Instruct: Given a question, retrieve relevant passages that can help answer the question.
Query: Who first discovered Botulinum toxin?
In 1895 (seventy-five years later), Émile van Ermengem, professor of bacteriology and a student of Robert Koch, correctly described "Clostridium botulinum" as the bacterial source of the toxin. Thirty-four attendees at a funeral were poisoned by eating partially salted ham, an extract of which was found to cause botulism-like paralysis in laboratory animals. Van Ermengem isolated and grew the bacterium, and described its toxin, which was later purified by P Tessmer Snipe and Hermann Sommer.
In all cases, illness is caused by the botulinum toxin produced by the bacterium "C. botulinum" in anaerobic conditions and not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that fire (depolarize) at a higher frequency first.
In the 1970's, Scott started to experiment with Botox as a therapy for strabismus, due to its muscle relaxing features. In 1978, he received permission from the FDA to test Botox in clinical trials with humans, which was at that time groundbreaking, as Botox in higher dosages could paralyze and ultimately kill humans. After successful clinical trials on patients, the treatment received FDA approval in 1989. Two years later he sold the patent to Allergen for $9M. Allergen which changed the name for Oculinum to Botox. Its 1991 revenue amounted to $13M, as it was solely used for medical treatments. As Allergen conducted further studies with Botox for its cosmetic wrinkle reducing quality, it received FDA approval in 2002. Today, Botox annual revenue is estimated to be more than $2.5B. Scott has published numerous articles on the subject of strabismus. He founded the Strabismus Research Foundation in San Francisco, and continues to conduct research on strabismus and related topics together with Joel M. Miller and Talita Malta e Cunha.
Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium "Clostridium botulinum". The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. Vomiting, swelling of the abdomen, and diarrhea may also occur. The disease does not usually affect consciousness or cause a fever.
Botulism can be spread in several ways. The bacterial spores which cause it are common in both soil and water. They produce the botulinum toxin when exposed to low oxygen levels and certain temperatures. Foodborne botulism happens when food containing the toxin is eaten. Infant botulism happens when the bacteria develops in the intestines and releases the toxin. This typically only occurs in children less than six months old, as protective mechanisms develop after that time. Wound botulism is found most often among those who inject street drugs. In this situation, spores enter a wound, and in the absence of oxygen, release the toxin. It is not passed directly between people. The diagnosis is confirmed by finding the toxin or bacteria in the person in question.
Prevention is primarily by proper food preparation. The toxin, though not the organism, is destroyed by heating it to more than for longer than 5 minutes. Honey can contain the organism, and for this reason, honey should not be fed to children under 12 months. Treatment is with an antitoxin. In those who lose their ability to breathe on their own, mechanical ventilation may be necessary for months. Antibiotics may be used for wound botulism. Death occurs in 5 to 10% of people. Botulism also affects many other animals. The word is from Latin, "botulus", meaning sausage. Early descriptions of botulism date from at least as far back as 1793 in Germany.
For decades biologists had been at work on the medicine that became penicillin. In 1928, Scottish biologist Alexander Fleming discovered a substance that killed a number of disease-causing bacteria. In 1929, he named the new substance "penicillin". His publications were largely ignored at first, but it became a significant antibiotic in the 1930s. In 1930, Cecil George Paine, a pathologist at Sheffield Royal Infirmary, used penicillin to treat sycosis barbae, eruptions in beard follicles, but was unsuccessful. Moving on to ophthalmia neonatorum, a gonococcal infection in infants, he achieved the first recorded cure with penicillin, on November 25, 1930. He then cured four additional patients (one adult and three infants) of eye infections, but failed to cure a fifth.
The genus "Neisseria" is named after the German bacteriologist Albert Neisser, who in 1879 discovered its first example, "Neisseria gonorrheae", the pathogen which causes the human disease gonorrhea. Neisser also codiscovered the pathogen that causes leprosy, "Mycobacterium leprae". These discoveries were made possible by the development of new staining techniques which he helped to develop.
Botulinum toxin therapy of strabismus is a medical technique used sometimes in the management of strabismus, in which botulinum toxin is injected into selected extraocular muscles in order to reduce the misalignment of the eyes. The injection of the toxin to treat strabismus, reported upon in 1981, is considered to be the first ever use of botulinum toxin for therapeutic purposes. Today, the injection of botulinum toxin into the muscles that surround the eyes is one of the available options in the management of strabismus. Other options for strabismus management are vision therapy and occlusion therapy, corrective glasses (or contact lenses) and prism glasses, and strabismus surgery.
A few strains from organisms genetically identified as other "Clostridium" species have caused human botulism: "C. butyricum" has produced type E toxin and "C. baratii" had produced type F toxin. The ability of "C. botulinum" to naturally transfer neurotoxin genes to other clostridia is concerning, especially in the food industry, where preservation systems are designed to destroy or inhibit only "C. botulinum" but not other "Clostridium" species.
