Synthetic life: the revolution begins

Craig Venter’s artificial organisms could lead to downloadable vaccines

Craig Venter, king of the genome, has been uncharacteristically quiet for a couple of years since his laboratory created the world’s first synthetic life form, a microbe whose genes were made entirely from inanimate chemicals. But he returned to the scientific limelight this month on a visit to Dublin for the Euroscience Open Forum, during which he gave two public lectures – and updated the FT on plans for “a revolution in synthetic life that is just beginning”.

Some critics downplayed Venter’s achievement in 2010 because he did not make a novel form of life. The project was a technical tour de force, a demonstration that scientists could move on from reading to writing genes, but it reproduced an existing microbe called Mycoplasma mycoides, with just a few “watermarking” additions to distinguish its DNA from the natural bacterium.

Now his teams – working in tandem at the non-profit J. Craig Venter Institute and Synthetic Genomics, a biotech company in California – are well on the way to making synthetic microbes distinctly different to anything in nature. “We have a design contest to come up with a genome designed completely in a computer,” Venter says. “Three different versions of the genome are being constructed now and we hope to know by the end of the summer whether any of these designs will work as a living cell.”

The designs are all attempts to find the “minimal genome”, the least DNA with the fewest genes capable of sustaining a free-living organism. The smallest microbial genome in nature belongs to Mycoplasma genitalium, with 525 genes encoded in 580,000 chemical “letters” of DNA. The question is how much DNA is truly essential for life and how much is unnecessary clutter resulting from undirected Darwinian evolution.

Venter sees an efficiently designed minimal genome as the key step in his ambition to create organisms that will help to solve some of humanity’s big problems: for example, through pollution-free fuel production and growing food more efficiently than conventional agriculture. The idea is to find a basic chassis for life, which synthetic biologists can then engineer to carry out specific functions.

“Life evolved in a messy fashion through random changes over three billion years,” he says. “We are designing it so that there are modules for different functions, such as chromosome replication and cell division, and then we can decide what metabolism we want it to have. For instance, do we want it to live on sugar or sulphur or to turn carbon dioxide into methane?”

Venter and his colleagues are focusing on bacteria because these are the simplest microbes. But most of the practical applications will be developed in single-cell algae, whose metabolism and cell structure are better suited to turning out large quantities of food and fuel.

Some natural algae make liquid hydrocarbons similar to transport fuels, though not in the huge quantities that would be required to replace standard petrol and diesel. “It’s clear that production from natural algae could never approach the amounts we need, because they have not evolved to do anything with so much oil,” Venter says.

Although synthetic biology will be required, this need not involve redesigning the whole algal genome. Rather, he says, it may be better to supplement it by adding an extra synthetic chromosome designed for maximum fuel production.

The longer Venter talks, the clearer it becomes that the field in which he made his name – human genomics – holds less fascination for him today than the marriage of computing and biology represented by synthetic genomics.

“Digital life and actual life are getting closer and closer together,” he says. “We can digitise a genome and transmit the information down the internet to a digital-biological converter, which can turn it back into DNA in a real cell.”

Many applications are fermenting in Venter’s fertile imagination. “At some time in the future, you might have a little biological box attached to your computer,” he says. “You could use it, for example, if there is a pandemic. As soon as a vaccine is available, you could download the instructions and make it yourself, avoiding the huge delays and bottlenecks in manufacturing and distribution today.”

Always ambitious, Venter feels that he is just getting into his stride at the age of 65. Concluding our interview, he says: “We are trying to understand the fundamental principles for the design of life, so that we can redesign it – in the way an intelligent designer would have done in the first place, if there had been one.”

A less testing time for lab rats

Some campaigners see the extensive use of animals for research and safety testing as a moral outrage.

Most researchers reject that view and regard animal testing as a necessary evil, without which some of the life sciences would collapse. But many lament the inadequacies of using animals as an indicator of the way people will react to drugs and other chemicals.

This 'liver on a chip' may help to replace animal testing

“Seurat is primarily about providing better science for safety assessment rather than about the morality of using animals,” says Maurice Whelan, who leads the programme at Europe’s Joint Research Centre. “We believe animal testing does not provide the best scientific approach.”

The first phase of Seurat (Seurat-1) focuses on cosmetic ingredients, for which the EU will impose a complete ban on animal testing from next March. Half of the €50m funding comes from the cosmetics industry and half from the European Commission.

However, at the recent Euroscience Open Forum in Dublin, Seurat’s organisers made clear that their ambitions extend far beyond cosmetic testing, an emotionally sensitive but small user of animals.

The results will apply to safety assessments for a vast array of industrial chemicals, pesticides, household products – and medicines, where animal testing plays an essential role in the development of every drug.

“The body doesn’t see a chemical and say: ‘Oh, that’s a pharmaceutical or a cosmetic,’” observes Mark Cronin of Liverpool John Moores University.

The components of Seurat-1 illustrate the approaches taken by other programmes aimed at replacing animals.

One is to refurnish adult human cells as stem cells, which can then be directed to transform themselves into specialist cells like the ones that form human organs such as the liver, heart, brain or muscle.

Testing chemicals on specialist human cell cultures may give a better indication of their toxicity than using animals. Even better is to grow them into a whole human organ in a bioreactor – the subject of another Seurat project. A prototype bioreactor has already produced a “liver on a chip” from human liver cells, with sensors to measure toxicological effects that would normally become manifest only after long-term exposure.

Other parts of the programme use computer models of human metabolism, drawing on a database of 40,000 chemicals, which predicts the toxicity of untested products.

Pulling together all the elements of Seurat and other programmes, it should be possible to improve human safety while reducing the impact on animals. But Whelan says: “We are not saying that after five years we will never need to test a product on animals again. We have to look towards the long term and lay down a solid foundation.”

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