June 14 is a day to remember. On this day in 1868, Karl Landsteiner was born. Two hundred years before this date, on 15 June 1667, the first human blood transfusion was administered by JeanBaptiste Denis. Denis was accused of murder, because the person who received the transfusion died. For millennia, the life-preserving function of blood was strongly believed. For curing seizures, Romans who suffered from epilepsy drank the blood of bleeding gladiators.
Blood is considered a symbol of life in most religions and cultures. Even though blood has been considered as a substance that contributes to good health, the idea of transfusion was conceived because of two scientific breakthroughs; William Harvey’s discovery in 1628 that blood circulates in the body and Christopher Wren’s invention of the syringe in 1659. Withdrawal of blood, known as bloodletting, was one of the commonest medical practices to cure or prevent illness.
It was practiced from antiquity until the late 19th century. Leeches or razors were used to draw blood. Bloodletting was not done by physicians but by barbers, who were called barber-surgeons. During those times, physicians considered performing of surgery to be below their dignity. A 15-year old boy was suffering from uncontrollable fevers for two months. A barbersurgeon performed bloodletting by leeches 20 times, to no effect. With the assistance of Paul Emmerez, a barber-surgeon, JeanBaptiste Denis transfused, on 15 June 1667, about twelve ounces of lamb blood into the veins of the boy. Apparently, the boy’s condition improved the next morning. With this success, Denis became bold and performed a few more such transfusions.
However, while performing a third transfusion of calf blood into a notorious madman of Paris in November 1667, the patient started to shake violently. The transfusion had to be aborted. The patient died the next day. A court-case was filed by the patient’s wife accusing Denis of murder. After some hearings, the court cleared Denis. The court also banned blood transfusions. Soon thereafter, the French parliament, the Catholic Church, and the Royal Society also declared ban on blood transfusions. Until the mid-19th century, transfusion ceased to be a part of medical practice. James Blundell, an obstetrician and surgeon at the Guy’s Hospital in London revisited blood transfusion as a treatment option. Blundell’s humanitarian instincts were aroused by the frequently fatal outcome of women who bled profusely after childbirth.
He decided to revive what he called the “neglected operation” of blood transfusion. However, unlike his predecessors, he decided not to use animal blood, but to use human blood for transfusion to humans. Blundell’s procedure of transfusion was to collect blood of a donor in a cup and then to quickly infuse it into the recipient’s vein by using a syringe. After a series of failed transfusions, in December 1828, Blundell carried out an unquestionably successful blood transfusion on a woman who bled profusely after delivering her third child. A physician who was present during the transfusion was the donor. However, the bases of a failed or a successful blood transfusion was not understood.
In 1875, Landois noted in his book “The transfusion of blood” (in German) that when red blood cells of one species were mixed with the serum of another, clumping or lysing of the cells occurred. The full understanding was published by Karl Landsteiner in 1900 in his article titled “On the knowledge of the anti-fermentative lytic and agglutinating effects of blood serum and the lymph” published in a German science journal. Interestingly, the agglutination of human red blood cells was reported in a footnote. For the first time, Landsteiner pointed out the physiological behavior of the agglutination reaction among specimens of mixed human blood, discussing the possibility of individual variations. Before this publication, human red cell agglutination generally had been accepted as being caused by an abnormality in at least one of the reacting specimens.
The irony, in his article on blood groups, was that Karl Landsteiner did not recognize the importance of his contribution; “I hope this will be of some use to mankind,” he wrote. Eventually, in 1947, he published a book titled “The Specificity of Serological Reactions.” Landsteiner (fourth from left in accompanying photograph) was awarded the Nobel prize for his discovery of the blood groups in 1930. (Interestingly, this is the same year in which C.V. Raman was also awarded the Nobel prize.) He not only discovered the ABO blood groups, but also many other blood groups including the Rhesus blood group. When we say that my blood group is A, positive; the A refers to my blood group with respect to the ABO system (for which four types A, B, AB and O are possible) and the ‘positive’ refers to the Rhesus system (for which two types ‘positive’ and ‘negative’ are possible).
Landsteiner worked out the donor-recipient blood-group relationship to prevent fatal agglutination reaction. An interview for the newspaper Der Wiener Tag (The Vienna Day) on 15 November 1930 contained the following: When asked “What led you to the discovery of blood groups?” Landsteiner replied “I began these investigations 30 years ago, starting from the fact that differences exist in the blood of different animal species. I set out to examine the question whether individual differences are not present within a species. This led to the demonstration of individual differences, the blood groups in humans… but this will not interest the layman.” When asked by a New York Times reporter what other applications his discovery of blood groups might have, he answered, “I think this discovery may aid in determining the perpetrator at the scene of a crime.”
In fact, in 1903, with Max Richter, Landsteiner had already shown how a blood group could be determined from a sample of dried blood. Karl Landsteiner trained in medicine at the University of Vienna. He worked in Austria. In 1919, through the assistance of friends of his wife, he left impoverished Austria to accept an appointment at the Catholic Hospital in The Hague, Holland. Had it not been for several Dutch scientists who brought the talents of this remarkable man to the attention of Simon Flexner, Director of the Rockefeller Research Institute, Landsteiner and his son likely would have perished in a Nazi gas chamber. Landsteiner joined The Rockefeller in 1923 and worked there for 20 years until he passed away on 26 June 1943. Today there is a lot of discussion in scientific circles about personalized medicine.
It is now recognized that the same medicine may not work on all patients suffering from a disease, because the biological constitution of the patients is not the same. The first example of personalized medicine is transfusion medicine based on ABO blood groups; Karl Landsteiner should be recognized as the father of the concept of personalized medicine. Professor Herman Chiari, head of the Vienna Institute of Physical Anatomy, where Landsteiner made his blood group discoveries, in a lecture said, “Thus, by his untiring research in the tranquility of his laboratory, Landsteiner became one of the greatest benefactors of human suffering. Wherever in the world today a blood transfusion is performed, whenever a distraught mother finds her child’s life has been saved, Landsteiner is at her side, although we cannot see him.”
(The writer is National Science Chair, Government of India)