As noted in a previous entry in this blog, the use of certain genetically modified plants as feedstocks for biofuel production may be subject to regulations promulgated by the U.S. Department of Agriculture (USDA), that have been used for over two decades to regulate the agricultural biotechnology industry. In this posting I will briefly describe the history and rationale of this rule, and describe its provisions and requirements and how it may affect the development of transgenic plants as improved biofuel feedstocks. The next entry in the blog will discuss the growing number of transgenic plant varieties intended for biofuel use that have already been submitted for USDA review under this rule.
USDA’s biotechnology regulations, found in 7 CFR Part 340 of the Code of Federal Regulations, have been the major U.S. government rules that have covered uses of transgenic plants in agriculture and more recently the increasing interest in using plants for other industrial purposes, such as production of pharmaceuticals, industrial products, and phytoremediation. These rules were put into place in 1987 as an immediate outgrowth of the government’s “Coordinated Framework” for biotechnology regulation, which had its genesis in the early to mid 1980s as the Reagan Administration began to grapple with developing a suitable approach to regulating the commercial applications of biotechnology, a question which became wrapped up in political and public controversy. The government eventually decided to have biotechnology governed by existing laws and regulations to the greatest extent possible, and published its strategy for doing so in a Coordinated Framework document issued on the last day of 1984 and finalized in June 1986. In this Framework, USDA proposed to use existing statutory authority under a law then known as the Plant Pest Act to regulate certain genetically engineered plants intended for field testing and eventual commercial use in the open environment, to assess the potential environmental effects of such uses. The basis for this rule was the possibility (however remote) that such engineered plants might pose a plant pest risk. New regulations would be needed for this purpose – at that time, USDA maintained regulations governing the importation and interstate movement of specific microorganisms, fungi and plants known to be plant pests, but those regulations could not be used for transgenic plants that were merely considered “potential” plant pests, and so new rules were needed.
In the June 1986 Framework document, USDA published proposed rules under the Plant Pest Act that would allow it to regulate outdoor uses of transgenic plants. These regulations were finalized in June 1987 in essentially the same form as the proposed rule (52 Federal Register 22892- 22915). Technically, these regulations do not cover all genetically engineered plants, and instead cover only those plants engineered to contain nucleic acid sequences from certain genera that contain species that were considered to be potential plant pests. The regulations included a fairly broad list of such genera, and this had the practical effect of causing most transgenic plants to be captured by the regulations: this was because the genus Agrobacterium was on the list, and in practice, DNA sequences from Agrobacterium tumefaciens were almost universally used in plant transformation procedures, and the presence of A. tumefaciens DNA in the resulting plant would often be enough to subject the transgenic plant to regulation under this rule.
The regulations were to be administered by the division of USDA known as the Animal and Plant Health Inspection Service (APHIS), which already had responsibility for the existing plant pest regulations and other rules designed to protect plant or animal health. Today, the agency’s biotechnology program is handled through a dedicated office within APHIS called Biotechnology Regulatory Services (BRS). Under the original 1987 version of these rules, permits were required for almost all proposed field uses of genetically engineered plants. For those transgenic plants falling under the regulations, the rule required that permit applications be submitted 120 days before any proposed outdoor use. Applicants for these permits were required to submit a detailed description of the modifications made to the plant, data characterizing the stability of these changes, and a description of the proposed field test and the procedures to be used to confine the plants in the test plot, and submitters also had to assess potential environmental effects, such as the potential for the plant to gain weedy characteristics or the chances of the transgene outcrossing to related wild species (summarized in the Table below). Special requirements may also apply for industrial or pharmaceutical uses of transgenic plants, particularly that the field test must be separated by a “substantial distance” from any sexually compatible crops, and that a 50-foot fallow zone must surround the plot. Under the permit system, specific approval must be obtained for each desired field site, as well as for each new planting, although a single permit can cover multiple field sites, and recently USDA has begun issuing multiple-year permits for field tests involving perennial plant species.
Issues Addressed in USDA’s Regulation of Transgenic Plants
- Stability of vector and introduced genes.
- Presence of infectious, pathogenic, toxic or deleterious functions encoded by introduced DNA.
- Reproduction and pollen/seed dispersal mechanisms.
- Ability to outcross with related species (particularly wild relatives).
- Potential weediness (ability to compete, survive and spread in the environment).
- Need for physical isolation from sexually compatible species.
- Standard Operating Procedures for planting, maintaining and monitoring plants.
- Post-termination scouting for volunteer plants (i.e. progeny of the transgenic plant that might arise in growing seasons after the termination of the test).
After the agency gained experience with the issues posed by research field tests of transgenic plants, the regulations were substantially relaxed, first in 1993 (58 Federal Register 17044-17059), and then again in 1997 (62 Federal Register 23945-23958), with the creation of a much simpler notification process for those plant species deemed to have low potential risks. Under the current version of the regulations, transgenic varieties of most common agricultural crops and other familiar plant species can be used in research field tests simply upon 30 days advance notice to APHIS, and the submission of only minimal information about the modified plants and the proposed field use. Only less-familiar uses of transgenic plants are now required to undergo the longer permitting process, which is still administered much as it was under the original regulations. In addition, the revised regulations provided a procedure under which applicants can petition to have specific transgenic plant varieties “delisted” following several years of safe field tests, to proceed to commercial use and sale without the need for yearly permits. This is the procedure that has been successfully used by agbiotech and seed companies to have their transgenic seeds cleared for commercial sale and unlimited use by farmers, and the many varieties of transgenic seeds now on the market and grown throughout the United States have undergone this “delisting” procedure.
