“I was captivated by the marvels of the Galapagos Islands, and through them, Darwin’s writings on evolution. How glorious, that endless forms most beautiful and wonderful are wrought with neither knowledge nor intent! And how profoundly tragic, that the font of life is heedless of suffering. Perhaps we – gifted with the moral compass that evolution lacks – are burdened with learning its secrets, and with wisdom and loving kindness, remedying the flaw in creation.”
Kevin Esvelt’s description of how he was inspired to become “an evolutionary engineer, first and foremost” is worth bearing in mind when reading his new PLOS Biology perspective piece. Esvelt leads the Sculpting Evolution Group at Massachusetts Institute of Technology, and his article, co-authored with Neil Gemmell from the University of Otago, New Zealand, explores the risks of using self-propagating gene-editing systems to eradicate New Zealand’s invasive species. It’s a stark warning from the scientist who first identified the possibilities that such systems, based on a gene-editing technique known as CRISPR, could hold for conservation efforts. I interviewed Esvelt via email to find out more about this research and about how Esvelt’s own “moral compass” shapes his work.
You head up the “Sculpting Evolution” group at MIT. What does your group work on?
KE: We seek to understand, redirect, and harness evolution in a spirit of wisdom and humility. From evolving molecular tools to developing ways of altering entire populations and ecosystems, we aim to benefit the world while holding ourselves morally responsible for the consequences. To that end, we work to ensure that all research intended to alter the shared environment is open and community-guided from the outset.
What is CRISPR genome editing, and how can it be made heritable, so that it passes from parent to offspring?
KE: CRISPR is a molecular scalpel that can be programmed to cut and edit just about any gene in any organism. Encoding CRISPR in an organism’s genome can cause it to edit a particular sequence in every descendant that inherits the instructions. By ensuring that the instructions are themselves copied and therefore inherited by most or all offspring, we can build a standard “gene drive” system that, over many generations, could alter an entire population of organisms.
You were the first to identify that CRISPR-based “gene drive” systems could be used to alter wild populations of organisms. Why might this be useful?
KE: When we edit a genome – whether through selective breeding or CRISPR – we typically reduce the organism’s ability to survive and reproduce in its ancestral habitat, meaning natural selection will swiftly eliminate our changes. Gene drive systems ensure their own inheritance, so should not be eliminated in this way. CRISPR-based gene drive systems could potentially be a targeted, effective way to eradicate diseases such as malaria and schistosomiasis.
In your new PLOS Biology article, you caution against the use of self-propagating CRISPR-based gene drive systems. What are these systems, and why are you concerned about their use?
KE: If the encoded CRISPR system is programmed to copy itself, it can spread indefinitely. Our recent mathematical models (released as a bioRxiv preprint, “Current CRISPR gene drive systems are likely to be highly invasive in wild populations”) predict that this form of gene drive is highly likely to spread across international borders to every population of the target species. That may be necessary to eradicate malaria, but it’s hard to imagine countries agreeing to many other applications, and any unauthorized release of a self-propagating gene drive systems could seriously damage public trust in science and governance.
Could you describe “daisy drives” and how they differ from self-propagating gene drives?
KE: To build a daisy drive, we scatter the components of the CRISPR system across an organism’s genome and arrange them in a daisy-chain such that each link causes the next to be copied. The first daisy link isn’t copied, so some of the organism’s offspring won’t inherit it. That means that the next link won’t be copied, and so on down generations until eventually the last link is gone and the daisy drive stops. We refer to daisy drives as “self-exhausting” because they’re limited to a certain number of generations. A daisy drive could be used, for example, to spread infertility, precisely removing a population of invasive predators.
New Zealand is considering genetic technologies to help eliminate mammalian pests such as rats and stoats. If you were advising the country, what would you recommend?
KE: I would advise policymakers to use the smallest possible change capable of solving the problem, and to start small and local before scaling up. That can’t be done with a self-propagating gene drive system, so we shouldn’t even try. Daisy drives and equivalents systems may have potential, but only if developed openly with community guidance and independent assessment. I would recommend inviting advice and criticism from locals, for native wisdom may offer unique insights.
How do you hope and expect that CRISPR technology will affect conservation in future?
KE: The language of nature is written in DNA, a tongue we are only now beginning to learn. If approached with humility, inviting everyone to share their concerns and criticisms, I hope that we may learn to precisely solve ecological problems without using poisons and dramatically reduce animal suffering.
What do you hope that your PLOS Biology publication might achieve, and what are the next steps for your research?
KE: If we’re lucky, this note of caution may help remedy my earlier mistake by dissuading others from developing self-propagating gene drive systems for applications that would be neither wise nor practical. In the lab, we’ve just started to develop local, community-guided alternatives such as daisy drive systems in a variety of organisms, including invasive species. I hope that these will benefit conservation. More broadly, I hope that we can change scientific incentives so that all technologies intended to alter the shared environment are developed in the open light of day.
Images Credits: Gemmell and Esvelt, 2017; Kevin Esvelt