Team:Humboldt Berlin/Human Practices

Human Practices

Thought Process/Overview

Cancer is a very common and devastating disease that almost all of us have made or will have made experiences with in our lifetime, either by fighting against it ourselves or knowing people that have to deal with it.

Sadly, sometimes the affected groups have to decide whether they want to spend their last days trying to fight cancer by chemotherapy or other therapy methods, which can show a plethora of side effects and make you feel even more miserable, or whether they choose to enjoy the time they have left on this earth without those side effects. Nobody should have to deal with this dilemma. Ideally there would be a treatment method that is both effective and less straining for the body.

During our literature research, back at the beginning of iGEM, when we were trying to find an idea for this project, we stumbled upon a paper about minicells and their variety of possible uses. One of our first ideas was to use these minicells as vehicles to specifically target cancer cells and inject toxins or other effectors into them, using the injectisome of Salmonella Typhimurium (Salmonella). Of course this is just one of many possible uses of minicells but the whole team agreed that it was a fascinating idea and that we wanted to pursue this goal during our time in this competition.

We knew right away that we would not be able to complete the needed research to show that this was safe for medical use but we would be able to do foundational research and show a proof of concept, so that other researchers could maybe pick up on where we left off and continue working on this fascinating idea. So our goal for human practice was to reach both the general public to inform them about this potential new medical tool and maybe give those who are suffering from this awful disease some hope. Furthermore, we wanted to contact medical health professionals, other scientists and biotech companies to get input from different perspectives. Unfortunately the pandemic made all of this a lot more difficult than we first anticipated.

Advantages

The main concern we had when designing this idea, was to create a new and safe treatment method that could specifically target diseased cells and would not have a negative effect on healthy cells as well. Additionally, new therapy methods should be tested rigorously to make sure that the possible side effects do not outweigh the usefulness of the treatment.

Unfortunately for us, there have not been a lot of studies on the possible side effects minicells might have on the human body or how the immune system would react towards them in general but this is worth exploring. If the side effects would not be as extreme as for example in chemotherapy, then this would be a valid alternative. In table 1 you can see a short overview of common side effects of traditional cancer therapy methods.

The usage of minicells might also be a non-intrusive alternative to surgery. Unfortunately we do not know enough about the effectiveness of minicells and the body’s reaction to them, so more research and clinical studies are needed. Using only what we know so far, we tried to make working with minicells as safe as possible. We worked with attenuated Salmonella strains in the laboratory to ensure the safety of our lab team. Furthermore, minicells are not able to reproduce and die after a certain amount of time. So ideally, minicells that are introduced into the human body, should only live long enough to perform a given task and then die so that they can not do any harm to the body.

Table 1: Side effects of different cancer therapy methods in comparison.1 2 3
Radiotherapy Chemotherapy Surgery
inflammation of the mucous membrane, Skin irritation also attacks other quickly proliferating tissue risk of infected wounds
nausea, vomiting nausea, vomiting possible damage to healthy tissue
diarrhea fatigue, trouble focusing, memory loss the usual risks of general anesthetics
hair loss anemia, heightened risk of infection and of getting other types of cancer problems with wound healing
loss of appetite reduced fertility and irregular menstrual cycles

Risks

Of course we also had to think about the possible risks a treatment method like our proposed approach could harbor. First of all, minicells are very versatile in their usage. You could target any cells of which you know the molecular surface structure, when the minicells are equipped with the appropriate counterpart. By this, in theory, minicells could also be misused by inappropriate design to target healthy cells. Also, as we have already explored above, the effect minicells could have on the human body is not well understood, so caution is essential when working with minicells. Even though there are possible risks we did not want to paint Salmonella in such a negative light since the general public mostly knows this organism as a pathogen.

We believe that science communication is an important part of modern research. That is why we teamed up with UBCiGEM from Vancouver to inform the general public about the kind of cancer research we are aiming at and how Salmonella could help us with that - thus improving the image of this bacterium. Commonly people combine Salmonella with food poisoning, so it is understandable that they would be sceptical about our idea of introducing Salmonella to the human body as a form of therapy. The goal of our campaign was to show that it is possible to work safely with Salmonella and to educate people on the benefits of this alternative therapy. In order to boost our message, we set out a campaign on social media:

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A picture of our small social media campaign with UBC iGEM.

The content of our posts contained general information about cancer as a disease, the current therapy methods and Salmonella, as well as the advantages of using minicells in cancer therapy and how we want to ensure that these cells are as safe as possible for medical use. Some examples are listed below:

In addition to that, we also had the honor to release a short text, along with a picture of our team, in the German, scientific journal “BIOspektrum”. This enabled us to reach a broader scientific audience.

Statements

To get input on our project, how reasonable our ideas are and about possible uses of minicells, we have reached out to experts in their respective fields, like Marc Erhardt.

We believe that science communication is an important part of modern research. That’s why we teamed up with UBCiGEM from Vancouver to inform the general public about the kind of cancer research we do and to improve the public image of Salmonella. What people usually think about when they hear that name is food poisoning, so it is understandable that they would be sceptical about our idea of introducing Salmonella to the human body as a form of therapy. The goal of our campaign was to show that it is possible to work safely with Salmonella and to educate people on the benefits of this alternative therapy.

Chromosome-free bacterial minicells are highly attractive for biomedical applications because they are unable to replicate but contain all the necessary metabolic and biosynthetic machinery to produce proteins of interest. The iGEM team of the Humboldt-Universität zu Berlin developed an innovative approach of using engineered minicells of Salmonella to inject an anti-cancer peptide into cancer cells. They cleverly exploit the ability of the native type-III injection system of Salmonella to inject proteins into host cells and combine this with an engineered adhesion factor to be able to correctly target the minicells to cancer cells.

We also tried contacting two medical experts, but to no avail so far. Human practice during a pandemic is a real challenge, since you can not just go out and meet people as easily. So we were mostly bound to sending emails and trying to call people. However, we believe that our launched social media campaign with the Vancouver team (on the American continent) boosted our ideas and messages into the (locked-downed) world.

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A picture of the BIOspektrum article the iGEM team Humboldt_Berlin participated in.