Fostering an International Culture of Biosafety, Biosecurity, and Responsible Conduct in the Life Sciences

Second-year, GMU biodefense PhD candidate, and intern for the Department of Health and Human Services, Assistant Secretary for Preparedness and Response within the Office of Policy and Planning, Elise Rowe, is taking on the international role of biosafety! As part of the student internship program, all interns are required to work on an independent project and present to ASPR staff upon its completion. Elise will be presenting her project, titled “Fostering an International Culture of Biosafety, Biosecurity, and Responsible Conduct in the Life Sciences,” on Wednesday, April 5th at the Thomas P. O’Neil Jr. Federal Building from 2-3:30 pm.

The abstract for her project is below: Continue reading “Fostering an International Culture of Biosafety, Biosecurity, and Responsible Conduct in the Life Sciences”

ASM Biothreats 2017

screen-shot-2017-02-15-at-9-40-26-amGMU Biodefense sent four graduate students to give you a “boots-on-the-ground” viewpoint for the 2017 ASM Biothreats conference. In our special edition post we have a full range of coverage for this three-day conference on biological threats and safety.

Zach Goble is looking at international collaboration against biological threats and the importance of recognizing foreign organizations for their help in aiding research endeavors. Next, he looks to the symposium on national bioterrorism emergency response. Pointing to the work done by different states and the proposed model by David Ladd, he emphasizes that these are definite steps in the right direction, but will need continued work.

Greg Mercer reviews the panel session “Predicting Emergence by Understanding the Past: Methods that Move Us Towards Predictive Biology“. In his overview of this panel on efforts to get ahead of the evolutionary curve, Greg discusses each speaker and their contributions to the field, as well as where they think the future will take us.

Stephen B. Taylor covers Dr. Fauci’s talk on pandemic preparedness and his experience throughout the years. In this overview, Dr. Fauci points to the unique challenges that followed each health crisis and how certain administrations responded. Stephen also takes us through the melioidosis panel regarding this neglected tropical disease. He notes the high cost of treatment and the inability for most endemic countries to support response and prevention efforts.

HyunJung (Henry) Kim– takes us on a journey through the FDA Animal Rule and its path to success. Henry uses this plenary sessions to discuss the PEP, PrEP, and Passive Transfer aspects of animal modeling.

Predicting Emergence by Understanding the Past: Methods that Move Us towards Predictive Biology

By Greg Mercer

I attended ASM BioThreats 2017’s panel “Predicting Emergence by Understanding the Past: Methods that Move Us towards Predictive Biology,” where a panel of researchers presented their recent efforts to get ahead of the evolutionary curve and anticipate new developments in infectious disease.

Marco Vignuzzi, of the Pasteur Institute, described his efforts to monitor, predict, and target RNA virus evolution. RNA viruses mutate constantly; any response to them must into account incremental changes and variations. Vignuzzi described a large population of many low-frequency mutants as a quasi-species or “cloud.” One can sequence the average genetic profile of this cloud, known as the “consensus sequence.” This population exists across a fitness landscape, ranging from well-adapted to poorly-adapted. The natural evolutionary tendency of a fast-mutating RNA virus is to “climb” this landscape to the highest possible fitness—this is the most successful disease. But Vignuzzi suggests that a virus could be artificially altered to undergo exactly the wrong mutations, making it less fit and causing it to die off. Exactly how to do this remains a mystery, but it’s an exciting possibility.

Barbara Han, of the Cary Institute of Ecosystem Studies, presented her research on machine learning for forecasting zoonotic disease. Han takes a macro-ecological approach to disease, focusing on hosts. Factors like biodiversity and population density affect disease rates, so understanding zoonotic diseases means collecting a great deal of information about the animals that carry them. This information tends to be collected based on specific concerns about animal reservoirs; Han noted that since bats are a suspected reservoir for Ebola and other diseases, there’s been a massive surge in surveillance. It turns out, though, that they carry fewer zoonoses than we might expect. Right now, Han is studying bats to try to identify instances where viruses might spill back into bat reservoirs from human populations, making outbreaks harder to stop. She is also working with data about the health of rodent populations, with the hypothesis that lower biodiversity in a particular area will put humans at a higher risk for a spillover.

