Venter team creates first synthetic living cell

Posted by Emma Woollacott

In what is being hailed as the greatest scientific breakthrough in a generation, researchers have created the first artificial living cell.

A team at the J Craig Venter Institute (JCVI) has synthesized the 1.08 million base pair chromosome of a modified Mycoplasma mycoides genome to create what they've called Mycoplasma mycoides JCVI-syn1.0.

This was transplanted into a recipient cell to produce a new, self-replicating cell controlled entirely by the synthetic genome.
 
"To produce a synthetic cell, our group had to learn how to sequence, synthesize, and transplant genomes. Many hurdles had to be overcome, but we are now able to combine all of these steps to produce synthetic cells in the laboratory," said researcher Daniel Gibson.

"We can now begin working on our ultimate objective of synthesizing a minimal cell containing only the genes necessary to sustain life in its simplest form. This will help us better understand how cells work."

The team designed 1,078 specific cassettes of DNA that were 1,080 base pairs (bp) long, and designed so that the ends of each DNA cassette overlapped each of its neighbors by 80bp.

The first stage involved taking 10 cassettes of DNA at a time to build 110 10,000bp segments. Then, these 10,000bp segments were taken 10 at a time to produce eleven 100,000bp segments. In the final step, all 11 100kb segments were assembled into the complete synthetic genome in yeast cells and grown as a yeast artificial chromosome.

The complete synthetic M. mycoides genome was isolated from the yeast cell and transplanted into Mycoplasma capricolum recipient cells that had had the genes for the restriction enzyme removed.

The synthetic genome DNA was transcribed into messenger RNA, which in turn was translated into new proteins. The M. capricolum genome was either destroyed by M. mycoides restriction enzymes or was lost during cell replication.

After two days viable M. mycoides cells, which contained only synthetic DNA, were clearly visible on petri dishes containing bacterial growth medium.

With this successful proof of principle, the group will now work on creating a minimal genome by whittling away at the synthetic genome and repeating transplantation experiments until no more genes can be disrupted and the genome is as small as possible. This minimal cell could become a platform for analyzing the function of every essential gene in a cell.

Giving science fiction writers a wonderful plot on a plate, the reserchers inserted into the genome what they call 'watermarks'.

These are specifically designed segments of DNA that use the 'alphabet' of genes and proteins to spell out words and phrases. They prove that the genome is synthetic and not native, and identify the laboratory of origin.

Encoded in the watermarks is a new DNA code for writing words, sentences and numbers. In addition to the new code, there is a web address to send emails to if you can successfully decode the new code, the names of 46 authors and other key contributors and three quotations: "TO LIVE, TO ERR, TO FALL, TO TRIUMPH, TO RECREATE LIFE OUT OF LIFE." - JAMES JOYCE; "SEE THINGS NOT AS THEY ARE, BUT AS THEY MIGHT BE.”-A quote from the book, “American Prometheus”; "WHAT I CANNOT BUILD, I CANNOT UNDERSTAND." - RICHARD FEYNMAN.

The applications of the synthetic cell are, of course, practically endless, and hard to envision fully. The scientists foresee the technique being used to create biofuels, vaccines, pharmaceuticals, clean water and food products.

It remains to be seen what hard-line religious groups will make of this achievement. Needless to say, the research has been subject to rigorous review by an independent panel of ethicists. But Ventner acknowledges that any new discovery of this magnitude will have far-reaching effects.

"We have been consumed by this research, but we have also been equally focused on addressing the societal implications of what we believe will be one of the most powerful technologies and industrial drivers for societal good," he says.

"We look forward to continued review and dialogue about the important applications of this work to ensure that it is used for the benefit of all."

Full details will appear in Science.