Human Practices

Talking to experts

We talked with experts from different universities and research centers in the fields of biology, genetic engineering, biological modeling and cyanobacterial research. Many of these experts gave us much appreciated information and new aspects to our ideas that have guided our project towards what it is today. As the information has had a significant effect on the design of our project, it will be presented more deeply in integrated human practices section.

Finnish Environment Institute SYKE

In order to gain more insight into the problem of cyanobacteria in Finland, we contacted the Ministry of Environment and the Ministry of Agriculture and Forestry. They guided us to the Finnish Environment Institute (Suomen ympäristökeskus, SYKE), where we got to discuss the cyanobacteria problem and our project with experts.

We talked to Jari Silander, Senior Research Scientist specializing in monitoring and cost-benefit analysis, as well as Juhani Kettunen, Program Director responsible for modernization of environmental monitoring activities. We introduced our project and briefly talked about synthetic biology. They found our approach interesting and promising since they have been trying to deal with the blue-green algae problem for many years now. They described the full extent of algae detection problem in Finland and all the strategies used in the past and at the moment to deal with it both in research and industry.

They also discussed with us the business aspects of our project and gave us good advice on how to build our business strategy if we are to bring our algae detection and degradation methods to masses.

Meetings with companies

As we were looking for funding and contacting different companies and organizations, we got a chance to visit a few. We told them about our project, discussed synthetic biology and the use of biotechnology in Finland. We talked with ThermoFisher, Algol and LAL (Luonnontieteiden akateemisten liitto), and they showed great interest in our project, even helping us with the funding. In addition, ThermoFisher generously sent us various lab kits. We will visit some of them to give the final presentation about our achievements after we return from Boston.

Interviewing people on the streets of Helsinki

We decided to make a little survey on the streets of Helsinki. The goal was to find out what people actually knew about synthetic biology and cyanobacteria. We wanted to see what kind of need there was for informing the general public about all the possibilities synthetic biology offers, as well as, from our project’s point of view, the need to inform about the dangers of cyanobacteria. The interview can be viewed below with subtitles in English. It seemed that the general conception of synthetic biology was something quite foreign and that there is a need for raising awareness of the hazards of cyanobacteria.

LUMA centre

We met with high school students who were candidates for the Finnish team of the International Biology Olympiad. Our team gave them a presentation about our project and synthetic biology. The students got to design their own little iGEM projects and hopefully learned about molecular biology and synthetic biology. They also asked questions about our studies and how one needs to prepare oneself to study them. Hopefully we were able to inspire them to continue with the study of biology in the future and perhaps even try themselves in the field of synthetic biology.

Math seminar at the University of Helsinki

In addition to Luma we gave a talk on “Mathematical Modelling in Synthetic Biology” for math students at the University of Helsinki. After giving them a “Biology 101” lecture, they got to hear how modelling was done in our project. It was great to see that so many people were interested in our project as well as modelling in synthetic biology. Let's hope that some of these students will be members of Aalto-Helsinki 2017!

Media

Our project was on display in the media. We had quite a few articles written about us and we were even a part of a radio program. As we had also gotten sponsorships from certain companies they posted about us and our project on their web pages which was nice.

The University of Helsinki’s Faculty of Science wrote an article about our project and especially what the two mathematicians of our team had learned from this synthetic biology project. The article was later posted also on the university’s main news page. The articles are unfortunately in Finnish.

Faculty of Science https://www.helsinki.fi/fi/uutiset/suvi-sauna-ja-sinileva

The university’s news page http://www.helsinki.fi/ml/ajankohtaista/2016/igem-kilpailu.html

Also, Aalto University School of Chemical Engineering posted an article about our project, iGEM, and synthetic biology.

