The End of the GMO Debate?

Regulation of GMOs around the world roughly follows a conceptual divide between the US and Europe (Paarlberg 2001): permissive or precautionary.  In the US, regulations favor a notion of substantial equivalence: permission to plant means that no additional risk can be perceived from the new traits introduced into the GM crop compared to its non-GM equivalent. In Europe the ‘precautionary principle’ leans toward a position that there is insufficient evidence of the safety of most GMOs, necessitating further studies to prove that no additional risk exists. Precaution has added many years to development timelines for GM crops that could be grown and sold in Europe, thus blocking research and development of crops that could have local and global utility. There is no universal standard for how cautious is cautious enough. One direct consequence is the under-representation of GM crops in sub-Saharan Africa, where new traits are sorely needed but restricted due to Africa’s colonial history and trade dependency with Europe (Paarlberg, 2008).

The result of these two conflicting perceptions of GMOs on grounds or risk – to food safety and environment — has disrupted trade between the US and the EU and, as a result, among their trading partners. In addition of differences of risk assessment, a second objection to GMOs that divides publics is that of intellectual property and patents. Because relatively few firms have dominated existing technology, many worry that GMOs enable monopolization of the world’s food system by multinational corporations. Whether or not one can patent a crop cultivar varies widely across nations, but objections are widespread. Would genome-edited plants face similar objections on grounds of property?

It is too early to tell how property systems will treat the innovations described above. Nevertheless, genome-edited crops are a priori almost certain to be less susceptible the objections to biotechnology on grounds of monopoly built on intellectual property.

There are two reasons to expect more acceptability of genome-edited crops compared to ‘GMOs.’ First, patents are national and need not be universally accepted to invite investment in research and development: less is at risk. Moreover, patents are in no sense permanent rules of the game but are continually challenged in courts: these are not structures but playing fields on which contestants contend. In the US, the long contest of genome editing technology pitted a University of California Berkeley group against one at Harvard and MIT. The latter group seems to have won; the former will appeal. European patents will be years in the decision stage (Ledford et al 2016; Ledford 2017; Nature Editorial, 02/22/2017). It seems likely that the lower cost of entry and shortened development time will generate more players with a more competitive playing field. Monopoly or oligopoly will be far harder to establish or sustain. Concentration in the industry is bound to fall, and the dominance of internationally traded commodities such as cotton and maize will likely recede in favor of a broader palette of transformation of now-ignored crops.

Second, the objection to property rights is that first movers attain a privileged position leading to oligopoly or monopoly. First movers are favored by high capital requirements. Genome edited plants are less likely than are GMOs to face this social problem. This is because the process is inexpensive and fast, requiring less capital, infrastructure and staying power. Developers risk much less in terms of cost; more players would be able to compete on a more equal footing. Potential for industry concentration in the current major players geographically would also be reduced.

However, these advantages could be eroded, or eliminated entirely, by classification and regulation. The more heavily regulated genome-edited plants are, the more likely they are to be monopolized by firms with deep pockets, political heft and compliance staff – in contrast to universities, small firms and individuals who lack these resources and countries with weaker biosafety scientific capacity (Herring and Kandlikar 2009). Indeed, momentum in new technologies is emerging from university settings, not industrial life-science firms. Setting the regulatory bar too high would enable more monopoly and reduce competition and innovation, while simultaneously attaching a stigma to the plants, as happened with GMOs. Removing obstacles of regulation and stigmata of the GMO from genome-edited crops would presumably draw more investment in agricultural development (Kolady and Herring, 2014).

Will genome-edited plants be coded as ‘GMOs’ or not? Sweden, Canada and the US are saying, so far, no. The reasoning is the absence of transgenesis in genome-edited crops: no ‘foreign’ DNA need be involved. In this sense, genome-edited crops are more like precisely site-specific mutagenized plants than transgenic plants in which incorporation of a transgene is uncertain. Indeed, with the progress of synthetic biology, it becomes increasingly possible to synthesize a gene or sequence rather than to find, isolate and transfer it from another species. These facts should remove much of the objections on grounds of ‘unnatural’ plants that violate the order of species on Noah’s ark.

