Homework

Weekly homework submissions:

  • Week 1 HW: Principles and Practices

    Class Assignment — DUE BY START OF FEB 10 LECTURE 1. First, describe a biological engineering application or tool you want to develop and why. This could be inspired by an idea for your HTGAA class project and/or something for which you are already doing in your research, or something you are just curious about.

Subsections of Homework

Week 1 HW: Principles and Practices

water hyacinth

Class Assignment — DUE BY START OF FEB 10 LECTURE

1. First, describe a biological engineering application or tool you want to develop and why. This could be inspired by an idea for your HTGAA class project and/or something for which you are already doing in your research, or something you are just curious about.

I want to develop a low-energy, biologically engineered microbial consortium that selectively breaks down lignin and hemicellulose in water hyacinth biomass, enabling efficient cellulose extraction without harsh chemical pretreatments.

As an Innovation Fellow of the Royal Academy of Engineering, UK, I am developing a range of biomaterials—including biodegradable cat litter, compressed boards, alternate leather, and packaging materials—from water hyacinth through Project Pola. The project originated as my Fabricademy final project at IAAC, Barcelona, and has since evolved into a commercially viable initiative with the potential to scale as a distributed global model. Pola focuses on transforming water hyacinth—an invasive and environmentally damaging plant—into high-value, sustainable materials for industries such as packaging, construction, textiles, and pet care. Currently, Pola operates as a community-driven initiative in collaboration with the Jawahar Centre in the Kuttanad region of Kerala. As part of the ongoing research, I have also explored cellulose extraction from water hyacinth using both mechanical and chemical processes.

Water hyacinth(Pontederia crassipes) is one of the world’s most aggressive invasive aquatic plants. It causes ecological damage, disrupts waterways, and requires constant removal. Current valorization methods rely on alkali or acid processing that is energy-intensive, environmentally damaging, and inaccessible to communities that are most affected by the plant. My goal is to replace or significantly reduce these chemical steps by designing a living pretreatment system—a consortium of microbes and/or enzymes that work together to delignify water hyacinth under mild conditions.

The tool I want to develop is both biological and infrastructural: a modular, small-scale bioreactor that uses selected or engineered microorganisms producing lignin-degrading and hemicellulose-degrading enzymes (such as laccases, peroxidases, and xylanases). By tuning microbial composition, oxygen availability, and fermentation conditions, I want to achieve controlled, selective breakdown of non-cellulosic components while preserving cellulose integrity.

This work builds directly on my ongoing research into biomaterials derived from water hyacinth, where pretreatment remains the most chemically intensive and environmentally costly step. Biologically engineering this process would not only improve material yields and quality, but also create a pathway for distributed, low-tech biomass processing that can be deployed near wetlands, reducing transport, chemical use, and ecological harm.

I am interested in this project because it reframes invasive biomass as a biological resource rather than a waste problem, and explores how engineered microbial systems can function as sustainable alternatives to industrial chemistry.

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. Below is one example framework (developed in the context of synthetic genomics) you can choose to use or adapt, or you can develop your own. The example was developed to consider policy goals of ensuring safety and security, alongside other goals, like promoting constructive uses, but you could propose other goals for example, those relating to equity or autonomy.

A key governance goal for this project is to ensure that an engineered microbial consortium for water hyacinth delignification contributes to an ethical future by preventing ecological harm, misuse, and unintended social impacts. Because this system involves living organisms and is intended for use near sensitive wetlands, safety and responsibility must be included at multiple levels.

1. Prevent ecological and biosecurity risks

  • Design the consortium using non-pathogenic, well-characterized microbes with limited survivability outside controlled conditions.
  • Require operation only in closed or semi-closed systems, with clear protocols for microbial deactivation after processing.

2. Prevent misuse and perverse incentives

  • Ensure the technology is used exclusively on biomass collected through invasive species removal, not to encourage cultivation of water hyacinth.
  • Align deployment with wetland conservation and invasive species management goals.

3. Ensure community benefit and responsible access

  • Prioritize low-cost, decentralized systems accessible to local communities rather than extractive, centralized models.
  • Promote transparency through open documentation of methods, risks, and safety practices.

Together, these goals frame ethical governance as a core design constraint rather than an afterthought.

3. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”). Try to outline a mix of actions (e.g. a new requirement/rule, incentive, or technical strategy) pursued by different “actors” (e.g. academic researchers, companies, federal regulators, law enforcement, etc). Draw upon your existing knowledge and a little additional digging, and feel free to use analogies to other domains (e.g. 3D printing, drones, financial systems, etc.). 1. **Purpose:** What is done now and what changes are you proposing? 2. **Design:** What is needed to make it “work”? (including the actor(s) involved - who must opt-in, fund, approve, or implement, etc) 3. **Assumptions:** What could you have wrong (incorrect assumptions, uncertainties)? 4. **Risks of Failure & “Success”:** How might this fail, including any unintended consequences of the “success” of your proposed actions?

Governance Action (Actor)PurposeDesign (What makes it work)AssumptionsRisks of Failure & “Success”
1. Built-in biological containment as a design requirement (Academic researchers, bioengineers)Move safety from procedural rules to organism/process designUse non-pathogenic strains; limit survivability outside reactors; closed-system operation; safety documentation (analogous to fail-safes in hardware)Containment traits remain stable; users follow protocolsFailure: mutation or misuse; false sense of safety. Success risk: users attempt open-environment deployment
2. Use-context certification / standards (NGOs, standards bodies, companies)Guide responsible use without heavy regulationVoluntary certification tied to funding/partnerships; defines allowed contexts (closed systems only), waste handling (analogous to drone “indoor-only” rules)Certification influences behavior; accessible to small actorsFailure: symbolic compliance; exclusion of community users. Success risk: gatekeeping or privatization
3. Alignment with invasive-species management policy (Local/state regulators, wetland authorities)Prevent incentives to cultivate invasive biomassRequire sourcing from approved removal programs; integrate with wetland management plans (analogous to waste-to-energy sourcing rules)Enforcement capacity exists; coordination across agenciesFailure: weak enforcement; over-regulation. Success risk: economic value encourages preservation of invasives

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:

Option 1: Built-in biological containment as a technical design requirement

Option 2: Use-context certification / standards for living processing systems

Option 3: Policy alignment with invasive-species management regulations

Scoring key: 1 = best / strongest alignment 2 = moderate 3 = weak n/a = not really applicable

Does the option:Option 1Option 2Option 3
Enhance Biosecurity
• By preventing incidents122
• By helping respond211
Foster Lab Safety
• By preventing incident123
• By helping respond21n/a
Protect the environment
• By preventing incidents121
• By helping respond211
Other considerations
• Minimizing costs and burdens to stakeholders123
• Feasibility?123
• Not impede research123
• Promote constructive applications112

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. For this, you can choose one or more relevant audiences for your recommendation, which could range from the very local (e.g. to MIT leadership or Cambridge Mayoral Office) to the national (e.g. to President Biden or the head of a Federal Agency) to the international (e.g. to the United Nations Office of the Secretary-General, or the leadership of a multinational firm or industry consortia). These could also be one of the “actor” groups in your matrix.

Prioritized governance approach (Audience: Kuttanadu, Alappuzha, Kerala, India)

Based on the scoring, I would prioritize a combination of Option 1 (built-in biological containment) and Option 2 (use-context certification and standards) for early deployment of an engineered microbial consortium for water hyacinth delignification in Kuttanadu. Option 3 (formal regulatory alignment) is important but should be phased in only at later stages of scaling.

Biological containment should be the foundation because it embeds safety directly into the system, reducing ecological and biosecurity risks even in decentralized or low-oversight contexts. This is critical in Kuttanadu, where interventions occur close to sensitive wetlands and are often community-led. Use-context certification complements this by guiding responsible use—such as restricting operation to closed reactors and requiring post-processing deactivation—without imposing heavy regulatory burdens that could impede local experimentation.

The main trade-off is reduced formal enforceability compared to regulation. However, premature regulatory control could slow innovation or push experimentation into informal, less safe practices. This approach assumes that local actors will adopt low-cost safety measures and that containment mechanisms remain stable in real-world conditions. If economic incentives or large-scale deployment emerge, stronger regulatory alignment would then become necessary.

Reflecting on what you learned and did in class this week, outline any ethical concerns that arose, especially any that were new to you. Then propose any governance actions you think might be appropriate to address those issues. This should be included on your class page for this week.

Working with Pola water hyacinth project across India, and other parts of the world (UK, Spain, Netherlands, Japan, Colombia, and parts of Africa), I have seen how environmental technologies behave differently once they leave the lab. This week made me realize that risk is not only about pathogens, but about ecological imbalance and economic incentives. In places like Kuttanadu, where water hyacinth is both a burden and a livelihood opportunity, a successful microbial processing system could unintentionally encourage preserving the invasive species. I was also struck by the risks of distributed experimentation in low-resource contexts, where oversight is uneven.

