A short guide to answering a complicated question.
While Covid-19 has commandeered the world’s attention, an important debate that will weigh on the future of agriculture is in process in Europe. European regulatory agencies are assessing what constitutes a genetically modified (GM) product. This debate started in the last century, and it has been characterized by confusion, inaccuracy and inconsistency. Here is my ‘cheat sheet’ for what does — and what does not — qualify an organism as GM based on scientific discourse.
Settling GM vs. Non-GM
Broadest Definition: ‘GM’ means any genetic change in an organism. This definition is useless. Every food we eat — organic or not — is the product of genetic change. Without genetic changes fostered 10–12 thousand years ago by indigenous peoples in Mexico, corn would still be a tall grass with tiny kernels encased in tooth-breaking hard shells. Traditional plant breeding attempts to alter genes, as do all other plant-breeding techniques.
U.S. Regulatory Definition of GM: From a U.S. regulatory perspective, ‘GM’ is defined as introducing foreign DNA and inserting it into the genome in a place where it would not naturally occur. Organisms that do have such foreign DNA are called transgenic, and this applies to many large acreage row crops grown in the United States, such as Roundup Ready or insect-tolerant corn and soybean.
Additional Definitions: Certain non-government organizations (NGOs) have their own standards to classify a crop as ‘GM’. For certain groups like The Non-GMO Project, if any specific gene is targeted and altered (regardless of whether the technology introduces foreign genetic material into the genome), it is ‘GM’.
The question then becomes not if genes change, but how they are changed.
So, what technically constitutes a non-genetically modified organism, outside of the obvious? Non-GM can include selective breeding: a practice that farmers have been honing for millennia.
Selective Breeding (non-GM): Traditional plant breeding involves cross-breeding plants that possess desired traits, ultimately producing a plant with the better combinations of these traits. The process of looking at as many combinations as possible involves trial and error.
The Grey Area
And still, the GMO-classification debate has a murky grey area. Certain techniques such as mutagenesis and gene editing can fall into either camp, depending on how they are used.
Mutagenesis: This technique involves exposing the genome to specific chemicals or radiation with the goal of inducing mutations and the hope that among the mutants produced will be a plant with the desired trait. For the past 40 years, more than 3,000 products of mutagenesis have been sold and globally consumed without any negative effects.
Chemical mutagenesis produces beneficial mutations, as well as a large number of undesirable mutants (collateral damage). Conventional breeding techniques are used to retain the beneficial mutations and eliminate the collateral damage. Interestingly Canada has a product-based regulatory system — designed to ensure the quality of the product — novel traits are regulated. However, in the European Union, products of mutagenesis are generally accepted as conventional plant breeding. In both cases, mutagenesis technology is accepted as non-GM, or non-LMO (living modified organism) in Canada.
Gene Editing: This refers to the direct or indirect alteration of a plant’s genes. This category covers several different approaches with a wide range of processes and outcomes, and because of that it has generated significant confusion in the public, among NGOs, and even with policymakers.
Gene editing can take three paths: 1) gene knock out (inactivating specific genes), 2) precise changes in the genome at the smallest possible level, or 3) insertion of a transgene into a specific location within the genome. The first two outcomes occur regularly in nature, as typographical errors can occur each time DNA replicates. Further, methods using these techniques can either be transgenic — involving insertion of the editing tools themselves into the genome — or non-transgenic — without inserting tools. In some cases, transgenic tools are inserted and then removed from the final product, and in those instances, some regulatory authorities consider these crops to be non-GM.
Non-GM Gene Editing: As of today, we believe the non-GM gene editing technology with the greatest precision and flexibility involves the use of molecular scissors (where the editing tools are not integrated into the genome) in combination with a chemical construct (in scientific terms, an oligonucleotide) that triggers the genome’s own repair system to make precise changes in a particular gene. In other words, this technique — called Precision Gene Editing — triggers the genome’s spell-checking machinery to edit itself. Like a typographical error that can occur when the DNA sequence is copied, or even when chemical mutagenesis is used, the chemical construct leaves no trace once its work is complete. In no way does it become incorporated into the genome. Since transgenes are not involved at any stage in such edits, and because the oligonucleotide disappears after performing its job, this form of gene editing classifies as non-GM in many jurisdictions.
