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  Janet Parker’s admission to the isolation ward occurred amidst a scrum of activity.101 For one thing, it was essential to identify and isolate all individuals who had encountered the photographer. With her health quickly deteriorating, her ability to communicate was ever more limited, but officials could identify and isolate more than five hundred people, who were quarantined at home or sequestered within the Solihull isolation facility. In parallel, health officials identified and sterilized all of Janet’s belongings, both at home and at work. At the same time, public health and law enforcement officials were challenged by the fact that by 11:00 P.M. on August 20, members of the press had been alerted that smallpox could be running rampant in one of England’s largest cities. The problem with containment—not just of the virus but of widespread panic as well—was compounded by the fact that a photographer with no obvious exposure to smallpox or other high-risk behaviors had suddenly been diagnosed with one of the most deadly and infectious agents ever known to man, thought to have been eliminated in the United Kingdom years before.

  The detective work began in earnest and revealed that while Janet had not knowingly engaged in any behavior, either in her personal or professional life, that might have exposed her to smallpox, by coincidence, the location of her darkroom was immediately above a laboratory belonging to Professor Henry Bedson. Bedson had a history of working with smallpox but was equally known for not meeting the high safety standards needed to contain the pathogen. For example, the WHO informed the investigator that Bedson’s application to become a collaborating center had been rejected based on safety concerns that his facilities did not meet their minimal standards.102 Indeed, the Dangerous Pathogens Advisory Group, an expert committee of the Department of Health, had inspected and rejected Dr. Bedson’s laboratory on two separate occasions. Although Bedson had assured the WHO and local authorities that he was winding down his research on smallpox, a subsequent government inquiry (known as the Shooter Report, so named after its lead author) exposed the truth. Not only was the Bedson laboratory using unprecedented amounts of virus for their studies but the laboratory facilities necessary to contain the deadly pathogen lacked airlocks, adequate shower facilities, changing facilities, or specialized clothing. Likewise, the virus was handled and stored in open-air facilities and outside standard biological safety cabinets, which is a cardinal sin for any biological research, and even more so for a legendary killer such as smallpox.103 Consequently, the widespread use of the deadly pathogens without sufficient precautions or facilities had allowed the virus to enter the ventilation system and infect Janet Parker, who had the misfortune to work immediately above the laboratory.

  As authorities pieced together the string of events, a series of tragic episodes ensued. On September 5 (just over two weeks after Janet had been admitted), her 71-year-old father, Fredrick Whitcomb, died while in quarantine at the isolation hospital.104 The cause of death was presumed to be cardiac arrest. This was never confirmed, however, as an autopsy could not be performed, given the potential that the body might have contained smallpox. The next day, Professor Henry Bedson was found in his garden shed, bleeding to death from a self-induced wound while in quarantine at his home. Despite the potential for disease spread, he was transported to another Birmingham hospital but eventually passed away from his wound. Finally, Janet Parker lost her struggle against smallpox and died on September 11, 1978. A later investigation revealed that while Parker had been vaccinated for the disease years before, time had decreased the level of protection to a point where the amount of smallpox exposure she experienced proved fatal.105

  The 1978 smallpox outbreak in Birmingham led to an outcry to eliminate research on the virus and extirpate it once and for all. Specifically, all strains of smallpox, including those used for research or the production of vaccines, were destroyed in a systematic campaign. A mere two vials were allowed to survive, both were intended to serve as the seed stock for a future treatment or vaccine if needed. One vial was kept in strict isolation and under armed guard at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia.106 The other vial was in Soviet Russia. As we will see towards the end of our story, this effort to limit smallpox to two vials was largely, though not completely, successful. While one of the greatest killers of humankind has been contained in isolation, like an evil Hollywood villain, the potential for a sequel is hauntingly real.

  Now that the extraordinary benefits of vaccination to eradicate diseases such as smallpox and polio have been elaborated, we will turn our attention to a brief discussion of how vaccines work and, following that, the array of antagonists and adversaries to vaccines.

  3

  Becoming Defensive

  In the interest of full disclosure, it is important to warn the reader that much of this chapter is devoted to perhaps one of the least attractive concepts and words in the English language: pus. For as long as people have suffered wounds and infections—in other words, from time immemorial—pus has been a subject of considerable speculation, though understanding of its function, composition, and scientific beauty is comparatively recent.

  According to the venerable Oxford English Dictionary (OED), the first written description of pus is cited in the seminal manuscript Chirurgia Magna, first published in 1363.1, 2 This opus detailed contemporary knowledge of medical and surgical techniques. It was broadly used throughout Europe from the late 14th through the 17th centuries, having been translated from its original Latin to local languages. In part, the popularity of Chirurgia Magna reflected the fact that its author, Guy de Chauliac, was a bit of a celebrity physician, famous among the intelligentsia and courts of most western European monarchies.3 By the publication of the work, the low-born physician from the Lozere region of south central France who answered to the name Guido rose well beyond his expected station. His own personal story is at least as interesting as the subject of pus.

