Saturday, February 17, 2018

Future Genomics: Don't Edit A Rough Copy When You Can Print A Fresh New One

technologyreview  |  It took Boeke and his team eight years before they were able to publish their first fully artificial yeast chromosome. The project has since accelerated. Last March, the next five synthetic yeast chromosomes were described in a suite of papers in Science, and Boeke says that all 16 chromosomes are now at least 80 percent done. These efforts represent the largest amount of genetic material ever synthesized and then joined together.

It helps that the yeast genome has proved remarkably resilient to the team’s visions and revisions. “Probably the biggest headline here is that you can torture the genome in a multitude of different ways, and the yeast just laughs,” says Boeke.

Boeke and his colleagues aren’t simply replacing the natural yeast genome with a synthetic one (“Just making a copy of it would be a stunt,” says Church). Throughout the organism’s DNA they have also placed molecular openings, like the invisible breaks in a magician’s steel rings. These let them reshuffle the yeast chromosomes “like a deck of cards,” as Cai puts it. The system is known as SCRaMbLE, for “synthetic chromosome recombination and modification by LoxP-mediated evolution.”

The result is high-speed, human-driven evolution: millions of new yeast strains with different properties can be tested in the lab for fitness and function in applications like, eventually, medicine and industry. Mitchell predicts that in time, Sc2.0 will displace all the ordinary yeast in scientific labs.

The ultimate legacy of Boeke’s project could be decided by what genome gets synthesized next. The GP-write group originally imagined that making a synthetic human genome would have the appeal of a “grand challenge.” Some bioethicists disagreed and sharply criticized the plan. Boeke emphasizes that the group will “not do a project aimed at making a human with a synthetic genome.” That means no designer people.

Ethical considerations aside, synthesizing a full human genome—which is over 250 times larger than the yeast genome—is impractical with current methods. The effort to advance the technology also lacks funding. Boeke’s yeast work has been funded by the National Science Foundation and by academic institutions, including partners in China, but the larger GP-write initiative has not attracted major support, other than a $250,000 initial donation from the computer design company Autodesk. Compare that with the Human Genome Project, which enjoyed more than $3 billion in US funding.