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Thursday, April 8, 2021

Environmental impact of pesticides

From Wikipedia, the free encyclopedia
 
Preparing to spray a hazardous pesticide
 
Drainage of fertilizers and pesticides into a stream
 
How pesticides are used

The impact of pesticides consists of the effects of pesticides on non-target species. Pesticides are chemical preparations used to kill fungal or animal pests. Over 98% of sprayed insecticides and 95% of herbicides reach a destination other than their target species, because they are sprayed or spread across entire agricultural fields. Runoff can carry pesticides into aquatic environments while wind can carry them to other fields, grazing areas, human settlements and undeveloped areas, potentially affecting other species. Other problems emerge from poor production, transport and storage practices. Over time, repeated application increases pest resistance, while its effects on other species can facilitate the pest's resurgence.

Each pesticide or pesticide class comes with a specific set of environmental concerns. Such undesirable effects have led many pesticides to be banned, while regulations have limited and/or reduced the use of others. The global spread of pesticide use, including the use of older/obsolete pesticides that have been banned in some jurisdictions, has increased overall.

Agriculture and the environment

The arrival of humans in an area, to live or to conduct agriculture, necessarily has environmental impacts. These range from simple crowding out of wild plants in favor of more desirable cultivars to larger scale impacts such as reducing biodiversity by reducing food availability of native species, which can propagate across food chains. The use of agricultural chemicals such as fertilizer and pesticides magnify those impacts. While advances in agrochemistry have reduced those impacts, for example by the replacement of long-lived chemicals with those that reliably degrade, even in the best case they remain substantial. These effects are magnified by the use of older chemistries and poor management practices.

History

While concern for ecotoxicology began with acute poisoning events in the late 19th century; public concern over the undesirable environmental effects of chemicals arose in the early 1960s with the publication of Rachel Carson′s book, Silent Spring. Shortly thereafter, DDT, originally used to combat malaria, and its metabolites were shown to cause population-level effects in raptorial birds. Initial studies in industrialized countries focused on acute mortality effects mostly involving birds or fish.

Data on pesticide usage remain scattered and/or not publicly available (3). The common practice of incident registration is inadequate for understanding the entirety of effects.

Since 1990, research interest has shifted from documenting incidents and quantifying chemical exposure to studies aimed at linking laboratory, mesocosm and field experiments. The proportion of effect-related publications has increased. Animal studies mostly focus on fish, insects, birds, amphibians and arachnids.

Since 1993, the United States and the European Union have updated pesticide risk assessments, ending the use of acutely toxic organophosphate and carbamate insecticides. Newer pesticides aim at efficiency in target and minimum side effects in nontarget organisms. The phylogenetic proximity of beneficial and pest species complicates the project.

One of the major challenges is to link the results from cellular studies through many levels of increasing complexity to ecosystems.

The concept (borrowed from nuclear physics) of a half-life has been utilized for pesticides in plants, and certain authors maintain that pesticide risk and impact assessment models rely on and are sensitive to information describing dissipation from plants. Half-life for pesticides is explained in two NPIC fact sheets. Known degradation pathways are through: photolysis, chemical dissociation, sorption, bioaccumulation and plant or animal metabolism. A USDA fact sheet published in 1994 lists the soil adsorption coefficient and soil half-life for then-commonly used pesticides.

Specific pesticide effects

Pesticide environmental effects
Pesticide/class Effect(s)
Organochlorine DDT/DDE Endocrine disruptor

Thyroid disruption properties in rodents, birds, amphibians and fish

Acute mortality attributed to inhibition of acetylcholinesterase activity
DDT Egg shell thinning in raptorial birds

Carcinogen

Endocrine disruptor
DDT/Diclofol, Dieldrin and Toxaphene Juvenile population decline and adult mortality in wildlife reptiles
DDT/Toxaphene/Parathion Susceptibility to fungal infection
Triazine Earthworms became infected with monocystid gregarines
Chlordane Interact with vertebrate immune systems
Carbamates, the phenoxy herbicide 2,4-D, and atrazine Interact with vertebrate immune systems
Anticholinesterase Bird poisoning

Animal infections, disease outbreaks and higher mortality.
Organophosphate Thyroid disruption properties in rodents, birds, amphibians and fish

Acute mortality attributed to inhibition of acetylcholine esterase activity

Immunotoxicity, primarily caused by the inhibition of serine hydrolases or esterases

Oxidative damage

Modulation of signal transduction pathways

Impaired metabolic functions such as thermoregulation, water and/or food intake and behavior, impaired development, reduced reproduction and hatching success in vertebrates.
Carbamate Thyroid disruption properties in rodents, birds, amphibians and fish

Impaired metabolic functions such as thermoregulation, water and/or food intake and behavior, impaired development, reduced reproduction and hatching success in vertebrates.

Interact with vertebrate immune systems

Acute mortality attributed to inhibition of acetylcholine esterase activity
Phenoxy herbicide 2,4-D Interact with vertebrate immune systems
Atrazine Interact with vertebrate immune systems

Reduced northern leopard frog (Rana pipiens) populations because atrazine killed phytoplankton, thus allowing light to penetrate the water column and periphyton to assimilate nutrients released from the plankton. Periphyton growth provided more food to grazers, increasing snail populations, which provide intermediate hosts for trematode.
Pyrethroid Thyroid disruption properties in rodents, birds, amphibians and fish
Thiocarbamate Thyroid disruption properties in rodents, birds, amphibians and fish
Triazine Thyroid disruption properties in rodents, birds, amphibians and fish
Triazole Thyroid disruption properties in rodents, birds, amphibians and fish

Impaired metabolic functions such as thermoregulation, water and/or food intake and behavior, impaired development, reduced reproduction and hatching success in vertebrates.
Neonicotinoic/Nicotinoid respiratory, cardiovascular, neurological, and immunological toxicity in rats and humans

Disrupt biogenic amine signaling and cause subsequent olfactory dysfunction, as well as affecting foraging behavior, learning and memory.
Imidacloprid, Imidacloprid/pyrethroid λ-cyhalothrin Impaired foraging, brood development, and colony success in terms of growth rate and new queen production.
Thiamethoxam High honey bee worker mortality due to homing failure (risks for colony collapse remain controversial)
Flupyradifurone Lethal and sublethal adverse synergistic effects in bees. Its toxicity depends on season and nutritional stress, and can reduce bee survival, food consumption, thermoregulation, flight success, and increase flight velocity. It has the same mode of action of neonicotinoids.
Spinosyns Affect various physiological and behavioral traits of beneficial arthropods, particularly hymenopterans
Bt corn/Cry Reduced abundance of some insect taxa, predominantly susceptible Lepidopteran herbivores as well as their predators and parasitoids.
Herbicide Reduced food availability and adverse secondary effects on soil invertebrates and butterflies

Decreased species abundance and diversity in small mammals.
Benomyl Altered the patch-level floral display and later a two-thirds reduction of the total number of bee visits and in a shift in the visitors from large-bodied bees to small-bodied bees and flies
Herbicide and planting cycles Reduced survival and reproductive rates in seed-eating or carnivorous birds 

Air

Aerial application of a mosquito pesticide over a city

Pesticides can contribute to air pollution. Pesticide drift occurs when pesticides suspended in the air as particles are carried by wind to other areas, potentially contaminating them. Pesticides that are applied to crops can volatilize and may be blown by winds into nearby areas, potentially posing a threat to wildlife. Weather conditions at the time of application as well as temperature and relative humidity change the spread of the pesticide in the air. As wind velocity increases so does the spray drift and exposure. Low relative humidity and high temperature result in more spray evaporating. The amount of inhalable pesticides in the outdoor environment is therefore often dependent on the season. Also, droplets of sprayed pesticides or particles from pesticides applied as dusts may travel on the wind to other areas, or pesticides may adhere to particles that blow in the wind, such as dust particles. Ground spraying produces less pesticide drift than aerial spraying does. Farmers can employ a buffer zone around their crop, consisting of empty land or non-crop plants such as evergreen trees to serve as windbreaks and absorb the pesticides, preventing drift into other areas. Such windbreaks are legally required in the Netherlands.

