PHYSIOLOGY NOBEL LECTURES OR MEDICINE. Nobel Lectures in Physiology or Medicine ( ) Downloaded from

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1 NOBEL LECTURES PHYSIOLOGY OR MEDICINE

2 NOBEL LECTURES INCLUDING PRESENTATION SPEECHES AND LAUREATES' BIOGRAPHIES PHYSICS CHEMISTRY PHYSIOLOGY OR MEDICINE LITERATURE ECONOMIC SCIENCES

3 NOBEL LECTURES INCLUDING PRESENTATION SPEECHES AND LAUREATES' BIOGRAPHIES PHYSIOLOGY OR MEDICINE EDITOR Goran K. Hansson Karolinska Institute, Sweden World Scientific NEW JERSEY LONDON SINGAPORE BEIJING SHANGHAI HONG KONG TAIPEI CHENNAI

4 Published by World Scientific Publishing Co. Pte. Ltd. 5 Toh Tuck Link, Singapore USA office: 27 Warren Street, Suite , Hackensack, NJ UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE NOBEL LECTURES IN PHYSIOLOGY OR MEDICINE ( ) The Nobel Foundation ( ) Published with permission from Nobel Media AB in 2014 by World Scientific Publishing Co. Pte. Ltd. Nobel Prize and the Nobel Prize medal design mark are the registered trademarks of the Nobel Foundation. ISBN ISBN (pbk) Printed in Singapore by Mainland Press.

5 v PREFACE Nobel Week in December every year highlights the scientific and cultural accomplishments that are awarded with the Nobel Prize. It is a time of excitement not only for the Nobel Laureates who arrive in a wintry Stockholm, but also for the Committee members who have chosen them, for all those interested in science and literature, and for the general public that wishes to be part of the celebrations. Intense media coverage guarantees that everyone interested in science, literature, celebrities or festivities gets insights into the aspects of their particular taste. The week from December 6 to 13 is loaded with activities ranging from symposia to concerts and from cocktail parties to visits to local schools. However, only two of these activities are mandatory for the Nobel Laureates according to the Statutes of the Nobel Foundation: to accept the Nobel Prize at the Nobel Prize Ceremony on December 10, and to give a Nobel Lecture that describes the discoveries awarded the Nobel Prize. The lectures are scheduled a couple of days before the Nobel Prize Ceremony, to allow the Nobel Laureates to enjoy the subsequent festivities in a more relaxed way. The Nobel Lectures in Physiology or Medicine are given at Karolinska Institutet, the medical university that hosts the Nobel Assembly and the Nobel Committee for Physiology or Medicine. On the day of the Lectures, the main auditorium of the Institute is crowded with people faculty members, postdoctoral fellows, students, and others eager to hear the Nobel Laureates describe their work. Scientists all over the world are following the Lectures through webcast, adding to the excitement of the moment. Records of the Nobel Lectures are kept as videotapes on org and in written form in the Nobel Lectures series (previously Les Prix Nobel ). By reading the Nobel Lectures and autobiographic notes of the Nobel Laureates, the reader gets first-hand insights into the progress and breakthroughs of science over more than a century. Portraits of the Nobel Laureates, and the presentation speeches given by Nobel Committee members during the Nobel Prize Ceremony, add to the wealth of information available in this series. The present volume contains Nobel Lectures, autobiographies, portraits, and presentation speeches by the Nobel Laureates in Physiology or Medicine for the years The science contained herein presents a broad panorama of paradigm-shifting discoveries in medicine and life science. It includes fundamental principles of gene structure and regulation as represented by the discoveries of RNA interference and the telomerase machinery but also medical breakthroughs regarding the viral etiology of adult immune deficiency syndrome (AIDS) and cervical

6 vi Preface cancer, two major lethal diseases afflicting mankind. It ranges from breakthroughs in experimental genetics through the use of homologous gene recombination in embryonal stem cells, to the technology of in-vitro fertilization that offers new hope for infertile couples. As a member of the Nobel Assembly and its Nobel Committee since more than 15 years and presently as its secretary-general, I have had the privilege of meeting the Nobel Laureates from the time period included in this volume and the excitement of hearing them present their Nobel Lectures. I hope that the reader of this book will feel the same excitement of learning first-hand how major discoveries were made and also get a glimpse of the individuals who made them. Göran K. Hansson, M.D., Ph.D. December 2014

7 vii CONTENTS Preface v 2006 Andrew Z. Fire and Craig C. Mello Presentation by Göran K. Hansson 3 Biography of Andrew Z. Fire 7 Gene Silencing by Double Stranded RNA 8 Biography of Craig C. Mello 45 Return to the RNAi World: Rethinking Gene Expression and Evolution Mario R. Capecchi, Martin J. Evans and Oliver Smithies Presentation by Christer Betsholtz 71 Biography of Mario R. Capecchi 75 Gene Trageting 1977 Present 89 Biography of Martin J. Evans 109 Embryonic Stem Cells: The Mouse Source Vehicle for Mammalian Genetics and Beyond 115 Biography of Oliver Smithies 129 Turning Pages Harald zur Hausen, Françoise Barré-Sinoussi and Luc Montagnier Presentation by Jan Andersson 167 Biography of Harald zur Hausen 171 The Search for Infectious Causes of Human Cancers: Where and Why 177 Biography of Françoise Barré-Sinoussi 199 HIV: A Discovery Opening the Road to Novel Scientific Knowledge and Global Health Improvement 205

8 viii Contents Biography of Luc Montagnier Years After HIV Discovery: Prospects for Cure and Vaccine Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak Presentation by Rune Toftgård 247 Biography of Elizabeth H. Blackburn 251 Telomeres and Telomerase: The Means to the End 269 Biography of Carol W. Greider 295 Telomerase Discovery: The Excitement of Putting Together Pieces of the Puzzle 309 Biography of Jack W. Szostak 331 DNA Ends: Just the Beginning Robert G. Edwards Presentation by Christer Höög 375 Robert Edwards: Nobel Laureate in Physiology or Medicine 379 by Martin H. Johnson