My feeling of vulnerability while standing in front of the elementary school and believing the snipers were nearby pales in comparison with the vulnerabilities being faced every day by innocent victims who have no realization of the health dangers they face. It may be shocking for many to learn that most of the collegiate victims of the recent and ongoing resurgence in measles, mumps, rubella, and other outbreaks were in fact immunized against these diseases as children. Like virtually all types of medicines or any other product one can envision, vaccines wear out. As we grow older and gain experience with an expanding number of foreign microbial intruders, the immune system can focus less and less on any individual pathogen (or vaccine), particularly those last boosted years or decades before. Eventually, it becomes a “use it or lose it” proposition, and absent using it, the immune system tends eventually to lose its ability to respond.
The slow decay in the ability of the immune system to recall recognition of pathogens is compounded by a phenomenon discussed among vaccinologists and referred to as “the herd effect” (or social immunity). Sparing the reader the agonizing details and mathematical modeling that distinguishes the field of epidemiology, the herd effect can be visualized as a protective shield that arises when a large fraction of a population is rendered insensitive to a particular infection. If enough of “the herd” (or any community of individuals) is adequately protected, then even the unprotected will find a safe harbor from that pathogen. However, when the herd is thinned, sometimes even by just a small number, the consequences for the entire population can be disastrous, instigating a dangerous domino effect. This explanation is demonstrated by the current situation with measles, mumps, rubella, and a cadre of additional infectious agents that threaten not just our children but all Americans and indeed the entire planet.
Part of the concern with the rise of childhood diseases reflects the fact that while some pathogens, such as the virus that causes chicken pox (varicella zoster virus), cause a relatively minor rash that tends to resolve after a few days, the disease is far more aggressive in teens or adults.7 Not only is the severity of the skin rash increased but common responses include a potentially fatal swelling of the brain (known as encephalitis) and inflammation of the joints. Much worse is the situation with a mumps virus infection of teens and adults, which can trigger bouts of inflammation in or near the testes that render their victims sterile.
My goal for this book is to convey the stories of the remarkable history of science, technology, and disease that helped eradicate many of the deadliest plagues known to man. I also intend to convey the reality that the victory against vaccine-preventable diseases is not durable and they could reemerge like B-movie antagonists to kill or maim more victims. The ground covered will also highlight current and future challenges being confronted by the vaccine community, including old threats and new, including Ebola, Zika, antibiotic-resistant infections, and other deadly emerging and reemerging pathogens.
Not only do I seek to present the history of vaccines alongside the history of deadly pathogens and the role they’ve played in human history (toppling empires as well as causing intense heartbreak and loss on individual levels) but I also seek to shine a light upon the long history of vaccine hostility. Many readers might be surprised to learn that anti-vaxxers have always been around, even before the first vaccine was introduced in the 1790s. It might seem like a modern phenomenon, but in fact the history of vaccines is impossible to tell without discussing how each breakthrough has been hindered by a vocal pushback. The fears underlying this resistance have too often counterweighed the hope a new vaccine might bring. Such pushback was prominent even at times when diseases like smallpox or polio could devastate entire families or doom innocent children to short lives spent in a black lung. Too often, we dismiss the fringe elements of the anti-vaccine movement because they have not directly experienced the devastation wreaked by maladies such as polio or measles. However, the damage has clearly been done, as evidenced by the rising incidence of these deadly scourges. Although efforts have been expended to convey the benefits of vaccines, the hopes referred to in the title of this book have been trumped by a fear of an invisible menace perceived as worse than infectious microbes—namely, autism. These more negative sentiments have been winning the day and now present very real dangers to our societies and our families. So perhaps we need to look back at history—specifically to the history of vaccine naysayers and fear mongers—to help us as members of our community, in education, medicine, or in public health. In doing so, perhaps we can help develop a better approach to convey and appreciate the extraordinary benefits and hope that vaccines have imparted upon modern society.
1
Pox Romana
Most historians concur that the middle of the 2nd century of the current era (C.E.) was the apex for the most dominant realm the world had yet known (and would not witness again for millennia). The Roman Empire had emerged from the crisis of the Roman Republic and a period of intense civil wars which were finally concluded with the victory of Gaius Octavius (soon to be known as Augustus Caesar) over Marc Antony at the Battle of Actium in 31 B.C.E. Over the following century, the empire continued a campaign of merciless expansion, geographically, militarily, and in terms of what we today refer to as soft power, including cultural, architectural, and artistic contributions. A two-century period of relative calm demarked the Pax Romana (from the conclusion of the Battle of Actium through 250 C.E.). Unbeknownst to its citizenry, the end was nigh.
A strong central government (it was a dictator-run empire, after all) had committed substantial investments in vital infrastructure, including roads paved with innovative forms of a breakthrough composite material known as concrete (opus caementicum) that allowed for the building of large and durable buildings and roads, many of which remain fully functional two millennia later.1 Larger buildings increased the density of modern cities, and Rome itself is estimated to have housed as many as a million people in the 2nd century,2 a feat that would not be reproduced in Europe until the latter days of the Industrial Revolution. However, the combination of unprecedented mobility and population density would ultimately conspire against the empire.
