French neuroscience in the vanguard: the ICM is taking off

Prof Yves AGID, MD, PhD
Scientific Director of the ICM Research Foundation (Brain and Spine Institute/Institut du Cerveau et de la Moelle Épinière), CHU Pitié-Salpêtrière

French neuroscience in the vanguard: the ICM is taking off

An interview wi th Y. Agid, France

The Brain and Spine Institute (ICM) is a state-approved private nonprofit neuroscience research foundation, scheduled to start operating in the fall of 2010. Founded by two internationally renowned French neurologists, Yves Agid—also a neuroscientist—and Olivier Lyon-Caen, and an orthopedic and trauma surgery specialist, Gérard Saillant, it is an ambitious and innovative pilot project, located within the Pitié-Salpêtrière Hospital complex in Paris, France’s largest hospital and one of the world’s foremost centers for nervous system diseases. The ICM will provide state-of-the-art facilities for more than 600 researchers and technicians from all over the world. It aims to increase the efficiency of neuroscience research through translational research integrating the fields of molecular and cellular biology, neurophysiology, and cognitive science, to find practical answers in terms of basic knowledge and treatment, so as to relieve, cure, prevent, and repair the disorders of the brain and spinal cord. The ICM will closely interact with the Pitié-Salpêtrière Hospital, and benefit from its huge reservoir of patients and clinical, biological, and tissue databases. It will also establish close relationships with institutional and industrial partners, and interact with society at large through various scientific and cultural programs and activities. Nervous system diseases currently affect 1 in 8 persons in Europe, and their incidence is increasing. Among the ICM’s chief priorities will be to find treatments to halt the progression of, and cure, neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, and help sufferers of spinal cord traumas recover motor function.

Medicographia. 2010;32:319-329 (see French abstract on page 329)

Professor Yves Agid is a busy man and a man with a mission; catching him in between a flight from New York to Geneva and on to Tokyo is no mean feat, yet despite the jet lag and an overburdened agenda he is fresh and more than eager to start an early morning two-hour interview. He is an enthralling and fascinating speaker, with a Bill Bryson—like knack for explaining complicated things in layman’s terms.

Agid is also a happy man. As one of the founding fathers of the ICM (Institut du Cerveau et de la Moelle Épinière—Brain and Spine Institute) he is about, this fall, to cut the ribbon of his life’s project, an institute that probably does not possess its like in the world, slated to gain name recognition on a par with Harvard, MIT, the Karolinska Institute, or the Weizmann Institute. The building housing this ambitious project is nearly completed. Its “H” shape is fittingly—Agid claims this was the spontaneous result of the most efficient functional design—reminiscent of that of a brain, with its two all-glass-and-light “hemispheres” linked by a central “corpus callosum” that serves to ensure the “traffic” between the two halves of the building. It is now one of the most imposing structures in the sprawling complex of the Pitié-Salpêtrière, France’s largest hospital, which occupies more than 80 acres of prime real estate in the 13th arrondissement of Paris, a city within the city. Agid, after a career spanning more than 35 years as a neurologist and neuroscientist, will probably never again wield a reflex hammer nor peer into a test tube, deliberately choosing instead to give his full time to gathering around him some 600 of the savviest brains from around the world to bring research into neurosciences in France to a level of top-notch excellence. The ICM’s brief: to discover the treatments of tomorrow by plumbing the secrets of the human brain—which, despite breathtaking advances in our knowledge of its function over the past decades, still largely remains a terra incognita. Agid, never losing sight of the patients to whose welfare the Institute is dedicated, waxes poetic when he talks about the brain, the complexity of which he likens to the universe, with its planetary systems, stars, and infinitely spread out galaxies.

The nearly completed ICM building at the Pitié-Salpêtrière
Hospital. © ICM.

He likes to cite French 17th-century philosopher Pascal’s awe of the “infinite in which man is engulfed.” He hopes the ICM will contribute to the understanding of our species’ most precious and proud attribute—thought. But he grows solemn as he describes the “horror” of the neurological diseases that affect the very core of our being and personality, and lead to devastating disabilities that impose a heavy burden on patients, their families, society, and health care resources. Put in blunt, down-to-earth terms, Agid wants the research carried out at the ICM to contribute not only to treat, but—and this is new and very daring—to cure and prevent such scourges as Alzheimer’s disease, depression, chronic epilepsy, while also searching for treatments to help paraplegic traffic accident victims recover the use of their legs, to name but a few striking examples.

