Found: Forgotten Vials of Smallpox

Headline-making news today from the Centers for Disease Control and Prevention: Workers clearing out an old storage room on the Bethesda, Md. campus of the National Institutes of Health have found a forgotten box of vials that contain smallpox.

Yes, smallpox. The "most terrible of all the ministers of death," as Thomas Babington Macaulay called it in his 1848 History of England -- a disease that was the world's most dreadful killer, until it was declared eradicated in 1980. A disease caused by a virus that now is supposed to reside in only two highly secure laboratories on the planet, in Russia, and at the CDC.

Smallpox is the only human disease ever successfully eradicated -- pursued to elimination by a relentless dragnet that closed nooses of vaccination around every identified case. After the last natural infection, in Somalia in 1977, the World Health Organization launched a second dragnet, scouring lab freezers and storage rooms for any remaining samples of the virus, and consolidating them in Siberia and Atlanta.

Somehow, these six tubes of freeze-dried virus evaded the search. They were found in the storage room of a lab that now belongs to the Food and Drug Administration but was ceded to that agency by NIH in 1972. They may date back to the 1950s.

The vials were found July 1 and escorted to Atlanta by law enforcement last night. Here's the CDC's statement:

On July 1, 2014, the National Institutes of Health (NIH) notified the appropriate regulatory agency, the Division of Select Agents and Toxins (DSAT) of the Centers for Disease Control and Prevention (CDC), that employees discovered vials labeled "variola," commonly known as smallpox, in an unused portion of a storage room in a Food and Drug Administration (FDA) laboratory located on the NIH Bethesda campus.

The laboratory was among those transferred from NIH to FDA in 1972, along with the responsibility for regulating biologic products. The FDA has operated laboratories located on the NIH campus since that time. Scientists discovered the vials while preparing for the laboratory’s move to the FDA’s main campus.

The vials appear to date from the 1950s. Upon discovery, the vials were immediately secured in a CDC-registered select agent containment laboratory in Bethesda.

There is no evidence that any of the vials labeled variola has been breached, and onsite biosafety personnel have not identified any infectious exposure risk to lab workers or the public.

Late on July 7, the vials were transported safely and securely with the assistance of federal and local law enforcement agencies to CDC’s high-containment facility in Atlanta. Overnight PCR testing done by CDC in the BSL-4 lab confirmed the presence of variola virus DNA. Additional testing of the variola samples is under way to determine if the material in the vials is viable (i.e., can grow in tissue culture). This testing could take up to 2 weeks. After completion of this testing, the samples will be destroyed.

By international agreement, there are two official World Health Organization (WHO)-designated repositories for smallpox: CDC in Atlanta, Georgia and the State Research Centre of Virology and Biotechnology (VECTOR) in Novosibirsk, Russia. The WHO oversees the inspection of these smallpox facilities and conducts periodic reviews to certify the repositories for safety and security.

CDC has notified WHO about the discovery, and WHO has been invited to participate in the investigation. If viable smallpox is present, WHO will be invited to witness the destruction of these smallpox materials, as has been the precedent for other cases where smallpox samples have been found outside of the two official repositories.

DSAT, in collaboration with the Federal Bureau of Investigation, is actively investigating the history of how these samples were originally prepared and subsequently stored in the FDA laboratory.

So, on the one hand, the incident may have been over almost as soon as it began. Yet on the other hand, that these vials went overlooked for so long raises unsettling questions about something that has long worried smallpox experts: just how much might be out there.

The infectious basics, first: There hasn't been a case of smallpox in the world since 1978 (the very last case, in England, was due to a lab error) or in the United States since 1949. The US ceased vaccinating most of the population in 1972, because the vaccine had rare but very serious side effects that ceased to be worth the risk once the disease had fled. The US military continued to receive the vaccine until the 1980s. From 2002 to 2004, military members and some civilian health-care workers received the vaccine again, as protection against a possible bioterrorist attack. (That decision turned out to be based on the same bad intelligence that underpinned the decision to go to war in Iraq. The history of the vaccination program is recounted in this 2005 National Academies report.) The point, though is that except for participants in that 2002-2004 program, anyone born in the US after 1972 is not immune to smallpox. (Update: In the comments, military members say the vaccination program is continuing. Thanks for that; the National Academies report makes it sound as though the program ended in 2004 and I couldn't find any documentation otherwise.)

Is that a problem? That leads into the second question: whether the virus in the vials is viable. Absent the results of the lab work now being conducted at the CDC, federal officials seems to be disagreeing: according to the Associated Press, the CDC believes the virus may have been held at room temperature, possibly inactivating it, while the FDA thinks it may have been chilled and therefore could have survived. A prescient Nature News story last April, written by Sara Reardon, recounted CDC attempts to find smallpox virus in corpses and mummies. All thus far have been non-viable because of the temperature and conditions the bodies lay in -- but scientists keep raising the possibility that, as the world warms, permafrost graves may yield intact virus.

The final question, which can't yet be answered, is how this discovery affects the never-solved debate over whether to destroy the last two known stocks of virus. The World Health Assembly has considered the question six times without ever resolving it, most recently in its annual meeting last May (recounted by Declan Butler at Nature). One long-standing contention has been that the live-virus stocks are needed to conduct research, not just into what made smallpox so deadly, but also for a new and better vaccine if smallpox were ever released into the world again.

Following the World Trade Center and anthrax attacks in 2001, the main concern was that a smallpox release would come as a bioterrorist attack from a rogue state possessing an undisclosed viral stockpile. What today's news underlines, though, is that there may be innocent, forgotten "stockpiles" of the virus still in the world. In fact, according to the 2003 book Smallpox by David Koplow, neglected samples of variola have been found in lab freezers three times before. Its being found one more time -- and, of all places, inside an agency of one of the governments tasked with guarding it -- seems to make it less likely than ever that smallpox will meet its final death soon.