by Bryan Sykes
5
THE BLOOD BANKERS
If you have ever been a blood donor, or ever needed a transfusion, then you will know your blood group. You will know whether you belong to Group A, B, O or even AB. The reason for testing is to avoid a possibly fatal reaction if you were to be transfused with unmatched blood. You cannot tell, just by looking, what blood group a person belongs to. Unlike hair and eye colour or the shape of heads, blood groups are an invisible signal of genetic difference which can be discovered only by carrying out a specific test.
Though the first blood transfusions were performed in Italy in 1628, so many people died that the procedure was banned. As a desperate measure to save women who were haemorrhaging after childbirth, there was a revival of transfusion in the mid-nineteenth century. Though some patients had no problems accepting a transfusion, a great many patients died from their reaction to the transfused blood. What caused the reaction was a mystery.
The puzzle was eventually solved in 1900 by the Austrian physiologist Karl Landsteiner. After experimenting with mixing the blood of his laboratory dogs and observing their cross-reactions, he began his work on humans. He mixed the blood of several different individuals together and noticed that sometimes when he did this the red blood cells stuck together in a clump. This did not happen every time, but only with certain combinations of individuals. If this red-cell clumping was occuring in transfused patients, the blood would virtually solidify, which would explain the fatal reaction. It also explained why some patients tolerated a transfusion and showed no signs at all of a reaction.
Landsteiner interpreted the results of his mixing experiments by suggesting that people belonged to one of the three blood groups, A, B or O. Two years later a fourth group, AB, was discovered. This also explained the erratic pattern of transfusion complications. Giving a group A patient a transfusion of blood from a group A donor was fine; tranfuse a group A patient with blood from a group B donor and there would be trouble. But so long as the donor and patient blood groups were the same there was no problem.
It took a few years to discover the chemical basis for the different types of blood. The blood groups are the result of a simple genetic difference that occurs on the surface of red blood cells, the cells that carry oxygen and give blood its colour. On the outside of each red blood cell sits a molecule that can occur in two very slightly different forms, A or B. People in group A have, unsurprisingly, version A on the surface of their red cells while in group B, this is replaced by version B. In the rare AB group the cells have both A and B versions on their outer surface. People in group O have neither A nor B versions of the molecule. Their red cells are, in a sense, bald.
But these slight differences, which don’t affect the efficiency or the working of the cells at all, are not on their own sufficient to cause trouble on transfusion. The problem arises because, after a few months outside the womb, the blood serum begins to build up antibodies to the opposite version of the molecule on their own cells. People in group A build up anti-B antibodies in their serum. Again, this does not interfere with normal everyday life. People never make antibodies to their own blood cells, so people in group A don’t make anti-A antibodies, only anti-B. Since people with blood group AB have both versions on their red cells, they make neither anti-A nor anti-B antibodies while, for the same reason, people in group O, whose cells have neither A nor B, are free to make both anti-A and anti-B antibodies and they do.
The potentially fatal coagulation reaction occurs when the molecule meets its antibody. They stick to each other like glue and, what is worse, bind all the red cells into a sticky clump, the cause of all the trouble in mismatched transfusions. That’s why no one makes antibodies against their own cells. They would coagulate their own red blood cells and die.
Under normal circumstances blood cells never encounter their own antibodies, but transfusion opens up that possibility. Transfuse a group A patient with blood from a group B donor and the antibodies will play havoc. Two things happen. The group B cells from the donor are coagulated by the anti-B in the patient’s serum and the anti-A in the donor’s serum clumps the patient’s own cells. Group O blood is really bad news because its serum contains both anti-A and anti-B which will attach the cells of any other blood group. However, as good methods were developed to separate the donor’s cells from the liquid serum, things got a bit easier. Group O cells, separated then rinsed free of antibody-containing serum, can be transfused into any patient, and if red cells are all you need that’s fine. Group O is the universal red-cell donor, as long as you wash them thoroughly first to remove the serum antibodies. If you need serum, not cells, then a transfusion of AB serum, which is free of antibodies, will suit any patient whatever their blood group.