But let us hear him tell his own story…

How was the ICM founded, and how did you choose the name of the Institute?

I was reminded, a couple of years ago, by a nurse who was leaving on retirement, that all the way back in 1973, as a young senior registrar in neurology, I’d told her: “One day, you’ll see, we’ll need to coordinate all neurology, psychiatry, and related departments into a single structure, and have a big neuroscience research institute just a stone’s throw away…” In 1997, when I was head assistant to Professor Claude Griscelli, the then General Director of the National Institute of Health and Medical Research (INSERM), who was actively planning his own genetics institute, due to open any time now, we often talked about the necessity of a neuroscience institute. The actual decision to create the Institute came in 2002, when Gérard Saillant, a professor of orthopedic and trauma surgery, who initially had wanted to start a bone institute, began playing with the idea that rather than busying himself with bone, a more urgent priority was what lay under the (skull)- bone, ie, the brain. He then told me “I know that Olivier Lyon- Caen (a neurologist) and you want to create a neuroscience institute: why don’t we all do this together? The project really got jump-started when Gérard introduced me to Jean Todt, who was at the time Team Principal of the Scuderia F1 Team, before becoming CEO of Ferrari. Todt organized a dinner attended by a select group of personalities who immediately warmed to the idea and vowed to sponsor the Institute, and became it’s Founding Members. From then onward the project snowballed, and we got the support we needed from health, governmental, and regional and local authorities, including the Ministry of Research, the Île-de-France Region, Paris City Hall, and others. Funds and donations started trick- ling in and the Institute got off the drawing board. Gérard is now the CEO of the ICM Foundation, Olivier is the Coordinator of the Nervous System Diseases hub at the Pitié-Salpêtrière University Hospital, and I am the Scientific Director of the ICM Foundation.

Digitally enhanced MRI scan of the human head.

© Mark Lythgoe & Chloe/Wellcome Images.

Three of the Founding Fathers of the ICM in front of a new-generation 3-tesla MRI scanner.

From left to right: Drs Yves Agid, Gérard Saillant, and Olivier Lyon-Caen. © Michel Monteaux.

What we wanted to do was increase the efficiency of neuroscience research through translational research integrating the fields of molecular and cellular biology, neurophysiology, and cognitive science. Our aim is to bring practical answers both in terms of knowledge and treatment, so as to relieve, cure, prevent, and repair the disorders of the brain and spinal cord that are affecting a rapidly increasing number of persons to the point that they are reaching epidemic proportions, not only in France and Europe, but throughout the world.

As you can well imagine, much care was put into coming up with an adequate name. The “Brain and Spine Institute” is in essence a neuroscience research institute. We could easily have stressed that aspect, or found a catchy one-word name, but what we wanted to highlight above all was the patientand general-public–oriented specificity of the ICM. The ICM will of course carry out basic neuroscience research, but what we want is for it to come up with answers, and above all, practical answers: new treatments and new cures. Gérard Saillant played a decisive role in finding a name that would really mean something to the general public by specifically citing spinal cord disorders, chief among which are naturally the high number of victims of automobile and other accidents who are paralyzed after spinal cord injuries. We want these patients and their families to know that we are trying to do something very concrete about this.

What is the current situation of neurological diseases in France and Europe today, and what is so special about them?

To explain that, let me scroll down a few prevalence statistics for you. The brain is the body’s “conductor,” which controls all the body’s functions, such as sensitivity, movement, intellect, emotions, and consciousness— just to name the tip of the iceberg— so that any lesions have a potentially terrifying impact as they often result in devastating and irreversible handicap.

