by Bryan Sykes
3
FROM BLOOD GROUPS TO GENES
There are few things more distinctive about a person than their hair. It is one of the very first features we ask for in any description of a new baby, a stranger or a wanted criminal. Dark or blonde, wavy or straight, thick or balding: all these different possibilities add immediately to the picture we build up in our minds of someone we have never met. We certainly know how to manipulate the way our own hair appears. Salons are full as we pay to have our hair cut and shaped. Pharmacy shelves are lined with products to lighten, darken, straighten and curl. We are all working to make the best of the hair we were born with; but it is our genes which deal out the basic raw material. The difference between a natural redhead and a blonde lies in a difference in their DNA. Within the genes for keratin and the many others involved in the process of growing hair are small differences in the DNA sequence. These are responsible for giving the hair different characteristics of colour and texture. Most of these genes have yet to be identified, but they are certain to be inherited from both parents, although not necessarily in a straightforward way – which is why it is a fairly frequent occurrence that a new baby does not have the hair colour of either of its parents.
Hair type is a highly visible distinguishing feature by which we tell individuals apart, but by far the greatest inherited differences between us are invisible and remain hidden unless something brings them to our attention. The first of these inherited differences to be revealed were the blood groups. You cannot tell just by looking at someone which blood group he or she belongs to. You can’t even tell by simply looking at a drop of their blood. All blood looks pretty much the same. It is only when you begin to mix blood from two people that the differences begin to make themselves apparent; and, since no-one had any reason to mix one person’s blood with another until blood transfusions were invented, our blood groups stayed hidden.
The first blood transfusions were recorded in Italy in 1628, but so many people died from the severe reactions that the practice was banned there, as well as in France and England. Though there were some experimental transfusions using lamb’s blood, notably by the English physician Richard Lower in the 1660s, the results were no better and the idea was given up for a couple of centuries. Transfusions with human blood started up again in the middle of the nineteenth century, to combat the frequently fatal haemorrhages that occurred after childbirth, and by 1875 there had been 347 recorded transfusions. But many patients were still suffering the sometimes fatal consequences of a bad reaction to the transfused blood.
By that time, scientists were beginning to discover the differences in blood type that were causing the problem. The nature of the reaction of one blood type with another was discovered by the French physiologist Léonard Lalois when, in 1875, he mixed the blood of animals of different species. He noticed that the blood cells clumped together and frequently burst open. But it was 1900 before the biologist Karl Landsteiner worked out what was happening and discovered the first human blood group system, which divides people into Groups A, B, AB and O. When a donor’s ABO blood group matches that of the patient receiving the transfusion, there is no bad reaction; but if there is a mismatch, the cells form clumps and break open, causing a severe reaction. There is some historical evidence that the Incas of South America had practised transfusions successfully. Since we now know that most native South Americans have the same blood group (Group O), the Inca transfusions would have been much less dangerous than attempts in Europe, because there was an excellent chance that both donor and patient would belong to Group O and thus be perfectly matched.
Unlike the complicated genetics which governs the inheritance of hair, which is still not fully understood, the rules for inheriting the ABO blood groups turned out to be very simple indeed. Precisely because the genetics were so straightforward and could be followed easily from parents to offspring, blood groups were widely used in cases of contested paternity until recently, when they were eclipsed by the much greater precision of genetic fingerprints. Their significance for our story in this book is that it was the blood groups which first launched genetics on to the world stage of human evolution. For this debut we need to go back to the First World War and to a scientific paper delivered to the Salonika Medical Society on 5 June 1918. It was translated and published the following year in the leading British medical periodical The Lancet under the title ‘Serological differences between the blood of different races: the results of research on the Macedonian Front’. To give you a flavour of the sort of thing The Lancet published in those days, the article was sandwiched between a discourse by the eminent surgeon Sir John Bland-Sutton on the third eyelid of reptiles and a War Office announcement that those nurses who had been mentioned in dispatches for their work in Egypt and France would soon be getting a certificate from the King showing his appreciation.
The authors of the blood group paper were a husband and wife team, Ludwik and Hanka Herschfeld, who worked at the central blood group testing laboratory of the Royal Serbian Army, which was part of the Allied force fighting against the Germans. The First World War had a great influence on bringing blood transfusion practice towards its modern standards. Before the war it had been customary for physicians with a patient who needed a transfusion to test the blood groups of friends and relatives until a match was found, then bleed the donor and immediately give the blood to the patient. The high demand for transfusions on the battlefields of Europe meant that ways had to be found to store donated blood in blood banks ready for immediate use. All soldiers had their blood group tested and recorded so that, should they need an urgent transfusion to treat a serious battlefield wound, compatible blood of the correct type could be immediately drawn from the blood bank.
