Team:Chalmers-Gothenburg/Human Practices

Human Practices
Welcome

HUMAN PRACTICES

When working in the laboratory it is easy to focus only on the things in front of you (Hope my PCR gel will be alright this time!) and overlook the bigger picture. Our team made sure to put significant effort into the Human Practices part of our project from the very start to assure that our project is responsible and makes a valuable contribution to the world.

Throughout our project we did not only discuss and assess the values and needs within the team, but engaged with and learned from several experts and stakeholders. By consulting experts and stakeholders early in our project, we could benefit from their valuable input into the design process to meet current needs in both the scientific field and in the industry. The feedback we received caused us to adapt our project design and its execution multiple times.

Safety


Apart from current needs, we also thoroughly investigated the safety implications of our project (which are described in detail on the Safety page). By talking to experts, we were aware of safety concerns of our project and made choices to ensure our solution was designed to be safe for humans and the environment. Our solution is mainly intended for manufacturing and scientific discovery applications, and will therefore not be actively released into the environment. However, to further ensure that our system can only survive under certain conditions, selection markers are used which is described in detail on the Project Design page. The project complied with the local safety- and security regulations of the laboratories at the Division of Systems and Synthetic Biology at Chalmers University of Technology, which included handing in a Risk Declaration signed off by the responsible laboratory technician. The team also worked in close collaboration with researchers at the laboratory who have accumulated years of experience working with the techniques and microorganisms used in our project ensuring safe handling. Through literature studies and in silico simulations (described in on the Modelling page) we could predict how our microorganism would behave after introducing our target genes.

Identifying Stakeholders


The process of identifying key stakeholders is an important aspect of the Human Practices work and should affect how a proposed solution is implemented. Since our project design is intended to be programmable it can be used to produce multiple different fatty acid-derived compounds, which in turn can be used to produce a wide range of products currently based on either non-renewably, or ethically problematic resources (such as Cocoa fat, pharmaceuticals, surfactants, and Palm oil). We have been in contact with stakeholders from many different sectors that we identified would have an interest in synthetic biology solutions to these manufacturing challenges. We discussed both the advantages and the difficulties with the general use of Genetically Modified Organisms (GMO) and with implementing our solution in the real world. We engaged with local industries who are using fatty acid derived compounds in their current manufacturing processes, currently derived from non-renewable and/or non-sustainable resources. We received valuable input from local biotechnology start-up companies who are aiming to produce fatty acids for nutritional purposes. We also consulted with governmental agencies to gain insight into how synthetic biology applications can be used to solve societal problems, as well as how future GMO can purposefully regulated. We learned from these stakeholders about the challenges and opportunities of how to implement synthetic biology solutions into the world and the significance of what we were doing in the laboratory.

INTEGRATED HUMAN PRACTISES

The insights we gained from our Human Practice initiatives were integrated into our project in the following way:

  • Proposed implementation and continuations of our project, such as integrating various enzymes for producing high-value fatty acid derivatives, and their effect on sustainable manufacturing.
  • Ethical considerations for presenting our project as a solution to replace current unsustainable feedstock resources for fatty acid production, such as palm oil.
  • Improved design choices, such as using antisense RNA to downregulate the native fatty acid synthase.

INDUSTRY


We interviewed different companies with regards to the application of our project. First, we spoke with Professor Johan Leckner from Axel Christiernsson International AB, which is a leading lubricating grease manufacturer in Europe that uses fatty acids in for their production. Johan is a professor in Lubricant Design at KTH Royal Institute of Technology and Group Technical Manager at Axel Christiernsson. From him we got insight into the industry and the current demand of fatty acids. We then invited Kristofer Hellberg, Country Manager Nordics at Eurofins Genomics, an international testing laboratories company.

Axel Christiernsson


After our interview with Axel Christiernsson expanded the project and reflected on how we should niche our design for market success by creating high fatty acid derivatives. We ordered additional gene fragments to implement in our project such as CAR for producing aldehydes and AHR for producing alcohols (read more about this on our Implementation page).

Eurofins Scientific


Kristofer Hellberg helped us understand the company structure of Eurofins and how to best utilize their services in the development of biotechnological products, especially their sequencing and analysis offer. This allowed us to better understand and further improve the validation of our designs (read more about this on our Design page).

In general, a thing that was mentioned during discussions with many of our stakeholders were the cost of producing high quality fatty acid derivatives. This made us realise that our system would have to be very efficient in order to compete with other manufacturing methods. This is one of the reasons we implemented the antisense RNA system. This way we could make sure that our system was efficient in creating the products we programmed it to produce rather than products produced natively by the yeast that was not of interest for us.

GOVERMENT


We conducted interviews with the Swedish governmental agencies Environmental Protection Agency (sv. Naturvårdsverket) and Swedish Medical Products Agency (sv. Läkemedelsverket) to understand the laws and regulations concerning the use of GMOs.

Naturvårdverket

We discussed the difficulty to get GMO’s approved, and about the European frameworks for approving GMO’s. We also discussed ethical aspects of current palm oil manufacturing in South east Asia, where native population is displaced by factory workers where factory and manufacturing plants are located. This made us consider how the local populations would be affected if our solution were to be implemented taking over current manufacturing. A suggested solution to this would be to donate part of the profit to the population of heavily affected areas.

