Queen Victoria's Gene

by D M Potts

  When the Archbishop of Canterbury was ill and not expected to recover the Dean of Windsor wrote, ‘now as to the successor, Mr Gladstone was immediately in the field . . . and the proposition he made . . . coincided with the advice of Prince Leopold.’23

  The ugly duckling had now become a swan, if a lame one. At this time he began to disseminate sensible ideas in education. His own had been erratic but as an invalid he may have read more widely than if he had had an orthodox education. Too ill for regular schooling he attended Christ Church Oxford, leaving with an honorary Doctorate of Civil Law. He advocated the expansion of universities and technical training, as well as establishing a Royal Conservatory of Music. He became a Freemason.

  In 1881 Victoria created Leopold Duke of Albany and the now mature ugly duckling began looking for a bride. He dreamed of the lively and beautiful seventeen-year-old Frances Maynard, stepdaughter of the Earl of Rosslyn, but she fell in love and married Leopold’s equerry, the future Earl of Warwick. She was to succeed Lillie Langtry as a mistress of the Prince of Wales.24 Leopold turned instead to Princess Helena of Waldeck, sister of the Dutch queen. His mother noted in her diary: ‘1882 7th April: Dear Leopold’s birthday . . . How often has his poor young life hung by a thread and how many and wearisome illnesses has he not [sic] recovered from! Though the idea of his marrying makes me anxious, still, he has found a girl, so charming, ready to accept and love him in spite of his ailments. I hope he may be happy and carefully watched over.’

  They married later that month. The queen gave the newly weds Claremont House, where Charlotte had died and great-uncle Leopold had lived when in England. Shortly before the wedding Leopold was incapacitated with an episode of severe bleeding after slipping on an orange peel in a French hotel and on his wedding day the queen noted in her journal, ‘It is very trying to see the dear boy on the important day of his life still lame and shaking’. He was bedridden a second time at the birth of his daughter Alice in February 1883. Victoria had also injured her leg at the same time and when she visited her parturient daughter-in-law and sick son she wrote ‘and I came as a third helpless creature, it had quite a ludicrous effect’.

  The family of Prince Leopold. Carriers of haemophilia underlined, haemophiliacs boxed

  While Helena was carrying their second child, the royal doctors sent Leopold to Cannes to escape the unusually severe winter. His anxious mother noted: ‘21st Feb 1884: Leopold started for Cannes to stay at the Villa Merada, Capt. Percival’s little villa there, as he thinks he requires a little change and warmth but he is going alone as Helene’s health doesn’t allow her to travel just now. I think it a pity he should leave her.’

  Here Leopold fell on a staircase of his hotel and died of a brain haemorrhage a few hours later. Victoria wrote, ‘. . . there was another cipher coming from Mr Royle, saying he had to announce that my darling Leopold had died at 3.30 this morning quite suddenly in his sleep from the breaking of a blood vessel in his head. Am utterly crushed.’

  Helena’s second child, Charles Edward Leopold, was born after Leopold’s death in France. As the gene for haemophilia can only be carried on the X chromosome, which boys inherit from their mother, he had to be free of the disease. He lived to 1954 and had six children, all of whom, in turn, were without any risk of haemophilia or being carriers of the disease. In 1900 he inherited the old dukedom of Saxe-Coburg and Gotha from his uncle the Duke of Edinburgh and Saxe-Coburg: the Duke of Edinburgh’s only son had died childless the previous year and the Duke of Connaught, the next in line, had wisely renounced his claim in order to remain British. Charles Edward enthusiastically threw in his lot in his ancestral homeland, rising to the rank of General in the German Imperial Army. When the German Empire collapsed in 1918 he was forced to abdicate his dukedom but he went on to play a key role in Hitler’s rise to power, and this is a story we will return to in Chapter 10.

  During her reign Queen Victoria came to rule the largest empire the world had seen or was to see; more cities were founded in her name than Alexander the Great dreamed of; her engineers undertook works more ambitious than Rameses had raised and her troops fought on frontiers the Romans and Persians never reached. She was also the carrier of a lethal gene. Just as she had been manipulated to mate with a particular man, so she in turn chose thebrides and grooms for her own children. What she could not do was to control the genetics of haemophilia although, as we will see in the next chapter, the general principles of the inheritance of haemophilia were understood during Victoria’s childbearing years. Unfortunately, the relevant scientific knowledge did not penetrate to royal circles and the uncontrolled spread of the gene among her grandchildren was to change the course of world history.

  Would history have been different if Victoria’s eldest son, Edward Prince of Wales, had been the ugly duckling and Leopold had been a healthy child? Leopold became president of the Royal Society of Letters and vice-president of the Society of Arts. The contrast with his elder brother the Prince of Wales, whose interests rarely extended beyond wine, women, gambling and song was remarkable. Or what if Vicky had been a carrier and perhaps her son, the future kaiser, a haemophiliac, while Alice’s family had been normal? There might not have been world war in 1914 or a Russian revolution in 1917. Or what if the unfortunate haemophiliac Leopold had fallen on his head five months earlier, or if Charles Edward had inherited his father’s lethal gene and died young? There might not have been war in 1939 and thirty million people might have lived a lot longer.

