The US Food and Drug Administration (FDA) is in trouble. Last month's abrupt resignation of its commissioner, Lester Crawford, leaves the agency again bereft of leadership as it struggles to absorb the aftermath of last year's traumatic withdrawal of the painkiller Vioxx.

The Vioxx episode has left the agency in crisis, facing immense, conflicting pressures from watchdog groups and the pharmaceutical industry on how it should handle drug approvals. In these circumstances, the agency needs a commissioner who can rise above the political fray and convince the public that the FDA is in safe hands, while taking a sophisticated and innovative approach to drug approval. Unfortunately, there is little sign that it's going to get one.

The reasons for Crawford's departure, only two months after his confirmation in the position by the Senate, remain murky. The timing of the announcement — on a Friday afternoon as Hurricane Rita bore down on the Gulf coast — bore all the hallmarks of an effort by the Bush administration to bury the event (see Nature 437, 606; 2005).

To the surprise of the agency's supporters and detractors alike, the Bush administration announced that Crawford would be replaced on an acting basis by Andrew von Eschenbach — who would also continue to serve as director of the National Cancer Institute (NCI), a massive research agency with a stake in some of the FDA's toughest regulatory decisions. Last Friday, von Eschenbach admitted that this would be impossible, and said he would temporarily shelve his daily duties at the NCI and excuse himself from some cancer-related activities at the FDA (see page 802).

Crawford's record as acting and then permanent head of the FDA was underwhelming. He had little public visibility and seemed reluctant to back up his own scientific advisers when their advice ran counter to Bush administration doctrine, for example to make Plan B, the morning-after contraceptive, available over-the-counter from pharmacists (see Nature 437, 179; 200510.1038/437179a). Now his departure is being left wholly unexplained, prompting reports of financial conflicts, as well as a bipartisan congressional investigation.

It is not clear that von Eschenbach can do much better. The 63-year-old urology surgeon has exasperated NCI researchers by making it a goal to end suffering and death from cancer by 2015 — an improbable aim he describes as “within our grasp”. His public commitment to more rapid approval of experimental cancer treatments also deserves close examination in the light of several drug withdrawals, for safety reasons, in the past year alone.

This is not the prescription for an agency that has been rocked by serious crises and now needs a leader with a firm grasp of policy details.

In his three years at the NCI, he has become known as a hands-off manager who leaves the workings of bureaucracies under him largely to subordinates. This is not the prescription for an agency that has been rocked by serious crises and that now needs a leader with a firm grasp of policy details that ultimately affect millions of lives.

Yet if past inattention is any indication, it seems likely that the White House will leave von Eschenbach — a Bush family friend — holding the fort at the FDA while it is preoccupied elsewhere. That would leave an agency that has lacked a permanent head for most of Bush's presidency in limbo yet again. Three years ago, a government survey of 400 FDA scientists found 18% of them reporting that they “have been pressured to approve or recommend approval” for a drug “despite reservations about the safety, efficacy or quality of the drug”. In the absence of firm leadership, scientists at the FDA's headquarters in the Washington DC suburbs will be left to do battle with ideologues such as Scott Gottlieb, a 33-year-old physician and former Wall Street tipster who was appointed in July as deputy commissioner for medical and scientific affairs at the agency.

Perhaps the most worrying prospect is that of an agency left to drift and further neglect under a stop-gap commissioner for another three years, until Bush has served out his term. His administration needs to find a well-qualified, permanent FDA commissioner — and soon.