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IGEM Bordeaux 2015

Popularization

This year, IGEM Bordeaux has decided to invest time and energy in talking with people about synthetic biology and Genetically modified organisms. You'll find in this section a preview of what we did this year

Cap Sciences

Cap sciences is an animations center in Bordeaux, open to all which tries to help people discover and understand scientific phenomenons, new technologies and their industrial applications. They try to make science accessible to everyone and to engage a large variety of people in scientific activities. They were glad to hear about our project and we have been in contact with them all throughout the year, presenting what we've done on popularization. Here is a link to an interview we had with them at the beginning of the year:

Watch our interview!

This partnership also pushed us to go talk to people on the street to understand where their fear of genetically modified organisms comes from and to raise awareness on what is being done nowadays with synthetic biology in our everyday life. Caroline, Charlotte, Gilles and Diego spent a few afternoons in the streets of Bordeaux trying to get in contact with walkers. These conversations tought us that in Bordeaux the main concern about GMO's is that people are unaware about what they really are and the possibilities that synthetic biology offer us. Furthermore it made us start to realize the importance of scientific communication and for the need to think about our project from an ethical and safety point of view. For more information on the questions we asked ourselves please see the Ethics page!

SURVEY TO PUT HERE

Presentation of Synthetic Biology in Lycée Montesquieu

IGEM Bordeaux also wanted to raise teenager's awareness of synthetic biology. On 2015, May, 21st, Jean, Savandara and Lily made a presentation of synthetic biology at the school "Lycée Montesquieu" in Bordeaux, showing its interest by giving some interesting applications.

Lab Life

After a few years of thinking about it, our game is finally going to be created physically. It took some determination and long hours playing to optimize it but we're proud to present our 2015 Edition!

Ethical aspects of synthetic biology

Before analyzing the ethical aspects of synthetic biology, it seems important to clearly define this new area of biology.[1]

What is synthetic biology?

Synthetic biology is a new field of research in biology which mixes science and engineering. It focuses on the conception and the construction of new reliable functions through the creation of biological systems or the re-engineering of organisms which already exist. The singularity of synthetic biology compared to traditional biology is about engineering live beings to have a predictable behavior. In order to do so, scientists focus on optimizing existing biosynthetic pathways or creating new ones while bypassing or suppressing inefficient pathways in order to increase productivity.
Three different approaches exist in synthetic biology:

- The metabolic engineering of the living beings by using biobricks (DNA sequences whose functions and assembly conditions are known). The biobricks are free of access on the WEB and can be synthesized on request.

- The production of minimal genomes and simplified organisms where new functions can be added to realize a task. This approach is often used for the optimization of existing processes.

- The synthesis of a whole synthetic genome that will be inserted in existing cell hosts or in synthetic cells. This field of synthetic biology may help scientists to understand how living organisms are created.

The organisms which come from these approaches can be used in both industrial applications (for example to produce drugs, biofuels, biomass or biopesticides) and in basic research as tools like biosensors (E. chromi - Team Cambridge, 2009) or against pollution (Physco Filter - Team TU-Munich, 2013). With these new tools emerging from synthetic biology, many possible fields conducting to different experiments in science permit the intellectual and technical expansion. Bioethics is necessary to prevent researcher about its ethical limits.

The responsibilities of the researcher for synthetic biology

The advances in biotechnology techniques also lead to dangerous possible applications causing a general fear of modified organisms by the public. They may be afraid of the organisms that can be created by synthetic biology, afraid that these organisms will somehow grow out of our control or have unexpected properties and will become dangerous for humanity. Our iGEM team observed this while talking to the general public on the streets of Bordeaux. For more information, look at our Cap Sciences section on this page.

In order to limit this fear, the question of transparency is important for scientists. Besides publishing his results, the researcher has to be able to explain his research process and the challenges of the project by stating the explored and the ignored areas. The general audience has to be able to understand his whole scientific approach. Results found, thanks to this approach, contribute to the production of new knowledge and innovation that could be shared to the general public. It is also important for the researcher to analyze his results, looking at the possible negative impacts of his research and estimating the safety and environmental risks and as well the ethical problematic. However, the researcher cannot be the only one in charge of the safety and ethics of his research.

