NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
CASE TEACHING NOTES
for
“Why Was the 1918 Influenza So Deadly? An Intimate Debate Case”
by
Annie Prud’homme-Généreux and Carmen Petrick
Life Sciences, Quest University Canada
INTRODUCTION / BACKGROUND
The first recorded pandemic influenza outbreak took
place approximately 500 years ago in 1510 (Morens et
al., 2010). Since that time, an influenza pandemic has
occurred roughly every 30 years (Potter, 2001). In the
past century, there have been three influenza pandemics
(1918 Spanish flu, 1957 Asian flu, and 1968 Hong
Kong flu) and several more scares (1976 Swine flu, 1977
Russian flu, 1997 Avian flu, 2009 H1N1 flu). Pandemics
are created by antigenic shift, which is a large and sudden
change in the influenza virus’s virulence factors. Since
influenza carries its genes on eight separate pieces of
RNA, it is possible that a host infected with two different
strains of influenza can serve as a mixing vessel (Hilleman,
2002). As new viruses are produced by a co-infected cell,
RNA from either viral strain can be packaged together,
creating a virus with a novel genome. Since swine can
be infected by both human and avian flu (birds are the
reservoir species for influenza), they often serve as the
mixing vessel, converting avian strains into human ones.
As humans have not encountered the newly created strain
of virus, it is not recognized by the immune system, and
can replicate rapidly in an infected host.
The most devastating influenza pandemic took place
in 1918, when approximately 2.8–5.6% of the world
population (50 to100 million people) succumbed to the
disease (Johnson & Mueller, 2002). More people died of
influenza that year than died in combat during the First
World War. It is generally accepted that the 1918 strain
of influenza had biological characteristics that made it
particularly virulent, and hence the 1918 devastation was
due to biological factors (Reid et al., 2001). However, we
suggest that WWI was a very large confounding factor,
and that the war-time conditions may have exacerbated
what might otherwise have been an only moderately
virulent strain of the flu.
This intimate debate case was created to allow
students to explore the arguments supporting a biological
or a geopolitical-socioeconomic conditions (GPSEC)
explanation for the extraordinary 1918 influenza
devastation. Given the prospect of future influenza
pandemics, it is important to consider how both factors
can contribute to the pathogenicity of the virus (or even
magnify each other’s effects). Armed with this knowledge,
we will be able to respond with comprehensive measures
that address all factors that promote the virus’s
pathogenic effects.
This case was written for a sophomore undergraduate
course in infectious diseases. When students undertook
this case, they had received over six hours of lectures on
viral biology (three hours on viruses, and three hours on
influenza). Students had a solid background in the general
biology of viruses. This included basic morphology and
structure, classification systems, details about replication,
including a review of the replication of each of the
different types of virus (DNA, RNA, single-stranded,
double-stranded, retrovirus), pathogenicity of virus,
interaction with (and evasion of ) the immune system,
and the control and treatment for viral diseases. They
also had a solid foundation in the biology of influenza in
particular: an overview of influenza genera (type A, B, C),
influenza reservoirs, influenza A structure (with emphasis
on the role of hemagglutinin [HA] and neuraminidase
[NA]), strains of influenza, influenza replication,
influenza evolution (antigenic drift and antigenic shift),
history of flu epidemics with emphasis on the past
century (social history, antigenic determinants of each
pandemic, mortality and transmissibility of each strain),
review of studies about our population’s susceptibility to
1918 influenza, flu symptoms, prevention, treatments,
surveillance, and seasonality.
While specific knowledge about influenza biology
is an asset, it is not necessary to understand this case.
However, understanding influenza virus structure and
evolution greatly deepens the discussion.
This case could be used in an epidemiology,
microbiology, or even general biology course (if the
instructor supplies some viral biology background). The
Case Teaching Notes for “Why Was the 1918 Influenza So Deadly?” by Prud’homme-Généreux and Petrick
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format of this case is an intimate debate followed by a
whole class discussion. The case takes approximately one
hour to complete; these teaching notes include a number
of suggestions for follow-up assignments (below).
Objectives
At the end of this case, students should be able to:
• Weigh the evidence that the devastation wrought
by the 1918 influenza was due to the virus’s biology
and/or geopolitical-socioeconomic conditions
(GPSEC) prevalent at the time.
