About 10,000 years ago, […] Sapiens began to devote almost all their time and effort to manipulating the lives of a few animal and plant species. From sunrise to sunset humans sowed seeds, watered plants, plucked weeds from the ground and led sheep to prime pastures. This work, they thought, would provide them with more fruit, grain and meat.
— Yuval Noah Harari, Sapiens

The agricultural revolution has forever changed the way humans live and interact with plant and animal species. For thousands of years, farmers have been selectively breeding crops with desirable physical traits, resulting in the crop varieties that are abundant today. However, the agriculture industry must now deal with a growing population, repercussions from its own environmental impact, and a changing climate — issues it has never had to grapple with before.

The global population is projected to reach nearly 10 billion by 2050, and to meet the expected high food demand, agriculture production has to increase by 60-70% from current levels. The environmental impact of the agriculture industry is significant: half of the world’s habitable land is used for agriculture and livestock and agriculture irrigation uses about 70% of the freshwater supply worldwide. In addition, agriculture is particularly sensitive to extreme weather events induced by climate change, threatening food production and availability. What modern solutions can be applied to improve this millennia-old industry?

Gene editing may be the answer. Gene editing using clustered regularly interspaced short palindromic repeats (CRISPR) has revolutionized the field of biology in less than a decade since its discovery. Using a short customizable guide RNA sequence and a CRISPR-associated (Cas) protein, almost any DNA sequence can be precisely edited with insertions, deletions, or exchanges. CRISPR gene editing is already being used to generate model organisms for research and in clinical trials to treat certain genetic diseases. With these advances, CRISPR is now also making headway in the food and agriculture industry. CRISPR is the newest tool of genetic improvement in agriculture in the last 20 years, which also includes gene transfer, marker assisted breeding, and genomic selection. Using CRISPR, researchers are now exploring the possibilities of improving crops by increasing yield, requiring less resources, and conferring resistance to drought or cold.

CRISPR solutions for corn

Corn (maize) production accounts for 10% of global crop production and is mostly grown in the United States, concentrated in the Midwest. Additionally, corn is used for ethanol, livestock feed, and food products such as syrup and starch. Corn production requires substantial amounts of water, and has the highest water scarcity footprint of all food commodities produced in North America. Corn cultivation also requires nitrogen in the soil, often as a fertilizer, to sustain yield; however, excess nitrogen application is costly and an environmental pollutant. Thus, with the large consumption of these resources, high yielding crops would be more efficient for cultivation and beneficial for the environment.

Several gene sequences that could affect yield have already been identified in corn. For example, researchers at the Cold Spring Harbor Laboratory in New York and at the University of Massachusetts Amherst found that deleting sequences in the promoter region of CLE, a gene that controls the size of the meristem near the shoot of corn, increased yield-related traits such as ear diameter, cob diameter, and kernel row number. In addition, it has been found that the ARGOS8 gene is normally not highly expressed. Using CRISPR, researchers from the agricultural company Pioneer in Iowa replaced the ARGOS8 promoter sequence with that of a higher expressing gene. This method of increasing ARGOS8 resulted in more bushels per acre than non-edited crops, particularly during drought stress conditions. These methods of increasing corn yield could help to sustain the growing population as well as require fewer natural resources during cultivation.

CRISPR solutions for rice

Rice, another staple crop, is expected to have its yield reduced by about 3% per 1°C increase in global mean temperature without genetic improvement or significant efforts to curb climate change. This would affect the half of the world’s population that depends on rice daily. Consequently, researchers at Wuhan University in China have simultaneously edited three genes in rice using CRISPR: OsPIN5b to increase panicle length, which is the top part of the rice plant that produces grains, GS3 to increase grain size, and OsMYB30 to confer cold tolerance. This triple mutant rice strain had higher yield and better climate stress tolerance, which could help to stave off the impending devastating effects of climate change.

Rice cultivation itself, however, is not climate-friendly, because it releases methane and nitrous oxide into the atmosphere that significantly contribute to greenhouse gas emissions. Excess methane is released during controlled continuous flooding of rice paddies, a common practice used to prevent weeds. However, reducing continuous flooding to intermittent flooding of rice paddies releases nitrous oxide, a more potent greenhouse gas. The Information Technology and Innovation Foundation (ITIF), an independent nonpartisan research and education think tank suggests that greenhouse gas emissions from rice paddies, which is due to water metabolism and microbial populations in the soil, can be reduced with gene editing. For example, using gene editing techniques, researchers at the Fujian Academy of Agricultural Sciences in China and at the Swedish University of Agricultural Sciences were able to achieve a high starch and low methane rice variety by introducing the barley transcription factor SUSIBA2. Gene editing innovations such as this could help to reduce greenhouse gas emissions from rice cultivation, which currently has the highest greenhouse gas footprint of all food commodities, especially in Asia.

Gene editing applications in the private sector

Breakthrough research and development conducted in the private sector could speed up the process of planting CRISPR gene edited seeds into fields. Leaders in the industry include Pioneer, which is generating better performing hybrid crop seeds that addresses farmers’ needs using the latest breeding and gene editing tools to provide higher yielding and more resilient crops. Achieving sustainability in agriculture is also a top priority in the private sector. Bayer Crop Science, a sub-division of pharmaceutical giant Bayer, is aiming for a 30% reduction in field greenhouse gases, a 30% reduction in agriculture’s impact on the environment, and empowering 100 million smallholder farmers to access sustainable agricultural solutions by 2030.

