Week 1 HW: Principles and Practices
THEME MUSIC🎵
(listen as you read this :))
1. First, describe a biological engineering application or tool you want to develop and why.
I want to develop a biological engineering system for smarter nutrient liberation in agricultural soils, especially for sugarcane. The current nutrient management system depends heavily on chemical fertilizers that release nutrients in poorly timed pulses, leading to massive nutrient losses, soil degradation, and environmental damage. I do not want to sugarcoat it: the situation is bad. I am Brazilian, which also means I come from the country that exports the most sugar in the world, largely through intensive sugarcane monoculture. My goal is to explore how engineered soil microorganisms could sense plant-derived signals and release nutrients only when they are biologically needed, turning the soil from a passive substrate into an active, responsive system.
2. Next, describe one or more governance/policy goals related to ensuring that this application or tool contributes to an âethicalâ future, like ensuring non-malfeasance (preventing harm). Break big goals down into two or more specific sub-goals.
The sugar industry is a highly profitable one: the global sugar market was estimated to be valued at $46.4 billion in 2023. That being said, profitability also creates incentives for misuse. If a biological system significantly improves nutrient efficiency, it could be exploited to further intensify monoculture, expand cultivation into fragile ecosystems, or concentrate power in the hands of large agribusinesses rather than improving sustainability. A central governance goal, therefore, is to prevent technological gains from amplifying extractive or environmentally harmful practices. To do that, we can break down into sub-goals such as regulating deployment to avoid land-use expansion and establishing public or open-access frameworks that limit exclusive corporate ownership of engineered soil systems. This is important because it is very important that small and medium-scale farmers also have access to this technology.
3. Next, describe at least three different potential governance âactionsâ by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & âSuccessâ).
Action 1: Establishment of a biosafety and ecological oversight committee;
Purpose: Ensure that engineered soil microorganisms are biologically safe, ecologically contained, and function as intended. This includes preventing unintended persistence in the environment, horizontal gene transfer, or disruption of native soil microbiomes.
Design: Development of standardized biosafety evaluation protocols, including genetic safeguards (such as kill-switches or nutrient dependencies), controlled soil microcosm experiments, and long-term monitoring of microbial survival and gene stability. Ecological impact assessments would be required before any field deployment.
Risk of failure and “success”: Failure: engineered microorganisms persist uncontrollably in the environment, transfer genetic material to native species, or alter soil ecosystems in harmful ways.
Success: the system demonstrates predictable behavior, effective containment, and minimal ecological disruption under real soil conditions.
Action 2: Phased field trials and agronomic validation
Purpose: Test whether the engineered microorganisms actually improve nutrient synchronization with plant demand without causing harm, ensuring that efficiency gains are real, reproducible, and context-dependent rather than theoretical.
Design: Multi-phase field trials beginning with small, controlled plots and gradually expanding to larger agricultural settings. Always havinf a control group, including runnning comparative studies against conventional fertilization practices, measuring nutrient use efficiency, crop yield, soil health indicators, and environmental runoff.
Risk of failure and “success”: Failure: the system fails to improve nutrient efficiency, behaves inconsistently across environments, or introduces new agronomic risks.
Success: nutrient release becomes better synchronized with plant needs, fertilizer input is reduced, and soil quality is maintained or improved over multiple growing cycles.
Action 3: Governance frameworks to prevent extractive or monopolistic use Purpose: Prevent efficiency gains from being exploited to intensify monoculture, expand cultivation into ecologically sensitive areas, or concentrate control within large agribusiness corporations. Design: Creation of policy frameworks that tie deployment of engineered soil systems to sustainability metrics, land-use regulations, and open or publicly governed licensing models. This includes transparency requirements, public-sector involvement, and safeguards against exclusive proprietary ownership of essential soil biotechnologies. Risk of failure and “success”: Failure: the technology is captured by profit-driven actors and used to accelerate environmental degradation or deepen agricultural inequality. Success: the system is deployed in ways that promote long-term soil resilience, equitable access for small and medium-scale farmers, and environmentally responsible agricultural practices.
