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Genome Gambits

New genetic tools can do tremendous good—if we use them carefully.

My dad loved to hike in the rain forests near our home on the Big Island of Hawaii, often to hunt for mushrooms with Don Hemmes, his colleague at the University of Hawaii. The goal of these trips was not to harvest mushrooms but to photograph them for a research project that Hemmes was leading. When I accompanied them, I was always struck by the incredible diversity of the mushrooms we found. Having learned a little about genetics in school, I wondered what kinds of DNA changes were responsible for these organisms’ range of colors, shapes, and sizes. And how could we figure out such molecular signatures?

Jennifer A. Doudna
Jennifer A. Doudna

Fast-forward 30-odd years, and it’s become routine to sequence the entire genomes of organisms, and to interpret that information to reveal the underlying causes of observable traits. A simple and effective technology for making precise changes to those genomic sequences, developed by harnessing a system that bacteria use to fight viral infections, has exploded into widespread use. The technology, called CRISPR, relies on a programmable DNA-cutting enzyme called Cas9, together with its guide RNA, to let scientists alter the genetic information within cells, tissues, and whole organisms. Scientists have used it to generate new strains of wheat, to cure a genetic disease in the livers of adult mice, and to produce altered fungal cells capable of efficient biofuel synthesis. The CRISPR-Cas9 technology has opened up a world of research opportunities that were inconceivable just three years ago. The technology will benefit humanity in many ways.

There’s also a growing appreciation of the risks involved. CRISPR-Cas9 technology can, as an example, be used to alter the DNA in germ cells or embryos, resulting in permanent changes to the genetic makeup of every differentiated cell in a resulting organism—and to that organism’s progeny (see “Engineering the Perfect Baby”). The system is so efficient that genetic changes it introduces could become self-propagating. Such applications could be employed to cure genetic disease in humans or to limit the fitness of disease-carrying organisms—but the intricacies of genetic interaction mean those uses could also have unintended consequences, perhaps triggering other diseases.

Research is needed to understand the utility and risks of CRISPR-Cas9 in cells including human germ cells, as well as the risks inherent in any human clinical applications that might be possible in the future. We should research the ramifications of using genome engineering to control organisms, such as mosquitoes, that can spread malaria or dengue fever. While we should embrace this technology, scientists also must come together to guide peers and regulators as to its responsible use.

Jennifer A. Doudna is a professor of biology and chemistry at the University of California, Berkeley. She was one of the inventors of the CRISPR technology.

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