FIVE YEARS LATER: Microbes Made from Scratch
Custom-Built Pathogens Raise Bioterror Fears
Monday, July 31, 2006
Brook, N.Y.- Eckard Wimmer knows of a shortcut terrorists
could someday use to get their hands on the lethal
viruses that cause Ebola and smallpox. He knows it
exceptionally well, because he discovered it himself.
2002, the German-born molecular geneticist startled
the scientific world by creating the first live, fully
artificial virus in the lab. It was a variation of
the bug that causes polio, yet different from any
virus known to nature. And Wimmer built it from scratch.
virus was made wholly from nonliving parts, using
equipment and chemicals on hand in Wimmer's small
laboratory at the State University of New York here
on Long Island. The most crucial part, the genetic
code, was picked up for free on the Internet. Hundreds
of tiny bits of viral DNA were purchased online, with
final assembly in the lab.
intended to sound a warning, to show that science
had crossed a threshold into an era in which genetically
altered and made-from-scratch germ weapons were feasible.
But in the four years since, other scientists have
made advances faster than Wimmer imagined possible.
Government officials, and scientists such as Wimmer,
are only beginning to grasp the implications.
future," he said, "has already come."
years ago, deadly anthrax attacks forced Americans
to confront the suddenly real prospect of bioterrorism.
Since then the Bush administration has poured billions
of dollars into building a defensive wall of drugs,
vaccines and special sensors that can detect dangerous
pathogens. But already, technology is hurtling past
it. While government scientists press their search
for new drugs for old foes such as classic anthrax,
a revolution in biology has ushered in an age of engineered
microbes and novel ways to make them.
new technology opens the door to new tools for defeating
disease and saving lives. But today, in hundreds of
labs worldwide, it is also possible to transform common
intestinal microbes into killers. Or to make deadly
strains even more lethal. Or to resurrect bygone killers,
such the 1918 influenza. Or to manipulate a person's
hormones by switching genes on or off. Or to craft
cheap, efficient delivery systems that can infect
large numbers of people.
biological weapons threat is multiplying and will
do so regardless of the countermeasures we try to
take," said Steven M. Block, a Stanford University
biophysicist and former president of the Biophysical
Society. "You can't stop it, any more than you
can stop the progress of mankind. You just have to
hope that your collective brainpower can muster more
resources than your adversaries'."
Bush administration has acknowledged the evolving
threat, and last year it appointed a panel of scientists
to begin a years-long study of the problem. It also
is building a large and controversial lab in Frederick,
where new bioterrorism threats can be studied and
tested. But overall, specific responses have been
few and slow.
U.S. Centers for Disease Control and Prevention has
declined so far to police the booming gene-synthesis
industry, which churns out made-to-order DNA to sell
to scientists. Oversight of controversial experiments
remains voluntary and sporadic in many universities
and private labs in the United States, and occurs
even more rarely overseas.
experts say traditional biodefense approaches, such
as stockpiling antibiotics or locking up well-known
strains such as the smallpox virus, remain important.
But they are not enough.
a name for fixed defenses that can easily be outflanked:
They are called Maginot lines," said Roger Brent,
a California molecular biologist and former biodefense
adviser to the Defense Department, referring to the
elaborate but short-sighted network of border fortifications
built by France after World War I to prevent future
invasions by Germany.
themselves," Brent said, "stockpiled defenses
against specific threats will be no more effective
to the defense of the United States than the Maginot
line was to the defense of France in 1940."
to Make a Virus
artificial virus looks and behaves like its natural
cousin -- but with a far reduced ability to maim or
kill -- and could be used to make a safer polio vaccine.
But it was Wimmer's techniques, not his aims, that
sparked controversy when news of his achievement hit
the scientific journals.
the creator of the world's first "de novo"
virus -- a human virus, at that -- Wimmer came under
attack from other scientists who said his experiment
was a dangerous stunt. He was accused of giving ideas
to terrorists, or, even worse, of inviting a backlash
that could result in new laws restricting scientific
counters that he didn't invent the technology that
made his experiment possible. He only drew attention
most scientists and lay people, the reality that viruses
could be synthesized was surprising, if not shocking,"
he said. "We consider it imperative to inform
society of this new reality, which bears far-reaching
of the world's foremost experts on poliovirus, Wimmer
has made de novo poliovirus six times since his groundbreaking
experiment four years ago. Each time, the work is
a little easier and faster.
techniques developed by other scientists allow the
creation of synthetic viruses in mere days, not weeks
or months. Hardware unveiled last year by a Harvard
genetics professor can churn out synthetic genes by
the thousands, for a few pennies each.
