Dr Craig Venter

Doctor life

Dr Craig Venter's team have been replicating the human DNA code from a common bacterium in the laboratory.

If anyone is going to know where cutting-edge research into synthetic biology is leading us, then it should be Dr Craig Venter.

The founder of the J Craig Venter Institute came to national prominence when he announced he was the first to sequence the entire genome of a living organism. Later, he was one of a group of scientists to first sequence the human genome.

In May 2007 Dr Venter and his colleagues applied for the first patent for a synthetic lifeform - called Mycoplasma laboratorium. It sparked outrage, fear and quite a lot of scientific respect.

Some believe the achievement of realising this synthetic lifeform will finally convince people that synthetic biology can revolutionise the way we live, much as physics did in the 20th century.

However, ask Dr Venter where he sees the discipline heading in the next few years and he throws up his hands.

"It is hard to be certain about anything for the next year, let alone the next five or ten years because things are changing so quickly," he says.

Synthetic biology is the design and construction of new biological systems that do not exist in the natural world at the moment - or the redesign of existing systems to perform specific tasks. It is a multidisciplinary science, drawing heavily on advances in nanotechnology in particular.

One aspect can be seen in the dozens of laboratories dotted around the world that will produce small batches of DNA code on demand. These produce the tools; Dr Venter and his competitors are looking to turn them in to multi-million dollar applications.

In the case of the new lifeform, the members of his team took a simple bacterium, Mycoplasma genitalium, and then knocked out its genes one by one until they found the minimal genetic material needed for survival. Next came the re-synthesing of DNA sequences, welding them together and fitting them on to this 'chassis' to create a new organism. To succeed they needed to 'boot up' the organism to see if it would survive.

Breaking boundaries

"For the first time, God has competition," said Pat Mooney from the ETC Group which promotes socially responsible developments of technologies useful to the poor and marginalised.

She added: "Venter and his colleagues have breached a societal boundary, and the public hasn't even had a chance to debate the far-reaching social, ethical and environmental implications of synthetic life."

ETC nicknamed the new construct 'Synthia' as well as 'Pandora's Bug', just in case you hadn't got the message that they didn't like it.

According to Dr Venter, much of the fear and loathing that surrounds synthetic biology swirls around him because he is a public and quotable leader in its field - but it doesn't mean he believes everything attributed
to him.

It doesn't help that his career is a catalogue of feuds, spats and ego clashes that have mostly seen his enemies come worst off. The path he has chosen requires the development of a personality ironclad in its certainty.

As he told New Scientist: "I've been trying to survive outside the traditional funding system. You don't do that through false modesty, but you don't gain anything through false bravado either. I've not known anyone to be truly successful in any field that was immensely modest."

To be fair, he hasn't made specific claims for the glorious potential of synthetic biology - but plenty of others have.

Among the possible uses to which it could be put is an organism to eat pollution, alternatives to fossil fuels and cheap drugs. Part of Dr Venter's funding comes from the US Department of Energy, so it may well see some future in the biofuels spin-off.

For the apostles, synthetic biology offers bespoke solutions to some of humanity's basic needs. In an article in the New York Review of Books physics professor Freeman Dyson painted a pastoral vision of biotechnology in the future.

"Domesticated biotechnology, once it gets into the hands of housewives and children, will give us an explosion of diversity of new living creatures, rather than the monoculture crops that the big corporations prefer," he wrote.

Dyson extolled a 'green technology' that would revitalise small sustainable communities across the globe. It would be harnessed by small groups of people and adapted to their needs - not imposed from above by companies or governments.

The ETC group's vision is typical of many of who take a far darker view.

In its report 'Extreme genetic engineering' it said: "Extreme biotech is a dangerous technology that must not be developed in the absence of wide-spread societal debate and legally-binding regulation."

A miracle bug?

Some of the initial claims for what synthetic biology might achieve appear to have been dreamt up in order to to attract the maximum amount of attention. After all, a miracle bug to tackle pollution grabs a lot of column inches. However, the first things on the market were self-cleaning windows and better sun lotions - hardly life-changing.

The ETC group identifies treatment for malaria as one example where a synthetic biology fix may not be as wonderful as it first appears.

To treat malaria through drugs you need artemisinin. However, there is a worldwide shortage and the United Nations has made tackling this killer disease a priority. The ability to synthesise artemisinin offers a solution. However, it would put control of the drug in the hands of a small number of companies and there is unlikely to be a usable product for at least a decade. In the meantime, the thousands of small farmers, whose crops of sweet wormwood plants supply artemisinin at the moment, could find their market destabilised.

Instead of pursuing a long-term synthetic solution, more farmers could be encouraged to grow the plant supplying artemisinin, thereby offering a new revenue source and meeting demand.

Worst-case scenario

Attempting to seek positive uses and dealing with the unintended consequences is one thing. However, there is a worst-case scenario up for seizure.

Synthetic biologist Professor Drew Endy said: "I expect that this technology will be misapplied, actively misapplied, and it would be irresponsible to have a conversation without acknowledging that fact."

