Human Practices

Our Goal

With our project ENERGEM, Cornell iGEM aims to produce 7-methylxanthines, or 7-MX, more efficiently. Our goal was to make stakeholders the focus of our product, developing a product that had the potential to help a large group of people while providing research for others to build off of. Given that we are in the biomanufacturing track, our goal was to provide drug developers, researchers, physicians and more with a cost-effective and efficient way of producing 7-methylxanthines. However, we wanted to ensure that our product was used for the greatest amount of good. Through our research and interviews with various stakeholders, we determined that 7-MX were best used as a treatment for myopia considering the large, diverse group of people affected.

For our project, we wanted to develop a compound that could impact a broad range of people and have a wide variety of applications. With 7-methylxanthines, we have just that.

Evidence For Global Impact

Currently, myopia is the most common distance vision impairment in the world. Myopia often leads to serious ocular diseases including glaucoma and macular degeneration, especially if left untreated. By 2050, over 50% of the world’s population will have myopia. As the number of people who have myopia increases, the age of onset decreases. At the moment, current treatments of myopia are limited to Lasik surgery and eyeglasses; all treatments that either can’t be used for children, are invasive, or do not help slow the progression of the disease. This just shows how important and needed it is to have a biological treatment such as 7-MX.

Our team has conducted interviews with a wide variety of stakeholders including ophthalmologists, government officials, and drug development companies to understand how effective and needed our product is. From interviews with experts like Dr. Maria Liu, founder of the Myopia Control Clinic at the UC Berkeley Eye Center, we learned that 7-MX is currently the only viable biological treatment available that has shown significant preclinical and clinical promise. Physicians like Dr. Christina Cherny helped support that patients would be willing to use 7-MX in the form of an oral treatment. Drug developers like Dr. Aoife Brennan, the CEO of Synologic, spoke to us about how on a large scale, finding an innovative method of producing compounds like 7-MX can have a wide-range impact considering the prevalence of the disease.

Our Guiding Values

Initially, our primary motivations were primarily economic and environmental. 7-MX are biochemicals that have a high value across various industries. For instance, in the medical industry, they can be used to treat myopia, which has the potential to affect millions of lifes. However, these compounds are rare naturally and current chemical synthesis procedures often result in products that are both low in yield and purity, and can often be hazardous. Unfortunately, these issues often result in expensive market prices, as currently pure 7-MX can be up to 10,000 times more expensive than the cost of caffeine. This inspired Team Cornell to build a more cost-effective way to produce 7-MX and paraxanthine for the medical community. Our preliminary calculations indicate our method of producing 7-MX will result in a product that is 91.53% cheaper than standard 7-MX sold by ThermoFisher.

However, as we continued our research and spoke to further experts in the field, we learned more about the wide range of applications that methylxanthines as a class can have, ranging from myopia to respiratory diseases to plant growth stimulation. Thus we were inspired to pursue these scientific motivations to help provide an efficient and effective way for producing 7-MX. In addition, being in the biomanufacturing track, we also understand that our techniques can be used to produce a broad range of other methylxanthines, including theobromine. We aim to make our technique generalizable, providing the scientific community with an innovative way of manufacturing compounds similar to 7-MX.

In addition, as a future application to our project we aim to make sustainability and the environment a focus of our project. Our goal is to utilize leftover coffee grounds to produce paraxanthine and 7-MX from caffeine to help minimize waste from local coffee shops and coffee-related vendors. We will aim to keep a thorough record of byproducts produced by our reactor to minimize chemical waste products in order to be as environmentally friendly as possible while increasing yield.

Communities Consulted

Based on feedback we received from Dr. Ashty Karim, we chose to focus on methylxanthines because of the broad range of applications available; however, for our final compound, we still wanted to make sure that we were applying our project to the field that needed it the most. Therefore, based on our research on the applications of methylxanthines, we reached out to stakeholders both in the agricultural and medical field. After talking to local farmers like Ian Merwin and ecological experts like Dr. Jennifer Thaler and Dr. Christophe Duplais, potential agricultural applications (including a natural insecticide, a pollinating stimulator, and a way to stimulate caffeine production) were ruled out as plausible applications given the methylxanthine derivatives that we are producing.

When investigating the potential medical applications that ENERGEM may have, we met with physicians and medical experts in pulmonology and respiratory illnesses like Dr. Joanne Bishara who indicated its significance as a respiratory treatment was not optimal.

However, through further research we learned that 7-MX has been the only biological treatment to myopia to show promise. Current treatments for myopia are limited to care after a diagnosis rather than proactive care including eye glasses and invasive surgeries, suggesting the need for biological alternatives. After speaking to biotherapeutics researchers at Regeneron like Dr. Jingtai Cao and ophthalmologists like Dr. Christina Cherny, we were assured that myopia was the best application for 7-MX. After settling on myopia, we consulted further ophthalmologists, drug developers, and government officials to gain a better idea on how a 7-MXtreatment would be viewed by patients, how ethical it would be, and more. After our interview with Dr. Aoife Brennan, we were recommended to approach our stakeholders like concentric circles where the further we got from the center we got broader. We’ve displayed the image of relevant stakeholder groups below. Unfortunately, we were unable to speak to patients in an official manner due to privacy complications about patient information. However, we did speak to various possible patient groups including residents at the nursing homes we hosted outreach at including Kendal @ Ithaca and Longview Senior Living Community as well as visitors to our booth at the Ithaca Farmers Market. Across each of these groups, we learned that they would be willing to use our product to treat their myopia, especially considering that it was a derivative of caffeine, less invasive, and both a preventive and treatment.

Impact of our Project

Fortunately, 7-MX has a wide range of applications, leading to a wide variety of impacts to our project. Our primary goal is to use 7-MX as an effective therapeutic and preventive for myopia which by 2050, will impact over 50% of the world’s population, ensuring that our project will have far reaching effects globally. We aim to reduce the cost of 7-MX, improving the accessibility for the treatment.

Who are your proposed end users?

Our proposed end users include drug development companies to encapsulate into a tablet or pill for patients to use, physicians and nurses who can use these treatments in their clinics, and possibly university researchers who may use these compounds in their labs.

How do you envision others using your project? How would you implement your project in the real world?

We envision others using the compounds for their own uses given that 7-MX have a broad range of applications. Since the most effective use for 7-MX This includes medical applications in respiratory disorders including asthma and COPD as well as myopia. In addition, we have the potential to apply our technique to produce other derivatives of caffeine which can be used as a pesticide, agricultural growth stimulant, or respiratory disease therapeutic. These wide range of applications were a large part of why we chose to use this compound.

How would you implement your project in the real world?

In the real world, methylxanthines have a broad range of applications in the agricultural field and medicine. We have outlined these applications within our Applications of Methylxanthines handbook. We would implement our project as a possible therapeutic and preventive for myopia and other vision related diseases that are caused by myopia.

Reflection

How did you decide which needs or values to prioritize in your design? What compromises did you choose to make and why?

We were primarily inspired by the inefficiency of the production of the high demand and high value biochemicals 7-MXand paraxanthine. These chemicals are extremely valued in various industries for their potential roles in insecticide, asthma, and myopia treatments.

However, current production methods of 7-MX and paraxanthine are costly, low yield, low in purity and highly inaccessible, making it extremely difficult to access for the public. ENERGEM is designed to address these issues by creating a much cheaper and high yield process of synthesizing 7-MX and paraxanthine, thereby creating increased accessibility.

Additionally, we were particularly inspired by environmental concerns. Our method of 7-MXand paraxanthine synthesis is derived from caffeine waste. Even though caffeine disposal is cheap, sustainability is essential and a huge priority to Cornell iGEM. ENERGEM seeks to make use of all caffeine waste and convert it into usable biochemicals for agricultural and medicinal purposes, as opposed to disposal.

Now, as opposed to agricultural pursuits, we have largely shifted to medicinal interests, as we believe recent studies have shown a much greater need for 7-MXhere, especially in the novel potential treatment of myopia. We determined that this was the area to apply 7-MX to most directly due to the feedback we got from various interviews and stakeholders. Initially, our interviews with farmers and physicians specializing in respiratory therapies suggested that 7-methylxanthines were either not the appropriate caffeine derivative or not as effective as they once were. However, after conducting more research, we learned about the promise of 7 -MX in myopia treatments. Our interview with Dr. Jingtai Cao one of the first to suggest that myopia would be a good application for a biological treatment considering the severe limitations to the current treatments. After speaking to Dr. Maria Liu , one of the leader’s in clinical myopia treatments, we were sure that myopia treatments were the optimal area to apply our product.

Did you reach your initial goals or did you have to adjust them?

From a human practices perspective, our goal is to establish the best area to apply 7-mx to considering the broad range of applications. Initially, we thought that was in the area of respiratory diseases and asthma. However, we did have to adjust this given the feedback that we received from physicians, pharmacists, and others, integrating this into our project. Through that we ended up settling on myopia for which we got positive feedback from our stakeholders.

From a wet lab perspective, given the issues that we had with our Gibson assembly, we were required to switch to a more modeling focus. Initially, Gibson Assembly was supposed to take maximum a week but due to complications in our previous backbone, optimizing our protocol, and redesigning primers, the protocol took longer than expected. However, with the vast amount of literature review done by Team Cornell, a modeling focus was taken while the full plasmid was being created. This allowed us to gain a better understanding of the project in silico before fully starting in vitro trials and better predict the outcomes of in vitro.

How does your approach compare to alternative solutions to the same or similar problems, including approaches outside of synthetic biology and biotechnology?

Methylxanthines, specifically 7-MX and paraxanthine, are high value biochemicals in agriculture and medicine. Currently, methylxanthines are synthesized in a low yield and excessively complicated manner. ENERGEM aims to address this in a much more economic and efficient approach, allowing for increased accessibility and productivity of methylxanthines. Specifically, ENERGEM is expected to yield around an 83% yield in comparison to pure chemical synthesis based on prior literature. This is due to ENERGEM’s novel method of synthesis which relies on the use of better enzymes, enzymes NdmA and NdmB for more efficient and cheap production. Synthesis of 7-MX and paraxanthine is based on caffeine byproduct in ENERGEM, while other chemical methods aim to produce these methylxanthines through a purely chemical manner, which contributes to the lower yield. Through a methodical iterative design process, we aim to develop a strong proof of concept for industrial scale-up.

Currently, we still believe that our product will create a much more efficient methodology to produce methylxanthines, and has significant potential for industrial scale up for the agricultural and medicine industries. Compared to alternative methods that focus purely on chemical synthesis, ENERGEM still maintains a cost efficient method of production for 7-MX and paraxanthine using caffeine metabolizing enzymes.

From the perspective of myopia treatments, there are various treatments available. Current treatments include glasses, contacts, atropine eye drops, orthokeratology, and refractive surgery. These techniques are largely not related to synthetic biology and have a wide range of effectives, cost efficiency, and more. In comparison to these treatments, 7-MX is highly effective as a therapeutic as well as a preventive. In addition, the effects of treatment are long term and not invasive. We expand more on the comparison between 7-MX and current myopia treatments later on.

Responsiveness

Which resources or communities should you consult to ensure you are prioritizing appropriate values in the context of your project?

Some important resources and communities to consult to determine appropriate values would be those affected by the production and those involved in the production of 7-MX.

Initially, this meant looking at the agricultural and medical sectors generally to get a better idea of where they could be best applied. In agriculture, 7-MX has some pesticidal properties when applied to plants, so speaking with farmers and growers of fruits and vegetables would be important in determining the role 7-MX plays in this industry and how our improved production may affect this. We spoke to people such as Dr. Jennifer Thaler and Ian Merwin from Black Diamond Farms who articulated that while there was promise for methylxanthines in general, but that 7-methylxanthines were not the best choice of caffeine derivative.

We also looked at 7-MX and how it could be used for asthma. However, similarly, we learned that methylxanthines for asthma treatment hasn’t been used in years as it is not as helpful as other alternative treatments.

We then found myopia. Speaking with medical professionals in this area helped us to determine the main issues and values to consider when it comes to the impact of these compounds on patients and how to best use them. These perspectives are all key to our project as our goal is to efficiently produce a product that is meaningful for its target audience. We also need to consult patient populations to the best of our ability and researchers that currently do work in the area of biosynthesis and chemical synthesis to determine the effectiveness of our technique and to iron out any technical details.

How might you get feedback on the feasibility and desirability of your approach?

In order to get feedback on feasibility, we can speak with various synthetic biology experts specializing in areas such as enzyme immobilization and metabolic engineering that are important to our project. We can also speak with experts in fluid mechanics and porous materials when it comes to designing our reactor. For desirability, we aim to focus on the two areas where 7-MX have the greatest possible impact. We spoke with medical professionals who may want to use these molecules in the treatment of myopia. We can also speak with green chemistry experts and those within sustainability to evaluate how impactful our project would be when it comes to environmental concerns related to 7-MXproduction. Ultimately, we hope to target our product towards the industry where it is most desired by our stakeholders.

