Application of Software Engineering Principles to Synthetic Biology and Emerging Regulatory Concerns

As the science of synthetic biology matures, engineers have begun to deliver real-world applications which are the beginning of what could radically transform our lives. Recent progress indicates synthetic biology will produce transformative breakthroughs. Examples include: 1) synthesizing chemicals for medicines which are expensive and difficult to produce; 2) producing protein alternatives; 3) altering genomes to combat deadly diseases; 4) killing antibiotic-resistant pathogens; and 5) speeding up vaccine production. Although synthetic biology promises great benefits, many stakeholders have expressed concerns over safety and security risks from creating biological behavior never seen before in nature. As with any emerging technology, there is the risk of malicious use known as the dual-use problem. The technology is becoming democratized and de-skilled, and people in do-it-yourself communities can tinker with genetic code, similar to how programming has become prevalent through the ease of using macros in spreadsheets. While easy to program, it may be non-trivial to validate novel biological behavior. Nevertheless, we must be able to certify synthetically engineered organisms behave as expected, and be confident they will not harm natural life or the environment. Synthetic biology is an interdisciplinary engineering domain, and interdisciplinary problems require interdisciplinary solutions. Using an interdisciplinary approach, this dissertation lays foundations for verifying, validating, and certifying safety and security of synthetic biology applications through traditional software engineering concepts about safety, security, and reliability of systems. These techniques can help stakeholders navigate what is currently a confusing regulatory process. The contributions of this dissertation are: 1) creation of domain-specific patterns to help synthetic biologists develop assurance cases using evidence and arguments to validate safety and security of designs; 2) application of software product lines and feature models to the modular DNA parts of synthetic biology commonly known as BioBricks, making it easier to find safety features during design; 3) a technique for analyzing DNA sequence motifs to help characterize proteins as toxins or non-toxins; 4) a legal investigation regarding what makes regulating synthetic biology challenging; and 5) a repeatable workflow for leveraging safety and security artifacts to develop assurance cases for synthetic biology systems. Advisers: Myra B. Cohen and Brittany A. Dunca

A ROADMAP TO SAFE AND RELIABLE ENGINEERED BIOLOGICAL NANO-COMMUNICATION NETWORKS

Synthetic biology has the potential to benefit society with novel applications that can improve soil quality, produce biofuels, grow customized biological tissue, and perform intelligent drug delivery, among many other possibilities. Engineers are creating techniques to program living cells, inserting new logic, and leveraging cell-to-cell communication, which result in changes to a cell\u27s core functionality. Using these techniques, we can now create synthetic biological organisms (SBOs) with entirely new (potentially unseen) behaviors, which, similar to silicon devices, can sense, actuate, perform computation, and interconnect with other networks at the nanoscale level. SBOs are programmable evolving entities, and can be likened to self-adaptive programs that read inputs, process them, and produce outputs, reacting differently to different environmental conditions. With the increasing complexity of potential programs for SBOs, as in any new technology, there will be both beneficial as well as malicious uses. Although there has been much discussion about the potential safety and security risks of SBOs, and some research on predicting whether engineered life will be harmful, there has been little research on how to validate or verify safety of SBOs. In this thesis, we lay a foundation for validating and verifying safety for SBOs. We first present two case studies where we give insight into the difficulties of determining whether novel SBOs will be harmful given the vast combinatorial search space available for their engineering. Second, we explain how the current U.S. regulatory environment is fragmented with respect to the multiple dimensions of SBOs. Finally, we present a way forward for formalizing the architecture of SBOs and present a case study to show how we might utilize assurance cases to reason about SBO safety. Advisors: Myra Cohen and Massimiliano Pierobo

Application of Software Engineering Principles to Synthetic Biology and Emerging Regulatory Concerns

As the science of synthetic biology matures, engineers have begun to deliver real-world applications which are the beginning of what could radically transform our lives. Recent progress indicates synthetic biology will produce transformative breakthroughs. Examples include: 1) synthesizing chemicals for medicines which are expensive and difficult to produce; 2) producing protein alternatives; 3) altering genomes to combat deadly diseases; 4) killing antibiotic-resistant pathogens; and 5) speeding up vaccine production. Although synthetic biology promises great benefits, many stakeholders have expressed concerns over safety and security risks from creating biological behavior never seen before in nature. As with any emerging technology, there is the risk of malicious use known as the dual-use problem. The technology is becoming democratized and de-skilled, and people in do-it-yourself communities can tinker with genetic code, similar to how programming has become prevalent through the ease of using macros in spreadsheets. While easy to program, it may be non-trivial to validate novel biological behavior. Nevertheless, we must be able to certify synthetically engineered organisms behave as expected, and be confident they will not harm natural life or the environment. Synthetic biology is an interdisciplinary engineering domain, and interdisciplinary problems require interdisciplinary solutions. Using an interdisciplinary approach, this dissertation lays foundations for verifying, validating, and certifying safety and security of synthetic biology applications through traditional software engineering concepts about safety, security, and reliability of systems. These techniques can help stakeholders navigate what is currently a confusing regulatory process. The contributions of this dissertation are: 1) creation of domain-specific patterns to help synthetic biologists develop assurance cases using evidence and arguments to validate safety and security of designs; 2) application of software product lines and feature models to the modular DNA parts of synthetic biology commonly known as BioBricks, making it easier to find safety features during design; 3) a technique for analyzing DNA sequence motifs to help characterize proteins as toxins or non-toxins; 4) a legal investigation regarding what makes regulating synthetic biology challenging; and 5) a repeatable workflow for leveraging safety and security artifacts to develop assurance cases for synthetic biology systems. Advisers: Myra B. Cohen and Brittany A. Dunca

