As all research project, NeuroDrop followed its own development; initial ideas changed according to encountered learning and difficulties, but also to people we met outside the lab. All these people are recognized as expert of their field. We met them to assess our project’s viability and make it grow according to the expectations and constraints of actors involved. Thanks to their opinion, NeuroDrop became what it is today. When the team demonstrated its interest to work on tears and Parkinson disease, we looked straight for a professional opinions. The aim was to check the general viability of initial ideas before beginning manipulations in the lab. We started with Elena Moro.
“Alpha-synuclein alone is not viable as a diagnosis biomarker, however neurodegenerative diseases are a growing health issue. Most of them still don’t have curative treatment so every research project could be of use to any future breakthrough.” Elena Moro studied medicine in Italy. After a thesis, she left for Toronto to start her career as assistant professor before becoming a lecturer. She came in France as a specialized professor in neurology. She leads now the Movement Trouble Unit at Grenoble’s CHU and the Parkinson Expert Center. She is also a researcher at GIN and works on deep brain stimulation. Experimentations in the lab haven’t started yet when we met Elena Moro. The lack of ripeness of the project allowed her to adopt a critical point of view: her advices have been decisive for NeuroDrop’s development.
Once we defined a viable direction to our project, the team had its first big hesitations: should we manipulate by following the proven method or should we go off the beaten track? Should we use antibodies or aptamers? We met experts of each part to chose the most appropriate method to reach our goal.
“You could use antibodies but regarding your projects constraints, using aptamers would give you better flexibility at lower cost.” Corinne Ravelet did not have a clear representation of biotechnologies, that she defined as “the use of biology with a little more technicity, gathering technicals related to life and chemistry”. However, she clearly perceived hidden stakes behind its development. She agreed an ethical approach is necessary although she has never worked with researchers from social sciences and admitted her difficulties to picture such a collaboration, she thought it would help to frame biotechnology’s development. Before starting her interview, she laughed and told us another iGEM team contacted her to benefit from her pieces of advices on aptamers. According to her, using aptamers for our project was full of advantages..
“Aptamers are closer to a swiss knife than an final product.” Audrey Le Gouellec is currently working for the TIMC laboratory, an interdisciplinary research center where she works on molecular dialogue between human organisms and their microbes. She is also a teacher in School of medicine at the University Grenoble Alpes. Throughout the year, Audrey was our supervisor and gave early pieces of advice to help us. Moreover, she is a supervisor for the Grenoble team since several years. Her experience and knowledge regarding the competition was extremely valuable to us. We had a debate with Audrey about the definition of “synthetic biology”. According to her, aptamers are about synthetic chemistry: they are not specific to synthetic biology. Antibodies might be an interesting alternative proper to synthetic biology techniques, within the biotech field. Aptamers might be an efficient tool with high specificity, for the detection of biomarkers but developing a specific aptamer for a specific protein is a very complex and uncertain process.
Six months later in early september, we met Audrey Le Gouellec a second time. She said she was almost convinced by the way we used aptamers in NeurDrop. In our project, even though aptamers are not living entities, we’ve added a functionality to our bacteria: in such a configuration, it is currently changing these organisms “in a synthetic way.” After we chose to go for aptamers, we started wondering about the commercial opportunities for our project: an economic approach is necessary to sell and use a medical device. On top of these concerns, we started to focus on the ethical dimension of our project. While we read about neurodegenerative diseases and explored the contributions of transdisciplinarity within research teams for the Education and Public Engagement Award, one question came back quite often on the table: Is it ethical to announce a diagnosis for incurable diseases?