Pesticides that are sprayed on to fields and used to fumigate soil can give off chemicals called volatile organic compounds, which can react with other chemicals and form a pollutant called tropospheric ozone. Pesticide use accounts for about 6 percent of total tropospheric ozone levels.

Water

Pesticide pathways

In the United States, pesticides were found to pollute every stream and over 90% of wells sampled in a study by the US Geological Survey. Pesticide residues have also been found in rain and groundwater. Studies by the UK government showed that pesticide concentrations exceeded those allowable for drinking water in some samples of river water and groundwater.

Pesticide impacts on aquatic systems are often studied using a hydrology transport model to study movement and fate of chemicals in rivers and streams. As early as the 1970s quantitative analysis of pesticide runoff was conducted in order to predict amounts of pesticide that would reach surface waters.

There are four major routes through which pesticides reach the water: it may drift outside of the intended area when it is sprayed, it may percolate, or leach through the soil, it may be carried to the water as runoff, or it may be spilled, for example accidentally or through neglect. They may also be carried to water by eroding soil. Factors that affect a pesticide's ability to contaminate water include its water solubility, the distance from an application site to a body of water, weather, soil type, presence of a growing crop, and the method used to apply the chemical.

United States regulations

In the US, maximum limits of allowable concentrations for individual pesticides in drinking water are set by the Environmental Protection Agency (EPA) for public water systems. (There are no federal standards for private wells.) Ambient water quality standards for pesticide concentrations in water bodies are principally developed by state environmental agencies, with EPA oversight. These standards may be issued for individual water bodies, or may apply statewide.

United Kingdom regulations

The United Kingdom sets Environmental Quality Standards (EQS), or maximum allowable concentrations of some pesticides in bodies of water above which toxicity may occur.

European Union regulations

The European Union also regulates maximum concentrations of pesticides in water.

Soil

The extensive use of pesticides in agricultural production can degrade and damage the community of microorganisms living in the soil, particularly when these chemicals are overused or misused as chemical compounds build up in the soil. The full impact of pesticides on soil microorganisms is still not entirely understood; many studies have found deleterious effects of pesticides on soil microorganisms and biochemical processes, while others have found that the residue of some pesticides can be degraded and assimilated by microorganisms. The effect of pesticides on soil microorganisms is impacted by the persistence, concentration, and toxicity of the applied pesticide, in addition to various environmental factors. This complex interaction of factors makes it difficult to draw definitive conclusions about the interaction of pesticides with the soil ecosystem. In general, long-term pesticide application can disturb the biochemical processes of nutrient cycling.

Many of the chemicals used in pesticides are persistent soil contaminants, whose impact may endure for decades and adversely affect soil conservation.

The use of pesticides decreases the general biodiversity in the soil. Not using the chemicals results in higher soil quality, with the additional effect that more organic matter in the soil allows for higher water retention. This helps increase yields for farms in drought years, when organic farms have had yields 20-40% higher than their conventional counterparts. A smaller content of organic matter in the soil increases the amount of pesticide that will leave the area of application, because organic matter binds to and helps break down pesticides.

Degradation and sorption are both factors which influence the persistence of pesticides in soil. Depending on the chemical nature of the pesticide, such processes control directly the transportation from soil to water, and in turn to air and our food. Breaking down organic substances, degradation, involves interactions among microorganisms in the soil. Sorption affects bioaccumulation of pesticides which are dependent on organic matter in the soil. Weak organic acids have been shown to be weakly sorbed by soil, because of pH and mostly acidic structure. Sorbed chemicals have been shown to be less accessible to microorganisms. Aging mechanisms are poorly understood but as residence times in soil increase, pesticide residues become more resistant to degradation and extraction as they lose biological activity.

Effect on plants

Crop spraying

Nitrogen fixation, which is required for the growth of higher plants, is hindered by pesticides in soil. The insecticides DDT, methyl parathion, and especially pentachlorophenol have been shown to interfere with legume-rhizobium chemical signaling. Reduction of this symbiotic chemical signaling results in reduced nitrogen fixation and thus reduced crop yields. Root nodule formation in these plants saves the world economy $10 billion in synthetic nitrogen fertilizer every year.

Pesticides can kill bees and are strongly implicated in pollinator decline, the loss of species that pollinate plants, including through the mechanism of Colony Collapse Disorder, in which worker bees from a beehive or western honey bee colony abruptly disappear. Application of pesticides to crops that are in bloom can kill honeybees, which act as pollinators. The USDA and USFWS estimate that US farmers lose at least $200 million a year from reduced crop pollination because pesticides applied to fields eliminate about a fifth of honeybee colonies in the US and harm an additional 15%.

On the other side, pesticides have some direct harmful effect on plant including poor root hair development, shoot yellowing and reduced plant growth.

Effect on animals

In England, the use of pesticides in gardens and farmland has seen a reduction in the number of common chaffinches

Many kinds of animals are harmed by pesticides, leading many countries to regulate pesticide usage through Biodiversity Action Plans.

Animals including humans may be poisoned by pesticide residues that remain on food, for example when wild animals enter sprayed fields or nearby areas shortly after spraying.

Pesticides can eliminate some animals' essential food sources, causing the animals to relocate, change their diet or starve. Residues can travel up the food chain; for example, birds can be harmed when they eat insects and worms that have consumed pesticides. Earthworms digest organic matter and increase nutrient content in the top layer of soil. They protect human health by ingesting decomposing litter and serving as bioindicators of soil activity. Pesticides have had harmful effects on growth and reproduction on earthworms. Some pesticides can bioaccumulate, or build up to toxic levels in the bodies of organisms that consume them over time, a phenomenon that impacts species high on the food chain especially hard.