David O’Connor, from the University of Wisconsin-Madison, is looking at viruses that aren’t on the radar yet, though maybe they should be. O’Connor examines animal species to find traits that make spillover events likely. Specifically, he presented the theory that simian arteriviruses might be to blame for the mysterious simian hemorrhagic fever. There’s not enough information to know for sure without another outbreak, but O’Connor argues that there is enough information at our disposal to begin to make predictions “to the left of the surveillance curve,” and target surveillance at diseases that aren’t yet a top threat, but could emerge as one.

Melioidosis: Uncovering a Neglected Tropical Disease

By Stephen Taylor

The ASM Biothreats Melioidosis Panel on Tuesday, February 7th, shed light on a largely ignored infectious disease that runs rampant in developing Southeast Asian countries. The speakers, Dr. Direk Limmathurotsakul, the Head of Microbiology at Mahidol-Oxford Tropic Medicine Research Unit, and Dr. Frances Daily, of Diagnostic Microbiology Development Programme, brought a wealth of first-hand knowledge and experience diagnosing and treating this disease in Thailand and Cambodia.

Melioidosis is an infection caused by Burkholderia pseudomallei, a bacterium often found in soil and water.  It is known to cause fever, arthritis, and abscesses of vital organs.  Once inoculated with bacteria, carriers typically experience an incubation period between 1 and 21 days before melioidosis symptoms appear.  Humans acquire B. pseudomallei by inhaling contaminated dust, ingesting contaminated water, or coming into contact with contaminated soil.

In the United States, B. pseudomallei is classified by Health and Human Services and the U.S. Department of Agriculture as a Tier 1 Select Agent, meaning it poses a significant threat to human and animal health and safety and presents a great potential for deliberate misuse.  The Soviet Union and the United States are both believed to have studied B. pseudomallei as a potential biological warfare agent in the 1940s.

In his extensive work caring for patients in northeast Thailand, Dr. Limmathurotsakul documents numerous cases of melioidosis on an annual basis, many of them fatal.  Thailand’s Bureau of Epidemiology, however, only documents about 12 melioidosis deaths per year.  Dr. Limmathurotsakul chalks up the disparity to a poor public health surveillance apparatus and cultural barriers in reporting.  Public health laboratories in Thailand are poorly equipped for diagnostics. Furthermore, physicians in Thailand are not well trained to utilize laboratory diagnoses, nor are they well versed in the transmission and symptoms of melioidosis.  When local health professionals do detect outbreaks of the disease, they are hesitant to report them to the Bureau of Epidemiology for fear of being stigmatized as the only locale to have a significant melioidosis outbreak.

Dr. Daily has encountered similar problems working in Cambodia.  Due to climate change, the rainy season in Cambodia lasts longer every year and with it, the number of melioidosis outbreaks detected by her team also grows.  The Cambodian government, however, is unable to respond effectively to these outbreaks due to a lack of diagnostic capability, patient data, and funding.  Treatment for the infection, which averages a cost of 65 USD, is expensive compared to the Cambodian per capita income of just over 1,100 USD.  Many families struggle to pay for treatment, often going into debt or selling property to afford it.

What can be done to improve detection and treatment of melioidosis?  All of the panel members recommended improving the education and training of the public health and medical workforce.  Knowledge of melioidosis needs to be integrated into training for public health workers in laboratory diagnosis.  Protocols for diagnosis and treatment of melioidosis should be incorporated into medical school curricula.  The speakers also expressed hopes that Thailand and Cambodia would be able to build their capacity to detect and report infectious diseases. Combining his limited data on melioidosis with predictive modeling algorithms, Dr. Limmathurotsakul has estimated that there are 165,000 cases of melioidosis worldwide each year, 89,000 of which result in death.  He hopes the estimates will spur melioidosis researchers worldwide to compile confirmed-case data and paint a more accurate picture.  Then national and international policymakers will have better information to support clinicians and public health officials in their local efforts to fight the disease.

