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The Invisible Agent: How Ebola Teaches Us to Defend Against the Smallest Deadly Weapons

When bacteria were first seen under a microscope in the 1670s by Antonie van Leeuwenhoek, the “Father of Microbiology,” we caught a glimpse of these tiny seeds of infection. But biological warfare is an ancient and enduring tactic. Poisoned darts and arrowheads (tetanus and other germs), catapulted corpses (plague), and bullets filled with canine saliva (rabies) have been used to weaken and kill opponents. The British wrapped smallpox in blankets then presented the Native Americans with this intentionally devastating disease during the 18th century French and Indian War.

Cow Trebuchet from Monty Python and the Holy Grail (Python (Monty) Pictures, Sony Pictures)

Biowarfare is among the many infectious threats to human well-being. In modern times, infections kill about 20% of the world’s population annually. Anne Marie Slaughter, a former lead foreign policy advisor to Secretary Clinton, imagined that pandemic disease could wipe out humankind. The Institute of Medicine (now the National Academy of Sciences, Engineering, and Medicine) remarked in 1992 that an interesting consequence of globalization is the fluidity with which infections can spread across populations. The Committee on Emerging Microbial Threats to Health wrote in 2008, “In the context of infectious diseases, there is nowhere in the world from which we are remote.” Consider, the Zika virus has circulated in South and Central America, the Caribbean, Africa, and parts of Asia, and it has now arrived in the United States. Ebola has spanned continents.

Despite advancing diagnostics and treatments we remain vulnerable. The Ebola outbreak (2013–2015) killed more than 11,000 people, infected almost 30,000, cost several billions of dollars, and exposed ambiguity of authority, assigned roles and accountability as public, private, and non-profit bodies gathered to end a chaotic humanitarian tragedy. Though eventually successful, the global outbreak response was disorderly.

The questions before us now are these:  How could the Ebola response help us examine our bioterrorism readiness? What were the big lessons? How might we apply these findings to improve our military preparedness exercises?

U.S. Army Soldiers put their gas masks on for a simulated chemical attack during a training mission near Camp Ramadi, Iraq, Sept. 25, 2007. (U.S. Marine Corps photo)

Several substantive reviews of the Ebola emergency have identified similar operational deficiencies. The Independent Panel on the Global Response to Ebola embodied these shared sentiments with 10 actionable recommendations to improve future epidemic response. The Panel was directed by the Harvard Global Health Institute and the London School of Hygiene and Tropical Medicine with invited experts in Ebola, public and global health, international law, humanitarian assistance, and national and global governance. Foremost, the Panel emphasized assignment of accountable leadership and clear authority over disease outbreak, and designated this central role to the World Health Organization (WHO). If epidemics explode into public emergencies, the United Nations Security Council should partner with the WHO to convey political urgency. Since epidemics can evolve unpredictably and disrupt economic and political stability, outbreak response has a place on the world agenda as a human security concern.

The Independent Panel on the Global Response to Ebola’s Ten Recommendations:

Major outbreak prevention

  1. The global community must agree on and support a strategy to create a sustainable set of core capabilities for outbreak prevention in all nations (even the poorest countries).
  2. The WHO promotes early and accurate reporting of outbreaks. Additionally, the WHO should commend countries that rapidly report outbreaks, publicize countries that delay reporting, and also confront governments that implement trade or travel restrictions without justification.

Major Outbreak Response

  1. Within the WHO, a dedicated center (with a protected budget and accountable leadership structure) should be created to provide strong technical capacity during outbreak response.
  2. A transparent and politically immune Standing Emergency Committee within the WHO should be created with the responsibility of declaring public health emergencies.
  3. An independent United Nations Accountability Commission should be created for worldwide outbreak response assessment.

Research

  1. Governments, non-governmental organizations, scientific researchers, and various industries must work collaboratively during and between outbreaks to accelerate research and ensure wide access to the benefits of research.
  2. Research funders should establish worldwide financing capabilities for outbreak relevant diagnostics and treatments, even in the absence of commercial incentives.

Governance

  1. A Global Health Committee should be created within the United Nations Security Council to expedite political attention and action to health issues in times of major outbreak response.
  2. & 3. The WHO Executive Board should mandate reforms within the WHO that are not limited to, but include: redefining the core mission of the WHO with a focus on outbreak response, improving freedom of information, and standing up an Inspector General’s office. A more focused WHO and its member states should be empowered to protect public health, even in the face of uncooperative governments.

