Mission: Protect the warfighter from emerging and genetically engineered biological threats by providing a novel response capability, from identification of pathogens to the development of medical countermeasures.

Vision: To protect the warfighter and the nation from biothreats.

– From the Transformational Medical Technologies Mission/Vision Statement

It is a sad truth that many of the greatest advances in modern medical technology owe their development to the pressures of treating the victims of battlefield injuries. America’s “long wars” of the early 21st century have been the motivation of a whole host of new medical innovations, many of which are the stuff of science fiction. Early developments included bandages that instantly clotted severely bleeding wounds, and new generation tourniquets that could be carried by every at-risk warrior on a battlefield that was rapidly becoming one of the deadliest ever known. Along with traditional threats like small arms fire, mortars, and artillery, new threats like the improvised explosive device (IED) rapidly became weapons of choice for the terrorists and insurgents that made themselves the enemies of the United States and its allies in the 21st century.

But there are even more insidious threats in the world than those posed by roadside bombs and other weapons of ambush. Most people are familiar with the overt weapons of mass destruction (WMDs), such as nuclear and chemical weapons, along with large IEDs such as those used in Oklahoma City and the first World Trade Center attack in 1993. Less familiar, however, is the deadly threat posed by biological warfare weapons, including weaponized disease cultures and biotoxins. However, lack of knowledge or interest does not mean that such weapons are not a major threat to America’s military forces, and even the general population.

Documented cases of planned modern biological warfare are fairly rare, but their results are worth consideration. The one systematic campaign using weaponized biological warfare agents by Japan against China in the 1930s and 1940s is reported to have killed 400,000 Chinese. And what makes bioweapons even more dangerous is that they normally don’t kill instantly. Often they take some hours or days for symptoms to appear, often long enough for victims to spread communicable diseases and agents across great distances and into much larger populations. This is especially threatening when dealing with military personnel operating together in large numbers while deployed, or with civilian populations such as those in large urban centers with heavy commuting populations. Naturally occurring diseases are already major threats in a military force, as was shown by the “Spanish flu” pandemic of 1918 that occurred at the end of World War I. Now, however, the growing threat of genetically engineered bioweapons means that more proactive measures will be needed.

 

Beginnings: The Transformational Medical Technologies Initiative

Inoculations against naturally occurring diseases date back to the 1700s, and U.S. troops have been vaccinated against anthrax going back to Operations Desert Shield/Desert Storm in 1990-91. The events of 9/11 and the subsequent anthrax mail attacks, combined with the emergence of homeland security as a major mission for the Department of Defense (DoD), led to a new appreciation of the potential dangers of disease and biotoxins as weapons. DoD’s traditional approach to developing biodefense systems was to target specific organisms and toxins, and map their effects in what was called at the time the “one bug, one drug” strategy. However, advances in genetic engineering, biotechnology, and advanced chemistry have increased the possibility that enemies could develop, weaponize, and deploy a new generation of biological threats. The 2006 Quadrennial Defense Review (QDR) determined that a new strategy was required to reduce the U.S. military’s potential vulnerability to such weapons, and directed a $1.5 billion outlay to develop a family of broad-spectrum medical countermeasures against advanced biological threats and systems.

While medical and other technological advances have conquered diseases, mitigated exposure environments, and extended life, they have also paved the way for advanced weaponization of biowarfare agents capable of producing mass casualties on a scale that makes 9/11 pale by comparison. Today, the time required to develop and produce such agents is much shorter than the time necessary to develop, license, and produce a response treatment commercially. Additionally, many naturally occurring disease-causing pathogens have become drug resistant, and previously conquered diseases are reemerging to threaten the lives of the nation’s warfighters. DoD recognizes these threats and the urgent need to enhance our nation’s current response capability, which includes the following inadequacies:

• The capacity to rapidly deploy bioweapon countermeasures at the onset of an attack is presently slow and insufficient.
• Truly effective preventative prophylaxis (e.g., vaccines) must be administered weeks or months prior to a deployment or an attack.
• Present post-exposure remedies and therapies are limited, only moderately effective, and do not address emerging diseases and genetically engineered threats.
• The process to ensure a medical product is safe, effective, and suitable for regulatory approval, production, and distribution is both lengthy and expensive. Effective treatment reaction times in the event of a bioweapons attack will likely be measured in days or weeks before mass casualties overwhelm military and/or national heath care systems.
• Presently, in the commercial environment, it can regularly take over a billion dollars and more than a decade of development to bring a new product or treatment to market, assuming it is fiscally viable and clinically effective.

