CuresWho's Responsible?

Scott Summers was 14 years old when his father, an avid runner and fit 41-year-old, broke the news that he had been unexpectedly diagnosed with diabetes. Shortly after, the young teenager made his father a bold promise: He would find a cure. Summers has spent the past 34 years trying to make good on his word. But finding a cure for the disease that affects his father, along with 400 million people worldwide, has eluded him.

“I was convinced that I was smarter than everyone and my genius would save the day,” says Summers, Ph.D. “Turns out there are many brilliant minds who have been putting a lot of effort in trying to understand diabetes.”

Summer’s ambitious, if naive, teenage promise has led to a fruitful scientific career. Among his accomplishments, he figured out a way to prevent diabetes in mice. “That’s my claim to fame,” says Summers. He’s since started a company to find drugs that do the same in people, and he’s now the chair of the Department of Nutrition and Integrative Physiology at the University of Utah College of Health. Nevertheless, progress, Summers admits, has been much slower than father or son ever imagined. “Time is running out,” his father, now 75, recently told him.

“What my father doesn’t understand is that it’s not because of the ineptitude or lack of intellectual acumen of scientists,” says Summers. While tempting to blame politicians, or the stigma of laziness associated with the disease, Summers doesn’t go there. “They’re just hard questions to answer,” he says. “The reality is that the body is much more complicated than I realized and our understanding of it is still juvenile.”

Just as Summers feels he has disappointed his father, the world of science often feels it has come up short for the general public. We were convinced that the War on Cancer would have produced a cure decades ago. We were confident that the bipartisan decision to double the NIH budget in the late ‘90s would have realized cures for diabetes, heart disease and Alzheimer’s. We over promised, says Tom Parks, Ph.D., professor emeritus of neurobiology and anatomy and former University of Utah vice president for research. We created unrealistic expectations and disillusionment across all research.

“People’s imagination and hope often outrun what the world can provide. When I was a kid, we were all going to have flying cars and jet packs and travel in supersonic airplanes,” says Parks. “You don’t want to be defeatist, but you have to be realistic.” And, Summers adds, we haven’t communicated well what we’re doing, what the process is, and what success looks like. The reality is that most scientists will work their entire career and not contribute to a cure, says Parks. But that doesn’t mean they’re not contributing to our collective understanding of science.

Finding the lost child

Parks compares it to sending out a posse to look for a lost child. “We don’t say, ‘What a waste. We sent out nine people in the search party and only one found the child.’“ If we’re lucky as scientists, one of us will find the lost child, but most will not.

In 2010, Tom Lane, Ph.D., professor of pathology, seemed to have been the lucky one. He injected human neural stem cells into mice who were paralyzed from a condition similar to multiple sclerosis (MS), expecting them to be rejected. Two weeks later, much to his surprise, most of the mice were walking. The discovery renewed hope in the promise of stem cells to cure MS and other debilitating diseases. But “curing” a disease in rodents is a far cry from eradicating the disease in humans.

“There is little or no scientific evidence that these treatments actually work in humans,” says Lane. “And it’s quite possible that they could do harm.” What’s concerning for Lane and his colleagues is that the proposed REGROW Act would require the FDA to fast-track experimental stem cell interventions, even if the science hasn’t concluded that they’re safe or effective. Promising as it may sound to inject these neural stem cells into MS patients, it would be terribly irresponsible, says Lane. Just as troubling are the potential consequences for science. “If one person makes a false step, it kills the entire field,” he says.

Being cautious, circumspect and, some would argue, pessimistic goes with being a responsible scientist, says Lane. That doesn’t mean he lacks a sense of urgency. He hopes to move stem cells to clinical trials as soon as the science supports it. He works closely with clinicians to better understand the disease and often invites MS patients to tour his lab. Meeting a patient in a wheelchair reminds him that “this is a real disease that affects their lives,” says Lane. And patients appreciate seeing scientists working to solve this problem every day. “Our true goal is to make a difference in our lifetime.”

The Heart of the Matter

It is practically etched in scientific stone that heart failure is a one-way street that eventually dead-ends. But in 2000, world-renowned cardiothoracic surgeon Sir Magdi Yacoub, O.M.. F.R.S., noticed something strange: The hearts he was transplanting weren’t the same failing hearts he’d observed months earlier when he implanted an LVAD, a mechanical device as a bridge to transplant. They weren’t as enlarged and they squeezed better. It seemed they had miraculously recovered. “It was like waking up a dead heart, like Lazarus; people thought it must be a scam,” says Stavros Drakos, M.D., Ph.D., associate professor of internal medicine, who was training with Yacoub.

Drakos was fascinated by a fundamental question: Can you get a failing heart to recover? He made his way to Utah from his native Greece, 15 years later, to train with world-renowned cardiologist Dale Renlund, M.D., professor emeritus of internal medicine. Renlund was a driving force of the University of Utah’s advanced heart failure program, which included inventing and implanting the first artificial heart in 1982. Now, Drakos works alongside a team of clinicians, scientists and trainees committed to figuring out how and why and when the heart recovers.

