had used
1923 Farbwerke Hoechst, one of the forerunners of todays Sanofi Aventis, produces commercial quantities of bovine insulin in Germany
1923 Hans Christian Hagedorn founds the Nordisk Insulinlaboratorium in Denmark – forerunner of todays Novo Nordisk
1923 Constance Collier returns to health after being successfully treated with insulin in Strasbourg
1926 Nordisk receives a Danish charter to produce insulin as a non-profit
1936 Canadians David M. Scott and Albert M. Fisher formulate a zinc insulin mixture at Connaught Laboratories in Toronto and license it to Novo
1936 Hagedorn discovers that adding protamine to insulin prolongs the duration of action of insulin
1946 Nordisk formulates Isophane porcine insulin aka Neutral Protamine Hagedorn or NPH insulin
1946 Nordisk crystallizes a protamine and insulin mixture
1950 Nordisk markets NPH insulin
1953 Novo formulates Lente porcine and bovine insulins by adding zinc for longer lasting insulin
1955 Frederick Sanger determines the amino acid sequence of insulin
1965 Synthesized by total synthesis by Wang Yinglai, Chen-Lu Tsou, et al. 1969 Dorothy Crowfoot Hodgkin solves the crystal structure of insulin by X-ray crystallography
1973 Purified monocomponent (MC) insulin is introduced
1973 The U.S. officially "standardized" insulin sold for human use in the U.S. to U-100 (100 units per milliliter). Prior to that, insulin was sold in different strengths, including U-80 (80 units per milliliter) and U-40 formulations (40 units per milliliter), so the effort to "standardize" the potency aimed to reduce dosage errors and ease doctors job of prescribing insulin for people. Other countries also followed suit.
Symptoms of AHS typically manifest within six weeks of treatment using abacavir, although they may be confused with symptoms of HIV, immune reconstitution syndrome, hypersensitivity syndromes associated with other drugs, or infection. The U.S. Food and Drug Administration (FDA) released an alert concerning abacavir and abacavir-containing medications on 24 July 2008, and the FDA-approved drug label for abacavir recommends pre-therapy screening for the HLA-B*5701 allele and the use of alternative therapy in subjects with this allele. Additionally, both the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group recommend use of an alternative therapy in individuals with the HLA-B*5701 allele. Skin-patch testing may also be used to determine whether an individual will experience a hypersensitivity reaction to abacavir, although some patients susceptible to developing AHS may not react to the patch test.The development of suspected hypersensitivity reactions to abacavir requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients who do not possess the HLA-B*5701 allele. On 1 March 2011, the FDA informed the public about an ongoing safety review of abacavir and a possible increased risk of heart attack associated with the drug. A meta-analysis of 26 studies conducted by the FDA, however, did not find any association between abacavir use and heart attack

Immunopathogenesis
The mechanism underlying abacavir hypersensitivity syndrome is related to the change in the HLA-B*5701 protein product. Abacavir binds with high specificity to the HLA-B*5701 protein, changing the shape and chemistry of the antigen-binding cleft.