Some fear that, as synthetic biology techniques evolve, the threat of biowarfare, whether waged by states or terrorist groups, grows ever greater. The potential the science offers will be too much for some to ignore.

Already scientists have cobbled together strands of mail-order DNA to make a polio-like virus. The previously extinct Spanish Flu virus was next up for rebirth. Several investigations have found that not all companies, producing DNA fragments to order, check who wants the sequences and what use they might be put to.

The problem is, steps that might have taken hours a few years ago are now taking minutes and the process is improving at such a rate that it is coming into reach for more and more people.

A CIA report from 2003, 'The Darker Bioweapons Future', warned: "Growing understanding of the complex biochemical pathways that underlie life processes has the potential to enable a class of new, more virulent biological agents engineered to attack distinct biochemical paths and elicit specific effects."

Dr Venter told E&T that he perfectly understands these fears.

"We don't want anyone to be able to make a virus on their block," he said. "Some legal safety guards should be in place. However, having laws banning research does not stop it. We have to have vaccines if we want to eliminate bioterrorism."

Fundamentally, those warning about synthetic biology believe that at the moment the science is outstripping public debate and regulation. According to campaigners, scientists in this area are limited only by money and imagination - and the money keeps on flowing.

In its report on synthetic biology the ETC said: "The 'artificial life industry' is growing up in a 'wild west' free-for-all environment, with virtually no regulatory oversight.

"In fact, 'the synthetic biology community' - as the scientists refer to themselves - is making a concerted effort to stave off government scrutiny by making proposals that amount to self-regulation."

Stumped by furore

Dr Venter fiercely denies his research takes place in an ethical vacuum.

"We have asked for bioethical reviews because we want to have a broad discussion," he said.
"I do not know a scientist who doesn't ask ethical questions and I think that is one of the misnomers the public has."

He points out that all his research is published in scientific journals and that, by registering a patent, he puts his processes in the public domain. Therefore the work carried out is open to inspection and appraisal.

He confesses himself 'stumped' by the furore of the patent for Mycoplasma laboratorium.

"It's in the US constitution," he says. "I feel very comfortable with it. We did not patent something we found in nature."

What also drives Dr Venter is that he sees the traditional peer-reviewed funding process as safe, bland and unimaginative. This view was sharpened during the battles that took place over the human genome sequencing.

"How many thousands of scientists have been shot down because our consensus funding mechanism does not want to take risks?" he asked.

Synthetic biology research is still at an early stage but is growing rapidly.

In 2001, the number of published scientific papers on it was zero. In 2007 it was 65. Meanwhile, the market for supplying the DNA building blocks is about $600m a year. In 2015 it is expected to be worth around $3bn. Those are just the tools, not the actual products. That will bring in far more, but most observers expect it will be another 20 years before we can see those.

While the science may be new, the debates around where it is heading are, to some, wearily familiar.

Professor Sarah Franklin is the associate director of BIOS at the London School of Economics, an international centre for research and policy on the social aspects of the life sciences and biomedicine.

She characterises the language of public debate on this as impoverished, clichéd and just plain wrong. The argument is essentially that the science is unknowable, expanding faster than we imagine and therefore must be contained.

"This debate is dominated by worry and caution," she said. "Post-genetic modification, the cautionary principle reigns supreme. The discourse is that this is beyond our reach, it is too much to understand.

"The social hope that fuels much technological innovation exists in a constant tension with the application of strict controls of scrutinising innovation.

"These rote reactions are simply not adequate any longer."

On the side of caution

Perhaps surprisingly, when asked, Dr Venter supported a cautious approach.

"I find the scepticism very, very healthy. A lot of wild claims are made all the time," he said, adding with a twinkle in his eye: "I have always delivered on everything I have claimed."

One observer sympathetic to Dr Venter describes him a modern-day Alfred Nobel. If the 20th century was dominated by government-led research, then he speculated that Dr Venter and the other synthetic biology pioneers signal a return to the 19th century gentleman inventor and entrepreneur.

Dr Venter laughs when the comparison with Nobel is put to him. He may be thinking that the Swedish scientist was troubled at how posterity would view his explosive inventions and so bequeathed his fortune to recognising positive scientific endeavour. Dr Venter, who was a medic during the Vietnam war, offers a different comparison.

"When you look at Pasteur for example, he had to do things differently, to do what was necessary to move science forward because in that era it was also thought only government could do certain thing.

"I take a much more sanguine view of government. First look at Vietnam and then the Gulf War. That tells you something about governments."

Of course Pasteur also crossed disciplines, making advances in chemistry and microbiology, and is best known for work on germs and bequeathing pasteurisation. All very enlightened achievements. He also rode close to the wind legally and ethically on occasion.

In the current climate there seems little to hold back synthetic biology's development.

"If we are successful over the next few years in the new approach we are trying to develop, I imagine we can have a big impact on society," Dr Venter told E&T. "But the science has a very long way to go to do it."

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