Global Change and Infectious Disease—Biology 173
Fall 2012
Professor Fred Cohan
1
Date
Sept.
4
Subject
Primer on ecology and evolution of infectious diseases: diversity of pathogens;
proteins and DNA; natural selection; evolutionary trees.
Reading: (Wolfe 2011), Ch. 1*; (Sadava 2011), pp. 465-472*; (Madigan and
Martinko 2006), pp. 21-36‡; (Ridley 2006), pp. 6-10‡; (Klug 2006), pp. 5-7‡;
(Futuyma 2005), pp. 247-252‡. In our textbook, Wolfe gives a general introduction
to the diversity of pathogens. The Sadava text explains the concept of evolutionary
trees. Madigan and Martinko discuss the differences between bacteria and viruses.
Klug covers the basic of molecular biology, which you’ll need to understand how
evolutionary trees can be made from DNA or protein sequences. Futuyma
introduces natural selection, so that you’ll understand that any organism can
become more optimally adapted to its environment.
Globalization and infectious disease
2 Sept. Overview of course; Globalization and infectious disease in human history.
6
Reading: (Diamond 1997), Chapter 11*; (Shchelkunov 2009)†. Diamond’s chapter
introduces the concept of evolution of transmissibility in pathogens, and why
certain pathogens were more likely to evolve in Old World human populations than
in the New World. Shchelkunov discusses the geographic and animal sources of
smallpox.
3 Sept. Globalization and infectious disease in human history: Plagues of antiquity,
11
medieval Europe, and the conquests of the early Homogenocene (continued).
Reading: (Thucydides 1972), pp. 151-156†; (Papagrigorakis et al. 2006)†; (Diamond
1997), Chapter 11*; (Rosen 2007), pp. 1-11, 185-223†; (Kupferschmidt 2012a)†;
(Morelli et al. 2010)*; (Bray and Buller 2004). Thucydides provided a contemporary
account of the Plague of Athens. Papagrigorakis et al. present an analysis of fossil
DNA from the mass burials of the Plague of Athens to identify the microbe
responsible. Rosen explains the role of Plague in bringing the collapse of the Roman
Empire in the 6th century, also why the Plague was limited to the Mediterranean
region. Haensch et al. obtained DNA from human skeletons from Black Death
burials, and mapped the Plague bacteria to the phylogeny of currently existing
Plague organisms, establishing a route of geographic spread. The Morelli article is a
genomic analysis reconstructing the history of the Black Death of the 14th century,
including the source region and transmission routes. Pay particularly close
attention to Figure 2 (from which the order of geographic spread was determined)
and Table 1 (which associates each step of spread with a known historical event).
Diamond discusses the devastation brought about by the introduction of Old World
diseases into the New World, and why the effects of disease were so asymmetrical
(a topic to which we will return in a few lectures). Bray and Buller discuss the
evolution of smallpox virus and its origins, as well as the disease itself.
4
Sept.
13
Student pick: (ProMED-mail 2012), Sept. 11, URL:
http://www.promedmail.org/?p=2400:1000 (W. Johnston);
http://www.cnn.com/2012/10/09/us/california-squirrel-plague/index.html (D.
Kleckner) (plague is found in squirrels at a popular California campsite).
Globalization and human infectious disease today. I. HIV and West Nile Virus.
Reading: for I: (Wolfe 2011), Ch. 6*; (Gao et al. 1999)†; (Hahn et al. 2000)†; (Bailes
et al. 2003)†; (Worobey et al. 2008)†; (Peeters et al. 2002)†; (Zimmer 2011), p. 6469 †; (Walters 2003), Ch. 6†; (Lanciotti et al. 1999)†; (Kilpatrick 2011)†. Wolfe’s
chapter “One World” puts the rapid global spread of HIV into the context of how
modern transportation has led to the catastrophe of global pandemics in a diversity
of organisms. Gao et al. give the phylogenetic evidence for the origins of HIV in
humans from multiple infections from chimpanzees; more recent and extensive
data are given by Hahn et al. Bailes et al. demonstrate that the SIV of chimpanzees
originated as a hybrid between the SIV’s of two monkey species that are common
prey of chimpanzees. Worobey discusses phylogenetic evidence that the modern
plague of HIV began through infection from chimpanzees around 1900, with rapid
spread within humans from Kinshasa around 1960. Peeters et al. demonstrate the
dangers of future human infections from SIV’s from the bushmeat markets of
Cameroon. The Zimmer and Walters chapters give an introduction to the spread of
West Nile Virus from North Africa to a pandemic across the entire North American
continent. Lanciotti et al. provide the phylogenetic evidence for the geographic
source of WNV in the western hemisphere. Kilpatrick discusses the ecological and
evolutionary changes that have occurred in WNV in its brief time in the New World.
5
Sept.
Student picks: (Achenbach et al. 2012), Sept. 12, URL: http://wapo.st/SFRyVU (C.
Doyle); (Technabob 2010), Feb. 13, URL:
http://technabob.com/blog/2010/02/13/killing-mosquitoes-with-laser-beams/ (E.
Hazelett); (DuBois 2012), Sept. 10, URL:
http://www.popsci.com/science/article/2012-09/predicting-monkey-vaccinebehavior-could-improve-hiv-antiviral-development (E. Grund); (Boyle 2012a), Sept.
27, URL: http://www.popsci.com/science/article/2011-09/disarming-hiv-couldprotect-immune-system-and-potentially-lead-vaccine (E. Grund); (DuBois 2012),
Sept. 14, URL: http://www.huffingtonpost.com/2012/09/15/oregon-plaguewoman-disease-cat_n_1887053.html (S. Jack);
http://www.reuters.com/article/2012/09/23/us-virus-whoidUSBRE88M0FV20120923 (T. McAlear);
http://www.promedmail.org/?p=2400:1000: (novel Coronavirus) (W. Johnston);
(Fox 2012), URL: http://vitals.nbcnews.com/_news/2012/09/27/14127587-newvirus-in-africa-looks-like-rabies-acts-like-ebola?lite (S. Cohan)
Globalization and human infectious disease today. II; Globalization and agricultural
18
infectious disease.
Reading: (Wolfe 2011), Ch. 8*; (LeBreton et al. 2007)†; (Keim and Wagner 2009,
Kupferschmidt 2012b)†; (Mann 2011), p. 220-231, Ch. 7†; (Kupferschmidt 2012a)†;
(Fisher et al. 2012)*.
Wolfe discusses several changes in agricultural industry that increase the likelihood
of a dangerous new pandemic sweeping through humanity: bushmeat hunting in
areas never before accessed by human hunters; immunosuppression of many who
handle bushmeat; the huge densities of agricultural animals and their access to
pathogens from outside the stockyards; feeding diseased animals to other animals;
and the exotic pet industry. LeBreton et al. present data on how frequently
immunosuppressed people are potentially exposed to viruses through bushmeat
butchering. With the London Olympics soon to occur after its publication, the
Kupferschmidt (2012b) article discusses the likelihood of global-local-global
infection events, and compares Olympics and Hajj transmission opportunities. Keim
and Wagner trace the worldwide historical spread of three bacterial pathogens.
Fisher et al. make a compelling case that fungal diseases are emerging in nature and
agriculture at an alarming and increasing rate, that fungal diseases are much more
likely to cause extinctions than other pathogens, and they discuss the reasons why.
Kupferschmidt (2012a) gives a digest of the Fisher et al. article, but you’ve got to
read the amazingly scary article by Fisher. Also, don’t ignore the very useful
truckload of references at the end of Fisher’s article. The section in Mann’s book
1493 is a gripping account of the Irish potato blight, along with an explanation of
how changing agricultural practices in the early 19th century led to the blight.
Student picks: (Boyle 2012a), July 3, URL:
http://www.popsci.com/science/article/2012-07/loner-bats-may-survive-deadlywhite-nose-syndrome-study-says (E. Grund); (Boyle 2012b), Sept. 14, URL:
http://www.popsci.com/science/article/2012-09/touring-worlds-first-manmadebatcave-built-wild-bats (E. Grund); (Gorman 2012), Sept. 24, URL:
http://www.nytimes.com/2012/09/25/science/in-tennessee-building-a-bat-cave-tobattle-a-plague.html?pagewanted=1&hp (B. Packer); (King 2012), September 14,
URL: http://news.sciencemag.org/sciencenow/2012/09/plight-of-thebumblebee.html (G. Castanon).
The sources of emerging infectious diseases
6 Sept. Sources of human diseases in our history. I. The roles of hunting and savannah
20
living in early human disease history.
Reading: (Wolfe 2011), Chapters 2-3*; (McNeil 2011)†; (Wrangham and ConklinBrittain 2003)†; (Liu et al. 2010)†.
Wolfe’s Chapter 2 presents the fateful evolutionary transition in the chimp-human
lineage (after it separated from the lines leading to gorillas and other great apes,
but before humans and chimps diverged as separate lineages) toward hunting. His
7
emphasis, of course, is on how hunting yields a superhighway of infection
opportunities. What is really interesting about this chapter is that the entire story
of hunting and disease transmission is couched in the context of the history of HIV,
first in monkeys, then in their predators (chimps), and then in the chimps’
predators (humans). Chapter 3 deals with the transition of the human-only lineage
to the savannah (leaving the chimps and other primates behind), with the
consequences of microbial cleansing of our species, i.e., depletion of the pool of
our pathogens; he also deals with the effect of cooking on diminishing our
pathogen pool; moreover, the nearby animals of the savannah were less likely to
make us sick, since they were not our close relatives. While humans likely lost
many of our pathogens in the move to the savannah, still the apes maintained a
repository of horrible diseases, some of which they would pass on to us as our
paths crossed again. The Wrangham article discusses the evidence for very early
invention of cooking, and the evolutionary effects of cooking. Liu et al. provide
evidence that, indeed, the human malaria parasite recently emerged into our
species from gorillas.
Sept. Sources of human diseases in our history. II. The role of agriculture.
25
Reading: (Diamond 1997), Ch. 11* (already read); (Wolfe et al. 2007)*; Wolfe, Ch.
