Team:TU Eindhoven/Public Engagement

Education &
Engagement

• Outreach


• Patients


• Public opinion

Outreach

Next to developing our detection method for bacterial infections, we investigated the world of antimicrobial resistance (AMR) and the possible use of bacteriophages to solve this growing problem. We also attended some conferences, contests and meetups where we discussed our project and spoke about the importance of tackling the problem of AMR to spread awareness. We have been in contact with a few media platforms, who have published articles about our project and the problem of AMR, which was another opportunity for us to spread awareness.

One important group that we talked with about the struggles that come with antimicrobial resistance is a group of patients who have dealt with resistant bacteria and who fought against these infections using bacteriophages.

We were also curious about the public opinion on the current use of antibiotics and how the problem of antimicrobial resistance could be tackled with bacteriophages. We therefore conducted a small survey.

Phage therapy

We also did our own research into the use of bacteriophages for therapy. From some of our stakeholders we understood that research is being done concerning the use of phage therapy, but that it is difficult to carry out this research to get the therapy approved for general use. To find out what causes these difficulties we looked into information from our own government and the status of bacteriophages at the EMA (European Medicines Agency) and FDA (Food and Drug Association, USA).

From our own government we got our information from letters written by the minister of Medical care in response to parliamentary questions. Most of their information about the current status of research about phage therapy came from the Institute for Public Health and the Environment (RIVM). Right now, there is not enough research which proves that phages work as therapy in humans. However, there is also no research that disproves the functionality of phages. The lack of knowledge about the efficacy and safety of phage therapy causes the use of phages to be still experimental and not broadly applied in practice. The research that is needed can be done within or outside of the Netherlands. We believed that maybe the legislation for new medicine was too strict regarding phages. But it turns out that the rules are the same for each type of medicine, just more research is necessary.

One of the reasons for the lack of research might be the availability of money for research. Since phages are natural organisms, it is not possible to patent the phages themselves, which makes it less attractive for companies to invest money in research concerning phages. However, money is provided by organizations such as the Netherlands Antibiotics Development Platform (NADP), which has provided €20.000 for research into bacteriophages. Next to that, there are European or international funds dedicated to looking for alternatives to the current antibiotics. While these funds are not specifically meant for research into phage therapy, they can be another source of money for this research. The pharmaceutical industry also sees antimicrobial resistance as a big problem for which each possible solution and innovation should be stimulated.

February 2019 - Meet the student teams

Twice a year, the student teams of the TU/e organize a meet the student team event. During this event, all the student teams of the TU/e show the impact of joining them.

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February 2019 - Meet the student teams

Twice a year, the student teams of the TU/e organize a meet the student team event. During this event, all the student teams of the TU/e show the impact of joining them. The iGEM TU Eindhoven team also uses these moments to recruit new students for their next team. 2 team members of the 2019 team were recruited due to the meet the student team event.

Figure 1: Tim van der Hek, Roy van Mierlo, Pim Joostens and Sander Keij at the meet the student team event.

March to June, 2019 - TU/e Contest

The TU/e Contest provided an excellent opportunity to validate and get feedback on our project from a large network of stakeholders, resulting in exposure and sponsoring leads.

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March to June, 2019 - TU/e Contest

The TU/e Contest is a campus-wide innovation competition in which students and student teams can participate when they are eager to get their project to the next level. A large network of connected stakeholders helps students in their business development by giving content-specific feedback or business-related feedback on the overall process. Within the contest, several workshops and pitch-opportunities were organized with the goal to help students set up their online business profile.

Quickly after our first pitch, our project received partner interests from two sides. The Health Tech Yard could assist projects like ours by sponsoring equipment and helping us profile ourselves to move quicker through the medical hierarchy. Medtronic was even interested in partnering up if the project would continue after 2109, but could assist us in the field of medical prototyping nevertheless. Both leads are a valuable result of our participation and are currently further investigated.

All participants must fill in an extensive business profile to enable stakeholders to give more specific feedback. As our research isn’t commercial in its core, answering questions from unexpected angles and receiving business-oriented feedback gave insight how to profile our project to make it more interesting for different business perspectives.

As we progressed within the competition, our team received more careful consideration through several speed-dating events with corporate executives and professional workshops (such as finance, project management and business modelling). Integrating all this feedback and knowledge has helped us reach the finals, in which we were able to collect the most votes from the audience. In retrospect, the TU/e Contest was a valuable medium to gain more public and corporate exposure.

Most important conclusions:

• The problem is clear, but there is skepticism about us being able to disrupt the lucrative antibiotic market.
• There is little fear for the risks of implementing phage-based diagnostics within the audience.
• We should make the end-goal more realistic by splitting the whole process in smaller steps.

Follow-up:

• We are pursuing sponsor leads, such as the Health Tech Yard through Steven van Huiden and prototyping through Medtronic.
• We can explore getting IP rights for our project, as this facilitates corporate partnering after the competition.

June 13, 2019 - iGEM Europe meetup The Hague

We went to the first day of the iGEM Europe Meetup in The Hague, hosted by the Rathenau Institute and RIVM.

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June 13, 2019 - iGEM Europe meetup The Hague

We went to the first day of the iGEM Europe Meetup in The Hague, hosted by the Rathenau Institute and RIVM, where we acquired useful knowledge about making our project safe-by-design and how to best perform our Human Practices. We also got the opportunity to meet other iGEM teams to share our projects and ideas.

