Team:Aalto-Helsinki/HP/Gold Integrated
Integrated Human Practices
Background of the Project
From the very beginning it was clear that we would aim to create an actual application for the work done in the lab and through modeling. This was only natural, since our team has expertise well beyond the lab in the areas of product design and business. Having a concrete and familiar looking product might also be a great way to encourage conversation about synthetic biology with the public. All of the team members share a remarkably similar set of values, so we wanted our final product to be accessible, mainly thanks to it being low price, environmentally friendly, safe to use and ethical.
Brainstorming and Narrowing Down Ideas
Initially we came up with more than 30 ideas, so we had to narrow it down several times before getting to Dermcidin. In order to shape our ten best ideas and make some important contacts that could help us during our journey we visited The ChemBio fair (29.3.-30.3.2017) and Upgraded Life Festival (25.4.-26.4.2017). The ChemBio fair was unfortunately mostly focused on the lab equipment and therefore wasn’t as useful as we would have hoped. Upgraded Life Festival, however, was more focused on health tech and the health start-up scene in the Helsinki area in Finland. During the spring, two of our team members, Michal and Meo had worked for the two-day event as volunteers and so had quite a good picture of the companies and presenters. Thus, there were countless possibilities to approach different companies and alliances to discuss possible collaboration. Whilst attending the most interesting presentations, we also managed to approach nearly all parties that we thought were interesting or were related to our initial project ideas.
We also met and discussed with several deans from both universities and presented our top 10 ideas on a SynBio course to Aalto University students in order to get their insights and feedback. After accidentally stumbling upon the molecule Dermcidin, while looking into another idea, we also had a meeting with Bayer. The company has expertise in healthcare and at that point we were certain that we would end up going in that direction. We also discussed our ideas with the representatives of our sponsor ThermoFisher Scientic. From these visits, discussions with our suprevisors and scientific literature we came up with the idea to use Dermcidin as a coating for medical devices with the aid of a cellulose binding domain, connected to Dermcidin with a linker. In the beginning, we also investigated the possibility of 3D printing the Demcidin coating or medical devices themselves with the bound Dermcidin molecules. We consulted several experts from Aalto University to figure out if this approach would be beneficial to our project, but there were several problems like probable activity loss in high temperatures as well as uneven shrinking of dry cellulose, which would make many cellulose based applications like cathedrals basically impossible. Since 3D printing didn't seem to bring any additional value to the project, we decided to focus mostly on wound care and an alternative for silver containing dressings.
Business Thinking in iGEM Project?
From Biodesign Finland we met two medical doctors, Sami Elamo and Katja Ivanitskiy, who are part of Biodesign Finland, which aims to innovate new medical technologies in interdisciplinary teams. We discussed our idea of immobilizing Dermcidin on a cellulose surface and the possible aspects we should take into consideration. They emphasized that we should figure out how to produce things cheaply since that would help our product to compete with current wound dressings. We were also brainstorming on different applications for our peptide and how to improve the stability in the end product. We also got more knowledge about patenting innovations and were introduced to Provisional Patent. After the meeting we continued investigating the different application possibilities, but we also started to think about our project more from the business angle. This meant that we started to look into scale-up possibilities in order to make the product cheaper and also examined the patenting options in collaboration with a law student from iGEM team Tec-Chihuahua. At the end of the project we even made a full business plan.
Alejandra from iGEM team Tec-Chihuahua visiting us during July
Deciding Between Wound Care and Acne
We visited two hospitals, Jorvi Hospital burn unit and Helsinki Skin disese clinic's wound policlinic, in order to get a better grasp of the suitability of Dermcidin in different wound care applications. A specialist doctor, Andrew Linford, was kind enough to show us around the burn unit in Jorvi Hospital. We got a tour around the unit which was designed to serve the burn victims in every stage of their recovery. We learned about the different techniques and products used when treating burns but since the usage of antimicrobial agents was minimal, especially in the early stages of a healing burn, we decided not to focus too much on this subject.
At the wound policlinic, we met nurse Ulla Väänänen and dermatologist Kirsi Isoherranen. We had a lovely visit, during which we were allowed to follow the appointments of three patients with different kind of wounds and truly learn about wound care in detail and in practice. In addition to meeting patients and following the procedures, we were also introduced to a massive amount of wound care products and even got to take samples and brochures with us. We felt that we might not be able to compete with such a massive amount of products. Additionally, in deeper wounds, biofilms and some bacteria might prove to be a problem, so we felt that wound care might be too much of a challenge for our peptide.
Nurse Ulla Väänänen showing what kind of problems she has faced with current wound care products.
We had also noticed from literature that Dermcidin is active against Probionibacterium acnes, which is a common species on acne patiens, who also have lower Dermcidin levels than people without acne. This seemed intriguing, so in order to learn more about acne, we visited Antti Lauerma, who is a doctor of medicine, professor of dermatology and an allergologist. During our meeting, we learned that acne isn’t actually as studied as one would think of such a common disease. Even if people are usually well aware of its existence, they might not know that much about it. There is also still some widely distributed misinformation that we could hopefully help to correct with our project.
