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How one scientist has made it his mission to break the ultimate taboo: to create life itself

The US Department of Energy grants a controversial geneticist $3m for his attempt to answer the ultimate question

Science Editor,Steve Connor
Friday 22 November 2002 01:00 GMT
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Craig Venter's name is never far from controversy, and now he has embarked on what could be his most controversial project yet – a plan to build a synthetic life-form in a laboratory dish.

The former Vietnam veteran and US government scientist-turned-biotech entrepreneur said yesterday that he would set up a team of dedicated researchers to answer the ultimate question: what is life?

Dr Venter has been given $3m (£2m) from the US Department of Energy to begin the first stage of a project to synthesise the minimal amount of DNA needed to generate the spark of life and to keep the flame alive in a test-tube.

The plan is to insert a man-made genome into the empty shell of a dead, single-celled micro-organism to see whether a creature can be built that will grow, eat and reproduce just like those found in nature – except with some potentially valuable differences.

Dr Venter said the project could result in new breeds of microbes that can be used to generate alternative sources of energy by, for instance, producing hydrogen for fuel. Others could be engineered to soak up carbon dioxide pollution from the atmosphere.

Hamilton Smith, a Nobel laureate formerly of the Johns Hopkins University in Baltimore, will direct the research at Dr Venter's Institute for Biological Energy Alternatives (IBEA) in Washington DC. Dr Venter said: "IBEA was founded with the goal of exploring biological mechanisms for dealing with carbon sequestration and to study the creation of other potential energy sources such as hydrogen."

The project outlined yesterday has its roots in a scheme first publicised in 1999 when Dr Venter and Dr Smith said that they intended to study the minimal amount of genes necessary for life.

Dr Smith, who then worked at Dr Venter's Institute for Genomic Research, said at the time: "Defining the minimal genome is a very fundamental problem, and no one else seems to be approaching it experimentally."

His calculations suggested that the minimum number of genes needed to sustain a single-celled microbe would be somewhere between 256 and 350 – far fewer than the estimated 30,000 to 50,000 genes in the human genome.

About a hundred of these minimal genes had unknown functions, undermining the prevailing view that the fundamental mechanisms of a microbe's biochemistry are understood.

The latest research will concentrate on a microbe with a tiny genome. Mycoplasma genitalium, which lives in the human reproductive tract, consists of just 517 genes. Dr Venter was the first to sequence M. genitalium's genome and it is a relatively straightforward task to delete individual genes to see if they are vital for the organism's survival.

Ultimately, the aim is to empty the microbe's single cell of all its genetic material – in effect killing it yet leaving most of its biochemicals intact – and re-inserting artificial chromosomes containing machine-made DNA to see whether the microbe can be induced into life once again.

Once the life-form can grow and reproduce, further genes could be added to confer specific characteristics, such as being able to generate hydrogen or to absorb carbon dioxide. It will be genetic modification at its most extreme.

Dr Venter said the microbe would be disabled so that, for instance, it lacked the genes that would allow it to latch onto human cells. It would, he said, be too fragile to live outside the laboratory.

Ari Patrinos, a senior administrator at the Department of Energy, who will oversee the project, told the Washington Post yesterday that the project is a short-cut to find the minimal genome. "This is a case where we're trying to cheat a little bit, to take the smallest and simplest and make it smaller and simpler," Dr Patrinos said.

Anticipating the ethical and moral cross-fire that would greet his project, Dr Venter requested an independent assessment by a panel of ethicists and religious leaders, including a priest and a rabbi.

Led by Mildred Cho, a bioethicist at Stanford University in California, the panel concluded that there were no substantive technical, ethical or religious reasons why this work should not proceed.

"I'm less worried about the minimal genome project taking off and creating some kind of monster bug than I would be, partly because I have a sense that the scientists are aware of the possible risk of what they are doing," Dr Cho said.

When the ethics panel reported on the minimal genome initiative in 1999 it said that the microbes generated by the process would not necessarily pose any greater risk than other microbes engineered by existing techniques of DNA manipulation.

"Creating a minimal genome would represent an important step forward in genetic engineering as it would permit the creation of organisms [new and existing] simply from knowing the sequence of their genomes," the panel said.

However, in a clear warning about the potential misuse of this work, the ethics panel added: "The combination of large-scale sequencing of human pathogens [disease organisms], determination of the function of disease-associated products, and the development of technologies to assemble large pieces of DNA could lead to creation or release of organisms that could be used as biological weapons.

"It is disturbing that current regulatory methods provide little, if any, oversight of these technologies."

Man-made genome: What will it do?

* Craig Venter's latest project ­ to create life in a laboratory dish ­ is designed, in the first instance, to be one of pure scientific endeavour.

* Some of the greatest fears surrounding the project are that the findings and genetic breakthroughs could be used to create a new generation of biological weapons.

* The team of geneticists suggests, however, that the research could be used as the basis for detecting and combating biological weapons that are already in existence.

* The academic endeavours of Dr Venter and his team could give rise to a number of practical applications, such as being able to "soak up" polluting carbon dioxide from the emissions of power plants or producing hydrogen for fuel.

Self-belief and business drive give Darth Venter the edge

A heady mix of scientific achievement, self-promotion and an aggressive entrepreneurial spirit has ensured Craig Venter's fame has spread around the world. "Is my science of a level consistent with other people who have gotten the Nobel? Yes," he once said.

After early notable work in the field of genetics he joined the race to decode the human genome as the controversial head of a private American company.

The drive to decipher the three billion letters of the human genetic code pitted Dr Venter's company against a rival international, and publicly funded, team.

When, in 1998, the entrepreneur announced that his company, Celera Genomics, would get the sequence first and make it private property, it opened up a battle of philosophies.

At stake was one of the century's greatest scientific achievements and the chance to usher in a new era of genetic-based medicine promising a range of treatments. As the two teams were pitched against each other, Dr Venter, dubbed the "Darth Venter" of genetics, was criticised for trying to patent genes. The former surfer and Vietnam war veteran, who worked as an orderly in the naval hospital at Da Nang, revealed that he used his own genes as the source material.

The rival teams of scientists announced two years ago that they had independently decoded the human genome. The Venter project used a method known as the whole-genome shotgun approach, in which the entire genome was split into thousands of fragments before decoding.

Scientists from the Human Genome Project, based at the National Institutes of Health, in the US, used a slower and more methodical approach.

Paul Peachey

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