Bio-Medical Aspects of Bio-Terrorism and a Call to Action

Paul B. Roth, M.D., Dean and Professor of Emergency Medicine
Brian Hjelle, M.D., Associate Professor of Pathology
Infectious Diseases and Inflammation Program
John K Gaffney, BBA, CEM, TEMT-P
Director, emergency Planning and Operations
University of New Mexico, School of Medicine

Not since the height of the cold war has there been so much public concern over weapons of mass destruction. Many of the current fears focus on the threat of the intentional release of infectious agents.  The nightmare image of tens of thousands of bodies lining the streets of American cities accompanies these concerns. Such fears have been fueled by both popular fiction and actual accounts of deliberate exposures throughout the world.  The use of biological agents can be even more dangerous than nuclear weapons since a nuclear attack has a limited area of effect, albeit huge, and it is obvious when there is a nuclear explosion. Technology to detect and quantitate radioactive contamination is very widely available. In comparison to nuclear attacks, some biothreat agents can initially spread silently and unchecked through populations far from ëground zeroí.  

Biological agents have been considered for use as weapons on unsuspecting populations throughout history.  Recent examples are the use of Yersinia pestis-infected fleas by the Japanese on the Chinese during World War II, and more recently the threat of Bacillus anthracis use in the Gulf War.  In most cases, the results of the use of these kinds of weapons have been less than impressive in comparison to those obtained with more conventional weapons.  What, then, has changed to make bio-terrorism more of an issue than in the past?  

One answer is the psychological impact of this type of threat.  The public is much more aware of new emerging pathogens.  Gruesome photographs of bloodied bodies in Africa after exposure to the Ebola virus were widely distributed.  The unseen, and in all other respects undetected, attack which could result in the images described above make for a very effective terrorism weapon in and of itself.   

Another change which causes even the most conservative among us to be alarmed involves the incredible advances in biotechnology.  It is now possible to alter the most virulent bacterium or virus and make it both more pathogenic and less likely to be killed by conventional therapy. The molecular biology revolution has now been underway for more than three decades, and the sheer number of persons with dangerous technical expertise has increased exponentially since the 1960s.

Finally, our populations are routinely engaged in global activities, traveling easily and often to distant locations.  The likelihood of rapid dissemination of any type of biological agent worldwide in a very short period of time is high, and the general public is well aware of this fact.

The challenges facing our ability to effectively defend against bio-terrorism are much greater today.  In part, this is because of the ease in which high density population centers within the United States and elsewhere may be exposed to these agents. Further, infected individuals will spread these genetically altered organisms ñ with their high rate of mortality and/or morbidity -  with great rapidity.  Additionally, the current efforts to develop these defenses are uncoordinated and lacking vision.  There are hundreds of millions of dollars that have been identified to address a number of aspects of this defense but there does not appear to be a well defined strategic plan directing these efforts.

 While the scientific community is actively engaged in developing methods of early detection and customized, rapid treatment strategies (vaccines, anti-virals and/or other drug therapies, there is no national approach to coordinate these efforts. This must also be done in conjunction with other responses, including interdiction of additional attacks, containment of exposure and treatment of those infected.  Finally, the majority of funds for responding to a bio-terrorism event are currently given to the federal response community.  This must be shifted so that training and equipping of first responders (and health care providers) must be funded, planned and then implemented at the local level, where any initial response to a Weapon of Mass destruction (WMD) event will be.

A successful approach to overcome these challenges must include collaborative programs between federal and state governments, the private sector and academic institutions. When facing the threat of national security during World War II, the Manhattan Project was designed in this fashion with incredible results.  The problems described above that are associated with bio-terrorism pose a level of complexity man orders beyond those of ësimplyí developing an atomic weapon.

In an effort to better understand and create effective interventions against bio-threats the University of New Mexico School of Medicine has formed a coalition with Los Alamos National Laboratories (LANL), Sandia National Laboratories, the New Mexico State Department of Health and Lovelace Respiratory Research Institute.  Among the first projects of this Consortium is the development of a model for population surveillance utilizing real-time reporting by health professionals in an emergency department of all patients with presenting complaints consistent with a flu-like illness.  This model system expands and builds on existing systems of detection by employing network-based reporting through internet connectivity and simple computer screen displays for entering syndrome-based reports by touch screen entry.   

Although starting in a single emergency department, the intent is to quickly extend this system to public health offices and other major health centers throughout the state of New Mexico. The purpose of this initial project is to demonstrate the ability of the national labs, private industry and an academic health center to work cooperatively to address a common problem.  Specifically, the project will develop an efficient model for rapidly detecting new clusters of infections in a population, and to develop the informational tools and datasets that will lead us to the ability to distinguish natural from manmade outbreaks.  The model could yield immediate practical benefits such as the identification of  early outbreaks of naturally occurring illnesses caused by influenza, enteroviruses, or the respiratory syncytial virus. 

