Overview

As the project we were developing is a GMO-based therapy, public perception could significantly impact its future applicability. Therefore, human practices were an essential aspect of our project, where we wanted to examine our work in a social and environmental context.

We felt it was important to get people's views on our project so that we could identify their needs and provide better treatment options for them. To this end, we decided to carry out a survey, which ensured that our project met their needs and improved the quality of care.

To get a more detailed picture of the applicability of our project, we contacted several experts in the field for consultation. The feedback we received from these experts helped us to explore different aspects of our treatment, ensuring that we had a well-assembled and effective solution. Here we have highlighted the parts of the interviews that had the most significant impact on our project. Please visit the Interview page for more details.

On this page, You can read about how each interaction influenced our design.

Inspiration

From the very beginning of our project, we knew that we wanted to develop a bacteria-based cancer therapy, so we started to study the literature early in the design phase. In this way, we gradually get a clearer picture of what possibilities we have. However, even though we spent a lot of time and energy on research, we knew that to make our plans a success, we also needed to involve specialists who were more aware of the topic.

Dr. László Nyitray

Dr. László Nyitray (Ph.D.) is a Professor in the Department of Biochemistry, specializing in molecular biology, structural biology, and protein science. Right from the start, we knew that regulating gene expression was key to guiding the timing and location of bacteria-based therapy, so we considered several gene-expression strategies. We have planned to release cytotoxic protein by sensing tumor microenvironments, such as high levels of lactic acid, acidic pH, lack of oxygen, or increased body temperature. Talking with Professor Nyitray, we got the idea it may not be the right way because of two things: the targeted molecules are present in healthy tissues too, and also, these environmental conditions are not exclusive. Therefore, such a system would be like a double-edged sword, besides therapeutic effect, it would have certain leakage, and as consequence harm, healthy tissues and have side effects by design. For all these reasons we chose a light-inducible expression system since light-related techniques provide great spatiotemporal control of biological processes. However, we tried to build a system with as few parts as possible, as recommended by Professor Nyitray.

Dr. Imre Kacskovics

Dr. Imre Kacskovics (DVM., Ph.D., D.SC.) is the Dean of the Faculty of Science and Head of the Department of Immunology at Eötvös Loránd University. Outside the academy, he has also achieved success in his profession as the CEO of ImmunoGenes Ltd. During our discussions, Professor Kacskovics highlighted that we have to choose targets carefully since the main issue with bacterial therapy is its immunogenicity. Because of this, we decided to use a targeting molecule, a Nanobody displayed on the bacterial outer membrane that can bind to tumor cells selectively. He highlighted that our project may be the most applicable where not essentially necessary for the bacteria to penetrate the mucosal membrane. Based on all of this, the main target of our project can be colon or cervical cancer. Professor Kacskovics also drew our attention to the future of the illumination device we have created. After the conversation with him, we started to think more seriously about the potential of the hardware system, which can be found in more detail on the Entrepreneurship page.

Dr. Márton Bojtár

In our project's early stages, we consulted with Márton Bojtár (Ph.D.), a chemist in “Lendület” Chemical Biology Research Group of the Research Center for Natural Sciences. His field of research is developing photoactivatable compounds such as photolabile protecting groups or photocages. These molecules can be used to disable the biological activity of effector molecules, which can be restored upon light irradiation. Photolabile protecting groups are versatile tools, but he and his colleagues are mainly focusing on photoactivatable chemotherapy, where the caged compounds are chemotherapeutic agents. Accordingly, our conversation with him helped us better understand photoactivatable therapies and their research. We learned from him that photoactivatable therapies (such as PDTs) have been available for a long time, and the illumination of most organs is easy to do; the technical background is established. The biggest disadvantage of these photoactivatable compounds is their solubility. However, this problem does not apply to NanoBlade since it is a protein-based therapy; therefore, our application may have certain advantages compared to small molecule compounds. Since Mr. Bojtár uses illumination devices (LED panels) for in vitro experiments, we were curious about what details we should focus on more during the development of our hardware. According to him, one of the most important parts of these devices is the proper cooling system, as there is a significant heat output from the light sources, which can damage the cells used in the experiments. Another option that Mr. Bojtár suggested is to make the device programmable so that the light sources could be used in pulsed mode, which would reduce the amount of heat. An important aspect he also mentioned was the performance of the light sources. Based partly on these considerations, we created a highly programmable yet simple illumination device, which you can read more about on the Hardware page.

Survey

We wanted to conduct a survey to find out the perception, including the most common fears and misconceptions about GMOs and their medical uses. All of this has allowed us to specifically address these concerns in our project implementation and education activities (Please see the Implementation and Education page). Some of the key findings from our survey are set out below. In addition, we made the design of the completed questionnaire available on the Survey page, thus helping the work of subsequent iGEM teams.