Megan Palmer, Vice President of iGEM Human Practices, gave a presentation about how to best perform the Human Practices part of your project. From this presentation we could conclude that we are already well on our way with our own Human Practices. She strongly advised not to do a public survey, which we were discussing to do before. It might thus be better to make the survey more specific and for a more specific audience. Next to that we should think of other, more original, methods to approach human practices.

Will Wright, European Ambassador, gave a presentation about all the possibilities of continuing with your project after the iGEM competition. He has already helped 17 projects to start their own company and has also taught teams how to fundraise and to make an impact after the competition. He suggested to strongly focus on the problem you are trying to solve and engage with people on solving it, instead of focusing on the technological solution behind it. A tip to get sponsors was to tell companies that they are not just sponsoring the project itself, but are also investing in future talents and better researchers.

There was also a panel conversation with former iGEM team members, some of whom had already gone through the process of creating a start-up. They had some interesting take home messages including that you should have reflection moments in your team, and make sure you know everyone’s goals within the team and what you want to learn from iGEM. The team should talk about everyone’s capabilities, be aware of this and consider each other’s strengths and weaknesses. When integrating Human Practices, you should design something that stakeholders think is really valuable. The important thing is not coming up with ideas but letting all the stakeholders shape your project. Furthermore, storytelling is one of the most important aspects of creating awareness about your problem. The last message was to have a dare factor when asking for funding. Students are more likely to receive funding because of their innocence and enthusiasm, but you need to dare to ask for it.

In the afternoon there were a few workshops, which were mostly just fun, but not very profitable for our project. In between these workshops we got into contact with some of the other teams to discuss our projects. We talked to team Wageningen, who is also working with phages, and team Leiden who is willing to help us set up our crowdfunding page.

Most important conclusions:

• We are well on our way concerning Human Practices.

Follow-up:

• Contact Team Leiden for help with our crowdfunding.
• Possible collaboration with Team Wageningen.

June 13, 2019 - Med. Lt. Col. Patrick Soentjens, QAMH Brussels

We went to Brussels and had a conversation with doctor Patrick Soentjens from the Queen Astrid Military Hospital (QAMH). We talked about the history of the QAMH phage lab and the application of phage therapy coordinated by the hospital. We got a lot of interesting insights on how phage therapy is applied in Brussels. Doctor Soentjens also discussed some interesting cases of successful phage therapy coordinated by the QAMH.

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June 13, 2019 - Med. Lt. Col. Patrick Soentjens, QAMH Brussels

We went to Brussels and had a conversation with doctor Patrick Soentjens from the Queen Astrid Military Hospital (QAMH). We talked about the history of the QAMH phage lab and the application of phage therapy in the hospital. We got a lot of interesting insights about how phage therapy is applied in Brussels.

15 years ago a doctor came to Dr. Jean-Paul Pirnay (colleague of doctor Soentjens at QAMH) and wondered if there was a way to treat multi-resistant infections they commonly encountered in the military hospital. A typical military saying is: “one should know ones enemies”, and the same holds regarding the multi-resistant bacteria, especially Pseudomonas Aeruginosa O12, which were often seen in the burn wound center of the QAMH back then. Knowing the enemy is one thing, but how to tackle it? Jean-Paul Pirnay and his team looked into using bacteriophages as novel weaponry and came in contact with the Eliava institute of Bacteriophages, Microbiology and Virology in Tbilisi, Georgia.

The collaboration with the Eliava institute was fruitful from the start, they already had decades of experience with phage therapy. Jean-Paul Pirnay recognized the great amount of knowledge in Georgia on phages (in contrast to groups in France and The Netherlands, who tried to start all by themselves according to doctor Soentjens) and brought Dr. Maya Merabishvili from Georgia to his team in Brussels.

The Belgian Military pays for all the research and the small scale therapy performed in Brussels at the moment, hence no expenses are incurred by patients that can be treated with phages from the QAMH. The legal framework in Belgium allowing such therapeutic application of magistral preparations of bacteriophages is unique in the world. It allows only for case-by-case evaluations, large clinical trial studies are not allowed. Yet, we know from experience that phage therapy requires personalized application anyway. Phages mutate and evolve for instance, sometimes requiring multiple different sets of phages for certain infections that take a long time to eradicate.

One example is a well-known case of a professor from UC San Diego School of Medicine, Tom Patterson, who got infected by multi-resistant Acinetobacter baumannii during a vacation in Egypt. He could not be treated with the standard arsenal of antibiotics as the bacteria were resistant to almost all drugs. A combination of last resort drugs seemed to help, but a complication occurred resulting in his situation becoming acutely life-threatening and no more antibiotics were left to try. His wife, an infectious disease epidemiologist herself, looked for help in the phage research community. Unfortunately the QAMH couldn’t help, no suitable phage was available in Brussels. But the US Navy has a phage lab (NMRC) of their own and screened the sewage, which eventually led to a treatment with phages. However, resistance occurred, which was followed by the addition of new phages. This example shows that phages should not be regarded as a replacement for antibiotics, but rather as a complementary approach. Doctor Soentjens stresses that phages work synergistically with antibiotics and therefore complement each other, with phages being especially interesting in cases of multi-resistant bacteria or for instance for eliminating the last hiding bacteria from catheters and osteo-synthetic materials.

Since 2007 the QAMH has the capacity to produce therapeutic phages. Currently Jean-Paul Pirnay and his team have three different phages that are ready for use in infection treatment, of which one comes from the Eliava institute and one from Russia. Later on also Acinetobacter baumannii phages were retrieved from the sewage by Jean-Paul and his team themselves. In Georgia the phages used in therapeutic setting are continuously evolving as they are simply allowed to do so, cultivating them from new (evolved) bacteria every time a new batch of phages is prepared. This is good, the phages are allowed to adapt themselves to continuously evolving bacteria. However, such a medicine is difficult to regulate of course. Hence, in the QAMH previously, patients were treated with a fixed phage cocktail. This also made production cheaper, only requiring a single standardized workflow and the same controls every time (which also were improving over time). The new model, however, is individualized, which is convenient in the case of phage therapy.

