FBI conclusions in anthrax probe meet skepticism

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Aug 15, 2008 (CIDRAP News) – The Federal Bureau of Investigation's (FBI's) recently revealed conclusion that the late anthrax researcher Dr. Bruce Ivins committed the anthrax letter attacks of 2001 has been greeted with skepticism by many in the scientific community.

The FBI reported its conclusions and published a collection of documents about the long-unresolved case last week. The revelations came on Aug 6, only 9 days after Ivins, whom the FBI was about to charge in the case, died from an overdose of painkillers. In the anthrax attacks in the fall of 2001, five people died and 17 others were sickened after envelopes containing anthrax powder were mailed to two US senators and several media offices.

Ivins had worked at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) for many years, doing research that included work on anthrax vaccines. Early in the investigation, he analyzed some samples of anthrax from the 2001 attacks, according to media reports.

The FBI's case against Ivins is mostly circumstantial. But at its core is a claim that FBI experts and other scientists developed a new DNA fingerprinting technique that enabled them to match the letter anthrax to a batch of anthrax that was in Ivins' custody at USAMRIID in Frederick, Md.

"That science—creating a DNA equivalent of a fingerprint—allowed investigators to pinpoint the origins of the anthrax," the FBI said in its Aug 6 statement. "The FBI laboratory, in conjunction with the best experts in the scientific community, developed four highly sensitive and specific tests to detect the unique qualities of the anthrax used in the 2001 attacks. This took several years to accomplish, but in early 2005 the groundbreaking research successfully identified where the anthrax used in the mailings had come from."

But expert observers have said it's not possible to evaluate the FBI claims about the DNA evidence implicating Ivins because the agency has not published the details.

Dr. Martin Hugh-Jones, an anthrax expert at Louisiana State University in Baton Rouge, told CIDRAP News, "As others, including D.A. Henderson [who led the fight to eradicate smallpox], have said, we only have their word on this until they publish the details of this study."

In addition, some have argued that because Ivins was involved in analyzing the anthrax used in the attacks, cross-contamination in his work area might account for the match between the letter anthrax and the batch of anthrax that was in his custody.

Also, reports early in the investigation indicated that the mailed anthrax was a highly sophisticated preparation that Army scientists were unable to duplicate, which has caused observers to voice doubts about Ivins' ability to make the material on his own.

Previous stumbles
The history of the investigation has given rise to skepticism about aspects of the case other than the scientific and technical. Back in 2002, the FBI had publicly cited researcher Steven Hatfill as "a person of interest." But the agency never came up with any good evidence against him, and Hatfill eventually sued the FBI. He was awarded $5.8 million in damages, which the FBI paid in June.

Aside from the DNA fingerprinting link, the evidence cited by the FBI is circumstantial. As summarized in FBI documents and a recent Associated Press (AP) report, clues included the following:

  • In the days before the mailings, Ivins worked alone at night and on weekends in the lab where the anthrax spores and production equipment were stored, something he had not often done before.
  • Ivins did and said things that suggested consciousness of guilt and submitted a questionable sample of anthrax to the FBI.
  • He had frequently driven to other places to mail packages under other names.
  • He was a "prolific writer" of letters to Congress and the media—the targets of the attacks.
  • An e-mail he wrote used language similar to that in the anthrax letters, including the phrases "death to America" and "death to Israel."

A DNA fingerprint
But the linchpin of the FBI's case seems to be the DNA fingerprinting evidence. The agency discussed that evidence in documents released last week (and posted online), many of which were affidavits in support of requests for search warrants.

One of these says that the mailed anthrax was the Ames strain, which was first isolated in 1981. "As a whole, the collection of all of the genetic mutations found in the anthrax used in the 2001 mailings, serve to provide a 'DNA fingerprint' which can and has been used to investigate other Ames isolates collected from laboratories possessing the Ames strain."

"Four individual, highly sensitive, and specific molecular assays capable of detecting four of the genetic mutations discovered in the Bacillus anthracis used in the mail attacks have been developed and evaluated," the affidavit states.

