The imminent departure of Elias Zerhouni as director of the US National Institutes of Health (NIH) in Bethesda, Maryland, leaves large shoes to fill. Zerhouni, who announced last week he will quit his post by the end of October (see page 570), managed the agency with a blend of vision, toughness and dedication even as it faced stagnating funding, ethical uproars and an explosion of knowledge in biomedical research. It is to his credit that he leaves the agency with far more friends than enemies, and with a well-earned reputation as a public servant who tirelessly maintained his integrity during the administration of President George W. Bush.

Whoever follows Zerhouni faces unenviable challenges. Stem-cell research remains stymied by an outdated presidential policy. The conflict-of-interest scandal continues as Senator Charles Grassley (Republican, Iowa) has reported troubling instances of extramural NIH researchers failing to report five- and six-figure payments from drug companies that could benefit from their research. And with nothing but flat funding for the foreseeable future, NIH-supported labs are being squeezed nationwide. A new generation of academic scientists is being imperilled as many head for jobs in industry or elsewhere rather than face the daunting odds of ever landing an NIH grant.

All of this is occurring in the post-human-genome era with a knowledge base expanding at warp speed. Improved understanding and treatment of diseases have never been so tantalizingly close. So what qualities should the next president seek in a new NIH director? Three are key.

First, despite the fact that some two-thirds of the agency's budget is spent on basic research, the next director should be someone who understands, and is committed to, translating discoveries to the bedside. Zerhouni, a radiologist, did much to advance this agenda, although it was not his idea; the agency's mission statement makes it clear that the NIH is devoted to “science in pursuit of fundamental knowledge ... and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability”. The agency's next director should not throw money willy-nilly at translational research; accountability is vital as such work goes forward. But taxpayers who invest US$29 billion annually in the NIH deserve to see their lives and health improved because of it.

Second, the next director should be a gifted communicator who can speak with ease to the NIH's scientific constituency, to Congress and to the public. Translating complex research into terms meaningful to the public and to lawmakers is a crucial skill, especially as the NIH seeks its share of an ever-more-constrained federal budget.

Third, the next director should be an able manager willing to make and stick to tough decisions in times of ethical and financial stress. Although the ranks of current and former directors of the agency's 27 component institutes contain many amply qualified candidates for the top job, it may be worth reaching outside NIH circles for a candidate not beholden to long-time peers in Bethesda. Zerhouni, who came from the Johns Hopkins School of Medicine in Baltimore, Maryland, showed that this strategy can work well.

Overall, a director should be chosen with appropriate speed. Allowing the NIH's top post to sit vacant for months or years — as Bush did when he took more than two years to nominate Zerhouni — could do serious damage to the agency at a time when bold leadership is vital.