Hippocrates thought that disease was the result of an imbalance between the four ‘humours’ or fluids that circulate in the human body–black bile, yellow bile, phlegm and blood. If you were lethargic, you had too much phlegm, and the treatment was to eat citrus fruit. Galen, another Greek physician who lived about 500 years after Hippocrates, elaborated on that model, suggesting that people could be categorised by temperament according to which humour dominated in them. Black bile was associated with melancholy types, yellow bile with choleric or hot-tempered ones. A phlegmatic person was laid-back, a sanguine one hopeful. We retain the adjectives, but not the understanding of anatomy and bodily function that produced them. And yet, the Galenic concept of medicine dominated in Europe for a good 1,500 years, and his notion that ‘miasma’ or noxious air could trigger a humoral imbalance was still popular, in some parts of the world, in the twentieth century.
Hippocrates’ definition of an epidemic didn’t survive either. For him, an epidemic was all those symptoms experienced in a given place over a given period of time, during which its population was in the grip of sickness. In those circumstances, he did not distinguish between separate diseases. Later the term epidemic came to be associated with one disease, then with one microbe, then with one strain of microbe, but this process of refinement didn’t get underway until the Middle Ages, when the great plague epidemics forced a rethink. In modern terms, therefore, the people of Perinthus were probably suffering from influenza, diphtheria and whooping cough combined–perhaps with a deficiency of vitamin A thrown in.
Why should we care about a 2,400-year-old outbreak of flu in Greece? Because we would like to know how long flu has been a disease of humans, and what caused it to become one in the first place. Understanding more about its origins might help us to pinpoint the factors that determine the timing, size and severity of an outbreak. It might help us to explain what happened in 1918, and predict future epidemics.
The Cough of Perinthus probably wasn’t the first flu epidemic. And though the historical record is silent on the subject before 412 BC, that doesn’t mean there’s nothing to be said about flu in earlier times. Like humans, flu carries information about its origins within itself. Both of us are living records of our evolutionary past. An example is the human tail bone or coccyx, which is a vestige of our tree-dwelling ancestors. As the tail became less useful, natural selection favoured individuals in whom a chemical signal during embryonic development switched off spinal elongation before the tail grew. Very occasionally, a glitch occurs and that signal doesn’t get turned off in time. The medical literature contains around fifty reports of babies born with tails–a glimpse of the arboreal primate in all of us.
The flu virus has no tail, but it harbours other clues to its origins. It is a parasite, meaning that it can only survive inside another living organism, or ‘host’. Unable to reproduce on its own, it must invade a host cell and hijack that cell’s reproductive apparatus. The offspring of the virus must then leave that host and infect a new one. If they don’t, then the virus expires with the original host, and that is the end of flu. Just as our ancestors’ survival depended on their ability to swing through trees, so flu’s survival depends on its ability to jump from one host to another. This is where the flu story becomes interesting, however, because being a parasite, its survival depends both on its own behaviour and on that of its host. And though for a long time scientists were in the dark about flu’s past, they knew a few things about what humans were doing before 412 BC.
Flu is transmitted from one person to another in tiny infected droplets of mucus that are flung through the air by coughs and sneezes. Snot is a fairly effective missile–it should be, it was designed in a wind tunnel–but it can’t fly further than a few metres. For flu to spread, therefore, people must live fairly close together. This was a crucial insight, because people didn’t always live close together. For most of the human story they were hunter-gatherers and far apart. That all changed about 12,000 years ago, when a hunter somewhere in the vastness of Eurasia erected a pen around a couple of wild sheep and invented livestock. Plants were domesticated too, for crops, and these two developments meant that the land could now support a higher density of people, who could thus come together to compete, collaborate, and generally display all the ingenuity characteristic of human societies. The hunter’s innovation, known as the farming revolution, ushered in a new era.
