Safety

The yeast Saccharomyces cerevisiae has been in use by humans since at least the ancient Sumerians and is consumed daily, in various forms, by billions of people. As such, the organism is Generally Regarded As Safe (GRAS) by the United States Food and Drug Association (FDA). Our experiments utilize strains of the BY lineage, directly derived from the S288C strain, which has been undergoing laboratory propagation since its isolation from a rotting fig in Merced, California, in 1938. We think it exceedingly unlikely that this laboratory-adapted strain has retained the ability to replicate efficiently in the wild; for example this strain has lost its ability to form structures (pseudohyphae) thought to be important for it “forage” for nutrients. However, we know of no studies in which this assumption has actually been field-tested. Our experiments will be carried out in a contained laboratory environment and we have no plans for any field release of the engineered strains. All strains used carry auxotrophic mutations, making them dependent on particular lab-supplied nutrients, and likely to render these strains uncompetitive in the wild, where for example, free amino acids are unlikely to be readily available. Further, the strains used are haploid heterothallic strains, whereas wild yeast is homothallic and diploid (or greater-ploid). We believe that a likely byproduct of incorporating so many changes into the synthetic derivative strains will be substantially reduced fitness in the wild; however, we acknowledge that it is formally possible that by streamlining the genome and making it less likely to undergo rearrangement, the modified strain could acquire a growth advantage relative to wild type yeast, at least in laboratory conditions. We are considering incorporating additional safety features to prevent the viability of these strains in the wild (e.g., drug-dependency, orthogonal translation systems, and other types of “kill switches”).