Week 1 HW: Principles and Practices

Documentation

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 have a deep interest in Japanese fireworks culture and have incorporated fireworks into my artistic practice. In Japan, fireworks have long carried meanings of memorialization and life, making transience and cyclic time a shared embodied experience. At the same time, contemporary conditions—environmental footprint and responsible deployment—ask us to rethink what fireworks can mean today.

This project relocates the ideas that fireworks have historically held—one-time temporality, memorialization, and the bodily experience of light—into bio-art. Instead of treating an explosion as the engine, I treat a molecular-biology-inspired sensing→processing→reporting interface as the engine, producing a time-varying signal I call a “breathing” glow.

Conceptually, the work draws on gene-expression logic (signals that turn on, intensify, and shift over time) to imagine a living light interface: softly modulated patterns of light or color that evoke the pulse of living systems. The tool is intended to render biological rhythms and environmental changes as a poetic, legible experience of time.

Note: This is a conceptual art-research proposal and intentionally avoids procedural detail. Any implementation would require expert oversight, appropriate review, and clear public communication to prevent misinterpretation.

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：Biosafety (prevent harm to people and places)

  • Ensure robust containment and accident prevention across making, transport, storage, and exhibition.
  • Require risk assessment and independent review before any public-facing deployment, with staged scaling (small → larger) when appropriate.

B：Environmental responsibility (lifecycle accountability)

  • Define and minimize lifecycle impacts (materials, waste streams, cleaning, recovery, disposal).
  • Prepare clear response procedures for accidental release, contamination, or other environmental incidents.

C：Social integrity (prevent misinterpretation and protect trust)

  • Design communication to prevent audiences from mistaking the work for “diagnosis,” “certification,” or authoritative measurement.
  • Maintain transparency by stating limitations and uncertainties and avoiding overclaiming.

D：Misuse / repurposing prevention (biosecurity / dual-use)

  • Reduce the risk that materials, capabilities, or know-how could be repurposed for harmful uses.
  • Establish reporting, stop-work, and corrective-action pathways if safety/security concerns arise.

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.).

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1：Pre-deployment review (“safety case”) + clear accountability (actors: venue/operator + independent reviewers)

Purpose (what changes):
Currently, decisions can be ad hoc and person-dependent. I propose a standardized pre-deployment review that makes safety, environmental, and misinterpretation risks explicit before any public display.

Design (what’s needed; who acts):

  • A short “safety case” template + checklist (biosafety, disposal, signage/communication, incident plan).
  • An independent reviewer (or review panel) signs off; a named responsible person is designated.
  • Staged deployment: small-scale test → limited public pilot → broader deployment if evidence supports it.

Assumptions (what could be wrong):

  • Qualified reviewers are available and venues will actually enforce outcomes.
  • The process remains lightweight enough to be usable.

Risks of failure & “success”:

  • Failure: becomes a box-ticking exercise; inconsistent enforcement.
  • Success risk: creates gatekeeping and raises barriers for smaller/independent projects.

2：Communication standard (labels + website template) to prevent misinterpretation (actors: artist + venue)

Purpose (what changes):
Public-facing bio-art can be misread as scientific diagnosis or certification. I propose a communication standard that reduces misinformation risk while preserving artistic intent.

Design (what’s needed; who acts):

  • Required statements: what the work is/is not; what inputs/outputs mean; key limitations and uncertainties.
  • Simple FAQ and on-site signage; venues agree not to remove or rewrite essential safety/limits language.

Assumptions (what could be wrong):

  • Audiences will notice/read the information; venues will keep it intact.
  • Clear language will reduce, not amplify, confusion.

Risks of failure & “success”:

  • Failure: “warning fatigue” (people ignore it); signage is altered or minimized.
  • Success risk: over-standardization can flatten nuance and reduce poetic ambiguity.

3：Containment + disposal protocol (technical + operational) (actors: research collaborators + venue operations)

Purpose (what changes):
Containment, cleanup, and end-of-life handling are often unclear in public art contexts. I propose a containment-first design principle and an explicit disposal/recovery protocol.

Design (what’s needed; who acts):

  • Prefer sealed, recoverable display formats; define boundaries for scale and setting (e.g., indoor-only or other constraints as required).
  • Written procedures for handling, cleanup, waste streams, and documented disposal.
  • A basic incident plan (who to contact, how to pause, how to remediate).

Assumptions (what could be wrong):

  • Containment can coexist with the intended aesthetics and budget.
  • Operational staff can reliably follow the protocol.

Risks of failure & “success”:

  • Failure: higher cost and operational complexity; inconsistent compliance.
  • Success risk: responsibility can become diffuse (“everyone thought someone else handled it”), reducing accountability unless roles are explicit.

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…Safety case + accountabilityCommunication standardContainment+disposal protcol
Enhance Biosecurity
• By preventing incidents232
• By helping respond132
Foster Lab / Handling Safety
• By preventing incidents231
• By helping respond132
Protect the environment
• By preventing incidents231
• By helping respond231
Other considerations
• Minimizing costs and burdens to stakeholders213
• Feasibility ?212
• Not impede research212
• Promote constructive applications122
Prevent military / harmful repurposing232

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.

Recommendation:
I would prioritize Action 1 (pre-deployment “safety case” + clear accountability) and Action 3 (containment + disposal protocol) as the baseline, and require Action 2 (communication standard) for every public-facing display.

