August 13, 2015
For thousands of years, humans have used yeast as an essential part of recipes for bread, wine, and beer. But now we’re turning the tables on yeast. Instead of creating recipes with yeast, researchers are creating recipes for yeast.
Now of course we have been making minor tweaks here and there for years. But what we’re talking about now is changing out the whole recipe book: creating a whole new genome for S. cerevisiae.
The Synthetic Yeast 2.0 Project (Sc2.0) has the ambitious goal of re-designing and synthesizing the entire yeast genome, some 12 million base pairs. Along with the scientific challenges, the researchers face some tricky ethical issues as well. After all, they’re creating the blueprint for an entire living eukaryotic cell!
Fortunately, the Sc2.0 researchers have thought long and hard about these issues. They’ve issued a statement of ethics and governance in a new article in GENETICS that also reviews the current regulatory and ethical landscape for synthetic biology. The statement by Sliva and colleagues sets the course for Sc2.0 and serves as a model for oversight of other synthetic biology projects.
We wrote about the science in this space before, when the project published its first major milestone, the synthesis of chromosome III. It’s fascinating stuff: the scientists are not only re-synthesizing the genome, but are re-designing it to be leaner and more useful in the lab. They’re adding features like loxP sites that can be used to alter the structure of the genome for evolution experiments, and engineering the tRNA genes so that one codon can be repurposed to code for a novel amino acid.
But even though these are seemingly benign changes to a relatively harmless beast, there are ethical issues inherent in modifying a living organism in such a big way. While the authors focus on Sc2.0, the issues they discuss are relevant to other synthetic biology projects that combine genes from several organisms in novel pathways, such as the efforts to create an opiate biosynthetic pathway in yeast.
While we can only touch on the highlights of their statement here, one of the principles most strongly emphasized by Sliva and colleagues is that all Sc2.0 work will be done for peaceful purposes that benefit society. To promote transparency, they are making outreach a priority, engaging with and educating the public about the project. Sc2.0 will be a public resource, with no intellectual property rights or restrictions on data or materials.
The researchers are also committed to safety. They have engineered multiple auxotrophies into all working strains so that they need special media to survive, even though it seems unlikely that an Sc2.0 strain on the loose would be harmful or would have a competitive advantage over wild strains. And although it’s not required for working with organisms like yeast that are classified “Generally Regarded as Safe” by the FDA, all participants in the project receive biosafety training.
Currently, there is relatively little official policy in place for the field of synthetic biology. Two safety measures currently recommended for DNA synthesis companies by the U.S. Department of Health and Human Services are that the companies check that the sequences they synthesize don’t correspond to toxins or harmful organisms, and that they also verify the identities and institutions of their customers. While compliance with these guidelines is voluntary, the Sc2.0 project has decided to support only companies that follow these safety measures.
To ensure that the policies outlined in their Statement of Ethics and Governance are followed, the Sc2.0 project will maintain an Executive Committee comprised of people both internal and external to the project who have broad expertise in policy, ethics, and science. All of the participants in the project are accountable to this committee, which will actively monitor the work to ensure that the guidelines are followed.
It’s obvious that this is no half-baked scheme, but rather an impressively well-planned recipe for cooking up a yeast cell from scratch. But, we expect nothing less from our friend S. cerevisiae and the talented researchers in the yeast community than to be at the forefront of modern science!
by Maria Costanzo, Ph.D., Senior Biocuration Scientist, SGD
Categories: Research Spotlight