Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and Post-Traumatic Stress Disorder (PTSD) are poorly understood illnesses that have a broad impact on the body's communication and control systems (nervous and hormone systems) as well as its repair and defend functions (immune system). Traditional medical research looks for broken parts in these systems without paying much attention to how the parts fit together and whether or not the complete assembly is well tuned and operating at peak efficiency.

In this proposal we intend to examine how poorly tuned the fight-or-flight survival response may have become in patients with Gulf War Illness. In much the same way as pilots use simulators to understand the capabilities of their aircraft during flight training, we will use a computer mock-up of the human body's fight-or-flight response to improve our understanding of GWI. Using simulations we hope to map the new characteristics of this altered survival response in sick veterans and find safe ways of bringing it back into its normal performance envelope.

This map will help us in two ways. First, it will tell us what to look for in new recruits who might be especially at risk (screening) for developing GWI under the specific conditions. Second, it will also tell us where in the body, and how, this survival response should be adjusted in servicemen that are already ill. Because we will be working with a mock-up of the whole system, we expect to identify not only those treatment options that could help but, almost as importantly, those that could have dangerous side effects.

Computer simulations have accelerated the design of aircraft, cars, and other sophisticated machinery. In a similar way we expect that this computer-aided design approach will shorten the time to clinical trials and help improve the focus and quality of these trials. At the end of this 3-year project it is our objective to have in hand a set of blueprints for the most promising of these clinical trials. Finally, these simulations can be adjusted to mimic the response of a specific individual. As a result, this work could help lead to treatments that are customized on a person-to-person basis. This is important because we suspect that not all patients suffer from the same variant of GWI and we know from experience that not all patients react in the same way to the same therapy.