4*; (Mindell 2006), Ch. 3†; (Pearce-Duvet 2006)†; (Diamond 2002)†; (Bouckaert et
al. 2012)‽; (Parrish et al. 2008). Diamond’s chapter 11 gives a very nice
introduction for how to think about natural selection in pathogens and their
strategies for transmitting themselves efficiently from host to host, something we
will return to in lecture 11. The chapter also nicely introduces the epidemiology of
acute diseases and why they are diseases of crowds (something we’ll look at more
quantitatively in the following lecture) and cannot be sustained in small bands of
hunter gatherers. The chapter also describes the kinds of diseases that can be
maintained in small populations (chronic and zoonotic diseases). Diamond
presents the reasons why early farmers (and worse, city dwellers) were so prone to
diseases: their filthy lifestyle (and not leaving camp frequently as do nomads) and
the diseases they acquired from their domestic animals. And then to top it all off,
world trade routes. Diamond explains the evolutionary stages by which a zoonotic
disease improves its ability to transmit itself through a human population, to which
we will return in lecture 9. All in all, the Diamond chapter is a terrific introduction
to the idea that our social structures have a great impact on our diseases, which
will be the topic of Professor Johnston’s guest lecture. Finally, Diamond discusses
why the native Americans did not develop crowd diseases from their domestic
animals. The Wolfe article re-evaluates the hypotheses raised by Diamond a
decade later; this article will also be useful reading for lecture 9, on how zoonotic
microbes make the evolutionary jump to becoming human pathogens. In a
statistical analysis of the most significant pathogens from temperate and tropical
sources, Wolfe et al. show that the temperate-origin diseases tend to be the crowd
epidemic diseases, while none of the tropical-origin diseases are in this category.
Wolfe et al. chart the origins of our epidemic pathogens, finding the most coming
8
9
from domestic animals, then some from apes and rodents, and some origins yet to
be identified. Wolfe’s chapter puts the origins of domestication in greater
historical and biological perspective, and gives the reasons why any exercise in
domestication (whether by humans or ants) is likely to result in parasites and
pathogens. Wolfe claims (reasonably I think) that nearly all of the pathogens of our
domesticated animals that can infect humans have already done so, but there are
exceptions, e.g., Nipah virus. Mindell’s chapter discusses the importance of
phylogenetic thinking in public health (identifying unknown disease organisms and
finding their closest relatives) and in unraveling the history of our diseases. PearceDuvet presents a careful phylogenetic analysis of whether we actually acquired
many of our agricultural-era diseases from our domesticated animals, and she
concludes that in most cases the data are not conclusive. For example, without
more extensive sampling of animals that may harbor close relatives of our diseases,
it is difficult to rule out whether the domesticated animals may simply have been
conduits of transmission of diseases hosted normally by wild animals. Diamond’s
2002 paper is a wide-ranging short review of why agriculture developed in certain
localities and why agriculture led to the acquisition of new acute-disease
pathogens. Parrish et al. discuss the various challenges for a virus to move from a
zoonotic to an organism that is efficiently transmitted among humans, with
emphasis on influenza as a lineage that has recurrently made its way into humanity
from waterfowl (retro-assigned). Boukaert et al. show how a phylogenetic
approach to finding a species origin can be used in reconstructing the history of
languages.
Sept. The mathematics of epidemics or why city living is bad for you
27
Guest lecture by Prof. Danny Krizanc, Math & Computer Science Dept.
Oct.
4
Reading: (Black 1966)*; (Cliff and Haggett 1995)†; Wikipedia on Epidemic Modeling
(http://en.wikipedia.org/wiki/Epidemic_model)*. Black’s article is often cited
because it is one of the only empirical investigations into the minimal population
size required to sustain an acute epidemic disease in humans. The article shows
that in very small human populations, measles is almost always absent and needs
to be re-introduced from elsewhere. The Cliff and Haggett article re-evaluates the
study of Black, estimating the minimum host population size from a regression of
percent endemicity on population size. Cliff and Haggett also extend the theory of
island biogeography (especially the part relating the number of species in a region
to the region’s size) to the number of diseases that can be maintained on an island.
Review session for Exam 1: Monday, Oct. 1, 8-10 PM, Exley 150
Exam 1 on Lectures 1-8, Tuesday Oct. 2, in class
How pathogens jump host species
Reading: (Wolfe et al. 2007)*; (Woolhouse and Gaunt 2007)*; (Woolhouse et al.
2005)†; (Veyrier et al. 2009)†; (Allison et al. 2012)†;(Wolfe 2011), Ch. 5*;
(Anonymous 2009)†, URL: http://www.who.int/mediacentre/factsheets/fs262/en/
; (Jackson and Charleston 2004). Wolfe et al. (2007), which we have already read,
10 Oct.
9
has a section on the stages from being an occasional zoonosis to being a fully
human pathogen—Figure 1 is widely cited and is one of the only technical figures
Wolfe included in our textbook. Woolhouse and Gaunt provide a somewhat
simpler version of the steps toward becoming a human pathogen, and they discuss
sources of new human viruses. Woolhouse et al. discuss some interesting
examples of host jumps. (We don’t need to focus on their modeling.) Veyrier et al.
use a genomic analysis to show the role of horizontal genetic transfer in providing
new proteins for infecting new host species. Allison et al. show the potential
importance of “bridge hosts,” which can facilitate adaptation from one host to
another; in this case, the bridge host was raccoons, on the way from cats to dogs
for canine parvovirus. This also illustrates the importance of changes in existing
genes in yielding adaptation to a new host (in contrast to acquisition of new genes).
Jackson and Charleston use a phylogenetic approach to show how we can identify
viruses that easily jump hosts versus those that don’t. The WHO fact sheet details
transmission of Nipah virus, which apparently was able to sustain itself within
humans for some time before the R0 became too low.
How pathogens jump host species (continued); Diseases can get everywhere, but
where they will thrive?
Reading: (Jones et al. 2008); (Quammen 2012b), Chs. 1-7; (Parmesan and Yohe
2003)*; (Purse et al. 2005)†; (Peterson et al. 2002)†; (Batalden et al. 2007)†;
(Peterson et al. 2008)*; (Levine et al. 2007)†; (Peterson 2009)*; (Mayr 1989).
The Jones et al. paper shows that the number of zoonoses coming from wildlife is
much greater than from any other animal source; also they estimate the risk of a
future EID event for each point on the globe, based on past environmental
determinants of EID events. The Chs. 1-7 section from David Quammen’s new book
shows (among many other interesting things) the importance of testing for
antibodies in wild animals for estimating the percent of animals with past or
present infection by a given pathogen. Quammen’s Ch. 10 deals with the issue of
anthroponoses (diseases that are passed from humans to other animals), which is
particularly poignant in the case of introduction of human diseases to endangered
species of gorillas, by way of ecotourism. Mayr outlines the kinds of human
infectious diseases that are typically transmitted from humans to their pets.
Parmesan and Yohe present a meta-analysis of many studies and make the case
that global warming has changed the geographic distributions and seasonal timing
of activity of many wild species. The paper also discusses the difference between
the biological slant on such analyses (has there been a statistically significant
climatic effect so far?) versus the economic slant (OK, so there’s an effect, but is it
thus far been important?). The Purse et al. paper discusses the poleward
movement of Bluetongue Virus from North Africa into Southern Europe; the
troubling aspect is that, while the virus is transmitted by an insect vector native to
North Africa (which is moving into Europe), transmission in northern Europe will
not depend on the African vector—it can be transmitted by insects already native
to Europe. Peterson et al. (2002) introduces for us the concepts and algorithms of
Ecological Niche Modeling. This approach (here applied to predicted changes in
animal geographic distributions in Mexico over the next several decades) measures
the physical characteristics (relative humidity, temperature, sun exposure, etc.) of
where a species is currently found, and then predicts where in the world (and in
the future if we like) the species could be expected to prosper. Batalden et al.
demonstrate a limitation of Ecological Niche Modeling (by way of analyzing future
monarch butterfly distributions): animals do not eat rainfall and sun exposure,
etc.—they can only live where their resource species can be found. Peterson et al.
(2008) predicts where West Nile should be able to thrive in North America, based
on current distributions and the physical properties of where they already are.
Levine et al. introduce another issue limiting Ecological Niche Modeling (relating to
monkeypox)—that while a pathogen might be able to thrive in a particular place
based on the physical attributes of the place, it (or its hosts) might not be able to
get there. Peterson (2009) predicts the future geographic distribution of malaria in
Africa. While the total number of people within the geographic range of malaria
will remain the same (fewer people in the tropics, more in South Africa), the
introduction of malaria to a new region with no experience with malaria will be
extremely dangerous.
11 Oct.
11
Student pick:
http://www.youtube.com/watch?v=50Po7hnzaPs&feature=youtu.be&a (T.
Robbins)
Evolution of virulence (and niceness)
Reading: (Ewald 1993)*; (Walther and Ewald 2004)†;(Ariën et al. 2007)*; (Ariën et
al. 2005)†; (Knell 2004, Ariën et al. 2005)†.
The Ewald paper is a very brief synopsis of Ewald’s 1994 blockbuster book Evolution
of Infectious Disease. The Scientific American article explains Ewald’s hypotheses
about how the mode of transmission of a pathogen, as well as the pathogen’s
survival in the environment (outside of hosts), should be expected to determine the
level of virulence. The more recent Walther and Ewald paper gives some data
supporting the Ewald hypotheses regarding the effect of persistence in the
environment on virulence evolution. The Ariën 2007 paper explains two ways that
natural selection may have favored lower virulence in HIV-1: that lower rates of
opportunity for sexual transmission may select for less virulent viruses (the Ewald
hypothesis) and that higher levels of immune diversity in a human population may
result in lower virulence. Ariën in 2005 gives evidence that historical HIV viruses
were less virulent than more recent ones, in head-to-head competition
experiments. Knell offers evidence that there was an extremely rapid evolution of
lower virulence in syphilis shortly after it was introduced to Europe in the 16 th
century.
