Dr. Andre Marziali

From 2011.igem.org

Team: British Columbia - 2011.igem.org

Interview with Dr. Andre Marziali

Director of Engineering Physics; Associate Professor, Biophysics; Associate, UBC, MSL; Platform Director, GenomeBC Technology Development (Dr. Marziali's Bio)

1. Do you think synthetic organisms should be released into the wild?

This isn't something I've put a ton of thought into, since we don't work in that space, but my first impression is to be extraordinarily careful. Releasing something with an evolutionary advantage runs the risk of perturbing the system in a big way; looking to Australia, you can see examples of humans introducing new animals into the environment. At first glance you might not expect the impact to be huge but entire species go extinct as a result of a shift in the existing networks. These systems are so cross-connected and I don’t think there are any really good models of what an outcome might look like, at least not that I’m aware of. My take is that a release should be heavily controlled; it makes it harder to do research, but you have to watch the outcomes closely.

You can certainly decrease the risks, but ultimately it becomes a question of how big is the problem that you're trying to solve and how bad that problem is versus the potential and the size of the risk. That's going to be a difficult decision to make.

2. What standards would you recommend for their release?

To me it doesn’t even have anything to do with the fact that these organisms are synthetically engineered, it’s that they’re not not native. You could test it in a closed greenhouse-type environment where everything can be incinerated afterwards so that nothing escapes. But even if you show that it fixes the pine beetle problem your greenhouse isn't going to contain the entire ecosystem, so it's hard to predict what the ultimate effet will be and how well it will spread. Until we have a good model for knowing, which seems to me to be decades away because of the complexity, we can’t really predict how a synthetic organism would behave if released.

You could engineer susceptibility into the organism, but you'd have to study closely how well that would work and if it could evolve around it. Even then, these studies would depend heavily on time and number of organisms; say you release an organism and it takes you a couple of years to notice that it's spreading in ways you don't expect. Trying to control it at this stage, the population size is big enough so that you might get some evolution of resistance. And now you're in real trouble.

3. What challenges are there in terms of attaining public acceptance?

I think you have an enormous challenge there. We know there's an environmental shift happening and we know that that could be devastating but it will still be perceived as being largely natural, even if it's caused by human beings. Releasing an engineered pathogen into the system is going to alarm people and I think the biggest problem is with the fear of the unknown. If people understood what the negative scenarios might be, that might be better but they might envision it as becoming a human pathogen or something equally devastating.

We've seen this battle lost over GMOs, in general, and at some point the public will be able to weigh the need versus the outcome. For example, at this point people in this country aren't starving; when that day comes people might have less objections to genetically modified foods. I think what was learned from how GMOs played out was that we largely need to get the public involved early in the process. You can't go very far down the road and then expect that you're going to educate the public; that's sort of condescending. If you look at what the local Genome Organization's been doing over the last decade, a lot of it has been setting up public exhibits that discuss genetic risks. They've done a pretty good job of that, to the extent that there's not as much resistance, I suspect, to genetic testing for disease as there would've been ten years ago.

4. What future directions do you see for synthetic biology?

I haven't had a ton of interaction with people who work in that space, but we've had discussions around synthetic biology for petroleum degradation. But that's the only one I've heard of at all, and because it's in that industry I have no idea where it's at.

5. Do you think we should be rewriting the code of life?

Yes. I think there will be uses of synthetic biology that are confined enough and there could be human clinical applications that would be quite useful. Our understanding of complex networks is minimal and I don't know if we'll improve a whole lot; the numbers are just terrible, making it difficult for a lot of reasons to model. Things like internet, for example, evolved more than it was designed and it just happened to be largely beneficial but there's a lot of negative aspects to it that have occurred that we could never have been able to control and couldn't control now, things like the ability to spread information and self-organize.

Perturbations to networks are hard to predict. I'm not so concerned about engineering living organisms, but I'd be very worried about releasing them or what the impact would be because ultimately you're looking at an evolutionary process, something that's hard to predict. I certainly believe doing the research will help our understanding and since we're not the only people on this planet doing this kind of research, I think that we'd want to know what's possible and not possible.