The Lab Is Her Kingdom

The Lab Is Her Kingdom
October 2008 By Matthew Dublin
To try and encapsulate in a few sentences what Mary-Claire King has done, not only for genomics and female scientists around the world, but for the human race, is a futile pursuit. Clearly, this is one woman who needs no introduction, but it behooves us to mention a few key achievements for which King will surely be remembered in years to come.
To say that her career started with a bang is an understatement. In 1973 at the University of California, Berkeley, King published her doctoral dissertation - and it landed on the cover of Science. In it, she demonstrated through comparative protein analysis that the humans and chimpanzees are 99 percent genetically identical. Since the early 1980s, King used her skills to spearhead efforts fighting human rights abuses in South American, Asia, and Europe with a method she developed that used mitochondrial DNA and HLA-serotyping markers. In 1990, while at Berkeley, King developed techniques that led to the discovery of the BRCA1 gene, which is now well known to be strongly implicated in breast and ovarian cancer.
But King, currently a professor of genome sciences and medicine at the University of Washington, says that her graduate studies did not begin without some struggles. In fact, King says she grew frustrated while first attempting to complete her graduate work on the Berkeley campus during those wild and wooly days of the late 1960s, with the constant presence of the US Army and local police. "From the time I started graduate school and finished, it was long and fraught," King says. "I ended up dropping out in the middle and going to work for Ralph Nader and then coming back."
Upon returning, she began working in the lab of the late Allan Wilson, whom she credits with informing her on the finer points of running a successful lab. It is worth noting that it was Wilson who convinced King to stay at Berkeley and continue working on her PhD, rather than taking a job offer with Nader in Washington, DC. "Working with Allan was transformative. He was always focused on the science and focused on the data, and he allowed one to free oneself of all the insecurities," she says. "It didn't make failed experiments any less discouraging, but it did mean that you weren't being judged as a person, you just needed to do the experiment again."
She also says Wilson was great when it came to listening to what everyone in the lab had to say. The ability to hear what the people in one's lab are saying and try to give useful feedback is enormously important, she says - and it's something she is still trying to perfect in her own work to this day.
Confidence and funding
King says that the key characteristics she looks for in young researchers aiming to join her lab are curiosity and a strong work ethic. "Background can be learned and techniques can be taught, but only to a receptive person who is curious and is prepared to put in the time when experiments don't work," she says. "Those are the most valuable types of people I've found since doing this since 1974."
A key element of being a good leader is bringing home the proverbial bacon, and the ability to do so is one thing King makes an effort to instill in her postdocs as they venture out into the world. "Clearly you can't run a lab if you can't bring in the money, and the primary job of the lab director is to bring in the money and let the postdocs and students have at it," she says. "So you need to give them a sense of where the money is buried, and not to get discouraged when it takes multiple rounds to get it."
Eric Lynch, co-founder of Sound Pharmaceuticals, a biotech company focusing on drug discovery for the auditory system, remembers his time with King fondly. "She instilled in me a desire to take on really hard problems and pursue the answers doggedly despite the critics and status quo," he says. "She definitely gave me confidence in myself as a researcher and let me know that the results mattered. ... She was also an inspiration on how to build research teams."
One event during his stay in the King lab was particularly memorable: the presentation of the team's findings for BRCA1 at the Cold Spring Harbor Laboratory. "I went up to the podium showing a slide with a razor blade and a pulsed field gel. I then proceeded to explain how YACs could be gel isolated in sufficient quantity for radio labeling and screening of cDNA libraries - oh, and here are all the genes we found," he says. "People were pretty surprised and supportive, and with all of the genomic sequencing taking hold and the enamorization of exon trapping, here was the King lab getting it out and getting results."
King feels that it is important for would-be researchers to understand what being in a lab is all about, and that it's so much more than just science. "Very few people outside of experimental science recognize what a lab culture is. It's somewhere a cross between a kibbutz and a family, and it's very hard to convey to people who don't live it," she says. "The combination of the closeness day to day, the transition of people coming out and new people coming in so that people start as newbies and then end up mentoring other people, it's a very special kind of culture."
Naming Names
King says that more than 50 postdocs and graduate students have passed through her lab. Here are just a few of those who were lucky enough to do so.
Lori FriedmanDuring her time with King, Friedman was hard at work helping her mentor to further elucidate the role of BRCA1 in breast and ovarian cancers. After completing her graduate studies in 1995 and landing several fellowships, she eventually headed to her current position, director of cancer signaling and translational oncology at Genentech.
Jeff HallKing remembers former graduate student Jeff Hall fondly as the one who helped map BRCA1. After leaving academia, Hall jumped the fence to industry, serving as the vice president and director of several biotech companies. He is currently vice president of cell biology at Genoptix Medical Laboratory.
Jeanette McCarthyThis former King lab member is now focused on the dyslipidemia associated with chronic hepatitis C virus infection. McCarthy is currently an associate professor in the Department of Community and Family Medicine at the Duke Institute for Genome Sciences and Policy.
Ruth OttmanOttman's primary research area is genetic epidemiology and research designs for testing gene-environment interaction, methods for collection of valid family history data, and approaches to assessing familial aggregation. She is a professor of epidemiology at the Columbia University Mailman School of Public Health.
Nancy SpinnerSpinner left the King lab after finishing her PhD in 1984 and went on to focus her efforts on identifying genes that cause congenital diseases. Currently, she is a professor of pediatrics and genetics at the University of Pennsylvania School of Medicine.
Elizabeth SwisherSince her time as a grad student in King's lab, Swisher has continued to work on breast and ovarian cancers - both independently and with King. She is now an associate professor of gynecologic oncology at the University of Washington.
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