The Loom

New Life, New Patent

i-9b5a0eb0b125574f023f85bc789d18e6-venter smile.jpgFor the past few years, Craig Venter, the human genome pioneer, has been trying to build an organism from scratch. While Venter is no shrinking wallflower (see, for example, a recent interview in Newsweek), he has been keeping his synthetic-life cards pretty close to his vest. I spoke to Venter in 2003, shortly after he announced the project, and he provided some basic details which I wrote up in a news article in the journal Science (I’ve archived it here). I was startled to find my article being cited in scientific papers about synthetic biology, but one scientist (Eugene Koonin of NIH) told me that there was no scientific paper he could cite. But now it seems that Venter is turning over one or two of his cards.

Last night I got an email from Jim Thomson, a researcher at the environmental group Action Group on Erosion, Technology and Concentration (ETC Group for short). His group had dug up a patent application that Venter’s group has filed for their synthetic life project. You can read the patent application here.

The application is based on the J. Craig Venter Institute’s ongoing efforts to find the fewest number of genes essential for life. They started the project by selecting a microbe, Mycoplasma genitalium, that has only has 482 genes. They then introduced crippling mutations into each gene to figure out which ones are dispensable and which can’t be done without. In January last year they reported that 382 were essential. In the patent, the number drops to 381. As the application explains, it would be theoretically possible to synthesize a 381-gene genome and plug it into a genome-free cell, and–voila–boot up a new organism. This artificial genome could be engineered so that it can easily accept other genes to carry out new functions–such as producing cheap hydrogen fuel.

There’s no evidence in the patent that Venter has actually booted up a synthetic organism, but it’s worth bearing in mind that the patent was filed in October and is only now coming available. So at this point, Venter is claiming a patent for something he has yet to build. Another bit of murkiness (any patent lawyers out there?) is whether this patent only covers genes from M. genitalium, or covers any set of genes that are essential for any other species (or at least any subset of them). A lot of the essential genes in M. genitalium are probably relatives of essential genes in other species.

Despite the hypothetical nature of the patent, it does seem to mark a turning point. In the past, scientists have patented genetically modified organisms and individual genes. But now Venter is patenting an entire synthetic organism.

ETC says it is going to challenge the patent on the basis that it is contrary to public morality and safety. They claim that the public hasn’t had enough time to debate the ethics of Venter’s plan. These are definitely serious issues that need to be aired out as much as possible. And for some reason synthetic biology is not getting the careful scrutiny that stem cells are, despite the equally great hope and concern they inspire. So ETC is right on this score. But in the press release they’ve issued about Venter’s patent, they’ve thrown a few too many red herrings into tank.

“For the first time, God has competition,” says ETC’s Pat Mooney. Please. I’ve been nosing around in the history of genetic engineering for my upcoming book about E. coli, and remarks like Mooney’s give me a fierce sense of deja vu. In the early 1970s E. coli was the first microbe into which scientists inserted genes from another species. Much of the insulin diabetics use comes today from vast tanks of engineered E. coli. There was plenty of God-talk back then, with people claiming some sacred barrier had been breached. But no one has ever explained clearly why this barrier has any real biological or theological meaning.

Back in the day, people also warned of the grave dangers of genetically engineered E. coli, and ETC uses the same language. But rather than seriously considering the potential risks, they seem to be playing on the fear of the unknown. In the press release, Thomas tries to downplay the potential benefit of Venter’s beast and play up its potential harm.

“It’s purely speculation and hype that syns [synthetic living organisms] will be used to ameliorate climate change by producing cheap ethanol or hydrogen,” said Jim Thomas. “The same minimal microbe could be harnessed to build a virulent pathogen that could pose grave threats to people and the planet,” he said.

I don’t see how you can try to get people to ignore the benefits by calling them speculation and then turn around and get people scared about risks that are, at this point, speculation. In the thirty years that genetic engineering has existed, has anyone been killed by a genetically engineered microbe? When I interviewed synthetic biologist Jay Keasling for Discover last year, he put it bluntly: “If I wanted to do evil and do harm, I probably would not choose biology to do it. It’s damn complicated.” On the other hand, scientists are already making progress in producing ethanol from engineered E. coli and other microbes, so it doesn’t make any sense to call Venter’s proposal nothing but hype. Nor does the fact that BP is pouring hundreds of millions of dollars into synthetic biology as a way to make new sources of fuel.

