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Bull Session

Engineering Synthetic Biology

April 7, 2016          

Episode Summary

On The Digital Life this week, we chat about the intersection of computer science / engineering and synthetic biology and Cello, a programming language for living cells.

At the Massachusetts Institute of Technology (MIT) and Boston University (BU) synthetic biologists have created software that automates the design of DNA circuits for living cells. This software, called Cello, has the potential to help people, who are not necessarily skilled biologists, to quickly begin designing useful, working biological systems. Using Cello, oil companies, for example, could develop smart bacteria that could clean up oil spills. Cello, which is open source, can be downloaded from the online repository GitHub or accessed via a Web interface.

Resources
A Programming Language for Living Cells

Jon:
Welcome to episode 150 of The Digital Life, a show about our adventures in the world of design and technology. I’m your host, Jon Follett, and with me is founder and co-host, Dirk Knemeyer.

Dirk:
Greetings, Jon.

Jon:
This week on the podcast, we’re going to chat a little bit about a programming language for living cells and the intersection of computer science and synthetic biology. This programming language is called Cello, C-E-L-L-O, and it’s-

Dirk:
Maybe pronounced Cello. We don’t know.

Jon:
We have no idea. Yeah. It was put together by synthetic biologists at MIT and Boston University. It’s essentially software that automates the design of DNA circuits for living cells. The purpose of the project was to help people who are not skilled biologists to quickly be able to design working biological systems. The way Cello works is, the user specifies what kind of cell they’re using and what they want to do with it. For example, the cell might sense a certain metabolic condition and then produce a drug in response, or it could sense the presence of oil in the water and then produce an enzyme that degrades the oil for cleaning up after oil spills. You could have a bunch of bacteria that do that kind of work. It’s actually using an existing computing language called Verilog, which has been used by electrical engineers for a while. That’s how the circuitry, the DNA circuitry is specified, and then Cello translates that information to design the DNA sequence. Take it from there. You have this bacteria that can do any number of things for you.

This is a really significant step, I think, in that we’re beginning to see this abstraction layer being built for creating synthetic biology. It’s really enabling people who don’t have this biology background to operate in this abstraction layer much in the same way as you would with computer programming. The engineering underpinnings that go into the app explosion of recent years, or even if you just look at the way desktop software has exploded from the ninety eighties onward. There’s lots of things that you can do with your desktop computer that was created by folks who don’t necessarily know how the circuitry works or really even care. They’re able to program on top of this and then we have access to music, movies, what have you, e-commerce, any number of things. In the same way, Cello is giving access to these engineers to the biological circuitry. It’s not unfathomable that you or I could learn this programming language and download Cello from GitHub, like any other open-source project, and start hacking away and seeing if we could come up with the next, latest and greatest bacteria application.

To me, this is a first step in the explosion that I’m sure is to come for synthetic biology. Dirk, what’s your impression of this programming language?

Dirk:
You’re a lot more deeply steeped into synthetic biology as a field, so for me, I’m full of wonder and fright. If I download this and I can program in the language, could I program you to give yourself caner, if I got mad at you? Are we getting an amount of control at our fingertips over the biological self, that we could make our bodies revolt? That sounds like the path that we’re headed down, but obviously, the technology isn’t that far yet. Help me to better understand. What’s the gap between that dystopic future and where we really are today?

Jon:
In your example of programming cancer, I think you’d have a couple gaps there. The first of which, we’re talking about some very simple biology like these cells for E. coli or similar microorganisms that are much less complicated in terms of changing their DNA than you would encounter with a human being.

Dirk:
Sort of like Chess is a much simpler game than Go to figure out artificial intelligence solutions for.

Jon:
Yeah, that’s fair. I would say that you’re probably looking at more like Chutes and Ladders to Go. I’ll defer to the biologists in the audience to validate that particular metaphor. Regardless, I think part of it, too, is that the simple, single-celled organisms are also easily manipulated and have been for decades.