In summary, the core of a proactive stance is prevention. The ideal is to promote universal public health capabilities for early outbreak detection, even in the poorest nations. Preventions’ scope expands greatly when technologies and knowledge are collaboratively shared. Research can widen the reach of epidemic prevention and response. If outbreaks are not contained, the WHO needs to rapidly surge to higher capacity and widely employ qualified people, plans, and resources along an organized, nimble infrastructure. The full circle of governance is realized when overall responsibility is clearly defined and those responsible work together with engaged local, national, and international authorities to accomplish common goals. Finally, independent review and critique of outbreak response, by agencies such as the United Nations, provides an opportunity for unbiased guidance and optimized future preparedness. While not all the lessons from Ebola may pertain to biodefense, the most basic of these concerns, leadership and prevention, certainly do.

Leadership Focus

Presidential Decision Directive 39 was introduced in 1995 and designates the Federal Bureau of Investigation (FBI) as the lead agency for domestic terrorism response. The Federal Emergency Management Agency (FEMA) will manage and execute the response plan with assistance from the Department of Defense (DoD), National Institutes of Health (NIH), and the Centers of Disease Control and Prevention (CDC) for medical strategy. Additionally, a comprehensive response includes partnerships with police, fire, emergency medical responders, hospitals, local and regional government officials, the judiciary, the information technology sector and the media, and drug and vaccine distributors. Amidst chaos and fear, the success of a multi-level coordination is helped by agile leadership, and by each agency being familiar with the other’s capabilities and limitations. This degree of inter-agency preparation is resource-intensive. Despite the hefty exercise planning prerequisites and limited feasibility for recurring practice, a cost to benefit analysis still weighs in favor of being well rehearsed. The consequences for meeting a biological event unprepared are disastrous, with loss of human health and lives, breakdown in peace and order, and exaggerated spread of disease in the most extreme scenarios, which under the best circumstances all of these risks could be minimized.

Any joint military exercise designed to practice these competencies must acknowledge the complexities of inter-agency cooperation. In the absence of opportunities for hands-on, joint participation, a DoD exercise should aim to create realistic practice scenarios with surrogates or representatives from each of the necessary agencies (FBI, FEMA, and CDC) as well as local community networks (police, hospitals, locally elected officials, etc.).

Contagion Movie Poster (Warner Brothers)

Location is also a factor. The employment of a bioweapon in another country could significantly complicate an American response. As Ebola clearly demonstrated, if a bioweapon were deployed in another country, the United States would not be isolated from its impact. Who would lead the charge? Presidential Decision Directive 39 names the Department of State as the lead agency for international terrorist incidents, yet it maintains almost no capacity to respond, beyond diplomatic and political discussions. The WHO would also likely have a significant role. An international event presents greater potential for ambiguities of command and control.

Day to day biodefense strategy management also appears to be poorly defined, at least within Congress. Randall Larson of the WMD Center said “there are more than two dozen Senate-confirmed individuals with some responsibility for biodefense. Not one person has it for a full-time job, and no one is in charge.”

A clear chain of command is necessary, especially as roles of authority or expertise are divided amongst FBI, FEMA, DoD, NIH and CDC. Interestingly, a universal recommendation following the Ebola response was to streamline authority so that strong technical, medical and political leadership exists in one decision making body during outbreak response. So resounding was the international consensus surrounding this recommendation, that it seems wise to examine the applications for a consolidated leadership in biodefense. Of the existing agencies, perhaps the DoD is best equipped to lead. As a single entity comprised of intelligence and security forces, civil engineers, lawyers, first responders, health care providers, and public health experts, the DoD is a versatile and formidable force; however the DoD is and should be the agent in this problem, not the principal.

Prevention

Threat assessments underpin prevention planning, and experts in elected office, policy, public health, the military, medicine, biotechnology, academics, and think tanks are not able to agree upon or quantify the likelihood of a bioterror attack. In short, the U.S. biodefense field is significantly fragmented from a risk assessment perspective..

Predicting when or how an attack may occur (location, scale, and subsequent contagion) is not feasible. Therefore, answering the challenge of developing a strategy for prevention will require an impressive unity of governmental and non-governmental bodies, a common countermeasure mission, and an opportunity to rehearse scenarios ahead of time.