Neurological disorders affect over 1 billion persons throughout the world, according to WHO. In Europe, the figure is upwards of 94 million. Stroke is the main cause of motor handicap in Europe, affecting 3 million persons; Alzheimer’s disease affects some 4 million persons; Parkinson’s disease 700 000; epilepsy 2.5 million; multiple sclerosis 300 000. Brain and spinal cord trauma claim over 60 000 deaths every year while 1.5 million subjects lose their autonomy as a consequence of their injuries. If we look at psychiatric diseases, the picture is a gloomy one: 3.6 million people suffer from psychoses with delirium and are dangerous to themselves or others; manic-depressive disorder again has 3.6 million sufferers and a high risk of suicide.

As for depression and anxiety, both affect some 36 million people, ie, a staggering total of more than 72 million, for a total population of 450 million, ie, more than 15% of Europe’s population. In France alone, 3.5 million persons (out of a total of 60 million) are disabled due to neurological disorders, including 850 000 with motor disabilities (370 000 in wheelchairs); and 650 000 with perception disabilities, of which are 60 000 blind persons. A simple figure says it all: in Europe, more than 1 person in 8 today suffers from some form of disease of the nervous system.

This gives you an idea of the scope of the problem. And yet, contrary to, say, cardiovascular disorders or cancer and leukemia research, research into neurological disorders has been suffering from chronic underfunding and understaffing. The ICM wants to help change that. And the time is just ripe.

Why is that?

Today it so happens that the ICM, which will be inaugurated this fall, comes at an ideal juncture, and this for three reasons.

First of all, the time is just right in regard to the spectacular advances in our knowledge of how the brain works, thanks to neuroscience research over the past two to three decades. Before that, the brain was a black box for us: we knew that information entered, and that behaviors issued, but what actually took place within the brain itself remained a sealed book. Recent technological achievements have changed all that, and we are beginning to understand what is going on. Our imaging capacity is now simply unbelievable. Just think about it: thanks to high-field MRI imaging, the degree of precision is such that we are able to distinguish cellular layers in the brain! There have also been momentous advances in molecular biology, neurophysiology, and genetics, as well as in a field in which France is an uncontested leader—good old clinical symptomatology. I prefer the word “semeiology”—the science of interpreting signs and symptoms, to come to a diagnosis. It is important to realize that cerebral symptomatology has become nearly entirely behavioral: increasingly better-described subtle changes in behavior can now be pinpointed to specific neurological lesions. At first glance, this seems unexciting in comparison to technological wizardry, but make no mistake, this truly represents a cutting-edge field.

Second, the ICM also comes at the right time in view of the rising incidence of many of the diseases that the ICM will be studying, due to the aging of our Western societies (the typical example being Alzheimer’s disease, with, in France, 860 000 persons affected, with an incidence of 225 000 new cases per year, projected to reach 2.1 million in 2040). Not only the number of elderly affected is increasing, but that of younger persons as well—one need only mention traumas due to car accidents or sports—as well as that of the very young, and here I’m talking about rare genetic diseases, associated with motor and intellectual deficiencies, of which there are many kinds. All these diseases are a source of great misery for the patients and their families. The ICM will be putting its full power to work to understand, relieve, cure, prevent, repair: this really could be our motto! Finally, and in this we are truly precursors, the ICM comes at a time when successive governments in France have started to realize how important it is to create “competitive clusters” not only for industry in general, but for medical research as well. Research in France is of very high quality, but has been stagnating somewhat over the past couple of decades, and France was losing its competitive edge, lagging behind other countries in terms of discoveries, patents, publications, and Nobel prize awards. All of this impacts strongly on health economics and even just plain economics. This situation is largely due to structural complexity, regulatory constraints, and the smothering embrace of bureaucracy. Recent governments have begun to see the light, and a radical change is at last under way to put France on a par with the USA and other European countries that have long understood that staying at the top requires cutting down on administrative red tape and uniting individual efforts into larger wholes to increase the efficiency of research. This is the idea behind the so-called competitive clusters or “technopoles” or “poles of excellence and competitiveness” as they are dubbed in France. This is exactly what the ICM is intended to do and what makes it a “pilot project,” expected to have profound economic implications in terms of efficiency, savings, and industrial spin-offs.