Results

Our questionnaire was completely anonymous, and we received 136 responses online. As it was distributed via social media platforms, we expected some bias among our respondents. However, we were pleased to see that we managed to reach people of different educational backgrounds and ages, so we think that our data can provide some valuable insights into the general population's opinions (Figure 1).

Public attitudes on GMOs in general

The high level of social rejection of GMOs can significantly affect the future applicability of our project, which is why we thought it was essential to assess the general social perception of GMOs. We are pleased to note that the majority of respondents to our questionnaire do not show a high level of skepticism towards GMOs.The majority of people, 64%, find the use of GMOs acceptable under certain conditions, while 9.6% are entirely in favor. Only 8.8% of people answered that they completely reject their use, while 17.6% were unsure about the question (Figure 2).

While the results paint an encouraging picture of the social acceptance of GMOs, it should be remembered that our survey was primarily filled out by direct acquaintances of the team members, who could potentially be more polarized about the topic.

People's knowledge of GMOs

Most of the people answering our survey knew what the abbreviation GMO stands for (89%). To check how well they knew what a GMO is, we asked them to choose which ones they could be from our listed examples (Figure 3).

For example, 66.2% of respondents knew that the bacterium producing human insulin is a GMO. We also observed that 26.5% responded there may be chemicals that could be dangerous to the body, and 72.8% thought hybrid corn could be GMO too.

For the next question, we asked them about tumor colonizing bacteria, and only 39% knew about these, and 34.6% thought that certain bacteria could be in tumors (Figure 4).

Overall, we found that the majority of people had a lack of knowledge about GMOs, so we shaped our subsequent education activities based on the lessons learned from the questionnaire (Please visit the Survey form and Education pages).

Public opinion on the use of GMOs in medicine

We also wanted to know what people think about the role of GMOs in medicine.

83.8% of the respondents said they would take a GMO-based therapeutic agent, 61% as a diagnostic agent, and only 47.1% would choose a GMO as a preventive agent (Figure 5). As our project could facilitate both tumor diagnostics and therapy, based on this insight we should emphasize more the therapeutic effect of our product in combination with diagnostic in our marketing activities.

Most respondents prefer the oral tablet as the dosage form for bacteria-based therapy (Figure 6), and most people are somewhat concerned about the possibility of bacteria entering the bloodstream during the treatment (Figure 7). For these reasons, we have opted for oral capsules for the administration of our product (See Implementation page).

The survey also showed us that people are afraid of possible mutations in bacteria. Also, many people are worried that the introduced bacteria will multiply in the body (Figure 7). We also tried to assess what requirements GMO-based therapeutics would have to meet in the future to replace conventional treatment (Figure 8). Based on the answers received, efficiency and safety are the most important criteria for people. All of this led us to think about how we can provide even better treatment for patients in the future. Recently, the use of Minicells in cancer therapy has been investigated in several studies. Minicells are chromosome-free cells that are unable to divide and can be easily genetically manipulated. As Minicells are highly controllable, they represent a safer therapeutic option [1]. In the future, it may be worth exploring our project in MiniCells construction as well to provide an even safer treatment option for patients (See Implementation page).

Next, we wanted to find out what people think about the project we've created. We wished to know if people would dare to ask for a colon cancer treatment that contained GMO bacteria (Figure 9). 83.1% of participants said they would take this treatment, and 9.6% did not find it appropriate. This, combined with the overall high response, further indicates the positive attitude towards GMO treatment. As one participant mentioned:

“Of course, there is a risk behind every medical intervention. However, I feel that if we want to assess the risks of GMO-based therapies, the priority must be to fund their research and testing, wherever they may lead.”

Conclusion

Overall, we have successfully gathered public opinion on GMOs and our project. In addition, our questionnaire helped us understand where we need to improve our project in the future to provide even better treatment (Please visit the Implementation page for more details). However, our data suggest that educating people about GMOs could help this acceptance, so we have shaped our educational strategy accordingly (See Education page).

Survey collaboration

Through collaboration, we shared our results with the Wageningen team, who created another questionnaire on a similar topic (see Here for their questionnaire). The project they dreamed up is a probiotic that can be used to diagnose colon cancer at an early stage. Comparing our results gave us the opportunity to get a broader picture of the reception of our project. For example, although our respondents were from a wider range of age groups, we could reach fewer people aged 55 and over (8.8%), which is the risk group, than the Wageningen team (45%). Nevertheless, like us, they mainly received positive feedback on their project, which confirmed that people are basically accepting the use of GMOs in medicine. In some open answers, they also found people frequently mention the need to know if the GMO is safe or that they need to know proper research has been invested into ensuring this. In addition, the Wageningen team's questionnaire provided us with an exciting piece of information. 33% of their respondents felt more optimistic about their product after learning that GMOs can be used in the field of medicine in the EU if they comply with biosafety measures. So the vast majority of people are indeed accepting of GMOs if they are proven safe. Moreover, this data highlights for us even more than proper communication about GMOs is also important from the point of view of our product's marketing activities.

