The Living Regulatory Challenges of Synthetic Biology

• Author: Gregory N. Mandel & Gary E. Marchant
• Position: Associate Dean for Research and Peter J. Liacouras Professor of Law at the Beasley School of Law, Temple University/Regents' Professor of Law
• Pages: 155-200

The Living Regulatory Challenges of Synthetic Biology Gregory N. Mandel  & Gary E. Marchant  ABSTRACT: The rapidly emerging technology of synthetic biology will place great strain upon the extant regulatory system due to three atypical characteristics of this nascent technology: (1) synthetic biology organisms can evolve; (2) traditional risk structures do not apply; and (3) the conventional regulatory focus on end-products may be a poor match for novel organisms that produce products. This Article presents one of the first assessments of the regulatory and oversight challenges produced by the beneficial application of synthetic biology, for energy, environmental, medical, and other purposes. Due to the uncertainty present at this early stage of synthetic biology development, and the practical political context, it is unlikely that the significant statutory and regulatory gaps identified herein could be cured directly. This Article recommends instead a selection of “soft law” alternatives that could more quickly provide flexible and adaptive measures to help fill regulatory gaps in a manner that allows this promising technology to develop as rapidly as possible, while still adequately guarding against risks to human health and the environment.  Gregory N. Mandel is the Associate Dean for Research and Peter J. Liacouras Professor of Law at the Beasley School of Law, Temple University.  Gary E. Marchant is Regents’ Professor of Law, Lincoln Professor of Emerging Technologies, Law & Ethics, and Faculty Director of the Center for Law, Science & Innovation at the Sandra Day O’Connor College of Law, Arizona State University. We wish to thank Katharine Vengraitis and Marisa Johns for their outstanding research support on this project. The initial research on this paper was supported by the J. Craig Venter Institute (“JCVI”), as part of its project funded by the Department of Energy (“DOE”) on synthetic biology governance, for presentation at a workshop hosted by the JCVI. The authors appreciate the support of the JCVI and the feedback from the workshop organizers and participants. A report resulting from that workshop has recently been published. See generally SARAH R. CARTER ET AL., J. CRAIG VENTER INST., SYNTHETIC BIOLOGY AND THE U.S. BIOTECHNOLOGY REGULATORY SYSTEM: CHALLENGES AND OPTIONS (2014), available at http://www.jcvi.org/cms/fileadmin/site/ research/projects/synthetic-biology-and-the-us-regulatory-system/full-report.pdf. The views in this Article are the authors’ alone and do not necessarily represent the views of the JCVI or the DOE. 156 IOWA LAW REVIEW [Vol. 100:155 INTRODUCTION ............................................................................. 157 I. SYNTHETIC BIOLOGY ..................................................................... 159 A. S YNTHETIC B IOLOGY A LGAE FOR B IOFUEL P RODUCTION ........... 163 1. Advantages of Synthetic Biology Algae for Biofuel Production ..................................................................... 163 2. Risks of Synthetic Biology Algae .................................. 167 B. S YNTHETIC B IOLOGY O RGANISMS D ESIGNED FOR C HEMICAL P RODUCTION .......................................................................... 168 1. Advantages of Synthetic Biology for Chemical Production ..................................................................... 169 2. Risks of Synthetic Biology in Chemical Production ... 170 C. S YNTHETIC B IOLOGY M ICROORGANISMS D ESIGNED FOR B IOREMEDIATION .................................................................... 170 1. Advantages of Synthetic Biology Bioremediation ....... 171 2. Synthetic Biology Bioremediation Risks ...................... 171 II. REGULATING SYNTHETIC BIOLOGY ............................................... 173 A. T HE T OXIC S UBSTANCES C ONTROL A CT ................................... 173 B. T HRESHOLD C ONCERNS : A RE S YNTHETIC B IOLOGY O RGANISMS W ITHIN TSCA’ S P URVIEW ? ...................................................... 174 1. Are Synthetic Biology Organisms “Chemical Substances”? ................................................................... 175 2. Does the EPA’s Definition of “Intergeneric” Limit Synthetic Biology Regulation? ...................................... 176 C. L IFE -C YCLE A NALYSIS OF S YNTHETIC B IOLOGY M ICROBES U NDER TSCA ..................................................................................... 178 1. Research and Development .......................................... 178 2. Pre-Commercial Notification ....................................... 180 3. Safety Testing ................................................................. 182 4. Post-Market Surveillance and Risk Management ........ 184 5. Disposal .......................................................................... 