Miracle Cure
ALSO BY WILLIAM ROSEN
The Third Horseman
The Most Powerful Idea in the World
Justinian’s Flea
VIKING
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Copyright © 2017 by Jeanine Rosen
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LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA
Names: Rosen, William, 1955– author.
Title: Miracle cure : the creation of antibiotics and the birth of modern
medicine / William Rosen.
Description: New York, New York : Viking, [2017] | Includes bibliographical
references and index.
Identifiers: LCCN 2016029488 (print) | LCCN 2016030953 (ebook) | ISBN
9780525428107 (hardcover) | ISBN 9780698184107 (ebook)
Subjects: | MESH: Anti-Bacterial Agents—history | History, 19th Century |
History, 20th Century | History, 21st Century
Classification: LCC RM409 (print) | LCC RM409 (ebook) | NLM QV 11.1 | DDC
615.7/922—dc23
LC record available at https://lccn.loc.gov/2016029488
While the author has made every effort to provide accurate telephone numbers, Internet addresses, and other contact information at the time of publication, neither the publisher nor the author assumes any responsibility for errors or for changes that occur after publication. Further, the publisher does not have any control over and does not assume any responsibility for author or third-party Web sites or their content.
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CONTENTS
ALSO BY WILLIAM ROSEN
TITLE PAGE
COPYRIGHT
DEDICATION
PROLOGUE “Five and a Half Grams”
ONE “All the Worse for the Fishes”
TWO “Patience, Skill, Luck, and Money”
THREE “Play with Microbes”
FOUR “The People’s Department”
FIVE “To See the Problem Clearly”
SIX “Man of the Soil”
SEVEN “Satans into Seraphs”
EIGHT “The Little Stranger”
NINE “Disturbing Proportions”
EPILOGUE “The Adaptability of the Chemist”
ACKNOWLEDGMENTS
NOTES
BIBLIOGRAPHY
INDEX
PROLOGUE
“Five and a Half Grams”
The Smithsonian Institution’s National Museum of American History is home to more than ten million items, from Julia Child’s sauté pan to a twenty-foot-wide concrete chunk of the original Route 66. Less of a draw for crowds, but far more historically significant, is a thirty-page-long document—a hospital chart—covering a month in the life of a single patient: Anne Miller, whose fourth pregnancy ended in a miscarriage on Valentine’s Day, 1942. The written record of her hospital stay begins almost immediately thereafter, when, after experiencing severe chills and temperatures spiking to more than 106°, she was transferred from the maternity wing of New Haven Hospital to the intensive care unit. She had contracted hemolytic streptococcal septicemia; informally, blood poisoning.
Her condition, already poor, deteriorated. Each day, a box on Mrs. Miller’s chart recorded the number of bacterial colonies found in her blood. The one for March 1 contains the symbol ∞: infinity. She was given blood transfusions, rattlesnake serum, and even the new sulfa drugs. Nothing worked.
On March 11, her doctor, John Bumstead, approached another of his patients, John Fulton, a neurophysiologist from Yale University, who had been hospitalized for a bronchial infection he acquired on a survey of California laboratories. Dr. Bumstead knew that Fulton was a close friend of Howard Florey, an Australian pathologist working in London; so close, in fact, that Fulton had agreed to care for the Florey children for the duration of the war. Bumstead also knew that Dr. Florey was the world’s leading authority on, and advocate for, the therapeutic potential of a compound first discovered fourteen years before: penicillin.
Fulton agreed to call Florey’s colleague, Norman Heatley, who worked at the Merck & Co. pharmaceutical plant in Rahway, New Jersey. Heatley, in turn, importuned Randolph Major, head of Merck’s research labs, to secure a quantity of penicillin, then one of the rarest substances in the world, and one with such a high priority for the war effort that its release required approval from the National Research Council in Washington, DC. One of the NRC’s senior members was Major’s boss, George W. Merck.
The calls worked. Early on the morning of Saturday, March 14, a glass vial containing five and a half grams of brown powder—half the amount of penicillin then available in the entire country—left Rahway. By noon, it was delivered to Dr. Bumstead, who, with no way of knowing the size of a recommended dosage, invented one on the spot. He dissolved a portion of the powder in saline solution and gave Mrs. Miller a test dose intravenously at 3:30 P.M. Once she seemed to tolerate it, he gave her another dose every four hours through the night.
By Sunday, Mrs. Miller’s temperature had dropped to 99°. The fifth person in the world to receive a treatment of penicillin, and the first whose life was saved by it, was sitting up and eating. She would continue doing so for the next fifty-seven years. The eons-long war between humanity and infectious disease had a new order of battle, one that organized research hospitals, university laboratories, pharmaceutical corporations, and national governments into an army. The antibiotic age had arrived.
—
Some revolutions are only visible from a comfortable distance in time. Not so antibiotics. Through the first four decades of the twentieth century, and well into the fifth, the second leading cause of death in the United States was pneumonia, overwhelmingly caused by Streptococcus pneumoniae, a first cousin to the bacterium that nearly took Anne Miller’s life. The sixth deadliest killer, nearly every year, was Mycobacterium tuberculosis. By 1955, pneumonia had fallen to sixth place. Tuberculosis wasn’t even on the list.