School of Chemical Engineering http://www.aalto.fi/fi/current/news/2016-07-01-002/ (in Finnish)

TEK magazine, the magazine of Tekniikan akateemiset, an organization for Academics of Technology, published an article about us as well. The article was a part of their students page where they present different kind of career possibilities and such for their student members. The article is in Finnish. TEK https://lehti.tek.fi/opiskelijat/hiivalla-sinilevamyrkyn-kimppuun

Finland’s public broadcasting company YLE’s radio show about science called Tiedeykkönen featured an episode about synthetic biology and iGEM. The episode mainly focused on Aalto-Helsinki 2015’s journey in iGEM, but also our team and project was mentioned. The broadcast of the episode can be listened here: http://areena.yle.fi/1-3424583 (in Finnish).

We have also been or will be a part of our sponsors’ blogs. Algol has posted a few posts about our journey in iGEM on their blog, and want to also publish something once we return from Boston. In addition, LAL will publish an article in their member magazine about our iGEM experience after the Jamboree.

iGEM meetups

We attended two iGEM meetups, the Nordic iGEM Conference in Stockholm and the European Experience in Paris. We consider them a part of our human practices since we got a lot of input from them for our project, and got to talk about our ideas with other iGEMers. We have written about the meetups on the Community page.

Website

We have created a website in addition to the Wiki which includes team descriptions, as well as a brief introduction to our project and partners. It also contains a description of synthetic biology, a safety conscious statement, and an explanation of what iGEM is. We have been using our website for various purposes, e.g. to spread the word of iGEM as well as tell people about our project and about ourselves. We have also used it for fundraising purposes by including logos of our sponsors on our website.

This website also contains information about previous years’ Aalto-Helsinki iGEM teams. It gives similar information about them: who they are and what they have worked on. Our blog, facebook, twitter and instagram accounts can be accessed using the webpage as well.

http://www.aaltohelsinki.com/2016/index.html

Blog

During this summer we have been posting about our weekly achievements and activities in our blog. We hope that this has helped people follow our work better and in a way bring them closer to our research and what it is like to be a part of an iGEM team. Each of our team members has also presented themselves, so if you want to get to know our team a bit better, check out the blog:

http://blog.aaltohelsinki.com/

About future Human Practices

Even though Wiki Freeze and the Giant Jamboree are here, we have still some human practices left after all this. We will be presenting our project results and achievements from the Jamboree to some of our sponsors, as well as school representatives. As a part of the recruiting the next year’s team, we will present our project in a few different events, such as the Water Day of the Aalto Unviersity School of Engineering, where different projects related to the water industry are presented, and the Career Day of Faculty of Biological and Environmental Sciences of the University of Helsinki.

Integrated Human Practices

Meeting with experts

When our team started brainstorming for the project idea, our general knowledge of what would be feasible and what wouldn’t was quite insufficient. We had a many meetings right in the beginning of our project just to hear from different experts what they consider to be synthetic biology, what they thought of our various ideas and how they would proceed with the project. Especially talking with our primary PI Markus Linder directed our brainstorming and ideation, which finally led up to the final design of the project. Even though many experts gave us advice and guided our brainstorming, deciding about the topic and more precise plans were left for ourselves.

When we had decided on the top three project ideas, we met with researchers working with these different subjects as a part of the background research we did about the different options. We found about the Cyanobacteria research group of the University of Helsinki and met with them. And what a goldmine it was! Thanks to input from Kaarina Sivonen and her group, the decision about our project subject was finalized. We much appreciate that they truly dared to turn some of our ideas down, if they thought that these ideas wouldn’t result in a successful project. With ideas where they saw potential they encouraged us enormously. They have also helped us during the course of our project - for example the degradation part of our project would not have ended up being what it is without their help. We also practiced our Boston presentation and got feedback on that from them.

As we didn’t have much experience on protein production in yeast and as it was in a focal role in our project, we needed some help in planning our enzyme constructs. Alexander Frey from Aalto University turned out to be a great help in this. He helped us decide what kind of signal sequences we should have for protein secretion. He also questioned our choice to use yeast at all in the enzyme production, and made us broaden our thinking and justify our ideas. Putting a lot of thought into justifications for our choices at this point of our project turned out to be very useful, since after that, we didn’t have to regret that we should have done something in a completely different way.