Why:
Action 1 and 3 most directly reduce biosafety and environmental risks, while Action 2 reduces misinterpretation and protects public trust.

Trade-offs:
Stronger safeguards can increase cost and slow iteration, and may raise barriers for smaller projects. Clear communication can also reduce ambiguity, which is sometimes part of the artwork.

Assumptions / uncertainties:
Technical feasibility and long-term impacts are uncertain, so governance should be staged (start small, learn, then scale) and updated based on evidence.

Audience:
Museum/festival leadership and safety officers; university review boards for art–science collaborations; relevant national regulators.

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? (polymeraseのエラー率は？人間ゲノムの長さと比べると？そのズレを生物はどう解決するか)

Reference URL:

https://pmc.ncbi.nlm.nih.gov/articles/PMC4267634

https://www.genome.gov/genetics-glossary

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/dna-mismatch-repair

https://www.nature.com/scitable/topicpage/dna-replication-and-causes-of-mutation-409/

  • DNA polymerases replicate DNA with very high fidelity, but they are not error-free.
  • Replicative polymerases (with proofreading) are often described as making roughly one error per 106–108 nucleotide incorporations.
  • If we compare this to the human genome (~3 × 10^9 base pairs), polymerase-alone fidelity would imply on the order of tens to thousands of errors per genome replication if nothing else corrected them.

Biology resolves this discrepancy using layered fidelity mechanisms…

  • (1) intrinsic nucleotide selectivity during replication
  • (2) 3′→5′ exonucleolytic proofreading that removes misincorporated bases
  • (3) post-replication mismatch repair (MMR), which recognizes and fixes remaining mispairs

Together, these steps reduce the effective mutation rate to ~10-9–10-10 per base pair.

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?

（平均的ヒトタンパク質をコードするDNA配列は何通りあるのか？なぜ全部うまくいかないのか？）

Reference URL:

  • 遺伝暗号の冗長性（61のsense codonで20アミノ酸）

https://www.sciencedirect.com/science/article/abs/pii/S1046202305000885

  • 平均的（中央値）ヒトタンパク質の長さ：375 aa（BioNumbers）

https://bionumbers.hms.harvard.edu/bionumber.aspx?id=106445&s=n&v=4

  • タンパク質長の分布（参考：ヒト含む、Brocchieri & Karlin 2005）

https://pmc.ncbi.nlm.nih.gov/articles/PMC1150220/

  • コドン最適性がmRNA安定性に強く影響する（codon optimality → mRNA stability）

https://pmc.ncbi.nlm.nih.gov/articles/PMC4359748/

  • 同義コドンがmRNA二次構造・安定性・翻訳速度・折りたたみに影響（NAR review）

https://academic.oup.com/nar/article/41/4/2073/2414416

  • コドンバイアスと翻訳効率の関係（ゲノム規模解析）

https://pmc.ncbi.nlm.nih.gov/articles/PMC2840511/

  • 翻訳効率に対するコドン選択の強い影響（Science 2013）

https://www.science.org/doi/10.1126/science.1241934

  • The genetic code is “degenerate”: many amino acids have multiple synonymous codons.

  • So the same protein can be written in DNA in an astronomically large number of ways (especially for proteins with a few hundred amino acids).

  • But many synonymous versions don’t work equally well because codon choice can change:

    • codon usage vs the host tRNA pool (translation efficiency)
    • mRNA stability and secondary structure
    • translation speed and co-translational folding (protein quality)
    • unintended sequence motifs (accidental regulatory signals, etc.)

Homework Questions from Dr. LeProust: [Lecture 2 slides]

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

（oligo合成で一番よく使われる方法は？）

Reference URL:

  • ATDBio（Solid-phase oligonucleotide synthesis）：

https://atdbio.com/nucleic-acids-book/Solid-phase-oligonucleotide-synthesis

The most commonly used method for oligo synthesis is solid-phase phosphoramidite synthesis.

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

（なぜ200ntを超えると直接合成が難しい？）

Reference URL:

Direct chemical oligo synthesis becomes difficult beyond ~200 nt because each nucleotide addition cycle is slightly imperfect, so the full-length yield drops exponentially as length increases. Errors and truncated byproducts accumulate (including side reactions such as depurination), making it hard to obtain high-purity, full-length oligos at longer lengths.

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

（なぜ2000bpを直接合成できない？）

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”?

(すべての動物に存在する10種類の必須アミノ酸とは何か、そしてこれは「リシン・コンティンジェンシー」に対するあなたの見解にどのような影響を与えるか？)

[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:

（以下の2026年度助成プログラムの概要（各1段落）に基づき、いずれか一つへの回答を概説するか、あるいは独自の回答を考案してください：）

Lysine contingency?? https://jurassicpark.fandom.com/wiki/Lysine_contingency -lysine contingency : biocontainment idea: an organism is designed to survive only when lysine is supplied from the outside.　（リジンがある時だけ生存できる装置のような設計）

Contingency: conditional on / dependent on…lysine-dependent survival

  • Intuitively, if they escape, they should be unable to reproduce in the wild without ricin
  • lysine is widespread in real environments/foods, so lysine-dependence alone can be a weak containment strategy
  • Stronger containment typically requires layering safeguards, such as dependencies on something not found in nature (synthetic/non-natural metabolites or amino acids), rather than relying on a common nutrient alone