There are multiple phage labs in the world, but there is still much to gain regarding cooperation between them. Also, most don’t have the capacity to produce phages for clinical application, which the QAMH lab does have. Phages from other labs, can in principle be produced for clinical application here in Brussels and the magistral preparation can be made in the pharmacy.

Doctor Soentjens is coordinator of the medical team in the QAMH that coordinates phage therapy. They are not really a treatment centre and can’t handle patients en masse, so they have to narrow down the eligible patients list very selectively. Patients can e-mail the centre and have to include all medical information in their application and answer specific questionnaires. The centre performs patient eligibility testing to select those patients that can be treated. If eligible, informed consent is required and contact with the local hospital is made. Then the magistral preparation is made either at QAMH or at the local hospital and the patient is treated. Evaluation/follow-up is performed by the patients doctor from the local hospital in close contact with the QAMH and sometimes additional treatment is performed.

Unfortunately, the QAMH still has only a few phage species ready for therapy. Jean-Paul is currently working on E. coli and Klebsiella phages, but also more Pseudomonas and Staphylococcus Aureus phages would be very welcome for example. Meanwhile, many individual projects have been performed successfully with different phages already, often in collaboration with the Eliava institute (Georgia). So work is ongoing!

Since around 2008, about 40 patients have been treated at QAMH + about 8 in external centres. Doctor Soentjens does very rarely see any side effects of the phage therapy. Some interesting cases are described on the patient interviews wiki page.

Interestingly, to start phage therapy one should know what phage to use and for that a culture of the bacteria collected from the patient has to be grown, followed by generation of a phagogram. Both take about 2 days, meaning it now takes about 4 days before doctors know what phage to use. The detection method we develop could thus mean a significant reduction in required time if used in this regard. Dr. Pirnay is also developing a method to considerably shorten this time.

Most important conclusions:

• Phage therapy should not be portrayed as an alternative, but rather as a complement to antibiotics.
• Phage therapy requires an individualized treatment, which thanks to the recent magistral preparation framework is made legally possible in Belgium.
• The QAMH has treated over 40 patients successfully since 2008.

June 14, 2019 - Phage symposium, QAMH

Friday 14-07-2019 we were invited by Jean-Paul Pirnay to join the bacteriophages symposium organised by the Queen Astrid Military Hospital in Brussel. At this symposium 6 speakers talked about the biology, clinical use, and their experience with phages and phage therapy.

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June 14, 2019 - Phage symposium, QAMH

We were invited by Jean-Paul Pirnay to join the bacteriophages symposium organised by the Queen Astrid Military Hospital in Brussel. At this symposium 6 speakers talked about the biology, clinical use, and their experience with phages and phage therapy.

• Dr Pieter-Jan Ceyssens: about how to obtain phages an use them in therapy.
• Prof Mario Vaneenchoutte from UZ Gent: about phage biology.
• AJM Peggy de Leenheer from QAMH, Brussels: about the processes in clinical phage therapy.
• Prof Willem-Jan Metsemakers, Traumatology department of the university hospitals Leuven: about the Practical experience with phages therapy for osteomyelitis.
• Prof Dimitri van der Linden, Pediatrie, St-Luc, Brussels: about Long-term IV use of phage therapy in a bacteremic infant.
• Sarah Djebara, QAMH, Brussles: About the Belgium experience.

At the end we had a short talk with Prof Mario Vaneenchoutte about our project, and specifically about the idea whether he thought if there was free DNA available in the bacteria that we could measure with our system. The answer he gave was that he did not know it for sure. He thought that most, or almost all, DNA was packed into new phages and that it would be necessary to imply a heating step. He also provided us with his slides about the biology of the bacteriophage.

It was an interesting symposium that gave us new insight in the possibilities of phage therapy.

Quote of the day: Everybody needs to be on the same phages!

Most important conclusions:

• A lot is possible with phage therapy, but only as last resource after antibiotics.
• We probably need to incorporate a heating step in our method.

Figure 2: A presentation by Prof Mario Vaneenchoutte and a discussion at the phage symposium at QAMH.

July 17, 2019 - Cor Litsenburg, FMT gezondheidszorg

We met with Cor van Litsenburg of FMT gezondheidszorg regarding a collaboration. FMT Gezondheidszorg is a Dutch knowledge platform for technology and housing in healthcare.

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July 17, 2019 - Cor Litsenburg, FMT gezondheidszorg

Two members of our team went to a meeting with Cor van Litsenburg regarding a collaboration between FMT gezondheidszorg and our iGEM team. FMT Gezondheidszorg is a Dutch knowledge platform for technology and housing in healthcare. The goal of this meeting was to determine what both parties could mean to each other.

Cor had already posted an article online to see if our subject would be interesting to the public. If it has a significant amount of views, he wanted to post more articles and even share our crowdfunding page. He offered to help us contact companies for sponsoring. This is very beneficial for us, as he has a lot of connections and influence. Cor also suggested he would like to organize a symposium about antibiotic resistance and that he would be happy if we would give a presentation about phages and our project. Chances are that the symposium will be held after the competition, but this is not a problem for us.

Cor was very enthusiastic about our collaboration and we will remain in contact with FMT gezondheidszorg.

