Is the U.S. biomedical research system broken? If so, what can be done to fix it? Participants in the first-ever SLAS Leadership Forum grappled with these questions in a two-hour discussion held during SLAS2015 in Washington, DC.
For the Forum—a groundbreaking event that will become a regular feature of the SLAS International Conference and Exhibition—SLAS invited senior professional laboratory science and technology experts to discuss major issues in life sciences R&D. For this inaugural event, panelists and participants shared ideas and experiences prompted by a recently published paper that suggested the U.S. biomedical research system is broken. While Forum invitees agreed that the current system has shortcomings, many were not convinced that the recommended approaches (see Sidelines) were the best solutions. The discussion centered around current and emerging alternatives for funding innovative research; providing new opportunities for young scientists entering the field; and fostering collaborations among industry, academia and government for mutual benefit and for the advancement of life sciences research.
SLAS CEO Gregory Dummer, C.A.E., introduced the Forum, noting that it was the brainchild of SLAS Past President Jeff Paslay, Ph.D., Paslay Consulting, and SLAS Board Member Alastair Binnie, M.S., Bristol-Myers Squibb. The panel included moderator James Sterling, Ph.D., interim dean of Natural Sciences and director of Minerva Labs, Minerva Schools at the Keck Graduate Institute of Applied Life Sciences (KGI); Donald Ingber, M.D., Ph.D., SLAS2015 keynote speaker, professor of bioengineering, Harvard University, and founding director of Harvard's Wyss Institute; Alicia Löffler, Ph.D., associate provost, Innovation and New Ventures at Northwestern University; and Rob Nail, co-founder of Velocity 11 and associate founder of Singularity University.
Sterling provided context for the session, explaining that SLAS chose the topic to offer invitees opportunities to reflect on issues that were recently summarized in a research paper, Rescuing U.S. Biomedical Research from its Systemic Flaws, published in the Proceedings of the National Academy of Sciences and authored by Bruce Alberts, University of California, San Francisco; Marc Kirschner, Harvard Medical School; Shirley Tilghman, Princeton University; and Harold Varmus, National Cancer Institute. The authors contend that the current biomedical research model is "an unsustainable hypercompetitive system" that discourages students from entering the profession and seasoned investigators from doing their best work.
Problems with the system began with the doubling of the National Institutes of Health budget that occurred in the U.S. in the late 1990s and early 2000, Sterling explained. "Demands for research dollars grew dramatically during that time, fueled in large part by incentives for institutional expansion, rapid growth of the scientific work force and the rising costs of research." After that, slowdowns began, peaking during and after the 2008 recession and with the budget sequestration of 2013. Both intramural and extramural funding from NIH flattened, setting the stage for some of the issues discussed in the Forum.
In brief individual presentations, Sterling and the panelists described some of the approaches their organizations are taking in the areas of funding, education and innovation. KGI was launched largely in an effort to prepare students to move out of academia and go to work in industry, Sterling explained. As part of the effort, it has been pushing to make the Professional Science Master's degree the one that is needed for people who work in the life sciences, as the Master of Science degree is for many in engineering. At the same time, KGI offers a Postdoctoral Professional Master's degree for individuals who take several post docs and still cannot find a position in academia. The nine-month degree enables them to take courses in accounting, finance, project management and clinical and regulatory affairs, and work on team projects with industry. "From there, they can network and find jobs."
Löffler observed that academic environments are highly fragmented, with many redundant processes and activities. Overly focusing on efficiencies in academia, she said, can "kill creativity" because "innovation has to allow for chaos and serendipity." The trick is to find ways to manage costs while increasing those forces that contribute to innovation. "Cost will never be the driving force in an academic center; it is just part of the equation."
Like other panelists, Löffler noted that when looking at ways to reduce costs and improve efficiency, it's important to consider the health care industry as a whole. Increasing the efficiency of research alone will not make a significant difference in outcomes, since "the whole biomedical sector is highly inefficient and in need of restructuring, from research to the medical device, pharmaceutical and providers sides," she said. "If it takes 15 years to go from gene to bedside, then a 10% reduction in the entire value chain gains only a year and a half, meaning it will still take more than a decade to go from bench to patient."