Licensure under the FDA Animal Rule: A Path to Success

By HyunJung (Henry) Kim

Michael Merchlinsky, a subject matter expert from BARDA/CBRN, was the first speaker in this ASM Biothreats 2017 plenary session, overviewing history of the Animal Rule in the US. The Animal Rule is well-known as an innovative policy forming the foundation of U.S. biodefense policies. When no alternatives are available, the Animal Rule provides an investigational mechanism for figuring out “predictive” responses from new medical countermeasures (MCMs) relevant to calculating a dose in humans. Under the Animal Rule, licensure is a legal status awarded by FDA that assures the public that studies to demonstrate safety and efficacy have been performed. According to Merchlinsky’s presentation, it is worthy to note that the Animal Rule was born in the basis of national security purposes, increasingly apparent from Gulf War to 9/11. The primary purpose of the Animal Rule is to increase preparedness and provide means to confidently respond to a public health emergency. Based on the national security perspective at the state-level, Michael Merchlinsky reviews the pros and cons of the Animal Rule. He notes that the Animal Rule is the best course of action for assuring ‘safety’ and ‘efficacy’ where no other alternative is available. Moreover, MCMs under the Animal Rule can attain pre-EUA status during developmental path-MCMs saved in the Strategic National Stockpile (SNS). On the other hand, a critical limitation is that the Animal Rule is inherently longer, harder, and less predictive than traditional pathways.

Next, Dr. Mario Skiadopoulos and Christine Hall represented Emergent BioSolutions and spoke to the regulatory pathway for anthrax and botulism medical countermeasures. BioSolutions applies animal models based on the subject of rabbits as well as non-human primate (NHP) to develop vaccines against anthrax and botulism. It was very interesting to know that there are three types of experiments in animal modeling; Post-Exposure Prophylaxis (PEP), Pre-Exposure Prophylaxis (PrEP) and Passive Transfer. The PEP type demonstrates added value of vaccine over antibiotics alone, in post-exposure settings, whereas the PrEP type established correlation between pre-challenge TNA tilter and probability of survival. The Passive Transfer type demonstrates that neutralizing antibody alone is capable of protection. Compared with the speaker from government sector, speakers from the private sector point to more practical challenges that field researchers are facing under the Animal Rule. They argue that there is no regulatory precedent for licensing a vaccine under the Animal Rule. Technically speaking, it is not clear which time points or which kind of animal models can bridge animal-to-human data. For instance, we have never known which animal model is akin to human trials between rabbits and NHP, as well as which time point is appropriate to apply to humans among the 80%, 90% or 100% survival points from the result of animal models. Consequently, the Animal Rule is essential not only in MCMs development and the realm of national security, but also carries with it many challenges both in government and private sectors. Overall, the inclusion of both government and private sector viewpoints presented the full spectrum of the Animal Rule and its complexities regarding MCM development.

Should I Stay or Should I Go? National Bioterror Emergency Response Preparedness

By Zach Goble

The theme of this ASM Biothreats 2017 symposia was perhaps one of the more noteworthy callings for collaboration among groups. With more than 17 years of experience as the director of Hazardous Materials Emergency Response at the Massachusetts Department of Fire, David Ladd emphasized the need for a unified response when encountering any number of hazards. His slogan during his dialog, “what happens on the left coast, then happens on the right coast”, stressed the importance of initiating and maintaining communication with organizations near and far. No one stays unaffected in the world of today and without the exchange of ideas, experiences, and procedures disasters can have an overwhelming effect.

Rich Ozanich, from Pacific Northwest National Laboratory and Christina Egan, from the NY Dept. of Health, both echoed that close collaboration is a key factor in response. While Rich laid out the Department of Homeland Security’s framework for “The Onion”, which is a set of procedures to guide first responders in the event of a biothreat incident. The emphasis here was that to be successful the training for such events needs to be coordinated at a local, state, and national level.  Christina detailed the many training programs tailored to biological threat response within Emergency Management Departments specific to various states such as Minnesota and Wisconsin. The message here was that while many great programs exist at the state level, there is not a unified national response to confront CBRN threats with the United States.

David Ladd concluded the panel by presenting a proposed model for National Bioterrorism Response that was submitted by the Interagency Board in January, 2017. In the absence of a nationally recognized system for protecting the nation against bioterrorism, the need for such a system is certainly justified. This document provides a model for bringing together various organizations and departments to create a network of local bioterrorism response teams ready to deploy when the need arises. Models such as these represent steps in the right direction to achieving a unified response in ensuring the public remains safe from biological threats.

International Collaborations to Defend against Biological Weapons: The UK/US Experience

By Zach Goble

The second day of the ASM Biothreats 2017 conference focused on a range of topics from synthetic biology to host immune response. Perhaps one of the most interesting was the session on international collaborations to defend against biological weapons. Immediately the conversation began with talk of recognizing foreign organizations for their help in aiding research endeavors or providing resources to further science. Stuart Perkins, from the Defense Science and Technology Laboratory (DSTL) in the United Kingdom, highlighted the importance of shared resources and capabilities when responding to emerging infectious diseases. One organization doesn’t hold all the information, and nor should they, because while one strives for consistency in research methods, it is helpful to have differences to cast a wider net against the many research topics out there.

