Royal Netherlands Academy of Arts and Sciences Heineken Lectures 2002 Heineken Lectures 2002 The Heineken Lectures were presented on 23 September 2002 Roger Y.Tsien, Vrije Universiteit Amsterdam Aernout Mik, AKI Enschede Dennis Selkoe, LUMC Leiden Heinz Schilling, Universiteit Leiden Lonnie Thompson, Universiteit Utrecht Royal Netherlands Academy of Arts and Sciences Heineken Lectures 2002 Amsterdam, 2003 The Heineken Prizes: five prizes for outstanding contributions to the arts and sciences Every two years the Dr H.P. Heineken Foundation and the Alfred Heineken Fondsen Foundation award four prizes – a cash gift of 150.000 USD and a cristal symbol – for outstanding contributions to the sciences and one prize for the performing arts to a Dutch artist (50.000 EUR). The selection of the winners for the Heineken Prizes has been entrusted to the Royal Netherlands Academy of Arts and Sciences. The Academy’s Arts and Sciences Divisions have appointed special committees to carry out this task. The jury of the Dr A.H. Heineken Prize for Art consist of three members of the Academy complemented by experts in the particular artistic field. The Academy also organized the Heineken Lectures 2002. The five laureates were asked to give a lecture about their work for a broad audi- ence at universities across the country.This is the unique publication of those five very diverse lectures given by the prizewinners, every one of them excellent in his or her own discipline. Contents page 6 Willem J.M. Levelt Preface 9 Roger Y.Tsien DR H.P. HEINEKEN PRIZE FOR BIOCHEMISTRY AND BIOPHYSICS Unlocking Cell Secrets with Light Beams and Molecular Spies 29 Aernout Mik DR A.H. HEINEKEN PRIZE FOR ART Echt Onecht 49 Dennis J. Selkoe DR A.H. HEINEKEN PRIZE FOR MEDICINE Towards a Remembrance of Things Past 63 Heinz Schilling DR A.H. HEINEKEN PRIZE FOR HISTORY Europa in der werdenden Neuzeit – oder: ‘Was heißt und zu welchem Ende studiert man europäische Geschichte?’ 83 Lonnie G.Thompson DR A.H. HEINEKEN PRIZE FOR ENVIRONMENTAL SCIENCES Rapid Climate Change in the Earth System:Past,Present,Future 89 About the winners of the Heineken Prizes 2002 94 List of Prizewinners Preface The winners of the biennial Heineken Prizes 2002 are Roger Tsien, Aernout Mik, Dennis Selkoe, Heinz Schilling and Lonnie Thompson.What our laureates share is intel- lectual excellence. It is the primary concern of the Royal Netherlands Academy of Arts and Sciences to recognize and to promote such excellence. Our modern society is entirely dependent on intellectual expertise, be it scientific, artistic, moral.What is the constitution of an expert mind? What do our laureates have in common? Great scientists, scholars and artists alike, are highly skilled minds.They all operate in a culture that has accumulated sophisticated intellectual tools, methods, materials, information carrying devices, and so on, which make it possible for a well-trained mind to advance that same culture with new discoveries, new theories, new insights and explanations, new technologies, with a new understanding of its own structure, its own past and future, and with new artistic means of reflecting on its own existence and on the human condition in all its variation. Another hallmark of this elite is its intellectual independence.Although embedded in a rich cultural tradition, scientists, scholars and artists alike operate without recourse to authority,without making intellectual concessions to rulers, to churches, to the market or to the popular press. They all share the great legacy of the Enlightment, which is intellectual integrity and independence. Creativity,whether in the sciences, humanities or the arts, requires its practitioner to set his own intellectual agenda. Also, there exist major commonalities in the creative process itself. One essential ingredient of all creativity is serendipity.Only the skilled mind will immediately recog- nize the potential of the unexpected, the particular way an experiment happened to fail, the scribbled note in the margin of an historical document, the accidental affordance of an architectural feature for a particular kind of visual projection. Intellectual creativ- ity is hardly ever a deductive, fully planned rational process, whether in the arts or in the sciences. It is rather mostly Darwinian in the sense of capitalizing on the occasional, on the accidental. Closely related to this recognition of potential in the accidental is emotional invol- vement. That artists are emotional is the stereotype, but believe me, scientists are no better.The mechanism of serendipity is highly exciting.The role of emotion is to alert a person to something significant. An emotion tells you ‘this is potentially important. It deserves your attention’. Importance or significance is