The debate over priorities in the funding of biomedical research has become heated in the past few months, particularly in the United States, where the National Institutes of Health (NIH) is in the midst of a disappointing budgetary cycle. The April issue of the Journal of Clinical Investigation featured a rather intemperate editorial by Andrew Marks entitled “Rescuing the NIH before it is too late”. Marks declares that NIH director Elias Zerhouni is “not a scientist” and that he exhibits a “lack of understanding of how science is done”. He goes on to accuse the entire United States Congress of failing to understand “the key role of science in the nation's health, welfare, and economy”, a situation exacerbated by the fact that the Bush administration is “targeting the NIH for destruction”. Not to be outdone, one of the correspondents in the follow-up discussion published by the JCI refers to new initiatives at the NIH as “the subversion of original science to bureaucratic need” and suggests that working scientists are not likely to support “the shock and awe of NIH planning”.

Well. What does one have to do to provoke this kind of inflammatory rhetoric? Not much, it turns out. Zerhouni's most notable initiative since taking the reins of the NIH has been the 'Roadmap', an effort to encourage translational research, promote innovation (via the Pioneer Award for high-risk proposals), and support community databases. The Roadmap, which is in the spirit of the recommendations for the NIH made by the Institute of Medicine in 2003, and which even Marks lauds as “practical and even forward thinking”, is budgeted at $2.1 billion over five years. Where does this stand in relation to the NIH budget as a whole? It constitutes a grand total of about 1.2% for fiscal year 2006. Shock and awe indeed.

None of this occurs in a vacuum, of course. After the historic doubling of the NIH budget from 1998 to 2003, the hoped-for soft landing failed to materialize, and the most recent budgets have failed to keep pace with inflation. Success rates for investigator-initiated R01 applications have gone down. But as a rebuttal letter from NIH Deputy Director for Extramural Research Norka Ruiz Bravo makes clear, lower success rates have little to do with the Roadmap, a project that is entirely consistent with the NIH mission. The absolute numbers show no slackening of NIH support for basic research and the R01 mechanism of funding; rather, they show an increase in the average size of R01 grants and, from 2001 to 2004, a remarkable near-doubling of R01 applications from new investigators. As editors who regularly attend conferences and visit scientists in their labs, we are well aware of the impact of declining success rates on morale. But the scorched earth strategy seemingly advocated by some makes little sense. Researchers should do what they have always done—respectfully lay out the case for a restoration of reasonable funding increases. Thanks to the power of incumbency, many of the congressional supporters of the budget doubling are still on Capitol Hill, and presumably remain sympathetic.

When money is tight, every dollar spent receives extra scrutiny. For example, efforts to update the peer review system for NIH grants have taken on added urgency in light of the difficulties younger investigators face in securing support. As Keith Yamamoto noted in a recent story in Cell, “The peer review system looks like it is in crisis because of the funding situation. If money were plentiful, it would mask any problems with it.” Of particular interest to geneticists is The Cancer Genome Atlas (TCGA), which started out as a hugely ambitious 10-year, $1.5 billion plan to collect 15,000 clinically annotated tumors, with the aim of identifying genetic and epigenetic alterations for which the total frequency exceeds 5% in a given tumor type. Were money to individual scientists flowing more freely, one imagines that a project like this would have been welcomed by one and all. But just as early plans for the Human Genome Project were criticized as threatening the careers of young investigators during a period of tight NIH budgets, biomedical research once again feels like a zero-sum game. Perhaps the most visible criticism of TCGA came in the form of a letter to Science by Stephen Elledge and Greg Hannon, who argued in favor of a delay until sequencing costs come down and who also noted the importance of screens to identify targets whose inhibition kills cancer cells. Laudably, these criticisms were solely scientific in nature, and TCGA has now been launched as a smaller $100 million, three-year pilot project, focusing on two tumor types.

Coming back to the dramatic increase in R01 applications, it seems that we all have to come to grips with the fact that scientific progress inevitably creates a demand for more money. As John Todd asks at the close of his commentary on page 731 of this issue, “...are the funding agencies, despite an environment of shrinking funding, ready for a torrent of knowledge about the genes and mechanisms of human physiology, health and disease?” The answer, almost certainly, is no. Every new pathway identified by convincing whole-genome association studies, and every new 'druggable' target of the cancer genome, will inspire young investigators to apply for new grants to exploit new opportunities. With this backdrop, to pit important large-scale projects against the careers of new investigators is to foster a debate, as Geoff Duyk has observed in these pages, that “only serves to polarize the scientific community”. The goal should be to create a diverse portfolio of research investments that is governed by realistic expectations, with young investigators given every chance to make their mark. This will require the reasoned input of all scientists in the setting of priorities, an exercise that implicitly acknowledges the real constraints under which budgets are devised. These constraints will not disappear in the face of broadsides about the cluelessness of the bureaucracy.