In some cases, it seems that regulators are forcing researchers to go to near-impossible lengths to ensure safety despite no conceivable risk. (Hillman’s cavity-fighting tooth bug?) In other cases, researchers appear to be rushing ahead with no one stopping them.

Carl highlights what I consider a prime example of the latter issue in “Darwin at the Drugstore” (subsection “Skin of the Frog”). He describes how Michael Zasloff, the researcher who first began developing antimicrobial peptides (AMPs) as a new class of anti-infectives felt sure that bacteria could never develop resistance to them.

It took a clever evolutionary biologist, McGill’s Graham Bell, just one summer to prove Zasloff wrong.

But that hasn’t stopped other researchers from rushing forward with new AMP “antibiotics,” some of which have now entered clinical trials.

Why does that make some, including myself, so nervous?

Antimicrobial peptides are the human immune system’s front line of defense. As part of a concerted immune response, they don’t prompt the evolution of resistance in bacteria. But when used in isolation (like an antibiotic), we now know they can and do breed resistance.

So are we risking the rise of genes that will make bacteria resistant to the body’s own AMPs? We’ve seen how fast antibiotic-resistance genes proliferated through the bacterial world over the last 60 years. There’s no turning back the clock on that one. But this ups the ante!

So back to Carl’s wise question: “Are we really just getting started thinking about this stuff?”

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?

“So viruses may or may not be alive, but they are definitely a part of life.”

And as John and several commenters point out, viruses sure as hell evolve!

Still, I find myself in the gotta-have-metabolism camp. To me, that’s the dividing line between chemistry and biology.

As Carl notes in the section “The Shape of Life,” (page 20), “But on their own, genes are dead, their instructions are meaningless.”

I’ve heard viruses described as “escaped genes” … albeit inside nifty protein packages. But as Carl says, MICROCOSM is less about distilling definitions as it is about understanding the rules. In that vein, on page 21, he writes,

“The most obvious thing one notices about E. coli is that one can notice E. coli at all. It is not a hazy cloud of molecules. It is a densely stuffed package with an inside and an outside.”

So life has “boundaries,” an inside and an outside that must be actively maintained.

As cool as bacteriophages look with their lunar lander profile, they are mere snarls of chemicals in and of themselves.

First, as the other science writer on the panel, I’d like to express my appreciation for Carl’s way with a metaphor. I think for many of us, what makes science writing take flight are these wonderfully unexpected yet perfect comparisons that convey understanding along with a flash of sensory fireworks. For instance, Carl describes a (eukaryotic) cell’s stained chromosomes as looking like “crumpled striped socks.” Perfect! They really do. Another literary allusion made me laugh out loud. But I hesitate to give away for risk of spoiling its effect for those who haven’t read the book yet. It comes at the end of the first graph on page 21. My daughter, a Shakespeare fanatic, will love it.

Well, I’m posting from a VERY SLOW dial-up connection from a remote cabin off the coast of British Columbia. Friday I’ll catch a ride up island to the radio-connected Internet Center to post more. Till then, I’ll wrap up this plain post with a question for Carl. It’s an old question, I know. But since Carl’s book centers around “what is life?” I get to indulge my obsession with it.

Carl, twice in the book you refer to viruses as “creatures.” Perhaps you used the word metaphorically. In any case I’d love to know whether you think viruses qualify as being alive, and I’d love to hear your reasoning either way.