The revolutionary new road system permitted Roman citizens to travel and emigrate peaceably from as far north as the city of Eboracum (the present-day city of York, England) to Hieraskaminos on the Upper Nile (near contemporary Aswan, Egypt). Throughout this four-thousand-mile trip, a Roman citizen could interact with merchants using a common tongue and utilize the same currency throughout her travels and remain confident of her personal safety under the protection of a Roman militia, whose garrisons or relay stations were interspersed at fixed points and protected the traveler from the privations of highway robbers. This system in turn facilitated trade, both within the empire’s provinces as well as with distant lands such as the Indian subcontinent (by land or sea) and China (via the Silk Road). This same transportation system also greatly hastened the speed by which these travelers could spread disease throughout the Western world.
A period of such remarkable unity brought forth by these technologies was thus fated to implode, largely under its own weight. While the greatest causes of the Roman Empire’s decline have been the subject of considerable erudition, from Edward Gibbon in 1776 onwards,3 the smallest causes were quite literally microscopic and tied to a part of the empire that rarely if ever entered the history books or thoughts of even the most erudite Roman statesmen.
The ancient city of Seleucia is located on the west bank of the Tigris River, deep within the heart of the ancient Fertile Crescent. Lest the modern reader mistakenly assume that local turmoil in this region is a feature unique to our own time, this region, twenty miles southeast of downtown Baghdad, has remained a hotbed of political and military instability for millennia.
Three centuries before the usurpation of the Roman Republic by the empire, Seleucia was a hinterland of an empire aggregated by Alexander the Great.4 Having secured his Hellenic possessions
within a greater Macedonia, Alexander crossed the Hellespont in 334 B.C.E. with the goal of challenging the power of the Archaemenid Empire of Persia, which was ruled by Artashata, also known as Darius III. The Persian ruler and his vast holdings had been the target of Alexander’s father, Phillip II of Macedon, who used the Persian desecration of the Athenian temples a century earlier as an excuse for conquest. After Phillip’s assassination, an act for which Alexander is occasionally and probably unfairly implicated, Alexander began to realize the opportunities arising from a Persian conquest.
Leading a group of brilliant generals (later known collectively as the “Diadochi,” from the Greek word for ‘successors’), Alexander bested army after army, first at the Battle of the Granicus, near the site of ancient Troy, and a year later at the Battle of Issus in southern Anatolia.5 The Battle of Gaugamela in present-day Iraqi Kurdistan sent Darius into retreat, this time for good as the disgraced commander was murdered by his cousin, the Satrap Bessus. Rather than being relieved of a burden of his most dire enemy, Alexander was angered by Bessus’s rash actions, in part because greater prestige could have accompanied Darius’s becoming his prisoner and because the Macedonian leader had gained great respect for Darius. Consequently, Alexander had Bessus tortured and executed for his crime.6
After destroying the primary Archaemenid force and subjugating Bessus’s army, Alexander’s forces entrenched at a minor village on the western bank of the Tigris River in preparation for an invasion of the Indian subcontinent.7 During this period, Alexander’s expansionistic urges were slowed by the homesickness of his generals. The Diadochi were overcome not just with a longing for their homeland but by concerns that Alexander had embraced the habits of the civilizations he’d conquered perhaps a bit too much and, as a result, had “gone native.” As the armies prepared for one long, last push into India, the army was also fighting a malady altogether different from homesickness.
Alexander’s troops were encountering a disease endemic to the region. Specifically, the occupation of the Tigris River valley region was accompanied by a regional infection, characterized by a contemporary as “a scab that attacked the bodies of the soldiers and spread by contagion.”8 This is generally presumed to be an early written description of smallpox, a disease that slowly marched through Alexander’s army and would continue to play a prominent role throughout much of history.9 The much-anticipated Indian campaign itself would grind to a halt in 327 B.C.E. in large part because of the toll taken by smallpox upon Alexander’s troops. The commander himself may not have been exempt from the suffering (the records are insufficiently precise to verify such a diagnosis two and a half millennia later).
Though Alexander and his army survived the 327 B.C.E. smallpox epidemic, both were greatly weakened. The Indian campaign was abandoned, and Alexander focused his efforts closer to home (though not Macedonia, much to the chagrin of the Diadochi, but rather the region known as the Levant). Still not fully recovered from the strain imposed by smallpox four years earlier, the 32-year-old commander began complaining of fever and exhaustion in the early days of June 323 B.C.E. These symptoms progressed rapidly, and the young general was dead within a week. The premature passing has prompted all types of explanations, ranging from natural causes (malaria, typhoid fever, West Nile fever) to man-made (poisoning and alcoholic liver disease). While two and a half millennia precludes a definitive diagnosis, it seems likely the physical toll paid by the previous encounter with smallpox contributed to his later susceptibility and early demise.10
The sudden death of the world’s most charismatic and successful young dictator was unsurprisingly followed by a period of extended turmoil. Within days, the Diadochi turned upon one another in an attempt to sway the succession.11 Waves of intrigue, assassinations, and internecine fighting failed to resolve the vacuum left by Alexander’s absence, and the once-great empire fractured into a series of successor states that dotted the region throughout the remaining Hellenistic period. Despite periodic attempts, these never again coalesced into anything resembling a unified domain.
