An Unnatural History of Emerging Infections

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 An Unnatural
History of Emerging
Infections

RON B A R R E T T A N D
G EO RG E J . A R M E L AG O S

1
An Unnatural History of Emerging Infections. First Edition. Ron Barrett and George J. Armelagos
© Ron Barrett and George J. Armelagos 2013. Published 2013 by Oxford University Press.
 3
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 George: To Jack and Mary Kelso

Ron: To the ancestors, the Panchdevi, and Mike the Chimpanzee

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Acknowledgements

This book is a culmination of many years of work with many people. In particular, we would
like to thank Chris Kuzawa and Thom McDade, who were our co-authors on the seminal arti-
cle for this book. Credit also goes to James Lin for independently noting that the current
emerging disease trends represent a Third Epidemiological Transition. Thanks to Kristin
Harper, who contributed to our later thinking about these transitions. Thanks to all the stu-
dents in our emerging infections courses for their many questions and insights. Thanks as
well to Dennis Van Gerven, Alan Swedlund, Richard Meindl, Merrill Singer, Peter Brown,
Steve Hackenberger, Joe Lorenz, Ian Buvit, Brad Belbas, Erik Davis, David Woolsey, Gabe
Sibley, and John and Audrey Eyler. Special thanks to Scott Legge, Christy Hansen, and Steve
Sundby for their thoughts and comments on earlier drafts. Thanks to Clark Larson, Dennis
VanGerven, Dan Bailey, and Gwen Robbins Schug for permitting us to use their images in
this book. Special thanks to Justin Gibbens for his brilliantly provocative cover art. Ron would
like to thank his colleagues at Macalester Anthropology: Dianna Dean, Margo Dickinson,
Olga Gonzalez, Arjun Guneratne, Scott Legge, Sonia Patton, and Dianna Shandy, as well as
his family, Ron Sr., Dianne, Tara, Maya, Tiffany, Avena, Nic, and Taiya. And a very special
thanks to Lene Pedersen, Ron’s colleague, partner, and writing coach, who carefully read and
edited every draft of this book. And finally, we would like to thank our editors and supporters
at Oxford University Press: Ian Sherman, Helen Eaton, Lucy Nash, Muhammad Ridwaan, and
G. Hari Kumar for shepherding this project to completion.
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Contents

Introduction 1
Epidemiologic Transitions 5
Organization of this Book 8

PART ONE —The First Transition

1. The Prehistoric Baseline 15
1.1 Nomadic Foraging: Then and Now 18
1.2 Subsistence, Nutrition, and Activity 20
1.3 Population Structure and Settlement 24
1.4 Social Organization and Inequalities 26
1.5 Conclusion 27
2. Revolution and the Domestication of Pathogens 29
2.1 Measuring the Health of Dead People 32
2.2 Societies in Transition 35
2.3 Selecting for Infectious Diseases 39
2.4 Europe and the People without Smallpox 41

PART TWO —The Second Transition

3. Why Germ Theory Didn’t Matter 49
3.1 Germ Theory versus the Sanitary Reform Movement 50
3.2 The McKeown Thesis 54
3.3 McKeown’s Critics and a Rejoinder 59
3.4 Health Trade-offs and the Shape of Things to Come 62
4. The Worst of Both Worlds 65
4.1 Delayed and Incomplete Transitions 66
4.2 Chronic Diseases and New Syndemics 68
4.3 Aging and Poverty 70
4.4 Accelerated Globalization and Re-emerging Awareness 73

PART THREE —The Third Transition

5. New Diseases, Raw and Cooked 79
5.1 The Evolution of Invasion 81
5.2 Virulence and Vulnerability 88
5.3 The Ancient Determinants of Future Pandemics 92
x Contents

6. Inevitable Resistance 93
6.1 Long Before Antibiotics . . . 94
6.2 From Soil and Seed to Magic Bullets 97
6.3 Antibiotics and Human Use 100
6.4 Antibiotics and Agricultural Use 103
6.5 Antibiotics and Vulnerability 106
6.6 The Persistence of Resistance 107
7. Conclusion 109
7.1 Subsistence: Then and Now 111
7.2 Settlement: Then and Now 112
7.3 Social Organization: Then and Now 113
7.4 Moving Beyond the Third Transition 114

References 117
Index 137
Introduction

We ask the God of Plague: “Where are you bound?”

