Principles and Practices

I. PROJECT DESCRIPTION

HOW TO GROW BIOLUMINESCENT MENSTRUAL BLOOD? A SYNTHETIC BIOART PROJECT

Bioluminescence is the production of visible light by living organisms. The light is produced through the oxidation of luciferin, which is catalyzed by an enzyme called luciferase. This phenomenon is believed to have evolved 540 million years ago in Earth’s ancient oceans [1]. Present in the majority of marine species but also in land-based ones such as fungi, bacteria and fireflies, bioluminescence serves biological purposes such as mating, hunting, and defense behaviors [2]. Bioluminescence has become an essential tool in biological engineering not just for sensing but also controlling biological processes [3-4].

While bioluminescence unanimously elicits attraction and curiosity, one cannot say the same for menstruation. The social stigma around it has slowly receded with increased visibility in the media over the past five years, but menstrual health remains under-researched. In particular, the precise biological impact of hormonal variation during perimenopause, which can last up to 10 years, remains unknown. When it comes to transgender menstrual health, the gap is even wider. Insights into how hormone therapy affects the menstrual cycle in trans men are sparse and usually extrapolated from research carried out on menopausal cis women [5–6].

Ironically, synthetic biology holds extraordinary potential to revolutionize trans health. For instance, by unlocking the expression of genes implicated in genital growth or creating organs de novo, synthetic biology methods could dramatically improve the quality of life of transgender patients undergoing gender-affirming surgeries, which are currently highly risky and often associated with poor outcomes.

The art installation invites the public to immerse themselves in a softly glowing, living artificial womb and observe pulsating “menstrual” blood being infused into it. By using synthetic biology to transform menstruation from a hidden process into a shared contemplative experience, I aim to raise awareness of the societal impact of scientific bias and the urgent need to invest in neglected research fields such as menstrual and trans health.

Shining light into the abyss of a womb is also a metaphorical invitation to regain the senses. Beyond the previously mentioned primary goal, I want to show that synthetic biology can be used in ways other than a product-centered perspective. In a world that is suffocating, it is meaningful to be reminded of life’s evolutionary timescales, as well as how the race for productivity and overconsumption affects Earth’s wonders such as embryonic development and bioluminescent life. The piece is a call to slow down, and rethink our vision of what the future of the synthetic biology revolution should look like.

Methodological strategies The menstruation-like fluid can either be derived from menses or created artificially [7]. Two strategies can be considered to enable the production of bioluminescence:

1. Creating a menstrual-like fluid (e.g. serum extracted from menstrual blood) in which bioluminescent marine microorganisms can survive in culture, and in a second step modifying the genome of these microorganisms to elicit a photonic response under specific stimuli. Monitoring of the environment changes by use of living biosensors approach.
2. Inserting luciferase/luciferin genes into the genome of cells typically contained in menstrual blood, such as endometrial cells or vaginal microbiota [8]. Monitoring of the changes in cellular ecosystems approach.

Bibliography [1] Danielle M. DeLeo et al. Evolution of bioluminescence in Anthozoa with emphasis on Octocorallia. Proc Biol Sci (2024) [2] Martini S. et al. Quantification of bioluminescence from the surface to the deep sea demonstrates its predominance as an ecological trait. Nature Scientific Reports (2017) [3] Widder E. et al. Review of Bioluminescence for Engineers and Scientists in Biophotonics. IEEE Journal of Selected Topics in Quantum Electronics (2013) [4] Love A. et al. Seeing (and using) the light: Recent developments in bioluminescence technology. Cell Chem Biol. (2020) [5] Perrone A. Effect of long-term testosterone administration on the endometrium of female-to-male (FtM) transsexuals. J Sex Med (2009) [6] Buck E. et al. Menstrual Suppression. Treasure Island (2025) [7] Tindal K. et al. The composition of menstrual fluid, its applications, and recent advances to understand the endometrial environment: a narrative review. F&S Reviews (2024) [8] France M. et al. Towards a deeper understanding of the vaginal microbiota. Nat Microbiol (2022)

II. GOUVERNANCE & POLICY GOALS (Synthetic Biology & Bioart in Berlin, Germany)

Overarching goal Ensure that the use of synthetic biology in artistic contexts is safe, non-maleficent, socially responsible, and inclusive, while complying with German and EU biosafety, biosecurity, and human rights frameworks.