The synthetic biology legal framework in France and in Europe

Creating guidelines and a legal framework is essential for safety reasons and to reassure the general public. In Europe, there is no law specifically concerning synthetic biology but synthetic biology is framed by common biology laws. In France, the first laws concerning bioethics were put in place in 1994. [2] Before, general laws existed but did not deal with the particular ethical aspects which come from biology and using living organisms. On the 1st of July, the law n°94-548 presents guidelines for data processing in medical research. This updated the law n°78-17 (1978) relative to informatic and big data processing in all fields of research. Quickly after, on the 29th of July 1994, two laws were put in place: law n° 94-653 and 94-654 which deal with respecting the human body and products which come from the human body. These laws cover the protection of patients which was then introduced in the Civil code, organizational rules in medical sectors and guidelines to be put in place to protect people involved in medical research programs. In march 2002, patient rights are put in place and certain end of life guidelines are discussed. Futile medical care is banned. Ethic committees set up by the European Union also exist to complement these laws for example, the European Commission, the European Group on Ethics in Science and New Technologies, the Inter-service Group on Ethics and EU policies, and the Executive Management for Research and Innovation

Specifically for synthetic biology, a European project called SYNBIOSAFE approved by the European Commission has focused on ethics and safety of synthetic biology. In 2012, it published an article concerning the bioethical and biosafety attentions in iGEM competitions. These two types of frameworks help the researcher to answer to many ethical questions in the clearest way possible. Therefore, not only law may limit synthetic biology. Aspects concerning Politics, Economy, and Philosophy could influence the bioethics questions.

Why do we need Ethics commitees? Interview with Mr FAUCHER

On the 29th of July, Savandara and Charlotte had the possibility to meet with Mr Jacques Faucher, doctor, priest and founder of the regional Ethics commitee "l'Espace Bioéthique Aquitain". Mr FAUCHER generously accepted to come to our lab at the European Institute of Chemistry and Biology (IECB) in order to talk to us about the importance of bioethics in the field of synthetic Biology.

When Mr Potter, American oncologist and surgeon, invents the word ethics in the 1970's and writes his book Bioethics: a bridge to the future he pioneers the questions to come asking himsef questions which go beyond medecine such as: does life have a future on this planet? Questions which have lead to the conclusion that not everything that can be done should be done. Since the modification of a plant's genome or of a unicellular organism's genome is tolerated, what about the human genome? In other words, are there barriers to put on living organisms? Should we have the right to experiment on humans in order to widen our knowledge on the human body? In the case of human clinical trials, ethical aspects are judged on the quality of the scientific protocol. It would not be ethical to use humans as tests if researchers are not certain to have exploitable results. Furthermore, the question of consent also needs to be adressed. While we cannot ask an animal or a plant for their consent, ethical commites insist on having a proof of consent in the European Union. This is particularly important since Anglo-Saxon scientific reviews refuse to publish papers if the have not been approved by an ethics commite. We can ask ourselves if the importance researchers give to Bioethics is truly personal or if they do not regard it as only constraint for publication.

When it comes to bacteria however, what point of view do we have? Humans generally have a vision of the world which is anthropocentric, we consider ourselves superior to other organisms. For example, during the Nuremberg trials against Nazi doctors, Carl Brandt (health minister and part of the German military) was sentenced for having lead experiments on humans in concentration camps believing that he was superior to them. When do these acts become wrong? Recently, in China, certain tests are being done on human embryos. Where should we draw the line for embryonic therapy? In Europe, questions of ethics slows down research on such topics but in Asia, research seams to be without limits.

How is the intellectual property defined in synthetic biology?

