The history of blood transfusion

‘We few, we happy few, we band of brothers; For he today that sheds his blood with me Shall be my brother.’ Shakespeare: Henry V (act 4, scene 3) It is not possible in a review of this length to cover the history of all aspects of transfusion medicine comprehensively. This article focuses principally on the key developments in the early history of transfusion medicine, rather than on the more recent developments. The major landmarks are summarized in Table I. The basic techniques involved in this life-saving procedure are relatively simple and it is thus perhaps surprising that blood transfusion only became a part of routine clinical practice relatively recently. Blood-letting (venesection) was widely practised for a variety of medical conditions from the time of Hippocrates (≈ 430 bc) through to the nineteenth century in Europe and yet transfusion only became a commonplace therapeutic intervention less than 100 years ago. This is because both an understanding of the nature of blood as well the physiology of the circulation were required as a foundation for the development of blood transfusion and these were not forthcoming until the middle of the seventeenth century. The views of the Romans and ancient Greeks exerted a profound influence on both the traditions and practise of Western medicine for nearly 2000 years. The principal beliefs of the ancient Greeks and Romans were based on the writings of Hippocrates. The central doctrine of the humoral theory is set out in the treatize entitled ‘On the nature of man’, in which it was proposed that all living matter is composed of four basic ingredients, namely blood, phlegm, yellow bile and black bile ( Lloyd, 1978). Although recognized as a vital element in the constitution of man, blood was certainly not viewed as being more or less important than the other humours. Differences in personality were viewed as reflecting different mixes of humours in people and this belief extended well into the Renaissance period ( Fig 1). Indeed, words still used today such as ‘sanguine’, ‘phlegmatic’, ‘melancholic’ and ‘choleric’ can be considered to be linguistic fossils from that era. An important consequence of the acceptance of the humoral theory was that it encouraged a holistic approach to medicine, in which illness came to be regarded as being due to an imbalance of the four humours. Correction of the imbalance was thus required for restoration of health and this could be achieved by attention to diet and environment, although medical procedures such as dieting, purging and blood letting could also be used. Anatomical knowledge was also required for an understanding of the circulation of the blood, the cornerstone for the practice of transfusion. The anatomical knowledge of the Greeks was very limited and they believed that blood simply ebbed and flowed through the peripheral veins with some blood passing through the pores of the interventricular septum to mix with the ‘pneuma’ (or vital spirit) that was inspired with the air and which fed the brain. William Harvey (1578–1657), who studied medicine in Padua after graduating from Cambridge, was the first to understand the circulation of the blood and his treatize entitled ‘Exercitatio anatomica de motu cordis et sanguinis in animalibus’ was first published in 1628. Plates from a German calendar of around 1480 portraying the influence of the four humours (top left, phlegm; top right, blood; bottom left, black bile; bottom right, yellow bile) on personality. A preponderance of blood is associated with lust and arrogance according to the text. Experiments with blood transfusion proceeded in steps, initially involving transfusions from one animal to another and then transfusions from animals to man. The first written evidence of experiments with blood transfusion comes from Oxford in 1666, where the intellectual climate was particularly favourable for such physiological experiments. William Harvey spent a brief period in the city as Warden of Merton College. Distinguished scientists such as Robert Boyle, Thomas Willis, Christopher Wren and Robert Hooke formed the Oxford Experimental Philosophy Club during the 1650s. Wren conducted experiments that showed that intravenous injection of substances into animals could exert a systemic effect and Richard Lower (1631–1703) demonstrated that blood turned red after passage through the lungs. In 1666, Lower went on to conduct experiments in which blood was transfused from one dog to another which had been venesected. Samuel Pepys, who was subsequently elected to the office of President of the Royal Society in 1684, describes in his diary the events of an evening spent at Gresham College on 14 November 1666, where he witnessed such an experiment: ‘At the meeting of Gresham College tonight, there was a pretty experiment of the blood of one dog let out, till he died, into the body of another on one side while all his own ran out the other side. The first died upon the place, and