Team:Hannover/Human Practices

iGEM Hannover 2020

Human Practices

Summary: Throughout the entire duration of our project, we have included social and ethical aspects. We were able to talk to experts from the medical and scientific fields during the interviews and events. With the knowledge gained through the exchange, we designed and continuously evaluated our project.

The first part (silver criterium) of this page deals with the social and ethical aspects of our project. In the second part (gold criterium) we dicuss the impact on the world and our society.

Human Practices in the preparation and initiation phase

Even during the definition of our project InToSens, we were already intensively engaged with the social and ethical aspects. At the beginning of our project, it was clear to all of us that we would like to have a positive influence on people and that we would like to improve the health or recovery possibilities. How we wanted to implement this was not clear to us.
Therefore, we, first of all, researched intensively which urgent health problems exist in Germany and the whole world. We quickly agreed that we wanted to address the issue of implant-associated biofilms. After gathering and critically reviewing more information on this topic, it became clear to us that we wanted to develop a sensor that would enable early detection of a forming biofilm. For us, it was essential to guarantee a non or minimal invasive detection possibility to avoid pain for the patient. We wanted to make biofilm detection as inexpensive and easy as possible so that our cell-sensor is useable all over the world. To avoid unnecessary treatments, we also wanted to enable a double validation of the findings with our sensor.

Picture of the flipchart with our project ideas.
Figure 1: Picture of the flipchart with our project ideas.

Human Practices in the concept development phase

During this phase of concept development, we also discussed whether we should not only have proteins expressed that enable detection by the biofilms. Also, we considered combating the biofilm directly by producing antibiotics. After discussing this question ourselves, we decided to design a cell-based sensor only for detection. The main argument for us was that treatment should always be controlled and induced by a human being. In the phase of concept implementation, we continued to intensively consider and evaluate the ethical and social aspects of our project. Therefore, we conducted interviews with experts and presented our idea to an interdisciplinary scientific audience.

Presentation at events of the NIFE

The NIFE is the Lower Saxony Center for Biomedical Engineering Implant Research and Development. It is internationally one of the leading centers for biomedical research and development. Working groups from the Hannover Medical School, Leibniz University, and the Hannover Veterinary School work here, thus bundling concentrated competence in this center.

We have presented our project at various stages in the course of various NIFE events. The feedback we have received has involved us in the different stages of the project. The audience gave us suggestions for our experiments and also access to measurement instruments, which we were allowed to use for our project.

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Figure 2: (1) First project presentation at the Christmas Party 2019 at NIFE. (2) Presentation of the project and our results at the first NIFE colloquium in October 2020.

Interview with Prof. Dr. Jens Boch

Prof. Dr. Jens Boch
Figure 3: Picture of Prof. Dr. Jens Boch.

Prof. Dr. Jens Boch works at Leibniz University and is an expert in Plant Biotechnology and genome editing. He is not only well acquainted with the scientific aspects of genetic engineering, but also with the challenges that arise from the social viewpoint.
We were able to win Prof. Dr. Jens Boch for a discussion at an early stage. The interview gave us further insight into what the legal conditions in Germany are for the use of genetically modified cells. We were also made aware of the undeniable need for public discussion on the topics of genome editing and synthetic biology. From the interview with Prof. Dr. Jens Boch, it also became clear that he shares our assessment of the problem about concern regarding the uncontrolled release of antibiotics. He believes that even more intensive education is needed until society in Germany becomes more open to genetic engineering.

From the interview, we took away many points for the further implementation of our project. We have decided to stick to the concept of pure detection and to leave out the fight against biofilms by our sensor. Since we were made aware of the importance of public discussion, we also decided that we want to make a sustainable contribution to make this possible. Therefore, we have concentrated on informing students through projects on the topic of Synthetic Biology.

Project Presentation during the lecture on synthetic biology

In the course of the event, we discussed our project with other students and received positive feedback. We were also able to arouse the interest of other students in the iGEM competition and thus perhaps contribute to the possibility of an iGEM Team Hannover in the coming year.

Human Practices, Outlook and Future Perspectives

Many projects fail on the way to clinical application because not all influenced groups were involved, in the early stages of the project. Since the clinical use of our cell-based sensor InToSens is our vision, we have conducted further interviews to evaluate the perspective and possible implementation of our cell-based-sensor.