GOAL 1: Ensure bio safety and prevent harm Sub-goal 1.1: Regulatory compliance and containment. Sub-goal 1.2: Prevention of misuse of the art work. Key institution: Institutional biosafety committees (Beauftragte für biologische Sicherheit)

GOAL 2: Promote equity and justice in biomedical narratives Sub-goal 2.1: Address epistemic bias in research priorities. Sub-goal 2.2: Protect the dignity and the autonomy of transgender patients. Key institution: German Ethics Council (Deutscher Ethikrat).

GOAL 3: Foster responsible innovation and public engagement Sub-goal 3.1: Transparency and public understanding of the art piece. Clearly communicate what aspects of the work are biological, synthetic, or metaphorical, supporting informed public engagement with synthetic biology. Sub-goal 3.2: Encourage reflective, non-product-centered innovation. Use the artwork to challenge efficiency- and market-driven narratives of biotechnology, aligning with broader German and EU discussions on sustainability and responsible research and innovation (RRI). Key institutions: European Commission (RRI framework), German Federal Ministry of Education and Research (BMBF).

III. GOUVERNANCE ACTIONS

Action 1: Mandatory Biosafety & Ethics Review for Art–Science Projects

Actor(s): Academic institutions, art schools, biosafety committees, federal regulators (BVL)

1. Purpose Current state: Biosafety review in Germany (GenTG) is robust for academic research, but art–science projects often fall into grey zones, especially when hosted outside of traditional labs. Proposed change: Require formal biosafety and ethics review for any art project involving synthetic biology or GMOs, regardless of whether it is framed as “research” or “art.”

2. Design Extend existing institutional biosafety committee (Beauftragte für biologische Sicherheit) oversight to art institutions collaborating with labs. Require project registration and approval before exhibition, similar to IRB-style review but adapted for bioart. Low administrative burden by using existing regulatory infrastructure under the Gentechnikgesetz.

3. Assumptions Assumes that ethical risks in bioart are comparable to those in research. Assumes institutions are willing to take responsibility for hybrid practices.

4. Risks of Failure & “Success” Failure: Overregulation could discourage experimental art or push practices underground. Success risk: If normalized, review processes may become procedural and lose critical engagement, reducing ethics to box-ticking. Analogy: Drone registration systems that increased safety but initially slowed creative experimentation.

Action 2: Incentivizing Low-Risk, Contained Design Choices

Actor(s): Funding bodies (BMBF), foundations, academic labs, artists

1. Purpose Current state: Synthetic biology innovation is often optimized for scalability, performance, and commercial value. Proposed change: Create incentives (funding criteria, exhibition access) favoring contained, non-scalable, low-risk biological designs, especially in public-facing projects.

2. Design Funding calls explicitly reward projects that use Risk Group 1 organisms, non-reproductive systems, or synthetic analogues. Curatorial guidelines for public exhibitions prioritize containment and reversibility.

3. Assumptions Assumes artists and researchers respond meaningfully to incentive structures. Assumes “low-risk by design” can be assessed reliably.

4. Risks of Failure & “Success” Failure: Incentives may be ignored if prestige or novelty outweighs funding concerns. Success risk: Could unintentionally marginalize more radical or speculative research that challenges current risk models. Analogy: “Privacy-by-design” incentives in software development that improved norms but constrained some innovation paths.

Action 3: Transparency & Contextualization Requirements for Public Display

Actor(s): Exhibiting institutions, artists, regulators, public educators

1. Purpose Current state: Audiences often cannot distinguish between speculative, artistic, and clinical uses of biotechnology. Proposed change: Require clear public-facing contextualization for bioart using synthetic biology.

