Keeping Watch Over Synthetic Biology
The next Ethics Center forum: "Synthetic Biology: Who's Watching," is Wednesday, September 1, at 5:30 pm.
MAUREEN CAVANAUGH (Host): I'm Maureen Cavanaugh, and you're listening to These Days on KPBS. Some scientific research is easily understood by the non-scientist. If a study is looking into how alcohol affects the liver, or why bees are leaving their hives, we can all get the nature of the question and even grasp some of the methods involved in the research. But other forms of scientific endeavor are a lot more challenging to understand, such as synthetic biology. Now as I understand it, scientists are using chemicals to mimic and sometimes change DNA sequences and create new cells. This emerging field is opening up a world of potential and a host of challenges that this breakthrough is used in an ethical way. As part of our monthly series on ethics in science and technology, today we will be exploring the emerging field of synthetic biology. I’d like to introduce my guests. Mike Kalichman is co-director of the Center for Ethics in Science and Technology. Mike, welcome back.
MIKE KALICHMAN (Co-Director, Center of Ethics in Science and Technology): Good morning.
CAVANAUGH: And Bob Friedman is California director for the Venter Institute. And, Bob Friedman, welcome to These Days.
BOB FRIEDMAN (California Director, Venter Institute): Thanks very much.
CAVANAUGH: We’d like to invite our listeners to join the conversation. What is your reaction when you hear about scientists creating new cells or making synthetic DNA? Does it make you happy you live in a time with such possibilities? Or does it make you concerned about the misuse, the potential misuse, of this research? Give us a call with your questions, your comments. Our number is 1-888-895-5727, that’s 1-888-895-KPBS. Bob, before we talk about synthetic biology, give us a crash course. What is traditional genetic engineering?
FRIEDMAN: So we have been modifying organisms starting with bacteria, sometimes we move to plants, modifying their DNA to do useful things for about 35 years. And the DNA of a cell, using a not totally accurate but reasonably informative analogy to computers, is like the operating system. And scientists have figured out ways in the, quote, traditional genetic engineering recombinant DNA technology to take a gene, a piece of DNA that accomplishes a specific function, from one organism and put it into another or eliminate a gene from one organism so that that organism does things that we would actually prefer, something that we find useful. A classic example’s one of the first products was we engineered bacteria to produce human insulin. Prior to that, diabetics were beholden to the insulin supply that would come from cows and, you know, other mammals.
CAVANAUGH: Similar to us but not quite the same.
FRIEDMAN: Exactly. And now we are able to, using bacteria, produce human insulin that can then, of course, be a boon to diabetics all over the world. So that’s one of the products of recombinant DNA technology. Obviously we also all are familiar with genetically modified plants, the soybeans, corn that we all eat have been modified for resistance to herbicides, too, to help out against pests, so on and so forth…
FRIEDMAN: …so productivity goes up.
CAVANAUGH: And in this recombinant DNA engineering, so to speak, let me be clear there, you take the existing DNA from a cell and combine it with the DNA from another organism’s cell in order to be able to engineer that particular gene.
FRIEDMAN: That is correct.
CAVANAUGH: How long have we been doing that?
FRIEDMAN: So seriously since about 1975. I would say the products of biotechnology started appearing in about 1985, 1986. That is when actually the federal government began an effort to regulate the products of biotechnology and that, again, that regulation began in 1986. It’s now 2010, we have quite a few years of experience in dealing with the products of biotechnology.
CAVANAUGH: So now what we’re talking about, though, in synthetic biology is taking this idea one step further. Tell us what’s different about synthetic biology from what we just heard in genetic engineering.
FRIEDMAN: So, much of the activity that scientists in the lab would be involved in was just in this sort of physical manipulation of DNA, try…
CAVANAUGH: Sort of mix and match.