Wimmer continues to use methods available to any modestly
funded university biology lab. He reckons that tens
of thousands of scientists worldwide already are capable
of doing what he does.
paper was the starting point of the revolution,"
Wimmer said. "But eventually the process will
become so automated even technicians can do it."
method starts with the virus's genetic blueprint,
a code of instructions 7,441 characters long. Obtaining
it is the easiest part: The entire code for poliovirus,
and those for scores of other pathogens, is available
for free on the Internet.
with a printout of the code, Wimmer places an order
with a U.S. company that manufactures custom-made
snippets of DNA, called oglionucleotides. The DNA
fragments arrive by mail in hundreds of tiny vials,
enough to cover a lab table in one of Wimmer's three
small research suites.
a kind of chemical epoxy, the scientist and his crew
of graduate assistants begin the tedious task of fusing
small snippets of DNA into larger fragments. Then
they splice together the larger strands until the
entire sequence is complete.
final step is almost magical. The finished but lifeless
DNA, placed in a broth of organic "juice"
from mushed-up cells, begins making proteins. Spontaneously,
it assembles the trappings of a working virus around
simple on paper, it is not a feat for amateurs, Wimmer
said. There are additional steps to making effective
bioweapons besides acquiring microbes. Like many scientists
and a sizable number of biodefense experts, Wimmer
believes traditional terrorist groups such as al-Qaeda
will stick with easier methods, at least for now.
al-Qaeda is known to have sought bioweapons and has
recruited experts, including microbiologists. And
for any skilled microbiologist trained in modern techniques,
Wimmer acknowledged, synthetic viruses are well within
reach and getting easier.
he said, "is a wake-up call."
Parlor Trick to Bio-Bricks
global biotech revolution underway is more than mere
genetic engineering. It is genetic engineering on
hyperdrive. New scientific disciplines such as synthetic
biology, practiced not only in the United States but
also in new white-coat enclaves in China and Cuba,
seek not to tweak biological systems but to reinvent
holy grail of synthetic biologists is the reduction
of all life processes into building blocks -- interchangeable
bio-bricks that can be reassembled into new forms.
The technology envisions new species of microbes built
from the bottom up: "living machines from off-the-shelf
chemicals" to suit the needs of science, said
Jonathan Tucker, a bioweapons expert with the Washington-based
Center for Non-Proliferation Studies.
is possible to engineer living organisms the way people
now engineer electronic circuits," Tucker said.
In the future, he said, these microbes could produce
cheap drugs, detect toxic chemicals, break down pollutants,
repair defective genes, destroy cancer cells and generate
hydrogen for fuel.
less than five years, synthetic biology has gone from
a kind of scientific parlor trick, useful for such
things as creating glow-in-the-dark fish, to a cutting-edge
bioscience with enormous commercial potential, said
Eileen Choffnes, an expert on microbial threats with
the National Academies' Institute of Medicine. "Now
the technology can be even done at the lab bench in
high school," she said.
with synthetic biologists, a separate but equally
ardent group is pursuing DNA shuffling, a kind of
directed evolution that imbues microbes with new traits.
Another faction seeks novel ways to deliver chemicals
and medicines, using ultra-fine aerosols that penetrate
deeply into the lungs or new forms of microencapsulated
packaging that control how drugs are released in the
another group is discovering ways to manipulate the
essential biological circuitry of humans, using chemicals
or engineered microbes to shut down defective genes
or regulate the production of hormones controlling
such functions as metabolism and mood.
analysts have compared the flowering of biotechnology
to the start of the nuclear age in the past century,
but there are important differences. This time, the
United States holds no monopoly over the emerging
science, as it did in the early years of nuclear power.
Racing to exploit each new discovery are dozens of
countries, many of them in the developing world.
no binding treaty or international watchdog to safeguard
against abuse. And the secrets of biology are available
on the Internet for free, said Robert L. Erwin at
a recent Washington symposium pondering the new technology.
He is a geneticist and founder of the California biotech
firm Large Scale Biology Corp.
too cheap, it's too fast, there are too many people
who know too much," Erwin said, "and it's
too late to stop it."
May, when 300 synthetic biologists gathered in California
for the second national conference in the history
of their new field, they found protesters waiting.
creating new life forms cannot be allowed to act as
judge and jury," Sue Mayer, a veterinary cell
biologist and director of GeneWatch UK, said in a
statement signed by 38 organizations.
are not the only ones concerned about where new technology
could lead. Numerous studies by normally staid panels
of scientists and security experts have also warned
about the consequences of abuse. An unclassified CIA
study in 2003 titled "The Darker Bioweapons Future"
warned of a potential for a "class of new, more
virulent biological agents engineered to attack"
specific targets. "The effects of some of these
engineered biological agents could be worse than any
disease known to man," the study said.
is not just the potential for exotic diseases that
is causing concern. Harmless bacteria can be modified
to carry genetic instructions that, once inside the
body, can alter basic functions, such as immunity
or hormone production, three biodefense experts with
the Defense Intelligence Agency said in an influential
report titled "Biotechnology: Impact on Biological
Warfare and Biodefense."
far as is publicly known, no such weapons have ever
been used, although Soviet bioweapons scientists experimented
with genetically altered strains in the final years
of the Cold War. Some experts doubt terrorists would
go to such trouble when ordinary germs can achieve
the same goals.
capability of terrorists to embark on this path in
the near- to mid-term is judged to be low," Charles
E. Allen, chief intelligence officer for the Department
of Homeland Security, said in testimony May 4 before
a panel of the House Committee on Homeland Security.
