UNIVERSE’S CRUEL JOKE
ALS researcher now living with the condition
SAN FRANCISCO Rahul Desikan sits at his dining room table, a large computer screen before him, and works on his latest scientific paper. He types a single letter, then another, then another. For a man in a hurry, desperately trying to rid the world of terrible diseases, it’s an excruciatingly slow process.
Using a special mouse strapped to his forehead that detects his smallest movement, Desikan moves a cursor around an onscreen keyboard. When he finds the letter he wants, he clicks a button with his right thumb, and it appears in a white space to the side.
Repeating the process over and over, he debates research ideas with colleagues, analyzes reams of data and competes for grants.
He types so much that he occasionally wears out the clicker.
Moaning softly, he looks toward a caregiver sitting nearby. “Are you thirsty?” she asks. He shakes his head slightly. “Hot?” He makes another low sound, and she loosens his fleece vest and adjusts the neck brace supporting his head.
A year and a half ago, this scientist’s future seemed boundless. He was a rising star at the University of California at San Francisco, a researcher of degenerative brain diseases. He had just begun the biggest study ever of the genetics of ALS, or amyotrophic lateral sclerosis, the disease made famous by Lou Gehrig and Stephen Hawking.
Then his voice started changing. It got higher and took on an odd nasal quality.
He started noticing small muscle twitches in his left arm and weakness in his fingers. ALS was diagnosed five months later.
Today, at 40, he spends most days working from a wheelchair in his home south of downtown.
He is unable to talk, walk or hold his two young boys. He can move his thumb and turn his head a bit — but virtually nothing else.
A student of Greek tragedy, Desikan is acutely aware of the irony that ALS is now his personal nemesis. It seems like “the universe is playing a cruel joke on us,” he types, even a few sentences taking minutes to complete.
“I have lost my faith in God,” he continues. “I can’t believe that a loving being would ever do something so cruel.”
Yet that profound expression of despair doesn’t capture the full measure of Desikan’s existence — the undiminished brilliance and ambition, the bursts of outrageous humour and the moments of gratitude and joy.
His voice has been silenced. He hasn’t.
Since his diagnosis, Desikan has been an author, often the lead or senior one, of 25 papers in major academic journals on topics such as schizophrenia, Alzheimer’s disease and Parkinson’s disease. As part of his huge ALS study, he and fellow researchers announced in April the discovery of two genes newly linked to the disease.
His unique approach involves combining massive sets of genetic data, MRI exams of the brain, markers of brain pathology and patients’ symptoms. His immodest goals include trying to prevent and treat, or at least to better understand, ALS and Alzheimer’s.
“His work is really opening new areas of research in ALS that hopefully will benefit others down the line,” said Celeste Karch, a neuroscientist at Washington University School of Medicine who frequently collaborates with Desikan.
Already ravaged by that disease, he is unlikely to be saved by his own discoveries. But his scientific pursuits — along with the relatives and friends who pour into his house every week — remain his salvation.
“I love my research, and it gives me reason to live,” he types during an hours-long interview.
“Before, I felt that I needed to prove to others that I was good,” he types. “Now I don’t give a s--- about what people think. I do science because I love it and I’m good at it. It gives me purpose, and I feel that I can help people like me.”
When Hawking died in March at 76, after ringing up a lifetime of groundbreaking accomplishments in astronomy, friends immediately thought of Desikan.
“Rahul could do the same, if he gets the time,” said Leo Sugrue, a UCSF doctor who runs a neuroradiology lab with him.
“That’s the big question.”
Desikan first attracted attention during his medical and doctoral studies at Boston University, when he and researchers at Harvard University created a “brain atlas” that allows clinicians to label brain regions, measure their size via scans and track the effect of medication. In 2015, after a residency in San Diego, he moved to UCSF for a two-year fellowship in neuroradiology and began cranking out scientific articles at a torrid pace.
To the residents he trained, he was beloved for his skilful teaching, sense of fun and wickedly funny imitations. To his superiors, he was a rare talent — one of the few radiologists with a deep knowledge and love of genetics, which he coupled with imaging and clinical information to delve into neurodegenerative diseases.
“He was on the most rapid trajectory of an academic that I think I’d ever seen,” said Christopher Hess, chairman of the UCSF radiology 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 professorship 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 two-year-old, with his wife, also a UCSF professor and physician, just back to work.