Application of Software Engineering Principles to Synthetic Biology and Emerging Regulatory Concerns

As the science of synthetic biology matures, engineers have begun to deliver real-world applications which are the beginning of what could radically transform our lives. Recent progress indicates synthetic biology will produce transformative breakthroughs. Examples include: 1) synthesizing chemicals for medicines which are expensive and difficult to produce; 2) producing protein alternatives; 3) altering genomes to combat deadly diseases; 4) killing antibiotic-resistant pathogens; and 5) speeding up vaccine production. Although synthetic biology promises great benefits, many stakeholders have expressed concerns over safety and security risks from creating biological behavior never seen before in nature. As with any emerging technology, there is the risk of malicious use known as the dual-use problem. The technology is becoming democratized and de-skilled, and people in do-it-yourself communities can tinker with genetic code, similar to how programming has become prevalent through the ease of using macros in spreadsheets. While easy to program, it may be non-trivial to validate novel biological behavior. Nevertheless, we must be able to certify synthetically engineered organisms behave as expected, and be confident they will not harm natural life or the environment. Synthetic biology is an interdisciplinary engineering domain, and interdisciplinary problems require interdisciplinary solutions. Using an interdisciplinary approach, this dissertation lays foundations for verifying, validating, and certifying safety and security of synthetic biology applications through traditional software engineering concepts about safety, security, and reliability of systems. These techniques can help stakeholders navigate what is currently a confusing regulatory process. The contributions of this dissertation are: 1) creation of domain-specific patterns to help synthetic biologists develop assurance cases using evidence and arguments to validate safety and security of designs; 2) application of software product lines and feature models to the modular DNA parts of synthetic biology commonly known as BioBricks, making it easier to find safety features during design; 3) a technique for analyzing DNA sequence motifs to help characterize proteins as toxins or non-toxins; 4) a legal investigation regarding what makes regulating synthetic biology challenging; and 5) a repeatable workflow for leveraging safety and security artifacts to develop assurance cases for synthetic biology systems

Application of Software Engineering Principles to Synthetic Biology and Emerging Regulatory Concerns

As the science of synthetic biology matures, engineers have begun to deliver real-world applications which are the beginning of what could radically transform our lives. Recent progress indicates synthetic biology will produce transformative breakthroughs. Examples include: 1) synthesizing chemicals for medicines which are expensive and difficult to produce; 2) producing protein alternatives; 3) altering genomes to combat deadly diseases; 4) killing antibiotic-resistant pathogens; and 5) speeding up vaccine production. Although synthetic biology promises great benefits, many stakeholders have expressed concerns over safety and security risks from creating biological behavior never seen before in nature. As with any emerging technology, there is the risk of malicious use known as the dual-use problem. The technology is becoming democratized and de-skilled, and people in do-it-yourself communities can tinker with genetic code, similar to how programming has become prevalent through the ease of using macros in spreadsheets. While easy to program, it may be non-trivial to validate novel biological behavior. Nevertheless, we must be able to certify synthetically engineered organisms behave as expected, and be confident they will not harm natural life or the environment. Synthetic biology is an interdisciplinary engineering domain, and interdisciplinary problems require interdisciplinary solutions. Using an interdisciplinary approach, this dissertation lays foundations for verifying, validating, and certifying safety and security of synthetic biology applications through traditional software engineering concepts about safety, security, and reliability of systems. These techniques can help stakeholders navigate what is currently a confusing regulatory process. The contributions of this dissertation are: 1) creation of domain-specific patterns to help synthetic biologists develop assurance cases using evidence and arguments to validate safety and security of designs; 2) application of software product lines and feature models to the modular DNA parts of synthetic biology commonly known as BioBricks, making it easier to find safety features during design; 3) a technique for analyzing DNA sequence motifs to help characterize proteins as toxins or non-toxins; 4) a legal investigation regarding what makes regulating synthetic biology challenging; and 5) a repeatable workflow for leveraging safety and security artifacts to develop assurance cases for synthetic biology systems