Integrated Human Practices
This page describes the work we've done outside of the lab and the interactions we've had throghout our project, and how those interactions have affected our project. We asked the question: What non-technical challenges needs to be adressed in order for our vision to become real? We tried to find the answers be turning to experts, the general public, and to industry.
Influences
Throughout our project we’ve had many professionals and students influencing and changing our core idea and methodology. Read more...
Investigating the market
In order to investigate the market of our potential product, Prodeacc, we sought to investigate the public’s perceived danger of toxic metals as well as the public demand of our product as perceived by current companies within the field. We also investigated what precautions the layman was willing to consider in order to reduce the risk of ingesting these substances. Read more...
SynthEthics
What started as a collaborative effort between iGEM Lund, iGEM Copenhagen, iGEM Stockholm and students with the aim to update the current legislations and regulations with regards to genetically modified probiotics, grew to become a collaboration regarding bio-ethical concerns. Read more...
Influences
During the first weeks of brainstorming we had weekly brainstorming-meetings with mentors and professors at Lund University (such as Dr. Johan Svensson Bonde, Dr. Nelida Leiva Eriksson, Dr. Cedric Dicko). With their aid we specified and distilled our idea to the point that we knew we wanted to work with toxic metals. It was also with their help we came to the conclusion that a water-filter was extremely hard to attain due to the large bodies of water which would have to be cleansed, and we decided to work with probiotics.
One of our first influences was Dr. Tim McDermott, who deals with microbial transformations of arsenic. We contacted him during the primitive stages of our project, as we planned to transform arsenic in probiotic bacteria to increase its excretability, thus reducing the amount of accumulated arsenic in the body. However, a skype-conversation with Dr. McDermott led us to pursue the idea of bioaccumulation in the bacteria, thus radically changing the course of our project.
Our second major influence was Dr. Nelida Leiva Eriksson. She presented the idea of using E. coli Nissle 1917, instead of more common probiotic bacteria as planned (eg. Lactobacillus plantarum) and due to the convincing argument of painless handling in the lab, we readily adopted it as our new chassis.
To gain expertise regarding research on probiotics we visited Probi and BioGaia, both companies specializing in production and research of probiotic bacteria. During this stage of our project, we intended to use CRISPR-technology to insert our genes for absorption and accumulation into the genome of our chassis. At Probi, they advised us not to, and suggested we’d use plasmids instead. After some convincing arguments regarding the chances for off-targets when using CRISPR, we decided to take their advice, which drastically changed the course of our project. They liked our project and our enthusiasm to the extent that they agreed to be one of our sponsors!
During following meetings with experts and mentors at Lund University we decided to work with three toxic metals: arsenic, lead and mercury.
During the laborations we faced many problems which we frankly didn't have the experience to deal with. We were lucky to have people such as Eva Sjöblom, Jose Alfredo Zambrano Rodriguez, Karin Kettisen and Patrik Nilsson close to us whom we could ask for advice. Their help with everything from genetic engineering to cultivation guided us through the jungle of complications, disputes and headaches we call 'lab-work'.
At BioGaia we discussed the legal aspects of our probiotic, and they convinced us to compete in the track for Food and Nutrition due to the nature of probiotic supplements. This also led us to start thinking about the ethical and legal concerns of our product and synthetic biology (read more about SynthEthics).
To prepare for the toxicological and environmental hazards of our project we talked to Aniko Wendler, the work environment coordinator at Lund University. Following her advice we decided not to work with mercury due to troublesome regulations and major health risks.
Before we started our labs we contacted the geneticist and toxicologist Professor Karin Broberg from Karolinska Institutet. She is head of the Unit of Metal & Health who are leading experts on the impact of toxic metals on the human body. Karin discussed the toxic impact of arsenic, zinc, lead and cadmium and advised us to investigate how our project could be applied to other metals, especially cadmium, due to its impact on Sweden and Europe. She also explained why we should change our terminology, from the commonly used term “heavy metals” to the more appropriate “toxic metals”. During a later stage of our project Karin supplied us with information necessary for our model.
When planning our analysis experiments we reached out to Margareta Sandahl, who advised us to use external companies to measure the concentrations of toxic metals in our samples, since the process is both hazardous and tedious in a regular lab. Following her advice, we contacted Eurofins who were happy to measure the concentrations in our samples.
As our SynthEthics project got on its way, it was clear that we needed jurisdictional guidance regarding some of the legal aspects of the project. We contacted the lawyer Bo Benell, whom we met up with. He helped us write consent-forms and advised us on how to gather data in accordance with GDPR.