Clockwise from top left: Spinal cord motoneurons (photo by Dr David Becker); Neuropeptide
receptors (green), nuclei (blue), and neurofilaments (red) in the thalamus (photo
by MRC Toxicology Unit); Proteomics: protein gel with separated proteins forming part
of the brain mitochondrial proteome (photo by Nicoletta Baloyianni); Nerve cell bodies (red) and glial processes (green) in mesencephalic nucleus of the 5th nerve (photo by MRC Toxicology Unit).

© Wellcome Images.

So what exactly are the goals of the ICM and what makes it unique?

The first and most important aspect is that all of the ICM’s activities will be centered on the patient, who is the linchpin around which the entire ICM will revolve. And no matter the extent of pure science pursued and produced at the ICM, our immediate and constant concern is the patient, and what tangible benefits we will be able to provide. I’d like to insist again on what I have called our motto: we want to find out more about nervous system diseases in order to come up with better treatments—and we want to work on the full gamut of what “treatment” implies: relieve, cure, prevent, repair. Effective treatments exist to alleviate the manifestations of brain disorders (analgesics, antidepressants, tranquillizers, L-DOPA for Parkinson’s disease, lithium for bipolar disorders, etc), but these treatments are too few, not powerful enough, and not specific enough. Just to take two examples, depression is a syndrome, and probably has a huge number of different causes; similarly, there are probably scores of causes of Parkinson’s disease. Symptomatic drugs need to be far more specific than they currently are, and this is a field that the ICM intends to prioritize. But the ICM wants to go further than that: contrary to other fields of medicine, there is a real paucity of curative treatments: we relieve, we do not cure; again, the ICM intends to contribute to the discovery of genuinely curative, as well as preventative, treatments. We even want to look into the possibility of repairing lesions—although, because of the extreme complexity of the brain’s structure, this is far more problematic than in the rest of medicine, as one cannot just simply expect to graft cells and hope they will fully repair a cerebral infarct, for instance, and restore cerebral function to what it was prior to an accident.

3-D representation of the basal ganglia of a patient with Parkinson’s disease: placement of electrodes in the subthalamic nuclei.

© Luc Mallet/Eric Bardinet/Jérôme Yelnik/Inserm/ICM.

Second, to achieve its goals, the ICM is going to recruit the very best researchers, from all over the world. I’m sometimes asked whether the ICMwill help stemthe brain drain of French neuroscientists to the US. Like all French postdocs, they go there because they are better paid and have better working conditions. Let them stay where they are! I certainly don’t want them all to flock back in droves; what I want for the ICM is the best, only the very best, be they French, American, German, or Chinese! These elite researchers will be headhunted according to rigorous requirements and vetted by a completely independent international jury of experts. Of course excellence comes at a price: it requires attractive salaries and quality of life, and a working environment devoid of the vexing problems that beset so much of research in our country, all of which the ICM is pledged to provide.

The third characteristic feature of the ICM is translational research. To this end the ICM will strive to eliminate barriers between clinicians and scientists, and will go from bedside to bench and bench to bedside, and back and forth from the patient to the cellular and even molecular level. Our main fields of research will involve clinical research, state-of-the-art technologies, cell biology, molecular biology, neurophysiology, genetics, cognitive science, etc.

Fourth, these researchers will be free to do just what they want—provided they excel. Of course their research will be carried out within an overarching strategy at the service of public health–orientated concerns, comprising such priorities as neurodegenerative diseases, cerebral and spinal cord trauma sequelae, dementias, and the major psychiatric illnesses. Strategic choices mean that some fields will have to be left out, such as migraine—in spite of the over 6 million migraine sufferers in France—in favor of others, such as mental dysfunctions or neuroplasticity. Emphasis will also be put on topics that have hitherto been traditionally neglected in France, such as the study of consciousness and of emotional and mood disorders in relation to anxiety and depression. Another such neglected field is “brain computer interface” devices, for example to restore motor function by bypassing spinal cord lesions.

A fifth characteristic is the ICM’s location within the hospital complex of La Pitié-Salpêtrière. This is a feature thatmakes the ICM absolutely unique. Just think of it: this center, dedicated to neuroscience research, is situated right in the middle of the biggest hospital in France, and one of the biggest in all of Europe, where out of the 600 000 patients attending the hospital every year, more than 100 000 receive treatment in the Neurology, Psychiatry, Neurosurgery, or Neurological Rehabilitation Departments. “Bench to bedside—and back to bench” will be immediate, constant, with no loss of time and energy, providing ideal conditions for translational research and clinical trials. Not only will the ICM have onsite access to the patients, but also to the hospital’s biological data, brain tissue, and DNA bank resources, indispensable for research.