ETC does raise a very interesting point, though. Venter is taking a very different approach to synthetic biology than many others in the community. He’s locking down patents. ETC is right in suggesting Venter might become “Microbesoft”–controlling operating system for anyone who wants to build an organism from scratch. Other researchers, such as Keasling, are promoting a different way of doing synthetic biology–what they call open source biology. Scientists and their students are amassing an open inventory of parts that anyone can use to design organisms of their own. And it’s open source biology, these researchers argue, that will provide the best protection against any evil uses of synthetic biology. Instead of being hidden behind patents, the information about these parts would be available to everyone, and collectively solutions could be found. As this debate starts to unfold, I think open source biology will keep it from becoming nothing but deja vu.

Comments

  1. #1 matthew
    June 7, 2007

    This is all extremely interesting, have you attempted to contact Craig Venter about any of this?

  2. #2 Torbj�rn Larsson, OM
    June 7, 2007

    I think open source biology will keep it from becoming nothing but deja vu.

    Now that is a framing I can support. :-)

    Umm, that would be the Genetoo’s of biology ( http://en.wikipedia.org/wiki/Gentoo_Linux ) ?

    But actually, the debate could be a bit more aggressive this time around. Creationists like to point out the lack of constructed organisms. (And when they get one, they will use it as evidence that the first cell must have been designed.)

  3. #3 Ross
    June 7, 2007

    >And when they get one, they will use it as evidence that the first cell must have been designed.

    I’m not sure about that. The Designer’s M. genitalium has 482 genes. Venter’s hypothetical organism has only 381. The M. genitalium seems about as well designed as a Ford Pinto by comparison.

    If the US patent office is willing to grant a patent to a gleam in Craig Venter’s eye, I’d like to patent a perpetual motion machine.

  4. #4 Fred Ross
    June 7, 2007

    Back in the ’70′s, one of the guys who was developing genetic engineering got so annoyed at people talking about genetically engineering superbugs that he took an E. coli culture and drank it down, then searched for the critters in his feces for the next month or so. No sign of them. Lab strains of E. coli are completely unable to survive in the wild.

    And frankly, cleaning up global warming with synthetic bugs would be a lot easier than building a pathogen. People don’t seem to realize just how incredibly subtle and difficult pathogens are. Most bacteria either do as their told by the immune system or just avoid humans (and other critters with immune systems) like the plague (well, plague doesn’t really avoid…nevermind). It might be a great tool for immunologists, though. Knock out certain classes of cells in mice, import certain structures from a pathogen into you synthetic bug, and really measure the interaction.

  5. #5 Jud
    June 8, 2007

    Carl Zimmer said: “Instead of being hidden behind patents, the information about these parts would be available to everyone….”

    Either you have an odd idea about the patent system, or you have the right idea and aren’t expressing it understandably.

    Patented information is published, not “hidden.” That’s the classic patent tradeoff – the inventor is given an economic incentive (the patent, i.e., the value of the exclusive right to control economic development of the invention) in return for giving up exclusive access to the information, i.e., confidentiality.

  6. #6 Carl Zimmer
    June 8, 2007

    Jud–I’ve tried to get closer to what I meant by fixing the text. It’s tricky with genes, since the information is, in a sense, the product.

  7. #7 sailor
    June 8, 2007

    “And frankly, cleaning up global warming with synthetic bugs would be a lot easier than building a pathogen.”
    What about the viruses people created?

  8. #8 factician
    June 8, 2007

    I saw a talk by one of the principal investigators (PI) at the Venter Institute in Toronto a few weeks ago. Their project to build “new life” is pretty cool, and a fair amount cooler even than Venter has described (though I would tend to call it highly genetically engineered life, rather than new life).

    They’re actually building the bug with new codons, so that redundant codons aren’t being used. This gives them the opportunity to go back later and put in synthetic amino acids using codons that currently aren’t in use. Very cool.

    The PI in question wouldn’t say how close they were to doing it, but given some of the progress they’ve made, I wouldn’t be suprised if they unveiled their bug by the end of the year. They’re very close.

    In terms of patenting, I think this issue was solved 20 years ago. Wasn’t the Chakrabarty patent the first patent of a genetically-engineered living organism? Wouldn’t this be the same, from a legal standpoint? From a practical standpoint, it’s just a more sophisticated genetically-engineered bug.

