The Demon Under the Microscope
Copyright © 2006 by Thomas Hager
All rights reserved.
Published in the United States by Three Rivers Press, an imprint of the Crown Publishing Group, a division of Random House, Inc., New York.
www.crownpublishing.com
Three Rivers Press and the Tugboat design are registered trademarks of Random House, Inc.
Originally published in hardcover in the United States by Harmony Books, an imprint of the Crown Publishing Group, a division of Random House, Inc., New York in 2006.
Library of Congress Cataloging-in-Publication Data
Hager, Thomas.
The demon under the microscope : from battlefield hospitals to Nazi labs, one doctor’s heroic search for the world’s first miracle drug / Thomas Hager.—1st ed.
Includes bibliographical references and index.
1. Domagk, Gerhard, 1895–1964. 2. Sulphur drugs—History. 3. Antibacterial agents—History. 4. Bacterial diseases—Chemotherapy. 5. Medical scientists—Germany—Biography.
[DNLM: 1. Domagk, Gerhard, 1895–1964. 2. Physicians—Germany—Biography. 3. History, 20th Century—Germany. 4. Sulfonamides—history—Germany. WZ 100 D665h 2006] I. Title.
RM666. S9H34 2006
615'.2723—dc22 2006004510
ISBN 9781400082148
Ebook ISBN 9780307352286
rh_3.0_c0_r4
CONTENTS
COVER
TITLE PAGE
COPYRIGHT
EPIGRAPH
INTRODUCTION
PROLOGUE
I THE HUNT
CHAPTER ONE
CHAPTER TWO
CHAPTER THREE
CHAPTER FOUR
CHAPTER FIVE
CHAPTER SIX
CHAPTER SEVEN
CHAPTER EIGHT
CHAPTER NINE
CHAPTER TEN
II THE RIGHT SIDE
CHAPTER ELEVEN
CHAPTER TWELVE
CHAPTER THIRTEEN
CHAPTER FOURTEEN
CHAPTER FIFTEEN
CHAPTER SIXTEEN
III THE LEFT SIDE
CHAPTER SEVENTEEN
CHAPTER EIGHTEEN
CHAPTER NINETEEN
CHAPTER TWENTY
CHAPTER TWENTY-ONE
CHAPTER TWENTY-TWO
CHAPTER TWENTY-THREE
EPILOGUE
ACKNOWLEDGMENTS
SOURCE NOTES
BIBLIOGRAPHY
As a surgeon Asklepios became so skilled in his profession that he not only saved lives but even revived the dead; for he had received from Athena the blood that had coursed through the Gorgon’s veins, the left-side portion of which he used to destroy people, but that on the right he used for their salvation.
—THE LIBRARY OF APOLLODORUS
INTRODUCTION
IN 1931, humans could fly across oceans and communicate instantaneously around the world. They studied quantum physics and practiced psychoanalysis, suffered mass advertising, got stuck in traffic jams, talked on the phone, erected skyscrapers, and worried about their weight. In Western nations people were cynical and ironic, greedy and thrill-happy, in love with movies and jazz, and enamored of all things new; they were, in most senses, thoroughly modern. But in at least one important way, they had advanced little more than prehistoric humans: They were almost helpless in the face of bacterial infection.
For thousands of years, humans had sought medicines with which they could defeat contagion, and they had slowly, painstakingly, won a few battles: some vaccines to ward off disease, a handful of antitoxins. A drug or two was available that could stop parasitic diseases once they hit, tropical maladies like malaria and sleeping sickness. But the great killers of Europe, North America, and most of Asia—pneumonia, plague, tuberculosis, diphtheria, cholera, meningitis—were caused not by parasites but by bacteria, much smaller, far different microorganisms. Nothing on earth could stop a bacterial infection once it started.
