Owen Grayson Hosseinzadeh, Law Clerk in San Diego, contributed to the drafting of this post.
On March 7, 2022, the Center for Veterinary Medicine (CVM) of the U.S. Food and Drug Administration (FDA) determined that Acceligen Inc.’s genome-edited, heat-tolerant cattle, pose a “low risk to humans, animals, the food supply, and the environment.” This is the first such determination for a genetically engineered food-use animal and will allow the company to bypass many of the usual premarket approval requirements.
These cattle, called PRLR-SLICK cattle, produce a short and slick hair coat due to a modification made to the prolactin receptor (PRLR) gene. This slick hair coat phenotype gives cattle the ability to regulate body temperature more effectively. This is important for raising cattle in tropical climates and might mitigate the predicted negative effects on livestock productivity associated with climate change.
This intentional genomic alteration (IGA) was accomplished using CRISPR-Cas9 gene editing technology on in vitro fertilized calf embryos. Specifically, the IGA introduces a premature stop codon into the PRLR gene, and thereby truncates the encoded protein. IGAs like the alteration made to the PRLR gene in Acceligen’s cattle are intended to “affect the structure or function” of the altered animal, so FDA regulates them under its animal drug framework.
Marketing an animal drug typically requires premarket approval, which entails a lengthy New Animal Drug Application (NADA) process through which FDA can evaluate the animal drug for efficacy, safety to the animal, and safety to the consumer. The only other FDA-approved food-use animals—Revivicor’s GalSafe pigs (2020) and the AquaBounty AquAdvantage salmon (2017)—went through the full NADA determination process.
FDA discussed its intent to exercise enforcement discretion with respect to NADA requirements for IGA-containing animals as early as 2009, in guidance that has been updated several times, most recently in its 2017 Guidance #187, “Regulation of Intentionally Altered Genomic DNA in Animals.” But this is the first time that such enforcement discretion has been applied to an animal intended for food production.
When FDA exercises its enforcement discretion over the NADA requirements, it does not also conduct a National Environmental Policy Act (NEPA) review, which can add significant costs and time to the application process. FDA instead considers the potential environmental risks when determining whether to exercise enforcement discretion.
FDA examined four categories of risk factors in its risk assessment and concluded that PRLR-SLICK cattle pose a low risk to people, animals, the food supply, and the environment:
1. Molecular characterization
- PRLR-SLICK cattle have an IGA that mimics genomic sequences found in conventionally raised cattle
- Analyses of the genomic data found evidence of unintended mutations, but based on their types and locations, they are not expected to result in changes to protein expression
- PRLR-SLICK cattle have the same phenotype (i.e., short, slick hair coat) as conventionally raised cattle with naturally occurring slick mutations
- PRLR-SLICK cattle appear healthy based on visual observations and animal health records
- Conventionally raised cattle with the slick phenotype are routinely consumed as human food
- There is no expected change in the compositional or nutritional content of the edible tissues
- The slick phenotype is a well-established trait in several breeds of conventionally raised domestic cattle in the United States
- The likelihood of escape and establishment of PRLR-SLICK cattle in the U.S. environment is low due to the ability to rapidly recover escaped animals and the lack of feral cattle populations in the United States
The “low-risk” decision is limited to products (e.g., live cattle, semen, embryos, and meat) derived from the existing two cattle reviewed by FDA and their progeny. FDA also intends to treat facilities or farms engaged in standard agricultural practices for PRLR-SLICK cattle the same as facilities or farms that are engaged in these practices for cattle without IGAs.
According to FDA’s press release, meat products from PRLR-SLICK cattle are expected to be available for purchase by general consumers as early as 2024. PRLR-SLICK cattle meat and most other food products in which the cattle’s carcass is the predominant ingredient would not be subject to mandatory labeling under U.S. Department of Agriculture’s National Bioengineered Food Disclosure Standard.