Week 1 HW: Principles and Practices

GOVERNANCE MODELING

1. For this course, I’m planning a small-scale experiment around phytomining – a technique growing in popularity to extract metals from abandoned mine sites and petrochemical byproducts. Phytomining employs a special type of plant called a ‘hyperaccumulator’ to grow in a soil substrate rich in a particular metal. Scientists have identified hundreds of species of hyperaccumulators that can extract metals ranging from copper, nickel, cobalt, and even rare earth metals. However, this process is not widely used as an alternative to mining, due to the relatively long grow times required by plants, and the small amounts of metal that are eventually extracted. Additionally, research is being done to determine what/how microbial activity in the soil speeds along this process. **The project I’m interested in undertaking this semester is the development of a microbial species that can grow, “digest,” and extract metals at a faster pace, designed with the goal of it being used alongside phytomining for large scale bioremediation projects.

2. The main ethical quandry with this research is in the production of a synethetic/‘vector’ soil bacteria strain, and how it responds to and affects the biota it will belong to if allowed to grow outside of the lab. Goverance outlining containment strategies need to be outlined, including soliciting regular studies to see how this microbe responds to various stimuli, and under what conditions ensure protection against leaching. I’m also interested in the end markets for metals extracted this way. Many start ups that are pursuing this route have contracts with the US Department of Defense, for (most probable) use of these critical metals in defense technologies that are deployed or experimented with in war zones. Instead, I’m interested in the use of these extracted metals for advancing products that our typical, linear means of production: how can this technology be used to support companies and individuals who are invested in the circular economy, and interested in building repairable consumer technology (phones, laptops) or human-scale renewable energy products?

3. Potential actions

   • Patent the bacteria strain and license it to companies that have partnerships with companies and institutional labs that are B-Corp, Biomimetic, or TRUE Waste certified The purpose of this intervention is to pair bio-assisted extraction with organizations who have a keen interest in regenerative technologies. This intervention would borrow “terms of use” clauses in its patenting process. I recognize that patents are only viable for 20 years, and the technology, if not upgraded and reissued a patent, could belong to anyone after that set time.
   • Establish NSF funding paths specifically for investigating how this engineered microbe interacts in different climatic zones The purpose of this intervention is to establish a working relationship with universities and researchers to carry out the ‘uglier’ side of technological discovery: performing rigorous validity tests with increasing coverage to understand how this strain performs in (simulated) wild environments.
   • If using CRISPR, establish a limit to how many times this microbe can replicate Establishing a ‘kill switch’ further ensures that this synethetic strain doesn’t become a permanent strain, forever replicating in the environment. This likely would slow down research in the lab, if a new batch of this bacteria has to be grown from a starter mix, but it will better ensure containment.

4. See scoring sheet below:

5. I would prioritize the first action, limiting the use cases of metals extracted via this process, and the third, establishing a “kill switch” to prevent the generations of replications allowed for the bacteria.

   I priotize the first because of moral alignment, and because it restricts who gets access to this technology will allow for outbreaks to be traceable. The second because it plans for the worst case scenario. It’s designed for an audience of citizen scientists and institutional scientists opposed to the funding sources that accompany large research institutions. One downside of this method is that likely won’t benefit from the resources offered by partnering with large defense companies and departments, leading to a potential for stalled research.

   The third action is designed largely for research instutions and the landowners with high metal content in their soil, and by extension, EPA, NRDC, other environmental governance organizations, and the other inhabitants of a given biome. It begs the question - under what circumstances will a synethetic strain of bacteria be allowed to be intergrated into the wild?

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?
      - The error rate of polymerase is 1:10e6, or 1 out of every million base pairs (Mbp) (slide 8). The human genome has around 3.2 Gbp (slide 10). Polymerase has built in mechanisms that allow it to proofread the sequence and replace errors (slide 8). Because nucleotides have distinct pairs (A to T and C to G), errors are caught and the polymerase is allowed to try again to placing the corresponding nucleotide to form a bp.

  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?
      - Note: I struggled to find this answer in the slide deck, but when I visited the link in slide 6 ("Mathematical modeling and comparison of protein size distribution in different plant, animal, fungal and microbial species...proteomes"), I noted that they referenced 64 ways to encode an amino acid. If the question concerns the building blocks of proteins, there are 64 ways to code an average human, given that we have 4 nucleotides to start with. In that same paper, the researchers mentioned that stop codons are "biased towards A and T," which could cause a protein to be cut short before being completely coded.

From Dr. LeProust

  1. What’s the most commonly used method for oligo synthesis currently?
      - Phosphoramidite DNA Synthesis Cycle (slide 7)

  2. Why is it difficult to make oligos longer than 200nt via direct synthesis?
      - This process is far more prone to error that polymerase, 1:10e2 (slide 6). This error limits the number of nucleotides that are possible to be made accurately.

  3. Why can’t you make a 2000bp gene via direct oligo synthesis?
      - The 10e2 error rate also requires quality control that further limits the amount of nucleotides possible based on how many nucleotides a spectrometer can accommodate. Source: https://www.lubio.ch/blog/the-challenge-of-making-long-oligos

From Professor Church

  1. 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”?
      - 10 essentials: Arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine (Wikipedia). I don't know enough about these amino acids (yet!) but I'm curious why lysine was singled out + whether this fictious model is used when genetically altering species, like in CRISPR. Did Jurassic Park influence protocols around genetic engineering standards?