FALL BREAK—OCTOBER 16
Antibiotics and human health
12 Oct.
18
13 Oct.
23
The rise and fall of antibiotics; the biology underlying phage therapy
Reading: (Levy 1992), Chs. 1-2†; (Klein et al. 2007)†; (Sommer et al. 2009)†;
(Groopman 2012)*; (Spellberg 2009), Ch. 5†; (Bulletin of the World Health
Organization) http://www.who.int/bulletin/volumes/89/2/11-030211/en/ ;
(Walters 2003), Ch. 3†; (Nathan 2012), URL:
http://www.nytimes.com/2012/12/10/opinion/teaming-up-to-make-newantibiotics.html?hp ; (Zimmer 2011), “The enemy of my enemy”†; (Synnott et al.
2009)†.
Levy’s chapters give an introduction to antibiotics and the promise that they once
showed for solving all problems with bacterial infections. Groopman’s New Yorker
article is a chilling account of what has happened to antibiotic therapy in recent
decades, owing to bacterial evolution of antibiotic resistance. Klein makes a case
that addressing the proliferation of methicillin resistance, particularly in S. aureus,
should be a national priority. Sommer et al. discuss the ubiquity of antibiotic
resistance genes unknown to science, beginning with a search within our own guts.
The Spellberg chapter and the Bulletin of the WHO report describe how little
progress has been made on development of new antibiotics in recent decades;
Nathan describes a novel paradigm (following the bacterial model of sharing
information, in this case among pharmaceutical companies) to develop new
antibiotics. (The Nathan article is retro-recommended, FYI.) So, all this leads us to a
search for alternative therapies …. Zimmer’s chapter on phage therapy is a great
introduction to phage therapy to a general audience, and should prepare you for
the more technical accounts that follow (in the next lecture). Synnott et al.
illustrate how the phage infecting a given bacterial strain can be isolated.
Student pick: http://www.newser.com/story/152647/superbug-killed-6-at-nihhospital-last-year.html (T. McAlear).
ESSAY 1 IS DUE IN CLASS—OCTOBER 23
The promise and challenge of phage therapy; Global change and the human
microbiome
Reading: Phage therapy: (Sulakvelidze et al. 2001)*; (Housby and Mann 2009)†;
(Mattey and Spencer 2008)†; (Bull et al. 2002)†.
Human microbiome: (Specter 2012)*; (Gordon 2012)†; (Hvistendahl 2012)†;(Hanski
et al. 2012)†; (Grady 2012)† URL:
http://www.nytimes.com/2012/03/20/health/gut-infections-are-growing-muchmore-lethal.html?_r=1&pagewanted=all ; (Ayres et al. 2012)†; (Kamada et al.
2012)†; (Caricilli et al. 2011)†; (Hvistendahl 2012)†; (Wu et al. 2012)†; (Grady 2013),
URL: http://www.nytimes.com/2013/01/17/health/disgusting-maybe-buttreatment-works-study-finds.html?hp ; (Kelly 2013);(van Nood et al. 2013).
Phage therapy: Sulakvelidze et al. present a detailed account of the history of
development of phage therapy in the Eastern Bloc during the Cold War, and make a
thorough comparison of the relative advantages of phage and antibiotic therapy.
Housby and Mann also present a history of phage therapy, along with an account of
where major western pharmaceutical companies are now in the development of
phage therapy. Mattey and Spencer discuss the challenges that must be overcome
to fully develop phage therapy. Bull et al. re-enact a classical experiment to show
the conditions under which phage therapy is more efficacious than antibiotic
therapy.
Human microbiome: Specter explains in his New Yorker article why a scorched
earth policy of extermination of bacteria in our bodies would not be a good thing.
Gordon provides a not-too-technical introduction to the concept of microbiome
health. Hvistendahl’s news article “My microbiome and me” is about Liping Zhao’s
investigation of traditional Chinese medicine’s effects on improving the human gut
microbiome. Hanski et al. consider the importance of other kinds of global change
(beyond antibiotics) on the human microbiome, such as the effects of the animal
diversity levels around us on the health of our microbiomes. Grady’s NY Times
article explains how we become much more likely to become sick with a bacterial
infection and with norovirus if we’ve recently taken antibiotics. Similarly, Kamada
et al. show that a germ-free mouse is much less likely to be infected with a gut
pathogen than a mouse with a full gut community. Caricilli et al. show an extremely
interesting interaction between the genetics of a mouse and its microbiome. Wu et
al. show the effects of diet on the microbiome in humans, and show that this is a
long-term effect (i.e., greater than 10 days). The Grady article in the NY Times gives
recent evidence for the efficacy of fecal transplants in treating Clostridium difficile
infections; this is also reported on by Kelly. The original article is by van Nood.
Student pick: (Smith 2012), URL: http://www.nytimes.com/2012/09/19/dining/forgastronomists-a-go-to-microbiologist.html?pagewanted=1&src=dayp (S. Aracena);
http://www.genomeweb.com/sequencing/ucb-harvard-collaborate-humanmicrobiome-research (study of immunomodulatory organisms in the human
microbiome; M. Hartsoe);
http://www.sciencemag.org/content/338/6106/450.1.full?sa_campaign=Email/snt
w/26-October-2012/10.1126/science.338.6106.450-a (identification of six gut
bacteria that can cure an infection by diarrhea-producing Clostridium difficile; S.
Kopac); http://jcm.asm.org/content/50/10/3258.abstract (patients with Crohn’s
disease, a form of inflammatory bowel disease, have markedly different
communities compared to healthy people; S. Kopac).
Land use, climate change, and infectious disease
14 Oct. Forest fragmentation, change in land use, and disease
25
Reading: (Walters 2003)†, Ch.4; (Keesing et al. 2006)†; (LoGiudice et al. 2003)†;
(Keesing et al. 2009)†; (Vittor et al. 2006)†; (Guerra et al. 2006)*; (Kuo et al. 2012)†.
The Walters chapter gives an extremely accessible account of Richard Ostfeld’s
work on why Lyme disease is such a problem now, owing to changes in land use (in
particular, forest fragmentation). The 2006 Keesing article addresses generally how
species diversity among hosts affects the chance of a human picking up an infection.
You should pay particular attention to the part dealing with Lyme disease.
LoGiudice et al. show that the white-footed mouse (Peromyscus) is an excellent
transmitter of Lyme disease (by way of ticks that feed on the mice), and that
Peromyscus tends to be in highest density in small forest fragments. In 2009,
Keesing et al. show that most of the small mammals tend to reduce the tick
population by efficiently grooming themselves, while the Peromyscus mice tends to
increase the tick population. Vittor et al. show that the rate at which humans are
bitten by a particular malaria-carrying mosquito species is much greater at
deforested than at forested sites in the Peruvian Amazon. More generally, Guerra et
al. analyze worldwide how deforestation influences the rate of malaria
transmission. Kuo et al. demonstrate that abandonment of rice paddies in Taiwan
increases opportunities for opportunities for transmission of disease through
chiggers and ticks. In future issues of this class, I will discuss how recent changes in
land use in central Africa may have led to human outbreaks of various hemorrhagic
fever viruses (including Ebola), versus alternative hypotheses that Ebola and Lassa
have long been with us (Gire et al. 2012).
Viewing of Hurricane Sandy (lecture canceled)
15 Oct.
30
16 Nov. Climatology and the prediction of warmer and freakier weather worldwide
1
Guest lecture by Prof. Dana Royer, Dept. of Earth & Environmental Sciences
Reading: (Barnosky et al. 2012)*; (Schiermeier 2007)†; (Monastersky 2009)*; (Patel
2006)†; (Sherwood 2011)†; (Solomon et al. 2010)†; CNN article on Sandy and
climate change: http://www.cnn.com/2012/10/31/us/sandy-climatechange/index.html?hpt=hp_t1 ; (Sun et al. 2012).
Student pick: http://www.nytimes.com/2012/11/02/nyregion/bloombergendorses-obama-saying-hurricane-sandy-affected-decision.html?hp&_r=0 (A.
Isaacson).
Nov. 1,
8 PM
I’ve retro-assigned the Solomon article posted by Professor Yohe. This article nicely
deals with the long-term nature of the effects of greenhouse gases, a topic
emphasized by Prof. Royer in his lecture. I’ve also retro-assigned the Sun et al.
article, which describes the greenhouse earth of the early Triassic (250 million years
ago) as having tropical oceans so hot that they were lethal to most animals and
plants.
Showing of Contagion at Wesleyan Film Series for our class (attendance required)
Reading: (Lipkin 2011), URL: http://www.nytimes.com/2011/09/12/opinion/thereal-threat-of-contagion.html ; (Bray and Buller 2004), URL:
http://movies.nytimes.com/2011/09/09/movies/contagion-steven-soderberghsplague-paranoia-review.html?pagewanted=all&_r=0 ; (Quammen 2012b), Ch. 4*.
The review by Lipkin is particularly interesting for our purposes, as Lipkin is a
professional pathogen hunter and was a paid consultant for the film. He argues
that while the work is fiction, the threats shown in the movie are real. Quammen’s
Chapter 4 presents the story of SARS, which is eerily like our movie.
Review session for Exam 2, Monday, Nov. 5, 8-10 PM, in Exley 150
Exam 2 on Lectures 9-16, Tuesday Nov. 6, in class
17 Nov. Discussion of Contagion; Global climate change and disease
8
Reading: (Parmesan and Yohe 2003); (Hopp and Foley 2001); (Hales et al. 2002);
(Peterson et al. 2005); (Tanser et al. 2003); (Daniel et al. 2009); (Lindgren and
Gustafson 2001); (Kovats et al. 2004); (Lowen et al. 2007); (Stenseth et al. 2006);
(Dearing and Dizney 2010).
