Biowar for Dummies
How hard is it to build your own weapon of mass destruction? We take a crash course in supervirus engineering to find out.
Originally published on
Paul Boutin blog February 22, 2006. Reprinted with permission
on KurzweilAI.net July 11, 2006.
Anthrax. Smallpox. Ebola. For thriller writers and policy
crusaders, biological warfare was a standard what-if scenario long
before anyone mailed anthrax to government and media offices in
2001. Pentagon war games like Dark Winter, held just before 9/11,
and this year's Atlantic Storm suggested that terrorists could unleash
germs with the killing power of a nuclear weapon.
Scientists, though, have always been skeptical. Only massive, state-sponsored
programs—not terrorist cells or lone kooks—pose a plausible
threat, they say. As the head of the Federation of American Scientists
working group on bioweapons put it in a 2002 Los Angeles Times
op-ed: "A significant bioterror attack today would require the support
of a national program to succeed."
Or not. A few months ago, Roger Brent, a geneticist who runs a
California biotech firm, sent me an unpublished paper in which he
wrote that genetically engineered bioweapons developed by small
teams are a bigger threat than suitcase nukes.
Brent is one of a growing number of researchers who believe that
a bioterrorist wouldn't need a team of virologists and state funding.
He says advances in DNA-hacking technology have reached the point
where an evil lab assistant with the right resources could do the
job.
Gene hackers could make artificial smallpox—or worse—from
standard lab supplies.
I decided to call him on it. I hadn't set foot in a lab since high
school. Could I learn to build a bioweapon? What would I need? What
would it cost? Could I set up shop without raising suspicions? And,
most important, would it work?
"An advanced grad student could do it." —Roger Brent,
head of the Molecular Sciences Institute in Berkeley, California.
To find out, I meet with Brent at the Molecular Sciences Institute,
his company in Berkeley. The 49-year-old researcher has a few million
dollars a year in government funding and a staff of 25. He's the
co-author of the must-read lab manual Current
Protocols in Molecular Biology, and hardly seems like someone
in the grip of apocalyptic fervor. As he shows me around the lab—a
few quiet rooms of workbenches, pipette stands, pinky-sized test
tubes and the odd PowerBook—we plan our attack.
Experts used to think that distributing a killer germ would require
a few vats and a crop duster. Brent and I have a different idea.
We'll infect a suicidal patient zero and hand him a round-the-world
plane ticket. But we need a dangerous virus—smallpox, maybe.
We won't be able to steal a sample; we'll have to make our own.
Too dangerous, Brent says. He gives me a proxy mission: Modify
something mundane into something strange. In this case, rejigger
standard brewer's yeast to manufacture a glowing cyan-colored protein
usually found in jellyfish.
Great. I wanted to make something as lethal as an A-bomb, and instead
I'm brewing ultraviolet beer.
Brent smiles and shrugs at my disappointment. "All life is one,"
he says, and he's not just being Zen. All over the world, laboratories
like Brent's splice genes—the techniques are as common as the
Pyrex beaker, and getting easier every day. Getting yeast to sport
blue genes takes the same skills and gear as adding the genes for
something toxic. DNA is just the stuff that tells cells what proteins
to make—the only real difference between being able to insert
a single gene and inserting all the genes that make a virus is experience.
I start my to-do list: I have to acquire the right equipment. I
have to track down the genetic sequence I want, then learn how to
make the gene. Then I have to get it into the yeast. Brent offers
me lab space and staff advice, but insists that I do the work myself.
And not everyone has the knack, he says. "Some people are natural-born
labsters, some aren't." I know what he means. I used to be a software
engineer, and in that field, procedures are well documented and
the source code is readily available, but some people just aren't
hackers.
It's time to find out what kind of genetic engineer I am.
Making DNA turns out to be easy if you have the right hardware.
The critical piece of gear is a DNA synthesizer. Brent already has
one, a yellowing plastic machine the size of an office printer,
called an ABI 394. "So, what kind of authorization do I need to
buy this equipment?" I ask.
"I suggest you start by typing 'used DNA synthesizer' into Google,"
Brent says.
I hit eBay first, where ABI 394s go for about $5,000. Anything
I can't score at an auction is available for a small markup at sites
like usedlabequip.com. Two days later I have a total: $29,700—taxes
and shipping not included. Nucleosides (the A, C, T, G genetic building
blocks) and other chemicals for the synthesizer cost more than the
hardware—in the end, a single base pair of DNA runs about a
buck to make. Enough raw material to build, say, the smallpox genome
would take just over $200,000.
The ABI 394 synthesizer.
Think of it as an inkjet printer for DNA.
The real cost of villainy is in overhead. Even with the ready availability
of equipment, you still need space, staff, and time. Brent guesses
he would need a couple million dollars to whip up a batch of smallpox
from scratch. No need for state sponsors or stolen top-secret germ
samples. "An advanced grad student could do it," Brent says. Especially
with the help of some high schoolers who actually went to lab classes.
But how would I find the gene sequence? Simple. I went to the Web
site of the National
Center for Biotechnology Information (no password required)
and downloaded the DNA sequence for a 770-base pair gene called
the Enhanced Cyan Fluorescent Protein. That's what Brent wanted
me to program into my yeast. It took me about 15 minutes to find.
Far easier to track down was the 200,000-base pair sequence
for smallpox. Only two known samples of smallpox exist; the
blueprints are free online.
It's glowing. Is that good?
I load my nucleosides into the ABI 394, and it's as easy as replacing
a toner cartridge. I transmit a test sequence from my Mac and go
to lunch. When I come back, I have a custom strand of genetic material
waiting for me. This is the anyone-on-Slashdot-can-do-it part of
the job.