Birds

Index of number of common farmland birds in the European Union and selected European countries, base equal to 100 in 1990

  Sweden
  Netherlands
  France
  United Kingdom
  European Union
  Germany
  Switzerland

The US Fish and Wildlife Service estimates that 72 million birds are killed by pesticides in the United States each year. Bald eagles are common examples of nontarget organisms that are impacted by pesticide use. Rachel Carson's book Silent Spring dealt with damage to bird species due to pesticide bioaccumulation. There is evidence that birds are continuing to be harmed by pesticide use. In the farmland of the United Kingdom, populations of ten different bird species declined by 10 million breeding individuals between 1979 and 1999, allegedly from loss of plant and invertebrate species on which the birds feed. Throughout Europe, 116 species of birds were threatened as of 1999. Reductions in bird populations have been found to be associated with times and areas in which pesticides are used. DDE-induced egg shell thinning has especially affected European and North American bird populations. From 1990 to 2014 the number of common farmland birds has declined in the European Union as a whole and in France, Belgium and Sweden; in Germany, which relies more on organic farming and less on pesticides the decline has been slower; in Switzerland, which does not rely much on intensive agriculture, after a decline in the early 2000s the level has returned to the one of 1990. In another example, some types of fungicides used in peanut farming are only slightly toxic to birds and mammals, but may kill earthworms, which can in turn reduce populations of the birds and mammals that feed on them.

Some pesticides come in granular form. Wildlife may eat the granules, mistaking them for grains of food. A few granules of a pesticide may be enough to kill a small bird. Herbicides may endanger bird populations by reducing their habitat.

Aquatic life

Using an aquatic herbicide
 
Wide field margins can reduce fertilizer and pesticide pollution in streams and rivers

Fish and other aquatic biota may be harmed by pesticide-contaminated water. Pesticide surface runoff into rivers and streams can be highly lethal to aquatic life, sometimes killing all the fish in a particular stream.

Application of herbicides to bodies of water can cause fish kills when the dead plants decay and consume the water's oxygen, suffocating the fish. Herbicides such as copper sulfate that are applied to water to kill plants are toxic to fish and other water animals at concentrations similar to those used to kill the plants. Repeated exposure to sublethal doses of some pesticides can cause physiological and behavioral changes that reduce fish populations, such as abandonment of nests and broods, decreased immunity to disease and decreased predator avoidance.

Application of herbicides to bodies of water can kill plants on which fish depend for their habitat.

Pesticides can accumulate in bodies of water to levels that kill off zooplankton, the main source of food for young fish. Pesticides can also kill off insects on which some fish feed, causing the fish to travel farther in search of food and exposing them to greater risk from predators.

The faster a given pesticide breaks down in the environment, the less threat it poses to aquatic life. Insecticides are typically more toxic to aquatic life than herbicides and fungicides.

Amphibians

In the past several decades, amphibian populations have declined across the world, for unexplained reasons which are thought to be varied but of which pesticides may be a part.

Pesticide mixtures appear to have a cumulative toxic effect on frogs. Tadpoles from ponds containing multiple pesticides take longer to metamorphose and are smaller when they do, decreasing their ability to catch prey and avoid predators. Exposing tadpoles to the organochloride endosulfan at levels likely to be found in habitats near fields sprayed with the chemical kills the tadpoles and causes behavioral and growth abnormalities.

The herbicide atrazine can turn male frogs into hermaphrodites, decreasing their ability to reproduce. Both reproductive and nonreproductive effects in aquatic reptiles and amphibians have been reported. Crocodiles, many turtle species and some lizards lack sex-distinct chromosomes until after fertilization during organogenesis, depending on temperature. Embryonic exposure in turtles to various PCBs causes a sex reversal. Across the United States and Canada disorders such as decreased hatching success, feminization, skin lesions, and other developmental abnormalities have been reported.

Pesticides are implicated in a range of impacts on human health due to pollution

Humans

Pesticides can enter the body through inhalation of aerosols, dust and vapor that contain pesticides; through oral exposure by consuming food/water; and through skin exposure by direct contact. Pesticides secrete into soils and groundwater which can end up in drinking water, and pesticide spray can drift and pollute the air.

The effects of pesticides on human health depend on the toxicity of the chemical and the length and magnitude of exposure. Farm workers and their families experience the greatest exposure to agricultural pesticides through direct contact. Every human contains pesticides in their fat cells.

Children are more susceptible and sensitive to pesticides, because they are still developing and have a weaker immune system than adults. Children may be more exposed due to their closer proximity to the ground and tendency to put unfamiliar objects in their mouth. Hand to mouth contact depends on the child's age, much like lead exposure. Children under the age of six months are more apt to experience exposure from breast milk and inhalation of small particles. Pesticides tracked into the home from family members increase the risk of exposure. Toxic residue in food may contribute to a child’s exposure. The chemicals can bioaccumulate in the body over time.

Exposure effects can range from mild skin irritation to birth defects, tumors, genetic changes, blood and nerve disorders, endocrine disruption, coma or death. Developmental effects have been associated with pesticides. Recent increases in childhood cancers in throughout North America, such as leukemia, may be a result of somatic cell mutations. Insecticides targeted to disrupt insects can have harmful effects on mammalian nervous systems. Both chronic and acute alterations have been observed in exposes. DDT and its breakdown product DDE disturb estrogenic activity and possibly lead to breast cancer. Fetal DDT exposure reduces male penis size in animals and can produce undescended testicles. Pesticide can affect fetuses in early stages of development, in utero and even if a parent was exposed before conception. Reproductive disruption has the potential to occur by chemical reactivity and through structural changes.

Persistent organic pollutants

Persistent organic pollutants (POPs) are compounds that resist degradation and thus remain in the environment for years. Some pesticides, including aldrin, chlordane, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, mirex and toxaphene, are considered POPs. Some POPs have the ability to volatilize and travel great distances through the atmosphere to become deposited in remote regions. Such chemicals may have the ability to bioaccumulate and biomagnify and can biomagnify (i.e. become more concentrated) up to 70,000 times their original concentrations. POPs can affect non-target organisms in the environment and increase risk to humans by disruption in the endocrine, reproductive, and respiratory systems.

Pest resistance

Pests may evolve to become resistant to pesticides. Many pests will initially be very susceptible to pesticides, but following mutations in their genetic makeup become resistant and survive to reproduce.

Resistance is commonly managed through pesticide rotation, which involves alternating among pesticide classes with different modes of action to delay the onset of or mitigate existing pest resistance.[84]

Pest rebound and secondary pest outbreaks

Non-target organisms can also be impacted by pesticides. In some cases, a pest insect that is controlled by a beneficial predator or parasite can flourish should an insecticide application kill both pest and beneficial populations. A study comparing biological pest control and pyrethroid insecticide for diamondback moths, a major cabbage family insect pest, showed that the pest population rebounded due to loss of insect predators, whereas the biocontrol did not show the same effect.[85] Likewise, pesticides sprayed to control mosquitoes may temporarily depress mosquito populations, they may result in a larger population in the long run by damaging natural controls.[34] This phenomenon, wherein the population of a pest species rebounds to equal or greater numbers than it had before pesticide use, is called pest resurgence and can be linked to elimination of its predators and other natural enemies.[86]

Loss of predator species can also lead to a related phenomenon called secondary pest outbreaks, an increase in problems from species that were not originally a problem due to loss of their predators or parasites. An estimated third of the 300 most damaging insects in the US were originally secondary pests and only became a major problem after the use of pesticides. In both pest resurgence and secondary outbreaks, their natural enemies were more susceptible to the pesticides than the pests themselves, in some cases causing the pest population to be higher than it was before the use of pesticide.