Paper barges aflame and candlelight illuminate the sky.
Farewell to the God of Plague. Mao Zedong (1958)1

Microbes are the ultimate critics of modernity.2 Devoid of thought and culture, they can nev-
ertheless adapt to our latest technologies by the simple means of genetic mutation and rapid
reproduction. Bacteria, viruses, and other microparasites have evolved to operate in almost
any human environment: in our ovens and refrigerators, in our heating vents and air-condi-
tioning ducts. Some thrive in the industrial excrement of our oil spills, car mufflers, and
smoke-stacks. Others thrive in the human body itself. No matter how many personal hygiene
products we use, there will always be ten times the number of bacterial cells than human
cells in our bodies.3 Even within the human cells, we find that 8 per cent of our DNA is com-
posed of sequences from ancient viral infections (Ryan 2004).4 Despite our reigning civiliza-
tions, it is the microbes, not the humans, who are the colonial masters of the living world.
Outnumbered and outgunned, we should not be surprised at our inability to control path-
ogens, the particular subset of microbes that contribute to infectious disease. Yet for many
years, this unfortunate reality did not prevent authorities from making optimistic pronounce-
ments about the imminent demise of human infections. Sir Macfarlane Burnet, the pioneer-
ing Australian virologist and Nobel laureate, famously described the middle of the 20th
century as “the end of one of the most important social revolutions in history, the virtual

1
Mao Zedong was inspired to write this poem after reading a newspaper announcement that schisto-
somiasis had been eradicated from Yukiang Valley.
2
For the purposes of this book, we use the term “microbe” (a contraction of “microbiological organism”)
in the more expanded sense to include viruses and prions as well as other microscopic parasites. Some
authors exclude these entities insofar as viruses and prions do not engage in their own reproduction or
metabolism.
3
There are approximately 1013 human cells and 1014 bacterial cells in a human adult body. Yet because
they are much smaller, the total biomass of these bacterial cells is a mere kilogram.
4
These are known as Human Endogenous Retroviral sequences (HERVs). Most HERVs are “junk”
sequences that no longer code for functional genes. That said, a few active HERV genes have been identi-
fied that contribute to the cellular regulation of important human tissues and sometimes produce human
diseases (Ruprecht et al. 2008).

An Unnatural History of Emerging Infections. First Edition. Ron Barrett and George J. Armelagos
© Ron Barrett and George J. Armelagos 2013. Published 2013 by Oxford University Press.
2 An Unnatural History of Emerging Infections

elimination of the infectious diseases as a significant factor in social life” (Burnet 1962: iii). As
president of the American Association of Medical Colleges, Robert Petersdorf predicted that
there would be scant role for infectious disease specialists in the next century, unless, as he
wrote, they would “spend their time culturing one another” (Petersdorf 1986: 478). Such state-
ments reflected a clinical consensus that most major human infections would be eradicated
by the beginning of the 21st century, and that attention and resources would be focused on
eliminating the so-called chronic “diseases of civilization” such as cancer, diabetes, and heart
disease. Many health policies shifted accordingly, as did funding for the prevention and con-
trol of infectious diseases.
Odds notwithstanding, the medical community had reasons to be optimistic. Infectious
diseases had been declining steadily in the affluent world since the beginning of the Industrial
Revolution, and similar trends could be seen in many developing nations after the end of the
Second World War (Riley 2005). By 1980, smallpox had been completely eradicated from the
human race. The success of this program was a major inspiration for efforts toward the global
eradication of malaria, polio, tuberculosis, and other major infections (Henderson 1980).
After penicillin, new antibiotic molecules had been discovered every decade up until the
1970s (Amyes 2001). The revolutionary new field of molecular biology promised even smarter
medicines informed by the genetic sequences of disease causing microbes and their human
hosts. In the face of these developments, one might understandably conclude that pathogens
were on the eve of extinction.
Yet while medical leaders were dissuading would-be infectious disease specialists, the
AIDS pandemic was already well underway. The AIDS virus was among more than eighty
newly identified human pathogens discovered between 1980 and 2005, including Legionella,
Ebola, Marburg, and highly pathogenic strains of V. cholera and E. coli (Woolhouse and Gaunt
2007). International support for major disease eradication programs had declined, as had
domestic support for public health programs aimed at the prevention and control of infec-
tions among the poorest segments of the richest nations. In developing nations, an ever-
growing division between rich and poor impeded recent gains in infectious-disease mortality
(Armelagos et al. 2005). With global poverty as a reservoir, infections once thought to be
under control returned instead to cross borders and haunt the affluent as “re-emerging” dis-
eases. Tuberculosis (TB) was a prime example of this re-emergence. Long considered a reced-
ing plague of poverty, TB returned to the world’s wealthiest nations with a vengeance (Farmer
1997). Moreover, it did so at time when these wealthy nations were experiencing their first
increases in infectious-disease mortality after more than a century of decline (Jones et al.
2008).
Worse still, these new and recurring diseases demonstrated increasing resistance to anti-
microbial drugs. Since the early days of penicillin, bacteria had been steadily evolving resist-
ance to antibiotics within a few years of their development and use (Normark and Normark
2002). Although researchers continued to develop newer drugs, these substances were no
more than clever modifications of less than two dozen truly unique, core molecules. Even at
the time of this publication, no new core molecules have been discovered since 1961 (Amyes
2001). Meanwhile, an increasing number of serious infections, tuberculosis among them,
 Introduction 3

