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The 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.
May 21, 2010
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