Week 1 HW: Principles and Practices

📝 Homework — Due by start of Feb 10 lecture

Description

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 you are already doing in your research, or something you are just curious about.

Proposed Application

I would like to develop synthetic engineering technology that allows for the diagnosis of dengue cases (DENV-1, DENV-2, DENV-3, DENV-4) in sand flies or mosquitoes (Aedes aegypti) directly in the environments where these vectors live.

This is because dengue is a pandemic, epidemic disease in tropical and subtropical regions of the world. One of these regions is the Ecuadorian Amazon, where, despite efforts to promote development, public health remains a major challenge.

This is especially true for dengue, for which there is no widely effective vaccine, and treatment is mainly based on hydration. Determining the specific dengue serotype would allow us to carry out epidemiological analyses and prevent increases in the number of cases.

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.

My sensor idea fully helps prevent the spread of the disease by monitoring mosquitoes. The aim is to analyze the vectors, their behavior, and lifestyle and to apply an epidemiological model that prevents an increase in cases at the country level, such as in Ecuador, and worldwide. This alternative is also beneficial in economic terms, as we would reduce costs by preventing cases and therefore their treatment. It should also be noted that when a person contracts dengue for the second time and it is a type that has not affected them before, it can cause dengue hemorrhagic fever.

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 or rule, an incentive, or a 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.).

i. Purpose What is done now and what changes are you proposing?

Currently, analyses of climate change, vector frequency, and disease are being conducted, but despite this, the number of cases according to SIVE has not decreased in Ecuador. The aim is to implement a vector control strategy and epidemiological studies to control the spread of the disease.

ii. Design What is needed to make it “work”? This includes the actor(s) involved—who must opt in, fund, approve, or implement the action.

■ This requires academic researchers in the fields of ecology or entomology to identify dengue vectors, trained personnel to develop the sensor, considering that it must be lightweight and portable so that it can be used in different environments and areas, and epidemiologists to specifically study the spread of dengue and the role of vectors, hosts, and human mobility. Furthermore, this project proposes reductions in healthcare costs, which is why the state should invest in it.

iii. Assumptions What could you have wrong?

Consider incorrect assumptions, gaps in knowledge, or key uncertainties.

❌ El rastreo de vectores en diversidad áreas comprometen al personal de estudio ya que pueden estar directamente en contacto con vectores infectados o portadores del virus.

❌ Considerar que todos los vectores son portadores del virus, es un supuesto que podemos tomarlo en base a que es un individuo susceptible.

❌ Algo erróneo es considerar que el gen que permite la diferenciación es constante y altamente conservado para cada tipo.

iv. Risks of Failure & “Success” How might this fail, including any unintended consequences resulting from the “success” of your proposed actions?

⚠️ There is a possibility that the device may not be optimally efficient at distinguishing between dengue strains.

⚠️ It may not be able to cover all the locations and mosquito densities that need to be studied.

⚠️ We do not consider possible mutations of the identification gene.

4. Next, score each of your governance actions using a scale from 1–3

(1 = best performance, 3 = weakest performance, or n/a if not applicable) against your rubric of policy goals.

The following is one possible framework, but feel free to adapt it or create your own.

Option 1: Analyze reactions with genes to determine the type of virus Option 2: Design a lightweight prototype that can be portable Option 3: Conduct studies in local areas of the Amazon to evaluate the efficiency of the equipment.

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.

Based on the activity carried out, I would personally prioritize the affected patients. However, from a broader perspective, it is very helpful to focus on the cause of the disease in order to understand how it is transmitted and spread, and thus find a way to control it. The focus should be mainly on the action of the vectors, which is something we can control, unlike the hosts (humans), which we cannot control. This work would be carried out in conjunction with the Ministerio del Ambiente, Ministerio de Salud, and universities focused on the study of tropical diseases, with an emphasis on the Amazon region, where health services are poor, especially in areas far from the capitals.

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

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?

Error Rate:1:106 Throughput:10 mS per Base Addition The human genome is 3.2 Gbp in size, and the mutation rate is low. In addition, there is an exonuclease section of the polymerase that can correct certain errors during replication. Therefore, there are not many mutations. However, advances in molecular biology allow us to detect these posible mutations and correct them in the same way.

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?

On average, a human coding protein is made up of 345 amino acids. If we consider the formula, this indicates that 9.5×10^415 combinations are possible. However, not all of these possible combinations are feasible, because the functionality of a protein is mainly affected by its tertiary structure, and modifying the order of amino acids changes the tertiary structure, since not all amino acids have the same properties.

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

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

Electrochemical-based microarray by CombiMatrix, phosphoramidite DNA synthesis.

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

It is Because we have an error rate of ~1 error per 10² bases, and our base pairs exceed this minimum, which indicates that there will be errors or mutations during synthesis, meaning that we will not obtain the molecule we are interested in.

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

The same applies in this case. We have an error rate of ~1 error per 10² bases, and in this case we are talking about 2000bp, which would be like 20 errors in the molecule. If one already scares us, 20 would be worse. It probably no longer functions as we would expect, meaning its performance and efficiency would be very low.

Homework Question from George Church: [Lecture 2 slides]

1. Choose ONE of the following three questions to answer; and please cite AI prompts or paper citations used, if any.

[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 histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, and arginine. The Lysine Contingency refers to the fact that lysine is an essential amino acid that humans and animals cannot produce on their own. The only organisms capable of doing so are plants, fungi, and some bacteria, as they have the biosynthetic pathway for lysine. This means that we can only obtain this amino acid by consuming plants or fungi, i.e., we depend on the production of other organisms.