Talking to people from academia is of great relevance to us, especially on the scientific side of our project. These stakeholders are able to understand whether our project is scientifically feasible and give us valuable advice about certain details in our design, such as the cancer biomarkers we have chosen. We interviewed three different stakeholders in this consortium, all related to our project, but with different expertise.
- We decided to turn our living diagnostic into a short-lived self-test instead of a continuous test.
- We reduced the subjectivity of the test result of our living diagnostic by developing an app that can assess the colour of the faeces.
Gwenny Fuhler is a medical biologist at the Department of Gastroenterology & Hepatology of the Erasmus Medical Center (NL). She taught us more about the biology of tumours and brainstormed with us about solutions for several problems in our project. At the early stages of our project, we wanted to develop a test that is able to colonize the colon and thus continuously test for cancer. However, Gwenny informed us that it might be possible that our diagnostic would not colonise the gut and could interfere with the normal microbiome.
Additionally, Gwenny was sceptical about our biomarkers. She told us that there are different types of polyps which might have a different lactate production or CEACAM expression. Additionally, the lesions are expected to be very small, and hence the sensitivity of the assay is of importance.
We also talked about the current Dutch colorectal cancer screening programme. The test that is currently used in the programme, the Faecal Immunochemical Test (FIT), tests for blood in the stool. Gwenny told us that even though cancer is caught early in a lot of patients, there are still polyps that do not bleed. As a consequence, these are not picked up by the FIT.
She was of the opinion that our project should not be a stand-alone self-test, but its use should be controlled in some way. Patients generally trust a doctor better than when they have to check something for themselves at home.
- We chose to transition our tool from a continuous test to a self-test.
- We reconsidered the inducer metabolite for the kill switch.
- We considered integrating symptoms and lifestyle information in the app to help the diagnosis.
Markus Gwiggner is a gastroenterologist who is subspecialized in inflammatory bowel disease (IBD) and works at the University Hospital of Southampton (UK). In the past, he obtained a PhD in molecular biology. Now, he is also doing research related to digital health and collaborates with microbiome research in IBD.
In the UK, the colorectal cancer screening programme is the same as in the Netherlands: people over the age of 55 get invited for the FIT every second year. However, he claims that only 6-7% of patients with positive FIT results will have cancer-positive colonoscopy results, which leads to many unnecessary colonoscopies. Surprisingly, the perception of endoscopies by IBD patients is “overwhelmingly positive”. However, Markus thinks that the acceptability of endoscopies would probably be lower in asymptomatic patients.
Regarding our project, he gave us very valuable feedback. He thinks making our bacteria colonise the colon might be very complicated because people’s microbiomes differ a lot. He also believes the biomarkers we chose for colorectal cancer recognition might not be specific enough since they tend to increase in inflammation. His suggestion was for us to look for additional specific targets to decrease the false positive rate.
Concerning biosafety, he thinks the use of a GMO for diagnostic purposes is alright as long as it does not harm the resident gut microbiome. Also, we suggested the use of aspirin as an inducer for the kill switch and he strongly advised us to change the inducer molecule, as lots of people over the age of 55 have heart issues and take aspirin on a daily basis.
He believes that a very important characteristic of our project is that it does not need a kit, which makes it really user friendly. Also, he really likes the idea of implementing an app able to recognize the colour of the stool and help people through the screening process. He suggests including also an option to add symptoms and lifestyle in the app, so the diagnostic can be more accurate.
- Our tool transitioned from a continuous test to a self-test.
- We focussed on diagnosing instead of also localizing the tumour.
- We designed our tool to be implementable in the colorectal cancer screening programme.
- We created an app to help you verify if the test was positive or not.
Monique van Leerdam is a professor in gastroenterology, specialised in the prevention of hereditary tumours at the Leiden University Medical Centre (NL). She is also head of the department of Gastrointestinal Oncology at the Netherlands Cancer Institute in Amsterdam and she has been involved in the monitor and evaluation committee of the colorectal cancer screening programme in the Netherlands since 2014 but was already involved in the pilot screening studies since the start in 2004.