How can your team “close the loop” between your design and what is desired?

For closing the loop our goal was to do our best to meet the expectations of our stakeholders. This meant integrating their feedback into the progression of our project. For the most part this meant adjusting the field in which we applied our project. For instance, stakeholders like Dr. Bishara and Ian Merwin informed us that neither asthma nor the agriculture industry was the most appropriate application of 7-methylxanthines given the changes in their effects. We integrated their feedback into their project by shifting our focus from either of those industries to a myopia therapeutic given the positive outlook we got from drug developers and ophthalmologists.

In order to further close the loop, we re-contacted those who we had spoken with towards the beginning of our project, including those across all the fields, ranging from agriculture, medicine, and environmental areas among others, so that they may comment on how our project has evolved and how effectively it now meets their needs. We received responses from 4 of our stakeholders and technical interviewees all of whom were pleased with the direction that our project took and gave any last minute feedback that they had. We have expanded on these interviews within a timeline below in our interview section. Additionally, we closed the loop by reflecting ourselves over the course of the project to make sure it is still progressing to address the concerns of stakeholders.

How can you use your Human Practices work to inform your team's ethical, technical, safety and/or communication decisions?

Overall, our Human Practices work will be important in determining what we need to prioritize from all of these standpoints.

Compounds used in medicine are carefully regulated and it is all the more important that they be highly pure, thus speaking with technical biosynthesis experts will be important in understanding how we can optimize this.

From a safety and communication standpoint, connecting with medical professionals including ophthalmologists will give us an important understanding of whether patients will be willing to use this product and how we would have to communicate this to them. They reassured us that tablets were a form that patients were typically more comfortable with and the fact that 7-methylxanthines were a derivative of caffeine would help them be more willing to use the product. We also used these interviews as the inspiration for creating our Applications of Methylxanthines handbook because it would be a way to communicate to others the broad range of applications we have.

In addition, we used the broad range of outreach activities we had, including the Ithaca Farmers Market and Kendal @ Ithaca to get feedback from possible actual patient populations. They told us about how they would like to be taught about this therapy and whether they would use it, good feedback for us to incorporate into our project. This was a great opportunity for us because it felt like a dual learning opportunity where not only were we sharing our knowledge but we also learned from them and their experiences, encouraging a dialogue.

We also spoke to drug developers to get a better understanding of the ethical considerations we would need to keep in mind when developing chemicals for therapeutic uses. Not only did they give feedback on our project directly, but also on our ethics framework EUDI and how to improve it which we ultimately used to evaluate our project. In all, listening and integrating the feedback we received from all our experts as well as people we met while conducting outreach was a large part of our project this year and our project this year would not be the same without it.

Responsibility

Could your project be misused? Could your team's solution to one problem create other problems?

This product will be available to researchers, drug developers, and medical personnel including physicians. From a research and drug development perspective, it is easy for data and results to be misrepresented which can cause a wide range of other issues later on throughout the research and development process. In addition, physicians who prescribe 7-MX unnecessarily could possibly pose risks to their patients. It is very important that they prescribe their medication appropriately when it comes to dosage and not take advantage of their position. In addition, although methylxanthines are shown to be nontoxic, long term exposure to this product could result in unintended side effects. For instance, methylxanthines in general are adenosine receptor agonists and also act as nonselective competitive inhibitors of phosphodiesterases, which could in turn restrict necessary cellular responses from occurring. Symptoms include respiratory abnormalities, insomnia, nervousness, headache, nausea, seizures, and more. There needs to be extensive research both clinically and preclinically to establish the side effects.

While our method of producing 7-methylxanthines is drastically cheaper than the current chemical synthesis methods of producing 7-methylxanthines, it is still not economically comparable to other myopia treatments like glasses. This is why from a public health perspective, we could be worsening issues with medication access. We know that 7-methylxanthines are a worthwhile treatment considering how effective and permanent they are, we understand that this will not be a very cheap treatment. We hope that this will be covered by insurance programs considering that this is a preventive treatment, but even then there are high disparities when it comes to access to medication and insurance.

How does the iGEM community expect your team to be safe and responsible, both inside and outside of the lab?

Within the lab, the iGEM community expects us to adhere to safety protocols by wearing the proper personal protective equipment including safety goggles, gloves, and protective clothing. This will ensure that no one gets chemically harmed when manipulating chemicals in the wet lab. Every member on the team was also required to take a safety course and members on the wet lab and product development subteams went through special training to ensure safety precautions were taken seriously. In addition, we are expected to report our results accurately to show a fair representation of our product. With regards to research, we will take advice acquired throughout the process and integrate it into our final process to manufacture the most environmentally friendly and cost effective product. Outside of the lab, it is our responsibility to investigate the impact of our product on various facets of society. This includes analyzing bioethics related to public health and agriculture since ENERGEM is targeting the medical and agricultural industries. In addition, we are responsible for educating the community on our project and synthetic biology. By educating the public, we can improve the community’s perception of our project. Finally, by working with local organizations, we will be able to address critical issues that are plaguing the community.

Last year, our team developed a Policy Handbook that we used as our standard for safety, specifically focusing on understanding the institutional resources we’d have to use. We determined that we would not need to consult the Institutional Review Board given that we were not interviewing anyone on their personal experiences to do research on them but rather learning about their expertise in the field. This is part of the reason why we could not pursue any interviews with patients in an official capacity. Our lab space is biosafety level 2, so we received approval from the Institutional Biosafety Committee. Given that our team was not conducting any research with animals, there was no need for us to receive approval from our institution’s Institutional Animal Care and Use Committee.

Which communities will be most interested in or most affected by your project?

The communities that 7-MX production directly targets includes the drug development and research industry as well as the myopia patient population. Given that we are aiming to produce 7-MX more efficiently and cheaper, researchers who might use this product in their labs could be interested in using our final product. Drug developers could be using this product in any treatments they have that incorporate methylxanthines. With regards to the medical industry, methylxanthines have shown potential as the primary biological treatment to treat myopia. Ultimately, by creating a more cost effective method of producing 7-MX, we can help make 7-mx as a treatment more widespread considering that it can be used for children and a preventative treatment - something which most of the current treatments do not offer.

Which communities will be left out or negatively impacted if your project succeeds?

Although the goal of ENERGEM is to produce 7-MX in a more cost effective manner, there is a possibility that the process will be more expensive. As a result, the price of 7-MX will increase. This trend is observed across many industries when trying to produce something that is also environmentally friendly. Therefore, products that require methylxanthines may end up being more expensive. Consequently, this product may not be as available to underprivileged areas. This could worsen already prominent public health issues when it comes to access to medication or disparities in insurance coverage.

Interviews

Before we conducted our interviews, we wanted to ensure that we would conduct them that was mindful of the time that our interviewees were taking. All new members were required to practice hosting interviews , both in person and over Zoom, with wet lab and product development subteam leads in an effort to get practice with interviews. This gave members experience in explaining our project and asking questions similar to the real interview setting. We also used this as an opportunity to develop questions that were more catered to the interviewee’s area of expertise. The leads gave members valuable feedback on our interview skills and the way that we presented the project, helping to shape the way that we explained our project for our actual interviews.

In addition, when we interviewed experts, we had them fill out a consent form that we developed last year that was approved by Vanessa McCaffrey, an Institutional Review Board administrator at Cornell. We also had members from other subteams present at interviews to ask any follow up questions or expand on their areas of expertise if any questions were asked of us. We also conducted interviews not only for the project we chose, but also for the projects we were researching during brainstorming to ensure that the project that we chose had the highest feasibility and had stakeholders that would be interested in our work.

Throughout the entire season, we reached out to over 120 people and received interviews from at least 22 people, including 4 repeat closing the loop interviews where we re-reached out to those we had already spoken to ensure that the work we did was meeting their expectations.

Key Interviews

Below we’ve outlined the key interviews with stakeholders and experts that helped shape the direction of our project including information on the state of our project prior to the interview and how it changed in response to their feedback. Further information on these interviews and the remaining interviews are included later on the page.

Dr. Ashty Karim - February 27, 2023 Dr. Karim gave us a lot of preliminary information early on in our brainstorming process that allowed us to develop ENERGEM. As a cell free system expert, he shared with us possible methods that could be used to create an immobilized enzyme system, as well as the advantages of using such systems like modularity and direct control that is more difficult when using cells. He also said that it would be an interesting idea to create a pathway that could then be derivatized to create a broad range of molecules which was a thought provoking idea that we then used to shape our project later on.
Dr. Sijin Li - March 27, 2023 Dr. Sijin Li gave key advice on immobilized enzymes and its implementation into our reactor, providing a key direction into how we will immobilize our enzymes into a network to standardize consistency of production.
Dr. Christophe Duplais - April 5, 2023 Dr. Christophe Duplais helped to assess whether ENERGEM would have an application to the agricultural field. He was negative on its potential impacts given plants already produce the chemical however additional, more effective pesticides are needed to eliminate pests.
Dr. Matthew DeLisa - April 13, 2023 Dr. Matthew DeLisa helped us understand and utilize the concept behind protein folding and the scale of our reactor in relation to output. He gave key advice on how purification would be involved in 7-methylxanthine synthesis as well as modeling mutations.
Dr. Christopher Alabi - April 14, 2023 Dr. Christopher Alabi gave insight into the necessary techniques related to reactor flow and development, encouraging us to focus on flow in our reactor as well as HPLC and other concepts to ensure that the concepts behind our reactor are sound.
Dr. Joel Kaar - April 19, 2023 Dr. Joel Kaar gave insight into the methodologies behind the production of methylxanthines and specifically the directed evolution method, encouraging us to use an adaptive and directed evolution approach instead. He also suggested that HPLC should be performed when utilizing EP-PCR to optimize an enzyme.
Dr. Joanne Bishara - April 25, 2023 Dr. Joanne Bishara helped us understand current applications of methylxanthines with respiratory illnesses. She was negative on its potential impacts given that methylxanthines have been slowly phased out of use for asthma and other treatments for better and more targeted treatments, allowing us to switch applications.
Dr. Regina Langer - May 3, 2023 Dr. Regina Langer gave key insight into the pharmaceutical industry and how our projected product of 7-methylxanthines might compare to other medicines currently available in the market. She noted there was a heavy shortage of medicines in general, but unsure of the need for caffeine as it is relatively available.
Dr. Jeffrey Varner - May 8, 2023 Dr. Varner gave us information about modeling enzyme kinetics using various methods such as initial rates or characterizing the appearance of products/disappearance of reactants, which helped us when designing our bioreactor. He also told us to be sure to match the reaction and transport times as we would not want reactants to come in and flow out before the enzyme can get to it, which was an important consideration we made sure to take into account.
Dr. Jennifer Thaler - July 13, 2023 Although Dr. Thaler seemed interested in the topic, she said there was not enough research with regard to methylxanthine’s impact in the agricultural field to indicate if it would be an effective pesticide. This encouraged us to switch to a medical application for our project.
Dr. Maria Liu - August 15, 2023 Dr. Maria Liu gave insight into the prevalence of myopia and its relationship to our proposed product of 7-methylxanthine, allowing us to direct our application to specifically target myopia as the issue that ENERGEM will be targeting.
Dr. Christina Cherny - August 16, 2023Dr. Christina Cherny gave us a physician perspective on the formation of myopia and how it affects patients. She was positive on the potential application 7-methylxanthine will have on patients with myopia, and allowed us to have a more nuanced understanding of myopia onset.
Dr. Aoife Brennan - August 18, 2023Dr. Aoife Brennan helped us understand the ethics behind our project related to stakeholdership, allowing us to update our current ethics framework EUDI. She also helped us narrow down our focus on who our project is targeting and the proposition for it.
Dr. Luann Van Campen - August 30, 2023Dr. Luann Van Campen helped us elaborate upon our current ethics framework EUDI to include “Ethical Standards” which allows for a more focused understanding of the different perspectives involved in the project and how they can be addressed.
Amanda Fallon - September 28, 2023Amanda Fallon helped us understand how our project ties in with legislation and government regulation particularly at the level of New York State. She told us about how our product would be handled at the state level if it were to be FDA approved, for example how the state might schedule the drug as well as the access and insurance side when it comes to things like the state deciding whether to include a drug on the Medicaid list or not.

Closing the Loop Interviews

In an effort to learn about how our stakeholders felt about our project near the end and whether they thought we effectively addressed their preliminary feedback.

Dr. Joel Kaar - August 20, 2023 He expressed enthusiasm for our progress and articulated the importance of the switch to an adaptive and directed evolution approach. He offered further support if needed.
Dr. Rajesh Bhaskaran - September 13, 2023 After evaluating the changes we made, he recommended that we simplify our current CAD model and offered any support we required from him.
Dr. Aoife Brennan - September 14, 2023 We contacted Dr. Brennan to discuss further updates to our project ENERGEM. She greatly appreciated all the changes made to EUDI and believes that this project can be significantly impactful. She really appreciates the focus of the project and hopes to see it grow further.
Dr. Christina Cherny - September 21, 2023 We discussed with Dr. Cherny any updates on the progress of ENERGEM. She reviewed our Ethics framework EUDI and appreciated the updates we made to them. She believes our project is great and has potential to go very far in relation to myopia treatments and evaluations.

