1some methods of testing are excluded from the ban or the laws vary within the country
Cosmetic testing on animals is a type of animal testing used to test the safety and hypoallergenic properties of products for use by humans. Due to the harm done to the animal subjects, this testing is opposed by animal rights activists and others. Cosmetic animal testing is banned in the European Union, United Kingdom, India, Israel, and Norway.
Definition
Using animal testing in the development of cosmetics may involve testing either a finished product or the individual ingredients of a finished product on animals, often rabbits, as well as mice, rats,
and other animals. Cosmetics can be defined as products applied to the
body in various ways in order to enhance the body's appearance or to
cleanse the body. This includes all hair products, makeup, nail products
and soaps.
Re-using existing test data obtained from previous animal testing
is generally not considered to be cosmetic testing on animals; however,
the acceptability of this to opponents of testing is inversely
proportional to how recent the data is.
Methods
Methods
of testing cosmetics on animals include many different tests that are
categorized differently based on which areas the cosmetics will be used
for. One new ingredient in any cosmetic product used in these tests
could lead to the deaths of at least 1,400 animals.
Dermal penetration: Rats are mostly used in this method that
analyzes moment of a chemical, and the penetration of the chemical in
the bloodstream. Dermal penetration is a method that creates a better
understanding of skin absorption.
Skin sensitisation: This is a method that determines if a
chemical causes an allergic reaction. The chemical adjuvant is injected
to boost the immune system. In the past it was performed on guinea pigs,
and applied on a shaved patch of skin. Substances are assessed based on
appearance of skin.
Acute toxicity: This test is used to determine danger of exposure
to a chemical by mouth, skin, or inflammation. Rats and mice are
injected in lethal dose 50% (LD50). This test can cause animal
convulsions, loss of motor function, and seizures.
Draize test:
This is a method of testing that may cause irritation or corrosion to
the skin or eye on animals, dermal sensitization, airway sensitization,
endocrine disruption, and LD50 (which refers to the lethal dose which kills 50% of the treated animals).
Skin corrosivity or irritation: This method of test assesses the
potential of a substance causing irreversible damage to the skin. It is
typically performed on rabbits and involves putting chemicals on a
shaved patch of skin. This determines the level of damage to the skin
that includes itching, inflammation, swelling, etc.
Alternatives
Cosmetics manufacturers who do not test on animals may now use in vitro
screens to test for endpoints which can determine potential risk to
humans with a very high sensitivity and specificity. Companies such as
CeeTox in the USA, recently acquired by Cyprotex, specialize in such
testing and organizations like the Center for Alternatives to Animal
Testing (CAAT), PETA and many other organizations advocate the use of in vitro
and other non-animal tests in the development of consumer products. By
using safe ingredients from a list of 5,000 which have already been
tested in conjunction with modern methods of cosmetics testing, the need
for tests using animals are negated.
EpiSkin™, EpiDerm™ and SkinEthic are each composed of artificial
human skin as an option for alternative testing. Artificial skin can
imitate the reaction actual human skin will have to a product and the
chemicals it contains and can be altered to mimic different skin types
and ages. For example, using UV light on EpiSkin can cause it to
resemble older skin and adding melanocytes will turn the skin a darker
color. This helped create a spectrum of different skin colors that are
then used to compare the results of sunblock on a different variety of
people.
To address potential issues with other parts of the human body,
research companies such as NOTOX have developed a synthetic model of the
human liver, which is the main organ to detox the body, in order to
test harmful ingredients and chemicals to see if the liver can detox
those elements. Research companies can also use body parts and organs taken from animals slaughtered for the meat industry to perform tests such as the Bovine Corneal Opacity and Permeability Test and Isolated Chicken Eye Test.
History
In 1937, a mistake was made that ended up changing the pharmaceutical industry drastically. A company created a medicine (Elixir sulfanilamide) “to treat streptococcal infections”, and without any scientific research the medicine was out on shelves. This medicine turned out to be extremely poisonous to people, leading to large poisoning outbreaks followed by over 100 deaths.
This epidemic led to a law being passed in 1938, called the U.S. Food,
Drug, and Cosmetics Act, enforcing more rigorous guidelines on cosmetic
products.
After this law was passed companies looked to animals to test their
products, in turn, creating the first encounters of cosmetic animal
testing.
Non-profit organizations
This "Leaping Bunny" indicates that cosmetic products with this logo have not been tested on animals.
Cruelty Free International: Cruelty Free International
and its partners manage the certification of all the companies across
the world looking to be cruelty free. Companies producing beauty and
household products which do not test their products on animals for any
market can request membership of The Leaping Bunny Program, which allows that company to feature Cruelty Free International's
Leaping Bunny logo on their products. This program sets global standard
of operations and sales. Companies headquartered internationally can
obtain certification from Cruelty Free International.
Companies headquartered in the United States and Canada can obtain
certification from The Coalition for Consumer Information on Cosmetics
(CCIC). In 2013, over 500 companies were certified. However, some company's certifications were revoked after it was discovered they continued to test on animals in Asia.
Humane Society International: This is a global animal protection organization that works to help all animals—including animals in laboratories.
Procedures of animal testing
There is a strategy used in animal testing laboratories titled the
'Three R's:' Reduction, refinement, and replacement' (Doke,
"Alternatives to Animal Testing: A Review").
Reduction: This approach is built upon the ethics to have a minimal number of animal subjects being tested on for current and later tests.
Refinement: This suggests that the planned distress and pain
caused to an animal subject to be as little as possible. This approach
focuses on making a home for the animals before entering testing grounds
in order to elongate the life of laboratory animals. Discomfort to
animals causes an imbalance in hormonal levels which create fluctuating
results during testing.
Replacement: This provides the opportunity to study the
response of cellular models, but in other words, replacement searches
for alternatives that could be done rather than testing on animal
subjects.
Legal requirements and status
Due to the strong public backlash against cosmetic testing on
animals, most cosmetic manufacturers say their products are not tested
on animals. However, they are still required by trading standards and consumer protection
laws in most countries to show their products are not toxic and not
dangerous to public health, and that the ingredients are not dangerous
in large quantities, such as when in transport or in the manufacturing
plant. In some countries, it is possible to meet these requirements
without any further tests on animals. In other countries, it may require
animal testing to meet legal requirements. The United States and Japan
are frequently criticized for their insistence on stringent safety
measures, which often requires animal testing.
Some retailers distinguish themselves in the marketplace by their stance
on animal testing.
Legal requirements in Japan
Although
Japanese law doesn’t require non-medicated cosmetics to be tested on
animals, it doesn’t prohibit it either, leaving the decision to
individual companies.
Animal testing is required mainly when the product contains
newly-developed tar colors, ultraviolet ray protective ingredients or
preservatives, and when the amount of any ingredient regulated in terms
of how much can be added is increased.
Japanese Brands such as Shiseido and Mandom have ended much, but
not all, of their animal testing. However, most other leading cosmetics
companies in Japan still test on animals.
Jurisdictions with bans
Brazil, São Paulo
São Paulo in Brazil, banned cosmetic animal testing in 2014.
