earning both a master's degree and a doctorate, Holloway moved to Pennsylvania in 1985 to work at the pharmaceutical company Merck as a computational chemist. She was the first woman to work in her department. In the early 1990s her computer simulations showed that one particular drug candidate might be good at fighting HIV, the virus that causes AIDS. The molecule was synthesized and tested, and is now the protease inhibitor indinavir sulfate, which Merck sells under the trade name Crixivan.

Holloway's husband is also a computational chemist, working at another pharmaceutical company, Johnson & Johnson. The Holloways have three sons.

About Chen Zhao

Chen Zhao was born in 1956 in Beijing, China, the child of two scientists. She earned her Ph.D. from Beijing University. She and her husband, Qun Li, who is also a chemist, both came to the United States to do postdoctoral work at Boston College. After their time at Boston College the two went to work at Abbott Laboratories, a pharmaceutical company. Her husband was hired first but had to postpone his start there because the couple's first son was born on the very day he had been scheduled to begin work.

Not long after that, Zhao also went to work at Abbott. Eventually she became part of a team investigating a new treatment for AIDS and HIV infection. She synthesized many compounds before she created the one that did what everyone at the laboratory wanted it to do. That compound is the protease inhibitor ritonavir. Ritonavir turned out to be a powerful AIDS treatment, and Abbott began selling it under the name Norvir.