To anyone born in the last sixty years—and certainly anyone who has visited a hospital during those years—the conquest of so many mortal diseases is commonplace. To people who lived through the upheaval, it was astonishing. The physician and writer Lewis Thomas, writing forty years after his own medical education in the late 1930s, recalled that a doctor, in those days, could set a bone, deliver a baby, and predict the course of an illness. Actually treating someone, however, was almost entirely palliative: making the patient as comfortable as possible—when, that is, they could even do that. There are still millions of people living today who can remember when cutting a finger on a piece of barbed wire could mean—often did mean—an excruciating death from tetanus, bacteremia, or sepsis. Until the first antibiotics, medicine remained the oldest art. It had yet to become, in Thomas’s words, the “youngest science.”
The twentieth century is rightly acknowledged as an era of unimaginably rapid scientific advances, from internal combustion engines to telephones to digital computers. Famously, less than forty years separated Einstein’s relativity equations from Hiroshima; James Chadwick only discovered the neutron in 1932. Antibiotics moved from experiment to application even faster; all the gr
eat families of antibacterial therapies—the sulfa drugs, beta-lactams (like penicillin), chloramphenicol, tetracycline, erythromycin, streptomycin, and the cephalosporins—appeared in a span of less than ten years.
A hundred characters figured in the birth of antibiotics: physicians who weren’t scientists, scientists who weren’t physicians, government bureaucrats, philanthropists, and industrialists both venal and visionary. Their story played out in university laboratories, agricultural research stations, battlefield hospitals, and the boardrooms of huge multinational corporations. The origin story of antibiotics, and of modern medicine itself, was centuries in gestation.
The war between Homo sapiens and infectious disease, after all, was under way for untold millennia before humanity was able to fight back.
ONE
“All the Worse for the Fishes”
On the morning of Saturday, December 14, 1799, George Washington awakened before dawn, and told his wife, Martha, he was so sick that he could barely breathe.
The indicated treatment was straightforward enough. By the time the sun had risen, Washington’s overseer, George Rawlins, “who was used to bleeding the people,” had opened a vein in Washington’s arm from which he drained approximately twelve ounces of his employer’s blood. Over the course of the next ten hours, two other doctors—Dr. James Craik and Dr. Elisha Dick—bled Washington four more times, extracting as much as one hundred additional ounces.
Removing at least 60 percent of their patient’s total blood supply was only one of the curative tactics used by Washington’s doctors. The former president’s neck was coated with a paste composed of wax and beef fat mixed with an irritant made from the secretions of dried beetles, one powerful enough to raise blisters, which were then opened and drained, apparently in the belief that it would remove the disease-causing poisons. He gargled a mixture of molasses, vinegar, and butter; his legs and feet were covered with a poultice made from wheat bran; he was given an enema; and, just to be on the safe side, his doctors gave Washington a dose of calomel—mercurous chloride—as a purgative.
Unsurprisingly, none of these therapeutic efforts worked. By 10:00 P.M., America’s first president knew he was dying. His last words were, “I am just going! Have me decently buried, and do not let my body be put into the vault less than three days after I am dead. Do you understand me? ’Tis well!”*
Less than twenty-two years later, another world-historic figure had his final encounter with early nineteenth-century medicine. Napoleon Bonaparte, exiled to Longwood House on the South Atlantic island of St. Helena after his defeat at Waterloo in 1815, experienced bouts of abdominal pain and vomiting for months, while four different physicians (each of whom wrote a memoir about their famous patient) treated him by administering hundreds of enemas and regularly dosing him with the powerful emetic known chemically as antimony potassium tartrate—not, perhaps, the best treatment for a patient already weak from vomiting. The onetime emperor of France breathed his last on May 5, 1821.
Historians with a morbid bent have produced thousands of pages of speculation on the diseases that killed two of the most famous men who ever lived. Today, the prevailing retrospective diagnosis for Washington is that he was dispatched by an infection of the epiglottis, probably caused by the tiny organism known as Haemophilus influenzae type b, the pathogen that also causes bacterial meningitis. A popular minority opinion is that Washington died from PTA, or peritonsillar abscess, a strep infection that creates an abscess under the tonsil that swells with pus until it actually strangles the patient. (The other name for PTA is “quinsy” or “quinsey,” from the Greek word that means “to strangle a dog.”) One thing that didn’t kill Washington, despite its mention in just about every biography of the man, was his tour of Mount Vernon in cold, wet weather during the days leading up to his death, and his decision to dine with friends wearing still-wet clothing on the night of December 13. Infectious diseases aren’t caused by catching a chill.
