A few weeks ago, I posted two entries having to do with the possible open-pond use of genetically modified algae for fuel or chemical production, and how such uses would be regulated by the US EPA through the use of TSCA Experimental Release Applications (TERAs). These posts were (unknowingly) quite timely, since EPA just recently (December 6, 2013) posted on their website that they had approved the first TERAs submitted for the experimental outdoor use of genetically modified algae. These are a series of applications submitted by Sapphire Energy, Inc., the well-known San Diego company that is a leader in the algae biofuels field, for open-pond testing of five intergeneric strains of the photosynthetic green algae Scenedesmus dimorphus. Sapphire submitted these TERAs on August 1, 2013, and EPA approved them on September 25, 2013, within the 60-day review period allotted under the regulations.
As I described in the earlier post, small-scale, research uses of genetically modified algae or other microorganisms in an open-pond or other minimally contained reactor would not be eligible for the “contained structure” R&D exemption under EPA’s TSCA biotechnology rules, and would instead require EPA review before the research can be conducted, through the filing of a TERA. The TERA process provides an expedited review procedure for small-scale field tests and other outdoor R&D uses of new organisms. Applicants proposing such uses must file a TERA with the EPA at least 60 days in advance of the proposed activity. The data requirements for TERAs are outlined in §§725.255 and 725.260 of the regulations, and were also summarized in my earlier post. EPA would review the submitted information and decide whether or not to approve the proposed outdoor R&D activity within 60 days, although the agency could extend the review by an additional 60 days. If EPA determines that the proposed activity does not present an unreasonable risk of injury to health or the environment, it will notify the applicant in writing that the TERA has been approved, but EPA can also approve a TERA with limitations or conditions, such as a requirement to conduct certain monitoring of the experiments.
Prior to Sapphire’s filings, there had only been 25 TERAs submitted for field use of engineered microorganisms, almost exclusively for agricultural microorganisms, or for microbes to be used for bioremediation or for detection of hazardous contaminants in soil. None of these TERAs proposed the use of GM algae or any use related to biofuels. So the Sapphire applications and approvals represent a true “first” in the industrial biotechnology regulatory world.
As mentioned above, the Sapphire TERAs proposed the testing of five different intergeneric strains of Scenedesmus dimorphus in open ponds. The stated purpose of this testing, as summarized on the EPA website, is to (1) evaluate the translatability of the genetically modified strains from the laboratory to an outdoor setting, and (2) to characterize the potential ecological impact (dispersion and invasion) of the genetically-modified microalgae. The introduced intergeneric DNA sequences include certain “metabolism genes” and a marker gene that enables detection of the microorganism from environmental samples, and different genetic regulatory sequences were used as well. Although the details of the genetic engineering have been claimed as confidential (as allowed under the regulations), it appears that the so-called metabolism genes enable or enhance the ability of the strains to synthesize the mixture of compounds Sapphire refers to as “green crude”. The field trials were proposed to be conducted at the University of California San Diego Biology Field Station (BFS) in La Jolla, CA.
Further details of the proposed testing can be seen from the non-confidential version of the TERA submission, which can be obtained from EPA’s TSCA docket office (Sapphire filed a single document describing all five strains, which EPA treated as five individual TERA applications). The intergeneric genes have been integrated into the algae chloroplast, so that the encoded proteins are expressed within that organelle. Although the identity of these genes has not been made public, the application document indicates that they are codon-optimized versions of genes identified from public databases. Although all the details of the genetic construction are claimed as confidential, it is clear from the public version of the document that Sapphire submitted a great deal of information describing and characterizing the five modified strains it will be testing. The TERA notes that the wild type (non-modified) strain of the algal species that has been modified, Scenedesmus dimorphus, has been cultivated at Sapphire’s facilities for several years, both in closed reactors and outdoor ponds, and the TERA includes data and an extensive discussion to support the company’s belief that the use of these modified organisms in open-pond reactors will not pose unreasonable risks to human health or the environment. In particular, Sapphire performed and submitted studies in both soil and water to show that the strains showed poor survival (i.e., zero or negative growth) in these environments.
As required by the regulations, the TERA also included a detailed description of the proposed outdoor experimentation and the procedures that will be followed to minimize and monitor the potential release of the organism from the test plots. In the main portion of the experiment, the five modified algal strains will be grown semi-continuously in six to eight 1,200 liter capacity “miniponds” operating with volumes of 600-800 liters. To provide secondary containment, the miniponds are located in a sand/soil berm that has been lined with a puncture-resistant liner. This is the portion of the testing to determine how well the laboratory performance of the strains (presumably for green crude production) translates to performance in the open environment. The experiment also includes a number of “trap ponds” that will be filled with tap water and nutrients that might enable algal growth, and these ponds will be monitored on a periodic basis to determine if the experimental strains have spread in detectable numbers from the miniponds. Conducting such monitoring during a small-scale outdoor field trial of a GMO is a very important way of obtaining data on the potential for environmental dispersal that will be crucial in future regulatory reviews to assess the impacts of larger-scale testing and use.
From my brief review of the TERA document, I can say that Sapphire did a really nice job in preparing the submission, documenting how they’ve created and characterized the strains, and describing in detail how the outdoor testing would be conducted and monitored. It also seems that a great deal of care has gone into the design of the experiment, knowing that they would be the first to test the waters of the TERA process and the EPA biotech regulations with genetically modified algae. There has been some reluctance within the algae community to take this first step, and some uncertainty about how the open-pond uses of modified algae would be treated under the EPA regulations, and so it is good to see that the first TERA to be submitted was prepared so thoroughly and was approved, seemingly without issue, by EPA.
As I said in my earlier post, the TERA process is well-suited to allow outdoor uses of modified microorganisms to take place under appropriate agency oversight and risk assessments. Most importantly, the TERA process allows outdoor uses of GMOs to take place in a stepwise fashion, to enable environmental risk assessment questions to be addressed with data from actual small-scale environmental use, thus facilitating subsequent risk assessments for larger-scale uses. Although there is no doubt that outdoor uses of genetically modified algae and other microorganisms will receive greater regulatory scrutiny than uses in contained manufacturing, EPA’s TERA process should allow such uses to proceed through the normal phases of scaled testing in an orderly and responsible manner. I hope that other companies and research institutions follow Sapphire’s lead, to begin to establish a track record and publicly-available data to show that modified algae can be used in the open environment without adverse environmental effects.
D. Glass Associates, Inc. is a consulting company specializing in government and regulatory affairs support for renewable fuels and industrial biotechnology. David Glass, Ph.D. is a veteran of over thirty years in the biotechnology industry, with expertise in industrial biotechnology regulatory affairs, U.S. and international renewable fuels regulation, patents, technology licensing, and market and technology assessments. Dr. Glass also serves as director of regulatory affairs for Joule Unlimited Technologies, Inc. More information on D. Glass Associates’ regulatory affairs consulting capabilities, and copies of some of Dr. Glass’s prior presentations on biofuels and biotechnology regulation, are available at www.slideshare.net/djglass99 and at www.dglassassociates.com. The views expressed in this blog are those of Dr. Glass and D. Glass Associates and do not represent the views of Joule Unlimited Technologies, Inc. or any other organization with which Dr. Glass is affiliated. Please visit our other blog, Biofuel Policy Watch.
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