Dr. Ashty Karim February 27, 2023

During our brainstorming process early this year, we met with professor Ashty Karim from Northwestern University. Prof. Karim has extensive experience working with cell free systems, and so we spoke with him in order to learn more about these systems and how they might be best applied to our project. He shared with us possible methods that could be used to create an immobilized enzyme system, as well as the advantages of using such systems like modularity and direct control that is more difficult when using cells. He also said that it would be an interesting idea to create a pathway that could then be derivatized to create a broad range of molecules which was a thought provoking idea that we then used to shape our project later on. He also warned us of some problems that might arise, such as identifying enzymes that would be effectively expressed in E. coli as well as finding the appropriate enzymes for the different necessary steps in the pathway we aim to construct.

Dr. Sijin Li March 27, 2023

To learn more about ENERGEM and specific technical issues that we might run into, we had a meeting with Professor Li, a professor specializing in synbio for plant materials, which greatly aligned with our work with methylxanthines. She asked a lot of great questions regarding wet lab and product development, such as how we are separating the enzyme from the substrate and how we are designing the gibson. She answered a lot of our questions and gave a lot of clarifying answers and possible directions for next interviews. One such example was that we use 3-D printing to have the frame printed so we can personalize and customize the bead position. We also will have to look into the Km and Kcat equations. She also suggested that we reach out to Professor Alex Woltornist, Rong Yang and the Alabi Lab as further contacts for more technical information, and the aforementioned equations. I am planning on reaching out to those three on Wednesday/Thursday to set up meetings.

Dr. Christophe Duplais April 5, 2023

As part of a preliminary exploration into our project this year, we met with intern Christopher Duplais at Cornell University in the Department of Entomology. He studies the chemical interactions between plants and insects as well as the insect-microbe symbiosis. We spoke with him to learn more about the potential applications of methylxanthines in agriculture. He told us that marketing the methylxanthines that we are producing for agricultural purposes would be difficult. This is because plants already produce methylxanthines as an insecticide, however, this is not enough to protect them from insects so we must treat them with additional insecticides. There is not enough research or data currently to suggest that methylxanthines would be a good alternative to current insecticides. Also, if we do decide to have an agricultural application we would have to change the methylxanthines that we are producing since it does not have an agricultural application. He suggested that we focus on medical or energy drink applications. Meeting with Dr.Duplais helped us assess which direction we wanted to pursue our project.

Dr. Ian Merwin April 10, 2023

In order to target our project towards a specific industry, we began meeting with stakeholders in different areas such as agriculture. Ian Merwin works at Black Diamond Farms located in Trumansburg, NY and is also a Cornell professor emeritus in the horticulture section of the School of Integrative Plant Science. We reached out in order to ask him about the application of 7-methylxanthines in the agricultural sector as previous reading we had done had shown these molecules to possess insecticidal properties. Hoping to target the product of our project towards a specific industry, we wanted to evaluate if agriculture seemed a good fit. While he had not heard anything about 7-methylxanthines being used as insecticides, Dr. Merwin did give us an overview of the process required to register a pesticide with the US Environmental Protection Agency as well as New York state which has its own rules and regulations as well. He told us that Black Diamond Farms would be open to donating a small quantity of fruit for testing, and after thanking him we said we would check back once we had a more definitive plan in place / if we decided to move forward with the agriculture route for our project.

Dr. Matthew DeLisa April 13, 2023

We met with DeLisa to go over a bunch of technical issues relating to WL and PD such as our proposed ADE cycle, the flow reactor and the kinetics behind our reaction. He gave a lot of clarification regarding our work. He told us to be wary of alpha protein folds, as its folding might not be completely accurate. Additionally, he told us that we need to figure out how much methylxanthine we actually want to make and the scale of that for our flow reactor, which also feeds into P&P and how we are going to address that. Beyond that, he told us if we are going the medicine route for P&P, there might be issues with purity since we will need to prioritize both purity and output equally as important. He suggested modeling so we can mutate in the active site as opposed to random mutations, and pointed us to Mike Jewett (who we already contacted), Dan Luo, Pat Cirnio, and Christina Smolke as future technical contacts.

Dr. Christopher Alabi April 14, 2023

We met with Dr. Alabi to go over a bunch of technical issues relating to WL and PD such as our proposed ADE cycle, the flow reactor and the kinetics behind our reaction, similar to DeLisa. We specifically focused on industry scale up, and asked if it is feasible given the different markets we are currently looking at. He said that flow is much more flexible and feasible than batch, since batch is limited by diffusion, head transfer etc. He also provided a textbook for us to use regarding flow, and suggested we ask our ChemE majors (like Grace lol). He also gave a bunch of advice on the efficiency of the reaction, whether we should use continuous fixed flow, HPLC vs crystallization, and pointed us to various other sources such as Philip Milner, Emmanuel Gannelis and Nick Abbott for future references.

Dr. Joel Kaar April 19, 2023

When formulating the procedure that the wet lab subteam was going to use for the production of methylxanthines, we met with Dr. Joel Kaar, to discuss enzyme immobilization. Dr. Kaar is a chemical and biomedical engineering professor in the College of Engineering & Applied Science at the University of Colorado Boulder. He is interested in the intersection of protein engineering, biocatalysts, and new materials. We spoke with him to learn more about methodologies we should use for directed evolution and cell-free immobilized-enzymes. He told us that when combining an adapted evolution with a directed evolution method, we do not need to sequence every variant but the more information we have the better. To save time, we can freeze the bacteria and then go back later to sequence them. He also recommended that when using EP-PCR to optimize an enzyme, we should use HPLC. Meeting with Dr. Kaar helped us to narrow the methodologies of our project.

Dr. Joanne Bishara April 25, 2023

We met with Dr. Bishara to go over potential applications of methylxanthines in the medical field, specifically apnea of prematurity. She said it is mainly caffeine and it’s derivatives used in treating specifically apnea of prematurity, which is a good sign and something we should focus on. She said that asthma and COPD aren’t really treated with methylxanthines anymore, but directed us to talk to adult pulmonary diagnosticians to confirm. She clarified that there really isn’t a need for methylxanthines in medicine since she doesn’t know if there is a deficit in caffeine supply, but suggested we look into if there was a lack of caffeine supply from COVID-19, and connected me to a pharmaceutical expert in New York Presbyterian.

Dr. Philip Milner May 2, 2023

We met with Dr. Milner to go over the technical aspects of the use of alginate beads and our reaction kinetics. He basically confirmed that our current procedure and goals of using alginate is good. He also said we should focus on the mesh net way and scale up would look like making the reactor wider, which is what we confirmed as well. For medicine versus agriculture, he suggested we look more into agriculture to avoid the purity issue since the agricultural industry mainly looks for cheaper and efficient options, rather than medicine which would most likely prioritize purity. The main takeaway is that we should use alginate first as that is the simplest option, and to model the reaction we mainly just use math and change catalyst ratios.

Dr. Regina Langer May 2, 2023

We met with Dr. Langer, a clinical pharmacist, to go over stakeholder aspects of the pharmaceutical industry, whether our product is viable to market to hospitals and other locations and the like. She definitely suggested if we go the pharmaceutical route, we look into the specific medicines that methylxanthines are in (like with the drug name, what it targets etc.) She also suggested distinguishing between outpatient/maintenance drugs vs acute drugs, since that affects whether we target hospitals vs outpatient clinics for acute vs chronic symptoms. She said there was a heavy shortage and still is due to COVID-19 so that is definitely an area we should look into. She wasn't specifically sure about the need for caffeine, but other areas such as steroids and narcotics were definitely lacking. She also mentioned other potential issues such as whether we are based in the US vs outsourcing, since that affects supply.

Dr. Jeffrey Varner May 8, 2023

Continuing to gather information and feedback about our planned method of synthesis, we met with Dr. Jeffrey Varner hoping to get more information about metabolic engineering as it relates to our project. Dr. Varner is a professor at Cornell in the Chemical and Biomolecular Engineering department who is a specialist in this area. We asked him what software he uses for modeling enzyme kinetics and if he had any tips on this, to which he said that he writes his own software, but to determine enzyme kinetics would could use various methods such as initial rates, or characterizing the appearance of products/disappearance of reactants, and the formation of product v. time. He also said that developing a quick colorimetric assay/assay reader would be beneficial. When it comes to the reactor we plan to build, he told us to be sure the match the reaction and transport times as we don’t want reactant to come in before the enzyme can get to it, and that the Km would give the reaction time scale and the dilution rate (volumetric flow rate / volume in reactor) would give the transport time scale. He also advised us to keep the chamber of beads in the reactor mixed, possibly with a magnetic stir bar to keep things agitated. Lastly, when we brought up concerns about formaldehyde as a side product of our reactions, he said not to worry as it could be safely removed.

Dr. Magdalena Julkowska May 11, 2023

Hoping to gather more information about the potential for 7-methylxanthine use in agriculture, we spoke with Magdalena Julkoska who is Cornell professor specializing in plant environmental responses at the Boyce Thompson Institute. While she had not heard anything about the use of 7-methylxanthines in agriculture, she told us it may be beneficial to talk to an entomologist to learn more about the effect of these molecules on insects. She recommended Dr. Frank Schroeder and Dr. Georg Jander for us to reach out to.

Dr. Jennifer Thaler July 13, 2023

When investigating possible applications for ENERGEM, we met with Dr.Jennifer Thaler at Cornell University. Dr. Thaler is an expert in chemical ecology and researches the interaction between plants and insects. We spoke with her to discuss ENERGEM’s potential application as an insecticide. Dr. Thaler thought there was potential to use ENERGEM as an insecticide however there needs to be more research done to determine the effects that this may have on the environment and biodiversity. We also discussed other potential uses for this project including its ability to stimulate pollinators and to stimulate caffeine production in plants. An important takeaway from our meeting was that although methylxanthines potentially has a lot of application within the agricultural community, there needs to be more research conducted with reference to the lethal dose and its effect on plants and insects in order to definitively say that it would be beneficial as an insecticide. Talking with Dr. Thaler helped us assess which direction we wanted to pursue our project.

Joe Price - CEO of Evolutor July 19, 2023

Started the meeting introducing iGEM, what they do, and our project ENERGEM for the year. After talking about our project, we talked about what Evolutor does and how they have in-house molecular tools that can be used with E. Coli that allows them to switch on all the genes in E. Coli in any combo in a larger pool of biodiversity. They were also able to reverse engineer mutations like the ADE cycle wet lab is trying to do. After talking about potential sponsorship. They mentioned a potential collaboration with the University of Sheffield iGEM team since they do close collaborations with that team and offered a potential knowledge exchange of increasing metabolic rate of E. Coli using food proteins (which aligns with the caffeine metabolizing rates of caffeine CUGEM is working with). They are in the early days of producing this material so if their timeline aligns with ours, we could get more talks with them about their tools and being able to give tips specifically to food protein yield rate in E. Coli.

The meeting also discussed potential financial sponsorship from Evolutor but due to rounds of investments, money is a little tight, but a sponsorship package was still sent to them. They discussed more about how they became a startup out of university and mentioned getting the IP removed from the University of Sheffield, did market exploration, talked to stakeholders at conferences, and got to a startup position there. At the end of the meeting, Joe Price gave us verbal consent to mark this meeting as an interview that can be used to help our project, especially with a potential collaboration in the future about adaptive and directed evolution cycle. Lastly, he asked that we send a check on where we will add Evolutor’s notes once we have them in documentation. They were excited to focus on building relationships.

Charlie Maddox - CEO of Enzymatic inc. July 21, 2023

Started the meeting introducing iGEM, what we do, and our project ENERGEM for the year. Charlie immediately understood and empathized with our objective– securing funding and getting our team to Paris. Charlie expressed interest in supporting our team and asked if we could send over technical materials from the wet lab and product development. He seemed particularly interested in the bioreactor. Charlie said that because Enzymatic Inc. is a startup, they would need to scrutinize the technical details and assess our product’s viability and conduct their own assessment of its commercial potential to license, scale, and grow. He mentioned that their company currently designs enzymes and works with a CRO to manufacture them but they aspire to one-day produce the technology in house.

Charlie also advised us on the dangers of disclosing information to companies without taking proper precautions. He provided advice on how to make an NDA and to attach it to future correspondence that contains any important technical information regarding our potential product. He shared a story about one of his engineers learning this the hard-way. Charlie also explained the importance of going through the patent process and of securing IP.

