Raymond Mariella, left, and John Dzenitis
Exploring "Detect to Warn" Systems at Livermore
August / September 2005
Volume 3 Number 4
It didn't take hijacked airliners crashing into buildings and anthrax-tainted mail to convince engineer Ray Mariella, Jr., that the United States was vulnerable to bioterrorist attacks.
Motivated by Iraq's invasion of Kuwait and its use of chemical and biological weapons in its earlier war against Iran, Mariella has been working since the early 1990s on a variety of early warning systems aimed at sniffing out harmful biological agents.
And thanks to the foresight of Mariella and many colleagues at Lawrence Livermore National Laboratory and other national labs, sophisticated detection systems are now being deployed that can alert authorities in time to provide suitable treatment for people exposed to biothreat agents such as anthrax and plague. The worst effects of most of these pathogens can be headed off if treatment begins before symptoms appear.
Mariella acknowledges, however, that in the long run, such "detect to treat" strategies don't go far enough. The ultimate goal, as outlined in a report earlier this year by the National Research Council (NRC), is a "detect to warn" capability that would collect and analyze a biological sample and launch protective measures within three to five minutes, "and preferably one minute," of release.
"There is growing consensus," the report says, "that such detection systems could be deployed by 2010."
Mariella, who was invited to participate in the NRC review because of his and Livermore's longtime involvement in biodetection technology, says reaching that goal will require a national commitment to a phased-in strategy for dealing with biological agents, as well as the resources to develop and deploy both existing and emerging technologies.
Simply compressing the amount of time required for current detectors to respond to the presence of a bioagent would be too expensive, Mariella says.
"One of the main questions is, how would you even know you're under attack, and how expensive would it be to determine that?" Mariella says. "Our human activities are a constant source of aerosolized biological material. It might be a farmer spraying something on his crops or a passing garbage truck."
According to the NRC report, relatively simple and rapid "nonspecific" detection systems could be deployed within one to two years to help protect buildings and military installations. While these systems might not detect low levels of pathogens, and would run the risk of triggering false alarms, their fast reaction times could alert authorities to a possible attack.
"Less expensive technology would give you a warning that something bad might be happening," Mariella says. "It might miss a small attack, but there are good reasons for putting in these less specific, faster detectors. They can't tell the difference between bacteria, but they could tell you, for example, that the number of bacteria or spores in the air is much higher than you'd expect.
"It's like a smoke detector—€” when it goes off you don't run and call the fire department right away; first you check to see what set it off."
Mariella, director of the Center for Micro and Nanotechnology in LLNL's Engineering Directorate, helped produce the first drafts of the chapter in the NRC report on nucleic acid sequence (DNA)-based identification of bioagents, along with Dr. Mark Hollis from MIT's Lincoln Laboratory. Regarded as a leading expert in the field, Mariella helped launch the development of Livermore's Autonomous Pathogen Detection System (APDS) and Handheld Advanced Nucleic Acid Analyzer (HANAA) in the mid-1990s.
Both systems are now being developed for the commercial market. HANAA, the first truly portable battery-powered, PCR-based detector capable of detecting both bacterial and viral pathogens, is being marketed to firefighters, hazardous materials teams and other first responders by an East Coast company.
The mailbox-sized APDS continuously monitors for airborne pathogens and toxins. It uses two separate identification technologies, an immunoassay detector and a DNA amplification and detection system based on Livermore's rapid polymerase chain reaction (PCR) technology, to reduce the likelihood of "false positives" —€” incorrect results that could needlessly trigger an evacuation and arouse public concern.
APDS has been extensively field tested in airports and subway stations without a single false positive and it received a 2004 R&D 100 award from R&D Magazine as one of the year's top 100 technological advances. It was licensed to a company last year, and both APDS and HANAA are available for additional commercial licensing. Mariella, who holds a B.S. degree in math, chemistry and chemical engineering from Rice University and an A.M. and Ph.D. in physical chemistry from Harvard University, came to Livermore's Engineering Directorate in 1987 after ten years at the Allied-Signal Corporate Research Center in Morristown, VA.
A specialist in bioinstrumentation, he was soon asked by members of the Laboratory's Nonproliferation, Arms Control and International Security Directorate (NAI) to apply his skills to developing defenses against bioweapon
"Iraq had invaded Kuwait, and Desert Storm was going on," Mariella says. "Don Prosnitz (a division leader in NAI) made me aware that Iraq had bioweapons, that they had devoted considerable effort to making anthrax. He pointed out that this was an obvious weakness in our defense, and that we (Livermore) were in a position to do something about it."
Using their knowledge of genomics, biotechnology, microtechnology and engineering, Mariella and his colleagues went to work developing and field-testing portable DNA analyzers and bioagent detectors. A Laboratory Directed Research and Development director's initiative was launched in 1995, and by the fall of 1996, the technology had proven itself to the point where Mariella was able to prepare a successful white paper for the Department of Energy proposing lifecycle development of the APDS.
The NRC report says a relatively simple and rapid but "nonspecific" bioaerosol particle detection system, coupled with an automated, integrated system capable of identifying pathogenic microbes, could quickly detect a low-level biological attack with "very low false alarm rates." Such a system, the report says, could be developed over the next five years. "Ideally, both the bioaerosol detector and the rapid identifier would be operating continuously, making measurements every one to two minutes," the report says.
"We found that the only practical short-term solution was non-specific detection," Mariella says, "but we need to look at emerging technologies both for assay and identification. As that evolves, it would become more affordable to get a more sensitive system that would avoid the risk of having a passing garbage truck set off an alarm."
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Biological Warfare Has a Long History
Biological agents are of concern to homeland security officials partly because many of them can be easily manufactured, transported and dispensed. And because of the lag time between a biological attack and the appearance of symptoms in those exposed, biological weapons could be devastating if not detected promptly.
Many biological agents are contagious, and during this lag time, infected persons could continue to spread the disease, further increasing its reach.
Hundreds or even thousands of people could become sick or die if an undetected biological attack were to occur in a major metropolitan area.
The use of biological agents as weapons is not a new phenomenon. The Romans used corpses of diseased animals to poison the drinking wells of their enemies.
During the horrific Black Death of the Middle Ages, the bodies of bubonic plague victims were catapulted over fortress walls of besieged cities.
During the French and Indian wars, 1754-1763, the British gave smallpox-infested blankets as gifts to the Indians because of their suspected alliance with the French. During World War II, Germany and Japan produced bacteria capable of infecting humans.
In Europe, terrorist groups in Germany began producing botulinum toxin. In the late 1980s in Japan, the Aum Shinrikyo cult acquired anthrax bacteria and botulinum toxin and attempted to collect samples of Ebola virus.
Fortunately, biological attacks in the United States have been few and isolated.
One occurred in 1984, when followers of Baghwan Shree Rajneesh poisoned several salad bars in Oregon with salmonella bacteria. Five people died and two dozen were infected by anthrax spores sent through the mail in October of 2001.
According to a 1998 report by the Congressional Research Service (CRS), United Nations inspectors revealed the vast scope of Iraq's biological arsenal following the 1991 Persian Gulf War. Iraq was found to possess more than 150 bombs and 25 missile warheads filled with botulinum toxin, anthrax or aflatoxin.
What's more, Iraq had built sophisticated laboratories to study and produce a wide range of biological agents and toxins. Between 1991 and 1998, UN inspectors in Iraq oversaw the destruction of 38,000 chemical munitions, 480,000 liters of chemical warfare agents and precursors, 48 ballistic missiles, six missile launchers and 30 chemical and biological weapon missile warheads, the CRS reported.
Charles Osolin is an information officer at LLNL
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