the years, it has been a pleasure to work with the staff at Wiley, the publisher who has done all additions after the second. They have done a great job of producing, marketing, and distributing these multiple editions of the book.
Well now it has come to this. It has been a pleasure to write and produce this book for you and an honor that you found it valuable enough to obtain it. I hope this most recent edition will continue to meet your needs and help guide you in your career. I do not know whether there will be a sixth edition and if so whether I will be part of it. So I wish you a successful career and I hope this book might help you along the way.
My great admiration, affection, and respect for all those who passed through our fellowship program and those of you who have been kind enough to be a colleague and to include me in your life.
First you were of me and now I am of you.
1 History
Jeffrey McCullough MD
1.1 Ancient times
For centuries, blood has been considered to have mystical properties and has been associated with vitality. In ancient times, bathing in or drinking the blood of the strong was thought to invigorate the weak. For instance, among Ancient Romans it was customary to rush into the arena to drink the blood of dying gladiators [1]; among others, to drink or bathe in blood was thought to cure a variety of ailments [2]. Bleeding was practiced to let out bad blood and restore the balance of humors, thus hopefully returning the patient to health.
It is not known when and by whom the idea of transfusing blood was developed. It is said that the first transfusion was given to Pope Innocent VIII in 1492. According to this legend, the Pope was given the blood of three boys, whose lives were thus sacrificed in vain [1, 3] because the attempts did not save the Pope. In another version of the story, the blood was intended to be used in a tonic for the Pope, which he refused, thus sparing the boys’ lives [2]. Ironically, the concept of transfusion blood from younger donors to revitalize older individuals has reappeared recently, although without any scientific background or basis.
1.2 The period 1500–1700
Others to whom the idea for blood transfusion is attributed include Hieronymus Cardanus (1501–1576) and Magnus Pegelius. Little is known about Cardanus, but Pegelius was a professor at Rostock, Germany, who supposedly published a book describing the idea and theory of transfusion [1]. It can be substantiated that Andreas Libavius (1546–1616) proposed blood transfusion in 1615 when he wrote:
Let there be a young man, robust, full of spirituous blood, and also an old man, thin, emaciated, his strength exhausted, hardly able to retain his soul. Let the performer of the operation have two silver tubes fitting into each other. Let him enter the artery of the young man, and put into it one of the tubes, fastening it in. Let him immediately open the artery of the old man and put the female tube into it, and then the two tubes being joined together, the hot and spirituous blood of the young man will pour into the old one as it were from a fountain of life, and all of this weakness will be dispelled [1].
Despite these possibilities, it also seems unlikely that the concept of transfusing blood could have developed before William Harvey’s description of the circulation in 1616. Despite Harvey’s description of the circulatory system, there is no evidence that he considered blood transfusion. However, the concept of the “circulation” may have preceded Harvey’s publication. For instance, Andrea Cesalpino (1519–1603), an Italian, used the expression “circulation” and proposed that fine vessels (capillaries) connected the arterial and venous systems [1, 4].
A number of the major developments that led to the beginning of blood transfusion occurred during the mid‐1600s [1]. In 1656, Christopher Wren, assisted by Robert Boyle, developed techniques to isolate veins in dogs and carried out many studies of the effects of injecting substances into the dogs. It is not clear whether Wren ever carried out blood transfusion between animals. The first successful transfusion from one animal to another probably was done by Richard Lower [1, 5, 6]. Lower [6] demonstrated at Oxford the bleeding of a dog until its strength was nearly gone, but then revitalized the previously moribund dog by exchange transfusion using blood from two other dogs, resulting in the death of the donor animals.
Subsequently, a controversy developed over who had first done a transfusion. In 1669, Lower contended that he had published the results of transfusion in the Philosophical Transactions of the Royal Society in December 1666. In 1667, Jean Denis of France described his experiments in animals and applied the technique to human, which Lower had accomplished only in animals. Others mentioned as possibly having carried out animal‐to‐animal transfusions about this time are Johann‐Daniel Major of Cologne, Johann‐Sigismund Elsholtz of Berlin, don Robert de Gabets (a monk) in France, Claude Tardy of Paris, and Cassini and Griffone in Italy [1].
Denis apparently was a brilliant young professor of philosophy and mathematics at Montpellier and physician to Louis XIV. In 1667, Denis carried out what is believed to be the first transfusion of animal (lamb’s) blood to a human. A 15‐year‐old boy with a long‐standing fever who had been bled multiple times received about 9 ounces of blood from the carotid artery of a lamb connected to the boy’s arm vein. Following the transfusion, the boy changed from a stuporous condition to a clear and smiling countenance. During the next several months, Denis may have given transfusions to three other individuals [1]. The second patient, Antoine Mauroy, was an active 34‐year‐old who spent some of his time carousing in Paris. It was thought that blood from a gentle calf might dampen Mauroy’s spirits. On December 19, 1667, he received with no untoward effects 5 or 6 ounces of blood from the femoral artery of a calf. Several days later, the procedure was repeated. During the second transfusion, Mauroy experienced pain in the arm receiving the blood, vomiting, increased pulse, 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