Dr. Jingtai Cao July 25, 2023

While exploring different therapeutic uses for methylxanthines and related compounds, it was found that 7-methylxanthine may be helpful in treating myopia. Dr. Jingtai Cao, director of ophthalmology at Regeneron Pharmaceuticals and co-inventor of Eylea, explained that while he did not know much about the use of methylxanthines in treating myopia, the need for a biological treatment for myopia is high. Treatments such as LASIK eye surgery and automated lamellar keratoplasty (ALK) require patients to be at least 21 years old. This is due to the dynamic nature of eye biology. The eye undergoes constant change from birth to around 25 years of age. In particular, aggressive cases of myopia are caused by neovascularization, or the formation of new blood vessels, in the vitreous fluid. While LASIK and ALK have high success rates, they require cutting a piece of the cornea. Dr. Cao emphasized the need for biological treatment for those who are under 21 years old, as well as those with blood disorders such as haemophilia. Dr. Cao also mentioned that the effectiveness of biological treatments can be affected by lifestyle choices such as screen time, water intake, etc. Thus, using methylxanthines for myopia may be more effective for some patients but not for others.

Dr. Maria Liu August 15, 2023

We met with Dr. Liu, the head of the myopia clinic at Berkeley to go over applications. She said that myopia is such a huge issue currently (in 2050, 50% of the global population will have it) and that 7-MX is very well known in the ophthalmology community for being a huge potential treatment. She broke down how myopia progresses with first the chloroid being thinned or thickened, and then the sclera breaking down. She said 7-MX is huge because it can act not only as a CONTROL but also PREVENTION, since it makes the sclera much stronger and more robust. Also, since it is an oral treatment, it is so much less invasive, especially since it is derived from caffeine, so she can definitely see it being at the forefront of treatments instead. She basically said this could revolutionize myopia treatments as a cheaper and much more accessible method, and she sees this becoming the paradigm for myopia treatments. She said the only potential issues she sees with this treatment is that there is systemic absorption (but this is a double edged sword) and that trials would have to be dose dependent, but otherwise she thinks our project could change so much about myopia.

Dr. Christina Cherny August 16, 2023

Jatin, Jean-Luc and we met with Dr. Cherny, an ophthalmologist from Mt. Sinai to discuss potential applications for 7-MX specific to myopia. She noted that from her understanding, myopia can often occur from the cornea changing (becoming too steep), or from the eye itself elongating (which relates to what we previously discussed with Dr. Liu about axial elongation and sclera thinning). She noted that there are huge implications for potentially being myopic, and the higher of a myope you become, the higher the risk of other ocular diseases and afflictions developing. We asked specifically about how behavioral factors affect myopia progression. She stated that it is possible that time spent with screens can increase risk and, conversely, time spent outside can reduce risk. Possible things a patient can do to reduce progression of myopia are decreasing time on screens and going outside and looking at far away objects as much as possible, especially in children. Beyond that, she stated that this would be a product many different ophthalmologists would be interested in as myopia is an epidemic right now, and pointed us in the direction of Kerotoconus as another potential application. She also directed us to Dr. Alexandra Benavente-Perez as another contact for myopia research.

Dr. Aoife Brennan August 18, 2023

We met with Dr. Brennan, the CEO of Synlogic, a synthetic biology drug development company to discuss her work with drug development. She told us regarding grants and funding that outlining exactly the steps for generating data really helps with funding and grants, as funders and investors want to see progress. Regarding ethics, she said the main focus is usually first general ethical questions (i.e consent, controls, patient info etc.) then more specific questions pertaining to the project (i.e whether the bacteria can replicate in the body, what specific harm might it cause etc.). She said her company focuses on engagement very early along with transparency. That transparency comes in the form of publications and ensures that all patients have access to the research necessary so they can feel confident and reassured. For FDA approval, she said that there are a bunch of steps necessary, and the main thing to focus on is regulatory frameworks and proper protocol. She says we really have to elaborate upon our value proposition and what exactly our project is for (what specifically is it targeting with manufacturing and will anybody care). When I asked about our framework EUDI, she said she really loves it, but would expand upon the empathize part to include a larger sphere of influence (i.e patients family, doctors involved etc.) She believes this can be extremely impactful if we flesh out who it’s for a bit more, and is excited to see our next steps.

Dr. Nita Mehta August 22, 2023

We met with Dr. Mehta, an ophthalmologist that works at Northport Veterans Center. She mainly asked why wasn’t this work replicated in the USA yet if it was already done in Denmark. She told us to focus largely on the reasons for this, as it could lead to potential implications in cost, treatment and other factors such as FDA approval. Additionally, she told us to focus on ensuring 7-MX is safe, efficacious and cost effective, as she noted from a physician perspective, many parents would be highly resistant to a new kind of treatment, as often times, parents are hesitant about atropine drops or contacts for myopia in children, even though those are the main forms of treatment currently available. She proposed a few potential alternatives to oral tablets such as a topical application or a sustained release pill so children wouldn’t have to take as many pills a day and compliance to the treatment could be increased. Beyond that, she noted a strong advantage to our application is that it can be used in tandem with other treatments so multiple modalities can occur. This was an extremely important interview from a physician perspective and aided our understanding of application.

Dr. Luann Van Campen August 30, 2023

We met with Dr. Van Campen, the CEO of EthicsMatters, a bioethics company, regarding our company. She gave a lot of important information related to our framework and project in ethics. She said that for ethics, she breaks up drug development into three different parts, Research Ethics, Clinical Ethics and Public Health Ethics, and elaborated upon it in the biopharmaceutical perspective. She also elaborated upon the importance of including all stakeholders, and brought up the inevitability that you can’t please all stakeholders. With this, she proposed an update to EUDI to include Ethical Standards after Understanding. Ethical Standards in this case pertains to finding a consensus between perspectives, and understanding which ones can we implement and which ones will be more difficult. She also proposed for a more technical standpoint that we create different figures laying out the spectrum of impact of our treatment versus other treatments such as atropine eye drops, glasses, and lasik in different factors (cost effectiveness, side effects, invasiveness etc.). This was an extremely important ethical interview that greatly informed next steps.

Dr. Luca Zatrenau September 6, 2023

Notes: Zatreanau was proud of the work that we are doing. He researched 7-MX and read the Danish clinical trial paper after he had been reached out. He said that from the data that he had seen, 7-MX seems like a relatively promising treatment that is on-par with some classic treatment options such as multifocal lenses and atropine eye drops. He made the point that oral administration makes it really easy for kids to take it.

Zatrenau stated that when he was in training, 10 years ago, atropine became the “new kid on the block”. He saw that low-dosage atropine was routinely used. One of the benefits of atropine eye drops was that it was safe and was well-tolerated; much preferred compared to all-night contacts. He mentioned that there were cons with atropine eye drops. These cons involved dilation and the relaxation of accommodated muscles, light sensitivity when you’re outdoors, and you might have difficulty with blurry near-sightedness. He mentioned that some of the extreme effects include systematic effects on the central nervous systems.

When asked about the product, he said that oral applications are very easy for patients. For young kids, this is much easier than some of the other treatments, such as eye drops or contacts. However, from the results that he saw from the Danish study, the rapid metabolism of 7-MX poses a big problem. Patients (especially kids) would likely feel inconvenienced if they had to take a drug three times a day. This would likely lead them to forgetting doses or not taking the medication at all. He says that he is seeing progress (from a paper?) on sustained-release tablets, so that would be a possible answer.

Business Insights

Dr. Zatrenau gave some very helpful marketing insight. He said that because 7-MX is a caffeine-byproduct, parents will feel more comfortable getting the medication for their kids instead of a crazy new experimental drug. This will reassure parents.

Dr. Zatrenau described two main methods of getting this drug out there and prescribed them.

Top-down approach: convince physicians with data from a randomized control trial. He said these results will drastically alter our pitch– pitching an un-fda approved drug is a significant uphill battle. He said that we should get in touch with different ophthalmologists (he said that we would have more traction with pediatric ophthalmologists). We would gain interest from doctors and they would likely want to participate in our control trials if we have funding (from grants). He said that a randomized control trial would involve partnering with multiple centers and getting a good biostatician to design the study and power it correctly. He suggested that the study have two arms. One arm compares it to the standard of care (atropine? oral-k?). He suggested going based on Denmark dosage recommendations. Set end point. Set specific reqs.

Bottom up approach: Dr. Zatrenau shared an example of two companies that have done an excellent job saturating the markets for ads for injectable medications for retinal conduction. He said that patients have come to his office to ask specifically for those medicines. Lots of potential for 7-MX and this is one way to help thread the needle.

Regulatory: Dr. Zatrenau said he was not familiar with the regulatory aspects of this project as he has not run a clinical trial himself yet. He said that we would need a clinical trial coordinator. He said that this position would know the most about regulations and what we would need and those requirements. The feedback he has gotten from his colleagues is that this position will make your life so much easier or, hell.

Dr. Corrine Scown September 26, 2023

We interviewed Dr Corrine Scown, a sustainability expert who works with project management related to sustainability analysis. She posed many questions and hypotheticals related to ENERGEM such as distinguishing between long term sustainability and short term solutions. While she thought our idea related to coffee grounds and its use in the bioreactor to synthesize 7-methylxanthines was interesting and a decent idea, she didn’t believe our project would have a huge impact long term in terms of sustainability. She also discussed many business questions in terms of how we would format our proposals.

Amanda Fallon September 28, 2023

In order to get an idea of how our project ties in with legislation and government regulation, we spoke with Amanda Fallon who works in the office of New York State Senator Lia Webb, the senator for our district and also a member of the Senate Committee on Health. Overall, she told us that most work to regulate a pharmaceutical product like ours would be done at the federal level, in particular working within the framework of the Food and Drug Administration to recognize the validity of the compound and also scalability for it to be potentially picked up by a pharmaceutical company. However, she did also tell us a bit about how our product would be handled later on at the state level if it were to be FDA approved, for example how the state might schedule the drug and the access and insurance side when it comes to things like the state deciding whether to include a drug on the Medicaid list or not.

Applications of Methylxanthines

We were recommended to select a compound that has a wide range of applications by Dr. Karim. This is a large part of how we ultimately settled on 7-MX. Given this diversity and considering that our technique can be used to produce a wide range of methylxanthines, we decided to create an Applications of Methylxanthines handbook to illustrate the broad range of uses for methylxanthines. This is a handbook that we could share with researchers, drug developers, and other stakeholders. It can also be used as a simple education tool for those who are interested in learning more about methylxanthines and their uses.

7-Methylxanthines and Myopia

As a human practices team, our goal is to ensure that we are meeting a need in the community and providing a product that has the potential to do the most good for the world: a human-centered approach. This means that we would like to have a product that can be applied meaningfully even when our initial goal mainly was to produce 7-methylxanthines in a cost-efficient and effective manner. Through this, we decided that myopia was the best application for our product. We understand that there are currently multiple treatments for myopia out there currently. However, our treatment provides one of the first biological treatments which can be used by people of all age groups and is not invasive like surgeries are. As recommended by our stakeholders, we compared our treatment to current options. Below we expand on how 7-mx compares in terms of side effects, invasiveness, and cost-effectiveness.

Side Effects

For side effects, common myopia treatments were ranked based on the amount of side effects combined with the level of severity for each one (i.e permanent damage versus nausea). The rankings were done on a spectrum from least amount of side effects to the most side effects present per treatment. The least side effect of heavy treatment is lifestyle changes. Significant lifestyle changes such as outdoor engagement do not negatively affect the body, but actually involve some holistic benefits as well (i.e cardiovascular health).

The use of 7-methylxanthines in oral tablets was placed next in side effects, as there are very minimal to no side effects according to published literature. When tested in regards to myopic treatments, when compared to the placebo there was no difference in organ function, neurological function and pathological expression. The use of 7-MX is well documented as well as it is a common derivative of caffeine which is in cacao and coffee.

The third treatment that does not affect the body significantly are corrective eye glasses. This treatment involves prescription eye glasses such as bifocals to correct for vision. The only notable side effect from wearing the correct prescription of glasses can be eye strain, but even that treatment is minimally invasive.

The next treatment placed on the spectrum in terms of side effects was contact lenses. Contact lenses have well documented side effects related to eye irritation which, while not severe, still creates discomfort to the wearer. Side effects include sensitivity to light, itching and burning, redness, swelling and general discomfort. This treatment as such was placed in the middle due to the level of severity of each side effect, where while not severe is still extensive and will have an impact on general life.

Orthokeratology was next on the list, differentiated from contact lenses in terms of level of correctivity and permanence. In contrast to common contact lenses, orthokeratology aims to reshape the curvature of the eye through rigidity and adjustments of the eye. Corneal edema is very common along with eye strain, causing significant discomfort to the patient. Clouding is also potentially prominent, leading to vision problems long term.

Atropine eye drops have significant side effects, and are potentially toxic in large quantities. Beyond general discomfort caused, atropine eye drops can cause cardiovascular problems related to arrhythmia and significant vision changes. In addition, atropine eye drops can cause vein occlusion in the retina, pain, and dizziness. Other known common side effects include nausea, vomiting, constipation, headache, dizziness and the like.

