Young researcher's ALS attack plan is now a no-go

When Kelly Rich was at Ohio State, her research into ALS and other neuromuscular diseases was promising enough to win her a career training award from the National Institute for Aging.

Unlike federal grants that are tied to specific institutions, the training award is intended to support young researchers as they complete doctoral studies and transition from student to independent scientist, so Rich could have taken the grant anywhere. She chose the Harvard Medical School lab of David Sinclair because of his reputation for work that flips on its head conventional thinking around aging and disease.

Many of the health threats we fear the most, including heart disease, cancer, and dementia, occur more frequently with age. Medical research has answered or is striving to answer the most pressing questions about these conditions: What goes wrong in the body, how that malfunction translates into disease, and how we can fight back.

Sinclair looks at the situation more broadly: If the risk of a given condition rises with age, what is it about aging that increases the risk? His reasoning is that if we can find the answer to that question, we might be able to lower the risk of several diseases at once.

Researchers in his and other labs have made progress toward that goal in recent years. In 2020, Sinclair and colleagues—supported in part by the National Institutes of Health and NASA—made the cover of the journal Nature after they turned back the cellular clock in the optic nerves of lab mice. The team restored the neurons' ability to generate new axons—the connection between the eye and the brain—and repaired vision in mice with glaucoma and in older mice whose vision was fading with age.

Since the eye's nerve cells are the same type as neurons in the brain, the work attracted Rich to Harvard. She believes the approach used to reinvigorate the mouse optic nerve holds promise as a way to fight currently incurable conditions like amyotrophic lateral sclerosis and spinal muscular atrophy.

In recent weeks, however, her work has hit a roadblock. Rich, Sinclair, and other researchers across campus received grant termination notices linked to the government's campaign to force Harvard to comply with proposed changes to governance and hiring, as well as audits of faculty and student viewpoints.

"We're all just looking at each other going, 'What the hell just happened?' and it's slowly sinking in," Sinclair said. "We're really trying to be supportive to our lab members, the students who've staked their lives on this, and the postdocs, who are the ones most likely to be let go. It's extremely terrifying for them."

Sinclair's lab lost two major grants—a five-year, $1.5 million grant that provides its financial foundation and Rich's career award of $438,000 over six years, which funds her salary plus a technician to support her research.

"I'm still letting the dust settle a bit," Rich said. "This is an especially tough moment for early career scientists and postdocs and students. The effect of these cuts is to take early career scientists who want to be the next generation of academic leaders and erode their confidence, their trust in the infrastructure that has driven science and science careers. Academia looks very different today."

The termination of Sinclair's R01 grant—the NIH funding that supports his lab—casts his entire research program into doubt. He thinks that he has enough resources to avoid layoffs for a few months, but he has been scrambling to find private grants to replace federal funds.

"I'm traveling around the country and the world to see if I can raise money to keep going and it's just a race against time," he said. "I can keep going for a while, maybe a few months, but ultimately, we relied on government money. So I'm looking for support from companies and the public to replace what was lost."

Despite the unsettled environment, Rich said she's intent on not making "snap decisions" about her next steps. Her preference is to continue to work with Sinclair and move on to an academic career, but she's also not averse to transitioning toward an industry role, especially with the longstanding research partnership between the federal government and higher ed now in jeopardy.

"I'm going to stick with where I am for as long as I can right now," she said. "But I don't think you can ignore the fact that it seems tougher now than ever to start a lab in academia, given that the infrastructure of federal funding so many early career professors rely on is largely gone. I haven't made any decisions, but these are things that you can't ignore. You have to be practical when you're making decisions about that next step."

Provided by Harvard Gazette

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