Eliminating pesticides

Many alternatives are available to reduce the effects pesticides have on the environment. Alternatives include manual removal, applying heat, covering weeds with plastic, placing traps and lures, removing pest breeding sites, maintaining healthy soils that breed healthy, more resistant plants, cropping native species that are naturally more resistant to native pests and supporting biocontrol agents such as birds and other pest predators. In the United States, conventional pesticide use peaked in 1979, and by 2007, had been reduced by 25 percent from the 1979 peak level, while US agricultural output increased by 43 percent over the same period.

Biological controls such as resistant plant varieties and the use of pheromones, have been successful and at times permanently resolve a pest problem. Integrated Pest Management (IPM) employs chemical use only when other alternatives are ineffective. IPM causes less harm to humans and the environment. The focus is broader than on a specific pest, considering a range of pest control alternatives. Biotechnology can also be an innovative way to control pests. Strains can be genetically modified (GM) to increase their resistance to pests. The same techniques can be used to increase pesticide resistance and was employed by Monsanto to create glyphosate-resistant strains of major crops. In the United States in 2010, 70% of all the corn that was planted was resistant to glyphosate; 78% of cotton, and 93% of all soybeans.

Big Pharma conspiracy theory

From Wikipedia, the free encyclopedia

The Big Pharma conspiracy theory is a group of conspiracy theories that claim that the medical community in general and pharmaceutical companies in particular, especially large corporations, operate for sinister purposes and against the public good, and that they allegedly conceal effective treatments, or even cause and worsen a wide range of diseases. Specific variations of the conspiracy theory have included the claim that natural alternative remedies to health problems are being suppressed, the claim that drugs for the treatment of HIV/AIDS are ineffective and harmful, and the claim that a cure for all cancers has been discovered but hidden from the public. In each case the conspiracy theorists have blamed pharmaceutical companies' search for profits. A range of authors have shown these claims to be false, though some of these authors nevertheless maintain that other criticisms of the pharmaceutical industry are legitimate.

History and definition

The term Big Pharma is used to refer collectively to the global pharmaceutical industry. According to Steven Novella the term has come to connote a demonized form of the pharmaceutical industry.[Professor of writing Robert Blaskiewicz has written that conspiracy theorists use the term Big Pharma as "shorthand for an abstract entity comprising corporations, regulators, NGOs, politicians, and often physicians, all with a finger in the trillion-dollar prescription pharmaceutical pie".

According to Blaskiewicz, the Big Pharma conspiracy theory has four classic traits: first, the assumption that the conspiracy is perpetrated by a small malevolent cadre; secondly, the belief that the public at large is ignorant of the truth; thirdly, that its believers treat lack of evidence as evidence; and finally, that the arguments deployed in support of the theory are irrational, misconceived, or otherwise mistaken.

Manifestations

The conspiracy theory has a variety of different specific manifestations. Each has different narratives, but they always cast "Big Pharma" as the villain of the peace.

Alternative treatments

In Natural Cures "They" Don't Want You to Know About, Kevin Trudeau proposes that there are all-natural cures for serious illnesses including cancer, herpes, arthritis, AIDS, acid reflux disease, various phobias, depression, obesity, diabetes, multiple sclerosis, lupus, chronic fatigue syndrome, attention deficit disorder, muscular dystrophy, and that these are all being deliberately hidden and suppressed from the public by the Food and Drug Administration, the Federal Trade Commission, and the major food and drug companies.

HIV/AIDS

In a 2006 column for Harper's Magazine, journalist Celia Farber claimed that the antiretroviral drug nevirapine was part of a conspiracy by the "scientific-medical complex" to spread toxic drugs. Farber said that AIDS is not caused by HIV and that nevirapine had been unethically administered to pregnant women in clinical trials, leading to a fatality. Farber's theories and claims were refuted by scientists, but, according to Seth Kalichman, the resulting publicity represented a breakthrough moment for AIDS denialism.

Hidden cancer cure

The idea that big pharma has a cure for cancer and is suppressing it so that they can maintain a profit is believed by as much as 27% of the American public according to a 2005 survey. The argument is that pharmaceutical companies are slowing down research for a comprehensive cure for cancer by developing high-profit, single-purpose treatments rather than focusing on a supposed cure-all for all cancers.

Reception

A common claim among proponents of the conspiracy theory is that pharmaceutical companies suppress negative research about their drugs by financially pressuring researchers and journals. Skeptic Benjamin Radford, while conceding there is "certainly a grain of truth" to these claims, notes that there are in fact papers critical of specific drugs published in top journals on a regular basis. A prominent and recent example noted by Radford is a systematic review published in the British Medical Journal showing that paracetamol is ineffective for lower back pain and has minimal effectiveness for osteoarthritis.

In his 2012 book Bad Pharma, Ben Goldacre heavily criticises the pharmaceutical industry but rejects any conspiracy theories. He argues that the problems are "perpetrated by ordinary people, but many of them may not even know what they've done."

Steven Novella writes that while the pharmaceutical industry has a number of aspects which justly deserve criticism, the "demonization" of it is both cynical and intellectually lazy. He goes on to consider that overblown attacks on "Big Pharma" actually let the pharmaceutical industry "off the hook" since they distract from and tarnish more considered criticisms. He has also written, on Skepticblog, about the general misunderstanding and sensationalizing of cancer research that typically accompanies a conspiratorial mindset. He points out that cures for cancer, rather than being hidden, are not the cures they are initially touted to be by the media and either result in a dead end, further research goals, or a decrease in the mortality rate for a specific type of cancer.

Dave Roos and Oliver Childs have criticized the idea that holding back a cure for cancer would result in more profit than presenting one. Dina Fine Maron further notes that this view largely ignores the fact that cancer is not a single disease but instead many, and the fact that large strides have been made in the fight against cancer.

In 2016 David Robert Grimes published a research paper elaborating about the mathematical non-viability of conspiracy theories in general. He specifically showed that if there were a big pharma conspiracy to conceal a cure for cancer, it would be exposed after about 3.2 years due to the sheer number of people required to keep it secret.

Escherichia coli

From Wikipedia, the free encyclopedia
 
Escherichia coli
E coli at 10000x, original.jpg
Scientific classification edit
Domain: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species:
E. coli
Binomial name
Escherichia coli
(Migula 1895)
Castellani and Chalmers 1919
Synonyms

Escherichia coli (/ˌɛʃəˈrɪkiə ˈkl/), also known as E. coli (/ˌ ˈkl/), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but some serotypes (EPEC, ETEC etc.) can cause serious food poisoning in their hosts, and are occasionally responsible for food contamination incidents that prompt product recalls. The harmless strains are part of the normal microbiota of the gut, and can benefit their hosts by producing vitamin K2, (which helps blood to clot) and preventing colonisation of the intestine with pathogenic bacteria, having a symbiotic relationship. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for 3 days, but its numbers decline slowly afterwards.

E. coli and other facultative anaerobes constitute about 0.1% of gut microbiota, and fecal–oral transmission is the major route through which pathogenic strains of the bacterium cause disease. Cells are able to survive outside the body for a limited amount of time, which makes them potential indicator organisms to test environmental samples for fecal contamination. A growing body of research, though, has examined environmentally persistent E. coli which can survive for many days and grow outside a host.

