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.

In the very long run, we seek understanding and wisdom sufficient to remedy one of the greatest flaws in our universe: nature has no moral compass.

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

News

4 Oct 2018
In PLOS Pathogens, Kevin outlines a path towards universal screening of DNA synthesis, cautions against spreading information hazards relevant to powerful new technologies, and suggests trialing new models of early-stage peer review as a means of accelerating and safeguarding science. Ed Yong has more.

27 Jul 2018
Bronte Lord and her team have released a beautiful mini-documentary on Mice Against Ticks.

2 Jul 2018
John Oliver covers genome editing, Mice Against Ticks, the responsibilities of scientists, and limericks on Last Week Tonight. We’ll strive to avoid earning that limerick.

20 Jun 2018
Rowan Jacobsen has a thoughtful take on gene drive at Pacific Standard, influenced by a visit to our group.

19 Jun 2018
Our manuscript showing that current self-propagating alteration drives are highly invasive has been published by eLife. This one already had its fair share of media attention as a preprint, but we've added some evidence suggesting that it will hold for suppression drives as well.

31 May 2018
Dylan Mathews has penned an incredible piece on gene drive for Vox. Nuanced, thoughtful, and comprehensive.

23 May 2018
Many thanks to Larry Klein and his film crew for their stellar coverage of Mice Against Ticks on PBS' NOVA Wonders.

21 Feb 2018
We are deeply grateful to our Māori partners for hosting Kevin, Devora, and Ashton in Aotearoa New Zealand, where they sought Māori advice on whether and how to develop daisy drive to remove invasive rodents in ways of consistent with whakapapa.

20 Feb 2018
Emma Marris profiles Karl Campbell and the potential of gene drive to aid his conservation efforts – along with other ethical reasons for using it - in Wired. Whether or not we choose to move forwards, we are morally responsible for the consequences. The pic of Kevin's cat shows who was clearly the priority in photo selection.

15 Feb 2018
Together with 7 others at MIT, Kevin was awarded a Sloan Research Fellowship.

13 Feb 2018
Kevin joined Jennifer Doudna in addressing a crowd of 2,000 in Melbourne's Convention Center (full event; Kevin's talk). Thanks to Luan Ismahil and his team at the Convergence Science Network for organizing, and Charles Robin at University of Melbourne for the invitation.

28 Dec 2017
Our review on harnessing gene drive is up at the Journal of Responsible Innovation, laying out social and technological steps that may aid wise development and use.

17 Nov 2017
Our call to focus on local drive systems for conservation (w/ Neil Gemmell in PLOS Bio) and our new preprint suggesting that alteration drives are likely to be highly invasive were covered by Carl Zimmer, Ed Yong, and Brooke Borel, among others. However, in trying to remedy my original unwise suggestion that self-propagating gene drive might be useful for invasive species, I thoughtlessly wronged my Maori colleagues by failing to ask about the political ramifications in Aotearoa New Zealand. This is precisely why it is vital to seek local guidance.

17 Sep 2017
In a community meeting in Dunedin, Kevin requested that New Zealanders help guide our development of daisy drive systems in rodents, which one day might be used to eliminate invasive rats and mice from Aotearoa. A summary of the topic is available on Responsive Science (which is due for an update soon - stay tuned!).

19 Jul 2017
Our team's proposal to develop daisy drive systems has been selected for funding by Safe Genes. An introduction to our research plan as well as the technical Statement of Work detailing planned experiments are available on Responsive Science.

17 Jul 2017
We welcome Stephen Von Stetina, who joins the group as our leading research scientist!

27 Jun 2017
Undiscovered podcast covers the heritable immunization project to prevent tick-borne disease on the Vineyard and Nantucket, while BBC's The Inquiry covers gene drive.

1 Jun 2017
Kevin was honored to give the Marsilius Lecture on reforming science at Heidelberg University.


25 Feb 2017
Radiolab's update to their popular CRISPR podcast focuses heavily on gene drive (and features Kevin).

10 Feb 2017
Our letter in Science makes the case for open gene drive research proposals using preprints to pre-register experimental plans. We've posted a new preprint on a new local CRISPR-based gene drive system, termed 'daisyfield drive', that debuts the pre-registration model.

18 Jan 2017
Thanks to all the citizens of Nantucket who joined us for a productive town meeting today (slides and video), particularly Dr. Emily Goldstein Murphy, the newest member of the project Steering Committee. We will have a project page available very soon. Please contact me if you'd like to be notified by any email of the next meeting and/or project advances.

26 Dec 2016
Michael Specter beautifully describes our work in the New Yorker. For those interested in the systemic issues with closed-door science, this TEDxCambridge talk provides an overview.

16 Dec 2016
Kevin named one of Nature's 10 for 2016.

06 Dec 2016
Due to delays with our Responsive Science site, our grant proposals involving gene drive are shared in Proposals.

13 Oct 2016
Kevin spoke at President Obama's White House Frontiers conference (video: talk starts at 1:28:20; updated Chrome required).

