Team:Stanford/Human Practices

Human Practices

The primary purpose of any intervention for an iGEM project or a bioengineering construct should be to improve people’s lives. Understanding who your project benefits, how it benefits them, and how easy it is for it to benefit them are all important parts of how we assess a project as it is being developed.

This was a key part of all our considerations throughout the ideation process, the creation of our experimental design, and how we imagine our findings being used in the future. To fully integrate human practices into our work, we took a multiple pronged approach. Before we even began with creating our project, there were many impact related aspects of our project that we took into consideration when choosing our idea of working with the grapefruit-drug interaction. Once our team had decided on the idea, we took further steps to look at the impact our project would have on various populations. We conducted surveys and compiled a list of ethical considerations that would need to be addressed before we could begin experimentation. After completing this work, we compiled all of our findings into a policy brief.

Project Benefits and Ideation

The first thing we took into consideration when we were deciding which project idea to pursue was the potential impact that our work might have. We knew that the grapefruit-drug interaction is one of the best known food-drug interactions and that our work may have viable practical applications. During the course of our ideation, we also learned that there is no cure to the grapefruit-drug interaction and that the only available solution for the problem was to avoid grapefruits entirely. However, through both informal conversations with people in the Stanford community and online articles, we discovered that this is a problem that primarily affects senior citizens’ quality of life. The most popular drugs that interact with grapefruit-juice are blood thinners and cholesterol medications which are also drugs that are highly prescribed to eldery patients (Lynch & Price, 2007). Market analysis data also shows that the demographic population that exhibits higher levels of grapefruit consumption are older adults. Many older adults love having grapefruits consistently in their diet and are disappointed by the lifestyle shift caused by their medications. Another concern is that many patients continue to consume grapefruit despite the possibility for a food-drug interaction. Oftentimes, patients are not properly informed about the dangers of the food-drug interaction, or they simply choose not to heed the warnings of their healthcare providers. This could lead to potential overdoses and negative health effects. However, because the associated side effects of an overdose correspond with so many other possible ailments, it becomes difficult for medical professionals to identify which patients come into their offices with food-drug interaction related issues (Seden & Dickinson, 2010). For these reasons, our team felt that it was imperative to begin working on proof-of-concept work to try and find a solution to the grapefruit-drug interaction.

Surveys

One of the methods with which we gathered our data was through a survey. To get the largest sample size possible, we advertised our survey on campus wide email lists at Stanford and on the Collaborations site through iGEM HQ. We made sure to follow the survey standards published both by iGEM and Stanford University. Our population was college-aged students. In our survey, we asked about the subjects’ understanding of the grapefruit-drug interaction, their grapefruit consumption habits, how they are most likely to learn new medical information, and their conceptualization of probiotics. This information was invaluable in shaping how we structured and distributed our educational initiatives. The information that we gathered from these surveys was also used to shape how we imagined our work being used in the future to shape efforts to create a hypothetical commercially distributed solution.

Ethics and Safety Considerations

There were many ethical and safety considerations that our team also had to account for when designing our experiment. Because we imagined our proof of concept work to eventually be used to create a hypothetical probiotic pill to counteract the effects of grapefruits, many of the considerations we have made relate to design questions further downstream in the design process.

The most important consideration for our project was the microbe we were going to manipulate. Our team had to pick a microbe that had the ideal qualities for a probiotic. It had to be able to effectively and safely colonize the human large intestine. It also had to be a microbe that was easily accessible and could easily be manipulated for experimentation. For this reason, we chose to work with Saccharomyces cerevisiae (a.k.a. Brewer’s yeast). It is a strain of yeast that is commonly found in the human digestive system, is Generally Recognized As Safe (GRAS) by the FDA, and is one of the most commonly used microbes in biology research (Meyer & Segall-Shapiro, 2019).

The next most important safety consideration we took into account was deciding which enzyme with which to manipulate S. cerevisiae to have the desired effect. We went through many iterations at this stage of the ideation process. We had to find an enzyme that was easy to work with, had the desired effect of reducing the effect of the grapefruit-drug interaction, and was safe for human consumption. We eventually landed on the enzyme CYP6B1, which is a naturally occurring enzyme in the American black swallowtail butterfly (Myung, Manthey, & Narciso, 2008). This enzyme in butterflies has been found to naturally digest the compound in grapefruits that causes the food-drug interaction (furanocoumarins).

While these are the main safety considerations that we were able to fully develop during our ideation and experimentation, there are further steps that need to be taken in the future for our work to be turned eventually into a probiotic pill. However, they are beyond the current scope of our work. The dosing of the probiotic pill would need to be taken into account. We would need to answer questions such as how often consumers would need to take the pill in order to have the desired effect, how much they would need to take with every dosage, and how often consumers would be willing to take it.

Another important consideration we would need to study further is a kill switch. While it is a probiotic and we would want the pill to colonize the digestive tract, we would not want it to overcolonize the digestive tract to the point where the patients experience other adverse health effects. A precautionary measure would have to be designed and integrated into the pill design to make sure that overcolonization of the large intestine doesn’t occur. One final ethical consideration if our project were to eventually become a commercially viable product would be how the information about the product is communicated. Since our product would be a probiotic pill that contains insect-derived enzymes, we would need to advertise this aspect of the product design in an honest (but not off-putting) manner.

Integrated Human Practices: Policy Brief

To synthesize all of the information we collected throughout the work we’ve done in integrated human practices, our team has put together an ethics review and policy brief document. It details our project, the purpose of the project, how our work interacts with current federal regulations, and ethical considerations we accounted for in our experimental design. While this document is comprehensive, it is non-exhaustive as we continue to expand our project and take more considerations into account, it will continue to expand. The full text of the policy brief document can be read below.

How did we integrate our human practices work into the project?

While we integrated human practices into every aspect of our experiment, and this is elaborated on in greater detail later on in our integrated human practices discussion, we wanted to make it explicitly clear how we integrated our main considerations into our experiment. Throughout the summer, we conducted literature reviews and consulted expert scientists that have had experience working with microbes and the human gut microbiome, scientists such as Professor Justin Sonnenburg, graduate student Matt Carter, and professor Drew Endy on which microbe we should use to make our plasmids. Our team originally had found literature on specific types of fungi called citrus x paradisi and Aspergillus niger that had been used to remove or degrade furanocoumarins from grapefruit juice (Myung, Narciso, & Manthey, 2008). However, after consulting our mentors, they alerted us that these types of fungi might not be safe for human consumption. We then were directed towards different types of microbes that would be considered safe for human consumption. We eventually settled on Baker’s yeast, a microbe that is generally considered safe for human consumption and would fulfill the purpose of acting as a probiotic.

The second thing that we integrated from human practices into our experiment was the enzyme of choice to degrade the furanocoumarins. There were many methods we encountered during our literature review that detailed how to degrade furanocoumarins. However, many of them weren’t safe for humans. These included methods such as the dangerous fungi detailed above, and the use of UV radiation (Trumble et al.). Since we imagine our work eventually being turned into a therapeutic probiotic, these methods would obviously not be safe for use in a pill. Therefore, we settled on the use of the CYP6B1 enzyme as the mechanism for which to degrade furanocoumarins. The CYP6B1 enzyme is naturally occurring. The CYP6B1 enzyme is not known to interact with any other compounds besides furanocoumarins, meaning that it would not interact with any other human processes if it were to be consumed in a probiotic.