Ludwik Herschfeld had already demonstrated, some years earlier, that blood groups A and B followed the basic genetic rules laid out by Gregor Mendel. He was not sure what to make of blood group O and set it aside, though it was later shown to obey the same rules. Herschfeld saw the war as an opportunity to discover more about blood groups, and in particular how they compared in different parts of the world. The Allies drew soldiers from many different countries, and the Herschfelds set out to collate the blood group results from as many different nationalities as possible. It was a lot of work, but easier in wartime than later, when the research would, as they put it, ‘have necessitated long years of travel’. For the obvious military reason that they were on the other side, they did not have the German data to hand, and the figures published in The Lancet were ‘quoted from memory’.
When the Herschfelds came to review the results of their work, they found very big differences in the frequencies of blood groups A and B in soldiers who came from different ‘races’ as they called them. Among the Europeans, the proportions were around 15 per cent blood group B and 40 per cent blood group A. The proportion of men with blood group B was higher in troops drawn from Africa and Russia, reaching a peak of 50 per cent in regiments of the Indian Army fighting with the British. As the proportion of blood group B increased, there was a corresponding decrease in the frequency of blood group A.
In drawing their conclusions, the Herschfelds did not flinch from interpreting the significance of their results on a grand scale. They decided that humans were made up of two different ‘biochemical races’, each with its own origin: Race A, with blood group A, and Race B, with blood group B. Because Indians had the highest frequency of blood group B, they concluded that ‘We should look to India as the cradle of one part of humanity.’ As to how blood groups, and populations, spread, they go on: ‘Both to Indo-China in the East and to the West a broad stream of Indians passed out, ever-lessening in its flow, which finally penetrated to Western Europe.’ They were unsure about the origin of Race A and thought it might have come from somewhere around north or central Europe. We know now that their conclusions are complete nonsense; but they do illustrate that geneticists, then as now, are never shy of grandiose speculation.
The basi
c principle behind the evolutionary inferences drawn from the Herschfelds’ blood group results was that ‘races’ or ‘populations’ that have similar proportions of the different blood groups are more likely to share a common history than those where the proportions are very different. This sounds like common sense, and it looks like a reasonable explanation for the similarities found in the different European armies. But there were also some surprises. For example, the blood group frequencies of soldiers from Madagascar and Russia were almost identical. Did this mean the Herschfelds had uncovered genetic evidence for a hitherto unrecorded Russian invasion of Madagascar, or even the reverse, an overwhelming Malagasy colonization of Russia? Or take the Senegalese from West Africa, who were almost as close in their blood group frequencies to the Russians as the English were to the Greeks, which seems a bit unusual to say the least. What was happening was that because they were working with just one genetic system – the only one available to them – their analysis produced what appear to be some very reasonable comparisons between populations and others that look distinctly odd.
In the years after the First World War, it fell to the American physician William Boyd to compile the abundant blood group data coming from transfusion centres throughout the world. As he did so, he saw inconsistencies of the Russia/Madagascar kind revealed by the original Herschfeld results time and again, so frequently, in fact, that he actively discouraged anthropologists from taking any notice of blood groups. Boyd quotes a letter from one frustrated correspondent: ‘I tried to see what blood groups would tell me about ancient man and found the results very disappointing.’ Even so, the unsuccessful attempts to explain human origins using blood groups had had their compensations for the liberal-minded Boyd. 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.’
After the Second World War, William Boyd’s baton as compiler of blood group data from around the world passed to the Englishman Arthur Mourant. A native of Jersey in the Channel Islands, Mourant originally took a degree in geology but was unable to translate that training into a career. His very strict Methodist upbringing had caused him considerable emotional unhappiness, which he determined to resolve by becoming a psychoanalyst. To do this he decided first to study medicine and enrolled, at the relatively late age of thirty-four, in St Bartholomew’s Medical School in London. This was in 1939, just before the outbreak of the Second World War. To avoid the German bombing raids on the capital, his medical school was moved from London to Cambridge, and it was here that he met R. A. Fisher, the most influential geneticist of his day. Fisher had been working out the genetics of the new blood groups which were being discovered, and he had become fascinated by the particularly convoluted inheritance of one of them – the Rhesus blood group. This new group had been discovered by Karl Landsteiner and his colleague Alexander Wiener in 1940 after they mixed human blood with the blood of rabbits that had themselves been injected with cells of the Rhesus monkey (hence the name). Fisher had come up with a complicated theory to account for the way in which the different sub-types within the group were passed down from parents to their children, and this was being violently attacked by Wiener who had offered a much simpler explanation. Imagine Fisher’s delight when the new arrival, Arthur Mourant, discovered a large family of twelve siblings which provided the practical proof of his theory. Fisher found him a job at once, and the meticulous Mourant spent the rest of his working life compiling and interpreting the most detailed blood group frequency distribution maps ever produced. He never did become a psychoanalyst.
