Week 1 HW: Principles and Practices

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.

A biological engineering project I have been passionate about to bring into the world intersects art conservation, biology and design. My goal for the final project portion would be to create a conservation treatment for cultural heritage objects specifically that of ceramics and textiles utilizing synthetic biology.

The world of art conservation is a crucial field that serves to protect, and conserve the objects of our human ancestry. These objects include paintings, ceramics, textiles, baskets etc… Conservation scientists and art conservators do hands-on and theoretical work to ensure our histories are preserved for the future. They establish regulations around best practices and balance artistic intention with scientific treatment.

Conservation scientists specialize in chemistry, and though the field is inherently interdisciplinary, it wasn’t until recently that biology became a consideration in preserving cultural heritage objects. Bacteria, and fungi, are often the predators that eat away, and degrade these objects. Much of the work has come to preventing fungal growth on paintings, paper and textiles. However, in recent light of pressing issues, bacteria have come to the aid in conserving large scale monuments. Microbiologists and art conservators have been able to team up to “train” bacteria to eat specific solvents or to grow and bring filth up to the surface of larger monuments.

I graduated with a BFA in ceramics and specialized in biofabrication. After graduation, I was fortunate to land an internship at the Walters Art Museum under the Conservation Scientist, Annette Ortiz. I am passionate about the materiality of ceramics, as much as I am about the connective tissue it provides to our oldest relatives. Conservation science is a proactive investigation in understanding an object in all the ways it exists. Ceramic has macro and micro cracking as issues either from the firing process, or natural degradation of the material. I propose the process of biomineralization to fill in micro and macro cracks. Textiles is a semi-neglected sector of art conservation as the scale and nature of the work is arduous. This causes a gap in the kind of cultural heritage objects that get treated and assessed. Silk, for example, once it begins degrading, is no longer treatable as the fibers begin to split. What if there was a means to conserve silk working with protein design? In this case, fundamentals of biology become vital to conserving objects lost to time and neglect.

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.

The provided governance/policy goals are an amalgamation of goals from the AIC code of conduct for art conservators and goals from the NSCEB report.

Respect Cultural Property and Cultural Diplomacy

1. The Cultural heritage objects chosen for review will have gone through the institutional and cultural channels to properly determine necessity for treatments.
2. For objects institutionalized outside of the origin culture, cultural autonomy to origin peoples and governments offer consent to scientific treatment if and when applicable.
3. Assess artist intention, and cultural context to determine treatments.

Advocate for Preservation

1. Active pursuit of knowledge in obtaining novel possible treatments of cultural heritage objects to ensure the conservation of such objects is prioritized.
2. Consistent testing to ensure experimental treatments are safe for historical cultural heritage objects to minimize prolonged harm from biological treatment.
3. All conservation methods are reversible to allow for the evolution of treatments to be applicable to all cultural heritage objects in the present and future.

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.).

Implementation of Safe Scientific Examination:

1. Microbiologists and Art conservators have separate codes of conducts respective to their areas of research. Various qualities of these fields demand different responses and practices.
2. Due to the nature of the work, a new code of conduct decided and created by a group of art conservators and microbiologists would help in bridging these disparate practices together. This would require the merging of bio lab safety practices with conservation lab ethics in dealing with sensitive objects and materials. The implementation of Safe scientific examination would determine safe handling and transportation of both cultural heritage objects and biological materials between labs, determining various risk factors dependent on organism, object and scale, as well as institutional regulations of the participating researchers.
3. It could be assumed that a code of conduct may be difficult to implement due to the wide variety of needs and resources of a given project. Failure to ensure lab safety protocols are followed within treatments could lead to contamination, exposure and further degradation of objects.

Ethical Considerations of Cultural Heritage Object Context: <

1. Conservators are trained to determine the conditions fit for treatment. This often involves the context of the objects creation and artists intent if applicable. This framework is necessary to uphold in order to maintain best practices.
2. Art conservators, curators and the boards of cultural institutions will go through review to determine intention and impact of any recommended biological treatment. If biological treatment is recommended, consent from all parties including but not limited to, the institution, conservators, microbiologists, artists etc… A documented treatment plan will be developed evaluating cultural context as part of the treatment consideration. This will be shared with biologists entering the team.
3. By setting ethical standards of use and execution, it can be assumed objects of consideration will be appropriately chosen for treatment. It can also be assumed that defining the cultural context of an object, and therefore designing treatment, is an ambiguous process and requires a historical understanding of who is defining/defined the ethical framework and could this contain biases that effect treatment?

