Defense Research Agency Hunts for Biotech Innovators

Donald E. Ingber, a professor at Harvard University, has combined advanced electronics and biology to create a “lung on a chip,” a breakthrough device that could safely allow precise tests of risky new medical treatments before they are tried out on humans.

Just as eye-opening as his work, however, may be his source of federal financing.

It’s not the National Institutes of Health, the $30-billion agency that is the largest provider of federal basic-research money to universities. Instead it’s the Defense Advanced Research Projects Agency, or Darpa, an agency one-tenth as large as NIH and responsible primarily for meeting the military’s technological needs.

For Dr. Ingber, a professor of vascular biology and bioengineering with a zeal for pushing scientific boundaries, Darpa is an ideal partner—and not just because NIH is being hit especially hard by federal budget cuts. Darpa’s very mission embodies risk-taking, having been established after the Sputnik launches of 1957 to ensure that the United States would never again fall victim to technological surprise.

The enigmatic agency has earned fame as the originator of the Internet and other military and civilian technological advances, including stealth fighter jets and integrated computer chips. Darpa is also a popular plot device for animating conspiracy theories and suspicions about government power and intent.

The reality for Dr. Ingber and other university researchers is a bit more straightforward. After the Persian Gulf war, in which Iraq was feared to have biological weapons, Darpa embarked on a concentrated effort to develop countermeasures. And now, under its current director, Arati Prabhakar, the agency is moving more aggressively into biotechnology.

A centerpiece is its Living Foundries program, where goals are stated in military terms but—like much of what Darpa has done over the years—have unmistakable potential for wider value. The objectives include the creation of new fuels, medicines, and materials to help with problems that include equipment corrosion in environments that soldiers face worldwide.

Another big Darpa project is the Brain Initiative, proposed this year by President Obama. For that effort, designed to improve scientific understanding of the human brain, Darpa has taken a leadership role alongside the NIH and the National Science Foundation.

NIH leaders have described the Brain Initiative’s importance in terms of fighting disorders such as Alzheimer’s disease, Parkinson’s disease, and schizophrenia. Ms. Prabhakar sees value in helping soldiers deal with stresses and injuries, and make better and quicker decisions with increasingly complex tools and environments.

A Different Culture

Dr. Ingber began working with Darpa about 15 years ago, when the agency turned to the threat of biological weaponry. His entry into Darpa financing was typical for the time: He was brought by a colleague to a meeting of researchers where Darpa officials would press attendees for breakthrough ideas. Such sessions often lead to participation in the agency’s projects.

Researchers trying to follow him today might have an even easier time. In 2006, Darpa inaugurated a Young Faculty Award program, choosing some 25 junior academic researchers each year for grants worth up to $1-million apiece. It gives them exposure to the Darpa culture without all the performance-related pressures associated with a traditional agency contract.

“It’s kind of like a gateway award,” says Julius B. Lucks, an assistant professor of chemical and biomolecular engineering at Cornell University, who works on ways of using light to control aspects of gene regulation. “And I think it’s helped me win some of the other ones.”

Darpa’s culture does require adjustments for those more familiar with NIH. Research grants at NIH typically run about three years in length and are allocated through an extensive peer-review process. Paradigm-shifting proposals rarely make it through, says Anthony J. Tether, who led Darpa from 2001 to 2009.

Something truly innovative instead “suffers a death of a thousand cuts” during evaluations by professors who may feel threatened by an idea they hadn’t conceived or considered possible, he says.

Darpa, by contrast, relies on a small team of about 100 program managers, many university researchers themselves, who are given wide discretion to choose worthwhile projects and then closely follow their progress, quickly cutting off support if checkpoints prove the goal unreachable. The managers are expected to make “big bets on strong researchers,” says Ed Lazowska, a professor of computer science and engineering at the University of Washington who has worked with the agency.

Ethical Considerations

Some see signs that Darpa, over time, has eased its single-minded drive for results. It’s added a few more layers of management in the past 10 to 20 years, says Shaun B. Jones, a private technology consultant who financed Dr. Ingber’s initial Darpa work during his time as a program manager.