  Guy de Chauliac was born in 1290 to a family of peasants in a small town near Lyon. An only child, Guy demonstrated considerable interest and proficiency in the study of medicine. This fact became known to the local nobility, the Duke of Mercoeur, who underwrote Chauliac’s medical training in Toulouse.4 The promising Chauliac again impressed his mentors and began advanced training in medicine in Montpellier. Later he obtained what would today be considered a fellowship in Bologna under another luminary physician of his day, Bertuccio Lombardo (also known as Nicolo Bertucci).5 Bertucci’s fame as an educator derived in part from his technique of performing dissections on cadavers. The practice of adulterating sacred human flesh had been widely shunned as a Christian blasphemy, but the enlightened thinking of the early Renaissance ushered in many changes. Consistent with the iconoclastic nature of Renaissance thinking, Bertuccio’s own tutor at Bologna, Mondino de Liuzzi, had reintroduced dissection of the human body in January 1315, the first time the questionable practice had been openly performed since the adoption of Catholicism by the Roman Empire. Such practices launched a new age in which medicine would evolve from a medieval superstition into an empirical science. At the epicenter of this transition was the University of Bologna, whose reputation was established by faculty such as Liuzzi and Bertucci. Having thrived in the Bologna environment, Guy de Chauliac honed his training further with a stint in Paris before returning to south central France and beginning his practice in Lyon. The promising young mind was utterly unaware that established and brewing international crises would soon propel the humble physician into greatness.

  Two centuries before King Henry VIII of England broke with the Vatican, the 14th-century king of France, Philip IV, had his own quarrel with the Holy See.6 Philip was a notorious spendthrift, supporting the Crusades until the fall of Acre in 1291 and then declaring overt and covert war upon England, ostensibly over lands on the Continent that the French king felt rightfully belonged to him. To finance these excursions, Philip became deeply indebted to many creditors, including the powerful Knights Templar and Jewish financiers. Philip largely dealt
with these financial burdens using force.7 First the French king expelled all Jews (including his creditors) from France in 1306. Later he staged the assassination and outlawing of the Knights Templar on the infamous Friday the thirteenth in October 1307 (which gave rise to the contemporary superstition still associated with that date).

  As one means of procuring income, Philip imposed a tax on the Catholic clergy. This action precipitated a violent reaction from Pope Boniface VIII, who was already concerned about supporting a war between two Catholic countries at a time when the Crusades in the Holy Land were critically failing. In response, Boniface issued a papal bull, Clericis laicos, which forbade the transfer of papal property to any state (thereby preventing Philip from utilizing church holdings) in addition to threatening to excommunicate those who ignored the pronouncement.8 After a failed attempt at a diplomatic solution, the newly excommunicated Philip ordered the detention of Boniface and sent an army to Rome in September 1303 with the order to capture the pontiff and force his resignation. The French forces overwhelmed the weak standing army of the Vatican states. Although denied at the time, modern scholarship suggests Boniface was tortured in a failed effort to force his abdication.9 Perhaps realizing the brutality of their tactics and not wishing to be directly associated with the death of a pope, Philip released the 73-year-old pontiff from French custody. Boniface died within days.

  The vacancy was quickly filled by the Italian pope Benedict XI, who, unsurprisingly, was favorably inclined towards the French, whose troops remained bivouacked in Rome. The new pope rescinded the Clericis laicos. However, the installation of Benedict conveyed only a short-term solution, as he too would be dead within a year (though of more natural causes). Continuing the Roman occupation, the French king pressured the College of Cardinals to elect a French pontiff, and the Gascon-born Clement V was named pope in 1305. Rather than continue an expensive occupation of Rome to hold sway over the Vatican, the French king simply relocated the Vatican, or at least the head of that institution, to Avignon in southern France. This era became known as the Babylonian Captivity, a period that lasted from 1309 to 1377 and witnessed a succession of seven consecutive French popes.

  In 1342, the French pope Clement VI invited the preeminent local surgeon, Guy de Chauliac, to become his personal physician, an appointment that would include three more popes and continue until Guido’s own death in 1368.10 Arguably, the most defining event in the physician’s life was not the elevation to this prestigious position but the witnessing and recording of the greatest plague the world has ever experienced. The Black Death devastated Avignon in 1348.11 No one was immune, including Guido’s benefactor, Pope Clement VI, who fell victim in 1352. Indeed, even Guy himself became infected. Though Chauliac survived, he suffered from a chronic “axillary bubo,” a painful condition in which the infection is localized to a site, where a simmering infection continues to brew and destroy local tissues while being targeted by the body’s immune defenses.12 In Guy’s case, the infection was localized to what we now call a lymph node just below the shoulder near the armpit. Lymph nodes, as we will see, strain the body’s fluids to identify and eliminate infectious or cancerous cells. They are normally restricted to a few millimeters (a fraction of an inch), but an infectious agent localized to a lymph node can elicit a symphony of chemical and cell-based defense measures that cause dramatic and painful enlargement of that and other nearby lymph nodes. Indeed, these engorged lymph nodes were known as bubos and gave rise to the modern name of the plague.

