Mankind has been manipulating genetics since early civilizations realized that certain traits of crops, animals and humans themselves were hereditary. The modern-day mapping of all human genes raised the prospects of learning precisely which genes control which traits and then directly altering their DNA codes. For years, those tasks proved both cumbersome and hit-and-miss. But a new technology on every geneticist’s tongue is changing that. Called Crispr-Cas9, or more commonly just Crispr, it’s a gene-editing system so simple, cheap and effective, it promises to change our relationship with genetics — for better, worse or both. Its champions foresee using Crispr to control pests, increase food production and eliminate human diseases. They simultaneously worry that it could be used to create designer babies, dangerous mutants and biological weapons that could target specific populations.
Labs and companies in scores of countries are experimenting with Crispr. Their ambitions include killing off malaria-carrying mosquitoes, making wheat invulnerable to the blight of powdery mildew, producing eggs suitable for people allergic to them and bringing a woolly mammoth back from extinction. In experiments with human cells, researchers have used Crispr to repair a mutation that causes blindness, remove HIV from immune cells and correct the defect responsible for cystic fibrosis. Researchers in late 2015 published results on the successful use of the technique to treat mature animals. They repaired a defective gene in mice with Duchenne muscular dystrophy and watched as muscles throughout the animals’ bodies strengthened; these experiments could eventually lead to human trials. Controversially, a small but growing number of labs are using Crispr to experiment with human germline cells — such as sperm, eggs and zygotes — which pass genetic material to progeny. A group of Chinese researchers created an outcry in early 2015 when they published results of a Crispr experiment on human embryos, even though they said the embryos were nonviable. In February, after a year of studying the issue, a U.S. science and medicine advisory group decided to support the use of technologies like Crispr to modify human embryos for prevention of serious diseases and disabilities.
Crispr-Cas9 is a rudimentary immune system that Japanese scientists first noticed in bacteria nearly 30 years ago. Clustered Regularly Interspaced Short Palindromic Repeats are sequences of genetic code broken up by remnants of genes from past invaders that help bacteria identify them when they appear again so the Cas9 enzyme can slice through them. Understanding of how the system can chop through and then replace segments of DNA grew slowly until 2012, when researchers at the University of California, Berkeley published a paper on making molecular "guides" that allow Crispr to skim along DNA, targeting exactly the right spot to make a slice. Soon afterward, scientists at the Harvard-affiliated Broad Institute said they’d adapted Crispr for use in human cells. That led to a patent dispute, with implications for anticipated scientific prizes. In February, the U.S. Patent Office ruled that the Broad and UC Berkeley patents were sufficiently different; Berkeley is weighing an appeal. A researcher with basic skills and a few thousand dollars’ worth of equipment can employ Crispr, creating enormous space for innovation, and abuse. The gene-editing system isn’t perfect, at least not yet. It makes unintended cuts in DNA as often as 60 percent of the time in some applications, with effects unknown.
A Bloomberg video explores the transformative power of Crispr
Decisions about whether to use Crispr to treat people who are already sick could be made through traditional consideration of risks and benefits, once they are better understood. The issues arising from germline editing, however, are philosophical as well as medical. The potential to do good is enormous: eliminating a genetic disease from a family forever. But if something goes wrong, the consequences are potentially eternal, too, affecting future generations who could not give prior consent. Some scientists worry that germline editing would invite enhancements of babies for non-medical reasons. At the same time, philosopher Nick Bostrom and author Carl Shulman argued in a 2013 paper that cognitively enhanced individuals could produce positive effects for society through innovations used by everyone.
The Reference Shelf
- The Council on Foreign Relations offers a briefing on the state of Crispr development.
- A New Yorker article explains how Crispr works.
- An article in Wired explores the potential pros and cons of Crispr.
- A piece in Nature describes the ethical debates around Crispr.
First published June 7, 2016
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