Interview with Dr. Katharina Doll

Interview Katharina Doll
Figure 4: Picture of our interview with Dr. Katharina Doll

Katharina Doll is assosciated with the Department of Prosthetic Dentistry and Biomedical Materials (Prof. Stiesch) at Hannover Medical School and the NIFE Hannover. She is a group leader in NIFE and her main research interest is the formation of biofilms on implant materials. The interview began with the statement that implants are an integral part of medicine. 1.2 million dental implants alone are implanted in Germany every year. Due to the complex oral flora, biofilm-associated infections are frequent side effects, where there is no successful solution so far. The patient often loses the implant because of the material development on it. The local treatment of biofilm-associated infections is hardly possible, not even in the mouth, where it is easier to reach the implant than in the hip or knee.
Dr. Katharina Doll thinks that we have chosen a project with high medical and social interest. But she also pointed out that it could be challenging to get our sensor into clinical trials because of the genetically modified cells used. Since an approval or authorization by the German authorities will be a big hurdle. Nobody could say whether the genetically modified cells in the patient would continue to divide, which poses a potential cancer risk. Furthermore, Dr. Katharina Doll questioned whether the nutrient supply of the sensor-cells is sufficient to survive in the human body and whether the released toxin concentration realized by the biofilm is sufficient to generate detectable changes in protein expression. In our initial considerations, we imagined encapsulating the cells in alginate and attaching them to the implant. Dr. Katharina Doll said that bacteria able to degrade alginate and pointed out that we should look for alternatives if we want to pursue the project. She questioned the responsiveness of our sensor-cells to harmless bacteria such as those in oral flora, and whether this then falsifies the luciferase concentration in the blood/urine. For the usage of our cell-sensor on oral implants, this point has to be clarified.
Dr. Katharina Doll also gave us a lot of tips and suggestions on how we could avoid all these potential problems. She thinks that we should first concentrate only on an implant, where hardly any bacteria are present. A possible choice would be a hip or knee implant. Here, only gram-positive staphylococci are responsible for a biofilm-associated infection. She suggested that we should first remove ourselves from implants and devote ourselves to materials that do not remain in the body for several years, thus lowering the inhibition threshold of society and the risk of cancer. Bone fractures and the urine catheter would be an ideal application possibility for our cell-based sensor. Both are easily changeable, and infections around the materials are a problem. The urine catheter has to be changed weekly. With our cell-sensor, the urine catheter could remain in the patient longer, and antibiotic intake would be reducible, both resulting in less stress for the patient. At the same time, detection may be much easier because the luciferase is released directly into the urine. Testing for biofilm development would be performable every time the emptying catheter.

Dr. Katharina Doll is interested in knowing how patients would react to our sensor, so we should consider starting another patient survey. We also find such a survey very exciting and have directly created one. We will send it to patients if we continue the project.

Patient survey
Figure 5: Our Patient survey.

In summary, we were able to gain much useful information about biofilms and insight into the current state of research on implant-associated infections. This very productive conversation helped us a lot in our planning for a possible continuation of our project. Especially the presentation of cooperation possibilities with the working group encouraged us to continue the project.

Interview with Prof. Dr. Stichtenoth

Prof. Dr. Dirk O. Stichtenoth is the head of the Institute of Clinical Pharmacology. The core tasks of the Institute of Clinical Pharmacology include clinical practice, advanced clinical research, teaching, and continuing medical education. The Institute of Clinical Pharmacology at the MHH fulfills a cross-departmental interface function in the supervision and conduct of demanding clinical studies, competent support in all pharmacotherapeutic areas of patient care, and the management of the Drug and Ethics Commission.
From our conversation with Prof. Dr. Stichtenoth, we learned many important aspects of clinical research and approval procedures. In the course of our Proposed Implementation we have taken a closer look at these aspects. Among other things, how important it is to deal with all the players involved in the development of cell therapy at an early stage. The conversation also showed us that we should strive for an even more intensive exchange with medical professionals if we want to bring our cell sensor into the clinic at some point.

