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Politics on the Frontiers of Science

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"You could see that maybe this field of genetics had something to offer to human medicine," Dr. Collins recalls of the scientific mood when he began his career, "although in the 1970s most people thought that was a hundred years away." The potential was realized far sooner, in part because of Dr. Collins's pioneering 1990s work managing the Human Genome Project, which by 2003 had decoded all three billion chemical units that make up DNA—or what he calls "the instruction book of life."

Dr. Collins is now the director of the U.S. National Institutes of Health, the world's premier financier of medical inquiry, which he has run for the past four years. He visited the Journal offices earlier this month to discuss NIH-backed advances and to explain "the crunch we're in" during an era of limited fiscal resources and "all the political upheaval we're in the midst of."

The NIH's $30 billion or so annual budget, 84% of which underwrites peer-reviewed research grants in all 50 American states, is 22% less in purchasing power than it was in 2003. Behind Dr. Collins's geniality and avuncular manner, and his excitement about "this exponential curve of learning how life works and how things go wrong and how disease occurs," is an important warning: The U.S. may be putting its gains in science, technology and medicine at risk.

These advances include the reality that on current pace, every day you survive you add about five or six hours to your life, Dr. Collins notes. A person born in the U.S. today will live about 30 years longer than somebody in 1900. He credits these longevity dividends in large measure to NIH investment: "Whenever you hear about a research breakthrough in anything to do with cancer, diabetes, heart disease, HIV/AIDS, influenza, whatever, in the United States, it's extremely likely that NIH supported that effort."

Take oncology. Cancer is "a disease of DNA," he says, and the NIH's $400 million investment in the first human genome sequence has translated into $4,000 sequencing technologies that are now headed toward $1,000 per test. "It does make it look as if our means of defining cancer by what tissue it arose in is going to go by the boards pretty soon," he says. Lung, breast, blood—"it almost doesn't matter. What matters are the genes that are mutated, the mistakes in the instruction book."

This insight is leading to new and better therapies that don't simply hurt all cells that are growing too quickly, leaving doctors "always right on the edge of trying to kill the cancer without killing the patient." For the first time, Dr. Collins says, "we have a clear list of targets that are much more smart-bomb opportunities than carpet-bomb opportunities." The U.S. Food and Drug Administration is beginning to approve such specialized therapeutics, which he calls "gratifying indeed."

Dr. Collins is also drawn to what may be "the last frontier of medical research"—neuroscience. "There are 86 billion neurons in here," he says, tapping his forehead with an index finger. "Each of those has maybe a thousand connections. So the complexity of this structure exceeds anything else in the known universe, and some have even worried that our brains are not complicated enough to understand our brains."

Researchers don't yet understand how we lay down memories or retrieve them, for instance, or how we control our limbs, but the scientists are making astonishing advances. Dr. Collins points to an NIH team that developed a method to implant memories in rodents using bioelectric signals.

"We have the ability, in a live mouse who's running through a maze, to actually image thousands of neurons in the hippocampus and see what's happening as that mouse learns how to get from one spot to another," he explains. "In other experiments, researchers have transferred memories from a trained mouse to a naïve mouse, and that mouse seems to know how to negotiate a maze that it's never seen before.

"Now that's pretty freaky. Maybe we're starting to learn some of the language by which the brain operates."


Dr. Collins says "the paradox of my daily experience" is that the potential of medical research is unprecedented and yet he is trailed by "this sense that we are not taking full advantage of what is in many ways our most critical resource." NIH appropriations doubled in real terms between 1998 and 2003 but leveled off after that and then started to decline. "We're getting pretty close to being undoubled," he says. The NIH now turns down six of every seven grant applications; in 1979, it accepted two of five.

In some ways this competitiveness is a measure of biomedical success, to the extent that it reflects a larger scientific writ—more projects in more fields to choose from—and not merely less federal support. But Dr. Collins points out that research has grown more expensive to conduct. When the share of applicants who successfully apply for a grant drops below 20%, the grant process becomes "almost like a lottery."

Dr. Collins also appears almost physically pained by sequestration and its automatic caps on discretionary domestic spending that Congress adopted in January after failing to reach a budget deal: "It was supposed to be the poison pill that was so poisonous that nobody would consider swallowing it but, gosh, we did."

He was instructed to apply the 4.7% NIH cut for 2013 equally across its 27 institutes and research centers—in other words, cut the same amount over all scientific disciplines. The cuts meant, he says, that 640 projects that would have otherwise been funded were canceled over the last few months. "People say, 'Well you know, it's only 5%.' For those grantees, it was 100%."

The NIH director must be inherently political as well as scientific to secure a budget on Capitol Hill. But the genome is somewhat easier to decode than the political class. Dr. Collins has met one-on-one with more than 250 members of Congress over his NIH tenure and "I don't think I can remember a single one of those visits that went badly. Everybody cares about this, for themselves, for their families, for their constituents. Everybody wants to see advances made."

The interactions "are always really good," he continues. "But the conversation for at least the last three years always end up with: Buuut"—he draws out the word in his Shenandoah drawl—"there's nothing we can do about the fact that our country is in a fiscal crisis, and we've got to do something about the deficit, and until we work that out, you're just going to have to hold on. So we're holding on. But for how long?"

The administration of which Dr. Collins is a part would prefer that Congress simply turn off the sequester, and maybe the parties will cut the deal that is in the offing to trade more immediate spending for longer-term reforms. But another way of reading the situation—my view, not Dr. Collins's—is that the NIH is a casualty of Washington's chronic failure to set priorities.

The NIH is a line item in the $982 billion U.S. Health and Human Services budget, most of which automatically flows to programs like Medicare. The failure to modernize the entitlement state inevitably means there is less available for basic research. Every tax dollar spent developing the Affordable Care Act website that doesn't work, or enriching the corn lobby with ethanol subsidies, or propping up the 47 federal job retraining programs, is a dollar that Dr. Collins could have spent instead.

Whatever the cause, the consequences could have ramifications for decades. Dr. Collins warns that other countries are luring away U.S. scientific talent by offering better opportunities. Even more worrying: "My greatest concern—this is the thing that wakes me up at night—is that a whole generation of scientists are looking at this situation and getting increasingly discouraged and disheartened."

Research can't be turned on and off like a faucet, he adds. Since knowledge is incremental and builds over time, medical innovations may be delayed or never happen at all: "We can all think of findings that seemed completely irrelevant but ultimately changed everything and led to people's lives being saved, but began in the strangest way."


The NIH may be bankrolling such soon-to-be-watershed work right now. Dr. Collins invokes some of the more promising research: the "early days" of an AIDS vaccine that could be administered every three months instead of every day, pluripotent human cardiac cells beating in a petri dish, neurological stimulation that mitigates the tremors of Parkinson's disease.

Still nothing in the pipeline, however, that might cure Washington-style myopia.

Mr. Rago is a member of the Journal's editorial board.

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