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August 03, 2010

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Scientists report first cell made with artificial genes

May 20, 2010
Courtesy of the American Association 
for the Advancement of Science
and World Science staff

Sci­en­tists say they have de­vel­oped the first cell con­trolled by an ar­ti­fi­cial ge­nome. 

Al­though it’s a near-copy of a nat­u­ral ge­nome, the re­search­ers say their meth­od can be used to bet­ter un­der­stand the bas­ic ma­chin­ery driv­ing life, and to en­gi­neer bac­te­ria for tasks such as fu­el pro­duc­tion or en­vi­ron­men­tal clean­up.

The synthetic cells, dubbed JCVI-syn 1.0. (Courtesy AAAS)
The re­search group, at the J. Craig Ven­ter In­sti­tute in Rock­ville, Md., was al­ready cred­ited with chem­ic­ally pro­duc­ing a bac­te­ri­al ge­nome, and with trans­planting the ge­nome of one bac­te­ri­um to an­oth­er. In the lat­est work, re­ported in the May 21 is­sue of the re­search jour­nal Sci­ence, the team com­bined both meth­ods. The re­sult is what they call a “syn­thetic cell,” though only its ge­nome is syn­thet­ic, or ar­ti­fi­cial.

“This is the first syn­thet­ic cell... we call it syn­thet­ic be­cause the cell is to­tally de­rived from a syn­thet­ic chro­mo­some, made with four bot­tles of chem­icals on a chem­ical syn­the­siz­er, start­ing with in­forma­t­ion in a com­put­er,” said J. Craig Ven­ter, pres­ident of the in­sti­tute and lead­er of the re­search.

The ar­ti­fi­cial ge­nome con­sisted of a se­quence of DNA code on a sin­gle chro­mo­some; bac­te­ria need only one, cir­cu­lar chro­mo­some. The new ge­nome’s code was cop­ied from that of a bac­te­ri­um known as My­coplasma my­coides. How­ev­er, the sci­en­tists added DNA se­quences that “wa­ter­marked” the ge­nome to dis­tin­guish it from the orig­i­nal.

Be­cause cur­rent machines can only as­sem­ble rel­a­tively short strings of DNA let­ters at a time, the re­search­ers used the DNA repair mac­hin­ery of yeast and E. coli bac­te­ria to link these strings to­geth­er and form full chrom­o­somes. Af­ter three rounds of as­sem­bly involving transplanting between yeast and E. coli, the re­search­ers had pro­duced a ge­nome over a mil­lion base pairs, or ge­net­ic “let­ters,” long.

The sci­en­tists then trans­planted the syn­thet­ic M. my­coides ge­nome in­to an­oth­er, re­lat­ed type of bac­te­ria, My­coplasma capri­colum. The new ge­nome “booted up” the re­cip­i­ent cells. These be­gan to func­tion al­most like the orig­i­nal M. my­coides as judged by the chem­ical prod­ucts of their genes, pro­teins, and by the cells’ col­o­niz­ing prop­er­ties, said Ven­ter and col­leagues. Four­teen genes failed to func­tion in the trans­plant bac­te­ria, the re­search­ers said, but this did­n’t dis­rupt the overall ac­ti­vity of the new cells, which al­so could re­pro­duce.

“This is an im­por­tant step, we think, both sci­en­tif­ic­ally and phil­o­soph­ic­ally,” Ven­ter said.

Ac­knowl­edg­ing that re­search in­to the crea­t­ion of ar­ti­fi­cial life forms is sub­ject to eth­i­cal de­bates, Ven­ter said his team asked for a bioeth­i­cal re­view in the late 1990s and has par­ti­ci­pated in var­i­ous dis­cus­sions on the top­ic. “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,” he said.

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Scientists say they have developed the first cell controlled by an artificial genome. Although the genome is a near-copy of a natural genome, the researchers say their method can be used to better understand the basic machinery driving all life. It could also be extended to engineer bacteria for tasks such as fuel production or environmental cleanup, they said. The research group, at the J. Craig Venter Institute in Rockville, Md., was already credited with chemically producing a bacterial genome, and with transplanting the genome of one bacterium to another. In the latest work, published in the May 21 issue of the research journal Science, the researchers combined both methods. The result is what they call a “synthetic cell,” though only its genome is artificial, or synthetic. “This is the first synthetic cell that’s been made, and we call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer,” said J. Craig Venter, president of the institute and lead researcher on the probject. The artificial genome consisted of a sequence of DNA code on a single chromosome; bacteria need only one, circular chromasome. The new genome’s code was copied from that of a bacterium known as Mycoplasma mycoides. However, the scientists added DNA sequences that “watermarked” the genome to distinguish it from a natural one. Because current machines can only assemble relatively short strings of DNA letters at a time, the researchers inserted the shorter sequences into yeast, whose natural DNA-repair machinery linked the strings together. The scientists then transferred the medium-sized strings into E. coli bacteria and back into yeast. After three rounds of assembly, the researchers had produced a genome over a million base pairs, or genetic “letters,” long. The scientists then transplanted the synthetic M. mycoides genome into another, related type of bacteria, Mycoplasm capricolum. The new genome “booted up” the recipient cells. These began to function almost like the original M. mycoides as judged by the chemical products of their genes, proteins, and by the cells’ colonizing properties, said Venter and colleagues. Fourteen genes failed to function in the transplant bacteria, the researchers said, but this didn’t disrupt the overall activity of the new cells, which also could reproduce. “This is an important step we think, both scientifically and philosophically,” Venter said. Acknowledging that research into the creation of artificial life forms is subject to ethical debates, Venter said his team asked for a bioethical review in the late 1990s and has participated various discussions on the topic. “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,” he said.