Venter's build-a-bug workshop.

News reports on May 20, 2010, heralded a new era in scientific research, as well as a new way of thinking about the nature of life. Craig Venter and his team had created a cell controlled by an entirely synthetic genome. So, were the sensational headlines warranted? And just how much of an advance is the latest report from the Venter Institute? Craig Venter (Chairman and President of the J. Craig Venter Institute, Rockville, Md) always seems to be doing something scientifically brilliant and yet controversial. In the 1990s, he was sequencing the human genome through his then company, Celera, with the aim of owning the information and charging researchers for access. Then, in 2007, he sequenced the first complete diploid human genome of one individual—himself. An impressive, if some might say selfcentered, feat. His new article,1 reporting the first man-made cell, continues the brilliant-yet-controversial theme, with some claiming that Venter is now “playing God.” The motivation behind Venter’s latest work comes from his longstanding interest in deciphering the minimal genetic instructions required for cellular life. This interest was born back in the 1990s, and as a first step toward his goal, Venter chose to study a bacterium thought to have one of the smallest genomes of any replicating cell—Mycoplasma genitalium. Through extensive mutational analysis of the microbe, Venter and his team predicted that of its 480 protein-coding genes, only 300 or so were essential.2 Armed with this knowledge, Venter envisioned that he might be able to build his own minimal microbial genome from scratch. To show that such a synthetic genome is fully functional, he would then have to insert it into a genome-less cell and demonstrate that it could initiate and continue cell division.3 The challenge was on. In 2008, Venter and his team achieved the first step: they showed that they could synthesize an M. genitalium genome.4 This synthetic genome was identical to the naturally occurring one, except for the presence of DNA “watermarks”— DNA sequence changes or insertions that encode a secret message, such as a name or email address, and thus denote the genome’s synthetic origin. Step two—transferring the synthetic genome into a genome-less cell—proved more difficult, however. While figuring out this second step, the team decided to work with M. mycoides and M. capricolum—two faster replicating cousins of M. genitalium. This made each experiment speedier. The team eventually hit the jackpot earlier this year, when they managed to synthesize a full-size, DNA-watermarked M. mycoides genome, transfer it into an empty M. capricolum cell, and show that the genome could drive continuous cell replication. The M. mycoides genome is almost twice the size of M. genitalium’s, so the team is still a long way from achieving its ultimate goal—defining and synthesizing a minimal genome. However, they have made an impressive technical step forward, which has triggered equally impressive headlines, philosophical debates, and even a presidential inquiry: as a result of the article, Barack Obama’s recently formed bioethics commission has been tasked with investigating the ethical issues of synthetic biology.5 “In synthesizing novel organisms from scratch, synthetic biologists are playing God and doing so much more effectively than earlier genetic engineers. They are not just tinkering with life, they are designing and creating it,” reads a blog post by Julian Savulescu, Professor of Practical Ethics, University of Oxford, UK. Savulescu is more tempered on the telephone: “The playing God objection is reasonable as a The opinions expressed in News and Views are not necessarily those of the editors or of the American Heart Association. (Circ Res. 2010;107:444-445.) © 2010 American Heart Association, Inc.