COVID-19 is still the virus of the moment, but the emergence of a much older and more deadly virus is said to lurk just over the horizon.
This premonition comes from Microsoft founder turned vaccine-focused philanthropist Bill Gates. In a recent interview with Policy Exchange, Gates warned governments to prepare for bioterrorist attacks using smallpox. He urged the United States, the UK, and other nations to immediately begin investing billions in research and development to counter the impending threat.
“You say, OK, what if a bioterrorist brought smallpox to 10 airports? You know, how would the world respond to that? There are naturally caused epidemics and bioterrorism-caused epidemics that could even be way worse than what we experienced today,” Gates said.
Gates’s preparedness plan envisions governments pouring money into a new World Health Organization (WHO) Pandemic Task Force to address this deadly scenario predicted to besiege humanity in the near future. Just days after Gates’s announcement, vials labeled “smallpox” were found in a Merck laboratory in suburban Philadelphia.
The world is still struggling to recover from the economic devastation and death toll brought by COVID-19. So why smallpox and why now?
Smallpox is a contagious disease caused by the variola virus, with a reputation of being one of the most devastating diseases known to mankind. Symptoms include fever, severe fatigue, pain, and sometimes blindness. But the most characteristic sign is the red spots that sprout all over the body. The spots turn into fluid-filled blisters, which later develop into deep, pitted scars or pox marks. The disease has an infection record stretching back at least 3,000 years. And while most survived smallpox, it also claimed numerous lives.
In terms of modern health threats, however, smallpox is practically a forgotten relic. Although the disease is said to have killed 300 million in the 20th century alone, by the end of the century, it virtually disappeared.
Older generations may still sport a small scar on their shoulder—the unique signature of the smallpox vaccine—but immunization programs for this disease faded in the 1970s. By 1979, member states of the World Health Assembly declared the disease eradicated, and health experts concluded that the serious complications that the vaccine is known to cause outweighed the benefits in the absence of an actual outbreak.
According to the WHO, smallpox is the only disease ever to be declared eradicated, citing the accomplishment “among the most notable and profound public health successes in history.”
But ever since the disease made its exit, experts have feared that it would one day return, not as a force of nature, but as a weapon. Although the variola virus has appeared to have vanished in the wild, samples are kept in two labs, one at the State Research Center of Virology and Biotechnology in Koltsovo, Russia, and another at the Centers for Disease Control and Prevention (CDC) in Atlanta. The samples are kept for study, but the concern is they might fall into the wrong hands.
Twenty years before Gates made his prediction, the Center for Strategic and International Studies and the Johns Hopkins Center for Civilian Biodefense Studies hosted an exercise known as Operation Dark Winter. The exercise was aimed at examining how officials might address the challenges posed by a weaponized smallpox attack on America.
The worrisome conclusions drawn from the Dark Winter exercise prompted a renewed interest in a smallpox vaccination program, at least briefly. Given that it had been decades since this vaccine had been administered to the public, it presumably left millions of Americans vulnerable to an attack. And experts argued that reviving the vaccine could effectively protect the population.
A report from the Johns Hopkins Center for Health Security outlines the findings from the Dark Winter exercise. It explores the issues related to any biological attack—the threat of national security interests, the massive civilian casualties, the breakdown of essential institutions, civil disorder, loss of confidence in government, and reduced U.S. strategic flexibility abroad—but it also covered the concerns specific to a smallpox outbreak.
“Smallpox, because of its high case-fatality rates and transmissibility, represents one of the most serious biological warfare threats to the civilian population,” the report states. “Aerosol release of smallpox virus disseminated among a relatively small population could result in a significant epidemic. Evidence suggests the infectious dose is very small.”
We typically think of biological warfare as a relatively recent development, but smallpox was imagined as a weapon in the past. For example, during the French and Indian War (1754–1763), British general Lord Jeffrey Amherst wrote letters in which he proposed wiping out Native American enemies by offering them smallpox-infected blankets.
Historians dispute whether the plan was ever implemented, and if it was, question if it even worked. What is clear is that many Native Americans were killed by smallpox when Europeans arrived in the New World. With no immunity to Old World diseases, several tribes were decimated with exposure.
The Search for Risk-Free Immunity
For centuries, people observed that those who survived smallpox were rewarded with a special ability: immunity. This meant that if you got sick from it once and recovered, the disease couldn’t touch you again. In the past, various methods were employed to take advantage of this ability, while minimizing the threat. Throughout Asia and Africa, people discovered a procedure that involved smearing some smallpox pus or powdered scabs into a fresh scrape on the skin. Ideally, the process would produce mild symptoms and smallpox immunity, but it could also be fatal and cause outbreaks.
In England, a notable variation on this procedure led to the invention of the first vaccine. According to legend, an orphan boy heard a milkmaid proclaim that her complexion would never be blemished by smallpox marks because of her exposure to the bovine variety of the disease, known as cowpox. That orphan grew up to become a country surgeon named Edward Jenner who was eager to test the milkmaid’s claim. In 1796, Jenner exposed a young boy to a cowpox lesion in hopes of stimulating smallpox immunity and his experiment proved a success. Jenner named his new invention a vaccine after the Latin word for cow: vacca.
This invention is often credited with the eradication of smallpox, but some suggest that improvements in hygiene and nutrition may have played an even greater role in ending the scourge. Whatever the case, even the most ardent fans of the smallpox vaccine admit the treatment comes with significant risk. One big reason the world didn’t embrace a renewed vaccination program following the Dark Winter exercise was all the complications associated with the treatment, including serious infections of the brain and heart.
These problems are detailed in a 2003 article in the journal, Clinical Medicine and Research, titled “Smallpox Vaccine: The Good, The Bad, and The Ugly.”
“Current evidence suggests net harm would result if smallpox vaccine were made available to the general public on a voluntary basis. Such a policy would pose a risk to both the vaccinees and their close contacts (who presumably have not consented to vaccinia exposure) with little or no benefit under many attack scenarios. If this complex public health decision is delegated to individual citizens, some individuals will be unable to weigh the risks and benefits for true informed consent,” the article states.
Treatments Old and New
So what if a smallpox attack really does break out in the next few years? Another weak spot in our protection from an attack is that there hasn’t been a recognized treatment for it.
Drugmakers, however, are already gearing up to fill the gap just in case.
In 2018, the U.S. Food and Drug Administration (FDA) approved the first drug to treat smallpox, named tecovirimat. In June 2021, the FDA approved another drug to treat the disease named brincidofovir. Both drugs were approved under the FDA’s animal rule. Because of the ethical issues associated with infecting human subjects with smallpox to test the drugs, only animal trials were used to assess safety and effectiveness.
Another smallpox remedy not approved by the FDA comes from Native American medicine of the 1800s. The Micmac tribe of Nova Scotia in particular treated smallpox infections with a carnivorous pitcher plant known as Sarracenia pupurea. Herbert Miles, the assistant surgeon to the Royal Artillery, reported that during an outbreak, an old Indian woman treated the tribe with Sarracenia and “was so successful as to cure every case.”
In 1892, American botanist Charles Millspaugh described Sarracenia as “the greatest remedy known for the dreadful scourge.”
The remedy went largely forgotten for the next century. But in 2012, researchers at Arizona State University took a fresh look at the old remedy and conducted in vitro experiments with a Sarracenia extract. They found that it inhibited the replication of the variola virus.
The study, published in the journal PLOS ONE, concluded that Sarracenia was “the first effective inhibitor of poxvirus replication at the level of early viral transcription.”