Week 1 HW: Principles and Practices

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

I am interested in technologies that can enable an outside the body gestation and perhaps in the future, a pregnancy-free gestation and birth. Two such technologies are crucial to this future: artificial womb technology (AWT) and stem cell-based embryo models (SCBEMs).

Stem cell-based embryo models (SCBEMs) are stem cells that can form viable human embryos without the need for sperm or egg cells. SCBEMs are most useful in research identifying causes of miscarriage and are not legally allowed to be grown post 14 days. A code has been developed in the UK from Cambridge University that does not allow for the sperm and egg cell-free embryos to be implanted into carriers. Without such enforcements, we might see a future whereby we can build new species without physical nor emotional attachment to ourselves.

Artificial wombs are biobags that mimic uterus conditions including a high-tech amniotic fluid and correct air flow. AWT have currently been developed for the support of prematurely born lambs. AWT has the near-future possibility of replacing premature neonatal intensive care. Current intensive neonatal care is mostly effective but can leave the infants with life-long neurodevelopmental and behavioural conditions that impact its life. In this homework, I will focus on policy goals and governance actions of AWTs.

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.

ARTIFICIAL WOMBS | I think the following are the key problems/areas that require ethical clarity and enforced regulations:

• What is the value of the gestating entity?
  • What rights does this gestating entity have?
  • Who is allowed to control the gestating entity?
  • Does the gestating entity require ‘guardians’?
• Who is required to take responsibility when/if systems fail?
• Where and when is this technology allowed to be used?
  • Is anyone allowed to procure this technology? i.e. a womb for every home.
  • Can someone make an army with such a piece of technology?

STEM CELL-BASED EMBRYO MODELS (SCBEM) | I think the following are the key problems/areas that require ethical clarity and enforced regulations:

• What counts as a ‘human’?
  • Are you allowed to develop something that is akin but other than human? An entity with human consciousness
• Should we be allowed to build new species that are like us?

POLICY GOAL #1 | PROVIDE FAIR ACCESS TO ALL PEOPLE

This policy goal should establish regulations around the use of AWTs and ensure that they are available to all people without discriminating the sex, gender, race or wealth status. This would be an extension of current discrimination laws and would prevent the decision of preventing selection of certain types of parents. Equally, this policy would establish fair access across geographies through subsidisation programmes.

Ensuring fair and equitable access would require the following sub-goals:

• Continuation of current safety guidelines to prevent medical malpratice
• Extention of current Anti-Discrimination frameworks
• Subsidising AWTs across geographies through European funds

POLICY GOAL #2 | PROTECT THE RIGHT TO A GOOD QUALITY OF LIFE

This policy goal should mandate that each born life has a substantial ensured quality of life. This will require the defining of a ‘baseline’ QoL in the first seven years. The mandate should help guide and support parents in making the right decisions with regards to gestation and the child.

As part of this policy goal:

• A determined Quality of Life foundation should be established
• Duty of care framework for ensuring that an AWT entity will not be neglected

POLICY GOAL #3 | PROMOTE GUARDIANSHIP OVER AWT ENTITIES

All AWT entities should have legal and emotional guardians. This is important for an array of reasons. AWTs relieve humans from the emotional and physical burdens of pregnancy. to try to prevent the formation of giant armies. Gestating This will ensure that, even if the parent chooses not to undergo pregnancy, they will have ensured parental leave via the ‘duty of care’ over the gestating entity. Additionally, it will mean that gestating entities will not be left abandoned.

Sub-goals regarding guardianship of AWT entities:

• Defining the ‘duty of care’ of the guardians of AWT entities.
• Co-opting the current system of care of pregnant persons with guardians of AWT entities.

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

GOV ACT #1 | Mandated Parental Leave Irrespective of Carrying | National Governments

Purpose: Parental leave is split between maternity leave for the mother and paternity leave for the father. Maternity leave is further split into two groups: prenatal and postnatal leave. In the EU, there is a 14 week minimum parental leave. Current parental leave is determined by the gender of the person, with mothers tending to receive more parental leave. In the EU, there is a mandatory 2 week maternity leave with minimum being 14 weeks. Paternity on the other hand is only 2 weeks. ]] These were covered under the 1992 Pregnant Workers and the 2019 Work-Life Balance Directive.

