Every genome on the planet is now up for grabs, including those that do not yet exist
June 17, 2010
IF THE history books do come to recognise the idea of biology 2.0, then the date it began may well be recorded as May 20th 2010. That was the day when Craig Venter announced JCVI-syn1.0, the world’s first living organism with a completely synthetic genome.
The Frankencell project, as it was known jokingly at the beginning, had been going for 15 years—ever since Dr Venter started to wonder what was the minimal genome necessary to support a living organism. To find out, he took a bacterium called Micoplasma genitalium, which has a particularly short genome anyway, and knocked its genes out one at a time to see which the bug could live without (at least in the cushy circumstances of a laboratory Petri dish). The answer was around 100 of its original complement of 485.
The genetic flexibility this hints at—of a core set of genes and a penumbra of others useful in particular circumstances—has, over the past decade, been confirmed for many other species of bacteria. Indeed, the way biologists think about the whole idea of “species” when they study these micro-organisms is beginning to shift rapidly. This is part of a general broadening of genomics. Though navel-gazing into Homo sapiens’s own genome remains of intense interest, the study and manipulation of non-human genomes may ultimately have greater impact.
Dr Venter certainly hopes so. His company, Synthetic Genomics, based in San Diego, plans to patent the new bug. It argues that although it is a living organism, which would normally be outside the scope of patent law, it is also a true artefact, not just the product of selective breeding. The firm will then be able to use it, and the method used to construct it, in its programmes to make fuels and vaccines.
Technology and magic
On the other side of America, in Boston, George Church is taking a different approach. Unlike Dr Venter, who focuses his energy on one firm, Dr Church is a promiscuous entrepreneur. He has been involved in the foundation of several companies, including LS9 and Joule Biotechnologies (which hope to manufacture biofuels) and Microbia (which plans to make speciality chemicals). Like Dr Venter, Dr Church has something up his sleeve. This is MAGE, a somewhat contrived acronym for multiplex automated genome engineering.
Instead of making new genomes from scratch, Dr Church plans to make lots of parallel changes in existing ones. The idea is to induce simultaneous random mutations in all of the genes in a particular cellular pathway by introducing pieces of DNA which match parts of those genes, but which are attached to short sequences that do not. As a cell replicates, the foreign DNA is absorbed and the genes in question are modified by the non-matching short sequences. Thousands upon thousands of different versions of the pathway are thus created, and all are subsequently isolated and tested to see which are most effective. The process is then repeated on the winners until the desired outcome is achieved. This can replicate at a cost of thousands of dollars the sort of genetic modifications that have previously cost millions.
Even without the new platforms, non-human genomics is beginning to pay dividends. Several firms, including Synthetic Genomics, LS9 and Joule, are engineering micro-organisms (sometimes bacteria, sometimes single-celled algae) to turn out biofuels resembling the petrol, diesel and kerosene that people put in cars and aircraft. Existing biofuels, based on ethanol, are less good. Ethanol is corrosive and has less energy per litre than petrol and diesel.
One firm, Amyris Biotechnologies, is already scaling up to industrial production of such biofuel, but in Brazil, where cheap cane sugar provides the raw material, rather than in the United States, where it is based. Joule plans to use an even cheaper raw material: the carbon-dioxide exhaust from power stations. It is one of the firms working on single-celled algae, tweaking their metabolic pathways to improve the rate at which CO2 is fixed by photosynthesis and then converted into hydrocarbons that can be used in cars.
Fuels are an attractive alternative to drugs for the new generation of synthetic biologists because they are not subject to regulatory whim to the extent that drugs are. If anything, regulation is likely to favour them because their raw material is, either directly or indirectly, carbon dioxide that has come from the atmosphere or would end up there. That makes them green in the eyes of governments, and therefore a good thing.
The smell of money
Fuel, however, is a low-value commodity. A more profitable way to avoid the regulators may be to make complicated high-price chemicals such as fragrances. This is what Allylix, of San Diego, California, is doing. The firm’s founders realised that biological synthesis of certain sorts of molecule is much more efficient than chemical synthesis. Many organic molecules contain what are known as chiral centres. These are places where the atoms can be arranged either left-handed or right-handed. In biochemistry, handedness can matter. Left- and right-handed versions may, for example, smell different. Traditional chemical synthesis cannot distinguish between left- and right-handed versions, so they have to be separated afterwards, which is tedious. Moreover, if there are lots of chiral centres in a molecule, and each matters, the yield of the version with the right combination can be minuscule.
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