Week 1 HW: Principles and Practices
1. First, describe a biological engineering application or tool you want to develop and why.
I want to develop a plant stress-responsive synthetic gene circuit in a chloroplast-derived cell-free system that detects stress signals like pathogen RNA or heavy metals and produces a visible reporter output. This tool enables rapid, safe prototyping of plant gene circuits and allows assessment of biosecurity risks, such as misfires or misuse, without using live plants. The primary motivation for this project is to build upon and extend the work of the 2021 iGEM Marburg team, leveraging their foundational advances to develop more responsive and secure plant synthetic biology tools.
2. Next, describe one or more governance/policy goals related to ensuring that this application or tool contributes to an “ethical” future, like ensuring non-malfeasance (preventing harm). Break big goals down into two or more specific sub-goals.
Goal: Ensure safe and responsible use of plant stress-responsive synthetic gene circuits.
Sub-goals: Prevent misuse or accidental harm using logic gates, kill switches, and monitoring protocols. Promote constructive applications for crop protection and biosecurity preparedness. Maintain transparency and accountability through documentation and ethical guidelines.
3. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”): 1. Purpose: 2. Design: 3. Assumptions: 4. Risks of Failure & “Success”:
| Action | Purpose | Design | Assumptions | Risks of Failure & Success |
|---|---|---|---|---|
| 1. Circuit Safeguards | Require logic gates, kill switches, self-limiting designs | Researchers design safeguards; regulators certify | Safeguards reliably prevent harm | Failure: safeguards bypassed or misconfigured; Success: false sense of security reduces oversight |
| 2. Pre-Deployment Risk Assessment | Mandatory biosecurity assessment before field use | Researchers submit risk reports; regulators approve | Risks can be anticipated and mitigated | Failure: assessments become superficial; Success: bureaucratic compliance slows innovation |
| 3. Incentive-Based Governance & Responsible-Use Norms | Promote safe, transparent, and ethical plant synbio use | Funders require safety plans, audits, and training | Incentives motivate responsible behavior | Failure: voluntary uptake limits coverage; Success: norms diffuse unevenly across actors |
4. Next, score (from 1-3, with 1 as the best, or n/a) each of your governance actions against your rubric of policy goals. The following is one framework but feel free to make your own:
| Does the option: | Option 1: Circuit Safeguards | Option 2: Pre-Deployment Risk Assessment | Option 3: Incentive-Based Governance & Responsible-Use Norms |
|---|---|---|---|
| Enhance Biosecurity | |||
| • By preventing incidents | 1 | 2 | 3 |
| • By helping respond | 2 | 1 | 2 |
| Foster Lab Safety | |||
| • By preventing incidents | 1 | 2 | 2 |
| • By helping respond | 2 | 1 | 2 |
| Protect the environment | |||
| • By preventing incidents | 1 | 2 | 2 |
| • By helping respond | 2 | 1 | 3 |
| Other considerations | |||
| • Minimizing costs/burdens | 2 | 3 | 1 |
| • Feasibility | 1 | 2 | 1 |
| • Does not impede research | 2 | 3 | 1 |
| • Promote constructive applications | 2 | 2 | 1 |
5. Last, drawing upon this scoring, describe which governance option, or combination of options, you would prioritize, and why. Outline any trade-offs you considered as well as assumptions and uncertainties.
Based on the scoring, I prioritize a combined approach led by Option 1 (Circuit Safeguards) and Option 3 (Incentive-Based Governance & Responsible-Use Norms), with Option 2 (Pre-Deployment Risk Assessment) applied selectively to higher-risk projects. Circuit safeguards are most effective at preventing incidents by embedding safety directly into design, while incentive-based governance best preserves feasibility, equity, and research freedom. Risk assessments are valuable for response and preparedness, but can impose high burdens if universally required. Key trade-offs involve balancing prevention with flexibility. Ethical concerns include overreliance on technical fixes and inequitable access; tiered governance and ongoing safety education help address these risks.
Assignment (Week 2 Lecture Prep)
Homework Questions from Professor Jacobson:
Nature’s machinery for copying DNA is called polymerase. What is the error rate of polymerase? How does this compare to the length of the human genome. How does biology deal with that discrepancy?
The error rate of the polymerase is 1 in 10⁶ bases. The human genome is approximately 3 × 10⁹ base pairs long. Therefore, when compared to the length of the human genome, this error rate corresponds to about 3 × 10³ errors per genome. Biology deals with this discrepency by proofreading, mismatch repair (MMR) system, & redundancy and selection.
How many different ways are there to code (DNA nucleotide code) for an average human protein? In practice what are some of the reasons that all of these different codes don’t work to code for the protein of interest?
The number of different DNA sequences (theoretical): ~3⁴⁰⁰ ≈ 10¹⁹⁰ for a 400-amino-acid protein. Many DNA sequences don’t work in practice due to codon usage bias, mRNA structure, protein folding dynamics, regulatory elements, and mutation robustness/cellular context.
Homework Questions from Dr. LeProust:
What’s the most commonly used method for oligo synthesis currently?
Phosphoramidite (solid‑phase) chemistry.
Why is it difficult to make oligos longer than 200nt via direct synthesis?
Per‑cycle inefficiencies and side reactions cause the full‑length fraction to fall rapidly with length.
- Why can’t you make a 2000bp gene via direct oligo synthesis?
The cumulative yield of full‑length product becomes essentially zero; chemical synthesis is not scalable to kilobase lengths.
Homework Question from George Church:
- What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”?
Ten amino acids commonly treated as essential for animals: Lysine; Methionine; Tryptophan; Threonine; Valine; Isoleucine; Leucine; Arginine; Histidine; Phenylalanine. Lysine auxotrophy is a useful mitigation but not a reliable sole safeguard —it can be rescued by environmental lysine, cross‑feeding, or genetic escape, so treat it as one layer in a multi‑layered containment strategy.
(For completing the second part of the homework (Week 2 preparation), I verified my answers and summarized the lecture slides to clarify specific points, using ChatGPT as a support tool.)