Team:Nantes/Human Practices

Integrated Integrated

Part 1 : The problem of polymedication

« How could Synthetic Biology help you in your everyday life? » was the question we asked people around us while we were still in the brainstorming phase of our project. We asked many different people this same question but one answer hit home a little harder than the rest. Our grandparents mentioned the problem of polymedication. As our loved ones grow older, they often find themselves needing more medical assistance which is given, in most cases, in the form of pills, that greatly resemble each other in shape, size and color. This leads to confusion which, in turn, can lead to medication errors by omission or overdose. Some of them expressed that they felt like nothing was being done to treat this issue that they had been living with for years.

So we decided to dig into this idea a little bit more , and we discovered hundreds of papers describing medical errors as a public health problem. Here are a few numbers we found on this subject :

of medication errors resulted in an undesirable effect between 2013 and 2017, 50% of these were considered serious (2) .

of those medication errors are due to an error during the administration phase in France (3) .

is the annual cost of medication errors in the world estimated by the World Health Organisation (WHO). According to the WHO, medication errors cause at least one death every day and injure approximately 1.3 million people annually in the United States of America alone (4) .

(1)"Good practice guide on recording, coding, reporting and assessment of medication errors” European Medicines Agency, 23 October 2015, Pharmacovigilance Risk Assessment Committee (PRAC)
(2) Les Erreurs Médicamenteuses en ville ; Nathalie GRENE – LEROUGE, Patrick MAISON ANSM
(3) ANSM : Agence nationale de la sécurité du médicament et des produits de santé. Guichet Erreurs Médicamenteuses, june 2009
(4) Delivering quality health services: a global imperative for universal health coverage. Geneva: World Health Organization, Organisation for Economic Co-operation and Development, and The World Bank; 2018. Licence: CC BY-NC-SA 3.0 IGO

When discussing our research with Dr. De Marguerye, he agreed that medication errors were an underestimated issue. He told us, « Many people are hospitalized each year because of medication errors. I once treated a polymedicated elderly man who had been mixing up his cardiac deficiency pill with a sleeping pill. This man had been taking 3 sleeping pills a day and ended up at the hospital in a semi-coma. »

After we had exchanged with healthcare professionals who informed us on the most common medicine used by patients, and their associated diseases we decided to try to make a patch that would deliver the different types of medicine at different times and dosages throughout the day.

We wanted to discuss the idea of a patch further in detail with more healthcare professionals. The nurse Catherine Woyciechowski was excited with the idea of making patients more autonomous. In fact patches that deliver medicine already exist, in the treatment of cardiac deficiency, but they require a qualified person to change the patch at least twice a day.

Dr Dassonville also seemed quite enthusiastic about our idea, « A patch capable of a sequential medicine delivery is a very interesting idea because it does not yet exist on the market. » but he also added « such a patch would come with risk of infection » .

This remark made us rethink the theoretical design of our patch. We came up with a transdermal patch that would have a semipermeable membrane allows the medicinal active substances through at a constant speed while retaining the bacteria inside the patch.

These conversations also allowed us to pinpoint 2 main fear factors. A few of the polymedicated patients were a bit wary of using bacteria in the administration of their medicine and were worried about bacterial infection. This made us consider the worst case scenario. What if, despite the semi permeable membrane, our bacteria leaked out of the patch and into the public environment? This questioning allowed us to consider a kill-switch system, developed in the Safety page of our wiki, which would induce the death of a bacterium once it has expressed the desired genes.
The second fear factor, brought up by one of the doctors we met with, was the fear of the transfer of plasmids between our bacteria and other “wild bacteria”, which would in turn transfer antibiotic resistance. We decided the best way to prevent this from happening would be to design a toxin/antitoxin system that we also explain in further detail on our Safety page.

Part 2 : The position of Women in Hard Sciences

Professor Patricia Lemarchand

In studying the issue of medication errors we discovered another problem. When discussing Professor Patricia Lemarchand and Professor Pascale Kuntz we were made aware that statistical studies for the making of prototypes in science are performed mostly on men, and female data is often ignored in these studies in areas such as drug posology (1). The issue is that sex and gender differences between men and women alter drug activity, including pharmacokinetics and pharmacodynamics (the movement and effects of a drug in the body). The result is that women are 50 to 75 percent more likely than men to experience an adverse drug reaction.

« Over the past twenty years there has been a strong study of gender equality in the scientific domain originating in the United States, but it is just now arriving in France. This implies that diseases have mainly been described in men and drugs have mainly been tested on men. In doing so we miss some specific feminine characteristics which has significant consequences on public health. »

We read that transdermal patches were affected by temperature (2). To come back to our project, in researching the development of our main application, the biomedical patch, we discovered some studies suggesting that the average skin temperature significantly differs in between men and women (3). Even though there is a lot of debate (4) around this subject we decided to first of all test our tool’s sensitivity to temperature to know if it’s efficiency would vary with this possible change of temperature and second of all choose a position on the body where skin temperature is the same in men and women to apply the patch : the forearm.

But we decided to take this issue to another level. We built a survey that we sent out to our local scientific community on the position of Women in hard Sciences. We received 178 answers and carried out a statistical study on these answers that you can find here. We also met up with 6 professors of our University to have their opinion on the subject. You can find a summary of these interviews here.

Book Women on Sciences

(1)“Sex-based differences in drug activity.” - Lindsey W. Am Fam Physician. 2009 Dec, PMID: 19961138
(2) “Heat effects on drug delivery across human skin” Jinsong Hao, Priyanka Ghosh, [...], and Sam G. Raney, 2016 Jan 25, PMID 26808472
(3) “Effect of body fat and gender on body temperature distribution” Eduardo Borba Nevesab, Ana Carla Chierighini Salamunesa, Rafael Melode Oliveirab, Adriana Maria Wan Stadnika; Elsevier, December 2017
(4) Cyril Labbé, Dominique Labbé. Analyser les questions ouvertes dans les sondages. Comment con- vaincre ? Analyse scientifique de la campagne électorale 2012, Mar 2012, Grenoble, France. halshs- 00709115

Analysis of open questions surveys :

Part 3 : A change of thought

When we researched how could control gene expression in time for our patch, we stumbled across the article “Hierarchy of non-glucose sugars in E.Coli” "by Dr. Guy Aildeberg et al" which would prove to be the foundation and main source of inspiration for our project.

And where best to start the elaboration of our lab work than to speak to the master himself? And that is exactly what we did, we met up with Guy Aidelberg in Paris to talk about our idea and get his advice on the project. Thanks to this, we learned the best conditions in which to study and use the secondary sugar hierarchy we wanted to use for our project.

Around this time we had started presenting our project in scientific conferences, and going to scientific events where we were able to exchange with scientists from many different fields on our idea of controlling gene expression in time with the use of sugars. We received a lot of positive feedback from our local scientific community and a lot of new application ideas for our biological machine.

For example our tool could provide an alternative to the use of costly inducers such as IPTG. It would allow growth of bacteria on glucose until they reach the optimal cell population. Once all the glucose is consumed, the transformed bacteria would start the expression of pathways leading to the production of a compound of interest.

This broadening of prospects challenged us. With such a large spread of applications should we focus on building a patch, or should we focus on building a tool that could be used for many different purposes?

This questioning brought us to the decision of shifting from a specific application, the patch, to a fundamental tool.