The Specter of a New and Deadlier Smallpox

By RICHARD PRESTON

RINCETON, N.J.
Smallpox, or variola virus, is considered by many doctors to be the pathogen most dangerous to the human species. The virus was eradicated as a natural disease 25 years ago, and is now stored legally at only two sites: in a freezer at the Atlanta headquarters of the Centers for Disease Control and Prevention and at a Russian government laboratory in Siberia. Research on the virus is being conducted at both sites, but is tightly restricted by the World Health Organization. In 1972, the United States stopped giving routine vaccinations for the virus.

Now fears about smallpox have returned, with the possibility that this biological agent will be used as a weapon in terrorism or war. A number of countries, including Iraq, Iran and North Korea, are suspected by United States intelligence agencies of keeping clandestine stocks of smallpox for use as a weapon.

The United States government has begun a crash effort to create a national stockpile of vaccine for use in a smallpox emergency, at a cost of around $1 billion. Though the vaccine is being made with modern methods, it is designed to work against the natural form of the smallpox virus. This vaccine was developed in 1796. Would it work against a 21st-century biologically engineered smallpox? Probably not. And given rapid advances in molecular biology, genetic engineering of the smallpox virus is now feasible, not by amateurs or terrorist groups but by professional scientists in countries that have biowarfare programs.

In early 2001, a group of researchers in Australia surprised and scared pox virus experts when they reported that they'd put the interleukin-4 gene, the gene that controls immune responses, into the mousepox virus and found that it made mousepox into a killer virus in naturally immune mice and deadly even to some vaccinated mice. (Mousepox is related to smallpox but can't infect people.)

If this particular gene made mousepox vaccine-resistant, then there is the frightening possibility that the gene could be added to the smallpox virus, making it vaccine-resistant — a super variola. The interleukin-4 gene is one of the most commonly studied genes. Thousands of scientific papers have been written about it and it can be readily purchased on the Internet by scientists. (The gene typically comes as a pinch of dried bacteria in a small brown glass bottle.)

Few people realize how straightforward it is to put a gene into a virus. Genetic engineering of viruses, for peaceful research, has become routine and standardized. The cost of supplies for creating a strain of engineered virus for an experiment can be less than $1,000, and it can be done on a laboratory countertop that's three feet long.

Pox viruses are among the easiest viruses to engineer in the lab because they readily accept foreign genes. The first engineering of a pox virus was done more than 20 years ago. There is little doubt that Iraqi biologists know how to do it. Smallpox could probably be genetically engineered in a couple of rooms in a small facility with relatively simple safety precautions, and it might be very hard for inspectors to find it or prove what was going on. A nation that has clandestine stocks of smallpox might thereby be able to make a strain that would do an end run around the American stockpile of the vaccine, with severe consequences.

Recently Mark Buller, a pox virus researcher at the St. Louis University School of Medicine, began experiments with mousepox to try to answer the question of whether, in fact, the interleukin-4 gene really would turn natural smallpox into a superpox. His team is trying to develop a vaccine strategy that could work against such a virus. That research is ongoing and will take time.

The biologist community has reacted with troubled anxiety to the idea of genetically engineered bioweapons. The Australian scientists who worked on the mousepox virus wanted to alert scientists about how easy it might be to engineer a supervirus. Even so, many scientists prefer not to talk about how such research might be used, while others believe that no nation is likely to make a super smallpox because such a weapon would be uncontrollable and devastating for the world. Perhaps.

This logic of restraint, however, did not persuade Edward Teller and Andrei Sakharov, the distinguished American and Russian physicists who independently invented the hydrogen bomb, to stop their research. They sincerely believed it was the right thing for their countries, and they were attracted to the technical challenge. When something can be done in science, in the end it is almost always done.

Weapons are often simpler to make than peaceful technologies: a cannon is less complicated than a clock; a nuclear bomb is a simpler device than a nuclear power plant. Biologists are now in much the same position as physicists were during the late 1930's, when it was becoming apparent to some of them that, whether they liked it or not, they were learning that the forces of nature could be directed into a giant bomb — and that someone could really try to make it. The question now is whether scientists and policymakers can fully recognize that recent advances in molecular biology are making possible the creation of frightening new weapons — and whether they will be prepared to offer protection to ordinary citizens if or when such weapons become a reality.
 

Richard Preston is the author, most recently, of ‘‘The Demon in the Freezer: A True Story.’’