Pasteurized
Arguably, the individual most responsible for our modern understanding of infectious disease and vaccines was raised in a setting and started his career in a manner that would not have predicted such success. Louis Pasteur was born on December 27, 1822 in the eastern town of Dole, France.22 The glory days of the city, when it had served as the seat of Parliament for the region and host to its only university, had long passed after the government and academic institutions had been transferred to Besancon in 1422. Indeed, the city’s major claim to fame arose a century and a half later with the notoriety of Gilles Garnier, a hermit who confessed to the actual or attempted kidnapping, murder, and cannibalization of at least a half dozen of Dole’s youth.23 This loathsome killer gave rise to the myth of the “wolfman” and unknowingly spawned a genre of horror fiction that remains popular until the present.
This unhopeful setting nonetheless gave rise to Louis Pasteur, the son of a poor tanner. His academic training did not suggest much promise, as fishing and art were the primary passions of the young Louis. He did manage to graduate from the local university (which, you may recall, had been relocated to Besancon), though he failed in his first science examination (and scored particularly low marks in chemistry). Despite these setbacks, Louis continued diligently to develop as an academician, though failing at his first attempt to gain entrance to the prestigious Ecole Normale Superieure in Paris.24 Pasteur’s tenacity paid off with his eventual matriculation. His graduation with high honors brought him to the attention of Professor Antoine Jerome Balard, who recruited Pasteur to study a chemical wonder known as “chirality.” Pasteur’s work showed that solid crystals of the same molecule can exist in two different states that polarize light in different ways. Pasteur’s studies revealed a phenomenon that broadly distinguishes molecules as either right- or left-handed; the idea that biology had distinct left and right-handed features had the unintended consequence of influencing fiction writers such as Lewis Carroll’s Through the Looking Glass and James Blish’s 1971 Star Trek novella, Spock Must Die.25, 26, 27
As the professional life of Louis Pasteur was beginning to come together, tragedy devastated his personal life. Pasteur had married Marie Laurent in 1849, and the couple had gone on to have five children, four girls and a boy. As was all too common throughout the ages, the eldest daughter died of typhoid fever at the age of nine years. Sadly, the same disease would go on to kill their two-year-old daughter Camille in 1865 and twelve-year-old Cecile in 1866. This series of heartbreaks hardened Pasteur’s resolve, and he thereafter dedicated his life to understanding the bases of infectious disease and the microorganisms responsible for his children’s untimely deaths.
The chirality findings launched Pasteur into a career that balanced chemistry and biology. It was guided by the principle “Chance favors only the prepared mind,” a popular saying that was uttered first by Louis in 1854.28 This credo was put into effect during his early work on fermentation, when he explained the age-old basis of beer brewing: microscopic yeasts are responsible for transforming sugar into alcohol. He further applied this finding to wine (where yeasts are found on the skins of the grape) and his recognition that microorganisms cause food to spoil. In doing so, Pasteur debunked the antiquated theory of spontaneous generation (the sudden and frequent emergence of life from non-life).
From a practical standpoint, Pasteur translated this basic knowledge into practice by demonstrating that heating a liquid, such as milk, could kill the microorganisms within and thereby extend its shelf life and prevent food poisoning (indeed, products bearing the term pasteurized can still be found in virtually every food market today). Nonetheless, the adoption of pasteurization was slow, as most people, even in the scientific community, were skeptical about his ideas. This doubt is perhaps best captured in an 1860 editorial in the Paris-based newspaper La Presse, which announced, “I am afraid that the experiments you quote, M. Pasteur, will turn against you. The world into which you wish to take us is really too fantastic.”29 Having faced and overcome adversity during his early academic years served Pasteur well later in life, as he ultimately succeeded winning over the scientific community and the public with the same tenacity used to overcome his early academic failures and personal tragedies.