It was not for lack of trying. Like the two snakes entwined on the staff of Hermes—the symbol of Western physicians—the history of medicine comprises two twined skeins of inquiry: understanding how the body works and using that understanding to prevent its destruction. Great strides had been made in the first area. By 1931, physicians had a sophisticated knowledge of how the organs of the body and the systems they created—digestive, hormonal, nervous, and so forth—cooperated to create health. They had made a good start on moving from the level of organs and tissues down into the intricacies of molecular biology (a term invented in the mid-1930s). They knew a great deal about what happened to those organs, tissues, and systems when they were hit by disease. But there the knowledge stopped. The great prize eluded them.
That prize, sought since antiquity, was called panacea, a mythical substance that could cure the sick and raise the dead. (Panacea, literally “all-healing,” was also the name of the ancient Greek goddess of health, daughter of the physician-god Asklepios.) The Egyptians hoped that the art of mummification would lead them to it. The Greeks sang of it. Medieval monks believed that it could be reached through holy relics. Alchemists sought it as the Philosopher’s Stone, which would not only turn base metals into gold and transform the soul of the seeker but would cure all maladies. It appeared in legends and fairy tales as Achilles’ spear, Aladdin’s ring, Fierabras’s balsam, Medea’s kettle, and Prince Ahmed’s apple. Before the scientists took over, generations of magicians, mages, scholars, and snake-oil salesmen had pursued panacea. But no one had found it. Once a bacterial disease took hold in the body, humans in 1931 were as much the prey of the invisible killers as they had been since the beginning of history.
All that was about to change.
I STUMBLED across this story—which I now consider one of the most important in modern history—quite by accident, a method appropriate for a discovery comprising equal parts skill, mistake, luck, and bullheaded idealism. A reformed scientist—I studied medical microbiology for years before deciding that I would rather write about the beautiful, painstaking rigor of bench science than actually do it—I was happily thumbing through my dog-eared, spine-sprung copy of Asimov’s Biographical Encyclopedia of Science and Technology: The Lives and Achievements of 1510 Great Scientists from Ancient Times to the Present Chronologically Arranged, a delightful candy store of a book for science buffs. I started doing what Isaac Asimov intended his readers to do, I think, when he wrote the book with an emphasis on generous cross-referencing: that is, I began linking the work of one scientist to another, tracing currents of thought across nations and through time. I found my way to the entry on Emil von Behring, the stiff-necked Prussian bacteriologist, which led me to Paul Ehrlich, the Man with the Blue Fingers, whose entry contained a reference to a scientist I had never heard of before, a German physician named Gerhard Domagk. Reading the brief entry on Domagk was the first step on a two-year journey that resulted in this book.
I was intrigued not so much by the man—although Domagk grew into a more interesting character the more I learned—as by the ways in which his discovery was embedded in and affected so much of what we take for granted in modern medicine. Ours is an age of science; this is an archetypal story of our time.
I am part of that great demographic bulge, the World War II “Baby Boom” generation, which was the first in history to benefit from birth from the discovery of antibiotics. The impact of this discovery is difficult to overstate. If my parents came down with an ear infection as babies, they were treated with bed rest, painkillers, and sympathy. If I came down with an
ear infection as a baby, I got antibiotics. If a cold turned into bronchitis, my parents got more bed rest and anxious vigilance; I got antibiotics. People in my parents’ generation, as children, could and all too often did die from strep throats, infected cuts, scarlet fever, meningitis, pneumonia, or any number of infectious diseases. I and my classmates survived because of antibiotics. My parents as children, and their parents before them, lost friends and relatives, often at very early ages, to bacterial epidemics that swept through American cities every fall and winter, killing tens of thousands. The suddenness and inevitability of these epidemic deaths, facts of life before the 1930s, were for me historical curiosities, artifacts of another age. Antibiotics virtually eliminated them. In many cases, much-feared diseases of my grandparents’ day—erysipelas, childbed fever, cellulitis—had become so rare they were nearly extinct. I never heard the names.
