A Superbug for the Teeth

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The Food and Drug Administration (FDA) just gave its go-ahead for a clinical safety trial using a genetically engineered tooth bug to prevent cavities.

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As described in Good Germs, Bad Germs, oral microbiologist Jeff Hillman has spent nearly a decade trying to bring his cavity-fighting Streptococcus mutans to human trials. Ordinary Strep. mutans is the culprit behind tooth decay. It does its damage by excreting enamel-eroding acids.

Hillman needed three steps to create his "probiotic" replacement strain in the mid-1990s. First, he found a naturally occurring strain of Strep. mutans that could elbow out anyone's pre-existing version. One kind of Strep. mutans or another colonizes virtually all of us around the time we sprout our first baby teeth. And once in place, our native tooth bacteria tend to stick around for life.

Scores of researchers have spent decades trying to rid the mouth of its entrenched tooth bugs, with no success. Once Hillman found a natural Strep. mutans that could do the replacement job, he knocked out its gene for acid production. Unfortunately, that pretty much killed it. The bug needed to excrete acid to dispose of its waste.

So Hillman knocked in a gene for an alternate route of waste disposal--alcohol production. Hillman lifted this gene from Zymomonas mobilis, the bacterium used to make "pulque," or Mexican beer. No, the resulting creation didn't make enough alcohol to make anyone remotely tipsy. However, it crossed the line from natural probiotic to "transgenic organism." After years of successful tests in animals, in 1998, Hillman became the first to approach the FDA requesting permission to use such a live transgenic in people.

FDA reviewers required him to install a failsafe-a way to get rid of the bacterium should it ever, for unknown reasons, cause trouble. He knocked out more genes-rendering the microbe unable to survive without a twice-daily supplement of an amino acid. To keep the bacteria alive, volunteers would need to swish daily with a mouthwash containing this nutrient.

Still, the approval dragged on, with Hillman learning that the FDA had lumped his tooth bug in the same category as potential bioweapons. Finally, in 2006, Hillman's company-Oragenics-was allowed to proceed with a mini safety trial-two people with full dentures that they could plunk into bleach at the end of a week.

This week Hillman got word that the FDA has approved a real safety trial. "Actual humans with real teeth!!!" he exults. "Young, healthy males." The volunteers will be isolated in a biohazard ward for the study's one-week duration.

For all the Frankenbug implications around transgenic organisms, I'm excited to see this research move forward. Tooth decay is no mere nuisance for the hundreds of millions of children and adults without access to dental care. Even here in the affluent US, untreated cavities are again on the rise, most likely due to the rising costs of dental care and dental insurance.

Okay, this post is going on too long. For a more disturbing alternative to fighting tooth decay, here's a track back to a post on Antibiotic Gum. For Oragenic's somewhat slick description of Hillman's tooth transgenic--the company calls it SMaRT, for Strep. mutans Replacement Therapy-- go here. And for Hillman's scientific description of the bug's creation, go here.

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