The Study of Consciousness, Glimpses into the Life and Work of Great Thinkers in Neuroscience and Philosophy, Jean Pierre Changeux, Chen Lin Wang

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Glimpses into the Life and Work of Great Thinkers in Neuroscience and Philosophy

Jean Pierre Changeux

Chen Lin Wang

Jean Pierre Changeux is one of the fathers of modern neurobiology. His primary studies are on isolated acetylcholine receptors, specifically in the electric organs of some fish species. He found that those isolated acetylcholine receptors have been crucial to clarifying the path in which brain neurons communicate and interact. While being a first-class molecular and cellular biologist, Changeux is considered a maître à penser or master for thinking and a "humanist of the 21st century." He is rich in personality and has a unique ability to oscillate between the life sciences and the humanities.

Jean Pierre Changeux
Jean Pierre Changeux

Changeux earned a Bachelor degree in the école Normale Supérieure in 1955 and a Master's degree and received his agrégation in natural science in 1958. He pursued Ph.D. studies at the Pasteur Institute under the supervision of Jacques Monod and Francois Jacob. Later, he gained his doctorate in 1964 and left France for postdoctoral studies at the University of California Berkeley from 1965 to 1966, and one year later at Columbia University College of Physicians and Surgeons in New York.

Jean Pierre Changeux was born in Domont, France, in 1936. After his education, he returned to France as attaché to the chair of Molecular Biology held by one of his former guiding mentors, Jacques Monod. In 1972, he became the director of the Unit of Molecular Neurobiology at the Pasteur Institute, where he received his professor license in 1975. In 1975, Changeux was nominated for the professor at the Collège de France, chair of cell communications, and he held this position until 2006.

Changeux is an author of more than 600 scientific articles and books. His well-known books are Conversations on Mind, Matter and Mathematics, L' Homme neuronal, The Physiology of Truth: Neuroscience and Human Knowledge, What Makes Us Think?: A Neuroscientist and a Philosopher Argue about Ethics, Human Nature, and the Brain, and Gedankenmaterie.

Jean Pierre Changeux's expertise on isolated acetylcholine receptors applied the structure of allosteric protein and acetylcholine receptor in synaptic transmission at the neuromuscular intersection. Dr. Changeux found the first identification of a channel linked to neurotransmitter receptor protein. The acetylcholine nicotinic receptor was the first membrane receptor molecule that was isolated and characterized. Jean Pierre Changeux and his group later unraveled the fundamental characteristics of the receptor protein. They discovered the elementary physicochemical properties, the pentameric organization, and the first partial N-terminal amino acid sequence of one subunit that led to the cloning and complete sequencing of the acetylcholine receptor. They also identified the acetylcholine binding site. Jean Pierre Changeux further extended these results to neuronal nicotinic receptors in the brain.

Among Changeux's many awards, his most well-known one was the 2001 Balzan Prize for Cognitive Neurosciences. Professor Changeux greatly helped our understanding of the fundamental molecular mechanisms of chemical communication in the nervous system. Moreover, Professor Changeux has made a theoretical contribution to the epigenesis of neuronal networks via selective stabilization of developing synapses and on several aspects of cognition.

From the mid-1990s, Changeux focused on mathematical modeling to examine the neural bases of cognitive functions. This research was mainly conducted in collaboration with Stanislas Dehaene, like him, a French author and cognitive neuroscientist. The two neuroscientists prominently discovered the relations between the patterns of song in birds and the development of different birds' abilities. Lately, Dehaene and Changeux developed a neuronal model for access to consciousness based on the recruitment of networks of neurons with axons.

Changeux was also famously known for his book on the unique idea of the connection between mind and the physical brain. In his work, Conversations on Mind, Matter and Mathematics, Changeux strongly supports the view that the nervous system functions in a projective rather than reactive style. He believes that our brain has a direct connection with our ancestral environments, following Darwinian natural selection; in this context focusing more on what is inherent versus what arises from nuturing.

He raises several questions: As Plato supposed and many others have believed since, do we discover knowledge systems or do we construct them? Does mathematics establish a general language that would allow human beings to communicate with other civilizations in the universe, or is it just a natural language that owes its unexpected existence to the unique evolution of neuronal networks in our brains? Does the physical world accept and follow mathematical laws, or does it seem to agree to the laws simply because physicists have increasingly been able to make reasonable judgment of it?

The uncertain status of mathematical objects led Changeux and Connes to the organization and function of the brain, how its embryonic and postnatal development influences the unfolding of mathematical reasoning, cognitive processes, and human intelligence. The two great thinkers delved into ethical questions, querying within the natural foundations of morality and the chance that it may have a neural basis underlying varying social implications. Two questions highlighted the whole book: why logic and rule should exist in the world, and why it should be comprehensible to human beings. Dr. Changeux is pursuing his mission with great conviction. He revisited all the traditional standards of the empiricist, materialist, and nominalist critiques of Platonist idealism in mathematics. He summoned an impressive mass of scientific data, neurobiology and cognitive psychology. Overall, his great work has been highly praised and has had a worldwide influence on various scientific fields.

