Oscillator

What Synthia Means To Me

i-757b6d2043c776d6120ee4489b452694-usandventer-thumb-510x342-49505.pngThe reaction to the Venter Institute’s synthetic genome transplantation has been decidedly mixed. Is this the beginning of something new and wonderful, the ability to really design organisms from scratch? Is it something more sinister, the beginning of a dark era where techno-corporate (or terrorist) interests can design something that will destroy the environment in catastrophic ways? Is it just a technical advance or a conceptual breakthrough? A philosophical revolution? Is it a Big Deal or big whoop? Synthetic biology has never been just one thing and still has many different goals, with a synthetic genome being just one that most don’t have the resources to work on yet. While we can all hang out and all agree that Synthia is an important breakthrough, most agree that it’s still technically a small step rather than a giant leap, although a step that importantly brings synthetic biology to the attention of many people all at once.

My ScienceBlogs colleague PZ Myers compares the synthetic genome to Wöhler’s chemical synthesis of urea in 1828. In the 19th century, scientists debated whether or not the chemicals that make up living cells–organic chemistry–had to be made by a cell possessing a “vital spark” or could be made by humans in a test tube. By synthesizing urea from ammonium cyanate, Wöhler broke down some of the mysticism associated with living cells. From that point on, organic chemistry stopped being magic and became a science.

Does the Venter Institute’s achievement show that life is just chemicals? I don’t think so–the ability to synthesize DNA sequences chemically and insert them into already living cells has existed for decades, the JCVI achievement simply changes the scale and moreover, the synthetic genome still had to be assembled in live yeast cells, incubated with extracts from mycoplasma to process it, and then injected into a living cell to be “booted up.” Without life, Synthia wouldn’t be alive. What separates a bag of DNA from a living, replicating cell is still unclear and un-synthesizable. To me, life is still “special” and incredibly powerful and I don’t think that we have to burst that bubble to be able to engineer cells. I’m a biologist because I think life is awesome. I’m a synthetic biologist because I think it’s awesome to be able to see and experience just how robust and powerful biology is as we rewire, remix, and refactor living cells, not because I want life to be just chemicals, just DNA sequence.

Does Synthia affect my work as a synthetic biologist? Right now the answer is also no. Synthia’s genome is almost identical to the naturally occurring sequence of Mycoplasma mycoides and we are far from being able to design or even re-design organisms on a genome scale. Almost everyone in synthetic biology is struggling with adding genes to natural genomes up to ten at a time, it’s going to be many years before we understand how to get from these tens to the thousands in even a small bacterial genome. I’m interested in all those intermediate steps–how do enzymes work in different contexts? How do genetic networks interact with each other inside of a living cell? How can small changes to a genome have a large effect on behavior? What kind of things can biology do that can be nudged in different, interesting, useful directions? I’m not interested in minimal genomes or a universal chassis for synthetic biology because I think the diversity of living organisms that already exists is too valuable to ignore. A minimal organism almost by definition can’t do much, even when, for example, genes for biofuel production are added into the synthetic genome.

Furthermore, the sheer amount of work put into building Synthia also is instructive as to where we are now in synthetic biology and how far we still have to go. The project took fifteen years in all, countless postdoc hours, and millions of dollars. The work was tedious and slow, with a single base pair error in the synthesized genome setting back research for months. Right now I’m not that interested in doing this kind of brute force chemical synthesis of genomes (and almost no one can afford it), but as gene synthesis technology becomes better and cheaper (which is most certainly will, although I’m not as optimistic as some people as to how trivial it will become to synthesize a whole genome in the future) the ability to synthesize many different large DNA sequences will lead to the kinds of large-scale synthetic biology experiments that will let us understand how genes, gene networks, and genomes work inside of a cell. Many have also been asking whether as the technology improves, could it also lead to the creation of something dangerous?

Synthia, the transplant of a single synthetic genome, does not inherently change the biosafety landscape of synthetic biology (sometimes called the “halfpipe of doom”) but it does place the discussion in a more prominent, public and hopefully open and thoughtful position. A poll last year showed that while only 20% of people had heard of synthetic biology, 90% thought that the public should be better informed about groundbreaking research. Today, synthetic biology is harder to ignore and there are more ways than ever to learn about what is going on in labs around the world and to have your voice heard. Science magazine has set up an open forum on their website for questions, comments, and discussion on the topic with a lot of people contributing from many different viewpoints and perspectives.