Lloyd Hough, from the United States Department of Homeland Security, talked about how DSTL helped provided support to their department during the most recent Ebola epidemic. Prior to the Ebola outbreak, DSTL in the United Kingdom had conducted research on how Ebola virus thrived on various surfaces and this inspired new ways forward for the U.S. to aid the countries affected in 2015. When worldly public health events occur it is often unified efforts that bring about successful outcomes.

Andrii Pavlenko, from the State of Service in Ukraine, showed how support from the United States Defense Threat Reduction Agency (DTRA) helped provide equipment and laboratory upgrades to several Ukrainian facilities working with biological pathogens. Not only did these upgrades prevent unauthorized access to potentially dangerous pathogens, but also helped to prevent the spread of emerging infectious diseases. African Swine Flu (ASF), a virus with high mortality rates in pigs and prevalent in Eastern Europe region, was on the rise in Ukraine, but the equipped laboratories helped bolster biosecurity detection and thus prevented the spread of the disease.

The message was very clear that alone, organizations could not effectively deal with biological threats that have no borders and target unremittingly. Thankfully, the gears are already in motion towards international collaboration with the organizations in attendance, among others that exist around the world. The panel left the audience with a strong message in which trust of fellow organizations is needed for it is not always action that is needed, sometimes it is the non-action in letting your partner do the work, so you can tackle another issue. While replication is important, redundancy should be left at the wayside to make room for more knowledge as there is no shortage of scientific questions out there.

Pandemic Preparedness: Learning from Experience

By Stephen B. Taylor

On February 7, 2017, Dr. Anthony Fauci, Director of National Institute of Allergy and Infectious Diseases, National Institutes of Health, gave the keynote speech at the ASM Biothreats 2017 conference. Dr. Fauci has spent over 35 years advocating infectious disease preparedness with United States policymakers. In his speech, Dr. Fauci discussed the substantial progress made in this arena since the 1980s when he first entered the field during the Reagan administration. At the time, there was a lack of appreciation in the U.S. about the potential of the newly emergent Human Immunodeficiency Virus (HIV).  Though Fauci tried to publish some disturbing initial findings about the nascent threat, the medical community rebuffed him for being an alarmist.  As the 1980s progressed, HIV/AIDS spread to epidemic proportions in the U.S.

During George H.W. Bush’s presidency, Dr. Fauci began making headway with national health and policy leaders to take seriously the threat of emerging infectious diseases. President Bush visited Dr. Fauci at NIH for a personal tutorial on HIV and took time to visit with HIV/AIDS patients. After President Bush received Dr. Fauci’s expert counsel and made a personal connection with the HIV/AIDS crisis, public health resources directed at the epidemic increased dramatically.

From the Clinton years onward, Dr. Fauci maintained his connection to lawmakers and executive leadership.  When infectious disease emergencies like West Nile Virus and antibiotic resistance came to a head during the Clinton years, politicians had a stronger relationship with the National Institutes of Health and funding came more quickly.

During George W. Bush’s term, the United States experienced the “double whammy” of 9/11 and Amerithrax.  This was a watershed moment for infectious diseases. For the first time since the early 20th century, it became widely apparent that infectious disease outbreaks posed a major threat to U.S. public health and security.  As the U.S government turned its attention and resources toward developing countermeasures against a bioterror attack, Dr. Fauci urged Washington leaders not to lose sight of the threat posed by natural outbreaks. When the H5N1 bird flu hit in the latter half of Bush’s presidency, the Bush administration worked closely with experts in health security to affect a paradigm shift: instead of reacting to outbreaks as they happen, the U.S. should expend more resources on preparing for future ones.

During Barack Obama’s presidency, emerging and re-emerging infectious disease outbreaks came in rapid succession: the H1N1 flu pandemic in 2009, MERS in 2012, Ebola in 2014, and Zika in 2015.  In close conjunction with experts like Dr. Fauci however, policy-makers have learned important lessons about preparedness, surveillance, capacity building, and coordination in preparation for the next major outbreak. Indeed, even before Inauguration Day this year, the Trump transition team invited Dr. Fauci to the White House for a disaster-response exercise.  As the world grows more interconnected and its climate changes, the threat of emerging infectious diseases looms larger.  U.S. leaders should continue to heed the advice of subject matter experts like Dr. Fauci and work closely with health and defense institutions to prepare for the future.