In her experience, most people are willing to undergo a colonoscopy when testing positive in the FIT because they are afraid, they might have a serious disease. She believes the colonoscopy process itself is OK for most patients, while the preparation for it is a big burden, since it implies taking laxatives to clean the whole bowel.
When talking about Colourectal, she raised very valuable concerns and suggestions. We considered our living diagnostic to colonise the gut to allow for continuous cancer detection. However, Monique emphasized the complexity of colonisation due to microbiome differences among individuals. Additionally, she strongly suggested that we avoid the tumour localisation step with MRI or ultrasound. Since she believes colonoscopies are unavoidable, and ultrasounds or MRI would not be able to display clear results .
Colorectal cancer is a disease that develops very slowly, so Monique thinks taking our test once every year would be a good frequency if it is sensitive enough. In fact, she thinks Colourectal should be arranged as a national programme, from the start to end – maybe as an alternative to the FIT test. That way, it is also easier to collect population-based data on how effective the diagnostic is in detecting early-stage colorectal cancer. Furthermore, she suggested us to develop an app able to recognize if the colour of the faeces is abnormal or not by just taking a picture. That way, individual subjectivity and other problems, such as colour blindness, would be surpassed.
She thinks Colourectal is a clean, nice and user-friendly diagnostic tool. A big advantage is that it is possible to do at home. Since the samples do not need to be analysed in a lab, it would also be useful to implement colorectal cancer screening in third-world countries.
Colourectal was designed as a more efficient and accessible substitute to the current screening programmes for colorectal cancer. Currently, screening programmes are funded by governmental bodies. However, the actual test used is produced by the pharmaceutical industry, as would Colourectal. During our project we spoke with probiotic experts, drug developers, experts in medical technology (Medtech), and experts in biosafety and biosecurity. Their feedback helped us make our product more useful and feasible.
- We made our implementation more concrete by using the expertise from NIZO on treatment for storage of the living diagnostic and the delivery to the colon.
- We made an entrepreneurial guide, where we described all the insights into the process of getting a new product, like Colourectal on the market.
- We reformed our tool from a continuous test to a self-test, because it is preferable from a testing perspective as well as a business perspective.
We interviewed Dr. Janneke Ouwerkerk and her team of experts. Janneke is Department Head Microbiology and manages R&D projects at NIZO. NIZO is a world leading company in development and application of innovation in the global food industry. They focus on testing and optimizing the most challenging probiotics for established companies and acting as incubator for entrepreneurial projects like ours. Here are the points the NIZO experts advised us on:
Firstly, the choice to use E. coli Nissle 1917 as a chassis to build our living diagnostic was confirmed to be a great choice. This bacterial strain is widely used in industry, and a wide range of genetic tools are available to modify it. Further, this strain shows anti-inflammatory activities, which could be beneficial in the colon of the user of our living diagnostic. They also suggested that if we would like to make our product more modular, we could find other potential chassis in the QPS-list of food safe bacteria. Further we spoke about the delivery and in our case, they deemed the use of an acid resistant capsule with pH-based release as the correct to the colon. The living diagnostic will be treated by freeze drying and placed in this capsule. This way the pills can be stored for an extensive period.
Janneke and her colleagues did not know how long E. coli Nissle 1917 is able to colonize the colon. Colonisation of a novel microbe in the colon is dependent on many factors. For instance, an unbalanced microbiome is generally easier to colonise. The NIZO experts also mentioned that our diagnostic would be more feasible as a short-lived self-test rather than a continuous test that colonizes the gut.
NIZO confirmed that probiotics engineered for a different purpose cannot be called probiotics anymore. To confirm the suitability of this term we should look at the American market where legislations are less strict. Additionally, we discussed what considerations we must make if the product will be launched on the market, these can be found in the entrepreneurial guide and implementation page.
- We shifted our focus fully on the detection of cancer and not on localizing and treating the cancer.
For 22 years, Dr. Paul Soons has been working on clinical development of new medicines at Janssen, which is part of Johnson and Johnson. Starting six years ago, he has identified interesting projects where Janssen could collaborate. Due to this, he is an expert on the demands that the pharmaceutical industry has on new innovations, like Colourectal. We spoke with Paul in an early stage of our project.
