by Bryan Sykes
8
The Jews
Star of David.
Genetics has been welcomed with open arms by European Americans. At the same time as clearing up various historical uncertainties, it has become almost a routine tool for genealogists. In little more than a decade the field has made the welcome transition from academic laboratory to widespread public participation, most of it self-funded. While the contrast between the enthusiasm for genetics of European Americans and the understandable suspicion shown by Native Americans is stark, there is one group of Americans who might be forgiven for being extremely cautious about the application of genetics to questions about their ancestry and identity. Given the racial and eugenic underpinning of their persecution by Nazi Germany, not to mention centuries of more general anti-Semitism, it would be unsurprising if Jews avoided any involvement with modern genetics at all costs. In fact the opposite is true. Although they are certainly aware of the possibility of its misuse, the Jewish community, especially in the United States, was among the first to embrace genetics, and for one very practical reason. Jews in both the United States and Europe have a high incidence of an otherwise rare genetic condition known as Tay-Sachs disease. The effects of the disease are devastating. At first infants develop normally but after about six months a relentless and ultimately fatal set of physical symptoms makes its appearance. Gradually the child becomes blind and deaf and is unable to swallow. Muscles waste away, and paralysis gradually sets in. Death eventually occurs around the age of four. It is a heartbreaking condition for both the victims and their families.
The underlying biochemical problem in Tay-Sachs is the gradual accumulation of the waste products of fat metabolism, called gangliosides, in nerve and brain tissue. In normal babies these are cleared rapidly by the enzyme hexosaminidase A. In Tay-Sachs sufferers not enough of this enzyme is produced, and the gangliosides gradually build up until they begin to interfere with the proper function of the cells and the first symptoms of the disease appear. The ultimate cause of the enzyme deficiency is a genetic mutation in the hexosaminidase gene, a deletion of four DNA bases that not only removes a vital amino acid but also changes the amino acid sequence of the enzyme downstream of the deletion. This is the mutation that most commonly causes Tay-Sachs disease among Ashkenazi Jews, but there are now more than a hundred separate mutations known in different parts of the world, each interfering with the proper working of the enzyme. This raises the question of why the disease is so relatively frequent among Ashkenazi Jews and so rare elsewhere. One in twenty-seven Ashkenazi Jews in the United States is a carrier for Tay-Sachs, that is they have one normal and one mutated copy of the gene, compared with one in 250 of the non-Ashkenazi population.
The answer comes in two parts. Ashkenazi Jews have always lived as tight-knit communities and have tended to marry other Ashkenazim. In this respect they have something in common with other religious groups that have kept themselves physically apart and married within their communities—for example, groups like the Amish of Indiana and Pennsylvania. One consequence of this way of life is that married couples can both be descended from the same ancestor, even without knowing it. If this ancestor carried the Tay-Sachs gene, it can be carried down the two separate lines of descent to both husband and wife. Although everyone has two copies of the hexosaminidase gene, only one needs to be working properly to provide enough enzyme to clear the gangliosides. So, each with one normal and one mutant version of the gene, the parents are both carriers, but they do not have the disease. However, the basic rules of inheritance mean that there is a 25 percent chance, for each pregnancy, that the child will inherit two mutant versions. When that happens there is not enough enzyme, and the child is doomed.
This partly explains why Tay-Sachs is common in Ashkenazi Jews, but exactly the same argument would apply to other endogamous groups, like the Old Order Amish, among whom Tay-Sachs is unknown. Instead the endogamous traditions of the Amish have had genetic consequences in a much higher incidence of two other inherited disorders, Niemann-Pick and Gaucher’s. Interestingly the residents of two adjacent non-Amish communities, also in Pennsylvania, whose ancestors emigrated to America from Germany and Switzerland through Philadelphia in the early eighteenth century and who have been largely endogamous ever since, have a high incidence of Tay-Sachs. But why is Tay-Sachs and not another disease with the same inheritance pattern, like cystic fibrosis for example, found among the Ashkenazi Jews? This is a much harder question to answer.
The evolutionary reasoning behind the high frequencies of recessive diseases is that although the sufferers who carry two mutant versions of the gene are at a great disadvantage, and in Tay-Sachs they never reach reproductive age, the carriers, with one mutant and one normal version, have some sort of compensating advantage. If they did not, then the mutant gene would soon disappear as every time a sufferer dies, two copies are lost from the population. Although this admittedly theoretical argument applies to all recessive diseases that are at all common, in only one case is there a watertight explanation. This is not a disease that affects Ashkenazi Jews but another community in America. These are the African Americans, and the disease is sickle-cell anemia. We will go on to see how African Americans have dealt with it, but for now let us explore why this particular genetic disease is so frequent within that community. The answer lies not in America but in Africa.
Sickle-cell disease is caused by a mutation, not in hexosaminidase but in one of the genes for the red-blood-cell protein, hemoglobin. In common with Tay-Sachs, only people with two copies of the mutant gene develop the disease. Since it too is fatal, what can be the compensating advantage enjoyed by carriers? The answer lies in their resistance to malaria, an often-fatal disease that is endemic in many parts of sub-Saharan Africa, especially in West Africa, to which many African Americans trace their roots. It has been shown that the red blood cells of sickle-cell carriers are more resistant to the parasite that causes malaria, even though exactly why is still not known. For some reason the parasites find these red blood cells harder to get into, which is normally the first stage of the infection.
