Against All Odds

Against All Odds
Gerald Pier, PhD, a microbiology and molecular geneticist in the Division of Infectious Diseases, has seen dramatic changes in the biomedical research field in recent years.

In 1910, the average life expectancy for someone born in the United States was 50 years. A little more than a century later, a child born in 2012 can expect to live, on average, for more than 78 years—an all-time high. This astonishing leap forward is due in large part to the remarkable achievements in biomedical research supported by the National Institutes of Health (NIH) contributing to:

  • Decreasing heart disease deaths by more than 50 percent over the last 40 years
  • Cutting the rate of deaths from stroke by 30 percent since 1995
  • Reducing cancer deaths by more than 20 percent since 1991
  • Improving survival rates for childhood cancer to 80 percent from 50 percent in 1975

Thanks to federal investments in biomedical research, we already have much better treatments for these and other chronic diseases than we had just a few decades ago.

However, in 2013, federal budget cuts slashed NIH funding to historic lows. The scarcity of NIH grants threatens to thwart medical progress, at a time when our rapidly aging population is driving healthcare costs to record highs. Lives are at stake, as are the careers of promising investigators who have the potential to develop life-saving treatments.

For the nearly 4,000 physicians and scientists in the research community at Brigham and Women’s Hospital (BWH), rising uncertainties around government support for biomedical research have prompted an increased urgency around securing funding from philanthropic and industry partners to fill the gap. Three BWH researchers highlighted here are learning to adapt to the changing landscape, while remaining hopeful for smoother roads ahead.

Keeping hopes, and labs, afloat

Between 2012 and 2013, some 3,400 scientists across the U.S. lost their sustaining NIH grants.

“I was one of them,” says Gerald Pier, PhD, a microbiology and molecular genetics researcher in BWH’s Division of Infectious Diseases. “My last existing NIH [grant] ended in June. This is the first time since my first NIH grant in 1979 that I haven’t had NIH funding. Not long ago I had five grants at the same time.”

“I’ve been fortunate over the past few years to survive on donations, creative funding, and income from inventions, but it’s not sustainable in the long term,” Pier says. “Without NIH support or private funding, I’ll have to close down the lab.” Pier’s lab focuses on developing vaccines to treat or prevent infectious diseases in cystic fibrosis patients, staph infections, and infections caused by antibiotic-resistant organisms.

When Pier began his research career in 1970, more than half of all federal research dollars went to principal investigators (PIs) who were under age 40. Today, this group receives less than one-fifth of the federal funding. Despite the pinch he is feeling, Pier says, “The biggest impact of NIH budget cuts is on early career scientists.”

One of those is BWH neuroscientist Tracy Young-Pearse, PhD. Young-Pearse has churned out more than 50 grant applications since launching her own lab in 2010 to support critical investigations into the causes of Alzheimer’s disease.

Recent studies estimate that researchers like Young-Pearse spend at least three months of every year writing grant applications. That means three months away from the lab bench, away from “thinking about science and how to answer questions, analyzing and generating new data,” says Young-Pearse.

In addition to the time demand, there is the constant anxiety about money. Ben Humphreys, MD, PhD, whose lab is pursuing new therapies for kidney disease, keeps a running projection in his head of how far into the future he can keep his lab working until funding evaporates.

“That number is different for everyone. It could be two to five years with NIH grants. Sometimes, and this has been the case in my career, that number can be six months or less,” Humphreys says. “Biomedical research has always been cyclical, and there have always been periods where people have had to hold on, but this feels different. Even senior colleagues say it feels different to them, especially the length of time. There aren’t many signs it will end soon.”

Research: an investment, not a transaction

What is at stake in this climate of uncertainty are not only researchers’ jobs, but also the sciences to which they are devoted. Pioneering medical breakthroughs are the product of pioneering investigators, and great researchers are not born—they are intensively trained.

“There are no shortcuts for that investment in terms of training, because the amount of clinical knowledge required to care for a complex disease like kidney disease is enormous, and growing exponentially,” says Humphreys. “After I graduated from college, I had 14 more years of training before I could even begin to ask important questions. It took 17 years for me to gain an independent NIH research grant.”

Moving an idea from a testable hypothesis to a clinical trial can also take years. “After 36 years in this career, I’m finally seeing some of the vaccines we’ve made get into clinical testing,” Pier explains. “For one of them, I can mark the time when we started and knew nothing. It was 1985, and it took another 20 years before we had commercial interest. Then another five years until a first clinical trial. The second component of that trial we’ll see next year. That’s 30 years—a pretty typical timeline.”

Another reason it can take years to move research through the pipeline is the high failure rate that comes with chasing answers to medical mysteries. The setbacks can be disheartening, but dead ends to research questions can still bring opportunities to learn and prepare for the next investigation.

“You might spend all weekend, maybe three months, maybe a year on something, only to find out that your hypothesis was incorrect and it's all garbage,” says Young-Pearse. “And then there are times when you’re discovering something about the human condition for the first time, and making real breakthroughs. It's an amazing feeling. That keeps you going, but you still have to get through the heartbreak of the failures.””