“If social scientists as psychologists, sociologists… would have been in the team, maybe they would have directed us. Maybe we could have avoided - or at least reduce - the violence of the trauma caused by this super-fast diagnosis.” Isabelle Pelletier works since 30 years in life sciences. After studying law, she started her career at Sanofi as a legal expert and as vice-president of the diagnosis branch. Then, she co-founded Cellectis, a start-up specialised in enzymes and DNA where she was in charge of business development. Seven years later, she joined the Gustave Roussy Institute as Head of Innovation and development department where she helped start-ups to scale up, consortium to grow… She is now CEO of Atleva Conseil, a consulting company helping young entrepreneurs to develop their activities. According to her, synthetic biology suffer from a bad representation among the society. “People associate GMOs to processed food” as a little experimentation demonstrated her: when she asked a woman randomly met in a train if she would ever eat DNA, she answered an outraged “No! Never, are you mad ?!”. In her opinion, her reaction was representative about a huge lack of education, especially when it comes to therapeutics GMOs that can save lives. Her experience demonstrated how integration of humans, economics and political stakes in medical projects is essential. When she worked at the Gustave Roussy Institute, she worked on project designed to speed up female cancer diagnosis. Thanks to this project, patients could have known within a day either a tumour was malignant or benign. For most of the researchers authorized on the project, the faster the diagnosis was made, the faster treatments could begin. But when women were told within a couple of hours they had cancer, they had not enough time to accept the diagnosis: the announcement within a day “costs” 3 weeks of treatments, but the announcement is much more violent than a diagnosis that goes through several tests and weeks of anxiety. “If social scientist as psychologist, sociologist… have been in the team, maybe they would have directed us.”. However, she also pointed out that transdisciplinarity within research teams was not easy. As a lawyer working in biotech, she experienced some difficulties to work with scientists. She thinks that the main project’s strength is the pluridisciplinarity of the team.The fact that no curative treatment for Parkinson and neurodegenerative diseases exist today is deeply linked to a complex ethical issue regarding the diagnosis of incurable diseases. Beyond this ethical question, she was convinced by our project. She raised some critical points we needed to clarify before considering a commercial development: when and how is our test designed for? For what kind of professionals? How will it help? And what about intellectual property concerns? After answering these questions, we were ready to realize a market study and consider a clinic validation. Aptamers might be an efficient tool with high specificity, for the detection of biomarkers but developing a specific aptamer for a specific protein is a very complex and uncertain process.
“As innovation is not though on a collective scale, people tend to accept existing innovation - or future ones - without considering it could have been different. It’s true, people tend to naturally accept an innovation: with no upstream reflexions, it could get dangerous. We can achieve great things with biotechnology, but we have to think about how they will be used.” Mélanie Marcel studied at ESPCI, one of the biggest french engineer school specialized in chemistry in Paris. After her first work experience in Japan, she realized how research and technical sciences were disconnected from societal issues. She decided to create her own company specialized in Responsible Research and Innovation in 2014. SoScience is a start-up working with industrials and research institutes to promote a collaborative and inclusive research, linked with social and environmental issues. As expert of responsible innovation, Mélanie Marcel is aware of challenges raised by the development of biotechnology. She has a positive vision of biotechnology, that she describes as the scientific field of the XXIst century: “historically, we’ve known chemistry’s development followed by the one physics. This century is the ones of biotech.” In full expansion, it is also a sector that has known major scientific and social controversies (GMO, CRISPR…). The global population is not aware of these development and how they can be used. In the current context, biotechnology are not designed to solve or prevent societal challenges. Ethical communities are supposed to frame their development. But they often lack of resources and power to do their work properly, as they tend to respond to technological developments instead of frame them. Pluridisciplinary research teams are essential to scientific innovations. SoScience organized open innovation programs where social scientists are encouraged to participate. They brought new approach and questioning to the debate by encouraging technical scientists to think their research from another point of view. According to her, there is a real need for faster diagnosis regardless the diseases but she warned us about the “hype” that can generate such tools: people could come in droves to get tested, which would waste time and money that should be properly allocated. When we presented her our will to highlight the value of interdisciplinarity within research teams, she seemed very interested. She went ever further by telling us interdisciplinarity should be integrated as soon as possible at school and maintain in higher education program, regardless the discipline. The sooner transdisciplinarity would be encourage, the less disdain will be found between disciplines:“if only scientists would admire great names of social sciences, things would be different.”
