Manmade Genome Controls A Cell
IRA FLATOW, host:
This is SCIENCE FRIDAY from NPR. I'm Ira Flatow. Scientists report this week they have created what they call a synthetic form of life, a cell that is in part natural, part manmade, and the man who made the cell is here to talk about it. That would be Craig Venter, who says he has created a synthetic genome.
At a press conference yesterday, Venter said the new bacterial strain was, quote, "the first self-replicating species we've had on the planet whose parent is a computer."
The work, though, is not without its critics. Friends of the Earth, an environmental group, denounced the work, saying Dr. Venter has, quote, "taken genetic engineering to an extreme new level and that Dr. Venter should stop all further research until sufficient regulations are in place."
What do you think? You can join our conversation at sciencefriday.com, or you can tweet us @scifri. Also, you can give us a call, 1-800-989-8255.
Let me introduce my guest. J. Craig Venter is the founder, chairman and president of the J. Craig Venter Institute in Rockville, Maryland. He joins us from our NPR studios in Washington. Welcome back to SCIENCE FRIDAY.
Dr. J. CRAIG VENTER (Founder, Chairman, President, J. Craig Venter Institute): Thank you, Ira, nice to be with you.
FLATOW: Thank you. Let's talk about what you've actually done. You took the genome from one cell and put it into another strain of the same organism. Would that be wrapping up...
Dr. VENTER: Well, that's what we did in 2007. This time, we started with the digital code from reading the genome in the computer, four bottles of chemicals and chemically made the over one million base pairs of the genome.
It was finally assembled in the eukaryotic cell, Saccharomyces, which is the brewer's yeast. We then isolated the bacterial chromosome from the yeast cell and transplanted into a bacterial recipient cell.
After it was transplanted, it took over the cell and transformed that cell into an entirely new species dictated by the synthetic chromosome.
FLATOW: Did you have to take out the chromosomes from that cell first?
Dr. VENTER: No we didn't. Years ago, we thought we might have to do that. We think there's one of two possibilities. When the new synthetic chromosome goes in and starts being read, some of the genes that are initially expressed include the restriction enzymes that my friend and colleague Ham Smith got the Nobel Prize for in 1978.
We think they recognize the chromosome already in the cell as foreign material and chew it up. So we have the cell of one species and the chromosome of another, and as that new synthetic chromosome gets read, it starts making all the new proteins coded for by that chromosome, and then that cell turns into the new species coded for by the chromosome.
FLATOW: So basically you created the same cell that already had existed.
Dr. VENTER: So we absolutely, we copied, in this case, heavily from the Mycoplasma mycoides genome, the one that we'd been working out all these transplant experiments with over the last several years because if you can imagine, 99 out of 100 of our experiments haven't worked, and this has been almost a decade of complex problem solving to get to the point.
So we wanted to start the experiments with something that we at least knew would be compatible with life.
FLATOW: And how do you react to some of the criticism that I read at the beginning, that this is a little bit too dangerous at this point?
Dr. VENTER: Well, we expected - even though we've been raising issues and discussions on this since the 1990s. In fact, the first bioethical review was published in 1999 before we did the first experiments, and that's a review that we had asked for.
We were concerned that despite all the discussion there's over 100,000 blogs on the Internet before this publication that still this would be the first time the majority of people heard about this research. And we figured there would be some of the usual shock and responses to it.
So it's not anything new to the molecular biology community and people trying to understand something new and complex and having knee-jerk responses. But the fortunate thing, it's less than one percent of all the responses that have been out there.
FLATOW: In fact, some of the more well-known members of the molecular biology community, I'm just going to quote one of them, David Baltimore, who is a Nobel Prize-winning geneticist at Cal Tech, is quoted in the New York Times today as saying: To my mind, Craig has somewhat overplayed the importance of this. It's a technical tour de force, a matter of scale rather than a scientific breakthrough.
Dr. VENTER: Well, David's entitled to his opinion, but we haven't played up the importance of this at all. We've described what we've done. It's other scientists and people around the world that are attributing what the importance of this breakthrough is.
This is something we've worked 15 years on. It's a very critical milestone in our work and our ability to do things, and I think it is an important milestone in what can be done in science.
FLATOW: Well, tell us what the practical applications might be.
Dr. VENTER: Well, what we started out 15 years ago to do was to understand the minimal cell and to understand what those genes do in a cell. Despite all the knowledge that we supposedly have in the biological and scientific community, we do not know anything about the complete components of even the simplest bacterial cell.
We don't know what all the genes do. We don't know which ones are essential, which ones aren't, what makes them essential. So here we're trying to understand the human genome that my team sequenced 10 years ago, and we yet do not understand the simplest bacterial cell.
The goal was to create a synthetic chromosome so we could vary the gene content, understand what was important, understanding whether gene order was important. It had very basic science components and motivations.