Läkemedelsverket

Since the fatty acids produced by the yeast could potentially be used to develop lipid transport vesicles, we discussed the use of GMOs in drug development and what it takes to deliver a drug on the market. Unfortunately, we learned that getting our project approved for drug delivery production, it would require a lot of resources, both in finances and time. This made us rethink the pharmaceutical application of our project and instead focus our attention on other applications.

SCIENCE


As representatives of the scientific- and biotechnology community we spoke with David Bergenholm (PhD) the senior scientist at Melt&Marble, a start-up company based on the campus of Chalmers University of Technology that specialises in designing yeast strains for producing animal fats. We found our meetings especially exciting since their company purpose was similar to our project in many way - to replace a conventional and environmentally problematic manufacturing process with cell factories. During The Nordic iGEM Conference that we hosted at Chalmers University of Technology we gained many new perspectives from the other iGEM teams and the researchers and experts that participated in judging the competition. This included feedback on how to present our project to the public and the scientific community. The judges included Anne Farewell (a senior lecturer at the Department of Chemistry & Molecular Biology, University of Gothenburg), Linnea Österberg (a doctoral student at the Systems and Synthetic Biology, Chalmers University of Technology), Patrik Lundström (a senior lecturer at the Department of Physics, Chemistry and Biology, Linköping University), and Ganesh Mohite (a postdoc at the Department of Physics, Chemistry and Biology, Linköping University).

The Department of Systems and Synthetic Biology at Chalmers University of Technology (SysBio) provided invaluable resource and advice regarding all parts of our project. We received fantastic input about the ethical considerations of synthetic biology and biotechnology by talking to Carl Johan Franzén (a professor in Bioreaction Engineering at Chalmers University of Technology). We are thankful that Franzén allowed us to organize lecture presentations in his second cycle course ‘Ethics in Biotechnology’. We also received great feedback from his students which helped to improve our project.

Melt&Marble - David Bergenholm (PhD)

We the discussed the applications and potential impact of our project with David Bergenholm at Melt&Marble. He commented that tunable fatty acid profiles may be useful for quickly receiving information on how the proteomics of a strain change as a result of these profiles, helping to prototype new high producing and strains. During our discussions we realized that our design could be combined with another strain in the same medium to produce triglycerides with specific chain lengths useful for nutritional purposes. Similarly, a second strain could be tolerant to the overexpression of key enzymes that produce potentially toxic (but high value) derivatives. We also gained valuable insight into the future of synthetic biology from the perspective of a biotechnology start-up company.

Nordic iGEM Conference - Judges and iGEM Teams


Advice and feedback from the judges and iGEM team was valuable in helping is improve how the project was presented both to the public- and the scientific community. The conference also included workshops on biosafety, ethics and the shared experiences of doing iGEM. This allowed us to better understand the challenges we would encounter when using our design in a real application and how it would behave in an environment outside of the laboratory. Therefore, we planned to include a kill-switch in our final strain but due to time constraints of the project we unfortunately did not have time to implement this idea.

Department of Systems and Synthetic Biology

One of the major influences the scientists and experts at SysBio had on our project was in the choice of using yeast as our microbial chassis. The decision to use S. cerevisiae as a chassis (instead of other well studied model organisms such as E. coli) was based on its proven record as a reliable platform for industrial large-scale production of various compounds due to its robustness, genetic malleability, and tolerance towards harsh fermentation conditions, and some of the highest production titres of fatty acids in microbial fermentation have been reported for this organism. Being a model organism, substantial knowledge has been accumulated concerning the metabolism, genetics, and physiology of S. cerevisiae, with several well-established tools for genome engineering and fermentation technologies.

Professor Carl Johan Franzén and the ‘Ethics in Biotechnology’ students

Franzén made us contemplate on how we could make our project more sustainable from an ethics perspective. As the yeast strains we used in the laboratory need basic carbohydrates such as sugars for growth and as substrate compounds, on a larger scale this face issues regarding land use and the conversion of potential food sources for industrial applications. This caused us to research potential feedstock alternatives, such as those that would be considered as waste products. The students approached us both during the lectures and afterwards with great suggestions for potential implementations for our system. One being to fine-tune the fatty acid composition of palm oil-like products to increase the health- and nutritional value. This would not only be beneficial for human consumption, but could potentially have a significant environmental impact as such aspplications could compete with current unsustainable palm oil production.

Read more about our lectures in the ‘Ethics and Biotechnology’ course on our Communication page.

SOCIETY


To acquire valuable points of view from other stakeholder in society other than representatives from the industry- and the scientific community. We contacted the World-Wide Fund for Nature (WWF) and read about the current issues with conventional palm oil production, such as deforestation and its impact on local biodiversity. We also contacted the Swedish Society for Nature Conservation (sv. Naturskyddsföreningen). These are major non-profit environmental organizations (international and local, respectively) that heavily influenced our views on how to apply and present the project from a sustainable manufacturing perspective, such as the potential impact on palm oil production (as seen in our logo design).