Amerithrax (46 page)

1. Thursday, May 9, a call went out for a blanket vacci-
   

   nation program for all U.S. mail handlers to counter any further outbreaks. On the same day, TIGR researchers, led by Timothy Read, Claire Fraser, and chief of bioinformatics Steven Salzberg, posted their findings in the
   Science Express
   paper. They reported that comprehensive comparison of the Porton Down and the Florida letter anthrax isolates identi- fied slight differences in their DNA that could be used as genomic fingerprints in future analyses.
   

   STRAIN 26
   

   

   Anthrax Paper
   

   IN
   a pioneering use of genomics as a tool for the forensic analysis of microbes, TIGR had finished decoding the ge- nome of the anthrax bacteria used by Amerithrax. On the Science Express website researchers said they had isolated the strain used to contaminate mail at AMI, discovering that it was related to the Ames strain. Anthrax DNA had more than five million unique genetic components that had to be compared.
   

   “In different labs over twenty-one years,” said Fraser, “they have developed mutations [unique to each lab] in their DNA sequence. And these are the regions we are focusing on, regions that are different, because that gives us the in- formation we need to try to distinguish one from another.” Fraser was a member of a National Research Council panel drawing up a report about how scientific research can help counter bioterrorism.
   

   Because anthrax shows little genetic variability, it made fingerprinting the organism difficult. TIGR had identified sixty new, unique genetic difference sites in the genome that helped investigators eliminate some labs and concentrate on
   

   others. The new genetic markers distinguished the anthrax isolate used in the previous fall’s bioterror attack in Boca Raton from closely related anthrax strains. Those main differences include what the scientists described as four “high-quality” single-nucleotide polymorphisms (SNPs)— differences of a single DNA base—between the sequenced chromosomes of the Porton Down and Florida isolates. Most of those differences were found in the plasmids—circular units of DNA that are separate from the chromosomes that contain most of the organism’s genetic material.
   

   Of those sixty markers, Fraser said, eleven could help researchers discriminate between the Florida sample and others. Previous genetic-marker analysis had focused on a limited number of DNA segments, rather than the entire ge- nomic sequence. According to TIGR, “Specific attributes of the DNA of anthrax bacteria used in the Florida attack show the genetic fingerprints of the bacteria.”
   

   They detailed their findings to the FBI. Genome sequenc- ing of the bacteria used by Amerithrax would allow re- searchers to recognize the varieties should another attack occur and help scientists develop a new vaccine and a speedy means to detect infection. “Genome-based analysis will provide a powerful new tool for investigating unex- pected disease outbreaks—whether they are bioterrorism at- tacks or natural outbreaks of more familiar pathogens,” said Fraser.
   

   Dr. Read and his team planned to publish the integral sequence of the anthrax bacillus genome in a scientific re- view by the end of the year. He predicted that at least four- teen other strains or isolates of anthrax would be decoded in 2003, in cooperation with Northern Arizona University, which has twelve hundred isolates of the bacteria archived. “Building a comprehensive database of information related to gene content.. .” read their paper, “and inversions in the genomes of important pathogens will allow investigators to quickly pinpoint the isolate that is most closely related to an outbreak strain.” A database like that might deter future attacks.
   

   To support its claims TIGR posted four sets of anthrax data:
   

   1. the set of all assembled “contigs” (contiguous small segments of the genome) of all sizes
      

   2. the set of individual sequences that were used to create those contigs
      

   3. a file containing the quality values (estimates of error rates) for each individual sequence
      

   4. a set of one thousand base pair regions centered on each SNP to allow other scientists to identify and test the markers on other anthrax strains
      

Sequence data from the
B. anthracis
research were also placed in the Genbank repository.

New Scientist
revealed that the two reference strains that appear identical to the attack strain most likely originated at the Institute at Fort Detrick, Maryland, and Dugway Proving Ground in Utah. The new work also showed that substantial genetic differences can emerge in two samples of an anthrax culture separated for only three years. This means Ameri- thrax’s anthrax was not separated from its ancestors at the Institute by many generations. A handful of mutations arose some time after the bacteria left Detrick—very subtle dif- ferences, but it was now indisputable that the mailed mi- crobes were direct descendants of germs developed at the Institute.

The difference between the Dugway strain and the attack strain was not great—thirty-six adenines in a row, instead of thirty-five. The detailed genetic analysis of the anthrax letter bacteria revealed “minuscule but consistent differences between the terrorist strain and the nearly identical strain developed by the U.S. Army at Fort Detrick.” The FBI might pinpoint the exact lab, but not who there absconded with the microbes or to whom that person may have passed them along.

Friday, May 3, the FBI began analyzing the strain of anthrax mailed and comparing it to strains from around the world. Building an all-inclusive database of the genomes of important pathogens would allow investigators to quickly distinguish the isolate that is most closely related to an out-

break strain and calculate the age of the terrorist substrain. On Monday, May 20, frustrated FBI agents tried to nar- row the hunt for Amerithrax further. They began adminis- tering mass polygraph tests to current and former employees of the Institute, Dugway Proving Ground, Pine Bluff Arse- nal in Arkansas, and the Salk Center in Swiftwater, Penn- sylvania. Anyone who hadn’t taken a polygraph test would be asked to voluntarily submit to one. “It’s nothing we can force them to do,” said one official. “But it’s an effort to work through this list with a little more specificity.” The latest list consisted of over two hundred domestic scientists and lab workers who had had contact with the Ames strain used in the attacks and descended from stocks developed at

the Institute. Some would be reinterviewed.

