The Synthesis of Horsepox Virus and the Failure of Dual-Use Research Oversight

On January 19, 2018, the open access scientific journal PLOS One published an article that describes the de novo synthesis of horsepox virus, the first ever synthesis of a member of the orthopoxvirus family of viruses that includes the variola virus that causes smallpox. As I have written about before, this research crosses a red line in the field of biosecurity. Given the high degree of homology between orthopoxviruses, the techniques described in this article are directly applicable to the recreation of variola virus. The synthesis of horsepox virus takes the world one step closer to the reemergence of smallpox as a threat to global health security. That threat has been held at bay for the past 40 years by the extreme difficulty of obtaining variola virus which has been eradicated from nature and is only known to exist in two WHO-designated repositories.

The reemergence of smallpox would be a global health disaster.  Prior to its eradication, smallpox killed an estimated 300 million people, more people than all the wars of the 20th century combined. Most of the world’s population is susceptible to this lethal and contagious disease since routine immunization against smallpox was discontinued after the success of the WHO’s global eradication campaign.

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Trends in Global Health Security (June 17, 2015)

Recent events in Africa, Asia, and the United States have reaffirmed the significant enduring challenges to strengthening global health security.

While Liberia has not reported any Ebola cases since April 2015, Guinea and Sierra Leone continue to report approximately 20-30 new cases a week. Most of these new cases can be traced to previous cases along well-characterized chains of transmission, but a worrying number of them arose from unknown sources of infection and/or were associated with a large number of high-risk contacts. The emergence of Ebola cases of unknown origin in Guinea and Sierra Leone emphasizes the need for stronger surveillance and contact-tracing efforts in those countries and highlights the risk that the outbreak could spread uncontrollably again if containment measures are relaxed. The development of an Ebola vaccine continues apace, with three vaccine candidates entering Phase III clinical trials in West Africa. Vaccine testing hit a setback in Ghana, however, where the parliament suspended a planned trial of two vaccines after local protests.

South Korea has become the epicenter for the largest outbreak of MERS-CoV outside of the Middle East. South Korea now reports 161 cases and 19 deaths from the virus. The outbreak has been traced to a single infected traveler who returned to South Korea in May after visiting several Persian Gulf countries, highlighting the vulnerability of all countries in this globalized world to unexpected outbreaks of unusual diseases. According to the World Health Organization (WHO), gene sequencing does not reveal any significant differences between the strain responsible for the outbreak in South Korea and strains circulating in the Middle East. Transmission of the virus in South Korea, as in other hard-hit Middle East countries like Saudi Arabia, has been strongly associated with health care settings. So far, there is no evidence of sustained community transmission. A joint South Korean-WHO inquiry identified several reasons for the severity of the outbreak in South Korea including a lack of awareness among health care workers and the general public about MERS; weak infection prevention and control measures in hospitals; close and prolonged contact of infected MERS patients in crowded emergency rooms and multi-bed rooms in hospitals; the practice of “doctor shopping” (seeking care at multiple hospitals); and the custom of many visitors or family members staying with infected patients in the hospital rooms which facilitated the secondary spread of infections among contacts. An interesting parallel between the Ebola outbreak in West Africa and MERS in South Korea is the role of social practices and customs that amplify disease transmission. On June 17, WHO reaffirmed that the MERS-CoV outbreak, which has caused at least 1,320 infections and 466 deaths since 2012, still does not qualify as a public health emergency of international concern under the 2005 International Health Regulations.

The inadvertent shipping of live anthrax spores by the Department of Defense’s Dugway Proving Ground has expanded to 69 labs in 19 states and the District of Columbia and five foreign countries (Australia, Canada, Japan, South Korea, and the United Kingdom). The list of foreign countries that may have accidentally received samples of live anthrax may grow since the such samples might have been sent to U.S. bases in the Persian Gulf for proficiency testing of biodetection systems deployed in that region. The Pentagon’s inquiry into what human, technical, and/or procedural errors led to this long-standing unsafe handling and shipping of anthrax is due to be completed by early July. The Centers for Disease Control and Prevention (CDC) is conducting its own investigation, but there is no word on when it will be completed. In the meantime, USA Today has reported that Dugway was cited in 2007 for shipping live anthrax spores after using an unproven chemical inactivation method and ignoring results from sterility testing that showed that some of the samples still contained live bacteria. While the current inactivation technique used at Dugway is irradiation, this previous incident might reflect the lack of a strong safety culture at the facility which may have contributed to the current biosafety failure. Dugway’s biosafety problems are also similar to problems encountered by the CDC in 2004 and 2014 when it also failed to improperly inactivate anthrax and inadvertently shipped live samples of the bacteria to other labs. This recurring pattern of anthrax being inactivated improperly and not detected by post-inactivation testing raises serious questions about the scientific and technical foundations for this process.

