Difference between revisions of "Team:Toulouse France/Human Practices"

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Abstract: This year, chance has brought together 8 girls and only girls to create the 2016 IGEM Toulouse team. This peculiar and quite funny situation has somehow triggered our thinking about the actual position of women in Science, specially taking into account that our principal supervisors are only men…

Results of a vast survey on the role of women in scientific research conducted by the Boston Consulting Group were published in March 2014 in the European Union, show that only 11% of the highest academic posts are occupied by women in science subjects. The percentage of women heads of scientific institutions varies from one country to another: only 6% in Japan, 27% in the US, 29% in France or 34% in Spain. Clearly, women are underrepresented in scientific professions.

Nevertheless, these percentages are slowly increasing, mainly because women are fighting for to reach the goal that the parity would be respected in all levels of society. Regarding specifically the scientific area, many women have raised the flag of parity such as Caroline Herschel, the first woman recognized as scientist but also the first one to publish a scientific paper in 1786 about the discovery of a comet, or such as Marie Curie who obtained two Nobel prizes in physics and chemistry. However, efforts are still needed for a much fair treatment of women in order to grant full equality in all countries around the world.

Thus today, what is happening is that only 8 young women are involved in the iGEM adventure in Toulouse. Actually the selection to be part of the team was made based on the skill and motivation of the student and not on his gender. At the end of the selection process, it turned out that the most appropriate candidates were all women! Not to say, we are quite proud of the results!

We are of course aware of the statistical study from the 2013 iGEM Paris-Bettencourt team showing that parity inside a team positively influences its success. Against this statistic and for modestly contribute to the fight for men-women parity, we would like to demonstrate that only complementary skills are the secret ingredient to the success in this competition, beyond the gender.

ETHICS

At the heart of the synthetic biology iGEM competition is the modification of microorganisms and therefore the creation of genetically modified microorganisms (GMM), a sub-category of the genetically modified organisms (OGM) that also include higher organisms such as animals and plants. Although the issues raised by OGM in the public mainly concern plants (GMP) and more recently also animals (GMA) including Human because of the ease of manipulate organisms with the powerful CRISPR-Cas9 tools, we need to think about the ethics of our iGEM project and share our thinking with the public.

To fuel our thinking, beside reading few publications, we were lucky enough to be able to regularly discuss with Dr Vincent Grégoire-Delory, 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.

From all these readings and discussions, we realized that as far as ethics issues are concerned, there are two main point of views, anthropocentrism vs biocentrism, that would deeply impact on the outcome of any debate.



General considerations. The field of biology evolves very quickly thanks to the technological advances that we witness day by day. The definition of "biology" is also changing. Formerly simply meaning "study of the living", it is now more complex because we are able to transform the living. Indeed, the birth of synthetic biology has created a revolution in the world of biology as important as the discovery of the structure of DNA in 1953 by Watson and Crick or the first complete sequencing of a human genome in 2003. It is natural that suspicion emerges in the minds of the public when they only have a vague idea of ​​what this new discipline is, and the safety measures implemented to minimize the risks. Scientists everywhere have to work with integrity, communicate with transparency on their results, their doubts and their failures so that the public can gain more confidence.

Because respecting the living is or at least should be a value rooted in each one of us, it is only natural to be reluctant to projects that aim to modify organisms and living systems. Scientists therefore need to carefully explain the purpose of their projects. However, before doing so, to prevent a blurry debate, some basic concepts comprehensible by everybody need to be explained. First of all, how do we define a living being?

The definitions are very diverse and evolve over time. Actually more than 300 definitions have been collected by the astrophysicist Radu Popa (2010). For example, Vikipédia (an encyclopedia for children aged from 8 to 13 years old) gives the following definition: “A living being is an organism that is endowed with life, that is to say that this organism: is born, grows, nurtures itself, reproduces itself and dies”. For the NASA, “life is an auto-maintained system, capable of Darwinian evolution” (Gerald Joyce, 1992). Some definitions exclude, for example, viruses from their definition when others don’t. The limit has never been clear and yet we know is something lives almost intuitively. James Lovelock even said “The detection of life is part of our natural mental equipment”.