Senate and House bills anticipated spending $3 billion per year on anti-bioterrorism efforts, roughly the amount appropriated for the current fiscal year. Funds to finance first-year operations had been approved after the 9-11 ter- rorist attacks and subsequent spore-tainted letters were received on Capitol Hill. The bioterrorism authorization bill established a framework for allocating the money. It in- cluded provisions to prevent, detect, and treat terrorism- related health threats.

“Because of this bipartisan legislation, Americans will be able to sleep better at night in the knowledge that our nation is taking the steps necessary to protect them and their fam- ilies against the deadly threat of bioterrorism,” said Senator Edward M. Kennedy, who cosponsored the Senate version of the legislation with Senator Bill Frist.

The bill called for tighter regulation of labs and bio- weapon materials workers, new record-keeping require- ments, safety improvements at animal research labs, and vaccines and antibiotics stockpiles to protect against biolog- ical and chemical weapons. Funding was increased for state and local health officials to help them prepare for bioterror- ism attacks, research on prevention and treatment, and grants to help hospitals prepare for treatment of victims. It required community water systems serving more than three thousand people to conduct vulnerability assessments, tighten secu- rity, and prepare emergency response plans. In case of an

attack on a nuclear power plant, expanded supplies of po- tassium iodide would be made available to communities near the plants to handle contamination.

On May 29, the House and Senate negotiators agreed on the final version of legislation to make certain of a sustained, all-inclusive effort to bolster the nation’s defenses against bioterror attack. The bill, calling for initiatives to prevent and detect terrorism-related health threats, won swift ap- proval from Congress. The following day, the FDA, re- sponding to the threat of anthrax, adopted new rules to speed approval of new bioterror medicines. The FDA said that it would allow companies to base their new drug applications on animal testing alone when assessing whether a drug is effective. Previously, a drug’s effectiveness had to be tested on humans before the FDA would allow it on the market. “The terrorist attacks of last fall underscored the acute need for this new regulation,” said Lester M. Crawford, the FDA’s deputy commissioner. “Today’s action will help make certain essential new pharmaceutical products availa- ble much sooner—those products that because of the very nature of what they are designed to treat cannot be safely or ethically tested for effectiveness in humans.”

Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, said use of the new rule, which the agency considered “urgently needed,” would be limited. Woodcock said the FDA has “been struggling in a number of cases to persuade applicants to go forward” with drugs to treat biological, chemical, and nuclear attacks. It would still take a year or more for companies to design, undertake, and complete their animal studies. It was unethical to expose a human test subject to potentially lethal or permanently disabling agents, making it impossible to test a drug’s ef- fectiveness against biological and radiological threats.

The FDA has already approved Cipro use against bio- terror. It received “fast track” approval against inhaled an- thrax based on both animal tests and human studies of how it behaved in the bloodstream. Steve Lawton, chief lawyer for the Biotechnology Industry Organization, said the new rule is an “absolutely appropriate and necessary tool to com- bat terrorism... It’s a terrific combination of patriotism and

opportunity and there are a lot out there ready to respond.” “Federal agencies have come under fire,” wrote the AP, “for failing to realize that the postal workers at Brentwood were at risk for anthrax even after an anthrax letter was disclosed on Capitol Hill and treatment had begun for Senate staffers.” On June 7, Judicial Watch, a conservative watch- dog group, sued the Bush administration for access under the Freedom of Information Act to documents about the pre- vious fall’s anthrax attacks. The chairman of the group, Larry Klayman, had previously asserted that top officials might have known the bioterrorist attack was coming. He said some White House staff members had begun taking Cipro the night of September 11, before the anthrax attacks began. “We believe that the White House knew or had rea- son to know that an anthrax attack was imminent or under- way,” Klayman said. “We want to know what the government knew and when they knew it.... One doesn’t simply start taking a powerful antibiotic for no good reason. The American people are entitled to know what the White

House staffers knew nine months ago.”

“We did not know about the anthrax attacks. Period!” countered Gordon Johndroe, a White House spokesman. He did not know why staffers were given Cipro, but guessed it was “a precautionary measure in the early hours of Septem- ber 11, before the situation could be fully assessed.” In Oc- tober 2001, press reports said that White House workers, including President Bush and the staff accompanying Vice President Dick Cheney, had been taking Cipro nearly a month before anthrax was detected on Capitol Hill. There was a biological alarm at the White House on November 18, but it proved to be false.

“The American people deserve a full accounting from the Bush administration, the FBI, and other agencies concerning the anthrax attacks,” said Klayman. “The FBI’s investigation seems to have dead-ended, and frankly, that is not very re- assuring given their performance with the September 11th hijackers.” Judicial Watch said records showed the decision was made not to close Brentwood after the anthrax attacks began because it would have cost the post office a half- million dollars per day. Judicial Watch was seeking a crim-

inal inquest into the U.S. Postal Service’s handling of the anthrax contamination and presented documents to a federal prosecutor that it said proved postal and government offi- cials knew anthrax spores had leaked from a letter sent to Daschle into the Brentwood Processing Plant but neither warned workers nor shut down the site.

“The government does not have the right to injure peo- ple, to harm them, and that’s what [officials] did through their action and inaction,” wrote Klayman. “While Capitol Hill workers received prompt medical care, Brentwood postal workers were ordered by USPS officials to continue working in the contaminated facility. Health officials have said they did not realize then that anthrax could have es- caped a sealed envelope.” Klayman said the mistake goes beyond a bad judgment call. “They deliberately withheld information,” he concluded. “The political elite, they’ll be protected from day one. The ordinary folks will be treated in a lesser fashion.”