Some of the personalities attending the ICM Partners’ dinner
on March 18, 2009.

From left to right: Jean-Pierre Martel; Maurice Lévy; Olivier Lyon-Caen; Yves Agid; Roselyne Bachelot (Minister of Health & Sports); Jean Todt; Jean-Paul Huchon (President of the Regional Council of the Île-de-France); Michelle Yeoh; Gérard Saillant; Sir Lindsay Owen-Jones; Serge Weinberg. © Jean-Philippe Pariente.

A sixth characteristic is that the ICM will interact with society at large, with the community.We want the ICM to be a hotbed of intellectual activity, with a constant stream of seminars and lectures by international leading lights for in-house researchers, as well as for researchers in other fields, industrial leaders, and the pharma industry. We will also offer a variety of programs for the general public, such as lectures, exhibitions, and concerts…we’d even like schoolkids and students to come over to get a first taste of science and a whiff of hospital atmosphere in order to stimulate interest in neuroscience research as a career.

How is the ICM financed, what are your sources of support?

The ICM is a state-approved private nonprofit research Foundation, with mixed public and private funding, similar to the Pasteur or Curie Institutes. Again, this is something that is quite innovative, and not all that common in France. Our initial investment requirements were in the region of 67 million euros. The operating costs are estimated at 55 to 60 million euros per year, which is a lot of money. Most of these costs will be earmarked for salaries, which must be high enough to attract the best researchers available, and the cost of technological equipment. Again, if we want to be in the top league, we can only be satisfied with themost up-to-date cutting-edge equipment. Forty million euros of the running costs will be financed by public funds, but we still need to find more than 15 million euros every year to be in the black. And since we will not be producing any consumer goods, but research and publications, this will be quite a challenge!

Jean Todt, President of the FIA (Fédération Internationale de

© Reau Alexis/SIPA.

We receive funding from sponsors and partners from the public and private sectors. We are grateful to the administrations who authorized the allocation of the ICM’s construction site—INSERM, the Île-de-France Region, the City of Paris, and the Ministry of Research. We are of course very much indebted to the Assistance Publique – Hôpitaux de Paris (AP-HP), which gave the ICM a 4400-m2 plot within the Pitié-Salpêtrière hospital grounds—quite an appreciable gift considering the hefty price of real estate in central Paris. We have received support from the Pierre and Marie Curie University (Paris VI); the CNRS; and the Caisse des Dépôts (a public financial institution that granted the ICM an important loan). We are applying for subsidies from the European Union.

Among the private sector partners, there is the pharmaceutical industry, and of course Servier. Special mention should be made of the FIA Foundation (International Federation for Automobile Sports), currently headed by Jean Todt. The FIA is strongly committed to the ICM, consonant with its actions to promote road safety and prevent automobile accidents responsible for so many cases of brain and spinal cord trauma.

Architect’s representation of the ICM complex. Computer-generated image by Jean-Michel Wilmotte. © ICM.

We will rely on subsidies, to obtain grants and contracts from the French National Research Agency (ANR), or from European and other international institutions. We will also rely on industrial partnerships, including with people like Servier, who will sponsor and/or carry out research programs under copatenting and co-licensing agreements with all guarantees of the strictest confidentiality to preserve intellectual property rights.

And last but not least, we are counting very much on donations from private individuals. Whatever their amount, we consider none too trivial and are grateful for all!

