Thursday, August 7, 2008

Scientists Seek Answers, Ponder Future After Anthrax Case Suicide

[Source: Martin Enserink and Yudhijit Bhattacharjee, Science] - Did he really do it? That's the main question on the minds of many scientists this week after an Army researcher apparently close to being indicted for the worst bioterror attack in U.S. history took his own life. As researchers tried to make sense of scraps of information filtering out in the media, many were hoping prosecutors would soon reveal their entire case against Bruce Ivins of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) in Frederick, Maryland, so the country can scrutinize the evidence that led the Federal Bureau of Investigation (FBI) to believe he mailed the anthrax-laden letters in fall 2001. That evidence likely includes sophisticated and possibly debatable scientific analyses.

For those who knew Ivins, the question is personal. "He was a nice guy, a sweet guy," says fellow anthrax veteran Martin Hugh-Jones of Louisiana State University in Baton Rouge. "He wasn't on my shortlist of possible suspects." In the wider field, the case is prompting other questions: If one of their own committed the crimes, will the biodefense budget, which ballooned after 2001, shrivel? Will public confidence in the field decline, and will rules for handling possible bioterror agents become draconian?

Ivins, 62, died at a Frederick hospital on 29 July after taking an overdose of painkillers. An author on 54 PubMed-listed papers, he had spent most of his career developing drugs and vaccines against anthrax, studies for which mice, rabbits, and monkeys were frequently exposed to the deadly disease. As Science went to press, the FBI had not named Ivins as a suspect, saying more news would be forthcoming after survivors and victims' families had been notified. Ivins's lawyer, Paul Kemp of Rockville, Maryland, has declared his client's innocence, alleging in a statement that mounting FBI pressure had "led to his untimely death."

The case against Ivins is likely to rest on "a combination of investigations--including good old gumshoe work, science, and perhaps other sources of information and evidence," says Randall Murch, a bioforensics expert who worked for the FBI and is now a Virginia Polytechnic Institute and State University administrator based at the university's office in Alexandria.

In a statement, the FBI credited "new and sophisticated scientific tools" for the "substantial progress" made recently. That, and a report in the Los Angeles Times that the bureau recruited Ibis Biosciences, a California company specializing in high-throughput genetic analyses, leads microbial genomicists such as J. Craig Venter of the Venter Institute (JCVI) in Rockville, Maryland, to speculate that an approach called metagenomics--which looks for the genomic makeup of an entire population of cells instead of a single one--may have been used to try to link the Bacillus anthracis spores mailed to two U.S. Senators and media outlets to those used in Ivins's lab.

News reports early this week also said genomic analyses suggested that the anthrax powder was a mix of two strains, one obtained at Dugway Proving Ground, a testing facility in Utah, and the other from USAMRIID. Opinions differ sharply among experts about whether a so-called lyophilizer, which Ivins was reported to have used, would suffice to produce the extremely fine, floating powder found in the Senate envelopes.

Whatever the scientific evidence, it would face stiff challenges in court, experts say; in contrast to human DNA traces, whose utility has become well-accepted, microbial forensic evidence is largely untested. Now that Ivins won't face trial, it's even more important that scientists be able to pore over all the evidence, says anthrax researcher R. John Collier of Harvard Medical School in Boston. "I would love to see what they have," Collier says. Still, scientific scrutiny can't replace a court of law, some say. "What's the forum? Are we going to discuss genetic frequencies in a dark hall in a Marriott somewhere?" another anthrax scientist asks.

The questions are critical because the FBI was wrong before. Just 6 weeks ago, the government agreed to pay $5.8 million to Steven Hatf ill, a former colleague of Ivins's at USAMRIID whose life was turned upside down in 2002 after then-Attorney General John Ashcroft called him a "person of interest" in the anthrax attacks. Virologist Thomas Geisbert, associate director of Boston University's (BU's) emerging infectious diseases lab, says he can't help wondering whether Ivins's death could be the result of "another Hatf ill situation"--except that Ivins was unable to handle the intense pressure. There were signs of mental instability; Ivins had recently been hospitalized for erratic behavior, and on 24 July, a Maryland court issued a restraining order against Ivins at the request of a therapist who said he had a history of making homicidal threats.

The FBI, which had little microbial forensic experience back in 2001, relied on a network of labs--including Ivins's at USAMRIID--to aid its investigation. (The Institute for Genomic Research in Rockville, Maryland, not only sequenced many anthrax strains but worked on the case before it was integrated into JCVI, says Venter.) The bureau has ordered researchers not to discuss or publish that work. "As a scientist, I hope I'll be able to do that now," says Geisbert, who in his previous job at USAMRIID produced electron micrographs of the spores used in the letters sent to the Senate.

Many believe that the case is bound to have wider ramifications for the biodefense field. Before 2001, such research was largely confined to USAMRIID and the Centers for Disease Control and Prevention in Atlanta, Georgia. The anthrax letters, which plunged a nation reeling from 9/11 into further anxiety, helped spur a massive increase in the biodefense budget--now some $5.4 billion a year--and a construction boom in biosafety labs. "The entire rationale for that expansion was fraudulent," says Richard Ebright, a prominent biodefense critic at Rutgers University in Piscataway, New Jersey, because it assumed a threat from outside the country. The boom has made the country less safe, Ebright maintains: "The spigot needs to be closed."
Others say the threat remains real. "It would be unfortunate if people take away the message that the only individuals we should be concerned about are deranged biodefense scientists," says biosecurity expert Gerald Epstein of the Center for Strategic and International Studies in Washington, D.C. But he acknowledges that the debate about how much biodefense is enough will likely reignite.

There may be other consequences, says Paul Keim, an expert in microbial fingerprinting at Northern Arizona University in Flagstaff who has also been recruited by the FBI. After the anthrax attacks, Congress passed legislation to limit access to bioterror agents to licensed researchers and imposed strict rules on where and how they can be used. Although researchers have decried them as overly cumbersome, the anthrax case may renew pressure to stiffen them further, Keim says. Additional measures could include cameras in virtually every lab, speculates Alan Pearson of the Center for Arms Control and Non-Proliferation in Washington, D.C. "The solution may well be if you work with pathogens like smallpox and anthrax, be prepared to be watched," he says.

The involvement of a U.S. scientist would also give new ammunition to local groups that have tried to stop construction of new biosafety labs. At BU, now a major academic biodefense hub, "we have had a lot of opposition--and this is not going to help," Geisbert says.

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