Parmesan and Yohe provide a meta-analysis of changes in phenology and in
geographic distribution of many species previously studied. The most important
part of the paper, for our purposes, is Table 1 on changes in phenology and
geographic distribution. Hopp and Foley present a map of geographic distributions
showing the huge geographic extent over which the dengue mosquito lives but
where dengue is not yet present (including the Deep South of the US). They make a
case that absolute humidity predicts the distribution of Aedes aegypti mosquitoes,
and provide experimental evidence for increased survival of the mosquitoes at
higher humidities. Hales et al. predict the future geographic distribution of Aedes
aegypti assuming absolute humidity as the major determinant. Peterson et al.
provide a more inclusive (i.e., more parameters included) model of dengue
distribution in Mexico. Daniel et al. present evidence for the appearance of TBEV at
elevations above 1000 meters for the first time in the Czech Republic, and argue
that this is due to global warming. Lindgren et al. discuss the weather determinants
for high incidence of TBEV in Sweden, and argue that global warming will increase
the incidence of TBEV. Kovats et al. show how Salmonella-based food poisoning
increases with temperature, and how the functional response of food poisoning
rates to temperature varies across countries. Lowen et al. provide a compelling
argument for why influenza is transmitted at higher rates in cooler seasons, and
gives us reason to cheer for one health-benefiting effect of global warming.
Stenseth et al. identify the weather parameter values that predict high incidence of
plague in Kazakhstan; this analysis, applied to tree ring data on historical weather
patterns, predicts a high incidence of plague in Kazakhstan at the time of the 14 th
century Black Death and the 19th century Third Pandemic. Dearing and Dizney
discuss the effects of increasing El Niño events (predicted with global climate
change) on Hanta virus outbreaks, such as seen with the Sin Nombre virus outbreak
in the Four Corners region of the US. More issues related to global climate change
will be discussed in lecture 21.
Social causes and effects of infectious disease in a changing world
18 Nov. Wealth, health, and democracy in East Asia and Latin America
13
Guest lecture by Prof. James McGuire, Professor of Government
Reading: (McGuire 2010), Chs. 1† and 11*.
Student pick: URL: http://www.cnn.com/2012/11/13/health/infant-mortalitymississippi/index.html?hpt=he_t3 . This focuses on infant mortality caused by various
factors, including infectious disease, in Mississippi; you don’t have to be in a developing
country for poverty to have huge effects on infant mortality. (M. Delgado).
19 Nov. How culture and infrastructure affect the spread of infectious disease
15
Guest lecture by Prof. William Johnston, Professor of History
Reading: (Barr et al. 2001)*; (Farmer et al. 2011)*; (Farmer and Ivers 2012)†;
(Plucinski et al. 2011)†; (Talavera and Perez 2009)†.
20 Nov. How we can mitigate infectious disease threats caused by global climate change
20
Guest lecture by Prof. Gary Yohe, Professor of Economics
Reading: (Solomon et al. 2010)†; (Luber and Knowlton 2013)*; (Smith and
Woodward 2012)*
Thanksgiving break—Thursday Nov. 22
21 Nov. Various global changes and infectious disease (including some effects of climate
27
change not yet discussed)
A. More on global warming and infectious disease
Reading: (Lindgren et al. 2012)*; (Woodruff et al. 2007)†; (Gould and Higgs 2009)†.
Lindgren et al. discuss the emergence of various tropical diseases in Europe, as a
result of both climate change and increased rates of transfer of diseases across
continents. Woodruff et al. discuss the expansion of the range of dengue under
models of future climates. Gould and Higgs attribute many unexpected range
expansions of tropical diseases into Europe to global warming and precipitate
change.
B. Effects of weather extremes on infectious disease
Reading: (Yohe 2012)†, URL:
http://www.sbs.com.au/news/article/1706329/Hurricane-Sandy-the-new-normal ;
(Peeples 2012)†, URL: http://www.huffingtonpost.com/2012/10/29/hurricanesandy-flood-rats-disease-new-york_n_2041474.html; (Hunter 2003)†; (Chase and
Knight 2003); (Cuevas et al. 2007)†; (Curriero et al. 2001)†.
Gary Yohe discusses why Hurriane Sandy should be considered the harbinger of
weather to come, but argues that Sandy is not the new normal; weather will
actually get much worse. The news article by Peeples discusses how rats are being
displaced from their underground haunts by Hurricane Sandy and are infesting
homes in New York (featuring Rick Ostfeld). Maps of flooding of NYC and environs:
http://www.nytimes.com/newsgraphics/2012/1120-sandy/survey-of-the-floodingin-new-york-after-the-hurricane.html?hp . Hunter et al. discuss the effects of
extreme flooding on water-borne infectious disease. Curriero et al. discuss how
extreme precipitation events are associated with water-borne disease outbreaks in
the US. Chase and Knight describe the effects of climate-change-induced drought
on infectious disease. Cuevas et al. set up a kind of ecological niche modeling for
Neisseria-caused meningitis, and find an effect of drought on infection rates; they
they predict higher rates of infection into the future.
C. Economic vs. biological approaches to predicting our biological future
Reading: (Parmesan and Yohe 2003)*.
Parmesan and Yohe discuss some of the differences between the economist’s
versus biologists’ ways of knowing that an environmental factor has been
responsible for causing past change. I would also like to discuss (not in this paper)
the differences between economists’ versus biologists’ ways of predicting the
biological future.
D. Effects of AIDS and antibiotics on the emergence of new bacterial diseases
Reading: (Okoro et al. 2012)*; (Anonymous 2012)†, URL:
http://newyork.cbslocal.com/2012/09/27/city-health-officials-investigating-deadlybacterial-meningitis-outbreak-among-hiv-positive-men/ (K. Deane).
The (anonymous) CBS report describes one instance of the fallout of the global AIDS
epidemic—that there is a rash of new diseases that can infect immunocompromised
people. Similarly, the Okoro et al. study shows that a strain of Salmonella, which
normally cannot be transmitted directly between people, has evolved into a directly
transmitted pathogen, at least in immunocompromised AIDS patients.
E. Epidemics caused by various effects of modernity
Reading: (Pollack and Tavernise 2012)†, URL:
http://www.nytimes.com/2012/11/22/health/documents-show-fdas-failures-inmeningitis-outbreak.html?hp&_r=0; (Gayer et al. 2007)†; (Cirillo 2009)†; (Harris
2012), URL: http://www.nytimes.com/2012/11/25/world/asia/indian-prostitutesnew-autonomy-imperils-aids-fight.html?pagewanted=all&_r=0 .
The NY Times article by Pollack and Tavernise discusses how recent bad practices in
drug formulation by a small drug manufacturer have led to a nation-wide outbreak
of bacterial meningitis. Gayer discusses the problem of war in infectious disease,
including the effects of collapsed infrastructure. Note that this problem may be
particularly acute if a new spillover disease emerges in a war-torn region. Cirillo
discusses the effect of a 19th century war on infectious disease—that dysentery
caused more US soldier deaths in the war with Mexico than gunshot. The New York
Times article by Harris discusses an effect of cell phone use on infectious disease: it
threatens to reduce significant gains in controlling AIDS in India because prostitutes
can work more independently, outside of brothels.
Beyond single-species effects of disease
22 Nov. The effects of changing disease patterns on biological diversity and ecosystem
29
functioning
Reading: (Collinge et al. 2008)*; (Wolfe 2011)*, p. 115-118; (Kupferschmidt
2012a)†; (Fisher et al. 2012)†; (King 2012)†, Sept. 14, URL:
http://news.sciencemag.org/sciencenow/2012/09/plight-of-the-bumblebee.html
(G. Castanon); http://www.sfgate.com/science/article/Explosive-growth-in-suddenoak-death-3934216.php (N. Kosman-Wiener); (Grünwald et al. 2012)†.
Collinge et al. start with the concept of the keystone species, a species with a
disproportionate effect on community stability, such that local extinction of the
species would have catastrophic rippling effects through the community and
ecosystem. They then discuss the possibilities of such extinctions through infectious
disease. The Science news article by Kupferschmidt discusses the ability of some
fungal pathogens to extinguish multiple species; Fisher focuses on the potential
ecosystem effects of such extinctions. King discusses the pathogen that is ravaging
through native bumblebee populations in North America. (The bumble bee plays a
vital agricultural role in pollination of many crops and flowers.) The Grünwald
article on Sudden Oak Death describes rapid spread of this disease across many
trees of North America and Europe and describes the disease as a member of the
eukaryotic group Chromalveolata (not a fungus).
Bioinformatic analyses of infectious disease in a changing world
Dec. Essay 2 is due in class
4
23 Dec. Discovering the geographic and zoonotic origins of new human diseases; the role of
4
information technology in detecting the next epidemic (part 1)
Reading on detecting zoonotic origins: (Haydon et al. 2002)*; (Yip et al. 2009)*;
(Liu et al. 2010)†; (McMullan et al. 2012)†; (Grard et al. 2012)†.
Reading on information technology: (Quammen 2012a)†; (Achtman et al. 2012)†;
(Kopac and Cohan 2011)*; (Wiedenbeck and Cohan 2011)†; (Streicker and Pedersen
2012)‽.
Reading on detecting zoonotic origins. Haydon et al. present an overview of what
it takes to identify a zoonotic reservoir species. Yip et al. present the challenges
(and success) of locating the zoonotic reservoir for SARS and SARS-like viruses; they
also indicate the great potential for a future epidemic from an as-yet-unknown
coronavirus. Liu et al. present a huge survey of Plasmodium sampled from a huge
number of apes and monkeys, along with a phylogenetic analysis pointing to human
Plasmodium falciparum as a monophyletic lineage within the gorilla parasites. The
trick here wasn’t so much how to do the phylogenetic analysis once all the DNA
samples were in hand. Rather, it was how to sample Plasmodium from thousands
of great apes. Not so easy—see how it was done! It would be easy to ignore all the
incomplete findings about zoonotic sources because the full discovery of a zoonotic
virus and its natural host (and vectors when applicable) is a much more glamorous
story. Check out the report by Laura McMullan et al. It has the drama of a case
study, as told for example by David Quammen, but more in the deadpan style of Joe
Friday of Dragnet (“just the facts, ma’am”). While this was a huge discovery, there
is so much more sleuth work to be done. You’ll see in the Grard paper that
sometimes we don’t isolate the virus itself. Grard et al. present the virus genome
(although not the virus) that caused the hemorrhagic fever epidemic in central
Africa in 2009. It is distantly related from any other human-infecting member of the
Rhabdovirus family.