were showing resistance to more than one type of drug (Kim et al. 2005). It appeared that the
rates of microbial evolution had outpaced the technological revolutions of their human hosts,
and that we were rapidly moving toward a post-antibiotic era: a time when we would no
longer have the medicines to safely cure bacterial infections.
With increasing awareness of these developments, optimism turned to concern in the
1990s. During this time, health professionals coined the phrase “emerging and re-emerging
infections” to describe significant increases in new, recurring, and drug-resistant diseases.
The phrase was echoed in the titles of several conferences, a major publication by the Institute
of Medicine, and an academic journal produced by the US Centers for Disease Control and
Prevention (Lederburg et al. 1992; Satcher 1995). These projects pointed to factors of globali-
zation and shortcomings in public health policies and programs. They also shared a common
purpose of increasing public awareness, spurring new research, and rekindling previously
neglected health initiatives. But unlike the medical optimists of the previous decades, their
main objective was considerably less ambitious.

It is unrealistic to expect that humankind will win a complete victory over the multitude of existing
microbial diseases, or over those that will emerge in the future. . . Still, there are many steps that scien-
tists, educators, public health officials, policymakers, and others can and should be taking to improve
our odds in this ongoing struggle. With diligence and concerted action at many levels, the threats posed
by infectious diseases can be, if not eliminated, at least significantly moderated.
(Lederburg et al. 1992: 32)

By framing the problem as one of emerging and re-emerging infections, the medical commu-
nity succeeded in raising public awareness about a global health issue, but important lessons
were misunderstood or lost in translation. Despite good intentions, fear got the better of reason
as the concept of emerging infections spread to the popular media. Films such as Outbreak and
best-selling books such as The Hot Zone focused public attention on a few novel diseases with
putative origins in exotic foreign lands (Preston 1994). They cast gruesome images of people
bleeding from all orifices and rotting to death, while emphasizing that, in this interconnected
world, any infection was only a plane flight away (See Figures 0.1a and 0.1b). Perhaps more
damaging, these stories promoted high-tech and military-style interventions, over basic public-
health measures, as the most effective approach for controlling these diseases. Unfortunately,
the military approach was popular among policy-makers as well, even more so after the anthrax
attacks of 2001, when resources for preventing known disease threats were diverted to biosecu-
rity programs aimed at threats such as smallpox (Cohen et al. 2004; Barrett 2006a).
However well intended, the terms “emerging” and “re-emerging” are prone to misunder-
standing, especially when they convey a false sense that the problem of human infections is
new, or that their appearance is sudden and spontaneous. Neither is the case. To begin with,
not all newly identified pathogens are actually new to human populations—HIV and
legionella being two prominent examples. Physicians first became aware of AIDS in 1981
when an unusually large number of patients appeared in US hospitals with either a rare form
of cancer or a pneumonia not often found in younger adults (Centers for Disease Control and
Prevention 1981). Researchers identified HIV a few years later and developed a test for the
4 An Unnatural History of Emerging Infections

(a) (b)

Figure 0.1. Biosecurity then and now. The illustration on the left is an engraved copper plate of a 17th-entury
plague doctor wearing a protective suit. The beaked mask contained materials designed to filter out “bad air.”
The contemporary photograph on the right is a technician donning a positive-pressure biohazard suit before
entering one of the US Centers for Disease Control’s (CDCs) maximum containment laboratories. While con-
veying safety concerns, such images can also spread unnecessary alarm, stigmatize populations, and distort
public perceptions of risk. Engraving from Eugen Hollander 1921. Die Karikatur und Satir in der Medizin.
Stuttgart: Ferdinand Enke. Photograph by Brian Mahy, Centers for Disease Control and Prevention.

