Interview with Jean-Pierre Changeux 21.06.2010

France

Jean-Pierre Changeux

2001 Balzan Prize for Cognitive Neurosciences

Professor Changeux's broad and profound contribution ranges from the fundamental molecular mechanisms of chemical communication in the nervous system to learning and consciousness. In addition to his outstanding experimental work, Professor Changeux has made a theoretical contribution on the epigenesis of neuronal networks by selective stabilisation of developing synapses and on several aspects of cognition.
Jean-Pierre Changeux has established a new direction for the study of cognitive functions by rooting them at the molecular level.

Interview with Jean-Pierre Changeux
www.balzan.org June 21, 2010

Jean-Pierre Changeux, Balzan Prizewinner 2001 for Cognitive Neuroscience has opened a new area in his field. After having worked with the concept of Allosteric interactions, he has applied the concept of Allosteric proteins to the receptors of Acetylcholine used in synaptic transmission and has formulated a theory on the selective stabilization of the synapses during development.
Working first on the organs of the stingray and then on the neuromuscular joints, he was able to clone and to understand the complete sequence of the acetylcholine. He was then able to extend his research to other organisms and finally to more superior ones such as man.
Changeux has akways been interested in sharing his findings and their divulgation as part of the Darwinian scientific evolution dicussion. In this light, Jean-Pierre Changeux participated in the conference “La teoria dell’evoluzione, modelli e sviluppi ” (The Theory of Evolution: Models and Developments) which was organized by the Accademia delle Scienze di Torino, the Accademia Nazionale dei Lincei and the Berlin-Brandenburgische Akademie der Wissenschaften.
Balzan was able to meet with Changeux on this occasion and to interview him in Turin, on 28 May 2010.

After having worked with the concept of the allosteric interaction and applied the concept of the Allosteric protein to the Acetylcholine receptor, you were the first, thanks to these experimental works, to formulate a theory on the selective stabilization of synapses. From biochemistry to human thought: neural selection acts as a linear system?
I think that firstly we need to be prudent when we apply a system such as Darwin’s, in the context of evolution to other functions such as those of the brain or those that are linked to the development of the brain. That said, I think there are points in common. To begin with, the concept of variability which is essential. Variability at a genetic level, the variability of chromosome structure, of chromosomes, of DNA with all the mutations, copies of genes and so forth.
In terms of development, variability is located at the level of connectivity: there is in some way, one part of it that is purely by chance in terms of the composition of the neuron network inside the synaptic connections.In sum, this is a concept of variability that is in line with Darwin’s concept but with different practical applications.
The same can be said of Darwin’s principal of selection, in the case of evolution, it was a survival mechanism with the survival of the fittest. In terms of connectivity, the notion of the fittest is difficult to illustrate. I can say that the system, in terms of its globality tries to be at its most funtional. This is not necessarily at the level of the network but can be at the level of contributing to the network by doing a specific function, for example movement or perception.
Here as well, it is necessary to say that the selection is in principal analogous but in practice is different.
Getting back to your question: is this a linear or non linear system? I think that what comes forth from evolution processi is that at their base, they are not linear. What I mean is that evolution has produced at times aspects that appear to be “all or nothing” and that seem somewhat special or particular. I think that they are not exceptional or particular but rather simply mechanisms that amplify differences (this is the third element of Darwinian thought: variety, selection and amplification of the differences). Certainly, amplification means not linear, that which survives develops in a new manner from what existed before. There are, therefore, mechanisms which effectively can interviene and make systems non-linear which are entirely in line with scientific thought and are reasonable.

You spoke about “Neuronal man” (L’homme neuronal, Fayard – Paris 1983)  and how he came to acquire his knowledge, in other words, a neurological understanding of how man understands in two phases: the genesis of multiple pre-representations and transitions, then the selection of adeguate representations for the external world. Therefore, you believe that “Neuronal man” is an interpreter and builder in the world?
That’s an interesting question: I think that you try to understand the world, and on the basis of what you understand, you begin to construct the world. We understand the mechanisms of expression from genes and we are able to understand the nature of genetic materials, and therefore create organisms that are genetically modified. Therefore, building the world, follows understanding it. That said, of course there are limits in terms of reconstructing the world. The fact that we can construct or reconstruct the world is quite important for the evolution of society but I do think that man must think about the consequences of his actions and what he builds or rebuilds and that there is an ethical aspect that is extremely important that scientists often, unfortunately, don’t consider seriously enough. What I mean is that they create new instruments or a new object but you need to see what the long term consequences are, what dangers come along with these new developments. In France, there was a proposal to have a “principal of caution” but I consider this totally useless. It was even written into the constitution but I have no idea why. It isn’t what we need. Instead, it is the call for an examination of the consequences of our actions. Instead what we need is to try to anticipate what will occur when we introduce new technologies rather than try not to do something.