Readings on information technology. The Quammen article discusses the
inevitability of the “next big one,” meaning the next utterly awful human pandemic.
This is just to remind us, once again, that we need to be thinking about how to
anticipate and quickly discover and contain any new dangerous, newly emerging
pathogen. Achtman et al. introduce us to a problem in discovering the total
diversity within a closely related group of bacterial pathogens—that the most
common approach to classifying closely related bacterial diversity, involving
immunity types (serotypes) is not up to the task. They show how a multilocus
sequencing approach can accurately yield an accounting of the closest relatives of a
known pathogen. Kopac and Cohan present an approach our lab has developed to
find all the ecologically important diversity within a group of closely related
bacteria. As we explain, this approach provides the advantage that we can discover
ecologically distinct groups of bacteria before we even know what is ecologically
distinct about them. This allows us to hypothesize close relatives of a pathogen that
might have different disease-causing properties. The Wiedenbeck and Cohan paper
provides some figures and further explanations that might be helpful. Streicker and
Pedersen present a positive (and amusing) review of Quammen’s book Spillover.
24 Dec. Early warning systems for emergent infectious diseases—the Global Viral
6
Forecasting Initiative; the role of information technology in stopping the next
pandemic (part 2).
Reading: (Wolfe 2011), Ch. 9*, 10*, and 12†; (Paneth 2004)†; (Wolfe 2009)†;
(Cohan 2012)†; (Cohan 2011)‽.
Student pick: http://www.nytimes.com/2012/07/15/sunday-review/the-ecologyof-disease.html?pagewanted=all (R. Rubenstein). This summarizes much of what
we’ve covered in class, and will introduce our section on bioinformatic approaches
to predict and monitor emergence of infectious diseases.
In Ch. 9, Wolfe discusses how we need to get beyond dumb luck in discovering the
next epidemic among the great apes, and to invent a systematic approach that
quickly find any new epizootic among our closest relatives. In Ch. 10 he lays out
various ways that we can effectively monitor new epizootic diseases before they
become human pandemics. Ch. 12 wraps things up. My articles discuss the
importance, in this age of big data, of imagining how our data could possibly be
used not just by our own laboratories but by future researchers. (The point is made
most effectively in my Moneyball piece, but you might like the Koufax article just for
fun.)
Review session-Wednesday, December 12, 8-10 PM, in 107 Shanklin (please note: this is not
our usual classroom)
Final exam—Thursday, December 13, 2-5 PM, in 150 Exley Science Center (our classroom).
Bonus Jan. What is it about bats?
topic 1
Reading: (Quammen 2012b), Ch. VII, “Celestial Hosts”; (Plowright et al. 2011);
(Cliff and Haggett 1995); (McNeil 2013); (Olival et al. 2013)
There came a time in our course when we couldn’t help but ask, “What is it
about bats?” We saw that bats were the reservoirs for Hendra, SARS, and
Nipah, and it turns out that it just gets worse. Over the break, I’ve made some
progress toward finishing David Quammen’s new book Spillover, and he has a
wonderful chapter on the role of bats in emerging viruses of humans. First, we
see that added to the list of chiropteranoses (my invention for a bat zoonosis;
you heard it here first) is Marburg for sure, and likely its close relative Ebola.
Next, we see some extremely intriguing theory for why bats are responsible for
so many human diseases and why only now. One aspect of this is the huge size
of many bat populations, and their extremely high densities. This means that
SIR diseases can do just fine within bat species. Then the chapter gets into the
question of why now there have been so many diseases emerging into humans
from bats. An interesting hypothesis is being developed and tested by Raina
Plowright. (Here I found her article and included it.) The idea is that in previous
times bats lived in contiguous forest, with much dispersal of bats across a huge
set of highly connected populations. This would have led to a low level of
endemic disease everywhere. Then as forests became fragmented, and human
habitations and farms offered a great source of food, bat populations became
highly fragmented as well, with little migration between bat populations
associated with different cities. In this model, a large number of susceptible
bats would accumulate in any given locality until a migrating infected bat reignites the infection. Then there would be a huge number of bats at one time
that could potentially infect humans. Making the situation worse is that the
bats are largely living in close proximity to humans. Here you might re-read the
Cliff and Haggett paper to look at the effect of population size on the
magnitude of waves of infection. In the next offering of the course, I will
definitely set aside an entire lecture to deal with the role of bats in human
disease, along with the ecological and epidemiological theory. The McNeil
Times article and the Olival article present data that the Ebola Virus is in bats in
Bangladesh. This indicates what has been suspected, that bats can transport a
virus for which they are a reservoir immense distances.
* Required reading
‡ Required reading if you do not already know the material
† Recommended reading. You should read at least one of these for each session.
‽ Just for fun.
Text: Wolfe, N. 2011. The Viral Storm: The Dawn of a New Pandemic Age. Times Books, New
York.
Office hours
In our office hours, you are welcome to ask questions about lectures, class discussions,
readings, and other issues relating to the course material.
Fred Cohan (Professor)
Office hours: Monday 2:30-3:30 in my office (Shanklin 207), and by appointment
Weekly review sessions: Friday, 2:15-3:15, in Exley 113
fcohan@wesleyan.edu
x3482
Sarah Kopac (Graduate teaching assistant)
skopac@wesleyan.edu
Monday 10:00-11:00
Shanklin 208
Jacob Herman (Graduate teaching assistant)
jherman@wesleyan.edu
Thursday 11:00-12:00
Shanklin 312
Adele Bubnys (Undergraduate teaching assistant)
abubnys@wesleyan.edu
Tuesday 2:30-3:30
Hall-Atwater 227
Ethan Grund (Undergraduate teaching assistant)
egrund@wesleyan.edu
Wednesday 10:00-11:00
Hall-Atwater 265A
Alexandra Coluzzi (Undergraduate teaching assistant)
acoluzzi@wesleyan.edu
Tuesday 12:00-1:00
Exley 137
Course requirements
We will have two exams during lecture period, on October 2 and November 6. These
exams will be principally short answer, multiple-choice, and fill-in-blank questions. The exams
will be based on lecture material, class discussions, and required readings.
Our comprehensive final exam (covering material from the whole semester) will be on
the registrar-assigned date. This exam will include questions in the format of our three in-class
exams, plus essay questions.
Two short essays will be due on October 23 and December 4. Each essay will answer a
question dealing with lecture material, class discussions, or assigned readings. The essays must
be typed and submitted as a paper copy. Detailed instructions for each essay are provided on
the class web site under “Essay assignments.”
You will be required to participate in class. This will include answering questions in class
with your clickers. (These are hand-held radio transmitters that allow you to answer multiplechoice questions in class. You will be responsible for keeping your clicker in good repair and
equipped with charged batteries.) Also, you are encouraged to participate in class discussions.
Reading assignments will be posted on our class’s WesFiles web site. Access to the site
will be provided in an upcoming email.
Here are the credits for each assignment:
Exam 1
Essay 1
Exam 2
Essay 2
Final exam
Participation (through discussion contributions
and clickers)
150 points
150 points
150 points
150 points
250 points
50 points
Policy on accommodations for disabilities
It is the policy of Wesleyan University to provide reasonable accommodations to students with
documented disabilities. Students, however, are responsible for registering with Disabilities
Services, in addition to making requests known to me in a timely manner. If you require
accommodations in this class, please make an appointment with me as soon as possible, so that
appropriate arrangements can be made. The procedures for registering with
Disabilities Services can be found at www.wesleyan.edu/deans/disability-students.html .
Readings
Achenbach, J., D. Brown, and L. H. Sun. 2012. Does the West Nile outbreak signal an epidemic of viral
epidemics? Yes and no. Washington Post.
Achtman, M., J. Wain, F. X. Weill, S. Nair, Z. Zhou, V. Sangal, M. G. Krauland, J. L. Hale, H. Harbottle, A.
Uesbeck, G. Dougan, L. H. Harrison, and S. Brisse. 2012. Multilocus sequence typing as a
replacement for serotyping in Salmonella enterica. PLoS Pathog 8:e1002776.
Allison, A. B., C. E. Harbison, I. Pagan, K. M. Stucker, J. T. Kaelber, J. D. Brown, M. G. Ruder, M. K. Keel, E.
J. Dubovi, E. C. Holmes, and C. R. Parrish. 2012. Role of multiple hosts in the cross-species
transmission and emergence of a pandemic parvovirus. J Virol 86:865-872.
Anonymous. 2009. Nipah Virus. World Health Organization Media Centre. World Health Organization,
Geneva.
Anonymous. 2012. City health officials investigating deadly bacterial meningitis utbreak among HIVpositive men. CBS New York. CBS Local Media.
Ariën, K. K., R. M. Troyer, Y. Gali, R. L. Colebunders, E. J. Arts, and G. Vanham. 2005. Replicative fitness of
historical and recent HIV-1 isolates suggests HIV-1 attenuation over time. AIDS 19:1555-1564.
Ariën, K. K., G. Vanham, and E. J. Arts. 2007. Is HIV-1 evolving to a less virulent form in humans? Nat Rev
Microbiol 5:141-151.
Ayres, J. S., N. J. Trinidad, and R. E. Vance. 2012. Lethal inflammasome activation by a multidrugresistant pathobiont upon antibiotic disruption of the microbiota. Nat Med 18:799–806.
Bailes, E., F. Gao, F. Bibollet-Ruche, V. Courgnaud, M. Peeters, P. A. Marx, B. H. Hahn, and P. M. Sharp.
2003. Hybrid origin of SIV in chimpanzees. Science 300:1713.
Barnosky, A. D., E. A. Hadly, J. Bascompte, E. L. Berlow, J. H. Brown, M. Fortelius, W. M. Getz, J. Harte, A.
Hastings, P. A. Marquet, N. D. Martinez, A. Mooers, P. Roopnarine, G. Vermeij, J. W. Williams, R.
Gillespie, J. Kitzes, C. Marshall, N. Matzke, D. P. Mindell, E. Revilla, and A. B. Smith. 2012.
Approaching a state shift in Earth's biosphere. Nature 486:52-58.
