- The DNA sequence of the anthrax sent through the US mail
in 2001 has been revealed and confirms suspicions that the bacteria originally
came from a US military laboratory.
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- The data released uses codenames for the reference strains
against which the attack strain was compared. But New Scientist can reveal
that the two reference strains that appear identical to the attack strain
most likely originated at the US Army Medical Research Institute for Infectious
Diseases at Fort Detrick (USAMRIID), Maryland.
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- The new work also shows that substantial genetic differences
can emerge in two samples of an anthrax culture separated for only three
years. This means the attacker's anthrax was not separated from its ancestors
at USAMRIID for long and was therefore acquired relatively recently.
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- The new genetic sequencing work was done by the Institute
for Genomic Research in Rockville, Maryland (TIGR), and Paul Keim's team
at the University of Northern Arizona at Flagstaff. Before the attacks,
TIGR had started sequencing a non-pathogenic derivative of the "Ames"
strain of anthrax from the UK biodefence establishment at Porton Down.
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- It happened that the anthrax attacker used a pathogenic
Ames strain. So in January, TIGR added the bacteria isolated from the first
victim of the attack, Florida journalist Robert Stevens, to its sequencing
effort.
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- Incriminating evidence
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- The idea was to tease out subtle differences between
the two genomes that might identify the source of the attack strain. Full-blown
sequencing seemed necessary, as genetic differences in anthrax are notoriously
hard to find.
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- The teams found plenty of differences between the two
strains, as they now report in the journal Science. They then took these
"marker" stretches of DNA and tested them against five other
samples of Ames anthrax, looking for differences - or incriminating similarities.
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- One, from a goat that died of anthrax in Texas in 1997,
differed at four markers, proving that the markers can reveal divergence
among anthrax lineages.
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- But ironically, none of the other four - identified only
as A, B, C and D - differed at all from the attack strain at any of the
new markers revealed by sequencing. However, two, A and D, did differ at
one marker - a stretch of repeated alanines on pXO2, one of the two DNA
plasmids that give anthrax its virulence.
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- That marker had already been discovered by Keim and reported
at a meeting in June 2001. "It may be the most polymorphic site in
the genome," Keim told New Scientist. Strain A can immediately be
ruled out as the attack strain as it is missing a plasmid, and is non-pathogenic.
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- The identity of the strains apparently identical to the
attack strain - B and C - and strain D can be deduced as follows. In February,
Keim told New Scientist: "We can distinguish among different Ames
accessions. These are from collaborative laboratories and related to genetic
work we have been performing over the years."
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- Doubly sure
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- The strains from the collaborative labs appear certain
to be strains B, C and D. In that case, one was the reference Ames in Keim's
collection that came from a freezer at Porton Down, which in turn had got
it from USAMRIID. Another was a culture that came directly from USAMRIID,
and the last was from the US Army's Dugway proving ground in Utah.
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- TIGR spokesmen and other sources have stated that Keim
could find no differences between the attack strain and the reference Ames
in his collection at any marker tested in his lab. The tests reported in
Science are no better at doing this. So one of B and C is Keim's Porton
Down/USAMRIID reference strain. The other is likely to be the culture directly
from USAMRIID, as the reference strain originated there and had since languished
in a freezer.
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- So strain D seems to have come from Dugway. The difference
between D and the attack strain is not great - there are 36 alanines in
a row, instead of 35 - but Keim's team made doubly sure by sequencing that
part of the D strain's genome.
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- However, the new work does not prove irrefutably that
the attacker got his anthrax directly from USAMRIID because it is possible
that untested Ames cultures from other labs might also be identical. Those
tests are now underway.
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- Journal reference: Science
(DOI: 10.1126/science.1071837)
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