These days, many labs don't even bother synthesizing their own
genes. They order nucleotide chains online. That's right: mail-order
genes. Just to test this out, I buy a sequence from MWG
Biotech in High Point, North Carolina, and have it shipped to
my house. Three days later, I'm sitting on the train to Berkeley
holding a FedEx box. MWG didn't do anything wrong, but not long
ago New Scientist magazine approached sixteen
other custom DNA shops to find out if they scan incoming orders.
Could a terrorist order a killer virus piece by piece? Only five
of the sixteen said they screen every sequence.
Still, mail-order is cheating. If you were a smart terrorist, you'd
make the thing yourself to avoid suspicion. You can't order smallpox,
but anyone's allowed to buy raw genetic material and lab equipment—the
government only monitors certain radioactive, toxic, or otherwise
scary substances.
Getting living cells to absorb synthetic genes is where
biotech stops looking like IT and turns into French cooking. The
process, called transformation, happens in nature only rarely; it's
part of the way microorganisms evolve. In the lab, you can improve
the odds it'll work by softening up the host cells with chemicals
and removing sections of their DNA with tailor-made enzymes. Douse
the hosts with synthetic DNA and some fraction of them slurp it
up. And some fraction of those start making the protein that the
gene codes for. It doesn't matter if it's jellyfish fluorescence
or smallpox (though obviously smallpox is more complicated).
It sounds like submicroscopic surgery, but all you do is squirt
chemicals into a culture dish and let it all soak overnight. In
the morning you come back to see if it worked or, more likely, didn't.
My first batch flops. My second, too. One of the MSI researchers
offers to break Brent's rules and do it for me while I watch. It
doesn't work for him, either.
Eventually, we fumble our way to a plastic dish full of translucent
goop. If I'd been working on smallpox—and really committed
to my cause—this would have been the part where I'd inject
a lab animal with the stuff to see if it got sick. Then I'd give
myself a dose and head off on a days-long, multi-airport, transnational
suicide run. But it was just yeast. Set on top of a black light,
it glowed an eerie bright blue, like a Jimi Hendrix poster. My creation...
lived.
Biotech's growth curves
leave Moore's Law in the dust.
Would the nations of the world kneel before my awesome power? I
asked an expert. Three years ago, Eckard
Wimmer headed a team of researchers at SUNY Stony Brook that
made live polio virus from scratch, part of a Defense Department
project to prove the threat of synthetic bioweapons. So how much
of a leap is that from cyan-tinged yeast?
"A simple laboratory technician would have trouble," he says. With
smallpox, "the virus is very large and brings with it enzymes that
it needs to proliferate. If you just made the genome and put it
into a cell, nothing would happen."
In the wild, viruses hijack host cells and turn them into virus
replication factories. Wimmer was sure any one of the 2,847 members
of the American
Society for Virology could figure out how to do the same.
Soon, though, I might not even need that expertise. DNA synthesis
is following a kind of accelerated Moore's law—the faster and
easier it gets, the faster and easier it gets. Last year, a group
of researchers synthesized DNA strands of more
than 300,000 base pairs—longer than the smallpox genome—using
a method that eliminates most of the shake-and-bake lab steps I'd
spent weeks learning.
The rush toward DIY genetics is reflected in so-called Carlson
curves, plotted by Rob Carlson, a physicist-turned-biologist
(and Brent's former lab partner at MSI) who worked them out in 2003.
"Within a decade," Carlson wrote in the journal Biosecurity and
Bioterrorism, "a single person could sequence or synthesize
all the DNA describing all the people on the planet many times over
in an eight-hour day."
Today, when he's not tinkering with cellular-scale measurement
gadgets at the University of Washington, Carlson designs custom
proteins on a computer in his Seattle home. According
to his calculations, if the current pace of biotech proceeds
for another decade, cooking up a lethal bug will be as easy and
cheap as building a Web site. "You don't need a national program,"
Carlson says. "The technology's changing fast, and there's nothing
we can do about it."
Even if he's wrong about the timeframe, if someone solves the problem
of synthesizing RNA (the single-stranded adjunct to DNA), it would
open the door to modifying influenza or retroviruses
like HIV—and in 1918 the flu managed to kill 20 million people
without any help from bioterrorists.
"If we do what we need to for biodefense ... We could, as
a planet, eliminate large lethal epidemics." —Tara O'Toole,
Center for Biosecurity
Bolstered by what scientists like Carlson and Brent are saying,
bioweapon policy wonks are calling for an all-out biodefense program.
Worried about bacteria and viruses of mass destruction, the federal
government pushes nearly $6 billion a year toward research. Tara
O'Toole, director of the University of Pittsburgh's Center for
Biosecurity, says after-the-fact vaccines won't stop a plague; they
take months to develop and deploy. She believes the only option
is a general-purpose virus detector and destroyer, which has yet
to be invented. The cost would be enormous, but don't think of it
as just an antiterror tool. "If we do what we need to for biodefense,
we're going to do an enormous amount of good for routine health
care and global disease," says O'Toole. "We could, as a planet,
eliminate large lethal epidemics of infectious disease in our lifetime."
Brent agrees. He's been tinkering on a general virus detector as
a side project. "Of course I'd be thrilled to see a huge expenditure
on defense," he says. "But the truth is, it'll probably take an
attack to get us there."
We might not have long to wait. Every hands-on gene hacker
I polled during my project estimated they could synthesize smallpox
in a month or two. I remember that game from my engineering days,
so I mentally scale their estimates using the old software manager's
formula: Double the length, then move up to the next increment of
time. That gives us two to four years—assuming no one has already
started working.
© 2006 Paul Boutin
| 
