Difference between revisions of "Team:Virginia/Policy Proposal"

Summary

This proposal was developed to encourage discussion regarding the state of synthetic biology regulations in the United States. More specifically, this proposal discusses the regulation of biological containment devices that are exposed to ecological settings. This issue is under-discussed and relatively unknown. Our team surveyed current iGEM teams, and found that even in this group, who is very familiar with synthetic biology, over one third of the respondents did not know what biological containment was.

Revisions to this document were informed by discussions with experts in the field. These experts include Dr. Jessica Tucker from the NIH, Deputy Commissioner Charles Green from Virginia’s Department of Agriculture and Consumer Services, and Branch Chief Alan Pearson from APHIS. Please see our Wiki page for more details on these conversations.

Introduction

This proposal describes rules and regulations regarding the testing, application, monitoring, and termination of biological containment devices. As new applications emerge, it will become essential to have regulation regarding biological containment devices in place to facilitate the smooth and safe introduction of novel technologies. For the purpose of these guidelines, a biological containment device refers to a biological system that utilizes cellular frameworks to establish control over an organism and where it can survive in an environmental setting. Biological containment devices will henceforth be referred to as devices.

No current regulation exists for devices in synthetic biology systems in ecological settings. While devices are not yet regulated, synthetically modified organisms are incompletely regulated, largely by the US Environmental Protection Agency (EPA), the US Department of Agriculture’s Animal and Plant Health Inspection Service (USDA/APHIS) and the US Food and Drug Administration (FDA). Among these agencies, different authorities regulate the development and the deployment of synthetically modified organisms, which presents a challenge in selecting one agency to regulate biological containment devices.1 We suggest to expand the authority of one of these agencies to encompass the regulation of devices.

The NIH, in its 2016 Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, hereinafter referred to as the NIH Guidelines, describes the guidelines for laboratory research involving synthetic genetic material.2 In contrast, there are three primary regulatory agencies for synthetic biology products: the EPA, USDA/APHIS and the FDA. A 2014 report on Synthetic Biology and the US Biotechnology Regulatory System by the J. Craig Venter Institute cites that these agencies have an adequate level of authority to address most, but not all, environmental, health and safety concerns with regard to synthetic biology.3 Because APHIS’ authority extends over engineered plants and the FDA’s authority extends over foods and drugs, the EPA is the most appropriate of these three agencies to make regulatory decisions based on risks posed by genetically modified microbes to health and safety of humans, animals and ecosystems. This proposal goes beyond the current scope of the EPA, but if adopted, could enhance the current regulatory model.

In this document, all references to the agency adopting these recommendations are marked in italics.

Developer Submission

A developer must include the following items with every device submission:

• Chassis selections
• Environmental selections
• Genomic Protection Model (GPM): A GPM is a document that lists residue-specific mutations that render a device ineffective. The GPM will include all mutations that are experimentally confirmed.
• Implementation protocol
• Termination protocol
• Submission of devices is allowed at the beginning of each calendar year. After a device is submitted to the agency, it will undergo a series of confirmatory tests to determine its potential success and application.

Submission of devices is allowed at the beginning of each calendar year. After a device is submitted to the agency, it will undergo a series of confirmatory tests to determine its potential success and application.

Initial Testing of a Device

Initial testing will include an escapee propagation assay wherein the system using the device is grown within a standard laboratory environment. As prompted by the containment boundaries of the device, the rate of cell death will be recorded and used to demonstrate the viability of the device. If the device fails to prevent escapees, it will be terminated and the developer will be notified. If the device prevents escapees, it will continue to GPM testing.

A verification test will check the validity of the GPM. The agency will test the GPM by applying mutagenic stressors to the system to simulate mutagenic drift. For example, in bacteria, a fluctuation test in reference to the agent conferring containment will be conducted. Gene sequencing will be performed on multiple surviving units. Comparison between the sequences and the residues of interest in the GPM will confirm or refute the GPM documentation.

The GPM Threshold will be established by the agency and will serve as a comparative model for future tests. It will serve as an indicator of device failure prior to inactivation of the device. For example: if a device has three residues that, when all mutated, deactivate the biological containment mechanism, we recommend that the GPM Threshold is set at two out of three mutations. Devices that have two critical mutations will be terminated. This measure ensures that the device is still functioning when terminated and prevents escapees. A device’s GPM Threshold will be determined on an individual basis.

Upon GPM verification, the device proceeds to primary rating tests.

Rating a Device

A device’s rating is split into three categories: Revertant Susceptibility, Environmental Applicability, and Chassis Applicability. Once a device has been tested and rated, it will be listed on a centralized online catalog run by the agency. This catalog will include all necessary information about a device including the implementation and termination protocols, the GPM and GPM Threshold, and ratings. Each device’s information will be collected in a concise document, similar to the commonly used Materials Safety Data Sheet (MSDS).

Rating: Revertant Susceptibility

The Revertant Susceptibility rating measures the security of a GPM Threshold and designates the level of post-application monitoring a device will receive.

This rating is split into two classes:

• The Class A rating is granted to devices that are unlikely to develop revertants, and are less likely to require termination. Class A devices are best used in low turnover applications. One possible application that would suit this classification is a plot of GMO crops. This Class receives low level post-application monitoring.
• The Class B rating is granted to devices that have a significant revertant likelihood and are therefore more likely to require termination. Class B devices are best used in high turnover applications where a population will be refreshed and recycled in quick succession. One possible application that would suit this classification is a microbial approach to oil spill remediation. This Class receives a high level of post-application monitoring.

For example, the device mentioned in Section 3 that requires three mutations to deactivate would be a Class B device and require frequent monitoring. In contrast, a device requiring one hundred mutations would be a Class A device and require less monitoring. The agency will be responsible for quantifying the distinction between Class A and Class B designations.

Rating: Environmental Applicability

The Environmental Applicability rating is based on the developer’s environmental selection and subsequent verification testing. The verification testing is performed under specified environmental conditions which vary depending on the recommended class. Devices will be judged upon two criteria: cellular escapee propagation within specified environmental conditions; and genetic escapee propagation, which is measured by comparing genetic material from the chassis in testing to the GPM Threshold. The device fails if it does not prevent escapees or if mutation levels exceed the GPM Threshold. Passing these tests awards a specific class designation to a device. Devices can acquire multiple class designations, but each class must be individually tested for.

The possible classes are as follows:

• Freshwater
• Tropical Rainforest
• Savanna
• Desert
• Temperate
• Deciduous
• Coniferous
• Tundra
• Shallow ocean
• Deep ocean water
• Deep ocean surface
• Urban

Note: If implemented, a similar policy would require details about the migratory capability, pH, humidity, temperature range, UV exposure, native species, and other properties of each environment.

Rating: Chassis Applicability

The Chassis Applicability rating serves to designate possible chassis in which the device can be used. Verification testing is performed on the device in the chassis recommended by the developer’s data. For each chassis, the device is subjected to verification testing. Measurements will be taken in terms of both escapee propagation and the GPM, as described for the Environmental Applicability rating.

All tested chassis will be clearly labeled in a device’s Chassis Applicability class designation.

Acquiring a Device

Organizations adhering to correct procedures can acquire any device from the catalog that matches their intended chassis and ecological setting. An organization must apply to receive the device. The application must address the need for a device: any system that has been approved to interact with an ecological setting by the appropriate agency will be acceptable. The application must also demonstrate that the intended use of the device matches the rating of the requested device.