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

155

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 & Inn ovation 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 appreciat e

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. SYNTHETIC BIOLOGY ALGAE FOR BIOFUEL PRODUCTION ........... 163

1. Advantages of Synthetic Biology Algae for Biofuel

Production ..................................................................... 163

2. Risks of Synthetic Biology Algae .................................. 167

B. SYNTHETIC BIOLOGY ORGANISMS DESIGNED FOR CHEMICAL

PRODUCTION .......................................................................... 168

1. Advantages of Synthetic Biology for Chemical

Production ..................................................................... 169

2. Risks of Synthetic Biology in Chemical Production ... 170

C. SYNTHETIC BIOLOGY MICROORGANISMS DESIGNED FOR

BIOREMEDIATION .................................................................... 170

1. Advantages of Synthetic Biology Bioremediation ....... 171

2. Synthetic Biology Bioremediation Risks ...................... 171

II. REGULATING SYNTHETIC BIOLOGY ............................................... 173

A. THE TOXIC SUBSTANCES CONTROL ACT ................................... 173

B. THRESHOLD CONCERNS: ARE SYNTHETIC BIOLOGY ORGANISMS

WITHIN TSCA’S PURVIEW? ...................................................... 174

1. Are Synthetic Biology Organisms “Chemical

Substances”? ................................................................... 175

2. Does the EPA’s Definition of “Intergeneric” Limit

Synthetic Biology Regulation? ...................................... 176

C. LIFE-CYCLE ANALYSIS OF SYNTHETIC BIOLOGY MICROBES UNDER

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 OVERALL EFFECTIVENESS AND RELEVANCE .................... 187

III. SYNTHETIC BIOLOGY REGULATION BEYOND TSCA ...................... 188

A. THE FEDERAL INSECTICIDE, FUNGICIDE, AND RODENTICIDE

ACT ........................................................................................ 188

B. THE ENDANGERED SPECIES ACT ............................................... 189

C. THE RESOURCE CONSERVATION AND RECOVERY ACT ................. 191

D. THE COMPREHENSIVE ENVIRONMENTAL RESPONSE,

COMPENSATION, AND LIABILITY ACT ....................................... 192

E. NATIONAL INSTITUTES OF HEALTH GUIDELINES ....................... 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 p oorly

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., SYN THETIC 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 GOV ERNANCE COUNCIL, supra note 3; MICHAEL