“As Einstein said, if we knew what we were doing we wouldn’t call it research,” Pier says. “That’s the position we’re all in—we make educated guesses on what to do, and what will work. It’s very satisfying when we get it right, and frustrating when we get it wrong.”

“Failure is a big part of this job,” Pier adds. “Ninety percent of what we do fails. A lot of my colleagues might even say, ‘Wow! You only fail 90 percent of the time? That’s pretty good!’”

Mentors play a key role in sustaining investigators through the frequent failures that come with the territory. The role of mentorship in providing reassurance, especially to young investigators, can offer helpful perspective that, despite the challenges they are facing, they are not alone.

“One of my mentors in my early years was always so excited to see my results,” says Humphreys. “It was really infectious. I began to feel like I couldn’t wait to find out the next result myself. That never gets old. Mentors can provide perspective that you will come through on the other side of this.”

“My successes in my career have been dominated by good mentors,” Young-Pearse says. “There’s no way to know inherently that the direction you’re heading in is the best one. Having good mentors accelerates your progress to propel you forward.”

High risk, high potential

A 2005 study by the National Bureau of Economic Research examined the age at which more than 2,000 Nobel Prize winners and other notable 20th century scientists came up with their game-changing ideas. Most were between the ages 35 and 39. But today, more people over the age of 65 are funded with NIH research grants than those under age 35, as funders are increasingly risk-averse. This grim funding environment puts increasing pressure on academic medical centers like BWH to find ways to keep the most promising young researchers and their paradigm-shifting ideas from leaving the field.

“We have sent a loud and strong message to industry and to the venture capital community that the Brigham is open to new ways of partnering,” wrote BWH President Betsy Nabel, MD, in an editorial for The Boston Globe. “We are creating new collaborations with companies for sponsored research as well as licensing with biotechnology, pharmaceutical, and healthcare technology companies.”

In addition to collaborations with industry, philanthropy at all levels plays a key role in helping young researchers stay in the field, as well as sustaining BWH laboratories.

“Donations make a tremendous impact on early-stage projects, those high-potential, high-risk ideas,” says Humphreys. “Lots of us have used donations to leverage government grants. One donor can have a remarkable impact on the course of discovery in a particular disease.”

Young-Pearse agrees, “Philanthropy has been a big part of my funding over the past few years. Philanthropic support has allowed us to undertake more high-risk studies that NIH may have shied away from, and these studies are providing us with valuable insights into Alzheimer's disease.”

Even with these creative funding sources, the NIH remains the world’s largest single funder of biomedical research. “Without NIH support, medical research—especially basic science research—just wouldn’t happen,” says Pier. “In academic settings there is great reward for making discoveries, for finding new ways of looking at things. Almost none of that translates directly into profit. In that sense, it is a difficult enterprise for commercial entities to invest in, because it likely won’t pay off.”

Life is at stake

An infusion of funding would help the BWH biomedical research community speed up the pace of discovery and find new ways to tackle the world’s toughest medical challenges.

As seen in the recent Ebola outbreak, investing in research can be a life-and-death matter. In an interview with The Huffington Post, current NIH director Francis Collins, MD, speculated, “If we had not gone through our 10-year slide in research support…we would have been a year or two ahead of where we are [in having vaccines and other therapies ready to help control the Ebola epidemic.]”

Likewise, increased support would free scientists like Pier to pursue bigger questions. “One of my high-risk, high-gain ideas is around discovering vaccines more rapidly. My training and work is in microbiology, but I can see this applying to tumors. I’d like to set up collaborations with people doing cancer vaccines to see if we could develop the technology to go from a tumor to a vaccine in an individual in four to six months.”

For his part, Humphreys acknowledges, “Today, the best we can do is slow the progression of kidney disease. If I didn’t have to think about funding horizons and grant application deadlines, I would dedicate my lab to not only slowing disease progression, but actually reversing it. I strongly believe it’s possible.”

Young-Pearse’s ultimate goal is to unravel the riddles of neurologic diseases to determine why some neurons die while others are protected. “In someone with Alzheimer’s, their memory and cognition is severely impaired by the end of their life, but other functions of their brain are intact,” she says. “Why are some neurons dying and others protected? Right now we’re studying this question in stem cell-derived brain cells from our patients, and using these cells to test new therapeutic strategies to protect the vulnerable brain cells.”

Looking back at the achievements in medicine during the last half-century—including stunning improvements in survival rates for heart disease, stroke, and cancer—imagine where medicine could be 50 or 100 years from now if researchers have the tools to make more critical discoveries?

“Medical research is at an important crossroads,” Nabel wrote in her editorial. “Cures for diseases that have devastated families for generations are within our reach, and researchers are in hot pursuit. This is no time to turn our backs on patients and on the potential for life-giving breakthroughs.”