Synthetic biology: January 2009 Archives

The European Patent Office has awarded a patent to gene synthesis company Genearts for a technique to perform directed evolution in vitro instead of in vivo. Published in April last year, the patent describes a technique that, in effect, puts an evolutionary feedback loop inside a test tube.

The Genearts work is broadly similar to that of teams led by George Church at Harvard and Andrew Ellington at the University of Texas at Austin – both are pursuing the idea of transferring key enzymes out of cells where they can be more easily controlled.

According to the patent, which is written in German, the Genearts techniques revolves around the use of both an RNA polymerase to transcribe DNA and a reverse transcriptase to write new DNA. It's a variant of a process that has been put forward as an alternative to the ubiquitous polymerase chain reaction (PCR).

The process uses reverse transcriptase to produce more DNA of a favoured mutant protein in the tube than the original protein or less well-adapted mutants.

They do this using a molecule that attaches itself to the polymerase and which also binds preferentially to favoured mutant proteins. This molecule acts as a primer that allows reverse transcription to begin. Potentially, the molecule can be based on RNA or be a protein or peptide.

Genearts said it has applied for a similar patent in the US.

A group of ecological pressure groups have come together to produce an open letter warning against the industrialisation of second-generation biofuels – the fuels that are expected to make use of synthetic- and systems-biology techniques to improve efficiency over the first-generation biofuels, based mainly on corn and sugar, in production today.

The groups include the Global Justice Ecology Project, Rainforest Action Network, Food First, Family Farm International Grassroots International and ETC Group, which was one of the first to start issuing warnings on the potential risks of industrialised synthetic biology.

The letter argues that the agrofuels – which critics prefer to biofuels as a term – present a "false solution" to energy woes, that the cultivation of agrofuels exacerbate climate change and poverty and that the scale of demand expected cannot be met sustainably. Most controversially, the letter claims agrofuels do not represent renewable energy sources. Intuitively, this last claim sounds bizarre. But I know what they are getting at: that removing all the plant waste from cropland denudes the soil and render it barren although that point is not made clear in the letter, it's just left as a broad claim.

The letter closes with a list of options that the groups believe offer better prospects than agrofuels, although they mostly concentrate on consumption reduction rather than alternatives to fossil fuels.

Although the groups raise valid points, the habit among pressure groups to simply say that agrofuel work needs to stop, or whatever else it is, tend to marginalise them. Backing up with claims that the fuels worsen climate change when the comparison is against a situation where fossil fuels are not used just gives their opponents easy targets. The letter argues "agrofuels produce from 17 to 420 times more greenhouse gas emissions than would be saved by avoided use of fossil fuels". Although they go on to argue that increased nitrous oxide production from the use of fertilisers could cancel benefits, the study they cite does not say that all biofuel crops would suffer this problem.

There does need to be work on how much plant waste is needed to sustain soils – whatever the crop – and to establish how damaging monocultures are to ecosystems. We need much better analyses of the effects of land-use change and of how different crops will affect the carbon balance. Not only that, we need a better understanding of the economics involved because many of the people working on biofuels or agrofuels believe they can help bring development to poorer countries, not to displace existing populations. Will a call for an outright ban on agrofuel development help or hinder that process?

Giving a talk at the Wilson Center last week, bioethicist Arthur Caplan was keen to draw a distinction between ethics and all the other issues around synthetic biology that tend to get dumped in the lap of the ethicists in the hope that a bit of social-science magic will make the pain go away. And he very much wanted to put paid to the idea of there being an ethics lag in synthetic biology.

The trouble with the synthetic-biology ethics debate, according to Caplan, is that it has focused on things that do not really deal with ethics but matters of social and economic policy. I have, for not dissimilar reasons, argued that science cannot deal with many of those issues because they deal with economic decisions. But these issues are being discussed in the open and it's possible to argue that the synthetic biology community is doing a better job of taking them head-on than many other scientific sectors, inviting lobby groups such as ETC to the SB 4.0 conference, for example.

You pretty much can't get a grant from the government-funded research agencies to do synthetic biology research in the UK unless there is some kind of social element built in, to help explain the work to the outside world at the very least.

Although he argues there is no ethics lag as such, having written a paper on ethics in synthetic biology after seeing a presentation by Craig Venter more than nine years ago, he does see problems looming ahead for the technology in certain places. There is, potentially, a religion gap that goes to the heart of the problems that biology has had with vitalism for the past two centuries.

Vitalism didn't stop with Friedrich Wöhler and his 'synthetic' urea. Wöhler himself used an experiment later used to argue that there is no magic spell cast on molecules to make them live, but he thought of the experiment of a demonstration of vitalism as he realised that one of the sources of the chemicals used to make the urea came ultimately from an animal.

The problem lies in the way that reductionism in biology is gradually removing the distinction between the living and the inanimate. "There is a lot of poor genetic reductionism around," argued Caplan, referring to the God gene and the gay gene claims. Strands of DNA play a far more complex role in determining how an organism develops and science has barely scratched the surface of that. But the more the code unravels, the worse the situation gets for any vitalist view of biology. Synthetic biology takes it one stage further by presenting the idea that life can be created from the inanimate.

Caplan summed the religion gap up in one phrase: "You can do cost/benefit analyses until you turn blue. But if this guy thinks synthetic biology is bad because [it means] he has no soul, then doesn't care how many cost/benefit analyses you produce for the technology."

In practice, synthetic biology will not hit the Frankenstein issue for many years – in Mary Shelley's novel, Victor Frankenstein creates the creature from inanimate matter, not bits of dead bodies as seen in the James Whale movies.

Tom Knight of MIT reckons it will take to the end of the century to create a living organism entirely from scratch, using no concepts and parts that have evolved naturally in one way or another. However, the claims that scientists have created life will abound much sooner than that and the biologists themselves have little doubt about that. The introduction ahead of Caplan's presentation itself made similar claims.

Caplan has identified an area that may prove more of an obstacle to synthetic biology research than the ones that seem to be problematic today, such as biosafety or bioterrorism.

"Most of the biology ethics are done secularly," said Caplan, but he pointed to the recent Vatican bioethics statement as an example of a further area of how religion is taking a more active role in defining what is allowed and forbidden in biotechnology.