Khalaf Bushara and David Park were the first to demonstrate a nonmuscular use of BTX-A while treating patients with hemifacial spasm in England in 1993, showing that botulinum toxin injections inhibit sweating, and so are useful in treating hyperhidrosis (excessive sweating). BTX-A has since been approved for the treatment of severe primary axillary hyperhidrosis (excessive underarm sweating of unknown cause), which cannot be managed by topical agents.
The "Clostridium botulinum" bacteria are the cause of botulism. Vegetative cells of "C. botulinum" may be ingested. Introduction of the bacteria may also occur via endospores in a wound. When the bacteria are in vivo, they induce flaccid paralysis. This happens because "C. botulinum" produces a toxin which blocks the release of acetylcholine. Botulism toxin blocks the exocytosis of presynaptic vesicles containing acetylcholine (ACh). When this occurs, the muscles are unable to contract. Other symptoms associated with infection from this neurotoxin include double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Botulism prevents muscle contraction by blocking the release of acetylcholine, thereby halting postsynaptic activity of the neuromuscular junction. If its effects reach the respiratory muscles, then it can cause respiratory failure, leading to death.
Dopamine was first synthesized in 1910 by George Barger and James Ewens at Wellcome Laboratories in London, England and first identified in the human brain by Kathleen Montagu in 1957. It was named dopamine because it is a monoamine whose precursor in the Barger-Ewens synthesis is 3,4-dihydroxyphenylalanine (levodopa or L-DOPA). Dopamine's function as a neurotransmitter was first recognized in 1958 by Arvid Carlsson and Nils-Åke Hillarp at the Laboratory for Chemical Pharmacology of the National Heart Institute of Sweden. Carlsson was awarded the 2000 Nobel Prize in Physiology or Medicine for showing that dopamine is not only a precursor of norepinephrine (noradrenaline) and epinephrine (adrenaline), but is also itself a neurotransmitter.
On July 29, 2016, Food and Drug Administration (FDA), of the United States of America approved abobotulinumtoxinA for injection for the treatment of lower limb spasticity in pediatric patients two years of age and older. AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. In the United States of America, the FDA approves the text of the labels of prescription medicines. The FDA approves which medical conditions the drug manufacturer may sell the drug for. However, those approved by the FDA to prescribe these drugs may freely prescribe them for any condition they wish, called off-label use. Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.
Alexander Fleming had first discovered penicillin by accident in 1928, but at that time believed it had little application. When Florey and his team recognised the potential of the discovery for combating bacterial infection, they faced the problem of how to manufacture penicillin in sufficient quantities to be of use. Heatley, although the junior member of the team, possessed a natural gift for ingenuity and invention. It was he who suggested transferring the active ingredient of penicillin back into water by changing its acidity, thus purifying the penicillin.
The discovery of insulin at the University of Toronto in 1921 is considered among the most significant events in the history of medicine. The stem cell was discovered at the university in 1963, forming the basis for bone marrow transplantation and all subsequent research on adult and embryonic stem cells. This was the first of many findings at Toronto relating to stem cells, including the identification of pancreatic and retinal stem cells. The cancer stem cell was first identified in 1997 by Toronto researchers, who have since found stem cell associations in leukemia, brain tumors and colorectal cancer. Medical inventions developed at Toronto include the glycaemic index, the infant cereal Pablum, the use of protective hypothermia in open heart surgery and the first artificial cardiac pacemaker. The first successful single-lung transplant was performed at Toronto in 1981, followed by the first nerve transplant in 1988, and the first double-lung transplant in 1989. Researchers identified the maturation promoting factor that regulates cell division, and discovered the T-cell receptor, which triggers responses of the immune system. The university is credited with isolating the genes that cause Fanconi anemia, cystic fibrosis and early-onset Alzheimer's disease, among numerous other diseases. Between 1914 and 1972, the university operated the Connaught Medical Research Laboratories, now part of the pharmaceutical corporation Sanofi-Aventis. Among the research conducted at the laboratory was the development of gel electrophoresis.
The second half of the 20th century was the golden age of virus discovery and most of the over 2,000 recognised species of animal, plant, and bacterial viruses were discovered during these years. In 1957, equine arterivirus and the cause of Bovine virus diarrhoea (a pestivirus) were discovered. In 1963, the hepatitis B virus was discovered by Baruch Blumberg, and in 1965, Howard Temin described the first retrovirus. Reverse transcriptase, the enzyme that retroviruses use to make DNA copies of their RNA, was first described in 1970, independently by Howard Martin Temin and David Baltimore. In 1983 Luc Montagnier's team at the Pasteur Institute in France, first isolated the retrovirus now called HIV. In 1989 Michael Houghton's team at Chiron Corporation discovered Hepatitis C.
Secretin was the first hormone to be identified. In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion. It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion "secretin". Secretin was the first such "chemical messenger" identified. This type of substance is now called a hormone, a term coined by Bayliss in 1905.
Graphene was discovered at the University of Manchester in 2004 under Prof Sir Andre Geim and Sir Konstantin Novoselov.