The new collectives that farming supported gave rise to new diseases–the so-called ‘crowd diseases’ such as measles, smallpox, tuberculosis and influenza. Humans had always been susceptible to infectious disease–leprosy and malaria were causing misery long before the farming revolution–but these were adapted to surviving in small, dispersed human populations. Among their tricks for doing so were not conferring total immunity on a recovered host, so that he or she could be infected again, and retreating to another host–a so-called ‘animal reservoir’–when humans were scarce. Both strategies helped ensure that they maintained a sufficiently large pool of susceptible hosts.
The crowd diseases were different. They burned rapidly through a farming population, either killing their victims or leaving them immune to re-infection. They might infect other animals, but not as well as they infected humans, and some of them were so well adapted to humans that they became exclusively parasitic to our species. They needed a pool of thousands or even tens of thousands of potential victims to sustain them–hence the name, ‘crowd disease’. They would not have survived prior to the farming revolution, but after it, their evolutionary success was index-linked to the growth of human populations.
But if they would not have survived before farming, where did they come from? The clue is those animal reservoirs. We know that there are disease-causing microbes that only infect animals. There are forms of malaria, for example, that infect birds and reptiles but can’t be transmitted to humans. We know that there are microbes that infect both animals and humans (influenza falls into this category), and we know that there are microbes that infect only humans. This is the case, for example, with measles, mumps and rubella. According to current thinking, these different categories of infectious disease represent steps on the evolutionary path by which an exclusively animal disease becomes an exclusively human one. To be precise, scientists recognise five steps that a disease-causing microbe has to go through to complete this transition.1 Some diseases, like measles, have gone all the way; others have stuck at intermediate points on the path. But we shouldn’t think of this process as fixed. It’s highly dynamic, as illustrated by Ebola.
Ebola virus disease is primarily a disease of animals. Its natural reservoir is thought to be fruit bats that inhabit African forests, and that may infect other forest-dwelling animals that humans prize as bushmeat (humans eat the bats, too). Until recently, Ebola was considered a disease that infected humans poorly: it might be transmitted via contact with bushmeat, for example, but a person who was infected by that route would only infect a few others before the ‘outbreak’ fizzled out. That all changed in 2014, when an epidemic in West Africa revealed that Ebola had acquired the ability to pass easily between people.
It isn’t easy for, say, a virus to jump the species barrier. In fact ‘jump’ is entirely the wrong word–it would be more helpful, though still a metaphor, to think of it ‘oozing’ across. Cells are built differently in different hosts, and invading them requires different tools. Each step along the path to becoming a human disease is therefore accompanied by a specific set of molecular changes, but acquiring those changes is a very hit-and-miss affair. The virus will likely have to pass through many, many rounds of reproduction before a mutation arises that confers a useful change. But then, if the virus’s evolutionary fitness improves as a result–if by infecting humans better, it manages to produce more of itself–then natural selection will favour that change (if it doesn’t, it won’t). Other changes may follow, and their cumulative effect is that the virus moves another step along the path.
; The natural reservoir of influenza is generally considered to be birds, especially waterbirds. The big giveaway that a certain species plays the role of reservoir for a certain pathogen is that it doesn’t get sick from it. The two have co-evolved for so long that the virus manages to complete its life cycle without causing too much damage to its host, and without unleashing an immune response. Ducks, for example, can be heavily infected with flu without showing any signs of disease. After the farming revolution, ducks were among the animals that humans domesticated and brought into their villages. So were pigs, which are regarded as potential intermediaries in the process by which a bird disease became a human disease, since pig cells share features of both human and bird cells. For millennia, the three lived cheek by jowl, providing flu with the ideal laboratory in which to experiment with moving between species. Flu infected humans, but probably not very well at first. Over time, however, it accumulated the molecular tools it needed to make it highly contagious, and one day there was an outbreak deserving of the name ‘epidemic’.
