Better Teeth Through Biochemistry
Lie back in the dentist's chair. Open wide. Now smile. No cavities today, or ever again. That's the promise of a genetically modified mouthwash - soon to be gargled in human trials - that could eradicate tooth decay and have medical implications far beyond good oral health. And here's the fun part: Sugar actually plays a role in the treatment.
The theory is simple. Tooth decay is an infectious disease caused by oral bacteria that turn sugar into lactic acid. The acid erodes tooth enamel. Eliminate the acid, and you eliminate cavities.
Jeffrey Hillman has been trying to do that for 25 years. Pushing ahead with an almost inhuman persistence - work nearly stopped several times while genetic technology caught up to his research needs - the University of Florida professor designed a new bacterium capable of playing nice in the oral ecosystem.
First, Hillman's team isolated a strain of Streptococcus mutans that has a natural antibiotic enabling it to elbow into prime position on the tooth's surface. Hillman then used recombinant DNA technology to delete this superbug's acid-producing gene sequence. The result: a genetically engineered strep called BCS3-L1.
In animal experiments - yes, rats host S. mutans, too - BCS3-L1 displaced the old strep but didn't produce acid, even when the rats ate nothing but sugar. Six months later, this superstrep was still genetically stable, acid-free, and thriving in the rats' mouths. Cavities and side effects? Almost nil.
A magic bullet for tooth decay would work wonders in developing countries where access to dentistry or fluoride is limited. And, since cavities go hand in hand with Ho Hos, it would have an even greater impact in countries like the US, where more than half the population has tooth decay before hitting puberty and almost 90 percent of adults have cavities. The scourge costs $27 billion a year - about half the dental industry's annual revenue. "If it actually works, Dr. Hillman's treatment would change dentistry as we know it," says Kenneth Burrell, the American Dental Association's senior director on the Council for Scientific Affairs. Dentists would still fix chips and treat abscesses, but the old drill, bill, and fill model would be history.
In its place, picture this: A dental technician squirts a syringe of genetically modified mouthwash across your choppers. You sit for five minutes, chew on some sugary candy to activate the new bacteria, and then leave. If it works, OraGen, the strep's patent licensee, stands to reap billions.
But is it safe to colonize millions of mouths with genetically modified bacteria? Trials on humans in the US and UK next year will try to answer that question. Leading scientists like Floyd Dewhirst are optimistic. Bacteria modify themselves all the time, says Dewhirst, who heads the molecular genetics department at Boston's Forsyth Institute. Hillman is just speeding up this natural DNA swapping.
"People are afraid of recombinant DNA technology. It freaks them out. But this Streptococcus mutans has been mutating for millions of years," he says. "It hasn't created evil things."
Aside from its potential for wiping out one of mankind's most common infectious diseases, Hillman's bacterium is the first genetically tailored to displace another organism. Replacement therapy - substituting bad, disease-causing agents with their good cousins - has been around since 1885. The problem with it remains: Good bugs are hard to find. Hillman's version of replacement therapy could demonstrate to a whole generation of scientists that helpful bacteria aren't just born, they're engineered. Ulcers and arteriosclerosis are now thought to be infectious diseases, too, and could be the next targets of elegantly made bacteria. That's something to smile about.
- Charles Graeber
The theory is simple. Tooth decay is an infectious disease caused by oral bacteria that turn sugar into lactic acid. The acid erodes tooth enamel. Eliminate the acid, and you eliminate cavities.
Jeffrey Hillman has been trying to do that for 25 years. Pushing ahead with an almost inhuman persistence - work nearly stopped several times while genetic technology caught up to his research needs - the University of Florida professor designed a new bacterium capable of playing nice in the oral ecosystem.
First, Hillman's team isolated a strain of Streptococcus mutans that has a natural antibiotic enabling it to elbow into prime position on the tooth's surface. Hillman then used recombinant DNA technology to delete this superbug's acid-producing gene sequence. The result: a genetically engineered strep called BCS3-L1.
In animal experiments - yes, rats host S. mutans, too - BCS3-L1 displaced the old strep but didn't produce acid, even when the rats ate nothing but sugar. Six months later, this superstrep was still genetically stable, acid-free, and thriving in the rats' mouths. Cavities and side effects? Almost nil.
A magic bullet for tooth decay would work wonders in developing countries where access to dentistry or fluoride is limited. And, since cavities go hand in hand with Ho Hos, it would have an even greater impact in countries like the US, where more than half the population has tooth decay before hitting puberty and almost 90 percent of adults have cavities. The scourge costs $27 billion a year - about half the dental industry's annual revenue. "If it actually works, Dr. Hillman's treatment would change dentistry as we know it," says Kenneth Burrell, the American Dental Association's senior director on the Council for Scientific Affairs. Dentists would still fix chips and treat abscesses, but the old drill, bill, and fill model would be history.
In its place, picture this: A dental technician squirts a syringe of genetically modified mouthwash across your choppers. You sit for five minutes, chew on some sugary candy to activate the new bacteria, and then leave. If it works, OraGen, the strep's patent licensee, stands to reap billions.
But is it safe to colonize millions of mouths with genetically modified bacteria? Trials on humans in the US and UK next year will try to answer that question. Leading scientists like Floyd Dewhirst are optimistic. Bacteria modify themselves all the time, says Dewhirst, who heads the molecular genetics department at Boston's Forsyth Institute. Hillman is just speeding up this natural DNA swapping.
"People are afraid of recombinant DNA technology. It freaks them out. But this Streptococcus mutans has been mutating for millions of years," he says. "It hasn't created evil things."
Aside from its potential for wiping out one of mankind's most common infectious diseases, Hillman's bacterium is the first genetically tailored to displace another organism. Replacement therapy - substituting bad, disease-causing agents with their good cousins - has been around since 1885. The problem with it remains: Good bugs are hard to find. Hillman's version of replacement therapy could demonstrate to a whole generation of scientists that helpful bacteria aren't just born, they're engineered. Ulcers and arteriosclerosis are now thought to be infectious diseases, too, and could be the next targets of elegantly made bacteria. That's something to smile about.
- Charles Graeber
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