David T. Wong

from Nature Reviews Drug Discovery

David Wong's journey to becoming one of a team of scientists to revolutionize the treatment of depression by developing the drug fluoxetine (Prozac; Lilly) began at school in Hong Kong where the principal, Herbert Noble, "a wonderful teacher", first piqued his interest in chemistry, a fascination that he carried with him into college at National Taiwan University. With the encouragement of his parents, he left Hong Kong for the United States, where he majored in chemistry at Seattle Pacific University. "Being a small college, the classes were small, but we had wonderful professors who maintained my interest in chemistry, especially organic chemistry." Wong then had the opportunity to take a summer internship in synthetic chemistry and received his BS in 1961. A year later, he commenced graduate studies at Oregon State University where he received his MS in biochemistry in 1964 and obtained his doctorate in biochemistry at Oregon Health and Science University in 1966, followed by postdoctoral training at the University of Pennsylvania.

Wong found that writing grants in academia could be frustrating, so he decided to look for a job in industry, and he had only one company in mind. Having seen the Lilly logo on his grandmother's diabetes medicine and later at a conference, Wong knew that was the company he wanted to work for.

According to Wong, it was not popular for a newly trained postdoctoral fellow of a reputable mentor to join a pharmaceutical research laboratory in the late 1960s and early 1970s. But, despite objections from graduate and postdoctoral mentors, he went ahead and joined Lilly Research Laboratories in 1968. "I was surprised when Irwin Slater offered me the position of a senior biochemist at Lilly Research Laboratories, but I was even more taken aback by his response when I asked if there were particular areas of research he would like me to work on. He said, 'You are a well-trained biochemist. You should be able to decide on your own'".

After Wong's initial proposal to conduct research on the biochemistry of calcium as a potential target was rejected as unsuitable for drug discovery, he became bold. "I initiated studies of uptake processes of monoamines without asking for permission, and from then on much of my 32 years at Lilly was spent doing pretty much what I was interested in and excited by."

Those who suffer from depression might now be thankful that Wong decided that this was his interest. In 1993 he was a joint Recipient of the Pharmaceutical Manufacturers Association Discoverer's Award for his part in the discovery of Prozac, a drug that is now used to treat millions of patients with depression. "Prozac was definitely a team effort. The collaborations between Ray Fuller and I led to many successful projects besides the discovery of Prozac. Throughout my career I have been fortunate to have very effective partnerships with scientists. My colleagues in medicinal chemistry served as mentors to me in many respects. In the late 1970s, William Lacefield showed me how to create an Invention Disclosure Memorandum, which led to co-inventorship of a US patent; and then in the mid-1980s working with David W. Robertson we designed and synthesized new molecules that resulted in the discoveries of duloxetine (Cymbalta), an inhibitor of serotonin and norepinephrine uptake, and dapoxetine, another selective inhibitor of serotonin uptake. Finally, in the mid-1990s I worked with Yao Chang Xu, Vincent Rocco and Kumiko Takeuchi in shaping molecules from multiple chemical scaffolds to have bimodal activities as antagonists at serotonin-1A receptors and serotonin transporters.

Because of the wonderful mentorship that Wong received, he plans to give something back and has arranged a summer undergraduate internship for synthetic chemistry endowment fund and a scholarship endowment for majors in chemistry or biochemistry at two of the universities at which he studied. Wong particularly enjoys the opportunity to interact with students and work with them on ideas, and says he wants to give more time mentoring as an Adjunct Professor and engage in a neuropharmacology project of his interest. "There are times," he says, "when I get frustrated that I no longer have a laboratory in which to test my ideas!"

Wong advises that to move from academia into industry and carve a career requires a willingness to engage early in existing drug discovery projects and be an uplifting person with a 'can-do' attitude. "You need the ability to focus and persevere, and to have devoted associates and to nurture those associates and colleagues to understand your research so that they become partners in the projects." He cites his greatest achievement as the successful collaborations that have resulted in the discoveries of therapeutics for treatment of mental illnesses. "Although it would be presumptive to say that I could have foreseen the outcome of our effort, I hope that the work I have been part of has improved the quality of life for many people and perhaps has even saved lives."