Nail pointed to the Defense Advanced Research Projects Agency (DARPA) as a model funder, noting that NIH is only one source of funds (also see "Funding Sources," below). "I got involved with this industry by building a robotics company, but what we brought to the space was on the back of many years of heavy research that was funded through DARPA," he said. He urged that both DARPA and NIH funding be doubled again. "We know so little about the human body that more funding from those sources could help in significant ways."
Ingber said that the Wyss Institute started six years ago with a $125 million grant from philanthropist Hansjörg Wyss and nearly matching funds from Harvard, noting that private funding is another important source of research and education dollars. Wyss integrates students at all levels—from undergrads to post docs—with people who were hired from industry, he noted. "Students learn not simply by taking courses, but by being in the trenches and doing," Like Nail, Ingber also pointed to DARPA as a primary government funder for his work.
After panelist presentations, participants engaged in discussion of key topics, including:
Funding Sources: Panelists and participants agreed that NIH is only one source of funding, and it didn't make sense to focus exclusively on ways to "fix" it. "We can't equate NIH research with biomedical research; they're not equivalent," Sterling remarked. "There are plenty of other funding mechanisms for biomedical research that are outside of NIH." Ingber and Sterling emphasized the importance of private funding, from individual donors as well as foundations targeting specific diseases. Additional funding sources become available when institutions spin out a company, Sterling added. "At that point, you have the opportunity to get money from friends and family, angel investors and venture capitalists."
Big Problems: There was a general feeling that although "originality and risk taking" are appropriate funding criteria, NIH specifically should include a requirement that funded work connect to important real-world issues. Ingber commented, "People should have the freedom to research what they want, but in such a way that they're trying to solve problems that are meaningful for everybody. At Wyss, we tell researchers to go after the big unmet medical problems, not little incremental advances."
Nail observed that "the new generation is growing up feeling completely connected to everyone around the world, resulting in a level of empathy toward humanity and the planet that is different from anything we've seen before. This leads them to ask why they would want to go into an academic lab and work on some little thing that won't make a difference—and so we have to provide a context in which that little thing is going to make a difference somewhere."
Post Docs: Participants revisited issues related to post docs, including whether their numbers should be reduced and salaries increased. They also wondered whether students—both Ph.D. students and post docs—should be directed to a broader range of careers. One participant asked whether there are enough programs like the ones described by the panelists that provide opportunities for research as well as training to work in other areas.
Ingber said he agreed that post docs are paid poorly, given their level of training, and there is a feeling of "hopelessness" among many young people going into biomedical research that needs to be resolved. But he is not convinced the solution is to fund fewer post docs. He noted that many of the post docs he sees at Harvard come from outside the U.S., so it is unlikely that there will be fewer post docs simply because NIH decreases post doc funding. Moreover, he does not think there are too many post docs; rather, the problem is that they're being trained mainly for academic positions. "NIH is correct about the need to transition young people with scientific training to a broader range of careers, including businesses unrelated to medicine—for example, health care services, insurance and entrepreneurship."
"From the industry side," Nail added, "no one would argue that more diverse training wouldn't be useful."
Reproducibility: The issue of "reproducible" research—and lack thereof—was also discussed. Sterling said that an Amgen study published several years ago showed that researchers were unable to replicate results of 47 out of 53 papers that were seminal to launching drug discovery programs. Yet it's not always possible to reproduce results of major advances that require specialized knowledge of technologies, he acknowledged. An extreme example would be trying to reproduce the work of a group that produced a super collider. "To reproduce that, you need to build a super collider and that takes billions of dollars, so reproducing it is essentially impossible. You publish it understanding that it's a one-off example, and hopefully in the future somebody can reproduce it or the same groups can reproduce it with more information and detail later."
In a similar vein, Ingber recalled the mixed reactions to the work of cancer researcher Judah Folkman. One group who tried to replicate Folkman's results could not; however, another group did replicate the work and had similar findings. "This work is hard, and it may not be repeatable immediately," Ingber stressed. "Groups may need more time and knowledge before they can repeat it. But if one group can repeat it, it's repeatable."