FRIEDMAN: …trying to get it to do…
FRIEDMAN: …what you want the chemical sequence to be, the chemical sequence that you had…
FRIEDMAN: …imagined and various estimates that, you know, this might’ve been half the time is just sort of getting to that step that you could actually do some science to find out what it will do. Now, it is possible on one of the technologies that we can do now is that we can sequence DNA, we can read DNA, we can store the genetic code in a computer. It is now possible to take that genetic code—and, again, we have been doing this for quite a few years—and chemically assemble that DNA in the order that we would see it in nature and rather than have a scientist do all this work in the lab, they can order it almost as a commodity. Type in there ‘sequence the chemical’, sequence that they would like, order it from a company over the internet…
FRIEDMAN: …have it delivered and then they can use it for their science. And this has allowed us to do some things that we couldn’t do rather than to say, for example, single gene manipulations. We’ve been able to move up to perhaps 10 or a dozen genes and so rather than being limited to human insulin, which actually turns out to be a fairly – just a small number of genes involved in the synthesis, there’s a company up in the Bay Area that is now synthesizing artemisinin, an anti-malarial drug, that is actually a fairly complex biological synthesis and they’ve been able to do this using this new technique of synthetic biology where you can sort of mix and match in a way that you couldn’t do before with natural DNA.
CAVANAUGH: Now to get us to where we need to go in this conversation, I want to bring us up to just this past May. Your institute, the Venter Institute, Robert – Bob, made a pretty large discovery. You created the first synthetic cell. Tell us about that.
FRIEDMAN: So let me say a little bit about what that means and what we’re saying – what we’re calling a synthetic cell. So we started with, and as I mentioned before, now you can mail order a gene order from a synthesis firm, pieces of chemicals about a thousand bases long, each of those individual chemicals are called bases. That’s the size of a typical gene. You can order several together, maybe 10, and that’s kind of the limit of the synthesis, and use that in your biotechnology operation. What we did was to order lots of those individual pieces and were able to assemble what’s called the chromosome, the complete set of genes within a bacteria, about a million chemicals long, take that what could be considered the complete operating system of a cell and transplant that chromosome into another bacteria, a different…
FRIEDMAN: …essentially a different species, and watched it take over the characteristics of the chromosome that we synthesized from these pieces of chemicals. And one would say, again following the computer analogy, perhaps that’s like loading a new operating system into your computer but it’s a little bit different. If you were to buy a Mac operating system and put it into your Windows machine, you would all of a sudden get the better screen and your mouse would change…
FRIEDMAN: …and it would just all of a sudden look exactly like a Mac.
FRIEDMAN: That doesn’t happen. But that is what happened when we did that biologically by putting this chromosome in.
CAVANAUGH: Did you extract the chromosome that was originally there before you put the new one in? The synthetic one in?
FRIEDMAN: So it’s a very complex procedure to make sure that the original chromosome no longer reproduces.
CAVANAUGH: I see.
FRIEDMAN: The cell can accept. This was five years worth of work to figure out how to make a cell actually do that, how to accept, so on and so forth.
CAVANAUGH: So you, in essence, changed it into a new thing.
CAVANAUGH: We’re taking your calls at 1-888-895-5727, and we’re talking about synthetic biology, an emerging field that offers a world of possibilities but also is engendering some ethical concerns and that’s why we’re talking about it today. Once again, the number is 1-888-895-KPBS. Let’s go to the phones and hear from Al calling us from Normal Heights. Good morning, Al, and welcome to These Days.
AL (Caller, Normal Heights): Good morning. I’m 63, and when I was a young boy you could walk into any shoe store and have a clerk hit you with x-rays because at the time x-rays were new. Everyone was content that they couldn’t possibly hurt you. It sounds to me like genetic manipulation’s no further along. How do we know that genetic manipulation is not going to produce a new strain of disease maybe like ebola…
CAVANAUGH: Thank you. Thank you, Al, for that. Is that part of what you think about when you do your work, Bob?
FRIEDMAN: Absolutely. So the biosafety implications, what that means not only to an organism getting out of the lab—and, in fact, we carefully control the lab so that they cannot leave—but concern for our own workers and the federal government, through the National Institutes of Health, has very strict guidelines on how this sort of research must be undertaken, what sorts of protective measures must be taken. So I certainly agree with the caller’s concerns. I think that our understanding of the care that we must take with new technologies has changed considerably since those days when shoe stores were allowed to put x-ray machines in to help them sell shoes.
CAVANAUGH: We’re taking your calls at 1-888-895-5727. Izzy is on the line from Carmel Valley. Good morning, Izzy, and welcome to These Days.
IZZY (Caller, Carmel Valley): How’s it going? Thank you for having me.
CAVANAUGH: You’re welcome.
IZZY: My question is, is do you think synthetic biology will cause many people who are already on the border of atheism and theological beliefs, it’ll cause them to potentially tip over to more of an atheist viewpoint?
