A DNA Success Raises Bioterror Concern

January 12, 2005


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 pharmaceuticals.

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 wild.

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 laboratory bacterium.

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 Mycoplasma mobile.

"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 list.

The genetic sequences of smallpox and many other dangerous 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 support."

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.