Ethics

Introduction

There is no doubt that ethical questions play a large role in the field of synthetic microbiology. In a field of research that has a tremendous potential to impact our society and includes projects about, among other things, stem cells and cures to deadly illnesses, thinking about what is right and what is wrong is of crucial importance. However the field of ethics is surprisingly often overlooked by young scientists and students, such as the ones participating in the iGEM competition.

We think it’s important everyone in our team is aware of the ethical issues related to our project, as we think that in order to do research in an ethical way the scientists executing the research should be conscious of these issues and should know how to think about them. But we didn’t just keep the ethical questions we had confined to within the comfortable boundaries of our team. We wanted to get a broader viewpoint on the ethical questions related to our project and thus we found it important to also get the views of various experts and other outsiders on them.

An opportunity for a collaboration

This is where the Bordeaux team came in to play, their project is quite similar to ours, so the ethical questions and challenges they will face are naturally quite similar to the ones we will face. As they had been in contact with a number of experts on the field of ethics related to GMO’s (genetically modified organisms) and even organised conferences on the subject of ethics, meeting with the Bordeaux team should be very valuable.

In order to prepare for the meeting with the Bordeaux team we started out by reading introductory papers on the field of ethics related to microbiology. Especially the ethics handbook written by the 2017 Israelian team from Technion was of great use, giving us an overview of the different ways of looking the “badness” or “goodness” of actions.(1) Should we only look at the consequences or just at the intention or justification? Members of the Bordeaux team pointed us to the Asilomar Conference on Recombinant DNA, held in 1975, where for the first time international guidelines on the safety of recombinant DNA were drawn up. Besides reading up on ethics we made a whole list of questions to ask to both the Bordeaux team and to the experts they have been in contact in with.

Armed with proper background knowledge and a document full of questions we set out to collaborate. The Bordeaux team kicked of the meeting with a presentation on what the term GMO entails, and which ethical issues GMO’s raises. They then continued presenting about the conferences they organised, the experts they met and their findings on human practices so far. Besides just presenting the findings of their meetings with experts they also offered to bring us into contact with them.

The expert that seemed most valuable to us was Manguene Marc of the fondation Anthony Mainguéné. He and his foundation promote the responsible and forward-looking raising of awareness in innovative and creative ways. We asked the Bordeaux team to forward our most important questions to him. After their presentation we had a brainstorm session about ethical matters involved with the use of GMO’s and we discussed the questions we prepared in advance. We summarize the findings below:

Findings

Safety

Ethical issues concerning safety can entail large questions such as how big should the risk be before we ban further work, or in other words, what is the red line? These are the kind of questions scientists have tried to answer on large scale conferences such as the asilomar conference mentioned above. For our project we looked at the more concrete and smaller safety issues directly related to our project.

In our project, as with every project involving GMO’s, there’s a small chance of GMO’s escaping the lab. What happens to when such a leak occurs? There are a number of possible consequences, including the spread of new pathogenic strains and the release of toxic molecules in the environment, and the possibility of the escaped strain taking over an existing niche or creating of a new one. How do we tackle this issue? In theory the organism we modify could live outside of the lab however but if it it ever escapes into the wild it will most likely be out competed by wild type strains which grow more efficiently. Besides this we’re working on methods to make our cells grow only in very specific circumstances to limit the chance of it being able to live and procreate outside if the lab. A way to really force this is by implementing a kill switch, make sure the cell can only live when a certain compound is around. This particular compound will be fed to the cell when it’s safely contained in the lab, but it won’t be able to find it when it’s out in the wild. The environmental dangers are thus very small, but this is something we should verify with more experiments and definitely not just wave aside.

But then what about the danger to the people doing research with the yeast cells, or the people processing the styrene we produce? Saccharomyces cerevisiae can be an opportunistic pathogen.(2) The biological danger to the people using our styrene is as good as zero as we can simply make our end product completely sterile, but the researchers working on our project will have to work with a cell that can potentially be pathogenic. Besides the biological danger we also have to think about the chemical danger, styrene can be a toxic molecule and exposure to it should be limited.(2) This highlights that we will have to think carefully about the safety precautions taken in the lab both on handling the micro-organisms we work with and the molecules we produce.

Public Acceptance

Another thing that came up quite often during the discussions we had was public acceptance, and the importance of telling the public about what we are doing in the lab. There seems to be at least some hesitation in the public about the usage of GMO’s for production of food and materials. At least part of this hesitation might stem from not knowing exactly what a GMO entails. An example that nicely illustrates this is is that when we tell people about our project, even naming that we are using modified yeast cells, they are positive, but as soon as we drop the word GMO there are people that are directly less assured of our project. We also noticed this during our various outreach events, a lot of people we talked to appeared a lot less negative towards GMO’s after explaining what a GMO exactly is. We therefore deem it an import part of iGEM to tell the public of our project and hope to contribute in that way to getting rid of the ‘bad’ name of GMO’s. Important to realise here is that not all hesitance about GMO’s stems from ignorance, if people have objections because of for instance personal beliefs or religion, than that is completely valid as well.

Feasibility of using bio streams

Is it ethically fine to use already used waste streams for producing plastics? Most cellulose containing waste streams are already in use, for instance foodstock and bioethanol. Our yeast strain will be competing with the people and companies who currently use those waste streams. We will make plastics, something that possibly benefits the environment less than the current uses of cellulosic waste. It will definitely be very valuable to look into waste streams that are not already in use. We did this in a concrete way by talking to companies that process cellulose containing waste such as KNN cellulose who make recell: recycled toilet paper. Furthermore we will have to look into how beneficial it is to make plastic from cellulose compared to making it from fossil fuels. One of the ways we did this is by performing a carbon footprint analysis.

Breaking down cellulose with or without yeast?

One of the biggest difference between our project and the one of Bordeaux is the way in which we turn cellulose into glucose. We use our yeast cells for both the conversion of cellulose to glucose and the conversion of glucose to styrene while the Bordeaux team plans to perform the first step in a chemical way and only do the conversion from glucose to plastic with their micro-organism. It will be very interesting to compare which way is more optimal and efficient, not only by looking at the yield but also at the byproducts and the effects of the environment. While in order to completely weight all positive and negative sides of both strategies we need more experimental results there are already some things we can hypothesize about.

The chemical way, using acid hydrolysis, will entail using dangerous chemicals, however acid hydrolysis is is a process that’s used widely and can be done in a large reactor. There will be a byproduct consisting of polluted acid, which could potentially be reused, but this is something the Bordeaux team will have to look into. In contrast, our enzyme complex won’t have any dangerous byproducts as it just uses water. The efficiency of the enzyme complex will however likely be a lot lower than using acid hydrolysis. Furthermore we will have to take the growth medium our cells using the enzyme complex grow on into account.

Sources

1: Ethics Handbook by iGEM Technion 2017: https://2017.igem.org/Team:TECHNION-ISRAEL/ethics 2: Pérez-Torrado, R., & Querol, A. (2016). Opportunistic Strains of Saccharomyces cerevisiae: A Potential Risk Sold in Food Products. Frontiers In Microbiology, 6. doi: 10.3389/fmicb.2015.01522 3: Leibman, K. (1975). Metabolism and Toxicity of Styrene. Environmental Health Perspectives, 11, 115. doi: 10.2307/3428333