With Biotechnology, a Potential to Harm

http://www.nytimes.com/2001/11/27/health/anatomy/27VIRU.html?pagewanted=print

New York Times
November 27, 2001

With Biotechnology, a Potential to Harm

By ANDREW POLLACK

Some biological weapons experts fear that terrorists have gotten hold of the smallpox

virus, the last two official repositories of which are kept under guard in the United

States and Russia. But some experts say a sophisticated adversary would not have to obtain

the natural virus, but could make it from scratch.

"You don't really need the virus," said Robert L. Erwin, chief executive of Large Scale

Biology Corporation, a biotech company that does research involving plant viruses. The

complete genome sequence of the virus is freely available on the Internet and — in theory,

anyway — genetic engineers could use the information to transform a related virus into

smallpox itself, he said.

Other experts say such a feat would be next to impossible. But the debate itself shows there

is concern that the very same biotechnology that is bringing about a revolution in medicine

can also be used to create diabolical new biological weapons or make existing pathogens

worse.

"With genetic engineering you can make things a lot worse," said Dr. Steven M. Block, a

biology professor at Stanford who led a group of scientists that looked at how biotechnology

might be applied to weapons. Among the things the group envisioned were "stealth"

pathogens that would be hard to detect because they would infect people but not produce

symptoms until activated later by some chemical or food.

The Soviet Union created versions of the anthrax and plague bacteria resistant to more than

one antibiotic, according to "Biohazard," a book by Ken Alibek, a Soviet bioweapons

designer who defected to the United States. Russian scientists reported in 1997 that they had

made a strain of anthrax resistant to their own nation's vaccine.

Genetic engineering might also be used to transfer a gene for a toxin into a common microbe.

American scientists in the 1980's made E. coli, a common bug, more virulent by transferring

a dangerous gene from a relative of the plague bacterium.

It might also be possible to try to make combination pathogens — combining, say, the

lethality of one with the infectiousness of another. Dr. Raymond A. Zilinskas, a biological

weapons expert at the Monterey Institute for International Studies, said he had learned that

the Soviets had put a virus inside bacteria, so the virus would be activated when the bacteria

were killed by antibiotics.

For now, anyway, it is much easier to imagine ghastly new biological weapons than to create

them. Putting in a gene for antibiotic resistance, for instance, might also make a germ less

virulent or less stable in the environment. Dr. Zilinskas said that while antibiotic resistant

bugs can be made now, most other super pathogens won't be feasible for the next five years.

Moreover, some experts say, there is no need for bizarre new creations because natural

pathogens have evolved for millions of years and are dangerous enough.

"I'm not impressed with all this spooky stuff about genetic engineering of lethal bugs," said

Dr. Matthew S. Meselson, an expert on biological weapons at Harvard. "When the day

comes when we're protected from ordinary anthrax, then that will be an improvement."

But Dr. Block of Stanford argued that germs don't kill their hosts too quickly because that

would give them no place to reproduce. So there is room to make them more deadly.

"Diseases are not designed to be as bad as they can be," he said.

Concern about the potential of biotechnology was stirred earlier this year when Australian

scientists reported that by transferring an immune system gene into the mousepox virus in an

effort to design a contraceptive, they inadvertently created a highly lethal virus.

Another technology that has caused concern is directed molecular evolution, which involves

shuffling genes into new combinations in a test tube — compressing evolution that takes

millions of years into a few months. One of the first tests of the technology was to "evolve" a

strain of the common E. coli bacteria that was 32,000 times more resistant to an antibiotic

than the natural strain. Dr. Willem P. C. Stemmer, who led the work, said he destroyed the

strain.

But Dr. Stemmer, vice president for research at Maxygen, a biotech company, said the

technology would be "complex and cumbersome" to use to create weapons, and the same

technology is being used to create defenses against biowarfare.

The newest tool that might be used to create weapons is the genetic information becoming

available through the sequencing of the human DNA sequence and the sequences of dozens

of pathogens.

One fear is that such information could be used to create germs that hurt only a particular

ethnic group, by targeting a gene sequence unique to that group. But some experts say that

genetic markers unique to one group are not known to exist.

Another concern is that viruses can be recreated by chemically synthesizing the viral DNA

and then putting it into a related virus that has had its own DNA removed. Dr. J. Craig

Venter, president of Celera Genomics and leader of the effort to sequence the genome of the

smallpox virus, said of the synthesis of smallpox: `I'm convinced it's doable, though not by

an amateur."