Controversial ‘gene drive’ could disarm deadly wheat pathogen

The Fusarium fungus is the bane of every wheat farmer’s existence. Causing wheat scab—also known as head blight—it decimates harvests and contaminates grains with a toxin harmful to people and animals. Now, Australian researchers have come up with a new strategy to combat Fusarium graminearum, the most notorious wheat scab pathogen. In the lab, they have used a genome-altering technology called “gene drive” to get rid of the fungal genes that make this pest so toxic.

The new wheat strategy would be the first use of a gene drive to control a pathogen in plants. The findings are “very enticing” for both plant and human health, says John Leslie, a fungal pathologist at Kansas State University. Yet gene drives have never been deployed outside of the lab and plans to use them to eliminate mosquitoes and other pests have been controversial.

Wheat scab is a growing problem in North America, Europe, and China. Researchers are scrambling to breed wheat resistant to this fungus, with some recent success. Even so, “Disease management is reaching a crossroads,” says Peter Solomon, a molecular plant pathologist at the Australian National University.

It takes a lot of time and effort to develop new breeds of wheat. And producing significant resistance to this fungus will likely require introducing multiple genes. Even then, complete protection may not be achieved. Meanwhile, the fungus rapidly becomes resistant to any chemical treatments, and various countries are beginning to ban the use of these fungicides. For those reasons, Solomon says, “It’s important that we don’t shy away from considering new and novel methods for managing diseases.”

So Donald Gardiner, a molecular biologist at the Commonwealth Scientific and Industrial Research Organisation in St. Lucia, Australia, and his colleagues decided to see whether they could make Fusarium less potent by using gene drive. The process involves introducing DNA into an organism that causes one version of a gene to be passed on to the next generation but not another. Eventually, just the desired versions of those genes remain in the population.

Scientists typically use the gene editing tool CRISPR as the gene driver. That’s how researchers hope to fight malaria: They adapted CRISPR to spread a gene that transformed populations of a malaria-transmitting mosquito into all males so the species cannot reproduce. Given the many uncertainties about the long-term consequences of releasing a gene drive, scientists are proceeding cautiously with such work.

Although aware of those concerns, Gardiner and his colleagues still felt a gene drive was worth exploring for wheat scab. Their intent was to get rid of three Fusarium genes that make the pathogen highly infectious and the infected grains toxic, all while leaving the fungus otherwise intact DNA-wise.

They found that CRISPR did not efficiently spread the innocuous versions of these genes. But a gene in another fungus—what Gardiner calls a natural gene drive—proved up to the task, being more efficient than CRISPR and easier to work with.

Gardiner and colleagues linked that gene to innocuous versions of the three targeted genes. Once in the Fusarium, the gene-drive gene caused any sexually produced spores that wound up with the original versions of targeted genes to die. Thus, the innocuous versions were preferentially transferred to the next generation. Those subsequent generations were less able to cause wheat scab but otherwise were no different from the typical Fusarium, the team reports in a preprint posted this month to bioRxiv.

“It’s a bit like replacing a couple of sentences in the middle of a large book with some unrelated text,” Gardiner says. In just three generations, the three virulent genes were completely gone, he and his colleagues report. “We think the technology should be applicable to many other economically important pathogens,” Gardiner says.

Others are skeptical. “It’s a new idea, but not practical,” says Caixia Gao, a plant biologist at the Chinese Academy of Sciences in Beijing. She doesn’t think any Fusarium deprived of its virulence genes could survive in the wild and outcompete unaltered versions of the fungus or other Fusarium species. “The consequences will be that other pathogens may dominate,” she says, and the disease would still be a problem.

And Leslie stresses that many fungi, including some types of Fusarium, rarely or never reproduce sexually, which is a prerequisite for a gene-drive control mechanism to work. Furthermore, “Developing field tests will be very important and probably difficult to design,” he adds. The team will have to show the gene drive is effective in reducing wheat scab under natural conditions, Leslie says, and at the same time make sure that the modified fungus doesn’t escape into the wild. Even if the logistical issues can be worked out, getting regulatory approval to release a genetically engineered plant pathogenic fungus will be hard.

Yet, “The concept is worth exploring” Leslie says. “Even if it fails, we should learn a great deal about how to manage fungal populations.”