virus. Building on this knowledge, researchers then tested preserved blood samples from
patients who had died of similar opportunistic diseases, revealing HIV infections going back
to 1959 (Zhu et al. 1998). Similarly, after Legionnaire’s disease made its debut at an American
Bicentennial convention, retrospective studies of preserved tissue samples revealed that the
Legionella bacterium was responsible for at least 2000 deaths that had been previously diag-
nosed as nonspecific pneumonias (Meyer 1983). Because of examples like these, epidemiolo-
gists are often careful to use the phrase “newly identified pathogen” rather than “new
pathogen” when describing novel infections.
Furthermore, the term “re-emerging infections” is only relevant for diseases previously
assumed to be under control, assumptions usually made in affluent societies that have long
since benefited from declining infectious disease rates. The phrase makes little sense in
poor societies where the same infections had never declined in the first place. For example,
smallpox had declined for two centuries in Western Europe and North America until it
became a rare disease after the Second World War, but the infection nevertheless persisted
in underdeveloped nations, particularly in South Asia and sub-Saharan Africa. With
 Introduction 5

the permeability of national borders and social boundaries, smallpox periodically (and pre-
dictably) returned to the affluent West in the form of fifty-three limited outbreaks over the
next thirty years before its final eradication (Barrett 2006a). These outbreaks were known as
re-importation epidemics. Today they would be known as re-emerging infections.
Given these considerations, when does an infection qualify as an emerging or re-emerging
infection? Some public health workers joke that it is when the first white person contracts it.
Cynical though this may be, the joke reflects a global situation in which pathogens are freely
transmitted between nations and societies, but the solutions to these infections are often seg-
regated and contained (Farmer 1996). As such, wealthy societies are sometimes able to deny
attention and sufficient resources to certain diseases; that is, until they make a surprise return
to the developed world. Such is the situation today, which is notable less for emerging patho-
gens themselves and more for an emerging human awareness of long-standing problems that
never went away.
With the aim of emerging awareness, this book examines the human determinants of infec-
tious diseases from evolutionary, historical, and critical social perspectives. The current spate
of human infections is certainly a major global problem, and some of these diseases are indeed
new to our species. However, the underlying determinants of these problems are anything but
new. Our susceptibility to infectious diseases is primarily the result of human activity patterns
spanning human history and prehistory. These patterns involve changing modes of subsist-
ence, environmental disruptions, population shifts, and social inequalities. While the patho-
gens themselves are a natural and ever-present feature of our environment, the conditions in
which they evolve are highly unnatural insofar as they are shaped by deliberate human actions,
however unintended the consequences of these actions may be. Such infections are the arti-
facts of human culture and their history is essentially an unnatural history.

Epidemiologic Transitions
The current phenomenon of emerging and re-emerging infections is the result of shifting
health and population patterns known as epidemiological transitions (Barrett et al. 1998).
Currently, we are experiencing the latest of three major epidemiological transitions that
occurred between the Neolithic and the present day. The First Transition was linked to a
major shift in human lifestyles from nomadic foraging to a more sedentary lifestyle and the
beginnings of agriculture around 10 000 years ago (Armelagos and Harper 2009). The Second
Transition was linked to the Industrial Revolution beginning in Western Europe and North
America in the 18th century, and continuing in different forms among some developing soci-
eties after the Second World War. The Third Transition is marked by the accelerated globali-
zation, urbanization, and aging associated with the so-called emerging and re-emerging
infectious diseases of today (Barrett et al. 1998).
Abdel Omran first introduced the concept of the epidemiological transition as a theoretical
model to explain how changing disease patterns affected major population changes associ-
ated with the Industrial Revolution (Omran 1971). This model was built on a Demographic
Transition Model that population scientists had previously used to describe the shift from
6 An Unnatural History of Emerging Infections

