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October 23, 2001

 

Detection of a Biological Attack: How Fast is Fast Enough?
By David Currie

The first "germ attack" on the US may have occurred in 1984, when followers of Baghwan Shree Rajneesh poisoned salad bars in Oregon with Salmonella bacteria. The bacteria were cultured on the Baghwan's ranch and released in 4 restaurants in an attempt to prevent people from voting in a local election; presumably, votes by Baghwan's followers would then influence the outcome of a local election. The attack was detected when people fell ill in the days following the attack.

With a 4th case of respiratory anthrax confirmed on Oct 21st, many detection technologies still require hours to days to accurately identify specific pathogens (generally bacteria, but possibly viruses or chemical toxins). One exception to the rule is the Alexeter BTA pathogen detection system, described below. The Alexeter system is currently under testing by a number of government agencies. A primary factor limiting accurate detection for a number of other systems is the use of a technique called "polymerase chain reaction," or PCR. PCR is used to amplify (multiply) DNA of suspected pathogens to get enough DNA to examine using current assay systems. The need for PCR adds at least 1 day to analysis procedures. When we skip the PCR step, or when we rely on protein examination exclusively, and not DNA, we are more likely to experience "false positives," in which the wrong species is identified as the cause of symptoms, or "false negatives," in which specific strains of a pathogenic microbe cannot be identified.

The US Department of Energy, Centers for Disease Control and Center for Strategic and International Studies are following a number of strategies for rapid detection of "germ attack." Ideally, these techniques will make precise identification of "weaponized" strains of bacteria quicker (within hours to seconds) and possible using technology available in your home computer, palm pilot, cell phone or wristwatch. The advantage of a detection device within a communication device would be that early detection could be automatically transmitted to appropriate information processing systems. While many such detection systems likely remain classified, below are some interesting ideas with considerable promise:

  1. Alexeter's Guardian BTA BioDefense System - The Alexeter corporation produces a number of devices which allow rapid testing for the presence of pathogens like anthrax. Antibody-treated pathogen detection "strips," much like pregnancy detection test strips, are used to test for the presence of specific antigens like anthrax. Just don't try to order anthrax test strips right now ($495 for 25 strips); they are on backorder. Alexeter also provides a device to read the strips ($3500), another device to capture particles from the air and deliver them directly to a test strip (the Biocapture Air Tester, cost unknown), a practice kit for $195, a sample collection kit for $90, as well as additional training videos and classes. You have probably seen the Biocapture Air Tester sniffing out germs on recent television news broadcasts.

  2. Antibody-based Fluorescence Assays - in March 2000, Popular Mechanics described an assay developed by Defense Advanced Research Projects Agency. In the assay, genetically modified mouse cell lines express antibodies against specific pathogens (bacteria, viruses, toxins) that might be released in a terrorist attack. When the antibodies bind the right type of pathogen, a series of biochemical reactions takes place in the modified mouse cells. These reactions result in the entry of Ca2+ into the mouse cells. The Ca2+ binds to a special "epifluorescence molecule" added to the cells. When this special molecule detects an increase in Ca2+, it will fluoresce under UV light. The increase in fluorescence indicates that a dangerous pathogen has been detected. While the system might be pretty fast (hours), it requires labs, cultured cells, microscopes, UV light sources - and represents a lot of technology which cannot currently be adapted to your home computer - but never say never.

  3. Antibody-based Contractile Protein Assays - Dan Nicolau of Swinburne University of Technology in Melbourne and Cris dos Remedios of the University of Sydney are using proteins from muscles to detect microbes. They embed myosin molecules in channels that have been laser etched into polymer-coated disks. Actin and myosin are the same molecules that work together (along with a number of other regulatory, structural, and energy molecules, to cause muscles to contract). Actin molecules link to myosin and can be made to crawl along the myosin molecules (just the way they do in real muscle). The researchers hope to piggyback antibodies against pathogens to the actin molecules in the system. When the antibodies bind pathogens (germs), the actin molecules stop "crawling" along the myosin strands. The movement, or non-movement, of actin might be detected by attaching magnetic beads to the actin filaments. The moving magnetic beads generate an electric current in an induction coil… when the actin and magnetic beads stop moving, the electric current is broken. While this method shows great promise in terms of miniaturization and mechanization, there are some tough problems to resolve, like how to continuously provide the type of biological energy to keep the actin molecules moving.

  4. Flow Cytometry, or "Fluorescent Particle Analysis" - Flow cytometry derived its name from the way that cells flow by a detector, one at a time, and specific characteristics of cells, such as cell size, are compared. On the basis of such differences, cell proportions can be determined among mixed populations of cells. The technique has become increasingly refined such that particles much smaller than cells can be compared. It may soon be possible to accurately compare characteristics of bacteria, viruses, and chemical toxins. This technique has fewer biological restrictions than the techniques above, and it is fast and accurate, providing potentially highly reliable results within minutes.

  5. Microbes to detect microbes - One day it may be possible for harmless bacteria to detect the presence of pathogenic organisms. Upon detection, modified bacteria, which are otherwise harmless, would break down the pathogenic organisms and release detectable factors in response to the presence of the pathogen. Markers released by the harmless bacteria, upon encountering pathogens, would then be detected by some mechanical device. While the use of microbes to detect microbes is potentially very rapid, it again raises the requirement for significant lab facilities to support such testing.

  6. Intelligence Analysis Software - Affectionately known as KARNAC, Knowledge Aided Retrieval in Activity Context software does not rely on microbes, but rather organizes and sifts through millions of independent pieces of information looking for links. Applied Systems Intelligence thinks that this type of software could find important connections between seemingly disconnected events. That would allow the software to predict terrorist attacks based on purchases, hotel and automobile reservations, and travel patterns or determine important players among terrorist groups based on communication patterns. The software uses information from previous terrorist activities as a database to predict terrorist activity patterns.

During the current anthrax attack, the federal government has quickly and effectively organized, tested, analyzed, informed and protected. We applaud the efforts of all involved.

David Currie

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