Additions in recent years include panels of experts to evaluate ethical and safety considerations of the agency’s work. The idea grew out of concerns a decade ago about Darpa’s work in data mining, says David W. Rejeski, director of the Science and Technology Innovation Program at the Woodrow Wilson International Center for Scholars, who serves on a four-member panel that evaluates projects in the Living Foundries program.

“It’s not universally spread through Darpa,” he says of the assessment panels. “But it’s an interesting signal that they’re trying to deal with some of these issues and catch them early.”

Bioengineering is certainly an area that has raised worries about runaway technological powers, such as implanting codes into DNA to create highly infectious synthetic microbes that could not be detected by existing diagnostics.

For now, though, even cutting-edge work in bioengineering and synthetic biology shouldn’t cause concern, as it’s just at the stage of figuring out basic tools, Mr. Rejeski says.

When such concerns do arise, Darpa managers such as Daniel J. Wattendorf, an Air Force lieutenant colonel, say they are alert to them. Mr. Wattendorf is financing work that includes the pursuit of faster-acting vaccines, and he is intentionally seeking modifications of RNA rather than DNA, to ensure that any genetic effects are temporary. “We want to think of safety first,” he says.

And Darpa can’t simply avoid dark subjects, Dr. Ingber says. It must anticipate what adversaries might attempt. “If we constrain where we think, where we explore, to develop countermeasures, we have a problem,” he says.

Darpa’s style can also mean financial stresses for universities. Around 1995, computer scientists—long a favored specialty at Darpa—complained that Mr. Tether was de-emphasizing their work. Universities also worried that they were being bypassed in favor of corporate partners, Mr. Tether says.

In both cases, the truth was more complicated, he says. Mr. Tether favored letting big corporate partners run big projects, so that university researchers getting Darpa support often saw that money in the form of subcontracting work for the outside companies.

Typically, he says, universities would directly get about two-thirds of the $150-million that Darpa classifies as basic research spending. But university researchers were really getting about $450-million in Darpa money, taking into account the amounts distributed by companies, he says.

The practice may have angered some university technology-transfer managers, who want control over possible licensing revenue. But it also cleared the way for some scientists whose institutions didn’t necessarily welcome Darpa or its need for secrecy, Mr. Tether says.

No ‘Lone Cowboys’

Even those researchers sticking with NIH and NSF are feeling Darpa’s influence. Both agencies have emphasized their experimentation with freewheeling methods of distributing money outside the more traditional peer-review process.

But change in that direction is slow. Established constituencies at universities rely on a predictable supply of financing and use it as a standard method of assessing researcher quality and productivity.

And the bulk of basic research projects at NIH, while derided by some at Darpa as incremental, are recognized by the agency’s own leaders as crucial building blocks upon which its breakthrough technologies depend.

For Dr. Ingber, it’s not one or the other. His Darpa projects are generally regarded as applied research, although progress often requires him to go back and break through bottlenecks of basic research.

In one of his projects, Darpa was exploring the possible use of magnetism to switch living cells on and off, in the hope of inventing devices containing living cells as components that don’t require electrical power.

That led him to study the molecular basis of mechanotransduction, which amounts to basic research. “So I was able to advance my fundamental research, not because I asked for funding to do it, but because I helped solve their problem,” he says.

Working with Darpa also requires interdisciplinary cooperation, something that many universities and grant-making agencies preach but that Darpa actually achieves, by insisting first on the goal and then on the team—many of which have expertise outside conventional military specialties—that can accomplish it.

“There’s almost a cowboy atmosphere about the place—that they’re out there inventing the future” by doing whatever it takes to succeed, says Alex F. Roland, a professor emeritus of history at Duke University who wrote a book on Darpa’s quest for artificial intelligence.

Dr. Ingber agrees, to a point. Teamwork, he says, is essential for remaining competitive globally. “They’re not looking for lone cowboys,” he says of Darpa. “You can’t do it on your own anymore.”