high birth and death rates (fertility and mortality, respectively) to low birth and death rates in
wealthier nations undergoing industrial economic development (Caldwell 1976). This was an
important observation, but the Demographic Transition Model simply pointed to associa-
tions between economic and population changes; it did not address their underlying causes.
Omran sought to address this shortcoming by showing how the changing epidemiology of
major diseases affected population change. His goal was to focus attention “on the complex
change in patterns of health and disease and on the interactions between these patterns and
the demographic, economic, and sociological determinants and consequences” (Omran
1971: 510). It was an ambitious attempt to bring together experts from different disciplines to
understand the underlying determinants of a major shift in the health and demographic pat-
terns of large human populations.
To demonstrate his model, Omran collected historical population data from as many coun-
tries as he could. However, because the wealthier countries had more complete and reliable
data, he mainly focused on Europe and North America in what is often referred to as the
Western or Classic Transition Model. With less data, Omran also formulated a Delayed
Transition Model for underdeveloped countries undergoing more recent and modest forms of
this transition. We will return to the Delayed Model when we address the issue of re-emerging
infections in later chapters. For now, we will focus on the better-known Classic Model.
Omran divided the Classic Epidemiological Transition into three stages, the first of which
he called The Age of Pestilence and Famine. This age was characterized by populations in
which high fertility rates were offset by high mortality rates—families gave birth to many chil-
dren, but many of these children also died from infectious diseases and under-nutrition. For
instance, in 17th-century Sweden, a country now known for its excellent health statistics, birth
rates ranged from 5–10 per family, but at least a third of these infants died before the age of
one, and half the remaining children did not survive to adulthood (McKeown 1988). These
days, it would be difficult for any parent with reasonable means to imagine the loss of even a
single child, let alone the deaths of three children or more. But for many centuries, this was a
common experience in state-level societies around the world. One could easily characterize
this period as “the bad old days.”
Following this tragic baseline, Omran described an Age of Receding Pandemics, begin-
ning in Western Europe around the middle of the 18th century. In this period, countries
began to experience modest declines in the endemic, or day-to-day infections, that had
been typically present in their populations. More importantly, they also experienced sig-
nificant declines in the frequency of unusually large epidemics or pandemics, such as the
smallpox, plague, and typhus outbreaks that sporadically appeared every few decades and
swept away millions of lives in their wake. These changes brought an increase in life expect-
ancy to about 40–50 years of age. Of course, major infectious epidemics did not recede alto-
gether. The industrial world continued to experience major disease events. Overall levels of
endemic infections remained quite high as well, but with a noticeable leveling of the dis-
ease spikes that characterized centuries past. If we were to liken infection to a body of water,
one could say that the seas were calmer, even if overall water levels were high compared to
the present day.
 Introduction 7

The Age of Degenerative and Manmade Diseases is the third and final stage of Omran’s
Classic Epidemiological Transition. This brought major overall declines in infectious
disease mortality from the late 19th to mid-20th-centuries. Life expectancy increased
dramatically during this period, as much as thirty years in many countries. But life expect-
ancy is a special kind of average that can be easily misinterpreted. In this case, increased
life expectancy did not mean that adults were living to older ages so much as children
were surviving to adulthood, primarily because of declining infections. In place of these
infections, chronic degenerative diseases such as cancer and heart disease became the
major causes of death in the industrialized world. This Classic Transition was largely
responsible for the optimism in the 1960s and 1970s regarding the future demise of human
infections (see Figure 0.2).
Omran’s theory has been criticized for its emphasis on unilinear and universal change, its
selective focus on the health of white males, and its assumption that industrial development is
the primary engine for health and demographic change (Salomon and Murray 2002). We share
these concerns, but would rather address them in more fundamental terms and with an eye
toward improving the model. As Omran intended, the Classic Transition does help to explain
complex interactions between economics, demographics, and disease rates, but the model
has two important shortcomings. The first is historical: the concept of a single epidemiological
transition suggests that pre-industrial societies have always suffered from high rates of infec-
tious diseases, which is not the case. For the majority of our evolutionary history, human
beings lived in small nomadic forging groups, lifestyles that were not conducive to the spread
of acute and virulent infections. It was only after we began settling down and domesticating

1 2 3 4 5

Birth rate
Births/Deaths per 1000

Death rate

Total population

Time

Figure 0.2. Mortality decline resulted in overall population increases in affluent nations around the
time of the Industrial Revolution, despite declining fertility rates. While demographic transition theo-
rists described this phenomenon earlier, Omran’s classic epidemiological transition specifically linked
these changes to declining infectious diseases. Creative Commons Public Domain.
8 An Unnatural History of Emerging Infections

