Engineering biology in the light of evolution

Why Sculpt Evolution?

Evolved systems are very different from technologies designed by humans.

They're harder to predict and to design, and exhibit a frustrating tendency to evolve away from engineered behaviors.

At the same time, harnessing and directing evolution can generate useful organisms and biomolecules that we could never have rationally designed.

By working to understand why systems evolve in the ways that they do, we are learning to sculpt the evolutionary process and reliably engineer life in the laboratory and even the wild.

To learn more, see the introduction to evolutionary engineering , dive into our research, or jump straight to gene drives.

Research News

07 December 2015
A busy several weeks: our work on gene drive safeguards in yeast was published in Nature Biotechnology, where it appears atop the current most-read list of that journal. Next, Tony James and coworkers described an efficient CRISPR gene drive in An. stephensi, a minor malaria vector, paired with one of Tony's anti-malarial effectors. Finally, a European group including Austin Burt reported a beautiful example of a genetic load suppression drive in An. gambiae, the main malaria vector. These mosquito examples used ecological and barrier confinement as we advised and both worked well, though they are not evolutionarily stable and have expression problems. But if they use a new promoter (nos) and incorporate multiple guide RNAs, they will likely be active enough for release in a year or so. Ecological safety studies, education and informed consent, and international discussions (e.g. legal wrangling) will take far longer.

30 Jul 2015
Two major events concerning RNA-guided gene drive safeguards. First, we published a consensus piece in Science recommending safeguards for laboratory gene drive experiments. This was the fruit of convening 26 scientists in relevant fields - including Valentino Gantz and Ethan Bier - to discuss the relevant issues and provide guidelines. The upshot: always use multiple confinement strategies whenever possible, with any exceptions requiring great scrutiny. Moreover, we demonstrated that scientists can and will come together to act responsibly when needed. Second, I was honored to address the first meeting of a National Academy of Sciences panel convened to address the larger issues of gene drive potential, safeguards, and regulation.

19 Mar 2015 
Our predictions of Cas9 gene drive efficacy appear validated: Gantz and Bier describe a drive in fruit flies that is copied at 97% efficiency.  Unfortunately, they apparently were not aware of our research and developed it primarily as a genome engineering tool using only physical methods of confinement.  This is problematic as it encourages other laboratories to do the same, which will eventually lead to an accidental release. I've reached out to them and others in the Drosophila and gene drives fields, and we are now composing a consensus Perspective recommending the use of multiple confinement strategies.

19 Mar 2015
Our updated preprint now demonstrates that reversal drives work efficiently in yeast.  We also demonstrate the efficacy of two forms of molecular containment and call for all laboratories working with potential gene drives to use these in addition to other safeguards.

04 Feb 2015
Kevin was chosen as a Fellow of the Synthetic Biology Leadership Excellence Accelerator Program (LEAP), which seeks to foster leadership in advancing responsible practices in biotechnology. Our first gathering sparked many ideas on how to responsibly conduct gene drive research and outreach aimed at fostering transparent, broadly inclusive discussions.

20 Jan 2015
In a new preprint, we demonstrate that RNA-guided gene drives based on Cas9 can bias inheritance in wild yeast strains at least as effectively as naturally evolved gene drives. We validate several of our earlier designs and control strategies intended to prevent accidental gene drive escape. These are the first synthetic endonuclease gene drives that function in wild organisms.

29 Aug 2014
In a comment on our piece in Science, David Gurwitz suggests that all technical information concerning gene drives should be kept confidential. We strongly disagree for both scientific and biosecurity reasons, but encourage further discussion.

11 Aug 2014
I'm grateful for a K99/R00 award from NIDDK, which will be funding our efforts to engineer microbial ecologies using phages, conjugation, and CRISPR.

17 July 2014
In eLife, we describe how RNA-guided gene drives based on CRISPR could spread almost any genomic alteration through wild populations over many generations.  We also outline important safeguards to guide the responsible development of the technology. Our piece in Science focuses on mitigating risks and reforming regulations, while a popular science post at Scientific American explains the possibilities and associated ethical concerns. Learn more here.

2 June 2014
In PLoS ONE, we show that Cas9-mediated phage resistance is remarkably unimpeded by DNA modifications that block restriction enzymes.  Applications are on the way.

17 Feb 2014
We received an NSF grant to fund our collaboration with Ginkgo BioWorks, in which we are engineering more evolutionarily robust bacteria for sustainable chemical production.

29 Sep 2013
Our new Article in Nature Methods describes how we characterized several Cas9 proteins and showed that they could be used to mediate different activities in cells without interfering with one another.

27 Sep 2013
Our Perspective in Nature Methods explores the current use and remarkable future potential of Cas9/CRISPR systems as biotech tools.

1 Aug 2013
In work published in Nature Biotechnology, we show that Cas9 can be used as an RNA-guided transcriptional activator, profile its specificity, and demonstrate that paired nickases can reduce off-target cutting.

16 Jun 2013
Together with the laboratories of John Calarco and Monica Colaiacovo, we used Cas9 to precisely engineer the genome of the model organism C. elegans.  Our  manuscript was published in Nature Methods.

28 May 2013 In a project I began before leaving David Liu's lab that has been led by Bryan Dickinson, we used phage-assisted continuous evolution to show that protein evolution is not particularly reproducible and is highly dependent on the evolutionary path taken. The results are described in PNAS.

22 Jan 2013 I've written a comprehensive review of genome engineering together with Harris Wang for Molecular Systems Biology.

3 Jan 2013
In a pioneering study led by Prashant Mali of George Church's lab, we show that the RNA-guided endonuclease Cas9 can accomplish facile, robust, and multiplexable genome engineering in human cells. Our work was published back-to-back in Science with a similar study from Feng Zhang's lab.

Evolving Thoughts

  • Discussing gain-of-function research In the course of promoting safeguards and transparency in the field of gene drives, many have drawn a comparison to so-called “gain-of-function” (GOF) research on influenza and ...
    Posted Oct 19, 2015, 7:51 PM by Kevin Esvelt
  • Safeguards for laboratory gene drive research I recently convened a diverse group of scientists from relevant fields, including those who published a drive-based genome editing method at UCSD in March, to agree on recommended safeguards ...
    Posted Oct 19, 2015, 7:50 PM by Kevin Esvelt
  • Sculpting Futures I was fortunate to attend the MIT Media Lab's Knotty Objects celebration, which brought scientists and engineers together with artists and designers to spark creativity and new approaches. For ...
    Posted Jul 28, 2015, 4:15 AM by Kevin Esvelt
  • Gene drives for kids An explanation courtesy of the Up Goer Five Text Editor and inspired by xkcd: It would be nice if we could change how some animals and other living things act ...
    Posted Jun 24, 2015, 11:13 AM by Kevin Esvelt
  • Empirical grounding, legitimacy, and trust The question of whether it is ethical to insist that decision-making be empirically grounded remains difficult. To reprise, is it fair for us to initiate the terms of the ...
    Posted May 18, 2015, 6:22 PM by Kevin Esvelt
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