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 help to: | Option 1 | Option 2 | Option 3 |
|---|---|---|---|
| Ensure biological and ecological safety | |||
| ⢠Prevent unintended environmental harm | 1 | 2 | 3 |
| ⢠Limit uncontrolled spread or persistence | 1 | 2 | 3 |
| Validate real-world effectiveness and reliability | |||
| ⢠Demonstrate consistent performance across contexts | 2 | 1 | n/a |
| ⢠Identify failures before large-scale deployment | 2 | 1 | n/a |
| Prevent extractive or profit-driven misuse | |||
| ⢠Limit intensification of monoculture | 3 | 2 | 1 |
| ⢠Prevent concentration of control by large agribusiness | 3 | 2 | 1 |
| Promote equitable access to the technology | |||
| ⢠Enable access for small and medium-scale farmers | 2 | 2 | 1 |
| Maintain feasibility and avoid blocking research | |||
| ⢠Feasible to implement in practice | 2 | 2 | 3 |
| ⢠Does not unnecessarily slow scientific progress | 2 | 3 | 2 |
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
I would prioritize a combination of Option 1 (biosafety and ecological oversight) and Option 2 (phased field trials and agronomic validation) as the foundation for responsible governance. Because before thinking about the politics of how and by whom the technology will be used (although these questions should be considered from the beginning) we need to make sure it is actually safe to deploy. Establishing biological safety and ecological predictability should be (ALWAYS!) a prerequisite for any ethical discussion about scale, access, or commercialization.
FINAL REFLECTION
One ethical question that really made me stop and think during this project was whether making biological systems more efficient automatically makes them more sustainable. Engineering soil microorganisms to release nutrients in a smarter way could reduce fertilizer use and environmental damage, but it could also be used to push monoculture systems even further or expand agriculture into already fragile ecosystems (as I see it so frequently happening in Brazil :Brazil:). And honestly, Iâm not completely sure where the safety limits of genetic modification are, especially in complex environments like soil. That uncertainty is part of what excites me - and Iâm eager to explore, question, and learn more about this during HTGA :D
Week 2 lecture preparation
Homework Questions from Professor Jacobson:
1. Natureâs 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 makes about one mistake every one million bases copied (an error rate of ~10âťâś) after its built-in proofreading activity. The human genome is about three billion base pairs long, so if DNA were copied using only polymerase proofreading, each cell division would introduce thousands of errors 🤯. Biology solves this problem by adding extra layers of quality control after replication, especially mismatch repair and other DNA repair pathways, which reduce the final error rate to roughly one mistake per billion to ten billion bases.
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 donât work to code for the protein of interest?
An average human protein (~1036 bp, ~345 amino acids) can be encoded in astronomically many ways because most amino acids are specified by multiple synonymous codons; in theory this corresponds to roughly to 1 followed by 150 zeros (🤯) different DNA sequences that encode the same protein.
In practice, most of these sequences fail because of codon bias, effects on mRNA stability and secondary structure (as shown by studies linking codon usage to mRNA half-life and folding), translation speed and co-translational folding (as revealed by ribosome-profiling and folding-kinetics experiments), GC-content constraints, and embedded regulatory or splicing signals within coding regions. We can think of this problem as
Homework Questions from Dr. LeProust:
1. Whatâs the most commonly used method for oligo synthesis currently?
The typical method for Oligonucleotide synthesis is the phosphoramidite method
2. Why is it difficult to make oligos longer than 200nt via direct synthesis?
Chemical oligo synthesis accumulates errors because each nucleotide coupling step is slightly imperfect. Altoug there exists papers on
3. Why canât you make a 2000bp gene via direct oligo synthesis?
A 2000 bp gene would require thousands of sequential coupling steps, causing error rates and truncation products to completely dominate over correct full-length molecules. The yield of an error-free sequence would be essentially zero, so long genes must instead be assembled from shorter, high-quality oligos using enzymatic methods like PCR or Gibson assembly (ChatGPT helped me aswer. My prompt: The question + so what is usually done when a 2000bp+ gene is needed?.
Homework Questions from George Church:
1. What are the 10 essential amino acids in all animals and how does this affect your view of the âLysine Contingencyâ?
The ten essential amino acids in animals are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, and arginine