Elias Zerhouni: leaving this month. Credit: R. L. WOLLENBERG/NEWSCOM

Plaudits for departing director Elias Zerhouni may be echoing through the US National Institutes of Health (NIH) in Bethesda, Maryland — but underlying them is uncertainty about who will take over, and when. The White House has not yet named an acting director.

After six and a half years at the helm of the NIH, the world's largest biomedical research agency, Zerhouni announced last week that he will leave by the end of October. With this announcement, he sidestepped any notion that his decision is linked to the outcome of the 4 November presidential election. But it ushers in a transition period that will stretch for at least several months. The next US president will not take office until 20 January 2009, and high-level presidential nominations like that of NIH director can be achingly slow to make.

"We are all worried about what is going to happen in the interim and who the next director of NIH will be," says Story Landis, director of the National Institute of Neurological Disorders and Stroke, one of the NIH's 27 institutes and centres.

Zerhouni leaves as the $29-billion agency faces great financial stress. Its budget doubled between 1998 and 2003, but since then its purchasing power has eroded by 10% as slight budget increases have failed to keep up with biomedical inflation. Many say that Zerhouni's work in the face of nearly flat funding has, of necessity, been the defining feature of his directorship (see 'Difficult times to make an impact').

Anthony Fauci, the long-time director of the National Institute of Allergy and Infectious Diseases, remembers advising the newly appointed Zerhouni: "Elias, what happens to you is going to rely very heavily on circumstances that are totally beyond your control." The two men still joke about it.

Zerhouni had faced challenges before. As the fifth of seven sons of a homemaker and a maths and physics teacher, he arrived in the United States from his native Algeria at the age of 24 with $369 in his pocket. By the time he was recruited to the NIH in 2002, he was one of the top experts in magnetic resonance imaging (MRI), and, among other things, had pioneered magnetic tagging — an MRI method that can be used to track heart motions in three dimensions. He had also risen to become executive vice-dean and chair of radiology at the Johns Hopkins School of Medicine in Baltimore, Maryland.

But it was soon apparent that the NIH gig wouldn't be a cake walk. "He comes into NIH and almost as soon as he gets there the good old days are over," says Howard Garrison, public-affairs director at the Federation of American Societies for Experimental Biology (FASEB) in Bethesda. As the agency's budget stagnated, success rates for grant applicants — especially first-time grant-seekers — plummeted. Zerhouni responded in 2006 with the 'Pathway to Independence' awards for young scientists, and managed to bring the number of first-time awards back up to 1,600 last year after it had dropped below 1,400 in 2006.

One early and much-criticized initiative was his 'Roadmap for Medical Research', a series of measures promoting trans-institute, high-risk, innovative research. As the budget for this grew from $132 million in 2004 (0.47% of the total NIH budget) to $495 million (1.7% of the total NIH budget) in 2008, it was perceived by some as too costly during a time of scarcity. In April 2006, Andrew Marks, then editor-in-chief of the Journal of Clinical Investigation, penned an angry editorial that began by telling Zerhouni: "Obviously you are not a scientist."

To this day, Zerhouni remains unfazed by criticism of the Roadmap. "I needed to do something to recognize that the boundaries of science have changed," he says.

Zerhouni also battled a conflict-of-interest scandal at the agency, after Congressional examiners uncovered lucrative payments to moonlighting intramural NIH researchers by drug companies with financial stakes in agency recommendations or research. Zerhouni implemented tough new ethics rules for staff scientists — which he softened only a little after an outcry on the Bethesda campus.

"He's had to manage great expectations and stagnant resources," says Tony Mazzaschi, senior director of scientific affairs at the Association of American Medical Colleges in Washington DC. "And in that environment, he was able to add power to the director's role. That's not any mean feat."

The question is who will come next. Washington is rife with speculation, most of which will turn out to be wrong. "When Elias became director, his name was nowhere on anybody's radar screen," says Fauci. Fauci's own name is inevitably floated whenever the NIH directorship is vacant. And any shortlist could include a stable of current and former institute heads, from heart institute chief Elizabeth Nabel to Francis Collins, who recently departed as director of the genome institute.

One other top medical spot in the Washington area got filled this week. Robert Tjian, a biochemist at the University of California, Berkeley, will take over the presidency of the Howard Hughes Medical Institute in Chevy Chase, Maryland, next spring from departing leader Tom Cech.

Zerhouni's expected choice of acting director in his wake, deputy director Raynard Kington, is said to be a finalist for the chancellorship of the State University of New York. Doubtless the wisest shortlist reads: to be announced.