In an early design of our project, we considered including a diagnostic and localization system in our tool. Paul was of the opinion that including both was too extensive. He urged us to focus on creating an effective tool that is feasible and testable, and to focus on a single function. Therefore, he critically evaluated our project and determined that the localization system would be unnecessary. The current techniques to visualize the bacteria are not sufficient. Additionally, if our tool could be made more specific than current diagnostics, checking for false positives would not be needed. Furthermore, we had planned the possibility of including a therapeutic function, which Paul advised against. He said that society is reluctant to pay for a tool that treats diseases in a screening setting. The people that take part in the screening are not patients yet, which makes preventive treatment unnecessary and expensive.
Lastly, he mentioned that industry tries to avoid using GMOs, thus working around potential biosafety concerns. The legislations around GMOs are constraining. The chance of a product that needs biosafety measures reaching the market is thus meager. Therefore, Johnson & Johnson prefers to work with cell-free systems or specific compounds that are delivered at a specific location.
- We decided to create an inducer system pipeline where we can integrate the localization circuit if a suitable technique were developed.
Arjan works for OnePlanet, a company that focusses on bridging the gap between technical innovation and real-life systems like the human body and agriculture. Previously Arjan worked on cancer diagnostics. With this background he has a wide knowledge about the industry around cancer research and Medtech.
Sensitivity and specificity: It is important that we create a tool that is better than the current screening methods. The two biomarkers we use in our system are promising, and the localization system could further increase specificity. Therefore, Arjan is of the opinion that this system should not be discarded. Instead, the focus of our project should shift to the optimization of the induction. In this way, more effective circuits could be introduced later. Furthermore, the threshold systems that we developed could also finetune the detection of tumour formation. These systems are highly interesting for OnePlanet, because they are also working on them, and they are difficult to develop.
Arjan was intrigued by the AND-gate sensing system we developed. Using cells that live and function in a complex bio-matrix and are equipped with the required sensing tools is an attractive strategy and has many advantages compared to technology-based sensors which cannot work in natural environments.
- We referred to Inscripta to help us become fully aware of the bio-risks and get a check for all our biosafety systems.
Inscripta is a life science technology company that develops digital genome engineering solutions. Elizabeth Vitalis, a Biosecurity Specialist, showed us how to find bio-risks associated with our project. For example, by inserting genes into the EcN genome we could inadvertently add a function. Bio-error rather than bio-terror should be our primary focus, since it has been seen that EcN genome contains pathogenic-associated genes that alone do not confer pathogenicity unless the complete pathway is present. When inserting exogenous genes, the prudent approach is to check whether these complete a pathogenic pathway or not.
Common diagnostic tools are in vitro products. Hence, currently in Europe there are no regulations available for our living diagnostic. It cannot be considered as a probiotic, a therapeutic agent or an in vitro diagnostic. Therefore, we had to ask ourselves: what would the legislative and clinical trial processes look like for Colourectal? To solve this question, we spoke with scientific experts in the fields of medical GMOs and in vitro diagnostics, as well as representatives of regulatory governmental bodies.
- We aim to create a tool that can recognize polyps as well as early-stage colorectal cancer.
- We developed an app that analyses the colour of the participant’s stool. Want to find out more about the app? Go to Implementation
- We developed a mock leaflet with instructions on how to use our living diagnostic.
Iris works for the Dutch National Institute for Public Health and Environment (RIVM), where she is the manager of the Dutch screening programme for colorectal cancer. The screening programme consists of a faecal immunochemical test (FIT) and a follow-up colonoscopy if the FIT result comes back positive. The preparation for a colonoscopy consists of taking strong laxative medication and the procedure itself is invasive. Iris told us that a colonoscopy is an unpleasant experience for most people, but they will go through the procedure because they want to know if they have an abnormality. The screening programme in the Netherlands finds about 85% of the cancers, so there is still room for improvement. Therefore, Iris thinks a more sensitive test is needed. Furthermore, the screening programme is mainly focussed on cancers, while the detection of early-stage tumours, so called polyps, is also important. Therefore, she thinks the ability to detect polyps is a great advantage of our tool.