What can the carrier advantage be in Tay-Sachs? Here there are only theories, but like sickle-cell, the reason has to be a thumping good one and probably involves resistance to an infectious disease. It doesn’t have to be a disease that is still around. Even if malaria were to be eliminated tomorrow, the sickle-cell gene would still be there and store up problems for future generations. So the answer could lie in resistance to an infectious disease of the past. The likeliest candidate for Tay-Sachs is tuberculosis, which was endemic in the crowded urban ghettos that Ashkenazim were forced to live in for so much of their history. Although there is no direct evidence that carriers have a greater resistance to tuberculosis, and it is hard to imagine carrying out direct experiments to prove this, it is not a bad working hypothesis.
Whatever the reasons for the high incidence of Tay-Sachs among the Ashkenazi Jews, once the genetics were understood, there was a good chance that something practical could be done about reducing the number of babies born with this invariably fatal condition. Although a cure would be a great achievement, prevention would be better and also vastly more practical. The theory was simple: If carriers could be identified, they could either be discouraged from marrying each other or, more likely, never be introduced by the marriage brokers, though this is a profession that has now vanished among secular Jews. Also, carrier couples could be made aware of the one-in-four risk for each pregnancy and, in some cases, opt for prenatal testing and first-trimester termination of any affected pregnancies. No one likes terminations, but in many eyes they are so much better than bringing children into the world whose short lives will be ones of increasing suffering and pain.
It was the U.S. Jewish community itself that led the way, and the first carrier screening for Tay-Sachs began in 1971, based not on DNA but on a blood test for enzyme activity. Screening quickly spread to Jewish communities in Canada and Europe, and to Israel
. Once the hexosaminidase gene had been identified, direct DNA testing for the mutant version began in the early 1990s using a simple mouth swab. By 2000 more than 1.5 million people had been screened, and more than fifty thousand (3.3 percent) of these were found to be carriers. The same DNA test that detected the mutant version of the gene in carriers was also applied to pregnancies where the parents were both carriers. That fact was usually established in couples who had already had a child with Tay-Sachs, and though they often wanted more children, they were understandably extremely eager to avoid having another Tay-Sachs child. The DNA was taken by a biopsy of the chorionic villi lining the uterus, which are part of the placenta and made up of fetal tissue. The biopsies were performed under local anesthetic at between eight and ten weeks into the pregnancy and with little risk to the fetus. By 2000 more than three thousand pregnancies had been tested, just over six hundred of which were found to carry two copies of the mutant gene. All but twenty parents opted to terminate the affected pregnancies, and of those mothers who declined, all went on to have Tay-Sachs babies. Of the more than two thousand pregnancies that continued after being cleared of having two copies of the mutant gene, only three went on to develop Tay-Sachs due to one or both of the parents having other mutant versions of the hexosaminidase gene that were not known at the time.
Led by the Jewish communities in the United States, the Tay-Sachs screening program was one of the first great successes of the practical application of genetic knowledge to an inherited disease. Among Jews in North America the disease has been effectively eliminated, although about ten cases a year are born to American non-Jews, who are not routinely screened. This is not unexpected for, as I hope you will come to realize, no race or ethnic group can ever be accurately defined by the genes they carry. That is not to say, of course, that it has never been tried. In the early days of research into Tay-Sachs disease its apparently exclusive occurrence among Jews certainly appealed to the eugenics movement of the early twentieth century as proof that Jews were a biologically separate race that was constitutionally prone to neurological disorders, as this surprising quotation demonstrates:
In the present state of knowledge of the etiology of idiocy and imbecility in general the only cause of their frequency among Jews that may be considered is the neurotic taint of the race. Children descending from a neurotic ancestry have nervous systems which are very unstable, and they are often incapable of tiding safely over the crises attending growth and development. They are often idiots or imbeciles.
The surprise is not so much the content, which is a fairly standard racist rant, but that it comes from an entry in the Jewish Encyclopedia.1 The unexpectedly calm acceptance of the division of humanity into various different races was taken for granted in 1901 when this edition of the encyclopedia was published. It was written at a time when public opinion in the United States had turned against European immigration, especially from Russia and Eastern Europe. Leading opponents of Jewish immigration used the high incidence of Tay-Sachs disease as proof that Jews were an intrinsically inferior race incapable of adjusting to the American way of life: “The fact that Jewish immigrants continued to display their nervous tendencies in America where they were free from persecution was seen as proof of their biological inferiority and raised concerns about the degree to which they were being permitted free entry into the U.S.”2
There are six and half million Jews living in the United States today, and although most of them trace their recent roots to Europe, the pattern of their arrival in America is distinct from that of other Europeans. Though they are a community bound together by a common religion, Jews have also thought of themselves, and been considered by others, to be a distinct racial or ethnic group, the distinction between the two terms being blurred in common usage. Within Judaism there are three main branches: The Ashkenazim, who make up the great majority of those living in the United States, moved there from central and eastern Europe, including Russia, during the nineteenth and early twentieth centuries, Ashkenaz being the medieval Hebrew for “Germany.” The second group, the Sephardim, settled in Iberia for several centuries, and the name means “Hispanic” in Hebrew. Fewer in number than the Ashkenazim, the Sephardim in America settled earlier, many of them in the Southwest during the Spanish colonial period. The third main branch of Judaism, the Mizrahim, is a less geographically coherent group living mainly in North Africa and the Middle East. In comparison with the Ashkenazim and Sephardim, relatively few Mizrahim have settled in America.