 

Transformational Medical Technologies: Management and Oversight

In 2006, DoD created the Transformational Medical Technologies Initiative (TMTI) to evolve and enlarge its ability to protect U.S. military personnel from the threat of emerging and genetically engineered biological pathogens and toxins. Today known as Transformational Medical Technologies (TMT), the program is based on the Medical Biodefense Research, Development, Test and Evaluation Plan described in the QDR final report. TMT is especially focused on advanced biological threat agents, such as De Novo or genetically engineered pathogens. The plan lays out the nature and plans for TMT’s management and the strategy to achieve the aims set forth in the QDR, and aligns with the following additional policies:

• Homeland Security Presidential Directive/HSPD-10: Biodefense for the 21st Century, which outlines the national strategy for biodefense, including development of safe and effective medical countermeasures against biowarfare weapons and toxic agents of concern.
• Homeland Security Presidential Directive/HSPD-18: Medical Countermeasures against Weapons of Mass Destruction, which frames the strategy to develop medical countermeasures against WMDs through a two-tiered approach:

– Focused rapid development of agent/toxin-specific medical countermeasures; and
– Development of a flexible capability/capacity for new medical countermeasures, including those required following an actual attack or post-exposure detection.

• Homeland Security Presidential Directive/HSPD-21: Public Health and Medical Preparedness, which establishes a national strategy for public health and medical preparedness, aimed to protect the public health of the American people against all disasters, both man-made and naturally occurring.
• The 2007 Chemical and Biological Defense’s Medical Research, Development, Test & Evaluation Plan.
• The 2009 National Strategy for Countering Biological Threats.

TMT is presently working at combining the most promising efforts of government and public health agencies, academia, DoD, biotechnology, and the pharmaceutical industries – from pathogen identification through the development of broad-spectrum medical countermeasures. The key idea behind TMT is to provide a new kind of biowarfare response capability for the U.S military forces and public health agencies that addresses the traditional shortcomings of response scenarios involving pathogens. Personnel and recources from the Joint Science and Technology Office, the Defense Threat Reduction Agency, and the Joint Program Executive Office

support the TMT Program Office for Chemical and Biological Defense. Oversight comes directly from the Office of the Special Assistant to the Secretary of Defense for Chemical and Biological Defense and Chemical Demilitarization Programs, and has been well supported and funded since 2006. The planned budgets in the near future fiscal years (FYs) are broken out as follows:

• FY 2011 – Science & Technology (S&T) – $142.9 million, Advanced Development (AD) – $121.0 million.
• FY 2012 – S&T – $141.9 million, AD – $104.2 million
• FY 2013 – S&T – $142.3 million, AD – $119.2 million
• FY 2014 – S&T – $129.3 million, AD – $174.4 million
• FY 2015 – S&T – $95.9 million, AD – $204.5 million

 

TMT: Process, Programs, and Milestones

TMT was established to provide specific and rapid response capabilities against emerging and genetically engineered biological threats. The response process in the event of a “biological event” is well understood and established, and follows existing epidemiology and public health guidelines:

• Detect and Characterize the Pathological Agent – This includes pathogen identification, genetic sequencing, informatics analysis, and clinical validation of agent and its effects.
• Access and Develop a Medical Countermeasure (MCM) Strategy – Conduct a disease/agent pathogenesis, conduct a MCM strategy analysis, choose one or more target drugs, treatments, or vaccines, and finally risk mitigation and treatment approval.
• Enable Rapid MCM Delivery and Deployment – This normally includes evaluating MCM delivery platform suitability, MCM evaluation and safety validation, MCM production and delivery, and finally, regulatory compliance with federal laws and regulations, such as those set down by the Food and Drug Administration (FDA).
• To support the above course of action, TMT’s key performance goals include the following planned capabilities:
• Development – Developing rapidly adaptable platform technologies for generating MCMs, including distribution and deployment channels. This also will include processes for helping rapidly generate required efficacy and safety approvals from agencies like the Food and Drug Administration.
• Validation – Validating platform technology and pathogen identification processes and methods by developing broad-spectrum MCMs for viral hemorrhagic fevers and bacterial infections. This literally means one drug that can potentially deal with many different kinds of “bugs” and/or toxins.
• Continuing Research – Determining genetic sequences for pertinent pathogens against which to screen, identify, and characterize potential biodefense threats and to identify new target drugs, treatments, and vaccines.