Despite these considerable contributions, Pasteur’s most famous accomplishment was a test of his adage about chance favoring the prepared mind. During the summer of 1880, Pasteur and his 29-year-old assistant, Charles Chamberland, were performing a series of studies of the effects of anthrax on chickens.30, 31 As Pasteur was heading out for a much-needed vacation, he handed Chamberland a jar of bacteria and instructed him to finish up the work with a final study. For reasons that are not entirely clear (perhaps because the boss was out of town or because Chamberland himself was preparing for his own holiday), Chamberland became distracted and forgot to initiate the study before he left for his own vacation. When he returned to work, he realized the oversight and decided to correct the situation by finishing the study, presumably before Pasteur returned. However, the injected chickens thrived and did not die. Moreover, when the same chickens were again injected with anthrax, this time with the full-potency version, they showed no signs of disease.
Pasteur was later informed of the results by a dejected Chamberland (who was preparing to throw out all the old samples). Pasteur became quite excited and told Chamberland to repeat the experiment, including the delay. Both scientists were amazed to see the same lack of toxicity when the inoculum was used to infect a new batch of chickens. Even more staggering, the inoculated chickens had become immune to subsequent infection with other and even more deadly anthrax cultures.
We now know that bacteria are just as mortal as you and I and the culture that Chamberland was using to infect chickens was dead and acted as a vaccine. Specifically, the vaccine consisted of a dead or severely weakened dose of bacteria that, rather than causing disease, sensitized the immune system to repel infection. Ever quick to translate his work into a real-world solution, Pasteur soon looked at a chemical methodology for weakening bacteria to treat anthrax spores rather than waiting long periods for the bacteria to weaken. He goal was to ensure the bacterium was so feeble that it could not cause disease yet intact enough to elicit a durable immune response.
The chemical of choice was soon identified as carbolic acid (also known as phenol), a chemical with a rather storied history. Carbolic acid occurs naturally in many forms of whisky. It conveys the distinct and highly sought-after taste associated with Scotch produced on the island of Islay, just west of the mainland border between the Highlands and Lowlands. Phenol is also the principle component of throat sprays such as Chloraseptic®, though its use is rather controversial, given that phenol is known to be a carcinogen. Returning to Pasteur, some of his fame arose from an announcement in the summer of 1881 that he’d used phenol to create an attenuated form of anthrax to elicit immunity against the disease. This finding captured the public’s attention, and Pasteur named his new product a “vaccine” in honor of Edward Jenner’s—or, more accurately, Blossom the cow’s—earlier contributions to eradicating smallpox. As we will see in chapter 7, history has a way of simplifying stories to create visionary heroes (as we saw with Jenner), though the accurate background is far more interesting.
Hand Wringing and Washing
Coincident with Pasteur’s first and failed attempt to gain admission to the Ecole Normale Superieure, and fifteen years after the conclusion of Ehrenberg and Humboldt’s Russia expedition, a newly minted Hungarian physician graduated from the prestigious University of Vienna. Ignaz Semmelweis tried to make a go of being a specialist in internal medicine, but when he failed to find a proper position, he switched his specialization to obstetrics. In 1846, Semmelweis was appointed to the Vienna General Hospital, working under the direction of Dr. Johann Klein.32, 33, 34 Klein had taken the helm at the hospital after the forced resignation of his predecessor, Johann Lucas Boer. Boer, it seems, was a bit of an iconoclast.
In particular, he advocated minimal physician intervention in pregnancy, emphasizing the need for exercise and proper nutrition of the mother while arguing against the use of forceps and drugs during delivery.35
Infection had always been a major risk factor for pregnancy. A condition called puerperal sepsis was particularly problematic in birthing clinics of the mid-19th century. Known today by the rather self-explanatory name of “post-partum infection,” puerperal sepsis is an infection of the reproductive tract that still claims far too many victims in the days following labor. Outrageously (to his peers, at least), Boer adhered to the controversial practice of hygiene, which maintained that puerperal sepsis could be spread among infected patients. In contrast, the accepted practices of the day included active intervention, frequent bleeding, and the use of dirty medical instruments such as forceps, which were rarely washed or even wiped down between procedures. Based upon his radical views, Boer was dismissed on “the pretext of insubordination” and was replaced by Johann Klein in 1823.