In sciences, the question of intellectual property is recurrent. Concerning synthetic biology, all of the objects used can be patented. Among these are genes, plasmids, biobricks, genetic circuit broads, software modeling of mechanisms etc. Thinking about patentability of live being is very important in synthesis biology because we use living organisms. Apposing a patent allows appropriating a technical invention, as a produce or a process. This statute permits to protect the invention, it’s also called the “invention patent”. To elude an amalgam between creation and scientific discovery, we’ll try to define the difference between these two values.
We can define a discovery as a revelation of what was previously unknown, but already being. Indeed, the scientific discovery is supported by study publications which are in free access for who wants it. So, we can consider it is a part of the common knowledge, ownerless. However, the creation is a process or a product which brings a solution for a particular problem. So it is a new element, previously a lacking element. An invention is supported by a patent. In our case, in synthetic biology, it can be a whole organism, a gene or a DNA sequence. The National Consultative Ethics Committee (CCNE) try to delimitate those processes, it makes impossible to take ownership of organisms already being, with informations which are just revealed and makes sure that a discovery won’t become an invention. Also, the patentability of an element won’t be possible when it was extracted of its natural environment to live in a synthetic environment, or an element which was reproduced in a synthetic environment, but already naturally being.
Here, it is a polemical subject because in synthetic biology, we are making “organic inventions”. So, there is a question: “Is it acceptable to be a living being’s owner?” “What about an interior component of it?” In this last case, whose belong the interest element? At the individue? Or at that one who modified it?

The relation to living and its simplification

With the emergence of synthetic biology, the definition of living may be modified. Indeed, in this field, researchers can generate or modify the genome of an existing organism, insert a whole artificial genome in an existing organism or create a new artificial organism. We can wonder if these modifications made by humans will not have an impact in the nature of the organism. Can we consider that an organism is living if it has been totally or partially created artificially? Synthetic biology regards the “objects” which are created as living beings because they are built from the cell, the basic unit of life. They have the property of self-organization and identical or similar self-replication to those of natural living beings. So we can considerate that they are “alive”.
With these "new" organisms, a living being may be considerate as simple and easy to create. Once decoding the DNA of a organism, synthetic biologist is able to do everything with a bacteria, a yeast or animals bigger, thinking that are like "machines". We can wonder if we can considerate life as a tool and find the limit between an ethical scientific project and an unethical scientific project.

In conclusion, these ethical considerations make us think about the ethical aspects of our project Cured Vine.
First, it is important to us that our project was related with transparency, so that uninitiated people can apprehend our scientific approach. Our Wiki, in free access on the WEB, allows us to clearly and concisely expose all the thinking steps which governed our Cur’dVine project. It also allows us to share our knowledge and results to as many people as possible. New iGEM teams or other researchers could use our results to continue our project.
Then, our implication in annex projects such as Cap Sciences, making street interviews about GMO's or high school presentations of synthetic biology, makes democratizing synthetic biology to the general public. All these actions incited us to think about the ethical questions that the general audience would wonder.
That help us to consider his profits and risks. Without being paranoiac, we have to think of all potential dangers that may create our molecule. The ethical aspects of our project are strongly link to safety, that's why more details will be in the next section.

Literature Cited:

[1] : 5e avis sur la biologie de synthèse. Comité consultatif commun d'éthique pour la recherche agronomique. INRA - CIRAD.(2014)

[2] : La révision des lois de bio-éthique. Vie Publique(2010)

Safety

To avoid confusion about the terms "biosecurity", "biosafety" and "biohazard", some people gave a definition of each of these terms.

- Biosafety describes principles, technologies and containment practices put in place to avoid accidents and unintentional exposure to pathogens and toxins.

- Biosecurity describes the protection measures put in place and management of important biological materials in laboratories, in order to prevent them from being accessed without authorization.

- Biohazard includes, in this case, both biosafety and biosecurity.

Reference : http://www.ambafrance-uk.org/Biosecurite-dans-les-laboratoires

The team who worked in the lab has received instructions of lab safety with safety training.

- We learned about acting in case of an accident, where to find emergency showers, fire extinguishers and emergency doors.

- Some requirements were discussed as wearing gloves and lab coat for most procedures. In some cases, during the use of ethidium bromide, nitrile gloves are mandatory. Other experiments must be conducted with safety glasses. It is also recommended to wear clothes offering a minimum of protection.

- We also learned about working with chemicals products and how to dispose of them. Most products used are classified as non-hazardous (even for the sulfation protocol). Chemical products are just irritants and so handle it with gloves. In the lab, there is a specific solvent cabinet for liquid wastes.