  FIVE

  THE BLEEDERS

  Haemophilia, the disease carried by Queen Victoria, which was manifest in Prince Leopold and passed on by two of her daughters, was well recognized in her day. However, the nature of the disease, both genetically and physiologically, has only been understood since her death. The medical knowledge we have today enables us both to ameliorate most of the disease’s painful and life-threatening consequences and to ask some novel historical questions.

  Until very recently, haemophilia was, in the words of one twentieth-century victim of the disease, ‘an everlasting bloody nuisance’. In order to understand the condition it is necessary to understand why and how blood clots. Only the smallest animals can get by without a circulatory system. All other animals need a liquid carried around the body in a system of pipes to transport the products of digestion, waste materials, oxygen and carbon dioxide. In mammals like ourselves, the cardiovascular system works at relatively high pressure, carrying blood at high speed to every organ through literally miles of blood vessels and capillaries. Over a lifetime the human heart pumps the equivalent of about 300,000 tons of blood through the body and lungs – enough to fill the world’s largest supertanker – yet even a slow leak is potentially disastrous as we only have about eight pints of blood at any one time.

  All living animals face a profound problem in that some injury is almost inevitable, whether this is massive trauma breaking a major blood vessel or minor damage to relatively few capillaries. An automatic repair system is essential, but evolution has had to produce a mechanism that won’t be triggered accidentally, blocking essential blood vessels, yet will respond quickly to localized damage. Needless to say the system is necessarily complex and it has taken a great deal of scientific time and effort to understand how human blood clots.

  Throughout much of Victoria’s reign the nature of haemophilia was in doubt. Some pathologists thought it was due to a defect in the blood vessels and a follower of the phrenologist Gall said it was the male equivalent of menstruation. However, in 1891 Wright showed that the blood of haemophiliacs took longer to clot, when stored in a glass tube, than that of a normal person.

  Scientists had already demonstrated that blood contains a dissolved protein which they called fibrinogen. When a clot forms it is converted to a tangled network of fibrin, plugging any hole through which blood might escape. The conversion of dissolved fibrinogen into solid fibrin is rather like the action of rennet on milk, and we now know that an enzyme called thrombin i
s necessary for a fibrinogen to turn to fibrin. The origin of thrombin is the most complicated part of the whole story and only after a hundred years of patient laboratory work and meticulous observation of patients with various clotting disorders is the full picture being finally understood. Like a gourmet recipe, at least ten ingredients are needed to form thrombin, among them a factor from damaged tissue itself, blood platelets (the tiny scraps of cellular material that are even smaller than the thirty billion red blood cells in our body) and a number of enzymes and their precursors, such as prothrombin, and other factors. If one link in the chain of reactions necessary for blood clotting is broken then exceptionally serious consequences follow. Haemophilia (literally the love of blood) is a disease in which one link in the chain in the formation of thrombin is broken. It is an inborn, hereditary disease and it is found in horses, dogs and some primates, including humans. Dogs and horses with the disease generally die within three to six months of birth, but human beings with the disease, like Prince Leopold, can live to be adults.

  Although haemophiliacs are born with the disease, they do not bleed severely during birth or when the cord is cut. It is not known why. The baby, however, may bruise easily and when he begins to crawl may bleed into the knee and elbow joints. Unlike the normal person, relatively slight damage, perhaps not even recognized by the individual, may set off an episode of haemorrhage. Once the child begins to walk bleeding incidents become more common. Bleeding may be external or internal and can take place from practically any site, including the nose, mouth, gums, intestine, brain, kidney, skin or joints. Bleeding into the joints is common and excruciatingly painful. It gives rise to a hard, warm swelling of the joint, restricting movements of the limb and, as the blood is absorbed, causes a bodily fever. The victim is afraid of even the smallest movement and an accidental jarring of the bed can make a child scream with pain. Eventually, the blood in the joint will clot, but then it is partially replaced by fibrous tissue and repeated damage leads to severe deformities and lifelong handicap.

  The problems caused by haemophilia are not the same for all individuals, and may change during the life of the sufferer. Victims of the disease recognize ‘bleeding phases’, even though there is no physical explanation of why the condition should get better or worse. Some hardly recover from one episode before starting the next. Some may bleed internally, whereas others do not, although all respond severely to trauma. A tooth extraction, for example, can lead to exceptionally prolonged bleeding. Occasionally, a patient may bleed into his muscles or loose tissue under the scalp and produce enormous swellings containing literally pints of blood. ‘It doesn’t take much to bruise an over-ripe tomato’, commented one haemophiliac before modern therapies were available, ‘and that is what haemophilia is like.’ A medically qualified victim of the disease, writing about his own life in a medical journal in 1949, described episodes of bleeding as merely a dramatic worsening of a miserable condition and even when he was ‘well’ he had to live with contractures of his muscles, nerve pain, damaged joints, impaired circulation, anaemia and ‘almost constant pain’.

