Week 1 HW: Principles and Practices

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1. First, describe a biological engineering application or tool you want to develop and why.

My plan for the final project is a synthetic membrane that has Mesenchymal Stem Cells Microvesicules (which have scientifically proven regenerative and other positive properties) intercalating inbetween the membrane’s layers. Which could be used for burn wounds and/or donation organs preservation while in transportation.

I can’t seem to see much possibility for malfeasance after proper testing. But the two biggest questions that arise are: Reproductibility and Universal (or almost) access to the treatment. A. Reproductibility: This step is essential to make sure that the design is simple enough to be able to be reproduced by as many labs as possible even in the harshest conditions. Sub goals: Testing and optimizing the design so it uses the simplest technology possible. Trialing in several conditions and labs across the world.

B. Ensuring universal access: This step is to make sure that, after proper testing, the therapy is accessible by the general population and not just a select few. Sub goals: Collaboration with public health systems globally. Ensuring no malicious patenting of the design can be made.

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

Action 1: Creation of a bioethics and biosafety commitee; Purpose: Making sure that every material is non-harmful and is in fact composed of what it is expected to. Example: Making sure that the MV’s are indeed microvesicules and that their content is beneficial to health. Design: Proper lab testing protocols such as Flow Cytometry, Electron Microscopy and such; And parameters for consistency in the design. Risk of failure and “success”: Failure: the output is not as expected and the consistency of the therapy can’t be guaranteed. Success: the design is properly tested and may be applied to patients willing to test.

Action 2: Implementation of proper trials and validation; Purpose: Testing the therapeutic with willing and acknowledging subjects to ensure that the effects are real, beneficial and consistent. Design: Double blind studies. Risk of failure and “success”: Failure: the therapeutics has no effect or is harmful to whoever is subjected. Success: the effects are, in fact, benign and consistend independent of characteristics of the patient.

Action 3: Preemptive adoption of a framework for dealings with regulatory organs; Purpose: Making sure that, after the testing is done, the therapy can be introduced to as many patients as possible while being in concordance with local regulations. Design: Keeping proper documentation of all design steps, dialoguing with regulatory organs to plan proper introduction to new patients. Risk of failure and “success”: Failure: the design is proper and has effects but it can’t be introduced due to not fitting regulations. Success: the design is introduced properly to more populations.

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. The following is one framework but feel free to make your own:

Does the option:Option 1Option 2Option 3
Enhance Biosecurity
• By preventing incidents1n/an/a
• By helping respond1n/an/a
Foster Lab Safety
• By preventing incident2n/an/a
• By helping respond2n/an/a
Protect the environment
• By preventing incidents11n/a
• By helping respond13n/a
Other considerations
• Minimizing costs and burdens to stakeholders231
• Feasibility?121
• Not impede research121
• Promote constructive applications311

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

I would prioritize making sure that international and national regulations do not become an obstacle for the application of the therapy. While it may seem idealist to aim for it, I believe in universal healthcare and the feasability of more accessible therapies.

6. 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.

Mainly the use of creatures (animals and others) that may not consent to their usage in research. For governance actions, regulations and societies and maybe even the general public should make sure that the subjects of the research are treated in the most humane way possible.

Week 2 lecture preparation

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?

1:10⁶. The human genome consists of about 3.2 billion base pairs. The discrepancy is dealt with using proofreading mechanisms and other corrective measures.

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?

According to uniprot the average human protein consists of about 400 aminoacids. Most AA’s have multiple codons which encode them (being redundant). That makes it so that there are more possibilities of DNA coding than humanly possible to consider. In practice, some of the reasons why they wouldn’t work are: codon usage bias (some codons are preferred due to optimal functioning), formation of CPG islands promoting methylation and thus leaving the DNA useless. Other reasons include structural integrity and such…

Dr. LeProust:

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

Phosphoramidite chemistry on solid-phase synthesizers

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

Could not find this in the slides, had to make use of the emergencial AI resource through the use of Deepseek AI (Where I just made the same question as the homework). Apparently, it is because the efficiency of coupling is not 100%, accumulating various errors and unwanted reactions after said length.

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

Reffering to the answer above… The actual yield would be too low. Deepseek said that that’s the reason why “synthetic biology relies on assembly methods rather than direct synthesis for genes and long constructs.”

Mr. George Church:

6. [(Advanced students)] Given the one paragraph abstracts for these real 2026 grant programs sketch a response to one of them or devise one of your own:

I chose the BoSS – BioStabilization Systems program from Arpa-H. My response towards this problem would be to employ AI to find more stable molecular structures of existing or even of new proposed drugs. Simulating responses towards a multitude of different conditions, and trying to predict different environmental parameter threshholds that are supported by the molecules.