In 1989, Phillip A. Sharp, PhD, thought that his shot at a Nobel Prize might have passed after Thomas R. Cech, PhD, won the Chemistry prize that year (with Sidney Altman, PhD) for discovery of the catalytic properties of RNA.
In an exclusive interview with MedPage Today, Sharp recalled that he and Richard J. Roberts, PhD, independently discovered gene splitting and RNA splicing when they were at Cold Spring Harbor Laboratory in 1977, but a few years later Cech found an intron in Tetrahymena, and then discovered that the intron was self-spliced.
“Tom and I had shared a number of prizes including the Lasker Award [in 1988], and so when he got the Nobel with Altman in chemistry I sort of assumed at that level that was going to be the recognition in the field of RNA splicing,” he said.
But he was pleasantly mistaken because on Columbus Day in 1993, Sharp was awakened at 6 am by the ringing of his telephone. He was sleeping in that day because the holiday was a big deal in Massachusetts and he had intended to go into work a little later than usual.
“I didn’t expect anyone to call at that hour in the morning, but then I started to tingle a little bit, and when I picked it up it was a Swedish colleague telling me that I had been selected for the Nobel in Physiology or Medicine, and the next thing out of his mouth was did I have Rich Roberts’ telephone number.”
With a chuckle, Sharp recalled that he was befuddled at the time and in no condition to look up anything, so he told his colleague that he would have to find the number some other way since Roberts — his co-recipient — had recently relocated.
And so began a very surrealistic day, according to the molecular biologist and geneticist who is Institute Professor at the Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology and whose discovery of “discontinuous genes” in mammalian cells fundamentally changed the understanding of gene structure.
Sharp said that 10 minutes after the call his doorbell began chiming, and he sent his wife Ann to see who was there. It turned out to be a photographer who lived in the vicinity and monitored Nobel announcements in the Cambridge-area academic haven.
He asked her to wait until he showered and dressed before the photo session, and then at 7 am he learned that MIT wanted him to be available for a 10 am press conference, and to deliver a lecture about his discovery that afternoon for the entire MIT body.
The day continued as a whirlwind, including lunch with his dean, a champagne celebration with the biology department, and then an evening neighborhood party that lasted until the wee hours, Sharp said.
“It was one of the happiest times I ever had in my life.” He used his prize money to buy an old Federal-style house several blocks from his Victorian home in Newton, Massachusetts.
The Nobel and the Lasker are hardly the only honors bestowed on Sharp, a member of the U.S. National Academies and Britain’s Royal Society as well as a recipient of General Motors’ Alfred A. Sloan Prize for Cancer Research. A more personal honor was having his former middle school in Butler, Kentucky, named for him.
He shared with MedPage Today what these testaments have meant and how he’s been paying it forward in a number of ways including his relationship with the Entertainment Industry Foundation’s (EIF) Stand Up To Cancer (SU2C) initiative. An EIF communications official also listened to the phone interview.
Sharp was born in the rural northern hill country of Kentucky and raised on his family’s farm. He grew tobacco and raised cattle to help pay his tuition at Union College in Barbourville, Kentucky, and then received his doctorate in physical chemistry from the University of Illinois. He did his post-doctoral work at the California Institute of Technology, followed by another post-doc at Cold Spring Harbor where his mentor was Nobel laureate James D. Watson, PhD.
In 1974 Sharp was invited to join MIT’s Center for Cancer Research (now the Koch Institute) by yet another Nobelist, Salvador Luria, MD; he served as the center’s director from 1985 to 1991, before being named head of the Department of Biology, a position he held for 8 years. He was founding director of the McGovern Institute from 2000 to 2004.
He also helped found biotech companies Biogen in 1978, Alnylam Pharmaceuticals in 2002, and Magen BioSciences in 2006.
“I left the board of Biogen about 6 years ago after 29 years following a call for change by dissident stockholder Carl Icahn. I said if you want change, then I should be a source of it as well as others,” he told MedPage Today.
Today, Sharp’s MIT lab has about 10 people, and he’s involved on several corporate boards, as well as chairing Stand Up To Cancer’s Scientific Advisory Council.
Sharp said that for those in academia, receiving the Nobel is similar to being “anointed or ordained.”
“If you’re seeking a committee appointment or trying to impress people that your research is significant, and there’s a list of 10 people, it’s the laureate who will be chosen.”
He confided that he was only tempted once to leave MIT for industry and that was when Biogen moved to Cambridge.
“MIT was comfortable with the arrangement, but at the end of the day when I considered my lifestyle and interests, I realized I wanted to stay and could actually do more for Biogen there.”
Now, 43 years later he’s still at the Institute and has continued the tradition of research discussions among researchers and their post-docs and graduate students every Wednesday at noon.
Sharp said that back in the 1970s, he, Robert Weinberg, PhD, and 1975 Nobel laureate David Baltimore, PhD, began the meetings so their respective labs could learn more about each other’s ongoing work, and the junior researchers are encouraged to present.
But it’s been his role as chair of Stand Up To Cancer’s Scientific Advisory Committee that has given him additional public recognition during the last several years, including, he said, providing him some “street presence” beyond the scientific community.
He said that about 10 years ago he was invited to an American Association for Cancer Research meeting without having a hint about its purpose, and learned about a new initiative called Stand Up To Cancer that wanted to use scientific collaboration to help change the rate of progress in cancer research.
AACR was to be Stand Up’s scientific partner and Sharp was asked to be chair of its advisory committee.
“Many things ran through my mind,” he said. “The visibility of these people [the Hollywood establishment] was going to be part of the face of cancer research in this country, and the message of collaboration and focus on engaging patients now was a message that I thought the scientific community needed.”
“However, although they were very earnest and excited about what they were going to do, I thought they [Stand Up’s founders] were quite naïve about what had already been done and how difficult cancer is to treat.”
But that’s where his having been “ordained” could play a role, Sharp told MedPage Today, and he thought he could help make Stand Up’s dreams come true.
“I didn’t need another job, but I decided to do it and it’s worked out much better than I ever hoped.”
For a basic scientist Sharp has had a long history collaborating and focusing on the patient. When he helped start Biogen, he realized how impactful new science could be when translated into treatment for people, and has championed making bench scientists more sensitive to patients’ needs.
Much of this has been demonstrated in the creation of numerous SU2C “dream teams,” composed of clinical and basic researchers from multiple institutions who have to tackle specific cancer challenges with an endpoint related to patients. He has also created a few “shotgun marriages” between researchers who might not have volunteered to work together but whose collaborative efforts have exceeded what they could do independently.
In recognition of his accomplishments, SU2C established the Phillip A. Sharp Innovation in Collaboration Awards in 2014, to foster collaboration among members of Stand Up’s scientific community encouraging them to work together with researchers with whom they have not collaborated.
Another way that Sharp is giving back is through two scholarships established by him and his former schoolteacher wife at his high school that provides $6,000 a year for four years to one male and one female student if they attend college and live on campus. “In that area of the country it’s actually affirmative action for males,” he noted.