The canary in British pits was replaced in 1986 by the electronic gas detector. The first qualitative analytical method to detect carboxyhemoglobin emerged in 1858 with a colorimetric method developed by Felix Hoppe-Seyler, and the first quantitative analysis method emerged in 1880 with Josef von Fodor. Historical treatment
The use of oxygen emerged with anecdotal reports such as Humphry Davy having been treated with oxygen in 1799 upon inhaling three quarts of hydrocarbonate (water gas). Samuel Witter developed an oxygen inhalation protocol in response to carbon monoxide poisoning in 1814. Similarly, an oxygen inhalation protocol was recommend for malaria (literally translated to "bad air") in 1830 based on malaria symptoms aligning with carbon monoxide poisoning. Other oxygen protocols emerged in the late 1800s. The use of hyperbaric oxygen in rats following poisoning was studied by Haldane in 1895 while its use in humans began in the 1960s. Incidents
The worst accidental mass poisoning from carbon monoxide was the Balvano train disaster which occurred on 3 March 1944 in Italy, when a freight train with many illegal passengers stalled in a tunnel, leading to the death of over 500 people.Over 50 people are suspected to have died from smoke inhalation as a result of the Branch Davidian Massacre during the Siege of Waco in 1993. Weaponization
In ancient history, Hannibal executed Roman prisoners with coal fumes during the Second Punic War.The extermination of stray dogs by a carbon monoxide gas chamber was described in 1874.
Cerliponase alfa, marketed as Brineura, is an enzyme replacement treatment for Batten disease, a neurodegenerative lysosomal storage disease. Specifically, Cerliponase alfa is meant to slow loss of motor function in symptomatic children over three years old with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2). The disease is also known as tripeptidyl peptidase-1 (TPP1) deficiency, a soluble lysosomal enzyme deficiency. Approved by the United States Food and Drug Administration (FDA) on 27 April 2017, this is the first treatment for a neuronal ceroid lipofuscinosis of its kind, acting to slow disease progression rather than palliatively treat symptoms by giving patients the TPP1 enzyme they are lacking.The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. History
TPP1 was identified as the enzyme deficient in CLN2 Batten disease in 1997, via biochemical analysis that identified proteins missing a mannose-6-phosphate lysosomal targeting sequence. A gel electrophoresis was run for known brain proteins with lysosomal targeting sequences to see if a band was missing, indicating a deficiency in that protein. A band appeared to be missing at approximately 46 kDa, confirming its role in CLN2 disease, and almost the entire gene for this unknown protein was sequenced. The gene is located on chromosome 11. Today, it is known that varying mutation types occur in various locations of the gene including the proenzyme region, the mature enzyme region, or the signal sequence regions. After discovery, the recombinant form of TPP1, cerliponase alfa, was first produced in 2000, followed by testing in animal models until 2014.