Most important conclusions:

• FMT wants to share our crowdfunding page.
• FMT will post more articles regarding our project.
• FMT wants to organize a symposium about antibiotic resistance.
• Cor can bring us in contact more specific companies.

Follow-up:

• We keep Cor updated about our progress and remain in contact to organize the symposium.

July 23, 2019 - Cécile van der Vlugt, RIVM

On Tuesday July 23, 2019 we had a phone call with Cécile van der Vlugt from RIVM. During this phone call we asked her about the use of phage therapy and why we are not able to use this therapy in the Netherlands. Cécile van der Vlugt was really helpful and gave us a good insight in current developments of phage therapy in The Netherlands.

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July 23, 2019 - Cécile van der Vlugt, RIVM

On Tuesday July 23, 2019 we had a phone call with Cécile van der Vlugt from RIVM. Cécile is a GMO risk assessor and a member of SSC iGEM. She also helped in writing the RIVM report about bacteriophages and even visited the Eliava Institute in Georgia. During this phone call we asked her about the use of phage therapy and why we are not able to use this therapy in the Netherlands. Cécile van der Vlugt was really helpful and gave us a good insight in current developments of phage therapy in The Netherlands.

At the start of the conversation she mentioned that it is not an easy task to start the use of phage therapy in the Netherlands. This because too little is known about the effects of phage therapy, and more research is needed to study these effects. Also, a lot of doctors and clinicians may not know or do not trust the use of phage therapy. And more importantly, phage therapy is not available in the Netherlands. This could be the reason that patients who cannot be cured with antibiotics, are still not being notified about the fact that phage therapy could be a solution. Therefore, it is important that more research is done, because e.g. phage therapy may be a good alternative when you are dealing with antimicrobial resistance (AMR). Cécile advised us to have contact with the College ter Beoordeling van Geneesmiddelen (CBG) about phage therapy, as they approve the use of new medicines or not.

She has had a positive experience when visiting the Eliava Institute. It is a small institute where they can treat several patients at the same time. When there are more complex infections, they still send their patients to the hospital. Because of the positive stories of cured patients, the doctors at the Eliava Institute see no risk for infected patients to undergo phage therapy at their Institute. However, better documentation is needed before the positive results from the institute can be used in the Netherlands.

Cécile also had heard of the Queen Astrid Military Hospital in Brussel, where we have contact with Dr. Jean-Paul Pirnay. We heard that they have a special law, of magistral preparations of phages, so that they can give phage cocktails to specific patients to cure them, and asked whether it is possible to use this law in the Netherlands. This seems possible. However, before phages can be used for therapy several aspects have to be taken into account. For example, the preparation of phages needs to be well documented before they can be used. Also, it first needs to be approved by the European Medicines Agency (EMA). In 2004, Poland entered the EU. As they already used phage therapy, it was still approved to apply this therapy.

At the end we asked Cécile whether our detection method could help in the approval of using phage therapy in the Netherlands. She thinks that we are designing a promising detection method and is positive about the fact that you get a double confirmation about which bacteria is causing the infection and what phage you can use to threat the infection with. She also mentioned that the characterization of bacteria used to be done with the help of phages in the past, and advises to contact a (somewhat older) microbiologist to ask more about this, for example the Westerdijk Fungal Biodiversity Institute. She also mentioned that we are not using a GMO in our device, so from a legal perspective it is a great benefit of our diagnostic system.

Most important conclusions:

• RIVM is really helpful in providing information.
• A lot more research is needed before phage therapy can be applied in the Netherlands.
• Cécile thinks that our detection method is promising for the use of phage therapy.

Follow-up:

• Find contact with someone who can tell us more about the approval of phage therapy.
• Find someone who knows more about the old way of characterizing bacteria with phages.

July 30, 2019 - Prof.dr. Marc Bonten, UMCU

We had a phone call with Marc Bonten. During this call we asked him his opinion about phages, phage therapy and our project. We also asked what would be necessary to allow phage therapy and phage therapy research.

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July 30, 2019 - Prof.dr. Marc Bonten, UMCU

We had a phone call with Marc Bonten, who is a Professor in Medical Microbiology at UMC Utrecht. As he researches Antimicrobial Resistance, he is also familiar with bacteriophages and phage therapy. During this call we asked him his opinion about phages and phage therapy, his opinion about our project and what would be necessary to allow phage therapy and phage therapy research.

Marc thought our project could be beneficial. In the Netherlands (and other countries) it is a problem to conduct scientific research with humans and phages, but these problems do not exist for laboratory-based studies (not involving human subjects). Our project would be used as diagnostic point of care system, and not as treatment, so it could be applied in the Netherlands. In healthcare there is a huge difference between diagnostics and therapy, it is easier to test diagnostics. According to Marc, working with phage therapy will be possible, but it will still take some time.

According to Marc, the same rules for scientific research in humans with phages apply in America. What one would need for a medicine, is that they are produced according to Good Manufacturing Procedures (GMP). This is difficult with phages as they are made individually for patients. In America they want to make a mixture of several phages, so that they are not produced for individual patients. In this way, they can be produced according to GMP principles, allowing research with humans. When the research would be approved there, it would also be possible to do it here.

Marc is still skeptical whether phage therapy would work or not. He bases his opinion on facts and research, which are not sufficiently convincing for phage therapy. Studies that were done had disappointing results. Based on opinions and experiences from other people, one cannot conclude if the phages actually work in a patient. Marc also thinks that the use of antibiotics could still be optimized. That people need to get more specific antibiotics regarding their infection. There are cases where phage therapy worked (these were case studies), but this is not documented scientifically, so there is no actual proof that it will also work in other patients.

