Worms are fine. Mice and rats? Sure. Dogs and monkeys also have their value, especially to basic research. But what really interests Gholson Lyon are people. “I study humans because that’s what I’m interested in,” said Lyon, a child, adolescent and adult psychiatrist and researcher at Cold Spring Harbor Laboratory. “Humans are an incredibly complex species.”
An assistant professor at CSHL since March 2012, Lyon is establishing connections with Stony Brook as he builds a research and clinical team that benefits from an understanding of human genetics. “Part of the reason to partner with Stony Brook is that it’d be nice to work with clinicians who have done a lot of work with families,” he said.
Indeed, Lyon worked closely with a close-knit family in Utah in which some of their sons were born with unusual symptoms and died at young ages. Starting in 1979, five boys that were born in that family over a three-decade period got some aspect of the disease.
Looking closely at the family’s genes, Lyon found a mutation that, as he put it, has a “high expression.” He named the disorder Ogden Syndrome, after the town where the first family lives. While it would be hard to develop a treatment for Ogden Syndrome, “It’s about knowledge,” Lyon said. “Giving the family knowledge that it has this mutation helps to bring awareness.”
Indeed, knowing that a child is born with this genetic change can help alert parents to find ways to avoid various symptoms for their children.
In Ogden Syndrome, boys sometimes have trouble when food goes down the wrong tube, causing lung infections. In the future, with the family more aware of this problem, parents can work with doctors to prevent sending food to the lungs with the type of food choices or with earlier placement of a feeding tube, he said.
Lyon’s medical mission is to provide and encourage other doctors to offer individualized care. “There are lots of people who want to develop drugs,” he said. “I firmly believe that identifying illness before it begins and then working to prevent or decrease the severity of the illness is far easier than trying to fix a full-blown illness with drugs after the fact.”
He said he understood actress Angelina Jolie’s informed decision to have a double mastectomy based on her genetic predisposition to breast cancer.
“Every individual has their own risk-benefit analysis,” Lyon said. Lyon derives considerable satisfaction from working with the family with Ogden Syndrome. He found it similarly rewarding to work with someone who had such a severe obsessive compulsive disorder that he struggled to function.
For many months, Lyon treated this patient with Prozac, without any effect. After doing a full genetic analysis of his patient, he realized his patient had a gene that affects the metabolism of fluoxetine, the ingredient in Prozac. If he had known that upfront, he would have chosen a different drug.
Lyon used deep brain stimulation with this patient. The effort completely changed his life, enabling him to function at a higher level and even to date. His patient got married this past summer.
Deep brain stimulation is not the current standard of care, has potential side effects and is a more expensive treatment, costing tens of thousands of dollars. Lyon, however, believes the technique — in which a machine sends regular, controlled electrical signals into the brain — will prove useful for other patients.
It shows promise not only for treating severe obsessive compulsive disorder, but also for helping with other illnesses like Tourette Syndrome.
“Now is the time to be putting a lot of effort into advancing deep brain and precision medicine,” Lyon said.
The Cold Spring Harbor researcher said he has had patients for whom even individualized approaches haven’t improved the quality of life. “Medical doctors try their best to provide individualized care to each person,” he explained. “I have certainly had many times in which I could not help certain people due to the severity of their illness and the limited resource at hand.”
Eric Topol, the director of the Scripps Translational Science Institute and the chief academic officer at Scripps Health, called Lyon a “rising star” who is not afraid to “tell it like it is.” He said Lyon, whom he asked to give a talk on the future of genomic medicine last year, is making “major contributions to get the field moving forward.”