What can you tell us about the architecture of the ICM, and the facilities it will feature?
We pride ourselves on the choice of architect: Jean-Michel Wilmotte. He is a graduate of the École Camondo, and among his most celebrated achievements are the Incheon International Airport (Korea, 2000); the Palace of Congress of Bordeaux (2003); the Museum of Contemporary Art in Beijing (2007); the Collège des Bernardins, a spearheading catholic cultural institution inaugurated by Pope Benedict XVI in 2008. Wilmotte is currently working on the Korea Art Center in Pusan, a high-rise office building office in Azerbaijan, a hotel in Bahrain, and a Formula One racing track in France. The ICM building is a wonder of glass and light. It’s 8 floors, of which 2 are basement levels, offer a total surface area of 22 000 m2 and will provide ideal working conditions for its 600 investigators. The lower ground floor will contain a neuroimaging platform, with a 7-tesla MRI scanner for clinical research, which will produce exquisitely detailed 3-dimensional mapping images of human brain structures. The ICM will also boast two to three 3-teslaMRI scanners for patients and an 11.7-teslaMRI scan- ner for animals. The first floor will house a Clinical Investigation Center (CIC) with a capacity of 14 inpatients, to conduct research to determine the innermost mechanisms of nervous system diseases and test experimental treatments, under the most stringent ethical and legal constraints.

Sir Lindsay Owen-Jones at the first-stone laying ceremony at the ICM building site, on June 18, 2008.

© Jean-Philippe Pariente /SIPA.

To the casual, nonspecialist reader, this may seem like precious little for such a big research institute—in fact it is unusually large, as these investigations are not classic clinical trials of study drugs, but special investigations carried out on a case-by-case basis under very specific conditions.

Research laboratories for more than 40 research teams totaling 600 to 700 researchers, technicians, and other personnel will occupy some 11 000 m2 on the 4 upper floors, organized into modifiable modules on either side of the central linking section of the building, which will house the technology platforms. This is a very astute concept, aimed at centralizing the bulk of the technical facilities in order to optimize their use and save significant space, time, and money. The modules will allow great flexibility in use, either as labs, offices, or meeting rooms, at a moment’s notice. Communication between teams and individuals will be enhanced thanks to the centralization of the technological equipment and the liberal use of glass walls and partitions and the overall conception of the building.

The ICM will boast a generous offering of teaching and training facilities, with conference rooms, meeting rooms, a 180- seat amphitheater, spaces for industrial partners and startup companies, and even a museum dedicated to French neurology.

Yves Agid, Scientific Director of the ICM and Emmanuel Canet, President of Servier R&D.

© cndprod/cheik for Les Laboratoires Servier.

So what will the ICM do exactly?

First of all, we want to do a lot of research— a massive, multifaceted thrust of basic research in neurosciences and related fields. You just can’t compare our knowledge of the brain with that of any other organ: the brain is so infinitely complex that even though we have made giant strides, our understanding is still in its infancy.

This is particularly the case if you take the higher functions: how do neurons manage to produce thought, consciousness, and what happens when dysfunctional neurons produce dysfunctional thought? What exactly is memory, and what happens in dementias and degenerative diseases when one loses it, when one loses language? Just understanding how two neurons, which are universes unto themselves, manage to “talk,” exchange information, exchange “thoughts” is a conundrum. To record what is going on in a single neuron requires tremendous computational resources, to do this in time and space for groups of neurons is just mind-boggling! But researchers are starting to make some headway, and are even developing a few practical applications, like the “brain computer interface” programs I mentioned a little while ago.

Actor Jean Reno expressing his support for the ICM.

© B. Clément.

But to get back to how the ICM is going to operate, this is going to be in a “bottom-up” fashion: we are going to have scores of independent teams with a meticulous and rigorous selection of the best people in their respective fields. Of course there will be also be a selection of projects to fit in with the overall picture of the major fields that will have been defined by the ICM as our priorities, eg, there will be an overall program for neurodegenerative diseases (ie, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, etc), epilepsy and related disorders, as well as brain and spinal cord trauma.

But in essence, these teams will come to us already with their own projects and be completely independent, including financially: they will actually “pay rent” for the facilities they use—this will be made possible through their own research grants. Again what characterizes the ICM is that it will provide an ideal setting for translational research, cross-fertilization, and out-of-the-box creativity.

