Week 1 HW: Principles and Practices

1. Glowing Leather as a pilot for decentralized biomanufacturing of goods Bacterially produced leather is currently in the stage of being scaled up in centralized biomanufacturing plants around the world utilizing waste feedstocks from agricultural sources. Smaller scale experiments utilize kombucha SCOBYs to produce bacterial leather however they face variability in leather quality due to different growing conditions, feedstock, and SCOBY relationships in regards to each individual member’s reaction to the feedstock/growing conditions. The genetic drift that the SCOBY undergoes specifically the K. xylinus also makes it unreliable for consistent bacterial leather production.

I am interested in exploring the development of an open source decentralized protocol to make growing bioleather easier, more climate resilient than growing cows, and more equitable than current centralized operations.

2. Policy goals Our application being more systems based, I would like to promote:
   1. equitable use
      1. making sure that this technology is developed to minimize regulatory/IP hurdles
      2. create this technology so that its deployment may be done frugally by the end users
   2. minimizing regulatory and physical harm to users
      1. create/implement unobtrusive and robust licensing to encourage use
      2. utilize GRAS and/or BSL-1 organisms to minimize negative effects due to possible user error
   3. creating eco friendly supply chains.
      1. Utilize existing waste streams
      2. seek to use processing methods that do not produce toxic byproducts
      3. carbon neutral power sources and manufacturing methods (blue-sky option)
3. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”)
   1. Govt Regulatory Agencies
      1. Establish regulations and standards for the importation and use of GMOs
      2. Existing monitoring infrastructure for registered users of GMOs
      3. Advocate for countries to utilize a simplified and straight forward regulations for BSL-1 organisms
   2. Distributed Operations Network + Strain Banks
      1. Create and distribute certified sachets with starter culture to create bacterial leathers
      2. utilize a fluorescent reporter to verify the status/activity/viability of any given strain
      3. propagate the strain bank to regional banks in order to establish supply chain resiliency.
   3. Global Academic researchers
      1. develop strains for bacterial leather production that comply with ease of use guidelines
      2. require publishing to open source databases and open source licensing
      3. create global networks of test labs for low throughput validations and characterization optimizing for low volume and rugged deployment
      4. iterate on protocols to promote cross-lab reproducibility

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. 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.

Our action plan would first prioritize organizing a global collective of interested scientists and engineers (perhaps at HTGAA!) to develop the deployment protocol that takes into account regulatory actions, equitable use, and licensing considerations. This would allow us to organize the foundational work needed for deployment. Our main deliverable would be a published and verified protocol that would allow us to distribute our findings for use in an open source license.

We would then prioritize interfacing with regional regulatory bodies in order to further refine protocols for use in target regions using a BSL-1 organism.

In order to find revenue we would seek to target luxury goods and create a beachhead market and further fund distributed deployment of manufacturing. More research is needed but our main tradeoff would be international regulatory work would have to wait until initial revenue or funding is secured.

AI usage Summary can be found here

Week 2 Pre Reading

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 throughput error rate is 1:“10^6 and 10mS per base addition length of the human genome is 6.2 bil base pairs.

• Biology deals with this by having the polymerase be able to error correct in addition to having other proteins correct remaining errors. On slide 14 it describes the MutS repair system.

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 average human protein is 1036bp (345 amino acids). Due to how the dna folds at different structures it can change the shape of the DNA and RNA cleavage sites are variable.

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

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

• Phosphoramidite.

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

• It is difficult to make because the coupling process process if it has an error it would be replicated 1 to 4 times and once you get up to 500 replications any errors would be increase the yield decay.

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

• Due to the replication issues one would make 40nt segments and stitch them together to create a 2000bp gene with less errors

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”?

• Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine

• Turns out in the Jurassic Park franchise they’re just eating Lysine from sources in the environment.

• Would be more prudent to use an amino acid that’s not available in nature and controllable.