Man Has Created Life-What Next?

Let there be life
By Clive Cookson
Published: May 21 2010 22:56 | Last updated: May 21 2010 22:56

An aura about him: Craig Venter, who promises to license patents on synthetic organisms in order to benefit society
Some call it Synthia. Others offer designations that are rather less twee: dangerous is one of them. But beyond doubt, the creation of synthetic life in a US laboratory, announced on Friday in the journal Science, has aroused awe, admiration – and antagonism – around the world.

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A few commentators are lamenting the hype around the achievement of the genomics pioneer Craig Venter and his team in making bacteria in their laboratory “from four bottles of chemicals and a chemical synthesiser”. But no one denies the deep significance of the research – and some philosophers have gone into ecstasy.

“Venter’s achievement would seem to extinguish the argument that life requires a special force or power to exist,” says Arthur Caplan, bioethics professor at the University of Pennsylvania. “This makes it one of the most important scientific achievements in the history of mankind.”

From a more practical point of view, Dr Venter’s work – and the fast-growing field of synthetic biology, of which he is the most visible representative – promises to deliver a cornucopia of new applications in bio fuels, healthcare and elsewhere, which would not be possible with the type of simple genetic manipulation carried out over the past 30 years.

“In time this new research may make it possible to extend the range of purposes for which we are able to breed organisms, dramatically and in ways that we cannot yet imagine,” says Sir Ian Wilmut, director of Edinburgh University’s regenerative medicine centre and author of another biological revolution, with his discovery of mammalian cloning 15 years ago.

But as Dr Venter himself acknowledges, the technology “could also be used for negative purposes” such as creating germs for bioterrorism. “So-called dual-use technologies need to be carefully discussed and reviewed both in the US and globally,” he says.

Some pressure groups, such as Human Genetics Alert in London, say the risks are great enough to call for a moratorium on synthetic biology research “until there is an effective global system of regulation to deal with it”. David King, HGA director, says: “What is really dangerous is these scientists’ ambitions for total and unrestrained control over nature, which many people describe as ‘playing God’.”

For his part, Dr Venter maintains that his J. Craig Venter Institute, with its labs in Maryland and California, has led discussions of the risks and ethical and social implications of synthetic biology. And he rejects any suggestion of “playing God”. “That’s a term that comes up every time there is a new medical or scientific breakthrough associated with biology,” he says.

Synthetic biology makes the transition from “reading” DNA, which reached its apotheosis in the Human Genome Project completed almost 10 years ago, to the much harder job of “writing” genetic code. The Venter scientists built up the synthetic genome of a bacterium called Mycoplasma mycoides in steps. They started with relatively short stretches of DNA, each about 1,080 chemical letters in length. These were stitched together in three stages, producing DNA assemblies of first 10,000 and then 100,000 letters, before the final combination produced the full bacterial genome of 1m chemical letters.

The researchers transferred this completed genome into the shell of a related bacterium, Mycoplasma capricolum, whose own DNA had been removed. The transplanted genome “booted up” the host cell and took over its biological machinery. After 30 cell divisions, the lab dishes contained billions of synthetic Mycoplasma mycoides, behaving like the natural bacteria and producing the same biological molecules as them.

But the microbes – which some newspapers have called Synthia, to Dr Venter’s annoyance – could be distinguished by 14 “watermark sequences” of inert DNA that do not occur in nature. The researchers added these to show their man-made character.

There were also a few minor genetic differences that occurred inadvertently, as a result of errors in the DNA writing process. While these do not seem to have affected the microbes, the need for accuracy was demonstrated by another mistake – a lethal change in just one of the million letters in the bacterial genome – which held up the project for several months until the researchers discovered what had gone wrong.

While the synthetic bacteria are virtually identical to natural Mycoplasma mycoides, they are just a proof of principle for the technology. “From this proof of concept experiment, the team is now ready to build more complex organisms with useful properties,” Dr Venter says.

. . .

The first application for synthetic genomes may be the rapid development of new flu vaccines. The US government’s National Institutes of Health is funding a Venter project to make synthetic components of a very wide range of flu viruses, which could be slotted together to make new vaccines as new infectious strains arise.

“If this technology had been available last year, we could have cut the period needed to make a vaccine for H1N1 [swine flu] by 99 per cent,” says Dr Venter. “We could have done it in a day.”

But his personal priority – and the corporate aim of Synthetic Genomics, the company he co-founded in California – is to transform the production of biofuels and at the same time tackle the causes of global warming. Synthetic Genomics is the main funder of research at the non-profit J.Craig Venter Institute.

Dr Venter wants to design synthetic algae that capture carbon dioxide from the air and produce hydrocarbon fuels with the same chemical composition as the petrol and diesel that are refined today from crude oil.

The company reached a $600m agreement with ExxonMobil last summer to make algal biofuels – and Dr Venter says synthetic organisms are the only way to go. “We have looked hard at natural algae and we can’t find one that can make the fuels we want on the scales we need.”

Although algae are more complex organisms than bacteria, he says the leap from making a bacterial genome with 1m chemical letters to an algal genome twice as large is achievable.

The company paid for work at the institute in return for full intellectual property rights – and it has already filed 13 applications for patent families on genome synthesis.

Like any other biotechnology company, Synthetic Genomics insists that patents are essential “to ensure that this important area of basic science research will be translated into key commercial products and services for the benefit of society”, and it promises to provide licences to its patents.

While some experts are alarmed that Dr Venter and his company may gain a stranglehold on the intellectual property required to make synthetic organisms, others are more relaxed. Similar fears about a patent lock on human genes, expressed when Dr Venter was leading the private sector drive to sequence the human genome, turned out to be unjustified.

In synthetic biology several other companies and academic labs are developing alternative methods for writing and rearranging DNA. While no one else has attempted to synthesise an organism from lab chemicals like Dr Venter, their techniques may be just as useful as his for making biofuels or medicines.

Yet Richard Kitney, bioengineering professor at Imperial College London, says the prospect of powerful Venter patents – for example, on how to stitch together small sequences of synthetic DNA – should not be underestimated. “I think there will be a patent battle over a lot of this stuff,” he predicts.

Talking to Dr Venter himself, it is clear that while applications, patents and profits are important, he is fascinated by the intellectual implications of his research. “It has changed my own thinking, both scientifically and philosophically, about life and how it works,” he says.

Organised religion will have to take those changes on board, says the Church of Scotland. On Friday it issued the first “considered comment” of any church on Dr Venter’s achievement, which “has the potential to revolutionise much of our lives”. But it did not accept that synthetic biology “puts humanity on a par with God”; “our creatureliness remains”, it said.

“In trying to create new life forms, synthetic biology raises tough questions about what risks we are willing to take with our new knowledge,” says Rev Ian Galloway, convenor of the Kirk’s Church and Society Council.

If the risks can be managed, there is no reason to ban synthetic biology, according to the Church of Scotland. Indeed, the Christian world could welcome the innovation, in keeping with its belief in reducing human suffering and protecting the environment.

Reassuringly, the Venter scientists and all other synthetic biology researchers work only with micro-organisms. “It is anticipated that, given how little is known about human biology, no applications of this work will or should be attempted in humans,” the institute says – just in case anyone worries about making synthetic people. That would be a step too far, for science and for religion.

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