The bacterium can be grown and cultured easily and inexpensively in a laboratory setting, and has been intensively investigated for over 60 years. E. coli is a chemoheterotroph whose chemically defined medium must include a source of carbon and energy. E. coli is the most widely studied prokaryotic model organism, and an important species in the fields of biotechnology and microbiology, where it has served as the host organism for the majority of work with recombinant DNA. Under favorable conditions, it takes as little as 20 minutes to reproduce.

Biology and biochemistry

Model of successive binary fission in E. coli

Type and morphology

E. coli is a Gram-negative, facultative anaerobe (that makes ATP by aerobic respiration if oxygen is present, but is capable of switching to fermentation or anaerobic respiration if oxygen is absent) and nonsporulating bacterium. Cells are typically rod-shaped, and are about 2.0 μm long and 0.25–1.0 μm in diameter, with a cell volume of 0.6–0.7 μm3.

E. coli stains Gram-negative because its cell wall is composed of a thin peptidoglycan layer and an outer membrane. During the staining process, E. coli picks up the color of the counterstain safranin and stains pink. The outer membrane surrounding the cell wall provides a barrier to certain antibiotics such that E. coli is not damaged by penicillin.

Strains that possess flagella are motile. The flagella have a peritrichous arrangement. It also attaches and effaces to the microvilli of the intestines via an adhesion molecule known as intimin.

Metabolism

E. coli can live on a wide variety of substrates and uses mixed acid fermentation in anaerobic conditions, producing lactate, succinate, ethanol, acetate, and carbon dioxide. Since many pathways in mixed-acid fermentation produce hydrogen gas, these pathways require the levels of hydrogen to be low, as is the case when E. coli lives together with hydrogen-consuming organisms, such as methanogens or sulphate-reducing bacteria.

In addition, E. coli's metabolism can be rewired to solely use CO2 as the source of carbon for biomass production. In other words, this obligate heterotroph's metabolism can be altered to display autotrophic capabilities by heterologously expressing carbon fixation genes as well as formate dehydrogenase and conducting laboratory evolution experiments. This may be done by using formate to reduce electron carriers and supply the ATP required in anabolic pathways inside of these synthetic autotrophs.

E. coli have three native glycolytic pathways: EMPP, EDP, and OPPP. The EMPP employs ten enzymatic steps to yield two pyruvates, two ATP, and two NADH per glucose molecule while OPPP serves as an oxidation route for NADPH synthesis. Although the EDP is the more thermodynamically favorable of the three pathways, E. coli do not use the EDP for glucose metabolism, relying mainly on the EMPP and the OPPP. The EDP mainly remains inactive except for during growth with gluconate.

Catabolite Repression

When growing in the presence of a mixture of sugars, bacteria will often consume the sugars sequentially through a process known as catabolite repression. By repressing the expression of the genes involved in metabolizing the less preferred sugars, cells will usually first consume the sugar yielding the highest growth rate, followed by the sugar yielding the next highest growth rate, and so on. In doing so the cells ensure that their limited metabolic resources are being used to maximize the rate of growth. The well-used example of this with E. coli involves the growth of the bacterium on glucose and lactose, where E. coli will consume glucose before lactose. Catabolite repression has also been observed in E.coli in the presence of other non-glucose sugars, such as arabinose and xylose, sorbitol, rhamnose, and ribose. In E. coli, glucose catabolite repression is regulated by the phosphotransferase system, a multi-protein phosphorylation cascade that couples glucose uptake and metabolism.

Culture growth

Optimum growth of E. coli occurs at 37 °C (98.6 °F), but some laboratory strains can multiply at temperatures up to 49 °C (120 °F). E. coli grows in a variety of defined laboratory media, such as lysogeny broth, or any medium that contains glucose, ammonium phosphate monobasic, sodium chloride, magnesium sulfate, potassium phosphate dibasic, and water. Growth can be driven by aerobic or anaerobic respiration, using a large variety of redox pairs, including the oxidation of pyruvic acid, formic acid, hydrogen, and amino acids, and the reduction of substrates such as oxygen, nitrate, fumarate, dimethyl sulfoxide, and trimethylamine N-oxide. E. coli is classified as a facultative anaerobe. It uses oxygen when it is present and available. It can, however, continue to grow in the absence of oxygen using fermentation or anaerobic respiration. The ability to continue growing in the absence of oxygen is an advantage to bacteria because their survival is increased in environments where water predominates.

Redistribution of fluxes between the three primary glucose catabolic pathways: EMPP (red), EDP (blue), and OPPP (orange) via the knockout of pfkA and overexpression of EDP genes (edd and eda).

Cell cycle

The bacterial cell cycle is divided into three stages. The B period occurs between the completion of cell division and the beginning of DNA replication. The C period encompasses the time it takes to replicate the chromosomal DNA. The D period refers to the stage between the conclusion of DNA replication and the end of cell division. The doubling rate of E. coli is higher when more nutrients are available. However, the length of the C and D periods do not change, even when the doubling time becomes less than the sum of the C and D periods. At the fastest growth rates, replication begins before the previous round of replication has completed, resulting in multiple replication forks along the DNA and overlapping cell cycles.

The number of replication forks in fast growing E. coli typically follows 2n (n = 1, 2 or 3). This only happens if replication is initiated simultaneously from all origins of replications, and is referred to as synchronous replication. However, not all cells in a culture replicate synchronously. In this case cells do not have multiples of two replication forks. Replication initiation is then referred to being asynchronous. However, asynchrony can be caused by mutations to for instance DnaA or DnaA initiator-associating protein DiaA.

Genetic adaptation

E. coli and related bacteria possess the ability to transfer DNA via bacterial conjugation or transduction, which allows genetic material to spread horizontally through an existing population. The process of transduction, which uses the bacterial virus called a bacteriophage, is where the spread of the gene encoding for the Shiga toxin from the Shigella bacteria to E. coli helped produce E. coli O157:H7, the Shiga toxin-producing strain of E. coli.

Diversity

E. coli encompasses an enormous population of bacteria that exhibit a very high degree of both genetic and phenotypic diversity. Genome sequencing of many isolates of E. coli and related bacteria shows that a taxonomic reclassification would be desirable. However, this has not been done, largely due to its medical importance, and E. coli remains one of the most diverse bacterial species: only 20% of the genes in a typical E. coli genome is shared among all strains.

In fact, from the more constructive point of view, the members of genus Shigella (S. dysenteriae, S. flexneri, S. boydii, and S. sonnei) should be classified as E. coli strains, a phenomenon termed taxa in disguise. Similarly, other strains of E. coli (e.g. the K-12 strain commonly used in recombinant DNA work) are sufficiently different that they would merit reclassification.

A strain is a subgroup within the species that has unique characteristics that distinguish it from other strains. These differences are often detectable only at the molecular level; however, they may result in changes to the physiology or lifecycle of the bacterium. For example, a strain may gain pathogenic capacity, the ability to use a unique carbon source, the ability to take upon a particular ecological niche, or the ability to resist antimicrobial agents. Different strains of E. coli are often host-specific, making it possible to determine the source of fecal contamination in environmental samples. For example, knowing which E. coli strains are present in a water sample allows researchers to make assumptions about whether the contamination originated from a human, another mammal, or a bird.

