Integration of the investigated issues into the project
Everyone told us so: creating a biological solution to protect the Lascaux cave is a beautiful idea. But it was also a very complex task, with several issues to tackle beside synthetic biology questions.
First, we address a very fragile art work (not saying invaluable). We therefore had to contact the cave curators to discuss our ideas and adapt the design of our project on their specifications.
Second, using a biological solution in a complex ecosystem generated a mass of scientific questions about, bacteria, fungi, their interactions, their handling and how to safely use our modified strain in such an environment.
Speaking of safety, we had plenty of opportunity to speak about GMO and about our project in public events and actions. These discussions led us to modify our initial design to meet the high security standard required by the public. It also led us to talk with ethicists about the meaning of what we intend to do.
You will find summaries of these meetings and how they influenced our project in the following sections:
Ethics issues integration
The first issues we wondered about were about ethics. Why save art? Is it destined to disappear? Why Human needs art? What rights have we to interfere on an ecosystem? To fuel our thinking, beside reading few publications, we were lucky enough to be able to regularly discuss with Dr Vincent Grégoire-Delory, Ethician, Head of the “Ecole Supérieure d’Ethique des Sciences” in Toulouse. We have also participated to a workshop on Genetically Modified Microorganism organized by the “Plateforme Génétique & Société” whose guest stars were Pr Bernadette Bensaude-Vincent from Paris, members of ethics committees and Pr. Thierry Magnin from Lyon, Head of the «groupe d’épistémologie et d’éthique des sciences et technologies». We have also attended a seminar on genome editing given by the Pr. Père Puigdomenech from Barcelona, member of European ethics committees, co-organized by the “Académie des Sciences, Inscriptions et Belles Lettres” of Toulouse. While participating to an exhibition on genetics at the “Museum d’Histoire Naturelle” in Toulouse, we also have had the opportunity to discuss with Dr Anne Cambon-Thomsen, Head of the “Plateforme Génétique & Société” of Toulouse and member of European ethics committees.
As you will see in our page dedicated to the topic (see Ethics), we had an intense and productive introspection. Notably, we debated about the necessity of saving art and about using the powerful synthetic biology approach to do so. This also raised others themes we wanted to explore. Among them were the ethics of DNA modification and of synthetic biology in general. To put this controversy in perspective, we made a video accessible to everyone).
All these encounters and meetings comforted us in the legitimacy to develop a biological solution to protect the Lascaux cave.
Our project had a strong echo in the society, but this implied from us to answer to the public worries and fears. The synthetic biology was born recently and provoked a big step in the scientist world, but GMO has raised intense controversies, especially in France. Actually, at our first meetings with the public, we felt that the public was concerned, not by the objective itself, but by the means to reach it. Interestingly the reactions were age-dependent, the younger persons were rather enthusiastic whereas the older ones were more reserved. It also appeared clearly that there were some misconceptions about the GMOs, and a lack of concrete knowledge about what is DNA manipulations or Synthetic Biology. So from these feedbacks and keeping in mind that the Lascaux cave is part of the Human patrimony, we felt that we had to answer the public by modifying the design of our project.
We carefully investigated the way to minimize, if not prevent, dissemination of our strain. We designed a double toxin/antitoxin system to prevent genetic material dissemination and a device to securely use our strain. We also felt we had to explain what we were doing and remove the fears from the people. This was at the core of our Human Practice efforts, with educative videos, theatre play and participations to various scientific events (see Engagement).
Scientific community advice
All along our project, we got in touch with scientists studying the cave ecosystem. Our initial vision was simplistic, as we felt that all we have to do was eradicating the fungi from the cave. The scientists, notably Yvan Moënne-Loccose (microbiologist of the Lascaux cave), explained us that the cave has its own microbiota, whose balance has only recently been disrupted by man. We understood from there that we had to be humble and carefully define the steps from the lab to the cave. This also comforted us in the choice of Bacillus subtilis as our chassis.
We also have received the help of many experts in the physiology of fungi and bacteria (Acknowledgements). With their help, we realized that we could fight the fungi by two ways, attacking them directly, or indirectly by eliminating their nutriments sources provided by the action of Pseudomas fluorescens. Therefore, we designed an antifungal module as well as a bacteria predation module for B. subtilis. They also raised the difficult issue of what should be the optimum ratio of predator (B. subtilis) to prey (fungi) in order to get a significant result. That has led us to develop a friendly open source program to simulate the efficiency of killing of the preys depending on the prey/predator ratio.
Last but not least, they told us that we would be welcome to test our therapeutic agent in their laboratory cave models. This opportunity has led us to think about the iterative strategy: test our modified bacteria, Paleotilis, in an ecosystem similar to that of the Lascaux caves, identify the limits of our design, then back to our bench to improve it and test again in the cave's model and so on.
Lascaux curators advice
The Lascaux cave belongs to the World Heritage of UNESCO since 1979. The responsibility of its protection is in the hand of the cave curators. If the frescoes have not long been destroyed, it is thanks to these people. Among them, we are grateful to Muriel Mauriac who guided us since the beginning of our project and Jean-Jacques Cleyet-Merle, as director of the national prehistory museum, who has always been enthusiastic about our project. If they agreed that Paleolitis was an original way to conserve the frescoes, they were concerned by its initial design. Thanks to their feedbacks, we have strongly modified our project so that our modified bacterium would stay physically confined as long as there would not have any doubt about its risk of utilization. They also recommended to test our genetically modified bacteria in laboratories caves. They were at the starting point of our modeling iterative approach and their advices has opened the way to our strain validation.
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