Dr Craig Venter: So, Doctor, how does it feel to have created artificial life?

Steve Connor speaks to the scientist who created the first synthetic living cell

Sunday 23 October 2011 03:40

What have you done that is new?

This is the first time anyone has built an entire 1.08 million base pair chromosome, transplanted that chromosome into a recipient cell and for that chromosome to take over that cell, effectively converting it into a new species defined by the chromosome. So it's a whole new paradigm, the first time we have a cell that is totally controlled 100 per cent by a synthetic chromosome.

Do you consider this to be synthetic life?

We're defining it as synthetic life because it's totally determined by the synthetic chromosome. We do start with a living cell but the synthetic chromosome totally transforms that living cell to this new synthetic cell.

There are no single elements of the recipient cell. Our synthetic cell has undergone over a billion replication events and the only DNA in it is the synthetic DNA and the only proteins are those coded for by the synthetic DNA. We don't make the proteins synthetically, we don't make the cells synthetically. All that is dictated by the chromosome.

We do not consider this to be "creating life from scratch" but rather we are creating new life out of existing life using synthetic DNA to reprogram the cells to form new cells that are specified by the synthetic DNA.

Why did you choose the microbe Mycoplasma mycoides to be your guinea pig?

This is step one, a proof of the paradigm. It makes sense to us to start with something that we know should be biologically active, if we can make it accurately. Proving that this is possible is no minor feat. It changes the stage from hypothetical, which is where it was two months ago, to real.

So is this new form of life a replicating, free-living organism?

That is correct, only it is only free-living in the sense that it grows in the laboratory in a very rich culture media so it wouldn't survive in the outside environment. Given the right nutrients in the laboratory it is completely self-replicating on its own.

How difficult was this?

At one time there was just one error in over a million base pairs, and we found that as a result you don't get life. So this was very difficult. I was predicting for the past three years that we would achieve this breakthrough, so I've learnt not to do predictions. There were huge hurdles to overcome here. We had to learn and invent new systems to make this possible, so it wasn't trivial

What are you hoping to achieve eventually?

The purpose is to try to understand the basic nature of life, and the minimal sets of genes needed for life. We do not know all the gene functions in any single cell. We don't know what they do, we don't know how they all work so we've been trying for 15 years to come up with ways to be able to define that even for simple cells.

So that is the key part of the next stage. But over the years the uses of this technology have become much more apparent to us and to others. It's a powerful technology for actually trying to design specific functions into organisms, for example to manufacture new fuels out of carbon dioxide or to create new vaccines very rapidly instead of the long delays we have.

I liken it to the 1940s and 1950s when the electronics revolution was still getting going. The people then building circuits probably had very little notion about BlackBerry phones or iPhones or personal computers. It's probably hard to imagine all the applications of this technology. Our view is that we're going from 6.8 billion to 9 billion people in the next 30 to 40 years, and we can't provide the food, the energy, clean water or medicines for the 6.8 billion, so we need some radical new technology to be able to do that without destroying the planet for 9 billion people.

Are you playing God with life?

We've covered this before because it's almost a cliché every time there's a new breakthrough in science, particularly in biology. Science is understanding life at its most basic levels and trying to use that knowledge for the betterment of humanity so I think we are part of the progression of scientific knowledge and understanding of the world around us.

Are you concerned that this technology may be misused?

We have to be concerned. It's a powerful technology and I've proposed new regulations in this field because I feel the existing ones don't go far enough. Because we're the inventors and developers of this we want to see everything that can be done to prevent misuse of this technology.

I've proposed regulating the companies that synthesise DNA, to screen [the DNA being synthesised] against harmful agents, and we've given feedback on improving those screens and being more rigorous. I've been briefing the US Congress on this. We don't want people taken by surprise. We want to put this breakthrough into context in terms of what it means. We're trying to take every responsible step we can in that respect. I think this is the first incidence in science where the extensive bioethical review took place before the experiments were done. It's part of an ongoing process that we've been driving, trying to make sure that the science proceeds in an ethical fashion, that we're being thoughtful about what we do and looking forward to the implications to the future.

The scientists' view

Professor John Harris, Manchester University

"Craig Venter talks of 'writing the genetic code' of a cell which then becomes self-replicating. This is heady stuff which Venter admits has potential for both good and ill. He is very precise about the possible benefits but not about the dangers. This work deserves praise and enthusiasm, but only so long as the risks are given attention commensurate with the benefits."

Professor Julian Savulescu, Uehiro Chair in Practical Ethics, University of Oxford

"Venter is creaking open the most profound door in humanity's history. He is not merely copying life artificially, as Wilmut did, or modifying it radically by genetic engineering. He is going towards the role of a god: creating artificial life that could never have existed naturally. We need new standards of safety evaluation for this kind of radical research and protections from military or terrorist misuse and abuse."

Dr Gos Micklem, Dept of Genetics at the University of Cambridge

"This is a landmark paper. The group are leaders at synthesising and re-assembling large segments of DNA. There is already a wealth of simple, cheap, powerful and mature techniques for genetically engineering a range of organisms. Therefore, for the time being, this approach is unlikely to supplant existing methods. DNA synthesis is rapidly becoming cheaper, so this could change, but not soon."

Professor Paul Freemont, Co-Director of the EPSRC Centre for Synthetic Biology at Imperial College London

"The applications of this technology [could be] a key step in the industrialisation of synthetic biology, leading to a new era of biotechnology. It is not clear if this approach will work for larger and more complex genomes or for transplantation in different bacterial cells. Still, this is a landmark step in our abilities to produce man-made cells for man-made purposes."

Professor Douglas Kell, CEO of the UK BBSRC

"The ability to do all of the steps of protein synthesis, from genome to product, to make something useful is an important step in developing the potential of synthetic biology. As we become technically better at doing synthetic biology, the potential applications open up. Mainly, what it will allow us to do is harness useful biological processes so that we can make products that are difficult to synthesise with traditional chemistry and physics."

Factfile: Craig Venter

* Craig Venter first gained notoriety in the 1980s, when he left the publicly funded human genome project in the US to set up a privately financed initiative in direct competition with the government research programme. He developed a "shotgun" method of decoding the genome by splitting the DNA into thousands of fragments that could be decoded simultaneously. This technique was faster than the more laborious, but somewhat more accurate, method used by the public project.

* A former Vietnam veteran and beach bum, Venter became interested in medical science when he witnessed soldiers dying from a single bullet wound and others surviving horrific injuries. He went back to college to make up for his lost education and quickly made a name for himself, as well as making enemies on the way.

* He completed a draft of the human genome and agreed to share the publicity platform with scientists leading the publicly funded initiative. He shook hands with his arch-rivals in a White House ceremony presided over by Bill Clinton. He claims he was depicted wrongly by the media as a scientist more interested in financial gain than furthering the boundaries of scientific knowledge.

* His first big breakthrough in the field of synthetic life probably occurred in 1995, when he led the team that sequenced the genome of the microbe Mycoplasma genitalium, only the second free-living organism to have its genome sequenced at that time. He said that the decoding of a microbe led him to think about synthesising a genome from scratch to create a free-living organism.

* In 1999, he announced his intention to start the "minimal genome project" to find the smallest set of genes required for life. This led in 2008 to the production of a complete genome of a single-celled microbe, but it would take several more years for Venter and his team to get this synthetic genome to control a living cell.

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