Human Practices | Virginia

Introduction

We interviewed experts in the field with the goals of defining the problem and designing a solution that most accurately addresses patient needs. The outline above highlights the path we took through interviewing a range of medical professionals, dietitians, modeling experts, ethicists, and more.

Shaping the problem

Brainstorming solutions with expert feedback

Refining the solution

Step 1

Step 2

Synthetic biology beyond our project

Determining future steps for clinical implementation

Experimenting and revising design

Shaping the problem:

Medical Professionals

How does EPI complicate daily living for pancreatic cancer patients?

Dr. Raymond Wadlow, MD

Credentials: Dr. Wadlow is an Inova board-certified doctor in Medical Oncology and Internal Medicine. His clinical interests include Gastrointestinal (GI) Cancer, Pancreatic Cancer, Colorectal Cancer, Esophageal Cancer, and Liver Cancer. Dr. Wadlow helps run the PRECEDE study at Inova, which is a clinical trial that tries to improve early detection of pancreatic cancer for those with elevated risk, since it’s hard to diagnose early on.

Two-thirds of pancreatic tumors are in the pancreas's head and body, where surgery often leads to EPI which worsens malnutrition in cancer patients. Dr. Wadlow also expressed concerns about the current medication's affordability, side effects, and limited effectiveness. Using his feedback, we aimed to develop computational models to ensure our treatment delivered the required dosages within a desired timescale. Additionally, noting that chemotherapy patients should avoid probiotics due to infection risks, we plan to develop a cell-free treatment as a future iteration of our project.

A quote from Dr. Wadlow reading, 'if [patients on chemotherapy] have uncontrolled exocrine insufficiency resulting in steatorrhea, it's further compromising their ability to maintain adequate nutritional stores and deal with the toxicities of chemotherapy.'

How does EPI complicate daily living for cystic fibrosis patients?

Dr. Deborah Froh, MD

Credentials: Dr. Froh is a board-certified doctor in Pediatric Medicine and Pediatric Pulmonology at the University of Virginia (UVA). She specializes in cystic fibrosis and other respiratory issues in children. She is the director of the UVA Cystic Fibrosis Center and leader of its clinical trials program, and serves as the Cystic Fibrosis Foundation’s state representative for newborn screening for cystic fibrosis.

Dr. Kevin Lonabaugh, PharmD, BCACP, BCPPS, AE-C

Credentials: Dr. Lonabaugh is an Ambulatory Clinical Pharmacist in the Pediatric and Adult Cystic Fibrosis Center at the University of Virginia (UVA). He is dual board-certified in pediatrics and ambulatory care.

Kasey Wilburn, RD

Credentials: Ms. Wilburn is a Registered Dietitian at the University of Virginia (UVA) who specializes in genetic and metabolic disorders, including adult cystic fibrosis.

We learned that nearly all cystic fibrosis patients suffer from EPI, leading to early prescriptions of PERT medications to prevent malnutrition and lung weakness. Current PERT medication is burdensome, requiring up to 30 capsules daily. Thus, our solution should aim to minimize pill burden on patients, potentially through implementation of a switch/inducible mechanism. Additionally, it is crucial to ensure that our enzymes are protected from degradation in the stomach, similar to the protective coating on PERT capsules. Lastly, we aim to develop a dairy-free yogurt, as they highlighted our oversight that yogurt is not always vegan.

We learned EPI causes significant drains on quality of life and current medications are insufficient due to cost, ethics, and pill burden. Experts emphasized a need for a synthetic alternative.

What are important considerations for a synthetic alternative?

How can dietitians' insights inform EPI treatment considerations and our project design?

Amanda Barber, MS, RD, CNSC

Caitlin Benda, MBA, MS, RD, CSO

Emily Collins, MS, RD, CSO, CNSC

Kelsey Coulter, RD, CSO

Carrie Desai, MS, RD, CSO

Lauren Fay, MPH, RD-AP, CSO, CNSC

Marion Irvin, RD, CSO, LD, CNSC

Sara Negron, MS, RD, CSO

Molly Seys, RD, CSO, CNSC

Credentials: Emily Collins, Lauren Fay, Amanda Barber, Molly Seys, Sara Negron, Marion Irvin, Caitlin Benda, Kelsey Coulter, and Carrie Desai are all registered dietitians who are board-certified in oncology nutrition or nutrition support at Inova Schar Cancer Institute.