At the Calico Printers' Association in Manchester in 1941, John Rex Whinfield and James Tennant Dickson discovered polyethylene terephthalate, known as PET, a common polyester compound found in plastic bottles and food, and also known as Terylene or Dacron. Cheslene and Crepes of Macclesfield discovered crimplene (the fabric that is now referred to as polyester). ICI Dyestuffs at Hexagon House, in Blackley in north Manchester, discovered Procion dyes. At the Winnington Laboratory on 27 March 1933, Eric Fawcett and Reginald Gibson discovered polythene in an ICI laboratory in Northwich, when reacting benzaldehyde with ethene at a pressure of 2,000 atmospheres; the process was improved in 1935 by Sir Michael Perrin.
The Belgian company Plant Genetic Systems (now part of Bayer CropScience) was the first company (in 1985) to develop genetically modified crops (tobacco) with insect tolerance by expressing "cry" genes from "B. thuringiensis"; the resulting crops contain delta endotoxin. The Bt tobacco was never commercialized; tobacco plants are used to test genetic modifications since they are easy to manipulate genetically and are not part of the food supply.
In 1995, potato plants producing CRY 3A Bt toxin were approved safe by the Environmental Protection Agency, making it the first human-modified pesticide-producing crop to be approved in the USA, though many plants produce pesticides naturally, including tobacco, coffee plants, cocoa, and black walnut. This was the 'New Leaf' potato, and it was removed from the market in 2001 due to lack of interest. For current crops and their acreage under cultivation, see genetically modified crops.
The causative pathogen was first identified by Naosuke Hayashi in 1920. Confident that the organism was a protozoan, Hayashi concluded, stating, "I have reached the conclusion that the virus of the disease is the species of "Piroplasma" [protozoan] in question... I consider the organism in Tsutsugamushi disease as a hitherto undescribed species, and at the suggestion of Dr. Henry B. Ward designate it as "Theileria tsutsugamushi"." Discovering the similarities with the bacterium "Rickettsia prowazekii", Mataro Nagayo and colleagues gave a new classification with the name "Rickettsia orientalis" in 1930. ("R. prowazekii" is a causative bacterium of epidemic typhus first discovered by American physicians Howard Taylor Ricketts and Russell M. Wilder in 1910; and described by a Brazilian physician Henrique da Rocha Lima in 1916.)
The history of biochemistry can be said to have started with the ancient Greeks who were interested in the composition and processes of life, although biochemistry as a specific scientific discipline has its beginning around the early 19th century. Some argued that the beginning of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833 by Anselme Payen, while others considered Eduard Buchner's first demonstration of a complex biochemical process alcoholic fermentation in cell-free extracts to be the birth of biochemistry. Some might also point to the influential work of Justus von Liebig from 1842, "Animal chemistry, or, Organic chemistry in its applications to physiology and pathology", which presented a chemical theory of metabolism, or even earlier to the 18th century studies on fermentation and respiration by Antoine Lavoisier.
Pathologist Alfred Whitmore and assistant Krishnaswami first reported the disease among beggars and morphine addicts at autopsy in Rangoon, present-day Myanmar, in a report published in 1912. They distinguished it from glanders, a disease of humans and animals that is similar in presentation, but caused by a different micro-organism. "B. pseudomallei", also known as the Whitmore bacillus, was identified in 1917 in Kuala Lumpur. Arthur Conan Doyle may have read the 1912 report before writing a short story that involved the fictitious tropical disease "tapanuli fever" in a Sherlock Holmes adventure.
In 1820, Justinus Kerner, a small-town German medical officer and romantic poet, gave the first complete description of clinical botulism based on extensive clinical observations of so-called “sausage poisoning”. Following experiments on animals and on himself, he concluded that the toxin acts by interrupting signal transmission in the somatic and autonomic motor systems, without affecting sensory signals or mental functions. He observed that the toxin develops under anaerobic conditions, and can be lethal in minute doses. His prescience in suggesting that the toxin might be used therapeutically earned him recognition as the pioneer of modern botulinum toxin therapy.
Alan B. Scott first injected botulinum toxin into extraocular muscles since the early 1970s and published his results 1981, giving rise to a wide scope of clinical research on the use of the toxin.
The mechanism of botulinum toxin action – blocking the release from nerve endings of the neurotransmitter acetylcholine – was elucidated in the mid-1900s, and remains an important research topic. Nearly all toxin treatments are based on this effect in various body tissues.
In the United States, botulinum toxin products are manufactured by a variety of companies, for both therapeutic and cosmetic use. A U.S. supplier reported in its company materials in 2011 that it could "supply the world's requirements for 25 indications approved by Government agencies around the world" with less than one gram of raw botulinum toxin. Myobloc or Neurobloc, a botulinum toxin type B product, is produced by Solstice Neurosciences, a subsidiary of US WorldMeds. AbobotulinumtoxinA), a therapeutic formulation of the type A toxin manufactured by Galderma in the United Kingdom, is licensed for the treatment of focal dystonias and certain cosmetic uses in the U.S. and other countries.