Genome Editing: As Easy, Useful, and Safe as it Sounds?

Genome Editing: As Easy, Useful, and Safe as it Sounds?

Helping experts in crop biotechnology explain their work to non-specialists is a tough job – one to which I’ve dedicated a lot of time as a science writer/editor over the last 20 years. One rhetorical device that I’ve always found handy for getting my mind around biotechnology’s abstractions is the apt metaphor – like the image of a “pipeline” to depict how massive amounts of genomic data can be managed with sophisticated new software.

This is perhaps why I felt so relieved when I read a while back about a new approach called “genome editing.” Finally, I thought to myself, the molecular biologists are speaking a language that for me makes complete sense.

Does this mean that crop improvement will soon be as simple as “cut and paste,” “insert table,” and “save as” in word processing? Or to use a more old-fashioned metaphor, will plant breeders’ job become as straightforward as red-penciling plants? My chance to find out came when Joe Tohme, director of CIAT’s Agrobiodiversity Research Area, announced recently that a CIAT research team has been experimenting since 2014 with genome editing in rice. I couldn’t wait to find out more from the team’s leader, Paul Chavarriaga.

At a meeting in his office, Chavarriaga first explained to me the basics of how genome editing works. The idea is to remove, “switch off,” or otherwise modify genetic material in organisms to achieve a desired change. This is made possible by a new technology called CRISPR – for clustered, regularly interspaced, short palindromic repeat. Found in the genomes of some bacteria, it generates nucleases, notably one referred to as Cas9, which is an enzyme (or type of protein) that chemically cuts the links between the subunits of deoxyribonucleic acid (DNA) – the molecule that carries genetic instructions for the development, functioning, and reproduction of living things.

The cutting action catalyzed by CRISPR-Cas9 is guided by pieces of ribonucleic acid (RNA) – a molecule that decodes the instructions “written into” DNA for protein synthesis and regulates gene expression, among other functions. Tailoring the RNA to fit a particular genetic sequence, scientists can use the CRISPR-Cas9 system to cut DNA at specific sites recognized by the RNA. The DNA then repairs itself, incorporating some type of genetic change, such as gene mutation or insertion or the replacement or rearrangement of genetic sequences.

Many problems of plant and human health involve more than a single gene. Not to worry! The CRISPR-Cas9 system has proved capable of modifying several genes at a time.

Since 2011, when the technique was first developed, applications have proliferated, as reflected in the large number of publications (more than a thousand by 2015) now flooding the scientific literature. These articles document the use of Cas9 to modify cells in a wide variety of animals (e.g., mice, rabbits, frogs, and fruit flies) and plants (including rice, sorghum, tobacco, and wheat). In Brazil, for example, scientists have used the CRISPR/Cas9 system to show how mosquitoes can be rendered incapable of serving as carriers of malaria.

To demonstrate proof of concept in CIAT’s research, Chavarriaga’s team recently used the system to induce the “drooping leaf” effect in IR64, an elite rice line developed by the International Rice Research Institute (IRRI). Scientists in Japan had already performed the same feat with Japonica rice. IR64 has been incorporated into hundreds of improved rice varieties, which have been released in a dozen countries and are grown on millions of hectares. If genome editing for important agronomical traits could give more of an edge to this already superior rice, the benefits would reach many millions of people.

“The drooping leaf trait has only a minor effect on plant performance,” said Chavarriaga. “But it serves very well to show the effects of genome editing in a way you can easily see in rice plants.”

CIAT scientist Sandra Valdéz is preparing a note on this development, which will hopefully be CIAT’s first contribution to the growing scientific literature on genome editing. In this work, Valdéz is collaborating with Japan’s National Institute of Agrobiological Sciences (NIAS) and the University of Melbourne in Australia.

Another application of genome editing to which CIAT researchers are contributing involves eliminating the antibiotic used as a “marker” in transgenic rice possessing high levels of the vital micronutrients iron and zinc.

“The antibiotic is actually harmless,” said Chavarriaga, “but its presence in rice might arouse concern about the possibility of creating antibiotic resistance in humans. By using genome editing to eliminate the antibiotic gene, we hope to simplify the passage of this transgenic rice through the regulatory process, so that its nutritional advantage can be put to use more quickly.”

Further possibilities that Chavarriaga has in mind are using genome editing to enhance the presence in cassava of beta-carotene, the precursor of Vitamin A, or to create new mechanisms for resistance to bacterial and viral diseases of the root crop.

So far, so good. But as Chavarriaga spoke, I began to get a sense of déjà vu. Despite the mild metaphor, his description of genome editing sounded to me a lot like transgenics (i.e., genetic transformation or engineering). The sensation was reinforced by the fact that Chavarriaga also manages CIAT’s genetic transformation platform. An important difference, though, is that genome editing has not yet been used to introduce genes from other organisms but only to modify genetic material within a given organism. Still, there’s nothing to prevent scientists from using genome editing to introduce foreign genes.

Surprisingly, though, this does not appear to be among the main concerns that have people worried, as documented by recent articles in The Economist, The New York Times, and The New Yorker. Their main fear is about the use of genome editing on human embryos. Some 6,000 human diseases are caused by genetic malfunctions, and genome editing shows enormous promise for solving them. But what if the technique has unexpected effects on humans, creating new problems even as it solves old ones?

Another fear is that genome editing could have unanticipated environmental impacts, particularly if genetic modifications in animals or plants are passed on from one generation to the next by means of a technique called “gene drive,” which is being used in the work on mosquitoes mentioned earlier.

Cognizant of these concerns, researchers have begun to address them by establishing clear ground rules for the application of genome editing. They must also engage right away in public dialogue about the technique’s promise and perils to avoid getting bogged down in the sort of trench warfare scenario that overtook the debate on transgenics. The potential benefits of genome editing are far too great to be squandered for lack of a shared understanding across society about how the technique can best be used to improve human well-being.