Week 1 HW: Principles and Practices
Homework 1: Governance & Ethics
1. Biological Engineering Application
Project: Recombinant production of BmK CT (Scorpion Peptide) via Cloud-Lab Automation. Why: Venom-derived therapeutics are currently difficult to source sustainably. My goal is to engineer a microbial “cell factory” using E. coli to produce high-purity BmK CT for glioma (brain cancer) research, utilizing automated cloud-lab infrastructure for scalable access.
2. Governance/Policy Goals
My primary goal is to ensure Non-malfeasance (preventing harm) while promoting Constructive Use.
- Sub-goal A (Biosecurity): Preventing the diversion of synthesized neurotoxin sequences for harmful, non-therapeutic purposes.
- Sub-goal B (Equity): Ensuring that the digital blueprints and production protocols are accessible to researchers in developing regions like Pakistan to promote autonomy.
3. Governance Actions Matrix
| Aspect | Action 1: Automated Screening | Action 2: User Verification | Action 3: Ethical Peer-Review |
|---|---|---|---|
| Actor | DNA Synthesis Companies | Cloud Lab Platforms | Academic Communities |
| Purpose | Flags regulated toxin sequences. | Mandatory ID for remote users. | Standardizing “Dual-Use” data sharing. |
| Assumptions | All toxins are indexed. | Affiliation equals ethics. | Users will follow protocols. |
| Risks | False positives slow research. | Excludes independent scientists. | Security breaches are possible. |
4. Scoring Matrix
(1 = Best, 3 = Least)
| Does the option: | Option 1 | Option 2 | Option 3 |
|---|---|---|---|
| Enhance Biosecurity | 1 | 1 | 2 |
| Foster Lab Safety | 2 | 1 | 3 |
| Not Impede Research | 2 | 3 | 1 |
| Promote Constructive App | 1 | 1 | 1 |
5. Prioritization & Recommendation
I prioritize a combination of Action 1 and Action 2. This recommendation is intended for International Regulatory Bodies. We must implement “Know Your Customer” (KYC) rigor for Cloud Labs, similar to financial institutions. While this adds a burden to remote researchers, it is a necessary trade-off for handling potent neurotoxins safely.
6. Ethical Reflection
The concept of an “Information Hazard” was a significant new concern for me. Even if my physical lab work is safe, publishing a “perfect roadmap” for toxin production could be misused. I propose “Ethical Red-Teaming” as a governance action where students peer-review project documentation for potential dual-use risks before publication.
Week 2 Pre-Lecture Preparation
In preparation for “DNA Read, Write, and Edit” lecture.
Part 1: Questions from Professor Jacobson
- What is the error rate of polymerase? The error rate of DNA polymerase is approximately $10^{-7}$ to $10^{-8}$ per base pair.
- How does this compare to the length of the human genome? The human genome is about 3 billion ($3 \times 10^9$) base pairs long, meaning mutations are inevitable without repair.
- How does biology deal with that discrepancy? Biology utilizes Proofreading and Mismatch Repair (MMR) systems to reduce the final error rate to $10^{-9}$ or $10^{-10}$.
- How many different ways are there to code for an average human protein? Due to Codon Degeneracy, there are millions of potential DNA sequences for a single protein.
- Why don’t all of these different codes work? Factors like Codon Usage Bias, mRNA secondary structures, and cryptic splice sites can hinder protein expression.
Part 2: Questions from Dr. LeProust
- Most common method for oligo synthesis: The Phosphoramidite method is the current standard.
- Why is it difficult to make oligos > 200nt? Cumulative coupling inefficiencies lead to extremely low yields for long, pure sequences.
- Why can’t you make a 2000bp gene via direct synthesis? The error rate and yield drop make direct synthesis of long genes unfeasible; they must be assembled from shorter oligos.
Part 3: Question from George Church
- 10 Essential Amino Acids: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine.
- The “Lysine Contingency”: This is a Biocontainment strategy where organisms are engineered to depend on external amino acids to prevent survival outside the lab environment.