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New Facilities To Bolster Anti-Bioterror Effort

By Rich McManus

On the Front Page...

In order to address the threat posed by biological agents used as a means to spread terror, NIH is building several new research facilities to conduct studies on such pathogens, including a major new structure — Bldg. B — to be completed by 2005 on land that is now a carpool parking lot just east of Bldg. 31's C wing.

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The effort to build new laboratory space and upgrade existing research facilities answers not just the need to prepare for the use of such organisms as anthrax, smallpox, plague, botulinum toxin and tularemia as instruments of terror or war; it also is part of a 20-year effort mounted chiefly by the National Institute of Allergy and Infectious Diseases to counter emerging and re-emerging viruses and pathogens worldwide, including hanta virus, Ebola, and multidrug resistant tuberculosis.

On the same day that NIAID made public its counter-bioterrorism research agenda — the fruit of a 2-day meeting at Pooks Hill last February by a blue ribbon advisory panel — the institute's scientific director Dr. Thomas Kindt addressed a gathering of young researchers in Lipsett Amphitheater Mar. 14 to give an overview of the threat and how to combat it. "This topic has dominated our thinking for the last several months," he said.

The carpool parking lot just east of Bldg. 31's C wing will be the site of the new Bldg. B, which will be dedicated to research on agents used in bioterrorism, and on emerging pathogens.

Unlike biowarfare, which is aimed against troops to achieve military objectives, bioterrorism is targeted at civilians, and need not necessarily result in immediate casualties, Kindt explained. "One can instill a lot of terror even without a lot of death and destruction." He gave an overview of historical uses of bioweapons ranging from the Middle Ages, when the corpses of plague victims were catapulted toward the enemy, to 1763, when British troops used blankets and handkerchiefs to spread smallpox to the Delaware Indians at Ft. Pitt, to World War I, when an animal disease known as glanders (Burkholderia mallei) was used, not too successfully, by German soldiers to sicken the Allies' horses, mules and sheep, to the modern era. Within the past 70 years, developed nations have alternately embraced, and then rejected, use of such weapons in war.

Until about 20 years ago, bioweaponry was restricted to state vs. state warfare, which was a condition worrisome enough. But starting with the tainting of Tylenol with cyanide on store shelves in 1982, there has been a succession of incidents involving the use of pathogens by individuals or small groups to spread terror. Kindt touched briefly on some infamous cases: the Rajneesh cult's use of salmonella to poison salad bars in 1984, the attack by the Aum Shinrikyo group on the Tokyo subway system in 1995, when nerve gas killed 12 and sickened 5,000 people, and the discovery in 1995, based on information provided by defectors, that both Iraq and Russia had large and poorly managed bioweapons programs. With the world already on alert from these incidents, enter the anthrax poisonings of fall 2001, a crime that made bioterrorism a threat that Kindt said was, finally, "too real to ignore."

Focusing primarily on his institute's response to bioterrorism, Kindt first pointed out that NIAID and NIH play complementary roles with sister agencies within HHS in the event of an attack; CDC, FDA and the Office of Public Health Preparedness are also players in the response. While he conceded that there are "an incredible number of things" a clever and well-trained scientist could do to cook up a dangerous or novel pathogen, Kindt said that so-called "Class A" agents are the most likely candidates to be employed against civilians. These include smallpox, anthrax, plague, botulinum toxin, tularemia, and some hemorrhagic fever viruses, many of which share common characteristics: they result in high morbidity and mortality, they offer the potential for person-to-person transmission, a low infective dose is required to start large damage, and the pathogen can be aerosolized, or spread in a mist. Further characteristics of the most likely agents include an ability to contaminate food and water, a tendency not to be treatable, an ability to cause anxiety, and, finally, they can be weaponized.

Key factors in a federal reaction to an incident, said Kindt, include early detection of the pathogen, a rapid public health response, and the availability of vaccines or therapies for those exposed. NIH, he said, is contributing to readiness via basic research including genomics of the organisms and host responses to them, and the development of diagnostics, vaccines and antimicrobials.

Medicine's chief vulnerability to date has been a dearth of state-of-the-art research on pathogens due to a lack of facilities equipped to study such bugs safely, Kindt said. He emphasized that the "same levels of expertise and facilities" are needed to address such unintentional public health threats as MDR-TB and Ebola as are required to answer the deliberate threats posed by terrorists.

He reviewed the escalating series of safety rules governing pathogen research, ranging from BSL-1 (biosafety level 1), which is characteristic of most labs at NIH, to BSL-4, the level requiring the most extensive safety measures, including full-body suits, and sophisticated filtering and decontamination of everything going into and out of the lab.

At NIAID's Rocky Mountain Laboratories, in Hamilton, Mont., a new BSL-3 facility has just opened, Kindt said; it is focusing on TB and Q fever (Coxiella burnetii). RML scientists are also studying Yersinia pestis (plague), and have recently developed an animal model in which vaccine testing can begin, he reported. Other bugs under investigation within NIAID include strep, pox virus, vaccinia, anthrax, tick-borne encephalitis and West Nile virus, for which a vaccine is nearly ready for testing.

"But we need some new facilities to make our program really fly," Kindt added. He said a new BSL 3/4 facility at RML has been funded, and described a new campus building dedicated to counter-bioterrorism and emerging disease research — Bldg. B, which will include BSL-3 labs. "Bldg. B will feature 175,000 gross square feet of space, including six floors and a ground-floor vivarium. We're in the conceptual design phase now." Groundbreaking for the new lab building is expected in mid to late 2003, with completion anticipated in 2005.

Kindt also said that NIAID's Twinbrook III Bldg. is going to get an expanded BSL-3 capacity, which should be available by December 2003, and announced that a BSL-4 facility is in the planning stages for the Frederick Cancer Research and Development Center. He cautioned that it isn't just the recent anthrax attacks that have prompted the new push for facilities. "Two years ago," Kindt said, "the Raub report [written by former NIH acting director Dr. William Raub] and other reports concluded that we were neglecting a large number of infectious organisms, mainly due to a lack of facilities for studying them.

"There are major threats of bioterrorism out there," he concluded. "We must do the research and development necessary to defend against any of the agents that might be used."

(NIAID's bioterrorism research agenda can be found at www.niaid.nih.gov/dmid/pdf/biotresearchagenda.pdf.)
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