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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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May 20, 2010

A Synthetic Genome; A New Species

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Posted by Derek

As had been widely expected, Craig Venter's team has announced the production of an organism with a synthetic genome. All the DNA in these new mycoplasma cells was made first on synthesizer machines (in roughly 6 KB stretches), then assembled first enzymatically and finally in yeast into working chromosomes.
mycoplasmajpg.jpg
And we know that they work, because they then transplanted them into mycoplasma and ended up with a new species. The cells grow normally, with the same morphology as wild-type, and sequencing them shows only the synthetic genome - which, interestingly, has several "watermark" sequences imbedded in it, a practice that this team strongly recommends future researchers in this area follow. In this case, there's a coded version of the names of the team members, a URL, and an e-mail address if you manage to decipher things.

Nothing about this process was trivial - the team apparently worked for months on just the last genomic transplantation step until things finally lined up right. But there's been a lot learned by this effort, and the next ones will be easier. I'm not sure if I call this a synthetic organism or not, since the cytoplasm (and all its machinery) was already there. But whatever it is, it sure has a synthetic genome, designed on a screen and built by machine. And it works, and more will surely follow. Will 2010, looking back, be the year that things changed?

Comments (28) + TrackBacks (0) | Category: Biological News


COMMENTS

1. OHLEE on May 20, 2010 3:06 PM writes...

‘I have a hunch that . . . the unknown sequences of DNA [will decode into] copyright notices and patent protections’. -- Donald E. Knuth

This was decades ago . . .

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2. OHLEE on May 20, 2010 3:13 PM writes...

‘I have a hunch that . . . the unknown sequences of DNA [will decode into] copyright notices and patent protections’. -- Donald E. Knuth

This was decades ago . . .

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3. J-bone on May 20, 2010 3:24 PM writes...

Anybody else remember when James Watson said Ventner's machines could be run by monkeys? Good stuff.

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4. Mutatis Mutandis on May 20, 2010 5:33 PM writes...

Not sure I would call this a 'synthetic genome'. It's synthetic DNA. But the genome is still that of Mycoplasma mycoides, with a few changes such as the barcode.
Essentially that is the difference between a scribe copying a book (making a few changes along the way, intentional and unintentional) and an author writing a new book. Material representation versus abstract content.

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5. TwoYaks on May 20, 2010 6:30 PM writes...

Honestly, I think all the people splitting hairs over whether this really qualifies as a synthetic organism are missing the point. Yes, we're just copying someone else's book, but more importantly we can now reproduce the whole book. And if we can reproduce the whole book, who's to say we can't change a few paragraphs, or hell, chapters along the way? I seriously doubt this will fizzle. This is big-big-big.

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6. Anonymous on May 20, 2010 6:39 PM writes...

Much easier to make the mutations you want by directed mutagenesis than to re-create the entire chromosome(s). This is much ado about nothing. Just a big plasmid created by oligo synthesizers. The company the synthesized the DNA deserves most of the technical credit (Blue Heron). Basically useless from a scientific perspective.

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7. barry on May 20, 2010 8:01 PM writes...

Well the first cell into which they stuck the sythetic DNA isn't wholly synthetic, because the cytosol with all its machinery was already there. With each mitotic cycle, that contribution is diluted 2-fold and tends towards zero. This would be different in eukaryotes, where some of the organelles carry their own genetic information, and perpetuate it independent of the synthesized starter code.

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8. non-pharma chemist on May 20, 2010 8:50 PM writes...

I might be a cynic, but I call this a big non-event like Dolly the uselessly cloned sheep or Buckminsterfullerene, the useless carbon allotrope. Call me when Craig Venter can grow my arm back after it's been tragically amputated, or, you know, do anything else that can bring personal benefit to someone somewhere sometime.

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9. Anonymous BMS Researcher on May 20, 2010 10:50 PM writes...

Venter's been talking about this one forever; back when his outfit was called TIGR (and Claire Fraser was running the place) folks there called it the "Frankencell Project."

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10. Cassius on May 21, 2010 12:53 AM writes...