Once all this was understood, it was easy to see why so many transfusions failed. Without knowing in advance the blood group of donor and patient, blood transfusion was a really hit-and-miss affair. At least that was the case in Europe. Stories that the Incas of Peru had been successfully performing a form of blood transfusion without any adverse reactions were initially dismissed as nonsense. However, when it was discovered that practically all native South Americans were in blood group O, it no longer sounded so incredible. If Inca donor and Inca recipient were both in group O, as most were, then trouble-free transfusions are exactly what would be expected.
Before the First World War, blood transfusions were a personal business. Willing friends and relatives of the patient would be tested to find someone in a compatible blood group. The donor would then come to a hospital, usually the operating theatre if surgery was the reason for the transfusion, and be bled right next to the patient, who then immediately received the fresh blood. The huge increase of blood transfusions needed to treat the battlefield casualties of the First World War led directly to the setting up of blood banks and the recruitment of donors along modern lines. Under the right conditions it was found that blood could be stored for several days without losing condition and there was no need to transfuse casualties immediately with absolutely fresh blood.
Volunteer donors were bled at remote sites and the blood was despatched to the field hospitals at the Front to be matched and used as required. This soon became a large-scale activity and with it came the necessity for accurate records. Each army had its blood bank and they soon began to accumulate blood-group records from very large numbers of soldiers, each of whom was routinely tested in anticipation of being called either to give blood as a donor or to receive it as a casualty.
Hanka Herschfeld, from the Royal Serbian Army, was the medical officer in charge of the Allied blood bank on the Balkan Front. Her husband, Ludwig, had been one of the scientists who, before the war, had helped to work out the way the different blood groups were inherited. With this background it is no surprise that they became curious about the accumulating results from the blood bank. The Allies drew their troops from all over the world and the Herschfelds noticed that the frequencies of the blood groups in the soldiers of different nationalities were often quite different from one another. Certainly they were still all either A, B, AB or O, but the proportions of each were different depending on where they were from. For example, far more Indian Army soldiers belonged to blood group B than did Europeans, who were, symmetrically, higher in the proportion of group A.
The Herschfelds interpreted these differences in blood-group frequencies as having something to do with the distant origins of these different nationalities–and they were right. But in their now famous paper published in the leading medical journal the Lancet, just after the war, they went too far and divided the world into two separate races. Race A came from northern Europe, while Race B began in India. The varying blood-group proportions seen in the soldiers of different nationalities were explained by the mixing as people flowed outwards from these ‘cradles of humanity’, as the Herschfelds called them, to populate the world.
Their Lancet paper is a classic, and rightly so. It was the first of its kind and it opened up an entirely new fi
eld of research in anthropology. It follows on from the implicit assumption in John Beddoe’s research on physical appearance that inherited features can be used to explore the origins of people. Compared to the work on hair and eye colour, skull shape and so on, blood groups come one step closer to the fundamental controller of genetic inheritance, DNA. However, no one knew about the way DNA conducted the business of inheritance at the time the Herschfelds were at their peak, nor for several decades afterwards. Blood groups, though still an indirect manifestation of the underlying DNA, were a definite improvement on the earlier, subjective parameters which were all that were available to John Beddoe and his Victorian contemporaries.
For one thing, it completely removed prejudice and human error from the equation. Blood groups are tightly defined and there is no overlap between them. No matter who does the tests, someone in group B will always be in group B. It doesn’t alter with age. There is no room for doubt, at least not about the accuracy of the observation. But there is also a noticeable shift in the tone of the reports. There are no longer any barely concealed inferences of racial character, like the free-spirited, fair-haired Saxon who will not be tied to the drudgery of an urban existence but would rather make his fortune overseas, or the morose, dark-haired Shetlander driven to despair by drinking too many cups of tea. All that nonsense vanishes, as it is very hard to get worked up about the comparative personal characteristics of one blood group over another. The American physician William Boyd, who extended the Herschfelds’ work around the globe, expressed this new sense when he wrote, ‘In certain parts of the world an individual will be considered inferior if he has, for instance, a dark skin but in no part of the world does possession of a blood group A gene exclude him from the best society’. As a group A myself, that comes as something of a relief.
