BETTER MOUSETRAP IS BUILT, DETECTING DEADLY BACTERIA
11 Jul 2003
Source: New York Times, July 11, 2003
A Better Mousetrap Is Built, Detecting Deadly Bacteria
By KENNETH CHANG
Taking a biological approach toward detecting biological weapons, scientists at the Massachusetts Institute of Technology have genetically engineered white blood cells from mice to light up when they come into contact with deadly bacteria or viruses.
"It's extremely fast, much faster than the existing methods," said Dr. Todd H. Rider, a senior scientist at the M.I.T. Lincoln Laboratory in Lexington, Mass., and lead author of a paper describing the new sensor technology in today's issue of the journal Science.
The researchers said they had already developed cells that can detect a dozen different pathogens, including smallpox, anthrax, plague and equine encephalitis.
While fairly quick, accurate sensors exist for chemical weapons like mustard gas or sarin, reliable detectors of biological weapons have lagged. Accurate systems are slow, bulky and expensive, while the quick tests are prone to "false positives," finding danger where none exists.
"At this point, the false positive rate is too high, the number of agents that can be detected is limited," said Dr. Bradley Smith, a fellow at the Center for Civilian Biodefense Strategies at Johns Hopkins University. "We are in desperate need of new diagnostic technologies."
The Defense Advanced Research Projects Agency provided most of the financing for the research.
Detecting biological weapons usually involves two steps, latching onto the germ and reporting that it has been latched onto. In a typical sensor, an antibody, which has been attached to a fluorescent molecule, hooks onto a specific protein. Sifting out the latched-on antibodies and then identifying them involves fairly complex chemistry.
Dr. Rider and his colleagues exploited biological machinery of the immune system to perform the same tasks instead.
"I decided to just use the system nature had designed," Dr. Rider said.
The central component of the sensor, called Canary, an acronym for cellular analysis and notification of antigen risks and yields, are mouse white blood cells.
To detect a specific pathogen, the M.I.T. researchers add to the white blood cells a gene that produces antibodies that hook onto the pathogen. The researchers also added a jellyfish gene that produces a protein that glows blue when activated.
The joining of the pathogen to the antibody sets off a cascade of actions. The antibody, changing shape, opens a hole in the wall of the white blood cell. Calcium ions then rush in through the hole, which activate the jellyfish proteins, and the emitted blue light is easily detected. "It does signal amplification for you," Dr. Rider said.
White blood cells tailored for plague bacteria were able to detect as few as 50 bacteria within three minutes with a false positive rate of 0.4 percent. The cells did not respond to other types of bacteria nor did the other bacteria interfere with the cells' ability to detect plague.
The Canary sensors also could have medical and agricultural uses, including screening meat and vegetables for food poisoning bacteria. The M.I.T. researchers produced cells that detected a virulent strain of E. coli bacteria on lettuce. "But they won't light up in the presence of nonpathogenic E. coli., such as the E. coli that are normally found in the human intestines," Dr. Rider said. "We can even differentiate between different strains of the same organism if that's desired."
The researchers have also shown that the Canary cells can also detect chlamydia, a sexually transmitted bacterial disease, in urine.
M.I.T. is talking to companies that are interested in licensing the technology. Tests using the Canary technology could appear commercially in as little as a year, Dr. Rider said. More complicated devices that could continually monitor air for biological weapons are at least several years away.
"It is extremely intriguing work," Dr. Duane L. Lindner, deputy director for chem/bio at Sandia National Laboratories, said. "It's extremely interesting in a scientific sense."
But, he added, "A big concern of this work is the transition to practical applications. For example, cells are extremely fragile. Cells are hard to keep alive."
The test, while quick, also require some preparation including treatment with chemicals and a whirl in a centrifuge. "Given the centrifuge and all the sample prep, there's a lot of work that would have be done to turn this into an autonomous sensor application," Dr. Lindner said.
Dr. Rider, however, said the cells "require little or no maintenance." The cells live for a couple of days, unattended, at room temperature, a couple of weeks when refrigerated. With some care, primarily feeding, the cells can live several months. They can be frozen indefinitely at liquid nitrogen temperatures.
"They have been more rugged and robust than we could have hoped," Dr. Rider said.