TMT takes a strategic approach to developing capabilities that enable responses to biological threats and has made significant progress since its inception in building a balanced family of projects that are designed to improve our nation’s response capabilities to bioterrorism attacks and public health emergencies, including protection of deployed military forces. To this end, TMT has competitively developed a diverse pool of more than 50 projects and 100 subcontractors, drawn from some of the most advanced biotechnology firms, pharmaceutical corporations, and academic institutions in the world, most of which have not previously worked with DoD. In addition, there is a high level of support being tapped from existing government laboratories, many of which previously were dedicated almost exclusively to WMD research and development. TMT has also initiated a robust technology portfolio that rivals those of the civilian/commercial pharmaceutical industry, containing novel platform technologies and upwards of 20 potential investigational new drugs (INDs).

This includes two INDs with efficacy against the Ebola and Marburg hemorrhagic fever viruses. These will provide responders with a first-of-a-kind capability for real-world incidents, as there are currently no therapeutics available for these conditions. The FDA has already accepted these INDs for entry into human safety trials and they are providing proof-of-process data for a new and highly versatile drug development platform capable of generating therapeutics within days, instead of weeks or months. TMT has also developed access to a comprehensive database for evaluation of genetic sequences against potential drug targets from over 90 percent of the known pathogenic virus families capable of infecting humans. They also have initiated an integrated pathogen estimation capability for basic handling, rapid identification, and characterization of pathogenic and genetically modified bacteria and viruses, along with the discovery of potential new drug targets.

These kinds of real-world capabilities are going to be critical when America faces its next major biowarfare challenge, and also will be valuable in the event another major pandemic event such as SARS or H1N1 swine flu should occur again. To support these needs, TMT has implemented a platform for evaluating promising therapeutic candidates and re-purposing FDA-approved drugs. This new stream of data will improve recognition of biomarkers in high-speed testing and yield better understanding of a disease’s overall biology. This means that caregivers and responders will be better informed as to which drugs and treatments to use in a specific incident, and when to use them.

TMT has also developed for their vendor base a series of outstanding opportunities to advance first-in-class, broad-spectrum antibiotics, antivirals, and innate immunity activators. In one example, TMT partners were able to provide a number of promising H1N1 therapeutics within 15 days during a “live fire” exercise. TMT is currently planning studies designed to further develop these therapeutics for potential use if an actual emergency develops. In a related effort, TMT partnered with the U.S. Navy Medical Research Center (NMRC) and several industrial partners for preclinical development of an extremely innovative H1N1 DNA vaccine. The NMRC is the transition partner for Phase 1 human clinical trials, which are presently under way.

All of this translates into a real-world improvement in America’s capabilities to deal with emerging threats around the world, along with potential attacks on the homeland. Considering the lack of capability that was demonstrated during the Anthrax attacks in 2001, these efforts are both promising and encouraging. Nevertheless, there is much work ahead, and it will be a long-term commitment by the country and government to meet the minimum needs of the military and public health agencies.

The United States has been exceptionally fortunate not to be a victim of further bioweapons attack since the anthrax mail incidents of late 2001. And while the current thinking is that those attacks were the criminal actions of a single U.S. citizen with unique knowledge and access, the reality is that such attacks are very likely in the years and decades ahead. The likelihood of heavy casualty rates, contamination of key infrastructure and facilities, and the disruption of day-to-day business, travel, and other activities make advance planning and preparation against such attacks essential. TMT is providing an important start to that need, and is developing both the processes and infrastructure to rapidly and effectively deal with fast-breaking biowarfare attacks and medical crises.

This is not to say that TMT is the ultimate answer to the problem of potential bioweapons attacks on American military forces and the U.S. population in general. That said, however, TMT provides a series of necessary and valuable first steps on the way to providing national and military leaders real options in the event of a major bioweapons attack or public health emergency. The 2009 H1N1 pandemic provided a number of useful lessons and examples of the things that TMT has already done, and will have to do in future years. We can only hope that time will be on our side, before what some analysts feel is an inevitable biowarfare attack falls on U.S. military forces or the American homeland.

This article was first published in The Year in Veterans Affairs and Military Medicine: 2010-2011 Edition.