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Where's the Line?

By jessica.sachs on June 10, 2008.

i-7cce95b26c573f4aa3cee118155325b4-jessica_sachs.jpgYikes. Carl, how am I ever going to get that "parahuman" image out of my head!

I get your point. This image evokes the abhorrent reaction that early critics had against the idea of tinkering with any life, even "mere" E. coli.

Most people start to squirm when the transgenics concerns animals, especially when it produces visible "mutations." Today, I suppose that most people are comfortable with the idea of transgenic E. coli churning out useful chemicals inside sealed vats. We harvest and purify the chemicals. No harm done. Right?

So let's take the safety question one step further. In researching Good Germs, Bad Germs, I spent time with researchers who were busy seeding people's bodies with transgenic bacteria. Government regulators remain extremely jumpy about such research. For good reason?

One of the first examples involved using E. coli's kissing cousin, salmonella, to destroy cancer tumors. Researchers engineered the microbe to express a tumor destroying drug--but only when it reached cancerous tissue. It never went beyond one small clinical trial in one hospital, given the daunting task of convincing FDA regulators to approve expanded use.

Meanwhile, down in Florida, Jeffrey Hillman has spent a decade convincing the FDA to allow him to use his cavity-fighting Strep. mutans. Hillman isolated an unusually aggressive strain of this ubiquitous tooth bug and showed that it would elbow out a person's native Strep. mutans. He then engineered it to secrete alcohol (not enough to get you tipsy) instead of tooth-eroding acid.

Before allowing Hillman to introduce the bug into human mouths, FDA regulators required him to cripple it--so it could be removed in case of trouble. What kind of trouble? No one could say. But this is weird stuff, right?

Bottom line, Hillman knocked out the bug's ability to create a vital amino acid. So volunteers must feed it with a special mouth rinse to keep it alive.

A cavity-fighting tooth bug may not be a problem if it escaped and took up residents in other mouths. Heck, why not spread such a good thing?

But what about a microbe engineered with the ability to turn off the human immune system? That's what Lothar Steidler has created in Europe. In clinical trials, he's using it to treat patients with advanced cases of agonizing Crohn's disease--in which the immune system attacks the intestinal lining.

Here's the part that will scare some people: Steidler took a cheese bacterium and gave it a human gene for IL-10, the cytokine that tells the immune system to "stand down." He, too, knocked out genes to nutritionally cripple his transgenic. What's more, he did so in an elegant way that ensures that the bug can neither repair itself (to become nutritionally competent) nor spread its IL-10 gene to other bugs without making them nutritional cripples as well.

So does this stuff cross a line? Is it wildly reckless or the future of medicine?

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Can't it be both? It's reckless in that we can't "know" for a fact that something Really Bad won't happen, but until such time as it does or does not occur, these advances are the future of modern medicine.

As for crossing the line, I suspect there isn't one written in the sand. Every time we think that science won't go further, it does anyway, in some beneficial way.

So what happens if a non-Crohn's-having person takes Steidler's transgenic?

We saw the exact same thing in Jurassic Park--nutritionally crippling the sauropods so they couldn't live long without some special enzyme in their diet. And as everyone knows, it didn't work. Of course that's fiction, however just this week at least three Science Bloggers here, including Zimmer, posted on the evolution of E. coli in the lab due to nutritionally limited conditions that the bacteria evolved around. My question is, how would you prevent the same thing from happening to Strep. mutans, for example?

Can't it be both? It's reckless in that we can't "know" for a fact that something Really Bad won't happen, but until such time as it does or does not occur, these advances are the future of modern medicine.

As for crossing the line, I suspect there isn't one written in the sand. Every time we think that science won't go further, it does anyway, in some beneficial way...