How the Human Genome Project Mastered the Art of Big Science

What Have We Learned?
Oct. 11 2013 9:45 AM

The Big Sell

What ambitious scientists can learn from the Human Genome Project.

Illustration by Robert Neubecker

Illustration by Robert Neubecker

The Human Genome Project pulled off a remarkable feat: selling big, expensive, serious science to politicians and the public. Here’s how to do it—or not.

In his State of the Union address in February, President Obama made a nod to an emerging federal science project with an incredibly lofty goal: to understand how the brain works.

Obama’s oblique mention, delivered before the project was announced—“Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s”—spurred a suggestive tweet from the leader of the National Institutes of Health and a barrage of questions and speculations from the scientific community.

Big budgets ($300 million a year for 10 years) and big goals (measuring every spike from every neuron in the brain) were thrown out in the press. As the New York Times described it a few days after the State of the Union, the project was “seeking to do for the brain what the Human Genome Project did for genetics.”

That goal, however appealing, is not going to happen. It probably never had a chance of happening. And that’s not such a bad thing.

From the get-go, many neuroscientists were skeptical of the brain project. "Based on my conversations, there is great concern in the neuroscience community that this sounds like a big central planning project that will take resources away from creative work,” Cornelia Bargmann told Science in February. Partha Mitra warned against “irrational exuberance” and vague goals. Jason Pipkin wrote that the project would be undone by its own hype: “It's promising something it fundamentally can't deliver in any reasonable time frame.” Scientists who don’t study the brain were even more outraged.

The critics made an impression, apparently. By the time Obama officially announced this “next great American project,” in a 12-minute speech in April, its scope had narrowed to technology development, with a relatively modest budget of $110 million for 2014. Last month the NIH released a proposal for its contribution to the project, dubbed Brain Research through Advancing Innovative Neurotechnologies, or BRAIN. With nine specific aims—such as “integrate theory, modeling, statistics, and computation with experimentation,” “develop a suite of tools for circuit manipulation,” and “delineate mechanisms underlying human imaging technologies”—BRAIN seems to have gained scientific credibility, but at the expense of any mass-market appeal.

Don’t get me wrong—these are wonderful goals. I would be delighted if my tax dollars went toward any of these broad research areas. But I’m doubtful that this brain project, at least in its current packaging, will receive funding anywhere near the level its backers are hoping for.

BRAIN has fallen victim to the fundamental tension behind every Big Science project. The buyers—government agencies, controlled by politicians and ultimately the public—want a specific, sexy problem to rally around. They want to cure cancer or get to the moon or understand the human brain—and they want to do it now.

But the sellers—the scientists—are usually too scrupulous. They know their buyers have unrealistic expectations, at least in the short term, and they don’t want to sell them a bill of goods. On the other hand, if the scientists don’t market their products, their work won’t be funded.

It’s a difficult situation made even more difficult by today’s political climate, in which (pardon the strained metaphor) a few belligerent buyers are refusing to pay off their credit cards and barricading all of the sellers’ storefronts.

It wasn’t so long ago, though, that the leaders of the Human Genome Project pitched the American public a sweeping, $3 billion science product. And we not only bought it, but have come back for more and more. How’d they do that?

Lesson No. 1: Make government allies.

Like BRAIN, the HGP was a hard sell among scientists. The first organized discussion of the project happened in May 1985, at an intimate weekend workshop at the University of California–Santa Cruz. Twelve prominent scientists were there; half were in favor, and half thought it was a terrible idea.

The critics had several objections, according to a recent commentary written by genetics pioneers Leroy Hood and Lee Rowen. A big federal project, some critics worried, would mean less money for “real” biological science performed in the laboratories of individual investigators. Others thought the project wasn’t worth doing, or that it was so tedious that no talented scientist would ever sign up to do it. For the first several years after the workshop, “perhaps 80 percent of biologists were against it,” Hood and Rowen write.

But Congress quite liked the idea. “Those in Congress understood the appeal of international competitiveness in biology and medicine, the potential for industrial spin-offs and economic benefits, and the potential for more effective approaches to dealing with disease,” according to Hood and Rowen.

The Department of Energy was also eager to sign on, in part because it wanted to learn about how radiation causes genetic mutations. The agency’s lobbying helped convince everybody else. In 1990 the Department of Energy and the National Institutes of Health officially launched the HGP with an anticipated $3 billion budget—$200 million per year for 15 years.

BRAIN seems to have heard this first lesson loud and clear—it couldn’t have had a more prominent political placement, after all, than the State of the Union address. And it wasn’t just the president on board. “Mapping the human brain is exactly the type of research we should be funding,” Republican House Majority Leader Eric Cantor said in a statement.

But a Big Science project needs more than a few loud voices in Washington. Those politicians need a simple and specific pitch to proclaim from their soapboxes.

Lesson No. 2: Aim for something specific.

The HGP had a clear goal: to uncover the precise sequence of billions of DNA bases inside each of our cells.