We also learned a lot about the other current treatments and that some things about acne are still not known - even the exact cause of acne in general. For the application of our project, one of the most important pieces of information was that according to Lauerma, recent studies show that although Propionibacterium acnes can be found on the skin of acne patients, it is more likely a result than a cause for inflammation that is the main reason for acne. Therefore, we should stress that anti-inflammatory treatment might be the key to actual acne treatment, while our product would focus more on the cosmetic side, and therefore self-esteem, by preventing some of the new pimples from forming. This is the reason why, for example, isotretinoin and the antibiotic tetracycline with anti-inflammatory properties are effective as a treatment and we should recommend using also other products while using Porify.
It is to be noted that at least in Finland antibiotics and topicals are still prescribed more often than the harsher treatment isotretinoin, because a lot of patients with acne are treated by general practitioners, who cannot prescribe isotretinoin. In some countries isotretinoin is not available or is even banned, so there might be demand for new acne treatments and products.
Both options, wound care and acne, had several pros and cons and the decicion was not an easy one. Nevertheless, even if Dermcidin might have some wound care applications in the future, we felt that acne seemed more promising and matched our team's expertise better. It is also an ideal application to help spread information about synthetic biology since almost everyone experiences acne at some point of their life and therefore the familiarity of the subject might encourage them to have an actual dialog with us, despite their possible negative attitudes against GMOs in general.
Focus on Acne
In order to gain more insight on how acne affects the mental well-being of adolescents, we contacted psychotherapist Pepita Hänninen, who is specialized in working with young people. She has been interviewed for newspapers about acne and how parents should react if their kids are suffering from acne. She thinks that the problem should not be belittled since it can have a major impact on young people. Hänninen thinks that acne can worsen a person’s mental state if they are already feeling insecure or depressed, but the skin condition itself is rarely the main cause of mental health problems. Still, acne can be a major problem for young people, since adolescents form their identity during puberty and pimples often go hand in hand with the increased sex hormone levels. Appearance might have a bigger role in a young person’s life and sometimes it is difficult for adults to understand that. Then again, in some cases, parents might make a problem out of acne when it was not bothering the adolescent in the first place. It takes some discretion to find the right way to deal with the issue.
We also met vlogger Valtteri Sandberg who is a relatively famous Finnish fashion / lifestyle vlogger. He makes videos about skin care and makeup routines, and has been noticeably open about his acne. The vlogger was eager to be interviewed about his acne and especially its psychological effects. We were very happy about this chance. The interview can be found from here.
Acne's effect on self-esteem was important information for us, since together with literature we could be certain that acne really is an important problem that affects countless individuals in a negative way and new solutions are truly needed.
Market Research and Designing a Product
To get more information from the industries dealing with acne, we met cosmetologist Ida-Maria Rantala from Ihohoitola Lupaus beauty clinic. She was specialized in acne and told us about her patients, treatments and products they use in a beauty clinic and what they recommend patients to use at home. We got a lot of input about consumer behavior, for example what kind of products they are most often willing to use and how much money they are willing spend on acne treatments. We also talked about Rantala’s own point of view about genetically modified organisms, ongoing trends in skin care and what kind of product she believes will be on the market in future.
The Urlinski company designs and manufactures the equipment for production of cosmetics and medicines. We contacted the company representative to learn about the process of producing cosmetics in general, and to get opinions and advice regarding our skincare product concept. As for manufacture, they emphasized the importance of scaling-up from the laboratory to full production. They also presented how this transfer is done with the devices of different capacities in the company facility, which greatly helped us with our business plan. The first potential problem pointed out regarding our product was spoilage of the cellulose-based hydrogel due to microbial contamination. This led as to try several different preservatives with the hydrogel. We also talked about the growing popularity of preservative-free beauty products, however it seems that we cannot avoid using preservatives in our case. We also received feedback regarding our preliminary package idea for the container with separated compartments for different cosmetics components. According to our interviewee, customers prefer a ready-to-use product over the possibility to prepare individualized one by mixing components on their own. A special dispenser could be used; however, currently available dispensers are not so practical in use and fail to maintain good mixing of ingredients in a cosmetic formulation. This led us to go with a ready-to-use product.
We also wanted to interview people who have or have had acne in order to understand how the condition has affected their life and whether they tried to get rid of it. It was heartbreaking to learn what a huge affect acne can have on someone's life. The people suffering from acne where willing to go through many side affects and spend a lot of money to get rid of acne.
To get a better representation of our customer base, we conducted an online survey to find out how acne affects people's well-being and what they are willing to do to treat the condition. We got 193 responses in total. The answers were based on self-perception and personal opinions of our respondents.
