For thousands of years, farmers have been choosing which traits their crops and livestock carry by using selective breeding. The first genetically modified crops were commercialized in the 1990s. In 2012, a huge scientific breakthrough changed what is possible yet again.
Gene editing, led by the discovery of CRISPR-Cas, promises widespread, accelerated, and targeted discoveries. Areas of the genome linked to specific traits can now be precisely edited. Cut and paste, so to speak. Gene editing could eventually provide a catalog of options for farmers to order exactly what they need. Think of it like customizing a tractor. Don’t need a front-end loader? Remove it. Need dual rear wheels? Add them.
With gene editing, the ability to pick livestock traits will be just as easy. Don’t want to have to dehorn your dairy cattle? There’s an option for that.
In crops, the technology has the potential to improve drought tolerance, eliminate diseases, increase yields, and much more. The possibilities are endless.
Not Your Old GMOs
Gene editing allows scientists to genetically engineer organisms without inserting foreign (transgenic) DNA. This makes it different from GMOs and means it may not be regulated the same. In fact, the USDA has already ruled that certain uses of CRISPR-Cas technology, such as keeping mushrooms from turning brown, will not be regulated as GMOs. (CRISPR is the guide that controls the precise gene editing. Cas represents the molecular scissors that do the cutting.)
When GMO crops first came into widespread use in agriculture in the 1990s, the initial information from companies using the technology was vague, assuming the public would both understand and accept the technology. Today, those companies realize they need strategic plans to educate both farmers and consumers about the benefits of this technology. While few people question the use of GMOs to produce medicine (insulin-producing bacteria, for example), someone whose life depends on regular insulin injections might reject GMO crops.
Animal Welfare
People may be open to genetically engineered animals if it means more humane treatment, such as dairy calves that no longer require painful dehorning. Randall Prather, distinguished professor of animal sciences at the University of Missouri and director of the National Swine Resource and Research Center, helped develop pigs resistant to the deadly PRRS virus using CRISPR technology.“This could have a significant impact on animal welfare,” says Prather. “Nobody likes to see animals suffer.
“There are physiological and emotional costs of these diseases, as well as economic, when they hit family farms,” he explains. “When I give talks about PRRS, I look out in the audience and see a wife pulling close to her husband, leaning in and tearing up. When I see that, I know those people know exactly what I’m talking about because it happened to them.”
Scientists at the University of Edinburgh’s Roslin Institute are taking genes from warthogs resistant to African swine fever and inserting them into domesticated swine in an attempt to eventually eliminate this catastrophic disease from the earth. “That’s food security,” says Prather. Consumer acceptance is the main obstacle, he says. “It’s a hard thing to sell. People don’t understand it. When computers first came out, a lot of people were afraid of them because they didn’t understand them. Now, everybody runs around with smartphones without giving them a second thought.”
Using genetically engineered animal organs to save lives in humans (xenotransplantation) is the Holy Grail. Prather’s pigs are used to study cystic fibrosis, retinitis pigmentosa, diabetes, cardiovascular disease, cancer, phenylketonuria, and more.
“There are so many things we could do,” says Prather. “You are truly limited by your imagination. If there’s a biological way to do it in nature, we can probably do it.”
Not Sci-Fi
One of the early innovators in gene editing is Recombinetics in St. Paul, Minnesota. The company develops swine models that replicate human diseases, including heart disease, diabetes, and cancer. This fall, Recombinetics was awarded a grant from the National Institutes of Health to create a humanized swine model of Alzheimer’s disease.
For agriculture, the company creates desirable animal health and productivity traits to sell to producers for use in breeding programs. The discoveries include the world’s first gene-edited polled cows, heat-tolerant cattle, foot-and-mouth disease resistance, genetic castration, meat quality, and more.
“This is not science fiction,” says Tad Sonstegard, chief scientific officer for Acceligen, the food application arm of Recombinetics. “You can bring any trait into your favorite livestock breed without doing cross breeding. You can make an elite dairy animal polled.”One benefit for society, he says, is sustainability. Animals with better feed conversions help the planet. “If every animal is 10% more productive, you can feed 10% more people with 10% fewer inputs. If you are concerned about animal welfare and earth welfare, you should be pro gene editing.”
