Long before Virginia Man-Yee Lee earned international acclaim for her work on Alzheimer’s, Parkinson’s, and other diseases of the brain, a brief stint at a drug company left her unsure about her future as a scientist, and she hatched a backup plan:
In 1984, she earned an MBA at the University of Pennsylvania’s Wharton School.
Lee never needed a backup plan, soon making her mark as a neuroscientist at Penn, but that business degree might come in handy in coping with her latest achievement. On Thursday, she was announced as the winner of a $3 million Breakthrough Prize — one of seven such awards to be given to scientists at a Nov. 3 ceremony.
The high-profile prizes, now in their eighth year, are funded by a who’s who of the tech world: Google cofounder Sergey Brin; Facebook cofounder Mark Zuckerberg and his wife, physician-philanthropist Priscilla Chan; Tencent founder Ma Huateng; tech investor Yuri Milner and his wife, Julia; and 23andMe founder Anne Wojcicki.
Among the other winners are the team of more than 300 scientists that captured the first image of a black hole, announced in April. The seven prizes will be given at the NASA Ames Research Center in Mountain View, Calif., in a ceremony broadcast live on the National Geographic Channel.
Lee, director of the Center for Neurodegenerative Disease Research at Penn’s Perelman School of Medicine, seemed as excited by the chance to meet the funders of the prize as she was about the honor itself.
“These people are just superstars in their field,” she said.
Many would apply that term to Lee. In more than 30 years, she has made major discoveries about nearly every disease that is marked by abnormal, “misfolded” proteins in the brain: the chemistry of how they behave, where they are located, and what causes them to form. In 2006, for example, she showed that two of these diseases — frontotemporal dementia and ALS (Lou Gehrig’s disease) — were characterized by clumps of the same type of protein.
Much of her research is a joint effort with the codirector of her lab, pathologist John Q. Trojanowski, who also is her husband. The two are known especially for challenging the longtime theory that Alzheimer’s is caused by plaques of proteins called beta-amyloid, arguing that a key culprit may be a different kind of protein aggregate called tau. Dozens of drug trials based on the amyloid hypothesis have failed to stop the disease, though the tau approach also has not been successful. Some researchers now are studying whether infections might play a role.
It may be that such diseases will require “cocktails” of drugs to address multiple problems, Lee said.
The lack of good treatments for any of the neurodegenerative diseases has frustrated patients. But Lee and others have been tackling the problem for just a few decades — a near-blip on the time scale of scientific discovery. She remains optimistic that success is possible.
“We just have to work hard at this,” she said. “Hopefully at some point in the near future, maybe in five or 10 years, someone will have something that provides hope for people.”
Hard work is Lee’s calling card. She and Trojanowski oversee a lab with close to 50 employees, publishing 15 to 20 studies a year. The pair rarely spend more than a week each year on vacation, though they recently traveled to Uganda for 11 days to see gorillas.
Lee grew up in China in a traditional family that encouraged her to study the piano, which she did for years. But by the time she went to college in England, she shifted her sights to chemistry, later earning a doctorate in biochemistry at the University of California, San Francisco.
She and Trojanowski met in Boston while she was a postdoctoral fellow at Boston Children’s Hospital and he was at Harvard. Married in 1979, the two soon moved to Philadelphia for Lee’s job at what is now called GlaxoSmithKline.
But she found the job did not allow her to pursue her passion in neuroscience, so she switched back to academia, joining her husband at Penn. And just in case her research career did not take off, she earned the Wharton degree.
But take off it did. The two began collaborating in earnest in the mid-1980s, though they did not take up neurodegenerative disease until the end of the decade. The pair soon became known for having spirited arguments over their work.
Scientifically, it is a good match. As a pathologist, Trojanowski studies brain samples for signs of disease, while Lee teases out the underlying chemistry that causes it.
Though Trojanowski’s name is not on the Breakthrough Prize, the pair have won other honors together, and sometimes he is recognized by himself.
“I don’t bother myself about the whys and the wherefores,” Trojanowski said. “I’m just excited that our research is being recognized at a level of deserving such a phenomenal prize.”
Asked what she would do with the money, Lee said she had not given the topic much thought. While the money can be used for any purpose, she said she might set aside some of it to support her work — specifically, “out of the box” experiments for which it might be hard to win support from the government and other traditional funding sources.
Lee readily acknowledges that she and her husband are nearing the age when some people’s brains start to show signs of the very diseases that have consumed the couple’s careers. She demurred when asked for their ages, but said she is not concerned about slowing down, in part because she has no family history of such diseases.
Their continued success is the result of staying mentally and physically active, she said. The pair, who live in Center City, go to the gym three times a week and she spends another 20 minutes each day on an elliptical trainer.
“If you keep your body and mind active, you’re much better off than couch potatoes,” she said.
Mindful of her unusual career path, with the detours in industry and at Wharton, she mentors undergraduates and also invites two to five high school students to the lab each summer.
“My career was very zigzag,” she said. “I never had a role model. But it worked out."
The funders of the Breakthrough Prize would agree.
Other Breakthrough Prize winners include:
Alex Eskin (University of Chicago), mathematics
Jeffrey M. Friedman (Rockefeller University), life sciences
F. Ulrich Hartl (Max Planck Institute of Biochemistry) and Arthur L. Horwich (Yale University), life sciences
David Julius (University of California, San Francisco), life sciences
Sergio Ferrera (CERN), Daniel Z. Freedman (MIT and Stanford University), and Peter van Nieuwenhuizen (Stony Brook University), physics