A common theme throughout these outbreaks and incidents is the need for the scientific, public health, academic, private sector, and policy communities to work together to devise solutions to the most pressing problems in global health security.  Pandemics, Bioterrorism, and International Security is a three-day non-credit course offered by George Mason University that introduces participants to the challenges facing the world at the intersection of national security, the life sciences and public health. This course provides participants with an opportunity to learn about cutting-edge issues in global health security from a Special Agent in the FBI’s Weapons of Mass Destruction Directorate, the former commander of USAMRIID, the lead virologist and Ebola expert at NIH’s BSL-4 laboratory, and internationally recognized biosecurity experts from MIT, Dartmouth, and George Mason University. For more information and to register, please visit

ISIS and Chemical Weapons

The Washington Post has reported that ISIS used an improvised chemical weapon containing chlorine to attack an Iraqi police patrol in Balad, north of Baghdad, in September, injuring 11 officers. Chlorine is readily available in Iraq given its widespread use for water treatment.

The good news is that ISIS’s use of chlorine indicates that it has not gained access to more toxic agents located at Muthanna, Iraq’s former chemical weapon production complex, which the group seized in June. That complex contains two bunkers with abandoned and degraded chemical agents and munitions that were sealed shut with concrete by UNSCOM almost twenty years ago. Breaching the bunkers to obtain the material inside would be extremely hazardous and would not likely yield readily usable agent or munitions given their age and storage conditions.

The bad news is that this attack is probably only the beginning. ISIS is the latest incarnation of the group Al-Qaeda in Iraq (AQI) which has had a long-standing interest in chemical weapons. AQI conducted a string of attacks in 2006 and 2007 that combined chlorine gas tanks and improvised explosive devices (IEDs). Due to the poor design of these improvised chemical weapons, most of the casualties were caused by the explosive component of the bomb, not the chlorine. AQI stopped using chlorine-laced IEDs due to their perceived ineffectiveness and a concerted effort by US intelligence and military forces to break up the network that had been constructing the weapons. ISIS, like AQI, has demonstrated a willingness to engage in extreme levels of violence, such as beheading captured fighters and civilians and conducting mass casualty attacks. The use of chlorine or other chemicals by ISIS fits this pattern of escalating violence and violation of norms to maximize the shock value of their actions.

Given the large swath of Syrian and Iraqi territory that ISIS now controls, the inability of local forces to launch offensive operations against ISIS, and the unwillingness of the Obama Administration to deploy even small numbers of U.S. soldiers in a combat role in Iraq, ISIS will likely be able to continue carrying out such attacks if they desire. Hopefully they will not learn any lessons from AQI’s previous experiments with this form of chemical terrorism.

Is the NSABB Still Relevant to Today’s Biosecurity Challenges?

The National Science Advisory Board for Biosecurity (NSABB), the independent advisory group for biosecurity and dual-use research, is changing but not for the better. Science magazine is reporting that half of the group’s members are being replaced. Despite continuing uncertainty about the wisdom of certain types of “gain of function” research with influenza that generates novel strains of the virus, the board is set to lose some of its most experienced members.

Not that it really matters. The NSABB was effectively sidelined following the 2012 controversy over experiments that enabled H5N1 to be transmitted between mammals. Although the group’s charter calls for it to meet twice a year, it hasn’t met since November 2012. The National Institutes of Health (NIH), which runs NSABB, is now scheduling a one-day meeting for the fall. Since part of that meeting will be devoted to honoring the service of the members rotating off the board, don’t expect it to delve into substantive issues such as how well the dual-use research guidelines that NIH published in March 2012 are working, how much “gain of function” research with influenza is occurring in the US and abroad, or how developments in desktop gene synthesis will affect biosecurity.

