Beginning with cell samples of the anthrax that was mailed in 2001, investigators used advanced DNA fingerprinting techniques to identify unique sections of genetic code. With that, investigators tracked the anthrax back to the biological weapons lab at Fort Detrick in Frederick, Md., where the highly specific type of toxin was overseen by scientist Bruce Ivins.
A government scientist close to the investigation described the process to The Associated Press. He did so on condition of anonymity because he is not authorized to speak about the case.
The genetic case-cracker and other tools used to identify Ivins as the lead suspect in the attacks are believed to be described in court documents that remain sealed. Because Ivins committed suicide last week before he could be indicted on murder charges, the Justice Department is considering closing the "Amerithrax" investigation, possibly as early as Monday or Tuesday.
If so, the court documents could be released, capping what had been one of the FBI's most publicized unsolved cases.
Quoting federal officials close to the seven-year investigation, The Wall Street Journal reports that a bookcase in Ivins' office at an Army laboratory contained anthrax spores that have become central to the probe and a key link to the government's case against Ivins.
Critics of the investigation told The Wall Street Journal that the spores found on the bookcase, along with those found in a nearby men's changing room - which are both far from the military lab where scientists worked with anthrax - should have made Ivins a top suspect much earlier.
Among the other unanswered questions in the investigation is how Ivins could have created the fine anthrax powder that, distributed in the mail, killed five people and terrorized the nation. Ivins' lab didn't deal with powdered anthrax and there is disagreement over whether he could have created it - and if he did, how he kept it a secret.
"It takes time and privacy, especially working out the methods, which I wouldn't have guessed anyone really knew in the lab at that time," said former colleague David R. Franz, who added that Ivins probably could have figured out the science but would have had trouble going unnoticed.
It's also unclear how prosecutors went from the DNA analysis, which narrowed their focus to a small number of scientists, to being certain enough of his guilt to prepare murder charges and begin discussing plea deals and the death penalty.
The case also raises public policy questions. Ivins' therapist, Jean C. Duley, described him as a "revenge killer" who had been diagnosed by several psychiatrists asYet Ivins was cleared by the U.S. government to work with some of the world's most dangerous toxins.
That underscores a little-known security gap in the nation's biological warfare laboratory system: Many of the estimated 14,000 scientists working with these dangerous substances are not screened for lingering psychological problems.
Dr. Russell Byrne, a former colleague of Ivins' who said he had known him for 15 years, said he had not noticed anything amiss in Ivins' behavior during the years they worked together. Byrne said the deterioration in Ivins' mental state had become noticeable to his colleagues only in the last year and could have resulted from the pressure of knowing he was under investigation.
"The changes really began to accelerate in the last year. He would sit at his desk weeping," Byrne said Monday on NBC's "Today" show. "He really couldn't do his work any more. The pressure was tremendous."
Only those scientists working at military labs are scrutinized for mental health and behavioral issues. And that heightened level of screening was apparently not enough to flag Ivins. One former colleague, Kathleen Carr, said it's largely up to scientists to self-report psychological problems that might make them dangerous.
"People given these kinds of responsibilities, with this kind of power at their fingertips, we have to make sure that they are not likely to do harm to others or misuse that authority - be it intentionally or be it because of some mental problem," said Rep. Elijah Cummings, a member of the House Armed Services Committee. "These kinds of situations cry out for reexamination of our standards."
Jonathan B. Tucker, a Washington expert on biological weapons, said stricter rules will come with a price.
"You're basically going to scare off any scientist from wanting to work in this field if it becomes even more stringent," he said. "It is a balance. It's a policy decision about how stringent we want to be."