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[SANET-MG] synthetic pathogens for bioterror
The article below is about synthetic pathogens. Earlier I circulated
information about making cows with synthetic genes to to prevent
mastitis. Human, farm animal or crop synthetic pathogens may be
developed along with the synthetic genes for farm animals already on the
way. We all may need synthetic genes to fight off the synthetic
pathogens.Synthetic being are like the famous purple cow.
"I NEVER saw a Purple Cow;
I never hope to See One;
But I can Tell you, Anyhow,
I'd rather See than Be One. "
Custom-Built Pathogens Raise Bioterror Fears
By Joby Warrick
Washington Post Staff Writer
Monday, July 31, 2006; A01
STONY 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.
In 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.
The 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.
Wimmer 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.
"The future," he said, "has already come."
Five 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.
The 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.
"The 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'."
The 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.
The 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.
Bioterrorism 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.
"There's 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.
"By 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."
How to Make a Virus
Wimmer's 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
As 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 freedom.
Wimmer counters that he didn't invent the technology that made his
experiment possible. He only drew attention to it.
"To 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
One 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.
New 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.
But 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.
"Our paper was the starting point of the revolution," Wimmer said. "But
eventually the process will become so automated even technicians can do it."
Wimmer's 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.
Armed 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
Using 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.
The 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
While 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.
Yet 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.
"This," he said, "is a wake-up call."
From Parlor Trick to Bio-Bricks
The 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 them.
The 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
"It 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.
In 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.
Along 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 body.
Still 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.
Some 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.
There's 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.
"It's 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."
A Darker Side
In May, when 300 synthetic biologists gathered in California for the
second national conference in the history of their new field, they found
"Scientists 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.
Activists 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.
It 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."
As 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
"The 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
A 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.
"All it would take for advanced bioweapons development," Allen said, "is
one skilled scientist and modest equipment -- an activity we are
unlikely to detect in advance."
Genes for Sale
Throughout 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
Only 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.
In 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.
"It 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 or overseas."
While 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.
Blue 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
"The 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."
Some scientists also favor greater scrutiny -- or at least peer review
-- of research that could lead to the accidental or deliberate release
of genetically modified organisms.
In 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 biological weapons.
In 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 met.
Stockpiles Aren't Enough
New 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
Five 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 anthrax.
Despite 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.
In 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.
"We 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 attacks could."
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