In the investigation, the FBI used these four assays on more than 1,000 samples of Ames strain B anthracis obtained from 16 US labs and from others in Canada, Sweden, and the United Kingdom, the document states. Only eight of these samples were found to contain all four mutations.

"The . . . investigation has determined that each of the eight isolates . . . is directly related to a single Bacillus anthracis Ames strain spore batch, identified as RMR-1029," the affidavit says. After noting where this batch was kept, it adds, "RMR-1029 was compiled in 1997 by Dr. Ivins, the sole creator and custodian."

However, the document doesn't explain exactly how the eight isolates were linked to the anthrax Ivins had, other than having the same four mutations, nor does it give any details on the mutations or how they were identified.

That bothers Dr. C. J. Peters, a veteran virologist at the University of Texas Medical Branch in Galveston, who worked at USAMRIID from 1977 until 1990 and had considerable contact with Ivins there.

"I want to see the data. I want to see the valid scientific links made," Peters told CIDRAP News. He said forensic microbiology, unlike the use of human DNA in crime investigation, is a new area that has undergone little scientific scrutiny or testing in court cases.

"I just think it's a really unsatisfying conclusion," Peters said of the FBI claims. "I don't deny that Ivins might be the guy, and given his alleged psychiatric history, I would believe it even, but I don't see any evidence that really ties it down."

Referring to the four mutations reported by the FBI, he said, "They're talking about a substrain of the Ames strain. Well, where did that substrain arise? It arose during the preparation of the Ames strain. If Bruce Ivins propagated it and got this strain, and someone else propagated it, how do we know they didn't get the same substrain?"

Peters said the FBI should publish its analysis in a scientific journal so that people who work in bacterial genomics can examine it. "I think it's something that can be done and must be done. If they don't do it, nobody's ever going to believe it," he said.

The FBI didn't return phone messages asking if the agency plans to publish the details of its DNA analysis.

Cross-contamination?
Another problem is that, as has been widely reported, Ivins himself was recruited by the FBI to analyze some of the letter anthrax early in the investigation. Critics have raised the possibility that cross-contamination in his lab might explain the reported match between the anthrax used in the attacks and the anthrax in batch RMR-1029.

Gerry Andrews, a University of Wyoming microbiologist who was a friend and colleague of Ivins', made this point in a New York Times opinion piece on Aug 9. Andrews said Ivins worked on analyses of the letter anthrax for years. "Might that explain why the anthrax used in the attacks was later found to have the same DNA footprint as the other anthrax preparations in Dr. Ivins' lab?" he wrote.

Hugh-Jones agreed that this was a possibility. "[Given] that Bruce was involved in the early investigations on the letter contents and knowing its [anthrax's] great ability to fly, it's not at all unlikely that there may have been some laboratory contamination," he said.

If it is established that the anthrax in Ivins' custody matched what was used in the attacks, the FBI's case still requires acceptance of the proposition that he was the only person who had access to it. Some critics aren't buying that.

Barbara Hatch Rosenberg, PhD, who has closely followed the anthrax investigation and has criticized the FBI's efforts in the past, told CIDRAP News via e-mail, "Even if the evidence is perfect, it is not incriminatory because something like 100 others also had access to the same stock."

Rosenberg, a former cancer researcher and retired professor of natural sciences at the State University of New York at Purchase, added, "Record-keeping was not reliable at USAMRIID. If the FBI could really eliminate all the others of the 100, how come it took so long to 'eliminate' Hatfill and focus on Ivins?"

What was in the powder?
Other key questions in the investigation include the precise nature of the anthrax powder used in the attacks and whether Ivins could have prepared it. The FBI has not made clear whether the powder was a simple preparation of dried anthrax spores or a much more sophisticated product with special coatings or additives that enhanced its ability to spread through the air (which necessitated expensive cleanups of contaminated buildings after the attacks). The second possibility would make it less likely that Ivins was the sole perpetrator.