Uhhhh.... I'm not so sure this is a good idea. I see the nay-sayers' points, but this is a bit scary to me. Reminds me of a talk I heard Peter Schultz give in 2003 about his bacteria that could incorporate more than 20 amino acids into proteins. He made a comment that he would like to put his bacteria and God's bacteria in a parking lot, come back in 10,000 years, and see who won. Funny that at about that point in the talk, he started breathing really heavy and sweating profusely.... I was wondering if he was going to lose that war right there and then. Granted, that was the only live talk I've seen him give, so maybe he's always like that, but it definitely made an impression on me.

I hope that #7 is right and eukaryotes shut down any such attempt to hijack their machinery.

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11. RB Woodweird on May 21, 2010 6:30 AM writes...

You guys are still thinking inside the box.

Not these visionaries:

http://en.wikipedia.org/wiki/Splice_(film)

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12. alig on May 21, 2010 7:00 AM writes...

Just more evidence that intelligent design is a possible way to generate new species.

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13. noname on May 21, 2010 7:52 AM writes...

When is Schultz not sweaty and out of breath?

I have to agree with the "ho-hum" faction on this one. It's an impressive piece of oligo synthesis, and maybe the transfection method is groundbreaking (by the way, what happened to he "old" genome in the cell?). But it's still a known genome, known function, known phenotype. I'll be impressed when they design a new organism, with different cross-wiring of regulatory and signalling pathways that don't exist in nature. That should only take, oh, another 100 years.

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14. Hap on May 21, 2010 10:26 AM writes...

When you find the Easter eggs in H. sapiens, that would probably be more relevant as evidence that design happens and can generate new species in nature. Until then, this is more like nude mice and other such things - we already knew that we could make things and they could do new and novel things, but that design didn't mean that nature was designed analogously.

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15. Sigivald on May 21, 2010 12:16 PM writes...

Cassius: What's scary about it?

Call me back when they can actually design DNA sequences from scratch knowing what the result will be.

That's the interesting part; that you can copy DNA and have the copy still work is an unsurprising result. (One that's useful groundwork to confirm, but not surprising.)

And that interesting part is a very, very, very long way off.

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16. g on May 21, 2010 1:02 PM writes...

This is more proof of concept than anything else. Technically, this is immensely complicated. But this is more than a big plasmid inserted into a functioning organism. This is a functioning organism, turned into a phospholipid bicelle full of proteins by removing chromosomes, and hijacked into a new organism by adding synthetic chromosomes.

That is amazing, but I am uncertain as to how useful this will be. We can already insert and delete vast amounts of DNA from organisms. The majority of their DNA is useful after the genome is altered. So why go to all the bother of removing something and then adding it back as a replicate?

This is interesting stuff, but I agree with #8

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17. John FitzGibbon on May 21, 2010 1:32 PM writes...

Has anyone taken a look at recent patent applications? I'm really curious if naming this "synthetic life" is a publicity stunt to go along with a very broad set of patent applications making claims to some very important and profitable areas.
For my money on the synthetic life front I like szostac as being on the path to it as opposed to venter.

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18. Yggdrasil on May 21, 2010 1:39 PM writes...

The rationale behind Ventner's study should be familiar to chemists because it's the same rationale behind total synthesis. For example, in the paper, the authors write:

"No single cellular system has all of its genes understood in terms of their biological roles. Even in simple bacterial cells, do the chromosomes contain the entire genetic repertoire? If so, can a complete genetic system be reproduced by chemical synthesis starting with only the digitized DNA sequence contained in a computer?"

One of the original motivations behind Venter's institute was to try to identify the minimal genome required to create a self-replicating organism. Now, at least they have the tools to try and tackle this problem.

I agree with the other commenters that this result is not all that interesting in itself. However, this result enables so much more interesting science. Chemists study chemical processes by building new molecules to test and understand their properties. Geneticists are now beginning to have the tools to study genomes in the same way.

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19. Art on May 21, 2010 2:31 PM writes...

Those that are dismissing this accomplishment as unimportant have little imagination. Combining this new technology with techniques already out there opens up a tremendous set of possibilities.

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20. Anonymous on May 21, 2010 3:32 PM writes...

#18 exactly - smacks of early Woodward. Or the paclitaxel process.