CAVANAUGH: Thank you for the call, Izzy. And I think, Mike, this is why you have the Center for Ethics in Science and Technology. What – Can you take…?
KALICHMAN: Yeah, sure. Well, the purpose of the center is not to tip people to the atheist viewpoint.
CAVANAUGH: No, certainly not.
KALICHMAN: But it is to ask these questions. So, first, to address the caller’s question directly, I think science is what it is, whether it’s synthetic biology or anything else you see in science and technology and each individual has to look at that and decide whether that’s part of their world view. I could easily argue that this could tip people in the other direction. They could say if the beauty and the wonder of what humans are able to do would only be possible because of what my religious faith tells me. But the Ethics Center is asking these questions now to help address Al’s question, which came up first, and that’s the fear that a new technology might be misused or dangerous. We want to ask the questions up front, have the public understand better and the public have input into those questions so that we will proceed as well as possible.
CAVANAUGH: Bob Friedman, why go the step toward synthetic biology? Why not just continue doing traditional genetic engineering? Why take that additional step?
FRIEDMAN: So I think there are two real benefits to be achieved by the new technology. I think under the traditional approaches we’re limited by two things. One is just the physical ability to manipulate DNA. The second is our understanding of how cells really work, and some of that is related to just the physical difficulty of doing the experiments. The driving force behind this set of experiments, which our group, Craig Venter, Ham Smith, Clyde Hutchinson, John Glass, at least some of them have been pursing this for about 15 years. The real driving force was to produce a, quote, minimal cell, a cell that could be used as an experimental organism. Remove all the very specialized genes to really understand how biology works. When one understands how biology works and, again, being able to manipulate the technology is the reason or is giving one the ability to get to that very simplified cell, once you really understand the biology then that gives you the opportunity to produce products whether it’s bacteria that can help us produce renewable fuels that take carbon dioxide from the air or using sunlight or new pharmaceuticals, these sorts of things, but it’s that enhanced understanding that will let us get there. And I should add at this point that that chromosome that we synthesized, that operating that we synthesized, was really almost identical to a natural one. This was a proof of concept. This was a test of sort of the first baby steps getting us there. We made some changes. We made it less able to produce any sort of harm. We identified ourselves within the genetic code. But we’re still pretty much limited in the science into what we can actually create.
CAVANAUGH: Okay, so taking your analogy, Bob, with the operating system in a computer, you changed a PC into a Mac but as this research goes along will you be able to change the computer operating system into a computer operating system no one has ever seen before, not just switch it around to something that already exists but actually create something that does not exist in nature?
FRIEDMAN: So let me – does not exist in nature. Let me – let me just stop with that a little bit. I think the hope would be that we would create that sort of yet another operating system. Would it – When you look at similarities between a Mac operating system and a PC operating system, they really operate very much on the same set of principles. Are we going to be smart enough to design these entirely new set of principles? That’s a stretch. Will we be able to learn from nature and duplicate some of the things that happen in other organisms in other parts of nature and combine them in ways that may be more useful? I think that’s closer to the goal.
CAVANAUGH: I – I think that I understand. We have to take a short break. When we return, we will continue a really fascinating discussion about synthetic biology and take your calls at 1-888-895-5727. You’re listening to These Days on KPBS.
CAVANAUGH: I'm Maureen Cavanaugh. You're listening to These Days on KPBS. My guests are Mike Kalichman. He’s co-director of the Center for Ethics in Science and Technology. And Bob Friedman is California director for the Venter Institute. We’re talking about a synthetic biology. It’s in conjunction with an Ethics Center Forum, "Synthetic Biology: Who's Watching?" And we’re taking your calls at 1-888-895-5727. Let’s hear from Lance calling us from Escondido. Good morning, Lance. Welcome to These Days.
LANCE (Caller, Escondido): Good morning. My question is what’s the difference between what you’re doing and what a virus is doing?
FRIEDMAN: I’m not certain I exactly understand the question.
LANCE: A virus is coming in and interjecting its genetic code into an existing cell’s genetic code.
FRIEDMAN: Right. So to the extent that – I mean, that is correct that viruses can do that and can incorporate themselves and, in fact, perform useful or harmful functions. It’s all a question of what is the function of the gene of that piece of DNA that is being inserted. So, yes, we can incorporate pieces of DNA into the genetic code that are self-reproducing and, you know, the important part is what is the function of that piece of DNA and what do you hope to accomplish?
CAVANAUGH: Right. Yes, Mike.