Implementation of Fair Labor Contracts for Art Conservators and Interdisciplinary Collaboration:

1. Unfortunately, the gap in public perception and financial support between the life sciences and humanities is quite large. This cross interdisciplinary work provides room for negotiation for equitable contracts across fields as teams involve research and cultural institutions. In my proposal, I am interested in specifying ceramics and textiles. Textile conservators do not typically hold long term positions within institutions. Object, book, and painting conservators can obtain long-term positions, while textile conservators rely on project based contracts which contributes to job insecurity for specialized professionals.
2. Treatments and teams can be considered under several domains such as biotechnology, humanities and biology in which institutions can branch funding avenues to guarantee success of projects and also fair distribution of funds to contracted professionals. Cultural institutions can act as the “Principal Investigators” to projects and sub-contract microbiologists as “co-investigators” to define roles and designate appropriate funding.
3. It can be assumed that project based contracts can create wider cross institutional opportunities, however, it can also maintain the same initial problem. Defining the “principal” institution is project dependent as well as defining roles. This can must be established in the suggested code of conduct intially proposed. General questions to consider: What and who is the project for? Where is funding coming from and from there, what funds get allocated to supporting labor and operational costs?

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.

The governance action goals all feed into each other in various aspects. However, the Implementation of Safe Scientific Examination would be one I’d prioritize as both actors of cultural and research institutions and personnel are equally involved in defining the guidelines of safe use and treatment. It requires the participation and active collaboration of microbiologists and art conservators to inform each other on best practices considering the specifications and principles of the diverse fields. It is vital that communication is established and lab safety protocols for both conservation and biological labs are decided and mutually understood. I have become increasingly aware of how this practice would be financed and distinguishing private versus public funding. Especially when allocating funds to various institutions that operate separately and have various groups to support.

REFERENCES:

1. https://edition.cnn.com/style/article/bacteria-art-restoration#:~:text=Rome%2C%20Italy%20CNN%20%E2%80%94,the%20course%20of%20two%20weeks.
2. https://www.biocodexmicrobiotainstitute.com/en/bacteria-restorers-works-art-future-allies-heritage-conservation
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC10667932/
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC10667932/
5. https://www.si.edu/stories/care-victorian-silk-quilts#:~:text=The%20folds%20should%20be%20padded,the%20Smithsonian's%20Public%20Inquiry%20Services.
6. https://www.k18hair.com/
7. https://www.culturalheritage.org/conservation-at-work/uphold-professional-standards/code#:~:text=I,Mitigate%20Adverse%20Effects

Doctor jacobson

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 polymerase is ~1:10^6. The human genome is ~3.2GBP therefore, in comparison to the error rate of the polymerase, which accounts for 3,200 mistakes in copying DNA. Biology deals with this discrepancy via the MutS repair system.

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?

The different ways there are to code for an average human protein is 2^200 which is 1.6eX10. All of these different codes don’t work to code for the protein of interest because of codon optimization and bias.

Dr. Le Proust:

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

From what I can assume for the slides, the most commonly used method for oligo synthesis is Phosphoramidite method by Caruthers and Electrochemical-based microarray by CombiMatrix which can be found on the chronological timeline of development. Twist bioscience has new technology known as a silicone platform.

Why is it difficult to make oligos longer than 200nt via direct synthesis? It is difficult to make oligos longer than 200nt via direct synthesis because of the accumulative decrease in yield and is an exponential decay. https://www.glenresearch.com/reports/gr21-211#:~:text=Coupling%20Step,the%20concentration%20of%20phosphoramidite%20itself.

Why can’t you make a 2000bp gene via direct oligo synthesis? You can’t make a 2000np gene via direct oligo synthesis because oligos are generally limited to 100-200bp and yields decrease significantly. https://www.lubio.ch/blog/the-challenge-of-making-long-oligos#:~:text=There%20are%20several%20challenges%20to%20synthesizing%20long,a%20fidelity%20of%20only%2099%25%20or%2010.

Dr. Church

[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”?

Arginine (Arg) Histidine (His) Lysine (Lys) Isoleucine (Ile) Leucine (Leu) Methionine (Met) Phenylalanine (Phe) Threonine (Thr) Tryptophan (Try) Valine (Val) Lysine contingency is the concept of evolving past the production of our own Lysine and needing to obtain lysine externally. As Jurassic Park alarms, creating control factors such as a lysine contingency places a dependency of the organism we modify on researchers in an attempt to mitigate risk etc. However, like in Jurassic Park, the dinosaurs were able to obtain the lysine in their environment causing an experimental failure. This is an important ethical dilemma when designing experiments and genetically modifying organisms. https://open.oregonstate.education/animalnutrition/chapter/proteins-structure/#:~:text=List%20of%20Essential%20Amino%20Acids%20and%20Their,(Thr)%20*%20Tryptophan%20(Try)%20*%20Valine%20(Val) https://jurassicpark.fandom.com/wiki/Lysine_contingency

“The lysine contingency is intended to prevent the spread of the animals in case they ever got off the island. Dr. Wu inserted a gene that creates 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.” —Ray Arnold(src)

Week 1 Lab: Pipetting

Individual Final Project

Group Final Project