From the earliest days of recombinant DNA technology, there has been worry in the policy community and among the public about the release and consumption of genetically engineered (GE) crops, especially crops for human consumption. To address these concerns, GE food crops face multiple regulatory requirements before they can come to market.
Any plant that has received genetic material from an organism deemed a “plant pest” cannot be grown outside of the laboratory without a license from the U.S. Department of Agriculture under the Plant Protection Act. Under this law “plant pests” include viruses and bacteria (including the popular plant genetic vector Agrobacterium); because bacteria and viruses are widely used as genetic vectors, sources of structural genes and sources of regulatory elements, the majority of genetically engineered crops fall under this category.
In addition, any crop that produces compounds that are toxic to insects, weeds, fungi, or other kinds of pests must be licensed by the Environmental Protection Agency under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). This category includes widely grown crops that express the natural insecticide from Bacillus thuringensis, popularly known as “Bt.” Finally, any food crop that is engineered to contain new proteins or other biochemicals might be regulated under the Food, Drug, and Cosmetic Act (FDCA) as a new food additive.
Clearly developers of GE crops face many regulatory requirements. However, the USDA has taken the position in many cases that GE crops that have been modified only by deletions, and which contain no genetic material from other species, are not regulated under the Plant Protection Act. As a result, no permit is necessary from the USDA for field trials. For the first time the USDA has reached the same conclusion about a deletion mutant produced with the CRISPR/Cas9 system.
Researchers at The Pennsylvania State University have developed a white button mushroom (Agaricus bisporus) with a series of small deletions in its polyphenol oxidase gene (hereinafter “Penn State Mushroom”). A. bisporus is the most common species of mushroom sold in American supermarkets. The deletions in the Penn State Mushroom prevent the mushroom from browning when it is damaged. As a result, it can be harvested mechanically and is more resistant to shipping than the parental strain.
On October 30, 2015, the inventor of the Penn State Mushroom, Dr. Yinong Yang, wrote to the USDA requesting an opinion as to whether the Penn State Mushroom is a regulated GE crop. The Yang letter explained that, although a plasmid construct carrying Cas9 guidance RNA was used, the genetic material in the plasmid was only transiently expressed, and no foreign genetic material was present in the resultant mushrooms. In April of 2016, the USDA wrote back, concluding that the Penn State Mushroom does not require licensing under the Plant Protection Act. The USDA based this conclusion on the fact that although the plasmid contained genetic material from “plant pests” (bacteria and viruses), the mushroom itself contains no plant pest material and no foreign genetic material.
This milestone decision appears to confirm that the USDA believes that GE crops that contain only deletions pose fewer safety risks than do GE crops with other kinds of genetic alterations (especially those containing foreign genes). For agricultural biotechnology companies, this means that pure deletion mutants are a better business bet than other kinds of GE crops. Apart from regulatory concerns, the CRISPR/Cas9 system now allows the production of highly accurate deletion mutants in eukaryotic organisms. The potential ability to skip the regulatory process under the Plant Protection Act means deletion mutants can be brought to market more quickly, and at lower cost, than other GE crops. It does not remove other regulatory requirements (such as those under FIFRA and FDCA mentioned above), but as a matter of actual practice deletion mutants will not often contain new food additives or pesticides.
However, one could imagine scenarios in which a deletion mutant is still regulated under FIFRA and FDCA. This would not be true in an example like the Penn State Mushroom, in which a protein is not expressed due to the deletion. However, take another case, in which a region encoding a repressor protein is deleted, which results in overexpression of a second protein. In such a case the increased amount of the second protein might make the plant toxic to pests, in which case it would be a candidate for regulation under FIFRA. In another hypothetical case, only a portion of a protein-encoding region is deleted, resulting in a truncated protein. A truncated protein could have different properties than the full-length protein, so a truncated protein might be a candidate for regulation as a new food additive under the FDCA.
The USDA’s position on the Penn State Mushroom is further progress toward developing consistent and predictable rules in the regulation of GE crops, a relatively young legal area marked mostly by case-by-case decisions.