The Science of Matchmaking
Effie Wang Petersdorf, Transplant Physician-Scientist
DNA’s twisting double helix structure is one of the most beautiful and bewitching images in all of science. Dr. Effie Wang Petersdorf can still recall the moment she fell under its spell.
She was an undergrad in a large lecture hall, sitting transfixed as Prof. Watson — of Watson and Crick and Franklin — described the code of life. Or at least what was known about it in the late 1970s. Scientists had started to sketch crude maps of the genetic code, but much remained uncharted.
In the decades since, Petersdorf has blazed trails deep into one critical region of DNA. Her research has helped illuminate how genetics influence the success or failure of bone marrow transplants, lifesaving treatments for patients with blood cancers and other diseases. During these procedures, a patient’s diseased bone marrow is wiped out and replaced with a donor’s healthy, blood-forming stem cells.
Petersdorf studies the molecular rules that define good matches between donors and patients. The better the match, the lower the patient’s risk of complications from the transplant. Her work has helped expand the number of lifesaving matches that happen at transplant centers around the world.
But she knows there could be more.
“We’re still exploring this world and teasing apart the genetics of how both patient and donor are contributing to a successful transplant,” she said. “We owe it to our patients to keep exploring.”
She started down this path in 1983, when a medicine residency rotation brought her to Fred Hutchinson Cancer Center. She studied under Dr. Don Thomas, who would shortly join Watson as a Nobel laureate for pioneering bone marrow transplantation.
“It was just incredible being taught by Don,” Petersdorf said. “The idea that you could replace someone’s immune system and that it could work and save someone’s life was just mindboggling.”
Even back then, doctors knew it was important for patients and stem cell donors to share the same tissue type, or HLA.
HLA is a protein that plays a key role in the immune system, helping the body identify cells that are foreign. A good HLA match cuts down the risk that the patient will reject the donor’s cells, or that the donated cells will attack the patient.
The region of DNA related to HLA is one of the densest, most complex places in the entire human genome. Petersdorf followed in the footsteps of her mentor, Fred Hutch’s Dr. John Hansen, to fill in the blanks on the HLA map.
"We’re still exploring this world and teasing apart the genetics of how both patient and donor are contributing to a successful transplant. We owe it to our patients to keep exploring."
Over the years, that work has helped extend the curative power of transplants to more patients. When Fred Hutch’s transplant team performed the first procedures, the only candidates they would consider were those with well-matched sibling donors. Today, donors and patients can come from opposite ends of the globe.
And a global network strives to connect them. In the late 1990s, Petersdorf started the International Histocompatibility Working Group, whose diverse cast of scientists, labs and transplant centers is still collaborating to decipher the genetic code for the HLA system.
As much as she loves the lab — where both of her parents spent their careers — Petersdorf always wants to speed insights there to patients in the clinic. Because as much as research has helped save lives, as a cancer physician, she still sees people she can’t save. So she pushes on, deeper into that all-important region of DNA.
“One thing that Don taught me is that every patient teaches you something new,” she said. “If we continue to be open-minded and think out of the box, then the patients we see tomorrow or next year or 10 years from now, just like the patients before them, will enjoy better and better outcomes. And we're going to get to that cure.”
— Updated October 5, 2023