Before, I felt that I needed to prove to others that I was good,’ he types. ‘Now I don’t give a s--- about what people think. I do science because I love it and I’m good at it. It gives me purpose, and I feel that I can help people like me.’
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 hospitalized. 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 diagnosis.
“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 diagnosed 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 variations 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 progressed, 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, post-doctoral researchers and residents arrive with their laptops. Music, often one of Desikan’s electronic mixes, plays in the background.
A neighbourhood 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 post-doctoral fellow in neuroradiology who, as a resident, was trained by Desikan.
“The mood is cheerful. We really enjoy each others’ company.”
Through their work, they are exploring the genetic and molecular mechanisms of neurodegenerative diseases. How do abnormalities 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 wheelchair 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 obstacles.
“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 autocomplete.”
Occasionally, to steer their work in a certain way or to emphasize a point, Desikan addresses the entire group. Software on his computer 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 allows him to detect shared genetic risks for different diseases. He recently led a team that integrated genetic information into a score for predicting the age of onset of Alzheimer’s. The approach, which utilized information from more than 70,000 people, may help scientists design future clinical trials.
And as part of the ALS genetics study, Desikan and Karch used data from more than 120,000 people to show that the disease is related to a rare disorder called frontotemporal dementia but not to Alzheimer’s or Parkinson’s. He plans to keep going. “My intuition tells me that my time has not come, the same way I knew about my diagnosis,” he types. “But I could be wrong.”
The mainstay in Desikan’s world is his wife, Maya Vijayaraghavan, a petite woman with a no-nonsense manner. The two started dating in Boston when she was a fourth-year medical student. “He talked all the time,” she remembers. “He was the life of the party. Everyone wanted to be his best friend.”
Like Desikan, Vijayaraghavan had come to the United States from India when she was young. On their first date, the two realized that they both carried the same picture in their wallets — of Uppiliappan, an incarnation of the Hindu god Vishnu. And both sets of their parents had been married in the same Indian temple, which is dedicated to Uppiliappan.
“When we pulled out the same photo I knew we would be married, and I told her,” Desikan types.
Their 2008 wedding festivities, at the same ancient temple, involved 80 friends and relatives and went on for days. “We were in love,” he types, a smile lighting up his face.
The couple had one son, then another. The younger was six months old when ALS entered their lives. “The bomb that went off in our household,” Vijayaraghavan calls it.
She’s determined to give their children happy memories even amid the most challenging of circumstances.
“It is their childhood,” she says. “She is my rock,” Desikan types. She is also something of an organizational and logistical wizard. Desikan is 6-foot-1 and more than 230 pounds. Moving him from his bed or wheelchair is its own undertaking, and leaving the house is a daunting task. Their support team includes two full-time caregivers during the day. Her father and his parents come every week to help, and his sister is a frequent visitor.
They get Desikan out as often as possible — to the park, a coffee shop, a movie. The family recently went to a beach near the Golden Gate Bridge, where the boys played in the sand and their father revelled in the sun on his face. “It was so nice to smell the sea and sand,” he types.
One friend from New York moved his wedding to San Francisco so Desikan could attend.
“It’s been a major outpouring of love in so many ways,” Vijayaraghavan said. “We can never reciprocate. We don’t even have time to acknowledge it.”
But they try.
In December, Desikan invited his entire department to a holiday party at his home and used his computer setup to serve as the DJ. He threw another big celebration for his 40th birthday.
Still, the once-gregarious researcher sometimes feels trapped and often lonely, and he admits to dark moments. His weakening neck muscles are making it harder for him to keep his head up. He compares himself to the Minotaur in writer Jorge Luis Borges’ fantasy novel The House of Asterion.
“I live a solitary existence,” Desikan allows.
Most painful is what he misses with his older son, now four. “We were so close,” he types. “I wish so much that I could hold him in my arms.” Desikan keeps typing, though. Despite losing “so much,” he describes himself as “blessed.”
“In some twisted way,” he writes, “ALS has made me free and realize what my life and who I am — a human being that has given and received love to his family and friends.”
Still, the once-gregarious researcher sometimes feels trapped and often lonely, and he admits to dark moments. His weakening neck muscles are making it harder for him to keep his head up ... ‘I live a solitary existence,’ Desikan allows.