Löffler added, "there is no incentive today for a faculty member to reproduce or validate results. Once a publication is out, we move on to something else. There is no system within academic centers to validate the technology. Many experiments can't be reproduced because there are no standards in the methodology of common practices." While standards have been successfully used in many other fields, she said, few broadly implemented standards exist for reagents, assays, laboratory practices, data analysis and reporting, and quality overall in life science research.
One participant observed that the "methods" sections of published articles often are incomplete, so it would be impossible to duplicate someone else's work going by that alone. "Academics know this and don't trust the methods in papers," the participant said. "We send the authors an e-mail and ask for the details."
Another participant said that when work can't be replicated, it's often because those studies "reflect improper use of statistics and data analysis methods." Some journals require reviewers to determine that appropriate statistical methods were used when authors conclude that a finding is statistically significant. "That has become another sink hole for us. Now we have to pay for statisticians, who are not paid for in NIH grants," he said.
Public-Private Partnerships: Several participants pointed to public-private partnerships as a way of moving biomedical research forward without depending on NIH or other external funding sources. Löffler agreed that "collaboration is key," noting that her department has many agreements with pharmaceutical companies. Many are simply transactional, she said, but two are different. The collaborations with Baxter and Quidel involve investigators from the drug companies staying at Northwestern and working with students in the lab.
Nail said one of the tenets of his organization, Singularity University, is to encourage startups to target "the biggest problems facing humanity, such as food, water, education and global health." Every program includes thought leaders and academics, entrepreneurs, corporate executive leaders, government policy leaders, nonprofit and foundation leaders, as well as investors. "It's important from a global perspective to get all six of those demographics in a room to discuss a big problem, because you'll come up with a completely different outcome than you would otherwise," he said. Although "the IP question always comes up, if we're dealing with a problem that's big enough and meaningful enough, everyone will end up collaborating across all of those areas."
Forum participant Robert M. Campbell, Ph.D., editor-in-chief of the Journal of Biomolecular Screening and senior research advisor at Eli Lilly and Company, reflected on his experience with public-private partnerships. He pointed to the Structural Genomics Consortium (SGC) as a collaboration between various industrial and academic partners that supports early stage drug discovery via the identification of chemical probes or tool compounds. "We (Eli Lilly) and the other SGC partners each get early access to considerable information (crystal structures, probe molecules, assay methods, troubleshooting techniques, novel biology, etc.) through group update meetings, one-to-one meetings with each partner and ongoing email communication. Initially, I think there was some general hesitancy about what questions one could ask, but over time, the discussions became more and more open and collegial. This type of collaboration was new for Lilly (i.e., a private-public partnership to identify chemical probes), and I believe it's a great first step for the scientific community to move the science of epigenetics forward very quickly."
In a different type of partnership, Lilly, Merck and Pfizer joined together to form an independent non-profit company, the Asian Cancer Research Group, to accelerate research on treatments for underserved diseases—in this case, commonly diagnosed cancers in Asia, Campbell added.
"There's growing recognition in pharma and biotech that we can't do everything ourselves. The more we collaborate (with each other and academia), the more we see increased trust, synergies, shared learning and ultimately the acceleration of scientific progress," Campbell said. "We acknowledge that we need each other and this is the best way to go forward. If we do things individually, we could each end up spending large amounts of money dealing with the same problems. It's a waste of time and money to duplicate efforts. Most importantly, the goal is to get the right drugs to the right patients more rapidly."
Sterling emphasized that the SLAS Leadership Forum "was a great beginning to exploring where our members are on these issues, how their organizations are approaching some of the problems related to biomedical research funding and the role SLAS can play in supporting and moving the scientific community forward." As part of that support, SLAS President Dean Ho, Ph.D., University of California, Los Angeles, announced at the opening session of SLAS2015 that the Society is launching a new SLAS Graduate Education Fellowship Grant Program with $1M in funding to enable students to pursue advanced degrees, and ultimately careers, in quantitative biosciences.
May 11, 2015