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Will There Be Blood?

Shaun McCann writes: One of the most widely known forms of altruism is blood donation. In many countries blood is donated on a voluntary basis and the donor never knows the recipient of his/her gift. In some countries donors are paid, which I’ll come back to later. In Europe only about 3% to 4% of potential blood donors actually donate blood yet most people take it for granted that blood will always be available when needed. At the same time the use of blood transfusion to support cancer treatment, surgery and post partum haemorrhage continues to increase 

Blood donation is a relatively straightforward affair and apart from a rather intrusive questionnaire is usually fairly uncomplicated. The questionnaire is the result of the HIV epidemic in the 1980s when the spread of the virus was limited by such a questionnaire and voluntary self-exclusion by “at risk” groups. Thus the spread of HIV via blood transfusion had decreased even before the virus causing AIDS was discovered.

Was blood transfusion always available and to what extent did the science of blood grouping and preservation of donated blood without clot formation enable its central role in medical practice today? The history of blood transfusion is intriguing as it illustrates the complexity of human behaviour, with its prejudices and conservatism.

The first recorded attempts at blood transfusion were during the “Enlightenment”, when medical knowledge expanded through the concept of experimentation, observation and recording, rather than relying on philosophy. The men (and they were mostly men) who investigated the circulation of blood and the technique of blood transfusion also believed in alchemy and magic. The early days of blood transfusion were hampered by beliefs that had held sway for hundreds of years that blood contained special qualities such as memory or soul. The Greek historian Herodotus wrote that Scythians drank the blood of their slain enemies if they had fought bravely. This presumably was predicated on the belief that blood itself contained some element that contributed to bravery. Pliny the Elder contributed to the myths surrounding blood when he wrote: “Epileptic patients are in the habit of drinking the blood even of gladiators ... And yet these persons, forsooth, consider it a most effective cure for their disease, to quaff the warm, breathing blood from the man himself, and, as they apply their mouth to the wound, to draw forth his very life.”

The most famous belief, of course, is that during the celebration of the Eucharist, bread and wine become transubstantiated into the body and blood of Christ. On the other hand, in Sicilian folk-magic, menstrual blood served to a man in his coffee was a recipe for stimulating his sexual appetite! Probably the most widespread legend/belief in the Western world was that of vampirism. Made famous by Bram Stoker in his novel Dracula, the idea of drinking blood  to continue the life of the “undead” fired the imagination of many. Stoker was probably influenced by John Polidori, Sheridan Le Fanu and Emily Gerard but the most famous (infamous) character was Countess Elizabeth Báthory de Ecsed (1560-1624) of Slovakia, who was reputed to bathe in the blood of virgins to maintain her youth.

Allied to these myths was the belief of the ancients that blood was one of the four essential humours and an imbalance in the humours led to disease. Hippocrates and Galen are most widely known for their influence on Western medicine but were hampered by the fact that dissection of humans was forbidden. Erisistratus and Herophilus, however, working in Alexandria, performed autopsies on humans and Erisistratus came very close to describing the systemic and pulmonary circulation.

It is arguable that the idea of blood transfusion could not have developed without an understanding of the circulation. However as William Osler said: “In science, the credit goes to the man who convinces the world, not to the man to whom the idea first occurred.” This was certainly true for the circulation of the blood. The ancient Chinese in the second century BC believed “the blood current flows continuously in a circle and never stops”. Ibn al-Nafis, an Arab physician in the thirteenth century, described the pulmonary circulation but his views were not disseminated, probably because his writings were in Arabic and came before the invention of the printing press. Michael Servetus, a Spanish physician of the sixteenth century, described the pulmonary circulation but unfortunately he was burnt as a heretic, and his books suffered the same fate. Galen’s claim that blood passed from the right to the left side of the heart through small holes held sway for 1,500 years, although it was challenged by Realdus Columbus, Juan Valverde de Amusco and finally by William Harvey. Harvey’s experiments were seminal, although he did not publicise them for a number of years fearing criticism by his peers.

The proposal that blood could be transfused from one animal or individual to another was a hotly contested one. The main protagonists were Richard Lower (1631-91) at the Royal Society and Jean Baptiste Denys at the French Academy of Science, who believed that blood could be transfused from an animal into a human. Lower transfused blood from a lamb into a human in the belief that the transfusion could cure mental illness. The recipient was paid 20 shillings, hardly an altruistic act! Denys also believed that blood transfusion could cure mental illness and in what was one of the most notorious animal to human transfusions, he recommended transfusion of blood from a calf to a man who appeared to be mentally disturbed. Years later the French parliament deemed blood transfusion a criminal act and the Royal Society also began to distance itself from the practice. Pope Innocent X1 (1629-1691) banned it.

