Week 1 HW: Principles and Practices

1. First, describe a biological engineering application or tool you want to develop and why. This could be inspired by an idea for your HTGAA class project and/or something for which you are already doing in your research, or something you are just curious about.

Biosensors for Animal Health

I aim to develop molecular diagnostic biosensors for veterinary medice. Specifically, I am interested in creating biofluorescent biosensor kits capable of detecting animal pathogens in rural and remote areas. This application is particularly relevant in countries such as Peru, where many communities lacated far from urban centers depend on livestock for their livelihood but face limited access to laboratory diagnostic services. This often leads to delayed diagnoses and significant economic losses due to infectius diseases.

The biosensor would integrate a specific biological recognition element with a luciferase-based reporter system. When the target pathogen or its genetic material is present in the sample, it specifically interacts with the biological component of the biosensor. This interaction actives the luciferase enzyme, which catalizes a reaction that produces light. The chemical reaction underlying the proposed biosensor is based on a bioluminescence process in whitch an enzyme catalyzes the transformation of substrate, releasing energy in the form of light. To generate this luminescent signal, the luciferase enzyme is activated in the presence of a pathogen or biomolecule. This mechanism offers several advantages, including high sensitivity and rapid results compared to other molecular techniques. Furthermore, it enable non-invasive observation of biological processes and the detection of pathogens in animals.

Figure 1. AI-generated image created using Ideogram

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. Below is one example framework (developed in the context of synthetic genomics) you can choose to use or adapt, or you can develop your own. The example was developed to consider policy goals of ensuring safety and security, alongside other goals, like promoting constructive uses, but you could propose other goals for example, those relating to equity or autonomy.

Objective 1: Minimizing Harm Throught Safe Biosensor Design and Deployment This objective is essential to ensuring the principle of non-maleficience, meaning that the design and implementation of the biosensor must prioritize the prevention of harm to animals and the environment. Specific objectives - Establish biosafety guidelines for the use of pathogenic biological components and containment strategies. - Promote responsible use and ensure that biosensor is use for veterinary diagnostic purposes through user guidelines and target training,

Objective 2: Promoting fair and Inclusive Access Policies should promote the affordability and accessibility of the technology for small-scale livestock farmers.

3. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”). Try to outline a mix of actions (e.g. a new requirement/rule, incentive, or technical strategy) pursued by different “actors” (e.g. academic researchers, companies, federal regulators, law enforcement, etc). Draw upon your existing knowledge and a little additional digging, and feel free to use analogies to other domains (e.g. 3D printing, drones, financial systems, etc.).
   1. Purpose: What is done now and what changes are you proposing?
   2. Design: What is needed to make it “work”? (including the actor(s) involved - who must opt-in, fund, approve, or implement, etc)
   3. Assumptions: What could you have wrong (incorrect assumptions, uncertainties)?
   4. Risks of Failure & “Success”: How might this fail, including any unintended consequences of the “success” of your proposed actions?

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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:

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.

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.

🌿 My Reflection

Completing this task allowed me to become more aware of the ethical considerations involved in implementing a technology within a specific context. I came to understand that such implementing a technology within a specific context. I come to understand that such implementation requires close collaboration between researchers and government institutions to establish safaty protocols that ensure animal health.In addition, effective public policies are necessary to promote appropriate and equitable use in order to fulfill the mission of applicability in rural settings.

References:

• Biosensor Technology:https://doi.org/10.3390/vetsci12010023

• Advanced biosensors for detection of pathogens related to livestock and poultry :https://doi.org/10.1186/s13567-017-0418-5

Use of IA: deep reasearch : https://chatgpt.com/s/dr_698ab1fc72a88191b55e54fda9f92527 ChatGPT (OpenAI) was used as a support tool to analyze and organize the following prompts:

• Identification of the most common diseases in domestic animals in Peru that require molecular diagnosis and present high clinical demand.

• Exploration of current global solutions for these diseases within the fields of synthetic biology, biotechnology, and biological engineering.

• Detailed explanation of the molecular and biological mechanisms underlying these technological solutions.

• Comparative evaluation of isothermal molecular diagnostics (RPA and LAMP) and biosensor-based diagnostic approaches.