As an unfortunate coincidence, Klein’s own reputation was largely based on his own advocacy of the emerging field of anatomic pathology. This practice centers upon the idea that physical examination of a diseased body, and of cadaver organs following death, can convey information that is useful for diagnosis and treatment of the living. The unfortunate bit is that Klein instructed the students and physicians in his clinic to interact with diseased specimens in the mortuary, with emphasis on cadavers with puerperal fever, as this was a real-world problem routinely faced by the physicians of the Vienna General Hospital. Thus, physicians would routinely travel back and forth between the morgue and the delivery suites (without proper handwashing or cleaning their examination tools, as we will see).
Another change instituted by Klein was necessitated by an ever-increasing acceleration in births, as mid-19th-century Vienna seems to have been a particularly fecund place. To address the demand, Klein separated the obstetrical practice into two clinics at the beginning of 1833.36 A key event in the unfolding of our story arose because of a bureaucratic decision by the Kaiser’s government, which segregated the roles of male and female obstetrical caregivers. Clinic One was to be staffed by medical students and physicians (male), while Clinic Two would be managed by midwives (female). Patients entering the hospital would be randomly assigned to one clinic or the other based on their day of admission, a practice that unintentionally created the basis for what we now recognize to be a randomized clinical trial.
Six years after the decision to staff the clinics in such a manner, a newly hired Semmelweis was puzzled to note substantial differences in the rates of puerperal fever between the two clinics. Specifically, the rates of sepsis were generally twice as high in the physician-run Clinic One as they were in the midwife-based Clinic Two. Such knowledge was apparently well known within the community, as expectant mothers actively avoided being admitted to Clinic One. Based on the desire to avoid Clinic One, some local women preferred street or home births to avoid the risks. Semmelweis later deduced that the likelihood of dying of puerperal sepsis was lower for women who gave birth on the street than it was for those cared for in Clinic One. Despite this community knowledge, the mystery of why Clinic One was so dangerous remained unknown.37
In March of 1847, a tragic death saved the lives of countless women. Jakob Kolletschka was a 43-year-old Bohemian-born professor of pathology and a close friend of Ignaz Semmelweis.38 While Kolletschka was using an autopsy specimen to instruct a team of students in the pathological diagnosis of puerperal fever, one of the students pricked Kolletschka’s finger with a dirty examination tool. Within days, the pathologist began to manifest the classic symptoms of puerperal fever. He died shortly thereafter. The tragic event preoccupied Semmelweis, who struggled with the fact that the assumption of the day was that puerperal fever was only found in women.
As he sorted through his emotions and the evidence, Semmelweis realized the disease was clearly not unique to women and that something in the dead woman’s body had caused Kolletschka’s death. He incorrectly deduced that decaying or dead tissues from cadavers could kill the tissues of the living (the fallacy being that the dead tissues themselves, and not the invisible microorganisms in them, were the cause of disease). Armed with this new theory, Semmelweis realized that the practice of working with autopsy samples and then with patients had the effect of introducing “cadaverous particles” into the delivering mothers and causing disease. These deductions preceded Robert Koch’s work by almost a half century. The fact that the midwives in Clinic Two practiced what we now know to be better (though still imperfect) hygiene and did not convey detritus from autopsy samples to the birth canal was responsible for the lower rates of puerperal fever.
Unfortunately, the medical community remained as intransigent as it had been with Johann Lucas Boer. Semmelweis’s advocacy of proper hygiene led him into conflict with Klein, but fortunately for our protagonist, the senior doctor was on the verge of retirement.39 Semmelweis was suspended for his improper encouragement of septic procedures, such as washing hands with chlorinated liquid, but he was reinstated by Klein’s successor. The practices advocated by Semmelweiss were adopted more widely in Clinic One, and the rates of puerperal sepsis decreased accordingly. Nonetheless, Ignaz Semmelweis was informed in 1849 that his two-year contract would not be renewed, largely as a consequence of his past feud with Klein. Despite the positive results with Clinic One, Semmelweis became a leper within the Viennese medical community and was figuratively run out of town. In response, Ignaz increasingly lashed out at his critics. Even a return to his native Hungary did not resolve the situation, as Hungary was in the midst of an independence movement. The Viennese-trained Semmelweis was seen as a symbol of the Habsburg Empire and was shunned by his professional colleagues. Rejected by his own countrymen, Semmelweis began a long emotional decline, becoming obsessed with his theory for the last years of his life. Sadly, the perceptive physician died an angry soul in a Viennese asylum at the age of forty-seven. Ironically, the cause of his death was attributed to septic shock arising from the infection of wounds received after a severe beating by the guards. His contributions to medicine however lingered, and the name Semmelweis now adorns a Budapest medical school, as well as multiple women’s clinics. In 2008, the memory of Semmelweis was commemorated with an Austrian coin.