  Ever an observant scientist, Chauliac recorded his observations and distinguished between a bubonic form of the plague (characterized by the swelling and occasional bursting of lymph nodes) and an even more dangerous pneumonic form, which devastated the lungs and was almost invariably fatal. Beyond discriminating between the two forms of the disease, Guido was intrigued with the creamy white pus that exuded (or suppurated) from the burst lymph nodes in plague patients.13 Chauliac contrasted clear or white secretions against the characteristic scarlet hue of blood or colored secretions (ranging from red to yellow and green). In recording his observations, Guy described the fluid emerging from burst lymph nodes as “pus.”

  Although Chauliac was the first to utilize the world pus in the European medical literature, these secretions were well known to the Athenian medical writer Hippocrates. Hippocrates’ fame for many millennia (beyond his oft-repeated oath) rested largely on a bold assertion that most diseases were caused by natural processes rather than as a punishment from the gods or a curse from past or present enemies.14 These ancient notions had held sway for most of history, and Hippocrates’ radical but more correct view is rightfully still celebrated. Nonetheless, many of Hippocrates’ underlying beliefs in how the body and disease worked were less accurate. In the 5th century B.C.E., Hippocrates described an exudate arising from battlefield wounds suffered by soldiers during the Peloponnesian Wars.15 Like his 14th-century counterpart, Hippocrates noted that white pus (one of the four bodily fluids, according to contemporary Greek thinking) related to a positive outcome, whereas a smelly, turbid, and colorful fluid, which he labeled as an “ichor” (leading to the modern term “icky”), generally boded poorly for a wounded soldier.16

  These views of pus and infection date from the 5th century B.C.E. in Athens. They remained almost unchanged for more than two millennia. According to Queen Victoria’s personal physician, Frederick Treves, “Practically all major wounds suppurated. Pus was the most common subject of converse, because it was the most prominent features in the surgeon’s work. It was classified according to degrees of vileness.”17

  Evolution & Immunity

  By the time Hippocrates and Thucydides were reporting their experiences with battlefield wounds and the Plague of Athens, respectively, the biological system known today as immunity, which includes pus, had been evolving for billions of years. As long as life has existed on planet Earth, competition among organisms has reigned supreme. This rivalry extends well beyond conventional passive interactions, such as two individuals competing for the same food source, and often degrades to active combat among mortal enemies.

  Recent evidence reveals that life began as single-celled organisms emerging as far back as four billion years ago (almost immediately, in geological terms, after the planet solidified from its molten beginnings—a suggestion that life is a default, rather than an exception). The emergence of the first free-floating organisms initiated a life-versus-death competition entailing ever-evolving means of attack-and-parry tactics. This interspecies arms race continues to this day. As evidence of the importance of this combative tendency, as many as 10 percent of the genes found in even the oldest known organisms were designated for defense against invaders.18 The targets of these defense mechanisms included both bacterial and viral attackers. One way to think of this is that the fraction of genes in a cell is roughly proportional to the energy usage of that organism. Consequently, at least a tenth of the resources utilized by our earliest ancestors were devoted to fighting off predators. This is quite an investment of energy, given the many other things that life must accomplish (not the least of which are simple survival and reproduction).

  The study of bacterial genetics is extraordinarily complex, and we will restrict our discussion to bacterial structures that will play a role in our story in this chapter and beyond. The primary genetic element in a bacterium is a piece of circular deoxyribonucleic acid (DNA) known as a chromosome. Chromosomes in bacteria remained steadfastly present in virtually every cell in the body, and this trait continued over the eons. In humans, twenty-three pairs of linear (rather than circular) chromosomes are found in virtually every cell in the body and provide the blueprints needed to produce all our molecules and cells.

  Over time, an additional type of DNA element evolved. Unlike the large mass of chromosomal DNA, which encodes for thousands of different genes, miniature circles containing only a few genes, a structure known as a “plasmid,” began to be produced and passed among different
microorganisms through intimate physical interactions.

  The genes encoded by plasmids often conveyed the means to deal with a changing environment. Indeed, the discovery of plasmids in the late 1940s arose from efforts to determine why some bacteria could adapt to antibiotics—a new set of wonder drugs developed during the Second World War. These studies revealed that some plasmids encoded for genes that allowed the bacteria to escape the toxic effects of antibiotics such as penicillin. Indeed, penicillin is yet another example of the interspecies arms race; it is produced by certain types of mold in order to combat bacterial interlopers. Humans merely borrowed this trick, which was useful until plasmid-based conjugation events passed along genes that rendered penicillin largely ineffective.