Marc also organized a phage symposium with the TU Delft and OneHealth, but he was disappointed with the conclusions of that day. There was no actual data about the effectivity of phages with humans. People there were also not really convinced phages would be a new solution. There will be more studies concerning phage therapy, but these will be executed very slowly.

Most important conclusions:

• Our project could be used in the Netherlands as it is a diagnostic method.
• A mixture of several phages could make human research possible (GMP approved).
• Use of antibiotics could still be optimized.

August 20, 2019 - Introduction week TU/e

During the introduction week for new students on 20-08-2019, we got the opportunity to present our student team at the “green strip market”.

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August 20, 2019 - Introduction week TU/e

During the introduction week for new students on 20-08-2019, we got the opportunity to present our student team at the “green strip market”. Together with student team T.E.S.T., the TU/e team that participates in the SensUs competition, we came up with a guessing game to attract students during the market. In a large flask we added around 500 1.5 ml tubes. The student who guessed the right amount of tubes, or was close, won an anti-hangover package! Next to that we explained to the students what our competition is about and asked them whether they were interested in joining in a later phase of their study. We had a lot of interesting talks and responses from the new students.

Figure 3: Rody Mens from team T.E.S.T. and Yvonne van Mil from iGEM TU Eindhoven.

September 4, 2019 - Article Cursor

On September 4, 2019 we had an interview with Cursor. Cursor is the independent news site of, about and for the Eindhoven University of Technology.

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September 4, 2019 - Article Cursor

On September 4, 2019 we had an interview with Cursor. Cursor is the independent news site of, about and for the Eindhoven University of Technology. They post about everything that is happening at the TU/e. We talked about our progress and the problem of AMR.

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September 20, 2019 - Article FMT

FMT Gezondheidszorg is a Dutch knowledge platform for technology and housing in care. On their website they have published two articles about our iGEM team and our fight against antibiotic resistance.

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September 20, 2019 - Article FMT

FMT Gezondheidszorg is a Dutch knowledge platform for technology and housing in care. On their website they have published two articles about our iGEM team and our fight against antibiotic resistance. They also referred to our crowdfunding page, which helped us in reaching our goal of €2500. For more information read the articles below (only in Dutch):

• July 17, 2019
• September 20, 2019

Future

In November, FMT will publish a special about Antimicrobial Resistance. For the special, our iGEM team will write a scientific article about our fight against AMR and the results we obtained during the Giant Jamboree in Boston.

Next to the article, our iGEM team is organizing a symposium about AMR together with FMT. At this symposium, we will present our research about our diagnostic device and phage therapy. This symposium will be held on November 28 at the Eindhoven University of Technology. The symposium will be hosted by one of our professors: Prof. dr. J.C.C. Arts, who is also a proud supporter of the iGEM TU Eindhoven team.

From the special and the symposium, our team will receive financial compensation. This makes FMT Gezondheidzorg a proud sponsor of the iGEM TU Eindhoven team.

September 21, 2019 - Article ED

On September 21, 2019 the Eindhovens Dagblad (ED) published an article about our iGEM team. ED is a newspaper that spreads the news from North-Brabant and the south-east of the Netherlands.

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September 21, 2019 - Article ED

On September 21, 2019 the Eindhovens Dagblad (ED) published an article about our iGEM team. ED is a newspaper that spreads the news from North-Brabant and the south-east of the Netherlands.

In the article, our team manager Jeroen and lab captain Claire talked about the goal we want to achieve: to fight antimicrobial resistance by improving the diagnostics of bacterial infections. “If we do nothing, we go back in time, before Alexander Flemming discovered Penicillin”, was one of the quotes that Claire used to point out the threat of our problem. For more information read the article below, by clicking on the photo (only in Dutch):

September 25, 2019 - Article Brainport

Brainport Eindhoven is Europe’s leading innovative top technology region in The Netherlands. They dare to focus on technologies that are still in development, and therefore support the iGEM TU Eindhoven team by sharing the problem, and our solution, about AMR.

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September 25, 2019 - Article Brainport

Brainport Eindhoven is Europe’s leading innovative top technology region in The Netherlands. They dare to focus on technologies that are still in development, and therefore support the iGEM TU Eindhoven team by sharing the problem, and our solution, about AMR. Read the articles here:

• September 25, 2019
• October 6, 2019

September 26, 2019 - Radio 4 Brainport & Studio040

On September 26, 2019 Gerard Lokhof visited our office for an interview about iGEM. Gerard works for 2 radio stations in the Eindhoven region: Radio 4 Brainport and Studio040.

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September 26, 2019 - Radio 4 Brainport & Studio040

On September 26, 2019 Gerard Lokhof visited our office for an interview about iGEM. Gerard works for 2 radio stations in the Eindhoven region: Radio 4 Brainport and Studio040.

Radio 4 Brainport is a 24 hours a day English language program consisting of music, news and information about culture, science and technology for the international community in the Brainport region. We gave an extended description of our team, goal and project to the listeners of Radio 4 Brainport.

Studio040 is a Dutch local radio and television channel from Eindhoven, Geldrop-Mierlo and Waalre. We gave the listeners a brief description of who we are and what we do, to give them more insight in the developments within their region.

Listen to the fragment of Radio 4 Brainport here:

October 12, 2019 - Bachelor open days TU/e

Three times a year, the TU/e organizes a bachelor open day. On this day, new students can become acquainted with the TU/e campus, the programs and student life.