The Herschfelds’ final legacy was less glorious. Their grand conclusions about the dual origins of humanity turned out to be completely wrong. It took the discovery of other blood group systems, unimportant in transfusion, and the amalgamation of results from several of them to get a more reasonable interpretation of human evolution. Slowly the searchlight illuminating the ‘cradle of humanity’ turned away from Europe and Asia and settled firmly on the plains of East Africa.
After the Second World War, the task of sifting through the, by then, thousands of sets of blood-group data from transfusion centres all over the world settled on the shoulders of one man, Arthur Mourant. Born in Jersey in the Channel Islands, and emotionally attached to it throughout his life, Mourant wanted at first to become a psychoanalyst and, in order to do so, he had to enrol as a medical student. He was forced to abandon his ambition after he underwent analysis himself and was judged to be ‘emotionally unsuitable’ to continue with his training. Despite this disappointment, he did not abandon his medical training. During the Second World War his medical school, St Bartholomew’s in the City of London, was evacuated to Cambridge and he found himself working with one of the greatest geneticists of the twentieth century, R. A. Fisher.
Fisher, among many other interests, was engaged in a bitter rivalry with the American physician Alexander Wiener on the inheritance of the Rhesus blood groups. Rhesus is another type of human blood group, discovered, as its name implies, through research in Rhesus monkeys. Unlike Landsteiner’s comparatively simple ABO system, the genetics of the Rhesus blood group are fiendishly complicated. There was a furious race to unravel the genetics by following the Rhesus group through families, and the young Mourant was assigned to the task of finding and typing suitably large families. He quickly found the solution to the inheritance, thanks to his particularly fruitful research on a local East Anglian family. Fisher was understandably elated by this triumph and Mourant soon found himself an established member of Fisher’s team with a bright career ahead of him. This career he dedicated to extending William Boyd’s pre-war surveys on the geographical distribution of the ABO blood groups around the world. He also set out to enlarge on Boyd’s work by including as many of the newly discovered blood groups, like Rhesus, as possible and to build up the most complete maps of blood-group distributions in every part of the globe. Mourant, like Beddoe before him, was an extremely avid collector of information.
In front of me as I write is his final masterpiece, The Distribution of the Human Blood Groups, published in 1976. It is an impressive tome, 6 centimetres thick and weighing 2.4 kilograms. It has 1,055 pages, 3,179 bibliographic references, 661 pages of tables and several pages of beautifully drawn maps. It has the gravitas of a life’s work. To give you a taste of the scope of Mourant’s encyclopaedic enterprise, there are tables of Rhesus blood-group data from the Bilwa, Sanpuka and Ulwas tribes of Nicaragua, the ABO blood groups of 13,000 blood donors from Benghazi in Libya, the MNS (another blood group) results from French and Spanish Basques and the Duffy (yet another) blood-group results from hundreds of New Guinea highlanders.
But what did it all mean? Surely there was enough information here to resolve any lingering uncertainties about the whereabouts of the ‘cradle of humanity’ and how our ancestors had moved from there to populate the planet. But even a cursory inspection of the maps shows the optimism is misplaced. Working along the commonsense lines that if two peoples have similar proportions of the different blood groups, then they are more likely to be related than two with very different proportions, you soon run into trouble. For example, the highest frequencies of blood group A are found in two very different parts of the world: among native Australians on the one hand and Saami reindeer-herders of northern Norway on the other. It would be preposterous to propose that these two peoples, about as far away from each other as it is possible to be, were closely related and shared a recent common ancestry. However, when you factor in the results of the other blood groups, the relationship becomes far more reasonable. The native Australians might have the same proportions of the ABO blood groups, but the composition of the other groups, like Rhesus, MNS and Duffy, are utterly different. Bit by bit, blood groups began to draw out connections between the different peoples of the world, including western Europeans and the people of the Isles.