If the Cyanobacteria group and professor Frey along with his group affected the degradation aspect of our project the most, Jussi Jäntti and his research group from VTT likely contributed the most to the detection part. They gave us valuable input on our thoughts of harnessing the yeast stress response, and for example commented on our transporter constructs and gave ideas on tags to facilitate the verification of its expression. They also gave us input on our results and gave ideas on possibilities to take things further, e.g. giving the idea about using flow cytometry to verify stress promoter functionality. Without them we probably wouldn’t have thought to use flow cytometry, which ended up providing important support and verification for our other results!

Even though our team had students from fields ranging from biotechnology to mathematics, there wasn’t anyone who really understood both fields well enough to have a clear idea of what modelling is like in the field synthetic biology. That’s why meeting Merja Oja, who works with modeling biological systems, was very important in the beginning of our project. After that we were able to also think about the modelling part of our project and how it could support the experimental parts of our work. We ended up creating two different models: a molecular model and a mathematical model, both on our detection system. Integrating modeling as part of our project provided interesting new challenges for our mathematicians.

Meeting with SYKE

The most valuable information from our meeting with SYKE, the Finnish Environment Institute, was that we learned what kind of solutions already exist for the blue green algae problem. It came up that all the present methods dealt with the problem causing algal blooms, eutrophication. There was thus a real need for solution like our that could be effective in a smaller scale. This convinced us that we were on right track with the degradation.

We also discussed current detection methods and according to them, all the available detection methods are rather expensive and hardly any of them is available for the public. They guided us to plan our detection device so that it would correspond to the current need - being available for the public and not be too expensive. If the use of GMOs was legal, our yeast based detection system could provide an easy and affordable solution.

It was also nice to hear that there was no available method for the present day to get rid of the cyanobacteria or the toxins. All the present methods dealt with the problem by nipping it in the bud, i.e. fighting eutrophication, but none tried to get rid of the toxins once they have been produced. They advised us that one measurement should cost less than 25 euros in order for it to be an improvement to existing methods. We used these considerations when choosing the best option for our preliminary detection methods to continue with. Their input greatly affected our choice of using modified yeast as the detection chassis organism.

We also talked about the possibility to use genetically modified yeast as a sensor in the natural environment and it was nice to hear that they didn’t turn this idea down even if it is not allowed by the Finnish legislation at the moment. This gave us additional courage to choose our GMO yeast sensor as our project idea.

Besides affecting our choice of topic, SYKE gave us information about how we could develop our project after establishing our proof of concept. We talked quite a lot about what kind of models are currently used to follow the development of algal blooms and cyanobacterial movement in seas. From this conversation, we got an idea to develop their Levävahti sensor app. This was supposed to be part of our project, but unfortunately time constraints prevented us from doing this. Perhaps after the Giant Jamboree we might have time for this.

Interviewing people on the streets of Helsinki

From interviewing people in the streets, we learned that public knowledge about synthetic biology was rather restricted. Most people associated it with man-made biology or just something that they need to know nothing about. Based on this, we really thought that there was a need to increase knowledge about synthetic biology. We didn’t leave this on the level of thought, as we tried to raise the level of knowledge by talking in university lectures, in a biology olympiad training camp, and by telling about synthetic biology in magazine and radio interviews. In the beginning, we didn’t really understand how scary and strange a branch synthetic biology seems to be for people not involved in it, but during the project we started to understand this. It is probably also one reason for why investors are not so easily attracted to projects related to this branch - they don’t know enough about it. Our team participated also in a bioeconomy seminar hosted by VTT, where this subject was brought up. It was discussed that communication really is the key when trying to create business in this field, and that researchers should learn how to communicate about this seemingly outlandish field to the general public. For this reason, too, we see a huge need to spreading knowledge, and we hope that in some years, it will start to show.

Besides gaining information about the need of synthetic biology outreach, we wanted to see what people know about blue green algae and if it has caused problems for them. All of the interviewed people were familiar with it but didn’t know much about the health or economic problems it causes. Still, as each of the interviewed people had encountered blue-green algae, it means that our project can touch their lives and possibly to facilitate their life in the future.