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October 12, 2019 - Bachelor open days TU/e

Three times a year, the TU/e organizes a bachelor open day. On this day, new students can become acquainted with the TU/e campus, the programs and student life. Also, student teams get the opportunity to promote their team. We, as iGEM TU Eindhoven 2019, talked to potentially new students about how you can broaden your experience at the university by joining a multidisciplinary student team. We got a lot of enthusiastic responses.

Figure 4: Anouk Marinus at the TU/e bachelor open day.

October 17, 2019 - Article Innovation Origins

We had an interview with Linda Bak from Innovation Origins. Innovation Origins is an independent journalistic platform that focuses on innovation, the business of innovation and the people behind it. They are: Your Sneak Preview of the Future!

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October 17, 2019 - Article Innovation Origins

We had an interview with Linda Bak from Innovation Origins. Innovation Origins is an independent journalistic platform that focuses on innovation, the business of innovation and the people behind it. They are: Your Sneak Preview of the Future!

The article will be posted after our wiki freeze and before we are going to Boston. In the article we explained that we participated in the iGEM competition and our project. Also, we are going to broadcast our presentation in Boston live on Facebook. Innovation Origins will spread the word about that.

Patients

What if antibiotics do not work anymore? Different patients in the Netherlands became untreatable because of antimicrobial resistance (AMR), which resulted in diagnoses like amputation or even death. However, a solution was found. While our project focuses on using bacteriophages for detection of bacterial infections, bacteriophages can also be used to treat bacterial infections. Because this is an interesting link to our own project, we investigated the experiences of patients who coped with infections of resistant bacteria for years, and how they were treated with bacteriophages. 

The general knowledge about phage therapy is still very limited. Also, patients who became untreatable do not always know that there is another option. Therefore, we had contact with two intermediaries who form the bridge between Dutch patients and the Eliava Institute, Georgia, where patients can be treated with phage therapy. Both these intermediaries came in contact with Georgia due to an episode on March 21, 2017 of “Dokters van Morgen” (Doctors of Tomorrow) on Zorg.nu about bacteriophages as alternative for antibiotics. They both have their own story about how and why this contact was started. The first intermediaries are Taco and Rachel from bacteriofaag.info. After watching the episode of “Dokters van Morgen” they realized how big the problem of AMR is, and wanted to help. One week later they were on an airplane, headed for Georgia, and started to help hundreds on Dutch patients with phage therapy.

The other intermediary is Lies Planje from bacteriofagentherapie.nl. Her father of 84 had an untreatable Klebsiella Pneumoniae bacterium in his body, and it was not sure if he would survive. Also, after watching the episode of “Dokters van Morgen” she came in contact with the Eliava Institute in Georgia which provided the cure of bacteriophages for her father. This was also the moment she decided she wanted to help more patients in the Netherlands by bringing them in contact with phage therapy in Georgia.

Both the intermediaries said the work is very grateful, because they can help so many people. They also notice that in the past few years, more doctors are willing to help their patients by informing them about phage therapy and helping them with preparing the test samples for Georgia. Also, the contact between the patients, the intermediaries, and the Eliava institute is smooth, and urgent patients can be treated fast. There are no other intermediaries in the Netherlands besides the two we talked to. This is because the Eliava institute wants to keep their network rather small.

Due to the intermediaries we came in contact with four different patients who wanted to share their story with us and with the world. Next to these intermediaries, we also came in contact with two patients from the Queen Astrid Military Hospital (QAMH) in Brussels. Because of their special opportunity to work with phages due to magistral preparations, they are able to apply phage therapy to certain patients.

The interviews with the different patients are listed below.

Patients from QAMH, Brussels

2016 - A Dutch patient with hefty decubitus wounds

First patient treated intravenously, because of septic infection with Pseudomonas aeruginosa after surgery in Brussels. These bacteria are quite common in the Brussels hospitals already since about 15 years (in contrast to Dutch hospitals), and the consumption of antibiotics is also way higher than in The Netherlands. The patient was treated with colistin for 14 days (often enough to stop the bacteraemia), then renal failure occurred, but the bacteraemia was not yet cured. This patient would have died, if not for the (Western-) world’s first successful IV mono-phage therapy.

2019 - A recent case of a young Algerian boy treated at Saint-Luc in Brussels for multiple infections

The patient was in need of a liver transplant due to cirrhosis and had received a transplant from his father, but this failed unfortunately. He got infected with a multi-resistant Pseudomonas and was placed on a waiting list for another liver transplant, and meanwhile the infections had to be treated. This failed with multiple cocktails of antibiotics and the QAMH was called in desperation. They started IV phage therapy blindly, without waiting for the phagogram (which would later turn out to be correct). They also injected phages in the cavity during liver transplantation (so before placing in the new liver). In total the patient was treated for 86 days, but then finally was cured. The phage therapy took very long in this case, but considering the patient being highly immunosuppressed and having a severe infection this might not be that peculiar at all. One of us met the young boy and his parents in Brussels and saw a now fully healthy and happy child, which was a wonderful experience considering the severely life-threatening condition he had been in a couple of months ago.

Figure 1: Dr. Jean-Paul Pirnay, QAMH (left) and Harm van der Veer, iGEM TU Eindhoven (right) with the patient and his mother.

Ger van het Einde

On Saturday June 27, 2019, Chris Tomassen and Mandy Shao got the chance to interview Ger van het Einde. He is a Dutch patient who got saved from his daily pain caused by the bacterium Pseudomonas Aeruginosa by bacteriophages.

