The Magic Molecule that has improved the lives of millions Börje Svensson Copyright The publisher will keep this document online on the Internet – or its possible replacement – for a considerable time from the date of publication barring exceptional circumstances. The online availability of the document implies permanent permission for anyone to read, to download, or to print out single copies for his/her own use and to use it unchanged for non- commercial research and educational purposes. Subsequent transfers of copyright cannot revoke this permission. All other uses of the document are conditional upon the consent of the copyright owner. The publisher has taken technical and administrative measures to assure authenticity, security and accessibility. According to intellectual property law, the author has the right to be mentioned when his/her work is accessed as described above and to be protected against infringement. For additional information about Linköping University Electronic Press and its procedures for publication and for assurance of document integrity, please refer to its www home page: http://www.ep.liu.se/. Linköping University Electronic Press Linköping, Sweden, 2015 ISBN: 978-91-7519-076-1 © Börje Svensson, 2015 [email protected] Photo at the front page: “White leghorn rooster” by Sándor Szirmai. Gift from the artist to Endre Balazs (May 22, 1962) 2 Contents Preface ................................................................................................................................. 5 Part I: The early years of the Healon project (1971-77) ............................................... 11 CHAPTER 1: Introduction .................................................................................................... 11 CHAPTER 2: The Healon project is adopted by Pharmacia ................................................ 17 CHAPTER 3: Promising start followed by unforeseen setbacks .......................................... 25 CHAPTER 4: License agreement with restrictions ............................................................... 29 CHAPTER 5: License agreement re-negotiated .................................................................. 33 CHAPTER 6: New production plant - an ill-conceived decision ........................................... 37 CHAPTER 7: My own participation in the Healon project .................................................... 43 CHAPTER 8: The Healon project evaluated ........................................................................ 45 Part II: Healon - a revolution in cataract surgery .......................................................... 51 CHAPTER 9: The discovery of the cataract surgery market ................................................ 51 CHAPTER 10: Healon’s development according to Pharmacia’s annual reports ................ 59 CHAPTER 11: Four key players at Pharmacia Ophthalmics ............................................... 66 Part III: Biomatrix – a successful manifestation of frustration ..................................... 77 CHAPTER 12: The creation of Biomatrix ............................................................................. 79 CHAPTER 13: Biomatrix’ first ten years ............................................................................... 81 CHAPTER 14: Biomatrix’ Swedish subsidiary ...................................................................... 95 CHAPTER 15: Biomatrix 1992-2000 – fast growth and big ambitions ............................... 101 CHAPTER 16: In the wake of success: Three unforeseen legal disputes ......................... 111 CHAPTER 17: What became of Synvisc? .......................................................................... 115 Part IV: Xalatan – the spin-off that became a blockbuster .......................................... 117 CHAPTER 18: The project no one wanted ......................................................................... 117 CHAPTER 19: The Xalatan saga from different perspectives ............................................ 121 CHAPTER 20: László Bitó – the man who pushed on despite his critics ........................... 131 Part V: Hyaluronic acid and facial aesthetics – a mere coincidence ....................... 143 CHAPTER 21: New products emerge from the quest for eternal youth ............................. 145 CHAPTER 22: The discovery of hyaluronic acid’s potential within the beauty industry ..... 149 CHAPTER 23: The origin of Restylane and Juvéderm ...................................................... 153 CHAPTER 24: A pioneer in the early development of Hylaform and Restylane ................ 167 CHAPTER 25: Spin-offs generate yet more spin-offs ........................................................ 173 CHAPTER 26: What became of Hylaform? ........................................................................ 177 3 Part VI: Some final thoughts .......................................................................................... 179 CHAPTER 27: Management of conflict .............................................................................. 181 CHAPTER 28: Factors for success .................................................................................... 189 Appendix A: The origins of the book and the facts on which it is based ............................ 209 Appendix B: References ..................................................................................................... 211 Appendix C: History timeline of the Magic Molecule .......................................................... 215 Appendix D: Acknowledgements ........................................................................................ 219 Appendix E: About the author………………………………………...................................... 221 4 Preface Millions of people all over the world are granted better vision thanks to a seemingly magic molecule. The molecule makes it possible to remove the eye’s lens and replace it with an artificial one. Cataracts are the cause of most lens replacements. The disease clouds the lens which in turn blurs vision. Until the early 1980’s, lens transplants were a very complicated affair, so much so that many eye surgeons avoided the procedure altogether. The revolutionary events that have taken place since, now allow surgeons to perform a lens transplant in less than 15 minutes, the results of which are successful nearly every single time. This medical breakthrough was made possible by the magic molecule described in this book. The same molecule has also helped to ease ailing knees affected by arthritis. Despite the controversial nature of the molecule’s use in treating arthritis, the fact remains that many of the millions of people treated yearly report significant relief as a result. Furthermore, the molecule’s use in treating joints is not limited to those of humans, but also includes horses. Then working as product manager for the Swedish pharmaceutical company Pharmacia, I was personally involved in introducing Healonid® Vet., a product based on the magic molecule, into the French equestrian market some forty years ago. As if eyes, knees and horses were not enough, the magic molecule has even revolutionized the global beauty industry during the past twenty years. Commonly used as the main ingredient in dermal fillers, the molecule has enabled many of the most successful wrinkle reducing products developed by world leading companies. The magic molecule I speak of is a sugar molecule called hyaluronic acid. The modern term for the molecule is hyaluronan, often shortened HA. For the purposes of this book, the term hyaluronic acid will be used, since this is still the term most frequently used. Hyaluronic acid is found in a number of areas within the human body. In the human skin, hyaluronic acid works as a moisturizing and filling agent. In the human joint it acts as a lubricant and shock absorber. It is also found in the eye and the umbilical cord. Hyaluronic acid is also found in sources outside the human body. The hyaluronic acid described in this book originates from rooster combs or synthetically, through a process of bacterial fermentation. Hyaluronic acid was discovered in 1934 by Karl Meyer and John Palmer, researchers at Columbia University. A Hungarian researcher by the name of Endre Balazs was the first to develop hyaluronic acid for commercial use. In 1943, Balazs received a patent for a method using fluid from knee joints of cows to be used as an egg white substitute in baking. The product itself was not very successful, but Balazs was inspired to search 5 for other commercial uses for hyaluronic acid. In particular, he was eager to discover medical benefits of its use. Endre Balazs is still driven by this eagerness, at 95 years of age. Throughout his career, he has successfully transformed research into practical benefit to an extent that most researchers only dream of. Part I: The first six years (1971-77) – if not for the placebo effect If it is possible to call a molecule magic, hyaluronic acid is certainly deserving. That which has been accomplished as a result of its discovery has been truly astounding. Hyaluronic acid’s commercial journey within medicine began some 43 years ago, marked by Endre Balazs crossing paths with Torvard Laurent, professor at Uppsala University, and Harry Hint, Chief Scientific Officer at Pharmacia, a pharmaceutical company located in Uppsala, Sweden. Both Laurent and Hint knew Balazs from his time as guest researcher at Karolinska Institutet (KI) in Stockholm in the late 1940’s.