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a nosebleed, pressure in the chest, and pain over the kidneys; the next day he passed black urine. This is probably the first reported hemolytic transfusion reaction. Mauroy died about 2 months later without further transfusions. Reportedly, members of the Faculty of Medicine who were opposed to transfusion and hated Denis bribed Mauroy’s wife to state that he had died during the transfusion [1]. Denis was tried for manslaughter but was exonerated. It was later revealed that Mauroy’s wife had been poisoning him with arsenic and that was the actual cause of his death [7]. Also in late 1667, Lower performed a human transfusion before the Royal Society in England. The man received 9–10 ounces of blood from the artery of a sheep and was said to have “found himself very well” afterward [1]. However, the death of Mauroy was used by Denis’s enemies as an excuse to issue an edict in 1668 that banned the practice of transfusion unless the approval of the Faculty of Medicine in Paris was obtained. This series of events led to the discontinuation of transfusion experiments, but more importantly to the abandonment of the study of the physiology of circulation for approximately 150 years [1].

1.3 The 1800s

      Interest in transfusion was revived during the early 1800s, primarily by James Blundell [8], a British obstetrician who believed it would be helpful in treating postpartum hemorrhage. Blundell carried out animal experiments and avoided the error of using animal blood because of the advice of a colleague, Dr. John Leacock. Blundell reported to the Medico‐Chirurgical Society of London on December 22, 1818, the first human‐to‐human transfusion. It is not clear whether the transfusions given by Blundell were ever successful clinically [1]. However, Blundell’s [8] contributions were very substantial. Unfortunately, his warnings about the dangers of transfusing animal blood into humans were not generally heeded.

      Dr. Andrei Wolff carried out a human‐to‐human transfusion in St. Petersburgh, Russia, in 1832, having learned of blood transfusion from Dr. Blundell on a previous visit to London [9]. There is no evidence of additional transfusion in Russia until the 1920s, when a transfusion institute was established in Moscow.

      Key work in understanding the problems of using animal blood for human transfusions was provided by Ponfick and Landois [1]. They observed residues of lysed erythrocytes in the autopsy serum of a patient who died following transfusion of animal blood. They also noted pulmonary and serosal hemorrhages, enlarged kidneys, congested hemorrhagic livers, and bloody urine caused by hemoglobinuria and not hematuria when sheep’s blood was transfused to dogs, cats, or rabbits. Landois observed that human red cells would lyse when mixed in vitro with the sera of other animals. Thus, evidence mounted that interspecies transfusion was likely to cause severe problems in the recipient.

1.4 First transfusions in the United States

      In the United States, transfusions were first used in the mid‐1800s, but it is not clear where they were first performed. They may have been done in New Orleans in about 1854 [2]. During the Civil War, the major cause of death was hemorrhage [10]. However, at that time blood transfusion had not been developed, and it appears to have been used in only two to four patients [2]. Two cases are described by Kuhns [10]. One was transfused at Louisville and one at Alexandria within about 10 days of each other. There is no evidence that the procedures were jointly planned or that the physicians involved communicated about them. In both cases, the patients improved following the transfusions [10].

1.5 The discovery of blood groups

The accumulating experiences began to make it clear that transfusions should be performed only between members of the same species. However, even within species, transfusions could sometimes be associated with severe complications. Because of this, and despite the experiences during the Civil War, few transfusions were carried out during the last half of the 1800s. The discovery of blood groups by Landsteiner [11] opened a new wave of transfusion activity. It had been known that the blood of some individuals caused agglutination of the red cells of others, but the significance of this was not appreciated until Landsteiner [11] in 1900 reported his studies of 22 individuals in his laboratory. He showed that the reactions of different combinations of cells and sera formed patterns and these patterns indicated three blood groups [11]. He named these blood groups A, B, and C (which later became group O). Apparently, none of the staff of Landsteiner’s laboratory had the less common group AB, but soon this blood group was reported by the Austrian investigators Decastello and Sturli [1]. Soon thereafter, several other nomenclature systems were proposed, and the American Medical Association convened a committee of experts who recommended a numerical nomenclature system [12] that never gained widespread use [11]. Others later demonstrated that the blood groups were inherited as independent Mendelian dominants, and that the phenotypes were determined by three allelic genes. Hektoen [13] of Chicago first advocated the use of blood grouping to select donors and recipients and to carry out transfusion, but it was Ottenberg [14] who put the theory into practice. These activities are the basis for the widely held belief that blood banking in the United States had its origins in Chicago.

1.6 Anticoagulation

      Another factor that inhibited the use of transfusions during the late 1800s was blood clotting. Because of the inability to prevent clotting, most transfusions were given by direct methods. There were many devices for direct donor‐to‐recipient transfusion that incorporated valves, syringes, and tubing to connect the veins of donor and recipient [15].

      Although there were many attempts to find a suitable anticoagulant, the following remarks must be prefaced by Greenwalt’s statement that “none of them could have been satisfactory or else the history of blood transfusion would have had a fast course” [1]. Two French chemists, Prévost and Dumas, found a method to defibrinate blood and observed that such blood was effective in animal transfusions [1]. Substances tested for anticoagulation of human blood include ammonium sulfate, sodium phosphate, sodium bicarbonate, ammonium oxalate and arsphenamine, sodium iodide, and sodium sulfate [16, 17]. The delays in developing methods to anticoagulate blood for transfusion are interesting because it was known in the late 1800s that calcium was involved in blood clotting and that blood could be anticoagulated by the addition of oxalic acid. Citrates were used for laboratory experiments by physiologists, and by 1915 several papers had been published describing the use of sodium citrate for anticoagulation for transfusions [1]. It is not clear who first used citrated blood for transfusion [1]. It could have been Lewisohn [18], Hustin, or Weil [19]. In 1955, Lewisohn received the Landsteiner award from the American Association of Blood Banks for his work in the anticoagulation of blood for transfusion.

1.7 Modern blood banking and blood banks

      Major stimuli for developments in blood transfusion have come from wars. During World War I, sodium citrate was the only substance used as an anticoagulant. Early in the war, transfusions were vein to vein, but in 1917, Dr. Oswald Robertson of the U.S. Army Medical Corps devised a blood collection bottle and administration set similar to those used several decades later [1] and transfused several patients, some estimate hundreds of patients, with preserved blood [20].

Between World Wars I and II, there was increasing interest in developing methods to store blood in anticipation of rather than response to need. It has been suggested that the first “bank” where a stock of blood was maintained may have been in Leningrad in 1932 [1, 2]. A blood bank was established in Barcelona in 1936 because of the need for blood during the Spanish Civil War [21]. In the United States, credit for the establishment of the first blood bank for the storage of refrigerated blood for transfusion is usually given to Bernard Fantus at the Cook County Hospital in Chicago [22]. The blood was collected in sodium citrate and so it could be stored for only a few days. In England, blood donations were begun within days of the outbreak of WWII in 1939. The British established a Home Depot for collecting blood and shipped blood to Europe even during the Dunkirk campaign.

1.8 Cadaver blood

      Cadavers served as another source of blood during the 1930s and later. Most of this work was done by Yudin [23] in the USSR.

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