Our research will involve three major fields. First, molecular biology, to identify abnormal genes and assess the role and the consequences of gene mutation in cell and animal models. We will also use gene therapy to protect the nervous system by modifying gene expression and reconstructing lesioned tissue by implanting genetically modified cells. Second, cell biology, to modify abnormal metabolic chains by acting on nerve cell nuclei via receptors at the cell membrane, or through transplanted cells or stem cells. Third, neurophysiology studies, supported by computational or simulation and modeling tools, in vitro or in vivo, to understand how abnormal activity of one or a group of nerve cells can alter a neuronal circuit, and subsequently one of the brain’s functions. Research today is a totally globalized endeavor, and can only function through an international network of teams in close collaboration with each other. One of our aims is to set up strategic alliances with institutions throughout the world. Another goal will be to set up satellite teams or affiliated institutes in France and abroad, like the Pasteur Institute. We’ve already got plans for this…

One of our first priorities will be tackling neurodegenerative diseases, and trying to stop the progression, or even cure, amyotrophic lateral sclerosis—you know, cosmologist Stephen Hawking’s disease—or Parkinson’s disease, or Alzheimer’s disease.

Actress Michelle Yeoh.

© L’Oréal-Paris.

So tell me, when do you expect the first drug to come out of the ICM? What’s the first disease you expect to find a cure for?
We’re looking at finding a treatment for stopping the progression of one of the neurodegenerative diseases within, say, 5 years, and a cure perhaps in 20 years—but figures don’t really mean anything in this context. If you’re talking of tangible results, a box of pills on the patient’s bedside table, your question is more for the pharmaceutical industry than for the ICM!

In fact, our role will be to pave the way for the drug industry to develop effective treatments, ie, to assist in drug discovery, and this in a twofold way. Firstly, by identifying or confirming specific therapeutic targets, and this will be amajor help to the industry, which will know where to focus the screening process. Secondly, by providing the setting to rapidly test promising drug candidates, ie, to fast-track a new potential drug within a very small-scale yet genuine clinical pharmacology setting in humans, once its absence of toxicity has been confirmed, in Phase 2a and b–like trials in very small numbers of patients to evaluate the “proof-of-concept.” This will save a lot of money, but above all time, in that only drugs with a proven potential will then be subjected to the gauntlet of standard clinical trials in large numbers of patients.

strong>F1-champion Michael Schumacher.

© Race of Champions.

To conclude, what are your hopes for the ICM?

To answer that, I need to run through a few figures. The brain, all 1350 g of it, is infinitely more complex than any other organ or system in the human body. It is composed of more than 2500 different types of cells. It contains 100 billion (1011) neurons; each neuron has some 10 glial cells catering to it—so that’s a grand total of 1012 cells!; each neuron establishes between 10 000 and 100 000 contacts with neighboring neurons and emits thousands of signals per second. This means that, right now, your brain is producing billions of billions of signals every single second, dwarfing into complete insignificance the most complex computers designed by humans—now, and probably that ever will be! Just try to imagine what takes place in a single cubic millimeter of brain tissue, which contains more than 10 000 neurons! Blaise Pascal, the 17th-century mathematician and father of the first computer—a calculating machine with a complex ratchet wheel mechanism—and a physicist who discovered the properties of vacuum and pressure, was also a philosopher who was completely awestricken by the infinite. One of his “thoughts,” or “pensées,” which he used to scribble on little slips of paper stowed away in his pockets, states: “For after all, what is man in nature? A nothing in relation to infinity, all in relation to nothing, a central point between nothing and all, and infinitely far from understanding either” (Pensées 72). I feel that way when thinking about the brain, with its infinite cells, signals, biochemical processes, thoughts, emotions. In complexity and beauty, it can only be compared with the Universe itself, with its trillion upon trillions of asteroids, planets, nebulae and galaxies, and mysterious dark matter. Our latest models of the brain involve mathematical-computational theories, which only take into account time and space, and are probably already obsolete. Future models will probably need to include a fourth, a fifth, or even more dimensions. What we now need is a paradigm shift, a quantum leap in our understanding of how the brain works.We need a new Claude Bernard, the father of experimental medicine who introduced the revolutionary concept of “milieu intérieur” to explain how the body’s organs communicate with each other to ensure homeostasis. We need a new Einstein, a new Heisenberg, a new Schrödinger, whose relativistic and quantum mechanics theories completely superseded Newtonian physics and transformed our grasp of reality. My dream is that the ICM will one day produce such a person! _