How a strategy based on testing helped eradicate smallpox

This is an Inside Science story.

"Testing, testing, testing" has become the mantra of the fight against the coronavirus. Scientific experts all seem to agree the virus cannot be controlled without adequate testing.

If you want to know why, think of Ali Maow Maalin.

Maalin, a young cook in the small coastal village of Merca, Somalia, was the last person to catch naturally transmitted smallpox. He volunteered to drive an infected family to a hospital in October 1977, and the next week came down with the disease. He was discovered because the World Health Organization set up a surveillance system that reported his illness, and vaccinators swarmed Merca blocking transmission. He survived and did not pass the disease on to anyone else. (Maalin died of malaria in 2013.)

They knew exactly where the virus was in real time, thanks to a worldwide surveillance system that found Maalin even in a remote village in sub-Saharan Africa. I had a glimpse of this process reporting for the Philadelphia Inquirer and researching the book that eventually became "The Invisible Fire," published in 1979.

It was an adventure. The Somali Democratic Republic barred Western reporters, so I had to sneak in under false pretenses, as a WHO researcher. A real WHO researcher took me to meet Maalin.

Are there lessons to be learned from what happened a half century ago?

A vulnerable virus

Epidemiologists had several advantages in fighting variola, the smallpox virus, that they lack in battling the coronavirus. For one, variola is a very large virus, so big it can be seen with a normal microscope. Unlike many viruses, it had no animal reservoir. It survived by transmission between humans only, so it had no place to hide.

Most of that is not true of the new coronavirus, but there are crucial lessons connecting the two. Testing that confirms the presence of a virus will tell you where a disease is so you can do something about it. And testing can give information as it moves.

Experts agree the reported numbers of people who have tested positive for SARS-CoV-2, the type of coronavirus that causes COVID-19, represent a substantial undercount. One controversial study at Stanford suggested confirmed cases are a small fraction of the true number. Without more testing we don't know what percentage of cases have been detected so far.

Another difference between COVID-19 now and smallpox in the 1970s is the availability of an almost perfect smallpox vaccine, developed in 1796, by the English physician Edward Jenner.

Jenner realized that farm workers who contracted a similar disease, cowpox, never seemed to catch smallpox. To test it, Jenner inoculated an 8-year-old boy, James Phipps, with scabs from the cowpox lesions of dairy maid Sarah Nelms. A few weeks later he tried to give Phipps a mild case of smallpox and found the boy protected; Jenner had discovered a safe vaccine and invented immunology in the process.

The vaccine was almost 100% effective with few side effects. It was used until smallpox was eradicated in 1977.

Two other factors helped: The vaccine could be freeze-dried so it was stable and transportable, and scientists at the drug company Wyeth developed the perfect delivery system, a bifurcated needle that administered an exact amount of vaccine into the dermis, the layer of skin below the epidermis, when the needle was jabbed twice -- essentially painless, no injections needed.

Some people with COVID-19 can walk around without exhibiting symptoms. No one is sure when in the course of infection the tests can pick up the signs, according to Tina Tan, professor of pediatrics at Northwestern University and an infectious disease expert. "If someone has been significantly exposed to COVID-19, regardless of the test results, that person pretty much has the infection," Tan said.

In contrast, smallpox victims were often hard to miss and there were no asymptomatic cases, said Gigi Gronvail, senior scholar at the Johns Hopkins Center for Health Security. They looked ghastly, with sores, sometimes bleeding, all over much of their bodies. The incubation period for smallpox was seven to 17 days, and people were infectious only when they had symptoms.

Tests, vaccines and consistent visible symptoms were the weapons medicine needed for the eradication of smallpox. Next came the strategy.

Winning the smallpox war

In 1958, to the surprise of the world, the Soviet Union urged the WHO to eradicate smallpox and offered funding to develop a plan. The U.S., the WHO's major funder, agreed. No one knows why Russians made the humane offer, but it became perhaps the single best cooperative arrangement between the Soviets and the U.S. during the Cold War. Russian and American scientists, along with epidemiologists from around the world, toiled side by side, chased variola all over the developing world, and won.

For most of the world, it was possible to stop transmission by simply vaccinating everyone in sight. An elaborate intelligence network was set up to find where the virus was: Rewards were offered to people who reported a case, and teams of investigators and vaccinators would swarm into the area showing pictures of smallpox victims and asking if people had seen someone like that.

But when epidemiologists thought they had variola cornered someplace in a developing nation, it would pop up someplace else. Then in 1966, a medical missionary in Nigeria, Edward Foege, and colleagues at the agency now known as the Centers for Disease Control and Prevention, found the winning strategy.

Foege and his team discovered that if you can spot outbreaks of smallpox quickly, ideally when only one person in an area is sick, all you need to do is vaccinate people in the immediate area and track contacts to interrupt transmission. Mass vaccinations were unnecessary.

That's what they did in Merca, and except for two laboratory accidents in England that killed three people, Maow was the last human to catch smallpox. Ever.

Lessons for coronavirus

COVID-19 is very different from smallpox. It seems to be more infectious and harder to track. But one thing remains true of both diseases: You have to know where the cases are before you can contain the spread and that requires testing.

"We don't know how many people in the United States or around the world are infected," said Tan. "It is really a key piece of data that we need to know."

Without a vaccine or reliable visible signs like the smallpox pustules, it probably won't be possible to completely eradicate COVID-19 anytime soon. But with more widespread testing, we may have a chance of keeping it under control.

With the testing, epidemiologists would use the same type of contact tracing the smallpox field workers did. This would tell researchers who needs to be quarantined, as well as which techniques work and which do not, said Gronvall.

It would be impossible to test all 330 million Americans, noted Tan. But the numbers from a good testing program could determine where resources should go as the virus spreads, and they could help officials decide how and when to ease social distancing restrictions.

"There has to be widespread available and accessible testing, including in many areas of the country where there is health disparity, including rural areas and areas with lower socioeconomic conditions," she said.

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