Sverdlovsk, Three Mile Island, and Government Oversight of Biological Safety

To those of us who follow the world of biodefense, it seems as though every week brings news of a high-profile lapse in biosafety. In just the past month, we’ve seen an employee from the Pasteur Institute Korea transport samples of the coronavirus that causes Middle East respiratory syndrome (MERS) on a commercial airliner and reports that the Centers for Disease Control and Prevention (CDC) shipped chikungunya virus without first performing tests to ensure that the specimens had been completely inactivated. These come on top of such disturbing stories as the US Army’s Dugway Proving Ground accidentally shipping live anthrax to almost 200 facilities and slip-ups at the CDC involving ebolavirus and avian influenza.

While each of these incidents would be alarming in its own right, collectively they imply a systemic failure to properly control biological agents. Determining the extent and severity of the problem is made even more difficult because consistent rules for reporting these types of biosafety events do not exist under the government’s Select Agent Program (SAP). For example, a review this year by the Government Accountability Office found that the number of incidents of incomplete inactivation between 2003 and 2015, similar to what occurred with the Dugway anthrax samples, was at least twice as high as initially reported. Clearly, a more comprehensive and thorough accounting is needed.

The corrosive impact that a lack of oversight can have on biosafety is apparent in the admittedly extreme case of the Sverdlovsk anthrax leak in 1979, in which a Soviet biological weapons facility near present-day Yekaterinburg, Russia unintentionally infected the city with a cloud of anthrax spores. Coincidentally, the incident occurred only five days after the Three Mile Island (TMI) nuclear accident in Pennsylvania, and the two events actually contain a number of similarities. Both were caused, in large part, by errors in maintenance: at Sverdlovsk, technicians neglected to replace an exhaust system filter, while at TMI, staff had isolated an auxiliary feedwater pump during routine maintenance in violation of US Nuclear Regulatory Commission (NRC) rules. Both resulted in the release of toxic materials into the environment: about a gram of anthrax at Sverdlovsk and 370 PBq of (biologically-inert) radionuclides from TMI. The consequences of both were severe as well: casualty estimates from the anthrax release range from 60 to over 100, and while no direct health effects from the Three Mile Island accident have been conclusively documented, the economic cost may have been in excess of $1 billion, in addition to the permanent damage done to the US nuclear industry’s public image.

If the events themselves bear similarities, the official responses to them could not have been more different. The Soviet government responded to the Sverdlovsk incident in its typical manner with a campaign of disinformation, blaming the anthrax cases on contaminated meat and destroying associated hospital records. Biopreparat, the Soviet biological weapons program, added yet more layers of secrecy to hide its involvement, making it even less accountable to the government of the Soviet Union, let alone its people. By the time the Soviet Union collapsed, the government had almost entirely lost operational control over the bioweapons program.

In stark contrast, the Three Mile Island accident prompted the NRC to make significant changes to how US nuclear power plants are regulated and operated. The agency instituted a number of policies such as tracking significant events and safety system actuations to determine which initiating events that might result in a radiological release were most common and issuing guidance to operating plants to reduce their frequency. In the years since TMI, accident precursors, reactor trips, and occupational radiation exposures at nuclear plants have decreased precipitously, in some cases by an order of magnitude. The NRC has also taken steps to increase transparency in its findings, such as publishing safety and performance assessments for all operating plants. This allows for public scrutiny and an informed conversation regarding the risks associated with civilian nuclear power.

What lessons can we take away from Sverdlovsk and Three Mile Island? The most obvious insight is that operational safety can be greatly enhanced by effective oversight, and effective oversight requires a well-informed regulator. A consistent and uniform mechanism for tracking biological safety incidents, perhaps through the SAP, would provide regulatory agencies with a better idea of the nature of the problem and allow them to spot trends. By publishing data on laboratory failures, organizations could be held accountable for poor performance and best practices could be more easily identified. The real lesson from Three Mile Island and the Nuclear Regulatory Commission’s response is that with enhanced scrutiny, the likelihood and severity of an accidental release drops and biological research can become safer and more secure. And in the end, isn’t that what biodefense is all about?