Peters said anthrax is relatively easy to grow, but growing it in quantity and turning it into a powder that is easily aerosolized is much harder. "The details of that powder have never really been divulged. The real analyses of the powders in the letters to [Sen. Tom] Daschle and [Sen. Patrick] Leahy have never been made public, so we don't know how good they were," he said.

News reports based on the FBI information released last week said Ivins worked with lyophilizers, or freeze-drying devices, which can convert anthrax to powder form. However, Peters said it wasn't clear to him whether Ivins ever worked with powdered anthrax. In Peters' time at USAMRIID, anthrax preparations used to "challenge" animals in vaccine tests always involved liquid aerosols, not powders.

"The fact that he's the guy who made the materials to challenge the animals has absolutely nothing to do with making the powder," Peters said.

Various press reports early in the investigation indicated that the mailed anthrax was a highly sophisticated preparation; Rosenberg traced some of these in an article titled "Gaps in the FBI's Anthrax Case," which she circulated through an e-mail forum of the Geneva-based Bio-Weapons Prevention Project.

For example, in 2002 the FBI asked the Department of Defense's Dugway Proving Ground in Utah to try to reproduce or "reverse engineer" the mailed anthrax. Close to a year later, in 2003, an FBI official acknowledged that this effort had failed, which convinced the agency that the culprit had special expertise, according to Rosenberg.

Richcard Spertzel, former head of the biological weapons section of the UN Special Commission and a member of the Iraq Survey Group, added support for this view in an Aug 5 opinion piece in the Wall Street Journal. He said information released by the FBI over the years pointed to "a product of exceptional quality," with particles just 1.3 to 3 microns in diameter.

"Apparently the spores were coated with a polyglass, which tightly bound hydrophilic silca to each particle," Spertzel wrote. "That's what was briefed (according to one of my former weapons inspectors at the United Nations Special Commission) by the FBI to the German Foreign Ministry at the time."

Spertzel asserted that USAMRIID does not have the equipment to produce such a substance and that, in any case, it could not have been made there without many other people being aware of it.

By e-mail, Rosenberg told CIDRAP News that the FBI in recent years has tried to downplay the idea that the mailed anthrax was a very sophisticated product. This effort included an article published in Applied and Environmental Microbiology in August 2006 in which the FBI called the idea "a widely circulated misconception." Rosenberg said the FBI's effort seems to have worked, "since no one is questioning the assumption that the spores were merely purified and dried."

Hugh-Jones summed up the issue this way: "We are getting all sorts of stories now on the nature of the letter product, from claims that it was naked to a highly sophisticated coating and additives. It is said that it took some 18 months to not be able to replicate it at Dugway, which, if true, would indicate that something had been added. Confusion. All in all this would seem to have been beyond Bruce's [Ivins'] experience and capabilities. But if he couldn't make it, who at Detrick could have?"

Proposing a 'court of science'
Another infectious disease expert, Michael T. Osterholm, PhD, MPH, suggested that a full and fair consideration of the FBI evidence in the case will require a special task force or process. In the wake of Ivins' death, the FBI wanted to quickly present its case to the anthrax victims and families and the public, but in acting quickly, the agency couldn't present the case fully, as it would have in a trial, he said.

"Now we have to find a way for that case to be completely shared within the scientific community in such a way as to create a court of science as opposed to a court of law," said Osterholm, who is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of CIDRAP News.

"At this point I for one am completely open-minded as to whether or not the FBI data are sufficient to provide a convincing scientific argument that he [Ivins] was the source," he said. But he added that he has seen people becoming polarized on the issue, despite the incompleteness of the available information.

"I think the next step will be a critical one for the FBI, and that is finding a proper venue for a comprehensive scientific review of the information," Osterholm said. "I would suggest, for example, that the Institute of Medicine or a special advisory committee to the attorney general, made up of scientists who have expertise in these areas and who have no obvious conflicts of interest. That's the process I hope happens soon."

See also:

Aug 6 FBI statement on case
http://www.fbi.gov/page2/august08/amerithrax080608a.html

Page with links to FBI anthrax investigation documents
http://www.fbi.gov/anthrax/amerithraxlinks.htm

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