Even if the NSABB did have regular meetings, it has been stripped of its ability to review dual-use research of concern like the H5N1 transmission experiments. In a little-noticed maneuver, NIH removed a key provision from the NSABB’s charter in April 2012 after its review of the H5N1 research had landed the NIH in hot water (NIH had funded the research without recognizing its dual-use implications) . Prior to 2012, the NSABB’s list of responsibilities included “Review and provide guidance on specific experiments insofar as they exemplify a significant or particularly complex permutation of an existing category of dual use research, or represent a novel category of dual use research that requires additional guidance from the NSABB.” After the H5N1 controversy highlighted the bureaucratic and political risks of having independent experts review dual-use research of concern, NIH got rid of NSABB’s ability to exercise this oversight function.

As the CDC’s mishandling of anthrax and H5N1 and the discovery of live smallpox in an old FDA lab on the NIH campus in Bethesda demonstrate, scientists are human too: they make mistakes. But when these mistakes have the potential to cause outbreaks or even pandemics, there need to be safeguards to ensure that the appropriate biosafety and biosecurity measures are in place. NSABB is not a silver bullet solution to these problems but without oversight of the kind provided by NSABB, the risks posed by bioerrors will only grow.

The Elimination of Syria’s Chemical Weapons: Beginning of the End or End of the Beginning?

Ahmet Üzümcü, Director-General of the OPCW, has announced that the last shipment of chemical warfare agent precursors has been loaded onto the Danish ship Ark Futura at the Syrian port of Latakia. Syria is now officially free of chemical weapons.

The OPCW deserves a lot of credit (and yes, the Nobel Peace Prize) for its Herculean efforts to disarm Syria of its chemical weapons in the middle of a civil war. While this final shipment closes a chapter on the elimination of Syria’s chemical weapons program, it does not mean the story is over. Here are five things to keep in mind before we break out the “Mission Accomplished” banner.

First, Syria should have completed this final shipment over four months ago. The OPCW’s original deadline for removing all chemicals from Syria was February 5, The delay was due to the civil war, Syria’s use of the stockpiles as a bargaining chip, and domestic politics (Syria stopped making shipments during the Syrian presidential election).

Second, the process of actually destroying these chemicals, which is supposed to be completed by June 30, has only just begun. The most dangerous chemicals, including mustard agent and sarin precursors, will be destroyed on board the MV Cape Ray. It is estimated it will take the Cape Ray between 60 and 90 days to complete its mission but since this is an unprecedented at-sea chemical destruction process, the process could take even longer depending on the weather and unforeseen technical issues.

Third, the OPCW has only eliminated Syria’s declared stocks of chemical agents. During April and May 2014, rebels reported over a dozen attacks by government forces with air-dropped barrel bombs filled with chlorine. Although chlorine is not one of the chemicals that Syria was required to declare, the use of any chemical as a weapon is outlawed by the Chemical Weapons Convention. Just last week an OPCW fact-finding mission found that “toxic chemicals, most likely pulmonary irritating agents such as chlorine, have been used in a systematic manner in a number of attacks.”

Fourth, Syria has still not destroyed 12 chemical weapon production facilities located in aircraft hangars and in underground tunnels. Syria was supposed to have destroyed these facilities over three months ago but has been dragging its feet while insisting on the right to disable, instead of demolish, the facilities.

Fifth, serious questions are starting to emerge about “gaps and inconsistencies” in Syria’s declaration of its chemical weapon program to the OPCW. Syria’s repeated delays in removing its chemical stockpile, refusal to destroy chemical weapon production facilities, and continued use of chemical weapons does not inspire confidence that it is in compliance with other aspects of the CWC. Now that the last of the declared chemicals are out of Syria, the OPCW will have more time and energy to devote to verifying the accuracy and completeness of Syria’s declared chemical weapon research, development, testing, production, and storage. Priority should be given to the 200 tons of mustard agent that Syria reportedly destroyed unilaterally before joining the CWC, Syria’s possession of the Volcano rocket which has been implicated in the August 2013 sarin attack, and Syria’s use of chlorine-filled barrel bombs.

To paraphrase Winston Churchill, this is not the beginning of the end of efforts to eliminate Syria’s chemical weapons, but the end of the beginning.