Future development

As we progressed more and more in our project, we had more and more questions about its future. The most important of these was how we would implement our project in the real world effectively and safely. The results of our questionnaire partially helped us to understand the challenges we have to face. However, we were not satisfied with that and sought to find answers with the help of experts. The lessons learned from the interviews greatly influenced our project's implementation, which you can read more about on the Implementation page.

Dr. David T Riglar

Seeing that people are sensitive to the safety issues of genetically engineered bacterial therapies, we interviewed a professional from the Imperial College of London, Dr. David T Riglar(Ph.D.). His lab is constantly trying to develop innovative technologies, such as living-engineered probiotics.

After consulting with him, we became even more confident that we would like to administer our product as an oral capsule in the future. Our conversation with him made us even more aware of the role of biosafety. Therefore, we concluded that we would definitely try the already-mentioned Minicell technology in the future development of our product.

Dr. Árpád Patai

We were lucky to consult Dr. Árpád Patai, gastroenterologist, and internist. During his Ph.D., he studied the epigenetics of colorectal cancer and is currently involved in the treatment of various gastroenterological diseases at the 2nd Department of Internal Medicine of the Semmelweis University. The conversation with him was beneficial for us, as it highlighted many factors that could greatly influence the future applicability of our project.

Dr. Patai noted that the targets we chose (EGFR, CEA) are not expressed in some cancer types. Therefore, he recommended that we look for additional potential targets to make our product even more universal. Based on this, we searched the literature and found several potential targets such as VEGFR, IGF-1R, and DR5 [2][3]. During the development of our product, in the future we would like to broaden the range of our display system by knowing the additional targets, so we could even increase the performance of our product by using them in combination. In addition, at the suggestion of Dr. Patai, we plan to perform our experiments on additional cell lines during the in vitro testing of our product due to the genetic variability of tumor cell lines mentioned earlier.

During our conversation, we also discussed what other options we have for dosing our product. We were curious, for example, about the potential of suppository-based delivery. Dr. Patai pointed out that that may give bacteria a higher chance of entering the circulation, so if our target is colon cancer, then we do not recommend choosing this administration method, but in the case of other tumors, this solution may also arise. In addition, we have found that we can even introduce bacteria into colon cancer sufferers' bodies through fecal transplantation or direct administration using endoscopic methods. We were worried that patients may find endoscopic delivery too invasive, but Dr. Patai assured us that the inconvenience caused by the procedure is not a real concern for patients with (potential) diagnoses. He pointed out that tissue sampling is essential to proper diagnosis, therefore it is inevitable, and our bacteria could complement current imaging techniques. Moreover, our system would be less invasive compared to other treatments (surgery, chemotherapy), so it would be a great addition to the clinician practice. We should mention, though, he has imagined our application as adjuvant therapy.

In addition, we asked Dr. Patai what he thinks about the fact that, according to our questionnaire, the majority of people have a positive attitude toward GMO-based therapies. Based on his experience, patients would accept these types of therapies more than current treatments (surgery, chemotherapy), since they have a bad reputation and people are often dismissive of them. In our questionnaire, 39% of the respondents said they would be happy to have a GMO-based therapy if their doctor also recommended it (Figure 8), so we wanted to know how doctors perceive it. To our delight, according to the opinion of Dr. Patai, these new types of therapies are completely accepted among doctors.

[1] Ali, M. K.; Liu, Q.; Liang, K.; Li, P.; Kong, Q. Bacteria-Derived Minicells for Cancer Therapy. Cancer Lett. 2020, 491, 11–21. https://doi.org/10.1016/j.canlet.2020.07.024.

[2] Françoso, A.; Simioni, P. U. Immunotherapy for the Treatment of Colorectal Tumors: Focus on Approved and in-Clinical-Trial Monoclonal Antibodies. DDDT 2017, 11, 177–184. https://doi.org/10.2147/DDDT.S119036.

[3] Hwang, K.; Yoon, J. H.; Lee, J. H.; Lee, S. Recent Advances in Monoclonal Antibody Therapy for Colorectal Cancers. Biomedicines 2021, 9 (1), 39. https://doi.org/10.3390/biomedicines9010039.