The treatment with the most side effects are refractive surgeries, commonly involving laser correction. Beyond prolonged discomfort and irritation, lasik may incur light sensitivity, astigmatism, corneal ectasia and permanent vision loss. This treatment was placed as the most extreme level of side effect mainly due to the level of severity of each side effect and its permanent damage related to vision.

References

Center for Devices and Radiological Health. (2018). Contact Lens Risks. U.S. Food and Drug Administration. https://www.fda.gov/medical-devices/contact-lenses/contact-lens-risks

Jain, M. (2019). Quetiapine associated Central Serous Chorioretinopathy: Implicit role of serotonin and dopamine pathways. Indian Journal of Ophthalmology, 67(2), 292. https://doi.org/10.4103/ijo.ijo_929_18

Liu, L., Trier, K., & Cui, D. (2023). Role of 7-methylxanthine in myopia prevention and control: a mini-review. International Journal of Ophthalmology, 16(6), 969–976. https://doi.org/10.18240/ijo.2023.06.21

Liu, Y. M., & Xie, P. (2016). The Safety of Orthokeratology—A Systematic Review. Eye & Contact Lens: Science & Clinical Practice, 42(1), 35–42. https://doi.org/10.1097/icl.0000000000000219

Invasiveness

Lifestyle changes were treated as the least invasive. This change involves no actual changes or modifications to the body, which make it a relatively less invasive method of treatment and change to myopia. Common changes involve going outside more often, change in diet and minimal screen exposure would impact myopia onset without bodily changes

Eyeglasses were placed as second least invasive largely because of the lack of changes made directly to the body. Eyeglasses are easily removable, can be modified to fit the body, and can be changed often without excessive touching of the eyes.

The administration of 7-MX was designated as the next stage of invasiveness. This involves ingesting an oral tablet, which while considerably more invasive than eyeglasses, do not involve the touching and modification of the eyes themselves, making oral 7-MX tablets less invasive in terms of constant modification and the prolonged exposure to the treatment itself.

Atropine eye drops were placed next onto the invasiveness scale due to its administration. Eye drops are administered through the eye, making it more invasive than 7-MX, but it is administered through only one to two droplets rather than constant exposure throughout the day. That administration technique makes it less invasive through a lack of constant contact to the eye.

Contacts were placed higher on the invasiveness scale due to the method of implementation. Contacts must be applied directly to the eye, which many patients find invasive and potentially irritating if not administered correctly.

While orthokeratology is administered in the same method as regular contacts, it involves more substantial implementation. Orthokeratology contacts are rigid, and as such might not perfectly fit the eye so modifications are necessary. Additionally, invasiveness here was determined based on the level of constant feeling of the treatment. While contacts fit the eye much better and are easier to forget about, orthokeratology contacts are more rigid and don’t fit the eye perfectly as they are designed to gradually modify the eye shape. As such it is much more difficult to ignore.

The most invasive treatment was refractive surgery, as that involves directly modifying the structure of the eye through surgery. Doctors create an incision in the eye to make a “flap” in the eye, and then use lasers to reshape the cornea. Due to the level of modification involved in the treatment itself, this treatment was deemed the most invasive, and as such was placed at the end of the spectrum.

References

Cost Effectiveness

The cost effectiveness of 7-MX was additionally compared to other current costs on the market, ranked in place of how much the treatment would cost per year. For extenuating cases such as surgery where treatment does not span long time frames, total cost of the surgery was used. In addition, the cost effectiveness was supplemented by an additional graph demonstrating permanence of the treatment. In this vein, cost was compared with how long the treatment will last versus needing replacement to provide a more holistic view of the cost of treatment versus the longevity.

The least expensive treatment was lifestyle changes, as its implementation requires little to know monetary intervention. For example, going outside can dramatically decrease the risk of myopia, and is an activity that is not extremely costly. It is important to note that this may be impacted by location, as some areas do not get as much sunlight as others, and as such the prevention of myopia might not be as prevalent.

The second least expensive treatment was the use of eye glasses. While cost for glasses may vary depending on brand and prescription, the average cost for eye glasses is $200 and eye glasses may last up to two years, making it one of the cheapest options available. It is important to note that this is not a preventative measure, but rather a corrective measure where it does not treat myopia but instead corrects the vision itself. Hence, vision may continue to degenerate even with the use of glasses.

The third treatment is atropine drops, costing a range of ~$700 to $1100 a year. Treatment involves around one droplet a day in the eye, requiring around 10 ml for about 3 months of treatment. This treatment must be prescribed and the cost changes varies based on a multitude of factors such as concentration (5% vs 1%), amount needed, brand versus generic and production costs.

Contacts reside in the middle of the spectrum at about $1500 per year. Similar to glasses, contacts are not a preventative measure but rather a corrective measure to temporarily ease the problem. The cost is dependent on a few factors, such as if the contacts are daily versus weekly, daytime versus nighttime and hard versus soft contacts.

Orthokeratology contacts have a range of ~$1000 to $2000 dollars, but typically cost upwards to $2000. Orthokeratology contacts involve a gradual reshaping of the eye utilizing hard contacts, and as such they need to be precisely fitted to the patient, which involves more time and money as a result.

7-MX oral tablets were placed next on the scale at around $3943 per year if successfully implemented. This cost was based on a few factors but included production costs both on the wet lab side (i.e plasmids, reagents) and product development (bioreactor creation). While this is expensive, it is important to consider longevity of the treatment, as will be covered later.

The last treatment and the most expensive is refractive surgery, which involves substantial costs for both healthcare costs and the salaries for providers. The full treatment is extremely invasive and does also require healing after around 4 to 5 weeks.

References

Compounding, T. & C. (2021, August 13). Atropine Eye Drops for Children with Nearsightedness (Myopia). Town & Country Compounding. https://tccompound.com/article/medication-compounding/atropine-eye-drops-children-nearsightedness-myopia/

How Much Does LASIK Cost In 2023? (2021, October 19). Forbes Health. https://www.forbes.com/health/eye-health/how-much-does-lasik-cost/#:~:text=The%20cost%20of%20LASIK%20eye%20surgery%20varies%20drastically%2C%20ranging%20anywhere

Permanence

Cost effectiveness was supplemented by longevity of the treatment and its results, as that would paint a more thorough image of the cost-benefit and whether certain treatments are more worthwhile than others. This was showcased by a graphic titled “Effectivity via Permanence” where the scale was how long lasting the treatment results were.

The least permanent but near equal in ranking were eyeglasses and contacts. This is because both of these solutions are not preventative nor treatments, but rather corrective instead. As such, they do not prevent nor try to fix the issue at hand regarding myopia, but serve as a way to temporarily correct the vision for patients to go about their daily lives. This ranking also included the amount of times needed to replace the solution in regards to eye glasses and contacts, as these require replacements every one to two years due to changing prescriptions. The next ranking of permanence was orthokeratology contact lenses. Even though these lenses are designed to treat myopia by reshaping the eye, they aren’t long lasting changes, and the eyes gradually revert to their previous myopic shape after about 2 to 3 days. As such, orthokeratology lenses must be continuously worn to maintain the changes to vision, and even so these changes are not permanent.

Next on the ranking are atropine eye drops, as even though these drops are aimed to correct vision, they are not permanent changes as well. Atropine eye drops, once administered, can last up to two years in slowing but not preventing myopia progression. As such, these are substantially longer lasting than orthokeratology, but are not permanent as well.

The next change is lifestyle changes, as these mainly serve a preventative measure for myopia progression, but are extremely variable and not very measurable. If proper lifestyle changes are implemented, then myopia progression can be limited for decades, but as such, it is still very dependent on the individual and confounding factors.

7-MX oral tablets were ranked the second highest in permanence, as they not only serve to treat myopia, but also prevent the further onset of it. According to an interview with Dr. Maria Liu, the director of the myopia clinic at Berkeley, 7-MX can have long lasting preventative treatments, as it restructures and strengthens the eye so that it is unable to re-elongate after myopia has been successfully treated.

Finally, refractive surgery was listed as one of the longest lasting treatments primarily based upon how long its benefits persist. It is notable however that sometimes benefits decrease over time in patients, but it is dependent upon the individual as well. Additionally, about 10-12% of patients will require enhancement surgery due additional anatomical changes in the eye.

References

Myopicare | Frequently Asked Questions. (n.d.). Myopicare.com. Retrieved October 11, 2023, from https://myopicare.com/faq#:~:text=Is%20Orthokeratology%20Permanent%3F

Researching Policies and Practices

Bioethics

Generally defined, bioethics means the ethical, legal, and social aspects of the areas of biology and medicine. When it comes to synthetic biology, or a field where the tools of biology are altered and redesigned by humans in order to accomplish a specific goal, it is especially important to keep these aspects in mind. Changing what occurs naturally in the world and involving living organisms brings up a lot of ethical and legal questions: When is it acceptable to manipulate natural processes and other living organisms in our projects? How do we treat these organisms with kindness and respect? What are the rules and regulations around doing so? How might the outcome of a project affect the greater human society and also the environment and other living creatures? Thus, when brainstorming, designing, and then carrying out any synthetic biology project, the consideration of bioethics is key to creating a project that contributes meaningfully to our world but is also ethical and respectful while doing so. This is what we hope to accomplish with ENERGEM.

For our project specifically, our process to create 7-MX does pose some ethical questions. Since we are creating a production process for a chemical with the potential for industrial scale up, it is important to consider the impact of this process on the environment and also any side products that may be produced. While our goal is to create a synthesis that is actually less harmful to the environment than the one currently in use, formaldehyde is produced as a byproduct of the reactions involved. To address this, we spoke with various synthetic biology experts, such as Dr. Jeffrey Varner. He told us that though it may take an extra step, it can safely be removed and disposed of safely which helped us to address this concern. Thus, our project should not be introducing any additional harm into the world while we accomplish our goal.

Another ethical consideration for our project is what our product will be used for. Currently, we hope to target the 7-MX we produce towards industries where it has shown useful, such as agriculture or medicine. While we would not be releasing any engineered organisms used in our synthesis into the environment, our product could ultimately be used for something that we had not intended, good or bad. Thus, this is also a question of ethics that we must consider when setting out to produce these molecules. While we have only good intentions for the application of our product, we must also take into account that it could potentially be used for something else once released.

Law and Policy

ENERGEM has applications in many different fields and thus needs to adhere to different laws and regulations depending on the purpose of the project. The two major applications for this project revolve around respiratory therapy and a natural pesticide.

According to the Food and Drug Administration (FDA), 7-MX will be classified as a drug. To be approved as a drug there must be an analysis of the medical disease and available treatments, an assessment of benefits and risks of the drug from a clinical trial, and strategies for managing risks. Therefore, the product will need to withstand numerous iterations of analysis before determining if it is safe for human use. We have spoken to various experts including Amanda Fallon and Dr. Brennan to get a better understanding of what would be required for the FDA approval process. We expand on this further on our entrepreneurship and business page as it will be required if we choose to pursue this project beyond the research and development process.

If this project was targeting the agricultural sector as a pesticide it would need to satisfy regulations created by the U.S. Environmental Protection Agency (EPA). According to the EPA, in order to be a viable pesticide, the ingredients of the pesticide, particular crop it will be used on, the amount of pesticide, and disposal methods must be investigated. During the assessment, its effects to human health as well as the ecosystem are examined to determine its risk assessment. The Food Quality Protection Act of 1996 also states that the pesticide cannot pose any threat to society. In order to be sold in the US, the pesticide must be approved by the EPA. Furthermore, the FDA requires that pesticide tolerances are advertised to indicate the highest amount of pesticide that can be consumed without being lethal. Furthermore, when packaging the product, the pesticide label must indicate how to safely use the product.

Safety

Cornel iGEM is committed to ensuring the safety and well being of all team members, the environment, the greater community and all those our projects aim to help. We understand and recognize the risks that come with working in a laboratory environment, and continue to dedicate ourselves to minimizing all such potential dangers.

Training - Each team member must first go through extensive training before being allowed to work in a laboratory setting. Members in the wet lab must go through two safety certifications through Cornell University’s Environment, Health and Safety division (EH&S). Additionally, all team members who work in the lab were expected to complete training with Dr. Shivaun Archer, senior lecturer in Meinig School of Biomedical Engineering via a laboratory tour, safety lectures and in person training.

Product development experienced similar training in handling electrics and machinery. Since this project deals with building a free flow reactor, the only main safety hazards present here deal with electrical risks, and are avoidable with proper precautions as outlined in training.

All new members were expected to complete online training through Cornell University’s EH&S division as well. This training covered proper safety procedures related to chemical handling, laboratory equipment and proper overarching safety protocol.

Safety officers were also present, team members who were selected to maintain safety practices at all times. They were in charge of ensuring proper protocols were in place during experimentation and lab work, and acted as liaisons between Cornell iGEM and the International Biosafety Committee.

