This bloody history has saved countless lives.

With the introduction of the concept of precision medicine, transfusion medicine will stride forward towards more precise transfusion indications, transfusion of genotype-matched blood products, development and use of genetically recombinant blood products and blood substitutes, and precision cell therapy.

Produced by | Science Popularization China

Author | Li Qiang (Institute of Hematology, Chinese Academy of Medical Sciences)

Producer | China Science Expo

Blood transfusion is a commonly used treatment method in modern medicine, and is widely used in various trauma treatments, surgical treatments, and tumor treatments. However, how was blood transfusion discovered, developed, and continuously improved in human history? Today, let's briefly talk about the history of human blood transfusion.

Image source: Veer Gallery

01

Early exploration, trial and error

The exploration of blood transfusions for the treatment of human disease began as early as 1667, when a man named Jean-Baptiste Denis (1635–1704) performed the first recorded human blood transfusion. He gave 12 ounces of sheep's blood to a 15-year-old boy who had bled excessively from leeches. The boy survived the transfusion and "soon recovered from his lethargy, grew fatter, and amazed all who knew him."

Dennis' blood transfusion treatment | Image source: References

Dr. Dennis later successfully transfused another patient with sheep blood. A third patient, a Swedish baron, also recovered partially with cow blood, but died after a second transfusion. A fourth patient, after a successful transfusion of cow blood, developed severe symptoms of what is now considered a hemolytic transfusion reaction.

"As soon as the blood entered his veins, he felt a heat in his arms and underarms, his pulse quickened, and soon we observed that his face was covered with perspiration. His pulse varied greatly at this moment, and he complained of pains in his kidneys and an upset stomach. He was forced to lie down and fall asleep, and slept all night until daybreak. When he awoke he passed a large glassful of urine, as black as chimney soot."

Although the patient did not die from the blood transfusion, the court still banned human blood transfusion therapy without the permission of the Paris Medical School. On April 17, 1668, the French Parliament banned blood transfusion, and the British Parliament quickly followed suit.

02

Blood transfusion research resumes after 150 years

In the following 150 years, blood transfusion, which had once caused a sensation in the medical community, was ignored until the early 19th century, when James Blundell (1790-1878), a British physiologist and obstetrician, witnessed many women dying from excessive bleeding during childbirth. He once again proposed whether blood transfusion could be used to avoid death from hemorrhage.

He believed that the early blood transfusion accidents were probably caused by transfusing "livestock blood" and that blood should not be transfused between different species because they are very different from each other. He then performed many blood transfusions and published his attempts at blood transfusion in the academic journal The Lancet, also known as the famous Lancet.

In 11 years, he gave blood transfusions to 10 patients, 5 of whom were saved. While performing blood transfusions, Dr. James invented the direct blood transfusion method between people and created the gravity transfusion device (a chair, a funnel, a catheter and a brass syringe), which was used for nearly 100 years.

He also invented a method of indirect blood transfusion, which used a simple syringe and cannula to draw blood from the donor's vein and then immediately inject it into the recipient's vein, but the air in the syringe had to be emptied. He also described the serious problem of blood clotting in this method.

Gravity blood transfusion device | Image source: References

In 1900, Austrian doctor Karl Landsteiner (1868-1943) conducted an ingenious experiment. He separated the blood cells and serum from his own blood and the blood of 22 other people including his assistant, and reacted them with each other. According to the results, he divided the blood into Group A and Group B. He proposed the blood type theory of type A, type B and type C (later changed to type O), and published an article in the Vienna Medical Journal in 1901.

Since the number of people with AB blood type is relatively small, accounting for only 3%-5%, his two students discovered AB blood type only when the number of participants in the experiment was increased to 155. The existence of AB blood type was not confirmed until 1906. Karl Landsteiner was the first scientist to study the immune process of blood transfusion. He won the Nobel Prize in Physiology and Medicine in 1930 for discovering the ABO blood type in humans.

In 2001, more than a hundred years after Karl Landsteiner published his article, the World Health Organization, the International Federation of Red Cross and Red Crescent Societies, the International Federation of Blood Donor Organizations and the International Society of Blood Transfusion jointly advocated that his birthday, June 14, be designated as World Blood Donor Day. June 14, 2004 became the first World Blood Donor Day.

After the blood type system was discovered, Reuben Ottenberg first implemented cross-matching for pre-transfusion testing in 1908, marking the arrival of a new era of safe blood transfusion. Although more than a hundred years have passed and the method of cross-matching has been continuously improved, the basic principles of the test to ensure safe blood transfusion have been used to this day.