European Union
The
European Union (EU) followed suit, after it agreed to phase in a
near-total ban on the sale of animal-tested cosmetics throughout the EU
from 2009, and to ban cosmetics-related animal testing. Animal testing is regulated in EC Regulation 1223/2009 on cosmetics. Imported cosmetics ingredients tested on animals were phased out for EU consumer markets in 2013 by the ban, but can still be sold to outside of the EU. Norway banned cosmetics animal testing the same time as the EU.
In May 2018 the European Parliament voted for the EU and its Member
States to work towards a UN convention against the use of animal testing
for cosmetics.
European Free Trade Association
The rest of the EFTA, including Norway, Liechtenstein, Switzerland, and Iceland also banned cosmetic testing.
Guatemala
In 2017, Guatemala banned cosmetic animal testing.
India
In early
2014, India announced a ban on testing cosmetics on animals in the
country, thereby becoming the second country in Asia to do so. Later India banned import of cosmetics tested on animals in November 2014.
Israel
Israel banned "the import and marketing of cosmetics, toiletries or detergents that were tested on animals" in 2013.
New Zealand
In 2015, New Zealand also banned animal testing.
Turkey
Turkey "banned any animal testing for cosmetic products that have already been introduced to the market."
UK
Animal testing on cosmetics or their ingredients was banned in the UK in 1998.
In Australia, the End Cruel Cosmetics Bill
was introduced to Parliament in March 2014, which would ban local
testing, which generally doesn't happen there, and importation of
cosmetics tested on animals. In 2016 a bill was passed to ban the sale of cosmetics tested on animals, which came into effect in July 2017.
Brazil
Brazil's legislation will vote on a nationwide animal testing for cosmetics ban by the end of March 2014.
Canada
Canada
has not banned animal testing for cosmetics. It got very close to
instituting a ban in June 2019, but the bill ultimately failed. https://www.straight.com/news/1282096/v-victoria-shroff-canada-could-have-been-40th-country-ban-animal-testing-beauty
by Vancouver Animal Law Lawyer and adjunct Professor of animal law, V.
Victoria Shroff: Canada could have been the 40th country to ban animal
testing for beauty products | Georgia Straight Vancouver's News &
Entertainment Weekly.
United States
In March 2014, the Humane Cosmetics Act
was introduced to the U.S. congress which would ban cosmetic testing on
animals and eventually would ban the sale of cosmetics tested on
animals. The bill did not advance.
South Korea
South Korea is also potentially "making strides toward ending cosmetics testing on animals."
Taiwan
In 2015, Taiwan launched a bill proposing a ban on cosmetic testing on animals. It passed in 2016 and goes into effect in 2019.
Other statuses
China
China
passed a law on 30 June 2014 to eliminate the requirement for animal
testing of cosmetics. Though domestically-produced ordinary cosmetic
goods do not require testing, animal testing is still mandated by law
for Chinese-made "cosmeceuticals" (cosmetic goods which make a
functional claim) which are available for sale in China. Cosmetics
intended solely for export are exempt from the animal testing
requirement.
As of March 2019, post-market testing (i.e. tests on cosmetics after
they hit the market) for finished imported and domestically produced
cosmetic products will no longer require animal testing.
Russia
In 2013,
the Russian Ministry of Health stated "Toxicological testing is
performed by means of testing for skin allergic reaction or test on
mucous tissue/eye
area (with use of lab animals) or by use of alternative general
toxicology methods (IN VITRO). In this manner the technical regulations
include measures which provide an alternative to animal testing".
Wild animal suffering is the suffering experienced by nonhuman animals in nature through causes such as disease, injury, parasitism, starvation, natural disasters, and killings by other animals. Wild animal suffering has historically been discussed in the context of the philosophy of religion as an instance of the problem of evil.
More recently, a number of academics have considered the suspected
scope of the problem from a secular standpoint as a general moral issue,
one that humans might be able to take actions toward preventing.
There is considerable disagreement around this latter point, as
many believe that human interventions in nature, for this reason, would
be either unethical, unfeasible,
or both. Advocates of such interventions point out that humans
intervene in nature all the time—sometimes in very substantial ways—for
their own interests and to further environmentalist goals
and that there are many ways that humans already successfully intervene
to help wild animals such as vaccinating and healing injured and sick
animals, rescuing animals in fires and natural disasters, feeding hungry
animals, providing thirsty animals with water, and caring for orphaned
animals.
Advocates also argue that although wide-scale interventions may not be
possible with current knowledge, they could become feasible in the
future with increased knowledge and advanced technologies.
For these reasons, they claim it is important to raise awareness about
the issue of wild-animal suffering, spread the view that we should help
animals suffering in these situations and encourage research into
effective measures which can be taken to improve the welfare of wild animals without causing greater harms.
Extent of suffering in nature
In his autobiography, Charles Darwin acknowledged that the existence of extensive suffering in nature was fully compatible with the workings of natural selection, yet maintained that pleasure was the main driver of fitness-increasing behavior in organisms. Evolutionary biologist Richard Dawkins challenged Darwin's claim in his book River Out of Eden, wherein he argued that wild animal suffering must be extensive due to the interplay of the following evolutionary mechanisms:
Selfish genes – genes are wholly indifferent to the well-being of individual organisms as long as DNA is passed on.
The struggle for existence – competition over limited resources results in the majority of organisms dying before passing on their genes.
Malthusian checks – even bountiful periods within a given ecosystem eventually lead to overpopulation and subsequent population crashes.
From this, Dawkins concludes that the natural world must necessarily
contain enormous amounts of animal suffering as an inevitable
consequence of Darwinian evolution. To illustrate this he wrote:
A litter of mice with their mother. The reproduction of mice follows an r-selection strategy, with many offspring, short gestation, less parental care, and a short time until sexual maturity.
The
total amount of suffering per year in the natural world is beyond all
decent contemplation. During the minute that it takes me to compose this
sentence, thousands of animals are being eaten alive, many others are
running for their lives, whimpering with fear, others are slowly being
devoured from within by rasping parasites, thousands of all kinds are
dying of starvation, thirst, and disease. It must be so. If there ever
is a time of plenty, this very fact will automatically lead to an
increase in the population until the natural state of starvation and
misery is restored.
Building on this, others have argued that the prevalence of r-selected animals
in the wild indicates that the average life of a wild animal is likely
to be very short and end in a painful death. According to this view, the
average life of a wild animal should thus contain more suffering than
happiness, since a painful death would outweigh any short-lived moments
of happiness in their short lives.
In "Bambi or Bessie: Are Wild Animals Happier?", Christie Wilcox
argues that wild animals do not appear to be happier than domestic
animals, based on findings of wild animals having greater levels of
cortisol and elevated stress responses relative to domestic animals.
Additionally, unlike domestic animals, animals in the wild do not have
some of their needs provided for them by human caretakers. Welfare economist Yew-Kwang Ng
has written that evolutionary dynamics can lead to animal welfare which
is worse than necessary for a given population equilibrium.
Philosophical status
History of concern for wild animals
The idea that suffering is common in nature has been observed by several writers historically.
Italian polymath Leonardo da Vinci,
in his notebooks (written between 1487–1505) lamented the suffering
experienced by wild animals due to predation and reproduction,
questioning: "Why did nature not ordain that one animal should not live
by the death of another?"
