Basic research efforts in the medical sciences related to military missions address four areas: infectious diseases of military significance, combat casualty care, Army operational medicine, and medical CBD. The first relates to protection/prophylaxis of personnel deployed to a mission area from indigenous organisms or to biological agents; the second to care of personnel following acute injury; the third to enhancers/sustainers of performance in the field; the fourth to treatment and care of persons following exposure to biological agents. These areas of investigation are dual use and impact general health care delivery, although the military aspects often differ from civilian concerns in several critical instances. For example, deployed military personnel may be more susceptible than indigenous populations to infectious agents because of a lack of prior exposure. Also, developing novel means useful in delaying onset of clinical disease in the face of the physically and mentally demanding nature of combat is of critical importance, as incapacitating military forces for short periods may have profound effects on the outcome of operations. Table E–33 summarizes international capabilities in medical research.

Basic research in infectious diseases of military significance concentrates on prevention, diagnosis, and treatment of infectious diseases affecting readiness and deployment.

The Human Genome project has identified those gene profiles that render specific populations more susceptible to disease than other populations. This project is a multinational effort spearheaded by the United States, EC, and Japan; the information is freely available on the Internet. Novel combinatorial chemistry strategies have allowed the synthesis of nonpeptide molecules that bind gene fragments, receptors, or cell proteins and thereby offer the potential of protection against threat agents. These same materials also may provide utility in multiarray sensors used for the detection of biological agents. Combinatorial chemistry strategies are being pursued in many developed nations through the pharmaceutical sector. Switzerland, Sweden, and Israel have expertise in these areas, as do the above–mentioned nations.

The critical areas of care for combat casualties in the next decade include treatment for fluid loss and accompanying shock, management of impact injury on the nervous system including the spinal cord, increased susceptibility to infection at points of projectile entry because of stress related events, and prevention of biological agent dissemination by friendly forces exposed to agents. Biocompatible materials that bind oxygen and have utility as blood expanding agents are in development in the U.S., EC, and Japan. Cellular growth factors acting on neural tissues have been found to stimulate the repair of transected spinal cord and other central nervous system regions. Macromolecular growth factors, acting on tissues other than the nervous system, have been shown to enhance the rate of wound healing and to increase resistance to disease. This research is actively explored in the the United States, Canada, Germany, the U.K., France, Japan, Israel, Italy, and Sweden.

Basic research within the Army operational medicine research area provides a basic understanding of the pathophysiology of environmental and occupational threats affecting soldier health and performance. In addition to the risks to health and performance from operations in extreme climatic environments, and the rigors imposed by military operations in and of themselves (e.g., sleep deprivation, jet lag, stress), operation of Army systems may present additional health hazards (e.g., EM radiation, noise, vibration, blast, and toxic chemical by–products).

Biomarkers for toxicant exposure in humans and animals have been identified as materials that are body catalysts and enzymes that serve to detoxify chemicals. The absence of some of these normally occurring enzymes in specific persons has been shown to increase susceptibility to disease. It is now possible to screen blood and urine samples and determine the concentration of these biomarkers in selected persons. It is likely that biomarker profiles will have utility in selection of persons resistant to toxicants (for special operations) and for reviewing fitness for duty. The Human Genome project is likely to increase the number of biomolecules that can serve as biomarkers for exposure. The United States, Canada, EC, and Japan have expertise in this area.

Foreign efforts in medical chemical defense closely parallel those in medical biological defense. For the most part, countries that are engaged in one are also active in the other. The one exception for countries listed is the Netherlands. The Dutch effort in medical chemical defense is not as extensive as in medical biological defense. All countries listed have world leading capabilities and none is expected to pull ahead of the others.

Normally occurring biomolecules have now been identified that enhance or degrade the immune response of persons to infectious material or to toxins. These materials are called biological response modifiers (BRMs). Treatment with novel BRMs, of military forces who may have been exposed to pathogenic agents as a consequence of deployment or through biological agent attack, may enhance the survival or sustain the performance of the affected personnel. In the past few years, it has been shown that transport of infectious materials across cell membranes is a critical element in viral replication and maturation. Chemical treatment that interferes with the ability of a virus to bind to a target cell or with intracellular transport can impede viral multiplication and infectivity; such treatments may sustain performance of affected personnel for long periods after exposure to such agents. The United States, Japan, France, the U.K., Germany, Sweden, and the Netherlands are leaders in this area.

The following highlight a few selected examples of specific facilities engaged in medical research:

Russia—State Scientific and Technical Program. Organized through the Russian Academy of Medical Sciences, the program has developed of number of R&D projects unified in six thrust areas. These include development of medicinal substances to regulate immune processes, development of agents affecting hemostasis processes, computer designing of new medicinal substances, and pharmacokinetic and biopharmaceutical principles of improvement in medicinal preparations. The program oversees the collaboration of over 3,500 specialists and 75 organizations, including the Russian Academy of Sciences, Russian Academy of Medical Sciences, the Russian Federation (RF) Ministry of Health Care, and the medical industry. Recent research results include the development of a number of medicinal substances that regulate immune responses, including antitumoral agents, immunomodulating agents, and antiarrythmic preparations.

Japan—Chemical Research Center. The Cytoprotein Network project involves the codification of human proteins through the synthesis of full–length cDNA rather than fragments. This technique produces proteins both in vitro and in vivo directly from full–length cDNA clones and is thus able to rapidly identify a large number of proteins as well as the genes that are coded for them. The functions of some of these 10,000–20,000 intracellular proteins (cytoproteins) are known. Many of them have a maintenance function, whereas others are specific to certain cells. Research to better understand them, their movements (by tagging the proteins with fluorescent markers) and functions is concentrated into three areas. These include the cloning of full–length cDNAs, a search for novel sorting signal sequences, and in vitro translation of cDNAs to find receptors and their ligands.

France—National Health and Medical Research Institute (INSERM). INSERM was founded in 1964 as France’s central agency for health research. It performs basic and applied research, technical development, and medical surveys. The primary objective of INSERM is to participate actively in biomedical research in order to increase knowledge of human health and thereby improve the diagnosis, therapy, and prevention of illness. Its supplementary missions include applications development, information exchange, research training, and international relations. INSERM participates in a number of European Science Foundation programs, including projects on environmental and health, the European Neuroscience Programme, molecular neurobiology of mental illness, and toxicology programs.

United Kingdom—Department of Medical Microbiology, University of London. Research in this department within St. Bartholomew’s and the Royal London School of Medicine and Dentistry has thrusts in microbial pathogenicity, antibiotics, and molecular epidemiology. The microbial pathogenicity research group studies the molecular and genetic basis of microbial infection and attempts to apply this knowledge to clinical problems. Specific research focuses on the fundamental pathogenic properties of enteric pathogens. Within this area, individual projects focus on the genetic regulation of virulence, bacterial host cell interactions and the development of vaccines and vaccine delivery systems. Future goals include the exploitation of available genome sequence data from several bacterial pathogens with a view to the development of improved vaccines, diagnostic, epidemiological and therapeutic agents.

Japan—National Cancer Center. Located in Tokyo, Japan, this center is developing applications of VR technology in medicine. It specializes in medical imaging and development of enhanced VR tools for image–guided surgery. Research goals include improving patient amenity with VR and the development of new diagnosis methods for medical imaging using VR technology. These VR systems have several advantages for surgical applications, including ease of repetition of medical procedures, application of surgical experiences to develop models from individual patients’ medical images, self–training on surgical procedure in real time, and objective evaluation by remote supervisors.