At least 45 % of our respondents had had acne for more than 1 year. Thus, it can be concluded that there is a need for continuous treatment. Almost 6 % respondents had been suffering from the disease for over 10 years from when most of them had turned young adult age till they were 30+. Over-the-counter medicines are the most common form of treatment (almost 60 %). However, they might have been used as secondary treatment on top of topical antibiotics (~40 %), oral antibiotics (33 %) or retinoids (~16 %). People spend an average of 270 € per year for acne treatment, where as severe acne treatment costs can exceed 4000 € per year. At the same, a great fraction of the respondents (~75 %) would not mind adding another product to their daily skin-care routine. About 80 % said that they would use a product containing ingredients produced with genetically engineered bacteria. We also asked people about four potential topical products containing an antimicrobial agent. Their preferences were as follows: cream for daily use (41 %), face cleanser to use every now and then (26 %), exfoliating pad (17 %), and overnight face mask (13 %).
Based on the survey and interviews, it seems that the treatment could be continuous and an over-the-counter product. Being cheap might be a considerable advantage and adding another product to our customers' skin-care routine would hardly be a problem, even if it contains ingredients that have been produced with genetically engineered bacteria. This was very encouraging for our product design, but an exfoliating pad and an overnight face mask seemed to be a lot less popular options for daily use than a cream or a face cleanser. Those were the two application options where the cellulose binding domain would have been necessary. To support other possible acne product applications, we still weren't entirely sure if Dermcidin would remain active when bound to cellulose, even though we had managed to prove that without the cellulose binding domain Dermcidin showed some antimicrobial activity and the molecules with the binding domain really could bind to cellulose. Therefore we shifted our focus to creams and face cleansers.
Even if cellulose based exfoliating beads and overnight face masks didn't seem to please our potential customers, we wanted to hold onto the cellulose aspect of our project while shifting our focus a little. We visited Aalto Bioproduct Centre in order to see what forms of cellulose even exist. There, we were introduced to hydrogel which we decided to use in our final product. In application design we got a lot of help from a PhD student Andreas Lindberg, doctoral candidate from Aalto University, School of Chemical Engineering. He is specialized in cellulose materials and working with designers at Chemarts school and Aalto Bioproduct Centre. He made it possible to work with cellulose hydrogel (CMC) by providing us with the raw material and helping us to proceed with it. What ever problem we had with the application design, he was very willing to help us to solve those problems and encouraged us to keep on looking for the best possible solution.
Ethics, Environmental Impact and Safety
Since we are working with Safety level 1 organisms, the produced product Dermcidin can already be found on human skin and cellulose is a natural material, our project can be considered to be relatively safe and the potential harm in a situation of our modified Escherichia coli escaping outside the lab is relatively small and it would be difficult to use it to do harm even on purpose. This does not mean that it would be entirely safe or responsible to free them into nature since their antibiotic resistance to Kanamycin or Chloramphenicol could spread to other bacteria in nature and cause some trouble in the future.
Considering our concept and product design, the end product needs to be safe to use on the human skin, on an everyday basis. We are lucky in this regard, as the Dermcidin peptide (DCD-1L) we worked with is already present on the human skin. The only thing that needs to be considered is whether abnormally high concentrations of the peptide risk the development of microbial resistance against it. In that case, the body would lose its natural mechanism of defense against acne among other pathogens. One article [1] hypothesizes, however, that it may be much less likely that resistance develops against this peptide, as the peptide is evolutionarily very recent and resistance would require big changes in the constitution of the bacterial cell wall or membrane. Compared to antibiotics, which are used to combat far more dangerous diseases, resistance against our peptide does not pose a huge public health risk.
We didn't want to use any synthetic and oil based materials like micro plastic exfoliation beads that are commonly used in skin care products currently on the market. Since cellulose is abundant in Finland, and less and less paper is used throughout the world, our product is one good use for the wood. Thinning of the forest is a good way to acquire wood without disturbing the growth of the forest. Cellulose is a safe foundation for a product and it does not pose a threat to humans or the environment.
In package design, we had several potential material candidates like biodegradable wood based plastic PLA, paper and wood. We decided to go with a wooden package because we had a somewhat humorous idea of wood based product packaged inside a wooden package. With a wooden package we also represented Finnish nature, which was an inspiration in whole design process. The package is made out of curly birch wood, which has a naturally beautiful structure and outlook. Our product name was laser engraved on top of the package and ingredient information can be engraved on bottom of the package. In actual production process, a wooden package will most probably prove too expensive. For now, however, we wanted to focus on a showpiece; an idea of a beautiful package that can be used after the product has run out. With a wooden package we will also get more attention. In the future, the package could be a PLA tube or a coated paper tube which is easy to recycle or burn.
More about the ethics of our project in our Ethics page.
More about the safety of our project in our Safety page
References
[1] Schittek, B. (2012). The multiple facets of dermcidin in cell survival and host defense. Journal of innate immunity, 4(4), 349-360.