A colony of E. coli growing

Serotypes

E.coli colonies on agar.
E. coli on sheep blood agar.

A common subdivision system of E. coli, but not based on evolutionary relatedness, is by serotype, which is based on major surface antigens (O antigen: part of lipopolysaccharide layer; H: flagellin; K antigen: capsule), e.g. O157:H7). It is, however, common to cite only the serogroup, i.e. the O-antigen. At present, about 190 serogroups are known. The common laboratory strain has a mutation that prevents the formation of an O-antigen and is thus not typeable.

Genome plasticity and evolution

E. coli colonies
E. coli growing on basic cultivation media.

Like all lifeforms, new strains of E. coli evolve through the natural biological processes of mutation, gene duplication, and horizontal gene transfer; in particular, 18% of the genome of the laboratory strain MG1655 was horizontally acquired since the divergence from Salmonella. E. coli K-12 and E. coli B strains are the most frequently used varieties for laboratory purposes. Some strains develop traits that can be harmful to a host animal. These virulent strains typically cause a bout of diarrhea that is often self-limiting in healthy adults but is frequently lethal to children in the developing world. More virulent strains, such as O157:H7, cause serious illness or death in the elderly, the very young, or the immunocompromised.

The genera Escherichia and Salmonella diverged around 102 million years ago (credibility interval: 57–176 mya), which coincides with the divergence of their hosts: the former being found in mammals and the latter in birds and reptiles. This was followed by a split of an Escherichia ancestor into five species (E. albertii, E. coli, E. fergusonii, E. hermannii, and E. vulneris). The last E. coli ancestor split between 20 and 30 million years ago.

The long-term evolution experiments using E. coli, begun by Richard Lenski in 1988, have allowed direct observation of genome evolution over more than 65,000 generations in the laboratory. For instance, E. coli typically do not have the ability to grow aerobically with citrate as a carbon source, which is used as a diagnostic criterion with which to differentiate E. coli from other, closely, related bacteria such as Salmonella. In this experiment, one population of E. coli unexpectedly evolved the ability to aerobically metabolize citrate, a major evolutionary shift with some hallmarks of microbial speciation.

Scanning electron micrograph of an E. coli colony.

In the microbial world, a relationship of predation can be established similar to that observed in the animal world. Considered, it has been seen that E. coli is the prey of multiple generalist predators, such as Myxococcus xanthus. In this predator-prey relationship, a parallel evolution of both species is observed through genomic and phenotypic modifications, in the case of E. coli the modifications are modified in two aspects involved in their virulence such as mucoid production (excessive production of exoplasmic acid alginate ) and the suppression of the OmpT gene, producing in future generations a better adaptation of one of the species that is counteracted by the evolution of the other, following a co-evolutionary model demonstrated by the Red Queen hypothesis.

Neotype strain

E. coli is the type species of the genus (Escherichia) and in turn Escherichia is the type genus of the family Enterobacteriaceae, where the family name does not stem from the genus Enterobacter + "i" (sic.) + "aceae", but from "enterobacterium" + "aceae" (enterobacterium being not a genus, but an alternative trivial name to enteric bacterium).

The original strain described by Escherich is believed to be lost, consequently a new type strain (neotype) was chosen as a representative: the neotype strain is U5/41T, also known under the deposit names DSM 30083, ATCC 11775, and NCTC 9001, which is pathogenic to chickens and has an O1:K1:H7 serotype. However, in most studies, either O157:H7, K-12 MG1655, or K-12 W3110 were used as a representative E. coli. The genome of the type strain has only lately been sequenced.

Phylogeny of E. coli strains

Many strains belonging to this species have been isolated and characterised. In addition to serotype (vide supra), they can be classified according to their phylogeny, i.e. the inferred evolutionary history, as shown below where the species is divided into six groups. Particularly the use of whole genome sequences yields highly supported phylogenies. Based on such data, five subspecies of E. coli were distinguished.

The link between phylogenetic distance ("relatedness") and pathology is small, e.g. the O157:H7 serotype strains, which form a clade ("an exclusive group")—group E below—are all enterohaemorragic strains (EHEC), but not all EHEC strains are closely related. In fact, four different species of Shigella are nested among E. coli strains (vide supra), while E. albertii and E. fergusonii are outside this group. Indeed, all Shigella species were placed within a single subspecies of E. coli in a phylogenomic study that included the type strain, and for this reason an according reclassification is difficult. All commonly used research strains of E. coli belong to group A and are derived mainly from Clifton's K-12 strain (λ+ F+; O16) and to a lesser degree from d'Herelle's Bacillus coli strain (B strain)(O7).

Genomics

An image of E. coli using early electron microscopy.

The first complete DNA sequence of an E. coli genome (laboratory strain K-12 derivative MG1655) was published in 1997. It is a circular DNA molecule 4.6 million base pairs in length, containing 4288 annotated protein-coding genes (organized into 2584 operons), seven ribosomal RNA (rRNA) operons, and 86 transfer RNA (tRNA) genes. Despite having been the subject of intensive genetic analysis for about 40 years, many of these genes were previously unknown. The coding density was found to be very high, with a mean distance between genes of only 118 base pairs. The genome was observed to contain a significant number of transposable genetic elements, repeat elements, cryptic prophages, and bacteriophage remnants.

More than three hundred complete genomic sequences of Escherichia and Shigella species are known. The genome sequence of the type strain of E. coli was added to this collection before 2014. Comparison of these sequences shows a remarkable amount of diversity; only about 20% of each genome represents sequences present in every one of the isolates, while around 80% of each genome can vary among isolates. Each individual genome contains between 4,000 and 5,500 genes, but the total number of different genes among all of the sequenced E. coli strains (the pangenome) exceeds 16,000. This very large variety of component genes has been interpreted to mean that two-thirds of the E. coli pangenome originated in other species and arrived through the process of horizontal gene transfer.

Gene nomenclature

Genes in E. coli are usually named by 4-letter acronyms that derive from their function (when known) and italicized. For instance, recA is named after its role in homologous recombination plus the letter A. Functionally related genes are named recB, recC, recD etc. The proteins are named by uppercase acronyms, e.g. RecA, RecB, etc. When the genome of E. coli was sequenced, all genes were numbered (more or less) in their order on the genome and abbreviated by b numbers, such as b2819 (= recD). The "b" names were created after Fred Blattner, who led the genome sequence effort. Another numbering system was introduced with the sequence of another E. coli strain, W3110, which was sequenced in Japan and hence uses numbers starting by JW... (Japanese W3110), e.g. JW2787 (= recD). Hence, recD = b2819 = JW2787. Note, however, that most databases have their own numbering system, e.g. the EcoGene database uses EG10826 for recD. Finally, ECK numbers are specifically used for alleles in the MG1655 strain of E. coli K-12. Complete lists of genes and their synonyms can be obtained from databases such as EcoGene or Uniprot.