Syria and Chemical Weapons: Unfinished Business

Syrians go to the polls today for a presidential “election” in the midst of a civil war that has killed an estimated 150,000 people, displaced 6 million internally, and generated 3 million refugees. President Bashar al-Assad, who has ruled Syria since 2000, is expected to win handily over the two virtually unknown candidates running against him. The election is not expected to contribute to an end to the violence in Syria, but might actually make the fighting worse as the government and the rebels both dig in their heels. Oddly enough, the only winner on election night (aside from Assad himself) might be the international effort to eliminate Syria’s chemical weapons. Syria’s remaining chemical weapons have been held hostage for the last month by Syrian domestic politics. Once Assad is re-elected for his third seven-year term, he may feel secure enough to implement the final stages of Syria’s chemical disarmament.

Since announcing its intent on April 21 to hold presidential elections, Syria has largely suspended its efforts to implement a plan brokered by the United States and Russian and overseen by the Organization for the Prohibition of Chemical Weapons (OPCW), the international organization charged with implementing the Chemical Weapons Convention (CWC), to get rid of its chemical weapons. Under the plan, Syria agreed to either destroy or transfer to international custody its stockpile of 1,300 tons of chemical warfare agents and precursors. Since January, Syria has been slowly shipping chemicals to the port of Latakia where they are loaded onto Norwegian and Danish ships for eventual transport to destruction sites in Europe and a US ship equipped with a sophisticated chemical destruction system.

The deadline for Syria to remove the last of its chemicals expired on April 27 with 8% of its stockpile, approximately 100 tons of nerve agent precursors and other chemicals, still inside of the country. The most recent shipment of chemicals out of Syria occurred on April 24. The remaining chemicals are believed to be located at a military airbase east of Damascus in an area that has been the scene of heavy fighting lately between the government and rebel forces. On April 28, the Syrian government informed the OPCW that it was no longer able to access this last chemical weapon storage facility by road due to the fighting. That same day, President Assad announced that he was entering the presidential race and the campaign swung into high gear in areas loyal to the regime.

Although the outcome of the election is not in doubt, the government has used the past month and a half to bolster its support among groups in the country that remain loyal to the regime. What matters to Assad is not how “free and fair” the international community views the election, but how effectively it consolidates his power and reinforces his legitimacy among the elites and masses who make up his base. The regime will no doubt manipulate the results of the election to try to send a signal to the opposition that Assad’s hold on power remains strong and that he retains the ability to prosecute his war against so-called “terrorists” with unrelenting vigor.

So why do I think the Syrian presidential election will affect the level of Syria’s cooperation with the OPCW? If Syria shipped the last 100 tons of its chemicals out of the country during the middle of the election, it would have provided the United States and its allies with a much-needed victory to trumpet. Given the sad lack of progress on any other aspect of the Syrian conflict, the United States and its allies would have trumpeted this achievement quite loudly. At the same time, this milestone in the elimination of Syria’s chemical weapons would have reminded Syrians that they were forfeiting a major pillar of their national security and that Assad agreed to the deal out of fear of American airstrikes. All of this risked undermining the narrative that the regime has been trying to cultivate that Assad is the only leader strong enough to keep Syria together, fight the “terrorists,”  and resist foreign intervention. Even dictators understand the importance of “staying on message” during an election, no matter how rigged it is. Once the election is over, the United States and its allies need to increase the pressure on Syria to complete the unfinished business of destroying its chemical weapons program.

Ebola Infection: Same Disease, New Name

If you have been reading about the latest emergence of Ebola virus infection in Africa that has so far claimed over 140 lives you might have noticed something unusual. I’m not talking about the fact that the outbreak is occurring in Western Africa, a region that has not previously seen human cases of this disease. And I’m not talking about the fact that at least 50 cases have occurred in Conakry, the densely populated capital of Guinea.

The current outbreak in Western Africa marks the public debut of a “new” name for one of mankind’s most dreaded diseases. Goodbye, Ebola hemorrhagic fever. Hello, Ebola virus disease. For those of you with fond memories of Richard Preston books or Dustin Hoffman movies featuring horrific scenes of Ebola victims “bleeding out,” dropping hemorrhagic from the name of this virus may seem blasphemous.