Dietitians have more hands-on involvement in EPI treatment than other medical professionals. The dietitians emphasized the importance of probiotic variety in diets, and thus encouraged us to consider a yogurt formulation that contains many types of probiotic bacteria. Additionally, they informed us that an enteric coating for our bacteria is not necessary as our bacteria will continuously produce enzymes and will be stable in the digestive tract. Most importantly, as dietitians have active involvement in EPI patientcare, they highlighted the importance of our device and indicated that they had many patients who are uncomfortable with current porcine-derived enzymes.

What is important to consider when developing a medication for EPI patients?

Dr. Shahid Ali, MD

Credentials: Dr. Ali is a board-certified doctor in internal medicine and gastroenterology and currently works as a gastroenterologist at Memorial Hermann hospital in Houston, Texas. He has clinical interests relevant to our project in general gastroenterology including diagnosis and treatment of digestive disorders.

We learned that naturally-occurring probiotics in fermented foods are preferred over capsules/supplements. Thus, we seek to identify a yogurt formulation with B. subtilis as a starter. Additionally, Dr. Ali stated that a flexible dosage (possible with our solution design) is favorable, as treatment is tailored to individual symptoms and severity. It is thus crucial for us to determine, experimentally and computationally, the amount of enzyme produced per volume of yogurt. He also assured us that hyperlipasemia is rare, so slightly increased lipase production by our bacteria should not pose health risks.

Dr. Daniel Strand, MD, FACG, FASGE

Credentials: Dr. Strand is a board-certified gastroenterologist and director of pancreatobiliary endoscopy at the University of Virginia. He serves as the director of the UVA National Pancreas Foundation (NPF) Chapter, and he has clinical interests relevant to our project in acute and chronic pancreatitis and pancreatic cancer.

We learned that current medications are inaccessible to Dr. Strand’s patients due to high cost, as well as religious and ethical barriers. Additionally, patients with Alpha-Gal Syndrome may also react to this treatment. Dr. Strand affirmed that over-the-counter non-FDA approved alternatives to PERTS are ineffective and essentially “heated organ meat.” We determined that our target yield for one cup of yogurt is roughly 70,000-80,000 units of lipase, as this is the average amount required per meal. Lastly, Dr. Strand reiterated Dr. Ali's findings that hyperlipasemia is extremely rare, indicating that our goal to maximize lipase production poses minimal risk to patients.

We learned enzymes break down in the stomach so enteric coatings may be needed; therefore, we decided a probiotic is beneficial since the bacteria deposits the enzymes directly into the small intestine. We learned the optimal amount of lipase for therapeutic purposes is 70,000-80,000 units and there’s a very rare complication of excess lipase called hyperlipasemia, which is why our team decided to model lipase production from our modified B. subtilis.

Modeling Experts

Dr. Anders Nelson, PhD

Credentials: Dr. Nelson is a Computational Biologist at AstraZeneca who received his doctorate in pharmacology from the UVA School of Medicine. He was on the Virginia iGEM team in 2016 where he spearheaded public education and outreach.

Austin Rivera, Master's Student

Credentials: Austin Rivera is Senior Specialist in Data Strategy & Innovation at Merck; he is also a current master’s student in Data Science at UVA. He received his master's degree in management from the Stephen M. Ross School of Business at the University of Michigan. A member of the 2016 Virginia iGEM team, he was involved in wetlab research and created educational synthetic biology videos.

We learned that the best way to create an ethical device is to recognize and minimize unintended harmful effects. We are addressing this by having a kill switch mechanism that kills the bacteria if it were to leave the body. Additionally, we are ensuring safe dosages through modeling and experimentation. We learned that there may be objections to ingesting engineered or synthetic bacteria as a treatment but since our medicine increases the options for treatment of EPI, our project increases patient autonomy. Lastly, to increase inclusivity and options for patients, having dairy-free or allergen free yogurt is our goal.

What flaws exist in our current design and how can we design an effective biocontainment strategy?

Synthetic Biologists

Are there any flaws in our current design in terms of efficacy and safety and what changes would be necessary for clinical implementation?

