Can Arena Bioworks upend the traditional scientific research model in the U.S.?

I’ve spent a good deal of my career thinking about how we structure and fund research in the biomedical sciences in the U.S. and questioning whether the U.S. model of embedding research in universities is the right one. So to me, the launch of Arena BioWorks is welcome news. As media reports have highlighted, the new effort — a press release says that it was “inspired by the success of Bell Labs” — promises to let scientists engage in research without first getting funding from NIH or other sources, as well as the option, if the results are promising, to spin off a for-profit company. Investors are spending considerable amounts of money to lure scientists away from academia, and there are big names involved: Stewart Schrieber, co-founder of the Broad Institute, is leading the effort; investors include Michael Dell, founder of Dell Technologies, Elisabeth DeLuca, Subway heiress, Steve Pagliuca, former co-chair of Bain Capital.

Yes, Arena BioWorks is great news for the lucky few who will work at an Arena facility, and they may make some major scientific breakthroughs. But it is also important to put its launch in perspective, to follow it, and study whether the Arena model is an effective and efficient way to “organize” science in order to produce results sooner rather than later. What I find particularly noteworthy about the Arena BioWorks initiative is the vision of its founders to build a biomedical research institute outside the university. The physical location of Arena is at Kendall Square in Cambridge, Ma., between MIT and Harvard. A second facility, according to Dell, is in the works and will be in Houston.

The commitment to creating the institute outside the university is noteworthy for at least two reasons. First, university labs have typically been staffed with graduate students and postdoctoral fellows, in part because they have been a bargain. Jobs in industry until recently have been scarce and universities have shied away from staffing labs with staff scientists, who are “quasi-permanent” and receive higher pay. Postdoctoral scholars who aspire to a faculty position often stay in a postdoctoral position for a number of years, waiting until they have gotten what I have referred to as a “get-out-of jail card” such as first authorship on an article published in Cell, Nature, or Science. Understandably, many trainees have felt betrayed by this system.

The institute model lessens the coupling between research and training by not being in the business of training more Ph.D.s. It could employ postdocs but not produce Ph.D.s. “Abstinence,” as I have said before, “is the most effective form of birth control.” Decoupling of the training of Ph.D.s from research is common practice in certain areas of physics where, because of the scale of the equipment, national labs play a prominent role — but Argonne Brookhaven, and Fermilab are not Ph.D. mills.

The university-based model for biomedical research also arguably discourages risky research. There are at least two drivers of this risk aversion. First, faculty in soft money positions find themselves in a “funding or famine” situation, as the physicist Stephen Quake has put it. This can encourage faculty in such positions to engage in research that carries minimal risk. (The situation in medical schools is somewhat different. While medical schools offer tenure to some basic science faculty, only about half of the 119 medical schools that do offer tenure equate it with a specified financial guarantee.)

Moreover, and importantly, the funding model in the U.S., in which faculty submit grant proposals, discourages risk-taking — funders tend to invest in projects that have strong preliminary results. To quote Stewart Schreiber, the scientist leading Arena, “It got to the point where I realized the only way to get funding was to apply to study something that had already been done.” The Arena model short-circuits this step, thereby encouraging risk-taking. It also minimizes the time researchers spend writing and administrating grants, freeing up time for the lab.

A willingness to fund risky projects, and the time to engage in them, is crucial if science is to advance at a reasonable pace. Vaccines for Covid-19 likely would have been available several years earlier if funders had been more supportive of the work of Katalin Karikó and, eventually, Drew Weissman, on making synthetic mRNA applicable to treat human diseases, a recent paper argues.

Karikó came to the U.S. in 1985, first as a postdoctoral fellow at Temple University, then the Uniformed Services University. In 1989, she moved to a faculty position at the medical school of the University of Pennsylvania where she was expected to obtain grants to support her research. According to Karikó, she submitted more than 20 grant applications, initially for small sums, to the university and the American Heart Association, then for much larger sums to NIH.  As hard as she tried, she repeatedly failed to get funding for her research. “Every night I was working,” Karikó told STAT and the Boston Globe in 2020. “And it came back always no, no, no.”

Her inability to support her research on grants eventually resulted in the university removing her from her faculty position. In 1995 she accepted a non-faculty position, that she describes as “more like a post-doc position” at the University of Pennsylvania, without any prospect of advancing. Two years later she met Drew Weissman while waiting for the copier; in talking they recognized that they shared an interest in developing a synthetic mRNA, and they began to work together.

But as promising as Arena Biotech sounds, it is important to remember it is a relatively small-scale experiment. The impressive sums of money involved are small potatoes compared with the amount annually available from the federal government. By way of example, the annual extramural research budget of General Medical Sciences, the NIH institute that supports the most basic research, is three times the amount that Arena has raised or hopes to raise. The entire annual extramural budget of NIH for research is around $40 billion — at least 50 times larger than what Arena currently has in its war chest.

It is also important to examine whether the Arena model is an effective and efficient way to “organize” science in order to produce results that can have a major impact. To this end, I strongly encourage Arena to invite social scientists to study their model with the goal of seeing the extent to which it fosters innovation and if so, what parts of the model might be transferable to other research settings, including the university. Of special interest are the degree to which the Arena model fosters risky research and the job satisfaction of staff scientists working at Arena. At a minimum, social scientists need to be included at the very beginning, so that relevant data are available to examine such issues and guide other philanthropists as they ponder how to invest their resources and encourage universities to make changes in their research model.

Paula Stephan is professor emerita at Georgia State University and research associate at the National Bureau of Economic Research. She has served on numerous National Academy of Sciences committees, including The Next Generation of Biomedical and Behavioral Researchers and on the Advisory Council of the National Institute of General Medical Sciences.