To address this, I would prioritize built-in biological containment, closed-system use standards, and policies that require biomass sourcing from certified removal efforts. It also shows the need for a regulatory body akin to FDA or MHRA that oversees safety and ethical standards.

Assignment (Week 2 Lecture Prep) — DUE BY START OF FEB 10 LECTURE

Homework Questions from Professor Jacobson: Lecture 2 slides

1. 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?

DNA polymerase has an error rate of approximately 10⁻⁵ errors per base per replication when inserting nucleotides. However, most replicative polymerases also have proofreading activity (3’→5’ exonuclease function), which reduces the error rate to about 10⁻⁷ per base. After replication, additional mismatch repair mechanisms further correct errors, bringing the final mutation rate down to roughly 10⁻⁹ to 10⁻¹⁰ per base per cell division.

The human genome is about 3 × 10⁹ base pairs long. Without proofreading or repair, an error rate of 10⁻⁵ would result in tens of thousands of mutations per replication—far too many for viability. Even at 10⁻⁷, hundreds of mutations would occur per division.

Biology resolves this discrepancy through layered error correction: high-fidelity polymerases, proofreading during replication, post-replication mismatch repair, and cell-cycle checkpoints. Together, these mechanisms reduce replication errors to roughly 0.1–1 mutation per genome per cell division, maintaining genomic stability while still allowing rare mutations that drive evolution.

2. 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?

An average human protein, consisting of roughly 300-400 amino acids, can be encoded in an astronomically large number of different DNA sequences, often exceeding 10 100 combinations. This extreme degeneracy is due to the genetic code having 64 possible codons for only 20 amino acids, with many amino acids having multiple synonyms

In practice most of these sequences would not function well.

  1. Disruption of Co-translational Folding: Replacing “rare” (slow) codons with “optimal” (fast) codons can cause the ribosome to move too quickly, causing the polypeptide chain to misfold or aggregate.
  2. mRNA Instability and Premature Termination:
  3. Hidden Motifs and Hidden Functions: The new sequence might accidentally introduce hidden splice sites, restriction sites, or binding sites for internal regulatory proteins that destroy the mRNA or cause mis-splicing.

Homework Questions from Dr. LeProust: Lecture 2 slides

1. What’s the most commonly used method for oligo synthesis currently?

Solid-phase phosphoramidite chemical synthesis. It builds DNA one nucleotide at a time on a solid support, using protected nucleotides and iterative cycles of coupling, capping, and oxidation. It's automated, scalable and reliable.

2. Why is it difficult to make oligos longer than 200nt via direct synthesis?

Each nucleotide addition has a small failure rate (~0.5–1%). As length increases, these errors accumulate, reducing the yield of full-length product. Beyond ~200 nt, the proportion of correct full-length molecules becomes too low for practical use without extensive purification.

3. Why can’t you make a 2000bp gene via direct oligo synthesis?

At 2000 bp, cumulative coupling inefficiencies would make the yield of a perfect full-length molecule essentially zero. Error rates compound and chemical synthesis becomes impractical. Instead long genes are assembled from shorter, high-quality oligos.

Homework Question from George Church: Lecture 2 slides

Choose ONE of the following three questions to answer; and please cite AI prompts or paper citations used, if any.

  1. [Using Google & Prof. Church’s slide #4] What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”?
  2. [Given slides #2 & 4 (AA:NA and NA:NA codes)] What code would you suggest for AA:AA interactions?
  3. [(Advanced students)] Given the one paragraph abstracts for these real 2026 grant programs sketch a response to one of them or devise one of your own:

I choose to answer question 1.
The 10 essential amino acids that most animals cannot synthesize in sufficient quantities and must obtain from their diet are: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine.

The “Lysine Contingency” in Jurassic Park imagined disabling lysine biosynthesis so dinosaurs would depend on supplementation as a control mechanism. In reality, most animals already lack the ability to synthesize lysine, making such a strategy biologically implausible as a containment switch.

This changes how we think about metabolic dependency- many organisms can’t make certain essential amino acids on their own, but in real environments they can often get around engineered limits by finding those nutrients elsewhere. As an animal rescuer, I see parallels in taurine dependency in cats—dietary reliance does not ensure control. Similarly, water hyacinth, introduced for ornamental and research purposes, spread rapidly despite human oversight. The Lysine Contingency highlights a broader lesson: biological “control switches” must account for ecological redundancy and evolutionary workarounds, especially when engineering systems within already invasive contexts.
AI Prompt used: Rewrite to less than 150 words and make it tighter.