Team:Evry Paris-Saclay/HP/Silver

IGEM Evry Paris-Saclay

Human Practices: Silver

First things first, the human practices are intended to present the project to society, in a safe and responsible way, to bring something new and innovative to people by answering a societal issue.

Diabetes Prevention

During our brainstorming sessions, we explored a lot of fields and areas reviewing global health concerns. We then decided to focus on an issue that spoke to all of us: Diabetes. Nowadays, research spends a lot of time and money to cure this complex disease. Currently, there are no treatments against such a disease. Most treatments cure symptoms, trying to improve the life of diabetic people. As we noticed on our Human Practices FrontPage, the number of diabetics is increasing and tends to double by 2025 to reach 330 million people which nearby represents 1 in 14 people (6,3% of world population). Conclusions of the WHO are alarming, Obesity, Atherosclerosis, Cardiovascular Diseases, Dementia all create favourable context for Diabetes. To contain the epidemic, prevention is the only way to help people become healthier. The main issue in such diseases is overconsumption of fats and sugars. To better understand consumption, we interviewed people in Paris around the theme of sugar to know their food habits. It appeared that people were aware of the dangers of overconsumption but were addicted to its taste.

This in mind, we began our research on possible sugar substitutes that could prevent from such bad consequences in the controversial world of sweeteners. These molecules mimic the taste of sugar but are mostly not metabolised in our bodies. However, some can be split into toxic molecules such as the most common Aspartame that decomposes into Methanol which is a neurotoxic substance. Others are suspected to be carcinogenic or unexpectedly involved in Type II Diabetes because their sugar taste is too sweet and addictive.

At this point, we understood that a good alternative to food sugar would be a natural sugar which contains nearly 0 calories: a whole new category of natural sweeteners. Some already exists like the Stevia, but the problem with those is that its sweet taste is still high and it’s not very well liked according to our survey that we conducted in France (Click here to fill the survey). The taste of sugar is defined by the sugar power, a subjective relative scale defined around the taste of food sugar which stands for 1. Stevia for example has a sugar power near 300. Most sweeteners contain either too much sweetness or deleterious effects (Click here to find out more). One sugar stood out thanks to its amazing properties. Psicose is presented in studies as a sweetener with 70% of the sweetness of food sugar, has no cariogenic effect, slows down the absorption of other sugars and preferentially induces fatty acid metabolism. All of these properties made this sugar the perfect one for Diabetes prevention and even Obesity.

To learn more about specific needs of diabetics and to discuss the relevance of Psicose compared to other sugars we chose for a diabetic diet, we met Mr. Bastien Roux, Business relationship Manager in the French Federation of Diabetics in Paris (Click here to see how we turned it into integrated human practices).

Manufacturing Process: Economic Context around Psicose

Confirmed by our interview with Mr. Roux, we continued on the track of Psicose. Further, we investigate in the human practices the current state of Psicose production. As a matter of fact, Psicose is present in very low quantities in plants so we call it a rare sugar and it cannot be produced profitably this way. The fun part is that Psicose is a simple epimer of Fructose. So, this slight conformational Carbon change is therefore the cause of all Psicose properties. Another fact, this slight change raises tremendously the cost of the sugar. Food sugar from Great Value for instance costs $3.06 per lb in Walmart whereas Allulose (the other name for Psicose) costs from $35.99 per lb that is to say an increase of rather 12 times the cost. The price of Psicose is expensive because this molecule is currently chemically produced at low yield. Moreover, Fructose epimerisation is quite complex (See details on our Scientific Project Part) but also produces Glucose, Mannose and other sugars reducing the yield of production.

In order to make Psicose accessible for diabetics, we decided to work on its bioproduction looking for an enzyme that could perform the epimerisation. Bioproduction is a common process in life that men have exploited without even knowing it since the dawn of humanity to produce wine, bread, yogurt and other food. This empirical use of these living organisms has slowly become industrial when biotechnologies and biomanufacturing started to develop alongside our knowledge on microorganisms.

There are different bioproduction techniques from bioreactors to the cell-free system (Click here to find out more). Scientists of the team searched the literature to find a bacterium able to produce Psicose: Agrobacterium tumefaciens (See details on our Scientific Project Part). Bacteria used in bioproduction must be Generally Recognized As Safe (GRAS) which is a title given to organisms by the Food and Drug Administration in the USA to the bacteria that does not produce toxins nor food poisons.

Legal Investigation: Psicose Allowance

The project set, we have decided to go beyond the competition. To provide diabetics with our natural sweetener our lawyers aimed to better understand how to place it on the market. Surprisingly, it must be mentioned that Psicose is not authorized/produced in food industries in Europe. Our lawyers then investigated the legal issues surrounding the use of Psicose. Before any legal research, lawyers had to legally qualify the molecule of interest. It was great to see scientists and jurists of the team working together trying to understand each others issues. Psicose can be legally qualified as a sugar or a sweetener depending on whether it substitutes another sugar in food or is a food additive. In both cases, legal procedure to allow it is different. According to our lawyers, the food additive aspect was the simplest to investigate.

In Europe, the placing on the market of such a molecule is ruled by the European Commission. This commission of lawyers and attorneys appeal to the European Safety Food Authority (EFSA) as a scientific authority to check whether the molecule of interest presents a health risk or not. By default, any molecule which did not undergo a demand to the EFSA is not allowed nor produced on the market. This explains why Psicose is not allowed yet. Our main jurist, Maxime, wrote an entire dossier about Psicose legal issues (Find the complete file here)

We had several discussions with the EFSA to learn the scientific criteria we needed to complete the dossier. The society that wants to put a new molecule on the market must fill in a file concerning the characteristics and studies about the molecule and its effects. Animal experimentations must support the data to be followed by human trials.

We then determined the chemical identifications of the additives, its manufacturing process, the methods of analyses, the proposed uses and the toxicological data. This information helps the EFSA to determine the acceptable daily intake. There are several additional conditions such as the improvement of the quality or the stability of food and ethics.

This procedure is quite long and can last several years. As a matter of fact, the application process goes back and forth through different organisations. In Europe, the European Commission after consultation with EFSA addresses the application to the French National Food Safety Agency (NFSA) which allows it to be placed on the national market. Then, food monitoring and marketing is controlled by the French Directorate-General for Competition, Consumer Affairs and the Prevention of Fraud (DGCCAPF) that can withdraw any substance from the market if necessary after a justified complaint alongside the NFSA.

Industrial Application: Improvement of Bioproduction

Our first results of Psicose bioproduction presented a low yield but still better than the chemical one. Unlike the chemical method, bioproduction of Psicose can be improved given that it’s biologic so can be under control of gene expression or mutagenesis as we performed to create a whole mutant bank of epimerases to find the one with the best yield of production. (See details on our Scientific Part). We had several discussions with specialists in bioproduction that introduced us to mutagenesis. Then, we decided to generate a bank of mutant epimerases to find an enzyme with a better yield. In industries, biologists and PI informed us about the difficulties in enzyme screening. Characterising enzyme efficiency and activity is difficult, time-consuming and requires expensive equipment such as mass spectrometer or chromatography machines. The team decided then to have an appointment with a specialist in bioproduction, Dr. Alain Fournier from Sanofi-Aventis, to discuss possible ways to improve the bioproduction methods that the team developed: the bioscreening system (See details on our Scientific Part). The conversation we had with this specialist helped us to develop and improve our bioscreening system to be more user-friendly (See how we turned it into integrated Human Practices)

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