The debate about the cause of Napoleon Bonaparte’s death is, likewise, fueled by enough raw material that it seems likely to go on forever. The initial autopsy concluded that l’empereur had died of stomach cancer, the same disease that killed Napoleon’s father in 1785. Hepatitis has its advocates, as does the parasitic disease known as schistosomiasis, which Napoleon is thought to have acquired during his Egyptian campaign of 1798. Neither is as popular among amateur historians as arsenic poisoning, either as a murder weapon or an accident caused by exposure to wallpaper more or less saturated in the stuff.
An equally honest answer for both former generals is that they died of iatrogenesis. Bad medicine. Or, more accurately, heroic medicine.
The era of heroic medicine is generally used to describe the period, roughly 1780–1850, during which medical education and practice was highly interventional, even when the interventions did at least as much harm as good. The dates are slightly deceptive. Medical practice, from Hippocrates to Obamacare, has constantly oscillated between interventional and conservative approaches; the perfect point of balance is a moving target for physicians, and seems likely always to be.
Consider the persistence of the humoral theory of disease. Bloodletting, for example, was first popularized by the second-century Greek physician Galen of Pergamon as a way of balancing the four humors: blood, phlegm, and black and yellow bile. The doctrine that gave a vocabulary for distinct individual temperaments based on the relative amounts of these bodily fluids—sanguine personalities had a high level of blood; bile led to biliousness—was originally a guide to medical practice: Too much bile caused fevers, while too much phlegm resulted in epilepsy.
Humoral doctrine, in one form or another, dominated Western medicine for nearly two thousand years. It didn’t persist because following its dictates improved the chances that patients would recover from disease, nor even because it was an accurate guide to physiology. Blood, in classic humoralism, was produced by the liver; what the humoral physician believed to be “black bile” was likely blood that had been exposed to oxygen. As much as anything else, the appeal of humoralism seems to have been the belief that, since health was a sign of balance, disease must represent an imbalance of something. It also reinforced a nearly universal belief in elementalism, which suggested that all phenomena could be reduced to interactions among fundamental elements like air, earth, water, and fire.
The real secret to humoralism’s durability was the lack of a superior alternative. And it was nothing if not durable. Humoral balancing was still being recommended in the 1923 edition of The Principles and Practices of Medicine by Sir William Osler, one of the four founders of the Johns Hopkins School of Medicine. The sixth-century Byzantine physician Alexander of Tralles may have treated his patients with powerful alkaloid extracts like atropine and belladonna, purged them with verdigris (copper[II] acetate), and sedated them with opium. But he also cared for them in hospitals whose primary function was not treatment, but support: making patients as comfortable as possible while waiting for either recovery or death. The best-known words of the fifth-century B.C. Father of Medicine, Hippocrates, are “do no harm” and “nature is the best healer.”*
If a further reminder is needed that the practice of heroic medicine began long before the eighteenth century, its greatest icon lived nearly two centuries before his successors turned him into a cult figure. The Swiss German physician, astrologer, and master of all things occult named Philippus Aureolus Theophrastus Bombastus von Hohenheim—as a kindness to modern readers, he is generally remembered by the honorific Paracelsus—was, like Galen, a protoscientist: a careful observer of nature limited by the lack of a mechanism for testing his hypotheses experimentally. Though he recognized the inadequacies of the humoral theories of Galen, he substituted an equally unlikely schema built on the balance of three different elements: mercury, sulfur, and salt. From the sixteenth century on, mercury especially became a remarkably popular remedy for virtually every medical condition. In 1
530, Paracelsus recommended mercury with such enthusiasm that he inspired the Austrian physician Gerard van Swieten to prescribe it in the form of mercuric oxide—more soluble in water and, therefore, even more toxic than the mercurous chloride known as calomel prescribed by Washington’s physicians—as a cure for syphilis. One syphilis treatment from 1720 called for four doses of calomel over three days, separated by a modest amount of bleeding—only a pint or so. Concoctions that contained mercury remained part of the materia medica for centuries because of a confusion between potency and effectiveness. Doctors cheered when patients exhibited the ulcerated gums and uncontrollable salivation that are the classic signs of mercury poisoning, as evidence that the medicine was clearly working.
Mercury therapy was only one of a collection of techniques and beliefs that seem, in retrospect, ghoulish in the extreme. True, some areas of medical knowledge had increased dramatically in the sixteen centuries after Galen. The Brussels-born physician Andreas Vesalius, the first European physician allowed to dissect human corpses, revolutionized anatomy; William Harvey discovered that blood circulated from the heart to the extremities and back again. Even the enthusiasm for mercury, and a number of other toxic substances, wasn’t complete nonsense. As a more scientific group of physicians would soon demonstrate, mercury actually does kill some very nasty disease-causing pathogens. The great weakness of Washington’s and Napoleon’s physicians wasn’t ineptitude—they were probably the most skilled men on the planet when it came to making their patients bleed or vomit—but theory. Eighteenth-century physicians knew as little about the causes of disease as a cat knows about calculus, and certainly no more than their predecessors had known in the second century. A doctor could set a broken bone, perform elaborate-though-useless tests, and comfort the dying, but hardly anything else. As the eighteenth century turned into the nineteenth, the search for reliable and useful treatments for disease had been under way for millennia, with no end in sight.