obviously determined by the person’s system of values, by the intellectual agenda, by the accumulated professional experience.What is usually called ‘intuition’in both Wissenschaft and Kunst is precisely the 6 ROYAL NETHERLANDS ACADEMY OF ARTS AND SCIENCES HEINEKEN LECTURES 2002 outcome of this emotionally guided intellectual focussing.The creative process is always emotional and value-driven, whether in the sciences, the arts, or the humanities. Shared among our laureates is also an appreciation of simplicity in complexity. Scientists, scholars and artists alike are problem solvers.They all spend their lives estab- lishing order, structure in complexity.The major problem for the scientist is to discover the underlying mechanisms, be they cognitive, biological, chemical, physical, that govern surface, phenomenal complexity.Ideally,these mechanisms are cast in terms of mathematical equations or computational theories.The scholar, no less, is always in the business of reducing bewildering documental complexity to coherent and verifiable patterns. Similarly,unity in diversity has always been a core notion in theories of artis- tic experience. The intended effect of visual art, however complex, is the observer’s creation of perceptual order.The artist establishes the conditions for the observer to do the work, namely to discover structure in complexity. Let me finally mention one more commonality among the minds that we honor today. It is respect for their objects of scrutiny and manipulation. It is not remotely possible for great scholars, scientists or artists to say ‘too bad for the data, too bad for the texts, too bad for the materials; I am above that’. Johann Wolfgang von Goethe put it this way: ‘In both art and science it is all important that the objects are conceived in clarity and treated according to their nature.’ In previous years, our laureates gave their Heineken Lectures during the course of a single Academy session at the Trippenhuis in Amsterdam, the headquarters of the Royal Netherlands Academy of Arts and Sciences. Last year, on 23 September 2002, the Heineken Lectures were given in the late afternoon at five different locations throughout the Netherlands, drawing more people than ever before. We have once again published the lectures in a single volume.This was certainly more than justified, as it was not possible to attend them all. Willem J.M. Levelt President of the Royal Netherlands Academy of Arts and Sciences 7 PREFACE Heineken Lecture Roger Tsien hoogleraar farmacologie, chemie en biochemie aan de University of California, San Diego winnaar van de Dr. H.P.Heinekenprijs voor de Biochemie en de Biofysica 2002 Unlocking Cell Secrets with Light Beams and Molecular Spies over de methoden om de processen in een cel ‘live’te volgen maandag 23 september 2002, 16.30 uur Vrije Universiteit, zaal KC 137, De Boelelaan 1081,Amsterdam De lezing is vrij toegankelijk; na afloop is er een borrel. Inlichtingen: Koninklijke Nederlandse Akademie van Wetenschappen, Amsterdam www.knaw.nl/heinekenprizes [email protected] telefoon 020-5510759 8 ROYAL NETHERLANDS ACADEMY OF ARTS AND SCIENCES HEINEKEN LECTURES 2002 Unlocking Cell Secrets with Light Beams and Molecular Spies DR H.P. HEINEKEN PRIZE FOR BIOCHEMISTRY AND BIOPHYSICS ROGER Y.TSIEN The Dr H.P.Heineken Prize for Biochemistry and Biophysics 2002 was awarded to Professor Roger Y.Tsien for his extraordinary and unique contribution to the development of a series of methods and techniques for measuring and visualising processes within and between cells. In some ways, the cells in our bodies are a bit like social communities.The proteins and other molecules inside the cell interact with each other rather like the people of a medi- um-sized town (Fig.1). I say medium-sized, because the sequencing of the human genome last year indicated that we contain only about 25,000-35,000 genes1, which specify roughly the same number of protein types. Many people were surprised that the number was so finite and that Homo sapiens did not have significantly more genes than other species. A genome sequence is at best a sort of telephone directory or census list of the names of all the citizens: valuable reference information, but not something one would read from cover to cover for fun. It also gives little hint as to how the inhabitants actually live. Like town dwellers, individual protein molecules in a cell are born, get modified or ‘educated’, travel around, and cooperate or compete with each other for partnerships. Some proteins emigrate from the cell. A few have the job of killing other proteins. Eventually all the proteins will die at varying ages and their components will be recycled. Suppose you were an anthropologist from a distant continent, or an alien from outer space.You