  Haemorrhage into the brain, as occurred with Prince Leopold, is one of the most serious complications of haemophilia. Children with haemophilia are usually forbidden to play sports, but may do so surreptitiously. If what appears to be a mild head injury occurs, they may be afraid to tell their parents, only to become unconscious later and perhaps die. Living with a painful, incurable, unpredictable disease may make great demands on the sufferer and on the parents, especially as families may hand down a legacy of misery and despair experienced by earlier generations. It is difficult for a mother not to be over protective and a son passive and overdependent. But surrounded by ‘don’t do this’ and ‘don’t do that’, a child, particularly an adolescent, may take on a dare-devil, fatalistic attitude. Some haemophiliacs seek out potentially dangerous situations, driving dangerously, or, in one contemporary case, even deciding to be a butcher. The young tsarevitch had to be left behind at Tobolsk for a while, under the care of his sisters, after his parents had been moved to their final prison at Ekaterinburg. The daughter of the family physician, Dr Botkin, later recalled that while there he used to play a wild game, sliding down the stairs from the second floor in a wooden boat. The crash made the inhabitants of the house cover their ears. ‘It was as if he were trying to prove something to himself.’1 In the nineteenth century haemophiliacs had even more difficult times than those alive today. One artisan contemporary of Prince Leopold became a cobbler and died of haemorrhage twenty days after pricking his gum with a nail, which like all cobblers, he held between his lips. Others died from accidents involving horses or farm animals. It is possible that fear and depression react directly on blood clotting and, conversely, reassurance and a calm commanding person in charge of treatment may hasten recovery.

  One of the best-documented families of haemophiliacs lived in the Swiss canton of Valais, near the source of the Rhine. The church registers of the little town of Tenna record that, ‘Albrecht Gartmann, legitimate son of the late Hans Gartmann, born 11th June 1699, died in 1730 on the 26th of September at 31 years of age, after all the blood flowed out of him’. Again in the same locality a few years later. ‘Samuel Walther was buried here on the 8th of May 1741. He was during 33 years a pious and honourable Councillor, lived for 26 years, 5 months, 16 days with his second wife, bled 7 days and nights continuously in the mouth and died therefore when he was 65 years and 3 months old.’

  The Tenna bleeders have been followed over seven generations, and five out of twenty males had children, including twenty-three daughters, each of whom would have been a carrier. There are many records of nineteenth-century haemophiliacs marrying and having children, including Prince Leopold. One severely affected man married twice and another married his dead brother’s widow. One German haemophiliac was conscripted into the Franco-Prussion War and survived being wounded in battle.

  From families like the Tenna bleeders the peculiar characteristics of the inheritance of haemophilia were empirically elucidated but the complicated nature of sex-linked inheritance prevented any understanding of the details of the mechanism.

  The earliest historical references to the disease relate to circumcision. A second-century Jewish writer gave permission for a woman not to have her third son circumcised after her first two died from the ritual. Another rabbi exempted a woman whose sister had sons who died after circumcision, demonstrating an emerging understanding of the inheritance of the disease. Unfortunately, these examples of rabbinical advice were not always followed and one nineteenth-century Ukrainian Jewish family lost ten sons from circumcision.

  The great tenth-century Arabian physician Maimonides described a village where several of the male children bled to death, and in the eighteenth century a number of family trees of haemophiliacs were drawn up. An anonymous German writer gave a good description of the disease in 1793, and in 1803 John C. Otto (1775–1845), an American physician working in Philadelphia, gave what has become a classic description of the disease in a family whose history he was able to trace back to settlers who landed in America in 1720.

  Like several hereditary diseases, the physical basis of haemophilia has become increasingly well understood over the years and this in turn has led to improved therapies. Insight into the physical basis of the disease has been closely linked to knowledge of genetics and of the chemical structure of genetic material.

  The laws of genetics were first unravelled by a quiet monk who had failed his examinations to become a high school teacher, but who went on to conduct elegantly simple experiments in the pollination of sweet peas in a monastery garden. Father Gregor Mendel was born in Moravia, a province of the Austro-Hungarian Empire, three years after Queen Victoria. He chose to study sweet peas because they were easy to fertilize and possessed easily distinguished characteristics which appeared to be inherited. He demonstrated that inherited characteristics could be explained by postulating discrete factors (genes) which cam
e from each parent and were distributed to the offspring in predictable ways. The biochemical structure of the gene was discovered a hundred years later at Cambridge University, England. Working in temporary accommodation, Francis Crick and a visiting American colleague, James Watson, used X-ray crystallography, a knowledge of the architectural rules of biochemistry and, like Mendel, a good share of genius, to arrive at an understanding of the way in which molecules carry genetic information.

  All living animals are composed of cells. Between the work of Mendel and Crick it had been established that all cells have a nucleus containing chromosomes which, under the microscope, can be seen to split into identical groups at each cell division so that each cell retains a full complement. In the human being there are twenty-three pairs of chromosomes. In each pair one will have been contributed from the father’s sperm and one from the mother’s egg. When eggs and sperm are formed the number of chromosomes is halved so that at fertilization a full complement is restored.