Proteomics

Proteome

Several studies have investigated the proteome of E. coli. By 2006, 1,627 (38%) of the 4,237 open reading frames (ORFs) had been identified experimentally. The 4,639,221–base pair sequence of Escherichia coli K-12 is presented. Of 4288 protein-coding genes annotated, 38 percent have no attributed function. Comparison with five other sequenced microbes reveals ubiquitous as well as narrowly distributed gene families; many families of similar genes within E. coli are also evident. The largest family of paralogous proteins contains 80 ABC transporters. The genome as a whole is strikingly organized with respect to the local direction of replication; guanines, oligonucleotides possibly related to replication and recombination, and most genes are so oriented. The genome also contains insertion sequence (IS) elements, phage remnants, and many other patches of unusual composition indicating genome plasticity through horizontal transfer.

Interactome

The interactome of E. coli has been studied by affinity purification and mass spectrometry (AP/MS) and by analyzing the binary interactions among its proteins.

Protein complexes. A 2006 study purified 4,339 proteins from cultures of strain K-12 and found interacting partners for 2,667 proteins, many of which had unknown functions at the time. A 2009 study found 5,993 interactions between proteins of the same E. coli strain, though these data showed little overlap with those of the 2006 publication.

Binary interactions. Rajagopala et al. (2014) have carried out systematic yeast two-hybrid screens with most E. coli proteins, and found a total of 2,234 protein-protein interactions. This study also integrated genetic interactions and protein structures and mapped 458 interactions within 227 protein complexes.

Normal microbiota

E. coli belongs to a group of bacteria informally known as coliforms that are found in the gastrointestinal tract of warm-blooded animals. E. coli normally colonizes an infant's gastrointestinal tract within 40 hours of birth, arriving with food or water or from the individuals handling the child. In the bowel, E. coli adheres to the mucus of the large intestine. It is the primary facultative anaerobe of the human gastrointestinal tract. (Facultative anaerobes are organisms that can grow in either the presence or absence of oxygen.) As long as these bacteria do not acquire genetic elements encoding for virulence factors, they remain benign commensals.

Therapeutic use

Due to the low cost and speed with which it can be grown and modified in laboratory settings, E. coli is a popular expression platform for the production of recombinant proteins used in therapeutics. One advantage to using E. coli over another expression platform is that E. coli naturally does not export many proteins into the periplasm, making it easier to recover a protein of interest without cross-contamination. The E. coli K-12 strains and their derivatives (DH1, DH5α, MG1655, RV308 and W3110) are the strains most widely used by the biotechnology industry. Nonpathogenic E. coli strain Nissle 1917 (EcN), (Mutaflor) and E. coli O83:K24:H31 (Colinfant)) are used as probiotic agents in medicine, mainly for the treatment of various gastrointestinal diseases, including inflammatory bowel disease. It is thought that the EcN strain might impede the growth of opportunistic pathogens, including Salmonella and other coliform enteropathogens, through the production of microcin proteins the production of siderophores.

Role in disease

Most E. coli strains do not cause disease, naturally living in the gut, but virulent strains can cause gastroenteritis, urinary tract infections, neonatal meningitis, hemorrhagic colitis, and Crohn's disease. Common signs and symptoms include severe abdominal cramps, diarrhea, hemorrhagic colitis, vomiting, and sometimes fever. In rarer cases, virulent strains are also responsible for bowel necrosis (tissue death) and perforation without progressing to hemolytic-uremic syndrome, peritonitis, mastitis, sepsis, and Gram-negative pneumonia. Very young children are more susceptible to develop severe illness, such as hemolytic uremic syndrome; however, healthy individuals of all ages are at risk to the severe consequences that may arise as a result of being infected with E. coli.

Some strains of E. coli, for example O157:H7, can produce Shiga toxin (classified as a bioterrorism agent). The Shiga toxin causes inflammatory responses in target cells of the gut, leaving behind lesions which result in the bloody diarrhea that is a symptom of a Shiga toxin-producing E. coli (STEC) infection. This toxin further causes premature destruction of the red blood cells, which then clog the body's filtering system, the kidneys, in some rare cases (usually in children and the elderly) causing hemolytic-uremic syndrome (HUS), which may lead to kidney failure and even death. Signs of hemolytic uremic syndrome include decreased frequency of urination, lethargy, and paleness of cheeks and inside the lower eyelids. In 25% of HUS patients, complications of nervous system occur, which in turn causes strokes. In addition, this strain causes the buildup of fluid (since the kidneys do not work), leading to edema around the lungs, legs, and arms. This increase in fluid buildup especially around the lungs impedes the functioning of the heart, causing an increase in blood pressure.

Uropathogenic E. coli (UPEC) is one of the main causes of urinary tract infections. It is part of the normal microbiota in the gut and can be introduced in many ways. In particular for females, the direction of wiping after defecation (wiping back to front) can lead to fecal contamination of the urogenital orifices. Anal intercourse can also introduce this bacterium into the male urethra, and in switching from anal to vaginal intercourse, the male can also introduce UPEC to the female urogenital system.

Enterotoxigenic E. coli (ETEC) is the most common cause of traveler's diarrhea, with as many as 840 million cases worldwide in developing countries each year. The bacteria, typically transmitted through contaminated food or drinking water, adheres to the intestinal lining, where it secretes either of two types of enterotoxins, leading to watery diarrhea. The rate and severity of infections are higher among children under the age of five, including as many as 380,000 deaths annually.

In May 2011, one E. coli strain, O104:H4, was the subject of a bacterial outbreak that began in Germany. Certain strains of E. coli are a major cause of foodborne illness. The outbreak started when several people in Germany were infected with enterohemorrhagic E. coli (EHEC) bacteria, leading to hemolytic-uremic syndrome (HUS), a medical emergency that requires urgent treatment. The outbreak did not only concern Germany, but also 15 other countries, including regions in North America. On 30 June 2011, the German Bundesinstitut für Risikobewertung (BfR) (Federal Institute for Risk Assessment, a federal institute within the German Federal Ministry of Food, Agriculture and Consumer Protection) announced that seeds of fenugreek from Egypt were likely the cause of the EHEC outbreak.

Some studies have demonstrated an absence of E.coli in the gut flora of subjects with the metabolic disorder Phenylketonuria. It is hypothesized that the absence of these normal bacterium impairs the production of the key vitamins B2 (riboflavin) and K2 (menaquinone) - vitamins which are implicated in many physiological roles in humans such as cellular and bone metabolism - and so contributes to the disorder.

Incubation period

The time between ingesting the STEC bacteria and feeling sick is called the "incubation period". The incubation period is usually 3–4 days after the exposure, but may be as short as 1 day or as long as 10 days. The symptoms often begin slowly with mild belly pain or non-bloody diarrhea that worsens over several days. HUS, if it occurs, develops an average 7 days after the first symptoms, when the diarrhea is improving.

Treatment

The mainstay of treatment is the assessment of dehydration and replacement of fluid and electrolytes. Administration of antibiotics has been shown to shorten the course of illness and duration of excretion of enterotoxigenic E. coli (ETEC) in adults in endemic areas and in traveller's diarrhea, though the rate of resistance to commonly used antibiotics is increasing and they are generally not recommended. The antibiotic used depends upon susceptibility patterns in the particular geographical region. Currently, the antibiotics of choice are fluoroquinolones or azithromycin, with an emerging role for rifaximin. Oral rifaximin, a semisynthetic rifamycin derivative, is an effective and well-tolerated antibacterial for the management of adults with non-invasive traveller's diarrhea. Rifaximin was significantly more effective than placebo and no less effective than ciprofloxacin in reducing the duration of diarrhea. While rifaximin is effective in patients with E. coli-predominant traveller's diarrhea, it appears ineffective in patients infected with inflammatory or invasive enteropathogens.