Impact Evaluation (Gold)

Summary: Overall, we are sure that our project will have a positive impact on the world and our society. Our research has a positive influence, but also our commitment to the Education Project is good for the community. Furthermore, we dealt with the criteria that are crucial for the continuation of the project. For more information, see Proposed Implementation. Altogether, we are sure that our cell-based sensor has the potential to establish itself in the clinic.

Project

Impact on our team

With the means at our disposal and under the difficult conditions caused by corona, we were able to develop a new and unique cell sensor and provide the Proof of Concept of it. As a team, we are proud of this and the many other great results. Also, we all learned a lot while working on the project, gained insights into other areas, and developed further. We have mastered the challenges and created solutions that can be used by other researchers. The work on this project, especially the teamwork and the solved challenges, contribute to the development of each team member. Altogether we consider the work on this project to be positive.

Impact on others

We are sure that our results, generated in the course of our project, can be used by other working groups and thus our project will have a far-reaching positive impact. Our genetic construct and the designed parts will serve as a starting point for the establishment of cell-sensors for various applications. Not only because most of the materials and methods we have used are available in most laboratories, but also because we have demonstrated the detection capability by co-expressing the two reporter proteins. The fact that an MRI was not readily available in our laboratory helped us to design the microfluidic chamber. Thus, we created a measuring instrument that can be reprinted by other working groups and adapted to their own needs. With the help of the software we designed, it is possible to simulate the first growth phase. Due to the ubiquitous distribution of biofilms, this is interesting for a variety of fields of application.

The Vision of a cell-based sensor

To evaluate the impact of our cell-based-sensor, we decided to analyze it with a matrix, which lists the different actors and factors.

As shown in the matrix, our cell-based sensor would have a very positive impact on the different actors. The prerequisite for this is that the legal conditions allow the use of the sensor and that gene/cell therapies are society approved. We assume that early detection with our sensor can prevent serious complications. It would not only benefit patients and physicians and the entire healthcare system. The ease of use and the commonly used materials and specimens are factors that would favor the clinical establishment of our sensor.

One can consider the adaption of infrastructure as a challenge, but cell therapeutics will become daily threading in future medicine, which will make the clinical establishment of our sensor easier.
Biological safety is not foreseeable for us at this point but should be a high priority in planning. During our project, we have introduced the construct transiently into a general-used cell line via transfection. In the further development of the cell-sensor, the stable expression of the proteins is essential, which requires a considered selection of a vector system. The choice of the final cell influence also biological safety.

Table 1: Matrix to validate the impact of our project.
Groups Innovation Early detection Rapidity for results delivery Reliance Biosafety Easy to use Accessible Ethical concerns
Patient (++)
profit health-wise most from the biosensor
(++)
early treatment and no loss of the implant
(++)
fast results a small period of uncertainty
(-)
must have high confidence in the research group & detection procedure
(0) (++)
co-implantation and easy control measurements, when the sensor is implanted
(++)
all patient, health insurance pay
(+)
has to be open for cell therapy
Doctor (0)
have to learn new techniques that fit the requirements of the cell sensor
(++)
less mental strain, no second operation
(++)
fast results, can quickly initiate treatment
(0) (0) (++)
easy co-implantation and measurement
(-)
access to sensor-cells needed
(+)
has to be open for cell therapy
Diagnosis center (++)
fast & reliable diagnosis
(++)
new analysis to offer
(++)
more samples per day, higher incomes
(0) (+)
urine and blood are common samples
(++)
easy detection
(+)
blood analysis is a common method, MRI required for MagA detection
(-)
unclearly dependent on legislation
Hospital (++)
usage of innovative techniques means a good reputation
(++)
better chances of treatment success, a better reputation
(++)
shorter patient stays and fewer patients due to complications
(0) (-)
new infrastructure needed
(0) (++)
all hospitals and dental surgeries
(-)
unclearly dependent on legislation
Health insurance (-)
more expensive implants
(++)
fast and cheap detection
(++)
shorter patient stays and fewer patients due to complications, lower costs
(0) (0) (0) (-)
unclearly dependent on legislation and hospitals offering the treatment
(-)
unclearly dependent on legislation, the decision has to be made that Health insurance pays for the cell-sensor