Philosopher David Hume in his 1779 posthumous work Dialogues Concerning Natural Religion
made reference to the antagonism experienced and inflicted by wild
animals upon each other, observing: "The stronger prey upon the weaker,
and keep them in perpetual terror and anxiety."
One expression commonly used to express suffering in nature comes from Alfred Tennyson's poem "In Memoriam A.H.H.": "Nature, red in tooth and claw", published in 1850.
In 1851, the German philosopher Arthur Schopenhauer
also insisted on the extent of suffering in nature, drawing attention
to the asymmetry between the pleasure experienced by a carnivorous
animal and the suffering of the animal it consumes: "Whoever wants
summarily to test the assertion that the pleasure in the world outweighs
the pain, or at any rate that the two balance each other, should
compare the feelings of an animal that is devouring another with those
of that other".
In the 1874 posthumous essay "On Nature", utilitarian philosopher John Stuart Mill wrote about suffering in nature and the imperative of struggling against it:
In sober truth, nearly all the things which men are
hanged or imprisoned for doing to one another, are nature's every day
performances. [...] The phrases which ascribe perfection to the course
of nature can only be considered as the exaggerations of poetic or
devotional feeling, not intended to stand the test of a sober
examination. No one, either religious or irreligious, believes that the
hurtful agencies of nature, considered as a whole, promote good
purposes, in any other way than by inciting human rational creatures to
rise up and struggle against them.
[...] Whatsoever, in nature, gives indication of beneficent design
proves this beneficence to be armed only with limited power; and the
duty of man is to cooperate with the beneficent powers, not by
imitating, but by perpetually striving to amend, the course of nature -
and bringing that part of it over which we can exercise control more
nearly into conformity with a high standard of justice and goodness.
It is of the utmost importance to emphasize the fact
that, whatever the legal fiction may have been, or may still be, the
rights of animals are not morally dependent on the so-called rights of
property; it is not to owned animals merely that we must extend our
sympathy and protection. [...] To take advantage of the sufferings of
animals, whether wild or tame, for the gratification of sport, or
gluttony, or fashion, is quite incompatible with any possible assertion
of animals' rights.
Salt argued that humans are justified in killing wild animals in
self-defense, but that "[...] we are not justified in unnecessarily
killing—still less in torturing—any harmless beings whatsoever." English writer. In 1782, Member of Parliament Soame Jenyns
argued that this should apply to insects as well: "We are unable to
give life, and therefore ought not to take it away from the meanest
insect without sufficient reason."
In his 1906 book The Universal Kinship, J. Howard Moore argued that the egoism of sentient beings—a
product of natural selection—which leads them to exploit their sentient
fellows, was the "most mournful and immense fact in the phenomena of
conscious life", and speculated whether a sufficiently sympathetic human
could significantly improve this situation if given the chance: "[One]
cannot help wondering whether an ordinary human being with only
common-sense and insight and an average concern for the welfare of the
world would not make a great improvement in terrestrial affairs if he
only had the opportunity for a while."
In 1991, the environmental philosopher Arne Næss
critiqued what he termed the "cult of nature" of contemporary and
historical attitudes of indifference towards suffering in nature. He
argued that we should confront the reality of the wilderness and that we
should be prepared to disturb natural processes—when feasible—to
relieve suffering.
Ecology as intrinsically valuable
Holmes Rolston III
argues that only unnatural animal suffering is a morally bad thing and
that humans do not have a duty to intervene in natural cases.
He celebrates carnivores in nature because of the significant
ecological role they play. Others have argued that the reason that
humans have a duty to protect other humans from predation is because
humans are part of the cultural world rather than the natural world and
so different rules apply to them in these situations.
Others argue that prey animals are fulfilling their natural function,
and thus flourishing, when they are preyed upon or otherwise die, since
this allows natural selection to work. This can be seen by some as an appeal to nature.
Wild animal suffering as a reductio ad absurdum
That people would also be obliged to intervene in nature has been used as a reductio ad absurdum against the position that animals have rights.
This is because if animals such as prey animals did have rights, people
would be obliged to intervene in nature to protect them, but this is
claimed to be absurd.
An objection to this argument is that people do not see intervening in
the natural world to save other people from predation as absurd and so
this could be seen to involve treating non-human animals differently in
this situation without justification, which is due to speciesism.
However, this argument already grants the premise in question that
animals should have rights, and that preferring human interests is
wrong, and therefore it is begging the question.
Relevance to the theological problem of evil
The problem of evil has been extended beyond human troubles to include the suffering of animals over the course of evolution.
Interventions to reduce suffering
Arguments for intervention
Some
theorists have reflected on whether we should accept the harms that
animals suffer in nature or try to do something to mitigate them.
The moral basis for interventions aimed at reducing wild animal
suffering can be rights-based or welfare-based. From a rights-based
perspective, if animals have a moral right to life or bodily integrity,
intervention may be required to prevent such rights from being violated
by other animals.
From a welfare-based perspective, a requirement to intervene may
arise insofar as it is possible to prevent some of the suffering
experienced by wild animals without causing even more suffering.
Advocates of intervention in nature argue that nonintervention is
inconsistent with either of these approaches. Some proposed courses of
action include removing predators from wild areas, refraining from reintroducing predators, providing medical care to sick or injured animals, and rescuing wild animals from natural disasters.
Practicality of intervening in nature
A
common objection to intervening in nature is that it would be
impractical, either because of the amount of work involved, or because
the complexity of ecosystems would make it difficult to know whether or not an intervention would be net beneficial on balance. Aaron Simmons argues that we should not intervene to save animals in nature because doing so would result in unintended consequences such as damaging the ecosystem, interfering with human projects, or resulting more animal deaths overall. Philosopher Peter Singer
has argued that intervention in nature would be justified if one could
be reasonably confident that this would greatly reduce wild animal
suffering and death in the long run. In practice, however, Singer
cautions against interfering with ecosystems because he fears that doing
so would cause more harm than good.
Other authors dispute Singer's empirical claim about the likely
consequences of intervening in the natural world, and argue that some
types of intervention can be expected to produce good consequences
overall. Economist Tyler Cowen
cites examples of animal species whose extinction is not generally
regarded as having been on balance bad for the world. Cowen also notes
that insofar as humans are already intervening in nature, the relevant
practical question is not whether we should intervene at all, but what
particular forms of intervention we should favor. Philosopher Oscar Horta
similarly writes that there are already many cases in which we
intervene in nature for other reasons, such as for human interest in
nature and environmental preservation as something valuable in their own
rights.
Horta has also proposed that courses of action aiming at helping wild
animals should be carried out and adequately monitored first in urban,
suburban, industrial, or agricultural areas. Likewise, moral philosopher Jeff McMahan
argues that since humans "are already causing massive, precipitate
changes in the natural world," we should favor those changes that would
promote the survival "of herbivorous rather than carnivorous species."
Peter Vallentyne
suggests that, while humans should not eliminate predators in nature,
they can intervene to help prey in more limited ways. In the same way
that we help humans in need when the cost to us is small, we might help
some wild animals at least in limited circumstances.
