VITAMIN C A 500-Year Scientific Biography from Scurvy to Pseudoscience Stephen M. Sagar Essex, Connecticut 2222__00003399--SSaaggaarr..iinnddbb 11 33//2211//2222 22::1177 PPMM An imprint of Globe Pequot, the trade division of The Rowman & Littlefield Publishing Group, Inc. 4501 Forbes Blvd., Ste. 200 Lanham, MD 20706 www.rowman.com Distributed by NATIONAL BOOK NETWORK Copyright © 2022 by Stephen M. Sagar All rights reserved. No part of this book may be reproduced in any form or by any electronic or mechanical means, including information storage and retrieval systems, without written permission from the publisher, except by a reviewer who may quote passages in a review. British Library Cataloguing in Publication Information Available Library of Congress Cataloging-in-Publication Data Names: Sagar, Stephen M., author. Title: Vitamin C : a 500-year scientific biography from scurvy to pseudoscience / Stephen M. Sagar. Description: Lanham, MD : Rowman & Littlefield, [2022] | Includes bibliographical references and index. | Summary: “Vitamin C: A 500-Year Scientific Biography from Scurvy to Pseudoscience is the compelling story of the history and science behind vitamin C”— Provided by publisher. Identifiers: LCCN 2021060986 (print) | LCCN 2021060987 (ebook) | ISBN 9781633888265 (cloth) | ISBN 9781633888272 (epub) Subjects: LCSH: Vitamin C—History. Classification: LCC QP772.A8 S24 2022 (print) | LCC QP772.A8 (ebook) | DDC 615.3/28—dc23/eng/20211220 LC record available at https://lccn.loc.gov/2021060986 LC ebook record available at https://lccn.loc.gov/2021060987 The paper used in this publication meets the minimum requirements of American National Standard for Information Sciences—Permanence of Paper for Printed Library Materials, ANSI/NISO Z39.48-1992. 2222__00003399--SSaaggaarr..iinnddbb 22 33//2211//2222 22::1177 PPMM For Susan 2222__00003399--SSaaggaarr..iinnddbb 33 33//2211//2222 22::1177 PPMM [R]esearch is not a systematic occupation but an intuitive artistic vocation. —Albert Szent-Gyorgyi, “Lost in the Twentieth Century,” 1963 I don’t think anything is ever just science. —Siri Hustvedt, What I Loved, 2003 2222__00003399--SSaaggaarr..iinnddbb 44 33//2211//2222 22::1177 PPMM CONTENTS PREFACE vii INTRODUCTION xi Part I Buccaneers and Bureaucrats: The History of Scurvy 1 A DISEASE OF MARINERS 3 2 CATASTROPHE AND ENLIGHTENMENT 21 3 AN UNLIKELY HERO AND A PARTIAL VICTORY 37 4 STEPS FORWARD AND BACK 53 Part II The Chemists Take Over: The Discovery of Vitamins 5 A DIFFERENT KIND OF NUTRIENT 71 6 THE VITAMIN HUNTERS 93 v 2222__00003399--SSaaggaarr..iinnddbb 55 33//2211//2222 22::1177 PPMM COnTenTS 7 SCURVY FOR SCIENCE 107 8 NORMAL SCIENCE 117 Part III The new Buccaneers: The Business of Vitamins 9 THE PASSION OF LINUS PAULING 131 10 VITAMINS, BUSINESS, AND POLITICS 149 11 LESSONS LEARNED 161 12 A GUIDE FOR THE PERPLEXED 167 APPENDIX: SELECTED FOOD SOURCES OF VITAMIN C 181 NOTES 183 BIBLIOGRAPHY 201 ACKNOWLEDGMENTS 215 INDEX 217 vi 2222__00003399--SSaaggaarr..iinnddbb 66 33//2211//2222 22::1177 PPMM PREFACE If irst encountered pure ascorbic acid, the chemical name for vitamin C, in 1977. Having just completed medical school and residencies in internal medicine and neurology, I aspired to be a clinician-scientist and went to work in a neuroscience laboratory in Boston. In that job, I used ascorbic acid virtually every day. But I was not interested in the compound; it was merely a substance to prevent the oxidation of other reagents. I did not bother to weigh it out, adding the few milligrams picked up on a spatula tip. Vitamin C first piqued my interest in the early 1980s when it earned me funding for a pilot research project. One of the Sackler brothers invited my mentor to New York to discuss his laboratory’s work. The Sackler family is now infamous for owning Purdue Pharma, promoting OxyContin, and, in the minds of many, igniting the opioid crisis. But that was before OxyContin. The family had gotten rich advising big pharmaceutical companies how to promote drugs directly to doctors. They devoted some of their wealth to a foundation that supported medical research, and my mentor asked his trainees for brief grant proposals to take to his meeting to try to capture some of that wealth for his laboratory. vii 2222__00003399--SSaaggaarr..iinnddbb 77 33//2211//2222 22::1177 PPMM VITAMIN C My proposal concerned the neurobiological actions of capsaicin and, like most writings about capsaicin, contained a statement that it is the active, pungent ingredient of Hungarian paprika and Mexi- can chili peppers. The Sackler brother who perused the proposal was not interested in capsaicin or in my science. He decided to fund the grant because Hungarian paprika had been a commercial source of vitamin C. Unbeknownst to me, his foundation was sup- porting the research of Linus Pauling, the Nobel Prize–winning chemist and most publicly visible proponent of megadose vitamin C. My grant proposal had nothing to do with vitamins and nothing of importance came of the project, but this small windfall was one example of the serendipity that punctuated the history of vitamin C. My research went in other directions and I had little more to do with vitamin C until I switched tracks and entered the phar- maceutical industry. In 2012, I prepared a talk for a job interview at a small biotech company. The same mechanism that transports one form of vitamin C into the brain also transports the drug that I would have worked with at this company. This led me to inves- tigate the neurological manifestations of scurvy and delve into the history of that disease. I did not take the job, but as I read more, the intriguing stories and fascinating characters in the history of vitamin C convinced me that it was a story worth bringing to a wider audience. The five-hundred-year saga is rich with compelling stories and interest- ing characters, with tales of courage and callousness, of brilliant insight and folly, and of strokes of luck, both good and bad. The protagonists include flamboyant personalities with conflicting egos—swashbuckling sailors, Arctic explorers, penny-pinching bu- reaucrats, scientists working in malaria-infested jungle laboratories, and investigators utilizing the latest tools of molecular biology. The story provides examples of our failure to learn from history and to repeat the mistakes made by our ancestors hundreds of years ago. viii 2222__00003399--SSaaggaarr..iinnddbb 88 33//2211//2222 22::1177 PPMM PrefaCe The history of vitamin C illustrates how medical science works in the real world and how it has changed over the centuries. It shows that the human brain can penetrate the mysteries of biology but also can be led astray. It illuminates the fitful progression of sci- ence as scientists struggle against the limitations of human intellect while society attempts to deal with the implications of those discov- eries. The COVID-19 pandemic convinced me even more of the importance of looking to the history of science to better understand our current dilemmas. ix 2222__00003399--SSaaggaarr..iinnddbb 99 33//2211//2222 22::1177 PPMM