GMO vs. Gene Editing for Plants: A Closer Look

This article was originally published Nov. 19, 2018 in SeedQuest

By Brad Fabbri, Ph.D, TechAccel Chief Science Officer

It’s easy to look at the vast array of upscale restaurants and groceries touting non-GMO (genetically modified organism) offerings and conclude that it is hazardous for your health to consume genetically modified organisms. The anti-GMO movement has effectively stoked fear and apprehension, often invoking discredited ‘scientific’ rationale and being guided by a ‘precautionary principle’ that even if there is no credible scientific reason for avoiding GMO foods, they should still be avoided because there might be a downside identified sometime in the future. This well-organized and -funded anti-GMO movement has effectively drowned out the arguments in favor of GMO including the significant overall improvements for agriculture sustainability.

Some in the anti-GMO movement argue there is a need for more scrutiny and regulation of certain breeding techniques including gene editing. The European Union, with its recent ruling that gene edited crops are to be treated like GMOs with respect to regulation, sows even greater confusion.

This EU ruling calls plants created using CRISPR and other gene-editing tools the same as genetically modified organisms and subject to the same stringent regulations. But the ruling also nods to an exception, allowing that plants developed using conventional mutagenic techniques with a long safety record are exempt.

The head-scratching nature of the ruling cries out for an understanding of the science involved. So, what is gene editing? And is it different from transgenesis or GMO crops? How can gene edited crops be regulated if they are indistinguishable from crops developed by traditional plant breeding?

There isa distinction between gene editing and creating genetically modified organisms. Understanding this distinction is crucial to making choices that are good for consumers and investors and for the future of the global food supply. It starts with a better understanding of mutagenesis.

Mutagenesis as Historic Means of Identifying Improved Plant Varieties

The fact is: We—humans—have consumed genetically modified foods as long as we have been eating plants.

Spontaneous mutagenesis—a change, or mutation, in DNA—happens naturally all the time. It occurs due to natural radiation such as ultraviolet or cosmic rays, chemical reactions, or errors in DNA replication. When this chemical change to the DNA occurs in a part of the genome that encodes something important for the plant, the change is often deleterious. But sometimes, the change is beneficial, and the resulting mutant plant is better than its parents.

Humans have been selecting improved mutant plants for at least 9,000 years. Modern crops including corn, watermelon, and peaches are radically different from their wild forebearers, a result of the long history of plant breeding where humans have selected for desirable qualities. Early farmers would select crop lines with advantageous mutations such as bigger grain, tastier fruit, or other desirable properties (like, a large gourd size with utility as a container). And season to season, seed from the best plants was saved and re-planted. Farmers were always looking for good seed, just as they do today. Over many generations of cross-breeding farmers have created genetic improvements and stronger, better-yielding crops. In essence, farmers have been genetically modifying cropsfor thousands of years—at least via selection of mutants and careful crossing of different varieties.

These traditional means are still in use today. In addition, over the last 90 years or so, plant breeders have employed new methods to increase efficiency for generating mutations with the goal of selecting improved varieties. Starting around 1930, various types of radiation including X-rays, gamma rays, ultraviolet and neutrons have been used to ‘mutagenize’ plant populations to generate high frequencies of induced plant mutants that the breeder can select from. Starting in the 1940s, mustard gas and similar compounds were used as another means of generating mutants. And even today, chemicals such as ethylmethane sulphonate (EMS) and similar compounds are commonly used to generate mutant plant populations. And these methods have been useful – a highly cited article published in 2004 estimated at the time that more than 2,250 plant varieties derived from mutagenized populations had been released.

A critical aspect of ‘spontaneous’ or ‘induced’ plant mutation is that the process of mutagenesis is random. Now, there are methods of introducing variation into plants that are not random and are highly planned.

These are the sophisticated gene-editing tools like CRISPR/Cas9, homing endonucleases (‘meganucleases’), oligonucleotide-directed mutagenesis, and zinc-finger nucleasesthat all can be used to generate mutations that are indistinguishable from those identified from spontaneous or induced populations.


Directing Desirable Mutations

We are experiencing rapid strides in genomic sequencing and analysis technologies, with prices dramatically dropping, and capabilities markedly increasing each year. This means that plant scientists and breeders can identify key desirable mutations, and these new gene editing tools can make the precise edits in a plant variety. This is a big advantage for time and resources over the traditional plant breeding steps required to develop mutant varieties and combine multiple desirable mutations into the same plant variety. There is significant interest in using this technology for improvement of plants, and companies including CalyxtPrecision Biosciences, and Pairwise are all focused on developing and delivering improved plant varieties using genome editing.

While each of these tools has a different mechanism, the change itself is in principle indistinguishable from a spontaneous, natural mutation. In the final product, no trace of a foreign substance remains, and the genome of the edited organism is essentially the same as that which came before.


Genetically Modified Plants: Another Means to Introduce Improvements

Genetically modified plants have had more substantial changes introduced into the plant’s genome that do not resemble natural mutations. What makes a GMO unique is the introduction of genetic material from one organism into the genome of another. When the introduced DNA comes from the same species of organism as the recipient, the technique is sometimes referred to as ‘cisgenesis’. For example, some disease-resistant traits in wild fruits have been inserted into their cultivated counterparts to achieve healthier fruits without sacrificing taste. In principle, this could also be accomplished via crossing the different plant varieties, but the cisgenic approach might be more efficient and faster.

