Years after Completion, Kevin Esvelt's Thesis Keeps On Evolving

July 9, 2018

Hertz Fellow Kevin Esvelt is today best known for his efforts to fight disease through so-called “daisy drives,” limited-range gene drives that propagate genetic changes throughout a population – but which are self-limiting to stay within a particular community. These efforts have in the last few weeks been featured in a NOVA documentary, a Vox feature, and even on comedian John Oliver’s Last Week Tonight.

But Esvelt’s work during his Hertz Fellowship – not on gene drives, but on using directed evolution to improve individual protein-synthesizing genes in the lab – is quietly fueling a revolution of its own. Esvelt’s PhD thesis, for which he shared the Hertz Foundation’s 2011 Thesis Prize, described a new tool for using bacteriophages to rapidly evolve enzymes and other proteins in the lab. Where it had previously taken days to mutate, express, screen, and select new and improved genes in the lab, it could take Esvelt’s automated system, called PACE (Phage-Assisted Continuous Evolution), less than an hour.

David Liu’s lab at the Broad Institute, where Esvelt developed the technology, still uses the method to develop now proteins. This month WIRED described how the tool is being used to develop improved versions of the CRISPR-associated proteins, that Liu hopes will address genetic diseases by editing the human genome far more safely and effectively than natural CRISPR-Cas9 systems.

So while Esvelt continues to build his career around engineering ecosystems to fight infectious diseases, his thesis has taken a life of its own fighting the diseases that arise within our own DNA.

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