“Our current economic model is based on petrochemistry, the intensive exploitation… it is precisely why biotechnology can represent great hopes, especially to cut off our dependencies. If you watch the ecosystem balances, we can develop a healthy economic model.” Thomas Landrain is already familiar with iGEM: he was one of the members of the first team during his student years. After his thesis on synthetic biology in a laboratory he created himself, he realized he could not work with people from other research field. Then he created La Paillasse, a non-academic lab in a parisian squat. This new laboratory allowed him to work on ink production from bacteria and created PILI, a start-up specialized in ecological coloration. In 2017 Thomas chose to leave La Paillasse to develop Just One Giant Lab, an online platform aiming to make research accessible and create scientific collaboration for tomorrow. As former iGEM participant and doctor in bacteria ribo-switch, Thomas has a sharp knowledge on biotechnology. He started to explain potentials and possibilities unlocked by biotechnology, especially the one of synthetic biology which can, in his opinion, reconcile nature and technology. But “as they allow us to have a look on what compose us”, the setting of strict ethical framework is needed. People are sceptical regarding biotechnology because they are more frequently exposed to damages caused by the industrial approach of biotech. However, he thinks “mission companies” will emerge with a social/environmental purpose and will change this common opinion. This switch could occur if citizen are involved at the relevant time in biotechnology development. “But how can we build inclusive ecosystems? How can we create new format to include different type of communities?”. While bearing in mind that technology alone cannot solve big societal issues, “we need to adopt a complex point of view to undertake challenges to come and create a new decision-making process based on participatory democracy.” After introduced him the project, he started to ask questions about the project: do we really make the diagnosis process easier? Do we make it less difficult for the patient? If this technology is modular, how can we prove its reproductive capacity? On a technical point, he drawn our attention on extracellular methods to test our aptamers. According to him, cell free system are more stable, practical and handy. This method is more and more popular for diagnosis purpose as it allows to decrease noise. His last advices were specific to the competition: “you should demonstrate your will to enrich the iGEM spirit through a good Human Practices approach, strong collaborations… you should show your will to mark the competition!”
Juliette Verseux
Arnaud Le Tiec
Juliette Verseux is freshly graduated from Biotech Paris. After an internship at CEA on cell tech model applied to neurodegenerative diseases and “mini brain”, she joined the BPI for her last internship at the direction of high technology innovation expertise, at the “Ecotechnologies” department. Arnaud integrated Les Mines Saint-Étienne with a specialization in biomedical engineering. After his internship in a prosthesis company, he spent his last internship at BPI in the same section as Juliette, at the “Health and Deep Tech” department. When Juliette defined biotechnology as “the use of life for industrial, societal or health purposes”, Arnaud underlined the difference between biotech oriented toward chemistry, and medtech related to technological innovation within the medical sector. Juliette claimed she is not afraid of biotechnology: according to her, the mistrust from citizens is coming from “the demonization” of GMOs in media. Arnaud agreed and added the importance of education: “the word “biotech” is very often used by media and I think we retain more easily a word that inspire us danger, manly because we don’t know them.” We asked them about the level of transdisciplinarity within team that submit project to the BPI. Social sciences are poorly represented: there is more and more collaboration of experts on projects to meet criteria fixed by the BPI but it is mainly between technical scientists (collaboration of researchers specialized in neurodegenerative diseases and data scientists for example), although “personalized medicine development will necessite experts from differents formation, including social sciences” said Juliette. As innovation experts at BPI, we asked Juliette and Arnaud to evaluate our project as if we applied at funding program from the public bank. While they assessed NeuroDrop, they explained us how they proceeded. To benefit from a grant, the project must meet the requirements described in the grant notice, show some market possibilities and of course meet all the legal requirements. The project is evaluated according those criteria but the composition of the team is also judged: are members qualified enough? Is there a business profile among the team? Do they get on well? On this basis, they advised us to check technical details, patient’s interest, ethical concerns, intellectual property matters and to check if our test would generate financial gain to the french wealth care system.