• Reach a complex understanding of why the 1918 Flu
was so devastating, synthesizing information from
both a simple virulence model as well as a simple
GPSEC model, and which considers the interaction of
these two factors in magnifying one another’s effects.
• Assimilate information quickly and work with a
colleague to effectively teach peers.
• Apply information learned about a past pandemic
condition to predict future pandemic outcomes.
BLOCKS OF ANALYSIS
Below is basic information on the biology of the influenza
virus to assist instructors. Several excellent review papers
and books are suggested at the end of these teaching
notes to help supplement this background.
The influenza virus belongs to the family
orthomyxoviruses. Viruses in this family are enveloped
and have a segmented genome that is composed of
negative single-stranded RNAs. There are three genera
of the flu: Influenza types A, B, and C. All three types
can infect humans. Type A can infect other mammals
and birds (swine, birds, horse, seals), type B is strictly a
human virus, and type C can cause mild infections in
humans and in pigs. The overall structure of type A and
B viruses is similar and consists of 8 RNA strands, and
the proteins HA, NA, and M2 on the surface. These
viruses are responsible for epidemics and pandemics.
Type C is composed of 7 RNA strands and has the
protein HEF (functions like HA and NA) on its surface.
This viral type only causes mild infections. Within each
type, there are many variant strains.
Influenza A is the type of influenza of most concern
to human health. Its reservoir is waterfowl. In the
gastrointestinal tract of these birds, the virus reproduces
(mostly) asymptomatically. Waterfowl shed the virus
in their feces. The route to humans usually follows the
path from wild bird to domestic bird and swine, and
from then on to humans. Close proximity of birds and
pigs and humans, as well as the presence of specific bird
species in certain geographical areas, explains the more
frequent emergence of new influenza strains in some
regions of the world (e.g., Asia).
The structure of influenza A consists of eight singlestranded RNA strands that code for all of the viral
proteins. The RNA strands are given names based on the
major viral protein they encode. Here is a description of
the encoded proteins.
HA—Hemagglutinin: There are approximately 500
copies of this protein present on the exterior of each virus.
Its role is to bind to the carbohydrate sialic acid, which is
attached to the tip of certain cell surface proteins. Thus,
HA is pivotal in recognizing and binding the virus to
potential host cells and determining which cells will be
infected. Avian HA and human-adapted HA vary slightly
in sequence, resulting in the two viral strains preferring
different arrangements of sialic acid on the surface of
a cell. The one preferred by avian HA is found on the
surface of cells in bird intestine, while human-adapted
HA binds to cells of the human respiratory tract. This
(and also the distribution of a protease required for HA
maturation) explains why influenza replicates in the gut
of birds and in the lungs of humans.
NA—Neuraminidase: There are about 100 copies
of this protein per virus. NA is required for the virus
to escape from the host cell. It cuts sialic acid off of
glycoproteins that coat the host cell, allowing the virion
to be released to infect other cells.
M1—Matrix (coat) protein for the virus: Used to
shape the envelope of the virus.
M2—Channel protein: This is produced by an
alternate reading frame from the same RNA as M1
(hence the similar protein names). Upon infection,
the virus is endocytosed into a host cell and it needs
to escape the endosome in order to carry out genome
replication. The low pH environment of the endosome
induces changes in the shape of M2, which is important
for the virus’s release into the cytoplasm.
NP—Nucleoprotein: This is a protein that packages
the RNA genome.
NS1—Non-Structural Protein: This protein is
involved in repressing the immune system so that
viral replication can be carried out. It is an interferon
antagonist (interferons are chemicals that are released by
infected cells to warn neighboring cells of the infection
so that they can protect themselves against infection—
NS1 quells this signal). It is not part of the virion, but is
synthesized using viral RNA once inside a cell.
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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
NEP—Non-Structural Protein: It is unclear at this
time what the role of this protein is in the virus.
PA, PB1, PB2—Viral RNA Polymerase: Carries out
viral genome replication.
PB1-F2: Induces apoptosis in infected cells.
Synthesized from the same RNA fragment as PB1, but
using an alternate reading frame.
HA and NA stick out of the virus and are the viral
proteins that are most likely to interact with the immune
system (the main antigenic determinants). Mutations
in these proteins produce different influenza strains.