  9. #9 Jud
    June 8, 2007

    Thanks, the change is an improvement IMO. Possibly better yet: “Instead of having their use restricted by patents, these parts would be available to everyone….”

  10. #10 Kurt9
    June 8, 2007

    ETC is way off base here. The issue of whether Venter should receive the patent or not should be based exclusively on if the patent covers original, unique work or not. ETC’s complaint has nothing to do with this issue and is, therefor, without merit.

  11. #11 Jud
    June 8, 2007

    Kurt9 said: “The issue of whether Venter should receive the patent or not should be based exclusively on if the patent covers original, unique work or not. ETC’s complaint has nothing to do with this issue and is, therefore, without merit.”

    Actually, it has been held that inventions whose use would violate public morality lack the “utility” necessary to obtain a patent under U.S. law. The law under which the European Patent Office operates has a similar provision.

  12. #12 Jason_Usborne
    June 9, 2007

    I do so love this ethical puzzles! On the one hand we have a brilliant individual who is discovering various properties of nature which may be used in various ways to help or harm or to make new discoveries. In order to prosper in the current economic environment, the individual (or corporation, what have you) applies for patent protection from the holders of power. On the other we have a group of persons that feel that this somehow violates some universal fundamental, whose repercussions may unravel the very order of nature. Based on my current working model of how the mind is set up, I am sure there may be others in the world who are pursuing similar researches. Since this is a possibility, I feel that the discovers be allowed to continue their work. However, there is also the possibility that this work may in the long run disrupt other life forms or processes in unexpected ways. Therefore, I propose that work in these experimental areas of biotech or nanotech be conducted in orbit. Not only will the microscopic life forms and processes grow quicker and be protected from contamination, the current life fomrs wil lbe protected from the experiments. Do I hear a second?

    Oh yes… funding for spacelift: I propose a public lottery at around $20-$100 per person. Winner gets spacelift for 2 into orbit. It would be the ultimate honeymoon no? We could contract Richard Branson and his Virgin Galactic consortium or NASA or the Russians in Kazakstan.

  13. #13 Matt Bryson
    June 9, 2007

    All I can say is good on them if they actually manage to create a totally synthecised organism. The potential for this kind of breakthrough is huge (Not to mention the amount of money they could earn of it, which would be significantly larger than huge)

  14. #14 Bob M
    June 10, 2007

    The real root of this issue was the granting of patent rights for biological processes and entities. The research would still go on, with or without patents, just as the bugs will mutate once removed from the lab. Then what’s your patent worth? It’s like Linux vs Windows. Does it really matter in the long run who wins what, as long as people have a choice? Some will take one side and some the other. Arguing about which is right or wrong is moot. I agree with you Carl; a tempest in a teacup over deja` vu. Life goes on regardless, that’s biology!

  15. I was searching for a good comment on Craig Venter’s new patent and I’m glad I ran into yours! My whole issue is the notion of patenting processes (not just biological, but virtually any manufacturing process) and patenting organisms in itself.

    Patenting processes stunts innovation and creativity aside from being generally unfair. Patenting organisms is just ludicrous. Even if the organism is made in a lab. Bartonella rochalimae was “discovered” in a lab, I don’t think that means it’s a patentable commodity.

    I’m definitely for open source biology. And chemistry. And physics. And hopefully many of us atheists could start another front through which to criticize these corporate ambitions.

  16. #16 Merry
    June 14, 2007

    Carl, in defense of the safety of synthetic life, you wrote: In the thirty years that genetic engineering has existed, has anyone been killed by a genetically engineered microbe? Clearly, this was a “witty” comment to score a point for your side. You probably assumed that anyone reading your blog would have enough sense to know that safety in these situations is not defined by immediate human fatalities, but would include lesser damage to human health AND any damage to the web of life on which we are completely dependent. But jazzy comments like this get quoted out of context and passed around and soon you find your neighbor telling you that scientists say that such developments are safe.

    Re: another point, you and some of your commenters have joined Venter in dangling the carrot of cheap, limitless bio-produced fuels in front of a gullible public. Many people don’t stop to think that for every calorie of energy we get out of such fuels, more than one calorie had to be “fed” to the bacteria. We can ask the bacteria to transform energy from one form to another which suits us better, but they can’t make energy from nothing. Perhaps people are thinking of photosynthetic bugs harnessing unlimited energy from the sun. It ain’t so. In 2001, human energy consumption was 2-4 times the total global photosynthetic energy production.