For example, with the technology, you can raise heat-tolerant productive dairy cows in Sub-Saharan Africa, he says. “You change a single gene that allows the cow to thermoregulate better in heat. It is precision breeding.”
You engineer the tool for specific situations, he explains. “You put your scissors at the spot responsible for that trait, knock it out (or put in instructions for a one-base deletion), the repair happens, and now you’ve introduced a Senegal gene into an Angus.”
Farmers are astute and will accept the technology, predicts Sonstegard.
“It’s just another type of breeding. We are selecting and using genetics already in the species. It’s different than GMO, which pulls genes from one species into another. ”
Start-Ups
CRISPR is not the only game in town for gene editing. Cibus, for example, is one of many molecular plant biology start-ups trying to release products and secure patents for genome-editing technologies. Cibus already has a crop on the market, a herbicide-tolerant canola.
Cibus’s core proprietary technology is the Rapid Trait Development System (RTDS). The focus is on weed control, disease control, healthier oil profiles, and more.
“Farmers will have the opportunity to obtain these traits quickly and affordably,” says Greg Gocal, chief science officer with Cibus, based in San Diego.
Effectively, RTDS tells a plant cell to rewrite part of its own DNA. The changes are made without directly adding foreign DNA (as with GMOs). The effect is not exactly the same as CRISPR, but it is similar. Many start-ups steer clear of CRISPR because of ensuing patent and licensing disputes with the technology.
“Cibus will bring traits and products to farmers in more crops faster and with less cost than CRISPR,” says Gocal. “Our goal is to have traits in every major crop within the next decade. We already have herbicide-tolerant SU Canola. We will see a release in the 2019-2021 time frame of glyphosate-resistant flax, herbicide-resistant rice, and numerous others.”When GMO crops first came out, the technology was focused on a small number of traits, says Gocal. Gene editing covers more traits and more crops. Hopefully, he says, the public will accept it.
“The keys for us are to remain transparent and to keep educating people on the benefits of these new gene-editing technologies,” he says. Getting it to Farmers
Designing gene-edited crops and livestock is the first step. Getting the products onto farms is next. The PRRS-resistant pig may be commercialized by PIC within five years if the company receives the necessary regulatory approvals, says Matt Culbertson, director of global product development for PIC, the world’s largest swine breeding stock company (a division of Genus).
“We’ve been an early investor in gene editing as a way to create new and beneficial genetic variation,” says Culbertson. Besides diseases, PIC is funding work on animal well-being, productivity, and sustainability.
“When Prather and his team started working on this a long time ago, it seemed like blue-sky type of science,” says Culbertson. Now the science is here, and the challenge is marketing.
“We need to introduce it to the marketplace domestically and around the globe in a positive manner so there isn’t an impact on exports.”
In the end, says Culbertson, gene editing “can revolutionize the output and efficiency of livestock production. The technology can influence items like animal well-being, sustainability of the industry, feed efficiency, mortality and morbidity, and meat quality. It offers huge opportunity to genetically change the landscape of livestock production.”
One unknown is how the licensing of the CRISPR technology will play out. At some point, any company using this technology will have to pay either Berkeley or MIT, depending on the results of the patent lawsuit (see below). Historically, companies in the GMO arena have been extremely guarded when it comes to their seeds. Once farmers have gene-edited pigs or cows, will they be allowed to breed them in their herds? Stay tuned.
What is CRISPR?
CRISPR stands for clustered regularly interspaced short palindromic repeats. These repeats were discovered in the genomes of bacteria. In bacteria, CRISPR acts as an adaptive immune system. It uses RNA to guide molecular scissors (Cas) to cut up invading viruses.
Using these same molecular tools, scientists reprogrammed the molecular scissors to cut and edit, or correct specific spots in DNA. CRISPR-Cas tools can now be engineered to cut out the DNA at the exact site of a mutation for a disease in a pig, for example.
The original discovery of CRISPR dates back to the 1980s. In 2012, Jennifer Doudna at the University of California, Berkeley, with Emmanuelle Charpentier from Umeå University in Sweden demonstrated that CRISPR can be made to specifically edit a genome.
In 2013, Feng Zhang at MIT successfully adapted CRISPR for genome editing in cells. (There is a patent dispute over the discovery.)
Researchers at other universities have now reported similar findings, and the technology has taken off. BY BETSY FREESE.