Synthia is important for showing what big budgets and bigger patience can do, and for continuing and broadening the public discussion on synthetic biology. Synthetic biology will continue to grow slowly from many different directions, with new and potentially useful genetic networks designed and inserted into natural or redesigned synthetic genomes. It’s important to understand how these technologies work, their potential benefits and risks, as well as their limitations. Synthia isn’t going to make you live forever and there probably won’t ever be any mer-Venters, but designed bacteria growing in controlled environments have been producing useful chemicals for a while now and the technology will certainly get better over the next few years with more advances in synthetic biology. After that, who knows? The possibilities are endless and it’s up to all of us to make sure that it’s good for everyone.

Comments

  1. #1 darwinsdog
    May 21, 2010

    Be impressed when all the macromolecules of a synthetic cell, and not just its genome, have been assembled synthetically and made to function & replicate.

  2. #2 Lucas
    May 21, 2010

    Your post is one of the clearest and most balanced of all the coverage I’ve read so far. Thanks =).
    I think that in the future, we will look back to this research as a milestone, much like the human genome was. That project also didn’t mean the work was done, far from it. The good stuff, the understanding, the insights.. all of that is still to come.

  3. #3 Sean
    May 22, 2010

    Very balanced post.

    My question relates more to the politics of the base materials being used. Are these synthetic in the sense of petroleum-based or derived from natural source like yellow dent number 2?
    In some ways I think of the pandora’s box filling the gulf right now – preventable tragedy with enforced oversight that would account for contingency. Questions of contamination, unforeseen vectors and of course renegade proteins(prions).

  4. #4 andrew b
    May 22, 2010

    I’ve been trying to think of something to say but I’ve just been psyched out by the “merman” effect with ventor

  5. #5 andrewb
    May 23, 2010

    Christina, give me a sec..
    ————–

    So right now I’m lying in a room. Air molecules are right in front of me, going 500 m/s cluttering the pathway from the light of my screen to my eyes.. yet the lights goes straight thru them and i see perfectly. simulataneously im being bombared with 670 million mph radiation from the monitor this very instant. also right now.. me and my body are being ghosted by invisible gravitational particles originating from the center of the earth. on top of that 2 feet behind my nose.. just south.. are rhyhmic cells at the bottom of the heart.. causing it to pump the air ive just inhaled… with each red blood cell.. one right now.. returning to that same spot 60 seconds from now (fast huh).. and i’m spinning at crazy speeds. upside down, with the air, around a star.. around a cluster.. which spins around the galaxy.. around a cluster of galaxies.. with others running away from me.. and all this is happening right now while i blog on the agapakis oscillator bio blog. pretty cool.
    so im done with my imagination oscillator exercise. but give me a sec.

    One of the cells.. near the tip of my finger.. if i could put it under a micrscope and zoom in to the dna (prolly cant but its imagination) has its replication fork zooming along.. bam bam bam.. preparing it for a cell division that won’t happen completely until its ready..

    With all this stuff.. it just seems to me that the ‘s field’ entails the insertion of sequences into a genome or bacterial circular chromosome which these ppl ‘think does something’ .. and hope that the cell will incorporate and maintain the creation and maintenance of that something?

    I know this seems like a superficial understanding but i counted the number of times u used the word synthetic in your post (not synthesized or synthia) and it was 18. Try talking about what you’ve found out about this field without ever using that word again. It sorta forces u to know what u know, and recognize what u don’t know (you’re a genius and smart so never worry) – it makes nature much more interesting and exciting. It also (crappily) shows the Ventersque idea behind the field – If the history of humans can be seen at one level as unconscious selection of dna at the phylogenic level, i dont understand how inserting or altering dna sequences directly (which account for inheritable traits) is any different than the insertion of nice tasting tomatoes. Or even the selection of disease, which is (unfortunately) selected and synthetically derived by humans through it being successfully incorporated.

    You mentioned biofuel –
    below the ground right now is some molecules from someone who died long ago.. and perhaps somewhere right now there is a flood of black liquidy stuff which is composed of similar decaying stuff.. and we call it oil and use it for all sorts of purposes.. but this is the most biologic of anything ever – oil. yet someone is going to alter the properties of it, manufacture it more directly and add in the term ‘bio’ to it? I understand the manipulation effect and thus adding the ‘bio’ marker but it seems like the ‘organic food’ trend  . my general message here is the synthetic word seems like a misnomer – it makes sense only if you ignore that humans are themselves life, and every thing we do is at some level synthetic.

