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 Moreover, entire genomes have been replaced by others by our hand (we've cloned mice, sheep, even humans if only the Raelians hadn't been called back to the mothership).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:

Sunday, May 9, 2010

Being an Off-Roadie

My sister came to tour through Europe. For those of you who I haven't mentioned this to so many times you want to stuff cotton in your ears my sister is Amanda Palmer and she has a job as a rock star. Being the sister of someone whose job it is to be widely adored is a uniquely advantageous position, one that finds most of the lovely trappings without having to do any of the actual work. A fine example of this fact is the past week.

Amanda arrives in Amsterdam for a show in the middle of the European tour exhausted. The ashcloud had grounded her flight in, sadly, Iceland, and then forced upon her several ferries over the North Channel involving many sick bags. She has professed her disgust for the whole event by showing up in a tshirt loudly stating "F*CK THE ASHCLOUD". She is not very shy, my little sister. For her troubles she did, however, command an impressive headline in the Boston Globe which read something like, "Amanda Palmer Late, Still has Twitter Access". I'm still shaking my head.

Holly Gaiman has also arrived from London to work the merch table.
Holly is the daughter of Amanda's fiancee, Neil Gaiman, a very nice man who writes for a living. I have felt very protective towards his daughter ever since I went to rescue her from a date in a London club my sister had auctioned her off on for $750.

The show in Amsterdam is a Wednesday night at the Melkweg, a club found on one of the city's many incredibly narrow streets across from a police station. The driver of the band's van celebrates this setting by smashing into the side of a police car parked on the street and breaking off the mirror. Apparently this happens all the time, and they are all released in time for sound check. The show begins with more of a musical theater act consisting of conjoined twins named Evelyn and Evelyn, the other twin being played by Amanda's sidekick for the tour, Jason Webley. They play a number of instruments with one of each of their hands including the piano, guitar, drums, accordion, and the ever-present ukulele. Even I, with less musical talent than Vanilla Ice, know that this must have taken an enormous amount of practice. A few more wrong notes than usual, but highly impressive nonetheless.

A lovely shadow puppet story explains the background of the twins and involves a murderous physician and a truckload of chickens. It is unfortunately marred by the stage getting the wrong light, which ends up incinerating the eyes of the entire left side of the floor audience. Then Jason and Amanda each play solo acts and that's it. The show has delighted the large number of students from my lab who I have saturated the guest list with, although I pay for it dearly the next day at work by everyone singing the "Chicken Man" song incessantly.

Speaking of the next day, my sister had asked if I would like to get on the van with them and drive to their next show in Hamburg and then onto Berlin for the weekend, where I already had a train ticket booked. I said no, I had to work, be a respectable citizen, excuses that led her to spit out that I needed much more rock and roll in my life. Perhaps she had a point, for I find myself sitting at my desk that day staring at the 98th draft of the paper that I still haven't submitted feeling like the biggest twit. Luckily Europe is famous for low budget airlines that you have never heard of, and within a few minutes I'm happily booked to Amanda's show in Prague the following week on the unfortunately named Wizz Air.

But first Berlin. It's Queensday in Holland as I take leave, much to my delight since this holiday turns the country into the equivalent of Bourbon Street on Mardi Gras except even worse because it's raining and everyone is wearing orange. Five hours of pleasant slack jawed window staring later I'm at the Berlin train station. This is another of the brilliant things about Europe, the trains. It's so quick and easy to step on and find yourself in the center of another country before you've even finished your beer in the club car. Of course it helps that I live in a tiny place bordered by three different countries, all of which I can see from my roof, but still. Love a good train ride.

Berlin is a very cool city. It has all of the magnificent grand old buildings that are found in most major European cities, but is also permeated with a more recent and fascinating history that can make the antiquity seem somewhat irrelevant.Our British cousin lives there with his wonderful German wife and kid, who were the gracious hosts of Amanda's birthday party that night. At least a dozen close friends and family members turn up including a guy playing a show that night whose band was subtly named Kill Hannah after his ex-girlfriend.