Potential conflict between animal rights and environmentalism
It
has been argued that the environmentalist goal of preserving certain
abstract entities such as species and ecosystems and policy of
non-interference in regard to natural processes is incompatible with
animal rights views which place the welfare and interests of nonhuman
animals at the center of concern. Examples include environmentalists supporting hunting for species population control, while animal rights advocates oppose it; animal rights advocates arguing for the extinction or reengineering of carnivores or r-strategist species, while deep ecologists defend their right to be and flourish as they are;
animal rights advocates defending the reduction of wildlife habitats or
arguing against their expansion out of concern that most animal
suffering takes place within them, while environmentalists want to
safeguard and expand them.
Oscar Horta has argued that there are instances where environmentalists
and animal rights advocates may both support approaches which would
consequently reduce wild animal suffering.
Welfare biology
Welfare biology is a proposed research field for studying the welfare of nonhuman animals, with a particular focus on their relationship with natural ecosystems.
It was first advanced in 1995 by Yew-Kwang Ng, who defined it as "the
study of living things and their environment with respect to their
welfare (defined as net happiness, or enjoyment minus suffering)".
Such research is intended to promote concern for nonhuman animal
suffering in the wild and to establish effective actions that can be
undertaken to help these individuals.
History of interventions
In 2016, 350 starving hippos and buffaloes at Kruger National Park were killed by park rangers. One of the motives for the action was to prevent the animals from suffering as they died.
In 2018, a team of BBC filmmakers dug a ramp in the snow to allow a group of penguins to escape a ravine.
In 2019, 2000 baby flamingos were rescued after they were abandoned by their parents in a drought in South Africa.
Cytokine release syndrome (CRS) is a form of systemic inflammatory response syndrome that can be triggered by a variety of factors such as infections and certain drugs. It occurs when large numbers of white blood cells are activated and release inflammatory cytokines, which in turn activate yet more white blood cells. CRS is also an adverse effect of some monoclonal antibody drugs, as well as adoptive T-cell therapies. Severe cases have been called cytokine storms. When occurring as a result of drug administration, it is also known as an infusion reaction.
Signs and symptoms
Symptoms
include fever, fatigue, loss of appetite, muscle and joint pain,
nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low
blood pressure, seizures, headache, confusion, delirium,
hallucinations, tremor, and loss of coordination.
This can occur when the immune system is fighting pathogens, as cytokines signal immune cells such as T-cells and macrophages to travel to the site of infection. In addition, cytokines activate those cells, stimulating them to produce more cytokines.
CRS has also arisen with biotherapeutics intended to suppress or activate the immune system through receptors on white blood cells. Muromonab-CD3, an anti-CD3 monoclonal antibody intended to suppress the immune system to prevent rejection of organ transplants; alemtuzumab, which is anti-CD52 and used to treat blood cancers as well as multiple sclerosis and in organ transplants; and rituximab, which is anti-CD20 and used to treat blood cancers and auto-immune disorders, all cause CRS. Adoptive T-cell therapies with T-cells modified with chimeric antigen receptors (CAR-T) also causes CRS.
It appears that interleukin 6 is a key mediator of CRS.
CRS
needs to be distinguished from symptoms of the disease itself and, in
the case of drugs, from other adverse effects—for example tumor lysis syndrome
requires different interventions. As of 2015, differential diagnoses
depended on the judgement of doctor as there were no objective tests.
Mild reaction, infusion interruption not indicated; intervention not indicated
Grade 2
Therapy or infusion interruption indicated but responds promptly to
symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV
fluids); prophylactic medications indicated for <=24 hrs
Grade 3
Prolonged (e.g., not rapidly responsive to symptomatic medication or
brief interruption of infusion); recurrence of symptoms following
initial improvement; hospitalization indicated for clinical sequelae
(e.g., renal impairment, pulmonary infiltrates)
Grade 4
Life-threatening consequences; pressor or ventilatory support indicated
Severe CRS caused by some drugs can be prevented by using lower doses, infusing slowly, and administering anti-histamines or corticosteroids before and during administration of the drug.
In vitro assays have been developed to understand the risk that pre-clinical
drug candidates might cause CRS and guide dosing for Phase I trials,
and regulatory agencies expect to see results of such tests in investigational new drug applications.
A modified chandler loop model can be used as a preclinical tool to assess infusion reactions.
Management
Treatment for less severe CRS is supportive, addressing the symptoms like fever, muscle pain, or fatigue. Moderate CRS requires oxygen therapy and giving fluids and antihypotensive agents
to raise blood pressure. For moderate to severe CRS, the use of
immunosuppressive agents like corticosteroids may be necessary, but
judgement must be used to avoid negating the effect of drugs intended to
activate the immune system.
Tocilizumab, an anti-IL6 monoclonal antibody, has been used in some medical centers to treat severe CRS.
Although frequently used to treat severe CRS in people with ARDS, corticosteroids and NSAIDs have been evaluated in clinical trials and have shown no effect on lung mechanics, gas exchange, or beneficial outcome in early established ARDS.
The first reference to the term cytokine storm in the published medical literature appears to be by Ferrara et al. in 1993 in a discussion of graft vs. host disease;
a condition in which the role of excessive and self-perpetuating
cytokine release had already been under discussion for many years. The term next appeared in a discussion of pancreatitis in 2002, and in 2003 it was first used in reference to a reaction to an infection.
It is believed that cytokine storms were responsible for the disproportionate number of healthy young adult deaths during the 1918 influenza pandemic, which killed 50 to 100 million people. In this case, a healthy immune system may have been a liability rather than an asset. Preliminary research results from Taiwan also indicated this as the probable reason for many deaths during the SARS epidemic in 2003. Human deaths from the bird flu H5N1 usually involve cytokine storms as well. Cytokine storm has also been implicated in hantavirus pulmonary syndrome.
In 2006, a medical study at Northwick Park Hospital in England resulted in all 6 of the volunteers given the drug TGN1412 becoming critically ill, with multiple organ failure, high fever, and a systemic inflammatory response. Parexel,
a company conducting trials for pharmaceutical companies, in one of its
own documents, wrote about the trial and said TGN1412 could cause a
cytokine storm—the dangerous reaction the men experienced.
The Spanish flu, also known as the 1918 flu pandemic, was an unusually deadly influenza pandemic.
Lasting from January 1918 to December 1920, it infected 500 million
people—about a quarter of the world's population at the time. The death toll is estimated to have been anywhere from 17 million to 50 million, and possibly as high as 100 million, making it one of the deadliest epidemics in human history.
To maintain morale, World War I censors minimized early reports of illness and mortality in Germany, the United Kingdom, France, and the United States. Papers were free to report the epidemic's effects in neutral Spain, such as the grave illness of King Alfonso XIII, and these stories created a false impression of Spain as especially hard hit. This gave rise to the pandemic's nickname, "Spanish flu". Historical and epidemiological data are inadequate to identify with certainty the pandemic's geographic origin, with varying views as to the origin.
Most influenza outbreaks disproportionately kill the very young
and the very old, with a higher survival rate for those in between, but
the Spanish flu pandemic resulted in a higher than expected mortality
rate for young adults.