Barr, R. G., A. V. Diez-Roux, C. A. Knirsch, and A. Pablos-Mendez. 2001. Neighborhood poverty and the
resurgence of tuberculosis in New York City, 1984-1992. Am J Public Health 91:1487-1493.
Batalden, R. V., K. Oberhauser, and A. T. Peterson. 2007. Ecological niches in sequential generations of
eastern North American monarch butterflies (Lepidoptera: Danaidae): the ecology of migration
and likely climate change implications. Environ Entomol 36:1365-1373.
Black, F. L. 1966. Measles endemicity in insular populations: critical community size and its evolutionary
implication. J Theor Biol 11:207-211.
Bouckaert, R., P. Lemey, M. Dunn, S. J. Greenhill, A. V. Alekseyenko, A. J. Drummond, R. D. Gray, M. A.
Suchard, and Q. D. Atkinson. 2012. Mapping the origins and expansion of the Indo-European
language family. Science 337:957-960.
Boyle, R. 2012a. As Deadly White-Nose Syndrome Ravages Bat Population, Bats Change Social Strategy
to Survive. PopSci. Bonnier Corporation.
Boyle, R. 2012b. Inside the World's First Manmade Batcave Built For Wild Bats. PopSci. Bonnier
Corporation.
Bray, M. and M. Buller. 2004. Looking back at smallpox. Clin Infect Dis 38:882-889.
Bull, J. J., B. R. Levin, T. DeRouin, N. Walker, and C. A. Bloch. 2002. Dynamics of success and failure in
phage and antibiotic therapy in experimental infections. BMC Microbiol 2:35.
Caricilli, A. M., P. K. Picardi, L. L. de Abreu, M. Ueno, P. O. Prada, E. R. Ropelle, S. M. Hirabara, A.
Castoldi, P. Vieira, N. O. Camara, R. Curi, J. B. Carvalheira, and M. J. Saad. 2011. Gut microbiota is
a key modulator of insulin resistance in TLR 2 knockout mice. PLoS Biol 9:e1001212.
Chase, J. M. and T. M. Knight. 2003. Drought-induced mossquito outbreaks in wetlands. Ecol Lett
6:1017-1024.
Cirillo, V. J. 2009. "More fatal than powder and shot": Dysentery in the U.S. Army during the Mexican
War, 1846-1848. Perspectives in Biology and Medicine 52:400-413.
Cliff, A. D. and P. Haggett. 1995. The epidemiological significance of islands. Health and Place 1:199-209.
Cohan, F. M. 2011. Koufax’s perfect game—the tale of the data. Los Angeles Times. Tribune
Newspapers, Los Angeles.
Cohan, F. M. 2012. Science needs more Moneyball. American Scientist 100:182-185.
Collinge, S. K., C. Ray, and J. F. Cully, Jr. 2008. Effects of disease on keystone species, dominant species,
and their communities. Pages 129-144 in R. S. Ostfeld, F. Keesing, and V. T. Eviner, editors.
Infectious Disease Ecology: The Effeccts of Ecosystems on Disease and of Disease on Ecosystems.
Princeton University Press, Princeton.
Cuevas, L. E., I. Jeanne, A. Molesworth, M. Bell, E. C. Savory, S. J. Connor, and M. C. Thomson. 2007. Risk
mapping and early warning systems for the control of meningitis in Africa. Vaccine 25 Suppl
1:A12-17.
Curriero, F. C., J. A. Patz, J. B. Rose, and S. Lele. 2001. The association between extreme precipitation
and waterborne disease outbreaks in the United States, 1948-1994. Am J Public Health 91:11941199.
Daniel, M., J. Materna, V. Honig, L. Metelka, V. Danielova, J. Harcarik, S. Kliegrova, and L. Grubhoffer.
2009. Vertical distribution of the tick Ixodes ricinus and tick-borne pathogens in the northern
Moravian mountains correlated with climate warming (Jeseniky Mts., Czech Republic). Cent Eur
J Public Health 17:139-145.
Dearing, M. D. and L. Dizney. 2010. Ecology of hantavirus in a changing world. Ann N Y Acad Sci 1195:99112.
Diamond, J. 1997. Guns, Germs, and Steel: The Fates of Human Societies. Norton, New York.
Diamond, J. 2002. Evolution, consequences and future of plant and animal domestication. Nature
418:700-707.
DuBois, S. 2012. Oregon Plague: Woman Contracted Disease From Cat. Huffington Post.
TheHuffingtonPost.com.
Ewald, P. W. 1993. The evolution of virulence. Sci Am 268:86-93.
Farmer, P., C. P. Almazor, E. T. Bahnsen, D. Barry, J. Bazile, B. R. Bloom, N. Bose, T. Brewer, S. B.
Calderwood, J. D. Clemens, A. Cravioto, E. Eustache, G. Jerome, N. Gupta, J. B. Harris, H. H. Hiatt,
C. Holstein, P. J. Hotez, L. C. Ivers, V. B. Kerry, S. P. Koenig, R. C. Larocque, F. Leandre, W.
Lambert, E. Lyon, J. J. Mekalanos, J. S. Mukherjee, C. Oswald, J. W. Pape, A. Gretchko Prosper, R.
Rabinovich, M. Raymonville, J. R. Rejouit, L. J. Ronan, M. L. Rosenberg, E. T. Ryan, J. D. Sachs, D.
A. Sack, C. Surena, A. A. Suri, R. Ternier, M. K. Waldor, D. Walton, and J. L. Weigel. 2011.
Meeting cholera's challenge to Haiti and the world: a joint statement on cholera prevention and
care. PLoS Negl Trop Dis 5:e1145.
Farmer, P. E. and L. C. Ivers. 2012. Cholera in Haiti: the equity agenda and the future of tropical
medicine. Am J Trop Med Hyg 86:7-8.
Fisher, M. C., D. A. Henk, C. J. Briggs, J. S. Brownstein, L. C. Madoff, S. L. McCraw, and S. J. Gurr. 2012.
Emerging fungal threats to animal, plant and ecosystem health. Nature 484:186-194.
Fox, M. 2012. New virus in Africa looks like rabies, acts like Ebola. NBCNews.com. NBC, New York.
Futuyma, D. J. 2005. Evolution. 2nd edition.
Gao, F., E. Bailes, D. L. Robertson, Y. Chen, C. M. Rodenburg, S. F. Michael, L. B. Cummins, L. O. Arthur,
M. Peeters, G. M. Shaw, P. M. Sharp, and B. H. Hahn. 1999. Origin of HIV-1 in the chimpanzee
Pan troglodytes troglodytes. Nature 397:436-441.
Gayer, M., D. Legros, P. Formenty, and M. A. Connolly. 2007. Conflict and emerging infectious diseases.
Emerg Infect Dis 13:1625-1631.
Gire, S. K., M. Stremlau, K. G. Andersen, S. F. Schaffner, Z. Bjornson, K. Rubins, L. Hensley, J. B.
McCormick, E. S. Lander, R. F. Garry, C. Happi, and P. C. Sabeti. 2012. Epidemiology. Emerging
disease or diagnosis? Science 338:750-752.
Gordon, J. I. 2012. Honor thy gut symbionts redux. Science 336:1251-1253.
Gorman, J. 2012. Building a Bat Cave to Battle a Killer. New York Times. New York Times Company, New
York.
Gould, E. A. and S. Higgs. 2009. Impact of climate change and other factors on emerging arbovirus
diseases. Trans R Soc Trop Med Hyg 103:109-121.
Grady, D. 2012. Gut infections are growing more lethal. New York Times, New York.
Grady, D. 2013. Disgusting, Maybe, but Treatment Works, Study Finds. New York Times. New York Times
Company, New York.
Grard, G., J. N. Fair, D. Lee, E. Slikas, I. Steffen, J. J. Muyembe, T. Sittler, N. Veeraraghavan, J. G. Ruby, C.
Wang, M. Makuwa, P. Mulembakani, R. B. Tesh, J. Mazet, A. W. Rimoin, T. Taylor, B. S.
Schneider, G. Simmons, E. Delwart, N. D. Wolfe, C. Y. Chiu, and E. M. Leroy. 2012. A novel
rhabdovirus associated with acute hemorrhagic Fever in central Africa. PLoS Pathog 8:e1002924.
Groopman, J. 2012. Sex and the superbug. Pages 26-30 The New Yorker, New York.
Grünwald, N. J., M. Garbelotto, E. M. Goss, K. Heungens, and S. Prospero. 2012. Emergence of the
sudden oak death pathogen Phytophthora ramorum. Trends Microbiol 20:131-138.
Guerra, C. A., R. W. Snow, and S. I. Hay. 2006. A global assessment of closed forests, deforestation and
malaria risk. Ann Trop Med Parasitol 100:189-204.
Hahn, B. H., G. M. Shaw, K. M. De Cock, and P. M. Sharp. 2000. AIDS as a zoonosis: scientific and public
health implications. Science 287:607-614.
Hales, S., N. de Wet, J. Maindonald, and A. Woodward. 2002. Potential effect of population and climate
changes on global distribution of dengue fever: an empirical model. Lancet 360:830-834.
Hanski, I., L. von Hertzen, N. Fyhrquist, K. Koskinen, K. Torppa, T. Laatikainen, P. Karisola, P. Auvinen, L.
Paulin, M. J. Makela, E. Vartiainen, T. U. Kosunen, H. Alenius, and T. Haahtela. 2012.
Environmental biodiversity, human microbiota, and allergy are interrelated. Proc Natl Acad Sci U
S A 109:8334-8339.
Harris, G. 2012. Cellphones reshape prostitution in India, and complicate efforts to prevent AIDS. New
York Times. The New York Times Company, New York.
Haydon, D. T., S. Cleaveland, L. H. Taylor, and M. K. Laurenson. 2002. Identifying reservoirs of infection:
a conceptual and practical challenge. Emerg Infect Dis 8:1468-1473.
Hopp, M. J. and J. A. Foley. 2001. Global-scale relationships between climate the the dengue fever
vector, Aedes aegypti. Climatic Change 38:441-463.
Housby, J. N. and N. H. Mann. 2009. Phage therapy. Drug Discov Today 14:536-540.