Additionally, communicating the test instructions is very important. Since it only takes place indirectly (via internet and leaflet), you need to explain everything very clearly (and in different languages). To simplify the test, she suggested to use an app where people can upload a picture to verify their stool colour.
- We decided to design the project with the EcN strain that does not possess the potentially toxic genes.
- We conducted a survey to assess the general public’s opinion on GMOs in health care.
RIVM is the Dutch National Institute for Public Health and Environment. They give advice and share their knowledge with the government, professionals and the general public. Moreover, RIVM coordinates the Dutch colorectal cancer screening programme.
We spoke with Cécile van der Vlugt and Wessel Teunisse from the Centre for Safety of Substances and Products. They find that our project’s aim is very clear: as people are suffering from the current screening programme (based on the FIT) because results are not clear due to false positives, new screening technologies are welcome.
During our meetings, they emphasised the importance of the concept “safe-by-design”, explaining that the kill switches we designed are a part of our tool, but we should also consider safety issues in other fields such as the design of the product, the laboratory, or the introduction of our living diagnostic in the market. The RIVM informed us that EcN possesses genes that are potentially harmful to humans. They advised us to knock these genes out to prevent health issues for the users.
Then, we addressed the regulations related to the incorporation of health-related GMOs in the market. We were told that it is possible to introduce them in the market if they are assessed with negligible risk for the human health and the environment. Yet, they also said acceptance of GMOs is unfortunately not high within the general population, although it could be different for a product related to medicine. The acceptance, however, will be higher if our product works well, is cost effective and is easier to use than the current method. Additionally, they suggested us to find answers to some questions related to public/governmental perception of GMOs and gave us some advice and steps to follow for the approval and commercialisation of an ingestible GMO diagnostic tool.
Finally, they encouraged us to make sure we provide patients with clear guidance on how to use Colourectal. This step-by-step guide would help people through the process and prevent them from feeling anxious.
- We learned that there is no legal framework for in vivo diagnostic tools, so Patrick advised us to talk with someone that is an expert in GMOs. Therefore, we spoke with Gorben Pijlman
Patrick Vrijlandt is a senior clinical assessor at the Medicines Evaluation Board, involved in the evaluation of medicines used as diagnostic tools, and in in vitro diagnostics being used to select patients for certain therapies. We spoke with him about the current regulations for in vitro diagnostics and possible improvements for our project.
Approval of in vitro diagnostic: Even though there is no current legal regulation for our tool, we learned about the authorization for in vitro diagnostics, which is a complicated legal procedure. It consists of submitting complete documentation that includes data on how the product is manufactured and how the supplier aims to guarantee the quality of the product delivered over time. Other information, such as sterility conditions and the pharmaceutical/diagnostic tool’s mode of operation needs to be specified. There is also a complete framework on what tests to perform in order to get an authorization. The results from animal testing and clinical trials, proving that the product is effective and safe must be supplied. He told us that, even though there might not be legislations for our living diagnostic, the principles should be similar. The focus should be on safety and cost-effectiveness, which are key factors to have approval upon.
- We only refer to our living diagnostic as a tool that needs to be ingested, preventing the relation to food and diet.
- We wanted to learn more about the general public’s opinion on GMOs, so we conducted a survey on this topic.
Dr. Pijlman is an associate professor in virology and a member of the Netherlands Commission on Genetic Modification (COGEM). COGEM is an independent advisory committee consisting of active researchers in the field of GMOs that advise the Dutch government, on request. During our discussion, he explained to us that there are two levels of safety assessments for the use of GMOs, called contained use (in the laboratory) and deliberate release (into the environment). They mainly evaluate potential risks associated with GMOs regarding human health and the environment, with humans meaning other people than the ‘treated patient’ and environment in the broadest sense.
The perception of food is quite connected to personal emotions, that is also why GMOs are not widely accepted for crops in Europe. When the GMO is used to diagnose cancer, people’s perception will probably change, making them more willing to participate in the screening process with our engineered living diagnostic.
