FIRST BASE | By Kevin Davies
“An important part of the last few weeks has been … to distinguish reality from fantasy. Fantasy has been ‘the race’ – New York Times profile, 60 Minutes, guys on motorbikes in Time magazine… Reality is having the gene, not knowing what it does, and the realization that in the 20 years since we have been working on this project, more than 1 million women have died of breast cancer. We very much hope that something we do in the next 20 years will preclude another million women dying of the disease.”
—MARY-CLAIRE KING, ASHG Montreal 1994
November 1, 2012 | One of the most electrifying scientific presentations I’ve ever heard—complete with a rare standing ovation—came nearly two decades ago at the American Society of Human Genetics (ASHG) annual convention. The woman who gave those remarks—Mary-Claire King—is now the president of ASHG and will likely inspire thousands in attendance once again when she deliver’s her presidential address next week in San Francisco.
Back in It was 1994, King, for years the personification of the war against breast cancer, had suffered the scientific equivalent of a death in the family. King had been studying the genetics of breast cancer for two decades, stubbornly believing that the disease must have a hereditary component when most so-called experts rubbished the idea.
In 1990, her small team at UC Berkeley published a landmark paper in Science mapping the gene for the BRCA1 tumor suppressor gene to chromosome 17. (“BRCA” stands for breast cancer although at the time King joked it signified “Berkeley, California.”) The breakthrough had come when King’s group sorted their families by age-of-onset. Seven affected families with early-onset disease provided unequivocal data supporting linkage of a DNA marker on chromosome 17 to breast cancer susceptibility; the signal tailed off in other families, indicating the confounding role of other genetic (and environmental) factors.
King jubilantly announced those results to a packed session at the ASHG conference in Cincinnati, competing for attention on the same evening that the hometown Cincinnati Reds were extending their lead in the baseball World Series a few blocks away. But four years later, the tone was very different. After a massive search, the gene had been found—not by King but by her arch rivals, Myriad Genetics, a biotech company in Salt Lake City, Utah. By one estimate, King’s group was just 6 weeks behind.
At the 1994 conference in Montreal, a packed house gathered for a 60-minute “late breaking research” session in which a trio of Myriad researchers would discuss how the coveted gene was found. The talks were well received, but most of the audience was fascinated to see how King, generously invited to offer some brief closing remarks by the session host, Duke University’s Hunt Willard, would react.
What happened next was fairly extraordinary. King described how her team had had to wait until they were faxed a copy of the Science paper just before publication before they could even synthesize the PCR primers that would allow them to amplify the crucial gene segment and begin to glimpse the mutations in their unparalleled collection of breast cancer families. From that point on, it mattered little who had actually isolated the gene first—her group was going to work night and day regardless.
For the next 15 minutes or so, she presented pedigree after pedigree in which the molecular basis for the disease had been described, and moving stories of the impact of the carrier testing. For any casual observer who hadn’t been following the BRCA1 saga, it would have been easy to assume that it was King’s group that had isolated the gene, not Myriad (King congratulated her rivals but refused to mention the company by name). I’ve rarely heard about, let alone participated in, a standing ovation for a scientific presentation, and doubt I will experience a more emotional tribute than the outpouring for King that day.
Of course, for countless women and their families, the result of BRCA1 being isolated by a for-profit biotech rather than King or one of the other academic teams involved were profound. The far-reaching consequences of Myriad’s BRCA1 patent and subsequent monopoly on testing have reached all the way to the U.S. Supreme Court and continue to reverberate.
The death rate in 2011 in the U.S. from breast cancer was just under 40,000. As King dared hope in 1994, the rate has declined over the past two decades, and part of that is due to earlier detection better screening, and increased awareness. It’s a start, but also a sobering reminder of the painstaking process of turning genetic discoveries into targeted therapies.
As King prepares to address the ASHG delegates next week, she previews her presidential address in a guest editorial in this week’s Science magazine, “The Scientist as World Citizen.” She tells the story of a young citizen scientist filing reports from Tahrir Square during the uprising last year that aired on National Public Radio, whom she later discovered was studying the BRCA1 gene. King might see a little of her idealistic youthful self in the selfless and passionate Egyptian blogger.
“Solving complex problems, whether scientific, social, or political, requires honest and critical appraisal of data,” King writes. “Truth ultimately matters more than consolidating power, securing funding, or furthering agendas. In my experience, the most important questions often come from people on the front lines, and no question is too big to ask.”