186 D. TSCA’ S O VERALL E FFECTIVENESS AND R ELEVANCE .................... 187 III. SYNTHETIC BIOLOGY REGULATION BEYOND TSCA ...................... 188 A. T HE F EDERAL I NSECTICIDE , F UNGICIDE , AND R ODENTICIDE A CT ........................................................................................ 188 B. T HE E NDANGERED S PECIES A CT ............................................... 189 C. T HE R ESOURCE C ONSERVATION AND R ECOVERY A CT ................. 191 D. T HE C OMPREHENSIVE E NVIRONMENTAL R ESPONSE , C OMPENSATION , AND L IABILITY A CT ....................................... 192 E. N ATIONAL I NSTITUTES OF H EALTH G UIDELINES ....................... 192 IV. INNOVATIVE SYNTHETIC BIOLOGY GOVERNANCE ......................... 193 CONCLUSION ................................................................................ 199 2014] REGULATORY CHALLENGES OF SYNTHETIC BIOLOGY 157 INTRODUCTION Synthetic biology is one of the fastest developing and most promising emerging technologies. 1 It will permit scientists to design living organisms unlike any found in nature and to redesign existing organisms to have enhanced or novel qualities. 2 While traditional biotechnology involves the transfer of a small amount of genetic material from one species to another, synthetic biology will permit the purposeful assembly of an entire organism. Synthetically designed organisms, it is hoped, might be put to myriad beneficial uses, including better detection and treatment of disease, the remediation of environmental pollutants, and the production of new sources of energy, medicines, and other valuable products. 3 Engineered life forms, however, also might pose risks to human health and the environment. Exactly what those hazards are and how they might be controlled cannot be fully determined in advance of the very research necessary to develop this novel science in the first instance. This Article discusses potential regulatory challenges under the existing U.S. regulatory system concerning the first synthetic biology organisms that are anticipated to be commercialized. Much of the policy and ethical commentary on synthetic biology to date has focused on biosecurity concerns associated with synthetic biology, such as the potential malevolent misuse of the technology for bioterrorism, or the possibility of accidental or intentional release of a harmful engineered organism into the community by “do it yourself” (“DIY”) synthetic biology users. 4 While these implications of synthetic biology are of great importance, our focus here is different. We address regulatory and oversight concerns and challenges, and provide recommended strategies for dealing with the potential risks to human health and the environment from the purposeful, beneficial application of synthetic biology. Private companies, universities, and other entities are fast developing numerous legitimate uses of synthetic biology, in areas such as energy production, chemical synthesis, and bioremediation. 5 These anticipated uses 1. Synthetic biology has been described as “arguably the world’s hottest and most poorly defined scientific discipline.” Paul Voosen, Synthetic Biology Comes Down to Earth , CHRON. HIGHER EDUC. (Mar. 4, 2013), http://chronicle.com/article/Synthetic-Biology-Comes-Down/137587/. 2. PRESIDENTIAL COMM’N FOR THE STUDY OF BIOETHICAL ISSUES, NEW DIRECTIONS: THE ETHICS OF SYNTHETIC BIOLOGY AND EMERGING TECHNOLOGIES 36 (2010), available at http://bio ethics.gov/ sites/default/files/PCSBI-Synthetic-Biology-Report-12.16.10_0.pdf. 3. See INT’L RISK GOVERNANCE COUNCIL, POLICY BRIEF: GUIDELINES FOR THE APPROPRIATE RISK GOVERNANCE OF SYNTHETIC BIOLOGY 18–20 (2010), available at http://irgc.org/wp-content/ uploads/2012/04/irgc_SB_final_07jan_web.pdf. 4. See, e.g. , MICHELE S. GARFINKEL ET AL., J. CRAIG VENTER INST., SYNTHETIC GENOMICS: OPTIONS FOR GOVERNANCE 11–15 (2007), available at http://www.synbiosafe.eu/uploads/pdf/ Synthetic%20Genomics%20Options%20for%20Governance.pdf; Laurie Garrett, Biology’s Brave New World: The Promise and Perils of the Synbio Revolution, 92 FOREIGN AFF. 28, 29–30 (2013). 5. Other analyses have addressed these issues from a more general and sometimes international perspective. See, e.g. , INT’L RISK GOVERNANCE COUNCIL, supra note 3; MICHAEL 158 IOWA LAW REVIEW [Vol. 100:155 do not come without risk, risk that is sometimes referred to as “bioerror” as opposed to “bioterror.” 6 To date, the capacity of the existing regulatory system to address these bioerror risks has received limited attention and investigation, particularly in the legal literature. Our analysis reveals that although the extant regulatory system is capable of sufficiently handling several aspects of these novel synthetic biology organisms, there are also a number of potentially troubling regulatory gaps. These gaps arise because synthetic biology presents particular challenges for the existing U.S. regulatory regime due to three atypical characteristics of this nascent technology: (1) synthetic biology organisms can evolve; 7 (2) the traditional assumed relationship between mass and risk may break down for synthetic...