plants and animals that infectious diseases became a major human problem—this was
actually our first major epidemiological transition.
Even with recognition of delayed transitions in developing nations, the second major
shortcoming of Omran’s model is that it primarily addresses economic changes in affluent
societies, implying that developing societies will experience similar changes once they have
become sufficiently modernized. Although many poorer societies underwent some degree of
transition in the decades following the Second World War, these declines were more modest
than in their affluent counterparts, and more dependent on antimicrobial medications facing
an increasing threat of drug-resistant infections (Riley 2005). At the same time, these coun-
tries were experiencing the challenges of aging populations and chronic degenerative dis-
eases, a situation that could be characterized as the worst of both worlds.
Far from a single, universal, or unilinear event, these epidemiological transitions have
arisen in various forms and trajectories in different societies and historical periods. Yet with
the rapid globalization of these different societies, humankind is now converging into a single
disease ecology, one that involves a convergence of disease patterns as well as the transmis-
sion of pathogens across populations and national boundaries. This convergence represents
a Third Epidemiological Transition, characterized by the accelerated evolution of human
transmissibility, increased virulence, and drug resistance among infectious pathogens.
Globalization notwithstanding, the underlying determinants of this latest transition are much
the same as the first. Although industrial technologies have accelerated and expanded these
problems, the same human activities have shaped and reshaped the evolution of human
infections for the last 10 000 years.

Organization of this Book

Our unnatural history begins in Chapter 1 with the prehistoric baseline preceding the first major
rise of acute infectious diseases in the human species. This baseline consists of nomadic foraging
lifestyles and their health implications during 99.995 per cent of our evolutionary history. While
there is much debate about the particulars of these lifestyles and the supporting evidence, there
is general agreement that the basic parameters of nomadic foraging could not sustain the kinds
of acute and highly virulent infections that we see today. Such diseases require large, densely
populated, and highly interconnected populations for sustained transmission. Transmission of
acute infections would not have been possible in the small and sparsely distributed groups that
characterized the social organization of our nomadic ancestors.
Nutritional states are closely linked to disease susceptibility, and we know from studies of
contemporary foragers that hunting and gathering leads to richly varied diets high in lean
protein and fiber, and low in unhealthy cholesterols and fat. While foraging societies may
have dealt with seasonal shortages and lower overall caloric intake, they were less likely to
experience the micronutrient deficiencies that would compromise immunity and increase
susceptibility to the infections that we see in their agricultural counterparts. Additionally, for-
aging does not entail prolonged contact with animals, an important factor when we consider
that the ancestry of many human infections can be traced to strains that were originally
 Introduction 9

adapted to domesticated animals. Finally, it should be noted that while known foraging
societies are by no means free of conflict and cruelty, they do not display the degree of social
hierarchy and inequalities that are commonly seen in state-level societies, populations where
the destitute often serve as points of entry and reservoirs for infection.
In Chapter 2, we apply the tools of bioarchaeology to examine ancient societies undergoing
the transition from nomadic foraging to sedentism and agriculture. Comparing the health states
of human remains before and after this transition, we find that the foraging groups were signifi-
cantly healthier than their agricultural descendants. This evidence—situated in the context of
dense populations, poor diets, animal-borne diseases, and social inequalities—strongly sup-
ports the theory that the Agricultural Revolution resulted in diminished nutritional status and
higher infectious-disease mortality for human populations around the world. These were the
first truly emerging infections in the human species.
Agriculture begat the First Epidemiological Transition, characterized by a major rise in
acute infectious diseases, which would persist at high levels in densely settled societies of the
Old World until the 18th century. Human populations increased as well, displacing foraging
societies and transforming the lands around them. Indeed, such increases were necessary to
meet the demands of labor and military forces. But they also came at the terrible cost of high
childhood mortality for diseases like smallpox, plague, yellow fever, and malaria that would
become endemic to the Eurasian continent. These and other food and water-borne infections
would later sweep Native-American populations following the Columbian invasions of the
New World. Enabled and perhaps exceeded by human violence, these New World pandemics
were the tragic consequence of sudden contact between pre- and post-transition societies.
Moving on to the Industrial Revolution, Chapter 3 examines the decline of infectious dis-
eases in affluent nations of Europe and North America from the 18th–20th centuries. This
Second Transition gave rise to the medical optimism in the decades prior to the so-called
emerging and re-emerging infections of today. Much of this optimism was based on a strong
belief in the efficacy of modern medicine, as well as its theories and technological advance-
ments. Yet in contrast to these beliefs, the development of Germ Theory had little to do with
the Second Epidemiological Transition in industrialized societies. Furthermore, with the
exception of smallpox vaccination, infectious diseases underwent most of their declines
before the advent of effective antimicrobial medicines. Rather than new medical theories and
technologies, the determining factors of declining infections were improved nutrition and
living conditions, and better distribution of these essentials across social groups. Although
scholars debate the relative contributions of particular factors, few disagree with the primary
role of changing lifestyles in this transition. Viewed from a much deeper time line, we could
say that the lifestyle factors associated with this Second Transition—those concerning sub-
sistence, settlement, and social organization—were essentially improved versions of those
that instigated the emerging infections of the First Transition thousands of years earlier.
Chapter 4 examines the Second Transition in developing societies from a critical perspec-
tive that helps explains today’s so called re-emerging infections. In the years following the
Second World War, many poorer nations experienced declining rates of infectious-disease
mortality. These declines, however, were more modest than those experienced by their
10 An Unnatural History of Emerging Infections

