During the year where President Reagan started his famous tax cut, I was a master student in Biochemistry at Univ. Paris 6- UPMC,  lucky to learn the concept of protein allostery from a great professor, Daniel Blangy. Years before, he was one of the PhD student of Jacques Monod at Institut Pasteur, helping him with Henri Buc to discovering this elegant concept at a time where most of the Parisian students were protesting in the street asking for peace and love. Allostery is a simple biomolecular concept explaining that a protein can switch between an inactive and an active state under the cooperative control of a third party. This curiosity-driven discovery totally changed the understanding of how a protein works in a cell and inspired many innovation projects in pharmacology. Still today! At this time, research was not supposed to present final data that had to fit with the initial goals in order to respect the granted project. Just to develop the most brilliant ideas in progress!

Very recently, six years after the famous Giving Pledge campaign, but two months before the publication of the Panama Papers, I was in the same place  (now named UPMC-Sorbonne University) but this time it was my turn to teach to master students. My topic was indeed not so far from allostery: an emerging protein concept that provided great explanations to my own, obscure research and was referred as the quinary interactions. I was fascinated by this missing link, an obscure matchmaking between the cellular and the macromolecular dimensions. It obliged me to prepare my lecture reading many scientific publications until savouring the original one.

In 1982, Edwin Mc Conkey presented his conclusions in a highly inspired article : there should be a fifth order of protein organization based on weak forces that gently glue the many proteins within a cell! Nowadays, we still consider four orders of organization when we evoke the proteins, the pillars of our living world. Asking many questions to my PC as usual when an idea invades my poor brain, I discovered that a human cell was containing not less than 2 000 000 000 copies of proteins according to the experimental measurements made by biochemists, maybe up to 10 000 000 000 if we consider the theoretical calculations of the physicists.

My god! So many! Studying proteins since 35 years, I never went through this crucial detail! It was only clear  for me that we have close to two meters of DNA in each of our cells, once unwound! So we need these quinary interactions for our many proteins to fit together in the highly crowded cell space… and of course to tightly pack our DNA. These interactions are intelligent and genetics takes care about them to maintain a high level of dynamic cooperativity in our own interior helped by the dual RNA family, messenger and scaffold at the same time. Without this quinary dimension, no way for us! And for all the living world.

If you ask for quinary and protein in the biggest bank of scientific publications, PubMed, it scores only 26 publications since 1982! Almost nothing! While John Ioannidis told us in 2005 that most of the published research findings are false, he recently called for more quality in an EuroScientist’s interview.  Quality to publish, also quality to drive out pieces of lost knowledge! An essential concept was waking up recently after being asleep since its publication and internet allowed me to find it just at the right moment!  I am convinced that it will become a hot topic soon with, hopefully, high expectatives for the publication we are close to submit with my partners. Let’s the quinary force be with us.

The lesson here is that our policy decision-makers should really take care about quality in research, following the San Francisco call and fostering basic, blue-skies research. Basic research needs more supports from diversified sources as for example in the US with the Philantropy Science Alliance or in Spain with La Caixa Obra Social. What about a European Giving Pledge campaign after the disaster of the Panama papers? What about a European cooperative of fundations issued from the “social economy” community? Basic research is an essential part of the common good in our societies. We need solutions when the earth temperature seems to increase faster than Cop21’s promise. Many talented, inspired young people are dreaming to find new, original, unpredictable knowledge that would certainly lead to fruitful applications. Cutting-edge research needs more attractive and stable jobs for them to be successful in a long-term perspective!

If you believe in… the basic research, you are welcome to sign in our good old open letter “They have chosen ignorance” if not already done.


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About Gilles Mirambeau

I am a teacher of molecular biology/biochemistry at the UMPC- Sorbonne University*. At EuroScientist, heading its Editorial Board in close partnership with Sabine Louet and looking for a sustainable model, I am deeply involved in its concomitant development with the HSE community. Having an irrepressible vocation for making science at the frontiers of knowledge in a multidisciplinary and cooperative atmosphere, I focused my research during the 80s on the unexpected highly tensed state of the DNA found in archae living at high temperature. Then I switched to HIV and its macromolecular machine in the early 90s. Following my teaching activity at UPMC, I jumped from Paris to Barcelona, where I am engaged in my slow and non-dogmatic research about the HIV viral machine, emphasizing the quinary, weak forces as the fifth level of protein organization in the living world. *

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