Week 1 HW: Principles and Practices

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

I am interested in developing a biological engineering approach that uses living organisms to help us understand and preserve archaeological materials and sites. Specifically, I want to explore how microorganisms could be used to study how materials such as stone, soil, or ceramics change over time, or how biological growth can be guided to protect fragile archaeological surfaces.

This idea is interesting to me because archaeological materials are shaped by long-term interactions between the environment and living systems. Instead of seeing biology only as a source of damage, I am curious about how biological processes could become a tool for analysis or conservation. For an HTGAA project, I want to explore how growth, decay, and environmental conditions can be treated as design variables to better understand the past and develop new, more sustainable conservation methods.

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.

One key governance and policy goal for this application is to ensure that biological tools used in archaeological contexts do not cause harm to people, sites, or cultural heritage. Because archaeological materials are fragile and often irreplaceable, it is important that biological interventions are carefully controlled and ethically guided.

A first sub-goal is non-malfeasance, meaning preventing physical or biological damage. This includes ensuring that any microorganisms used cannot spread uncontrollably, alter archaeological materials in irreversible ways, or disrupt surrounding ecosystems. Strict containment, reversibility, and testing protocols would be essential before any real-world application.

A second sub-goal is cultural and community respect. Archaeological sites are often connected to living communities and cultural identities. Governance frameworks should ensure that local stakeholders are informed, consulted, and involved in decisions about the use of biological technologies on heritage sites. This helps prevent extractive or colonial practices and supports ethical collaboration.

A third sub-goal is responsible knowledge use. Research outcomes, data, and tools should be shared transparently for conservation and educational purposes, while avoiding misuse, commercialization without consent, or applications that prioritize novelty over preservation. Together, these goals help ensure that biological engineering contributes to an ethical, respectful, and sustainable future for archaeology.

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

Action 1 : Ethical Review Requirement for Biological Interventions in Archaeology

(New rule / requirement — actors: universities, museums, heritage authorities)

• Purpose Currently, ethical review processes mainly focus on research involving humans, while biological interventions on archaeological sites are often evaluated only for scientific merit. I propose creating a specific ethical review requirement for any use of living organisms in archaeological contexts, focused on protecting sites, materials, and surrounding ecosystems.

• Design This action would require interdisciplinary review committees including archaeologists, biologists, conservation experts, and ethicists. Universities, museums, and heritage authorities would require approval from these committees before allowing biological tools to be tested or deployed at archaeological sites. Researchers would opt in by agreeing to this process as a condition of site access.

• Assumptions This proposal assumes that such committees can be formed with sufficient expertise and that ethical review will meaningfully guide research rather than becoming a purely bureaucratic step. It also assumes researchers will accept additional oversight.

• Risks of Failure & “Success” This approach could fail if reviews become symbolic or overly slow, discouraging exploratory research. If highly successful, it could unintentionally favor large institutions with more resources, making it harder for smaller or community-based projects to participate.

Action 2: Incentives for Reversible and Low-Risk Biological Methods

(Incentive — actors: funding agencies, research sponsors)

• Purpose At present, research funding often prioritizes novelty and impact over safety, reversibility, or long-term risk. I propose creating funding incentives that prioritize biological methods which are reversible, low-risk, and environmentally contained when used in archaeological contexts.

• Design Funding agencies and foundations would include ethical and safety criteria in grant calls, explicitly rewarding projects that minimize ecological and cultural risk. Researchers would voluntarily design projects to meet these criteria, and reviewers would need guidance on how to evaluate risk and reversibility alongside scientific merit.

• Assumptions This proposal assumes that funding incentives can meaningfully influence research behavior and that risk can be reasonably assessed in advance. It also assumes that safer approaches will still allow for meaningful scientific insight.

• Risks of Failure & “Success” The action may fail if incentives are too weak or applied superficially. If overly successful, it could discourage more experimental or unconventional approaches, potentially slowing innovation in the field.

Action 3: Community Co-Governance of Bio-Archaeological Applications

(Governance strategy — actors: local communities, researchers, heritage organizations)

• Purpose Decisions about technological interventions at archaeological sites are often made by researchers or institutions, with limited involvement from local or descendant communities. I propose a co-governance approach in which communities connected to archaeological sites participate directly in decisions about the use of biological tools.