KALICHMAN: Yeah, this isn’t my area of expertise but I would sort of expand on it a little bit. A virus is bringing in a limited amount of genetic information, hijacking an already functioning cell and taking – making use of the machinery that’s in the cell. The difference here, as I understand it, what the Venter Institute has done, is the entire genome has been, in effect, replaced in that cell so it’s not hijacking the existing machinery but actually inserting machinery from outside and…
FRIEDMAN: That is correct.
KALICHMAN: …Bob can tell me if I’m correct.
FRIEDMAN: That is exactly correct and I’m sorry, Lance, if I misinterpreted your question.
CAVANAUGH: But that – Yes, okay. Lance thank you for that call. Let’s hear from Gail calling us from Tecate in Mexico. Good morning, Gail. Welcome to These Days.
GAIL (Caller, Tecate, Mexico): Good morning. Thank you. Interesting program, as usual. We talk about ethics in medicine and that seems to come to a full stop when we look at the experimentation that’s done on millions of animals in this country. Does synthetic biology use animal experimentation or are you moving away from that?
FRIEDMAN: So the capabilities that we have right now with synthetic genomics—and I’m delighted that you asked this question—is the bacterium that we were able to create used a chromosome that it was about a thousand letters of genetic code long. Humans are about six billion letters. We are so far away with this technology at this point to actively synthesize an animal chromosome that it is hard to – it’s hard to envision the sort of laboratory techniques that one would use to get there.
CAVANAUGH: So, in other words, you’re not anywhere near testing on animals.
FRIEDMAN: No, not even close.
CAVANAUGH: Okay. What could this be used for? What could synthetic engineering translate, though, into real world applications as you move down the line on this, Bob?
FRIEDMAN: So I think there are a couple that are most promising. Obviously, San Diego is sort of – is a hotbed of biotechnology activity and one of those areas where lots of folks are trying to come up with renewable ways to produce fuels for our – transportation fuels, transportation fuels that perhaps can use sunlight to collect energy and be neutral in terms of the carbon dioxide that they give to the atmosphere, so that’s one. A whole host of more complicated pharmaceuticals than are within reach right now, and then mention a third area, being able to synthesize DNA also allows us—it’s not just a chromosome of a bacteria but we can synthesize and, more simply, we’ve been able to do this for years, a virus. And why would we want to simply – to synthesize a virus? Right now we’re working on a project where we hope to anticipate next year’s seasonal flu, and perhaps pandemic flu as well. Rather than having to wait for a specimen to be collected, for example, in Indonesia or Thailand and shipped to the United States and then sequenced and then worked on by our current traditional methods, it is possible to sequence the virus that we observe in nature right away, take a look at it, perhaps even, if we’re smart enough, have those all on the shelf already synthesized knowing what it is. We think these thousand – that next year’s virus will come from these thousand alternatives, and cut off about a month of time that then the vaccine manufacturers need to start production.
CAVANAUGH: Right, right.
FRIEDMAN: So these are some of the opportunities that this new technology should allow.
CAVANAUGH: We’re taking your calls about the emerging field of synthetic biology, its promise and its challenge, and taking your calls at 1-888-895-5727. Maurice is calling from Oceanside. Good morning, Maurice. Welcome to These Days.
MAURICE (Caller, Oceanside): Ah, thank you so much. Thank you for receiving my call.
CAVANAUGH: Yes. What is your question?
MAURICE: Well, my question is, you know, all that sounds really wonderful, you know, how that bioengineering, genetic manipulation will help humanity, etcetera, etcetera. You know, but how we doing with the, you know, Monsanto? The Monsanto mega corporation example that have been able to manipulate seeds to the point that, you know, practically have destroyed the lives of many small farmers in Mexico, for example. You know, you know, like they have grown so big, they have so many lobbyists, you know, they have grown incredibly out of control, you know. What you do when that happens?
CAVANAUGH: Maurice, thank you. And, Mike, the idea – has anybody been thinking about the commercialization of synthetic biology?
KALICHMAN: Well, I’m sure that many people in the field are thinking about eventually commercializing what they have. But I think if we take Maurice’s question more broadly, it’s one of the reasons we want to talk about these issues up front, is to anticipate where the challenges are. He’s absolutely right. There’s a potential, when you come up with a new technology that some people, such as small farmers, might get shut out in one way or another. I’m not going to speak to specifically what’s happened with Monsanto because I can’t say exactly how that’s played out in Mexico but I understand the concern. But counterbalanced against that is the reason that this technology’s being pursued, which is, for example, in a world where we do have scarce food resources, we’re looking for ways to try and deliver product, do better, and society needs to be involved in conversations about what we’re looking for in that and how we’re going to balance the needs, for example, of small farmers.
