Nathan A. Billings Ph.D. Director Indigo Ag, Inc.
Nishat Shaikh Attorn
Brian Reese Ph.D. Attorney Choate, Hall & Stewart LLP
The Next Generation of GMOs and Public Policy and Opinion
Genetically modified organisms, or GMOs as they are commonly known, have been a controversial topic since their inception, and pose unique challenges for governments to regulate effectively. Recently, both the U.S. and EU have evolved their thinking regarding GMOs, including whether or not modifications made with new breeding technologies (NBTs), specifically gene-editing technologies, should fall into the same category as that of organisms modified via previously known transgenic techniques. However, we observe that while regulation over these technologies is evolving, the debate may not be fully informed and/or is centered on only some of the relevant issues.
Agricultural crops are some of the GMOs most visible to the general public, and will serve as the emphasis for this article. The first GMO crops were created via transgenesis—a process by which a plant genome is permanently altered by inserting foreign gene sequences from a different, non-sexually compatible plant or other organism, e.g., sequences that could not appear in the genome through non-genetic breeding techniques [see EMBO Rep. 7(8): 750–753 (2006)]. In contrast, gene-editing technologies allow for the modification of a plant genome to alter single or a few nucleotides, or targeting the insertion of genes to a specific location. They also allow for both intragenesis (the modification of portions of one or more genes) and cisgenesis (the insertion of one or more genes in the correct orientation and including natural expression signals). These technologies are capable of providing astounding improvements to crops, such as improving disease resistance or increasing metabolic efficiency; and this has led to a flurry of activity as many researchers and companies seek to expand and further develop gene-editing technologies in plants.
Public Policy Issues
In both the U.S. and the EU, transgenic genetically modified (GM) crops must be approved by regulatory agencies before they can be marketed. Both the U.S. and EU have mandatory GM labeling requirements, though the structures of the U.S. law, which was passed in July, are far less imposing and rigorous than that of the EU.
Regulation of transgenic GM crops by the USDA is rooted in the Plant Protection Act (PPA), which broadly gives the USDA authority to regulate plant pests or noxious weeds, including GM organisms that are, or have the potential to be, plant pests. However, the USDA has signaled that genetically engineered crops that do not contain “foreign” DNA are not considered to be GM crops, and thus do not require USDA regulation. Thus, the advent of gene-editing technologies has allowed for new business strategies in the production of crops having one or more genetic modifications. In the U.S., gene-editing technologies have already allowed more than 30 types of engineered crops to entirely bypass regulation by the USDA [see Nature, vol. 532, p. 293 (April 2016)]. One such crop is the CRISPR/Cas9-edited white button mushroom. The mushroom was engineered to resist browning by making 1–14 base pair deletions in a specific polyphenol oxidase gene and contains no foreign DNA integrated into the mushroom genome, thus escaping regulation by the USDA (see Letter from M. Firko, APHIS deputy administrator to Dr. Y. Yang, associate professor at PSU, dated April 13, 2016).
While in the past much of the EU has been reluctant to embrace GM crops, recent pressure from trade partners has led to speculation that the EU will move toward the position that crops which have been altered using NBTs should be exempt from the regulations that currently control transgenic GM crops.
In summation, under current U.S. and contemplated EU regulation, when CRISPR is used to modify a handful of nucleotides to knockin or knockout one or more endogenous gene pathways in a crop organism, the resulting organism is not viewed as a GMO. In contrast, if CRISPR is used to introduce an entire exogenous gene sequence into an organism, it would be considered a GMO. While on its face this is a clear line of distinction, consider if CRISPR is used to introduce multiple copies of an endogenous gene to obtain higher levels of expression, without the introduction of foreign DNA. Should the U.S. or EU view this as a GMO? How would consumers react? An important question that remains to be resolved is whether or not the division of GM crops into two groups based solely on the presence or absence of exogenous DNA is legitimate.
Public Engagement and Transparency
In the U.S., the majority of people view eating GM foods as unsafe and suspect that scientists do not understand the long-term effects of eating GM foods on health (see Pew Research Center, July 1, 2015, “Americans, Politics and Science Issues”). This is fueled, at least in part, by public distrust of consuming crops containing genetic material from insects or bacteria, as well as public perception of the business practices of large agribusinesses [see HHMI Bulletin, p. 32 (Winter 2015)]. The classification of CRISPR-engineered crops as non-GM has the potential to exacerbate public distrust around GMOs if communication with the public regarding these technologies is not handled in an open and engaging way.
Importantly, there has been little public discourse around scientifically relevant issues including potential environmental impacts resulting from widespread use of GM crops. For example, an extensive amount of plant genetic diversity has been lost as agriculture has adopted genetically uniform crop varieties, and the widespread use of GMOs reinforce this perceived decline in biodiversity. The Irish Potato Famine in the mid-1800s is a sobering reminder of the real-world effects of genetic diversity (or lack thereof) on agriculture. This trend was not the result of using GMOs per se, but has nevertheless increased distrust in GMO technologies.
Instead, much of the popular conversation has been directed at the “horrors” of GMOs, such as GM crops causing the alleged increase in food allergies. Perhaps the overarching problem is a lack of education of the lay populace, or perhaps even a miseducation thereof? In fact, early commercialization of transgenic/GMO technologies either did not place education of the general populace as a priority, or did a very poor job of it. The opinions of many non-scientists appear to have been shaped as much by the business and marketing practices of GMO companies as by the technology itself, if not more so.
The agricultural biotech industry has not been well served by historical GMO messaging efforts. However, unlike historical GMOs, the awesome power of CRISPR to easily and inexpensively copy and paste genetic information has captured the public’s imagination and been picked up by the popular press. NBC is even rumored to be developing a “CRISPR TV drama” featuring Jennifer Lopez as the heroine saving the world from a mad scientist. Popular press coverage and general public awareness, combined with the need to revisit and reshape outdated GMO regulations, offers a fresh opportunity for the industry to engage the public and shape policy and perception together, rather than after the fact. In order to properly position gene-editing technologies for mass-market acceptance, and thus maximize value creation, industry stakeholders would be well served to coordinate and seize this rare opportunity.
Nathan A. Billings, Ph.D., is director of intellectual property at Indigo Ag, Inc. Nishat Shaikh and Brian Reese, Ph.D., are attorneys at the Boston-based law firm of Choate, Hall & Stewart LLP.