Galvanized by the recent anthrax attacks, molecular biologists who had previously sought to distance themselves from bioweapons as biology's disgrace are warning that genetic engineering has the potential to create even more fearsome germs.

In doing so, they are acknowledging that biotechnology--for all its promise in diagnosing, treating and curing disease--can also be turned to malevolent purposes. Scientists who wish to help cure disease, they say, must consider how their work could be misused and how to fight back with new medicines or other techniques.

There is "an increasing tide of concern, among both the scientific and security communities, that the revolution in biology could be misused in offensive biological weapons programs directed against human beings and their staple crops or livestock," according to a commentary in the latest Nature Genetics journal.

The National Institutes of Health have set up urgent meetings with biologists, drugmakers and government officials to begin addressing the bioweapons threat, and the National Academy of Sciences will hold special forums this month to begin assessing the dangers posed by bioterrorism.

Scientists warn that technology has made it possible to manipulate the genes of viruses and bacteria to the point where a competent molecular biologist could make supergerms that could be far more lethal and disruptive than naturally occurring pathogens.

"Ironically, the very same technology that can insert good genes and fix you can insert bad genes and hurt you," said Steven Block, a Stanford University molecular biologist. "As we proceed with this technology, there is inevitably a dark side, but it's the white side of biology that's going to save us."

No longer science fiction

For biologists the attacks have been an agonizing awakening to the reality that science can be misused, raising moral and ethical questions about how far science should go, what kind of research should be permitted and who should be allowed to conduct it.

Scientists paint a scenario that, until a few months ago, seemed more like science fiction--undetectable superbugs; "stealth viruses" that invade a person, lie dormant and are triggered on command to cause infection; "designer diseases" that affect specific organs, such as the brain.

The Soviets were the first to attempt to bioengineer natural pathogens into more virulent ones when, in the 1980s, they secretly produced anthrax spores to be resistant to some antibiotics. They also unsuccessfully tried to combine smallpox with the Ebola virus to make a hardier killer.

These efforts, however, are considered primitive compared with the sophisticated technology available today, which can not only identify all the genes that make up disease-causing germs but also manipulate the genes to give the bugs chilling new properties.

`Available to anybody'

Some biotech companies are developing the technology to take individual genes apart and reassemble them in different ways that give the genes new capabilities. This technology has been hailed as a possible important development in curing genetic diseases, but it is now also seen as a way to make genes with incredibly efficient killing powers.

The genetic blueprints of plague, smallpox, cholera and other pathogens, for example, are already identified and posted on the Internet and in scientific journals for anyone to see.

"Many of the genomes for agents that could be used in biological warfare are now matters of public knowledge. They are available to anybody in the world," said Barry Bloom, dean of the Harvard School of Public Health. "If they want to mutate genes, or splice them and take them out, all they need is a couple of DNA primers, some DNA and a little skill, and that can be done."

In the next two years genetics laboratories around the world are expected to complete the genetic makeup of more than 70 major bacterial, viral, parasitic and fungal germs that infect humans, animals and plants.

"The ever-expanding microbial genome databases now provide a parts list of all potential genes involved in pathogenicity and virulence, adhesion and colonization of host cells, immune response evasion and antibiotic resistance from which to pick and choose the most lethal combinations," said the Nature Genetics commentary, which was written by Claire M. Fraser, president and director of the Institute for Genomic Research, and Malcolm R. Dando of the department of peace studies at the University of Bradford in Britain.

Countering bioweapons

If a terrorist builds an antibiotic-resistant germ, then science must develop new drugs to overcome the resistance, and a thorough understanding of all disease genes will make it possible to develop faster methods of diagnosing and then disabling them. Harvard researchers, for example, recently found a gene that makes mice resistant to anthrax, a discovery that could lead to better vaccines and drugs.

"The same technology that can bring us these potential weapons of devastation is precisely the technology that we'll need to counter them," Block said.

A greatly expanded offensive against bioweapons is also expected to pay dividends in improved health. As scientists increase their mastery of germ genes to defeat bioterrorists, they will also be gaining the knowledge to develop anti-microbials, vaccines and other compounds to tame the infections that are the second-leading cause of death in the world.

Ethical norms

The ethical dilemmas in biology recall those that have arisen with other great scientific accomplishments. Most of the physicists who built the first atomic bombs, for instance, opposed their use on population targets, and many became involved in campaigns to ban nuclear weapons.

The first molecular biologists who learned how to transpose genes from one species into another in the mid-'70s called a moratorium on their research until it could be shown that such genetic engineering would not accidentally create dangerous organisms.

"How do you keep new bioweapons from happening?" Bloom said. "You have to . . . create a very strong moral culture of scientists that worry about the uses of science."

For universities, that means facing critical issues about bioterrorism as they train people to do molecular science.

"We need to create a culture where students know what the accepted norms are," Bloom said. "Just as doctors need to know what are the accepted ethical norms for human subjects in research, we need the same for biological knowledge."