That’s not to say the project was obviously worth doing or that it was expected to be easy. From the onset, the scientists involved knew that the existing technologies for DNA sequencing would be too cumbersome and slow to do the whole genome. They knew—just as the organizers of BRAIN know—that the first wave of investment would have to go toward technology development.

The HGP was also similar to BRAIN in that it was conceived as a series of complementary projects distributed across many laboratories. It would tackle not only the sequence of the human genome, for example, but the DNA sequences of worms, fruit flies, and mice.

Unlike BRAIN, though, the HGP boosters were smart enough to focus their marketing around one specific end goal. It was spelled out explicitly in the first sentence of its first five-year plan: “The Human Genome Initiative is a worldwide research effort that has the goal of analyzing the structure of human DNA and determining the location of all human genes.”

Contrast that with the vague and befuddling aims of BRAIN. As Obama put it in his April announcement: “[T]here is this enormous mystery waiting to be unlocked, and the BRAIN Initiative will change that by giving scientists the tools they need to get a dynamic picture of the brain in action and better understand how we think and how we learn and how we remember.” Oh, is that all?

(The pathetic infographic that accompanied the White House announcement was even worse. According to it, BRAIN money would help the Defense Advanced Research Projects Agency in “understanding the dynamic functions of the brain,” as well as allowing the NIH “to develop new tools” and the National Science Foundation “to support research that spans physical, biological, social, and behavioral sciences.”)

The only thing that’s clear about BRAIN’s intentions is that it doesn’t have clear intentions.

There’s no doubt that investing in basic neuroscience will have payoffs, probably huge payoffs. But without a specific goal, there’s no way to evaluate the success of such a project. And more to the point, there’s no way to convince people of its value. There’s no way to sell it to the masses.

Lesson No. 3: Always be closing.

To recap: The Human Genome Project benefited from its friends in government and its concrete and specific goal. There was also a crucial third ingredient to its success: hype.

Scientists and science journalists (me included) often get irritated by hype, and understandably so. It’s just a sugarcoated way of lying to the public. But our complaints are no match for hype’s swagger and effectiveness.

The HGP launched with the expectation that the human genome would “be the source book for biomedical science in the 21st century” and “help us to understand and eventually treat many of the more than 4,000 genetic diseases that afflict mankind,” according to its first five-year plan. That hype only grew over the next decade, as the project rapidly met its goal. When President Clinton announced the completion of the genome’s first draft, in 2000, he said it would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.”

That turned out not to be true, not even close. And though outside scientists have repeatedly berated the project for its hype—sometimes in major newspapers, even—the criticism hasn’t mattered much. The scientists got their money, did good science, and haven’t suffered any real consequences: Genomic science continues to get a big slice of the federal funding pie.

So it makes sense that the BRAIN project, too, came with a giant dose of hype. Here’s a taste from Obama’s April announcement:

But think about what we could do once we do crack this code. Imagine if no family had to feel helpless watching a loved one disappear behind the mask of Parkinson’s or struggle in the grip of epilepsy. Imagine if we could reverse traumatic brain injury or PTSD for our veterans who are coming home. Imagine if someone with a prosthetic limb can now play the piano or throw a baseball as well as anybody else, because the wiring from the brain to that prosthetic is direct and triggered by what's already happening in the patient's mind. What if computers could respond to our thoughts or our language barriers could come tumbling down. Or if millions of Americans were suddenly finding new jobs in these fields—jobs we haven’t even dreamt up yet—because we chose to invest in this project.

In BRAIN’s case, though, there’s no clear plan to back up the hype, no goal to rally around and feel good about once we’ve completed it.

For all of those reasons, I highly doubt that the BRAIN project will be the next Human Genome Project, or receive anywhere close to its fame. But perhaps that’s for the best.

Despite the trendiness of Big Science, it’s not a good strategy for every scientific problem. As recently argued in a commentary on biomedical innovation, there’s been woefully little research on the effectiveness of Big Science. Nobody’s really studied when the approach is likely to be effective — and when it’s not.

In fact, the biggest successes in Big Science—the Human Genome Project, the moon landing, the Manhattan Project—were essentially engineering projects, not basic discoveries. Take the Large Hadron Collider, which the European Organization for Nuclear Research built over 10 years to find the elusive Higgs particle. “It tested a hypothesis rather than developing it,” writes neuroscientist Paul Matthews in a review of brain projects.

A lot of scientists—most scientists, I’d guess—don’t have any big, sweeping projects to sell the public. They just want to do the unsexy-yet-indispensable work of testing specific hypotheses and gradually filling in the mysteries of how the world works.

For most scientists, then, Big Science is probably not the answer. They depend instead on small-scale government grants, of the kind that are all in limbo now thanks to the government shutdown. If these scientists want the government to keep funding their work, then they—we—have to figure out how to better sell the public on the big benefits of Little Science.

Virginia Hughes has written for Nature, New Scientist, and Popular Science. Her blog, Only Human, is on National Geographic's Phenomena. Follow her on Twitter.