Long before it became the topic of hourly news bulletins, monkeypox was a virus of interest to US researchers intent on creating safer smallpox vaccines and treatments. Some hope now that monkeypox's Western Hemisphere debut will spread the wealth of scientific knowledge back to central and western Africa, where monkeypox is endemic and sometimes fatal.

"Monkeypox has not been established as a top-priority disease, and it should be," said Joel Breman, who chaired the World Health Organization's monkeypox study committee and is now senior scientist at the National Institute of Health's John E. Fogarty International Center. "It should be a higher priority because of its potential for exportation, number one, and number two, because the natural history of monkeypox remains unknown even 30 years after its discovery in humans and 45 years from its first discovery in nonhuman primates."

Labs at the US Army Research Institute for Infectious Diseases (USAMRIID) and at the National Institutes of Health (NIH) labs in Maryland use monkeypox as a substitute for smallpox because it is easier to handle in the laboratory and less likely to spread among humans.

"Our main goal has been to look at therapeutics. We use monkeypox because it is a BSL-3 [biosafety level 3] agent so we can use it under slightly less strict conditions in the lab," said Robert Baker, a USAMRIID virologist.

Science and logistics make monkeypox a good surrogate for the more lethal pox. "Monkeypox produces a disease in monkeys and people that is essentially identical to smallpox," Baker told The Scientist.

Animal models created at USAMRIID are being used to test therapeutics against smallpox, such as the antiviral cidofovir as well as safer versions of the smallpox vaccine, such as the modified vaccinia Ankara (MVA) vaccine, that potentially pose less of a threat to immunocompromised people.

"There are whole groups of people contraindicated for vaccination," Baker said. "One of our goals is to find an option for people who shouldn't be taking the vaccine. In addition, we are trying to extend the window of protection so we can treat post-exposure."

In collaboration with Donald Smee, research professor at Utah State University's Institute for Antiviral Research, Army scientists are developing rodent models to replace the more expensive primate test subjects for monkeypox. Monkeypox's importation to this country, probably by way of a giant Gambian rat, was "a total surprise," Smee, who has published extensively on monkeypox, told The Scientist. And no, Baker said, prairie dogs were never on the list of candidates to serve as rodent models. Cotton rats show the most promise, Baker said.

Bernard Moss, chief of the viral disease laboratory at NIH, is evaluating highly attenuated MVA against primates infected with monkeypox at USAMRIID. Ongoing work is also looking at recombinant proteins, Moss said, and he expects to report results before the end of the year.

"The top priority is to control and mute this epidemic so there aren't more cases," Breman told The Scientist. "This is a huge opportunity both to look at treatments and possibly prevention, to look at how the disease will be acquired and spread in an environment where you can actually do surveillance properly."

Editor's note: A reader responded to this article by e-mail, pointing out that according to the Center's for Disease Control and Prevention guide, Biosafety in Microbiological and Biomedical Laboratories (BMBL), 4th ed., May 1999, monkeypox is a BSL-2 agent. Dr. Baker explained to The Scientist why USAMRIID chooses to work with monkeypox at BSL-3: "Monkeypox is very stable in the environment, a very hardy virus. It is rather infectious, has a good fatality rate, easily transmissible by aerosols which are generated in laboratories, for example, with centrifuges... At USAMRIID we use the CDC guidelines at a minimum, but if our safety people feel they want to be a little more secure, they may require additional personal protective equipment. We generally follow the CDC guidelines and sometimes we choose to go a little higher. Monkeypox may be listed...as BSL-2, minimum, but because it is so stable, we are going to do what we need to feel secure and that means BSL-3."