Oct. 20, 1999 A new biochip technology developed by Russian and American scientists may help stem the global resurgence of tuberculosis.
The technology, developed by the U.S. Department of Energy's Argonne National Laboratory and the Russian Academy of Sciences' Engelhardt Institute of Molecular Biology, is expected to help health organizations deal with the new variety of drug-resistant strains of the disease.
According to the World Health Organization, tuberculosis kills more youth and adults than any other infectious disease, including AIDS and malaria combined. Every year, 7 to 8 million people become sick with the disease and more than 3 million die.
The biggest problem associated with the new tuberculosis epidemic is that several different bacterial strains can cause the disease, and each is resistant to different drugs. Finding which strain is affecting a patient, and knowing which antibiotic is best equipped to combat that strain, is key to controlling the disease.
Argonne will use the biochip technology in research to distinguish between different tuberculosis strains. The tests will be done on harmless segments of genetic material removed from tuberculosis bacteria. Clinical research - involving patients - is not expected to begin until the method has been proven successful.
The biochips are designed to carry out thousands of biochemical reactions simultaneously, and have performed well in laboratory tests. "But this will be their first test in the realm of real-world medical diagnostics," said Harvey Drucker, Argonne associate director.
"We chose tuberculosis for the tests," he said, "because new drug-resistant strains have sprung up and can easily spread to the whole world. If we can quickly identify specific strains, it will help doctors prescribe the best treatments quickly and possibly help prevent a worldwide epidemic."
Today, tuberculosis patients are often prescribed several antibiotics simultaneously because it takes weeks or months to identify specific tuberculosis strains, and patients can die during this time. "If our biochip can do the job," Drucker said, "physicians can prescribe the most effective treatment without delay."
If successful, these initial studies will set the precedent for similar evaluations of other bacterial and viral diseases. Antibiotic resistance results from the natural selection of stronger bacteria over weaker ones. Stronger bacteria have mutated genes that help the disease resist antibiotics.
Because tuberculosis cells grow slowly, patients must take antibiotics daily for at least six months to ensure that all the bacteria are eliminated. If treatment is shortened, or inconsistent, surviving bacteria - those most resistant to the treatment -- can reproduce, passing their resistance on to their offspring.
In impoverished nations, where people cannot afford months of medication, victims effectively become incubation chambers for new drug-resistant strains. In some Russian institutions, roughly 80 percent of tuberculosis patients were found resistant to at least one antibiotic, and 50 percent showed multiple resistance.
Although airborne, tuberculosis is not remarkably contagious compared to other viral and bacterial infections. With only one exposure, the body's defenses normally keep the bacteria at bay, unless the immune system is weakened by a disease such as AIDS. However, with continued exposure, as when living with a person with active tuberculosis, someone can develop the disease quickly.
Like computer chips, which perform millions of mathematical operations per second, biochips can perform thousands of biological reactions in a few seconds. The Argonne/Englehart biochip is a glass slide containing up to 10,000 tiny gel pads, each serving as a mini test-tube. Attached to each gel pad is a short strand of DNA, the unique set of blueprints that determine the building blocks of every living species. The information in DNA is encoded in long sequences of four molecular units, or bases - adenine (A), cytosine (C), guanine (G) and thymine (T). The precise pairing of A on one strand with T on another strand and G with C, allows DNA to form its "double helix."
By fixing only one strand of the double helix to each gel pad, the chip takes advantage of the natural tendency of each DNA base to pair with its complementary base. When tests begin, a sample of unknown single strands of tuberculosis DNA will be spread on a chip and allowed to naturally pair up in the gels with single strands of tuberculosis DNA with identified drug resistance. A direct match will identify drug resistant tuberculosis strains. By changing the DNA samples in the gels, scientists can also use this technique to diagnose an unlimited range of other diseases quickly and efficiently. One of the biggest advantages of Argonne's biochips over conventional biochips is that they can be cleansed and reused up to 50 times, making them more economical than conventional biochip technology. Also, the gel's greater size allows them to hold up to 1,000 times the material, making them more sensitive than any other biochip.
"With the advanced biochip technology, we'd be able to get all the information we need in a couple of hours," Drucker said, "without any false positives." The researchers are optimistic about this project, he added. "The fact that it has been shown to work, and that the test wasn't difficult to perform, shows us that this has a lot of potential," he said.
However, bringing the test from this research effort into the clinical setting is another giant leap. "We're using DNA for the research study, not actual fluid from patients," said Drucker. "But it does give us a good idea of the direction we want to go."
If successful, Drucker says, they would move to a larger scale study with more patients, using fluid samples from active tuberculosis patients.
"We'll be doing a full scale clinical diagnosis but it'll take years to get to the market," Drucker said. "Considering that tuberculosis is becoming a global epidemic, some urgent steps must be taken to speed up the process."
The nation's first national laboratory, Argonne National Laboratory supports basic and applied scientific research across a wide spectrum of disciplines, ranging from high-energy physics to climatology and biotechnology. Since 1990, Argonne has worked with more than 600 companies and numerous federal agencies and other organizations to help advance America's scientific leadership and prepare the nation for the future. Argonne is operated by the University of Chicago as part of the U.S. Department of Energy national laboratory system.
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