There are a number of other, more fully developed pilot projects underway involving members of the Consortium. UNM School of Medicine faculty and scientists from Sandia National Laboratories and LANL are working on  several  pilot projects to  develop  ultrasensitive biosensors for directly detecting pathogenic viruses in the environment, as well as a project that uses near-infrared spectroscopy to detect changes in cells that may mimic the changes that occur very early in the infection of an animal. Scientists from the School of Medicine as well as the UNM Main Campus and Sandia are also writing an NIH grant that further expands the effort toward early detection of exposure to biothreat agents utilizing genomic microarray technology. The School of Medicineís Infectious Diseases and Inflammation Program (IDIP) is using the Consortiumís expertise to train a new generation of basic scientists whose highly interdisciplinary, broad-based training in infectious diseases and immunology will equip them to lead future efforts. The IDIP program has been awarded an NIH T32 training grant to support the development of students trained to use the latest technologies to address infectious disease threats both natural and manmade. 

Future projects in the planning stages include: rapid detection and genomic analysis of suspected biological threats; bioinformatics tools for pattern recognition of unusual events; and tools for rapidly identifying the appropriate intervention and response.  Detection of pathogens by using conventional markers for infection such as specific antibodies, nucleic acids or propagation in culture is intrinsically very slow and will not be suitable for many types of biological attacks, especially with engineered agents.  However, investigators at UNMís IDIP are developing novel tools to examine host responses to infection with the goal of categorizing infectious processes into groups based upon host responses.  It is their hypotheses that identification of common molecular pathways of host responses by specific agents will enable them to examine the agentís pathological ëfootprintí - long before conventional specific tests become positive.  Thus anthrax may be clustered together with another bacterial process and enable investigators to make the immediate step toward therapies that interfere with the harmful host response while simultaneously adding antimicrobials that treat all of the candidate agents, which were previously assigned a similar ëfootprintí.

An additional important role for this Consortium will include training of physicians and first responders as well as young scientists in the fields of toxicology and infectious disease through the School of Medicineís Center for Disaster Medicine (CDM).  The CDM not only provides the educational expertise to accomplish this training, but also fields the nationís largest disaster medical team, thus providing a test bed for hardware, software, and procedures developed by the Consortium.  It will thus provide a mechanism for translating the knowledge developed in the laboratory into the practical application of this knowledge in the field during actual releases of bio-terrorism agents.  

Barriers to successfully achieving these local consortium goals are the inherent bureaucracies of our respective institutions on one hand and the lack of access to special facilities, specifically Bio-Safety Level 4 (BSL-4) labs.   These laboratories are designed to allow scientists to safely study the lethal organisms that bioweaponeers are most likely to release.  Currently, these high-containment labs are located in only a few areas in the country with only limited access by the general scientific community.  At this time, there are only four of these laboratories located in this country  (NIH, Bethesda, Maryland;  CDC, Atlanta, Georgia; US Army Medical Research Institute of Infectious Disease, Fort Detrick, Maryland and Southwest Foundation for Biomedical Research, San Antonio, Texas).  Prior to two years ago there were only two Level 4 labs, and they were for the most part restricted to government use.  Although there are four more labs being planned (three in Texas and one on Plum Island, New York) access and therefore scientific discovery will still be limited. Even if all of those planned facilities are built, the US will still be markedly lacking in the high-throughput vaccine and therapeutic testing capability that is demanded to meet the threat of bioweapon attack. 

The current threat of a deliberate release of highly contagious and virulent micro-organisms by individuals who intend to terrorize the American public is a very real one.  It is therefore imperative for federal, state and local governments to forge effective alliances with the public and private scientific communities in mounting a meaningful mitigation and response strategy. This plan should include several critical aspects.  First, further research in the fields of microsystems for the development and wide distribution of devices for the early detection of selected organisms in the environment.  Second, continued research in bio-medical sciences in an effort to rapidly recognize individuals who are infected with bio-threat organisms and in the development of customized therapies.  Third, to slow and eventually halt the spread of these bio-terrorism agents there must be rapid containment strategies and facilities.  And finally, mass training of first responders and health care providers who may be called upon to deal with these types of situations in local communities must be developed and implemented. 

Given the aforementioned lack of coordination and unified leadership in the bio-terrorism community, there should be a special blue-ribbon panel should be created.  It should be  composed of federal, state and local government representatives, members of the scientific community (private sector, national laboratories and universities) and private industry.  This panel should be charged with identifying a unified strategy to defend the American people against this immanent threat. Thereafter, a similarly unified structure must be developed and empowered to implement this strategy.