Before the discovery of blood types in 1901, doctors experimented with transfusing patients with milk, wine, and animal blood.

Before the 20th century, the medical community lacked a fundamental understanding of hematology. In the mid-17th century, physicians like Richard Lower and Jean-Baptiste Denys performed xenotransfusions, moving blood from sheep and calves into humans. These experiments often resulted in immediate death due to severe hemolytic reactions, leading to bans on the practice in both France and England.In the 1870s, some American doctors even attempted to inject milk into patients, believing the fatty globules would transform into white blood cells. These attempts were largely abandoned as patients suffered from high fever and rapid pulse. The breakthrough finally came in 1901 when Austrian immunologist Karl Landsteiner identified the presence of antigens on the surface of red blood cells.Landsteiner categorized blood into three groups: A, B, and C (later renamed O). He demonstrated that mixing blood from different groups caused agglutination, a process where red blood cells clump together and burst. This immune response releases toxic hemoglobin into the bloodstream, which can lead to kidney failure and death.His research was published in the journal 'Wiener klinische Wochenschrift' and fundamentally changed surgical safety. By 1907, Dr. Reuben Ottenberg performed the first successful blood transfusion using cross-matching at Mount Sinai Hospital in New York. Landsteiner's work eventually earned him the Nobel Prize in Physiology or Medicine in 1930.