    Anyway, you are incredibly wise and your videos kick ass.
    Here is something you probably already saw but neat – 8 ‘synthetic biology experts’ asked to poll their opinions on ventors thingy in Nature.

    http://www.nature.com/nature/journal/vaop/ncurrent/pdf/465422a.pdf

  6. #6 Richard Feynman
    May 23, 2010

    For fun!@!@!@!@!

    What the manipulation of Carbon to some other molecule is for the electro transport chain will be what the story of Adam and Eve is for the human race.

    The significance of cellular respiration – electron transport – mitochondria – all of life is we know – is you don’t need carbon for electron transport, you need something with enough electronegativity to get the process going so the gradient can add phosphates to ADP. It’s fun to think about. Almost like all our lives is a game, we roam around and work for these ‘carbon’ foodstuffs.. only to have this whirl some windmill so cells can have their own food – ATP. Like we’re just being tricked and along for the ride. (ATP Synthase is our muse.. and we are drones which spin her windmill!)

    You don’t even need the carbon! The possibility for switching it for another molecule is there, you could actually use electricity to get the transport than and gradient running. Imagine mitocochondria’s ATP foodstuffs being supported by a plug – truly rankensteinian!

    These are just interesting ideas. Plants sit there and eat the carbons in the air, and I have to move around and stick things down my mouth, when they can just stand there. Boo hiss.

    “See this is what happens when you start to think – you can go on and on. You wonder where this carbon from the tree came from? it came from the air!”

    http://www.youtube.com/watch?v=ITpDrdtGAmo#t=2m15s

  7. #7 anon
    May 24, 2010

    Darwin – “Listen to your heart”
    Remix Video/draft

    http://www.youtube.com/watch?v=OpYk3dbYf7o

  8. #8 Lab Rat
    May 26, 2010

    @andrewb: I’m sorry, this is a very nit-picky thing to say (especially as your post was so wonderfully poetic) but red blood cells don’t have any DNA in them. They are mostly just ‘empty’ cells stuffed full of haemoglobin to carry oxygen around. They can’t replicate either – they’re made in the bone marrow (I think) and then broken down in the liver.

    But I do like your point about the use of the word ‘synthetic’. In this case I wouldn’t really like to call what was made in Venter’s lab a ‘synthetic cell’, more a man-made (or synthetic if you like) *working genome* that has been inserted into a DNA-less cell.

  9. #9 andrewb
    May 26, 2010

    Very astute of you, and interesting. Thanks!

  10. #10 JohnV
    May 27, 2010

    In the theme of nitpicking, the synthetic genome was inserted into a DNA-full cell.

  11. #11 Christina Agapakis
    May 27, 2010

    Oh yeah? Wow, that’s interesting! How did the cell handle two genomes? Did it end up only replicating the synthetic one eventually to get the full “transplant” or was there something else that removed the native DNA?

  12. #12 JohnV
    May 27, 2010

    Ok so I spent some time reading this series of papers. Why I don’t go upstairs and find someone in the synthetic bio group and ask them I don’t know.

    From the 2007 paper they “presume that organisms carrying both donor and recipient cell genomes occurred at least transiently at early times after transplantation.” but they figure that the extremely low transformation efficiency means that it’s a very low frequency event. Apparently the growth conditions for the recipient cells induce nucleotide starvation which gives long branched cells.

    So if I were to make a really speculative guess, I’d think that big, branched cells would make it easier to end up with a cell with 1 of each chromosome who then divides and ends up with 2 cells with a single chromosome?

    In the early work the donor chromosomes had a tetracycline marker so presumably at that point selection will move you towards cells only containing the synthetic chromosome.

    I’m also pretty certain that the synthetic chromosome had a restriction system that the recipient cell’s chromosome did not, while the recipient cell’s native restriction system had been inactivated.

    If I feel social later I’ll try and track someone down for verification.

  13. #13 andrew b
    May 28, 2010

    nothing to do with any of it

    but a mitochondria mystery of life video i made a while back

    http://www.vimeo.com/9634563

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