[>Htech] The bioweapon is in the post

Thu Nov 10 09:03:27 PST 2005

http://www.newscientist.com/channel/opinion/mg18825252.900.html

The bioweapon is in the post

# 09 November 2005
# NewScientist.com news service
# Peter Aldhous

YOU might think it would be difficult for a terrorist to obtain genes from the
smallpox virus, or a similarly vicious pathogen. Well, it's not. Armed with a
fake email address, a would-be bioterrorist could probably order the building
blocks of a deadly biological weapon online, and receive them by post within
weeks.

That's the sobering reality uncovered by a New Scientist investigation into
the
bioterror risks posed by the booming business of gene synthesis. Dozens of
biotech firms now offer to synthesise complete genes from the chemical
components of DNA (See "A dollar a base pair"). Yet some are carrying out next
to no checks on what they are being asked to make, or by whom. It raises the
frightening prospect of terrorists mail-ordering genes for key bioweapon
agents
such as smallpox, and using them to engineer new and deadly pathogens.

Customers typically submit sequences by email or via a form available on a
company's website. The companies then construct the specified genes and mail
them back a few weeks later, usually spliced into a bacterium such as
Escherichia coli. New Scientist approached 16 such firms, identified by a
Google
search, to ask whether they screened orders for DNA sequences that might pose
a
bioterror threat. Of the 12 companies that replied, just five said they screen
every sequence received. Four said they screen some sequences, and three
admitted not screening sequences at all (see Table).

The risks posed by gene synthesis first hit the headlines in 2002, when a team
from the State University of New York at Stony Brook made infectious
polioviruses from synthetic DNA. And just last month, researchers with the US
Centers for Disease Control and Prevention in Atlanta, Georgia, said that they
had used similar means to recreate the virus that caused the 1918 flu (New
Scientist, 8 October, p 16).

In theory, a terrorist group could try to emulate the latter feat, or create a
virus such as Variola major, which causes smallpox. However, the Variola
genome
comprises some 190,000 base pairs of DNA, and while some companies will make
sequences 20,000 or more base pairs long, an attempt to order all the genes
necessary to launch a smallpox attack would probably arouse suspicion. "That
would stand out from a technological point of view," suggests Drew Endy, a
bioengineer at the Massachusetts Institute of Technology.

A more realistic risk is that terrorists could order genes that confer
virulence
to dangerous pathogens such as the Ebola virus, and engineer them into another
virus or bacterium. They could also order genes for a hazardous bacterial
toxin
- although many of these are also available by isolating the microorganisms
from
the environment.

Virulence genes are typically no more than a few thousand base-pairs long.
Their
sequences are publicly available, so screening gene-synthesis orders for
potential bioweapons shouldn't pose a huge challenge. Indeed, a company called
Craic Computing, based in Seattle, has written open-source software called
Blackwatch that does just that. It is used by one of the leading
gene-synthesis
companies, Blue Heron Biotechnology of Bothell, Washington.

Robert Jones, president of Craic Computing, says that Blackwatch "casts a wide
net", comparing orders against sequences from organisms identified by the US
government as "select agents" that raise bioterror concerns. But not all of
these sequences are dangerous, and some customers may have the clearance to
work
with those that are. So even legitimate orders may be flagged up as
suspicious,
and that means companies must employ biologists to carefully examine any
matches
that crop up.

The need for expert human checks may be one factor deterring some companies
from
screening orders. Others like to reassure customers who may be worried about
commercial confidentiality that their sequence data will remain secret. But
whatever the reasons, some firms freely admit that they run no sequence
screens.
"That's not our business," says Bob Xue, a director of Genemed Synthesis in
South San Francisco.

Even if they don't routinely perform sequence checks, some companies say that
they do investigate their customers. But the scope of these checks varies
widely. While some firms say they conduct thorough probes into customers'
affiliations and scientific publications, others are less exhaustive. For
instance, Jennifer Wang, general manager of Bio Basic, based in Markham,
Canada,
says that her company examines email addresses to see if orders come from a
legitimate research organisation.

Such a check would have spotted one suspicious order, sent from a Hotmail
address to BaseClear of Leiden, the Netherlands. This was for a modified
sequence from a hepatitis-like virus. BaseClear itself rejected the order
after
the would-be customer failed to respond to requests for more information, says
Gerben Zondag, the firm's scientific director.

But email addresses are notoriously easy to fake. And even orders from
legitimate institutions may not be what they seem. Alfred Lasher, who manages
Picoscript in Houston, Texas, says that he turned down one order placed by an
individual at a US biotech firm, after Picoscript's enquiries revealed the
gene
was being ordered on behalf of a friend in another country.

Experts are concerned that the checks currently employed by some companies
aren't sufficient to exclude orders placed by terrorists. "We're taking this
very seriously," says Endy. Together with the J. Craig Venter Institute in
Rockville, Maryland, and the Center for Strategic and International Studies in
Washington DC, Endy's research group at MIT has launched a study into the
risks
and benefits of synthetic genomics, and aims to produce a set of policy
recommendations by late 2006. The US National Science Advisory Board for
Biosecurity, set up last year to advise the US government on which advances in
biology could be exploited by terrorists, is also considering the issue.

Some gene synthesis companies say they would welcome more detailed rules. John
Mulligan, president of Blue Heron, says it would be helpful to have a list of
"select sequences" that are off-limits for gene synthesis without explicit
government permission, rather than having to make difficult judgments based on
the list of select agents. "Tell us what we can't make," he implores.

But with gene synthesis firms springing up all over the world, and the
underlying technology becoming cheaper and more widely available, it is
unclear
whether regulations enacted in any one country will be enough. "It's going to
be
virtually impossible to control," predicts David Magnus, director of the
Stanford Center for Biomedical Ethics in Palo Alto, California.

Endy argues that what's needed is better self-regulation: if researchers only
do
business with companies that are diligent in sequence screening and other
security checks, then terrorists would soon find themselves unable to place
orders for dangerous genes. Otherwise, he fears a crackdown that could close
valuable avenues of research. For instance, gene synthesis can be used to make
DNA vaccines, which may eventually provide a means of responding rapidly to
emerging diseases - or bioterrorist attacks.

"As soon as people start dying from a bioengineered organism, there will be a
huge security response and research will be clamped down," warns Endy.
 From issue 2525 of New Scientist magazine, 09 November 2005, page 8

A dollar a base pair

Biochemists have long known how to build DNA from its component "bases" - the
chemical letters of the genetic code. By adding the bases in a prescribed
order
and carefully performing a series of chemical reactions, they can create
precisely tailored stretches of DNA.

The process became significantly less laborious with the debut of the
automated
DNA synthesiser in the 1980s. But a full gene - a DNA sequence up to several
thousand base pairs long - involves a formidable jigsaw puzzle.

Commercial gene synthesis has only really taken off in the past few years with
advances in automating this assembly process. And as the main players jostle
for
position, the costs of gene synthesis are plummeting. Prices have dropped
about
tenfold in five years, and some firms now supply genes for less than $1.50 per
base pair.

--
Brian Atkins
Singularity Institute for Artificial Intelligence
http://www.singinst.org/

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