There are 16 known HA versions, which are referred
to as H1, H1, H3, etc., to H16 (named in the order
in which they were identified). H1, H2, H3, H5, H7,
and H9 have been reported in human strains, with the
remainders so far only known in birds. Similarly, there
are nine known NA variants, called N1, N2, etc., to N9.
When describing a strain, the convention is to refer to
the HA and NA protein found in the virus; e.g., H1N1
or H5N1. The complete name for a flu virus has the
following structure: Subtype (A, B, or C) / Geographic
origin (where the virus was first isolated) / Strain number
(the number of the strain identified from this location,
listed in order of discovery) / Year of Isolation / HA and
NA sub-strain. An example of this flu nomenclature is: A
/ Moscow / 21 / 99 / H3N2. In addition, most epidemic
strains have a common name, such as Hong Kong Flu
or Swine Flu.
Influenza replication begins by fusion of the virion
with a host cell. HA must recognize and bind to the
sialic acid component of glycoproteins on the surface of
a suitable cell. Clathrin-coated pits form and endocytose
the virion. The virion is now in an endosome inside
the infected cell. The acidic pH of the endosomal
environment allows for the release of the RNA genome
and virion proteins into the cytoplasm by two cooperating
mechanisms. First, the low pH changes the shape of HA,
which exposes a fusion peptide that catalyzes the fusion
of the viral and endosomal membranes. Second, the viral
protein M2 transports protons from the endosome into
the virion. This pH change within the virion breaks apart
protein-protein interactions, and facilitates the release of
the RNA genome from the capsid. Viral –ssRNA enters
the nucleus and is replicated to +ssRNA using viral
RNA polymerase. Note that influenza replication takes
place inside the nucleus, which is unusual for an RNA
virus (which usually replicate in the cytoplasm). Viral
proteins are made using the host’s ribosomes. Virions are
assembled and bud off the host cell. The assembly process
has been described as “random,” where an average of 11
RNA segments are packaged into a virion. The virus
requires a copy of all 8 segments of the influenza genome
to be functional. Thus, by chance, many virions are
defective. However, recent evidence suggests that virion
assembly is not as haphazard a process and packaging
is more selective than previously thought. The NA is
required for the release of the new budding particle
from the host cell and to ensure that there is no virion
clumping. It does this by cutting the terminal sialic acid
from the ends of glycoproteins. Epithelial lung cells
infected with influenza sometimes die, disrupting the
organism’s first line of defense and making the infected
organism susceptible to bacterial infection. The bacteria
Haemophilus influenza was inaccurately assigned as the
cause of the 1918 Flu at the time of the epidemic due to
its presence in the lungs of many of the flu victims.
When HA and NA genes suffer point mutations,
they bring about small variations called antigenic drift.
Every two years or so, the changes are substantial enough
to cause the virus’s escape from immune recognition
and result in small local epidemics. Antigenic shift is
brought about by more substantive changes in the virion
genome. If two different strains of influenza infect the
same cell at the same time, the new virions that are
produced will contain RNA segments from each strain.
This reassortment of RNA strands forms virions with
HA and NA combinations not previously encountered
by the host. Swine, which are susceptible to both avian
and human-adapted strains of influenza, serve as an
ideal mixing vessel for the creation of new influenza
strains. These strains may be able to infect human cells
even though they have not previously encountered the
immune system of a human host. This immune naivety
can lead to pandemics.
It is possible to follow the evolution of the influenza
virus and the strains that have caused human pandemics
in the past century. The 1918 Spanish Flu was an H1N1
strain.1 It was replaced in 1957 through an antigenic
shift by the Asian Flu (H2N2). Note that both the HA
and NA proteins were changed. In 1968, the Hong
Kong Flu (H3N2) replaced H2N2 through another
1
As noted in the case, this was determined in the late 1990s by
ingenious work by Taubenberger and his team which involved
RT-PCR from tissue samples preserved from 1918 victims. Some
of the samples were obtained from army tissue repositories, while
others were obtained from the remains of a victim preserved in the
Alaskan permafrost. These stories make very captivating storytelling
for students. An excellent account is available in the book Flu by
Kolata (1999).
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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
antigenic shift. In 1977, the Russian Flu (H1N1)
emerged. Interestingly, it did not replace H3N2, but
rather continues to co-exist with H3N2 to this day.