1 Sep 2016
Welcoming Devora Najjar and Avery Normandin to Sculpting Evolution!

26 Aug 2016
Kevin was named an Innovator Under 35 (TR35) by MIT Technology Review.

15 Aug 2016
Epigenie's piece titled "The Safer, Prettier Gene Drive" is likely the best news coverage of a preprint we will ever see.

20 July 2016
We held our first public meeting on Martha's Vineyard on permanently immunizing mice against Lyme disease: 100+ attendees, great discussion (video). Special thanks to Sam Telford and Dr. Michael Jacobs for joining us!

08 June 2016
Kevin's views on gene drive were published as a Nature World View.

07 June 2016
We discussed a proposal to alter white-footed mice to disrupt the cycle of Lyme disease transmission with the Nantucket Board of Health and local residents yesterday (video). We went to them before doing any experiments in the lab or obtaining funding so that the process could be owned and directed by the community from inception. The story was beautifully told by Amy Harmon in the New York Times. We hope for a similarly fruitful discussion on Martha's Vineyard next month.

05 June 2016
We've released two new preprints:
- Daisy drives are a local and temporary form of CRISPR-based gene drive that cannot spread indefinitely due to the successive loss of non-driving elements from the end of a daisy-chain. They should allow local communities to accomplish effects that would otherwise require a global CRISPR gene drive - including suppression - without imposing those changes on others (PDF).
- In a collaboration with Martin Nowak's group, we show that the multiple-guides approach we originally suggested is required for global drive systems to affect most organisms, and most certainly to suppress populations reliably. This can be done using the highly sequence-diverse guide RNAs that we characterized in the daisy drive paper to enable the use of many guides without risking recombination.

01 June 2016
We're delighted to welcome Joanna Buchthal, a first-year graduate student in the Media Lab. A graduate of the Rhode Island School of Design, Joanna is a former entrepreneur who has been learning molecular biology at the Wyss Institute. A resident of Chilmark, she will be leading the project to prevent Lyme and other tick-borne diseases by permanently immunizing mice.

16 March 2016
We're delighted to welcome Cody Gilleland, who has joined the group as a Research Scientist. Cody earned his PhD in Mechanical Engineering from MIT, where he was a pioneer in laser neurosurgery and invented an automated microinjection system for high-throughput transgenesis (Regeneron Prize 2013, Lemelson-MIT finalist 2014). Cody will be continuing to develop his high-throughput transgenesis system in preparation for commercialization, including applying it to transgenesis in many organisms. We hope to help his startup, Hive Biosystems, to make transgenesis an industry like DNA sequencing: one in which most labs outsource their needs to centralized firms who can screen orders for potential hazards - in this case, unauthorized or unsafe gene drive systems.

16 January 2016
The Sculpting Evolution Group has officially launched at the MIT Media Lab! We now have four group members: Kevin Esvelt, Georgiana Ujomu, John Min, Erika DeBenedictis. Georgiana has a background in environmental health and will keep everything running as group administrator and safety officer. John is a second-year graduate student, now a joint student shared with George Church's lab, from the Harvard Medical School BBS Program. He earned his undergraduate degree at Boston University and has previously worked with William Shih at the Wyss Institute on DNA nanotechnology. Erika is a first-year graduate student from MIT Bioengineering, now a joint student with Bruce Tidor's group. She earned her degree from Caltech in computer science after winning the Intel Science Talent Search in 2010 for her work on spaceflight software. Because our research laboratory will be undergoing renovation for the next several months, we will be focused on setting up, ordering equipment, planning experiments, obtaining bureaucratic approvals, and writing grants.

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 and Andrea Crisanti 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

  • Moral responsibilities for animal suffering There is a clear moral case for Africans to make use of gene drive to help eradicate malaria, but what of the non-humans who suffer? In Leaps Magazine, I ...
    Posted May 28, 2018, 6:52 PM by Kevin Esvelt
  • In tribute The currents of time carry us onwards, until the day comes when we can swim no longer. We are not wholly gone, for the ripples of our actions continue to ...
    Posted Jan 9, 2018, 7:15 AM by Kevin Esvelt
  • Aotearoa: Mistakes and Amends Publicly acknowledging a failure and trying to make amends can strengthen moral resolve. On November 16, I failed my partners. Researchers should hold themselves morally accountable for all of the ...
    Posted Jan 9, 2018, 7:13 AM by Kevin Esvelt
  • The morality of nature I've received many communications in response to the profile by Michael Specter in the New Yorker; more than I can answer. They've all been quite positive except for ...
    Posted Jan 9, 2018, 7:12 AM by Kevin Esvelt
  • Why Open Science? Most researchers keep their plans to themselves for a very good reason: the system punishes us if we don't. Share a brilliant idea, and another laboratory can throw more ...
    Posted Dec 26, 2016, 8:12 AM by Kevin Esvelt
Showing posts 1 - 5 of 19. View more »