The idea that transfusion of blood could be performed from one species to another was finally abandoned thanks to the arguments of Emil Ponfick and Leonard Landois in the latter part of the nineteenth century and it was also in the nineteenth century that physicians began to realise that bood transfusion could be used to save lives. Although transfusion was advocated during the Franco-Prussian war the suggestion did not come to fruition. James Blundell, a Scottish obstetrician, performed the first recorded human-to-human blood transfusion for post-partum haemorrhage and also made the prophetic suggestion that blood transfusion could be used to save the lives of wounded soldiers. An important ancillary observation by Louis Pasteur and Joseph Lister demonstrated that bacteria and fungi could be transferred via blood transfusion and that sterilisation of blood transfusion instruments was essential.

A number of technical problems, however, needed resolution before blood transfusion could become safe and widespread. The Czech serologist Jan Jansky classified blood into four types and subsequently Karl Landsteiner identified the A, B and O blood groups. Landsteiner’s name, rather than Jansky’s, is always associated with the discovery of blood groups, providing another example of Sir William Osler’s saying above about ideas in science. The problems of blood clotting during storage and the ability to keep red cells alive were other issues resolved by Albert Hustin, Louis Agote and Rous and Turner respectively

Although the stage was now set for widespread blood transfusion, remarkably large scale transfusion was not undertaken during World War 1 due to a large extent to the conservativism of the medical profession in spite of the above scientific advances. George Crile, now almost forgotten, was convinced at the end of the nineteenth century that blood was the fluid of choice for the treatment of haemorrhagic shock, while Captain Oswald Hope Robertson, from Harvard Medical School, showed in 1917 that it could be safely transfused to soldiers on the battlefield, an idea that was to gain traction much later.

Yet pioneering ideas persisted. In 1921 Percy Lane Oliver set up a volunteer panel of blood donors in London in spite of opposition from many doctors because of doubts about the safety and benefits of the process. Alexander Bogdanov, a Bolshevik physician, persuaded Joseph Stalin to provide funding for the first Institute of Blood Transfusion in 1926. Bogdanov, in spite of his scientific initiative, also believed that blood contained magic qualities and that transfusion could delay the ageing process.

The term “Blood Bank” is credited to Dr Bernard Fantus in the USA, who developed a blood preservation laboratory in 1937 and called it the “Cook County Hospital Blood Bank”. The development of blood transfusion, however, as we know it today, owes a lot to two little known individuals who featured in the Spanish Civil War, Frederick Durán-Jordà and Henry Norman Bethune. Both were doctors, one Spanish and one Canadian. Presumably prompted by the large number of civilian casualties during that war, Durán-Jordà developed a service in Barcelona while Bethune did so in Madrid. They both worked on the idea of James Blundell that blood transfusion could be used to save lives and that it was preferable to transfuse casualties “on the spot” before transporting them to hospital. This idea was put into practice again during the British evacuation at Dunkirk where it undoubtedly saved many lives. Durán-Jordà emigrated to England, with the help of Dr Janet Vaughan, in 1938 but died of leukaemia in 1953. Bethune eventually ended up in China, where he worked for Mao Zedong and died during the civil war. Interestingly, Bethune is “air brushed from history” in America (perhaps because he was a communist) but is a hero in China and Canada.

As the Spanish Civil War morphed into World War II the huge number of casualties prompted a number of other developments. The separation of whole blood into red cells and plasma, the manufacture of liquid albumin and Charles Drew’s “Plasma for Britain” campaign are a few examples. However racial prejudice was one issue involved in the latter as Dr Drew fought unsuccessfully to prevent the Red Cross from labelling blood so that blood taken from black volunteers could not be given to white soldiers.

One of the most important innovations in blood transfusion was again prompted by war, this time the Korean War. Carl W Walter, a surgeon at Harvard Medical School, and his colleague, William Murphy Jnr, invented the plastic bag for collection and transfusion of blood. The suitability of the bag was tested extensively during the Korean War (heretofore blood had been collected into glass bottles) in the early 1950s but, remarkably, it was not until the mid-1970s that plastic bags were routinely used in the United Kingdom for storage and transfusion of blood.

The other major innovation in blood transfusion was the development of antibody testing of donor blood to prevent the transmission of infectious agents and more recently the use of so-called nucleic acid testing (NAT) to detect the presence of infectious agents in blood rather than trying to detect the body’s response to these agents. The issues surrounding AIDS and the transmission of the HIV virus via blood and blood products, remain a black spot in the story of blood transfusion but a detailed account is beyond the scope of this article. With the development of NAT testing, the ban on gay men becoming blood donors has been lifted in many jurisdictions, albeit with numerous restrictions.

