fb-pixel
OPINION

The ethical way to alter organisms

One of the inventors of CRISPR-based gene drive has some advice to improve science, ethics, and the odds that these technologies will one day save millions of lives.

Anopheles stephensi by RFBSIP/Adobe/RFBSIP - stock.adobe.com

Just as a single tongue of flame can grow into a raging wildfire, the tragedy of COVID-19 has demonstrated the power of self-spreading biology. While most current efforts necessarily focus on stemming the flames, we have an opportunity to prepare for a future in which natural self-spreading agents are joined by the engineered variety.

To be clear: We don’t currently know how to build new pandemic agents. If we’re lucky, we never will. What we can do — the technology that could set a precedent for safety and ethics — is edit the DNA of organisms in the lab in ways that, if released, would cause those edits to spread through wild populations of the species. From blocking the transmission of diseases to controlling pests without toxic poisons, ecological editing could offer humane ways to benefit health and the environment.

Advertisement



As my colleagues and I first described in 2014, we can use CRISPR genome editing to duplicate the most powerful form of “gene drive,” a ubiquitous natural phenomenon that happens when a genetic change is inherited more frequently than usual. Encode the CRISPR machinery next to a useful edit we’ve made in the genome, and genome editing will reoccur in every generation, replacing the original with the edited version without limit. In principle, releasing such organisms would gradually alter entire wild populations and associated ecosystems.

Thankfully, driven changes spread slowly and can be readily overwritten, which means that, unlike pandemic viruses, gene drive would be hard to misuse. If developed wisely, safe and controllable ecological editing could help eradicate animal-borne diseases such as malaria, humanely control rodents and insect pests without using poisons, and solve increasingly urgent conservation problems by harnessing tools already present in nature.

Unfortunately, many of these applications are being developed in secret — not because my colleagues prefer it that way, but because current scientific incentives still favor secretive research.

Advertisement



That was deeply troublesome even before the pandemic. Today, it sets a precedent that scientists can pursue self-spreading technologies with no required safeguards and negligible public oversight.

Moreover, developing interventions to change our environment is fundamentally different from medical research. If your doctor recommends that you take a new drug, you can always decline. But if we develop interventions to change our environment, and a community decides to use them, everyone there will be affected. We know that actively inviting and responding to concerns and criticism from the public can identify and correct flaws early enough to make a difference — so why not here?

A 2016 report by the US National Academies concurred, noting, “The best course of action is to ensure that the people who could be affected by a proposed project or policy have an opportunity to have a voice in decisions about it. Experts acting alone will not be able to identify or weigh the true costs and benefits of gene drives.”

It’s now 2020, and most research still takes place out of public view. Society rewards the first to publish, causing most scientists to keep their experimental plans to themselves lest someone else throw more money and hands at a promising idea and take all the credit. The system endures, even though closeted research is both less efficient and more dangerous: Small teams of similarly trained specialists working in isolation can’t reliably predict the consequences of their work, nor invite others to help them improve their designs.

Advertisement



Despite years of lobbying by many of us in the field, funders of gene-drive research have struggled to agree on which safeguards should be required to prevent accidental releases of gene-drive systems into the wild, let alone require transparency and community guidance. Publishers of high-profile journals have similarly declined to act. Crucially, both have cited the absence of a central organizing body to establish standards.

Unlike COVID-19, this is a problem that the World Health Organization can easily solve — in this case, by creating a registry for ecological editing research just like they did for CRISPR gene therapy. Doing so would improve our science, our ethics, and the odds that these technologies will one day save millions of lives, not to mention set a better precedent for future research into self-spreading agents.

The question is what should be required to register a project. Based on our work with the communities of Nantucket and Martha’s Vineyard on immunizing the local white-footed mice to prevent transmission of Lyme disease — which by community preference doesn’t involve gene drive or any DNA not found in wild mice — we’ve identified a few key criteria:

▪ Scientists should disclose the nature of the proposed alteration and why it’s worth considering. People deserve to know enough about the project to suggest changes and share concerns.

▪ Researchers should assess the risk of accidental spread and detail any safeguards that would prevent it from happening if organisms should escape or be deliberately released from a laboratory or field trial site.

Advertisement



▪ Any projects aiming to edit an organism responsible for a real-world problem should require sponsorship by a community interested in pioneering the application who will help to guide the research.

▪ Most important, scientists should be required to register their plans before any technology development begins. It’s easier to make changes in response to advice from peers and interested communities before becoming too invested and, in a field where a single mistake could affect millions, it’s best to invite external advice early on.

An ecological editing registry endorsed by funders, major journals, and scientific societies would enable the high-profile discipline of gene-drive research to serve as a field trial for open and community-responsive technology development, with beneficial effects that could spread far beyond genome editing.

That’s not to say that all research should be open; we certainly don’t want to disclose how to make a pandemic, should we be so unlucky as to live in a universe in which it’s possible. Rather, we should establish transparent, publicly accessible standards to help determine whether, when, and how research that could impact everyone should proceed. Speaking as a scientist who bears a share of moral responsibility for the most prominent self-spreading technology, the best time to do this was several years ago — but this year will do nicely.

Kevin Esvelt is an assistant professor at the MIT Media Lab, where he directs the Sculpting Evolution group. An evolutionary engineer, he is an inventor of CRISPR-based gene drive and a founder of the community-guided Mice Against Ticks project to prevent Lyme disease.

Advertisement