Research papers:
Our project has had major influences from past iGEM teams and research papers. Here are some of the main ones:
- Chakraborti D, Singh SK, Rahman MM, et al. Groundwater Arsenic Contamination in the Ganges River Basin: A Future Health Danger 2018-01-23, Taken from [internet]: https://www.ncbi.nlm.nih.gov/pubmed/29360747
- Kostal J., Yang R., Wu C.H., Mulchandani A., Chen W., “Enhanced Arsenic Accumulation in Engineered Bacterial Cells Expressing ArsR” 2004-08, Taken from [internet]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC492386
- Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ., “Heavy metal toxicity and the environment”. 2014-08-26, Taken from [internet]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4144270
- Masindi V., Muedi KL., “Environmental Contamination by Heavy Metals” 2018-06-27, Taken from [internet]: ttps://www.intechopen.com/books/heavy-metals/environmental-contamination-by-heavy-metals/li>
- Mok T., Chen JS., Shlykov MA., Saier Jr MH., “Bioinformatic Analyses of Bacterial Mercury Ion (Hg2+) Transporters” 2012-06-02, Taken from [internet]: https://link.springer.com/article/10.1007%2Fs11270-012-1208-3
- Hložková K., Šuman J., Strnad H., Ruml T., Paces V., Kotrba P., “Characterization of pbt genes conferring increased Pb2+ and Cd2+ tolerance upon Achromobacter xylosoxidans A8”, 2013-10-12, Taken from [internet]: https://www.sciencedirect.com/science/article/pii/S0923250813001873?via%3Dihub#!
- Yang HC., Fu HL., Lin YF., Rosen BP., “Pathways of Arsenic Uptake and Efflux”, 2015-09-22 Taken from [internet]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578627>
- Edinburgh 2006 https://2006.igem.org/wiki/index.php/Arsenic_Biosensor
- FAFU 2017 https://2017.igem.org/Team:FAFU-CHINA
- Exeter 2017 https://2017.igem.org/Team:Exeter
- University of Connecticut 2016 https://2016.igem.org/Team:UConn
- Lanzhou 2016 https://2016.igem.org/Team:Lanzhou
- Colegio Franklin Delano Roosevelt 2018 https://2018.igem.org/Team:ColegioFDR_Peru/About
The main iGEM-teams that inspired and influenced our project were:
Investigating the market
To investigate the current demand for our product we reached out to companies and employees. Mohsen Mahdavi, a former rice importer and distributor, stated that the rumoured dangers of arsenic in rice in Sweden is indeed true. He stated that the [translated from Swedish] “levels of arsenic naturally varies between different geographies, and can also vary from one patch of land to another [within the same farm]” which makes it difficult to control the amount of arsenic in imported rice dependent on its source. He agreed that the market would therefore benefit greatly from a product like a probiotic remedy that is closer to the consumer in the chain of arsenic accumulation.
We also contacted the geneticist and toxicologist Professor Karin Broberg from Karolinska Institutet. Specializing in the toxicological effects of toxic metals, she educated us on the impact toxic metals has globally, and specifically in Sweden. Karin confirmed that arsenic is a huge problem worldwide, and that toxic metals like lead and cadmium pose severe risks in certain geographies, for example in Sweden. The estimated cost of fractures due to brittle bones caused by the toxic effect of cadmium is 4 billion SEK (~400 000 USD) in Sweden alone, and that isn’t remotely close to being the only implication cadmium has on the human body. In many countries implementing water filters proves impossible due to a lack of infrastructure, and Karin was intrigued by our perspective of using probiotics, something she hadn't thought of before. Karin stated that if we’re able to give a proof of concept and if the legal system allows for the production of our bacteria, an implementation of it could result in huge medical and economical gain.
To investigate the probiotics-market we visited Probi and BioGaia. They state that our product would be hard to incorporate due to the current legislation, but that our product had great potential and could be easily adapted and accepted by consumers. This led us to investigate the current legislation governing synthetic biology in the EU and US (read more about SynthEthics).
To get a grasp of the public's opinions we constructed a survey and spread it via indirect sources to reduce the connections and biases those familiar with our project might have. The questions of our surveys were designed to raise no suspicion of our intentions, and inquiries irrelevant to our research were therefore included in the survey. The survey was purposefully constructed in Swedish to reach the local market.
Firstly, the questionnaire asked for your perceived danger of various substances on a scale from 1-5. The average is shown in figure 1.
Figure 1: The figure shows an average of perceived dangers of the following substances: aspartame, fat, sugar, cholesterol, arsenic, lead and mercury.
Secondly, the survey asked for you to identify what groceries you think contain dangerous substances. The answers resulted in an apparent majority amongst the four groceries: diet-products (75%), red meat (72%), fish (67%) and rice (64%). We then asked what precautions you take to reduce the ingestion of dangerous substances in these groceries. The answers mainly consisted of the following: stay away from diet-products, be vegetarian (or pescetarian), wash and rinse rice thoroughly.
Thirdly we asked similar questions regarding other products, such as laptops, plastic bags, and cellphones, to investigate if absorption of toxic metals from gadgets and technology such as laptops or cellphones was a public concern. We concluded that it was, however, not to the same extent as that of microplastics from plastic bags and toys.
In Summary
In the beginning of our project we asked ourselves the question: "What non-technical challenges needs to be adressed in order for our vision to become real?". By interacting with experts, the public and the industry, we can gladly say that we've come far in answering that question. However, we've also recognized that our efforts in ethics and legislation regarding synthetic biology on our way to reaching that goal need to be intensified, and we've therefore launched SynthEthics.