What can you expect in developed countries today? The blood donation station will be bright, clean and clinical and rather than being a fixed building may actually travel to your place of work. You will be interviewed by trained personnel and asked to answer an intrusive questionaire containing many questions about your sexual activity. Blood will then be drawn into a plastic bag and after a short rest you will be allowed to depart with a few words of advice such as not to smoke a cigarette for twenty-four hours.

The blood service therefore depends largely on volunteer or altruistic donation. The word altruism was coined by the French philosopher Auguste Comte in the nineteenth century although the concept had been around for some time. Altruism (altruisme originally) is defined as a willingness to do things that bring advantage to others, even if it results in disadvantage for yourself. Richard Titmuss’s book The Gift Relationship, had a profound effect on the blood transfusion service in the UK and was probably more important than anything else in determining the altruistic nature of the NHS service. Yet the question of whether donors should be rewarded for their gift is still widely debated. Evidence published in 2013 shows positive effects of offering economic rewards on donations and that guidelines recommending against economic rewards to motivate blood donors should be reconsidered. Research from Sweden suggests that a monetary reward reduces the number of potential blood donors but that a chance of turning a monetary reward into a charitable donation has a positive effect. In most countries blood is donated on a voluntary basis but in the US the FDA does not ban the payment of blood donors but insists that blood collected from paid donors is labelled as such. Hospitals are reluctant to use such blood even though its collection is not illegal. Plasma donation does not come under the same restriction, presumably because steps to inactivate infectious agents can be applied to plasma but not red cells. However, like all philosophical concepts, the concept of altruism has many interpretations and not everybody is in agreement with Titmuss’sapproach.

In France, during the early 1980s, at the height of the AIDS epidemic, prisoners were encouraged to donate blood. This was presented as a means to repay society for anti-social behaviour. However, inadvertently, infectious agents were introduced into the blood transfusion service. So what seemed to be an altruistic act proved to pose a danger to innocent recipients of blood and blood products.

In the USA, where in some instances blood and plasma donors are remunerated, a recent controversy erupted because of a disturbing judgement by I Glen Cohen in the Ninth Circuit of the US Court of Appeal that the ban on selling bone marrow (for transplantation) does not apply to “peripheral blood stem cells”. As most people consider the donation of bone marrow for transplantation to be a truly altruistic act and the use of peripheral blood (which under selected circumstances contains adequate numbers of haemopoietic stem cells for transplantation) the idea that peripheral blood for transplantation could be sold was an anathema. The European Haematology Association (EHA) responded with an on line letter and the Europdonor Foundation, in association with the National Marrow Donor Program (based in the US) and centres in Europe, Australia and Taiwan had already outlined the World Marrow Donor Association’s view that donation should always be altruistic and that there was no conceptual difference between stem cells collected from peripheral blood  and bone marrow.

In 2011 the Nuffield Council on Bioethics published a document, Donation for Medicine and Research. This document, of over 250 pages, is concerned primarily with solid organ and tissues other than blood. It maintains that while a behaviour, such as blood donation, may appear altruistic, it may be selfishly motivated. Eamonn Ferguson, from the University of Nottingham has written extensively on the concept of altruism in relation to blood donation. He has attempted to construct a means of measuring mechanisms of altruism which he calls MOA, which if understood could provide methods to increase donation rates.

Altruism, like most philosophical concepts, is more complicated than it appears at first glance. I totally agree with Ferguson when he says: “From the perspective of policymakers, clinicians, researchers, donors, recipients and the general non-donating public, pure altruism is assumed to be the bedrock of blood donation”, and a number of publications attest to the observation that a blood donor acts voluntarily for the benefit of another at a personal cost. Ferguson and others, however, have evidence that blood donors gain some personal “warm-glow” from the act of donation.

Whatever about the debate about altruism and its motivation, the medical profession and the public depend on the altruistic nature of blood donation, which facilitates numerous medical interventions and can be lifesaving. Strategies to increase the numbers of volunteer donors are welcome and hopefully the realisation of the increasing need for blood in medical treatments (e.g. in cancer care) will act as an impetus for future donations.

I am grateful to Eamonn Ferguson, professor of health psychology, University of Nottingham, UK, for reading this piece and offering useful comments.

5/10/2017

Shaun R McCann Hon FTCD was invited to become national director of the Irish Blood Transfusion Service by the minister of health Michael Noonan during the hepatitis C crisis. He is professor emeritus of haematology and academic dedicine at St James’s Hospital and Trinity College Dublin.