US - INDIA GLOBAL REVIEW

33 US-INDIA GLOBAL REVIEW JULY-SEPTEMBER 2018 which he coupled with imaging and clinical information to delve into neurodegenerative diseases. "He was on the most rapid tra- jectory of an academic that I think I'd ever seen," said Christopher Hess, chairman of the UCSF radi- ology department. "I have met very few people who have true genius, and he would be at the top of the list." In the fall of 2016, UCSF offered Desikan an assistant pro- fessorship and his own lab. It was around then that his voice started to change. He initially assumed he had a sinus infection. A few weeks later, while bathing his older son, his left arm felt weak. He told friends he was worried about ALS. "You're crazy," Sugrue retorted; he was too young and too healthy to have ALS. More likely, he was exhausted. He was juggling a demanding job, an infant and a 2- year-old, with his wife, also a UCSF professor and physician, just back to work. By early November, however, Desikan was slurring words so badly that he sounded drunk. He went to the emergency room, and Hess stayed up half the night examining his brain scan. "There's nothing on it," he told Desikan. A muscle test was inconclusive. More months passed, his symptoms coming and going. Doctors treated him for a vitamin B12 deficiency and a rare form of a neuromuscular disease called myasthenia gravis. He kept working. In early 2017, he identified the two new genes associated with ALS. The next month, he suddenly became so short of breath that he was hospi- talized. The same muscle test was repeated, and this time it showed twitches throughout his body, a telltale sign. He was discharged on Valentine's Day and referred to the university's ALS clinic. Three days later came the official diag- nosis. "I felt like I was getting a death sentence, and my wife and I are shattered," he types. "What would happen to our kids?" ALS destroys the nerve cells that control voluntary muscle movement. The disease is diag- nosed in about 6,000 people in the United States every year. Most die within five years, usually of respiratory failure. The majority of cases, including Desikan's, aren't inherited, although genetic varia- tions may make some people more susceptible to the disease. He counterattacked with drugs, acupuncture and massage. He tried alternative treatments in India and energy healing in Dubai. He sought out a stem-cell clinical trial but wasn't eligible because his breathing was too weak. Inexorably, as the year pro- gressed, he lost his voice and the use of his hands and legs. By late summer, he was in a wheelchair unable to do anything on his own. The neuroradiology lab run by Desikan and Sugrue is not far from the San Francisco Giants' baseball stadium, although these days much of its work occurs in the second-floor living room of Desikan's blue-frame house. Bookcases topped with family photos line one side of the room. A few times a week, postdoctor- al researchers and residents arrive with their laptops. Music, often one of Desikan's electronic mixes, plays in the background. A neighborhood restaurant has a standing order for vegetarian pizza. Senior faculty members stop by to collaborate. "It's like a 21st-century family gathering where everyone comes with a device," said Matt Barkovich, a postdoctoral fellow in neuroradiology who, as a resi- dent, was trained by Desikan. "The mood is cheerful. We really enjoy each others' company." Through their work, they are exploring the genetic and molecu- lar mechanisms of neurodegener- ative diseases. How do abnormali- ties seen on the images of Alzheimer's patients, for example, reflect the activities of genes and cells potentially implicated in the disease? Desikan and Sugrue think Alzheimer's and ALS may have many subtypes that must be approached in different ways. While Desikan sits in his wheel- chair at one end of the table, researchers take turns sitting on a bench next to him, briefing him on their progress and getting his advice on how to deal with obsta- cles. "He'll start typing a series of words, and if he pauses and looks at me, it means that he wants us to make a guess and finish the sentence," Barkovich said. "I know him so well, I can be his autocom- plete." Occasionally, to steer their work in a certain way or to emphasize a point, Desikan addresses the entire group. Software on his com- puter converts his typed words to speech and then broadcasts them through a speaker. "That is his voice," Barkovich said. The synthetic version is named "Alex." Everyone tries to clear out by midafternoon when Desikan begins to tire. A little while later, his wife and children come home. Desikan already has made big contributions to the understanding of ALS, Alzheimer's and other afflictions. Colleagues say his skill at mining enormous data sets allows him to detect shared genetic risks for different dis-

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