Hunter, P. R. 2003. Climate change and waterborne and vector-borne disease. J Appl Microbiol 94
Suppl:37S-46S.
Hvistendahl, M. 2012. My microbiome and me. Science 336:1248-1250.
Jackson, A. P. and M. A. Charleston. 2004. A cophylogenetic perspective of RNA-virus evolution. Mol Biol
Evol 21:45-57.
Jones, K. E., N. G. Patel, M. A. Levy, A. Storeygard, D. Balk, J. L. Gittleman, and P. Daszak. 2008. Global
trends in emerging infectious diseases. Nature 451:990-993.
Kamada, N., Y. G. Kim, H. P. Sham, B. A. Vallance, J. L. Puente, E. C. Martens, and G. Nunez. 2012.
Regulated virulence controls the ability of a pathogen to compete with the gut microbiota.
Science 336:1325-1329.
Keesing, F., J. Brunner, S. Duerr, M. Killilea, K. Logiudice, K. Schmidt, H. Vuong, and R. S. Ostfeld. 2009.
Hosts as ecological traps for the vector of Lyme disease. Proc Biol Sci 276:3911-3919.
Keesing, F., R. D. Holt, and R. S. Ostfeld. 2006. Effects of species diversity on disease risk. Ecol Lett 9:485498.
Keim, P. S. and D. M. Wagner. 2009. Humans and evolutionary and ecological forces shaped the
phylogeography of recently emerged diseases. Nat Rev Microbiol 7:813-821.
Kelly, C. P. 2013. Fecal Microbiota Transplantation — An Old Therapy Comes of Age. New England
Journal of Medicine.
Kilpatrick, A. M. 2011. Globalization, land use, and the invasion of West Nile virus. Science 334:323-327.
King, A. 2012. Plight of the bumblebee. ScienceNOW.
Klein, E., D. L. Smith, and R. Laxminarayan. 2007. Hospitalizations and deaths caused by methicillinresistant Staphylococcus aureus, United States, 1999-2005. Emerg Infect Dis 13:1840-1846.
Klug, W. S. 2006. Concepts of Genetics. 8th edition.
Knell, R. J. 2004. Syphilis in renaissance Europe: rapid evolution of an introduced sexually transmitted
disease? Proc Biol Sci 271 Suppl 4:S174-176.
Kopac, S. and F. M. Cohan. 2011. A theory-based pragmatism for discovering and classifying newly
divergent bacterial species. Pages 21-41 in M. Tibayrenc, editor. Genetics and Evolution of
Infectious Diseases. Elsevier, London.
Kovats, R. S., S. J. Edwards, S. Hajat, B. G. Armstrong, K. L. Ebi, and B. Menne. 2004. The effect of
temperature on food poisoning: a time-series analysis of salmonellosis in ten European
countries. Epidemiol Infect 132:443-453.
Kuo, C.-C., J.-L. Huang, P.-Y. Shu, P.-L. Lee, D. A. Kelt, and H.-C. Wang. 2012. Cascading effect of
economic globalization on human risks to scrub typhus and tick-borne rickettsial diseases.
Ecological Applications.
Kupferschmidt, K. 2012a. Mycology. Attack of the clones. Science 337:636-638.
Kupferschmidt, K. 2012b. Public health. Do sports events give microbes a chance to score? Science
336:1224-1225.
Lanciotti, R. S., J. T. Roehrig, V. Deubel, J. Smith, M. Parker, K. Steele, B. Crise, K. E. Volpe, M. B. Crabtree,
J. H. Scherret, R. A. Hall, J. S. MacKenzie, C. B. Cropp, B. Panigrahy, E. Ostlund, B. Schmitt, M.
Malkinson, C. Banet, J. Weissman, N. Komar, H. M. Savage, W. Stone, T. McNamara, and D. J.
Gubler. 1999. Origin of the West Nile virus responsible for an outbreak of encephalitis in the
northeastern United States. Science 286:2333-2337.
LeBreton, M., O. Yang, U. Tamoufe, E. Mpoudi-Ngole, J. N. Torimiro, C. F. Djoko, J. K. Carr, A. Tassy
Prosser, A. W. Rimoin, D. L. Birx, D. S. Burke, and N. D. Wolfe. 2007. Exposure to wild primates
among HIV-infected persons. Emerg Infect Dis 13:1579-1582.
Levine, R. S., A. T. Peterson, K. L. Yorita, D. Carroll, I. K. Damon, and M. G. Reynolds. 2007. Ecological
niche and geographic distribution of human monkeypox in Africa. PLoS One 2:e176.
Levy, S. B. 1992. The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle. Plenum, New
York.
Lindgren, E., Y. Andersson, J. E. Suk, B. Sudre, and J. C. Semenza. 2012. Public health. Monitoring EU
emerging infectious disease risk due to climate change. Science 336:418-419.
Lindgren, E. and R. Gustafson. 2001. Tick-borne encephalitis in Sweden and climate change. Lancet
358:16-18.
Lipkin, W. I. 2011. The real threat of 'Contagion'. New York Times. New York Times Company, New York.
Liu, W., Y. Li, G. H. Learn, R. S. Rudicell, J. D. Robertson, B. F. Keele, J. B. Ndjango, C. M. Sanz, D. B.
Morgan, S. Locatelli, M. K. Gonder, P. J. Kranzusch, P. D. Walsh, E. Delaporte, E. Mpoudi-Ngole,
A. V. Georgiev, M. N. Muller, G. M. Shaw, M. Peeters, P. M. Sharp, J. C. Rayner, and B. H. Hahn.
2010. Origin of the human malaria parasite Plasmodium falciparum in gorillas. Nature 467:420425.
LoGiudice, K., R. S. Ostfeld, K. A. Schmidt, and F. Keesing. 2003. The ecology of infectious disease: effects
of host diversity and community composition on Lyme disease risk. Proc Natl Acad Sci U S A
100:567-571.
Lowen, A. C., S. Mubareka, J. Steel, and P. Palese. 2007. Influenza virus transmission is dependent on
relative humidity and temperature. PLoS Pathog 3:1470-1476.
Luber, G. and K. Knowlton. 2013. Human health. National Climate Assessment.
Madigan, M. T. and J. M. Martinko. 2006. Brock Biology of Microorganisms. 11th edition.
Mann, C. C. 2011. 1493: Uncovering the New World Columbus Created. Alfred A. Knopf, New York.
Mattey, M. and J. Spencer. 2008. Bacteriophage therapy--cooked goose or phoenix rising? Curr Opin
Biotechnol 19:608-612.
Mayr, A. 1989. Infections which humans in the household transmit to dogs and cats. Zentralbl Bakteriol
Mikrobiol Hyg B 187:508-526.
McGuire, J. W. 2010. Wealth, Health, and Democracy in East Asia and Latin America. Cambridge
University Press, Cambridge.
McMullan, L. K., S. M. Folk, A. J. Kelly, A. MacNeil, C. S. Goldsmith, M. G. Metcalfe, B. C. Batten, C. G.
Albariño, S. R. Zaki, P. E. Rollin, W. L. Nicholson, and S. T. Nichol. 2012. A New Phlebovirus
Associated with Severe Febrile Illness in Missouri. New England Journal of Medicine 367:834841.
McNeil, D. G., Jr. 2011. Chimp to Man to History Books: The Path of AIDS. New York Times, New York.
McNeil, D. G., Jr. 2013. Link to African Ebola found in bats suggests virus is more widespread. New York
Times. New York Times Company, New York.
Mindell, D. P. 2006. The Evolving World : Evolution in Everyday Life. Harvard Univ. Press, Cambridge,
Mass.
Monastersky, R. 2009. Climate crunch: A burden beyond bearing. Nature 458:1091-1094.
Morelli, G., Y. Song, C. J. Mazzoni, M. Eppinger, P. Roumagnac, D. M. Wagner, M. Feldkamp, B. Kusecek,
A. J. Vogler, Y. Li, Y. Cui, N. R. Thomson, T. Jombart, R. Leblois, P. Lichtner, L. Rahalison, J. M.
Petersen, F. Balloux, P. Keim, T. Wirth, J. Ravel, R. Yang, E. Carniel, and M. Achtman. 2010.
Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity. Nat
Genet.
Nathan, C. F. 2012. Let's gang up on killer bugs. New York Times. New York Times Company, New York.
Okoro, C. K., R. A. Kingsley, T. R. Connor, S. R. Harris, C. M. Parry, M. N. Al-Mashhadani, S. Kariuki, C. L.
Msefula, M. A. Gordon, E. de Pinna, J. Wain, R. S. Heyderman, S. Obaro, P. L. Alonso, I.
Mandomando, C. A. Maclennan, M. D. Tapia, M. M. Levine, S. M. Tennant, J. Parkhill, and G.
Dougan. 2012. Intracontinental spread of human invasive Salmonella Typhimurium
pathovariants in sub-Saharan Africa. Nat Genet.
Olival, K. J., A. Islam, M. Yu, S. J. Anthony, J. H. Epstein, S. A. Khan, S. U. Khan, G. Crameri, L. F. Wang, W.
I. Lipkin, S. P. Luby, and P. Daszak. 2013. Ebola virus antibodies in fruit bats, bangladesh. Emerg
Infect Dis 19:270-273.
Paneth, N. 2004. Assessing the contributions of John Snow to epidemiology: 150 years after removal of
the broad street pump handle. Epidemiology 15:514-516.
Papagrigorakis, M. J., C. Yapijakis, P. N. Synodinos, and E. Baziotopoulou-Valavani. 2006. DNA
examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague
of Athens. Int J Infect Dis 10:206-214.
Parmesan, C. and G. Yohe. 2003. A globally coherent fingerprint of climate change impacts across
natural systems. Nature 421:37-42.
Parrish, C. R., E. C. Holmes, D. M. Morens, E. C. Park, D. S. Burke, C. H. Calisher, C. A. Laughlin, L. J. Saif,
and P. Daszak. 2008. Cross-species virus transmission and the emergence of new epidemic
diseases. Microbiol Mol Biol Rev 72:457-470.
