A DNA Success Raises Bioterror Concern
January 12, 2005
By NICHOLAS WADE
Researchers have made an unexpectedly sudden advance in
synthesizing long molecules of DNA, bringing them closer to
the goal of redesigning genes and programming cells to make
But the success also puts within reach the manufacture of
small genomes, such as those of viruses and perhaps certain
bacteria. Some biologists fear that the technique might be
used to make the genome of the smallpox virus, one of the
few pathogens that cannot easily be collected from the
The advance, described in the Jan. 6 issue of the journal
Nature by Dr. George M. Church of the Harvard Medical
School and Dr. Xiaolian Gao of the University of Houston,
involves the use of a new technique to
synthesize a DNA molecule 14,500 chemical units in length.
The molecule contained a string of 21 genes used by a harmless
The full power of the technique is still being explored,
but genomes like that of the smallpox virus - 186,000
chemical units long - seem well within reach. Dr. Church
has completed the first part of a plan to synthesize the
777,000-unit genome of a small bacterium known as
"This has the potential for a revolutionary impact in the
ease of synthesis of large DNA molecules," said Dr. Richard
Ebright, a molecular biologist at Rutgers University with
an interest in bioterrorism.
"This will permit efficient and rapid synthesis of any
select agent virus genome in very short order," he added,
referring to the list of dangerous pathogens and toxins
that possessors are required to register with the Centers
for Disease Control and Prevention. Dr. Ebright said any
facility possessing the new DNA synthesis equipment should
be assumed capable of making any virus on the select agent
The genetic sequences of smallpox and many other
pathogens are easily obtained because they were deposited
in public databases as an aid to medical researchers at a
time when synthesizing large DNA molecules seemed
prohibitively expensive or impossible.
Dr. Church is developing automated methods of DNA synthesis
for a variety of research purposes including vaccines and
pharmaceutical production. He has no interest in
synthesizing dangerous pathogens but is aware of the
technique's potential for misuse. Last year he proposed
that the machines and ingredients for synthesizing DNA
should be controlled, with manufacturers selling supplies
only to facilities whose DNA machines had been registered.
The manufacturers have expressed willingness to adopt the
proposal, Dr. Church said in an e-mail message, "but it
would be reassuring to get some official governmental
Some experts say bioterrorists would find it much easier to
collect pathogens in the wild than to synthesize the
organisms' genetic material. But this is less of an option
for smallpox, now officially held by only two laboratories
in the world, and for the increasingly rare polio virus.
In part to draw attention to the dangers of bioterrorism,
Dr. Eckard Wimmer of the State University of New York at
Stony Brook spent three years synthesizing DNA
corresponding to the 7,500 units of polio virus, a feat he
announced in July 2002. "It will be possible in 10 to 15
years to make smallpox," Dr. Wimmer told the Knight
Ridder/Tribune Business News at the time.
Dr. Wimmer said last week that the method described by Dr.
Church and Dr. Gao was in technical terms "a tremendous
step forward." But the technology would be impossible to
control, he said, since any restraints that might be agreed
to in the United States would not necessarily be followed
by other countries. The only protection against harmful
agents, in his view, is for the government to step up
development of efficient vaccines.
The genetic sequence of many pathogens has been determined
and published by the Institute for Genomic Research in
Rockville, Md. Dr. Claire M. Fraser, the institute's
president, said the new DNA synthesis method was a big
advance in speed, cost and accuracy, but it was not yet
clear if it would be possible to synthesize the genomes of
large bacteria like anthrax.
"I think we are going to see some point in the future when
there will be a need for additional oversight on research,"
Dr. Fraser said.
But scientists abroad, whose cooperation would be needed,
seemed to her less concerned about the dangers. "We don't
want to handicap science in the U.S." if others will not
join in the effort, she said.
Once scientists have synthesized the genome of an organism,
it must then be "booted," or made to operate in a cell. Dr.
Wimmer was able to reboot his polio virus genome so as to
generate infectious particles, and a method for rebooting
the cowpox genome, which is similar to that of smallpox,
has already been reported.