The memoirs of Désiré Collen The memoirs of Désiré Collen A HEART’S DESIRE BLENDING ACADEMIC RESEARCH AND BUSINESS ENTERPRISE Désiré Collen Translation into English from the Dutch original Memoires Désiré Collen Een hart voor onDerzoek en onDernemen © 2009 – Désiré Collen/Uitgeverij VanDen Broele, Brugge X + 228 p. Foto cover: Bart Van Leuven ISBN 978 90 4960 056 3 D/2009/0783/82 NUR 681 Vormgeving en Druk: Grafische groep VanDen Broele TekstreDactie: Peter Raeymaekers CONTENTS Preface .......................................................................................................................................... 1 t-PA and thrombolysis ... the context of a life's story ..................................................................... 7 A simple experiment .............................................................................................................................. 7 Lifesaving option against heart attack ................................................................................................... 7 Heart and vascular diseases - a heavy toll ............................................................................................. 8 Plaques and clots ................................................................................................................................... 9 "Open-Artery" hypothesis ................................................................................................................... 10 Cause or consequence? ....................................................................................................................... 11 Endurance of the stubborn .................................................................................................................. 11 Little enthusiasm ................................................................................................................................. 12 Renewed interest ................................................................................................................................ 13 Section I. The pre-history of the t-PA story .................................................................................... 15 Double qualifications .................................................................................................................... 17 First disciplined, then undisciplined and finally hard working ............................................................. 17 First research experience .................................................................................................................... 18 Medicine and chemistry ...................................................................................................................... 19 In the grip of research ................................................................................................................... 21 Clinical training hampered by revalidation and reorientation ............................................................ 22 New York ............................................................................................................................................. 24 Stockholm ............................................................................................................................................ 25 Back in Leuven ..................................................................................................................................... 26 Concluded ............................................................................................................................................ 27 Molecular mechanism of fibrinolysis elucidated ............................................................................ 31 Life and death of a blood clot .............................................................................................................. 31 The lytic trio: plasminogen activator, plasminogen and fibrin ............................................................ 32 An unknown inhibitor .......................................................................................................................... 34 Discovery of α2 antiplasmin ................................................................................................................ 36 Future entrepreneur? ................................................................................................................... 39 Under contract with LR&D ................................................................................................................... 39 Farmer-entrepreneur .......................................................................................................................... 40 V Section II. The t-PA story ............................................................................................................... 43 A difficult protein .......................................................................................................................... 45 Fibrin specific ....................................................................................................................................... 45 The rolling snowball ............................................................................................................................. 46 A drug against cancer? ........................................................................................................................ 46 Production champion .......................................................................................................................... 48 Run out of luck ..................................................................................................................................... 48 Assumptions become facts ............................................................................................................ 49 Rescuer from the Netherlands ............................................................................................................ 49 A short sprint ....................................................................................................................................... 50 A patent and a cont (r) act … with the alleged daughter of a professor .......................................... 55 Good advice from the Rector, Pieter De Somer .................................................................................. 55 A first patent ........................................................................................................................................ 55 Too early, too late … or just in time ..................................................................................................... 56 A piece of cake ..................................................................................................................................... 56 A new industry ..................................................................................................................................... 57 LR&D on a mission ............................................................................................................................... 58 18/24, 7/7 ............................................................................................................................................ 59 A beautiful protein ............................................................................................................................... 59 A headwind .................................................................................................................................. 61 Fat in the fire ....................................................................................................................................... 61 Loyalty in collaborations ...................................................................................................................... 61 Collaboration with Genentech continues ............................................................................................ 63 A first patient ................................................................................................................................ 65 Attending a Rotterdam conference ..................................................................................................... 65 A critically ill kidney transplant patient ............................................................................................... 65 Preclinical t-PA research ............................................................................................................... 69 American dogs ..................................................................................................................................... 69 Recombinant t-PA, indistinguishable from natural Bowes melanoma t-PA ........................................ 70 Taking no risks ..................................................................................................................................... 70 A lost friend ......................................................................................................................................... 71 The first clinical studies with t-PA ................................................................................................. 73 Double record ...................................................................................................................................... 73 First randomized study .......................................................................................................................