Pauline Armand worked as an innovation manager for various organizations. She has a master’s degree in innovation management. She has experience in the management of R&D innovation and started working for MEDICALPS two years ago. MEDICALPS is the healthcare industry cluster in the French Alps (medtech, biotech, e-health). It gathers more than 105 members; most of them are start-ups and SMEs which are designing and developing medical devices. The cluster has also the support of large companies, research centers, universities and the public authorities. MEDICALPS is delivering support and advices regarding market access, business development and industrialization issues through a network of experts. Pauline Armand sees biotechnologies through the prism of medical innovation. She didn’t make any value judgment regarding this sector. On the contrary, she immediately focused on technical details of our project. Her advices were precious, especially for engineers. She asserted that any engineer working - in particular, for the medical sector - have to master reglementary processes. It takes time and can be deadly for the project if not managed correctly. Our project was really interesting to her but she told us to precise our thought regarding the project’s development: to whom do we want to sell it? For how much? The price is a major variable for the launching of our device on the marketplace. She also advises us to interrogate a KOL (Key Opinion Leader) to have the point of view of professionals on our device.
After these enriching meetings and discussions with experts, we understood that biotechnology innovations is not only about having great ideas and creating them. It is also about making them manageable on the industrial scale and suitable for the entire society. While we were deepening our reflection about innovations, engineers met some unexpected issues with the device. We decided to take advantages of the Grenoble ecosystem and meet Yves Fouillet, a recognized expert of Electrowetting on Dielectrics, to test and improve our project.
“EWOD is not a widespread technique in medtech: its main application is for high resolution screen.” Yves Fouillet is one of the biggest experts in Grenoble on EWOD (Electrowetting on Dielectrics). After his thesis on fluid mechanics at ENS Cachan, he joined the CEA LETI in Grenoble to develop pressure sensors for printers. In 2002, he started a big research program on EWOD for health applications. Since almost 10 years, he works closely with Advanced Liquid Logic, a pioneer in EWOD redeemed by Illumina. To make the EWOD works better, Yves Fouillet gave us three pieces of advice:
For the manipulation, he also told us that he used alternative currents for his measures, at relatively high frequency (3kHz). However this is not feasible with the chips we used.
While ethical questions raised by our project remained unsolved, we decided to keep exploring this wide and difficult field with Anne-Marie Benoit.
“Tears are Rest Nillus objects. First of all, you have to comply with the legal framework on this matter.” Mrs Benoit started to work on the computer law and freedom domain, which is a really dynamic field of research in the European Union. Through the years, she got interested intellectual property questions, especially regarding Health sciences. Mrs Benoit is the vice-president of the ethical review board for the protection of people in clinical research. Mrs Benoit is enthusiastic regarding the major advancements made by medicine every year. Nevertheless, she is declaring herself as a sceptical person and tend to show resistance to research project without clear purposes and guarantee of utility. Experimenting on human beings has to be regulated with rigor. She is open and curious of the progress made on the Health sector, but she pays as much attention on staying aware of the consequences of “the global rush forward” of science. When we presented her the project, she was enthusiastic by the scientific aspect of the project but also of the integration of social sciences students to the team. For her, this a major asset as our project as various “dark spots” on the legal and ethical sphere.
After her interview, we realized ethical question cannot be solved. There are “no ending questions” with answers that vary in time and space: it is impossible to provide a clear-cut answer. The best we can do to move our project forward is to show to the society we are aware of those issues, allowing nevertheless to draft solutions to improve project’s viability. We have to show that we saw and understood risks triggered by our project and fully explain how we will managed them. That is why we went straight to Thierry Bontems.
