Week 1 HW: Principles and Practices

Assignment 1

1. Describe a biological engineering application or tool you want to develop and why.

   • I have recently been thinking about bio-mining/bio-leaching solutions. The bio-engineering tool I’d like to develop for this assignment would be a bacterial strain that could collect and concentrate Neodymium metal from soils into a purifiable mass.

2. 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.

   • 1st: Ensuring that the synthetic genes & the synthetic strain itself does not spill out and impact the existing microbiological ecology
   • 2nd: Ensuring that the process of employing the strain/purifying the metal from the strain does not produce a toxic waste stream nor impact the local macro-ecology

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.).

   • a. Action 1: Ensure that the strain is only ever applied to soil in a secure bio-processing facility
     • Purpose: an engineering control to keep the novel strain from impacting microbial ecology.
     • Design: Prospective soil would be dug up, transferred to the bio-facility, incubated w/ the microbe, sterilized, and returned to the initial site or sold for use in construction/other commercial endeavors.
     • Assumptions: ***
     • Risks of Failure & “Success”: Digging up enough soil to make commercial viability might result in soil clearing on the scale of open-top mining & similar levels of macro-ecology destruction. Additionally, sterilizing such quantities of soil would be energetically expensive & would probably kill any soil microbes present.
   • b. Action 2: Making sure that the metal as concentrated/purified remains biologically inert throughout my biochemical process
     • Purpose: This will make it more difficult for workers to absorb the metal into bloodstream from chronic exposure
     • Design: Make the strain give that function. Which is hard
     • Assumptions: That only neodymium salts can be absorbed/cause toxicity in humans/ that dermal exposure to the metal would not cause toxicity.
     • Risks of Failure & “Success”: Literally might not be possible to keep strain alive & segregate metal in bio-inert way.
   • c. Action 3
     • Purpose: What is done now and what changes are you proposing?
     • Design: What is needed to make it “work”? (including the actor(s) involved - who must opt-in, fund, approve, or implement, etc)
     • Assumptions: What could you have wrong (incorrect assumptions, uncertainties)?
     • Risks of Failure & “Success”: How might this fail, including any unintended consequences of the “success” of your proposed actions? 4 Score (from 1-3 with, 1 as the best, or n/a) each of your governance actions against your rubric of policy goals.

       Does the option:	Option 1	Option 2	Option 3
       Enhance Biosecurity
       • By preventing incidents	1	n/a
       • By helping respond	3	n/a
       Foster Lab Safety
       • By preventing incident	2	1
       • By helping respond	2	2
       Protect the environment
       • By preventing incidents	1	1
       • By helping respond	3	3
       Other considerations
       • Minimizing costs and burdens to stakeholders	2	1
       • Feasibility?	1	3
       • Not impede research	1	1
       • Promote constructive applications	1	1

4. 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. These could also be one of the “actor” groups in your matrix.

5. 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.

Homework Questions from Professor Jacobson: [Lecture 2 slides]

• 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? Error rate of (10^–4). They use an exonuclease activity (i.e. proof-reading).
• 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? Not sure. tRNA concentration & Kinetic effects on translation? Homework Questions from Dr. LeProust: [Lecture 2 slides]
• What’s the most commonly used method for oligo synthesis currently? Solid-phase oligonucleotide synthesis
• Why is it difficult to make oligos longer than 200nt via direct synthesis? Practical Yield over 200nt is too low
• Why can’t you make a 2000bp gene via direct oligo synthesis?

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.

[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”? Histidine (H), Isoleucine(I), leucine (L), lysine (K), methionine (M), phenylalanine (P), threonine (T), tryptophan (W), valine (V) This makes me find the “Lysine Contingency” to be an exercise in hubris & foolishness. I can’t synthesize lysine, and yet I do not require lysine supplements to live because I get it from my food! Better to make the dinos dependent on a xeno-amino acid that wouldn’t be synthesizable by the plants & animals on the isle.

[Given slides #2 & 4 (AA:NA and NA:NA codes)] What code would you suggest for AA:AA interactions? [(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: https://arpa-h.gov/explore-funding/programs/boss https://www.darpa.mil/research/programs/smart-rbc https://www.darpa.mil/research/programs/go

Week 1 Lab: Pipetting

Individual Final Project

Group Final Project