Nor did I understand the word “physician” in the same way. To my grandparents a physician was a poorly paid, selfless caregiver who made house calls, kept vigil over the sick, and comforted the families. To me a physician was a wealthy technician in a white coat who did a quick exam in the office and wrote a prescription. Prescriptions had changed, too. Before 1935, narcotics were practically the only drugs that required a prescription. Everything else was sold over the counter. Today virtually every powerful medicine requires a prescription. Before 1935, patent medicines were one of the biggest businesses in the United States. Today they no longer exist. What had happened?
Sulfa happened. It started in the mid-1930s, with a series of findings made in Germany and France, discoveries that were at the time hailed as “the miracle of miracles” in modern medicine, advances that secured humans their first effective way to stop bacterial infections once they started. The work then spread to Great Britain and the United States, where tests of the still-experimental drug on humans, including the son of the president of the United States, confirmed its power. The story became stranger and more colorful the more I researched it, the characters and stories more intense, featuring Congo Red and methylene blue, the Holy Fire of Viennes, vats of Scottish tar, Roehl’s infected carbuncle and Duisberg’s Council of the Gods, Queen Victoria’s armpit and St. Anthony’s bones, impossibly small animals and impossibly huge business cartels.
This is that story.
A NOTE ON USAGE: The family of medicines now generally called sulfa drugs includes thousands of related molecules that have been called many other, often more specific things in the scientific literature. I use “sulfa” throughout this book as a generic term for any medicine whose activity can be traced back to a relatively simple set of atoms called sulfanilamide (sulfa is a relatively common nickname for sulfanilamide and its related substances). I use “sulfa” and “sulfanilamide” interchangeably; the phrase “sulfa drugs” as I use it in this book encompasses the myriad sulfanilamide-containing substances created after the discovery of its therapeutic powers, including those substances that physicians and chemists call sulfonamide drugs. The term “antibiotic” is defined two different ways in the literature; the first, more strict, definition dictates that for a medicine to be called an antibiotic it must be produced by a living microorganism, as penicillin is produced by a mold. Thus some experts refuse to call purely synthetic chemicals like the sulfa drugs, made in laboratories rather than by nature, antibiotics. The more reasonable definition, to my way of thinking and that of a number of medical experts, instead ties the word “antibiotic” to what a substance does rather than where it comes from. Used in this way, an antibiotic is any substance that can selectively destroy a spectrum of bacteria within the body without significantly damaging the body itself. This is how I employ the word throughout the book. By this definition, sulfa was the world’s first antibiotic.
PROLOGUE
JOHN J. MOORHEAD, a lean and intense New York surgeon, was thrilled to be in Hawaii. One of the leading trauma surgeons in the United States and an expert in wound treatment, Moorhead had been invited by the Honolulu County Medical Society to speak to doctors and nurses in December 1941. He gratefully accepted. It provided him a welcome chance to trade the winter winds of Manhattan for the tropical breezes of Oahu. He arrived on schedule and spoke to two large groups on the subject of trauma surgery. His second talk, “Treatment of Wounds, Civil and Military,” proved especially timely. America was not at war yet, but rumors were flying. Everyone was talking about the possibility of a Japanese attack on the Hawaiian Islands.
On his way to deliver a third lecture on the morning of December 7, Moorhead and his driver heard an announcer on the car radio say the U.S. naval base at Pearl Harbor had been attacked. “You hear all kinds of things out here,” his driver said, and they continued to the lecture hall. There Moorhead found only about fifty doctors and nurses in their seats instead of the three hundred he had expected. Moorhead went ahead anyway; he had just started to speak when a man burst into the hall and asked all physicians in the audience to come immediately to Tripler General Hospital, Hawaii’s largest military medical facility. The attack had been real. The hall emptied. Moorhead, too, reported to Tripler.
He and his driver arrived to find stretchers covering the lawn in front of Tripler’s main building. A stream of ambulances, trucks, and private cars had been making the four- or five-mile trip back and forth from Pearl Harbor, dropping off the wounded wherever they could find space under the flowering trees. Aides were running from man to man, improvising tourniquets from belts, gas-mask cords, pistol holsters, and strips of sheets. Moorhead went inside, was informed that he was now a colonel in the Army Medical Corps, and scrubbed up. Eight surgical teams were quickly formed from arriving physicians and nurses, most of them civilians. They shared three operating rooms and worked without pause for the next eleven hours, passing medical instruments from room to room, performing hundreds of operations, filling garbage barrels with amputated limbs. One surgical saw was used and sterilized so many times it remained hot to the touch all day.