Dr. Nikhil Nair, PhD

Credentials: Dr. Nair is an Associate Professor of Chemical and Biological Engineering at Tufts University with interests in synthetic biology and systems bioengineering. He has experience teaching classes and conducting research in these areas, previously having engineered probiotics for therapeutic purposes. Additionally, Dr. Nair served as a past iGEM advisor for Tufts University.

We learned that for clinical applications of our project, we would need to make changes to our design to make the probiotic more viable to survive in the stomach and optimally produce therapeutics. We decided to dedicate a page on our website that outlines potential design modifications for clinical applications of our device. Dr. Nair indicated the most important thing for our team to focus on is producing lipase and colipase in vitro. Additionally, Dr. Nair believes our kill-switch is suitable for our device and biocontainment.

There are aspects of our design that need to be addressed before the therapeutic could move to clinical stages which we decided to address in a “future plans” page. We also confirmed a design for a kill switch that can mitigate harmful effects of our device on the environment.

How will the public respond to our design and are there any special considerations we should implement into our design?

Ethics Expert

Are there any flaws in our current design in terms of efficacy and safety and what changes would be necessary for clinical implementation?

Dr. Elizabeth Barnes, PhD

Credentials: Dr. Barnes is a professor and director of diversity, equity, and inclusion at the University of Virginia with a PhD in philosophy. She teaches philosophy of health and healthcare, current issues in healthcare ethics, and health and well-being courses at UVA. She also works on metaphysics, social philosophy, and feminist philosophy.

A quote from Dr. Barnes reading 'If there was an alternative out there, you would allow people to sidestep that dilemma. That increases their autonomy because the more range of options we have, the more choices we have, the more we’re able to exercise our power of choice.'

Beyond our project, how can we positively impact the broader synthetic biology community?

Homeschooling Experts

Is there a lack of science resources in the homeschool community and how can we best develop a resource for this demographic?

Eleanor Nicholson, MA

Credentials: Mrs. Nicholson has a Master of Arts from UVA in English. She is a homeschooling mother of 5, an award-winning novelist, and a Catholic literary scholar. Mrs. Nicholson also teaches high school literature for a company called Homeschool Connections.

What we learned: Homeschooling is increasingly popular due to its in-depth, student-driven education. However, there are few synthetic biology resources for homeschool educators. Furthermore, the biggest barriers to teaching science at home are the cost and quality of at-home experiments, which often aren’t rigorous enough. Therefore, a free, online synthetic biology handbook featuring practical experiments with common household supplies would be useful to the homeschool community. Additionally, based on Mrs. Nicholson’s feedback, we’ve added post-labs to evaluate learning and a teaching guide with a deeper dive into synthetic biology. We also decided to conduct a survey with homeschool educators, students, and parents for further feedback and suggestions for improvement.

A quote from Mrs. Nicholson reading, 'If you take [...] something as specific as synthetic biology and really teach them - not only feed their interest but teach them how to go deep into a subject - they get really excited and then the subject becomes student driven which is amazing, which is always our goal.'

How can we improve our handbook and make it more accessible for homeschool education?

Sudhita Kasturi

Credentials: Sudhita is a Certified ADHD Life Coach who draws from her extensive experience as an educator, entrepreneur, and program manager. As the founder of Leverage Your ADHD, she has worked with Fortune 500 executives, federal employees, physicians, medical residents, and program managers, to name a few. She has homeschooled her children from 2008-2020, and her background in Chemistry and Cell and Molecular Biology equipped her to teach various science classes including Synthetic Biology and an Integrated science class from 2010 onwards.

Ms. Kasturi’s experience teaching homeschooling classes, working with students with learning disabilities, and her background in molecular biology proved to be very helpful. She gave us feedback on our handbook to make it more engaging, detailed, and accessible to a wider audience and we used this feedback to revise our handbook. She also affirmed the need for this handbook in the homeschool community as science, and specifically synthetic biology, resources are severely lacking, listing cost and materials as the main barriers. She also offered a new perspective as a secular/academic homeschool educator, explaining it can be difficult to find homeschool science resources not affiliated with religion. Thus, our goal is to make a handbook that is educational, accurate, and accessible to all.