"Just because the technology is available doesn't
mean terrorists can or will use it."
far more likely source, Allen said, is a "lone
wolf": a scientist or biological hacker working
alone or in a small group, driven by ideology or perhaps
personal demons. Many experts believe the anthrax
attacks of 2001 were the work of just such a loner.
it would take for advanced bioweapons development,"
Allen said, "is one skilled scientist and modest
equipment -- an activity we are unlikely to detect
the Western world and even in developing countries
such as India and Iran, dozens of companies have entered
the booming business of commercial gene synthesis.
Last fall, a British scientific journal, New Scientist,
decided to contact some of these DNA-by-mail companies
to show how easy it would be to obtain a potentially
dangerous genetic sequence -- for example, DNA for
a bacterial gene that produces deadly toxins.
five of the 12 firms that responded said they screened
customers' orders for DNA sequences that might pose
a terrorism threat. Four companies acknowledged doing
no screening at all. Under current laws, the companies
are not required to screen.
the United States, the federal "Select Agent"
rule restricts access to a few types of deadly bacteria,
viruses and toxins. But, under the CDC's interpretation
of the rule, there are few such controls on transfers
of synthetic genes that can be turned into killers.
Changes are being contemplated, but for now the gap
is one example of technology's rapid advance leaving
law and policy behind.
would be possible -- fully legal -- for a person to
produce full-length 1918 influenza virus or Ebola
virus genomes, along with kits containing detailed
procedures and all other materials for reconstitution,"
said Richard H. Ebright, a biochemist and professor
at Rutgers University. "It is also possible to
advertise and to sell the product, in the United States
scientists tend to be deeply skeptical of government
intrusion into their laboratories, many favor closer
scrutiny over which kinds of genetic coding are being
sold and to whom. Even DNA companies themselves are
lobbying for better oversight.
Heron Biotechnology, a major U.S. gene-synthesis company
based in suburban Seattle, formally petitioned the
federal government three years ago to expand the Select
Agent rule to require companies to screen DNA purchases.
The company began voluntarily screening after receiving
suspicious requests from overseas, including one from
a Saudi customer asking for genes belonging to a virus
that causes a disease akin to smallpox.
request turned out to be legitimate, from a real scientist,
but it made us ask ourselves: How can we make sure
that some crazy person doesn't order something from
us?" said John Mulligan, Blue Heron's founder
and chief executive. "I used to think that such
a thing was improbable, but then September 11 happened."
scientists also favor greater scrutiny -- or at least
peer review -- of research that could lead to the
accidental or deliberate release of genetically modified
theory, such oversight is provided by volunteer boards
known as institutional biosafety committees. Guidelines
set by the National Institutes of Health call on federally
funded schools and private labs to each appoint such
a board. A 2004 National Academy of Sciences report
recommended that the committees take on a larger role
in policing research that could lead to more powerful
reality, many of these boards appear to exist only
on paper. In 2004, the nonprofit Sunshine Project
surveyed 390 such committees, asking for copies of
minutes or notes from any meetings convened to evaluate
research projects. Only 15 institutions earned high
marks for showing full compliance with NIH guidelines,
said Edward Hammond, who directed the survey. Nearly
200 others who responded had poor or missing records
or none at all, he said. Some committees had never
techniques that unlock the secrets of microbial life
may someday lead to the defeat of bioterrorism threats
and cures for natural diseases, too. But today, the
search for new drugs of all kinds remains agonizingly
years after the Sept. 11 attacks, the federal government
budgets nearly $8 billion annually -- an 18-fold increase
since 2001 -- for the defense of civilians against
biological attack. Billions have been spent to develop
and stockpile new drugs, most of them each tied to
a single, well-known bioterrorism threat, such as
efforts to streamline the system, developing one new
drug could still take up to a decade and cost hundreds
of millions of dollars. If successful, the drug is
a solution for just one disease threat out of a list
that is rapidly expanding to include man-made varieties.
a biological attack, waiting even a few weeks for
new drugs may be disastrous, said Tara O'Toole, a
physician and director of the Center for Biosecurity
at the University of Pittsburgh Medical Center.
haven't yet absorbed the magnitude of this threat
to national security," said O'Toole, who worries
that the national commitment to biodefense is waning
over time and the rise of natural threats such as
pandemic flu. "It is true that pandemic flu is
important, and we're not doing nearly enough, but
I don't think pandemic flu could take down the United
States of America. A campaign of moderate biological
2006 The Washington Post Company