I, for instance, familiar with a biodegradable plastic product that was created by bacteria back probably about fifteen years ago, where the bacteria were engineered to suck in sugar and spit out this biodegradable plastic. The science, I think, is pretty well advanced in terms of tweaking microorganisms, whereas I think we’re still in the nascent stages of … You outlined the opposite of personalized medicine, which is more like a curse or something.

Dirk:
Attack my enemies.

Jon:
Poison, right?

Dirk:
Yeah.

Jon:
That is a major concern. Boston, in addition to having all this wonderful synthetic biology technology, also has within its reaches a research center for chemical and biological warfare, mainly to try to figure out what to do if any of these reagents ever surface. There’s a number of levels to the type of security clearance that you would need for this chemical and biological weapons, and I think it’s the highest level of clearance or close to it, that research center. The idea that these biological agents could be used for ill, it’s not lost on the scientific community in addition to maybe the fantastic, “Okay, we’re going to spill oil and then let loose the bacteria to clean it up.” There’s certainly the dark side to that, which we can see with hacking any sort of systems. We had that episode a few months ago about hacking our power grid, right?

Dirk:
Exactly.

Jon:
It’s interesting because I don’t think the level of attention has been paid quite yet to what the outputs of synthetic biology will be, and I think it will largely remain slightly under wraps, much in the same way that genetically modified foods have been off the radar. There’s a bit more hubbub now about wanting to label these foods, but for the most part, you’re eating genetically modified corn and other grains. We’re the big experiment in terms of whether or not these things are going to be detrimental or have no reaction to the human body at all.

I do think that there is, for whatever reason, and I don’t know if that’s especially strong lobbying or just ignorance on the part of people when it comes to biological organisms versus everybody’s now plugged into computers and grasp what identity theft and hacking and all those things are, it’s just not in the vocabulary of our culture right now to be discussing these negative consequences to biological alterations. Everybody now has a laptop or a mobile phone where back in the eighties, nobody had computers. I think we’re all going to start getting familiar with bio-inspired and synthetic biology products, so perhaps you’re hinting at a conversation that’s coming down the road in a little bit as people start getting more alarmed by the things that are possible.

Dirk:
It’s definitely where I’d jump. If you think about, in the physical world, the notion of a virus, we’re exposed to real viruses, and they materially change our bodies sometimes in rapid and horrific ways. Once we created the internet and once we created the virtual world, so to speak, now humans create viruses that attack that, similar to the Ukraine power issue that you mentioned earlier and destroy those things. This is sort of like the third level. We’re changing the world in a way that code can change our bodies, that code could, in theory, operate as a virus within us. The technology’s not there yet, yadda, yadda, yadda. It’s coming. That’s why I made the Chess Go poke.

What does that look like, and how can it be controlled? We sure as hell don’t control viruses on the internet. We certainly don’t control viruses in the hardware and software that we have today. That’s relatively easy to fix. You wipe your computer. It’s a day or two of hassle, and then you’re back and ready to go. If people can start rewriting the code inside of us in malicious ways, that’s nasty. This is science fiction at this point, of course, but because I’m not very well educated on these areas of science and engineering, that’s certainly where I go, not from the standpoint of like, “Oh my God. I’m so scared about this. We can’t let it continue.” I kind of take for granted that it’s coming inevitably, but I think we talk about a lot of technology and future things on this show. Of all the things we talk about, this is probably the one that I think is, for me at least, most alarming in terms of the potential consequences.

Jon:
I have a little bit of knowledge in this area, but I’m certainly no expert in terms of being able to evaluate the security or lack thereof of our human biology and what’s possible in terms of changing it as a result of some synbio product. I will say, however, that the outputs of synthetic biology, at least ones that I’ve seen so far, the results that you’re looking for in terms of when you make these changes to DNA, these things don’t always go the way you think they’re going to go when you’re programming.