Alongside agriculture technology giants, the industry also welcomed Inari in 2016, a startup based in Cambridge, Massachusetts. Its ambitious goals for gene editing in corn include increasing yield by 20% and reducing water and nitrogen usage by 40%. Using its proprietary genetic design software powered by machine learning, Inari is researching genetic interactions and pathways instead of single genes to edit multiple genes at once using CRISPR, ultimately generating a variety of seeds that are ideal for different growing conditions. CRISPR agricultural technology startups in Europe include PlantEdit, founded in 2017 and based in Ireland. Along with academic researchers in Japan and China, PlantEdit has since optimized a protocol to introduce CRISPR gene edits without using additional DNA into apple and grapevine, which is reported to be faster, more efficient, and can be adapted to other crops. Hudson River Biotechnology, founded in 2015 and based in the Netherlands, uses a proprietary workflow called TiGER, which stands for Target identification, Guide selection, Entry into the cell and Regeneration, to gene edit a variety of crops to achieve desirable traits. With the experience of the technology giants, novel solutions proposed by startups, and collaborations with academic researchers, innovative solutions for the agriculture industry could be on the near horizon.

Governmental regulation and public acceptance

As with any new technology, CRISPR gene editing in crops must pass assessments for safety and risks. So far, the United States Department of Agriculture (USDA) does not classify CRISPR gene edited crops as genetically modified organisms (GMOs) and has stated that it would not regulate gene edited crops as it does GMO crops. GMOs are defined as having foreign DNA introduced from other species using gene transfer technology, whereas CRISPR technology simply edits existing DNA and represents a faster version of selective plant breeding and evolution. The safety and nutritional profile of gene edited foods are still regulated by the Food and Drug Administration (FDA) while the Environmental Protection Agency (EPA) oversees the use of pesticides on gene edited crops. This deregulation by the USDA could lower the cost of generating CRISPR gene edited crops and lower the hurdle to public acceptance. However, a patchwork of mismatched global regulations still presents a major hurdle for acceptance worldwide. For example, the European Court of Justice has defined site-direct mutagenesis using CRISPR as a GMO, which would undergo strict regulation in the European Union. Optimistically, the definition of CRISPR gene editing is now being revisited by the European Commission.

Deregulation of CRISPR edited crops by the USDA does not mean that scientists and innovators have free rein. “It is always good to ask questions and hold innovators to high standards of safety,” said Val Giddings, a Senior Fellow at the ITIF during a panel discussion titled “Gene Editing for the Climate” in September 2020. However, “no one has yet identified a novel hazard associated with any method of genetic improvement to adapt plants, animals and microbes to better serve human needs,” speaking of decades of hybrid breeding, genetic engineering, GMOs, and now CRISPR gene editing. Thus, there would be no basis for excess regulation and extreme caution with CRISPR gene edited crops.

In the same panel discussion, Scott Knight, Head of Genome Editing and Yield, Disease and Quality Research at Bayer Crop Science, has said that farmers are generally excited about gene editing. “Not only are farmers running sophisticated operations, but they are also embracing new technology and are always looking for solutions to challenges, especially if they are sustainable solutions,” he elaborated. Indeed, having higher yield, reducing the need for additional resources, and being resistant to extreme weather in crops generated by CRISPR gene editing would benefit farmers’ livelihoods in the long term.

Progress in the agriculture industry would require aid and initiatives from the government. In line with this, Senator Michael Bennet of Colorado has proposed a bill to establish a new agricultural research organization, known as the Advanced Research Projects Agency (ARPA)-Terra Act of 2019. ARPA-Terra would grant funds to researchers to study innovative technologies in agriculture that would benefit farmers and the environment, which could help to drive faster innovations with gene edited crops.

Complete acceptance and application of the CRISPR gene edited crops would require a purposeful collaboration between research organizations, agricultural technology companies, governmental bodies, farmers, and the general public. Although CRISPR gene edited foods are not yet available in the market, scientists, regulators, and farmers seem confident about the new technology, and public opinion may be the last and biggest hurdle to widespread acceptance. GMO foods were already deemed unfavorable by the general public, and CRISPR gene edited foods may be similarly scrutinized by consumers. In addition, when presented with a hypothetical CRISPR edited rice variety, consumers were only willing to pay for such products with a high discount rate. However, public trust can and must be gained with effective science communication and transparent policies.

Future outlook

CRISPR gene editing in crops have been shown to increase yield, for example in corn kernel number and rice grain size; reduce the agricultural environmental impact, for example by requiring less water for corn and limiting methane gas release in rice paddies; and produce drought and stress resistant crop varieties. Concerted efforts by scientists, agricultural technology companies, governmental organizations, and farmers are necessary to persuade public acceptance as CRISPR gene edited crops make their way out of research labs, into fields, and eventually into supermarkets. With the innovative gene editing solutions, the agriculture industry can more likely sustain a growing population, reduce its environmental impact, and withstand extreme weather events brought on by climate change.

Cally Xiao, PhD is a Project Administrator in the Laboratory of Neuro Imaging at the University of Southern California.