From the start, it is complex to define what we work with. In spite of the absence of definite answer, we can question ourselves differently: when is an organism considered “modified”? Indeed, we are not capable of changing the whole system of an organism, we can only change some functions or metabolic pathways. Is it a lack of respect to nature and the living in general to insert a gene controlling insulin production into a bacterium if that means saving thousands of human lives? from an anthropocentrism point of view the answer might be no, however from a biocentrism point of view the answer might be yes.

Whatever would be the answer, we believe that respecting living beings first and foremost rests on scientific integrity and rigor, a realization of all the implications of the scientific project, the precise knowledge of its content, and finally the establishment of security measure. We should never consider Nature and living beings solely as work tools.

In the European Union, the legal definition of GMO is mentioned in the 2001/18 directive: a GMO (Genetically Modified Organism) is “an organism, with the exception of human beings, whose genetic makeup has been modified via methods that do not occur in nature and/or through traditional crossbreeding methods”.

However, the regulation regarding GMOs varies from a country to another as far as research, production, marketing and their use are concerned. The US consider that a GMO is an organism whose “genetic makeup has been modified, either using classic selection, recombinant DNA methods (also called gene splicing) or gene modification”. The regulation is based on other criteria than the ones applied inside the European Union. Indeed, American policy is based on the product of gene modification techniques, not on the process itself. The regulation is founded on verifiable risks and does not focus on the risks that were not proven. (for more details see the precautionary principle).

As mentioned in the introduction, distinction must be done between different kinds of GMOs (GMMs, PGMs, etc…). As far as the iGEM competition is concerned, only genetically modified microorganisms are pertinent.

In France, the confined use of GMMs is subject, via the 2009/41/CE directive, to a system of notification and authorization. Even though MGMs in France are under a strict regulation because of their potential effects on health and their dissemination, they’re commonly used for medical purposes (insulin production by E. coli), or in the food industry (modified yeast for beer production).

Their irruption in the production processes went almost unnoticed. They were even perceived well since they were able to engender more reliable products, as it was the case with the production of the growth hormone. It is with the PGMs that the debate has emerged. The questions raised are often linked to them, but the confusion is present and the reluctance seems to affect all GMOs.

The risks are not the same for each category of GMOs, and to the best of our knowledge, for the moment no major health or environmental problems associated to MGMs have been reported despite more than 70 years of MGMs manipulation in academic or private laboratories. This observation has been recently confirmed to us by eminent scientist from various European ethics committees (Pr Père Puigdomenech; Dr Anne Cambon-Thomsen)

Precautionary principle in France. A very interesting law was written in 1995: the Barnier’s law, more known as the precautionary principle. It states that “the lack of certainties, given the scientific and technical knowledge of the moment, shall not delay the adoption of effective and proportionate measures that aim to prevent a risk of severe and irreversible harm to the environment to a cost economically acceptable”. It was written in response to the problems related to contaminated blood and the mad cow disease. This law applies to a lot of areas like health, environmental health, or the governance of economy and stock exchange. Thus it enables taking safety precautions even if the risk in question is not demonstrated or proven. However, no state has given this law a constitutional rank, except in France, Germany and Brazil.

The philosopher Hans Jonas tackles this subject in his book “Le Principe de Responsabilité”. According to him, every technology that contains a risk –no matter how small- of destroying humanity should be forbidden. He adds that if there are many consequences possible when using a technology, one has to decide [to use the technology or not] according to the most pessimistic hypothesis.

In France, this principle is applied for the use of GMOs and allows avoiding to the maximum the risks endangering health and the environment. However, it is sometimes difficult to quantify the risks and visualize the limit between what could be really dangerous for humanity and what is not.

Thereby, thanks to the awareness raised to this debate, numerous precautions have been taken to avoid the dissemination of GMOs, because the scientific community does not know their exact effects on the environment. Thorough studies in order to bring answers are still necessary to adapt our security measures in an efficient manner. It is thus important to act responsibly, with integrity and full conscience, and to evaluate the risks linked to using GMOs.

