Joseph Altman, Arturo Álvarez-Buylla and Giacomo Rizzolatti Prince of Asturias Award for Technical & Scientific Research 2011

Speech by Arturo Álvarez Buylla:

Your Majesty,

Your Highnesses,

Distinguished Authorities,

Fellow Laureates,

Ladies and Gentlemen,

It is a true honour to be here today in the company of colleagues and personalities who have contributed so much to humanity and whom I so admire.

I wish to describe –in a simple and personal way– the gratitude and emotion that I feel to find myself in this delightful corner of Spain. Throughout my childhood far away in my beloved Mexico, my father and my grandfather shared with us their memories of Asturias, which they missed so much. Stories of green meadows and mountains, of hórreos , of rugged coastlines bathed by the Cantabrian Sea and, above all, of the upright, hardy folk born of this mountainous land. Their stories also carried a sense of idealism regarding knowledge, culture, nature and –on my father’s part– science. On account of all these memories, this visit to Asturias is particularly special to me. It combines both recognition for the work I love and my family’s affection for this land, home to fabada and the culín of cider in addition to Clarín’s Regenta.

Immersed in the throes of recognition, it is easy to forget the challenge that we face in trying to understand and repair the nervous system. Before continuing, I would like to give some thought to the following. Ordinary people think that these awards reward extraordinary personalities who are few and far between: as they say in Spain, “unos tíos fuera de serie”… “outstanding guys”. However, on getting to know my co-workers and colleagues during my formative years at the UNAM, at Rockefeller University and, now, at the University of California at San Francisco, I have come to realize that the world of science is full of outstanding people. We live in an age in which, were it not for the enthusiasm, knowledge and encouragement of teachers, co-workers and students, it would not be possible to break through the tough frontier of the unknown. I therefore share the excitement I feel with these teachers, co-workers and students, and most especially, with a very close co-worker, Jose Manuel Garcia Verdugo, who for so many years has accompanied us in this venture.

When we look into the lens of a microscope and see nerve cells –neurons– shining like illuminated signs, it is impossible not to be in awe of their complexity, diversity and extraordinary beauty. A beauty that captivated the great scientist, writer, painter and thinker Don Santiago Ramon y Cajal. Over a century ago, he correctly inferred the cellular individuality of neurons, which communicate with one another via their frond-like tentacles so as to establish the circuits that control animal behaviour, the very soul of a human being. The progressive loss of these wonderful biological semiconductors can disrupt our fragile neural circuitry and trigger imbalances such as those we observe in neurodegenerative or psychiatric disorders.

The identification of neurons as cellular individuals is only the first step along the difficult path towards understanding how this organ inside our head is assembled, works or deteriorates. The true beauty of the nervous system lies in the content of its cell assemblies, in its neuronal circuits and in what these are capable of achieving; for instance: memory, behaviour, perception, imagination, emotion. However, let us not claim that the wonder of the brain is a quality exclusive to human beings. The beauty of the nervous system is shared by all animals.

After a century of intense effort, we are only just beginning to understand how the brain is capable of such wonders. I would, however, go as far as to say that we are on the threshold of a genuine conceptual revolution in neurobiology. New information on the mechanisms for assembling neuronal circuits, molecular studies and integrated functional studies, such as the work by Rizzolatti and the identification of mirror neurons, presage the next stage in our understanding of the brain.

Part of this progress also stems from abandoning dogmatic points of view. It was thought for many years that it was impossible to replace nerve cells. How can some of the elements of an already established neuronal circuit, which harbours within itself memories and codes polished by experience, be replaced by inexperienced newcomers? The matter has been a battlefield ever since the days of Ramon y Cajal’s. For this to be able to occur, progenitor cells would be needed to generate young neurons. These youngsters would also have to be able to move within the truly complex maze of the adult brain in order to reach their destination, where they would somehow need to connect to a circuit and contribute to its function. All of this would have to occur in a pre-assembled working nervous system. Faced with these drawbacks, it is not surprising that many of the scholars studying the nervous system predicted that the birth of new neurons was simply impossible.

As often happens, biology showed us this was not so. All these surprising processes are possible in an adult brain. It was precisely the pioneering work of Joseph Altman in the 1960s that provided the first evidence of the presence of new neurons in some regions of the adult brain.

A definitive leap forward came some time later from the least expected of places, the study of the mechanisms of birdsong. In the 1980s, Fernando Nottebohm and his co-workers obtained electrophysiological and anatomical evidence as well as evidence related to connectivity that leaves little room for doubt: namely, that new neurons could integrate in the circuits controlling birdsong in adult canaries. The groundbreaking studies by Altman and Nottebohm have allowed us to understand how everyhing that had been assumed impossible is, in fact, possible. In the following decades, the study of the mechanisms of adult neurogenesis revealed new forms of nerve migration and orientation, new mechanisms for nerve integration in neuronal circuits and a paradigm shift as regards the very origin of neurons.

A truly important factor that motivates us in our work is the defining of new strategies to repair the nervous system. New neurons are thought to be synonymous with the curing of neurodegenerative diseases. However, this is not as straightforward as it sounds. To begin with, there are many different types of nerve cell and only a few of these are produced in adults. In neurodegenerative disorders, the neurons that die often correspond to the basis of cerebral assemblage, which makes their replacement difficult or even impossible. In addition, the purpose of natural (endogenous) mechanisms of neurogenesis in adults does not appear to be that of repairing the brain, but rather of restoring its plasticity, of providing a certain degree of flexibility that enables circuits to adapt to the changing environment. In fact, many neuronal elements are formed in embryonic and foetal stages and, surprisingly, last all our lives, toiling away ceaselessly. Despite all these limitations, the process of neuronal replacement is possible for certain types of neuron, a fact that encourages us to continue exploring cell mechanisms for neuronal repair.

The ease with which humans incorporate new findings into their everyday lives is astounding. For many, knowledge is only palpable when reduced to novel technological advances: a new drug, a mobile phone, the Internet, aviation, new diagnostic devices and so on. However, knowledge has another very important role: it provides us with new perspectives with regards to the world we live in; it is part of individual and collective consciousness. Knowledge is like a large expanding sphere; we live inside it, limited by the harsh frontier of the unknown. The scientific and technological progress achieved over the last century overwhelms many young people, who think that there is nothing left for them to discover. My impression is that the best is yet to come; providing, of course, we do not destroy the planet or curb the imagination and creative activity of its peoples first.

As for technology, living organisms still outshine us in their capabilities: think of limb regeneration in a salamander; the leap of a grasshopper; the ocean voyages of the albatross; the simple flight of a dragonfly; or a dog’s sense of smell. Nature always reveals to us its amazing technology, in units that self-assemble (as in the enigmatic development of the embryo) and self-recycle to integrate fully into the environment –without leaving a carbon footprint in the atmosphere or piles of waste that endanger the planet. Increasingly, we scorn and annihilate life forms that have a great deal to teach us. As living beings, our future lies with biology. We have so much to learn from other organisms, as well as from ourselves.

In this respect, the simple act of enhancing knowledge through the fostering of imagination, exploration and creativity is what makes a people great. The great leap forward that Spain has made as a driver of Science, Culture and the Arts over the last 30 years will hopefully serve as an example to other countries and, in particular, to Latin America.

My gratitude to Your Majesty, to the Prince and Princess of Asturias, to the Prince of Asturias Foundation, to the distinguished members of the Jury and to Spain for this recognition and for promoting Science and Culture. But, above all, thank you so much to all those “outstanding” people in my life: my family, my teachers, my students and colleagues, who have made these small incursions into the world of the unknown possible.