- Moreover, all biological waste will be autoclaved before disposal. All work is done on benches or under open-front hoods.

- We worked with non-toxic organisms as Escherichia coli (BL21) and Saccharomyces cerevisiae (Invsc1) but, all waste that has been in contact with bacteria was put to bacterial waste in aseptic conditions.

On another hand, our project intends to use a polysaccharide which is synthetically produced by our genetically modified organisms but it already exists in nature. This molecule is naturally present in yeast’s wall, and doesn’t have a bad known impact on the environment. Compared to copper sulfate which is a toxic compound this molecule seems to be more eco-friendly. Indeed, this metal isn’t biodegradable; used many times to treat Downy Mildew, it is accumulated on the soil and the vineyards are polluted. For worms and micro-organisms living in vineyards soils, this compound is toxic, so it alters the biosphere. The hydric and air erosion contribute to the diffusion of copper in the transfer of pollution.

Economy

A bit of French Touch

The production of Bordeaux is 6.4 million hectoliters with only 14% for white wines. More than 850 million bottles are sold every year and worth almost € 3.7 billion. Today, the red wines represent 86% of total volumes produced by the vineyards of Bordeaux, 89% of exports in volume and 92% in value.

The Bordeaux vineyard now covers 123,000 hectares for 270,000 hectares of farmland. The climate and the terroir is particulary favourable for a exceptionnal vineyard. Indeed, soils and Girondins basements are rather shallow. The Gironde, the Garonne and the Dordogne make the climate cool and provide the water needed by the vineyard. On the left side of the Gironde and Garonne, there is gravelly, sandy, clay soil made by the erosion of the Pyrenees. On the other side, soils are likely limestone wich is suitable for vineyard. The warm ocean current of the Gulf Stream accentuates the temperate climate and the Landes forest forms a protective shield against the winds of the ocean.

One of the caracteristics of the bordeaux vineyard is the great diversity of the grape variety, we can find lots of grapes :
Reds: Merlot, Cabernet Sauvignon, Cabernet Franc, Malbec, Petit Verdot.
Whites: Sauvignon, Semillon, Muscadelle, Ugni Blanc, Colombard.

Some mildew key figures

15 is , on average, the number of treatments that had to make a winemaker in 2012 to fight against mildew.
11 ° C is the minimum temperature required for initiation of primary infections in the spring.
€ 246 per ha is the average investment of a winemaker in France in 2012 for his fight against mildew.
4 days this is the optimal time necessary to complete mildew its entire cycle from contamination by spore until the following sporulation.
1878 is the year when the mildew , Plasmopara viticola , was observed for the first time in France.
Treatments against mildew have a cost that varies between € 50,000 and € 164,000 per year.

You can find on the vinopôle website the evolution of mildiou risk every week !

Over the last 20 years, no less than 3 mildew epidemics were recorded in France . These outbreaks have a direct impact on the production of wine. As shown in the graph below, represents the number of hL (millions) produced over time , production in 1998 , 2001 and 2006 dropped by over 50 % compared to previous years.

In 2010, each hectar or grapevine had received around 16 chemical treatments (this number was 15 in 2006) and varies greatly between regions. Amongst the biological threats on grapevine, mushroom parasites are far ahead of insects and fungi (12 fungicides are used against 2 insecticides and 2 weedkillers). Over 95% of the fongicide treatments in 2010 were due to mildew and oidium, sicknesses that are favorized by rain, humidity and heat. They bring the global quality of the wine down by reducing it's composition in phenols and sugars.
The risc of contamination on the leaves begin during the period where the floral buds and futur grapes are growing and lasts until the moment when the grapes touch each other. The sensibility period between oidium and mildew have common momments and vinyards don't heasitate to mix anti-mildew and anti-oidium solutions making the concentrations of these chemicals twice more concentrated in the grounds.
Downy mildew requires optimum conditions to reproduce and infect. A warm, moist, and humid environment is required. Studies in Sicily have shown optimum time for oospore germination is between the end of February and the middle of March. With this understanding, if fungicides are used just before these conditions occur, and have proven to be efficient measures. Other methods include proper watering, and a good location where the plant can receive continual sunlight.