Scientists offer several possible explanations for the high mortality
rate of the 1918 influenza pandemic. Some analyses have shown the virus
to be particularly deadly because it triggers a cytokine storm, which ravages the stronger immune system of young adults. In contrast, a 2007 analysis of medical journals from the period of the pandemic found that the viral infection was no more aggressive than previous influenza strains. Instead, malnourishment, overcrowded medical camps and hospitals, and poor hygiene promoted bacterial superinfection. This superinfection killed most of the victims, typically after a somewhat prolonged death bed.
The major UK troop staging and hospital camp in Étaples
in France has been theorized by researchers as being at the center of
the Spanish flu. The research was published in 1999 by a British team,
led by virologistJohn Oxford.
In late 1917, military pathologists reported the onset of a new disease
with high mortality that they later recognized as the flu. The
overcrowded camp and hospital was an ideal site for the spreading of a
respiratory virus. The hospital treated thousands of victims of chemical
attacks, and other casualties of war, and 100,000 soldiers passed
through the camp every day. It also was home to a piggery, and poultry
was regularly brought in for food supplies from surrounding villages.
Oxford and his team postulated that a significant precursor virus,
harbored in birds, mutated and then migrated to pigs kept near the front.
A report published in 2016 in the Journal of the Chinese Medical Association
found evidence that the 1918 virus had been circulating in the European
armies for months and possibly years before the 1918 pandemic.
United States
There have been statements that the epidemic originated in the United States. Historian Alfred W. Crosby stated in 2003 that the flu originated in Kansas, and popular author John Barry described Haskell County, Kansas, as the point of origin in his 2004 article.
It has also been stated by historian Santiago Mata in 2017 that, by
late 1917, there had already been a first wave of the epidemic in at
least 14 US military camps.
A 2018 study of tissue slides and medical reports led by
evolutionary biology professor Michael Worobey found evidence against
the disease originating from Kansas as those cases were milder and had
fewer deaths compared to the situation in New York City in the same time
period. The study did find evidence through phylogenetic analyses that the virus likely had a North American origin, though it was not conclusive. In addition, the haemagglutinin glycoproteins of the virus suggest that it was around far prior to 1918 and other studies suggest that the reassortment of the H1N1 virus likely occurred in or around 1915.
China
One of the few regions of the world seemingly less affected by the 1918 flu pandemic was China, where there may have been a comparatively mild flu season in 1918 (although this is disputed due to lack of data in the Warlord Period of China).
Multiple studies have documented that there were relatively few deaths
from the flu in China compared to other regions of the world. This has led to speculation that the 1918 flu pandemic originated in China.
The relatively mild flu season and lower rates of flu mortality in
China in 1918 may be explained due to the fact that the Chinese
population had already possessed acquired immunity to the flu virus.
However, a study by K.F. Cheng and P.C. Leung in 2006 has suggested it
was more likely because the traditional Chinese medicine played an
important role in prevention and treatment.
In 1993, Claude Hannoun, the leading expert on the 1918 flu for the Pasteur Institute, asserted the former virus was likely to have come from China. It then mutated in the United States near Boston and from there spread to Brest, France, Europe's battlefields, Europe, and the world with Allied soldiers and sailors as the main disseminators.
He considered several other hypotheses of origin, such as Spain, Kansas
and Brest, as being possible, but not likely. Political scientist Andrew Price-Smith published data from the Austrian archives suggesting the influenza had earlier origins, beginning in Austria in early 1917.
In 2014, historian Mark Humphries argued that the mobilization of 96,000 Chinese laborers to work behind the British and French lines might have been the source of the pandemic. Humphries, of the Memorial University of Newfoundland in St. John's,
based his conclusions on newly unearthed records. He found archival
evidence that a respiratory illness that struck northern China in
November 1917 was identified a year later by Chinese health officials as
identical to the Spanish flu.
A report published in 2016 in the Journal of the Chinese Medical Association
found no evidence that the 1918 virus was imported to Europe via
Chinese and Southeast Asian soldiers and workers and instead found
evidence of its circulation in Europe before the pandemic.
The 2016 study suggested that the low flu mortality rate (an estimated
1/1000) found among the Chinese and Southeast Asian workers in Europe
meant that the deadly 1918 influenza pandemic could not have originated
from those workers.
A 2018 study of tissue slides and medical reports led by
evolutionary biology professor Michael Worobey found evidence against
the disease being spread by Chinese workers, noting that workers entered
Europe through other routes that did not result in detectable spread,
making them unlikely to have been the original hosts.
Spread
As U.S. troops deployed en masse for the war effort in Europe, they carried the Spanish flu with them.
When an infected person sneezes or coughs, more than half a million virus particles can spread to those nearby. The close quarters and massive troop movements of World War I
hastened the pandemic, and probably both increased transmission and
augmented mutation. The war may also have increased the lethality of the
virus. Some speculate the soldiers' immune systems were weakened by
malnourishment, as well as the stresses of combat and chemical attacks,
increasing their susceptibility.
A large factor in the worldwide occurrence of this flu was
increased travel. Modern transportation systems made it easier for
soldiers, sailors, and civilian travelers to spread the disease.
In the United States, the disease was first observed in Haskell
County, Kansas, in January 1918, prompting local doctor Loring Miner to
warn the US Public Health Service's academic journal. On 4 March 1918, company cook Albert Gitchell, from Haskell County, reported sick at Fort Riley,
a US military facility that at the time was training American troops
during World War I, making him the first recorded victim of the flu. Within days, 522 men at the camp had reported sick. By 11 March 1918, the virus had reached Queens, New York. Failure to take preventive measures in March/April was later criticised.
In August 1918, a more virulentstrain appeared simultaneously in Brest, France; in Freetown, Sierra Leone;
and in the U.S. in Boston, Massachusetts. The Spanish flu also spread
through Ireland, carried there by returning Irish soldiers.
The Allies of World War I came to call it the Spanish flu, primarily
because the pandemic received greater press attention after it moved
from France to Spain in November 1918. Spain was not involved in the war
and had not imposed wartime censorship.
Mortality
Around the globe
The
difference between the influenza mortality age-distributions of the
1918 epidemic and normal epidemics – deaths per 100,000 persons in each
age group, United States, for the interpandemic years 1911–1917 (dashed
line) and the pandemic year 1918 (solid line)
Three pandemic waves: weekly combined influenza and pneumonia mortality, United Kingdom, 1918–1919
Estimates vary as to the total number who died. An estimate from 1991 says it killed 25–39 million people.
A 2005 estimate put the death toll at probably 50 million (less than 3%
of the global population), and possibly as high as 100 million (more
than 5%). But a reassessment in 2018 estimated the total to be about 17 million, though this has been contested. With a world population of 1.8 to 1.9 billion, these estimates correspond to between 1 and 6 percent of the population.
This flu killed more people in 24 weeks than HIV/AIDS killed in 24 years. The Black Death, which lasted much longer, killed a much higher percentage of the world's then smaller population.
The disease killed in many parts of the world. Some 12-17 million people died in India, about 5% of the population. The death toll in India's British-ruled districts was 13.88 million. Arnold (2019) estimates at least 12 million dead.
