Article: B. Kadlec

Smallpox: Gone—But Should Not be Forgotten

Smallpox, a natural occurring disease eradicated from the face of the planet in 1979 was responsible for an estimated
250 million deaths in the 20th Century alone. A highly effective vaccination program organized by the World Health Organization
(WHO) eliminated this disease as a natural threat. Is there a threat remaining?

Health ministers and senior representatives from 193 countries attended the 64th World Health Assembly in Geneva Switzerland in early May 2011. Among the many issues discussed was the fate of the remaining samples of smallpox virus that exist in the two official sanctioned repositories at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia and State Research Center for Virology and Biotechnology in Koltsovo, Russia. Smallpox, a natural occurring disease eradicated from the face of the planet in 1979 was responsible for an estimated 250 million deaths in the 20th Century alone. A highly effective vaccination program organized by the World Health Organization (WHO) eliminated this disease as a natural threat. Why should health ministers spend their valuable time to debate about a disease long gone? 

Simply stated, the highly effective program that eliminated the natural occurring disease did not consider the potential long-term consequences of eradication or ensure that any residual clinical specimens were either turned in or destroyed. It is possible and likely that some countries either knowingly or unknowingly still have the virus. There are additional worries that certain countries deliberately retained the virus for the purpose of biological warfare or bioterrorism. Episodic natural outbreaks of human cases of smallpox-like diseases such as monkeypox and camelpox add additional concern about the potential natural re-emergence of smallpox-like disease.[i],[ii],[iii]

Further complicating the ministers’ deliberations is a growing concern that developments in synthetic biology could permit reconstituting the virus sometime in the future.[iv],[v],[vi] This concern has grown since researchers demonstrated the feasibility of assembling the entire genome recreating the poliovirus and the Spanish influenza virus.[vii],[viii] While it may not be possible today to recreate the smallpox virus, public health officials see the risk increasing over time. In 2008, the WHO Advisory Committee on Variola (Smallpox) Virus Research observed that currently available technology could allow the recreation of the smallpox virus by chemical synthesis.[ix]

As noted by Dr. David Baltimore, 1975 Nobel Prize winner in Physiology or Medicine, viruses “are relatively simple to make and control and some are quite lethal. Smallpox, for example, is very potent, and we are not protected against it. The smallpox sequence is published, so you could recover it by synthesis if you had the lab facilities to do that. But getting the pieces of DNA to make smallpox is not a backyard experiment. You need a large lab with significant biosafety precautions. I don't see this as something that would happen clandestinely in the U.S., but a well-funded lab outside of this country could do something quite nefarious.” [x]

It would seem that issues surrounding these recent deliberations should not be so onerous; however, as the means originally used to eradicate smallpox still exist. The smallpox vaccine, called vaccinia, is still available. Though many of the historic stockpiles of this vaccine are aging or expired. It would be logical to produce and stockpile more of the historic vaccine as a hedge against uncertainty. But the vaccinia vaccine is not recommended for use in an increasing percentage of the world population that has underlying immune deficiencies such as HIV and atopic dermatitis.[xi] Even in healthy subjects, there is a risk to individuals receiving the vaccinia vaccine for the first time to experience unpredictable and potentially life threatening side effects.[xii]Further, while vaccinia vaccine is effective preventing the disease if given before exposure or within three days of exposure; it does not treat the disease or mitigate the outcome once smallpox becomes clinically manifest. So while producing more of the "old" vaccine is necessary, it is not sufficient to prepare for the potential of a future smallpox outbreak.

That was why health ministers and representatives attending the World Health Assembly in 1995 first delayed the destruction of the official virus samples. Realizing there were new scientific tools to study the historic smallpox virus, they recognized the opportunity to develop better, safer and more effective vaccines to prevent smallpox and antiviral drugs to treat the disease. For the last 15 years, such research has been conducted under strict safety and security. The findings from this collaborative multinational research were widely available to researchers and have resulted in several new candidate vaccines and antiviral drugs. Now in 2011, the health ministers have once again delayed destruction of the smallpox samples for at least another three years to ensure the necessary safety evaluations and effectiveness testing of these new medical countermeasures can be completed.

The WHO, the U.S. and other countries take this issue seriously. The WHO has established a stockpile of vaccinia vaccine from donor countries to ensure it is available should an outbreak or attack occur. The U.S. decided in 2003 that it would stockpile 300 million doses of vaccine, enough for every American. It also recently began acquiring 20 million doses of newly developed 3rd generation vaccine. Unlike earlier first and second generation vaccines, this 3rd generation is a non-replicating vaccine that could be given to individuals whose pre-existing medical conditions preclude using the “old” vaccine. The U.S. also recently announced the procurement of a smallpox antiviral drug awaiting the Food and Drug Administration (FDA) approval and continues to fund the development of another one. Other countries have followed suit by creating national vaccine stockpiles and other nations are considering doing so.

As the U.S. Secretary of Health and Human Service Kathleen Sebelious said in Geneva on May 17, 2011; “we are committed to the eventual destruction of the virus stocks. But we also believe that this Assembly should authorize continued research to develop the countermeasures needed to ensure that we’re prepared for a potential smallpox outbreak. By retaining stocks of the virus in highly-secured locations, we’ll be able conduct that research, and the results will be made widely available."[xiii]

Health ministers in Geneva strongly reaffirmed the decisions of previous Health Assemblies that the remaining stocks of smallpox virus should be ultimately destroyed;

but agreed to delay doing so until "research outcomes crucial to an improved public-health response to an outbreak so permit."[xiv] Their decision and progress towards more effective medical defenses will be reviewed in another three years. Until then, researchers, health ministers and countries will continue their quest to ensure that smallpox will remain a disease of the past by being prepared for whatever the future may bring.

Date: 05/02/2018

Source: MCIF 4/2011

3rd Annual Operational Medicine Symposium

September 28-29, 2021


The 3rd Annual Operational Medicine Symposium will focus on DoD initiatives to enhance military medicine in an era of great power competition. This symposium will bring together highly regarded medical professionals from all services to discuss the practice of medicine in expeditionary environments.