Queen Victoria's ambition
In the colonial era, with the great expansion of British national power and the decline of traditional colonial powers (Spain, Netherlands, etc.). ), relying on active colonial aggression and commercial development of workers and peasants, Britain successfully won the reputation of "the sun never sets on the empire". However, Queen Victoria, who led the British empire to prosperity, also plunged the whole European royal family into turmoil in the following century. It is hard to imagine that the origin of this storm is not Queen Victoria's external expansion, but just a "marriage" she participated in.
Data Map: It was painted by Queen Victoria's painter Franz Xaver Winterhalter from 65438 to 0859.
In the European royal family, marriage is a long tradition. The marriage between the royal families of the two countries can not only maintain the "aristocratic lineage" of the royal families, but also indirectly become a symbol of harmonious relations between countries. Queen Victoria has nine children, among whom alice maud mary married Ludwig IV, Grand Duke of Hesse-Rhine, in 1862, and Princess Beatrice married Prince Henry of Batenburg in 1885. Later, alice maud mary's two daughters were married to the Prussian royal family and the Russian royal family respectively, and the youngest daughter married to Moscow became the last queen of Russia, Alexandra fyodor Rovna; Victoria Eugenia, the only daughter of Princess Beatrice, also became the wife of Spanish King Alfonso XIII. Although her married life in Spain was not happy, she even went into exile in her later years because of the Spanish revolution.
Judging from the above information, Queen Victoria's marriage seems to be quite successful, and many prominent royal families in Europe have successively brought British royal blood through marriage. Unfortunately, however, Queen Victoria herself is a disease-free carrier of hemophilia B, and the two princesses who participated in the marriage also carried the gene of hemophilia B, which made many royal families, including the British royal family, suffer from it later.
Prince Leopold, the son of Queen Victoria, died of cerebral hemorrhage caused by hemophilia in 1884 at the age of 30.
Prince Friedrich, the son of alice maud mary, died of cerebral hemorrhage caused by hemophilia on 1873 at the age of two and a half.
Prince Heinrich of Prussia, grandson of alice maud mary, died of hemophilia in 1904 at the age of 4;
Crown Prince Alexei, the grandson of alice maud mary, died of hemophilia in the February Revolution of 19 18;
Prince Leopold of Batenburg, the son of Princess Beatrice, died of orthopedic surgery on 1922 at the age of 32.
Alfonso, Prince of asturias, grandson of Princess Beatrice, 1938 died of massive bleeding in a car accident at the age of 3 1.
The genetic route of European "royal disease" from the British royal family, in which the yellow box shows the map of diagnosed hemophiliacs: Shakko Kitsune.
After that, hemophilia was "famous all over the world" because it was not in harmony with the royal family, and it was nicknamed "royal disease"; However, the lives of these princes with hemophilia can be described as terrible. Even in the 20th century, when blood transfusion was developed, they carefully told doctors to prepare whole blood for emergencies before going out and completing physical examination or surgery. As for the complications caused by long-term internal bleeding (such as joint diseases), due to the medical level at that time, they could only endure it silently.
Hemophilia, "Christmas disease" and "royal disease"
Although the story between the British royal family and hemophilia has been known for many years, the medical knowledge of hemophilia has little to do with the royal family. 1803, a surgeon in Philadelphia, John Connard Otto, described "bleeding tendency in a specific family" in his paper, and thought that according to the evidence available at that time, it could be concluded that the disease was mainly male and spread through "healthy" women in the family. This paper not only describes the symptoms and genetic characteristics of hemophilia in detail for the first time, but also becomes the second article in the world to report X-linked genetic diseases (diseases caused by X chromosome genes and transmitted to the next generation with reproduction) after Dalton reported red-green color blindness.
Then at 1828, hopf, a student at the University of Zurich, used "hemophilia" to describe this "bleeding tendency" for the first time, which also means that hemophilia as a disease began to be widely recognized by the medical community. 1937, two doctors from Harvard University officially isolated anti-hemophilia globulin (coagulation factor VIII) from human plasma. It was soon discovered that its lack was the direct cause of hemophilia A, and it seemed that human beings were infinitely close to the truth of hemophilia.
However, while the world was amazed at the discovery of coagulation factor VIII, some scholars began to question the view that the lack of coagulation factor VIII led to hemophilia. The climax of questioning occurred in 1947. An Argentine doctor conducted an in vitro experiment with the blood of two hemophiliacs with the same blood type. He found that when the two kinds of blood were mixed in vitro, the blood itself did not agglutinate, but the mixed samples could not detect any signs of hemophilia. According to this result and previous studies on coagulation factor VIII, many people boldly speculate that there may be another coagulation abnormality unrelated to coagulation factor VIII in the world, but it has been classified as "hemophilia", which leads to the lack of relevant research.
Many things happen, and the process of finding these evidences didn't waste too long-1952, a 5-year-old British-Canadian boy named Stephen Krismer was admitted to the hospital for hemophilia while visiting relatives in London, and the doctor sent a blood sample of him to the Oxford Hemophilia Center as usual. However, hematologists Biggs and MacFarlane found that Krismer's blood sample did have the characteristics of hemophilia, but the level of coagulation factor VIII was completely normal. Soon, researchers isolated Krismer's lack of protein-coagulation factor IX (then known as "Christmas factor") from the plasma of normal people, which can help patients with similar diseases recover their coagulation ability after infusion.
Data Map: Churchill Hospital of Oxford University, where the Oxford Hemophilia and Thrombosis Center was established.
In order to distinguish this disease from typical hemophilia, scientists named it "Christmas Disease" after Krismer. After decades of rapid development of biotechnology, molecular studies have proved that both hemophilia and Christmas disease are caused by the lack of coagulation factors, but the types of coagulation factors that patients lack are different, so the mechanisms of coagulation abnormalities are different. Based on this discovery, "hemophilia" and "Christmas disease" were renamed as hemophilia A and hemophilia B.
Interestingly, Krismer, who played a key role in the discovery of hemophilia B, probably thanked the doctors for their discovery. Later, he studied medical imaging at Ryerson Institute of Technology (now Ryerson University) and became an imaging doctor at Toronto Children's Hospital after graduation. After work, he has been committed to the rights and interests of hemophiliacs. As a core member of the Hemophilia Association of Canada, he called for attention to blood safety. Unfortunately, due to years of dependence on blood transfusion, Krismer was infected with HIV and quickly developed into AIDS. 1993 died at the age of 46.
The main reference materials of this paper:
Giangrande str. Looking for the author's six words: the history of coagulation factor naming. Egyptian ruby121(5): 70312. doi: 10. 1046/j . 1365-2 14 1.2003.04333 . x
Biggs R, Douglas AS, Macfarlane RG, Dacie JV, Pitney WR, Merskey C, O 'Brien Jr. Christmas disease: a disease that was previously mistaken for hemophilia. BMJ 2(4799): 137882。 doi: 10. 1 136/BMJ . 2.4799. 1378
Luo Gaeff, Grigorenko AP, Fashu Tynova G, Kitler EL, moglia Kayk. Genotype analysis determines the cause of royal diseases. Science 326(5954):8 17. doi: 10. 1 126/science . 1 180660。