Epidemic here is meant in its modern sense–that is, as an increase, often sudden, in the number of cases of a given disease in a given population. An ‘endemic’ disease, in contrast, is always found in that population. A crowd disease can be both endemic and epidemic, if it is always present in a region but also produces occasional outbreaks there. This is where the definitions of the two terms become a little blurred and vary according to the disease in question. We might say, for example, that the relatively mild outbreaks of seasonal influenza that we see each winter are the endemic form of the disease, and reserve the term epidemic for when a new strain emerges, bringing a more severe form of flu in its wake–though not everybody would agree with that distinction.
We have no written accounts of the first epidemics of the first crowd diseases, but they are likely to have been very deadly (witness the 2014 epidemic of Ebola, which might yet go on to earn the title ‘crowd disease’). We know, for example, that one of the deadliest crowd diseases of all, smallpox, was present in Egypt at least 3,000 years ago, because mummies have been found with pockmarked faces, but the first written account of a (probable) smallpox epidemic doesn’t turn up until 430 BC, when a contemporary of Hippocrates, Thucydides, described corpses piled up in the temples of Athens.
When did the first flu epidemic occur? Almost certainly in the last 12,000 years, and probably in the last 5,000–since the first cities arose, creating ideal conditions for the disease to spread. It too must have been horrific. We find this hard to understand, because today, in general, influenza is far from lethal. Yet even today, a small proportion of people come off badly each flu season. These unlucky individuals develop acute respiratory distress syndrome (ARDS): they become short of breath, their blood pressure drops, their faces take on a bluish tinge, and if they aren’t rushed to hospital they will very likely die. In a few cases, their lungs may even haemorrhage, causing them to bleed from their noses and mouths. ARDS is a glimpse of the carnage that first flu epidemic wrought.
There is no record of it (the oldest full writing system wasn’t developed until 4,500 years ago), so we don’t know when or where it happened, but Uruk in what is now Iraq might be a good candidate. Considered the largest city in the world 5,000 years ago, Uruk had around 80,000 inhabitants living inside a walled enclosure of six square kilometres–twice the area of London’s financial heart, the City. Nobody had any immunity. Nobody could help anybody else. Many would have died. Other flu epidemics must have followed, and they were probably milder: though the strains that caused them differed from that original one, and from each other, they were similar enough that the survivors gradually acquired some immunity. Influenza gradually came to look more like the disease we recognise today, though at the cost of a great many lives.
‘Against other things it is possible to obtain security,’ wrote the Greek philosopher Epicurus in the third century BC, ‘but when it comes to death we human beings all live in an unwalled city.’2 From the moment influenza became a human disease, it began to shape human history–though we had to wait for Hippocrates to write the first (probable) description of it. Even after Hippocrates, it’s hard to be sure that what is being described is influenza as we know it. Not only have concepts of epidemic and disease changed, but the disease itself has gone by different names, reflecting changing ideas about what causes it. On top of that, flu is easily confused with other respiratory diseases–most obviously the common cold, but also more serious diseases such as typhus and dengue fever, that start out with flu-like symptoms.
Treading carefully, aware of the traps that time inserts between words, historians have nevertheless speculated that it was flu that devastated the armies of Rome and Syracuse in Sicily in 212 BC. ‘Deaths and funerals were a daily spectacle,’ wrote Livy in his History of Rome. ‘On all sides, day and night, were heard the wailings for the dead.’3 It may have been the respiratory disease that raged through Charlemagne’s troops in the ninth century AD, that he knew as febris Italica (Italian fever). Probable flu epidemics were documented in Europe in the twelfth century, but the first really reliable description of one doesn’t appear until the sixteenth century. In 1557, in the brief interlude when Mary I was on the English throne, an epidemic eliminated 6 per cent of her subjects–more Protestants than ‘Bloody Mary’, as she became known, could dream of burning at the stake.
By the sixteenth century, the age of discovery was well underway. Europeans were arriving in ships in the New World, bringing with them their newfangled diseases to which local populations had no immunity. They had no immunity because they had not been through the same harrowing but tempering cycle of epidemics of animal origin. The fauna of the New World lent itself less easily to domestication than that of the Old, and some inhabitants were still hunter-gatherers. Flu may have been the disease that travelled with Christopher Columbus on his second voyage to the New World, in 1493, and that wiped out much of the Amerindian population of the Antilles after he stopped off there. That year, the Caribbean experienced something similar to what happened, several millennia earlier, in a Eurasian city like Uruk–only this time one group was left standing: the conquistadors.
