Week 1 HW: Principles and Practices
1. First, describe a biological engineering application or tool you want to develop and why.
I want to work with Geobacter bacteria to create a living soil contaminate sensor: where electric signals modulate based on the prescence of heavy metals in the ground. Geobacters are already well studied bacterias that produce electric signals under ground. This makes them a useful organism to modify and use as a biosensor.
Heavy metal soil tests exist but by having living bacteria that emit electric signals one can track the growth and spread of these metals. This can lead to better pollutant mapping and detection of the source of the issue. With genetic engineering we can also customize the bacteria to respond to local problems by genetically modifiying the GeoBacters to respond to specific heavy metals.
The specific mechanism I would study would be how to add a metal-inducible promoter to express the gene in Geobacters related to their electron transfer (electricity) trait. That way the electricity would increase when there are heavy metal contaminants present in the ground and this would be a measurable way of tracking soil health overtime.
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.
Environmental Health: Non-malfeasance to ecosystems. This living soil contaminate sensor will improve environmental health by providing constant monitoring about the state of soil health.
Reduced Inequality: Making the sensors accessible to all. By having a living biosensor that is all around us, it removes the barrier of entry when it comes to education about soil quality. Tracking the changes in electric signals in the modified Geobacters requires limited technology.
Human Health: Protect people from heavy metal exposure. By having constant, easy to understand living soil sensors, communities of people will be empowered with data and knowledge to advocate for better environmental protections from their lawmakers. The monitoring will also allow them to know which parts of their community have been most impacted and how to avoid harmful proximity.
3. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”).
Biocontainment and a Kill-Switch for Geobacters
Purpose: To have a mechanism in place to stop Geobacters from spreading and ruining the balance in the ecosystem they are introduced in. Or to keep them contained in one specific area.
Design: This would involve engineering a specific kill-switch for the modified Geobacter bacteria. This could be having the bacteria be susceptible to a specific type of antibiotic, or making the bacteria be dependent on a specific synthetic nutrient that has to be administered regularly to ensure geobacter survival.
Assumptions: The assumption is that this kind of kill-switch would be effective. And the assumption is that having a specific antibiotic for geobacter would not affect other nearby living organisms.
Risks of Failure & Success: Failure would be if the engineered Geobacteria spread uncontrollably and endangered the balance of the microorganism ecosystem. Success looks like well contained Geobacters that do not harm any other living organism but instead works symbiotically with them.
Open Source Community Science
Purpose: To make sure that the information being collected from the Geobacter soil sensors is open to all members of the nearby communities and beyond.
Design: There would be public dashboards accessible to all that show the data collected by the sensors. There would also have to be open source documentation about how to create your own low-cost “readers” that would be able to evaluate the electronic signals emitted by the sensors.
Assumptions: Communities implicated have basic knowledge of electronics, and have access to digital media.
Risks of Failure & Success: Failure would be if this information became privatized and used in a way that would be harmful or exploitative of local communities. Success would be if all the data collected remained transparent and accessible to all.
Reporting System for High Heavy Metal Levels
Purpose: To ensure that there is a way that authorities are notified when toxic metal detection reaches a dangerous threshold. To encourage action is taken if a threat to human or animal health is detected.
Design: Create a policy where there is a threshold level that activates an alert system either to the local community, the relevant environmental authorities, etc. Also have a trigger that would alert a non-profit or similar body of scientists to verify the findings from the biosensors.
Assumptions: The biosensors are accurate and reporting correctly. There are competent authorities in the area that are able to help restrict dangerous high-contaminant areas, to prevent people from being affected.
Risks of Failure & Success: A failure would be if the system works improperly and gives false negatives or false positives, eroding trust in the biosensors. A success would be if the biosensors report accurately and their findings can be confirmed by a third body in the case of heavy metal detection, and communities and people become more aware of the quality of their soil and issues related to pollution.
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:
| Does the option: | Environmental Health | Reduced Inequality | Human Health |
|---|---|---|---|
| Biocontainment and Kill-Switch | 1 | 3 | 2 |
| Open Source Community Science | 3 | 1 | 2 |
| Reporting System for High Heavy Metal Levels | 1 | 1 | 1 |
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.
Resources
Bazhenov, S. V., Novoyatlova, U. S., Scheglova, E. S., Prazdnova, E. V., Mazanko, M. S., Kessenikh, A. G., Kononchuk, O. V., Gnuchikh, E. Y., Liu, Y., Al Ebrahim, R., Zavilgelsky, G. B., Chistyakov, V. A., & Manukhov, I. V. (2023). Bacterial lux-biosensors: Constructing, applications, and prospects. Biosensors and Bioelectronics: X, 13, 100323. https://doi.org/10.1016/j.biosx.2023.100323
Webster, C. F., Kim, W.-J., Reguera, G., Friesen, M., & Beyenal, H. (2024). Can bioelectrochemical sensors be used to monitor soil microbiome activity and fertility? Current Opinion in Biotechnology, 90, 103222. https://doi.org/10.1016/j.copbio.2024.103222
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?
The error rate of polymerase is 1:106. The length of the human genome is approximately 3.2 gigabase pairs (gbp). This discrepancy is fixed in part by error correcting polymerase that go back and “check their work.” There is also the MutS Repair System which is where a protein (MutS) detects mismatches in DNA and activates other proteins to “cut out” the mismatched protein allowing the DNA polymerase to recreate the missing segment.
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?
There are 20 amino acids in biology. An average human protein is about 300 - 400 amino acids long. An amino acid can have 4 possible codons which means the number of different ways to code for an average human protein would be (using the upper limit) 4400 which is huge. There are many reasons why not all the different codons would work. One of the reasons is some organisms prefere use of certain codons over others. Another reason is that protein folding is sensitive, and not all codon pairings would work.
Homework Questions from Dr. LeProust:
1. What’s the most commonly used method for oligo synthesis currently?
Currently the most commonly used method for oligo synthesis is solid‑phase phosphoramidite. This refers to a way of growing DNA in a way where it is on a stable support using chemically protected DNA letters to create a smooth process.
2. Why is it difficult to make oligos longer than 200nt via direct synthesis?
It’s difficult to make oligos longer than 200nt via direct synthesis because the number of errors accumulates with the length of the oligonucleotide.
3. Why can’t you make a 2000bp gene via direct oligo synthesis?
According to slide 59 there is an error rate of 1:2000 nt. Which means the likely hood of errors in making a 2000bp gene is high and its better to synthesize small fragments and stitch them together later.
Homework Questions 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”?
The 10 essential amino acids in all animals are: phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, histidine, arginine (non-essential for mammals though), leucine and lysine.
The Lysine Contingency is an idea from the fictional book/movie Jurassic Park which was about how engineered dinosaurs could not make their own lysine so they depended on human’s supplementing it for them. So there was a sort of kill-switch for the engineered dinosaurs.
However lysine is already an essential amino acid for animals, meaning they can’t make it on their own and need to supplement it. So the dinosaurs would naturally get lysine from their environment – not such a great fail-safe in the end!