So what is the USDA’s proposal for the regulation of genetically engineered animals? In a nutshell, it proposes moving regulation of food animals that are genetically engineered for agricultural purposes such as human or animal food, fiber, and labor from FDA to USDA. This means that intentional genomic alterations in food animals would no longer be automatically and mandatorily regulated by the FDA as “drugs”. That is good news, because genetic variation between individuals cannot reasonably be considered a drug. All life on Earth is made up of genetic alterations. It is the very foundation of all selection programs, and indeed evolution itself. In some ways it is going back to the future, as APHIS oversight of agriculture and forestry products developed by modern biotechnology was envisioned in early discussions of the regulation of biotechnology.
APHIS would conduct a safety assessment of animals that have been modified or developed using genetic engineering subject to the Federal Meat Inspection Act (FMIA), and the Poultry Products Inspection Act (PPIA) with a specific eye to alterations that may increase the animal’s susceptibility to pests or diseases of livestock, including zoonotic diseases, or ability to transmit the same. The Food Safety and Inspection Service (FSIS) would also conduct a pre-slaughter food safety assessment to ensure that the slaughter and processing of certain animals modified or developed using genetic engineering would not result in a product that is adulterated or misbranded, as they do with animals produced using conventional breeding.
This is a definite improvement over the FDA approach. Period. Clearly the approach being proposed has been used in plants, and has allowed at least some genetically engineered crops to come to market, albeit mostly those developed by large biotechnology companies. However, there are still some logical inconsistencies in the proposal as it stands. And I realize that perfect is the enemy of good enough, but I can’t help but look at this from my perspective as an academic working in livestock improvement, who has seen the promise of genetic engineering wither on the vine. Regulatory evaluations have included “Alice-in-Wonderland” evaluations that include questions that have no right or wrong answer. If there is no hypothesis to test it is not possible to do a power analysis or design a sensible experiment. Studies that product developers have conducted to try to address these questions have been used by groups opposed to the technology to suggest the whatever data is provided indicates unacceptable risks as discussed here. At least the USDA proposal is seeking to identifying “plausible” risks, suggesting the need to test at least some hypothesis, rather than a fishing expedition.
First, lets look at what genomic alterations are covered. Specifically, those that are introduced into animals of the “amenable species” (cattle, sheep, goats, swine, horses, mules, other equines, fish of the order Siluriformes (catfish), chickens, turkeys, ducks, geese, guineas, ratites, and squabs) modified or developed using genetic engineering that are “intended for agricultural purposes” such as human or animal food, fiber, and labor. FDA would continue its review of amenable species modified or developed using genetic engineering intended for non-agricultural purposes, including medical and pharmaceutical purposes (other than veterinary biologics), and gene therapies; and in non-amenable species. So genomic alterations in non-food animals remain with the FDA, and so does non-agricultural genetic engineering. Sorry dog and cat people – you remain with the FDA, irrespective of the nature of your edit.
And what is “genetic engineering” in this case? It is defined to mean “techniques that use recombinant, synthesized, or amplified nucleic acids to modify or create a genome”. Note how this is a technique-based definition. Already, we have run afoul of the 1986 Coordinated Framework for Regulation of Biotechnology which states, exercise of regulatory oversight should be product-risk based…”and should not turn on the fact that an organism has been modified by a particular process or technique.”
The proposed rule goes on to clarify it would “not include conventional breeding methods such as directed breeding, artificial insemination, embryo transfer, selective breeding, cross breeding, genetic backgrounding for purposes of studding, or other practices commonly available to and employed by producers.” I have worked in animal genetics my entire career, and have not the slightest idea what “genetic backgrounding for purposes of studding” means. Seriously. NO IDEA. I am also not sure the difference between directed breeding and selective breeding, but maybe I do not get out enough.
Onwards to some other concerns, there does not seem to be any clear distinction between genome edited animals without intergeneric DNA combinations that could have been achieved using conventional breeding, albeit likely less efficiently that can be achieved using traditional approaches, and genetically engineered animals harboring an rDNA transgene. This distinction was clearly made in the SECURE revision of APHIS’ biotechnology regulations for plants; but not in this contemplated regulatory framework for animals. This seems strange.
The proposal reads “The regulatory framework that USDA is considering would be conceptually similar to the recently updated USDA regulations for the movement of organisms, notably plants, modified or developed using genetic engineering, (i.e. SECURE). However, due to the differences in experience, biology, and breeding practices of animals as compared to plants, there would be some differences between these regulatory frameworks. For example, although SECURE includes up-front exemptions from the regulations for certain types of modifications [i.e. plants without intergeneric DNA combinations that could have been achieved using conventional breeding], we envision that all amenable species modified or developed using genetic engineering and intended for agricultural purposes would be subject to permitting requirements for their import, interstate movement, or environmental release until they have undergone an expedited safety review or an animal health risk assessment and been determined not to pose an increased risk to animal health. We do seek comment on this issue.“
Well I certainly have some comment on this issue! What are the “differences in experience, biology, and breeding practices of animals as compared to plants” that make a SNP in a plant eligible for an up-front exemption from the regulations, but a SNP in an animal not? Crops naturally produce allergens, toxins, or other anti-nutritional substances, and some rare safety issues that have been associated with conventional plant breeding, such as allergens in Kiwi fruit, or high levels of solanine in potatoes. I have a hard time coming up with analogous examples from animal breeding despite intensive selection for traits of interest. So what is uniquely hazardous, or even risky, about genomic alterations that could have been achieved using conventional breeding in animals, but not plants, that makes cisgenics, SNPs and deletions ineligible for an up-front exemption from the regulations? At the end of the day – both kingdoms provide food, and different regulations for the different kingdoms makes little scientific sense.
I have many more specific comments on this proposal, but they all will come back to this basic point. Regulation should be proportionate to risk, and agnostic to method. If regulations are being proposed that mandate a more onerous pathway for identical products produced one way as compared to another, or differ between kingdoms, or require additional testing only of products produced using one method, then they will tilt the scale to the less onerous pathway. This may not always be in the best interests of society. For over 30 years now animal geneticists have had little ability to employ genetic engineering in animal breeding programs. This comes with an opportunity cost as detailed here.
In contemplating an improved regulatory approach for genetically modified animals, perhaps it is time to ditch the process-based trigger which requires additional regulatory scrutiny of plants and animals that could have been achieved using conventional breeding, and rather take the advice of the 1996 Coordinated Framework, and that is that regulatory review should be confined to organisms deliberately formed to contain an intergeneric combination of genetic material from sources in different genera (aka foreign or transgenic DNA that could plausibly produce a toxin or an allergen), and that oversight should be exercised only where the risk posed by the introduction is unreasonable, that is, when the value of the reduction in risk obtained by additional regulatory oversight is greater than the cost thereby imposed.