Colorectal cancer profoundly impacts the lives of many people. We designed a non-invasive, early diagnostic tool that people can perform at home. Since the general public will be the end users of our tool, inclusion of societal stakeholders was important for our project. During our project we spoke to several colorectal cancer survivors, to people involved with the Dutch colorectal cancer screening programme and to the general public. Their feedback shaped our project. Below you can find summaries of six societal stakeholders, as well as an explanation of our survey and cookbook. The survey and cookbook were both created for the general public and were made while keeping the comments and recommendations of our stakeholders in mind.
- We designed an app and leaflet to make our living diagnostic more user friendly.
Ray Brouwer is an old colleague of one of our team members, Josia. The family of Ray’s father has a history with colorectal cancer. He had a colonoscopy at 23 years old. Fortunately, he had no cancer or polyps. His next follow-up will be in 15 years, but he can request an earlier check-up.
When we asked about the procedure, Ray told us that the colonoscopy procedure is not the worst part. However, the preparation is, since a lot of laxatives are needed and the person undergoing the colonoscopy cannot eat before undergoing the procedure. Ray told us he lost sleep because he was constantly on the toilet during the colonoscopy preparation. The main thing that worried him about the colonoscopy procedure was its outcome, so he felt relieved to know that no signs of cancer were found.
When talking about our project, Ray reacted positively. He was especially excited about the possibility of our tool to give a more immediate, at-home answer than the current screening method. Moreover, he did not mind that our bacteria are genetically modified, stating that once it is available then he assumes it is well tested and safe.
One thing he mentioned that we should look out for is the user friendliness of the test: the preparation should not be too complicated or uncomfortable.
- We wrote both a cookbook and several colorectal cancer awareness social media posts to raise awareness for colorectal cancer.
Lizette is a member of the board of Stichting Darmkanker (Colorectal cancer foundation), a Dutch patient organization for colorectal cancer. Stichting Darmkanker advocates for patients and offers advice from a patient perspective on the Dutch screening programme and scientific research. They advocate for lowering the age at which you can get screened for colorectal cancer from 55 to 50, since this is the European standard. Lizette is also chair of a patient advisory board in the Catharina hospital in Eindhoven, the Netherlands. Here she makes sure that the patient pathway and any clinical research is as little of a burden as possible on patients. The board also judges suggested improvements and gives advice to researchers based on a patients’ perspective.
Even though Lizette was eligible for the national screening programme of colorectal cancer, she did not participate. To her surprise, she was diagnosed with rectal cancer in 2019, for which she was treated at the hospital where she is now chair of the patient advisory board.
Lizette was positive when we told her about our project, saying that swallowing a pill is always better than having to take your own stool sample at home. She also stressed that people need to be made aware in general to check their stool for irregularities once in a while, even if there is no possibility that it turns blue.
- We designed an app to help users assess if the colour of their stool changed due to a positive test or not.
Alex is a volunteer for Stichting Darmkanker, where they assess applications for grants for scientific research from a patient perspective. In their opinion, the most difficult thing about the current colorectal cancer screening programme is the waiting. When they heard about our project, they were worried about the fact that people have to assess the colour of their faeces themselves; the responsibility is with them instead of with a medical professional.
When talking about the way in which the self-test would be used, Alex was of the opinion that it should not be sold generally in shops. This would not be fair to people that cannot afford such a test. Instead, they suggested imbedding our living diagnostic in the current colorectal screening programme. So instead of receiving a FIT, people would receive our test. Apart from this, Alex had another reason for wanting to embed the test into the screening programme. They were afraid that allowing people to do the test themselves, whenever they want, would be dangerous for the (mental) health of that person. Alex believes that when someone is concerned about their health, they should go to a general practitioner instead of doing a self-test.
We also discussed the legal aspect of our living diagnostic. There are currently no rules or regulations for genetically modified in vivo diagnostics. We shared our worries on this, but Alex did not think this was too much of a problem at the current stage of our project. Of course, we would need legal approval before our living diagnostic could be used, but they said that it can become something wonderful then.
- We incorporate questions about people taking a genetically modified bacteria into our survey, which Petra also reviewed for us.
- We thought of every practical aspect surrounding our tool. This includes what kind of pill you have to take and each step a potential user would have to go through in detail.
