Abstract:
This thesis explores biosecurity and animal well-being through the lens of synthetic biology. The main project evaluates whether current synthesis screening systems for DNA synthesis orders are able to prevent the purchase of sequences that could be assembled into potential hazards. Orders for lightly camouflaged sequences designed to conceal fragments of potentially hazardous DNA were split across 38 commercial DNA synthesis providers, with 36 providers fulfilling the orders. Several providers later said they fulfilled the order because they did not know other portions of the hazard were ordered from other companies. Laboratory validation demonstrated that sequences with similar composition were readily assembled, highlighting the importance of future policy changes that make order screening systems resilient to both split-order attacks (where a hazard is split into fragments that can each be ordered from different providers to avoid detection) and future advances in synthetic biology. Two additional projects focus on designing new mouse strains for improved well-being in captivity. One mouse design utilizes multiplexed antiviral arrays for broad-spectrum viral protection and targeted disruption of the faah gene to elevate levels of endogenous anandamides to reduce pain and anxiety. The other design uses targeted gene expression of modified mu-opioid receptors designed to produce elevated signaling in specific neuronal regions associated with reward. These designs not only demonstrate novel synthetic biology applications but also raise perhaps unsettling questions about what it means to prioritize the well-being of captive mice. Specifically, the designs probe the question of whether external interventions like housing and enrichment adequately address the negative effects of adaptations that improve the chance of survival in the wild, especially when it may be possible to fine-tune or remove adaptations that cause mice suffering in captivity. This thesis balances technical descriptions with a discussion of broader implications for policy, industry, and ethics.
Committee members: Professor Ed Boyden (chair), Dr. Canan Dagdeviren, and Professor Kenneth Kenneth Oye