Saturday, May 22, 2010

Hail Mycoplasma

My cousin posted a request on my facebook wall for my thoughts on the synthetic cell news. I'm answering by blog because I'm still shocked and appalled with the recent revelations that Mark Zuckerberg is going to sell the name of the high school I attended to the Kraft marketing department for something like 40 million dollars.

I'm considering the issues and controversy surrounding this new strain of mycoplasma, the smallest known organism, now being entirely driven by a synthetically created genome in a lab run by Craig Venter. Additionally, since I think that one reason why the general public maintains this area as such a hotbed of brawl is that many scientists like to awe their audiences by explaining things in terms that no one can understand, leaving the ordinary lay person with just their imaginations. I don't think this is the right approach, and I hope to be able to describe the science in a coherent manner. But in terms of the issues surrounding the synthetic cell, I think they can be broken down to potential benefits (including both human health and agriculture/energy), potential hazards (terrorism and epidemics), and the moral question of playing God.

What Venter's group did was to piece together a mycoplasma genome designed using only a skeleton crew of genes required for the organism to live, remove the genome of a natural mycoplasma, and inject the new synthetically created genome. The first thing to point out is that this kind of genetic manipulation has been going on for a long time, where in essence scientists harness the machinery of a living cell to respond to and interact with whatever gene or genes you care to transmit into it. Artificial DNA has been shuttled into all different sorts of cells, plants, and animals for years. Moreover, entire genomes have been replaced by others by our hand (we've cloned mice, sheep, even humans if only the Raelians hadn't been called back to the mothership). What's unique about this event is that the entire genome being replaced in the mycoplasma is artificial. But to say that we've made some huge leap in biological technology with this synthetic cell is inaccurate.

But what is huge is the future potential.

Venter has a vision where he repeats the same procedure on algae, using a stitched-together genome whereby the new synthetic cell would consume CO2 and emit biofuel. Exxon has promised his company something like $600 million if he succeeds. The other major use in the health care industry is practically limitless in scope. Insulin-producing cells for diabetics, healthy blood stem cells for leukemia patients, degenerative diseases cured, spinal cord injuries gone...all possible. Abundant and sustainably designed crops, nanotechnology, everything Gibson and Stephenson wrote about, all likely.

Sounds great, right? As a biological scientist I can say with absolute certainty that yes, the possibilities flood my mind. Especially given the current work I'm doing unraveling a signaling pathway that keeps cells in an undifferentiated stem cell-like state, it's tremendously exciting to think about the potentials. And yet like everything, the fact that there are so many possibilities means that the potential for harm may likely come from a direction we never considered.

The scary flipside to the fact that this technology is not wildly difficult to carry out, coupled to the public availability of every gene sequence, is that it opens an avenue for harm which is as limitless as the potential benefits. And unfortunately, unlike nuclear non-proliferation treaties where the technology in question is rather complicated, the ability of a global genetically modified organism treaty to effectively suppress bioterrorism is pretty low. The technology to create a genome expressing whatever disease-causing gene you like is here, and the hundreds of sequences of these genes are all available to anyone with internet access. From this vantage point, the genie is already out of the bottle. What then would be able to stop some whackjob from creating an artificial viral genome in his basement that expresses an airborne HIV? Probably not much.

Equally as unsettling is the impact of unforeseen changes that may occur in the new genome. Venter's group took care to remove any known pathogenic elements from the mycoplasma genome they built, necessary steps to save the goats (a known animal to be infected by mycoplasma). Funny that didn't calm the bleating goat activists down, but their point isn't a baseless one. It's unknown what the effects could be if some spontaneous mutation changes the organism so that it goes viral resulting in something that infects the planet like kudzu and turns us into rapid zombies. Put that way sounds unlikely, however the fact remains that although we are able to translate the genetic code, the meaning behind it still remains mostly elusive. We know of many mutations that are linked to disease, but the mechanisms behind the mutations are still largely unknown. Thus it may absolutely be said that we scientists by tinkering with genomes are opening an untold number of Pandora's Boxes.

Well, yes, that is in fact our job. Most of the best discoveries in the lab have been because some researcher with a mischievous glint in their eye decided late one night to mix some things together just to see what happens. It's a rare event that a discovery of something anticipated occurs. So the day I stop tinkering is the day I'm out of a job.

The last issue about "playing God" I find to be something of an irritating knee-jerk reaction that may be due in part to the lack of education the public receives about genetic technology, which is unquestionably the industry's fault. First off, to reiterate, genetic manipulations have been occurring for years and so far as I know there are still no C.H.U.D.s after us. More importantly, I truly believe that our ability to grasp the technology and interpret the genetic code is in fact evolution, therefore it's in the natural order of things to be able to manipulate it as well. Clearly some government oversight is necessary such as for human cloning, but even more important is that counter-terrorism labs are established that stay one step ahead of technology that could cause potential harm. Ignoring the technology would be the worst course of action.

Overall though I think it's a great thing, I prefer Madam de Stael's suffering to boredom and think that facing these things head on is superior to head in sand. A careful and thoughtful approach is necessary, starting with how this technology is introduced to the public. I was struck the other day when I read the chirpy term "green biotechnology" to refer to the once ominous "genetically engineered crops". Discourse matters, and having a fearful, uninformed general populace helps no one. That's what we could focus on today, and hopefully by tomorrow, I will have figured out how to make these new mycoplasmas do my laundry.

Lastly, there's a great TED talk by Venter a couple of years ago where he discusses his project. You can find it here:
http://www.ted.com/talks/craig_venter_unveils_synthetic_life.html

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