Petra is a high school math teacher and had colorectal cancer 3 years ago. She told us about her first experience with the colorectal screening programme, which unfortunately did not manage to diagnose her cancer. She taught us that apart from the false positives, the test can also cause false negatives. Half a year after her negative test, Petra decided to go to the doctor because her symptoms grew worse. It turned out she had colorectal cancer all along.
Petra volunteers for Stichting Darmkanker, where she is part of both the advocacy and patient participation group. The former group represents patients in the evaluation of the Dutch screening programme. According to Petra, the RIVM takes all feedback seriously and tries to continuously improve the screening programme.
Even though Petra was positive about the screening programme, she thought the FIT test could be improved on from a patient perspective. With the FIT, the user has to sample their own stool, which she believes is not user friendly. When we told her about our project, Petra immediately thought about how easy it would be for a potential user. She agreed that having to take a pill is perfectly fine and not invasive to people. She did tell us to think about the circumstances the living diagnostic would have to be taken; do people have to fast or can they not drink alcohol or not eat certain foods? Petra also suggested us to do some kind of public research to get people’s opinion on our living diagnostic.
We were wondering how the general public would feel about our living diagnostic and were curious to know what their opinion would be and what they would improve if given the chance, so we developed a survey in three different languages (English, Dutch and Spanish). Through this survey, potential future users of Colourectal from different age groups and different nationalities could get to know our project and share their insights and concerns. 130 people from 8 different countries responded.
The survey was developed by our team, but we understand colorectal cancer is a delicate topic, and it needed to be carefully phrased. For that reason, we asked our stakeholder Petra Kellerhuis (colorectal cancer survivor and volunteer for Stichting Darmkanker) for feedback on the content, and our supervisors Julia Rijssenbeek and Dr. Zoë Robaey to make sure it was appropriate, understandable and ethical. We made the survey completely anonymous so that answers could not be traced back to the respondents, we made sure to always include a “prefer not to say ” answer, and we included a consent clause at the end of the survey.
Regarding the content of the survey, we included some personal questions in the beginning about age, gender and nationality, and then we asked the participants about their experience with colorectal cancer. A brief explanation of the current screening method in the Netherlands was given, and we asked about their experience with the FIT and colonoscopies. After that, we summarised the way Colourectal works in simple words, and asked some questions about their opinion on different aspects of it. Finally, we explained that in order to achieve such a living diagnostic, genetic modifications need to be made in the bacterium, and asked people about their perspective on GMOs.
We obtained valuable information from the survey, which we took into account during our project.
When we asked what people thought about our tool being genetically modified, the responses varied. Some respondents felt concerned, while others had faith that proper testing of the procedure would make it safe. One of the respondents, a woman from Spain between the ages of 55 and 75, had a combination of these responses: “Me da reparo, pero pienso que cuando esté en el mercado será porque estará muy probado. Confío en la Ciencia” (“I feel insecure about it, but I believe it being in the market means it has been tested enough”).
Below, the results of several survey questions are highlighted in pie charts. After explaining our project, we asked whether people would be willing to use it to test themselves for colorectal cancer. The results were positive; 82% percent of the 130 participants answered that they would.
Before developing the app, we asked the respondents’ opinion on it. Again, more than half of the participants said an app to verify the colour change of the faeces would make them feel safer. To see all the questions, we asked in our survey, have a look at the pdf below!
- We developed a cookbook with healthy and affordable recipes to reach every socioeconomic class. We looked for easy recipes that can be made in a short time with easy, available ingredients.
Daniëlle Grashuis has worked for the University Fund Wageningen for 10 years. She has family and a friend belonging to the risk group for colorectal cancer. Unfortunately, her best friend cannot be cured as the cancer was detected in a late stage. He is 54, so was not invited for the screening programme yet. He assigned his symptoms to backpain and haemorrhoids, because he never thought of colorectal cancer. When he went to the doctor the cancer was already metastasized. Her friend’s disease made Daniëlle look differently at colorectal cancer as she had never realised how late too late was. She said our method could save a lot of lives by screening cancer in an early stage. Daniëlle emphasized that a healthy lifestyle is important, not only for cancer prevention but in general.
- We changed the title of cookbook to not include the word ‘cancer’.