Biodefense in Gaming: Enjoyable but Inaccurate

By Greg Witt

With pathogens like Zika, Ebola, and West Nile now household names, biodefense has rarely been more culturally relevant. One needs look no further for proof than the sudden proliferation of TV shows and movies taking on these themes, including The Last Ship, Containment, and Helix. Depictions of biodefense topics in popular culture are not limited to traditional media, though; numerous video games and board games have been released in the past few years in which biodefense plays an important role. Here are a few of the more notable games:

Dead Island: This 2011 video game involves a genetically-modified version of kuru that is transmissible by blood and turns people into zombies. The disease is released by a shadowy corporation as a biological weapons test on some fictional islands off the coast of Papua New Guinea. With respect to scientific accuracy, the developers make a number of major errors; for example, they repeatedly refer to kuru as a virus when it is actually a neurodegenerative condition caused by a prion. Such creative liberties are understandable considering that a disease with an incubation period of 10+ years would make for a rather boring game. In the end, these epidemiological details are merely window dressing intended to give the game a pseudoscientific backstory in the name of narrative expediency and exciting gameplay.

Tom Clancy’s The Division: In the world of biodefense, few pathogens are as feared as variola, and rightly so. Playing on this concern, The Division follows government agents attempting to restore order in New York City as society collapses in the aftermath of a smallpox attack in the heart of Manhattan. While the specifics of the disease and the outbreak are largely glossed over, the game’s depiction of the aftermath of such an epidemic is eerily plausible, including misdiagnosis of the initial infections, exponential spread of the virus, and the collapse of the public health system under the unprecedented strain of massive casualties. The premise for the story is almost identical to Operation Dark Winter, a simulation conducted in 2001 to analyze US government preparedness for a hypothetical smallpox attack. Ultimately, the variola outbreak is just a plot device to set the stage for a post-apocalyptic shooter, but the game does succeed in bringing some long-overdue attention to the potential threats posed by biological terrorism and the genetic engineering of pathogens.

Plague Inc.: This strategy game presents a twist on biodefense, as players take on the role of a pathogen, starting as a bacteria, virus, or parasite, and attempt to eliminate humanity. As time passes and more people are infected, the disease can be upgraded by adding new symptoms (such as coughing, pulmonary edema, or kidney failure) and modes of transmission (such as airborne or vector-borne). Humanity does not go gentle into that good night, however, and fights back by trying to develop a cure and by taking interim measures like the closure of land borders and airports. For a free smartphone app, it actually provides a surprisingly accurate and comprehensive simulation of a pandemic. For example, players must balance transmissibility, infectivity, and lethality in order to maximize the spread of their pathogen.

Pandemic: If you prefer saving the world to destroying it, the cooperative board game Pandemic offers you and 1 to 3 companions the chance to work together to save the human race from not one, but four different virulent and highly contagious pathogens. The game starts at the Centers for Disease Control and Prevention headquarters in Atlanta as biodefense experts and medical personnel scramble around the world in an attempt to contain major outbreaks and ultimately discover and disseminate a cure for each illness. Taking on such roles as “Quarantine Specialist” and “Epidemiologist”, players must contend with scarce resources and the frustration of always having to play catch-up to a constantly morphing and unpredictable threat, a feeling that real biodefense experts know all too well. While never delving too deeply into the specifics of the pathogens or the actual science behind epidemic response, Pandemic provides invaluable insight into the world of those working every day to keep our society safe from biological threats.

When judging the accuracy of these games, a noticeable pattern begins to emerge. Action and shooting games tend to gloss over the epidemiological details and use biological agents and epidemics as merely a plot device or a token justification for the setting. Since these titles are usually focused on fast-paced action and interpersonal relationships, it is understandable that the developers would take poetic license with their depictions of pathogens and epidemics. Strategy games, on the other hand, tend to explore the complexities of pandemic response and provide the player with much better insight into the worlds of epidemiology and biodefense. Other than biological inaccuracies, the most glaring flaw in the depiction of epidemics in gaming is the assumption that some omnipotent intergovernmental organization can take all steps necessary to contain and cure the outbreak. In reality, it could be argued that the greatest challenge is presented not by the contagion itself, but by the inability of different stakeholders to cooperate, in addition to the obviously extreme differences in response infrastructure.

One crucial commonality between all four games is the depiction of virulent and contagious pathogens as existential threats that must be confronted sooner rather than later. So while the actual science and politics on display can often be questionable, these games are an invaluable tool for bringing biodefense to the attention of the general public. And of course it doesn’t hurt if we get to play some enjoyable games along the way!