Continuing the local tradition, an 1815 outbreak of botulism in the Wurttemberg town of Weisberg was documented by the local physician, Justinius Kerner. A report on the incident by the 29-year-old physician and part-time poet sufficiently impressed Kerner’s former professor—Autenrieth—that it became his first published work, albeit scientific prose rather than poetry.44, 45 Over the following years, Kerner amassed case histories of scores of botulism poisoning victims and began to experiment on extracts from improperly cooked blood sausages. Kerner’s work with a variety of animals, from flies through cats, revealed that a poison secreted from the bacteria exerted its toxic effects upon the nervous system by altering the transmission of signals from nerve endings to the brain. To confirm such findings, he utilized himself as a guinea pig and recorded the effects of poisoning. These reckless actions garnered Kerner a sharp rebuke from Autenrieth, who, upon learning what Kerner had done, directed his fiery temper against his foolhardy former student. While Kerner went on to an internationally recognized career as a poet and author of medical treatises, one unfulfilled wish was to isolate the toxin responsible for botulism. This wrinkle to an otherwise flawless career was not simply a cosmetic desire to finish his interest in food poisoning; it was based on a belief that botulinum toxin might convey medical value. It would likely please but perhaps confuse Kerner to know that this substance (known as Botox®) is intentionally injected into the faces of millions of people today.
The steps towards discovering the botulinum toxin would require additional calamities. On December 14, 1895, in the small Belgian village of Ellezelles, a funeral was held for one of the town elders, the 87-year-old Antoine Creteur. As was the custom of the place and time, a local brass band with the name of Fanfare Les Amis Reunis was hired to play at the funeral. They were later feted with a dinner at La Rustic, the local inn.46 The menu that evening at Le Rustic included smoked ham. Although smoking meats had been popular for years, the process tended to occur at a low temperature insufficient to kill all bacteria, spores, or toxins. These inadequacies were unfortunately realized by the ill-fated band members, all of whom became ill, with three dead. While such outbreaks had occurred innumerable times, this outbreak was unique, as the autopsies (and the remaining ham) were analyzed at the University of Ghent by pathologist Pierre Maria Van Ermengem at a time when the modern understanding of bacteria was just emerging. Ermengem had trained under Robert Koch in Berlin prior to his position in Ghent. As such, Ermengem was familiar with the means of culturing many types of bacteria, including the anaerobic bacterium that had infected the ham. As suggested by the name (the translation of the Latin anaerobic is ‘without air’), these bacteria do not care for air and will not grow on petri dishes left in the open. Using approaches that deprived the cultures of oxygen, Ermengem could isolate a bacterium that fulfilled all of Koch’s postulates. After a few name changes (as understanding of bacteriology increased), the organism came to be known as Clostridium botulinum.
The discovery of the toxin responsible for the nervous system paralysis caused by Clostridium botulinum required an additional three decades of research but was eventually attributed to a team at the University of California, San Francisco, led by Dr. Herman Sommer.47, 48 Subsequent work within academia and germ warfare laboratories throughout the interwar years revealed purified botulinum toxin to be the most toxic substance known to man (a record that still holds true today).
Concern about the potential use of botulinum toxin propelled the United States to establish the U.S. Army Biological Warfare Laboratories at Camp (later Fort) Detrick in Frederick, Maryland, at the height of the Second World War to explore both the offensive and defensive needs of biological warfare.49 Fort Detrick has remained to this day a center of biodefense (though not offense). Along with the Centers for Disease Control and Prevention, it plays a frontline role in countering biological threats, both natural and man-made.