What are the problems with these treatments ? Are they really efficient ?

To have a really efficient treatment what would we need?

iGEM Bordeaux !

Reference : www.oenologie.fr / www.vins-bordeaux-negoce.com / www.vignevin.com / www.vinopôle.com

Business time

SWOT ANALYSIS

Using Strengths to take Advantage of Opportunities

The reproducibility of our project and the high quantities of E. coli and Saccharomyces c. are in line with the future demand of vineyards.

Using Strengths to avoid Threats

The Curdlan ecological argue will convince biovineyards to use it. Indeed, we told you before that Bouillie Bordelaise wasn't good for the ground whereas Curdlan hasn't side effect on it.

Overcoming Weaknesses by taking Advantage of Opportunities

The Lack of expertise and our limited synthetic biology knowledge are overcome by our PhD presence.

Minimizing Weaknesses to avoid Threats

Being undergraduate and inexperienced team leaves us in a questionnable position compete against experienced laboratories. Moreover, our no recoil on the project may not be interested laboratories and societies.

iGEM Bordeaux: Contacting vineyards

To try to see the effect that mildew has on wine producers, iGEM Bordeaux contacted numerous castles in the region and attended the two biggest wine assemblies in Bordeaux: La foire au vin and Vinexpo. This allowed us to speak to the producers on how much their production is threatened by oomycetes such as mildew and to see if they would eventually be interested in an alternative preventive solution that would be eco-friendly. At the same time, this allowed us to search for sponsors in the region to raise money for our lab work.

to be continued ...

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          <img style="width:38vw;height:28vw;align:center;" src="https://static.igem.org/mediawiki/2015/e/e0/Bordeaux_Ethics.jpg ">
          <p align="justify" style="text-indent: 3vw;"> When Mr Potter, American oncologist and surgeon, invents the word <b> ethics </b> in the 1970's and writes his book <i> Bioethics: a bridge to the future </i> he pioneers the questions to come asking himsef questions which go beyond medecine such as: does life have a future on this planet? Questions which have lead to the conclusion that <b> not everything that can be done should be done.</b> Since the modification of a plant's genome or of a unicellular organism's genome is tolerated, what about the human genome? In other words, are there barriers to put on living organisms? Should we have the right to experiment on humans in order to widen our knowledge on the human body? In the case of human clinical trials, ethical aspects are judged on the quality of the scientific protocol. It would not be ethical to use humans as tests if researchers are not certain to have exploitable results. Furthermore, the question of consent also needs to be adressed. While we cannot ask an animal or a plant for their consent, ethical commites insist on having a proof of consent in the European Union. This is particularly important since Anglo-Saxon scientific reviews refuse to publish papers if the have not been approved by an ethics commite. We can ask ourselves if the importance researchers give to Bioethics is truly personal or if they do not regard it as only constraint for publication. </p>
-         <p align="justify" style="text-indent: 3vw;"> When it comes to bacteria however, what point of view do we have? Humans generally have a vision of the world which is anthropocentric, we consider ourselves superior to other organisms. For example, during the Nuremberg trials against Nazi doctors, Carl Brandt (health minister and part of the German military) was sentenced for having lead experiments on humans in concentration camps. When do these acts become wrong? Recently, in China, certain tests are being done on human embryos. Where should we draw the line for embryonic therapy? In Europe, questions of ethics slows down research on such topics but in Asia, research seams to be without limits. </p>
+         <p align="justify" style="text-indent: 3vw;"> When it comes to bacteria however, what point of view do we have? Humans generally have a vision of the world which is anthropocentric, we consider ourselves superior to other organisms. For example, during the Nuremberg trials against Nazi doctors, Carl Brandt (health minister and part of the German military) was sentenced for having lead experiments on humans in concentration camps believing that he was superior to them. When do these acts become wrong? Recently, in China, certain tests are being done on human embryos. Where should we draw the line for embryonic therapy? In Europe, questions of ethics slows down research on such topics but in Asia, research seams to be without limits. </p>