Estimates for the death toll in China have varied widely, a range which reflects the lack of centralised collection of health data at the time due to the Warlord period.
The first estimate of the Chinese death toll was made in 1991 by
Patterson and Pyle, which estimated China had a death toll of between 5
and 9 million. However, this 1991 study was later criticized by later
studies due to flawed methodology, and newer studies have published
estimates of a far lower mortality rate in China.
For instance, Iijima in 1998 estimates the death toll in China to be
between 1 and 1.28 million based on data available from Chinese
port-cities. As Wataru Iijima notes,
"Patterson
and Pyle in their study 'The 1918 Influenza Pandemic' tried to estimate
the number of deaths by Spanish influenza in China as a whole. They
argued that between 4.0 and 9.5 million people died in China, but this
total was based purely on the assumption that the death rate there was
1.0–2.25 per cent in 1918, because China was a poor country similar to
Indonesia and India where the mortality rate was of that order. Clearly
their study was not based on any local Chinese statistical data."
The
lower estimates of the Chinese death toll are based on the low
mortality rates that were found in Chinese port-cities (for example,
Hong Kong) and on the assumption that poor communications prevented the
flu from penetrating the interior of China.
However, some contemporary newspaper and post office reports, as well
as reports from missionary doctors, suggest that the flu did penetrate
the Chinese interior and that influenza was bad in some locations in the
countryside of China.
In Japan, 23 million people were affected, with at least 390,000 reported deaths. In the Dutch East Indies (now Indonesia), 1.5 million were assumed to have died among 30 million inhabitants. In Tahiti, 13% of the population died during one month. Similarly, in Samoa 22% of the population of 38,000 died within two months.
In New Zealand, the flu killed an estimated 6,400 Pakeha and 2,500 indigenous Maori in six weeks, with Māori dying at eight times the rate of Pakeha.
In Iran,
the mortality was very high: according to an estimate, between 902,400
and 2,431,000, or 8% to 22% of the total population died.
In the U.S., about 28% of the population of 105 million became
infected, and 500,000 to 675,000 died (0.48 to 0.64 percent of the
population). Native American tribes were particularly hard hit. In the Four Corners area, there were 3,293 registered deaths among Native Americans. Entire Inuit and Alaskan Native village communities died in Alaska. In Canada, 50,000 died.
In Brazil, 300,000 died, including president Rodrigues Alves. In Britain, as many as 250,000 died; in France, more than 400,000.
In Ghana, the influenza epidemic killed at least 100,000 people. Tafari Makonnen (the future Haile Selassie, Emperor of Ethiopia) was one of the first Ethiopians who contracted influenza but survived. Many of his subjects did not; estimates for fatalities in the capital city, Addis Ababa, range from 5,000 to 10,000, or higher. In British Somaliland, one official estimated that 7% of the native population died.
This huge death toll resulted from an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by cytokine storms. Symptoms in 1918 were unusual, initially causing influenza to be misdiagnosed as dengue, cholera, or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred". The majority of deaths were from bacterial pneumonia, a common secondary infection associated with influenza. The virus also killed people directly by causing massive hemorrhages and edema in the lungs.
Patterns of fatality
The pandemic mostly killed young adults. In 1918–1919, 99% of
pandemic influenza deaths in the U.S. occurred in people under 65, and
nearly half of deaths were in young adults 20 to 40 years old. In 1920,
the mortality rate among people under 65 had decreased sixfold to half
the mortality rate of people over 65, but 92% of deaths still occurred
in people under 65. This is unusual, since influenza is typically most deadly to weak individuals, such as infants under age two, adults over age 70, and the immunocompromised. In 1918, older adults may have had partial protection caused by exposure to the 1889–1890 flu pandemic, known as the "Russian flu".
According to historian John M. Barry, the most vulnerable of
all – "those most likely, of the most likely", to die – were pregnant
women. He reported that in thirteen studies of hospitalized women in the
pandemic, the death rate ranged from 23% to 71%.
Of the pregnant women who survived childbirth, over one-quarter (26%) lost the child.
Another oddity was that the outbreak was widespread in the summer and autumn (in the Northern Hemisphere); influenza is usually worse in winter.
Modern analysis has shown the virus to be particularly deadly because
it triggers a cytokine storm (overreaction of the body's immune
system), which ravages the stronger immune system of young adults. One group of researchers recovered the virus from the bodies of frozen victims and transfected animals with it. The animals suffered rapidly progressive respiratory failure
and death through a cytokine storm. The strong immune reactions of
young adults were postulated to have ravaged the body, whereas the
weaker immune reactions of children and middle-aged adults resulted in
fewer deaths among those groups.
In fast-progressing cases, mortality was primarily from pneumonia, by virus-induced lung consolidation. Slower-progressing cases featured secondary bacterial pneumonia, and possibly neural involvement that led to mental disorders in some cases. Some deaths resulted from malnourishment.
A study conducted by He et al. (2011) used a mechanistic
modeling approach to study the three waves of the 1918 influenza
pandemic. They examined the factors that underlie variability in
temporal patterns and their correlation to patterns of mortality and
morbidity. Their analysis suggests that temporal variations in
transmission rate provide the best explanation, and the variation in
transmission required to generate these three waves is within
biologically plausible values.
Another study by He et al. (2013) used a simple epidemic model
incorporating three factors to infer the cause of the three waves of
the 1918 influenza pandemic. These factors were school opening and
closing, temperature changes throughout the outbreak, and human
behavioral changes in response to the outbreak. Their modeling results
showed that all three factors are important, but human behavioral
responses showed the most significant effects.
The second wave of the 1918 pandemic was much deadlier than the
first. The first wave had resembled typical flu epidemics; those most at
risk were the sick and elderly, while younger, healthier people
recovered easily. By August, when the second wave began in France,
Sierra Leone, and the United States, the virus had mutated to a much deadlier form. October 1918 was the deadliest month of the whole pandemic.
This increased severity has been attributed to the circumstances of the First World War. In civilian life, natural selection
favors a mild strain. Those who get very ill stay home, and those
mildly ill continue with their lives, preferentially spreading the mild
strain. In the trenches, natural selection was reversed. Soldiers with a
mild strain stayed where they were, while the severely ill were sent on
crowded trains to crowded field hospitals, spreading the deadlier
virus. The second wave began, and the flu quickly spread around the
world again. Consequently, during modern pandemics, health officials pay
attention when the virus reaches places with social upheaval (looking
for deadlier strains of the virus).
The fact that most of those who recovered from first-wave infections had become immune showed that it must have been the same strain of flu. This was most dramatically illustrated in Copenhagen,
which escaped with a combined mortality rate of just 0.29% (0.02% in
the first wave and 0.27% in the second wave) because of exposure to the
less-lethal first wave.
For the rest of the population, the second wave was far more deadly;
the most vulnerable people were those like the soldiers in the trenches –
adults who were young and fit.
Devastated communities
A chart of deaths in major cities, showing a peak in October and November 1918
Coromandel Hospital Board (New Zealand) advice to influenza sufferers (1918)
Even in areas where mortality was low, so many adults were
incapacitated that much of everyday life was hampered. Some communities
closed all stores or required customers to leave orders outside. There
were reports that healthcare workers could not tend the sick nor the
gravediggers bury the dead because they too were ill. Mass graves were
dug by steam shovel and bodies buried without coffins in many places.