Based on its sequence (which had not changed in many
years, as might have been expected through antigenic
drift), some have suggested that this H1N1 is a virus
that has escaped from a laboratory environment where it
was stored and was accidently reintroduced into the wild.
Would we be susceptible to the 1918 Flu if it reemerged? Some people have suggested that we would be
immune, given that 5 of the 8 RNA strands in current
pandemics strains were inherited from the 1918 Flu.
Therefore, our immune system should not be naïve
about this virus, and should be effective in fighting it.
However, when this was tested in the laboratory, it was
found that the blood of people born after 1930 did not
appear to contain antibodies that recognize the 1918
H1N1 proteins (Kobasa et al., 2004).
Roughly 50% of flu infections are asymptomatic. For
the remainder of afflicted people, common symptoms
include fever and chills, headache, malaise, fatigue, and
myalgia (body ache) that begin approximately 1–4 days
after infection. These symptoms are induced by the
immune system, which triggers a cytokine response.
Coughing and sneezing is induced by the virus in the
upper airways, where it attacks cells. Influenza’s mean
transmission rate (R0) is 2–10. The best way to prevent
infection is through vaccination, quarantine, and to
prevent a person from touching their eyes, nose, and
mouth. Two antivirals are effective if taken in the first
48 hrs of infection. M2 ion channel inhibitors (e.g.,
Amantadine and Rimantadine) block the escape of the
influenza virus from the endosome. NA inhibitors (e.g.,
Oseltamivir and Zanamivir) block the release of virions
from infected cells. Each year, personnel at the World
Health Organization (WHO) and at associated public
health organizations throughout the world monitor
influenza outbreaks and track changes in the HA and NA
antigen of emerging strains. Based on this information,
they make predictions about the strains most likely to
affect the population that year. Flu vaccines are made of
inactivated viruses from the two most likely A type and
one most-likely B type strain to affect the population
that year.
Excellent readings are suggested below. These will
assist instructors in becoming even more familiar with
this topic.
CLASSROOM MANAGEMENT
This case study is an intimate debate. The steps needed
to lead this activity, as well as the time allocated to each
part, are described below. Instructors should make
available to students a sufficient number of handouts.
1. Introduction to 1918 Influenza pandemic and its
devastation
a. Provide handout “Part I: The 1918 Influenza
Pandemic” to each student.
b. Students can be asked to read aloud to the class,
or quietly and individually.
c. Answer any student questions that arise.
d. As a hook, you may wish to point out that
Edward Cullen in the Twilight saga was dying
of the Spanish flu when he was turned into a
vampire.
e. Instruct students that you will direct them
throughout the case and that they should listen
to your instructions throughout.
2. Students become experts
a. Class is divided into two equal groups (Team A
and Team B).
b. Students in Team A are each given a list of facts
that argue that geopolitical-socioeconomic
conditions are to blame for the pandemic’s
devastation (document entitled “Team A—
Geopolitical-Socieconomic Conditions Prevalent
in 1918 Exacerbated the Effects of a Moderately
Virulent Virus”).
c. Students in Team B are given a list of facts
containing arguments that support a biological
explanation for the pandemic’s devastation
(document entitled “Team B—Biological
Explanation: The 1918 Influenza Strain was
Exceptionally Virulent”).
d. Working individually, each student has 15 minutes
to read and understand the arguments. They are
encouraged to take notes. The information sheet
is taken away at the end of this period.
3. Convince the other team
a. Each student pairs with another student from the
same team (i.e., two Team A students pair up).
b. Each pair discusses the main arguments for their
position and agrees on a way to convincingly
present their argument to the other team (5 min).
c. Each Team A student pair meets with a Team B
student pair.
d. The Team A pair presents to the other team the
arguments that favor a GPSEC explanation for
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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
the epidemic. The team has 5 minutes to do this.
Team B students may ask clarification questions
along the way.
e. The roles are switched, and the Team B pair now
presents their evidence for a biological cause to
the pandemic’s effects.
f. Meet with another group of the opposite team
(for example, Team A meets with a different
Team B). Each team has 5 minutes to once again
describe their argument to the opposite team.
This promotes exposures to different arguments
and to different ways of explaining the evidence.