Although there is no evidence that the United States ever deployed an offensive biological weapon during the Second World War or thereafter, much speculation remains that our British allies might have. Specifically, a biological agent has been implicated in the assassination of the man who is arguably the most nefarious character of the Second World War (excepting Hitler himself). Reinhard Tristan Eugen Heydrich was the progeny of the opera composer Richard Bruno Heydrich (the name Reinhard being the name of one of his father’s favorite characters from his own opera, Amen, and Tristan being a tribute to Wagner’s Tristan and Isolde).50 Heydrich matured into a professional sailor and a handsome ladies’ man, known for his many romantic liaisons, before settling down after a remarkably short two-week courtship and proposing to Lina von Osten. Lina had been an early adopter of Nazism. After Reynard was suddenly discharged from the navy in April 1931, Lina encouraged him to join the party. Heydrich then assisted Heinrich Himmler in establishing a counterintelligence division of the Schutzstaffel (better known as the SS). Heydrich was a hardworking and organized administrator, and his influence on Himmler and later Hitler grew quickly. Within a year, Reinhard was named as head of the Sicherheitdienst, Hitler’s security service and later the dreaded Gestapo. Heydrich’s malevolence included a variety of cloak-and-dagger operations to undermine, arrest, and eliminate “persons endangering German security.” In this capacity Heydrich was a key instigator of, among other things, anti-Jewish pogroms such as Kristallnacht and the formation of the Einsatzgruppen tasked with the elimination of Jews in occupied territories. Later he was tapped to lead the Final Solution.
Among his various other responsibilities, Heydrich was the acting Reich protector of Bohemia and Moravia (formerly Czechoslovakia). In a biography of the fuehrer entitled Adolf Hitler, preeminent WWII historian John Toland suggests that Heydrich’s efficiency in managing Bohemia and Moravia was such that these territories risked conversion from occupied territories to loyal members of the Third Reich. Such concerns prompted the exiled Czech government, domiciled in London, to attempt to assassinate Heydrich.51
On December 28, 1941, the British initiated Operation Anthropoid, involving the airdrop of two Czech soldiers, Jans Kubis and Jozef Gabcik, into occupied Czechoslovakia outside Prague. The assassins spent half a year analysing Heydrich’s daily routines. On May 27, 1941, the two assassins were armed with specially modified grenades and Sten guns. The pair waited at a key hairpin intersection on Heydrich’s daily commute. As the Mercedes convertible staff car slowed during its approach, the two soldiers attempted to open fire, but their Sten guns jammed. Rather than speed off, Heydrich unsheathed his sidearm and ordered the driver to halt so that he could shoot the assassins. As Heydrich took aim at Gabcik, Kubis lobbed the modified grenade into the Mercedes. The explosion wounded Heydrich, though an adrenaline rush allowed Heydrich to continue to pursue Gabcik for a few blocks before the Nazi leader’s wounds caused him to collapse in the middle of the street. 52, 53
Still conscious, Heydrich had convinced himself his injuries were suffered upon his exit from the Mercedes. He was aided by a local woman, who flagged down a truck that transported him to Bulokova Hospital. The hospital staff detected fragments from the grenade in his abdomen and lung and removed Heydrich’s spleen. The protector’s postoperative recovery was unremarkable, and a full recovery was anticipated. However, Heydrich’s condition suddenly degraded a week later, and he was dead within a day. An autopsy by senior Wehrmacht pathologists indicated a cause of death by bacteria or poisons carried by bomb splinters. This speculation proved unremarkable until the 1982 publication of A Higher Form of Killing, by Robert Harris and Jeremy Paxman.54 In a story that reads like a Hollywood thriller, the authors reveal that the head of the British biological warfare program, Paul Fildes, bragged about modifying the grenades used in the Heydrich assassination to include botulinum toxin. The boasts attributed to Fildes include, “[I] had a hand in his death” and “He was the first notch on my pistol.” While the principals involved in the operation have long since expired, these accounts may eventually be
proven or dismissed with the declassification of relevant British archives, which is expected within the next two decades.