The worst of the early cases came from Hickham Air Field, where a Japanese bomb had hit the mess hall at breakfast time. Thirty-five young airmen had been killed outright. Dozens more arrived at Tripler with “wounds too terrible to describe,” a nurse said. The bomb had blown out the mess hall’s walls and windows; the men’s wounds were contaminated with shrapnel, shards of glass, bits of mortar and brick, and partially digested food.
Six years earlier this would have been a recipe for disaster. It was a military fact of life then that regardless of the care of the physician and the success of the initial operation, wounds often got infected, and many times infected wounds killed the patient. The dirtier the wound, the greater the risk. Once a wound infection started, almost nothing could be done. There were no antibiotics. In America’s last war, World War I, infected wounds had killed hundreds of thousands of men—more soldiers, by one estimate, than died by enemy bullets. In World War II, however, the numbers would be so low that wound infections no longer presented a major medical problem.
The difference was a new family of drugs—sulfa drugs—made public in the United States just five years before the attack on Pearl Harbor. They were the most effective, most important medicines ever discovered. They had already saved the life of President Roosevelt’s son and those of tens of thousands of other patients around the world. They were revolutionizing medicine. At Pearl Harbor they received their toughest test yet.
Luckily, Tripler Hospital was well stocked with sulfa. Every wounded man who could swallow was given sulfa tablets. The rest got shots or had it sprinkled into their wounds. If someone’s abdomen had been opened, the physicians cleaned it out as well as they could, stopped the bleeding, and packed the cavity with sulfa. When the burn patients began arriving from the harbor, sailors who had been in water covered with blazing oil—“roasted men,” as one observer put it—their burns were cleaned, the dead tissue stripped away, and the injured area frosted with sulfa.
“The casualties were numerous, varied, and severe,” Moorhead wrote in his official report. It was a grisly test of the new medicine’s power. It had been just thirty-six hours since he had delivered lectures on the best methods for wound treatment. Now his advice was being used, step by step, to handle the men at Tripler: Cleanse the wound with soap and water; carve away all dead and damaged flesh (an old World War I method called debridement) until tissue is reached that is normal color or, if muscle, capable of contraction; tie off everything bleeding; pack the wound with sulfa; leave it covered with gauze bandages, unsutured for three days or until it is certain that no infection has set in; then close if appropriate. During the entire recovery period, every patient was to be given a gram of sulfa every four hours. “No one then thought,” Moorhead wrote, “that these principles of treatment were so soon to be put to a large scale test in a proving ground only a short distance from the lecture platform.”
For the next ten days, Moorhead and the other physicians tracked their patients’ progress. The most feared type of wound infection, gas gangrene, was a virtual death sentence for wounded soldiers. At Tripler the gas gangrene cases were isolated in their own ward, their wounds opened and cleaned a second time, then sulfa repacked into the wound. More sulfa was given by mouth. Every patient with gas gangrene recovered, without a single additional amputation. Of the wounded at Pearl Harbor who did not die directly from the trauma of the injury during the first week, not a single one was subsequently lost to infection. Nothing close to it had ever been seen in the annals of military medicine. The official U.S. history of World War II later credited the low mortality rate to “skilled surgery and the use of sulfa drugs.” John Moorhead returned to New York with a deep appreciation for sulfa. His feelings were shared by every physician who treated wounds during the war.
Ironically, the medicine that helped the United States in World War II was discovered in a laboratory in Germany, in the year Hitler came to power, by a corporation whose executives would be put on trial for war crimes at Nuremberg. It would change the way new drugs are developed, approved, and sold. It would transform the way physicians deal with patients. It would usher in the era of antibiotics and lay the foundation for what we now consider modern medicine.