Amanda celebrates her birthday with true gusto and aplomb, the result of which is the necessity of a large blue bucket being present next to her on the stage the following night. Luckily she doesn't need to use it, but it's close. Watching her cringe and suffer this category five hangover under blistering spotlights and I have never been so glad not to be a rock star. Calling in sick one day just isn't an option. A car in Belfast once ran over and broke several bones in her foot yet she still hobbled on stage that night to do her job, whereas any other sensible person would have been propped up on ten pillows demanding ice cream and another Percocet.

It is therefore no surprise that when we meet up in Prague the next week she announces to me that she's quitting her job (this is something she assures me that she says at the end of every tour). However this time I believe her sentiments are exacerbated by the venue's poster of her, which looks like something you might receive at the deli counter if you ordered melons with Serrano ham. (If you look closely you can see her reflection seething). So I take her out for a nice Czech beer and she calms down.

Prague is a very beautiful city that like many other Eastern European cities maintains an eerie juxtaposition of lavish old empires frozen in time by the Iron Curtain. Like every American in her 20's I backpacked through Prague years ago, and was happy to find that the relative inexpensiveness of the city still held true. However so did the taxi scams, one of which attempted to charge me the equivalent of over €60 for a 3km fare. Only by threatening to call out my hotel concierge (in my experience, the only ones actually concerned about you getting ripped off and having a bad stay) did the driver let me out of the cab for a quarter the fare and not take me to the police station or nearest ATM, as he was threatening. Which leaves me wanting the share the following advice, when in Prague, use the metro.
Now is when it really starts to get fun.

I arrive backstage. Backstage, unless you were with Guns and Roses in the mid 80's, is usually a place best avoided. The crew is either running around cursing under their breath because they've misplaced the hex wrench or can't fit everyone on the guest list or trying locate the one corner of the room that has decent enough wifi to skype their girlfriend and where the hell is their laptop anyway. You do not want to be in their way.

Amanda first has to entertain 3 televised interviews in a row, including Czech MTV. As far as I can tell they all ask the exact same questions, but then again I'm helping myself to the cheese plate and miss most of it. Adrian Stout of the Tiger Lillies shows up, the self professed "World's most foremost Death Oompah band", who I remember as the only band at the Fringe Festival to feature a song about hamster buggery. They are, in short, a band worth getting to know.

As this Prague show is a last minute add-on, they do rock star sets instead of the more theatrical Evelyn and Evelyn, which is fine because it means more rowdy people can be packed in without the chairs lining the floor. Gaba Kulka who's down from Warsaw opens, then Jason plays. To me he's a bit like Tom Waits with a few of Ian Curtis's seizures thrown in. One of those, "I just smoked a pack of Camel straights with a quart of JD and I can't wait to do the same thing after lunch.." voices.
But truly great songs.

Amanda is in fine form, covers Billie Jean, has Adrian on stage to play the musical saw (with a violin bow) to the Tiger Lillies "Flying Robert",
and celebrates her tour manager's birthday with a sparkling cake followed by letting him sing "I Love How You Love Me" to send through youtube back to his boyfriend in Seattle who he still hasn't been able to skype. Then everyone gets on stage for the obligatory drinking song and the tour is over. Not quite, there's a sea of people who want merch (unfortunately the venue's poster sells out first) and various bits of things signed by the band who, despite being utterly knackered, are stand up enough to do it. Backstage Adrian and I use the puppets to celebrate with an impromptu "There Ain't Nobody Here but us Chickens" by Louis Jordan follwed by a hazy late night dinner that involved roast duck and some nice police officers, but I don't really remember.

The next day is drizzly so I take in the lovely Uměleckoprůmyslové Museum, which I think is Czech for "little old gorgeous things that look like a pain to polish". Lunch is at Ariana, a small Afghan restaurant that 13 of us literally crash like downloading every google map at once. It's not so much that there is only one waiter and even fewer people in the kitchen, it's more that said waiter is so starstruck by one of Jason's friends, a Czech celebrity, and more to the point that his hero has brought a pile of books for the boyfriend of the American girl with no eyebrows to sign. I thought the poor guy was going to wet himself, or at least take three hours to get the lunch out and forget my entree (he ended up 2 for 3, at least as far as I know).

Great week.