“When you present your project to potential investors, showing them you’ve not only identified but also worked on managing risks is a guarantee of professionalism.” After graduating from the Grenoble Ecole de Management (Grenoble Graduate School of Business) and a master’s degree specialized in strategy, Thierry Bontems joined the CNRS. He is now a researcher, risk analyst and a teacher in the Grenoble School of Management. He helps evaluating risks and also delivers training to entrepreneurs to help them manage risks with accuracy. He works around the world for a wide variety of projects. Beside its main activities, he works on developing a project management tool (the Avoid project) available in Open Source. He offers to help us analysis the strengths and weaknesses of Neurodrop. He is keen on the idea of transmitting his knowledge and experiences. Mr Bontems was really interested in NeuroDrop. He found our project complex and challenging. He immediately highlighted several risks and quality issues linked with it and suggest to work more deeply on our SWOT analysis to establish a cartography. The latter will be established through the Avoid Project program designed to present a project to potential investors, exposing its risk management. The tool helped us to consider the project on its globality and being fully aware of its risks and potential. We let you review our risks cartography and the SWOT we made below !
“A mathematical model helps in the study and assimilation of the mechanisms of biological systems” Delphine Ropers is a researcher in molecular biology. She has a master degree in microbiology, enzymology and Nutrition. Then, she made a thesis in molecular biology on HIV. Mrs Ropers is working in the Inria (National Institute of Computer sciences and automation). Her research work consists in modelling and analyzing cellular regulation system in bacterias. She is experienced in mathematical modelling of biological systems (qualitative and quantitative models). Ambitious project and interesting research that can help in the future of diagnosis. The project is a bit complicated to finish it in a year of work. It would have been better if we had started the mathematical modelling of the system at the beginning, so that it can help us to adjust the ideas and the methods used in a highly effective way, and we can test it and validate it with experimentation. To create a model, we first have to define what we want to know and to study; do we want to create a descriptive, dynamic or kinetic model? The needs we face determine the type of model to choose. In our case, in which we want to model the relation between the concentration of the alpha synuclein protein in the sample and the production of bioluminescence, a kinetic model seems to be the best solution. We then have to simplify the interactions in the biological system by considering lots of hypotheses that need to be backed up by an experimentation phase or at least solid bibliography. Once the model is executed, we can add more complex considerations to get more accurate results. We let you review our risks cartography and the SWOT we made below !
After a year of inquiry outside the lab, from Grenoble to Paris and Amsterdam, we are amazed by the way NeuroDrop has turn into. We met scientists, researchers, jurists, industrials, business developers… to get their opinion on the reliability, but also the sustainability and the inclusiveness of the project. The funny thing is the more people we met, the more we discovered issues we had not foreseen at the very beginning of the adventure and for some of them, not even imaginated. We have discovered how deep ethical questions can be, how important it was to realize a risks cartography. Their advice challenged us to better design our device and make it more suitable for real uses. Thanks to them, we have not only enriched our initial idea but also our own knowledge. We are well aware that projects can always be improved: ours does not expel to the rule, we simply had to make choices within time and money constraints we had. We wanted to thanks all these interesting and passionate people for their time, the knowledge they shared and their contribution to our project. Thanks to them, we are proud to present NeuroDrop has it is today.IHP Interview Analysis
Elena Moro
Professional background
Opinion on NeuroDrop
Lessons and implementations
Corinne Ravelet
Professional background
Opinion on NeuroDrop
Audrey Le Gouellec
Professional background
Opinion on NeuroDrop
Lessons and implementations
Isabelle Pelletier
Professional background
Opinion on biotechnologies
Opinion on NeuroDrop
Lessons and implementations
Mélanie Marcel
Professional background
Opinion on biotechnologies
Opinion on NeuroDrop
Lessons and implementations
Thomas Landrain
Professional background
Opinion on biotechnologies
Opinion on NeuroDrop
Lessons and implementations
J. Verseux & A. Le Tiec
Professional background
Opinion on biotechnologies
Opinion on NeuroDrop
Lessons and implementations
Pauline Armand
Professional background
Opinion on biotechnologies
Opinion on NeuroDrop
Lessons and implementations
Yves Fouillet
Professional background
Opinion on NeuroDrop
Lessons and implementations
Anne-Marie Benoit
Professional background
Opinion on biotechnologies
Opinion on NeuroDrop
Lessons and implementations
Thierry Bontems
Professional background
Opinion on NeuroDrop
Lessons and implementations
Delphine Ropers
Professional background
Opinion on NeuroDrop
Lessons and implementations
NeuroDrop