However, like ‘GMOs,’ genome-edited cultivars vary. For example, several nucleotide substitutions or a small deletion in a plant genome, using genome-editing technology, closely resembles the breeding mutagenesis process described earlier and used for over half a century without any differences in regulation from conventional crops. A nuclease used in genome editing to cleave DNA resembles the effect of a chemical or irradiation mutagen used in mutagenesis breeding. Repair pathways employed by the cell for correcting double-stranded breaks in DNA caused by either process are identical – an a natural part of the plant’s cellular machinery. As a result of these similarities, crops edited in this fashion currently bypass the regulatory frameworks of many regions of the world (Wolf et al., 2016). Organic farmers can grow mutagenized crops, without labels or special regulatory approvals, and do, all over the world.

In contrast to these minimally edited genomes, however, other genome-edited crops have undergone more substantial editing. Some of these editing events may include the incorporation of hundreds or thousands of nucleotides through a template that can be added in conjunction with the nuclease. In this way, a single transgene can be added to the target site during the genome editing transformation process, resulting in the incorporation of what could very well be genetic material from another organism.

We often use the essentializing and biologically meaningless short-hand of ‘human genes’ and ‘fish genes’ – eg in the attack on ‘fish genes in tomatoes’ – when in fact genetic instructions are constant regardless of organism in which they appear. Many ‘human genes’ are the same as those in not only simians, but bananas and protozoa as well.

The outcome of this breeding process could thus resemble a transgenic crop more than a simple product of mutagenesis (Jones, 2015). Moreover, the genome editing transformation event can even be repeated to incorporate other transgenes, precisely into the same target site, in a stacked manner. Although crops developed using genome editing in this fashion differ from transgenic plants because the technology is much more precise and construct sequences derived from plant pathogens are lacking, the fact that heterologous sequences derived from other species can be added to the plant’s genome suggests that the genome edited crop has a lot more to it than just simply a new mutation. To complicate matters further, does it matter if the sequences actually come from living material or are synthesized de novo?

The vector sum of regulatory politics may end up splitting rather than lumping genome-editing technologies. In that case, the degree of regulatory oversight of genome-edited crops in these latter cases could depend on the type of DNA repair process used, the nature of the trait added and the pre-existing regulatory structure for any particular country. There will be uncertainty, delay and variance, but we can be fairly certain there will be no global standard soon. We can also be fairly certain that if a global standard is ultimately agreed to, it will lack means of enforcement and will further complicate international trade.

The variance among genome-edited plants described above adds another layer of difficulty in defining what exactly is a ‘GMO’ (Jones, 2015, Wolf et al., 2016). Are all genome-edited crops “GMOs,” or some, or none? Do they all belong in the same category, or require disaggregation? By what criteria do we go lumping and splitting new cultivars? In the absence of demonstrated hazard, how is risk assessed differentially? If there are no traces of transgenic material or transformation, how could a regulatory regime possibly claim to be practicable? This conceptual and practical morass suggests the end of the GMO as a workable frame for regulating plant breeding (Johnson 2015).

Because the category ‘GMO’ itself is artificial, in no sense natural, or recognized by nature, its boundaries are not robust for any significant predictive purpose in agriculture. Nature does not code plants as GMOs or not GMOs – these are purely political conventions based on social mobilization and regulatory precedents. These human constructions vary over time and space. Nature does not care, and makes its own transgenic and mutagenized plants, completely indifferent to how our species codifies them (Kyndt et al 2015).

We can confidently predict that there will be significant controversy over how to classify and regulate or normalize genome-edited crops. Or what regulatory structures will be allocated authority to decide their fate in the market. Ministries of Environment and their political bases tend to lean toward precaution, Ministries of Agriculture toward permissive or promotional stances. Because CRISPR is so versatile as a platform, we expect regulation to be product  not process, based. Whatever the regulatory forum or politics in particular places or times, the legal status of CRISPR-derived products is unlikely to be consistent, generalizable or enforceable. Like the problem with transgenes in oils or processed products, traceability will present a huge hurdle.

We can less confidently predict the destabilization, perhaps disappearance, of the GMO as a regulatory construct. There is now great incoherence and inconsistency in the concept of ‘GMO,’ making it ‘practically impossible to define’ in law or biology (Johnson 2015). The dominant criterion has been cross-species transfers of genetic materials — transgenesis. Objections to the ‘GMO’ include dominance by multinational firms capable of investing resources and leaping over regulatory bars that discourage competition. Genome-editing technologies have less potential for monopoly, greater utility, broader applicability, and evidently universal applicability  —  more democratic access on a more level playing field. Transgenic technologies will wither away, and with them the ‘GMO.’