Week 1 HW: Principles and Practices

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HTGAA Homework 1

Describe a biological engineering application or tool you want to develop and why:

Bioremediation of heavy metal contamination from soils in former industrial, or military areas to allow for future development.

At present there are an estimated 1,340 superfund sites on the EPA’s National Priority List (NPL) in the United States and according to a 2023 study, 23 million people live within 1 mile of a site.

I come from an architectural background and have a passion for reuse and restoration. I have watched the attempts, successes, and mistakes made during the remediation processes at some former superfund sites that have since gone on to be used as multi-unit housing, and commercial sites. Many of these sites used traditional removal and sequestration practices that disturbed topsoil and introduced contaminants into the surrounding air and water, creating toxic conditions for new residents.

I am interested in the use of engineered bacterial biofilms to remediate as much of the heavy metals present as possible to allow for access to previously uninhabitable land to allow for construction of housing, new community infrastructure, and other resources.

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-goal:

Goal 1: Prevention of harm to flora and fauna

  • Bioremediation would require the introduction of engineered bacteria, such as B. subtilis, that is capable of not only thriving in the soil but also in the roots of plants, that could result in unintended and harmful consequences.

    1. Establish testing protocols before introduction into the environment.
    2. Establishment of a biosafety certification

Goal 2: Accessibility allowing use for diverse development

  • This must be developed in a way to remain an approachable alternative to conventional remediation techniques in order to allow for development of otherwise inaccessible land for all socio-economic groups.

    1. Find charitable stakeholders willing to subsidize research and testing.
    2. Keep all research and findings open source

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

Action 1. Transparency & education for public knowledge

  • Purpose: Develop transparent protocols for development and testing that allow for public transparency at all levels.
  • Design: Establish oversight and peer review
  • Assumptions: Misunderstanding of existing review mechanisms.
  • Risks of Failure: Public fear regarding bioengineering

Action 2. Establishment of funding

  • Purpose: Attract institutional, or private funding for development of an accessible process
  • Design: Work with stakeholders with an interest in earth regeneration or restoration
  • Assumptions: Funding exists to allow for this work
  • Risks of Failure: Lack of capital. Lack of interest.

Action 3. Establishment of oversight and cooperation with existing governance

  • Purpose: Work with existing regulatory organizations
  • Design: Create a board of scientists and stakeholders to enforce governance
  • Risks of Failure: restrictive regulatory environment.

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:

Governance Graphic Governance Graphic

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.

The best chances of success for this require the prioritization of transparency and oversight, without which the availability of funding, public opinion and approval of outside governance will be possible. Assuming that any public communication or work with larger regulatory bodies will take time and multiple iterations towards approval, this process could take some time before it becomes available. This work was done without an extensive review of available in-situ engineered bioremediation strategies, and as such can assume that there are a number of existing or in research solutions that could achieve the same ends, but that might not meet the criteria of transparency and availability to all socio-economic classes.

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 majority of ethical concerns within this process were the possible effects of the introduction of an engineered bacteria into an uncontrolled and future publicly accessible area. Without foreknowledge of the mechanisms of the synthesis, and release of this, I was and largely still am in the dark. I was pleased to learn about the existence of regulatory bodies that review these concerns in various capacities and was able to find a number of papers outlining the creation of bioengineered bacteria that met the criteria for treatment of contaminated soils. I would without a doubt work with the existing regulatory bodies and establish a group dedicated to public transparency and education to encourage the use of safe and effective solutions for soil treatments.

Week 2 Homework Questions

  • 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?
  • 1:10e6 . The human genome is cited as 3.2:10e9 . Biology relies on the MutS repair system to identify and repair mismatched base pairs.
  1. 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?

  • Slide 6 references 1036bp for average human protein. I’m uncertain about this question, but if this refers to human proteins, I can see that there are error correction issues at longer lengths, and that existing human protein sequences contain encoding that would contribute to them not folding correctly for another application.

  • Dr. LeProust

  1. What’s the most commonly used method for oligo synthesis currently?
  • Phosphoramidite chemistry
  1. Why is it difficult to make oligos longer than 200nt via direct synthesis?
  • Though Phosphoramidite chemistry has a high degree of accuracy (`>99% per coupling), the small errors accumulate and approaching 200nt become disproportionate to the whole.
  1. Why can’t you make a 2000bp gene via direct oligo synthesis?

  • Again, error limitations in a combined fragment 2kbp gene. (I did find other citations citing higher limits)

  • George 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”?
  • Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valine
  • OK. If we’re talking Jurassic Park here.. Lysine is readily available in nature (and required by all animals to survive) from animal meat, so carnivore/omnivores would have no issues, and herbivores could find it readily in vegetation in varying amounts. You’re gonna need a bigger boat for that BS, Dr. Arnold.