One Diadochi commander of the cavalry, Seleucus, was appointed Satrap of Babylon and quickly began to consolidate and strengthen his grip upon the central regions of the former Persian Empire. Seleucus renamed the site of Alexander’s former resting spot on the west bank of the Tigris after himself. Seleucus and a string of his successors progressively extended the domains of the Seleucid Empire for the next two and a half centuries. At its peak, the empire encompassed most of modern-day Iraq, Iran, Pakistan, Afghanistan, Israel, Lebanon, Syria, and Turkey, as well as parts of India. While impressive when viewed on a map, the political and military power of the Seleucid Empire was largely illusory and constantly overstretched.
The fragile grip of the Seleucids became apparent in the late 3rd century B.C.E. when delusions of grandeur drove its shortsighted leaders to emulate the deep power of Alexander’s realm and establish a partnership with a new generation of Macedonians. The now-minor Hellenistic kingdom of Macedon, led by a descendent of another of the Diadochi, struck an alliance not just with the Seleucids but also with the Carthaginian general, Hannibal.12 Hannibal, one of a handful of personages in history whose strategic and tactical prowess could accurately be compared with Alexander’s, was the bane of the Roman Republic. The Carthage-Macedon partnership came at a high-water point during the Second Punic War, as Carthaginian troops occupied much of the Italian peninsula. It seemed merely a matter of time until the upstart city-state of Rome would succumb to Hannibal’s offense.
Yet looks could be deceiving. Despite the appearance of a winning position, Hannibal was in the third year of an arduous attempt to engage the Roman consul Quintua Fabius Maximus Verrucosus in a decisive battle.13 The Fabian strategy avoided a pitched battle at all costs and instead sought to wear down Hannibal through attrition, a tactic that has been successfully replicated many times, including by the American generals George Washington and Robert E. Lee. The tactic remains quite effective in modern times as evidenced by experiences in Afghanistan. Nonetheless, the avoidance of a decisive battle was highly controversial, and the Roman Senate, hinting at cowardice, sacked Fabius in favor of another commander who would espouse a more direct approach to dealing with Hannibal. Such folly led to the appointment of the more aggressive Gaius Terentius Varro as consul. The sought-after battle was soon gained and resulted in a decisive defeat of Varro in 216 B.C.E. at the Battle of Cannae (a name synonymous with a resounding victory still to this day). Returning to a Fabian strategy, Rome survived Cannae and outlasted the Carthaginian invaders, whose troops were far from home with overextended supply lines and surrounded by hostile locals. By 201 B.C.E., the Romans had brought the war across the Mediterranean Sea to Carthage, to the defeat of Hannibal. These events allowed Rome to become the unchallenged superpower of the central and western Mediterranean.
All the while the Roman and Carthaginian forces were wrangling over the Iberian Peninsula and North Africa, the eastern Mediterranean remained a cauldron of geopolitical instability. In the months following the extirpation of Carthaginian power in the Second Punic War, Roman concern turned eastwards. The Romans had scores to settle with the old Carthaginian allies, the Macedonians. In the years the Romans were forced to focus their efforts upon containing Hannibal, the Macedonian threat had been countered through an alliance with the Aetolian League, a loose confederation of Greek city-states in central Greece and a longtime rival to the Macedonians (employing the approach of the enemy of my enemy is my friend). Victory against Hannibal meant that the Romans could now concentrate upon the Macedonians, and they were swiftly and soundly defeated in 197 B.C.E.
The Aetolians might have been rid of their long-standing Macedonian rivals, but they now had to contend with the powerful and ambitious Roman victors. The Aetolians had always viewed the Roman alliance as one of convenience based on a shared enemy, and the presence of Iberian soldiers on Greek shores soon dissolved whatever friendship had existed. As the alliance betwee
n the two realms rapidly deteriorated, the southern Balkan peninsula again dissolved into chaotic political and military clashes.
The resulting perception of a power vacuum in Greece might have repelled a pragmatic leader of a paper tiger such as Seleucia but instead triggered visions of grandeur by the Seleucid king, Antiochus III. The delusional leader clung to the belief that expansion into Europe in general, and Macedonia in particular, would create an opportunity to equal the glories of Alexander the Great. However, Antiochus’s views of his own greatness were soon ended by decisive defeats at the hands of the Romans at the Battle of Thermopylae in 191 B.C.E. (this battle is not to be confused with the more famous Spartan-Persian battle near the same site a few centuries before, nor the six other battles of the same name fought since then). In the Romano-Seleucid version of the Battle of Thermopylae, the domination of a small Roman army against a much larger Seleucid force foreshadowed the even more strategically important Battle of Magnesia a year later. The resulting peace treaties with the Roman Republic stripped the Seleucids of much of their conquered lands, including not only the loss of their European possessions but the loss of most holdings on the Anatolian peninsula as well.
Between Hope and Fear Page 2