Prevention

ETEC is the type of E. coli that most vaccine development efforts are focused on. Antibodies against the LT and major CFs of ETEC provide protection against LT-producing, ETEC-expressing homologous CFs. Oral inactivated vaccines consisting of toxin antigen and whole cells, i.e. the licensed recombinant cholera B subunit (rCTB)-WC cholera vaccine Dukoral, have been developed. There are currently no licensed vaccines for ETEC, though several are in various stages of development. In different trials, the rCTB-WC cholera vaccine provided high (85–100%) short-term protection. An oral ETEC vaccine candidate consisting of rCTB and formalin inactivated E. coli bacteria expressing major CFs has been shown in clinical trials to be safe, immunogenic, and effective against severe diarrhoea in American travelers but not against ETEC diarrhoea in young children in Egypt. A modified ETEC vaccine consisting of recombinant E. coli strains over-expressing the major CFs and a more LT-like hybrid toxoid called LCTBA, are undergoing clinical testing.

Other proven prevention methods for E. coli transmission include handwashing and improved sanitation and drinking water, as transmission occurs through fecal contamination of food and water supplies. Additionally, thoroughly cooking meat and avoiding consumption of raw, unpasteurized beverages, such as juices and milk are other proven methods for preventing E.coli. Lastly, avoid cross-contamination of utensils and work spaces when preparing food.

Model organism in life science research

Escherichia coli Bacterium, 2021, Illustration by David S. Goodsell, RCSB Protein Data Bank
This painting shows a cross-section through an Escherichia coli cell. The characteristic two-membrane cell wall of gram-negative bacteria is shown in green, with many lipopolysaccharide chains extending from the surface and a network of cross-linked peptidoglycan strands between the membranes. The genome of the cell forms a loosely-defined "nucleoid", shown here in yellow, and interacts with many DNA-binding proteins, shown in tan and orange. Large soluble molecules, such as ribosomes (colored in reddish purple), mostly occupy the space around the nucleoid.

Because of its long history of laboratory culture and ease of manipulation, E. coli plays an important role in modern biological engineering and industrial microbiology. The work of Stanley Norman Cohen and Herbert Boyer in E. coli, using plasmids and restriction enzymes to create recombinant DNA, became a foundation of biotechnology.

E. coli is a very versatile host for the production of heterologous proteins, and various protein expression systems have been developed which allow the production of recombinant proteins in E. coli. Researchers can introduce genes into the microbes using plasmids which permit high level expression of protein, and such protein may be mass-produced in industrial fermentation processes. One of the first useful applications of recombinant DNA technology was the manipulation of E. coli to produce human insulin.

Many proteins previously thought difficult or impossible to be expressed in E. coli in folded form have been successfully expressed in E. coli. For example, proteins with multiple disulphide bonds may be produced in the periplasmic space or in the cytoplasm of mutants rendered sufficiently oxidizing to allow disulphide-bonds to form, while proteins requiring post-translational modification such as glycosylation for stability or function have been expressed using the N-linked glycosylation system of Campylobacter jejuni engineered into E. coli.

Modified E. coli cells have been used in vaccine development, bioremediation, production of biofuels, lighting, and production of immobilised enzymes.

Strain K-12 is a mutant form of E. coli that over-expresses the enzyme Alkaline Phosphatase (ALP). The mutation arises due to a defect in the gene that constantly codes for the enzyme. A gene that is producing a product without any inhibition is said to have constitutive activity. This particular mutant form is used to isolate and purify the aforementioned enzyme.

Strain OP50 of Escherichia coli is used for maintenance of Caenorhabditis elegans cultures.

Strain JM109 is a mutant form of E. coli that is recA and endA deficient. The strain can be utilized for blue/white screening when the cells carry the fertility factor episome Lack of recA decreases the possibility of unwanted restriction of the DNA of interest and lack of endA inhibit plasmid DNA decomposition. Thus, JM109 is useful for cloning and expression systems.

Model organism

E. coli is frequently used as a model organism in microbiology studies. Cultivated strains (e.g. E. coli K12) are well-adapted to the laboratory environment, and, unlike wild-type strains, have lost their ability to thrive in the intestine. Many laboratory strains lose their ability to form biofilms. These features protect wild-type strains from antibodies and other chemical attacks, but require a large expenditure of energy and material resources. E. coli is often used as a representative microorganism in the research of novel water treatment and sterilisation methods, including photocatalysis. By standard plate count methods, following sequential dilutions, and growth on agar gel plates, the concentration of viable organisms or CFUs (Colony Forming Units), in a known volume of treated water can be evaluated, allowing the comparative assessment of materials performance.

In 1946, Joshua Lederberg and Edward Tatum first described the phenomenon known as bacterial conjugation using E. coli as a model bacterium, and it remains the primary model to study conjugation. E. coli was an integral part of the first experiments to understand phage genetics, and early researchers, such as Seymour Benzer, used E. coli and phage T4 to understand the topography of gene structure. Prior to Benzer's research, it was not known whether the gene was a linear structure, or if it had a branching pattern.

E. coli was one of the first organisms to have its genome sequenced; the complete genome of E. coli K12 was published by Science in 1997

From 2002 to 2010, a team at the Hungarian Academy of Science created a strain of Escherichia coli called MDS42, which is now sold by Scarab Genomics of Madison, WI under the name of "Clean Genome. E.coli", where 15% of the genome of the parental strain (E. coli K-12 MG1655) were removed to aid in molecular biology efficiency, removing IS elements, pseudogenes and phages, resulting in better maintenance of plasmid-encoded toxic genes, which are often inactivated by transposons. Biochemistry and replication machinery were not altered.

By evaluating the possible combination of nanotechnologies with landscape ecology, complex habitat landscapes can be generated with details at the nanoscale. On such synthetic ecosystems, evolutionary experiments with E. coli have been performed to study the spatial biophysics of adaptation in an island biogeography on-chip.

Studies are also being performed attempting to program E. coli to solve complicated mathematics problems, such as the Hamiltonian path problem.

In other studies, non-pathogenic E. coli has been used as a model microorganism towards understanding the effects of simulated microgravity (on Earth) on the same.

History

In 1885, the German-Austrian pediatrician Theodor Escherich discovered this organism in the feces of healthy individuals. He called it Bacterium coli commune because it is found in the colon. Early classifications of prokaryotes placed these in a handful of genera based on their shape and motility (at that time Ernst Haeckel's classification of bacteria in the kingdom Monera was in place).

Bacterium coli was the type species of the now invalid genus Bacterium when it was revealed that the former type species ("Bacterium triloculare") was missing. Following a revision of Bacterium, it was reclassified as Bacillus coli by Migula in 1895 and later reclassified in the newly created genus Escherichia, named after its original discoverer.

In 1996 the world's worst outbreak of E. coli food poisoning occurred in Wishaw, Scotland, killing 21 people.

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