griculture giant Monsanto has licensed CRISPR-Cas9 genome-editing technology from the Broad Institute for use in seed development, the company announced on Thursday, a step that will likely accelerate and simplify the creation of crops that are resistant to drought or have consumer-pleasing properties such as soybean oil with fats as healthy as those in olive oil.
But the deal comes with restrictions that speak to the startling power of CRISPR, as well as widespread public anxiety about genetically modified crops: Monsanto cannot use it for gene drive, the controversial technique that can spread a trait through an entire population, with unknown consequences.
Since 2013 the Broad has issued more than a dozen licenses for commercial research using CRISPR-Cas9, including to Editas Medicine, GE Healthcare, and Evotec. This is the first for agricultural use. Genome-editing of crops offers the potential of increasing yields, reducing the use of chemical pesticides (a plant can be genetically modified to thwart insects), and making strains tolerant of the droughts that are becoming more frequent with global climate change.
But “just as in biomedicine, the use of genome editing in agriculture raises important ethical and safety concerns,” Issi Rozen, the Broad’s chief business officer, wrote in a blog post.
Leading the list of those concerns is gene drive, in which CRISPR-based genome editing alters normal inheritance in such a way that traits are always passed on to offspring. That could spread a new gene throughout an entire population in only a few generations. If the trait is, say, the ability to kill insects, then making that gene ubiquitous in a crop could pose unknown threats to ecosystems, a recent National Research Council report warned.
The Broad also stipulated that Monsanto not use CRISPR-Cas9 to create sterile (“terminator”) seeds. In this approach, genetically altered crops do not produce fertile seeds, so farmers must buy them every year, a financial burden to them but a boon for the seed companies. No such crops have been commercially deployed, and the United Nations Convention on Biological Diversity recommended they not be developed.
The non-exclusive license also cannot be used for any R&D on tobacco that’s related to smoking. That might include making the plants tolerant to temperature extremes or pests, which could increase the yields that farmers get on their harmful product.
Monsanto, which agreed this month to be acquired by German drug and pesticide maker Bayer, has long been a leader in the controversial development of GMOs (genetically modified organisms). Starting in the 1990s it introduced corn, soybean, canola, and other crops that are genetically modified to withstand its Roundup herbicide, for instance, allowing farmers to apply it without collateral damage and increase their yields. Because the safety of GMOs to ecosystems has not been proved to the satisfaction of many environmental groups, and because their presence in foods has until recently not required labeling, they have incited worldwide controversy for more than a decade.
Monsanto believes CRISPR will be much more powerful than the decades-old technique behind GMOs. That technology inserts foreign genes at random sites in a plant’s genome. The vast majority of those insertions don’t work as intended, said Tom Adams, who leads Monsanto’s biotechnology efforts, so changing a crop’s traits takes years.
“But with genome editing, you can target a trait where you want it to go, and you can link traits so they’re next to each other” and are reliably passed down together in future generations, he told STAT ahead of the licensing announcement.
In addition, he said, in GMOs “you still have the gene that was there originally,” which can act as a brake on the new trait. When CRISPR alters a gene into a form that makes a plant tolerant of stress, disease, or pests, however, the original non-tolerant gene is gone, like a corrected typo. Because of its precision and power, with CRISPR, “I think we’ll see an acceleration” on changing crops’ traits compared with the pace that traditional GMO-creation allowed, Adams said.
CRISPR is tantalizing to seed companies for another reason. The US Department of Agriculture has said that because the technique does not insert a foreign gene into plants, but either deletes or modifies an existing one, CRISPR’d crops (such as a mushroom that doesn’t turn brown when cut, or drought-tolerant corn being developed by DuPont Pioneer) do not need regulatory approval as GMOs do.
That has alarmed some traditional GMO foes. “We’re not happy with the current regulatory approach,” said Patty Lovera, assistant director of Food and Water Watch. CRISPR’d crops might present “similar safety concerns” as GMOs do, she said: “Do we really understand what the proponents say we do — that genome editing is so precise there is nothing else it affects? That presumes a level of knowledge about intricate biochemical processes that I’m not sure we have.”
Adams said gene drive and terminator genes “are not things we wanted to do with the technology anyway. We agreed that gene drive is something better not brought forward at this time. We see that there is a lot of potential, so it’s really tempting to use,” but will not do so “until we know how to control it.”
Several other companies are hot in pursuit of genome-edited crops. The Calyxt subsidiary of Cellectis, based in Minnesota, is using a genome-editing technology that preceded CRISPR-Cas9, called TALEN, to make wheat that produces less gluten, soybeans whose oil resembles olive oil, and potatoes that, when fried, do not contain the carcinogen acrylamide. Calyxt has not yet partnered with any seed companies.
DuPont is collaborating with Caribou Biosciences to CRISPR corn and wheat for drought tolerance and other traits. A spokeswoman said the company is “unable to disclose” whether the DuPont agreement permits the use of CRISPR to develop gene drive in crops.
Caribou was cofounded by CRISPR pioneer Jennifer Doudna of the University of California, Berkeley, which has challenged the CRISPR patents issued to the Broad. Monsanto isn’t concerned.
“The IP [intellectual property] will be complicated for some time,” Adams said. “But it will all work itself out.”