1. First, describe a biological engineering application or tool you want to develop and why.

Gut health has been all the rage in recent years, becoming a major focus in both research and wellness technology. Trends such as social media discussions, prebiotic beverages, and rising awareness of gut-related conditions highlight its importance, especially as more people face gut issues due to processed diets. I am particularly interested in exploring different methods for testing gut health, including non-invasive sampling from sweat or saliva, and identifying key biomarkers for inflammation and microbiome balance. My goal would be to develop a tool or approach to monitor gut health in a practical, real-time way, combining biological insights with engineering design. Unlike existing doctor visits or direct-to-consumer tests, which provide only one-off snapshots, a wearable or non-invasive sensor could offer continuous monitoring, helping individuals understand and take proactive steps to maintain gut health, perhaps even predict flare-ups. Although I am not entirely sure how feasible this is, I am excited to explore the intersection of wearables, synthetic biology, and daily health applications.

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 1: Prevent Harm (Non-Malfeasance)

• Ensure physical safety of the user and avoid damage/harm to the body. Consider all other physical risks.
• Ensure measurement reliability/unreliability. Inaccurate readings should not cause harmful decisions, for example unnecessary dietary restrictions or medical panic among users

Goal 2: Promote Responsible and Constructive Use

• Encourage the device to be used as a tool for monitoring and proactive health management, not as a replacement for medical advice.

3. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”)

Drawing from what I know about direct to consumer genetic testing/23andME

Action 1: Data Privacy

Purpose: Many consumer health companies collect and share data in ways consumers may not fully understand (e.g. selling data to big pharma). I propose regulations requiring explicit consent, local data storage, and limits on secondary use of gut health data.

Design: Federal regulators, wearable companies, and healthcare providers would implement consent disclosures, anonymization, and limits on commercial data sharing. Users would maintain control over their data, including opt-in permissions for research use.

Assumptions: Assumes that users understand consent forms and that companies comply with privacy regulations.

Risks of Failure & Success: Failure could lead to data breaches or misuse of personal health information, reducing trust and adoption.

Action 2: Device Safety and Accuracy Certification

Purpose: Ensure the wearable gut sensor is safe to use on the body and provides accurate readings. Unlike standard consumer electronics testing, this would specifically assess biological risks and measurement reliability which naturally poses more risks.

Design: FDA/Goverment, manufacturers, and academic labs would collaborate to test electrical safety, skin compatibility, and sensor accuracy. Devices must meet benchmarks before public release.

Assumptions: Assumes testing standards for gut biomarkers can be established and that manufacturers will comply.

Risks of Failure & Success: Unsafe or inaccurate devices could harm users or undermine trust and on the flipside reliable, safe devices increase user confidence.

Action 3: User Education and Interpretation Guidelines

Purpose: Help users correctly understand and act on gut health readings, reducing anxiety or misinformed decisions.

Design: Companies or healthcare providers provide clear instructions, disclaimers, and educational materials. Could include in-app tutorials or alerts.

Assumptions: Assumes users engage with the educational material and interpret data appropriately.

Risks of Failure & Success: Users may ignore guidance or misunderstand readings, causing harm, Users make informed decisions and rely on the device responsibly, improving outcomes.

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.

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 would prioritize Data Privacy and Usage Regulations as the primary governance action. Protecting users sensitive gut health data ensures ethical use, fosters trust, and supports responsible adoption of wearable or non-invasive gut health sensors. While device safety and measurement accuracy are also important, focusing first on privacy addresses the most immediate ethical risks related to misuse, consent, and autonomy. Some tradeoffs include assuming consumers understand consent forms and that companies comply with regulatory standards. relevant Audiences include 1) federal regulators to implement and enforce privacy and consent rules and 2) wearable device companies to ensure compliance with consent disclosures, and 3) academic researchers and healthcare providers for optional pilot studies and oversight. Some ethical considerations include data misuse/gut health information is highly personal and could be exploited if not properly protected.

Assignment (Week 2 Lecture Prep)

Homework Questions from Professor Jacobson:

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 Polymerases have a typical error rate of ~10^-5 (1 in 100,000 wrong bases). The length of a human genome is ~3 × 10⁹ base pairs. Biology deals with this discrepency by proofreading! DNA polymerases check and correct mistakes as they add nucleotides. Additional enzymes also scan DNA post-replication to fix mismatches. Additionally not all errors affect critical genes for example some occur in non-coding regions.This combination ensures that even a very large genome can be copied accurately enough for life to function.

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?

Proteins are composed of amino acids which are made up of codons (3 nucleotides long). Each human protein can consist anywhere from 400-500 amino acids leading to 3^{400 to 3}500 possibilities. In practice not all of those codes work because of factors including codon usage bias (not all codons are used equally).

Homework Questions from Dr. LeProust:

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

Phosphoramidite chemistry is the most commonly used method for oligo synthesis. It works by sequentially adding protected nucleotides to a growing chain on a solid support, using chemical reactions to form the phosphodiester bond. This allows precise control over the sequence of short DNA fragments.

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

It’s difficult to make oligos longer because efficiency drops with each added nucleotide. These errors accumulate, making sequences >200 nt unreliable.

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

Direct synthesis is limited by length and error rates so a 2000 bp gene would be too long to synthesize accurately in one piece. Instead in practice, long genes are constructed by assembling multiple shorter oligos using techniques like PCR-based assembly or Gibson assembly, which stitch them together into the correct full-length sequence.

Homework Question from George Church:

1. What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”?

10 essential amino acids:

1. Arginine
2. Histidine
3. Isoleucine
4. Leucine
5. Lysine
6. Methionine
7. Phenylalanine
8. Threonine
9. Tryptophan
10. Valine

Lysine Contingency: I didn’t catch this when first watching Jurassic Park but after thinking about it the “Lysine Contingency” seems flawed. All animals, including humans, cannot produce their own lysine and need to acquire it through diet. Given this, dinosaurs would have naturally obtained lysine from their environment and would survive, even if they were bioengineered to be unable to produce it themselves. This also explains why they survived in the next 6 movies without any administered lysine supplements.