Now that we have seen the inspiring and often sad history of the birth of bacteriology, our attention will turn to understanding how and why some of the smallest organisms rank among the deadliest.
No Stomach for Sausages
The Latin term botulus refers to the belly or womb. Its modern-day negative connotation reflects the notorious side effects too often experienced by diners following a filling meal of sausage-filled pig stomachs. The link between consumption of this delicacy and food poisoning was sufficiently prominent that Byzantine emperor Leo VI (also known as Leo the Wise for reasons that will be self-evident)40 outlawed their manufacture during his reign in the 10th century. At the time, the Byzantines had a strong predilection for pig stomachs (Blunzen) filled with otherwise unused bits of meat combined with blood. The salted mixture of animal fats and blood congealed (or, more accurately stated, clotted) prior to cooking. As the inclusion of salt was known to delay spoilage, such prepared meats could linger in the butcher shops for many days, unlike fresh meat. Unknown to the butchers or their customers was the fact that this mixture often created an ideal incubator for the growth of bacteria that would feast upon the putrefying contents of a rich mixture of proteins, fat, and blood. The sickening aspects of the lethal brew could, however, be overcome with proper and thorough heating. Unfortunately, sufficient heat and time were not always achieved, resulting in a disease that gained the moniker of botulism based on this association with sausages.
Despite the best attempts by Leo VI and others to eliminate sausage making, the annual tradition of Oktoberfest continues to this day and is testament to the fact that native Germans and their dias
pora have continued to relish sausages despite occasional outbreaks of botulism. Arguably, the worst wurst poisoning occurred in 1793 in the Wurttemberg village of Bad Wildbad. The mountainous region, tucked into the southwest corner of modern-day Germany near the French border, was known for sausage making. The location of Bad Wildbad made it the epicenter of upheaval in times dominated by the French Revolution, ever-changing borders, and civil unrest. As still occurs today, political and pecuniary turmoil joined hand in hand, and the locals increasingly sought ways to economize, which included increased emphasis upon sausage making. A few years before the dawn of the 19th century, thirteen residents of Bad Wildbad dined upon insufficiently cooked blood sausage.41 All the diners became ill, and six died. Despite this calamity, the continued economic chaos in Wurttemberg throughout the Napoleonic years favored the continued use of Blunzen, and an epidemic of botulism persisted throughout the region.
An unintended consequence of this regional misfortune was that local universities became an epicenter of food poisoning research. A University of Tubingen professor with the daunting name of Johann Heinrich Ferdinand von Autenrieth was an early founder of the field of medical forensics (think CSI Wurttemberg).42 As the scion of a relatively wealthy civil servant, the young Autenrieth enjoyed the benefit of being educated by some of the most important scientists of his day, including Georges Cuvier (the father of paleontology), Antonio Scarpa (who pioneered otolaryngology and cardiology research), and Johann Peter Frank (who developed the record-keeping approaches that Ignaz Semmelweiss used to relate puerperal sepsis with sanitary practices, as we saw above).43 Within Wurttemberg, Autenrieth was renowned and widely feared for chastising housewives who undercooked blood sausages. The practice of undercooking was quite common, as overcooking blood sausages could rupture the pork stomach and allow the contents to spill out into the boiling water. Therefore, many housewives tended to err on the side of rarity, and the outcomes often were sickening.
Between Hope and Fear Page 14