Genome-editing revolution: My whirlwind year with CRISPR, by Jennifer Doudna, Nature, December 2015
Adam Rifkin stashed this in CRISPR
Stashed in: Accelerating Returns
CRISPR is moving faster than even she imagined.
Some 20 months ago, I started having trouble sleeping. It had been almost two years since my colleagues and I had published a paper1 describing how a bacterial system called CRISPR–Cas9 could be used to engineer genomes (see ‘Based on bacteria’).
I had been astounded at how quickly labs around the world had adopted the technology for applications across biology, from modifying plants to altering butterfly-wing patterns to fine-tuning rat models of human disease. At the same time, I'd avoided thinking too much about the philosophical and ethical ramifications of widely accessible tools for altering genomes.
Questions about whether genome editing should ever be used for non-medical enhancement, for example, seemed mired in subjectivity — a long way from the evidence-based work I am comfortable with. I told myself that bioethicists were better positioned to take the lead on such issues. Like everyone else, I wanted to get on with the science made possible by the technology.
Yet as the uses of CRISPR–Cas9 to manipulate cells and organisms continued to mount, it seemed inevitable that researchers somewhere would test the technique in human eggs, sperm or embryos, with a view to creating heritable alterations in people. By the spring of 2014, I was regularly lying awake at night wondering whether I could justifiably stay out of an ethical storm that was brewing around a technology I had helped to create.
Nature special: CRISPR
“I hope you're sitting down because it's unbelievable how well it's working.” That was the verdict, delivered in December 2012, of a colleague who had been experimenting with CRISPR–Cas9. It reflected my own lab's experience, and that of others who had contacted me that autumn to share their excitement about the genome-editing technology.
It often takes years for a new molecular tool to take hold. Yet even before the end of 2012 — just a few months after my colleagues and I had published our initial study — at least six papers describing different uses of CRISPR–Cas9 for genome engineering had been submitted for publication.
In early 2013, several papers, including some describing how the technology could be used to edit the genomes of human stem cells and to alter a whole organism (the zebrafish), were an early indication of the coming tsunami2, 3. By the end of 2014, scientists had — among other things — used CRISPR–Cas9 to enhance pest resistance in wheat, reproduce the carcinogenic effects of specific chromosome translocations in mouse lungs and correct a mutation in adult mice that in humans causes the disease hereditary tyrosinaemia4, 5, 6.
An ethically more complicated potential use of CRISPR–Cas9 was underscored in February 2014, when researchers described how they had used it to make precise changes to the genomes of cynomolgus monkey embryos 7. (Cynomolgus monkeys are so genetically close to humans that they are commonly used to model human genetic disease.) The monkeys that developed — through implantion of the embryos into surrogate mothers — carried the genetic changes in most of their cells, including their eggs or sperm. This meant that the alterations could be passed down to future generations.
I was alerted to the paper by reporters seeking my comments on the research. After reading the preprint, I gazed out of my office window and across the San Francisco Bay and pondered how I would feel if the next reporter to contact me wanted to know about genome-editing work involving human embryos. “How long will it be before someone tries this in humans?” I wondered aloud to my husband over breakfast the next day.
At the same time, I had been receiving e-mails from people facing potentially devastating genetic predicaments. In one message, a 26-year-old woman told how she had discovered that she carried the BRCA1 mutation, which gave her a roughly 60% chance of developing breast cancer by the time she was 70. She was considering having her breasts and ovaries removed, and wanted to know whether the approaches made possible by CRISPR–Cas9 meant that she should hold off.
The monkey study and interactions with patients or their relatives weighed on me. Every day brought a new influx of papers describing research using CRISPR–Cas9. My inbox was full of requests from researchers seeking advice or collaboration. All this activity could have a direct impact on human life, yet most people I knew outside of work — neighbours, extended family members, parents of my son's classmates — remained largely oblivious. I felt as though I was living in two separate worlds.
Towards the end of 2014, my unease outweighed my reluctance to step into a more public discussion. It was clear that governments, regulators and others were unaware of the breakneck pace of genome-editing research. Who besides the scientists using the technique would be able to lead an open conversation about its repercussions?