In 2006, the first of in total 13 surgeries started due to his shoulder problems. This was when a new shoulder was placed for the first time. This shoulder prosthesis was taken out by 2007 to replace it with a new one.

In 2009, the bacterium Pseudomonas Aeruginosa was found after an operation. On the day itself, it became clear that Ger was dealing with Pseudomonas Aeruginosa, a superbug that is resistant to almost all antibiotics. Before his operations Ger never took antibiotics. But as each operation came, Ger had to deal with the bacterium. Due to the bacterium, the shoulder prosthesis was replaced several times. Within 2-3 years he received antibiotics for 6-8 weeks up to 3 times. It started with antibiotic pills after which he received it with the tube the body in. He said: "My life was destroyed, it affected my kidneys, my liver, my intestines, and my teeth went black."

In 2018, a friend from Ger contacted him about bacteriophages which he saw in a tv program: Dokters van morgen. At this point Ger had no shoulder, he was in pain 24/7 for the past 7 years and according to his surgeon, there was nothing left to do anymore. His spacer, a prosthesis made of antibiotic-loaded material, was removed urgently and he was put on antibiotic infusion. They may have needed to amputate his right arm. So Ger started to research the bacteriophages on the internet and came in contact with inforbacteriofagen.nl where he started the process of ordering the bacteriophages from Georgia in Europe. This had to be secretive, which was a long detour because he did not go to Georgia. The DHL, an international courier, picked up the tube with the fluid from his shoulder from Ger’s own house. This couldn’t be sent from the hospital in case DHL would start to ask questions. This was then sent to the George Eliava Institute where they found that 2 bacteriophages could target his bacterium: Pyo and Intesti. It also became clear that the bacterium was resistant towards 22 of the 23 antibiotics and the other one only worked superficially.

The Eliava institute had these two bacteriophages ready in their bacteriophages bank. Ger had to pick up his package from Georgia in Belgium because it couldn’t be delivered in the Netherlands. He drank the bacteriophages for the next 3 months, even though he did not know if it would work and his surgeon was being difficult about the bacteriophages. After the 3 months, he went back to his surgeon to ask for a biopsy however he refused, he did not believe the bacteriophages worked. So Ger went to the UZA in Antwerpen where professor Verborgt helped him by performing an open biopsy. No bacterium was found which meant Ger was free from Pseudomonas Aeruginosa and that he could get a shoulder again.

At this point Ger has a new shoulder, he is free from bacteria, he has no pain anymore and there were no side effects from the bacteriophages.

To help other people, he is going to publish a book called ‘Dankzij een virus’ which means ‘Thanks to a virus’. The book is about his whole experience with antibiotics and bacteriophages to create awareness.

Trijntje Zijlstra

On Wednesday July 31, 2019, Noëlle Gerards and Jo-Anne Ewald had a phone call interview with Trijntje Zijlstra. She is a Dutch patient who suffered from bladder infections for 40 years.

Trijntje has been taking antibiotics for 40 years now. Several new bladder infections were caused by different bacteria, so it was hard to determine which specific antibiotics needed to be administered every time. She suffered from severe side effects and the bacteria turned more aggressive when they got more resistant to the antibiotics. She tried to find another way to handle this problem as she was getting desperate. She learned about bacteriophages through a television program: ‘Dokters van morgen’. Subsequently, she contacted people from the ‘Bacteriofaag/Bacteriofagen’ page on Facebook and she started to investigate the possibilities of phage therapy. After more intensive contact her sample was sent to the Eliava Institute in Georgia to determine if she was suitable for phage therapy. Eventually, phage therapy was possible, and she could be treated in the Queen Astrid Military Hospital in Brussels.

She also consulted her general practitioner and her urologist about phage therapy. They supported her idea to start phage therapy, but they could not provide any help. Trijntje started phage therapy against the E.coli bacteria last November. The treatment was successful, and she was cured in the beginning of July. In contrast to antibiotic treatment, she did not experience any side effects. However, she said that phage therapy does not work as fast as antibiotics, so treatment takes longer.

Sadly, she recently got a new infection with the Streptococcus bacteria. Again, a sample was sent to Georgia and she is currently waiting for the result. It takes longer to get treatment than for the E.coli phages, since she needs a specialized phage this time. To design the treatment and produce the phages takes about two months. In addition, specialized treatment is more expensive than the standard phage treatment.

Trijntje also follows a Facebook page concerning bladder infections. She notices that other people are often desperate to find an alternative to antibiotics. Like she mentioned before, antibiotics are often not very effective for people with multiple bladder infections caused by different bacteria. Another concern about phage therapy is the fact that health insurers do not cover the costs. She contacted patients who want to get phage therapy, but simply cannot afford it.

To summarize, Trijntje has had a positive experience with phage therapy. She believes they are a possible alternative to antibiotics and should be available in the Netherlands.

Mieke ter Heijne

On Thursday evening August 1, 2019, Jo-Anne Ewald had a phone call interview with Mieke ter Heijne. Mieke is a Dutch patient who has been suffering from many different diseases for 56 years. She has two deficiencies that are not related to bacteria. On top of that, she suffers from bronchiectasis, which means you have abnormal dilated bronchi. These dilated bronchi are a source for bacteria, especially the pseudomonas bacteria. Mieke has been treated with antibiotics for the past 50 years, but without much result, since the bacteria got resistant to the antibiotics. In addition, she experienced many side effects during treatment with antibiotics. Two years ago, she got very sick and could not be treated anymore. Via a friend she heard about a Dutch television program where they discussed treatment for the pseudomonas bacteria. She did some research herself and ended up on the Facebook page of ‘Bacteriofaag/bacteriofagen’, where they treat bacterial infections with bacteriophages.

