When proposing a very patient-focused technology, well-integrated human practices are necessary to avoid harm to the users. Our methods for human practices centered around conversations with professionals involved in cancer and oral mucositis-related research and treatment and personal testimony. Our team members also engaged in self-education through online resources such as https://www.mucositisawareness.org.
Overview
- Our Goals and Establishing a Values System
- Discussions with John Essigmann, Ph.D.
- Discussions with Stephen T. Sonis, DMD, DMSc
- Attempts to Connect with the Local Community
Our Goals and Establishing a Values System
One of our main focuses concerning social values was ensuring a level of respect for the users' quality of life. Cancer patients undergoing therapies are under a high level of physical, emotional, and even economic stress. Some of this stress is also exacerbated by painful side effects. Therefore, we wanted to ensure that any product we proposed to alleviate these side effects did not result in more stress in a different aspect.
Comfort for the patient was important, so we wanted to design a patch that, in addition to providing a therapeutic service with glutathione, wouldn’t be bothersome for the user to wear and would serve as a barrier from further irritants. Additionally, when such a product is implemented, it would be important to ensure that patients are informed about what GMOs are and how they work, so they may feel comfortable with the use of genetically modified yeast in their mouth.
Additionally, minimizing risk and harm was an important factor in our design process, especially when working with a vulnerable population. Toxic side effects are to be avoided. For example, we wanted to ensure that the glutathione does not escape into the bloodstream, where it could travel to the tumor site and enhance tumor growth.
Discussions with John Essigmann, Ph.D.
Early in our project development, we met with John Essigmann, a professor in Chemistry and Biological Engineering at MIT. Essigmann’s initial feedback stemmed from his personal experience with cancer treatment and oral mucositis. He suggested developing a patch that could be worn to sleep, providing protection overnight. He also emphasized the need for the patch to feel benign in the mouth and to not cause additional discomfort on top of OM pain. Not only was this initial advice extremely helpful, but it also inspired us to search for more oral mucositis patients to talk to about their experience (3).
He also gave us feedback on our initial design plans. In particular, he expressed that we must ensure that the glutathione treatment does not interfere with the chemotherapy, as the ROS processes that cause healthy cell death and OM also help with fighting tumors. He cited previous attempts at oral mucositis treatments. One involved a Vitamin B therapy proposed to doctors at Massachusetts General Hospital by MIT, but doctors were concerned that it would make the tumor more difficult to treat. There was a similar case involving a Glutathione S-transferase (GST) based therapy.
With this feedback, we continued our literature review and landed on the conclusion that the glutathione would be localized enough and small enough to not affect the chemotherapy treatment. Although the patch will be applied to the oral cavity as that is where the OM arises, the tumors could be present in any part of the body and not adjacent to the mouth. Additionally, Essigmann posited that as long as the glutathione does not enter the tumor, the risk can be minimized . However, this is something that we would continue to focus on if the project continued into animal models.
Discussions with Stephen T. Sonis, DMD, DMSc
While in the ideation phase of our project, we reached out to a local DMD, DMSc, Stephen T. Sonis. He has had extensive experience in research of head and neck cancer treatment side effects, with a strong focus in oral mucositis (OM). His work includes a book titled Oral Mucositis in which he comprehensively explains the symptoms, path, recognition and management of OM. He also wrote various papers on the disease which our team was able to utilize in our project creation.
Fortunately, we had the pleasure of meeting with him over Zoom, where we presented our project and had a discussion on the applicability and potential concerns. One of the biggest concerns brought up in the meeting was the plausibility of our delivery system – namely using a patch design to target the sores. Dr. Sonis explained that there isn’t a way to feasibly predict where the sores will form on the mucosa. As a result, we looked to other methods of delivery. One idea included a bacterial cellulose rinse that would cover the whole mucosa allowing it to account for sores forming in any location. Another idea was a smart patch that would be able to detect the oxidative stress caused by the ROS release during the sore formation, and react by growing a patch in that area. In the end we decided to put these ideas for the project on hold in order to focus on the effectiveness of the therapeutic aspect of the project. We prioritized the therapeutic to ensure that we could effectively scavenge the ROS, before addressing how to deliver the therapeutic to the spot of damage. However, they are ideas we would like to implement in the future.
Dr. Sonis also brought up significant questions on the timeline of our treatment. Under his advice, we were able to decide that the patient would start wearing the patch before receiving their first dose of radiation therapy in order to allow the therapeutic to play a preventive role. He also asked how long the patch would last before it was ineffective. This question on the durability of the patch led us to decide that the yeast in the patch would be alive. This allows the yeast to continuously release the glutathione until the ROS is fully scavenged. We would then implement a kill switch once there is no more ROS to stop the yeast from growing.
At the end of the meeting Dr. Sonis offered us various papers that included other oral mucositis research and attempted therapies that gave us a broader knowledge on the subject. He also invited us for a lab visit, at the company he works at, Biomodels LLC, which we luckily got to follow up on at the end of August. It was a meaningful experience to get to see and talk about the development and execution of these types of projects at a later stage.
Attempts to Connect with the Local Community
Additionally, we made various attempts to connect with people with OM in our area. We reached out to cancer support groups and developed a qualitative study to receive additional information about people’s experiences with OM and feedback on different treatment options. The proposed study would be conducted with adult participants through interviews via phone or Zoom call, with an additional questionnaire option to accommodate those for whom audio/visual communication is not accessible. Before reaching out to the local community we consulted IR at MIT to make sure that our methods were legal and ethical. To this we had to ensure that the data we would gather would be handled properly. This included the involved parties on the team taking COUHES Research Involving Human Subjects training and meeting with IR to determine what questions were acceptable and advantageous to ask. However, we were ultimately not able to obtain data from this approach. The recruitment flier is provided below, for reference.