the other very well and likely to do well. This did give occasion to many pretty wishes, as of the blood of a Quaker to be let into an Archbishop and such like; but may if it takes be of might us to man’s health for the mending of bad blood by borrowing from a better body.' Jean Denis, Professor of Philosophy and Mathematics at Montpellier in France, published an account of his work in the Philosophical Transactions of the Royal Society in July 1667 ( Keynes, 1967). He transfused the blood of calves and lambs into humans, and it is interesting to note that the indication was not blood loss but usually symptoms of mental illness. In line with the humoral theory, he believed that the transfusion of a docile animal might exert a calming influence on a troubled and deranged mind. Lower himself went on to transfuse Arthur Coga, a Cambridge university student described by Pepys as ‘cracked a little in the head’, with the blood of a sheep on 23 November 1667, and he also survived a second transfusion on 12 December. However, others were not so lucky and transfusion soon fell into disrepute and thus no further advances were made for some time. The first person credited with transfusing blood from one human to another was James Blundell, an obstetrician at Guy's and St. Thomas' Hospitals in London. He had seen many cases of postpartum haemorrhage and this stimulated research into blood transfusion using dogs. He showed that death from haemorrhage could be prevented in dogs by transfusion and venous blood was just as effective as arterial blood for resuscitation. He concluded that ‘only human blood should be employed’ after observing that dogs given human blood invariably died. He developed a syringe with a two-way stopcock and this was used with a considerable degree of success to treat women with postpartum haemorrhage ( Blundell, 1828; Jones & Mackmul, 1928). He gave his first report of a blood transfusion from man to man in a paper to the Medico-Chirurgical Society of London presented on 22 December 1818. This represented the beginning of the modern era of transfusion medicine. It is remarkable that blood transfusion was initially carried out with considerable success even without any knowledge of blood groups. Differences in compatibility of blood between species were recognized before differences within a species. Landois had published a treatize entitled ‘Die Transfusion des Blutes’ in 1875 in which he reported the observation that mixing of blood cells from one animal with serum from another species often resulted in lysis within 2 min. Karl Landsteiner (1868–1943), an assistant at the Pathological–Anatomical Institute in Vienna, was aware of this work and carried out experiments to see whether there were demonstrable differences between individuals in man. He published his results in 1901, in which he described the reactions between the red cells and serum of 22 subjects ( Landsteiner, 1961, text in translation). He observed that the addition of serum from some individuals would cause clumping of the red cells of others and realized that this was a phenomenon with an immunological basis. He initially identified only three blood groups, which he termed A, B and C. Serum from group C subjects clumped the cells of those from groups A and B. The following year, Decastello and Stürli, two of Landsteiner's pupils in Vienna, confirmed his findings in a larger study of 155 individuals and also identified four subjects (2·5%) with no agglutinins in their own serum but whose red cells were agglutinated by serum from subjects with all of the three previously identified blood groups (group AB). They also reported that isoagglutinins were also found in healthy individuals and were certainly not merely associated with disease ( Decastello & Stürli, 1902). The importance of Landsteiner's work, written in German and published in an Austrian journal, was not recognized immediately and blood grouping did not become part of universal practice until the 1920s. 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Indeed, this is still used in many for the of A and The of on an to the of as the of for A in developed by the the of from of a of with and to be a particularly both and had a on in in recent years. and been and but there still be a for for many years to in the this review focuses on the early history of transfusion medicine, but recent developments The of other in blood been recognized for many years. 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For may be to of human at The of peripheral blood cells to of cells is also an are being conducted with for and but it is that there to be a for blood for to people the of blood for and do not the required around the to of the of blood at all year, the for and from for blood to in and used some of blood and by the years ( However, it is the who the very cornerstone of the Transfusion The in the as in many other been on the of and of the in the their blood of that we are all upon the of this