Several Pacific island
territories were hit particularly hard. The pandemic reached them from
New Zealand, which was too slow to implement measures to prevent ships,
such as the SS Talune, carrying the flu from leaving its ports. From New Zealand, the flu reached Tonga (killing 8% of the population), Nauru (16%), and Fiji (5%, 9,000 people).
Worst affected was Western Samoa, formerly German Samoa, which had been occupied by New Zealand in 1914. 90% of the population was infected; 30% of adult men, 22% of adult women, and 10% of children died. By contrast, GovernorJohn Martin Poyer prevented the flu from reaching neighboring American Samoa by imposing a blockade. The disease spread fastest through the higher social classes among the indigenous peoples, because of the custom of gathering oral tradition from chiefs on their deathbeds; many community elders were infected through this process.
In New Zealand, 8,573 deaths were attributed to the 1918 pandemic
influenza, resulting in a total population fatality rate of 0.7%. Māori were 8 to 10 times as likely to die as Pakeha, because of their relative poverty, more crowded housing, rural population and lesser immunity to disease.
In Ireland, the Spanish flu accounted for 10% of the total deaths in 1918.
Data analysis revealed 6,520 recorded deaths in Savannah-Chatham County, Georgia
(population of 83,252) for the three-year period from 1 January 1917 to
31 December 1919. Of these deaths, influenza was specifically listed as
the cause of death in 316 cases, representing 5% of all causes of death
for the total time period.
Less-affected areas
China may have experienced a relatively mild flu season in 1918 compared to other areas of the world.
However, the view that China's experience of the flu in 1918 was mild
has also been challenged. Though there was no centralised collection of
health statistics in the country at the time, some reports from its
interior suggest that mortality rates from influenza were perhaps higher
in at least a few locations in China in 1918.
However, at the very least, there is little evidence that China as a
whole was seriously affected by the flu compared to other countries in
the world.
Although medical records from China's interior are lacking, there was
extensive medical data recorded in Chinese port-cities, such as then British-controlled Hong Kong, Canton, Peking, Harbin and Shanghai. This data was collected by the Chinese Maritime Customs Service, which was largely staffed by non-Chinese foreigners, such as the British, French, and other European colonial officials in China. As a whole, accurate data from China's port cities show astonishingly low mortality rates compared to other cities in Asia.
For example, the British authorities at Hong Kong and Canton reported a
mortality rate from influenza at a rate of 0.25% and 0.32%, much lower
than the reported mortality rate of other cities in Asia, such as Calcutta or Bombay, where influenza was much more devastating. Similarly, in the city of Shanghai – which had a population of over 2 million in 1918 – there were only 266 recorded deaths from influenza among the Chinese population in 1918. If extrapolated from the extensive data recorded from Chinese
cities, the suggested mortality rate from influenza in China as a whole
in 1918 was likely lower than 1% – much lower than the world average
(which was around 3–5%). In contrast, Japan and Taiwan
had reported a mortality rate from influenza around 0.45% and 0.69%
respectively, higher than the mortality rate collected from data in
Chinese port cities, such as Hong Kong (0.25%), Canton (0.32%), and
Shanghai. Some researchers have proposed that traditional Chinese medicine may have played a role in the low influenza mortality rate in China.
1919 Tokyo, Japan
In Japan, 257,363 deaths were attributed to influenza by July 1919,
giving an estimated 0.4% mortality rate, much lower than nearly all
other Asian countries for which data are available. The Japanese
government severely restricted sea travel to and from the home islands
when the pandemic struck.
In the Pacific, American Samoa and the French colony of New Caledonia also succeeded in preventing even a single death from influenza through effective quarantines. In Australia, nearly 12,000 perished.
By the end of the pandemic, the isolated island of Marajó, in Brazil's Amazon River Delta had not reported an outbreak. Saint Helena also reported no deaths.
The death toll in Russia has been estimated at 450,000, though the epidemiologists who suggested this number called it a "shot in the dark". If it is correct, Russia lost roughly 0.2% of its population, meaning it suffered the lowest influenza-related mortality in Europe. Another study considers this number unlikely, given that the country was in the grip of a civil war,
and the infrastructure of daily life had broken down; the study
suggests that Russia's death toll was closer to 1%, or 2.7 million
people.
Aspirin poisoning
In a 2009 paper published in the journal Clinical Infectious Diseases, Karen Starko proposed that aspirin poisoning
contributed substantially to the fatalities. She based this on the
reported symptoms in those dying from the flu, as reported in the post mortem reports still available, and also the timing of the big "death spike" in October 1918. This occurred shortly after the Surgeon General of the U.S. Army and the Journal of the American Medical Association both recommended very large doses of 8 to 31 grams of aspirin per day as part of treatment. These levels will produce hyperventilation in 33% of patients, as well as lung edema in 3% of patients.
Starko also notes that many early deaths showed "wet", sometimes
hemorrhagic lungs, whereas late deaths showed bacterial pneumonia. She
suggests that the wave of aspirin poisonings was due to a "perfect storm" of events: Bayer's
patent on aspirin expired, so many companies rushed in to make a profit
and greatly increased the supply; this coincided with the Spanish flu;
and the symptoms of aspirin poisoning were not known at the time.
A street car conductor in Seattle in 1918 refusing to allow passengers aboard who are not wearing masks
As an explanation for the universally high mortality rate, this
hypothesis was questioned in a letter to the journal published in April
2010 by Andrew Noymer and Daisy Carreon of the University of California, Irvine,
and Niall Johnson of the Australian Commission on Safety and Quality in
Health Care. They questioned the universal applicability of the aspirin
theory, given the high mortality rate in countries such as India, where
there was little or no access to aspirin at the time, compared to the
death rate in places where aspirin was plentiful.
They concluded that "the salicylate
[aspirin] poisoning hypothesis [was] difficult to sustain as the
primary explanation for the unusual virulence of the 1918–1919 influenza
pandemic". In response, Starko said there was anecdotal evidence
of aspirin use in India and argued that even if aspirin
over-prescription had not contributed to the high Indian mortality rate,
it could still have been a factor for high rates in areas where other
exacerbating factors present in India played less of a role.
End of the pandemic
After the lethal second wave struck in late 1918, new cases dropped
abruptly – almost to nothing after the peak in the second wave.
In Philadelphia, for example, 4,597 people died in the week ending
16 October, but by 11 November, influenza had almost disappeared from
the city. One explanation for the rapid decline in the lethality of the
disease is that doctors became more effective in prevention and
treatment of the pneumonia that developed after the victims had
contracted the virus. However, John Barry stated in his 2004 book The Great Influenza: The Epic Story of the Deadliest Plague In History that researchers have found no evidence to support this position.
Another theory holds that the 1918 virus mutated extremely
rapidly to a less lethal strain. This is a common occurrence with
influenza viruses: there is a tendency for pathogenic viruses to become
less lethal with time, as the hosts of more dangerous strains tend to
die out.