Because the end product of ENERGEM is a synthesized biochemical, proper protocols concerning biochemical synthesis were rigorously enforced. This project deals with the synthesis of 7-methylxanthine, which is non toxic via enzymatic reactions. Specifically, enzymes NdmA and NdmB were used from Escherichia Coli, a BSL 1 organism. Even though this organism is relatively mild, Cornell iGEM treats each organism with careful consideration and caution. Proper safety procedures such as PPE usage and handling of the bacterium in the biosafety hood.

The enzymes NdmA and NdmB from E. Coli undergo a hefty purification process involving affinity chromatography. The resulting E. Coli will then be disposed of via lysing and vacuum filtration. Additionally, once extracted, the NdmA and NdmB will be contained in alginate beads which are further contained in a sealed reactor, preventing exposure and potential contamination.

Since this project deals heavily with a produced biochemical that has implications in medicine, it is important to assess the potential risks and all possible chances of error. The resulting product must be extremely high in purity. As such, extreme testing must be done to the produced methylxanthines to ensure no risk of contamination and safety issues, first in animal based clinical trials and then human trials once successful.

Implementing and Expanding on Human Practices Frameworks

SEG

SEG is a framework we discovered from the Exeter 2018 team which stands for Safe, Ethical, and Good for the World. After evaluating our project using this framework, this is how it applies to us:

Safe

While working on ENERGEM, we adhered strictly to Cornell’s project team safety guidelines. All new members were required to complete an online safety training course through the staff of Student Project Teams in Cornell’s College of Engineering as a part of onboarding to the team, and members on our wet lab and product development subteams received additional training when it came to starting work in the labs. Personal protective equipment is always used when working with biological materials, and the bacteria being used, or E. coli, is a BSL-1 organism which is considered to present minimal hazard to the environment and those working with it.

Ethical

While working on our project, we are planning to consult with bioethics experts at Cornell and beyond in order to discuss the ethicality of what we are doing. Thus far, our project appears to follow ethical guidelines as it uses E. coli, or a widely accepted model organism in synthetic biology. Additionally, it does not introduce harm into the world as any side products, such as formaldehyde, can be safely disposed of. The only remaining ethical questions is what our 7-MX might be used for after production, but we are planning to do our best to target them towards use in the medical industry where they are considered valuable.

Good for the World

Overall, the goal of ENERGEM is to produce valuable and medically important molecules, or 7-MX, in a more efficient and environmentally friendly way than what is currently being done. These compounds have been used in the treatment of medical conditions like chronic respiratory conditions, and so our project would be “good for the world” because it would make 7-MX more accessible to those who need them. Additionally, it seeks to do this in a way that is less environmentally costly than current production methods which makes it “good for the world” as well. Myopia is likely to impact over 50% of the world’s population by 2050, making our product all the more important to pursue.

AREA

The AREA framework was designed by the Exeter team in 2017 which stands for anticipate, reflect, engage, and act.

Anticipate

Anticipating includes the process of evaluating societal issues and designing a project to address them. This is a repetitive project as we continuously reflect on how the purpose and methodology of our project changes as we develop our ideas. This ideology also allows us to evaluate how our product will be innovative and how it will shape society.

We designed a project which is versatile and can approach issues plaguing different sectors of our community including: medicine and agriculture. Contacting experts in agriculture (for example Dr.Jennifer Thaler, Christophe Duplais, and local farmers), experts in medicine (such as Dr.Joanna Bishara) helped us to evaluate which sectors would be a good product for our project. As we continued to receive feedback, the purpose of this project was brought to a more niche subject, thereby supporting the reflection part of this framework.

Beyond the applications of this project, the actual methodology is novel. We are first engineering enzymes via directed evolution and implementing a cell-free immobilized-enzyme reactor for the high efficiency production of 7-MX and paraxanthine. This unique procedure could be applied to other fields to shape synthetic biology research and development.

Reflect

Reflection allowed us to revisit our initial idea and ensure that despite alterations made to the project it still targeted the societal issue of concern. With regards to determining an application for this project, it forced us to understand why this project was so important.

Stakeholders were crucial to this step of the framework. Their advice shaped how the methodology was altered and the potential application for the project. Interviews with Dr. Joel Kaar, for example, recommended HPLC as a method to optimize enzymes. In addition, while agricultural connections were difficult to find, Dr. Jennifer Thaler helped identify potential sectors within the agricultural industry that we could target, for example caffeine production or pollination, thereby steering us away from our initial idea as a natural pesticide. Given that methylxanthines are versatile, determining which industry to target took significant reflection.

When closing the loop, we received feedback from professors that we had interviewed before and organizations that we had collaborated with on outreach events. This made it possible to engage better with people and have a better understanding of how our project improved.

Engage

Engaging encapsulates two ideas: communicating with stakeholders and the community. Interviewing experts in different fields provided feedback on how our product could be produced, how it could be perceived by the community, and its possible applications. Engaging professors, people in agricultural industries, and professors allowed us to reflect on what the importance of the project was, thereby helping to shape our project. Reaching out to the community not only made them more comfortable with our project, but also synthetic biology and the future of science. Visiting the science center and creating educational videos allowed us to reach a wider audience.

Act

Finally, act is the response to the feedback received by stakeholders. Without implementing the feedback, the rest of the framework lacks purpose. The first parts of the framework essentially lead to this point, allowing us to implement these suggestions to improve our product. As we implement these solutions, we continue to iterate throughout this framework to ensure that we manufacture the best possible product. Reflecting on the actual execution of these ideas was crucial to the development of this product.

ELSA

ELSA is an ethics framework also devised by Exeter. It stands for Ethical, Legal, and Social Aspects. Below, our team has applied to our project for the year:

Ethical

Ethics are something that Cornell iGEM holds very dear, and aim to be conscious of through the entire development of the project from conception to finalization. This was no different for the development of ENERGEM. From conception, the main issue that we aimed to tackle included the increased prices limiting accessibility of the vital biochemical methylxanthine. Upon reviewing and analyzing many guidelines and legislation related to methylxanthines, interviewing many experts in bioethics, and even creating our own handbook regarding methylxanthine usage, we found our project to be extremely ethical from conception to finalization. Our specific goal for this project was to create a synthesis method of methylxanthines that was more eco friendly, more cost efficient and more accessible to the general public. Our project ultimately is able to accomplish all three overarching goals.

We might also consider the synthesis and execution of our project. All lab work was conducted in a safe and ethical manner compliant with Cornell and iGEM standards. Additionally, interviews with the Policy and Practices Team were conducted with the consent of the interviewees with the knowledge that the interview may be used to inform ENERGEM work.

It is also important to consider the uses of our project. We targeted ENERGEM to focus on particularly vital industries such as agriculture and medicine. The bacteria used will not be released into the environment, limiting any potential risk of environmental contamination. However, the produced methylxanthines must be pure, especially in the case of medicinal usage. While our project is mainly focused on scale up and accessibility, purity ensures that safety regulations are rigorously enforced. In agriculture, purity in methylxanthine usage allows for more efficient insecticide application and stronger antifungal properties. In medicine, applications such as COPD and myopia need rigorous testing to ensure FDA compliance is met. Any less can place the patient at unnecessary risk.

Legal

Since our project largely concerns the synthesis of biochemicals, it is extremely important to adhere to all international and local laws and regulations regarding synthetic biology, including those related to the production of a synthesized product. All laws and regulations related to lab safety and restrictions were adhered to and upheld both in wet lab and dry lab work related to product development. All credit from interviews and other research was given when due, and nothing from this project was included without consent. There was additionally nothing dangerous or biochemically changed released into the environment, and EPA standards were rigorously upheld as well.

Since this product deals with agriculture and medicinal applications, it is important to note all FDA and EPA regulations were upheld. On the medicinal side, the product would undergo rigorous FDA standard testing and inspections to maintain human health and safety once synthesized. On the agricultural side, both regulations from the FDA and EPA will be followed from synthesis to production.

Social

While this project is largely related to manufacturing and production, there are many social implications to consider. The main scope of ENERGEM was to create a much more affordable and accessible process to synthesize methylxanthines. Since methylxanthines are a highly prevalent chemical in both the agricultural and medicinal industries, increasing accessibility is tantamount to increasing consumer affordability.

Beyond this, we continued our quest to expand public awareness on synthetic biology. We consulted bioethics scientists and led many outreach and educational projects to reach many different stakeholders. Such projects included a virtual recorded lecture style class that teaches about iGEM and leads students through the process of creating a project, as well as a student-led class that addresses the variety of applications of synthetic biology.

Designing Human Practices Frameworks and Tools

EUDI

Emphathize: Empathize by hearing stakeholders voice opinions and challenges that they face. Include a larger sphere of influence beyond common stakeholders to gather a much broader perspective on the issue being addressed and the various diverse understandings of it. We added this earlier on our page.

Dr. Brennan: Concentric Circles should be involved where you go beyond the intended stakeholder audience to include others who might potentially be affected such as family and disposal to create a more nuanced viewpoint of the issue

Understand: Understand these aforementioned challenges through a variety of perspectives. Including a subcategory known as “ethics standards”, which involves the categorization of the perspectives gathered to find a general consensus between perspectives and which aspects can be feasibly addressed.

Dr. Van Campen: Including ethics standards allows for a deeper understands of which perspectives and stakeholder issues can actually be addressed by the project, and which perspectives cannot and how we can rectify these differences
Sciencecenter: How do the youth understand the issue and how can we effectively reach them?
Retirement Homes: What perspective do older people have on this issue and how does it change our own perspective?

Develop: Develop the technical components behind it

Dr. Sijin Li: Understanding the technical components behind the immobilized enzymes and genetic engineering necessary
Dr. Alabi and Dr. DeLisa: Understanding the technical components behind the reactor

Implement and Assess: Implement ENERGEM and evaluate its effectiveness in addressing the issue of myopia

Farmer’s Market: Outreach
SPLASH: Education

In comparison to what we had last year, we decided to specifically update the two sections regarding stakeholdership known as Empathize and Understanding after extensive research and interviews. With regards to Empathize, after an interview with Dr. Aoife Brennan, we learned that through our previous definition of Empathize, many stakeholder perspectives could be lost. For example, even if we reach a patient as a stakeholder, we might neglect to include how the proposed treatment might affect the patient’s family, disposal methods, and so on. As such, Empathize was updated to include a much broader sphere of influence to more accurately understand the issue at hand and possible solutions.

Understanding was also updated to include a subsection known as “Ethics Standards”. Per our interview with Dr. Van Campen, it was understood that even if we do gather all these perspectives, we must find a consensus between them all to hone in to what perspectives can be addressed by us, and which ones unfortunately cannot. As such, finding the lines that connect all the different perspectives and focusing on those key similarities would allow for a more focused and targeted answering of the problem at hand.

EUDI is a framework used by our team last year that takes into consideration empathy, understanding, development, implementation, and assessing

Applying EUDI to our Project

Empathize

While designing our project, we tried to do so with the opinions and challenges faced by potential stakeholders in mind. In particular, when we spoke with Dr. Christina Cherry, she said that currently myopia is an epidemic, and this was seconded by Dr. Maria Liu who said that myopia is a huge issue currently, and most methods to treat it are invasive and not very accessible. Thus, for patients of myopia we tried to learn about their current struggles in receiving treatment through the doctors who are treating them, and then we aimed to incorporate this into a project that would make a newer treatment for myopia, or 7-MX, more readily available for them.

Understand

Additionally, we tried to understand these challenges from a variety of perspectives. Through our outreach events at senior living centers such as Kendal and Longview, we were able to speak with older generations about ENERGEM and myopia, and they were able to share their experiences with us which let us consider their perspectives as potential stakeholders. We also had events at places like the Ithaca Farmers Market and the Sciencenter which enabled us to talk to a wider range of people in the Ithaca area and in particular kids and their families. We were then able to incorporate their perspectives on the myopia issue and our proposed solution into our project as well.

Develop

After this, we were then able to develop the technical components behind our project, ENERGEM, which aimed to meet the various needs that we had previously identified. Some key interviews we conducted in order to develop our project included speaking with Dr. Sijin Li, who was very helpful in giving us information about how to go about immobilizing our improved enzymes for use in the reactor, as well as an interview with Dr. Christopher Alabi who gave us insight into reactor flow. We also spoke with Dr. Joel Kaar who was key in encouraging us to use an adaptive and directed evolution approach to improve the enzymes involved in the synthesis of 7-MX.

Implement & Assess

As we neared the end of our project, we began to consider how our 7-MX could potentially be scaled up and implemented in a larger setting, such as in the context of a pharmaceutical company, and then assess what would go into this and how it would affect our stakeholders. In doing so, we spoke with Dr. Aoife Brennan, who gave us advice about how to apply ethics to our project in terms of first concentrating on general ethics questions and then those more related to our project, and advised us to really focus on our value proposition and who the project is really for. We also spoke with those in government as well such as Amanda Fallon who gave us advice about what it would take to get our product approved at a federal and state level, and our business subteam spoke to those in industry as well to get information about how our project could potentially be implemented and scaled up. From all of these interviews, we were then able to assess the steps necessary to getting ethical and legal approval, and also how our project would overall affect stakeholders if ultimately implemented.