As well as being instrumental in getting Arthur Mourant a job, the Rhesus blood groups were also about to play a central role in what people were thinking about the origins of modern Europeans and in identifying the continent’s most influential genetic population – the fiercely independent Basques of north-west Spain and south-west France. The Basques are unified by their common language, Euskara, which is unique in Europe in that it has no linguistic connection with any other living language. That it survives at all in the face of its modern rivals, Castilian Spanish and French, is remarkable enough. But two thousand years ago, it was only the disruption of imperial Roman administration in that part of the empire that saved Euskara from being completely swamped by Latin, which was the fate of the now extinct Iberian language in eastern Spain and south-east France. The Basques provided us with an invaluable clue to the genetic history of the whole of Europe, as we shall see later in the book, but their elevation to special genetic status only began when Arthur Mourant started to look closely at the Rhesus blood groups.
Most people have heard about the Rhesus blood groups in connection with ‘blue baby syndrome’ or ‘haemolytic disease of the new-born’ to give it its full medical title. This serious and often fatal condition affects the second or subsequent pregnancy of mothers who are ‘Rhesus negative’ – that is, who do not possess the Rhesus antigen on the surface of their red blood cells. What happens is this. When a Rhesus negative mother bears the child of a Rhesus positive father (whose red blood cells do carry the Rhesus antigen), there is a high probability that the foetus will be Rhesus positive. This is not a problem for the first child; but, when it is being born, a few of its red blood cells may get into the mother’s circulation. The mother’s immune system recognizes these cells, with their Rhesus antigen, as foreign, and begins to make antibodies against them. That isn’t a problem for her until she becomes pregnant with her next child. If this foetus is also Rhesus positive then it will be attacked by her anti-Rhesus antibodies as they pass across the placenta. New-born babies affected in this way, who appear blue through lack of oxygen in their blood, could sometimes be rescued by a blood transfusion, but this was a risky procedure. Fortunately, ‘blue baby syndrome’ is no longer a severe clinical problem today. All Rhesus negative mothers are now given an injection of antibodies against Rhesus positive blood cells, so that if any do manage to get into her circulation during the birth of her first child they will be mopped up before her immune system has a chance to find them and start to make antibodies.
The significance of all this to the thinking about European prehistory is that Mourant realized that having two Rhesus blood groups in a single population did not make any evolutionary sense. Even the simplest calculations showed that losing so many babies was not a stable arrangement. There was no problem if everybody had the same Rhesus type. It didn’t matter whether this was Rhesus positive or Rhesus negative, just so long as it was all one or the other. It was only when there were people with different Rhesus types breeding together that these very serious problems arose. In the past, before blood transfusions and before the antibody treatment for Rhesus negative mothers, there must have been a lot of babies dying from haemolytic disease. This is a very heavy evolutionary burden, and the expected result of this unbalanced situation would be that one or other of the Rhesus blood groups would eventually disappear. And this is exactly what has happened – everywhere except in Europe. While the rest of the world is predominantly Rhesus positive, Europe stands out as having a very nearly equal frequency of both types. To Mourant, this was a signal that the population of Europe was a mixture that had not yet had time to settle down and eliminate one or other of the Rhesus types. His explanation was that modern Europe might be a relatively recent hybrid population of Rhesus positive arrivals from the Near East, probably the people who brought farming into Europe beginning about eight thousand years ago, and the descendants of an earlier Rhesus negative hunter-gathering people. But who were the Rhesus negatives?
Mourant came across the work of the French anthropologist H. V. Vallois, who described features of the skeletons of contemporary Basques as having more in common with fossil humans from about twenty thousand years ago than with modern people from other parts of Europe. Though this kind of comparison has since fallen into disrepute, it certainly catalys
ed Mourant’s thinking. It was already known that Basques had by far the lowest frequency of blood group B of all the population groups in Europe. Could they be the ancient reservoir of Rhesus negative as well? In 1947 Mourant arranged to meet with two Basques who were in London attempting to form a provisional government and were keen to support any attempts to prove their genetic uniqueness. Like most Basques, they were supporters of the French Resistance and totally opposed to the fascist Franco regime in Spain. Both men provided blood samples and both were Rhesus negative. Through these contacts, Mourant typed a panel of French and Spanish Basques who turned out, as he had hoped, to have a very high frequency of Rhesus negatives, in fact the highest in the world. Mourant concluded from this that the Basques were descended from the original inhabitants of Europe, whereas all other Europeans were a mixture of originals and more recent arrivals, which he thought were the first farmers from the Near East.
From that moment, the Basques assumed the status of the population against which all ideas about European genetic prehistory were to be – and to a large extent still are – judged. The fact that they alone of all the west Europeans spoke a language which was unique in Europe, and did not belong to the Indo-European family which embraces all other languages of western Europe, only enhanced their special position.