In a future where a part of us or the majority no longer use our bodies for pregnancy, there needs to be a directive that looks past the sex/gender of the parent and the ensuing work-life balance. The future requires a directive that encourages the duty of parental care at the forefront of the keeping an AWT entity.

GOV ACT #2 | ESTABLISHED STANDARDS OF CARE FOR AWT ENTITIES AND LEGISLATION ON DUTY OF CARE FOR GUARDIANS OF AWT ENTITIES | Medical Organisations

Purpose: Currently, AWTs are still a distant future. The project EXTEND (the Extra-uterine Environment for Neonatal Development) at the Children’s Hospital of Philadelphia is negotiating potential human trials to support children are born earlier than expected. Establishing standards for the care for AWT entitites and the duty of care for their guardians would Design: This would require the cooperation of medical organisation stakeholders and doctors including OBGYNs, primary care physicians, midwives and nurses. The standards would be published under a global conglomerate such as the World Health Organisation, whereupon each nation state would agree to them and use them in national/regional regulations. Assumptions: Risks of Failure & Success:

GOV ACT #3 | SUBSIDISATION OF AWTs | National Governments & Bloc Ruling Organisational Bodies (EU)

Purpose: This act would extend the current grants availale for processes such as in-vitro fertilisation. Design: Reproductive institutes in nation states would Assumptions: Risks of Failure & Success:

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.

I would prioritise government action #2 ESTABLISHED STANDARDS OF CARE FOR AWT ENTITIES AND LEGISLATION ON DUTY OF CARE FOR GUARDIANS OF AWT ENTITIES.

Week 2 HW: DNA Read, Write, & Edit

PART 1: Benchling & In-Silico Gel Art

Lecture Prep Homework questions from Professor Jacobson

1. The human genome is ~3.1 billion base pairs long. DNA polymerase makes roughly one error per 10 to the five nucleotides. Without correction, this is fairly error prone as it would make roughly 30,000 errors per genome replication. Luckily, human biology has interesting error correction measures including the mismatch repair system. The mismatch repair system recognises base-base mismatches and insertion/deletion mispairs through the complexes of MutS-related proteins that recognise nicks in the DNA strands.
2. There are over a million ways to code an average human protein. Not all the possible codes can work for a protein of interest due to codon rarity and context-dependent protein production.

Homework questions from Dr. LeProust

1. The most commonly used method for oligo synthesis is solid-phase phosphoramidite synthesis.
2. It is difficult to make oligos longer than 200nt via direct synthesis due to a reduction in coupling efficiency and the buildup of truncated sequences.
3. You cannot make a 2000bp gene via direct oligo synthesis because there is a break down in sequences as we try to assemble longer ones. The longer the synthesis, the lower the yield and efficiency and the higher the truncated products generated.

Homework questions from George Church

1. The 10 essential amino acids in all animals are: Leucine (L), Lysine (K), Isoleucine (I), Valine (V), Histidine (H), Methionine (M), Phenylalanine (F), Threonine (T), Tryptophan (W), Arginine (R).

Week 3 HW: Lab Automation

Python Script found here.

Find my three project ideas here, but here is a draft outline

Post Lab Questions Find and describe a published paper that utilizes the Opentrons or an automation tool to achieve novel biological applications.

I read the paper “High-Throughtput Microbial Culturomics Using Automation and Machine Learning”

This paper describes a process utilising lab automation and machine learning to enable faster strain isolation and characterisation. Isolating individual bacterial from the collected microbiome is an arduous process.

The paper proposes and tests the following approach:

1. An AI-guided selection process that works on analysing images of colony morphology.
2. Robotic device that chooses specific colonies and isolates them.
3. Pipeline for genotyping and taxonomy
4. Physical isolate biobank and digital database with searchale colony morphology.

Write a description about what you intend to do with automation tools for your final project. You may include example pseudocode, Python scripts, 3D printed holders, a plan for how to use Ginkgo Nebula, and more.

Week 1 Lab: Pipetting

Individual Final Project

Group Final Project