A life-altering experience
Rice student Thomas Segall-Shapiro played role in creation of synthetic cell

BY MIKE WILLIAMS
Rice News staff

For a budding scientist, this has to be the greatest payoff ever to a summer job.

	THOMAS SEGALL-SHAPIRO

Thomas Segall-Shapiro ’10 earned his Rice University undergraduate degree a few weeks ago and last week got something else that was pretty great: co-authorship of what may be the most significant scientific paper of the 21st century so far.

Segall-Shapiro is one of 24 authors of the paper published online by the journal Science that announced the creation of a bacterial cell controlled by a chemically synthesized genome.

The native of Chevy Chase, Md., spent his last two summers in the Maryland lab of the J. Craig Venter Institute (JCVI), founded by the entrepreneurial scientist who in the 1990s challenged the federal government in a race to decode the human genome. (Their success was announced jointly in 2001.)

Venter’s group assembled and implanted a synthesized genome into a mycoplasma capricolum and replaced the cell’s original DNA. The new genome successfully “rebooted” the cell, took over its operation and reproduced normally. Imbedded in the genome are “watermarks” that contain the names of people, famous quotes and, according to the authors, a website address.

The paper was widely discussed in the days after its debut, with some scientists claiming the project is a step toward discovering the origin of life itself. President Barack Obama immediately ordered a study of the research and its implications.

Segall-Shapiro is no stranger to notoriety. He was part of Rice’s bio-beer team that, in 2008, won a gold medal in the International Genetically Engineered Machine (iGEM) competition and earned worldwide media attention for its process to brew beer with resveratrol, a naturally occurring health supplement.

Segall-Shapiro agreed the new paper would look good on a resume as he prepared for graduate studies in synthetic biology at the University of California at Berkeley, though “it’s kind of intimidating,” he said. He noted another recent paper, on which he was the second of three authors, dealt more specifically with the type of error-correction research he did at JCVI.

“I will be able to say ‘I knew him when,'” said Segall-Shapiro’s mentor, Jonathan Silberg, a Rice assistant professor of biochemistry and cell biology.

“I think this is great for incoming freshmen to see,” Silberg said. “Thomas was able to get involved in a synthetic biology project during his freshman year through participation in the iGEM competition. Because he got involved in research so early, he was in great position to make a contribution to this cutting-edge project during his internship at JCVI.”

Segall-Shapiro talked this week about the paper, the reaction and what it all means.

Rice News: How long has the synthetic cell study been complete?

Thomas Segall-Shapiro: They got the final results to verify the paper relatively recently. But they’ve had some of the piecemeal parts for a while. … They were able to fully synthesize a bacterial genome in 2008, for example – though the synthesis of the genome used in the most recent work was begun only a little over a year ago.


RN: So it happened pretty fast?

TSS: There was a lot of previously published work leading up to this accomplishment, and this was the final pass-through. If you look at the sources they cite and you see how many came out of JCVI, it’s around half, I think. You can see how much work went into the project – they broke it down and published each section individually. And this was their “We’re done” paper. It’s pretty cool.

RN: How did an intern get to be co-author of such a significant paper?

TSS: The Synthetic Biology Department has 20 to 30 people. There were a couple of interns there, and it really depended on what you were working on. If you got a little chunk of the project and worked on it for a while, and they considered that you contributed enough or something you did got put in the paper specifically, you got credit. The scientists at JCVI tend to be pretty generous with putting interns on papers – I definitely know a few others who got published.


RN: What was your part?

TSS: I was working on an alternate strategy for the troubleshooting and error-correcting part of the paper, in case the method they ended up using didn’t work as well as they thought it might. And their method worked. But some of the other stuff I did, an approach for checking to see if the genome was fully assembled, ended up in the paper. It’s a tiny, tiny part, but they figured it was good enough, I guess. 


RN: How did you get the internship?

TSS: I just applied. I’d seen their paper on synthesizing the (genome of mycoplasma) genitalium, and realized they were on the cutting edge of synthetic biology. I got selected by a bioenergy researcher in the synthetics group my first year. Then last year I was set up with my mentor (co-author Ray-Yuan Chuang), who was working on the synthetic cell project.

RN: What’s been the reaction at Rice?

TSS: I’m pretty low on the authorship list, so a lot of people just miss it, which is fine with me.

RN: And you’ve already had a share of notoriety around here, as part of the bio-beer team. …

TSS: Yeah, but considering this project actually got to a close, I hope it supersedes the bio-beer stuff.

RN: A bioethicist called this discovery “as momentous to our view of ourselves and our place in the universe as the discoveries of Galileo, Copernicus, Darwin and Einstein.” What do you make of that?

TSS: It’s a little bit overboard. I’ve read some stuff that’s a lot less enthusiastic than that. A lot of people are going for synthetic life from the angle of, “Can you make all the molecules that are required to start life in the first place?” That’s clearly not what was done here.

Eventually this method will define a whole life form because it all comes from the genome, but it’s still missing the creation of that spark of life. I think that’s still out there to be done.

RN: Do you think it will be done?

TSS: Probably. There’s a lot of very interesting research on that front. A lot of RNA work with self-replicating molecules that’s getting closer to life.

RN: Is that what you will pursue?

TSS: It’s interesting, but that’s theoretical and basic evolutionary biology, and I want to stick with more established organisms to go for more useful stuff. 


RN: Do you see potential to cure diseases and make synthetic fuels?

TSS: That’s where this is probably going to end up being really useful.

RN: Some point out that the technology created in this project is the major achievement.

TSS: I agree with that completely. It’s really all the little papers leading up to this one that will see the most use. This just showed, “Look, all our methods are good enough that we can do this. Now go and use the pieces.”

RN: When the paper was released last week, President Obama immediately ordered a study of its implications. Do you have any concerns about safety?

TSS: At the moment, it’s really not any more dangerous than current DNA manipulation or genetic engineering. … I don’t really see this technology as being more dangerous until we get a much greater understanding of how genomes work, at which point, I hope, some of the dangers will be mitigated.