primates (Rambaut et al. 2004). An infinite array of patterns that yield favorable opportunities for a pathogen probably does not exist, and conversely, defense mechanisms that the host is capable of generating are probably few.

If the host is a collection of different environments and opportunities for exploitation by a pathogen, then a successful pathogen must bring the proper tools to exploit that opportunity (tailored adaptation strategy), and those tools probably fit into (recognizable) major patterns (mechanisms of pathogenesis). Any pattern or patterns of specific adaptations by these pathogens may be targeted for medical countermeasures, and mechanisms of pathogenesis that are similar or shared by different host species (human and nonhuman) may be used to demonstrate comparable efficacy of countermeasures when such assessment cannot be performed in humans.

ADDRESSING THE UNKNOWN THREAT THROUGH THE TRANSFORMATIONAL MEDICAL TECHNOLOGIES INITIATIVE2

The Transformational Medical Technologies (TMT; see Box 1-1) reflects a key transition point in the DoD’s philosophy about biological threats and the approach to developing medical countermeasures (MCMs). The overarching strategy for the TMT, conceived for the Quadrennial Defense Review (QDR) in 2006 by the DoD in its Chemical and Biological Defense Program Medical Research and Development, Testing & Evaluation (RDT&E) Plan, is as follows:

 

  • The key to defending against unpredictable or unknown threats (e.g., bioengineered pathogens) lies not in expending resources to uncover the types of advanced agents that humans could face but rather in exploring and comparing the underlying pathophysiological patterns in the interaction of pathogen and host by using advanced scientific approaches, such as systems biology.
  • In addition to the traditional method of looking for vulnerable pathogen targets, the strategy assumed the possibility of targeting broadly used host pathways for intervention. The TMT could ostensibly achieve broad protection against a variety of threats by looking at both host- and pathogen-based targets.
  • The TMT’s strategy hypothesized that the key to defending against unknowns could be found in understanding potentially commonly evolved pathways and developing medical countermeasures focused on pathogenesis patterns, rather than on specific pathogens and the traditional “one-bug, one-drug” approach.
  • The strategy suggested that pathogens that occupy similar “pathogenesis niches”, e.g., viruses that produce hemorrhagic responses in hosts, or bacteria that survive by exploiting an intracellular niche, acquired evolutionarily similar mechanisms or biochemical tools to achieve these niche-specific outcomes.

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2 The Transformational Medical Technologies Initiative (TMTI) became Transformational Medical Technologies (TMT) and is referred to as such throughout the report. In 2011 the Department of Defense moved the TMT to a Program Manager under the auspices of the Joint Program Executive Office for Chemical and Biological Defense, as the efforts have matured to advanced development. The Committee has addressed its report to the TMT.



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