• Identification of relevant scientific literature supporting isothermal amplification methods and biosensor technologies.

  All interpretations, critical analysis, and conclusions derived from these prompts are the author’s own.

Assignment (Final Project) – Due as part of your Final Project presentation (not Feb 10)

As part of your final project, design one or more strategies to ensure that your project, and what it enables, contributes to growing an ethical biological future.

Assignment (Lab Preparation) — DUE BY START OF FEB 10 LECTURE

Lab Training (failure to complete this will jeopardize your acceptance into the course)

• Complete Lab Specific Training in Person.
• Complete Safety Training in Atlas
  • Navigate to atlas.mit.edu and on the right-hand side, click “Learning Center”
  • Head to the Course Catalog and find the following two courses:
    • General Biosafety for Researchers (EHS00260w)
    • Managing Hazardous Waste (EHS00501w)

Assignment (Week 2 Lecture Prep) — DUE BY START OF FEB 10 LECTURE

In preparation for Week 2’s lecture on “DNA Read, Write, and Edit," please review these materials:

1. Lecture 2 slides as posted below.
2. The associated papers that are referenced in those slides.

In addition, answer these questions in each faculty member’s section:

Homework Questions from Professor Jacobson: [Lecture 2 slides]

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 natural polymerase is aproximatly 1 in 10^6 nucleotides. When this is compared to the human genome (3 billion base pairs) the discrepancy is significativa. It is important to emphasize the mechanisms used by cells, particularly enzymes such as exonuclease 3-5 and exonuclease 5-3

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, which can generate a large number of comabinations. Nevertheless, some factors limit functionality, such as extreme GC content homopolymers, and free energy.

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

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

   Currently, the phosphoramidite method is the most commonlty used approach for oligonucleotide synthesis. This technique was introduced by Caarathers in 1981. This chemestry process involves the sequential addition of nucleotides onto a polymer-supported chain.

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

The first limitation is yield. In some cases, the error rate can reach approximately 1 in 100. As a result, the yield decreases exponentially with each additional base. Another important limitation is error accumulation. Chemical synthesis has a higher error rate than synthesis performed by biological polymerases.

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

Las principales razones se deben a la complejidad de la secuencia de 2000 pb que las regiones poco visibles tienen contenido GC muy alto o bajo. Otro aspecto es el rendimiento ya que el metodo de fosforamidita no funcionaria con eficiencia.

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.

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”?

The 10 essential amino acids are Lysine(K),Leucine(L),Arginine (R), Histidine (H), Methionine(M), Isoleucine (I),Tryptophan (W), Threonine (T), Valine (V), Phenylalanine (F). The lysine contingency is Lysine Contingency functions as a genetic safaty mechanism. In my view, this idea presents interesting implications. First, desingning an organism that lacks an essential amino acid, as it would be considered biologically fragile from the outset.That is, it creates the illusion of a biological switch; howeve, even in the hypothetical case that it works,the organism would be too fragile under normal conditions, as it would depend entirely on dietary availability, leading to imbalance and massive metabolic constraints. From a synthetic biology perspective, it is important to incorporate additional safety features such as dependence on non-standard amino acids for engineered organisms.

References:

• USE OF IA : https://chat.deepseek.com/share/akupvqutdgu3uhjvif

• Amino acids: metabolism, functions, and nutrition:https://pubmed.ncbi.nlm.nih.gov/19301095/

3. [Given slides #2 & 4 (AA:NA and NA:NA codes)]   What code would you suggest for AA:AA interactions?
4. [(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:
   • https://arpa-h.gov/explore-funding/programs/boss
   • https://www.darpa.mil/research/programs/smart-rbc
   • https://www.darpa.mil/research/programs/go

Assignment (Your HTGAA Website) — DUE BY START OF FEB 10 LECTURE

1. Begin personalizing your HTGAA website in in https://edit.htgaa.org/, starting with your homepage — fill in the template with information about yourself, or remove what’s there and make it your own. Be creative!
2. As with all assignments in HTGAA, be sure to write up every part of this Homework on your HTGAA website in order to receive credit.