Further Reading

1. Neuronal Man, Princeton University Press; Reprint edition (April 2, 1997)

2. The Physiology of Truth: Neuroscience and Human Knowledge, Belknap Press: An Imprint of Harvard University Press (March 31, 2009)

3. Conversations on Mind, Matter, and Mathematics, Princeton University Press (May 7, 1995)


Ruminations on Consciousness


In Neuronal Man, I tackled the issue of consciousness and the neuronal bases of "becoming conscious" and stated that the relevant explanation had to be found at the level of a system of neuronal regulations functioning as a global entity. In my 1992 course at the College de France, I suggested that the formal neuronal network that Stanislas Dehaene and myself had proposed for the Wisconsin Card Sorting task could serve as a starting point for the development of a more general model that would include a "conscious workspace." Two events prompted us to tackle this modeling in a direct way. On the one hand, Stanislas Dehaene had created a very active independent research group dedicated to brain imaging and started to apply this technique to investigate conscious versus nonconscious tasks. On the other hand, Antonio Coutifio gave us the opportunity to present our ideas in Portugal to a group of experts brought together by the Gulbenkian Foundation in the monastery of Arrabida in the summer of 1998. Our position differed from Francis Crick's 40-Hz reductionism, from Gerald Edelman's complexity dialectic, and from Rodolfo Llinas' thalamocortical oscillations. Rather, our intention was to imagine a neuronal architecture that would explain altogether the global and unitary character of the conscious workspace, as suggested by the psychologist Baars (1989) and the diversity of the underlying processes. It was elaborated as a computer model. Dehaene, Kerszberg, and myself (1998) proposed that neurons with long axons connecting distinct cortical areas, even different hemispheres, play an essential role in the genesis of the conscious space. In effortful tasks, such as the Stroop test, "global" representations would differentially mobilize these neurons together with components from specialized processes through mechanisms of evaluation from the outside world, but also through mechanisms of self-evaluation toward the subjective inner world. The proposed computer model is able to successfully simulate the Stroop task. The model also accounts for the top-down control of these global representations upon the activity states of the underlying processes by a simple neuronal mechanism. A tentative answer was brought, in neuronal terms, to the paradox raised by Sperry of the mysterious top-down control of consciousness over lower neuronal processes.

Von Economo's (1929) studies on the microarchitecture of the cerebral cortex underlined the abundance of pyramidal neurons with long axons in layers II and III of the cerebral cortex. Interestingly, these layers are specially dense in the so-called association areas which include the prefrontal cortex. Moreover, brain imaging studies, particularly those performed by Stanislas Dehaene and his group, revealed a strong activation of the prefrontal areas during the accomplishment of conscious tasks requiring an effort. Finally, everyone knows about nicotine's effects on wakefulness and on attention.

Was it reasonable to link these theoretical thoughts and the experimental studies carried out with the neuronal receptor? A first link was established by a discovery made by the Australian neurologist Bercovic and the German molecular biologist Steinlein (Steinlein et al., 1995). Bercovic had recognized that several members of the same Australian family suffered from a rare form of autosomal dominant nocturnal frontal lobe epilepsy, which causes loss of consciousness and convulsions. This was the first genetic epilepsy to be identified at the amino acid level; moreover, it resulted from a mutation of the gene coding for the ~4 subunit of the acetylcholine nicotinic receptor. My surprise and delight was even greater when I read in the paper that the particular amino acid whose mutation resulted in seizures was homologous to serine 261 in the MII segment that we had initially labeled with chlorpromazine in the Torpedo receptor! Spontaneous mutations revealed, independently of any preconceived idea, the same amino acid as the one we had labeled in a deliberate way to identify the ion channel. Can a more "objective" validation of these results be conceived? The subject of the neural bases of consciousness and of its chemistry is henceforth opened to scientific research. The nicotinic receptor may again play a role. Is it a new start for the chemistry of consciousness and cognitive functions? It will require, in order to progress, a multidisciplinary approach that unites life sciences and human sciences at multiple levels of organization, together with human sciences. It is our duty and that of the younger generations to make it work. We are far from the end ....

Source: Excerpted from: The History of Neuroscience in Autobiography, VOLUME 4, Edited by Larry R. Squire.


The Study of Consciousness

Human interest in the nature of consciousness dates far back to our ancestral past. However, it is only in the last century or so that researchers and philosophers have been able to tackle the problem in a more scientific way. This is primarily due to our increasing understanding of human physiology and how our brain functions. With the advent of ever more sophisticated technology—from fMRI scans, functional magnetic resonance imaging, to DARPA's neural engineering program, understanding neural “dust”—we are now able to not only create vivid simulations of cerebral activity but also to systematically reverse engineer the brain. Whether such empirical observations will unlock the secrets of self-reflective awareness is still open to vigorous debate. Nevertheless, the study of consciousness is now considered to be of elemental importance and has invited a large number of brilliant thinkers—from a wide range of disciplines, including mathematicians, quantum physicists, neuroscientists, and philosophers—to join in the discussions and offer their own contributions.

The following essays briefly explore the life and work of pioneers in the field of consciousness studies. Included in this eclectic mix are such notables as Giulio Tononi (University of Wisconsin), Paul and Patricia Churchland (University of California, San Diego), Noam Chomsky (M.I.T.), the late Timothy Leary and Terence McKenna, and Jean Pierre Changeux (Collége de France) among others.

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