Covid fiction by Michael Reth
The worldwide pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting one’s daily life in the entire world. Given the major impact on the society, scientists are mobilized worldwide in order to better understand the virus and find new measures to contain its spread. This also applies to scientists of the excellence cluster BIOSS which has been instrumental in establishing the field of synthetic biology at the university of Freiburg. The public relation office discussed with Dr. Michael Reth, the Co-director of BIOSS, how synthetic biology which has the potential to solve many problems in the future, could contribute to counteracting the spread of the virus.
Q: Do you think synthetic biology can contribute to the containment of this virus?
MR: Yes, synthetic biology is a field that nurtures creative thinking in medicine and biology and this is urgently needed in this global health crisis. As Joshua Lederberg, one of the pioneers of microbial genetics pointed out ”The future of humanity and microbes likely will unfold as a drama that could be entitled-Our Wits versus their Genes”. Indeed, microbes and especially viruses are genetically more successful and we only can try to be cleverer than they. So yes, we do have some ideas how to better detect and counteract the spread of SARS-CoV-2.
Q: What are your ideas on this matter?
MR: Well, you have to know that the SARS-CoV-2 virus predominantly enters our body via the nose and mouth where it first proliferates for some time before it ends up in the lung and other organs if it is not directly stopped by our immune system. Our oral cavity is inhabited by millions of different bacteria which are part of the human microbiome. Sometimes these bacteria can cause diseases but often they are rather our friends and help us to digest food and protect us against infectious agents, for example, by controlling the gut barriers. The idea we came up with is the possibility to mobilize our oral microbiome for the rapid detection and inhibition of the SARS-CoV-2 virus.
Q: How should this look like and how can it help to end the pandemic?
MR: What is important in stopping the spread of the virus is first a rapid detection method for the presence of the virus and second a way to stop its proliferation already in the mouth. We think this could be achieved with the help of the oral microbiome if we provide it with the tool to do so. For example, the bacterium Streptococcus mitis AF003929 is a prominent member of this community and this bacterium can easily be cultured and genetically modified. In the Signalhaus Freiburg the home base of BIOSS we know a lot about receptors and signaling circuits. Following our moto “Signale verstehen und steuern” (Understanding signals in order to control them) we could alter a bacterial receptor system so that it detects the spike protein of the SARS-CoV-2 virus. For example, we can graft the ACE-2 protein domain bound by the spike onto the chemotaxis receptor of Streptococcus mitis AF003929. The binding of SARS-CoV-2 to the streptococcus bacteria would then activate a signaling process resulting in the activation of several genes which would be genetically implanted into the bacteria. Some of these genes would activate the synthesis of a small green fluorescent molecule thereby making visible all bacteria that were in contact with the virus. The SARS-CoV-2 infected persons would then have a green tongue which would easily be seen under exposure to UV light. Thus, the virus could no longer hide in our body as its detection would be an easy exercise. Sticking out the tongue would make it possible to distinguish infected from uninfected persons.
However, this is not the end of the story because we want to send the modified Streptococcus mitis AF003929 on a search-and-destroy mission. The altered chemotaxis receptor could also induce another gene circuit that results in the synthesis of several anti-viral components, thereby stopping the expansion of the virus on the track. In addition, the modified bacteria could also be made to express a special adhesion protein which would keep the bacteria firmly attached to the mouth and prevent them from migrating into the gut. In this way the virus-fighting bacteria would stay where they are most needed when SARS-CoV-2 tries to enter our body.
Q: How do you envision to deliver these SARS detectors and counteractor bacteria?
MR: The Streptococcus mitis AF003929 bacteria can easily be grown and expanded in culture and then lyophilized. One could produce delicious orange-tasting drops containing the bacteria. Taking every other day one of these drops will be enough to install and keep the virus-fighting bacteria in the mouth.
Question: How will the modified anti-SARS bacterium be maintained in the oral cavity?
MR: Well, whenever we eat something, we also feed the oral bacteria. However, while under anti-SARS bacterial treatment one should somehow control the food one is eating. We found that the bacterium likes sweet cakes such as Black Forest cherry cake as long as it does not contain too much alcohol. So, enjoying a Black Forest cake from time to time makes not only you but also the anti-SARS bacterium happy.
Question: Several of the oral cavity bacteria can also cause diseases. How do you want to avoid your modified bacterium being harmful?
MR: It is true that certain oral bacteria can cause diseases, especially in immunodeficient patients. To avoid this, we could install in the anti-SARS bacterium a security circuit that is activated by peppermint. So, simply drinking peppermint tea would eliminate this bacterium from the oral cavity.
Question: How was this idea received by the public?
MR: Well, we have not yet published our ideas but we plan to talk to some people in the Freiburg administration. The mayor of Freiburg was actually quite interested but would prefer that we use red instead of green color as readout of the tongue. However, as the tongue is already somewhat reddish, we think that the green color is better and more appropriate for Freiburg.
Question: When could this new product of the Freiburg synthetic biologists become available?
MR: Currently, many of these systems are still thought experiments but we hope that, in not too long a time, such a bacterium, once it has passed the administration hurdles, can become available. As anti-viral bacteria are something new, such administration control may take some time, but, on the other hand, in corona times things can move rather fast as demonstrated by companies currently developing vaccines against the virus.
Question: When will this pandemic end?
MR: I am looking each day on a picture from Max Ernst that for me symbolized the spread of the Corona virus and the end of its expansion and final elimination. So, I am optimistic that at the next two years we have learned enough about the virus and means to counteract its spread that this pandemic is over and maybe we are better prepared for the next one to come.