We didn’t change much in our project topic itself based on the interviews but we increased the importance of talking to the public. Additionally, as we learned how restricted the knowledge about our topic is, we have been able to adjust our presentations better for the targeted audiences. Some of the most important modifications we did in our presentations to people with limited biological background was dismissing almost all scientific terms, assuming no background information, focusing on what we can achieve with our project instead of the exact methodology, and leaving more time for questions. One result of our efforts to communicate with the non-scientific community was our project introduction video “Matti and the cyanobacteria”, found on our Project page.

iGEM meetups

We participated in two iGEM meetups, the ones in Stockholm and Paris, which gave us many things to consider in our project. In Stockholm we participated in an ethics workshop. This gave us a lot to think, since our project’s final product was designed to be a genetically engineered organism used outside the lab. We want to stir up the conversation about GMO legislation, and be part of the discussion about how GMOs could be used outside of the lab and by general public. More about our ethical considerations can be read below.

In both meetups, we were presented with the idea of patenting one’s work. In Stockholm, the SDU team couldn’t present their full project because they were in the process of patenting it. In Paris, we participated in a panel discussion where part of the discussion was about patents and the openly communicated nature of iGEM projects. After hearing about this, we reconsidered our project from a broader point of view and decided to look into business aspects of it. Although neither the topic of our project nor the nature of iGEM made patenting seem like a relevant concern, we nevertheless thought it would be useful to gain an understanding of this aspect. We met up with Merja Penttilä from VTT to discuss these subjects. We received a lot of valuable information which would prove useful if at some point our project was developed forward and commercialization was a relevant question.

Meeting with companies

We got a chance to practice our presenting skills when we met with different companies and tried to convince them to sponsor us. What we got from them was advice on how to give presentations and how to emphasize our strongest points. We also got good practise on how to communicate with people who don’t have much background in biology, not to mention synthetic biology. Later in the project, we had a meeting with Algol, one of sponsors, where we presented our results. We were asked great questions on how we are going to motivate our choices and how we plan to explain the results at the Jamboree. Even though our presentation there was for people who don’t have a biological background, we had to think of e.g. how to explain that cyanobacteria are a problem for people who don’t live in Finland and don't have the same problems with it as we do.

When we met with companies, there was also a lot of discussion of the potential commercialization of our project, which meant patenting our idea. As discussed above, our conclusion was that it didn’t seem relevant to our project.

Ethics

Legislation and public opinion on GMOs in Finland

Finnish legislation towards genetically modified organisms (GMOs) is strict, similar to the rest of the European Union. In Finland, the Gene Technology Act regulates the use of GMOs and promotes the safe use and development of gene technology along with ethical practices and consideration of the precautionary principle (Geenitekniikan lautakunta). The precautionary principle is a concept used in risk management and according to it, if an action is suspected to be harmful for the public or the environment and there is no scientific agreement on the matter, then the burden of proof that it is not harmful lies on the party which is carrying out the suspected action.

The Gene Technology Act is based on the EU Directives 2001/18/EC and 2009/41/EC, which concern the deliberate release of GMOs into the environment and the contained used of genetically modified microorganisms (GMMs), respectively. It also includes genetically modified plants and animals for contained use. The Gene Technology Act is supplemented by Government Decrees and Decrees of the Ministry of Social Affairs and Health. (Geenitekniikan lautakunta)

As it is impossible to predict the cascade of consequences resulting from GMOs being released into the environment, caution in this respect is well-advised. The organisms themselves could undergo genetic changes and outstep their intended role, or have unexpected effects and interactions with the ecosystem. In addition, the genetic material of decomposed GMOs could be taken up by other organisms, leading to even more possibilities for unwanted consequences.

There are many measures that can be employed to improve the security of genetically modified organisms, though public opinion remains biased against GMOs. Public opinion is also one reason why we chose to work with yeast, as opposed to e.g. the bacterium Escherichia coli. In large part, negative attitudes towards GMOs can stem from connotations of certain words, as well as the perception of strangeness in the daily lives of people. We reasoned that by working with baker’s yeast (common name for Saccharomyces cerevisiae), an organism familiar to most people with neutral if not positive connotations, our work would feel more approachable to and less detached from people’s everyday lives.