• Design This would involve early consultation processes, accessible communication (non-technical language), and shared decision-making authority. Researchers and institutions would need to allocate time and resources to support meaningful participation and be willing to adapt or halt projects based on community input.

• Assumptions This approach assumes that communities wish to participate, that diverse perspectives can be reconciled, and that scientific and local knowledge can productively inform each other.

• Risks of Failure & “Success” Co-governance could fail if participation is symbolic rather than meaningful or if internal conflicts arise. If highly successful, it may slow down research or limit certain projects, but this may be an acceptable trade-off in contexts involving irreversible cultural heritage.

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:

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 a combination of Option 1 (Ethical Review Requirement) and Option 2 (Incentives for Reversible and Low-Risk Methods). This recommendation is directed to international organizations such as UNESCO and the United Nations, which play a key role in setting global norms for cultural heritage protection and emerging technologies.

Option 1 should function as a global baseline. It scores highest in preventing biosecurity, lab safety, and environmental harm, which is especially important for archaeological sites that are fragile and irreversible. An international ethical review framework, supported by UNESCO and the UN, could guide national and local authorities while allowing for contextual adaptation. The main trade-off is the potential increase in administrative complexity and slower research approval processes.

Option 2 should complement this baseline by encouraging safer and reversible biological methods through funding priorities and international research programs. This incentive-based approach preserves flexibility and innovation while reinforcing ethical behavior.

Option 3 (Community Co-Governance) should be promoted by UNESCO and the UN as a guiding principle, particularly in culturally sensitive contexts. While it may reduce speed and scalability, it strengthens legitimacy, equity, and long-term trust in the governance of biological tools applied to archaeology.

This approach assumes that UNESCO and the UN can influence national policies through standards, funding, and guidance, but there is uncertainty around consistent adoption and enforcement across different regions.

                       - 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 polymerase is the enzyme that copies DNA. It is very accurate, but not perfect:

• It makes about 1 mistake in every 10 million DNA letters.

• With correction systems, the final error rate is about 1 mistake in 1 billion letters.

The human genome has about 3 billion DNA letters, so without correction there would be many mistakes every time DNA is copied. How does biology fix this?

• DNA polymerase checks its own work (proofreading).

• Cells have repair systems that fix mistakes.

• Harmful mutations are reduced over time by natural selection.

3. 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?

Because the genetic code is made of three-letter codons and there are 64 possible codons but only 20 amino acids, most amino acids can be encoded by more than one codon. This means that the same protein can be written in many different DNA sequences. For an average human protein, the number of possible DNA sequences that could code for it is extremely large.

However, in practice, not all of these DNA sequences work equally well. Some codons are translated more efficiently in human cells, while others slow down protein production. Certain DNA sequences can form mRNA structures that interfere with translation or make the mRNA unstable. In addition, some sequences can disrupt regulatory signals or affect how the protein folds during synthesis. As a result, only a subset of possible DNA codes is actually effective for producing the desired protein in cells.

Homework Questions from Dr. LeProust:

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

Oligos are made using a chemical method where DNA is built one letter at a time on a solid surface. This method is called phosphoramidite synthesis, and it is the standard method used today.

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

Each time a new DNA letter is added, there is a small chance of error.When the oligo gets longer, these small errors add up. Because of this:

• Many DNA strands end up incomplete
• Many have mistakes
• Very few are perfect full-length oligos

After about 200 nucleotides, the number of correct oligos becomes very low.

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

To make a 2000 bp gene, you would need to add 2000 DNA letters in a row. With so many steps, almost every DNA molecule will contain errors. So, direct synthesis does not work for long genes. Instead, scientists make short oligos and then join them together to build long genes.

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”?

Animals need 20 amino acids to make proteins, but they cannot make all of them. The 10 essential amino acids (they must come from the diet) are: Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine, and Arginine (Arginine is essential especially during growth.)

Because animals cannot make these amino acids themselves, they depend on their food to get them.

The “Lysine Contingency” refers to the idea that lysine availability strongly limits animal growth, especially because lysine is often low in plant-based foods. Since lysine is essential and cannot be synthesized by animals, a lack of lysine can directly restrict protein synthesis and growth. This highlights how animal biology is dependent on plants and microbes, which can make lysine. It supports the idea that animal evolution and nutrition are constrained by the availability of lysine in the environment.