The last person on earth to die of smallpox was Janet Parker, a medical photographer in Birmingham, UK. She was working above a research laboratory in 1978 when the virus escaped through the ventilation system. It infected her, and she died.

The year before, 1977, marked the climax of an 11-year worldwide vaccination campaign, mounted by the World Health Organization, to eradicate smallpox once and for all. It was led by American vaccinologist Donald Henderson, who declared smallpox extinct.

The U.S. and the Soviet Union, which held the now-redundant viral cultures and vaccines, agreed to destroy these stocks at some future date. That commitment has since been postponed indefinitely. Meanwhile, the CIA says that four nations - Russia, Iraq, North Korea and France - possess undeclared samples of the virus. And the Bush administration cited terrorist organizations as having mentioned smallpox among bioweapons they are interested in acquiring.

Biostatistician Ira Longini Jr. at Emory University in Atlanta observed, "Donald Henderson now works in the Office of Homeland Defense. He's really the key person in smallpox policy in the White House."

Longini and Emory biostatistician Elizabeth Halloran are co-senior authors of a paper in the current Science, dated Nov. 15, 2002, titled: "Containing of bioterrorist smallpox." It compares, by computer-aided modeling, two basic and contrasting defensive strategies - targeted vaccination and mass vaccination.

"Targeted vaccination, if done quickly and properly," Longini told BioWorld Today, "could be competitive with mass vaccinations. The more herd immunity to smallpox we have in the population, the better targeted vaccination does. It's after an outbreak starts, you find all the reported cases of smallpox, isolate them, and vaccinate as many of their close contacts as you can find - which in the case of smallpox would be most of them

"In mass vaccination," Longini continued, "you simply vaccinate some proportion of the population, say 80 percent. And you can do mass vaccination before an attack or like targeted vaccination, as quickly as you can after the outbreak. It means you vaccinate everybody you decide needed to be mass vaccinated, regardless of whether they've had contacts with smallpox or not."

All Out For Vaccine-Spread Herd Immunity

"Before the WHO eradication campaign in 1966-77," Longini went on, "virtually all Americans were routinely mass vaccinated. Nowadays we vaccinate for measles and other childhood diseases, and try to mass-vaccinate for influenza. The goal of mass vaccination is to achieve herd immunity. This means that you have enough immune people in the population such that viral transmission is greatly slowed or entirely cut off. Transmission," Longini explained, "is a combination of inhalation or direct contact. Touching some material that an infected person may have handled, being exposed to body fluids of any sort, would all be ways of transmitting smallpox. To spread the disease, you have to have repeated close contact with an infected person. The probability is much higher in transmission in that setting than casual contact, which has a very low probability of transmission.

"Nobody has modeled smallpox as carefully as we," Longini allowed. "There hasn't been a need. But it's an extension of the model we used for influenza; we simply modified it for smallpox. Before we did this in the modern context in the U.S. right now I don't think anybody had any idea how targeted vaccination would perform in comparison to mass vaccination. The other thing is the role of prior residual immunity. We ran two scenarios: In one we assumed people vaccinated before 1972 had no residual protection. When there was residual immunity, we assumed people vaccinated 30 years ago or before were about half as well protected as the same people vaccinated today. We assume that 50 percent are likely to be infected compared to an unvaccinated person. Their death rate, given they're ill, would be reduced from 30 percent to 3 percent. And 80 percent less infectious to others if they did become infected.

"With fresh modern smallpox vaccine," Longini pointed out, "the estimated probability of infection and illness is reduced by a factor of 95 percent. We ran another set with no protection whatsoever on any level if they were vaccinated 30 years ago or before. We found that targeted vaccination works reasonably well with no residual immunity. That leads us to recommend that we probably should go ahead vaccinating first responders now, and also volunteers - people who want to be vaccinated and understand the risk. First responders are hospital workers who would come into contact with smallpox cases if there were an attack, such as vaccinators, ambulance drivers, anybody who potentially might be on the scene when the first cases appear."

Suicide Attackers Supply Low-Tech Terror

Asked how Homeland Defense planners imagine such a terrorist smallpox attack would be launched, Longini replied: "From what I've heard at meetings where some of those people were present, I picture the simplest low-tech attack. There would probably be a handful of dedicated suicide terrorists infecting themselves, then moving contagiously among the population. They'd incur a 30 percent possible death rate. So the suicide assault is the easiest way to do it. You don't need any high-tech technology to inoculate victims.

"You can easily control an attack," Longini noted, adding, "But you'd pay a price because, say, you protectively mass-vaccinated 200 million Americans, you'd have roughly 200 to 400 deaths, and at least 20,000 people with serious side effects from the vaccine. That's the argument against mass vaccination. With targeted vaccination, of course, if there were an attack, more people would probably get smallpox, but you'd certainly be doing less damage with the vaccine, and - according to our work - control the outbreak pretty quickly."

Longini explained why the vaccinia virus itself is so virulent: "It's an old vaccine developed decades ago. It gives very good protection but causes a vaccinia infection at the inoculation site. People who are immunosuppressed or have eczema or other skin conditions can suffer very serious complications. Even a perfectly healthy person, on rare occasions, may develop vaccinia infections, which are difficult to deal with.

"For smallpox, the development of a new, safe vaccine," Longini concluded, "is something to start looking for now."