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Science — Looking to gamble, newest U.S. health agency places first research bets

Science — Looking to gamble, newest U.S. health agency places first research bets

A year ago, when applied biologist Renee Wegrzyn took the helm of the Advanced Research Projects Agency for Health (ARPA-H), questions swirled around the brand-new agency, which was created by President Joe Biden to fund daring, cutting-edge biomedical research. Would the new organization be sufficiently different from the sluggish, risk-averse National Institutes of Health (NIH)? How would Wegrzyn, who had never run an agency, navigate pressures from Congress to shape the effort? And how quickly could she recruit the type of innovative scientific staff needed to identify out-of-the-box projects on which to spend a billion-dollar budget?

Now, answers are starting to emerge. ARPA-H has in recent months announced a growing list of research awards for efforts the agency says are more ambitious, and less certain to succeed, than what NIH would typically support. Among them: a plan to regenerate cartilage and bone in osteoarthritis patients and an unprecedented effort to build a functioning heart using 3D printing with living cells. The agency has hired 390 staffers, some of whom will take an unusually active role in shaping research without the outside peer-review NIH projects typically get. By the end of September, ARPA-H had already tentatively obligated close to $1 billion of its initial $2.5 billion budget.

“Nothing like this has ever existed inside the health ecosystem,” Wegrzyn told Science in an interview last week at ARPA-H’s current offices, a suite of rented rooms in Arlington, Virginia. “This is a place where we take very big risks that NIH can’t take.”

The fierce debate over whether ARPA-H is needed now awaits the results of the gambles placed by Wegrzyn and her staff. Onlookers say although the agency’s start has been slower than hoped, they are generally pleased with its initial slate of projects. “The investments that they’re making look pretty fantastic,” says consultant Michael Stebbins, a geneticist and former White House science staffer who pushed for ARPA-H’s creation.

“They have launched some novel and exciting projects” that are “complementary” to the work of NIH, adds Ellen Sigal, CEO of Friends of Cancer Research, a research advocacy group.

Pitched by the Biden administration in 2021 as a $6.5 billion agency, ARPA-H is meant to be the biomedical equivalent of the Defense Advanced Research Projects Agency (DARPA), known for developing GPS and the Internet. As at DARPA, a small group of program managers will have considerable freedom to choose many of ARPA-H’s efforts and specific awardees.

ARPA-H’s gestation was contentious. Some research groups worried the new agency would siphon funds from NIH, which has its own “high-risk, high-reward” programs. Other observers doubted it would have the autonomy it needed to succeed. Some said it should be completely independent from NIH, whereas others argued that an NIH link would provide key expertise and infrastructure. After Congress created ARPA-H in March 2022, Department of Health and Human Services Secretary Xavier Becerra ultimately placed the agency under NIH, but Wegrzyn reports directly to him. Congress also said ARPA-H can’t be physically on the NIH campus in Bethesda, Maryland, which helps explain why the agency is currently working out of a WeWork suite in Virginia. (The agency will announce permanent headquarters in the Washington, D.C., area soon.)

Wegrzyn is a former program manager in DARPA’s biology division who also spent time at the synthetic biology company Ginkgo Bioworks. Less than 6 months after she took the helm, ARPA-H released a call for proposals. Unlike NIH, it didn’t initially ask for long applications full of supporting data—just 3 pages outlining a vision or major goal and how to achieve it. It drew a “large volume” of such applications, Wegrzyn says, and invited select groups to submit fuller proposals. The agency has so far funded seven projects, mostly with academic teams, from the printed heart to a cancer treatment that relies on bacteria to better diagnostic tests to help combat antibiotic resistance. It is also making a push in medical information systems, with awards planned for developing ways to pool data from across health systems.

Several initial recipients are former DARPA awardees; that’s not surprising, says Brad Ringeisen, former director of DARPA’s biotechnology division and now at the University of California, Berkeley. “I think it makes sense to leverage some of those past performers,” he says. In contrast to DARPA research, which is meant to help the military or its soldiers, ARPA-H’s projects aim to improve the health of all Americans.

ARPA-H is not supposed to focus on specific diseases—that’s NIH’s remit. Some of the agency’s first projects do focus on cancer and fall under Biden’s reignited Moonshot, a plan to slash deaths from the disease in half by 2047. But Wegrzyn points out that the cancer efforts really aim to develop “platforms,” or technologies, that can also help treat other health problems such as autoimmune diseases.

If APRA-H successfully follows its namesake’s history, the backbone of the agency will be its “programs,” led by a term-limited manager who conceives an idea, then assembles an outside team of scientists to carry it out with funding that might top $100 million or more. ARPA-H has announced just four programs so far. They include an osteoarthritis effort to regenerate tissues, a precision surgery initiative, and a scheme to implant cell-loaded devices in the body that will deliver medicines and serve as disease sentinels. The fourth program, on computational strategies to design vaccines that protect against many strains of a virus, was announced today.

The agency is also forming what it calls “a hub-and-spoke health innovation network,” dubbed ARPANET-H, to help coordinate efforts such as clinical trials or tests of devices in community health centers or rural hospitals. Staff will be based in three centers: the agency’s Washington, D.C.–area headquarters; a Boston area “investor catalyst” hub aiming to get ideas to the market quickly; and a center in Dallas focused on “customer experiences”—such as diversifying the agency’s clinical trial participants. But ARPA-H managers—aware of lawmakers’ desire to have broad geographic reach—say the network will extend into all 50 states.

APRA-H staff have fanned out across the country to hold “proposers days,” where they explain to academic researchers how its model differs from NIH’s. Teams selected by ARPA-H, funded with contracts rather than grants, will work closely with the agency and could have awards pulled if they don’t meet milestones. “It’s a different way of thinking and it’s not for everybody,” says Ringeisen, who estimates only 10% to 20% of academic researchers will find it appealing.

Under instructions from Congress, which is closely following the new agency, Wegrzyn must provide quarterly updates to lawmakers. She says that part of her mission is to explain that aiming high means “we will fail sometimes.” And she notes it could be 10 to 15 years before program managers’ bets pay off with health benefits for the country. “There’s so much excitement and promise around ARPA-H,” but also a need to “set expectations,” she says.

Wegrzyn’s chief goal in her second year is to keep hiring program managers, whom she sees as the most important element of the agency. She hopes to have 20 on board by the end of the year and at least double that number in 2024. What happens after that will depend on future budgets, and it’s unclear whether Congress will even give ARPA-H a raise in 2024. (A Senate bill keeps the agency’s budget flat at another $1.5 billion, whereas the House of Representatives wants to cut it to $500 million; meanwhile the agency has 2 more years to spend its current funding).

“I don’t have a crystal ball” to predict the agency’s future budget, Wegrzyn says. But for now, “launching these programs is what I’m super, superexcited about.”