Why We Chose EUDI?

We chose the EUDI framework because it is the most applicable to our project. The first part of this framework takes into account the stakeholder’s opinions and challenges (whether that be with production methods or current myopia treatment). Current methods of production of 7-MX and paraxanthine are challenging given traditional methods, making this product short in supply to investigate its potential effectiveness and utilize it as a therapy. While investigating the appropriate field for ENERGEM’s application, stakeholders in both the agricultural and medical fields were interviewed to determine this project’s potential effectiveness. Interviews with professionals in the agricultural field elaborated on how this is unnecessary due to current pesticide usage. Respiratory therapists indicated that methylxanthines would be ineffective in comparison to current respiratory therapies. However, ophthalmologists were highly intrigued by our product as it could be used as a novel myopia treatment.

Therefore, via our Ethics criteria, we were able to compare these applications and select myopia treatment as the ultimate application of our project. Our project fulfills the “Understand” criteria as we followed up with myopia professionals and physicians such as Dr. Christina Cherny and Dr. Maria Liu who elaborated on challenges with current myopia treatments and how ENERGEM could revolutionize the treatment of myopia by improving the availability of methylxanthines who need them. With regard to the “Development” criteria, our team created a novel system of first producing relevant caffeine metabolizing enzymes via directed evolution and then implementing a cell-free immobilized-enzyme reactor for high-efficiency and lower-cost production of 7-MX and paraxanthine. Interviews with biology, chemistry, biomedical engineering, and biological engineering professors improved our methodology, allowing us to maximize our efficiency and cost-effectiveness. Finally, outreach events to Retirement homes, the local farmer’s market, and interviews with professionals allowed us to assess its need in the community and how they would perceive our product. If administered as an oral treatment, methylxanthines will transform the way optical treatments are administered and make optical treatments more attractive and accessible to potential users.

How can other teams build off of our work?

Similarly to how our team did with SEG, AREA, and ELSA, EUDI provides other iGEM teams and synthetic biology researchers with an opportunity to evaluate and design their project with EUDI as their guideline.

Education and Outreach

Our Goal

7-methylxanthines have diverse applications from medicine to agriculture, and our goal was to share this information with the broader community. To do so, our team created a handbook outlining the different applications of methylxanthines. However, through our education initiatives, we extended our outreach beyond just those who would use our product to educate children through events like Sciencenter and Splash, our science video series, and hosting ethics debates at various nursing homes. Every event was designed with a specific goal and group of people in mind. We loved speaking and engaging with the community as we learned much about their perspectives on synthetic biology and we hope they learned as much from us as well.

Splash

April 29, 2023

Final Bioethics Case Study Presentation

For Splash this year, we decided to focus on teaching students about bioethics. We felt that this was an area that a lot of schools don’t focus on when teaching students about science and biology, so we thought this would be a nice supplement to what they may be learning elsewhere. Our target group was high school students, many of whom have taken at least one semester of science (however, that was not a requirement). Splash brings students from all over the New York tri-state area, allowing us to reach not only students in the local Ithaca community but in the greater Northeast as well. We taught two sessions during the day, approximately fifteen students per section. We had three different stations that presented three different case studies addressing different issues within synthetic biology. The students were divided into small groups of 5 and rotated through each of the stations, having discussions and asking questions about the case at hand. We decided on this lesson plan because we thought this would be a great way to engage and encourage the students to think for themselves rather than following a traditional lecture style lesson plan.

Splash is an event that Cornell iGEM participates in on an annual basis. Last year, some of the feedback we got was that our activities, which included making slime and candy DNA, while fun and engaging, didn’t always feel age appropriate for high school students. That is also a large reason why we decided to move to a discussion and debate style class as it would give students the same chance to have fun and be engaged with others, but also be more intellectually stimulating and age-appropriate. We love that Splash has become a Cornell iGEM tradition, allowing us to build and improve from the work that we do in previous years.

After class, students were asked three questions: how excited are you to learn more about this topic, what was the difficultly level, and how engaging did you find this class? Students, on average, ranked their excited-ness level a 4/5, or more excited than they previously were. On average the difficult was a 3/5, or just right. Lastly the class was on average 2.5 for engaging, or between pretty engaging and very engaging. We loved that we were able to get feedback from them and hope to reincorporate this for our new Splash session in November.

Sciencenter

March 4, 2023

For our first Sciencenter event of the year, we decided to make the theme of our event synthetic biology in general as we hadn’t chosen a topic for our project yet. The age range for the Sciencenter is often children as young as 2-3 and as old as 8-10, so we wanted to have a range of activities that could appeal to all age groups. Throughout the couple hours we were there, we had approximately seventy children and their families come through and engage with us.

We had three different stations, each addressing different fields in bioengineering. We had one station that used the Building with Biology Kits that was meant to teach children about Bio Bricks and the potential applications of synthetic biology. This station was more geared toward our older childrenwho were more comfortable reading, but we did our best to explain the concepts and read the materials out to the younger children who were interested in this station. Our second station had candy DNA where we taught the children about DNA structure including nucleotide base pairs and its double helix structure, and our last station was focused on polymer chemistry and had children making slime while learning about polymers and chemical bonding. We thought this would not only cover a wide range of age ranges but also interests and focuses within synthetic biology.

Overall, the event was a success as we had many students come through and state that they learned a lot from our activities. We look forward to returning to the Sciencenter soon.

CURIE Academy

July 20, 2023

The CURIE Academy at Cornell aims to help high school junior and senior girls from underrepresented backgrounds develop engineering skills as a potential future career. This week-long program was designed specifically to prepare these students for a future in engineering specifically in a collegiate academic setting, with exposure to robust STEM resources, experiences and other educational opportunities.

During this week, wet lab members from Cornell iGEM were able to help give insight on experiences both in the engineering field, and in a narrower context in an academic setting through research. They hosted a panel discussion on the goals of iGEM, provided insight into the field of synthetic biology, as well as explained the current planned project for this year, ENERGEM. In addition to this panel, students were given a guided tour of the lab and performed various different experiments under the supervision of the lab coordinator and following all safety protocols in place. Students were also allowed to ask any questions pertaining to synthetic biology, career planning, as well as general college advice. Students were extremely interested in Cornell iGEM’s work, and were appreciative of the guided lab tour and the advice provided by wet lab.

Sciencenter

August 5, 2023

Over the summer, we returned to the Sciencenter again in August. This time, in addition to the slime, model DNA, and Biobrick activities, we also added in a fourth activity to represent our project for the year, which we did with Orbeez. Since we are using alginate beads in our reactor to encapsulate our engineered enzymes, we thought that the Orbeez could represent these beads. We inflated the beads, set them out in bowls and when children visited the station they were able to play with the beads and we told them about alginate beads in connection to our project.

For the other stations, they all stayed the same aside from a change to the model DNA station. Last time we went to the Sciencenter, we noticed that the kids became a bit distracted with the candy we used to make the DNA at that station. It also was not as safe to have candy out for the kids when many people were touching it and they wanted to eat it. In order to help with this, we decided to switch over to using pipe cleaners to construct the DNA instead. At the event in August, while the kids were definitely not as interested as when we used candy, we overall thought that they were able to better absorb the information about DNA as they were not focused on consuming the candy.

In general, we thought that the event went well. We were also able to collect some feedback from the parents of children through a survey we asked them to fill out at the end. Results of this survey are summarized below.

Overall, based on survey results the experiments that were most enjoyed were slime and orbeez based on responses from parents.

Ithaca Farmer’s Market

August 20, 2023

Another event we held over the summer was tabling at the Ithaca Farmers Market, which is a weekly market and local favorite that runs every Saturday and Sunday in Ithaca during the spring, summer and fall. At the market, we set up a table with various infographics we had made about our project as well as ones about iGEM and synthetic biology in general. We were able to talk with a lot of different people while we were there, from retired professors to families living in Ithaca. Overall, we went to the market to get a chance to talk to a wider audience about our project and synbio in general than we could on campus alone, and after the event we did feel that having a table at the farmers market definitely allowed us to speak with a greater diversity of people.

Kendal at Ithaca

September 14, 2023

We presented and hosted a bioethics debate comprised of many different ethical issues in synthetic biology at Kendall at Ithaca, a retirement home. We first presented on what Cornell iGEM does, who we are, and our overarching mission regarding synthetic biology. We then expanded upon it with our current project, ENERGEM, and current ethical questions in it, such as the regulations behind 7-methylxanthine testing, pre-clinical and clinical trials involved and the differences in testing in different world locations. Then, more prevalent issues in synthetic biology such as genetically engineering animals to target invasive species, and genetically engineering crops to be more nutritious were discussed.

We were able to have an extremely engaging conversation with the seniors about all the topics previously discussed. They brought up nuanced point of contention and questions that were extremely beneficial to our own understanding of our project and synthetic biology as a whole. Often times, conversations can branch off and another topic in synthetic biology that was different but still relevant to the conversation would be addressed, such as the impact of toxicity in food and population changes. It was a very interesting discussion and we will definitely be returning for another discussion.

Longview Senior Living Community

September 18, 2023

Since we wanted to get as many perspectives as possible, we decided to host another event at Longview Senior Living Center. Similar to what we did at Kendal, we prepared synthetic biology case studies for a bioethics debate, including one about our own project ENERGEM. We started off with a general introduction to what our team does and iGEM in general, followed by a discussion about our project and a question and answer session about it. We then moved on to the other case studies which were the same ones previously described we went through at Kendal.

Overall, hosting this event was a great way to hear different perspectives on our project as well as on topics in synthetic biology in general. The participants brought up a lot of great ideas and suggestions that we had not thought about previously, and they also seemed genuinely interested in the topics and integrated their personal experiences as members of an older generation than ours. When collecting feedback, we learned that they really enjoy engaging in scientific discussion such as this and are actually looking for more activities of this type at their center, so we would love to return in the future as it seemed that everyone involved including ourselves really enjoyed and benefited from it.

Final Bioethics Case Study Presentation

Beverly J. Martin Elementary School

October 4, 2023

Cornell iGEM conducted an outreach event at the Beverly J. Martin Elementary School located in Ithaca, NY. About 50 students between grades 3 and 5 attended the event. We divided the students into groups to maximize individual interaction with students and maximize their learning and engagement with the material. This event was similar to the Sciencenter, where we had three different stations that children rotated through including chemistry polymerization, DNA Synthesis, and Orbeez (which relates to our project ENERGEM). This outreach event was popular amongst students as it challenged them to think about the potential of biology in an engaging manner. The after school program supervisor expressed her delight for the event and desire for us to return. The students were also eager to participate and learn in the event. When taking pictures of the event we made sure to get consent from the supervisor. The one comment that the supervisor had was to have an additional event where students in grades kindergarten through second could also participate since it was such a big hit. In addition, for future events we would love to include a survey for kids to fill out so they could indicate how much they learned and if this changed their perspective on science. We look forward to continuing to partner with the elementary school to host these educational outreach events and raise interest in synthetic biology.

Science Experiment Video Series

This year, we decided to create a video series for children that focused on teaching them important science concepts related to iGEM and our project. We wanted to be as engaging as possible and interactive so we filmed a series of experiments, the majority of which people can do from their home. We wanted them to be as accessible as possible, which is why we filmed them online. We had 4 total videos, focusing on topics ranging from DNA, polymer chemistry, to 7-methylxanthines and released them throughout the end of the summer and the fall.

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Pipe Cleaner DNA

For the first video in our summer science experiment series we showed students how to make pipe cleaner DNA. DNA is one of the most important and first science topics that students are exposed to. It is also important to understand DNA to manipulate cellular organisms when synthetically engineering organisms. Throughout the video we explain what DNA is, its monomers, its structure, and its importance in biology. Afterwards, we showed viewers how to construct their own DNA using pipe cleaners and beads.

Slime

As a part of our summer science experiment series, we produced a slime video. Throughout the video we went through a slideshow reviewing the chemistry of polymerization - the fundamentals of what makes slime possible. Since this is a complex scientific topic that many do not learn about until college, we used an analogy of a necklace to make the topic more understandable. We were able to relate the covalent bonds to the chain of the necklace which connects the monomers (or the beads on a necklace) to create a larger complex (which is represented by the necklace). At the end of the presentation, we connected this topic back to synthetic biology to indicate its importance with respect to how biological engineers can use this principle to manufacture biological organisms. After explaining the basic chemistry behind this phenomenon, we demonstrated how to make slime. By creating an interactive experiment, we are able to engage a younger community and show them the possibilities as to how fundamental science topics can be fun and interesting!