- We made our cookbook and outreach accessible to as many people as possible. Additionally, we kept in mind mistakes, that are often made in educational material.
Beatrijs Haverkamp is a researcher of philosophy at Wageningen University & Research, specialised in bioethics, political theory, health and society. We told her the idea of our cookbook and discussed the influence of social-economic inequalities on food and health.
Beatrijs explained that the life expectancy of lower socio-economic groups is 6-7 years lower than the average life expectancy. Factors like bad living circumstances (for instance, a lot of moisture), smoking and stress contribute to this. Another important factor is diet. Unhealthy foods (rich in fat and sugar) are relatively cheaper than healthy food when looking at the price per kilocalorie. Additionally, in some neighbourhoods there are less opportunities to buy healthy food, making it easier to go for an unhealthy option [1].
During her research Beatrijs found that education on healthy lifestyle can be one important factor to decrease health inequalities, if it is accessible and relatable for people from many different backgrounds. In order to make accessible and relatable content, she referred us to a fact sheet made by Pharos about common mistakes in educational material. Text should for instance be concise and easy to understand, and illustrations should not contain unnecessary distracting details.
Beatrijs thought that including colorectal cancer in the title of our cookbook could create the illusion that with our recipes people can definitely prevent colorectal cancer. Besides this, she was enthusiastic about our cookbook collaboration with BalanceBuddy since children are their target audience. On the long term, it is good to start educating children early about a healthy lifestyle. Eventually, children might inspire their parents to change their eating habits together.
While diagnosis and treatment of colorectal cancer are very important, preventing it entirely would be best. There are several risk factors related to colorectal cancer. Some of them, like family history or having other colon-related diseases, cannot be changed. Other factors that increase the likelihood to develop colorectal cancer, on the other hand, can be avoided. Factors that increase the likelihood of colorectal cancer include following a poor diet, smoking and drinking. To decrease the likelihood of developing cancer, a healthy diet should be followed with plenty of exercise.
It has been shown that eating a fibre-rich diet that is low in red- and processed meats and not drinking alcohol are all beneficial to the gut [2]. However, several stakeholders, like Daniëlle Grashuis and dr. Beatrijs Haverkamp, told us that it is often difficult for people to follow a healthy, affordable diet. This is why we decided to write a cookbook full of recipes that contain ingredients that could lower the risk of getting colorectal cancer.
Not only are the recipes healthy, but they are also affordable and delicious. In this way, we hope to make it easier for people to follow a healthy diet.
We wrote the cookbook in collaboration with BalanceBuddy, an association that focusses on kids struggling with weight issues, working together to create a healthy diet for them. The cookbook contains an introduction by cancer and nutrition expert Dr. Dieuwertje Kok, who also proofread our recipes. We made the cookbook in both Dutch and English and distributed the online version for free so as many people as possible can benefit from it. Check out the pdf of the cookbook below!
We also organised a book launch that was accessible to everyone who wanted to join. Here, Dr. Dieuwertje Kok gave a lecture on nutrition and cancer, and BalanceBuddy and we explained our goals and presented the cookbook. We provided the audience with snacks from the cookbook and organised a discussion hour after the talks. Here, the audience could give their input and discuss any questions they had.
After integrating the feedback we obtained from stakeholders into our project, we organised a stakeholder meeting in September, with representatives of our different consortia. Our aim was to explain our project to them again, emphasising the points that we had modified in response to their advice, and then to offer them two points of discussion on which we still did not have a clear answer. Five of our stakeholders joined the meeting: Iris Seriese (Government), Markus Gwiggner and Monique van Leerdam (Academia), with Alex (name changed due to privacy reasons) and Petra Kellerhuis (Society). Unfortunately, none of the stakeholders from the Business consortium was able to participate. Our Human Practices supervisor and expert in ethics of technology, Dr. Zoë Robaey, assumed the role of mediator during the round table discussions.
The way we structured the discussion was as follows: we presented the first point of discussion, explained it in detail, asked the stakeholders individually about their opinion, and then had a round table discussion. Next, we proceeded in the same way with the second statement. At the end, as a wrap up, we spent some minutes summarising the conclusions we had drawn and had a short general discussion about our project.