At the end of the book, “Man of Truth” (L’homme de verité, Odile Jacob – Paris 2002) it reads: “I tried to open a debate about the possibiity of objectifying our cerebral functions, the acquisition of knowledge and its objectification based on language, leaving the future writes an more detailed analysis of the communication between ethics and art. Is there a Neuronal art? Or a Neuronal ethic?
Yes. The idea of development of neuroscience and in particular cognitive neuroscience, allows us to better understand human activity in general and is evidence that these activities are the creation of knowlegde and science itself. This is why I wrote this book “L’homme de verité” because I believe that these are the fundamental activities of man that are really progress. But why then should we restrict these ideas to science only and not use them in other important areas such as art, for example? Why not look for ways to understand the perception of artistic creation in neurological terms? I have many colleagues who are working on this theme which I am personally very interested in but which is still quite speculative. I think this is the same thing as creating a “ethical norms.” I know that in the United States this is called neuroethics and that it is not only applied to
research on the human brain; ethics is fundamental and it is that which allows us to see what we can consider the “norm” in terms of brain functionality, which must be looked at in social, cultural and historical terms as well as in the creation of moral codes. This area must be taken into consideration: we should do more research on the subject. Science, at this level, is quite basic. The coming years should see work in this area. If we do research in this field, surely we will have a better understanding of human beings and perhaps be able to create a more harmonious relationship between people.

You have dedicated half of the Balzan Prize money to a project that intends to connect neural functions of the brain with the cognitive functions in genetically modified ice. The project has been completed. Can you summarize your findings for us?
I want to refer to an article I wrote for Nature Reviews Neuroscience on nicotine receptors and the dependance that is created by nicotine. It is a problem of the highest level of brain functioning. It is not simp;y a problem of a nicotine addition but of a loss of control by the person wjo smokes. The title of the article  “Nicotinic receptors and nicotine addiction : lessons from genetically modified mice”. It is exactly the project that I had proposed and I think that it picks up our theme and that we can seriously understand nicotine addiction if we consider genetically modified mice. The other aspect of this is that we need to consider access to the conscience in molecular terms, with long distance connections, and that we were able to show that in a genetically modified mouse who doesn’t have nicotine receptors, these connections were not as important, and there is an alteration in terms of accessing the conscience of the mouse.

Do you know Brenda Milner, Balzan Prize winner for Cognitive Neuriscuence 2009? Are there links between Milner’s research with your areas of study?
I know Brenda Milner but there are not really links between her research and mine because she works primarily on man and his memory, both short and long term. What she has done is absolutely fundamental research while we have worked at a more basic level hoping that our research which works for the mouse will work for man as well. I think that the link between her work and our mouse experiments can be attempted.

When you received the Balzan Prize in 2001, you said that “research is a game. It’s not important if you win or lose. Sometimes though, thinkers have babyish traits. As they love to win, they also love to be recompensated.” You have had wonderful results, how have you be recompensated or are you still waiting? It is the right attitude to want to win?
I was extremely happy to receive the Balzan prize which was a wonderful recognition in and of itself and moreover it enable me to finance my research which I wouldn’t have been able to do otherwise. This is a very important aspect.
The second aspect of your question brings me to say that I think that research is somewhat Darwinian, meaning that lots of attempts are made and errors are committed. The only way to move forward is through trial and error. We don’t always have great ideas, even scientists are sometimes wrong.
Clearly we need time to have correct ideas but you have to be able to recognize your errors as well. Sometimes they aren’t big errors. Some scientists have always made progress but you must learn to deal with the limits of your research and your interpretations. It is not theology, science isn’t dogma but the search for scientific truth.
I think scientists must have new ideas and reflect on the theory. Scientists need to have their research be open to reinterpretation, integration and successive progress.
I think research, science and primarily the search for truth can’t be a declaration of a truth . There should constantly be the search for truth. If I can say something to young researchers, it is to become involved with enthusiasm because this is a game that is worth playing.

Marcello Foresti
for www.balzan.org

translation: Susannah Gold