Strawberry DNA

For our third video of the summer, we decided to record a how-to video on how to extract DNA from strawberries. Even though we had an earlier video on the structure of DNA, we thought this would be a good opportunity for children to see actual DNA for themselves using just materials found in their own household. Given that the previous videos were focused on DNA structure, we thought it would be a good idea to focus on the central dogma of biology, explaining to them how DNA is transcripted into RNA and then how RNA is translated into proteins. In addition, considering that this experiment was the first in our series with more extensive steps, we thought it would be a good idea to also explain why we used the materials we did and followed the steps we did. For instance, we used dish soap to burst the strawberry cells open, allowing us to access the DNA for the experiment. We also thought this was a good experiment, not just because we hoped it would be interesting for the students to see actual DNA for themselves, but also because understanding DNA and how it gets translated into proteins is important for understanding how we can edit genetic information to produce proteins of interest in synthetic biology and iGEM.

Sodium Alginate Beads or Popping Boba

In our fourth video of the summer, we decided to focus on a project that is specific to ENERGEM. Making popping boba was an apt lesson because of its relation to spherification, a key component of the design of the cell-free immobilized enzyme reactor. In the video, we created a slide show that introduced the purpose of ENERGEM and the reason behind creating methylxanthines. This then led into the chemistry behind popping boba via spherification. Since this is a decently complicated topic in chemistry and engineering, spherification was explained in terms of chemical purposes. For example, the chemical sodium alginate was explained as a key component in making the liquid condensed enough to properly be encased. The calcium chloride was explained as a sort of activator, where the sodium alginate can not start until it comes in contact with the calcium chloride solution. These chemicals were then shown in a proper demonstration using coca cola as the encased popping boba liquid. Through this interactive experiment, we were able to create an engaging, educational video that related to Cornell iGEM’s current project while still being fun and interesting.

BioBuilder: The Game

Over the course of this past semester we developed a synthetic biology game which also relates to our project for this year (ENERGEM). The purpose of this game is to introduce fundamental synthetic biology projects. The game teaches users about synthetic biology techniques (including separation and recrystallization) and biobricks (DNA sequences that are used for larger biological circuits) by providing definitions as to what each component does. The gamer has to combine various biobricks and techniques to manufacture their own synthetically engineered project. We have also included previous iGEM projects such as Lumiderm (a model cancer bacteriotherapy system), Lead it go (a genetically engineered bacteria that combats heavy metal pollution problems), and ENERGEM (Cornell iGEM’s current project to produce 7-methylxanthine and paraxanthine). Essentially, the user learns about the process of synthetically engineering bacteria, what components to include and think of when generating a new product. By making this game a website online, we are allowing individuals from different backgrounds and demographics to have access. People of any age can easily utilize the app to learn about the synthetic biology process as well as potential projects or applications that their projects could have on the environment. Given video games popularity, this is a great way to reach a larger audience and introduce them to the potential of synthetic biology.

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Infographics

Another way we aimed to reach a broader audience was through the use of social media, mainly Instagram. We thought that this would target age groups such as our peers in college as well as high school students and possibly those younger. On our Instagram, we posted informational infographics about our project as well as synthetic biology in general. We also included some fun content, such as TikToks made by our Wet Lab subteam which we thought would capture the attention of viewers and show how synthetic biology can be fun too. At some of our events such as the Sciencenter, we did a series of Instagram stories to show what was going on as we hoped to give an inside look at some of the events we do. Overall, we thought that Instagram and social media in general would be a way to involve a broader audience in an easy way, that being right from their phones.

Conclusion

This year, Cornell iGEM focused on engaging members of different generations in the community on general synthetic biology, methodologies in synthetic biology, and information regarding this year’s project ENERGEM. General synthetic biology information as well as basic foundation in science was taught in educational events including the Sciencenter, Beverly J. Martin Elementary School, Kendal at Ithaca, the Ithaca Farmers Market, and the Science Experiment Video Series. These introduced individuals of different ages both in our local community and beyond to synthetic biology concepts, peaked adolescents’ curiosity in science, encouraged high schoolers to pursue a career in biological engineering, and challenged adults’ thoughts about synthetic biology.

These events sparked conversation in controversial topics and allowed us to determine how receptive the community would be to our product. Bioethics debates with local nursing homes gave us the opportunity to engage in meaningful discussion about recent research and gain new perspectives from different groups of people. The video game worked on teaching users of all ages about synthetic biology techniques and procedures. Its entertaining factor helps to make difficult concepts more digestible, thereby reducing the amount of people who find it overwhelming, and encouraging engagement.

Finally, project specific educational events were incorporated into each program as a way of receiving community input about the project. By educating the community, raising awareness about synthetic biology and its potential benefits and concerns, we stimulate discussion about what needs to be done to make the community more comfortable with these novel approaches. It is ultimately the community’s perception of synthetic biology along with scientific evidence that decides if this new technology is utilized by the government, the community, and stakeholders. Therefore, educating the community is key in improving their receptiveness, scientist’s production methods, and bridging the gap between production and application. In other words, without community engagement and feedback, our innovative solutions serve no purpose.

Inclusivity

Outreach

Through our outreach, we wanted to engage a large range of people from diverse backgrounds to garner different perspectives about synthetic biology and its larger context. The Sciencenter and Elementary School outreach event provided us with the opportunity to connect with young students fascinated by science. We have a variety of different topics shown through interactive and fun experiments designed to keep the children engaged while still being informative. We had more traditionally youth oriented experiments such as slime and orbeez, which reflected scientific principles such as polymerization and spherification. Through this, we were able to get a much deeper understanding of youth engagement not just in synthetic biology, but in science as a whole. This helped inform our contextual understanding of science through a youth perspective, such as what gathers the most interest, what concepts are most engaging and how we can work to further increase youth engagement and involvement in science.

Our Splash outreach event gave us the opportunity to interact with high schoolers who are strengthening their foundation in science. During the event, we were able to evaluate what high schoolers are currently being exposed to in school and how they can apply that knowledge to novel fields. While high schoolers are typically exposed to scientific facts in high school, they aren't typically exposed to the bioethics of what is being developed or how novel technologies can influence the world around us or the legal implications of it. Therefore, this event tried to incorporate a more inclusive and holistic approach to synthetic biology rather than simply focusing on solely scientific novelty which is typically the focus when discussing synthetic biology. Exposing high schoolers to this part of the scientific process and manufacturing revealed considerations that corporations must take into consideration when manufacturing these products. As the next generation enters the workforce, it is important to emphasize a more inclusive educational approach that will make emerging scientists more analytical as to how their technology will impact the world. Responses from the class showed that the students were engaged and challenged by the material. They were forced to look through a different lens, other than a scientific one, to analyze these scientific concepts, making this a more engaging class than previous years.

On the other hand, we also wanted to get a more nuanced understanding of the age demographics invested in science. To do this, we hosted a variety of bioethics debates with senior living communities to reach older members of the community. We worked specifically with Kendal Retirement Community and Longview Senior Living Center to gain a much stronger insight into a different demographic’s perspective about synthetic biology. In these bioethics debates, we tried to garner different perspectives on a variety of current topics, including gene editing and compound manipulation. The events consisted of presentations regarding real life case studies, and fostered an active dialogue about whether it is ethical to change DNA, what laws and regulations might synthetic biology fall under, and even where should the line between what is acceptable and what isn’t be drawn. They asked many interesting questions that both challenged and enhanced our perspective of synthetic biology. Questions included: how would our product be administered, how our project is being developed in an ecofriendly way, the safety of our product, and how different countries would respond to our product and synthetic biology in general. After explaining our project into greater depth and indicating that this would be an orally administered drug instead of the typical eye drops and that it would be manufactured from caffeine, the audience was more receptive to methylxanthines as a potential treatment. If more testing was conducted, they would fully consider this as a viable treatment. We wanted to include a different generation that has a different understanding and perspective of biology and science as a whole. This experience was very informative and helpful for us. We were able to work with them to learn more and generate discussion about the most important ethical issues to them as a different generation. For example, with regards to synthetic biology, the main concern was safety. While the younger generation is investigating novel solutions and is more open minded to this new technology, older generations are more conservative. Genetically modified fruits and vegetables with a greater concentration of bioactives, for instance, was perceived as unnecessary. The potential to have more risks with an increased dose or unintentionally cause allergies. This was seen in Ultimately, it was their experience with past biological incidents that fueled this conversation and concerns of repeating history. Later generations cannot provide this insight as they haven’t had the same experiences, thereby offering a unique and valuable perspective on synthetic biology. Furthermore, to account for nearsightedness, which is more popular amongst older individuals, we formatted the presentation with larger text and images so they could read the text and be involved in the discussion. We were also able to receive feedback about how older members of the community felt about the event. The event was received very well as they engaged with each project, asked questions, and discussed amongst each other. In fact, they requested that we attend more often. Therefore, in the future, we hope to hold consistent discussion groups where we can discuss different synthetic biology issues in depth. We can also get feedback on the development of our project from senior citizens.

Additionally, to gain a better perspective of our project, ENERGEM, and current public understanding, we hosted a table at the local farmers market to discuss methylxanthines and their various different applications. We talked to a variety of different local citizens, with different professions, age groups, and perspectives as a whole. We asked different citizens attending the farmers market what they knew about methylxanthines and how they felt about the different applications listed. We specifically made a methylxanthine pamphlet detailing what methylxanthines are and the various different fields they can be applied to. Throughout the event we met beekeepers, farmers, and people diagnosed with myopia who had interest in the product. Those affected by myopia were intrigued by the non-invasiveness of our product. We also interacted with other college students, talking about synthetic biology and iGem. Therefore, this not only was an educational event about our project specifically, but we were also able to talk about synthetic biology in general and introduce an emerging field to students who will be entering the workforce soon and may be interested in going into this field. It was great getting to know the many different perspectives that exist on our project and on methylxanthines. The Cornell Daily Sun also wrote a paper on our event at the farmers market thereby raising awareness to the entire community about Cornell iGem, synthetic biology, our goals, and our project specifically.

Finally, we aimed to be as accessible as possible for any interested members of the general public to learn more about what we do and about synthetic biology. At first we wanted to host an in person synthetic biology science summer camp where students would develop their own science project. However, after reflection we wanted to reach a wider audience, leading to the development of an educational video series on science activities and experiments that can be conducted at home. This also allowed for discussion in the comments section as viewers could interact with each other, ask questions, and post their reaction to the videos. Furthermore, we also created subtitles to make our videos accessible to a wider audience and not prohibit those with auditory disorders from interacting with the video. As part of our educational series, we made a published playlist of scientific experiment videos, as well as a related educational game accessible online to everybody. Additionally, we continued working on establishing a stronger online presence via instagram and tiktok to increase awareness and accessibility of the goals of Cornell iGEM.

Myopia Treatment

Currently LASIK, a corrective eye surgery that indefinitely reshape your cornea is a common treatment for myopia. This surgery essentially alters the refraction problems in the eye. However, since this is an invasive form of treatment, children who are suffering from myopia are not candidates for this treatment since their eyes are still developing. Given that myopia is becoming more prevalent at younger ages, this will only become a greater concern for more individuals at a younger age and therefore, we need a response to target a larger range of the population. While there are current treatments that are available to a younger population such as eye drops or contacts that help to reshape your eye, they are uncomfortable to most, making these treatments undesirable. In fact, these treatments (such as Atropine eye drops) have also been shown to have multiple side effects and can even cause systemic toxicity with increased dosages.

On the other hand, 7-Methylxanthines provides an alternative, novel, and more attractive manner of administering optical medications. This medication would be delivered orally, making it significantly less invasive compared to current forms of treatment. This form of treatment allows for myopia treatments to reach a wider population of individuals affected by the disease. Furthermore, our interview with Dr. Maria Liu, an associate professor of clinical optometry at UC Berkeley, emphasized the novelty and benefits of this treatment. She explained that since it is a safer and cheaper alternative, it will be more accessible to people suffering from myopia. She continued by saying how this could also be used as a preventative treatment indicating that even those who are not yet suffering from the disease could potentially benefit from this. Overall, ENERGEM aims at eliminating age barriers for myopia treatments, given its increasing prevalence in our society.

Human Practices

Our Goal

Evidence For Global Impact

Our Guiding Values

Communities Consulted

Impact of our Project

Reflection

Responsiveness

Responsibility

Interviews

Key Interviews

Closing the Loop Interviews

Applications of Methylxanthines

7-Methylxanthines and Myopia

Side Effects

Invasiveness

Cost Effectiveness

Permanence

Researching Policies and Practices

Bioethics

Law and Policy

Safety

Implementing and Expanding on Human Practices Frameworks

SEG

AREA

ELSA

Designing Human Practices Frameworks and Tools

EUDI

Applying EUDI to our Project

Why We Chose EUDI?

How can other teams build off of our work?

Education and Outreach

Our Goal

Splash

Sciencenter

CURIE Academy

Sciencenter

Ithaca Farmer’s Market

Kendal at Ithaca

Longview Senior Living Community

Beverly J. Martin Elementary School

Science Experiment Video Series

Pipe Cleaner DNA

Slime

Strawberry DNA

Sodium Alginate Beads or Popping Boba

BioBuilder: The Game

Infographics

Social Media

Conclusion

Inclusivity

Outreach

Myopia Treatment