Patel, S. S. 2006. Climate science: a sinking feeling. Nature 440:734-736.
Pearce-Duvet, J. M. 2006. The origin of human pathogens: evaluating the role of agriculture and
domestic animals in the evolution of human disease. Biol Rev Camb Philos Soc 81:369-382.
Peeples, L. 2012. Hurricane Sandy could displace rats, spread infectious disease. Huffington Post. The
Huffington Post.com, Inc.
Peeters, M., V. Courgnaud, B. Abela, P. Auzel, X. Pourrut, F. Bibollet-Ruche, S. Loul, F. Liegeois, C. Butel,
D. Koulagna, E. Mpoudi-Ngole, G. M. Shaw, B. H. Hahn, and E. Delaporte. 2002. Risk to human
health from a plethora of simian immunodeficiency viruses in primate bushmeat. Emerg Infect
Dis 8:451-457.
Peterson, A. T. 2009. Shifting suitability for malaria vectors across Africa with warming climates. BMC
Infect Dis 9:59.
Peterson, A. T., C. Martinez-Campos, Y. Nakazawa, and E. Martinez-Meyer. 2005. Time-specific
ecological niche modeling predicts spatial dynamics of vector insects and human dengue cases.
Trans R Soc Trop Med Hyg 99:647-655.
Peterson, A. T., M. A. Ortega-Huerta, J. Bartley, V. Sanchez-Cordero, J. Soberon, R. H. Buddemeier, and
D. R. Stockwell. 2002. Future projections for Mexican faunas under global climate change
scenarios. Nature 416:626-629.
Peterson, A. T., A. Robbins, R. Restifo, J. Howell, and R. Nasci. 2008. Predictable ecology and geography
of West Nile virus transmission in the central United States. J Vector Ecol 33:342-352.
Plowright, R. K., P. Foley, H. E. Field, A. P. Dobson, J. E. Foley, P. Eby, and P. Daszak. 2011. Urban
habituation, ecological connectivity and epidemic dampening: the emergence of Hendra virus
from flying foxes (Pteropus spp.). Proc Biol Sci 278:3703-3712.
Plucinski, M. M., C. N. Ngonghala, and M. H. Bonds. 2011. Health safety nets can break cycles of poverty
and disease: a stochastic ecological model. J R Soc Interface 8:1796-1803.
Pollack, A. and S. Tavernise. 2012. Oversight failures documented in meningitis outbreak. New York
Times. The New York Times Company, New York.
ProMED-mail. 2012. PLAGUE - CHINA: (SICHUAN) BUBONIC, FATAL. ProMED-mail. International Society
for Infectious Diseases.
Purse, B. V., P. S. Mellor, D. J. Rogers, A. R. Samuel, P. P. Mertens, and M. Baylis. 2005. Climate change
and the recent emergence of bluetongue in Europe. Nat Rev Microbiol 3:171-181.
Quammen, D. 2012a. Anticipating the next pandemic. New York Times. New York Times Company, New
York.
Quammen, D. 2012b. Spillover: Animal Infections and the Next Human Epidemic. W. W. Norton, New
York.
Ridley, M. 2006. Genome: The Autobiography of a Species in 23 Chapters. HarperCollins, New York.
Rosen, G. 2007. Justinian's Flea: The First Great Plague and the Fall of the Roman Empire. Viking
Penguin.
Sadava, D. 2011. Life: The Science of Biology. 9th edition.
Schiermeier, Q. 2007. Polar research: the new face of the Arctic. Nature 446:133-135.
Shchelkunov, S. N. 2009. How long ago did smallpox virus emerge? Arch Virol 154:1865-1871.
Sherwood, S. 2011. Science controversies past and present. Physics Today 64:39-44.
Smith, K. R. and A. Woodward. 2012. Human health.in U. Confalonieri and A. Haines, editors. Climate
Change 2012: IPCC Fifth Assessment Report.
Smith, P. A. 2012. For Gastronomists, a Go-To Microbiologist. New York Times. New York Times
Company, New York.
Solomon, S., D. Battisti, S. Doney, K. Hayhoe, I. M. Held, D. P. Lettenmaier, D. Lobell, D. Matthews, R.
Pierrehumbert, M. Raphael, R. Richels, T. L. Root, K. Steffen, C. Tebaldi, G. W. Yohe, T. Warden,
and L. Brown. 2010. Climate stabilization targets: Emissions, concentrations, and impacts from
decades to millennia. National Academies Press, Washington, DC.
Sommer, M. O., G. Dantas, and G. M. Church. 2009. Functional characterization of the antibiotic
resistance reservoir in the human microflora. Science 325:1128-1131.
Specter, R. 2012. Germs are us. Pages 32-39 New Yorker. Conde Nast, New York.
Spellberg, B. 2009. Rising Plague: The Global Threat from Deadly Bacteria and our Dwindling Arsenal to
Fight Them. Prometheus, Amherst, NY.
Stenseth, N. C., N. I. Samia, H. Viljugrein, K. L. Kausrud, M. Begon, S. Davis, H. Leirs, V. M. Dubyanskiy, J.
Esper, V. S. Ageyev, N. L. Klassovskiy, S. B. Pole, and K. S. Chan. 2006. Plague dynamics are driven
by climate variation. Proc Natl Acad Sci U S A 103:13110-13115.
Streicker, D. G. and A. B. Pedersen. 2012. On the origins of zoonoses. Science 338:1030.
Sulakvelidze, A., Z. Alavidze, and J. G. Morris, Jr. 2001. Bacteriophage therapy. Antimicrob Agents
Chemother 45:649-659.
Sun, Y., M. M. Joachimski, P. B. Wignall, C. Yan, Y. Chen, H. Jiang, L. Wang, and X. Lai. 2012. Lethally hot
temperatures during the Early Triassic greenhouse. Science 338:366-370.
Synnott, A. J., Y. Kuang, M. Kurimoto, K. Yamamichi, H. Iwano, and Y. Tanji. 2009. Isolation from sewage
influent and characterization of novel Staphylococcus aureus bacteriophages with wide host
ranges and potent lytic capabilities. Appl Environ Microbiol 75:4483-4490.
Talavera, A. and E. M. Perez. 2009. Is cholera disease associated with poverty? J Infect Dev Ctries 3:408411.
Tanser, F. C., B. Sharp, and D. le Sueur. 2003. Potential effect of climate change on malaria transmission
in Africa. Lancet 362:1792-1798.
Technabob. 2010. Killing mosquitoes with laser beams. Technabob.
Thucydides. 1972. History of the Pelopennesian War. Penguin, New York.
van Nood, E., A. Vrieze, and M. Nieuwdorp. 2013. Duodenal infusion of donor feces for recurrent
Clostridium difficile. New England Journal of Medicine.
Veyrier, F., D. Pletzer, C. Turenne, and M. A. Behr. 2009. Phylogenetic detection of horizontal gene
transfer during the step-wise genesis of Mycobacterium tuberculosis. BMC Evol Biol 9:196.
Vittor, A. Y., R. H. Gilman, J. Tielsch, G. Glass, T. Shields, W. S. Lozano, V. Pinedo-Cancino, and J. A. Patz.
2006. The effect of deforestation on the human-biting rate of Anopheles darlingi, the primary
vector of Falciparum malaria in the Peruvian Amazon. Am J Trop Med Hyg 74:3-11.
Walters, M. J. 2003. Six Modern Plagues and How We Are Causing Them. Island Press, Washington.
Walther, B. A. and P. W. Ewald. 2004. Pathogen survival in the external environment and the evolution
of virulence. Biol Rev Camb Philos Soc 79:849-869.
Wiedenbeck, J. and F. M. Cohan. 2011. Origins of bacterial diversity through horizontal gene transfer
and adaptation to new ecological niches. FEMS Microbiology Reviews 35:957-976.
Wolfe, N. 2009. Preventing the next pandemic. Sci Am 300:76-81.
Wolfe, N. 2011. The Viral Storm: The Dawn of a New Pandemic Age. Times Books, New York.
Wolfe, N. D., C. P. Dunavan, and J. Diamond. 2007. Origins of major human infectious diseases. Nature
447:279-283.
Woodruff, R. E., T. McMichael, C. Butler, and S. Hales. 2007. Action on climate change: the health risks of
procrastinating. Aust N Z J Public Health 30:567-571.
Woolhouse, M. and E. Gaunt. 2007. Ecological origins of novel human pathogens. Crit Rev Microbiol
33:231-242.
Woolhouse, M. E., D. T. Haydon, and R. Antia. 2005. Emerging pathogens: the epidemiology and
evolution of species jumps. Trends Ecol Evol 20:238-244.
Worobey, M., M. Gemmel, D. E. Teuwen, T. Haselkorn, K. Kunstman, M. Bunce, J. J. Muyembe, J. M.
Kabongo, R. M. Kalengayi, E. Van Marck, M. T. Gilbert, and S. M. Wolinsky. 2008. Direct evidence
of extensive diversity of HIV-1 in Kinshasa by 1960. Nature 455:661-664.
Wrangham, R. and N. Conklin-Brittain. 2003. 'Cooking as a biological trait'. Comp Biochem Physiol A Mol
Integr Physiol 136:35-46.
Wu, G. D., J. Chen, C. Hoffmann, K. Bittinger, Y. Y. Chen, S. A. Keilbaugh, M. Bewtra, D. Knights, W. A.
Walters, R. Knight, R. Sinha, E. Gilroy, K. Gupta, R. Baldassano, L. Nessel, H. Li, F. D. Bushman,
and J. D. Lewis. 2012. Linking long-term dietary patterns with gut microbial enterotypes. Science
334:105-108.
Yip, C. W., C. C. Hon, M. Shi, T. T. Lam, K. Y. Chow, F. Zeng, and F. C. Leung. 2009. Phylogenetic
perspectives on the epidemiology and origins of SARS and SARS-like coronaviruses. Infect Genet
Evol 9:1185-1196.
Yohe, G. W. 2012. Hurricane Sandy: The new normal? World News Australia.
Zimmer, C. 2011. A Planet of Viruses. University of Chicago Press, Chicago.