First Flight | |
---|---|
Sex | Male |
Foaled | 1967/8 |
Died | 17 May 1999 Large Animal Research Facility, Fort Detrick |
Color | Black |
Owner | U.S. Army |
First Flight was a thoroughbred horse used in the production of the first botulism antitoxin. The horse was used as a research animal between 1978 and 1993 to produce antitoxin for military and civilian personnel. Until the 1990s, serum derived from First Flight was the only source of the antitoxin in the United States.
First Flight was originally bred as a racehorse, but there are no records of him competing in a race in the National Sporting Library & Museum. [1] He was trained to serve as a caisson horse during military funerals at Arlington National Cemetery. However, the 1,200-pound (540 kg) horse was skittish around crowds and prone to bolting. [2]
Botulinum toxin is a highly potent neurotoxin produced by the bacteria Clostridium botulinum, causing paralysis and often leading to death if untreated. [3] There are three naturally occurring subtypes of botulism toxin; however, the four other known subtypes could be weaponised as bio-agents. [4] Horses have been used in the production of antitoxin serum for various diseases since the 19th century due to their physical size and resilience. [1] At age 10, in 1978, First Flight was selected to participate in the botulinum antitoxin program at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland. [2] Another army horse named Abe was also part of the program initially, but experiments and large-scale production of antitoxin utilised only plasma from First Flight, [5] due to its reactivity against all subtypes of botulism toxin. [6]
Researchers injected First Flight with modified, less-deadly toxoids from all seven subtypes until he gained immunity via the production of antibodies from his immune system. Then, they injected live bacteria to increase antibody production. There were around ten to one hundred times the amount of antibodies within First Flight's bloodstream than needed to neutralise the toxin. Blood drawn from First Flight was used to develop the antiserum. [2] This program developed the first botulinum antitoxin, and First Flight was its only source until the 1990s. [4]
In November 1980, First Flight was moved to the University of Minnesota for large-scale plasmapheresis and long-term storage of antibodies. As part of this, First Flight was immunised every forty to one hundred days and plasmapheresed eight times, each removing 10–15% of the animal's blood volume, during the cycle. While at the University of Minnesota, First Flight was permitted periods of rest and regularly tendered to. He was fed a diet of high-protein grain pellets and a daily hay ration. [5] During his time as a research animal, he was often ill-tempered but not dangerous. [2] Antibodies were harvested from First Flight until 1993, [7] and nearly 1,600 litres (420 US gal) of blood were removed during his time in Minnesota. [2]
In 1990, the U.S. Army requested a large production of botulinum antitoxin from the stored antibodies. It was shipped to Saudi Arabia in 1991 as a precaution to treat soldiers and civilians during the First Gulf War due to concern that Iraqi President Saddam Hussein might use biological weapons containing Botulinum toxin. [2] The antitoxin serum has also been used to treat foodborne botulism and infant botulism. [8]
First Flight died from natural causes, aged 31, in his paddock at the Large Animal Research Facility in Fort Detrick. [2] The U.S. Army erected a stone memorial and planted a tree in his honour at Fort Detrick to commemorate his contribution to science. First Flight's ashes are buried nearby. [7] The National Museum of American History holds the horse's halter, lead chain and a vial of antitoxin derived from its blood in its collections. As of January 2024 [update] , they are not currently on display. [3]
In 2010, Heptavalent botulism antitoxin (HBAT) was introduced. It is effective against all seven botulinum toxin subtypes and replaces all earlier non-infant products. HBAT is produced by harvesting antibodies from horses that have been inoculated with botulism, building upon the earlier work developing antitoxin serum from First Flight. [4]
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.
Botulinum toxin, or botulinum neurotoxin, is a highly potent neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction, thus causing flaccid paralysis. The toxin causes the disease botulism. The toxin is also used commercially for medical and cosmetic purposes. Botulinum toxin is an acetylcholine release inhibitor and a neuromuscular blocking agent.
Clostridium botulinum is a gram-positive, rod-shaped, anaerobic, spore-forming, motile bacterium with the ability to produce botulinum toxin, which is a neurotoxin.
Emil von Behring, was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded in that field, for his discovery of a diphtheria antitoxin. He was widely known as a "saviour of children", as diphtheria used to be a major cause of child death. His work with the disease, as well as tetanus, has come to bring him most of his fame and acknowledgment. He was honoured with Prussian nobility in 1901, henceforth being known by the surname "von Behring".
Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks, the mortality rate approaches 10%. Signs and symptoms may vary from mild to severe, and usually start two to five days after exposure. Symptoms often develop gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat, which can block the airway, and create a barking cough similar to what is observed in croup. The neck may also swell, in part due to the enlargement of the facial lymph nodes. Diphtheria can also involve the skin, eyes, or genitals, and can cause complications, including myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets.
Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.
Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a specific treatment for envenomation. It is composed of antibodies and used to treat certain venomous bites and stings. Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved. It is given by injection.
An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.
An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, they can also kill bacteria and other microorganisms. Antitoxins are made within organisms, and can be injected into other organisms, including humans, to treat an infectious disease. This procedure involves injecting an animal with a safe amount of a particular toxin. The animal's body then makes the antitoxin needed to neutralize the toxin. Later, blood is withdrawn from the animal. When the antitoxin is obtained from the blood, it is purified and injected into a human or other animal, inducing temporary passive immunity. To prevent serum sickness, it is often best to use an antitoxin obtained from the same species.
Pierre Paul Émile Roux FRS was a French physician, bacteriologist and immunologist. Roux was one of the closest collaborators of Louis Pasteur (1822–1895), a co-founder of the Pasteur Institute, and responsible for the institute's production of the anti-diphtheria serum, the first effective therapy for this disease. Additionally, he investigated cholera, chicken-cholera, rabies, and tuberculosis. Roux is regarded as a founder of the field of immunology.
In immunology, antiserum is a blood serum containing antibodies that is used to spread passive immunity to many diseases via blood donation (plasmapheresis). For example, convalescent serum, passive antibody transfusion from a previous human survivor, used to be the only known effective treatment for ebola infection with a high success rate of 7 out of 8 patients surviving.
Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body. They are a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope.
A toxoid is an inactivated toxin whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, whereas toxoids are altered form of toxins; toxoids are not secreted by bacteria. Thus, when used during vaccination, an immune response is mounted and immunological memory is formed against the molecular markers of the toxoid without resulting in toxin-induced illness. Such a preparation is also known as an anatoxin. There are toxoids for prevention of diphtheria, tetanus and botulism.
On October 2, 1901, a former milk wagon horse named Jim showed signs that he had contracted tetanus and was euthanized. He was used to produce serum containing diphtheria antitoxin. Jim produced over 30 US quarts of diphtheria antitoxin in his career. After the death of a girl in St. Louis, Missouri, was traced back to Jim's contaminated serum, it was discovered that serum dated September 30 contained tetanus in its incubation phase. This contamination could have easily been discovered if the serum had been tested prior to its use. Furthermore, samples from September 30 had also been used to fill bottles labeled "August 24", while actual samples from the 24th were shown to be free of contamination.
Diphtheria antitoxin (DAT) is a medication made up of antibodies used in the treatment of diphtheria. It is no longer recommended for prevention of diphtheria. It is administered through injection into a vein or muscle.
In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.
Serum sickness in humans is a reaction to proteins in antiserum derived from a non-human animal source, occurring 5–10 days after exposure. Symptoms often include a rash, joint pain, fever, and lymphadenopathy. It is a type of hypersensitivity, specifically immune complex hypersensitivity. The term serum sickness–like reaction (SSLR) is occasionally used to refer to similar illnesses that arise from the introduction of certain non-protein substances, such as penicillin.
Diphtheria vaccine is a toxoid vaccine against diphtheria, an illness caused by Corynebacterium diphtheriae. Its use has resulted in a more than 90% decrease in number of cases globally between 1980 and 2000. The first dose is recommended at six weeks of age with two additional doses four weeks apart, after which it is about 95% effective during childhood. Three further doses are recommended during childhood. It is unclear if further doses later in life are needed.
The United States Biological Defense Program—in recent years also called the National Biodefense Strategy—refers to the collective effort by all levels of government, along with private enterprise and other stakeholders, in the United States to carry out biodefense activities.
The Botulism Antitoxin Heptavalent - (Equine), made by Emergent BioSolutions Canada Inc. – is a licensed, commercially available botulism anti-toxin that effectively neutralizes all seven known botulinum nerve toxin serotypes. It is indicated for sporadic cases of life-threatening botulism and is also stockpiled for the eventuality of botulinum nerve toxins being used in a future bioterrorist attack.