They found that in some patients, implanting an LVAD unburdened the damaged heart and even sparked recovery. A few do so well, they’re able to have their LVAD explanted. That discovery has led to many more fascinating questions, including: What makes these patients unique? Can you predict who will recover? “Now we’re trying to understand what their secret is,” says Associate Vice President for Research Dean Li, M.D., Ph.D. “The exciting thing is that, once again, patients are giving us the answers. They’re leading us to the cure.”

Virtually every end-stage heart failure patient in the state is now included in a longitudinal study, thanks to a partnership with Intermountain Healthcare and the Department of Veterans Affairs. Nothing is wasted, says Drakos, from actual tissue and serum that were often thrown in the trash after surgery, to clinical metrics and observations, to comments from patients about how they’re feeling. “We come across patients all the time who are doing great according to our metrics but tell us they don’t feel well,” says Josef Stehlik, M.D., M.P.H., associate professor of internal medicine. In the past, there wasn’t any way to make sense of it. “We’ve been so focused on survival that we haven’t paid attention to what patients were telling us about their quality of life,” says Stehlik. As part of a grant from the American Heart Association (see above), he’s figured out a way to systematically collect patient input and feed it back into research that spans from mouse models to population health. Eventually, we’ll be able to use all of this information to connect biology to quality of life to predict outcomes that are much more precise and meaningful for patients, says Stehlik.

There’s also no wasted time among team members, “When you walk into a basic science lab that hasn’t had interactions with the clinical world, you want to cry just thinking of all of the missed opportunities and knowledge lost in translation,” says Drakos. “That’s what’s so remarkable about this team. We’re always in context. We speak the same language. And we’re all working towards the same goal.”

Is there hope for a cure? Will they eventually figure out how to reverse heart failure? ”We’re not in the business of miracles,” says Stehlik. “We’re in the business of science and providing care to patients. If ‘cure’ is not a synonym for miracle, then I’m comfortable saying that is our goal.”

The power of inclusion

If our hopes for cures have been unreasonably high, our expectations that scientists would work together have been regrettably low. Academia has historically focused on supporting and rewarding individual scientists, not teams, and building departments instead of interdisciplinary bridges. But all of that is starting to change. Funding agencies are forcing the issue, requiring a translational and interdisciplinary focus on grant proposals. And academic centers are trying to redesign themselves to be accountable to these new priorities. “We owe it to the public to find ways for basic scientists and clinicians to do innovative work that is likely to move therapies for diseases forward,” says Senior Vice President for Health Sciences Vivian S. Lee, M.D., Ph.D., M.B.A.

A focus on teams doesn’t have to come at the expense of individual excellence, says Li. “Champions aren’t a team of mediocre players. They’re each great position players who come together and trust one another. Those are the teams we’re trying to form.”

Building authentic, highly functioning teams in real life is much harder than creating an interdisciplinary team on paper. The recipe calls for a certain amount of luck, serendipity and chemistry—which cannot be manufactured.

What can be crafted is an environment that increases the chances of those connections. “We need to create shared spaces so people don’t feel so isolated,” says Monica Vetter, Ph.D., chair of neurobiology and anatomy and founding chair of the Neurosciences Initiative. Vetter has met with almost every department, searching for ways to build bridges to alleviate the devastating effects of brain disorders. “If we don’t come together and work across departments, we won’t be able to compete—period,” she says.

From co-locating investigators around diseases to forming research interest groups to organizing seminars and guest lectures, she’s hoping to spark new connections. “Some of these people have never been in the same room before,” says Vetter. In the past, pairing an electrical engineer with a biologist might have been considered a mismatch, says Vetter, but now we’re learning that even talking to someone with a completely different perspective can hatch unorthodox ideas.

With a $10 million commitment from the institution, the Neurosciences Initiative launched a Collaborative Pilot Project that awarded 17 seed grants to interdisciplinary teams last year. One of those grants brought together investigators from ophthalmology, pharmacology and organic chemistry to pursue a new treatment for glaucoma. The trio of investigators already have a provisional patent in progress and several potential drugs in the pipeline. Now the team is “entering the Valley of Death” as they seek funding for Phase I clinical trials. “We’re excited but realistic,” says David Krizaj, Ph.D., professor of ophthalmology and visual science.

The hope in "never"

The truth is that science is a low-yield endeavor. If Summers is completely honest with himself, the answer to his father’s question of when he will find a cure for diabetes, is probably “never.” But he remains optimistic. “I’m still fighting the good fight,” he says. “With all of the new tools we have, I have to believe that something great is right around the corner.” So what’s keeping him up at night? “Right now it’s excitement about the next day,” says Summers. “I don’t sleep very well because I can’t wait to get started.”