Blood transfusion bottle invented by Oswald Robertson | Image source: References

Between 1914 and 1915, four scientists from Argentina, Belgium and the United States proposed the method of using citric acid for anticoagulation almost at the same time and applied it in clinical practice, which made large-scale blood transfusion possible.

03

The Two World Wars and the Development of Blood Transfusion Technology

After the outbreak of the First World War, the large number of casualties on the battlefield also put forward new requirements for blood transfusion and rescue, which directly promoted the development of transfusion medicine.

In the early days of the war, blood transfusions were rare because the technology was not perfect enough to meet the needs of battlefield emergency treatment. It was not until the United States entered the war in 1917 and after the U.S. troops arrived in Europe that a Canadian military doctor used a syringe to directly transfuse blood to the wounded without cross-matching, proving that blood transfusions could be used for battlefield emergency treatment and save lives.

Another American military doctor, Oswald Robertson, invented a method of preserving blood in glass bottles using citric acid and established the world's first battlefield blood bank on the Western Front. He summarized 200 blood transfusion cases in his paper and was the first to experimentally confirm the universality of type O blood, which is considered one of the most significant medical contributions in World War I.

The outbreak of World War II (1939-1945, referred to as WWII) caused 70 million deaths and 130 million injuries, which brought great pressure to battlefield medical treatment. At the same time, blood transfusion technology, which was an important means of rescuing the wounded in World War II, also developed greatly.

Blood transfusion medicine technology has completed the separation, testing and clinical application of plasma proteins; the improvement and large-scale promotion of blood preservation solution formula; at the same time, in 1940, the American Red Cross established the first blood bank "Blood for Britain" to supply blood to the British people and British army. In 1944, the average blood consumption of battlefield wounded was 224mL, and in 1945 it was 488mL. As a result, the mortality rate of war wounded was greatly reduced. In the 13 months around 1945, about 500,000 units of whole blood were transported to US military hospitals in the battlefields of World War II.

04

New development and application of modern blood transfusion technology

After the end of World War II, with the rapid development of science and technology, the technical level of transfusion medicine has also been greatly improved.

In the 1950s, the invention of plastic blood bags and blood collection and transfusion equipment, the proposal of the component transfusion theory, the adoption of plasmapheresis in the 1960s, the invention of the first continuous flow centrifugal blood cell separator, the invention and application of closed sterile blood collection and separation plastic blood bag system, blood cryopreservation technology, and large-capacity refrigerated centrifuges, these technological innovations have gradually moved component transfusion from scientific research to clinical application, which is a historic moment in the history of human blood transfusion. As an effective and rational method of using blood components, component transfusion has many advantages such as high purity, strong pertinence, and fewer adverse reactions to transfusion, while saving blood resources.

In the new century, based on the continuous development of biomedical technology, blood transfusion, as the most basic means of cell therapy, has continued to absorb and integrate, starting from hematopoietic stem cell transplantation at the end of the last century, and using years of clinical technology and experience in blood transfusion therapy to incorporate the field of cell therapy. Transfusion medicine has begun its new journey.

Transfusion medicine has been developing for more than 350 years, from the initial ignorance and continuous trial and error to the technological explosion during the two world wars. Countless scientists and patients have paid great hardships and even the price of their lives for it.

Today, transfusion medicine is an important part of clinical medicine and a multidisciplinary medical discipline that involves human genetics, biology of stem cells and blood cells, military medicine, psychology, ethics, sociology, informatics, evidence-based medicine and many other disciplines.

With the introduction of the concept of precision medicine, transfusion medicine will stride forward towards more precise transfusion indications, transfusion of genotype-matched blood products, development and use of genetically recombinant blood products and blood substitutes, and precision cell therapy.

References

[1] Yang Chengmin, Liu Jin, Zhao Tongmao, Chinese Journal of Blood Transfusion[M] Beijing: People's Medical Publishing House, 2021, 2nd edition

[2] Denis J. An extract of a printed letter, addressed to the publisher, by M. Jean Denis, D. of Physick, and Prof. of the Mathematicks at Paris, touching the differences rose about the transfusion of bloud. Philosophical Transactions. 1668; 3(36): 710-715

[3] Boulton, F. and DJ Roberts, Blood transfusion at the time of the First World War - practice and promise at the birth of transfusion medicine. Transfusion Medicine, 2014. 24(6): p. 325-334.

[4] Lefrere, JJ, Transfusion medicine history illustrated. Arming for war: the donor's arm. Transfusion, 2011. 51(6)

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