When the introduced DNA comes from a different species, the result is often referred to as a ‘transgenic’ organism. The best examples of transgenesis are the incorporation of insecticidal proteins from the soil bacterium Bacillus thuringiensis(‘Bt’) into corn to improve its insect resistance, and an enzyme (CP4) from another soil bacterium Agrobacterium sp. that provides resistance to the very popular herbicide glyphosate (Roundup). In transgenesis, the modified organism contains DNA sequences not found in the plant species and is enough to trigger regulatory review and classification as a genetically modified organism (GMO). Currently in the US, if a cisgenic plant is produced by transferring sequences from one plant variety or compatible species to another, and this could have in principle been done using traditional plant breeding crosses to generate viable progeny, the USDA has no current plans to regulate these plants. This is not currently the case for most of the rest of the world.


Regulatory Ambiguity for Gene-Edited Crops

Regulatory requirements in the United States are triggered by the genetic structure of the end product, not the method of mutagenesis. Because there is no scientific distinction between uncontrolled mutagenesis and mutagenesis caused by gene editing, there is no need for regulatory oversight from the USDA or other U.S. agencies. The U.S. Secretary of Agriculture Sonny Perdue recently reconfirmed the USDA has no plans to impose new or additional regulation on crops developed through new breeding techniques, including gene editing. This includes modifications that could have been generated through traditional plant breeding methods. And, this has no effect on the current U.S. regulatory process for GMO plants, those that could not have been generated by traditional plant breeding methods. In the U.S., this USDA regulatory position regarding gene editing tools for plant breeding will encourage innovation.

In sharp contrast to the science-based USDA regulatory position, the European Union decision ruled that crops produced using gene editing methods need to be subjected to the lengthy EU approval process used for GMO crops. It is not obvious that there is strong scientific rationale for this decision. And the expected result, for at least the EU, is that plant breeders and farmers will be at a decided disadvantage.

The regulatory outlook for gene edited plants in other parts of the world is still unclear. A big issue for seed companies is differences in regulatory requirements in different global markets. For instance, a wheat breeder using gene editing techniques to produce new wheat varieties that would be valuable for U.S. farmers may have regulatory barriers to releasing the improved varieties because of challenges in preventing the harvest from reaching markets that require an onerous regulatory process (such as the EU).


Expensive, Complex Global GMO Regulations

GMOs, on the other hand, face a complex and rigorous regulatory system, overseen in the United States by the USDA, the EPA and the FDA. This is because a GMO, by definition, contains traces of foreign DNA or the bacteria by which the DNA was introduced. The USDA's Animal and Plant Health Inspection Service (APHIS) regulates organisms and products that may be plant pests. APHIS assumes that any GMO plant is a pest and considers it a regulated article until petitioned to deregulate the plant.

Meanwhile, the EPA operates under its mandate to control the sale, distribution and use of pesticides, regardless of how the pesticide was made or its mode of action. That includes GMO seed varietals engineered to include herbicidal and insecticidal traits. Finally, the FDA is responsible for ensuring the safety and proper labeling of all plant-derived food and feed, including GMOs. While the FDA does not have as robust a set of GMO standards as the USDA and EPA, foods, drugs and biologics produced via a GMO have to meet the same rigorous safety standards as conventional organisms.

Given all this, it is entirely possible for a single GMO product to have to clear the regulatory hurdles of all three agencies before coming to market in the U.S.

There are similarly complex and rigorous regulatory processes in global jurisdictions that will need to be satisfied before a seed company attempts to release a GMO-improved variety for sale. For an example of the real risk of not properly executing this process, consider the case of Syngenta and its insecticidal MIR162 corn trait. The GMO passed U.S. regulatory scrutiny, but it was not approved in China, a major U.S. corn market. In 2013, China refused to accept corn shipments that had traces of corn harboring the MIR162 trait, resulting in significant economic losses for U.S. corn markets. Syngenta was sued. It was reported in 2018 that Syngenta settled the MIR162 suit for $1.51 billion. This is an expensive lesson, and an example of how regulatory status in one market affects decisions to commercially release or even engage in development for new varieties.


The Forecast: Cloudy, but a Chance for Clearing

Ultimately, investors in GMO products need to determine whether the potential value of the trait being produced is high enough to warrant the inherent risks of a long and expensive regulatory and production process. The “Big Five” seed companies have mostly focused on high-value crops where a GM variant might have a net present value of more than $200 million, and have resisted releasing GM veggies, fruits or lower-value row crops including wheat. If a GMO plant product does not need to be deregulated, this removes a financial barrier of at least $25 million from the equation.

There are tremendous opportunities for the employment of gene editing methods of plant breeding to bring value to not only the big-acre row crops that have benefited from GMO technology, but also to small-acre crops including fruits and vegetables. To the extent that there is a reasonable regulatory outlook for using these tools, consistent with the observation that they are biologically equivalent to traditional breeding methods, these newer tools have the potential to democratize plant breeding and allow companies—big and small—to advance their plant breeding objectives. This will likely result in improved varieties that have quality traits such as improved taste and nutrition, which will be attractive to the consumer.

The global plant breeding industry is in a somewhat ambiguous state regarding the use of gene editing tools. Rulings like those expressed by the EU will serve to slow and limit innovations that can provide tangible benefit to consumers and farmers. Our opportunity—and obligation—is to deliver a clear understanding of the science of genetic modification and the potential value of the traits produced. We look forward to a global recognition that these new breeding tools are biologically equivalent to traditional plant breeding methods, and deserve reasonable and appropriate regulatory pathways and requirements.

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