Where the Regulatory Debate Stands
During the 1990s, policymakers around the world developed and introduced regulations designed to assess the risks associated with the emerging transgenic technology that enabled developers to introduce foreign genes into crop plants. This technology was described as genetic modification (GM) technology and it enabled developers to introduce changes to plants that could not occur naturally. As this kind of change had not been seen before, policymakers adopted a precautionary approach and introduced very stringent regulations.
The stringent regulations have remained largely unchanged for over twenty years and have proved prohibitively expensive. As a result, they have limited the use of GM technology to a small number of large crops developed by a small number of large companies. Nonetheless, since 1994, more than six billion acres of GM crops have been planted worldwide.
Shortly after the dawn of the new millennium a technology emerged that could directly edit a plant’s genome without introducing foreign genetic material. For the past 10 to 15 years, policymakers have been working to understand the risks associated with the new emerging technology called gene-editing.
Among the scientific advisors to policymakers, there was an early consensus that when the gene-editing technology did not result in the introduction of foreign DNA, the resulting variety posed no more risk than conventionally bred varieties.
In 2015, the Argentina Biosafety Commission (CONABIA) was the first regulatory authority to address gene-editing. They determined that gene-edited varieties that contained no foreign DNA posed no greater risk than conventionally bred varieties and so they should be regulated in the same way as conventional varieties.
In the following years, the governments of Chile and Brazil adopted similar policy and in March 2018 the US Secretary of State for Agriculture, Sonny Perdue, issued a statement confirming that, under its biotechnology regulations, ‘… the USDA does not regulate or have any plans to regulate plants that could otherwise have been developed through traditional breeding techniques…’
In October 2018, the governments of Argentina, Australia, Brazil, Canada, the Dominican Republic, Guatemala, Honduras, Paraguay, the United States of America, and Uruguay issued a statement through the World Trade Organization with the primary objective to ensure that the regulatory approaches for gene editing are scientifically based and internationally harmonized in order to facilitate international trade.
In the years that followed, a growing number of governments, including Japan, Colombia, and the Philippines, have adopted similar policies. Announcements in countries including Russia, Kenya, and Indonesia have indicated a similar policy direction.
Against this backdrop, in September 2018, the European Court of Justice conducted a legal review of the applicability to gene-editing of the 2001 EU Directive regulating GM crops. The Advocate General appointed to advise the Court issued a statement concluding that because the products of gene editing contained no foreign DNA and could also have been developed through conventional breeding techniques, they posed a similar risk to conventional varieties and so should not be regulated in the same way as GM varieties. This position was supported by several Member States and EU Institutions. However, the final ruling of the court overruled the Advocate General’s position, and as a result, gene-edited products are considered GM in the EU at present.
The ruling produced a firestorm. It was supported by several NGOs but was harshly criticized by many groups, including EU Member States, National and EU Science Academies, trade and industry groups, and the Scientific Advisers to the European Commission. All these groups argue that the ruling was based on a legal interpretation of legislation written over twenty years ago and that it did not take into account scientific advances. They argued it was neither science nor risk-based, posed unjustified trade barriers, and could not be implemented for imported goods. In response to this broad-based backlash, in November 2019, the EU Council formally requested the European Commission to review the situation and propose changes to the law if needed.
The EU Council is currently scheduled to address the European Commissions proposed changes in the spring of 2021.
The goal is harmonized regulatory with all regulatory guidelines in all jurisdictions. It is our belief that, over the next two to three years, the Cibus gene editing technology will be uniformly confirmed as non-GM by the world’s regulatory agencies. That is what the science supports, and consequently, so do we.