Sarah Palin, the onetime candidate for the second-highest elected office in the U.S., once delivered a rant on the campaign trail about waste she perceived in federal support of fruit fly research.
Scientists everywhere were appalled. Regardless of whether Palin knew about the historic importance of the drosophila to genetics, they were furious that a national figure would launch an all-out attack on biomedical research funding in this country. Didn’t she understand that the National Institutes of Health has been the envy of the world for decades? Didn’t she understand the NIH made the U.S. the undisputed leader in biomedical research? Didn’t she understand that basic research, in all its messy glory, is the foundation for progress in patient care?
That story played out in 2008. Palin lost, and went on to a dubious career as a reality TV star, author, and political commentator. But while the public rants against biomedical research faded, the budget battles ever since have taken a toll on the U.S. biomedical research enterprise. The days of abundant NIH funding for bright ideas in America’s labs are over. Even in a golden era of biomedical research—think genomics, stem cells, RNA interference, and more—fewer and fewer competitive grant proposals are getting supported. Young scientists in their 20s and 30s are finding it extremely difficult to get their first break. If lawmakers can’t settle their differences over this latest “fiscal cliff,” then the world’s premier biomedical funding agency could suffer its worst body blow yet—an 8 percent budget cut that would whack 2,300 worthy NIH grant-winning projects.
It would be foolish to go over the cliff, and I doubt elected officials will allow it in the end. But no matter how the “fiscal cliff” conflict gets resolved, scientists have gotten the message that the age of abundance in biomedicine is over. The grand bargain between President Clinton and Newt Gingrich to double the NIH budget from 1997 to 2002 is ancient history. Scientists at America’s top institutions have been forced to think more seriously than ever about finding other sources of support. They are increasingly looking to disease-focused foundations and drug companies. And when those groups bring their different agendas to the table, it will change the complexion of biomedical research.
Thong Le, a managing director with WRF Capital in Seattle, says he can see a shift occurring in the mindset of researchers he meets at one of the nation’s biggest recipients of NIH grants—the University of Washington.
“It’s no longer a question of, ‘How does the zebrafish swim?’ It’s now, ‘Gee, we already know something, like the zebrafish produces a specific protein in its mouth that appears to be involved in coagulation. Can we synthesize that compound and see if it could be the next warfarin?’” Le says.
This development, to my mind, is a mixed bag. If the nation’s scientific brainpower is channeled properly by a leaner NIH, by foundations, and by drug companies, then we could see a real payoff in the form of new drugs, devices, and diagnostics over the next five to 10 years. The NIH has been beating the drum for more “translational” research for years now, trying to protect itself from budget hawks who love to ridicule research it holds dear, like that of the fruit fly. I personally want to see basic and applied research going on all at once—everything from the fruit fly through the next warfarin. It’s absolutely within our rights as citizens to demand that more valuable medical products come from all this investment in basic research.
The problem with shifting the focus toward “translational” research is that if we tip the balance too far in that direction, we could miss out on a whole series of bigger breakthroughs that can come only from asking basic, open-ended research questions about how genes, cells, and lower organisms work. Franklin Roosevelt’s science advisor, Vannevar Bush, famously wrote about “Science: The Endless Frontier” in a memo to the president that’s just as valid today as it was when he wrote it in 1945. This investment in basic research can really only come from the government. Foundations don’t have enough money. Shareholder-supported biotech and pharma companies will always have to be more focused on projects that carry lower risk, and that offer near-term rewards.
Ideally, government-funded academic researchers would work in collaboration with their counterparts in industry, but that’s rarely how it really works. It’s a fundamental flaw in our current biomedical R&D model that scientists can win grants for basic questions like how zebrafish muscles contract, but they lose interest and funding dries up when it comes time for the next series of experiments that could create a new drug for, say, kids with Duchenne Muscular Dystrophy.
Those next steps are supposed to be the domain of more “applied” research organizations, like drug companies. But drug company R&D divisions have a tradition of being risk-averse, and more recently they have been suffocated by financially motivated megamergers that have made them almost too big to innovate. Many of them just aren’t set up to pick up these relatively raw research ideas and give them the oxygen they need.
To use a football analogy, basic researchers at universities take the kickoff at the 1-yard line, and the good ones can advance it as far as the 20-yard line. Pharma and biotech companies may have once been able or willing to take the ball there and advance the remaining 80 yards downfield, but not so much anymore. Their own scientific failures and financial pressures have forced them to focus mostly on taking over possession in the red zone, and then running the ball up the gut for the last 20 yards to score a touchdown—a new FDA-approved product. That leaves a whole lot of area in the middle of the field where nobody’s playing very much.
Somebody needs to figure out how to best get that work done in the middle, and keep the ball moving downfield. It’s hard, because there isn’t much professional glory there for the scientists, and not much financial reward for the businesspeople. Some encouraging experiments are being run at the moment, in which companies like Pfizer, Sanofi, Johnson & Johnson, and others are working hard to improve the way they interact with scientists on university campuses. Some academic institutions, like UC San Francisco, have shown willingness to engage in this creative rethinking of the biomedical R&D continuum.
While those efforts are encouraging, this really should be a national conversation that involves a whole lot more players.
“The scientific enterprise of this nation is in the middle of one of the largest makeovers in its history. On the one hand we have at our fingertips ultra-advanced analytical tools that truly enable human investigation. We have biological insights and technological platforms that allow us to understand disease at the single patient level over the course of a disease. We are in the middle of making personalized medicine a reality—only one problem, ‘nobody can afford to care.’”
What it boils down to is this: We have an amazing opportunity to advance healthcare through biomedical research in the coming decades. We don’t have unlimited money to pursue this goal, and it would probably be counterproductive to throw massive new money into the system anyway. So the question becomes: How to get the most bang out of the $31 billion or so that goes to the NIH each year? In the past, NIH review teams sought to weed out shoddy proposals and reward clear thinking that could advance a field. But in an era of financial constraint, as Kuhn puts it, the emphasis should be more about making sure the necessary science gets done.
“The difference between the two is tremendous and must be thought through very carefully. The value of science comes from its impact on our lives. Those who care need to be around the table to shape it,” Kuhn says.
I have to agree. Scientists can’t just sit in their science caves and whine about how there isn’t enough money to support all their ideas. There’s never going to be enough money. The plan should be to advance both the basic and applied research fronts, with a goal of producing benefits for human health. Scientists can choose to take action and be a part of crafting this future framework for research. Or, they can stand by and be acted upon by people who may or may not know that fruit flies are important. I hope it doesn’t come to that.
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