Dr. Yuet Wai Kan: Pioneer in Molecular Genetics

reprinted from Issue 14, Spring 2012 of Frontiers of Medicine (PDF)

“Human genetics has completely changed. You have to change to the new techniques as they develop," said Yuet Wai Kan.

Yuet Wai Kan (pronounced “yoot WHY conn”), MBBS, DSc, a world-renowned leader in hematology and genetics, says his decision to pursue a career in medicine was simple.

“My father said, ‘You are going to be a doctor,’ and that was it – honest,” says Kan, now the Louis K. Diamond Professor of Hematology, with a smile. “I was the youngest of 12 children, and none of my siblings were in medicine, so mine was the last chance he had.”

Kan earned his medical degree from the University of Hong Kong Medical School, and received clinical training in Hong Kong, the U.S. and Canada. During his training, he saw a patient with thalassemia – a genetic blood disorder that can cause anemia – sparking his research interest in genetics and hematology. “This was in the ’60s, and very little was known about this type of thalassemia,” says Kan. “It could be very severe, so that the fetus actually died in utero.”

After serving on the faculty at Harvard Medical School, Kan was recruited in 1972 as chief of the Hematology Service at San Francisco General Hospital, and became a Howard Hughes Investigator in 1976. “That was a period of very rapid growth at UCSF,” recalls Kan. Among his collaborators at UCSF were future Nobel laureates Harold Varmus, MD (now director of the National Cancer Institute), and J. Michael Bishop, MD (former chancellor of UCSF), and Herbert Boyer, PhD, who later cofounded Genentech. “We learned some basic research techniques from them, and they helped us a lot,” says Kan.

Applying Genetics to Disease

Kan pioneered the use of recombinant DNA and DNA cloning to diagnose thalassemia and sickle cell anemia at the molecular level, detecting the exact genetic mutations responsible for these disorders. Kan also discovered and described restriction fragment length polymorphisms (RFLPs), now known as single nucleotide polymorphisms (SNPs), which he employed to diagnose sickle cell anemia prenatally, and which eventually made human disease gene mapping possible.

“Dr. Kan must be counted among the most distinguished molecular geneticists of the last half century,” says Robert Nussbaum, MD, chief of the Division of Medical Genetics and the Holly Smith Distinguished Professor in Science and Medicine. “His work in the molecular genetics of human blood disorders served as the foundation for much of the recent explosion of molecular diagnostics over the past four decades, while his discovery of DNA polymorphism ultimately paved the way for the Human Genome Project.”

Kan has been honored by almost every scientific society, including the National Academy of Sciences, the American Philosophical Society, and the Royal Society of London. He has received many prestigious awards, including the Shaw Prize in Life Science and Medicine, the Albert Lasker Clinical Medical Research Award, and many others. He was elected as a member of the Institute of Medicine, and with Sir David Weatherall, MD, FRCP, FRS, most recently shared the Karl Landsteiner Award at the annual meeting of the American Association of Blood Banks.

Despite his prolific achievements, Kan remains modest. “A lot of discovery, I found by accident,” he says. “Also, human genetics has completely changed. You have to change to the new techniques as they develop.” For example, he notes that the genetic sequencing work that used to require a year’s labor can now be done overnight.

Kan is currently developing stem cell therapies to cure sickle cell anemia and thalassemia. His lab is working to transform a patient’s ordinary skin or blood cells into stem cells, fix the genetic mutation, grow these corrected cells back into blood cells, and transplant them back into the patient. Because the original cells came from the patient, the hope is that the transplanted cells will not trigger rejection by the autoimmune system. He is also testing a similar approach to treat HIV infection.

Kan lives in San Francisco with his wife, Alvera, and on weekends enjoys cultivating a small vineyard in St. Helena.

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