4. Discuss the evidence
a. In a class discussion, some student pairs are asked
to report which of the evidence heard was the
most convincing for the other team. First sample
students from Team A, then students from Team B.
b. In a class discussion, some student pairs are asked
to report which of the evidence heard was the
least convincing for the other team. First sample
students from Team A, then students from Team B.
Instructors may wish to use this opportunity
to explore the validity of an experiment and the
role of the scientific procedure in developing
worthy data. It is of particular interest to question
students about experiments described in the first
paragraph for Team A, in which volunteers were
deliberately exposed to secretions from influenza
patients and “Not a single man became sick.”
These results are contrary to the expectations
for a pandemic that infected 28% of the human
population within a year.
c. Two new people from Team A (creating a new
pair) will meet with two new people from Team B
(also creating a new pair). Therefore, there should
be a group of 4 people who have never worked
together. Discuss how the evidence for both the
biological and GPSEC factors magnified each
other’s effects.
Possible Answers:
There are several GPSEC factors that occurred
during WWI that likely led to the evolution and
emergence of a more virulent strain. The first is
Paul Ewald’s hypothesis mentioned in the case
study. The conditions of the war promoted the
dissemination of viral strains that caused very
pathogenic symptoms over those strains that
did not. Through natural selection, the social
conditions favored the evolution of a virulent
1918 virus.
The second manner in which GPSEC may
have led to the emergence of a virulent strain of
influenza is gleaned from the study of Nelson et
al. (2001) on mice fed selenium-deficient diets.
The researchers found that the poor availability
of this nutrient put pressure on the virus that
led to an increased mutation rate and that
consistently resulted in increased virulence. Thus,
sub-optimal diets during war time may have
facilitated the evolution of a particularly virulent
strain of the flu.
The critical goal of this case study, beyond
having students understand facts of the 1918
pandemics, is to have students make the
cognitive transition from supporting a simple
model (virulence versus GPSEC) to developing
a complex model. Prior to this part of the case
students should have come to an understanding
of the arguments for one simple model of disease
causation:
• Simple Model Team A: Influenza Virus +
GPSEC = High Mortality
• Simple Model Team B: Influenza Virus +
New Mutations = High Virulence and High
Mortality
Now it is time for them to move toward a more
sophisticated understanding of the situation,
coming to grips with a complex model (hybrid
solution of A and B): GPSEC provide conditions
for the evolution of a more virulent strain and
rapid spread. Evolution requires both mutation
(mutations of the virus that lead to increased
virulence) and selection (conditions that favor
the new mutations and favor the spread [or
multiplication] of the virus).
Students should recognize (and instructors
should support this discovery) that some of the
arguments posted as supporting one of the teams
actually provide support for a complex conclusion
for the devastation caused by the 1918 Influenza
pandemic.
d. This case can be concluded with a whole-class
discussion. Ask students the following question: If
the 1918 strain of influenza re-emerged today, do
you believe that its effects would be as devastating
as the 1918 pandemic? Why or why not?
Possible Answers:
It would not be as devastating because:
• Our living and health conditions are much
better (better nutrition and access to diverse
Case Teaching Notes for “Why Was the 1918 Influenza So Deadly?” by Prud’homme-Généreux and Petrick
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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
foods, more knowledge of health, better
hygiene, etc).
• We have access to drugs and vaccines to
combat a viral epidemic (and a better scientific
understanding of the influenza virus).
• Global influenza surveillance systems exist,
and our virus identification techniques are
faster than ever, allowing us to respond with
appropriate public heath measures rapidly.
In addition, global organizations such as the
WHO can coordinate a world-wide response
to an epidemic.
• The world is not at war, and war typically
promotes conditions such as crowding,
emergency responses, and deficiencies which
favor the spread of a virus.
It would be just as devastating because:
• Our modern rapid and common travel culture
means that an outbreak at one location could
be rapidly carried all over the world (e.g.,
SARS).
• There are more people on the planet, and
therefore higher population densities and
more crowding, which could lead to the more
rapid spread of the disease.
• With regard to the 1918 Flu in particular, it
is unclear how virulent the virus would be to
our current population. The 1918 Flu is an
H1N1 subtype. This subtype is one of the two
strains that currently infects our population
(H3N2 is the other subtype), causing seasonal
and pandemic flu. In fact, our current H1N1
subtype shares 5 of its 8 RNA strands with
the 1918 strain. Thus, the subtype is known
by our immune system, making it less likely
to be virulent. However, in vitro experiments
(where the HA and NA proteins from the
1918 virus were mixed with currently living
people’s white blood cells to determine
whether the virus elicits an immune reaction)
have shown that people born after the 1930s
are immunologically naive to the 1918 virus
(Kobasa et al., 2004). This suggests that we
are susceptible to this virus.
