There was insufficient scientific evidence to support the FBI's assertion that anthrax sent to politicians and journalists in the wake of the September 11 attacks originated in Ivins' lab, said the National Academy of Sciences.
"It is not possible to reach a definitive conclusion about the origins of the B. anthracis in the mailings based on the available scientific evidence alone," said the NAS report.
The anthrax mailings, which killed five people and injured 17, rattled an already jittery American public just days after Al-Qaeda militants hijacked passenger jets and plunged them into the World Trade Center and the Pentagon.
The review found that anthrax contained in a flask, known as RMR-1029, in Ivins' lab shared genetic similarities with spores in the mailed letters but "was not the immediate source of spores used in the letters."
"One or more derivative growth steps would have been required to produce the anthrax in the attack letters," the report said, adding that the letters sent to Washington had different characteristics than those sent to New York.
"They have enough physical and chemical differences between the two that they must have come from separate batches," said lead author of the report Alice Gast.
The FBI concluded that the mailed anthrax must have come from a single flask of parent spores that Ivins had created and which he alone had maintained.
The type of anthrax contained in the letters, mailed to NBC anchor Tom Brokaw, the New York Post and senators Tom Daschle and Patrick Leahy, was correctly identified as the Ames strain of B. anthracis, which originated from a cow in Texas in 1981 and was shared with labs worldwide, the report said.
But a key problem arose from the way the FBI attempted to narrow down the source of the anthrax by creating a repository of potential samples provided by the labs that maintain them.
The repository was incomplete, leaving the possibility that other sources could remain unexamined, and also relied on scientists to provide their own samples, allowing for manipulation by potential suspects.
"Standards of custody of evidence would dictate that agents of the FBI should have obtained the samples," the report said.
"The sender could have been the instigator and may not have complied with instructions, as the FBI alleges with respect to Dr. Ivins."
Ivins, a bio-defense researcher at the US Army's Medical Research Institute of Infectious Diseases, committed suicide by taking drugstore medications in July 2008 as FBI agents were about to bring charges against him.
Investigators began focusing on Ivins in 2007 after new forensic scientific methods traced the anthrax back to him.
The NAS report was delayed in November 2010 when the FBI, which had just received the final draft for security review, decided to release more, previously classified information for the panel to consider.
FBI investigators had looked at anthrax evidence from "an undisclosed overseas site at which a terrorist group's anthrax program was allegedly located," the report said.
"The information indicates that there was inconsistent evidence of Ames strain DNA in some of these samples, but no culturable B. anthracis," it said, adding that the late-arriving information "deserves a more thorough scientific review."
The NAS reviewers also noted that their analysis of evidence was limited to "the biological, physical, and chemical sciences," and did not consider other traditional forensic science methods.
The FBI, which commissioned the NAS report, highlighted the panel's assertion that a definitive conclusion based on science alone "was not possible" and said a combination of factors led investigators to Ivins.
"The FBI has long maintained that while science played a significant role, it was the totality of the investigative process that determined the outcome of the anthrax case," it said in a statement.
Some lawmakers called for a new, independent probe of the government's response.
"The National Academy of Sciences report released today shows that the science is not necessarily a slam dunk," said Senator Chuck Grassley.
"There are no more excuses for avoiding an independent review and assessment of how the FBI handled its investigation in the anthrax case."
Congressman Rush Holt said he was re-introducing a 2008 bill to establish a legislative commission to investigate.
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