ETHICS OF OUR PROJECT

The Lascaux caves since 1979 belongs to the World Heritage of UNESCO. In 1946, representatives of 37 countries met in London to sign and enforce the Constitution UNESCO (The United Nations Educational, Scientific and Cultural Organization), defining the concept of world heritage and establishing an initial list of this heritage. This concept is unique by its universal application. Indeed, the World Heritage sites belong to everyone, irrespective of the territory in which they are located. Places as amazing and diverse as the Serra da Capivara National Park in Brazil, the Pyramids of Egypt, Trogir historic town in Croatia are the heritage of our world.

Sphinx and Chephren-Pyramid

Serra da Capivara National Park (Brazil)



Among the 1052 world treasures that need to be saved, the Lascaux cave and the impressive frescos by their number and aesthetic quality are listed since October 1979 (ICOMOS Recommendation). This prehistoric site is located in the French countryside. It includes 147 deposits dating from the Palaeolithic era and 25 decorated caves globally. There is no parietal cave in the world that matches it in terms of the quality and variety of the finds (skeletons, objects, flint, various utensils). The hunting scenes include 100 animal figures with amazing accuracy of observation, rich colors and lifelike quality. The site is particularly interesting from ethnological, anthropological and aesthetic point of views, marking a milestone in the history of prehistoric art and our human culture. Like the links of a long human chain, the Lascaux cave shows to future generations a work executed by ancient men. In order to preserve this chain, it is our duty to best protect this legacy. Indeed, the walls of the cave are partially and gradually covered with black and white mushrooms that hide the frescoes.

Why save art?

Art is a paradox in itself. Indeed, at the time of the Renaissance, an interesting definition of art appears: it is a disinterested and free activity, pleasant in itself, having no utility for production. But if art is aimless, why of all times, men made art and attempted to protect it?
In other words, is it really necessary to save art? Indeed, one may think that science is useful only when it is in the service of health or the environment. But why limit oneself? Combining science and disciplines based on beauty and aesthetics for example is an interesting combination. Art has existed for as long as we did, and has always seemed to be associated with what makes us humans.
However, isn’t a work of art destined to disappear? In the Tibetan Buddhist tradition, Buddhist conceived mandalas (support for meditation and visualization, symbol of the universe) in the sand (very sensitive material overtime). These disappear with the tide and weather. For Buddhists, a work of art made of sand then destroyed allows the artist to understand and accept the transience of material things and to detach oneself. Even today, ephemeral art is practiced for example in the Landart. This is a trend of contemporary art that uses the framework and materials of nature (wood, earth, stones, sand, water, rock, etc.). Thus, at any time, ephemeral art persists. Does it really make sense to save these frescoes? Moreover, despite all our efforts, the world tends toward entropy (second law of thermodynamics), which means that the universe tends toward disorder and disintegration. Will we actually counteract this law of nature by saving the frescoes in the cave? Or maybe, we could be satisfied with the survival to transmit this work as long as possible to the future generations? Humans have used art to fight oblivion and leave a trace of their passages on earth. Therefore, Art is an important part of our humanity. It is a proof of our intelligence and our necessity of expression. It is through the power and intelligence of men that we can organize the formless and chaos of the real world in a style, an expression. Thus, Nietzsche promotes art as the purest and spiritual entertainment. Although it is not directly useful, art can be engaged, be a witness and memory. Some works also have a decorative goal. They exist for their beauty, even though beauty is subjective. For the artist, art is also used to escape and to express themselves. Generally, art is a means of timeless communication. Thus, the Lascaux cave is a work of art, it deserves to exist, to be maintained and protected. It carries a message and a memory of the Paleolithic man.

Some philosophers of aesthetics, defined art as "sensitive knowledge": an autonomous knowledge which is opposed to knowledge through concepts. In this case, art is not for art, it has no goals but is a means of knowledge, and is necessarily a role in men’s evolution; it goes beyond the individual. It belongs to no one and is not the object of desire: it is there for contemplation of a generation, and then transmitted to the next.