To enrich the overall discussion, the instructor
can direct the groups to re-form to do this analysis
before engaging in a whole-class discussion.
STUDENT ASSESSMENT
Several methods may be used to assess whether a
complex understanding of the causes of the 1918 Flu
devastation (including an interaction of both the
virulence model and the GPSEC model to magnify each
other’s effects) was successfully achieved. One is to do
it informally, listening to the comments shared in class
discussion. More formal methods may include students
writing a short essay or creating a podcast in which they
explain the intricacies of the interactions of biological
and GPSEC causes in the 1918 devastation.
For more advanced students, the assignment could
consist of examining the HIV or SARS epidemics with
a similar type of analysis, suggesting ways in which
GPSEC and biological factors magnified one another
and contributed to the spread of the epidemic.
FOLLOW-UP ASSIGNMENTS
Students can be directed to use the references provided
in the case to explore one topic in more depth and write
an essay or do a presentation. Examples of topics that
can be further investigated include the following:
• Investigate the changes necessary to transform a
strictly avian strain that can only infect waterfowl
into a strain of influenza that can infect humans.
• The 2011 movie Contagion portrayed the spread
of a novel and highly lethal flu-like virus and its
consequences on our society. Using your knowledge
of outbreaks (and influenza in particular), critique
the validity of the scenario presented in this movie.
• In December 2011, influenza H5N1 received a
lot of media attention (for example, see Bird flu:
Research row as US raises terror fears, 2011; Brean,
2012; Gurney, 2012). Due to security concerns,
some governments and researchers have suggested
that recent findings on the genetic factors that cause
H5N1’s high virulence and lethality should not be
publicly disclosed (published in scientific journals).
In January 2012, the researchers agreed to a
voluntary moratorium on some of their results (e.g.,
Bioterror fears halt research on mutant bird flu, 2012;
Canadian Press, 2012). Should science be censored?
What are the pros and cons of this proposal? Since
the 1918 influenza sequence is already publicly
accessible, is this proposed ban too late?
• Evaluate the studies of infection rates performed
during the 1918 pandemic. How would you conduct
the study? What controls would you use? Who is
your control population?
Case Teaching Notes for “Why Was the 1918 Influenza So Deadly?” by Prud’homme-Généreux and Petrick
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• In 1918, the bacteria Haemophilus influenza was
proposed by some to be the cause of the flu epidemic.
It was found in the lungs of many of the victims
who succumbed to the flu. What criteria must an
infectious agent meet in order to be identified as the
one causing an epidemic? How would you determine
that the 1918 Flu was caused by a virus and not a
bacterium? (Note: Antibiotics were not yet available.)
• What are the biological and the GPSEC factors that
affect each of the following events of an epidemic:
emergence of a strain, spread of a strain, and
virulence change?
• What if the U.S. sees the emergence of HIV strains
very easily transmitted by sexual contact among the
heterosexual population? Use your knowledge of
the spread of the 1918 influenza to think through
the current GPSEC that might promote or help to
block the emergence and spread of such a virus.
• Investigate the role of the biological and geopoliticalsocioeconomic factors in the emergence and spread
of another infectious disease (e.g., another historical
flu pandemic, H5N1, SARS). Create a concept map
of the complex model that shows how the factors
interacted with one another. If the project is on
another flu pandemic, specify which of the factors
were similar and different to the 1918 pandemic, and
how this changed the outcomes of the pandemic.
SUGGESTED READINGS
Websites
Rapid Reference to Influenza Resource Center Team
(n.d.). Rapid Reference to Influenza. Elsevier Health
Sciences. Last accessed 9 December 2011 from http://
www.rapidreferenceinfluenza.com/resource-center.
A gold mine of information on all things influenza. The
website is well organized and contains subsections on
the biology of the virus, the immune reaction, the social
and political impacts of influenza, treatments, clinical
features and diagnosis, etc.
Review Articles
Bouvier, N.M., and Palese, P. (2008). The biology of
influenza viruses. Vaccine 26(Suppl 4): D49–53.
