A Foundation Funding Frontier

Abstract

As the federal funding of basic biomedical research started to decline 15 years ago (on the heels of a dramatic doubling of the NIH budget) much blame was cast about. Elias Zerhouni, the NIH Director at the time, advocated a “Road Map.” He had consulted many advisers, and the general idea was arguably correct: to fund high risk/high reward projects that would not have otherwise been supported by the institutes. Despite this reasonable premise and Dr. Zerhouni's skill in branding and marketing the concept (as I once witnessed at a dinner meeting), the Road Map was claimed by some skeptics to be a ruse, designed to merely lubricate NIH funding of large laboratories at academic medical centers that were engaged in, or claimed to be engaged in, the translational zone between the lab and the clinic. The current NIH Director, Francis Collins, has been thoughtfully nuanced about the balance of basic and translational research in his portfolio. Like his predecessor, he is unpopular in some basic science hallways of academia where investigators see their proposals being turned down, but we should bear in mind that the recent NIH application success rates for basic research proposals are actually a bit higher than those for translational research. Moreover, there are data that indicate that NIH has lost something like 20% of its purchasing power in the past 15 years. Dr. Zerhouni was trained in medical physics and radiology. Dr. Collins is an internist/human geneticist and there are many, including me, who know that he has a strong, constitutional admiration for basic research. As the post-2003 decline in NIH award rates became so starkly vivid, many investigators began to look elsewhere, and thus came upon disease-oriented organizations they knew about but hadn't yet tried. And tried they did, driving up submissions and causing many such organizations to create a Letter-of-Intent first filter. This trend has raised the question, in my mind at least, as to how the private foundations should step in. From the perspective of basic biomedical research scientists like me, the answer is easy: please love all basic research in every domain of biology and medicine, including the field I work in and including my particular research program. The role of private philanthropy in biomedical science in the United States is a vast topic and beyond the scope of this editorial. In brief, we can recall with admiration all the Rockefeller Foundation accomplished, including the elimination of a major parasitic disease in the Southeast United States (1), the creation of the first American university devoted to medical science (2), and the inaugural and institutionally transformative funding of a biology research program at Caltech (3). The philanthropic axis of Andrew Carnegie took a different route, the creation of the Carnegie Institution of Washington (recently renamed the Carnegie Institution for Science), with numerous departments located in proximity to leading universities (4). (The Carnegie Institution did make occasional grants as well, a most historically important one being a 5-year award of $30,000/year to Caltech in the early 1920s in support of research in physics and physical chemistry.) In more recent times, Bill and Melinda Gates have created a tremendous philanthropy devoted to many unsolved problems in global health, Paul Allen has created an institute devoted initially to neuroscience but now all cell biology, and Priscilla Chan and Mark Zuckerberg have done the same, although with somewhat different but complementary goals. One cannot praise these visionary philanthropists enough. Although the record indicates that the spouses of John D. Rockefeller Jr. and Andrew Carnegie were supportive of their husbands' philanthropies, the coequal and perhaps even greater roles of Melinda Gates and Priscilla Chan must always be borne in mind. The mathematics/hedge fund guru James Simons has taken the Carnegie approach, setting up a research institute rather than becoming a funding body (5). Let us applaud him, too. Of course, there are many smaller foundations that focus on specific diseases. When I was starting out as an independent investigator, I received a 5-year salary award from the Leukemia Society of America (now the Leukemia-Lymphoma Society). My institution was happy, but I was surprised that this philanthropy was so liberal. I was not working on leukemia but rather on cell cycle control in HeLa cells, quite a stretch. Today, the disease-centered philanthropies play a large role. But, all this said, is there a need for more private philanthropy to support basic biomedical research? I say yes, and here's why. The first reason is that the U.S. government, despite having had decades of bipartisan support from Congress for both basic biomedical and clinical research, cannot direct the Mint to print more money. The NIH budget is negotiated in the context of a broader annual appropriation bill and is sometimes miscalled “entitlement legislation.” Needless to say, we investigators feel entitled, but that doesn't cause money to flow. And it will be tight for at least another decade, in my opinion. The second reason is that the various private foundations, blessed though they may be, will continue to fund large-scale projects or, at the other extreme, small projects that fit their particular disease focus. Let us hope both work, but this pattern leaves a big hole. This hole is a need for private foundations, either already in operation or ones to be formed, to be “NIH-like.” That is, to focus on the best basic discovery science. There are, in fact, a few foundations that like to see letters of intent or proposals that are “not ready for prime time” (i.e., NIH R01 applications) and are very broad in their appetites as regards the specific research field. We need more of these. How to address this goal? We are not present when most nascent foundations that might have a latent interest in biomedical science are in deliberations as to philanthropic ideas. (That a majority of the estate of Howard Hughes was left for the creation of a biomedical research institute was due to treating physicians in Boston who had his ear. We do not have such perches.) So I call upon all the major foundations and those that may arise from more recently acquired wealth to take the long-term view, combining any specific medical goal with some portfolio allocation for the most basic, curiosity-driven inquiries into the unknown. This would be a perfect harmony of goals, annealing all that the 20th century wealth-based foundations hoped to achieve with the Endless Frontier presciently envisioned by Vannevar Bush (6) and by visionary clinical investigators (7, 8). I close with what Tom Insel, the former Director of the National Institute of Mental Health, said about private foundations that fund biomedical research (5): “Yes, sure, they have a lot of money and they can put in a lot of money, but they can also take it away and put it somewhere else. My concern is that the generosity of Jim Simons will let the rest of us off the hook. Will we decide that science can be supported as a private endeavor, and forfeit our commitment to use taxpayer dollars for science?”