She was not able to travel to the Eliava Institute due to her sickness, but nevertheless she could be treated. The pseudomonas bacteria she had could be treated with standard phages, so she did not need a personalized phage therapy. These standard bacteriophages could be taken to the Netherlands and she could therefore be treated at home. Mieke was treated with bacteriophages for two weeks, but she still did not feel much better. She made a doctor’s appointment to test for different bacteria. The test showed that the pseudomonas bacteria was not present in her system anymore, so the phage therapy was successful. Unfortunately, a second resistant bacterium was found; the Klebsiella Oxytoca. Since phage therapy had been successful for the pseudomonas bacteria, she wanted to be treated with bacteriophages again. A mucus sample was sent to the Eliava Institute, where they ran some tests. This time, she could not be treated with standard bacteriophages, so a personalized phage cocktail had to be prepared in Georgia. It took them two months to do this, but then the bacteriophages could be taken to the Netherlands by Taco and Rachel, who work for ‘Bacteriofagen’. Again, Mieke was treated with these personalized bacteriophages for two weeks. It was a successful treatment and the resistant bacteria were eliminated from her system. Also, she did not experience any side effects. Her recovery process had been very easy, and she currently feels much better. Mieke would recommend bacteriophages to other patients, since it was successful for her in treating two resistant bacteria.

We asked Mieke questions about phage therapy and she told us that she has never been afraid of bacteriophages, as they are widely used in Eastern Europe for many years. She believes that phage therapy could be a good alternative to antibiotics and that they should rapidly become legal in the Netherlands. However, she emphasized that the lack of insurance is a big problem for many patients. She started a crowdfunding platform that enabled her to pay for the phage therapy, but not every patient is able to raise money for treatment.

Herman Timmermans

On Tuesday August 27, 2019, Yvonne van Mil and Jo-Anne Ewald went to the home of Herman Timmermans in Eindhoven to interview him about his experience with phage therapy. Due to phage therapy he transformed from a patient whose foot had to be amputated to a patient with a cured infection.

Almost three years ago, in February 2017, Herman Timmermans went to the general practitioner because of a swollen foot. The general practitioner mentioned that this was due to diabetes and he had to take rest and come back after 5 weeks. In the meantime, Herman Timmermans went to the pedicure who discovered an infection beneath the calluses of the swollen foot and referred him to the podiatrist in the Maxima Medical centrum in Veldhoven. During this time, the wound had grown to a size of 5 by 6 cm. To cure him the doctors prescribed antibiotics, but unfortunately nothing helped. Herman got very ill and the wound got bigger and bigger, it was July 2017 in the meantime.

In the end the doctors thought the only option left was to amputate his foot. However, Herman didn’t accept this and, because of a short movie on a tv show “Dokters van Morgen”, he contacted the Queen Astrid Military Hospital in Belgium to talk about phage therapy. They referred him to Georgia, and within a week the Eliava institute accepted him as a patient. However, this would cost him around €6000 which was not insured by his insurance company. Still, he went, because everything was better than getting his foot amputated.

Herman has had a great experience in the Eliava institute in Georgia. The doctors worked mostly in teams with different specialists and after 2 days in Georgia they knew what kind of infection he had, and which phages could cure him. 10 days after the first administration of phages the wound was already significantly better and he was sent home with a suitcase full of phages to totally cure him, this took 2 months in total. A year later he got another similar infection in the same foot, and again used the phages to cure this infection. It still worked perfectly and within a few weeks, also this infection was cured.

Herman Timmermans knows he is not the only patient with the problem of AMR but still too few people know about the option of phage therapy. Herman is convinced that the therapy can be brought to the Netherlands, just by buying the knowledge they already have in Georgia. Because curing more patients with an AMR is more important than money.

For the whole story you can visit this website (only in Dutch). CAUTION: sensitive content.

Public opinion

Between August 22 and October 1, 2019, we investigated the general knowledge about antibiotics and bacteriophages among the world population. In total 150 participants around the world were investigated by sharing our questionnaire on social media. Below we discuss the most interesting outcomes.

80% of the participants are in the age category between 18-30, and 40% is studying or working in the medical sector. The participants came from 3 different regions: Europe, North America and Asia.

At the beginning of our questionnaire we asked the participants about their experience with antibiotics. Most of the participants (76%) have used antibiotics in their life, and different experiences were found:

Then, we asked the participants what they know about bacteriophages and whether they will use phages as potential replacement therapy for antibiotics. Of the 150 participants, 56% knows that a bacteriophage is a virus. Before and after watching a video about bacteriophages we asked the participants if they think bacteriophages are dangerous:

Thereafter, we introduced the participants to phage therapy. Only 33% of the participants had ever heard of phage therapy, but still 91% would consider trying phage therapy if they have a multidrug-resistant bacterial infection. This shows that people are willing to try other ways of treatment when the obvious treatment is not working anymore.

At last we asked the participants what they think could be done to increase the common knowledge and confidence in bacteriophages and phage therapy. Some interesting answers are listed below:

• More coverage in the news, newspapers, social media, flyers, with hard numbers that show that it really works.
• (News) articles the general public understands.
• People are afraid of the term viruses. We should start campaigns to educate the masses about their true characteristics.
• More scientific research and trials.
• Start educating about the therapy in high school.

To conclude, phage therapy is still not well known among the participants. And more research is needed before phage therapy will become a general legalized therapy. But still the need of alternatives for antibiotics is clear, and phage therapy can be a good option.

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