It's clear over the last 15 years of thinking about this research and other people thinking about it, it's a new toolset that has a number of potential applications.
When we started out doing this, nobody knew how to make even a 5,000-letter piece of DNA accurately. Now we're making a million base pair pieces of DNA accurately. So we had to develop a lot of this technology over time. And that technology, the first thing people probably see, possibly as soon as next year, is the flu vaccine that you get could come from these synthetic processes.
FLATOW: And so it's possible, and with this bit of advance of technology, to tailor-make, then a bacterium that will do, that will be a factory for something you want to make. Is that fair?
Dr. VENTER: That's clearly the hypothesis. And the reason for that is when you look at what's been capable from existing molecular biology techniques and anything that we know about that's out there, including all the GMO crops that Monsanto and others have, less than a dozen genes have been changed in any commercial product to date. It's a big deal even changing a few genes.
It took DuPont $100 million and over 10 years to make a dozen changes in E. coli, to go from sugar to making propanediol.
FLATOW: So now you think you might be able to just dial it up in a computer? Like you say, the parent of this was a computer, and tailor-make the genome and stick it back in a bacterium?
Dr. VENTER: If biological knowledge was sufficient to do it on first principles, yes, but we're not there yet. So there will be definitely a lot of empiricism with this, which is why it's important to get to a minimal cell, understanding what are the components that are absolutely necessary for life, and then can we add back components specifically that we want, for example in the case of trying to make fuels from carbon dioxide, to increase the efficiency of CO2 conversation into hydrocarbons that could go into refineries, as an example.
FLATOW: You went around the world collecting algae. Algae is a target of your research. I see from reading your articles that Exxon is prepared to spend up to $600 million.
Dr. VENTER: It's definitely a target to try and see if it can be scaled up. If these processes can't produce the billions of gallons needed to start weaning us off oil, they're not going to have any impact, and thus far, there's not a single naturally occurring algae strain that we're aware of that has the properties necessary to get to that scale. So it's going to need genetic engineering.
Whether the first strains used are just changing a handful of genes or not, it's not clear. The second generation and onward will all be synthetic organisms where we can control the 50-plus parameters to really get stable production of fuels.
FLATOW: Can we stop making vaccines with eggs?
Dr. VENTER: I sure hope so.
(Soundbite of laughter)
Dr. VENTER: You know, the synthetic genomics won't result in that change, but companies that we're working with, like Novartis have a $300 million plant in North Carolina ready to go with MDCK cells to get much more rapid and better production of the flu vaccine. So hopefully, the FDA will move us ahead two centuries now.
FLATOW: So it looks like this is a proof of concept.
Dr. VENTER: Absolutely. That's the best description.
FLATOW: Yeah, that you can get this done. So where do you go the next step? What other next step and proof of concept do you need?
Dr. VENTER: So, you know, some people have made a big deal that we started with an existing cell. That's been part of the strategy. We're trying to build on top of three and a half billion years of evolution.
But one of the key questions is: How far apart can the synthetic chromosome be genetically from the systems that are in the cell, the ribosomes to make the proteins? We need something to kick-start the genome. We don't know how few components we need, but we know we need to be able to make messenger RNA and to have proteins made initially. That may be all it takes because then the rest will come from the genome.
So how far afield can we go? These are pretty close relatives. These are about the same distance as human and mice are. So they're pretty compatible systems. We need to see if we can do this with more complex bacteria, microorganisms, such as algae cells, to really affect things.
Mycoplasmas are very simple cells, and you couldn't have described it better, and that's how we've described this, as a proof of concept. This organism wasn't designed to do anything practically except prove it's possible.
FLATOW: And so then you move up into more complex organisms and see if it works there.
Dr. VENTER: Yes.
FLATOW: Yeah. All right, well, thank you very much for taking time to be with us, and good luck to you in your research.
Dr. VENTER: Thanks, Ira.
FLATOW: J. Craig Venter is the founder, chairman and president of the J. Craig Venter Institute in Rockville, Maryland, and he joined us from our NPR studios in Washington.
We're going to take a break, and when we come back, we're going to talk about stem cell research, not quite the same sort of research that Dr. Venter was talking about in this case.
But we've heard a lot of news about stem cells. Where do we stand? What's the state of stem cell research? Are we going to see any real breakthroughs? Are there any things on the horizon? What about embryonic stem cells? Are people still talking as much about them as they are before? Are they still as valuable of a product to work with, or are people stuck on adult stem cells? We'll cover the whole waterfront on this. Our number, 1-800-989-8255. You can tweet us @scifri, @-S-C-I-F-R-I. Stay with us. We'll be right back, talking about stem cells after this break.
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I'm Ira Flatow. This is SCIENCE FRIDAY from NPR.
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