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 (antibodies against diphtheria toxin). Jim produced over 30 US quarts (7.5 US gallons; 28.5 litres) 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. [1]
These failures in oversight led to the distribution of antitoxin that caused the death of 12 more children, which were highly publicized by newspaper magnate Joseph Pulitzer as part of his general opposition to the practice of vaccination. [2] This incident, and a similar one involving contaminated smallpox vaccine in Camden, New Jersey, led to the passage of the Biologics Control Act of 1902, which established the Center for Biologics Evaluation and Research. Jim's misfortune, and the ensuing tragedy and reaction, thus established a precedent for the regulation of biologics, leading to the 1906 formation of the US Food and Drug Administration (FDA). [3] [4] The incident has since been referred to as "the first modern medical disaster". [5]
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.
Emil von Behring, born Emil Adolf 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.
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.
The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis, and tetanus. The vaccine components include diphtheria and tetanus toxoids and either killed whole cells of the bacterium that causes pertussis or pertussis antigens. The term toxoid refers to vaccines which use an inactivated toxin produced by the pathogen which they are targeted against to generate an immune response. In this way, the toxoid vaccine generates an immune response which is targeted against the toxin which is produced by the pathogen and causes disease, rather than a vaccine which is targeted against the pathogen itself. The whole cells or antigens will be depicted as either "DTwP" or "DTaP", where the lower-case "w" indicates whole-cell inactivated pertussis and the lower-case "a" stands for "acellular". In comparison to alternative vaccine types, such as live attenuated vaccines, the DTP vaccine does not contain any live pathogen, but rather uses inactivated toxoid to generate an immune response; therefore, there is not a risk of use in populations that are immune compromised since there is not any known risk of causing the disease itself. As a result, the DTP vaccine is considered a safe vaccine to use in anyone and it generates a much more targeted immune response specific for the pathogen of interest.
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.
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.
The Biologics Control Act of 1902, also known as the Virus-Toxin Law, was the first law that implemented federal regulations of biological products such as vaccines in the United States. It was enacted in response to two incidents involving the deaths of 22 children who had contracted tetanus from contaminated vaccines. This law paved the way for further regulation of drug products under the Pure Food and Drug Act of 1906 and the Federal Food, Drug, and Cosmetic Act of 1938. Biologics control is now under the supervision of the U.S. Food and Drug Administration (FDA).
The Center for Biologics Evaluation and Research (CBER) is one of six main centers for the U.S. Food and Drug Administration (FDA), which is a part of the U.S. Department of Health and Human Services. The current Director of CBER is Peter Marks, M.D., PhD. CBER is responsible for assuring the safety, purity, potency, and effectiveness of biologics and related products. Not all biologics are regulated by CBER. Monoclonal antibodies and other therapeutic proteins are regulated by the FDA Center for Drug Evaluation and Research (CDER).
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.
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 Food and Drug Administration is a federal agency of the United States, formed in 1930.
Dalla Lana School of Public Health is the school of public health at the University of Toronto. It was founded in 1927, and was home for 50 years to Connaught Laboratories, a manufacturer of vaccines, insulin, and many other pharmaceutical products. Having grown to be the largest cluster of public health scholars in Canada, the school was revitalized in 2008 with the support of a major gift from the Dalla Lana family.
The H. K. Mulford Company was a pharmaceutical company founded in Philadelphia, Pennsylvania. The company was founded in the late 1880s by Henry K. Mulford after his purchase of the Old Simes drugstore at 18th and Market Streets. The company was purchased by Sharp & Dohme Corp in 1929.
DTaP-IPV/Hib vaccine is a 5-in-1 combination vaccine that protects against diphtheria, tetanus, whooping cough, polio, and Haemophilus influenzae type B.
The Bundaberg tragedy was a medical disaster that occurred in January 1928, resulting in the deaths of 12 children in Bundaberg, Queensland, Australia. A royal commission concluded that the deaths were caused by the contamination of a diphtheria vaccine with the bacterium Staphylococcus aureus.
The Connaught Medical Research Laboratories was a non-commercial public health entity established by Dr. John G. FitzGerald in 1914 in Toronto to produce the diphtheria antitoxin. Contemporaneously, the institution was likened to the Pasteur Institutes in France and Belgium and the Lister Institute in London. It expanded significantly after the discovery of insulin at the University of Toronto in 1921, manufacturing and distributing insulin at cost in Canada and overseas. Its non-commercial mandate mediated commercial interests and kept the medication accessible. In the 1930s, methodological advances at Connaught updated the international standard for insulin production.