To help catalyze innovation in the health and biomedical sciences, research and development (R&D) paradigms with a track record of producing ‘moonshot’-scale breakthroughs - such as the Advanced Research Projects Agency (ARPA) model - stand at the ready. The Biden Administration has recognized this, proposing the establishment of an ARPA for health (ARPA-H) as part of its fiscal year 2022 budget request. Done right, ARPA-H would be created in the image of existing ARPAs - DARPA (defense), ARPA-E (energy), and IARPA (intelligence) - and be capable of mobilizing federal, state, local, private sector, academic, and nonprofit resources to directly address the country’s most urgent health challenges, such as the high cost of therapies for diseases like cancer, or antimicrobial resistance. During a recent House Energy and Commerce Committee hearing, Chairwoman Anna Eshoo (D-CA) raised the Administration’s proposal for ARPA-H with Department of Health and Human Services (HHS) Secretary Xavier Becerra, expressing her interest in exploring how to best position a potential ARPA-H for success.
Keys to the ARPA model
The success of the ARPA model is attributed in part to the high level of autonomy with which its program leaders select R&D projects (compared to those at traditional federal research agencies), a strong sense of agency mission, and a culture of risk-taking with a tolerance for failure, resulting in a great degree of flexibility to pursue bold agendas and adapt to urgent needs. Policymakers have debated situating a potential ARPA-H within the National Institutes of Health (NIH), or outside of NIH, elsewhere under the umbrella of HHS. Regardless, it is essential that ARPA-H retain an independent and innovative culture.
The first ARPA - DARPA - was established in 1958, the year after Sputnik was launched, and is credited with developing GPS, the stealth fighter, and computer networking. DARPA continues to serve its customer - the Department of Defense - by developing groundbreaking defense technologies and data analysis techniques. Nevertheless, DARPA operates separately from its parent organization. This is also true of ARPA-E, which was launched in 2007 based on a recommendation from a National Academies consensus study report which called for implementing the DARPA model to drive “transformational research that could lead to new ways of fueling the nation and its economy,” and IARPA, created in 2006, to foster advances in intelligence collection, research, and analysis.
If ARPA-H is organized within NIH, it is essential that it maintain the innovative spirit and independence characteristic of established ARPAs. NIH already has some experience overseeing a partially independent entity: the National Cancer Institute (NCI). Compared to other NIH institutes, NCI’s unique authorities include:
This level of independence has contributed to NCI achieving a number of significant milestones in cancer treatment, including developing a chemotherapy treatment to cure choriocarcinoma (a rare type of cancer that starts in the womb), publishing the now-widely-used Breast Cancer Risk Assessment Model, and creating an anticancer drug for ovarian cancer that was unresponsive to other treatments.
- Direct access to the president;
- A requirement to submit a completely separate budget proposal to the president each year without getting approval from NIH or HHS; and
- The ability of the NCI director to form new cancer centers and training programs, establish advisory committees, and independently collaborate with other federal, state, and local entities.
If the NCI model were to be used as the foundation for the launch of ARPA-H, insulation from political considerations, whether those of Congress or the Executive Branch, would be critical. With DARPA-like autonomy, a potential ARPA-H could help push the boundaries of enrichments to human health.
Antimicrobial resistance as a case study for an ARPA-H
An example of a grand challenge that an ARPA-H could take on is addressing antimicrobial resistance, a worsening situation that, without intervention, will lead to a significant public health crisis. Antimicrobial resistance occurs when “bacteria, viruses, fungi, and parasites change over time and no longer respond to medicines, making infections harder to treat and increasing the risk of disease spread, severe illness, and death.” Microbes have the potential to gain resistance to drugs when not all of the pathogens or parasites are killed by a treatment, either because the treatment was the not correct option for the illness (like using antibiotics for viruses), or refraining from completing a prescribed course of an antimicrobial drug. The organisms that are not killed, presumably because they harbor genetic factors that confer resistance, then reproduce and pass along those genes, which make it harder for the treatments to kill them.
The most immediate concerns regarding antimicrobial resistance come from bacteria and fungi. The CDC considers some of the biggest threats to be Acinetobacter, Candida auris, and C. difficile, which are often present in healthcare and hospital settings and mainly threaten the lives of those with already weakened immune systems. Every year in the U.S., almost 3 million people are infected with antimicrobial-resistant bacteria or fungi, and as a result, more than 35,000 people die. While the toll of antibiotic resistance in the U.S. is devastating, the global outlook is perhaps even more concerning: in 2019, the United Nations warned that if no action is taken, antimicrobial resistance could cause 10 million deaths per year worldwide by 2050.
Developing new and effective antibiotics can help counter antimicrobial resistance; however, progress has been extremely slow. The last completely new class of antibiotics was discovered in the late 1980s, and developing new antibiotics is often not profitable for pharmaceutical companies. It is estimated that it takes $1.5 billion to create a new antibiotic, while the average revenue is about $46 million per year. In addition, while pharmaceutical companies receive an exclusivity period during which competitors cannot manufacture a generic version of their drug, the period is only five to ten years, which is too short to recoup the cost of research and development. Furthermore, doctors are often hesitant to prescribe new antibiotics in hopes of delaying the development of newly drug-resistant microbes, which also contributes to driving down the amount pharmaceutical companies earn for antibiotics.
Early last year, the World Health Organization reported that out of 60 antibiotics in development, there would be very little additional benefit over existing treatments, and few targeted the most resistant bacteria. Moreover, the ones that appeared promising will take years to get to the market. This year, Pew Research conducted a study on the current antibiotic development landscape and found that out of 43 antibiotics under development, at least 19 have the potential to treat the most resistant bacteria. However, the likelihood of all, or even some of these products making it to patients is low: over 95 percent of the products in development are being studied by small companies, and more than 70 percent of these companies do not have any other products on the market.
There is both a dire need for new innovations in the space, such as using cocktails of different viruses that attack bacteria to treat infections, and a gap between the research into and commercialization of new antibiotics - a perfect opportunity for a potential ARPA-H to make an impact. With this new agency, experimental treatments could be supported through the technology transfer process and matured to the point that the private sector is able to take the baton and move a new antimicrobial to market. This would be revolutionary for public health, and, combined with improved messaging around best practices for the use of antibiotics, save many lives.
The need for, structure, and possible priorities of a potential ARPA-H will continue to be discussed over the course of the congressional appropriations process, with consultation between the Legislative and Executive Branches. We encourage the CSPI community to serve as a resource for Members of Congress and their staffs to ensure that the new agency will be properly positioned to contribute to significant advances in human health and biomedical technologies.