Coagulation factor VIII (FVIII) is an essential cofactor in haemostasis. Variants in F8, the gene that encodes FVIII, can cause haemophilia A, a rare congenital bleeding disorder that occurs in 1:5,000 male infants. Great efforts have been made over the past half-century to improve therapies for haemophilia A, which have now brought the life expectancy of affected patients close to that of the general population. Cloning of the F8 gene has been central to this effort.

In 1964, the groundbreaking discovery of the presence of FVIII in plasma cryoprecipitate led to the large-scale purification of plasma-derived FVIII concentrates, which enabled home-based replacement therapy by the 1970s and greatly improved patients’ quality of life. Devastatingly, this medical triumph was short-lived; by 1983, the US Centers for Disease Control had collected sufficient evidence to indicate that hepatitis B virus, hepatitis C virus and human immunodeficiency viruses were transmissible via blood and blood products, including FVIII concentrate. By 1985, viral inactivation processes were in place but approximately 80% of patients with haemophilia A were already infected with at least one of these viruses, which led to the deaths of many patients. An alternative treatment was urgently required to ensure the safety of patients.