CAVANAUGH: Let’s take a call from Robert calling from Anza, California. Good morning, Robert. Welcome to These Days.
ROBERT (Caller, Anza, California): Well, good morning. I really appreciate your programming and the gentleman that is speaking. A lot of adults are concerned about this. It seems to be I haven’t heard anything from housewives or children or whatever and maybe they’re all at school. Now this is a great area to get into. I know I heard one time that silk worms are getting engineered to produce different color silk. But my main issue here is how can children maybe from babyhood like a little kid there two years old playing golf on the internet, you know, for those of you have seen that, all the way up to where your job is, how can you design a roadmap, an educational roadmap, to get from there to where you are?
CAVANAUGH: Robert, thank you so much. Is there – We talked a great deal about getting kids involved in science on a program we did yesterday. Any quick tips, Bob or Mike, on how to get kids involved in becoming scientists?
FRIEDMAN: Well, one of our program areas at the Venter Institute, which we’re very proud of and which I must say is active in our – we have two campuses, one in Maryland and one in San Diego. San Diego is new. We are just starting out here. We have an active education program where we really focus on middle school kids because that’s where you really grab their interest in science. And we would dearly love to duplicate that program in San Diego. We’re in active discussions on that. We think it’s vitally important that the next generation of kids with as wide an exposure as possible, we concentrate on underserved areas right now, have the opportunity to benefit from all these new advances.
CAVANAUGH: Let me ask you, you know, Bob, from this analogy that you used with the computer and the computer operating system, you must talk about your work with non-scientists on a frequent basis. I wonder, what is their reaction?
FRIEDMAN: All over the board. I think there are some people who absolutely focus on the opportunities and others who focus on potential downsides. And, you know, I think it’s very important, as Mike said, that we sit down as a society and we just understand what those benefits will be and what those potential downsides will be.
CAVANAUGH: What do you hear about potential downsides most often? What are people most concerned about that you speak with?
FRIEDMAN: Well, so perhaps I am focusing – well, I’ll answer this in a way…
FRIEDMAN: …that I think is more of interest to a government audience but I would say the first reaction to this new technology was if we could synthesize a virus for a good person – for a good purpose, could a potential bioterrorist synthesize a virus for harmful purposes? And we undertook a two-year study along with colleagues at MIT and another Washington, D.C. think tank focusing on security issues, to come up with ways, which are now proposed in the government’s federal register…
FRIEDMAN: …to avoid the harmful effects. I would say from the general purpose, from the general audience, I think it’s probably the environmental potential and environmental concerns that are the issue at the top of that agenda. And, of course, we and others are working very hard to make sure that, you know, that the good from these technologies clearly outweighs the – any risks to the environment.
CAVANAUGH: Mike, I’m going to give you the last word. The title of your Ethics Center Forum is "Synthetic Biology: Who's Watching?” So do we know who’s watching?
KALICHMAN: Yeah, so there are a variety, as Bob just mentioned, there are a variety of government regulations that oversee what we’re doing here. And I think if we go back to your initial statement at the beginning of this segment, which was that this is really complicated, in some senses it’s not that complicated. There’s – These are things that have been done before and the first steps here are fairly clear. What’s complicated is that all of the possibilities are out there, and we can imagine things way down the line that haven’t happened and things that we know can happen. Right now, our question is, given where we are and what we worry about, what’s the best way to address it and that’s – and we may or may not have what we need in place now so that’s why the public, again, should be involved in talking about this so we can do as well as possible.
CAVANAUGH: Mike Kalichman, thanks so much.
KALICHMAN: Thank you.
CAVANAUGH: And Bob Friedman, thank you for speaking with us.
FRIEDMAN: Thank you.
CAVANAUGH: I want to let everyone know the next Ethics Center Forum: "Synthetic Biology: Who's Watching," is Wednesday, September 1st, at 5:30 p.m. And you can go to KPBS.org/thesedays for more information. You can also go to KPBS.org/thesedays to comment on what you’ve heard on the show. Stay with us for hour two. These Days continues here on KPBS.