2. Design Mandatory disclosure explaining what is biological, synthetic, symbolic, or hypothetical. Clear statements that the work is non-therapeutic and non-clinical. Oversight by exhibiting institutions, not law enforcement.

3. Assumptions Assumes transparency increases public trust rather than fear. Assumes audiences engage with contextual information when provided.

4. Risks of Failure & “Success” Failure: Contextualization may be ignored or misunderstood. Success risk: Overexplanation could domesticate or neutralize critical artistic ambiguity. Analogy: Financial product disclosures that protect consumers but often overwhelm them.

IV. GOVERNANCE ACTIONS: SCORING

(from 1-3 with, 1 as the best, or n/a)

V. PRIORITAZING STRATEGY FOR ACTION(S)

Action 01 should be prioritized because a foundational principle of academic biological research is the precautionary principle. Action 03 should also be prioritized because bioart can only be meaningful if it is conducted ethically and responsibly—not to create sensation, but to stimulate curiosity and deeper reflection.

VI. CONCLUSION: ETHICAL CONCERNS

Coming from an artistic perspective, I found it challenging to situate my project within the framework of the course. I was troubled by the fact that my proposal was not product-oriented: transforming the appearance of menstrual blood into light did not align with the “How To Grow” formulation.

As I am only beginning to engage with synthetic biology, it may seem presumptuous to question product-driven research. Yet, like many other fields, synthetic biology is shaped by the economic logics that have governed technological development since the Industrial Revolution. This raises the possibility of expanding its scope beyond productivity alone, toward applications that invite reflection, care, and alternative ways of relating to life.

AI support: ChatGPT. The tool was used to discuss the relevance of different final project ideas and to provide initial responses that served as a starting point for questions related to governance and policy, based on the prompts: project description and assignment questions.

Preparation Class 02

HOMEWORK QUESTIONS FROM STEVEN JACOBSEN

After proofreading, DNA polymerase has an error rate of 1:10⁶, meaning 1 error per 1 million base pairs. The human genome contains approx. 3 billions base pairs (3x10⁹bp) in haploid cells and thus, 6 billions base pairs (6x10⁹bp) in diploid cells. This means that thousands of errors occur during DNA replication, but the cell machinery has a post-replication mismatch repair (MMR) system that brings down DNA replication errors to only a few potential base pairs per division.

Human proteins are made of 20 amino acids (aa) whose code is stored in the DNA (A,C,G,T nucleotides coding). Ribosomes are macromolecules that synthesize proteins by translating messenger RNA (mRNA) into amino acid chains. This translation process is mediated by transfer RNA (tRNA) molecules that add a single amino acid corresponding to the mRNA code (A,C,G,U three-nucleotide codon/anticodon coding system). Because there are fewer amino acids than codon possibilities (4^3=64), multiple codons can encode for the same amino acid: a phenomenon called codon redundancy. Some codons are also associated to prompt the start and the end of the translation process. According to the genetic code, there are between two and four DNA code possibilities per amino acid. So in theory there are staggering possibilities to code for an average human protein (approx. 450-480 aa length).

But in practice, spatial configuration and kinetics can affect this process:

• Different codons have different translation kinetics due to tRNA availability https://www.nature.com/articles/nrm.2017.91?utm
• mRNA sequence influence its folding and affects the initiation and processivity of the translation https://link.springer.com/article/10.1038/msb.2013.32?utm
• Certain codons can destabilize the mRNA or trigger premature termination responses https://academic.oup.com/nar/article/47/17/9243/5549713?login=false&utm

AI support: ChatGPT. Prompt: Please read this research article thoroughly and answer “In practice what are some of the reasons that all of these different codes don’t work to code for the protein of interest?”: https://www.science.org/doi/10.1126/science.1241459

HOMEWORK QUESTIONS FROM EMILY LEPROUST

Solid-phase phosphoramidite chemical synthesis is the industry-standard, automated method for creating custom DNA/RNA oligonucleotides.