wealthier neighbors. They were also closely linked to the use of antimicrobial medicines, a
troubling issue given the recent rise of multi-drug-resistant infections. At the same time, the
developing world experienced the same rising rates of chronic degenerative diseases associ-
ated with the Second Transition in well-developed countries, a “worst-of-both-worlds”
syndrome (Bradley 1993).
At this point, we introduce the concept of syndemics: interactions between multiple
diseases that exacerbate the negative effects of one or more disease (Singer and Claire 2003).
Syndemics include co-infections, the best-known examples being AIDS-related infections
such as tuberculosis, cytomegalovirus, and cryptococcal meningitis. Less well-known but
very prevalent are co-infections of influenza and bacterial pneumonias; the latter are actually
the primary cause of flu-related deaths (Sethi 2002). Chronic respiratory diseases such as
asthma and emphysema increase susceptibility to influenza and other respiratory infections;
there is also a strong association between diabetes and tuberculosis. If we include the effects
of social diseases—violence, substance abuse, malnutrition, and so forth—then we could
easily argue that syndemics constitute the vast the majority of re-emerging infections.
With syndemics in mind, we must consider that the First and Second Epidemiological
Transitions did not proceed one from the other in direct, linear progression, nor were they
universally experienced or even fully complete. Moreover, the accelerated globalization of
human societies and their diseases are bringing these incomplete trends into collision, result-
ing in a Third Epidemiological Transition characterized by the entry of new pathogens to the
human species, and the evolution of virulence and antimicrobial resistance in long-standing
diseases. The remaining chapters of this book are dedicated to examining these phenomena.
Chapter 5 applies very old lessons to newly identified or newly virulent diseases. Given that
the majority of these infections are evolutionary descendants of zoonotic (i.e. animal borne)
infections, we consider the manner and conditions required for the entry and sustained trans-
mission of these pathogens within our species. Here, we re-encounter the same major themes
of the Neolithic—changing patterns of subsistence, settlement, and social organization—but
with more complex tools and larger, faster moving populations. Commercial agriculture has
driven marginalized groups into previously uninhabited environments, where practices such
as bushmeat hunting have increased the risk of blood-borne infections from wild animals,
including those apes most closely related to us, and other nonhuman primates (Wolfe et al.
2005). Commercial agriculture has also increased the size and density of domesticated animals
(and their stress levels) such that they are more likely to incubate zoonotic diseases and pass
them on to humans (Davis 2006).
In the early stages of contact with humans, zoonotic infections often exhibit “viral chatter”
in which a zoonotic pathogen evolves the ability to “jump” to human hosts, but not yet to the
degree that it can sustain further transmission in human populations (Wolfe et al. 2005). The
resulting “chatter” is a set of sporadic and limited outbreaks among people engaged in cer-
tain high-risk activities. Such was the case during recent outbreaks of pathogenic avian influ-
enza, in which the majority of infected people were people engaged in commercial poultry
activities, but with no further spread to immediate contacts (Dinh et al. 2006). Repeated inci-
dents like these increase the risk that a new pathogen will evolve the ability for human-to-
 Introduction 11

human transmission. However, even human-to-human transmission may not be sustainable,

