Team:Amsterdam/Human Practices

Forbidden FRUITS

Introduction

Human Practices and Public Engagement & Education have been important intrinsic drivers for our team to go out there and connect with people. Interviewing people and asking for their opinion/vision/expertise forms the basis for our work. From the beginning we were determined to make a real contribution to the world and add to the development of sustainable biotechnology. We hope to make an impact with our project by making biotechnology more accepted by the general public and giving biotechnology the tools to grow. On this page, we will report the insights from interactions with players from the industry.

Stakeholder Engagement

Scientists and engineers can get really caught up with their invention being the only solution to the problem. It is of vital importance to understand the different perspectives of the problem and the desired solution. Getting in touch with different stakeholders is necessary to get the right context of the environment your invention will be used into

In several stakeholder interviews, we talked with experts in the field to discover how we could apply Forbidden FRUITS and where. We conducted interviews with Prof. Dr. Jeroen Hugentholtz (University of Wageningen) to have an academic/industrial point of view. Furthermore, we interviewed Dr. Harald Ruijssenaars (Corbion) and Dr. Tjeerd van Rij (DSM) to provide us with specific industrial insights for our project. For a more regulatory-society point of view we also interviewed Dr. Cécile van der Vlugt (RIVM).

Industry

Prof. Dr. Jeroen Hugentholtz - University of Wageningen

Jeroen helped us in the beginning of our project to evaluate the potential of Forbidden FRUITS. He advised on compounds we should focus on, mainly secondary metabolites due to economic interest. Additionally, he pointed out one major issue; the public opinion about GMOs is what keeps the industry hesitant towards using GMOs. He also gave us tips on how to reach out to companies to get a conversation started with them.

Dr. Tjeerd van Rij - DSM

Tjeerd has been working at DSM for over 14 years. He gave us insights in the strategies used within DSM to design/select industrial strains. Furthermore, we talked about the translation from lab to large-scale settings and the unpredictability between these two worlds. He also enlightened us with the biggest challenge his organization faces for the upcoming future

Dr. Harald Ruijssenaars - Corbion

Harald has been working at Corbion for almost 8 years and serves as a corporate scientist at the biotechnology department. The vision of Corbion: “preserve what matters” relates to the preservation of food but also sustainability and health. He gave us insight in how they select industrial strains and the difficulties with large-scale settings. Additionally, we discussed the application of GMOs and the biggest challenges he envisions for the future of biotechnology.

Summary of interviews

Fermentation in the industry

For the industry the most important question is whether is it cheaper to produce a product with fermentation than it is to chemically produce it. Therefore it is essential that they use cheap substrates (as raw as possible), a simple fermentor (self-sustaining) and easy and cheap downstream processing. As of right now, the industry focuses mainly on high product prices and low production (i.e. medical industry) or does not use fermentation (i.e. chemical industry). Companies, such as DSM and Corbion, focus on a diverse range of products used in food processing or flavouring.

Strain instability: Is it a problem?

Still “the big elephant in the room” because it is an issue but not that much is done with it. In the first instance, it is not a problem in batch cultures but becomes a problem when we look at chemostats. Mostly in the lab, scientists have been trying to make stable products, however, this has not yet translated to the industry. Main reasons for this are the differences in products and processes, some do not require stable production as the desired product is drained and waste biomass is recycled thus making it profitable as it is

Designing strategies

The designing process for microbial production systems knows several steps. Firstly, this involves the selection of the product, the used substrate and calculation of biochemical yield of the product. Then the metabolic route for the to-be formed product is determined. From the theoretical metabolic route the productivity (e.g. titer, production rate, yield) can be estimated that result into optimistic but realistic assumptions. When the theoretical framework is established, it is time to make a proof-of-concept in the lab. This step also includes the selection of a microbial host organism, which depends on the product and the substrate. It is important to know that all the choices we make during the process affect the end process. Precision in design is therefore of vital importance.

Economically feasible compounds

We learned that secondary metabolites gain much interest due to their economic interest and their use in medicine production. More importantly, big margins are in the end what the industry strives for, thus mostly enzymes for food processing and yeast extracts are considered interesting. For example, stevia, glycosides and fatty acids for baby food.

Current issues in scalability

We were wondering what kind of problems the industry would run into during upscaling.

  • In fermentation processes, for mostly large-scale conditions like mixing behaviour knowledge is still lacking.
  • On the side of physiology, stability is the most important aspect. For this reason quality systems (e.g. genome sequencing) are used to check for viability, CFUs and genetic content.
  • In the industry it is common to use continuous fed-batch culture systems and separate biomass from product in the final step. This continuous process is able to prevent phenotypic instability.
  • Yet continuous fed-batch culture systems require extensive labor due to cleaning, vessel setup, and sterilization and, additionally, still face the problem of phenotypic instability overtime.

Current issues in scalability

We asked our experts what they thought the biggest challenge was their organisation or biotechnology was facing.

  • They pointed out the current status of GMO legislation and the public opinion. First of all, GMO definition differs from country to country. Secondly, GMO’s can be used to make food ingredients but the industry is hesitant due to public concerns about safety. Thirdly, the GMO itself can be removed and the product subtracted but this may increase industrial costs, which is undesired.
  • Another aspect they highlighted is the fastened pace at which technology is developing and, consequently, keeping up with this pace. Moreover, the use of single carbon sources instead of multi carbon sources have great potential

Key takeaways
  • Cheap substrates are of vital importance to reduce the costs during the production process. Whereas the highest conversion of substrate to product is the main goal in the industry.
  • Strain instability is not yet seen as a problem within the industry but could become a problem as the industry grows.
  • Most interest lies in economically feasible compounds like secondary metabolites that relate to medicine or enzymes for food processing
  • The development of industrial strains starts with the theoretical framework constructed by metabolic engineers followed by testing from smaller batches to large-scale settings.
  • GMO legislation restricts or keeps companies hesitant towards using GMOs to produce compounds.
  • Expertise in metabolic engineering is mostly kept in-house. However, the industry keeps an open view towards partnerships in the future.

Governmental/Safety

The RIVM — the Dutch National Institute for Public Health and the Environment — plays a crucial role in disease control and is involved in shaping the regulatory landscape of genetic engineering applications in the Netherlands. We were fortunate enough to engage with RIVM representatives in both an interactive brainstorming session and a subsequent presentation on the potential uses for Forbidden FRUITS in biotechnological strain risk assessment. More details about the implementation of Forbidden FRUITS in biotechnological risk assessment can be found on our Proposed Implementation page.

General Public

Our stakeholders include, above all, the general public; as Forbidden FRUITS could revolutionize biotechnology and thus affect many people. For this reason, we created a survey about the use of different compounds, which were produced by genetically modified organisms (GGOs), within products. The conciseness, appropriateness and ethical considerations were evaluated by fellow team members and the Ethics Review Committee from the Vrije Universiteit. Then the survey was adjusted, digitalized and distributed to the general public. A complete and detailed report of the results and the analysis can be found here. Additionally, we hosted several workshops to start a discussion with the general public and hosted a panel discussion at CRISPRcon 2020 about ethical considerations for our project.

Forbidden FRUITS

Find more information about the team, the project and the workshops that we're organising by visiting our social media.

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