Dirk:
Uh oh.

Jon:
What I mean is, in a lot of cases, they just don’t work. The DNA doesn’t come together in the way that you would expect.

Dirk:
The math and science suggests that doing this certain set of things would result in an outcome, but it doesn’t result I the expected outcome.

Jon:
Correct. I think I read there was a maybe seventy-five percent success rate with some of the DNA circuits that they were designing using Cello. It’s certainly not something that is a hundred percent certain right now. Even if someone had a malicious intent and was at the expert level that these scientists at MIT and BU are, which I would think you’d need to be, even then, it’s not really a guarantee that you’re going to get the results that you want.

Dirk:
I bet that’s changed remarkably by the time our children are our age.

Jon:
I’m sure of it. I think what we’re looking at is some of the early blips that come along when creating a new programming language, certainly. There is a question about … You can prototype code to see if things are going to work the way you want them to, and I suspect there will need to be some pretty robust ways to prototype synthetic biology, ways that are not dangerous to people. That’s an area that I’m very curious about, as well, because once you release things into the wild … I know I’ve heard folks talk about having, basically, biological kill switches, ways of preventing genetically modified organisms from reproducing or if they’ve run amok in some way that they can be shut down by introducing a certain enzyme to the system.

Dirk:
Say, this is where it goes very quickly, when we’re born, our DNA is immediately mapped, and if certain parts of our DNA are certain things, these things are turned loose in us to regulate or control or change our very programming right from the beginning.

Jon:
Right. I think we’re at the very edge of all of this science-

Dirk:
Meaning the beginning, way, way, way early. Yeah, I understand. It’s compelling, though. It’s interesting. Again, maybe it’s only compelling because of my ignorance. I need to get a long smarter on this stuff, but to me, it’s mind-blowing. The notion of robots and cyborgs and AI and some of the other things that we talk about, those have been prevalent in popular culture for so long. This, to me, is mind-blowing, the idea of the programming language over the biological structure is so different than what we’re used to. Certainly, some science fiction writers have written about it, but this is cool stuff. I really want to learn more.

Jon:
I think when I was doing some research and I’m sure this is old hat for folks who are generating DNA sequences in the lab, but you can create a DNA sequence and go and get that replicated at a lab now. If you had a particular one that you wanted to replicate, you could do that. Of course, they have their eye out so they’re not going to just go and create anthrax for you or what have you. You can go and order it and there’s a certain cost per base pair, and it’s relatively affordable. That really is nature’s design material in a lot of ways. It is mind-blowing, and at the same time, it’s very accessible insofar as we can see the results of what DNA does. I saw a quote that said, “You know, not everybody necessarily has access to computers, but we all understand inherently what biology is and what it does,” so in some ways, this is technology we all live with already. It’s just being made available for us to change it for the first time.

Dirk:
I’d put it differently. I’d say that it’s something that has always been part of the human experience and is now being revealed to simply be technology.

Jon:
I like that.

Listeners, remember that while you’re listening to the show, you can follow along with the things that we’re mentioning here in real time. Just head over to thedigitalife.com, that’s just one L in thedigitalife, and go to the page for this episode. We’ve included links to pretty much everything mentioned by everybody, so it’s a rich information resource to take advantage of while you’re listening or afterward if you’re trying to remember something that you liked. If you want to follow us outside of the show, you can follow me on Twitter @jonfollett, that’s J-O-N F-O-L-L-E-T-T. Of course, the whole show is brought to you by Involution Studios, which you can check out at goinvo.com, that’s G-O-I-N-V-O dot com. Dirk?

Dirk:
You can follow me on Twitter @dknemeyer, that’s at D-K-N-E-M-E-Y-E-R or email me, dirk@goinvo.com.

Jon:
That’s it for episode 150 of The Digital Life. For Dirk Knemeyer, I’m Jon Follett, and we’ll see you next time.

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