A very good description of the basic viral biology of
influenza, including an introduction to the basic viral
proteins and its reproductive cycle, described step by step.
Hilleman, M.R. (2002). Realities and enigmas of
human viral influenza: Pathogenesis, epidemiology
and control. Vaccine 20: 3068–3087.
This article reviews many different aspects of influenza
biology, from its genomes, to its evolution, to how the
1918 virus was sequenced, to drugs and vaccines that
combat the flu virus.
Klenk, H-D, and Rott, R. (1988). The molecular biology
of influenza virus pathogenicity. Advances in Virus
Research 34: 247–281.
The apparent contribution of each influenza virus
protein in the virus’s pathogenicity is explored in this
review article. While the article is a bit dated (and it is
difficult to obtain in electronic form), the information
is very clearly explained and still accurate.
Oxford, J.S., Sefton, A., Jackson, R., Innes, W., Daniels,
R.S., and Johnson, N.P.A.S. (2002). World War
I may have allowed the emergence of “Spanish”
influenza. Lancet Infectious Diseases 2: 111–114.
This article provides a basic primer in the emergence
of the 1918 Flu in the context of the First World War.
Reid, A.H., Taubenberger, J.K., and Fanning, T.G.
(2001). The 1918 Spanish influenza: Integrating
history and biology. Microbes and Infection 3: 81–87.
Taubenberger, J.K., and Morens, D.M. (2006). 1918
Influenza: The mother of all pandemics. Rev Biomed
17: 69–79.
The above two articles provide an overview of the biology
and epidemiology of the 1918 influenza virus. These
articles are written by Jeffrey Taubenberger, the researcher
who first isolated and sequenced the 1918 virus.
Webster, R.G., and Walker, E.J. (2004). Influenza.
American Scientist 91: 122–129.
This article describes how influenza changes through
antigenic drift and antigenic shift, and why this poses
a pandemic concern for the future. It is beautifully
illustrated, with diagrams that can assist instructors in
illustrating concepts associated with influenza.
Books
Crosby, A. (1989). America’s Forgotten Pandemic: The
Influenza of 1918. Cambridge University Press.
This book is a historical account of the 1918 influenza
epidemic focusing on the American experience. This
influential book is often cited by influenza researchers
as being the source of their interest in this virus.
Kolata, G. (1999). Flu: The Story of the Great Influenza
Pandemic of 1918 and the Search for the Virus That
Caused It. New York: Simon & Schuster.
This book, which focuses on the recent race to retrieve
preserved samples of the 1918 virus, covers many
aspects of influenza.
Case Teaching Notes for “Why Was the 1918 Influenza So Deadly?” by Prud’homme-Généreux and Petrick
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NATIONAL CENTER FOR CASE STUDY TEACHING IN SCIENCE
Wilschut, J., and McElhaney, J, (2004). Rapid Reference
to Influenza: Rapid Reference Series. A Mosby Title.
This concise book about influenza is well organized and
contains a gold mine of information on the biology of
the virus.
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Sodenberg, S (Director). (2011). Contagion [Motion
picture]. United States: Warner Bros. Pictures.
Bird flu: Research row as US raises terror fears (2011).
BBC News. Retrieved 23 January 2012 from http://
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Bioterror fears halt research on mutant bird flu (2012).
BBC News. Retrieved 23 January 2012 from http://
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Brean, J. (2012). Balance sought in debate over
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Canadian Press (2012). Reasons for bird flu studies’
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Morens, D.M., Taubenberger, J.K., Folkers, G.K., and
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Reid, A.H., Taubenberger, J.K., and Fanning, T.G.
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Thompson, W.W., Shay, D.K., Weintraub, E., Brammer,
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•
Acknowledgements: This case was published with
support from the National Science Foundation under
CCLI Award #0341279. Any opinions, findings and
conclusions or recommendations expressed in this
material are those of the authors and do not necessarily
reflect the views of the National Science Foundation.
Copyright held by the National Center for Case
Study Teaching in Science, University at Buffalo, State
University of New York. Originally published March 15,
2012. Please see our usage guidelines, which outline our
policy concerning permissible reproduction of this work.
Case Teaching Notes for “Why Was the 1918 Influenza So Deadly?” by Prud’homme-Généreux and Petrick
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