In all seriousness, this change was a long time in coming. The media-fueled perception that Ebola virus infection invariably causes massive internal bleeding is inaccurate. Indeed, the entire class of viral hemorrhagic fevers, which have dramatically different epidemiological profiles and fatality rates and include everything from Ebola to Rift Valley fever to Lassa fever, makes little medical or scientific sense. For several years, the World Health Organization (WHO)’s International Classification of Diseases 10 (ICD-10), the international standard diagnostic tool for epidemiology, public health, and clinical purposes, has listed the disease caused by Ebola as Ebola virus disease. In a post on ProMED, virologist Dr. Jens Kuhn, author of Filoviruses: A Compendium of 40 Years of Epidemiological, Clinical, and Laboratory Studies (or as I like to call it Everything You Ever Wanted to Know About Ebola and Marburg But Were Afraid to Ask) wrote, “EHF [Ebola hemorrhagic fever] is certainly used a lot in the literature but mainly by people who do not get in touch with patients and simply don’t know any better (i.e. do not have to classify diseases according to existing legal frameworks and therefore don’t know that ICD-10 exists or how important it is). Also, the term “hemorrhagic fever” is always problematic, as its definition has not been updated since the 1960s and early 1970s (Gajdusek, Smorodintsev). Everybody seems to know what a viral hemorrhagic fever is, until you ask them and push for an answer.”

Despite having written the book on how to diagnose diseases, as late as 2012 WHO publicly referred to outbreaks of Ebola virus infections in Uganda as causing Ebola hemorrhagic fever. The current outbreak of Ebola virus in West Africa, which began in March 2014, is the first time that WHO has publicly referred to the disease as Ebola virus disease (EVD). While this name change unfortunately does not leave us any closer to a cure or treatment of this disease perhaps it marks one small step in controlling the fear and anxiety that seems to spread faster than the virus itself.

International Cooperation to Eliminate Syria’s Chemical Weapons

While the delays in Syria’s transfer of chemical agents has received significant media attention lately, less attention has been paid to the impressive international coalition that has been assembled to remove and destroy these chemicals. Although the original agreement for Syria to join the Chemical Weapons Convention (CWC) and destroy its chemical weapons was the result of U.S.-Russian diplomacy, implementing this agreement has become a truly international initiative. Within only a few months, the international community devised a plan to eliminate Syria’s chemical weapons program and put in place the resources necessary to achieve this objective.

The extent to which Syria’s chemical disarmament has been internationalized is reflected in a recent fact sheet published by the Organization for the Prohibition of Chemical Weapons (OPCW), the international organization charged with implementing the CWC and destroying Syria’s chemical weapons. The fact sheet provides details on the financial and in-kind contributions made by states to the organization’s program to eliminate Syria’s chemical weapons. While the OPCW received approximately $1.2 million when it won the 2013 Nobel Peace Prize, this amount is only a fraction of the expected cost of destroying Syria’s stockpile of 1,390 tons of chemical weapons. So far, twenty-six countries have pledged or contributed more than $86 million to support this effort. Fifteen nations have also provided in-kind assistance to the United Nations or to Syria to facilitate Syria’s chemical disarmament. Granted, the provision of field kitchens by Belarus and ambulances by China might sound mundane, but in war-torn Syria such resources are in short supply.

An international flotilla of ships from six nations has assembled in the Mediterranean to support the removal and destruction of Syria’s chemical arsenal. So far, the Dutch and Norwegian cargo ships Ark Futura and Taiko have picked up three loads of chemicals from the Syrian port of Latakia, comprising about 11% of the Syrian stockpile. The centerpiece of this maritime “coalition of the willing” is the U.S.-supplied MV Cape May which will use a Field Deployable Hydrolysis System to destroy 560 tons of Syrian chemicals at sea. Italy has offered the use of the port of Gioia Tauro for the transfer of chemicals from the Dutch and Norwegian cargo ships to the Cape May. Warships from China, Denmark, Norway, Russia, the United Kingdom and the United States will protect these vessels during the removal and destruction process.

In addition to this at-sea destruction, the United Kingdom has agreed to destroy 150 tons of chemical weapon precursors at a commercial facility and a state-owned enterprise in Germany will dispose of the waste generated by the destruction of the chemical warfare agent mustard. On February 14, the OPCW awarded contracts to private firms in Finland and the United States to destroy and dispose of the remainder of Syria’s chemical stockpile.

Thanks to the efforts of the United Nations and OPCW, supported by the financial and material contributions of thirty nations, there is now a comprehensive system in place to safely and securely remove and destroy Syria’s stockpile of chemical agents. Syria has already missed two deadlines for getting rid of its stockpile. The time for delay is over. The international community has done its part. Now it is up to Syria to deliver on its promise of chemical disarmament.