On another topic, how about the Chinese claim to have transmitted quantum information between protons 10 miles apart (from io9, but still ...) - cool if it's true.

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21. Ronathan richardson on May 21, 2010 8:34 PM writes...

If your heart fails, and you get an artificial heart transplant, are you a synthetic organism?

It's a milestone, but not a particularly useful one. Really, the "getting synthetic Dna in" part is the easy part. Actually making something useful that you couldn't already do in e coli, that's what will stop them.

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22. Vince on May 23, 2010 1:24 AM writes...

#8 -- Call me when Craig Venter can grow my arm back after it's been tragically amputated

What an amazingly unfair comment. I'm sure, given the gift of hindsight, you'd still be there telling Goddard to take a walk and come back when his little experiments have brought him to the moon and back, right?

Oddly enough, while comment #8 was horrid, #18 was quite nice!

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23. bootsy on May 23, 2010 12:43 PM writes...

It is a technical achievement mostly, but I agree with Freeman Dyson (among many others) that most scientific revolutions are brought about by technological leaps first. This report, combined with cheap sequencing, really does seem like it could be a milestone on the road to things we can't yet imagine.

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24. Wavefunction on May 24, 2010 10:13 AM writes...

Here's a critical quip from Dyson about the achievement:

Freeman Dyson, the physicist, captured the full range of academic sentiment in this dry appraisal: "This experiment is clumsy, tedious, unoriginal. From the point of view of aesthetic and intellectual elegance, it is a bad experiment. But it is nevertheless a big discovery… the ability to design and create new forms of life marks a turning point in the history of our species and our planet."

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25. randcraw on May 24, 2010 10:14 AM writes...

I'm no expert on genomics, but it seems to me that if the status quo already allowed us to make single small changes to an organism's genome (e.g. splices), then Venter's method adds value only if you want to make changes that were not yet possible (e.g. multiple, larger, or interdependent changes). And it will be useful only if a complete synthetic genome can be constructed quickly and efficiently. (Something that I didn't see mentioned in the announcement.)

I wonder then, does Venter's method really serve an unmet need in genetic research? Or does it simply provide us the means to generate all possible variations on a bug?

If only the latter, then count me among the concerned.

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26. Paul on May 24, 2010 3:01 PM writes...

I wonder if they could take the genome and edit it so the coding segments only used a restricted subset of codons. The genetic code has a lot of redundancy in it (20 amino acids from 64 triplets). This would be the first step to extending the genetic code, using some of those freed-up codons for new amino acids (although designing the enzymes to make those amino acids, and designing tRNA to work with them, would sure be a challenge.)

Or perhaps they could find some compound that breaks DNA containing a sequence of some of the unused codons. The new organism would not be affected, but the compound could harm most anything else. Being able to kill all competing organisms would be useful in (for example) open-pond cultivation of algae for biofuels.

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27. gippgig on May 24, 2010 8:06 PM writes...

The genetic code has already been extended (see #10). E. coli has been engineered (JACS 125 935) to synthesize p-aminophenylalanine & incorporate it into proteins in response to the UAG codon (normally stop). The biosynthetic genes for this amino acid were taken from Streptomyces venezuelae (which uses them to make chloramphenicol) while the tRNA & aminoacyl-tRNA synthetase were mutated tyrosine-specific ones from Methanococcus jannaschii (an approach used to add many other amino acids to the genetic code). This is rather ugly however since UAG is still used as a stop codon in this organism. Reassigning codons as mentioned in #26 would be much more elegant.

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28. Anonymous on May 24, 2010 10:30 PM writes...

This is total hype. It's not just that there is no obvious application for Venter's approach (or, less generously, that he has managed to pioneer the most difficult way imaginable to engineer an organism's genome). The problem is that this paper provides so little useful insight. Everyone assumed that you could do this; no one else bothered to do it, because it is incredibly expensive and, as far as anyone can tell, totally pointless. Guess what? You can do it. And it is incredibly expensive, and completely pointless. Congratulations Craig, someone should put a gold star on your forehead! The rest of us are going to resume doing actual science.

The only thing that has been learned from this paper is that Venter is a clown, willing to perform any sort of publicity stunt in order to increases his personal fame.

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