All three branches of Judaism trace their origins to the Middle East two thousand years before the birth of Christ. Jewish tradition traces its ancestry back to Abraham, and as we shall see, there is some genetic evidence to support this genealogy. Abraham is also claimed by Islam as an ancestor of the prophet Muhammad, who lived in the seventh century AD and whose birth marks the start of the Islamic calendar.
As history informs us, the ancient kingdom of Judaea was overrun by the Babylonians at the start of the sixth century BC, at which time the First Temple, built by Solomon, was destroyed. The expulsions that followed the Babylonian victory marked the first of the many episodes of persecution and deportation that have punctuated the history of Judaism. The failure of two revolts against the Roman occupation, in AD 70 and AD 135, added to the Diaspora, as many of the population were scattered or sold into slavery. Yet despite this the Jews remained a cohesive group, and many of the exiled communities flourished. The Diaspora finally came to an end with the foundation of the State of Israel in 1948, though the term is now used to embrace all Jews living outside Israel.
The Ashkenazim emerged as a distinct group during the eleventh century, living in Alsace and along the Rhine, having arrived there from southern Italy after Charlemagne lifted restrictions on trade at the beginning of the ninth century. The period of stability for Jews that began with Charlemagne did not last, however. At the turn of the twelfth century the Ashkenazim suffered at the time of the First Crusade, when—in a classic example of the delusion of the masses—armed Christians set out for Palestine, the Holy Land as they called it, to reclaim it from Islamic rule. Less adventurous souls substituted the Jews as the enemies of Christendom, and began killing them instead of the harder-to-reach Saracens. Returning Crusaders, who had become deeply indebted to Jewish moneylenders, joined in the slaughter as an alternative to repayment.
To avoid the threat of massacre many Ashkenazim moved east to Poland, Lithuania and Russia. More expulsions followed from England in 1290, France in 1394, and again from Germany in the fifteenth century, all of which further increased the number of Jews living in eastern Europe. Jews were also the victims of mob violence, often condoned or even instigated by the authorities. Pogroms, as these acts of organized violence came to be called, occurred throughout the nineteenth and early twentieth centuries in countries like Poland, Russia, and Ukraine that had previously welcomed Jews. The numbers killed in pogroms ran into the thousands and triggered the beginning of large-scale immigration into the United States as Jews realized that they had a much safer and brighter future in America than in Europe. By 1880 more than a quarter of a million had already arrived in the United States, mainly from Germany, and these numbers climbed as a further two million from Russia and Eastern Europe arrived between 1880 and 1914. Terrible though the pogroms were, they pale in the face of the horrors of the Holocaust, which cost the lives of six million Jews during the Second World War. Tight restrictions on immigration imposed by the United States, Britain, and other nations limited the number able to escape persecution by the Nazis in the 1930s, but the great majority who survived the Holocaust eventually made their homes either in America or the newly founded nation of Israel.
On the face of it, given their troubled history of relocation and fragmentation over at least two millennia, the prospects for finding any common genetic ancestry among the Jews seem remote. Not only that, the search for any identifiable Jewish genes might seem an unwise “hostage to fortune” against future perse
cutions. And yet, as I have already mentioned, Jews have been among the most enthusiastic advocates of genetic research, not just for its medical aspects but for exploring their ancestry as well.
The first direct evidence that the Jews might have a separate genetic identity came from a study of the Cohanim, the hereditary priesthood of the Levites. According to tradition, the male descendants of Aaron, the brother of Moses, were chosen to serve as priests. The idea of testing this biblical tradition directly is attributed to Karl Skorecki, a Canadian physician and an Ashkenazi Jew himself, who thought of it when praying in a synagogue in a congregation with Sephardim. If the tradition was true and the patrilineal inheritance of the Cohanim from Aaron had been maintained over the three millennia since he lived, then they should share a Y chromosome inherited, ultimately, from Aaron himself.
Skorecki teamed up with a genetics research group from London, and between them they collected DNA from more than three hundred Jewish men from Israel, Canada, and the United Kingdom. Astonishingly, given the three millennia that have elapsed since Aaron’s time, the London team identified a common Y chromosome (and its close mutational derivatives) in nearly 70 percent of Ashkenazi and just over 60 percent of Sephardic Cohanim, largely identified in the study by the surname Cohen. Among other Jews the frequency of this chromosome was around 10 percent, so this was a very significant finding indeed. The genetic age of the shared Y chromosome was an uncannily accurate three thousand years. It looked as though this really was Aaron’s Y chromosome.