Continuous testing versus self-test.
Statement: In our survey we asked: “Would you prefer the diagnostic tool to be in a self-test format that you can take whenever you want and would disappear from your body after a short time (hence, not continuously detecting possible cancer cells) or would you like it to stay in your colon for a longer period of time?” and our respondents are divided on this.
We then explained that a continuous test would stay in the body and allow continuous detection of cancer. However, the effects this might have on the colon or microbiome of the gut are yet unknown, and it might create more anxiety in the user because their stool could unexpectedly turn blue at any moment. On the other hand, a self-test would only stay in the body for a short period of time and miss colorectal cancer that could develop after the test had been taken. A self-test would thus have to be taken multiple times.
The most important conclusions were:
- Colourectal should be in a self-test format as opposed to a continuous test.
- Our living diagnostic should be part of an organized screening programme, and not bought by the users themselves.
All our stakeholders unanimously agreed that the self-test format was a better option than the continuous testing setting. Iris thinks that if the two formats work equally well, self-testing is a better option because people would be more alert to the presence of a positive result than if they had the living diagnostic always detecting cancer markers. Markus added that being aware that the result could be positive every time you go to the toilet would make people very anxious, so the ideal setting would be a self-test that stayed in the colon for around a week. Petra explained that colorectal cancer grows slowly, so self-testing every approximately half a year would be a good frequency.
Monique introduced the idea of including Colourectal self-testing in a screening programme in order to prevent it from being used in a chaotic and disorganised way. This would also allow medical bodies to collect population-based data to evaluate sensitivity and specificity of the test. Alex and Markus raised the issue of affordability and added that another reason for Colourectal to be part of the screening programme would be that everyone would have access to it.
Finally, a discussion arose on how often the self-test should be carried out. Monique thinks that once a year or once every two years would be okay, while Iris believes once every two years should be enough.
Want to see what each stakeholder said? Hover over or click on the portraits below!
GMO rules and regulations.
Statement: Genetically engineered organisms are not legally allowed to be used as probiotics, while therapeutics can be engineered if they comply with the necessary safety measures. However, our product is going to be used as a diagnostic. There are currently no regulations on genetically modified diagnostic tools, as they are generally not ingested. How would you recommend us to frame our product?
We further explained then that we were considering framing our product as a probiotic, since EcN is commercialised as such. But then, we learned that a bacterium is not considered probiotic anymore when it is genetically engineered. Additionally, we were told by our “Government” stakeholders that GMO therapeutics can potentially be approved and commercialised if they prove to be safe for humans and the environment. However, we could not find any regulations related to the use of GMOs in diagnostic settings. Probably this is because there is no precedent for diagnostic methods that need to be ingested to work, since they usually consist of tests that take place outside the human body.
The most important conclusions were:
- We should frame it as what it is: a living diagnostic tool.
- We need to make sure it is safe for human use.
All our stakeholders emphasised the huge importance of making sure that our product is safe and that we know exactly how it works. Once we have confirmed these steps, we can consider about regulations. The stakeholders also all agreed that we should go straight ahead and call our product what it is: a living diagnostic.
Iris told us that in order to make Colourectal part of a national screening programme, it has to be proven safe by performing all the necessary tests. Markus added that apart from making sure it is safe, we need to know whether the toolworks as we expected. Petra also pointed out the importance of sticking to the rules, especially after the COVID-19 pandemic, because people are very suspicious of the government, and Alex said we need to be very clear about scientific issues to not leave any detail unexplained.
Monique introduced us to an example of a diagnostic tool that consists of a capsule that takes a video of the guts, so it also needs to be swallowed. She said that they struggled to surpass all the safety barriers, but in the end, they managed to go one step further and published a study about it. Markus also mentioned a trial they are performing in IBD patients where they take a test to check for inflammation in the bowels in their own home, which they achieved with a government grant.
After this, we had a short general discussion on our project. The stakeholders congratulated us on our project and encouraged us to continue working on it, since if it becomes a reality, it could be of great help to society. Markus even suggested to eventually make our project bigger through changing the biomarkers our living diagnostic recognises and use it for other conditions, such as IBD.