The Spanish Strangler
The symptoms of diphtheria begin with a minor sore throat, followed shortly thereafter by a low but nagging fever. Over the next few days, the symptoms worsen and are accompanied by growing patches of gray and white material (looking to a modern-day person like a piece of spent chewing gum attached to the back of the mouth) that first coat the tonsils and then spread to other parts of the throat. The growth of these patches progressively narrows the vital passageway needed for the flow of oxygen to the lungs. These growing obstructions are compounded by such an enormous swelling of lymph nodes that the victim’s skin around the neck can be stretched taut in a vain attempt to retain the infection within. The struggle to breathe is further complicated by a barking cough that closely resembled the sound of a baby’s struggle with croup, a sound unforgettable to the countless parents who have sacrificed hours of sleep and sanity agonizing over that characteristic hollow, barking cough. Eventually, the struggle with the disease resolves, culminating either in a recovery or a lethal shutdown of the lungs and heart (due in part to myocarditis as the heart also became the target of assault). A recent estimate suggests that even with modern supporting care, the case-fatality rate (how many infected individuals succumb to a disease) for diphtheria is at least 5 percent (one in twenty) and perhaps as high as 20 percent, or one in five (with an impact equally tragic for adults over the age of forty).55 To put that staggering statistic in perspective, roughly one in a thousand people infected die from diphtheria. The case-fatality rate for even the most devastating influenza outbreak in recent times, the so-called Spanish flu of 1918, was only 2.5 percent.56
The first historical record of diphtheria was logged in 1613, when Spain experienced an epidemic described as “El Anos de los Garrotillos” (the Year of Strangulations).57 The strangler continued to remain a problem throughout the Western world thereafter, with occasional outbreaks, such as one in colonial New England that started in 1735 and remained a pandemic until at least 1740. Diphtheria has been known by many different things in many places, such as the Strangling Angel of Children, Boulogne Cough, the Bull Neck, Canker Ail, Malignant Croup (or angina or quinsies), and Gangrenous (or putrid or pestilential) sore throat. It was not until 1826 that the French physician Pierre Bretonneau invoked diphtheria, the Greek term for ‘leather,’ labeling the disease with the name it’s still known by today.58
A half century after Bretonneau’s moniker, the disease struck the family of Queen Victoria’s daughter, Princess Alice. Alice had by then become matriarch of the Hessian court. She nursed her family to health and in doing so, allowed her bloodline to sustain multiple European royal families. Indeed, Alice is the great grandmother of the current Queen consort, Prince Philip.59 Over the next few years, extraordinary progress would be made in assessing the identity of the killer and prosecuting the murderer to the fullest. In 1883, the Prussian-born pathologist Theodor Albrecht Edwin Klebs worked with another Prussian colleague, Friedrich August Johannes Loeffler, to identify the bacterium responsible for diphtheria, a pathogen that for a time bore the honorific title “Klebs-Loeffler bacillus” but is now known as Corynebacterium diphtheriae (though a prominent genus of opportunistic bacteria discovered by Klebs retains the name Klebsiella).60
Further understanding of the disease arose from studies utilizing new filtering technologies (a subject to be discussed in greater detail later in our story), which helped identify the toxin produced by the diphtheria bacteria that is responsible for its pathogenicity. This achievement represents yet another contribution to human medicine from Emile Roux, the Frenchman and cofounder of the Pasteur Institute. Working with the itinerant Swiss microbiologist Alexandre Yersin, Roux was able to isolate the toxin, which would provide a key step that would eventually help manage (though not entirely eradicate) the disease, as we will see in chapter 6. (Yersin later went on to identify the cause of the ancient disease known simply as “the plague,” which today bears the eponyous moniker of Yersinia pestis.)
Too Much of a Good Thing
The toxins wielded by botulism and diphtheria are known as exotoxins, which simply means a toxin that is released from bacteria. These toxins can be insidious because even if the bacteria that have produced the molecules have been extirpated, say by antibiotics, the remaining toxins can convey deadly legacies unless neutralized (e.g., by high heat or chemicals). Another set of bacterial toxins, distinguished by the German scientist Richard Friedrich Johannes Pfeiffer, remain embedded within bacteria (live or dead). These endotoxins (meaning toxins from within) actively conspire with our host defenses in a manner that can be equally deadly.61 Endotoxins are generally large molecules composed of a lipid (fat-based) core. The core inserts into the bacterial membrane and is linked to a large and outward-projecting sugar-based polysaccharide. These components serve the bacterium by providing structural integrity to the cell membrane. Throughout the evolution of the immune system, these telltale signs of bacteria have also provided an early-warning signal that alerts the host to the presence of unwanted bacterial invaders.