These regulations have been extremely successful in fostering the growth of the U.S. agricultural biotechnology industry, and in allowing field testing and ultimately commercial use of transgenic plants to take place under an orderly, reasonable system in which potential environmental effects are reviewed and assessed. Through the date of this writing (May 2010), APHIS had authorized approximately 15,000 field releases of transgenic plants under permits or notifications, encompassing 175 different species. The great majority (about 90%) of the field releases have been under notifications rather than permits. To date, APHIS has approved 78 delisting petitions for commercialization of engineered crop varieties, and although many of these have proceeded swiftly to approval, several recent applicants have encountered significant delays and/or had to deal with specific questions of the environmental impact of the transgenic plant.
In 2003, USDA began requiring that certain proposed outdoor uses of transgenic plants be reviewed through the permit process rather than through the notification procedure. Covered by this policy change were plants engineered to produce pharmaceutical products, plants engineered to produce industrial enzymes or other specialty chemicals; and transgenic plants for use in phytoremediation. Although not explicitly stated, the outdoor growth of transgenic plants as biofuel feedstocks would very likely fall under this requirement, although some small-scale research uses of transgenic varieties of certain common crop plants or other familiar species might be allowed to go forward under notifications. Therefore, companies and academic research groups developing transgenic plants as improved biofuel feedstocks should anticipate that they will likely need APHIS permits even for small-scale field testing, and that they will need to go through the delisting process to certify the transgenic variety for commercial sale. As of this writing in May 2010, APHIS had issued about 75 permits for field tests of plants either expressing pharmaceutical or industrial products or engineered for improved phytoremediation. A number of permits have been issued for transgenic plants designed as improved biofuel feedstocks, and these will be discussed in the next entry in this blog.
For the past several years, APHIS has been developing plans to update and revise the biotechnology regulations, with the goal (according to the agency) of better positioning USDA to address new challenges, as well as meet current needs in evaluating and addressing the plant pest or noxious weed risks associated with the importation, interstate movement, and field release of certain engineered organisms. Another driving force for this change was Congressional passage in 2000 of a new law, the Plant Protection Act, that incorporated and combined the old Plant Pest Act and another longstanding law, the Noxious Weed Act, so that the USDA biotech regulations now drew their authority from the new 2000 law, which had a broader scope than the original Plant Pest Act. APHIS issued a Draft Environmental Impact Statement in July 2007 which summarized issues it was considering as it contemplated regulatory revisions, along with some specific options for such revisions. This Draft EIS was opened for public comment, and as a result, APHIS issued Proposed Regulations in October 2008, and these proposed rules included a multi-tiered permit system and the elimination of the notification procedure (the idea would be that the low-risk tests now conducted under notifications would require permits, but would qualify for the least-stringent tier of permits). USDA received comments from more than 15,000 people during the original 45-day public comment period, and the agency reopened the comment period in January 2009 to allow further opportunity for public input. The comment period was later extended until June 2009, and APHIS has also held a number of public meetings and workshops during this time. The agency has said nothing further since mid-2009, and a timetable for issuing a new Final Regulation is not known (see link above for current status of the proposed rule). Although the details that will emerge in final regulations are still unclear, it is likely that uses of transgenic plants for industrial purposes such as biofuel production would continue to require project-by-project permits, and in fact under the 2008 proposed rules, APHIS suggested that all industrial uses would likely qualify for one of the permit tiers requiring a greater degree of oversight.
Although the need for USDA permits can be seen as one more hurdle to be surmounted in the development of improved biofuel feedstocks, in reality the biotech regulation poses only a minor regulatory barrier. Agbiotech and seed companies have been living under this regulation for over 20 years, and they have found USDA APHIS easy to deal with, and that the agency’s Biotechnology Regulatory Services branch applies sound scientific principles to its review of notifications and permit applications. Many observers consider the USDA regulatory regime to be one of the reasons why the agricultural biotechnology industry has ultimately been successful in introducing into U.S. agricultural markets transgenic seeds for improved varieties of many important crop species, in that the regulations provided a predictable, scientifically-sound path to approvals of field tests and commercial use of engineered plants.
D. Glass Associates, Inc. is a consulting company specializing in several fields of biotechnology. David Glass, Ph.D. is a veteran of nearly thirty years in the biotech industry, with expertise in industrial biotechnology regulatory affairs, patents, technology licensing, and market and technology assessments. This blog provides back-up and expanded content to complement a presentation Dr. Glass made at the EUEC 2010 conference on February 2, 2010 entitled “Prospects for the Use of Genetic Engineering in Biofuel Production.” The slides from that presentation, along with more information on D. Glass Associates’ regulatory affairs consulting capabilities, are available at www.slideshare.net/djglass99 or at www.dglassassociates.com.