The basic pattern which Mourant found across western Europe, the area of most relevance for Saxons, Vikings, and Celts, showed that across the whole region west of the River Elbe in Germany, group A is high and group B comparatively low. East of the Elbe the opposite is the case. There is a gradual shift from B to A, a so-called genetic cline, as we get closer to the Isles. In the Isles themselves Mourant was able to call on absolutely vast amounts of material, both from his own unit, by now incorporated as an official laboratory of the Medical Research Council, the UK’s government funding agency for medical research, and from other published works. Among these were detailed records of blood-group frequencies from Ireland, Wales and the Scottish Highlands.
Mourant gave the task of collecting all the records from the ‘missing’ bits–that is to say England, lowland Scotland and Northern Ireland–to his long-term assistant Ada Kopec, who, with a librarian and a secretary, made up the entire staff of the Blood Group Centre. It is plain from reading the account of this mammoth piece of assimilation and statistical comparison of a grand total of 477,806 results that Ada Kopec was far more concerned with mathematical manipulation of the figures than with explanation. Indeed it is left to Mourant himself, writing in the Foreword, almost to excuse his assistant from any genetic or anthropological interpretation, which, he writes, ‘will have to be made by others’. Fortunately, there were ‘others’ prepared to stick their necks out.
The conclusions of Mourant and Kopec’s gigantic enterprise can be summarized very concisely. In Ireland there are very high levels of blood group O, the highest in Europe. The further west you go, the higher the group O proportions. And, as elsewhere in Europe, where O is high, A is low and vice versa, so in the eastern counties of Ireland, where O is lower than in the west, A is higher. The differences in different parts of Ireland are not dramatic, but because the number of individuals taking
part is so high, the figures can be relied upon to be statistically reliable. So whereas in County Clare, in the far west of Ireland, 80 per cent of people are in group O, this drops to 73 per cent in County Wexford in the south-east, with a mirror-image result for blood group A. Turning to blood group B, there is a slight reversal of the trend across the rest of north-west Europe. Instead of following the rule of the further west, the lower the proportion of B, there is a distinct and statistically significant rise in the far west of Ireland compared to the east. It goes from 6.6 per cent in Wexford to 8 per cent in Kerry.
Now comes the explanation. According to Professor Geoffrey Dawson from Trinity College Dublin, the high levels of A in south-east Ireland are a direct result of successive waves of immigration into Ireland from England. In the first of many papers on the blood groups of Ireland, written in the 1950s, Dawson kicks off with a summary history of Ireland. He explains the blood-group changes from east to west by the Anglo-Norman invasion in the twelfth century, which we will revisit in a later chapter, and by attempts to settle English immigrants under Queens Mary and Elizabeth in the late 1500s.
I much prefer it when authors do advance a theory to explain their results, rather than leave it to others. But how can Dawson possibly know this is the reason for the blood-group differences? Why could they not be equally well explained by other movements of people in prehistoric times? Or by a mixture of both? The whole thrust of the explanation is based on historical events that we already know about. If we had not had a reasonable explanation to hand, would the blood-group evidence be strong enough to come up with one on its own? I really doubt that. Instead of proposing something completely original, the genetic data is rationalized and fitted in to what we already suspect from other sources.
The rationalizations reach their peak in relation to Iceland. Iceland was unoccupied until the late 800s when the systematic settlement from Scandinavia began. The language, the culture, even the written histories recorded in the Icelandic sagas, including the Histories of Settlement, leave no one in any doubt that the great majority of settlers were Norse. And yet, the blood-group proportions in Iceland are very different from those of modern-day Norway and almost identical to those of Ireland, as the table shows.