  17. #17 factician
    June 15, 2007

    But jazzy comments like this get quoted out of context and passed around and soon you find your neighbor telling you that scientists say that such developments are safe.

    But they are safe. Or at least as safe as one can say that anything is “safe”. Any genetically engineered microbes used in industrial production are the bacterial equivalent of a lobotomized quadriplegic with hay fever. If they get out of industrial confinement, they won’t live very long. The synthetic organisms being built now are likely to be even more messed up. We’re designing organisms that will be very good at one job. That comes at a sacrifice, they’re much less able to survive in every other condition that they could find themselves.

    In 2001, human energy consumption was 2-4 times the total global photosynthetic energy production.

    That’s an interesting statement. If true, then we really are screwed when we run out of oil. Reference?

  18. #18 Carl Zimmer
    June 15, 2007

    Merry: I appreciate your raising some important points, although I’d also appreciate it if you didn’t also sneeringly imply I’m some sort of shill. My responses:

    1. Risk from genetically engineered organisms. If you’ll go back to the controversy in the 1970s, it was the opponents of genetic engineering who raised the specter of death–from epidemics of cancer to germ warfare. They made a prediction, and I see no evidence that this particular prediction was fulfilled. If you know of other evidence, please share it.

    It is certainly true that one could imagine there might be other effects of genetic engineering beyond immediate human fatalities, including environmental effects. But you do not offer any evidence that the E. coli that was modified in the 1970s to produce insulin, etc., had any such effect.

    It’s also conceivable that other examples of genetic engineering, especially modified crops, could have ecological effects. (See here for a recent study.) But there are some obvious differences between E. coli and these crops: the first are microbes that are feeble and can only thrive in laboratories, while the others are free-living and interacting with the environment. I’m not saying that Venter’s bugs are necessarily safe, but what is the evidence that they are necessarily dangerous?

    2. You say that I am “dangling the carrot of cheap, limitless bio-produced fuels.” Where did I say limitless? Why stick words in my mouth? The question of whether Venter’s bacteria could produce a viable alternative source of energy without a harmful downside is certainly a legitimate one, though. We are now supporting our energy needs by mining the photosynthesis of the past. Can any alternative–such as a synthetic organism that produces hydrogen–make up the gap?

  19. #19 Merry
    June 15, 2007

    Sneer not intended. As to “limitless,” my error. It was not you who had used that term. Would you please also comment on what you see as possible “food” sources for the hydrogen-producing bugs on the scale that we are considering here to “make up the gap.”

  20. #20 Emory K.
    June 16, 2007

    The ETC press release says “The same minimal microbe could be harnessed to build a virulent pathogen that could pose grave threats to people and the planet.”

    But wouldn’t a virulent pathogen require some quite sophisticated mechanisms to pump out or break down antibiotics, plus additional complex mechanisms to hide from or defeat the immune system? It seems to me that if someone wanted to develop a virulent pathogen, a minimal microbe lacking all the fancy offensive and defensive mechanisms would be the dumbest starting point.

  21. #21 Doug M.
    June 25, 2007

    Merry, I’d still like to see a cite for that comparison of total human energy use vs. photosynthesis in post #16.

    Doug M.

  22. #22 eric
    June 26, 2007

    yeah, I call bunkum on that Human>Photosynthesis energy figure:

    http://www.fao.org/docrep/w7241e/w7241e05.htm

    “Solar radiation striking the earth on an annual basis is equivalent to 178,000 terawatts, i.e. 15,000 times that of current global energy consumption. Although photosynthetic energy capture is estimated to be ten times that of global annual energy consumption, only a small part of this solar radiation is used for photosynthesis….”

  23. #23 Trinifar
    July 5, 2007

    castro rivadeneira (sorry my font can not display all the characters in your name):

    Patenting processes stunts innovation and creativity aside from being generally unfair. Patenting organisms is just ludicrous. … I’m definitely for open source biology. And chemistry. And physics.

    Open source software is working pretty well in spite of attempts to stiffle it by the likes of Microsoft. It’s a tremendous source of innovation and pretty much everyone benefits from it.

    When I was in corporate America I received a patent on some software I helped design. What foolishness. It’s like patenting a part of mathematics — but we do that now too. We are patent crazy and current system is broken.

    Open source might even save the world.