As anyone who owns a highly sensitive home alarm system knows, a strong defensive posture can often go awry. As our immune system evolved, the fine-tuning towards bacteria became so exquisite and overwhelming that misfiring could be deadly. Specifically, the immune system is so finely honed against endotoxins that the prevention can be worse than the disease. As one example, some endotoxins (appropriately named superantigens) can trigger a response so vigorous that up to 20 percent of all the T lymphocytes in the body are activated into a frenzy.62 The call to action also alerts other cells of the innate and acquired immune systems to discharge their pathogen-fighting chemicals; the result of these cytokine storms includes a dramatic (and unwanted) opening of the capillary walls throughout the body.
This response is intended to open the blood vessels to facilitate the passage of host defense from the blood into tissues to fight foreign invaders. If an infection is limited to a site in the body, the increased blood vessel permeability will cause vital fluids to transit into tissues, which can cause localized swelling characteristic of acne, paper cuts, and other damaging events. However, when such a response occurs throughout the body, the loss of fluids undermines blood pressure and causes a deadly event known as septic shock. According to the Centers for Disease Control and Prevention, septic shock is the thirteenth-largest killer of Americans. The most common triggers are superantigen-based infections of the urinary tract, lung, or sites of catheter insertion.63 More than 40 percent of septic shock occurrences are lethal, far outstripping many other events such as heart attacks (5 percent mortality), stroke (19 percent) or breast cancer (17 percent).
A dramatic reminder of the deadly nature of septic shock occurred in 1978. The sales of consumer products are notoriously humdrum and would hardly seem to provide the background for a dramatic tale of sudden death. In general, consumers tend to select a product and remain loyal for years to come. Such realization was problematic for the Procter and Gamble Company (P&G) of Cincinnati, Ohio, in the mid-1970s. P&G sought to enter the highly competitive and established field of tampons as an outsider. Tampon technology had remained remarkably unchanged for decades, and P&G executives believed the field was subject to potential disruption with new technologies. To this end, company researchers discovered that another consumer product, carboxymethylcellulose, might provide such a breakthrough.
Carboxymethylcellulose is a thickening agent that creates the consistencies of puddings, toothpastes, laxatives, and many other consumer products.64 Its thickening properties came from its ability to absorb impressive amounts of water, and the compound was known to be safe. During the development of P&G’s breakthrough tampon, researchers estimated that a single tampon could absorb all the fluids of a menstrual cycle without leaking. The experimental tampon could absorb twenty times its own weight. In doing so, it would
expand to conform to the vaginal cavity, thereby providing a leak-proof barrier that would prevent embarrassing accidents.65 The resulting tampon was therefore given the name Rely, and it was marketed with the catch phrase “It even absorbs the worry.”66
P&G began test-marketing the new tampon in 1974 but ran into an unwanted snag in 1976, when the Food and Drug Administration (FDA) announced a redesignation of tampons as “medical devices,” thereby increasing the requirements for objective data to verify safety and efficacy. Frustration turned to glee in the corporate suite of Procter & Gamble as company executives read the fine print of the new mandate, realizing that the new regulation provided a grandfather clause for existing products, which included Rely. The stars had aligned for P&G (consistent with their corporate logo), since this meant that their innovative new breakthrough would remain unchallenged for even longer, as future competitors would be required to meet the higher standards set by the FDA. The company launched Rely in August 1978. As part of their marketing strategy, they mailed forty-five million free samples to consumers throughout the United States.
Rely was a sensation, but the company and product suffered from its success. Many consumers were so impressed with the absorbency of the new product that they used it far longer than they had with conventional tampons. A representative example was documented in a 2011 report about a consumer, which stated:
Between Hope and Fear Page 15
