Week 1 HW: Principles and Practices

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 research, or something you are just curious about. Volatile organic compounds (VOCs) are a type of chemical linked to respiratory and cardiovascular diseases, neurological disorders, and cancer. Harmful levels of these chemicals are commonly released into the air by many modern indoor building materials and everyday products, making them especially a serious health hazard to construction and renovation workers who deal with paints, varnishes, and adhesives (among others) in indoor, confined workspaces. Currently, my team (The BTHS Inventeam) is working on a solution that would use bacteria to metabolize captured VOCs and release them as harmless gases. One of our possible ideas is to genetically engineer the bacterial strain(s) we use to increase their effectiveness by enhancing the pathways that the bacteria use to metabolize VOCs.

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.

Goal 1: Prevent harm to environmental and personal health a) Containment and Biosafety Ensure genetically modified bacteria are hyperspecialized and would not be able to survive out of the controlled environment, or at least not compete with native microbes Establish standards for physical containment appropriate to the safety level of bacteria. b) Avoid toxic byproducts Research shows potential for carcinogenic metabolites; the goals of the final product and the protocols for lab work should bear this in mind. Assess how bacterial death could affect health through the released chemicals

Goal 2: Just and equitable access to the invention Prioritize employing the device in areas that are severely affected by VOCs, such as indoor industrial/construction sites Keep costs low and accessible, rather than for wealthy consumers Goal 3: Continually research the invention’s effect on the intended audience/beneficiary community.

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.). 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?

Tiered Biosafety Certification for Engineered Metabolic Strains: (Information taken from Claude, Sonnet 4.5) Federal regulators, such as the FDA and USDA, create certification tiers to authorize the use of GMO organisms. We (or companies in general) must submit pathway data, validate kill-switches, and verify containment before commercial deployment This is a safety measure that regulates the use of GMOs until safety standards are met to prevent environmental escape. However, failure to be accepted by regulators can slow research down

Open-Source Metabolite Monitoring Database As far as we know, there is no standardized database for VOC-bacteria metabolite data. By documenting our data and allowing others to do the same, we would aid in the research of this field Assumption: We looked hard enough and are not unaware of an existing database; the database may or may not need verification of data. Risks: High responsibility to maintain database accuracy

Tax Incentives for Safer Building Materials Tackling the problem at the root cause would reduce VOC exposure of the intended beneficiary community However, transitioning from contemporary building materials may reveal other unintended effects. Incentivized materials must be heavily researched

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. The biosafety option would likely be most prioritized. The safety framework set up by regulators is what the team can most directly implement and would be a logical step in the development of the project. While the regulations might slow down research, they prioritize researcher and worker safety.

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.

The principles of managing equitable access were new to the team. Introduction of the invention must account for the price and feasibility of implementation in relatively less developed worksites. Analysis of cost must be done for the utilization of the invention, as it will likely not just have to be affordable, but also less expensive than other measures or outcomes.

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? The error rate of DNA polymerase, the enzyme that copies DNA, is about 1 mistake per 100,000 base pairs. Since the human genome has around 3 billion base pairs, this means that theoretically there could be around 30 million errors. Though biology has a way of dealing with this. There are mechanisms that are like proofreading and that correct a lot of these errors during replication. The DNA repair systems can fix the mistakes that may slip through. So even though the errors can happen, the body keeps up and works hard to make sure that the genome is accurate.

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? The genetic code is redundant. This means that multiple codons can code for the same amino acid. There are 64 possible codons. But there are only 2 amino acids that are used to make proteins. So there are actually many ways to code for the same protein. However, not all the combinations work perfectly because of outside factors. Codon bias, where some codons are used more frequently than others in certain species. mRNA stability and how efficient the translation is. Further, some codons can be more susceptible to errors or not fit well within the body’s translation inner workings.

Homework Questions from Dr. LeProust: [Lecture 2 slides] What’s the most commonly used method for oligo synthesis currently? The most commonly used method for oligo synthesis is solid-phase chemical synthesis. Why is it difficult to make oligos longer than 200nt via direct synthesis? Making oligos longer than 200 nucleotides is difficult because the longer the sequence becomes, there is greater the chance that errors will occur during the synthesis. Why can’t you make a 2000bp gene via direct oligo synthesis? Making a 2000-base pair gene via direct oligo synthesis is pretty impractical because of the accumulation of errors. The longer the sequence is, the more likely to is that mistakes will occur. The synthesis of such a long sequence is pretty likely to be expensive and time-consuming.

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”? [Given slides #2 & 4 (AA: NA and NA: NA codes)] What code would you suggest for AA: AAinteractions? The 10 essential amino acids that animals must get from their diet are Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine, and Arginine. The contingency is a situation where lysine becomes scarce in an environment, which can cause issues in an organism’s ability to produce proteins. This could also pose a challenge when animals or humans do not intake lysine in their diet. So it shows the importance of having a balanced intake of all the essential amino acids. We can’t make them, so we need to get them from food. The imbalances can create some health issues.