Direct synthesis of oligonucleotides (oligos) longer than 200 nucleotides (nt) is difficult primarily because of the cumulative, exponential decline in yield due to imperfect coupling efficiency and the accumulation of chemical errors. Cumulative Inefficiency: Standard oligo synthesis adds nucleotides one by one. Even if each step has a 99% success rate, the overall yield drops significantly as length increases. Longer sequences result in mostly truncated, incorrect, or incomplete products. Accumulation of Errors: With longer synthesis times, chemical side reactions increase, leading to a higher rate of sequence errors, such as deletions or misincorporations. Purification Challenges: As the length increases, it becomes difficult to separate the desired full-length, error-free product from the failed side products. Steric Hindrance: As the oligo grows, it can become tangled, making it harder for reagents to access the reactive end.

Making a 2000bp (base pair) gene via direct synthesis is currently not possible due to these limitations in efficiency, which result in a very low yield of the full-length, correct sequence. Exponentially Low Yield: Using standard 99% efficiency, a single-stranded DNA or RNA molecule that is 2000 bases in length would yield roughly effectively zero usable product. Error Rate vs. Length: The error rate is roughly one mistake per 200 bases, meaning a 2000bp strand would contain an average of 10 errors, making it highly unlikely to contain the correct sequence. Physical Limits of Support: The solid support material (e.g., controlled pore glass) becomes clogged by the growing DNA strands, preventing reagents from completing the synthesis.

AI support: ChatGPT, Gemini. Prompt: long oligonucleotide synthesis + “What’s the most commonly used method for oligo synthesis currently? Why is it difficult to make oligos longer than 200nt via direct synthesis? Why can’t you make a 2000bp gene via direct oligo synthesis?”

HOMEWORK QUESTIONS FROM GEORGE CHURCH

Lysine is one of the 10 essential amino acids found in all animals: Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, and Valin. An amino acid is classified as essential in a species if the organism can’t produce it and therefore is required in the diet (or any other external supply) in order to survive.

In the movie Jurassic Park (1993), scientist Ray Arnold explains how the research team modified the genome of the dinosaurs to prevent them from surviving in the wild in case the dinosaurs would escape the park: “The lysine contingency is intended to prevent the spread of the animals in case they ever get off the island. Dr. Wu inserted a gene that makes a single faulty enzyme in protein metabolism. The animals can’t manufacture the amino acid lysine. Unless they’re continually supplied with lysine by us, they’ll slip into a coma and die.”

Lysine is classified as an essential amino acid in all known animals, including vertebrates. The movie portrayed the “Lysine Contingency” as an engineered weakness but it is likely that dinosaurs likely didn’t have an endogenous lysine biosynthesis pathway to remove in the first place. The auxotrophic strategy presented in the “Lysine Contingency” concept is also not valid. Indeed, lysine is widely present in nature, particularly animals but also in some plants. Carnivorous dinosaurs representing the main threat on the island, they would likely have no difficulty in finding their lysine supply in the wild. The idea of making an organism dependent on a non-natural amino acid would have been more plausible than preventing biosynthesis of a normal nutrient like lysine.

In the real world, synthetic biologists use more robust strategies to design genetic safeguards: Genetic kill switches: circuits that trigger death in certain environments. Synthetic amino acid dependencies: organisms engineered to depend on non-natural amino acids that aren’t in nature. Multiple overlapping dependencies: not just one but many safety constraints. Genetic firewalling: preventing horizontal gene transfer.

In conclusion, movies like Jurassic Park make synthetic biology look inherently dangerous, even though real scientists focus heavily on safety and careful regulation. The media shape how society feels about science, thus also have the responsibility to spark curiosity without creating unnecessary stigma around technologies that can also bring major benefits.

AI support: Gemini. Prompt: What could the scientist of the “Lysine Contingency” have proposed instead?