Title Hormone Hunters: The Discovery of Adrenaline( Cover, Tableof Contents )

Author(s) ISHIDA, Mitsuo

Citation Kyoto University Press. (2018): 1-203

Issue Date 2018-09-05

URL https://doi.org/10.14989/234214

Right Copyright by Mitsuo Ishida, Japan, 2018; Cover image © ChisaMURAKAMI

Type Book

Textversion publisher

Kyoto University

1

Hormone Hunters — The Discovery of Adrenaline —

Mitsuo Ishida

Yokohama, Japan 2018

i

Hormone Hunters: The Discovery of Adrenaline

Published online in 2018

© 2018 Mitsuo ISHIDA

First published in Japan in 2012 by Kyoto University Press, Kyoto.

entitled “Hormone Hunters: Adrenaline no Hakken.”

Cover image © Chisa MURAKAMI

ii

To T. N., my honorable friend

Looking back in time, I smile

To have a friend such as you

Sets my mind at rest

Divided though we may be

By the limitless ocean

iii

Table of Contents

Prologue 1

Chapter 1 Making History with Hormones 6

1. Dawn in a foreign country 6

2. Steady progress 10

3. Aiming for commercialization 12

Chapter 2 The Quest to Unravel the Mystery of the Adrenal Glands 18

1. Searching in the dark 18

2. The steady advance of anatomy and embryology 21

3. Addison’s disease 24

4. What happens if the adrenal glands are removed? 25

Chapter 3 The Search for Physiological Functions 30

1. Submissions to Montesquieu’s Essay Competition 30

2. The dawn of physiology 32

3. Vulpian’s keen insight 35

4. Meanwhile, in other countries 38

5. Why was Vulpian doing this research? 39

6. Vulpian’s many friendships 41

7. Courageous human experiments 43

8. Professor Schäfer’s astonishment 47

9. The anguish of a minor language 50

10. Looking back over research into the functions of the suprarenal glands 52

11. Hemostatic effect and treatment of hay fever and asthma 55

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Chapter 4 In Pursuit of the Active Principles 62

1. Physiological curiosity 62

2. Painstaking explorations by chemists 66

3. The climax of the isolation race 69

4. The war of words between American, British, and German researchers 74

5. Success at Last 75

6. The gentleman of Parke, Davis & Co. 79

7. Reaction to the crystallization 81

8. Abel refuses to give up 86

9. Lack of a group to determine activity 87

Chapter 5 Good Fortune 93

1. Takamine’s first turning point 93

2. Takamine’s second turning point 97

3. Fighting back with a new idea 100

4. The meeting with Davis 106

5. The participation of Keizo Wooyenaka 109

6. The diligent preparations of Parke, Davis & Co. 111

7. Takamine’s continuous advertising 113

8. Ensuring stable product quality 115

9. An English translation of Vulpian’s paper 117

10. Wooyenaka stays faithful to Nagai’s teaching 118

11. Should Wooyenaka be a co-author? 119

12. Applied and pure science 122

Chapter 6 The Historic Ruling in the Patent Dispute 128

1. Unreliable nineteenth century medicines 128

2. Smooth commercialization 129

3. The appearance of a rival product 131

4. The Patent dispute and a landmark ruling 132

5. Maintaining the manufacturing method and product quality that were praised 135

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Chapter 7 Confusion over the Name 138

1. Four people, four names 138

2. Trademark rights 140

3. The War of Words 140

4. The struggles of a researcher: the fifth name 144

5. The letter that decided the name in the US Pharmacopeia 145

6. The review that caused an unfortunate misunderstanding 148

7. The name of the adrenal medulla hormone in different Pharmacopoeias 150

Chapter 8 Post Crystallization 155

1. Abel’s sad decline 155

2. Expanding fields of research 158

3. The name “hormone” 160

4. Synthesis and chemical structure 161

5. Discovery of noradrenaline, a sympathomimetic compound 169

6. More Nobel Prizes 174

7. New medicines developed by chemical structure modification 177

8. Later information on the two American scientists 179

9. A ring connecting Nagai, Takamine, and Wooyenaka 180

10. Adrenaline still in use today 182

11. Other contributions by Jokichi Takamine 184

12. Takamine as an unofficial ambassador 185

13. Here lie the Japanese hormone hunters 186

Column

1-1. The extraction and crystallization method developed by J. Takamine and K. Wooyenaka 15 1-2. The paper by Alfred Vulpian that first reported the adrenaline-specific color reactions 16 3-1. What is the truth of Oliver’s experiment on his son? 57 6-1. Hand’s philosophy 136 8-1. Optical isomers: The same elemental composition but completely different biological activity 162

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In Brief 2-1. The Copley Medal 23

4-1. The history of chromatography 66 4-2. Strasbourg (France): City of culture at the mercy of Franco-German disputes 72 4-3. Science at the end of the 19th century and the start of the 20th century 78 5-1. Parke, Davis & Co., the leader of the pharmaceutical industry 103

Epilogue 194

Acknowledgements 197

Profile of Jokichi Takamine 199

Profile of Keizo Wooyenaka 201

Personal History of Mitsuo Ishida 202

Postscript to English version of Hormone Hunters 203