For a long time historians ignored infectious diseases as historical players, not suspecting this imbalance in their effects on different populations. Right up until the twentieth century, European historians recounting Spaniard Hernán Cortés’ astonishing David-and-Goliath conquest of the Aztec Empire in Mexico generally failed to mention that an epidemic of smallpox did most of the work for him.4 For them, flu was a mild irritant, a cross to be borne in the darker months. They didn’t grasp the fear it struck into the hearts of Native Americans, Australians or Pacific Islanders, or how closely those peoples associated it with the coming of the white man. ‘There was a firm belief among all, that of late years, since they had visits from white men, their influenza epidemics were far more frequent and fatal than they used to be,’ wrote one nineteenth-century visitor to Tanna in the Vanuatu archipelago. ‘This impression is not confined to Tanna, it is, if I mistake not, universal throughout the Pacific.’ Once the historians had realised their error, some of them started calling crowd diseases by a different name: imperial diseases.5
It was the work of palaeoclimatologists that brought that error home to them. Palaeoclimatologists try to understand what the earth’s climate was like in the past, and why, by studying such things as sediment deposits, fossils and tree rings. Finding that the world grew cooler in the late Roman era, for example, they suggest that the Plague of Justinian–a pandemic of bubonic plague that killed approximately 25 million people in Europe and Asia in the sixth century AD–led to vast tracts of farmland being abandoned and forests growing back. Trees extract carbon dioxide from the atmosphere, and this reforestation led to so much of the gas being sequestered in wood that the earth cooled (the opposite of the greenhouse effect we are witnessing today).
Similarly, the massive waves of death that Cortés, Francisco Piza
rro (who conquered the Inca Empire in Peru) and Hernando de Soto (who led the first European expedition into what is now the United States) unleashed in the Americas in the sixteenth century caused a population crash that may have ushered in the Little Ice Age.6 The effect wasn’t reversed until the nineteenth century, when more Europeans arrived and began to clear the land again. The Little Ice Age was probably the last time a human disease affected the global climate, however. Though there would be other pandemics, the gradual mechanisation of farming, combined with the exponential growth of the world’s population, meant that even the deaths of tens of millions of farmers could leave no dent in the atmosphere–at least not one that palaeoclimatologists have been able to detect.
The first flu pandemic that experts agree was a pandemic–that is, an epidemic that encompassed several countries or continents–is thought to have begun in Asia in 1580, and spread to Africa, Europe and possibly America. Here, though, we have to introduce a caveat. Determining the origin and direction of spread of a flu pandemic is not easy–as we’ll see–meaning that every categorical statement regarding the source of historic flu pandemics should be taken with a pinch of salt. This is especially true since, from at least the nineteenth century, Europeans whose compatriots had once tracked lethal diseases through the New World were quick to see each new plague as blowing out of China, or the silent spaces of the Eurasian steppes.
Contemporary reports suggest that this first flu pandemic spread from north to south across Europe in six months. Rome recorded 8,000 deaths, meaning that it was literally ‘decimated’–roughly one in ten Romans died–and some Spanish cities suffered a similar fate.7 Between 1700 and 1800 there were two flu pandemics. At the height of the second, in 1781, 30,000 people a day were falling sick in St Petersburg. By then, most people were calling the disease ‘influenza’. The name was first coined by some fourteenth-century Italians who attributed it to the pull or ‘influence’ of the stars, but it took several centuries to catch on. We retain it today, of course, though as with the descriptors ‘melancholy’ and ‘phlegmatic’, its conceptual moorings have been swept away.
Pale Rider: The Spanish Flu of 1918 and How It Changed the World Page 2
