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ON 14 December 1967, Arthur Kornberg at Stanford University and colleagues announced that they had copied the DNA of the Phi X174 virus, producing an entity with the same infectivity as the wild virus. Though the DNA sequence in question was not known, Kornberg hoped the achievement would aid studies of genetics and the search for cures for diseases, and reveal the most basic processes of life itself. Kornberg鈥檚 claim to have come the 鈥渃losest yet鈥� to creating life and hailed it as 鈥渁 very spectacular breakthrough鈥�.

In 2003 we were able to go a step further, using DNA made from a sequence in a computer rather than a copy made by an enzyme. By 2008 we could synthesise a small bacterial chromosome over 20 times as big as that of Phi X174, though we were unable to activate it in a cell. With our publication in Science last week, we have now achieved this step with the 1.08-million-base-pair genome of Mycoplasma mycoides (see 鈥淪ynthetic life: where next?鈥�).

We did not create life from scratch: we transformed existing life into new life. Nor did we design and build a new chromosome from scratch. Rather, using only digitised information, we synthesised a modified version, a copy of the M. mycoides genome with 14 of its genes deleted and a 鈥渨atermark鈥� written in another 5000-plus base pairs. The result is not an 鈥渁rtificial鈥� life form; it is a living, self-replicating cell that most microbiologists would find hard to distinguish from the progenitor cell, unless they sequenced its DNA.

It took 15 years to get to this proof-of-concept experiment. And it is just that: proof that it is possible to use a computer and four chemical bases to create a cell with no biological ancestor. Of course, we began by modifying an existing genome. Where else to start? Had we tried a new genome design it wouldn鈥檛 have worked. Even so, we had 99 failures for every success.

Our synthetic cell is a small but highly significant step in synthetic genomics. Without this success, there would be no future for what has been, until now, a theoretical field. We now have a new set of tools to begin to understand cellular life, to test combinations of the 40 million sequenced genes in our computers, few of which have well-defined functions.

Nor is there any cell 鈥� and certainly not our synthetic cell 鈥� where the function of every gene is understood. We don鈥檛 know yet which genes are essential for life and why. It will be interesting to see how few components are needed to boot up a synthetic chromosome. Perhaps all it will take is a lipid vesicle and the ability to make messenger RNA and ribosomes 鈥� but we don鈥檛 know.

We now have the means to design and build a cell that will define the minimal set of instructions necessary for life, and to begin the design of cells with commercial potential, such as fuel production from carbon dioxide. We can assemble genome-sized stretches of DNA that can also be used to mix and match natural and synthetic pieces to make genomes with new capabilities.

Synthesising DNA in this way is still expensive, but we expect the cost to fall dramatically. This may make the complete synthesis of genomes competitive with the alteration of natural genomes to add new capabilities to bacterial cells. It should also be practical to synthesise simple eukaryotes, such as yeast, to which it is already possible to add extra chromosomes. The construction of large pieces of synthetic DNA and their introduction into a receptive cytoplasm is no longer a barrier. The limits to progress in synthetic biology are now set by our ability to design genomes with particular properties.

All potential applications of this science depend on review, discussion and debate, to ensure that the technology is used for positive purposes and that society understands the science and the issues. We intend to be part of this process. In this way, our first synthetic cell represents a new beginning. J. Craig Venter, Clyde Hutchison III and Hamilton Smith