depending on conditions such as the density of the host population and their overall suscep-
tibility to diseases.
Unfortunately, conditions for the sustained transmission of new human infections are rich
and plentiful. The majority of the human race now resides in dense, urban environments, and
the majority of these urban residents live in poverty (Dye 2008). Urbanization is often associ-
ated with decreased fertility, which in turn leads to increasing proportions of elderly over
time. This aging of human populations is not only occurring in affluent nations, but also in
developing nations with fewer resources to care for them (Kinsella and Velkoff 2001). Consider
that the immune systems of these poor, aging, and densely settled populations are further
compromised by food insecurity, industrial pollution, and diminished access to clean water
and sanitation, as well as associated pneumonias, parasites, and diarrheal diseases. Include
mosquitoes, substance abuse, and high-risk sexual practices in the mix, and then consider
how globalization has connected these populations within a day’s travel with everyone else in
the world. Accounting for all these conditions, we must conclude that our present world is a
fertile field for the germination and proliferation of new infections.
Many of these conditions are also ripe for the evolution of drug resistance in human and
animal pathogens. Chapter 6 explores whether this evolution will inevitably lead to a post-
antimicrobial era. To better understand the problem, we first examine the pre-human evolu-
tion of antibiotics as natural defenses of microorganisms in competition with one another.
We also consider evidence for the use of antibiotic substances, such as the tetracyclines, in
ancient and traditional healing practices prior to, or aside from, those informed by Germ
Theory. Without a concept of microorganisms, we can reasonably infer that these practices
were focused on patient characteristics and those of their surrounding environments. This
was certainly the case for the sanitary reform movements of the 19th century. Although mis-
taken about the microscopic causes of human infections, the sanitarians had very good ideas
about host susceptibility, disease-prone environments, and effective methods of addressing
these factors to prevent and control the spread of disease.
The sanitary approach changed little during the early years of Germ Theory, which initially
produced more academic discoveries than effective biomedicines. During this period, the
metaphor of “soil and seed” was regularly invoked by biomedical physicians who increas-
ingly believed in Germ Theory but continued to practise environmental medicine: just as the
growth of crops requires the right characteristics of both soil and seed, so the growth of infec-
tions requires the right characteristics of both environment and pathogen. Not much could
be done about most pathogens until the middle of the 20th century, so the focus was on inter-
nal and external environments: good nutrition, exercise, clean surroundings, and isolation
measures that minimized contact with other people and animals—an apt prescription for
Paleolithic living.
The clinical focus changed with the growing concept of “magic bullet” medicines that
could target pathogens, like military snipers, while leaving the host unharmed. The magic
bullet concept began with the bacterial selectivity of dye compounds and gained momentum
with the development of Salvarsan (also known as arsphenamine, or Compound 606) for the
12 An Unnatural History of Emerging Infections

treatment of syphilis (Amyes 2001; Winau et al. 2004). Applying evolutionary theory to bacte-
rial competition, biochemists discovered many antibiotic substances in soils and sewers
around the world and developed them into pharmaceuticals. But in many cases, drug-insen-
sitive and drug-resistant infections began to appear within a few years after the adoption of a
new antibiotic. In an effort to counter these developments, chemists would either search for
new molecules, or alter the original molecules into the next generation of drugs. Bacteria
would then develop resistance to these new drugs, and so on. In this way, the magic bullet
concept expanded to an arms race concept, with growing concerns that humans are losing
the race (Sachs 2007).
Returning to the prospect of a post-antibiotic era, we note with some irony that the mecha-
nisms of antibiotic resistance, like the antibiotics themselves, are natural products of micro-
bial competition that evolved prior to human interference (D’Costa et al. 2011). We then
examine major ways that humans have accelerated the evolution of drug resistance, begin-
ning with the overuse and misuse of these drugs around the world. But as with most health
practices, the solutions are not simple matters of education and behavior change. We must
consider the economies of time and money for patients and their healers alike. Second, we
turn to the role of commercial agricultural practices, which include the use of antibiotics as
animal growth factors. Third, we reconsider the role of syndemics with respect to susceptible
host populations that provide reservoirs for incubation at the early stages of drug resistance
(Barrett 2010). Finally, we examine evidence for the persistence of drug resistance despite
local changes in drug use (Andersson and Hughes 2011). Given these data, it may be that
resistance is inevitable, yet this may not be the worst scenario when we recall that our modes
of living have had far greater impact on the prevention and control of infectious diseases than
all our pharmaceuticals combined.
There was a time when a “social disease” referred only to a sexually transmitted infection
(Morrow 1904), but the recurring theme of this book is that all human infections are essen-
tially social diseases. With this in mind, we conclude our unnatural history with a discussion
of how the social lessons of three epidemiological transitions can be applied to improving the
prevention and control of infectious diseases. The most important improvement would be to
re-organize our approach to these problems. Most health institutions are organized verti-
cally, such that their attention and resources are divided according to certain diseases rather
than their underlying determinants. Yet if the same determinants can be found in nearly all
these diseases, then a horizontal approach would be more effective—one that addresses how
we feed ourselves, how we live in relation to our social and natural environments, and how
we distribute basic resources for our health and well being. This approach must also cross
national and social boundaries because now that we live in a global disease ecology, the
health of anyone can affect the health of everyone.
Part One
The First Transition