Week 1 HW: Principles and Practices

1 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.

Bio engineering Tool/application: Autonomous Space Biomanufacturing Platform for Active Pharmaceutical Ingredients (APIs) My biological engineering application is an autonomous, space-based biomanufacturing and analysis system capable of producing active pharmaceutical ingredients (APIs) and nutritionally relevant biomolecules during long-duration space missions. The system integrates:

• engineered microbial or cell-free biosynthesis platforms,
• automated microfluidic bioreactors,
• in-situ laboratory analysis,
• robotic sample handling and process control,
• edge-computing-driven optimization.

The motivation for this system arises from a fundamental constraint in human space exploration: mass and resupply dependence. Pharmaceuticals degrade over time due to radiation, storage and their own degradation constraints, and resupply from Earth becomes impossible for Mars-class missions. Current mission architectures rely heavily on pre-packed medications and Earth-based analysis.

There is a NASA capability gap described in a white paper by OSMED - Organization for space medicine, engineering and design. The white paper highlights that NASA currently lacks sufficient in-situ automated laboratory analysis capability, limiting the ability to monitor biological systems, diagnose health issues, and support medical decision-making during deep-space missions. This same gap directly limits the feasibility of onboard pharmaceutical manufacturing, since production requires real-time quality verification and process monitoring.

The proposed system addresses two linked challenges:

• Medical autonomy — astronauts can produce essential drugs (antibiotics, anti-inflammatory compounds, metabolic supplements) on demand rather than relying on pre-manufactured supplies.
• Utilization of the space environment — microgravity and radiation environments may enable production pathways or crystallization outcomes difficult to achieve on Earth, potentially improving yield or purity for certain molecules.

From a robotics perspective, the system functions as a self-driving laboratory, where robotic handling and microfluidic automation minimize crew cognitive load — a requirement explicitly emphasized in the NASA analysis, which identifies crew time and cognitive burden as limiting factors for biological operations in deep space. It could help in space as well as in earth, manufacturing source crystals and drugs that cannot be made on earth.

2 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.

Governance policy Goal: Enable autonomous biological manufacturing in space while ensuring safety, non-malfeasance, and equitable long-term use of space biotechnology.

This goal can be broken into three specific sub-goals.

• safety and containment - Prevent unintended hamrful leak of biological growth
• Security and responsible use - Only approved pathways can be executed. All executions transparent and open
• open-source, architecture - Interoperable standards available to any other organization as well

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

Governance Action 1: Certified Biological Production Libraries

Purpose Current biological research systems allow flexible modification of organisms and production pathways, which introduces safety and security risks in autonomous space environments. This action proposes restricting onboard biological manufacturing to pre-certified biological production libraries.

Design

• Space agencies and regulatory bodies define approved biological production libraries.
• Only certified organisms, enzymes, or cell-free pathways are permitted onboard.
• Production protocols are digitally verified before execution.
• Academic researchers and companies contribute to library development under safety review.

Assumptions

• Essential pharmaceuticals can be produced using a limited set of approved biological pathways.
• Certification processes can be updated fast enough to support mission needs.

Risks of Failure & “Success”

• Overly restrictive certification could limit flexibility during medical emergencies.
• Centralized approval systems may slow innovation or adaptation to new conditions.

Governance Action 2: Mandatory Autonomous In-Situ Quality Verification

Purpose Biological manufacturing in space requires reliable verification of product identity and safety without reliance on Earth-based laboratories. This action proposes requiring automated quality verification for any biologically produced medical compound.

Design

• Biomanufacturing systems must include integrated analytical tools for identity, purity, and contamination checks.
• Automated analysis prevents dispensing of products that fail quality thresholds.
• Space agencies and mission integrators enforce this requirement during system certification.

Assumptions

• Miniaturized analytical systems can reach sufficient reliability for medical decision-making.
• Automated verification can substitute for expert laboratory oversight during deep-space missions.

Risks of Failure & “Success”

• False negatives may prevent use of necessary medication in emergencies.
• Increased system complexity may introduce additional failure modes.

Governance Action 3: Open Interface and Data Standards for Space Biology Systems

Purpose Fragmented ownership and incompatible systems can prevent effective use of biological technologies in space. This action proposes standardized interfaces and data formats for biological analysis and manufacturing systems.

Design

• Space agencies, private companies, and academic partners agree on common data and interface standards.
• Biological production logs and analysis results follow shared formats.
• Systems support interoperable integration with robotic handling and automated laboratory platforms.

Assumptions

• Stakeholders are willing to cooperate on shared standards.
• Open standards will improve reliability and reduce duplication of effort.

Risks of Failure & “Success”

• Standards may become overly bureaucratic or slow to evolve.
• Successful standardization could accelerate widespread adoption faster than governance mechanisms adapt.

4 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

Professor Jacobson

• 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 = 1:10^{6 Length of the human genome is about 3 billion bases. Throughput Error Rate Product Differential: ~10}8 Biology doesnt just depend on polymerase for copying DNA, it uses other methods as well

• 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?

1036 base pairs maybe due to codon usage bias, certain organisms prefer to use certain codons, while others don’t

Professor Dr. LeProust

• What’s the most commonly used method for oligo synthesis currently? solid-phase phosphoramidite synthesis.
• Why is it difficult to make oligos longer than 200nt via direct synthesis? Each nucleotide addition has a small failure probability. This keeps accumulating.
• Why can’t you make a 2000bp gene via direct oligo synthesis? 2000 sequential chemical coupling steps is required, which is too much and will fail due to error accumulation. Not even a single full length molecule will be made.

Professor George Church

What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency"? Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine Arginine

Since the organisms cannot exist without lysine and a very fundamental one that is common among all animals, it is clear that there was one common ancestor who was also similarly limited. So the lysine contingency is a fundamental and deeply rooted biological limit that has not been overcome in a very long time. The 10 amino acids must be attained somehow, and that is a very profound insight.

HTGAA Website assignment

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