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Past Winner
2004 NSERC Award of Excellence

David Dolphin

Killam Research Professor

The University of British Columbia


A mere five years ago, the diagnosis of age-related macular degeneration was forewarning of a gradual descent into total darkness. Dr. David Dolphin changed that. He's the lead creator of VisudyneTM, the world's most widely used ophthalmic drug ever, which since 2000 has saved the vision of approximately 300,000 people.

For Dr. Dolphin, the wonder of the drug isn't simply its ability to help people see the light; it's in the drug's interaction with light. That's because VisudyneTM is a porphyrin, one of a class of coloured light-interacting organic molecules that drive some of life's most fundamental processes and that have fuelled Dr. Dolphin's curiosity for the past 40 years.

"The most critical part of the development of VisudyneTM was understanding how you change the wavelength of the light they absorb. Because we needed to make them absorb light that blood doesn't," says Dr. Dolphin, one of three nominees for the prestigious 2005 NSERC Gerhard Herzberg Canada Gold Medal for Science and Engineering.

To create VisudyneTM, Dr. Dolphin drew on his groundbreaking research in the synthesis and physiological behaviour of these chemicals, dubbed the pigments of life.

Porphyrins, with their hundreds of known forms – all variations on a doughnut-shaped molecular frame of 20 carbon and four nitrogen atoms – are in many ways a chemist's dream. They're coloured (therefore easy to see), stable and bond with almost any metal. Porphyrin with an iron atom is a heme, the basis of the haemoglobin that makes blood red. Green chlorophyll is a porphyrin with a magnesium core. Vitamin B-12 is a porphyrin-like molecule with a cobalt atom at its centre.

In 1963, Dr. Dolphin broke into the pages of Nature with his first scientific publication – a description of the biological mechanism of Vitamin B-12. In the mid-1960s, while at Harvard, he proved what happens when a chlorophyll absorbs a photon of light, revealing the first step in the photochemical engine that fuels all life on earth. The research was the start of his pioneering work in biomimetic chemistry, which uses simplified test-tube chemical experiments to explore and explain natural processes.

By 1980, he had established himself as a world-leading porphyrin scientist and the editor of the seminal seven-volume set of books, The Porphyrins.

"At the time I was quite naïve," Dr. Dolphin says. "I thought that the books had covered off most of what had been, and would be known about porphyrins. That turned out to be just the beginning. That work catalyzed a revolution in porphyrin chemistry and it just expands every year. I'm just amazed."

Indeed, porphyrins are now known to be the basis of the pain-killing chemicals used by some biting insects to numb their victims, and they're the molecules we can thank every time we burn CDs and DVDs.

But perhaps the greatest surprise lay in using porphyrins as healing chemicals in light-based medicine, known more technically as photodynamic therapy or PDT. In the early 1980s, Dr. Dolphin teamed up with then UBC microbiologist Dr. Julia Levy, at first with the aim of creating therapeutic porphyrin-antibody couplings. Their attention soon turned to the burgeoning field of PDT and its potential for cancer treatment. Their research, supported initially by a grant from NSERC and continued in partnership with Vancouver-based biotech company Quadra Logic Technologies Incorporated (QLT Inc.) (where Dr. Levy was until recently CEO) led to the discovery of light-activated porphyrin molecules that could shrink tumours by killing new blood vessels. It was a crucial insight that allowed the further leap to age-related macular degeneration. The leading cause of blindness, macular degeneration is caused by a tangle of new blood vessels that eventually destroys the retina.

For more than five years Dr. Dolphin, leading research groups at UBC (where he holds the NSERC – QLT Inc. Industrial Research Chair in Photodynamic Technologies) and QLT Inc. (where he's Vice-President Technology Development), worked to turn a porphyrin molecule into the light-activated tactical killer that would become known as VisudyneTM.

VisudyneTM's therapeutic beauty is that it preferentially accumulates in the new blood vessels, is activated by harmless visible light (at a wavelength that's not absorbed by blood) and has a highly localized toxicity. Zap VisudyneTM with light, and for two thousandths of a second it energizes oxygen to wreak havoc on nearby cellular machinery. Turn off the light and it's a harmless molecule that the body can eliminate in several days.

Dr. Dolphin says his research, which has led to about 50 U.S. patents, has benefited enormously from its strong industrial partnership. It's also earned UBC about $30 million in royalties.

"I get my kicks out of solving problems, whether they're basic ones or more applied," says Dr. Dolphin. "For those university researchers that get involved in commercialization their basic research productivity almost always increases. I know from my own graduate students that they're very excited about getting involved in research that might eventually benefit humanity."

And as he enters his fifth decade of porphyrin research, Dr. Dolphin sees the potential for a new universe of porphyrin-based photodynamic therapies, including applications from cancer to hair replacement.

Accomplishments

Dr. Dolphin is one of the founders of modern porphyrin chemistry. During the past 40 years he has published almost 400 scientific papers and has authored or edited 18 books. These books range from an encyclopaedic two-volume set on Vitamin B-12 to the seven-volume The Porphyrins. His UBC lab has also been a major training ground for organic and synthetic chemistry students from around the world. He's trained 45 graduate students and 88 postdoctoral fellows.

The beneficial application of his research has guided Dr. Dolphin's collaborations. During his career he's consulted for most of the world's major pharmaceutical companies. Since 1987 he's been the Vice-President, Technology Development at the Vancouver-based biotech company QLT, and since 1992 has held the NSERC – QLT Inc. Industrial Research Chair in Photodynamic Technologies. This university-industry partnership resulted in the creation of the vision-saving drug VisudyneTM for which Dr. Dolphin received a 2004 Heroes of Chemistry award from the American Chemical Society.

Along with his own outstanding research and training, Dr. Dolphin has also been a research leader at UBC. Since 1985 he's variously held the positions of Associate Dean of Science, Acting Dean of Science and Acting Vice-President of Research.

Background

Born in London, England in 1940, David H. Dolphin earned his B.Sc. in 1962 and his Ph.D. in 1965 at the University of Nottingham. This was followed by a year-long postdoctoral fellowship in the lab of Harvard organic chemist Robert B. Woodward during a time filled with the excitement about the great strides being made in synthetic chemistry (Dr. Woodward won the Nobel Prize for chemistry in 1965). Dr. Dolphin joined Harvard's chemistry faculty as an assistant professor in 1966. In 1974, he left Harvard to join the faculty of science at the University of British Columbia where he is presently the Killam Research Professor. He was elected to Fellowship in the Royal Society of Canada in 2001 and to Fellowship in the Royal Society (London) in 2002.