Haemophilia

Haemophilia: There are two types of haemophilia (A & B). In the human genome (all the genes put together) there are 23 pairs of chromosomes (clusters of genes) in every cell of which 22 pairs are called autosomes (common to both female and male) and one pair known as X-X in female and X-Y in male.

The X-X and X-Y pairs are called sex chromosomes. Haemophilia is an X-linked recessive (submissive) disorder characterised by the inability to properly form blood clots to arrest bleeding when there is a cut in a blood vessel.

The gene product known to be the crucial ingredient to clot blood is called Factor VIII (haemophilia A). Until a few years ago, the hemophiliacs did not live long. It affects males much more frequently (1 in 10,000) than females (1 in 100,000,000). This is because males carry only one X chromosome while females carry two X chromosomes. If the gene responsible for blood clot is defective, haemophilia shows up. In women even when one X chromosome is defective, the other will compensate (it is unlikely to be defective in both X chromosomes) and thus they escape the disease but they are called “carriers” who transmit the defective gene to their offspring and the male offspring are bound to be haemophiliacs while the female offspring will continue to be carriers.

The hereditary nature of this disease was known as early as the 6th century CE as detailed in a passage in Talmud (collection of Jewish oral tradition interpreting the Torah) which advised the avoidance of circumcision of a male baby if the baby’s maternal uncle was known to be a bleeder, long before Gregor Mendel (1822-1884) devised the rules of modern genetics.
Interestingly enough, haemophilia has an important royal and political history. Queen Victoria, who ruled Great Britain (and the British empire) from 1837 to 1901, was a carrier of the recessive disorder. She had a son (Prince Leopold) who succumbed to the disease at age 31. The queen also had two other daughters (of a total of nine children) who were carriers of the haemophilia gene. One of them (Alice) had a daughter by name Alexandra (also a carrier) who married Nicholas II, the last Tsar of Russia. The Russian royal couple had four daughters in a row and finally a son (heir to the throne) by name Alexis. Right from childhood Alexis suffered from haemophilia and the doctors could do nothing to help him. Rasputin, the notorious peasant-monk, came on the scene and was able to control the bleeding of Alexis through some mystical means. This ability gained him political clout but the resulting events alienated the monarchy from the masses. It was a major cause for the Russian Revolution of 1917 and the entire royal family of 7 was summarily executed in 1918.


Historians have remarked that if Alexis had not had haemophilia, Rasputin would not have gained power and there would have been no Russian Revolution. Haemophilia, a single mutation (change) in a single gene, may have helped change history’s course. It is a pathetic case of ‘For want of a horseshoe ……………..a kingdom was lost’.

Before the 1960s, blood transfusion and administration of plasma were the only remedies available and that too not quite reliable. In the ‘60s, a new method called cryo-precipitation was developed to separate the Factor VIII from blood plasma. This was a big improvement over blood transfusion. Later, in the 1970s, freeze-dried forms of Factor VIII were available which when reconstituted with pure water could be used for injection by the haemophiliacs anywhere. However, since the factor was isolated from human blood, there were problems with hepatitis C, and HIV infection.

In 1984, Bayer Corporation took the bold measure of undertaking a recombinant DNA technology to make Factor VIII in mammalian cells without any connection to blood. The healthy human gene for Factor VIII was isolated, packaged in a vector (agent) and incorporated in what are known as Chinese Hamster Ovary cells and grown in huge bioreactors. The product Factor VIII was made in large quantities which was purified and introduced in the pharmaceutical market as Recombinate® in 1992. Ever since then, haemophiliacs could lead a normal life just like any other human being expecting to live their allotted span of life. This would not have been possible without the help of genetic engineering and biotechnology. A case of conquering fate, indeed!