With our project, we hope to improve the understanding about synthetic biology and GMOs. We want to improve the public perception of GMOs this way, and through removing negative biases and public image, stir up conversation about steering legislation into a direction where it is informed by reason, not biased perception. To this end, we also want to bring attention to measures that can be taken in practice to design safe GMOs.

Ethics and related considerations in our project

We have given much consideration to the ethical implications of our work. This was evident from our brainstorming sessions, when the idea of targeting cyanobacterial toxins came about. The team’s acceptance of the idea was driven by how popular the problem was in Finland. We were addressing a serious, recurring environmental issue in the very country we were living in, though the problem is not exclusive to Finland. This would also let our project be more approachable and understandable to the the public as well as sponsors. Addressing a local problem creates an affinity between our project and the public, and also makes it easier for us to promote synthetic biology to them.

We wanted our products to have minimal side-effects on the environment and that meant limiting the reach of any genetically modified organism present in those products. Keeping this in mind and inspired by the Finnish nature and lifestyle, we decided to approach the problem of blue-green algae in the context of sauna water, thus limiting the scope of our products to a few drops of water and to maximum one bucket of water (~20 L) for the detection and degradation, respectively.

Our detection device would contain live yeast cells to produce the fluorescence signal, and is the main concern of our project when thinking about accidental release of GMOs. It is necessary to properly design the kit so that the yeast cells are contained within the device, in addition to placing biosafety measures for the possibility that the GMOs would escape the device, either caused by the device breaking or because of product misuse. This would have to be done in an especially fool-proof manner if the kit was to be commercialized. The best result would be achieved by introducing a combination of physical and biological containment strategies. An example of physical containment would be placing a filter (e.g. 0.22 µm) on the device sample wells in which the cells would be contained. Through this, water and small molecules such as toxins could pass but not yeast cells. This would allow detection of microcystin in the water while ensuring that the yeast stays inside the device. In addition, to adopt a biological containment strategy, we would engineer several essential proteins in our yeast cells to have a dependency on non-standard amino acids for their proper translation, folding and function, as described by Mandell et al. (2015).

The kind of synthetic auxotrophy described by Mandell can be considered a more advanced and secure method of biocontainment, and in particular if combined with still other containment strategies, it would make it highly unlikely that our yeast could bypass the biocontainment. As multiple genes would be dependent on the synthetic amino acids, escaping biocontainment via mutagenesis would require mutations in a large number of genes. Horizontal gene transfer could be prevented by engineering the synthetic amino acids into any protein-coding sequences we want to prevent from transferring. In addition, as the synthetic amino acid couldn’t be scavenged from the environment, the GMOs would survive only as long as they are externally supplemented by the amino acids.

Our degradation enzyme capsule, on the other hand, would not contain any living cells - only commercial lysozyme and enzymes derived from the genetically modified microorganisms. The enzyme has a specificity for the Adda-arginine bond, which is only present in cyanotoxins. As such, the enzyme does not pose any direct threat to any form of life, even when released in the open environment. However, there may be certain organisms whose growths are kept in check by microcystin, and if large quantities of the enzyme were released into open ecosystems, the microbial ecology in the water might be severely affected. In high concentrations, lysozyme could also have drastic effects on the ecosystem, as it can can lyse the cell walls of many bacteria. However, as our plan would be to use the capsules for small quantities of water (bucket-scale), releasing this capsule in just one bucket of water alleviates such concerns; as the enzymes are scaled for such a small quantity, they would be extremely diluted when released to the open environment.

References

Geenitekniikan lautakunta. Finnish legislation regarding the use of genetically modified organisms. http://geenitekniikanlautakunta.fi/en/article/-/asset_publisher/kansalliset-saadokset
Accessed 18 Oct. 2016.

Mandell DJ, Lajoie MJ, Mee MT, Takeuchi R, Kuznetsov G, Norville JE, Gregg CJ, Stoddard BL, Church GM., 2015. Biocontainment of genetically modified organisms by synthetic protein design. Nature 518 (7537):55-60.