These frescoes show the representation that men had of their world 18000 years ago. Notwithstanding, wildlife depicted on walls of the cave does not match the species hunted and consumed at the time. It includes mainly horses, buffalos and goats, and rare and often dangerous animals, such as bears, rhinos and big felines. A single reindeer engraved was found when it seems that it was very consumed at the time. This art does not represent the time of the hunting scenes as one might imagine. Still, the frescoes are extremely realistic in terms of morphology and attitudes of animals. For many prehistorians, the cave is actually a sanctuary, a sort of religious monument. Other theories circulated on the significance of the frescoes compared with the celestial constellations, shamanic worship, magic destruction of these terrifying animals, etc. Anyway, these frescoes carry the message of men 18,000 years ago, and they show us how they lived and what they believed in. They carry a page of humanity. Is it not necessary to keep this message alive as long as possible?

Why use synthetic biology to save art? Indeed, others techniques exist at present to try to slow the progression of fungi in the Lascaux caves. As said before, the walls of the cave are partially and gradually covered with black and white fungi that hide the frescoes. Alongside more traditional methods currently used against these fungi, we decided to act with the most modern means from this emerging science that is synthetic biology, to contribute to the preservation of an ancient heritage and to ensure its transmission to future generations.

Let’s not forget that the Lascaux cave is not an usual work of art, not only by age but especially by the presence of life. In fact, the cave has a very complex ecosystem, diverse and constantly interacting. It contains its own microflora as well as other living beings like insects. The opening of the cave by humans causing an imbalance in the ecosystem, one would think it’s only coherent that men attempt to repair their mistakes. As biologists, we offer to solve this biological problem, in this fragile ecosystem, with a biological solution. Physicochemical approaches have been partially successful and hopefully, combined with biological ones, one might expect the treatment to be completely successful.

However, our project is merely a proof of concept. We are aware that it won’t be possible to right away test our genetically modified bacteria in real conditions. Indeed, the ecosystem of the cave is very delicate and vital for the preservation of the frescoes. Thus, it is necessary to know what might be the impact of our modified microorganism on the environment before using it to treat the caves. We need to remove the black and white fungi while preserving the balance of the ecosystem. However, after getting in touch with scientists and people working in the Lascaux cave, it turned out that we will be able to test our genetically modified bacteria in a "cave test." Among others, we contacted Yvan Moënne-Loccoz, part of the scientific council of the Lascaux cave and Jean-Jacques Cleyet-Merle Director of the National Museum of Prehistory.

It is obvious that any project involving the release of genetically modified bacteria in an ecosystem, needs an in-depth studies to evaluate the evolution of the ecosystem following the addition of a genetically modified native bacterium. Such studies have been already done before. For example, a Canadian study analyzed changes in microbiota of rhizosphere (soil area directly formed and influenced by roots and microorganisms) and endorhiza (internal root tissue) cucumbers after adding a genetically modified native bacterium. This allowed the estimate of the risks associated with the future use of genetically modified microorganisms (GMMs) in crops. This study shows that the ecosystem’s modification in this project is not significant. It gives an encouraging result for the use of synthetic biology. It may be possible in the near future to get the same results for our project and why not imagine being able to reopen the cave to the public in the future?

1. Mahaffee, W. F. & Kloepper, J. W. Bacterial communities of the rhizosphere and endorhiza associated with field-grown cucumber plants inoculated with a plant growth-promoting rhizobacterium or its genetically modified derivative. Can. J. Microbiol. 43, 344–353 (1997).

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Confinement

The physical confinement of the bacteria is ensured by a device. It allows to locally spray the modified B. subtilis on the stains, taking care that the bacteria stay in a confined area.

The device will be placed against the wall of the cave, where there are black and white fungi. By a vacuum lifting system, it will match the wall and thus create a confined space. Our genetically modified bacteria will be locally sprayed from the device to the wall and take action against the cave’s microorganisms. The device will stay in place as long as the bacterium dies.

Estimating the quantity of our Bacillus subtilis strain is important to know when taking off the device. To this end, UV lights are installed on the device, and stimulate the natural green fluorescence of B. subtilis, which secretes fluorescein. This system will allow determining precisely when the bacteria will be sprayed to the wall, and when they will die, to remove the device without dissemination risk.