Also at the core of prevention is reducing American vulnerabilities (through intelligence, international relations, transportation security, etc.), enhancing disease surveillance, and deterring terrorism through clear public policies and actions that identify and reduce capabilities and support of terrorist groups. Disease surveillance is a key public health function for disease prevention. Like illness outbreaks, biological attacks are likely to be difficult to recognize before the effects gain a dangerous momentum within the population. The first casualties may be seen in clinics and emergency rooms. Early detection requires awareness of threat by health care providers, and access to adequate clinical and diagnostic tools for investigating causes of unusual or unexplained groupings of illness. If an attack is suspected, then the speed with which a microbe is accurately identified and the population receives appropriate vaccines or drug prophylaxis will certainly correlate with the cumulative casualty burden. Computer modeling of scenarios also provides useful information for guiding strategies and resource allocation planning for outbreak containment.

Well organized plans for a prevention strategy alone cannot stop outbreaks from progressing, as the early Zika response has shown. The Zika response is hindered by practical matters like funding delays, rampant disease transmission in countries struggling with basic public health, and continued absence of a clear and accountable leader for outbreak response (though WHO reforms following Ebola were proposed, implementation is taking time). Optimists will see that an expansive unity exists within Zika research with information transparency regarding the latest on transmission risks, cellular mechanisms of disease, exploratory treatments and vaccines, and data on outcomes of infection. Research drives the future’s prevention strategies.

Research

In biodefense, let’s examine possible barriers to research and development. Persuading more scientists to devote their expertise to bioterrorism is hindered by tight security classifications, poor consensus of actual threat, lack of sufficient funding, and the lack of collaborative opportunity with pharmaceutical partners (who often supply significant research dollars).

Free market incentives in biodefense are sparse at best. In contrast, simultaneous Ebola vaccine trials by Merck, GlaxoSmithKline, Johnson and Johnson, and several small biotechnology companies were commercially motivated. The speedy interest in Ebola vaccine discovery contrasts with the availability of a single FDA licensed anthrax vaccine. Emergent BioSolutions markets BioThrax, the original anthrax vaccine first licensed by the Michigan Department of Public Health in the 1950s. BioThrax is endorsed by the Food and Drug Administration and is safe and licensed for use in military personnel and occupationally exposed workers (veterinarians, livestock workers, laboratory personnel). Booster vaccines are required for optimal efficacy, although in epidemiologic data, even partially vaccinated workers with occupational exposure had protective immunity against anthrax.

Envelope connected with the 2001 anthrax attacks, and intended for Senator Tom Daschle, contained anthrax spores. (Wikimedia Commons)

The smallpox vaccine has a simpler history. Today’s smallpox vaccine is based on Edward Jenner’s cowpox blister fluid experiments from the 1790s. Today’s vaccine offered to military personnel and the smallpox vaccine offered to the U.S. general public through the 1970s were both derived from vaccinia virus, a close relative of Jenner’s blister fluid virus. The vaccine provides immunity and requires a booster every 5-10 years. The anthrax and smallpox vaccines are part of our military countermeasures, and their history shows the pharmaceutical industry’s persisting disinterest in biodefense.

Conclusion

Biodefense is a critical component of national security. The Ebola outbreak response is instructive for bioterrorism readiness. Recall that public, private and nonprofit sectors unified for Ebola. We should also imagine a multidisciplinary team coming together for biodefense. Success of a military posture against bioterrorism relies on strong and evolving relationships within a multidisciplinary team to develop well managed, funded, and rehearsed plans. Future dialogues on current command and authority assignments, prevention capabilities, and research barriers could clarify ambiguity, spark innovations, and guide implementation. A review of lessons learned from the Ebola response highlights the complexities in and challenges facing our current biodefense readiness.


Ki Lee Milligan, MD is a clinical investigator and immunologist at the National Institutes of Health. She is a former U.S. Air Force Flight Surgeon who served with helicopter search and rescue, F-16, and special operations units and has interests in humanitarian crisis response. This article was prepared by Ki Lee Milligan in a personal capacity. The opinions expressed are the author’s own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government.


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Header Image: Salmonella bacteria, a common cause of food-borne disease, invade an immune cell. (Popular Science and the National Institutes of Health)