Long-term effects
A 2006 study in the Journal of Political Economy found that "cohorts in utero
during the pandemic displayed reduced educational attainment, increased
rates of physical disability, lower income, lower socioeconomic status,
and higher transfer payments compared with other birth cohorts." A 2018 study found that the pandemic reduced educational attainment in populations.
American Red Cross nurses tend to flu patients in temporary wards set up inside Oakland Municipal Auditorium, 1918.
Academic Andrew Price-Smith has made the argument that the virus
helped tip the balance of power in the latter days of the war towards
the Allied cause. He provides data that the viral waves hit the Central Powers before the Allied powers and that both morbidity and mortality in Germany and Austria were considerably higher than in Britain and France.
Despite the high morbidity and mortality rates that resulted from
the epidemic, the Spanish flu began to fade from public awareness over
the decades until the arrival of news about bird flu and other pandemics in the 1990s and 2000s. This has led some historians to label the Spanish flu a "forgotten pandemic".
There are various theories of why the Spanish flu was
"forgotten". The rapid pace of the pandemic, which, for example, killed
most of its victims in the United States within less than nine months,
resulted in limited media coverage. The general population was familiar
with patterns of pandemic disease in the late 19th and early 20th
centuries: typhoid, yellow fever, diphtheria
and cholera all occurred near the same time. These outbreaks probably
lessened the significance of the influenza pandemic for the public. In some areas, the flu was not reported on, the only mention being that of advertisements for medicines claiming to cure it.
Additionally, the outbreak coincided with the deaths and media focus on the First World War.
Another explanation involves the age group affected by the disease. The
majority of fatalities, from both the war and the epidemic, were among
young adults. The number of war-related deaths of young adults may have
overshadowed the deaths caused by flu.
When people read the obituaries, they saw the war or postwar
deaths and the deaths from the influenza side by side. Particularly in
Europe, where the war's toll was high, the flu may not have had a
tremendous psychological impact or may have seemed an extension of the
war's tragedies.
The duration of the pandemic and the war could have also played a role.
The disease would usually only affect a particular area for a month
before leaving. The war, however, had initially been expected to end
quickly but lasted for four years by the time the pandemic struck.
1918 influenza epidemic burial site in Auckland, New Zealand
Regarding global economic effects, many businesses in the
entertainment and service industries suffered losses in revenue, while
the healthcare industry reported profit gains.
Historian Nancy Bristow has argued that the pandemic, when combined with
the increasing number of women attending college, contributed to the
success of women in the field of nursing. This was due in part to the
failure of medical doctors, who were predominantly men, to contain and
prevent the illness. Nursing staff, who were mainly women, celebrated
the success of their patient care and did not associate the spread of
the disease with their work.
In Spain, sources from the period explicitly linked the Spanish flu to the cultural figure of Don Juan. The nickname for the flu, the "Naples Soldier", was adopted from Federico Romero and Guillermo Fernández Shaw's operetta, The Song of Forgetting (La canción del olvido). The protagonist of the operetta was a stock Don Juan type. Federico Romero, one of the librettists, quipped that the play's most popular musical number, Naples Soldier,
was as catchy as the flu. Davis argued the Spanish flu–Don Juan
connection allowed Spaniards to make sense of their epidemic experience
by interpreting it through their familiar Don Juan story.
Research
An electron micrograph showing recreated 1918 influenza virions
The origin of the Spanish flu pandemic, and the relationship between
the near-simultaneous outbreaks in humans and swine, have been
controversial. One hypothesis is that the virus strain originated at
Fort Riley, Kansas, in viruses in poultry and swine which the fort bred
for food; the soldiers were then sent from Fort Riley around the world,
where they spread the disease.
Similarities between a reconstruction of the virus and avian viruses,
combined with the human pandemic preceding the first reports of
influenza in swine, led researchers to conclude the influenza virus
jumped directly from birds to humans, and swine caught the disease from
humans.
Others have disagreed, and more recent research has suggested the strain may have originated in a nonhuman, mammalian species. An estimated date for its appearance in mammalian hosts has been put at the period 1882–1913. This ancestor virus diverged about 1913–1915 into two clades (or biological groups), which gave rise to the classical swine and human H1N1
influenza lineages. The last common ancestor of human strains dates to
between February 1917 and April 1918. Because pigs are more readily
infected with avian influenza viruses than are humans, they were
suggested as the original recipients of the virus, passing the virus to
humans sometime between 1913 and 1918.
An effort to recreate the 1918 flu strain (a subtype of avian strain H1N1) was a collaboration among the Armed Forces Institute of Pathology, the USDAARS Southeast Poultry Research Laboratory, and Mount Sinai School of Medicine in New York City. The effort resulted in the announcement (on 5 October 2005) that the group had successfully determined the virus's genetic sequence, using historic tissue samples recovered by pathologist Johan Hultin from an Inuit female flu victim buried in the Alaskan permafrost and samples preserved from American soldiers Roscoe Vaughan and James Downs.
On 18 January 2007, Kobasa et al. (2007) reported that monkeys (Macaca fascicularis) infected with the recreated flu strain exhibited classic symptoms of the 1918 pandemic, and died from cytokine storms –
an overreaction of the immune system. This may explain why the 1918 flu
had its surprising effect on younger, healthier people, as a person
with a stronger immune system would potentially have a stronger
overreaction.
On 16 September 2008, the body of British politician and diplomat Sir Mark Sykes was exhumed to study the RNA of the flu virus in efforts to understand the genetic structure of modern H5N1 bird flu. Sykes had been buried in 1919 in a lead coffin which scientists hoped had helped preserve the virus. The coffin was found to be split and the cadaver badly decomposed; nonetheless, samples of lung and brain tissue were taken.
In December 2008, research by Yoshihiro Kawaoka of the University of Wisconsin linked the presence of three specific genes (termed PA, PB1, and PB2) and a nucleoprotein
derived from 1918 flu samples to the ability of the flu virus to invade
the lungs and cause pneumonia. The combination triggered similar
symptoms in animal testing.
In June 2010, a team at the Mount Sinai School of Medicine reported the 2009 flu pandemic vaccine provided some cross-protection against the 1918 flu pandemic strain.
One of the few things known for certain about the influenza in
1918 and for some years after was that it was, out of the laboratory,
exclusively a disease of human beings.
In 2013, the AIR Worldwide Research and Modeling Group
"characterized the historic 1918 pandemic and estimated the effects of a
similar pandemic occurring today using the AIR Pandemic Flu Model". In
the model, "a modern day 'Spanish flu' event would result in additional
life insurance losses of between US$15.3–27.8 billion in the United
States alone", with 188,000–337,000 deaths in the United States.
In 2018, Michael Worobey, an evolutionary biology professor at the University of Arizona who is examining the history of the 1918 pandemic, revealed that he obtained tissue slides created by William Rolland,
a physician who reported on a respiratory illness likely to be the
virus while a pathologist in the British military during World War One. Rolland had authored an article in the Lancet during 1917 about a respiratory illness outbreak beginning in 1916 in Étaples, France.
Worobey traced recent references to that article to family members who
had retained slides that Rolland had prepared during that time. Worobey
extracted tissue from the slides to potentially reveal more about the
origin of the pathogen.
