Handbook: "The language for this criteria this year has been changed this year, asking teams to demonstrate to the judges that they have thought carefully and creatively about whether their work is safe, responsible, and good for the world. They could, for example, consider the regulatory, economic, ethical, social, legal, philosophical, ecological, security or other societal aspects of their projects. We want to see thoughtful and inventive approaches to examining these complex issues in ways that are relevant to teams’ work. One way (but not the only way) teams may accomplish their examination is by engaging with stakeholders in their local, national and/or international communities. We also want to recognize other creative approaches to exploring these issues. If teams choose to use surveys, we expect them to follow best practices for conducting a scientific and legitimate surveys, and have provided resources and information on the HP Hub. Many good examples of Human Practices work and additional information can also be found on the hub" "Convince the judges you have thought carefully and creatively about whether your work is safe, responsible and good for the world. You could accomplish this through engaging with your local, national and/or international communities or other approaches. Please note that standard surveys will not fulfill this criteria."

We sought out widespread, real-world problems in order to take the first steps towards creating a healthier world.

Our preliminary research sought to answer the question, "What major environmental and health problems affect people today?" An important aspect of a biological engineering project is to first start with a problem that people want to have solved. We discussed the research on this issue and came up with yet more poignant and open-ended questions: What problem are we trying to solve? What is the scope of that problem? What current methods exist in addressing the problem, and what new approaches might be tried? How does engineering biology provide a tool, or act as a component in a larger plan of action to solve the problem? Is engineering biology a necessary or desirable approach in this solution? Before attempting any wet-lab work, or making any major design considerations, we considered these questions carefully. Our process of asking these questions, reaching out to doctors, and looking at current synthetic biology solutions were crucial in helping us determine the direction of our project.

To be more specific, we contacted health care practitioners around the world, including professionals in Brazil, Palau, Bolivia, Venezuela, Peru, Hait ́ı, Nicaragua, and The Dominican Republic. We asked these doctors what ailments are most common and what medicines are most needed. Nearly all the practitioners mentioned lack of adequate access to vitamins, pain relievers, and other pharmaceuticals due to insufficient supply, high cost, and high demand. Therefore, we chose to focus on the topics of vitamin deficiency and pharmaceutical shortages.

At this point, we asked further questions, “How would we address vitamin and medicine shortages? What questions do we consider, and who do we need to talk to about the implementation of an engineering biology approach?” We continued to ask the questions, "what is the purpose of an engineering biology approach?" and "what is the feasibility of producing a medicine using a host microorganism--is engineering biology a feasible approach for the scope of the problem?”

Further research into current methods of engineering biology approaches to medicine production led us to discover that a photosynthetic organism is an adequate host.

By focusing on an edible cyanobacteria, we hope to generate an easily consumable, photosynthetic culture of vitamin or pharmaceutical synthesizers. Thus we are working with cyanobacteria genus Synechococcus as a model for the FDA- approved Arthrospira platensis, commonly known as Spirulina.

However, the choice of host was also intimately tied to the medicines that we could produce. Of the three non-opioid pain reducers on the World Health Organization’s (WHO) list of essential medicines, we have decided to pursue acetaminophen, the active ingredient in TylenolTM, due to the feasibility of recreating the metabolic pathway in a cyanobacteria. With respect to vitamins, we aim to produce human usable vitamin B12 because it is one of the few vitamins that A. platensis does not adequately produce.

By asking questions at every step of the way, we were able to determine what problems we could adequately address in the scope of an iGEM project. We hope to accelerate a growing movement to shift production of medicine delivery to the regions that need them. While it is important for us to develop the technology, essentially a living factory synthesizing acetaminophen and vitamin B12, it is also important for us to address aspects of the problem unsolvable with science alone. We hope to analyze and understand how our project fits into existing policies and attitudes surrounding poverty and malnutrition.

Safety considerations:

It is important to consider that we are creating a proof-of-concept rather than an immediately implementable product. The safety concerns involved at the proof-of-concept stage are less complex than those of the implementation stage, and the safety concerns must be addressed at both stages to have a clear direction moving forward.

For example, one concern is that the project currently uses antibiotic resistance as the selectable marker for transformants. However, a future application of this in a clinical medical setting outside the laboratory would need to use a different selectable marker strategy in order to avoid the possible release of antibiotic resistance genes to the environment. This consideration brings us back to the research, outreach, design, and implementation questions that are a critical part of our human practices approach.

Another safety consideration is the dosage of the product, and the reliable determination of dosage. How will those using our product be able to know the dosage? What in our preliminary proof-of-concept and modeling provides insight on finding correct dosages?

The edibility of the future host organism was a key safety consideration. We considered the implications of using a non-toxic, non-pathogenic organism as a model for a GRAS organism.

How did we address the concerns around using this genetically modified organism as a food or medicine source? How did we reach out to people about this? What future work would need to be done to increase the safety of this medicine delivery method?