There is enormous excitement about the potential applications of genome editing, or GenEd. Billed as a set of techniques that promise more precision, flexibility and efficiency, these new breeding technologies are fast-replacing the biotechnology used to create the first genetically engineered crops. Scientific and agricultural communities are eager to foster a better understanding and greater acceptance of this technology in hopes of moving past the “Frankenfood” stigma shadowing genetic engineering technology.
Genetic Modification Through the Ages
TAMING THE TERMINOLOGY
Mutagenesis: Changes (mutations) in an organism’s DNA, which may occur spontaneously, as a result of exposure to a mutagenic agent or through direct manipulation.
Enhanced mutagenesis: The use of high-dose radiation and/or chemicals to produce mutations at a higher rate than would occur naturally.
Hybridization: Cross-breeding two closely related plants to create a new strain.
Genetic Engineering (GE): The manipulation of genetic material through means that bypass the reproductive process.
Transgenic: The transfer of genetic material from one organism to another through means other than reproduction.
Gene Editing/Genome Editing (GenEd): A type of genetic engineering in which DNA of a living organism is modified by inserting or deleting individual nucleotide bases.
Genetically Modified Organism (GMO): Although cross-breeding, hybridization and genome editing are all forms of genetic modification, the term “genetically modified organism” usually is used to refer to crops created by transgenic modification.
New Breeding Technologies (NBTs): Techniques such as CRISPR-Cas9, zinc finger nuclease technology and TALENs, which allow precise editing of an organism’s DNA.
CRISPR: Acronym for Clustered Regularly Interspaced Short Palindromic Repeats, a genetic feature used in the CRISPR-Cas9 genome editing technique.
Cas9: A protein used by certain bacteria to edit DNA and utilized in the CRISPR-Cas9 genome editing technique.
Genetic modification of organisms happens in nature, without any human intervention. As plants and animals reproduce, random genetic changes called mutations occur. Some mutations are beneficial, some are detrimental and some are neutral. Growers have long sought to take advantage of this natural phenomenon by selecting the most successful “mutants” as seed stock or by cross-breeding similar plants in an attempt to transfer desirable traits to other strains (a technique called hybridization).
Starting in the early 20th century, breeders began applying chemicals or high-dose radiation to seeds in order to create mutations at a higher rate than would occur naturally — called enhanced mutagenesis. Plants with desirable mutations could then be crossed with other seed stock or crossed back into the parent stock to improve the quality and characteristics of the original variety.
Regardless of how the mutations occur, opportunities for crossbreeding are limited by the ability of two plants to successfully reproduce. A grapefruit can be crossed with an orange, but not with a tomato, for example. This limitation was overcome in the 1970s by gene transfer technology that allowed scientists to transfer genetic material from one organism to another, called “transgenic modification,” regardless of whether the two organisms were closely enough related to cross naturally. The first transgenic plant (the Flavr Savr tomato) was approved for human consumption and brought to market in 1994 but was not sufficiently profitable to continue production. Although there are no genetically engineered tomatoes on the market, nine transgenically modified food crops are commercially available (corn, soybean, squash, papaya, alfalfa, sugar beets, canola, potato and apples) — most of which were modified to increase resistance to disease or pests or tolerance to a specific herbicide.
But with the advent of genome editing techniques, the gene splicing techniques used to create GMO crops are comparatively clunky and primitive. Instead of transferring genetic material from one organism to another, scientists now can edit an organism’s own DNA by deleting a few nucleotide bases (the basic units in DNA) or shifting them slightly. No foreign genetic material is involved. It’s like the difference between using a photo editor to paste one person’s head on another person’s body and editing a few pixels to remove a blemish or fix flyaway hairs in a picture.
Risks and Rewards of New Technologies
Out of the handful of genome editing techniques, the CRISPR-Cas9 method has emerged as the most promising. CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats — a sequence of nucleotides that acts as a DNA “bookmark,” making it easier to locate specific pieces of an organism’s genetic code. Cas9 is an enzyme produced by certain bacterial strains as part of the bacteria’s acquired immune response. Its function is to search for and edit, or “cleave” (inactivate), specific CRISPR sequences that belong to previously recognized pathogens. However, it also can be programmed to recognize and edit any CRISPR sequence and is now being used by genetic engineers to tweak the genetic code of plants and other organisms. The result is fewer unintended effects, and less desirable traits are revealed much more quickly. Research and development of new crops and traits is more efficient and less costly, and products can be brought to market more quickly. CRISPR technology is so much faster and more precise that many geneticists believe pursuing new transgenically modified crops no longer makes a lot of sense.
Genetic researchers working with gene editing, along with farmers and growers, are excited about the potential for CRISPR technology to expedite solutions to a wide array of pressing concerns including climate change, malnutrition and population growth. Existing food crops can be modified to increase yields and drought and pest resistance, and improve nutrient proles.
Coming Soon to a Shelf
Scientists from Penn State University used CRISPR-Cas9 gene editing to disable an enzyme that causes white mushrooms to brown, thereby extending shelf-life. The mushroom has been cleared by the USDA for commercial cultivation.
Genetic scientists hope CRISPR-Cas9 technology may provide a solution to the “citrus greening” disease that is decimating Florida orange groves by editing the genome of the trees to make them more resistant to the pathogen that causes the disease.
The global banana crop is currently under threat from a widespread fungal disease. Australian scientists already have succeeded in introducing resistance via transgenic modification. Now, they hope to use CRISPR-Cas9 techniques to produce disease-resistant bananas without introducing any foreign DNA.
Scientists in Spain have successfully used CRISPR-Cas9 techniques to modify the genome of wheat, producing strains that are significantly lower in gluten.
All breeding and agricultural methods have the potential to impact the environment and the genetic makeup of our food supply, and with any new technology, the unknowable looms particularly large — especially when advances have the potential to alter the landscape so quickly and dramatically. Genetically engineered foods have been part of the food system for more than 20 years, and despite scientific consensus that these foods are safe for human consumption, a 2016 NPD Group report found GMOs continue to be a growing concern for consumers — so much so that some food manufacturers have removed GMO ingredients from their products.
The evolution away from transgenics to genome editing renders certain issues moot. For example, questions about food allergens are largely obviated by CRISPR techniques because no foreign genetic material is introduced in GenEd foods. Other concerns, such as a loss of biodiversity or the development of pesticide and herbicide resistance, are not unique to new breeding technologies. Any use of pesticides or herbicides — including approved organic ones — has the potential to promote resistance. The process through which weeds and pests develop resistance to chemicals is the same process used by traditional breeding: mutagenesis. Random mutation can produce a pest or weed that is resistant to a given chemical, increasing its chance of survival and therefore its ability to pass that trait to the next generation.
Meanwhile, as society weighs the potential risks of new technologies with the real need for solutions to pressing problems, lawmakers are grappling with how new breeding technologies and their products should be regulated. Because CRISPR technology does not involve the transfer of foreign genetic material, it does not fit the current definition of a genetically modified food — making its regulatory status a bit of a gray area. So far, the USDA has opted not to regulate foods created with CRISPR technology as GMO foods. The FDA is reviewing its existing guidelines for determining the safety of new plant varieties and is seeking input from the scientific community.
To the extent that regulations are put in place, scientists are calling for a “product vs. process-based” review system, whereby as new foods are brought to market, they are evaluated according to the attributes and makeup of the food itself, not how these attributes were acquired.