The “synthetic cell” created by Craig Venter and his colleagues (D. G. Gibson et al. Science doi:10.1126/science.1190719; 2010) is a normal bacterium with a prosthetic genome. As the genome is only about 1% of the dry weight of the cell, only a small part of the cell is synthetic. But the genome is pivotal because it contains the hereditary information that controls so much of a cell’s structure and function. The ability to make prosthetic genomes marks a significant advance over traditional genetic engineering of individual genes. The prosthetic genome contains all the information in the natural genome that it supplants, except for a few minor differences (for example, some ‘watermarks’ were added). There is no technical reason to stop there; any of the information in a prosthetic genome can be changed. Tomorrow’s synthetic cell could be radically unlike anything encountered in the history of life. Putting prosthetic genomes into bacteria raises important scientific and societal issues, beyond those raised by biotechnology in general and genetic engineering in particular. I will mention just four. First, we now have an unprecedented opportunity to learn about life. Having complete control over the information in a genome provides a fantastic opportunity to probe the remaining secrets of how it works. Second, even the simplest forms of life have unpredictable, emergent properties. These properties are often useful and we want to control them, but their unpredictability presents a conundrum for traditional engineering. We must develop and perfect methods for engineering emergence. Third, these new powers create new responsibilities. Nobody can be sure about the consequences of making new forms of life, and we must expect the unexpected and the unintended. This calls for fundamental innovations ‘Bottom-up’ will be more telling