Haemophilia is sometimes referred to as “the royal disease”, because it affected the royal families of England, Germany, Russia, and Spain in the 19th and 20th centuries.

Born in the Old Austrian empire, Gregor Mendel was a Czech monk who worked out the basic laws of inheritance before the term gene had been invented. Mendel performed thousands of experiments with garden peas. He explained his results by describing two laws of inheritance that introduced the idea of dominant and recessive traits.

Frederick Miescher isolated DNA from cells for the first time and called it nuclein.

In 1940, Edwin Cohn, a professor at Harvard Medical School, developed the process of breaking down plasma into components and products. Albumin, a protein with powerful osmotic properties, plus gamma globulin and fibrinogen were isolated and became available for clinical use.

In 1941, Isodor Ravdin, a Philadelphia surgeon, effectively treated victims of the Pearl Harbor attack with Cohn’s albumin for shock.

James D. Watson and Francis H. Crick described the double helix structure of DNA. They received the Nobel Prize for their work in 1962.

The modern management of haemophilia really began in the 1970s with the production of coagulation factors. This innovation greatly improved the quality of life and longevity of people with haemophilia, permitting the widespread adoption of at-home replacement therapy.

The successful cloning of the factor VIII gene in 1984 was a major breakthrough, allowing production of recombinant human factor VIII. Cloning of factor IX was first reported in 1982.

In 1982, products derived from contaminated blood led to the first CDC-reported cases of patients with haemophilia A developing pneumonia and other infections that met the case definition of AIDS.

In October 1984, Dr Barrie Carter published A Human Parvovirus, Adeno-Associated Virus, as a Eucaryotic Vector: Transient Expression and Encapsidation of the Procaryotic Gene for Chloramphenicol Acetyltransferase, an article first describing the use of adeno-associated virus as a vector.

Expression of Active Human Factor VIII From Recombinant DNA Clones by Dr Gordon Vehar and his colleagues reported on the successful cloning of factor VIII, a breakthrough advancement.

A 4-year-old girl suffering from adenosine deaminase (ADA), a condition in which people cannot resist common infections, became the first person to receive a non-AAV gene therapy treatment.

Throughout the 1990s, synthetic factor products were manufactured using recombinant technologies. In 1992, the first recombinant factor VIII product was approved by the FDA. In 1997, the first recombinant factor IX product was granted FDA approval. In 1996, rFVIIa was approved in the European Union and in 1999 in the United States for use as a bypassing agent in patients with haemophilia A or B (factor VIII or factor IX deficiency) and an antibody inhibitor.

Founded in March 1997, with a $1.5 million investment from Glyko Biomedical Ltd., BioMarin was open for business.

Lessons were learned from serious problems that highlighted the potential toxicity of viral vectors in earlier trials of gene therapy, leading to new and different technologies.

The Human Genome Project (HGP) was an international research effort to sequence and map all of the genes—together known as the genome—of members of our species, homo sapiens. Completed in April 2003, the HGP gave us the ability, for the first time, to read nature’s complete genetic blueprint for building a human being.

In a 2005 clinical gene transfer trial, it was found that the human liver can be transduced by recombinant adeno-associated viral (rAAV) vector after in vivo delivery of the vector.

Over the years, BioMarin has extended its commitment to those communities with rare diseases.

After years of scientific study and collaboration with world experts, in 2015 BioMarin began the BMN 270-201 clinical trial—evaluating the safety, proper dosing, and efficacy of a gene therapy for adults with severe haemophilia A.