Roy Smith Looks Ahead

Roy Smith retires this month as chair of the Department of Metabolism and Aging on The Scripps Research Institute (TSRI) Jupiter, Florida campus. Smith is best known for his work on the discovery of a small molecule, and its orphan receptor (GHSR), that restores the physiological profile of growth hormone secretion in elderly subjects to that of young adults. This work subsequently led to the identification of ghrelin, a small peptide hormone made in the stomach. Pharmacological doses of ghrelin increase food intake; therefore, ghrelin was widely believed to be the obesity hormone.

Ghrelin is elevated in Prader-Willi Syndrome, whose symptoms include insatiable appetite, low growth hormone levels and low sex steroid production. As recipient of the Prader-Willi Research Fellowship, Cristina Grande in the Smith lab has been advancing understanding of the disease—and looking for drug candidates to counteract it.

Eric Sauter of News&Views recently spoke with Smith about his passion for science in general and Prader-Willi research in particular, as well as his plans as an emeritus professor.

News&Views: How do you think the business of science has changed?

Smith: It’s quite different, even just over the last few years. Back when I was starting out in science as an assistant professor at Baylor College of Medicine, the young faculty members used to sit around and say, “Can you believe we get paid to do this? This is so much fun.” But there was a good chance of getting funding then. Today, everyone I talk to is having difficulties with NIH [National Institutes of Health] funding. I think there’s the same enthusiasm for science for those of us who do it—it’s just harder to do.

N&V: How has the study of aging has changed in the years since you arrived at Scripps Florida in 2008?

Smith: The U.S. Food and Drug Administration (FDA) has become more aware that there’s a need to do research on aging. Individuals in aging centers and departments of aging are saying, “Wait a minute—this is important; this is a huge cost to our health care system.” Ironically, the National Institute of Aging is the only NIH institute that doesn’t actually have a disease, because the FDA says there’s no such thing as an aging disease. However, this year the FDA agreed to a five- to six-year trial with an inexpensive diabetes drug, metformin, that might slow down the appearance of age-related diseases—all of them, which I think is kind of a wild idea.

N&V: What do you have planned after Scripps Florida?

Smith: I have joined a small company to help get FDA approval for Phase IIb and Phase III small molecules. I shall also be leading the effort to modify one of these molecules to enhance brain penetration.

In addition, I will continue research on Prader-Willi. Yesterday I met with the group that funds our Prader-Willi research. This research is based on discoveries made by Andras Kern of heterodimers formed between ghrelin and dopamine receptors, followed by collaborations with Pat Griffin and Ted Kamenecka. We’ve gotten such amazing results—not only can we normalize feeding behavior, which was our target, but also relieve anxiety and improve intellectual function in a mouse model of Prader-Willi Syndrome. Our supporters are ecstatic. That’s what excites me about science—that we can actually get to a point where we might be able to cure a disease. Although I’m retiring, I told them I would be happy to continue to do this as a volunteer. The work will go on.

N&V: Do you feel lucky you’ve come so close to something that can change people’s lives for the better?

Smith: I really do. I have always been lucky with my selection of drug candidates at Merck and at my own startup. The Prader-Willi group asked me what the probability is of this potential therapy we’ve been exploring going all the way to approval. I said, “Look, anything can go wrong so I can’t make promises, but if luck holds out, it looks good.” We just need to keep working, and we need more money to make newer compounds. We’ve shown it’s possible—I am actually amazed by the data that’s coming out of our animal studies on Prader-Willi.

N&V: Have you enjoyed living in Florida?

Smith: I have, but I miss Houston. I am a city person. I’m here to work at Scripps Florida, because I don’t play golf; I don’t fish, although I love the ocean and boating.

N&V: So, as of September 2, you’re a professor emeritus?

Smith: Yes, I plan to be here at least one week out of every month, because I want to make sure that support for the Prader-Willi work continues and make sure people in my group find good jobs. I have agreed to remain on two graduate student committees and to participate in the drug discovery graduate course, so I plan on keeping very busy.

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