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Karl Landsteiner - Blood Transfusions:
Every source quoted an amazing number of transfusions and potential lives saved in countries and regions worldwide. High impact years began around 1955 and calculations are loosely based on 1 life saved per 2.7 units of blood transfused. In the USA alone an estimated 4.5 million lives are saved each year. From these data I determined that 1.5% of the population was saved annually by blood transfusions and I applied this percentage on population data from 1950-2008 for North America, Europe, Australia, New Zealand, and parts of Asia and Africa. This rate may inflate the effectiveness of transfusions in the early decades but excludes the developing world entirely. Since the late 1980s blood donations have declined and the surplus will soon end. Call this efficiency, but there’s also a risk of future transfusion demands not being met. If you’re blood type is 0 negative (like me) your phone line is probably hot with calls from the local Red Cross!
--Amy R. Pearce, PhD
Click HERE to learn About the Numbers
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(June 14, 1868 - June 26, 1943)
Born in Austria
Year of Discovery: 1902
Superman of Science Makes Landmark Discovery - Over 1 Billion Lives Saved So Far!
Karl Landsteiner was born in Vienna, Austria, in 1868. He was essentially raised by a single mother, as his father died when he was only six. He finished medical school at age 23 and then began traveling to study under other famous scientists of the day. He often couldn't find research jobs (which were his passion) and he would make his living by doing autopsies at "deadhouses," which we call morgues today. But he always persevered and no matter what his circumstances, he would carve out a space to do research. Somewhat reclusive and pessimistic by nature, he felt at home in the laboratory and made it the focus of his life.
One of the topics he researched and found interesting was human blood. Doctors had tried giving people transfusions (a dose of another person's blood) but it was actually just pure luck
In 1901, Landsteiner discovered that different people's blood had different characteristics that made it "incompatible" with other people's blood that didn't carry those same traits. He discovered the A, B, and O blood types. His discovery of the differences and identification of the groups that were alike made it possible for blood transfusions to become a routine procedure. This paved the way for many other medical procedures that we don't even think twice about today, such as surgery, blood banks, and transplants.
Landsteiner is known as the "melancholy genius" because he was so sad and intense, yet he was so systematic, thorough, and dedicated. He wrote 346 papers during his long career contributing to many areas of scientific knowledge. He is considered the father of Hematology (the study of blood), Immunology (the study of the immune system), Polio research, and Allergy research.
by Martha Pat Kinney
Table of ContentsIntroduction
Key Experiment or Research
Quotes by the Scientist
Quotes About the Scientist
Excerpt from Science Heroes Greater than Einstein
Fun Trivia About The Science
The Science Behind the Discovery
Key Contributing Scientists
Science Discovery Timeline
Recommended Books About the Science
Books by the Scientist
Books About the Scientist
Major Academic Papers
Links to Science and Related Information on the Subject
Landsteiner was known for his attention to detail and thoroughness. By the time he finished working on a problem, and proposing a solution, there was little room for doubt. When he turned his attention to the problem of blood incompatibility, he started with the most basic problem and designed a simple, elegant experiment to figure out why this happened. He repeated this experiment many times to rule out random error and to prove that the reaction was always present and was always the same. He then charted out all the reactions. After carefully studying this, he proposed that the agglutination (clumping) was caused by two variables - A and B. Some samples had one, some had the other, and some had none. He called the types A, B, and zero. Zero was later renamed "O". He proposed that this was what caused some blood to be compatible with others and some to react with others. Later, the AB group was discovered as someone who has both the A and B substance on their red blood cells. Today, we refer to these as the blood group antigens. This experiment laid the groundwork to establish the modern practice of blood banking.
Blood has several components. It can be separated into its separate parts by letting it sit for a few hours in a tube, or the process can be speeded up by centrifuging (spinning) it. After separation, there will be the red cells at the bottom, with a layer of white blood cells and platelets on top of that, and on the very top there is a clear yellowish liquid (serum). Landsteiner tested the red cells at the bottom of one sample against the serum at the top of a different sample. He had noticed that when different people's blood were mixed together there was a phenomenon known as agglutination (clumping) that sometimes occurred. So, the clumping became his test to see if one person's blood reacted with another. He collected blood from himself and five of his fellow lab workers and separated the samples into cells and serum. Then he mixed each sample's cells, diluted with 0.6% saline (salt water), with the serum from each of the other samples until he had tested all the possible combinations. If it clumped visibly (you could see it just by looking at it with your eyes - no microscope needed) he confirmed it by looking at the sample with a microscope. He called the cells that clumped "positive" and the ones that did not "negative". After thinking about his results, he decided to make sure it wasn't just normal blood clotting - that agglutination was different than clotting. So, he found a hemophiliac (a person whose blood does not clot normally) and tested their blood. As he suspected, their blood agglutinated also with some samples and did not with others. So, this proved that the phenomenon he had noticed and studied was not just clotting - it was something different. Then he thought he should prove that the clumping he observed wasn't caused by a disease. So he tested newborn babies' cells, since they were unlikely to react due to a disease as they hadn't been in the world long enough to catch one. Finally after studying and testing blood from 22 different patients he declared, "the experiments demonstrate that my data require no correction. All 22 examined sera from healthy persons gave the reaction." He charted all his results and studied them carefully. When thinking about his results mathematically he noticed that there were probably two variables that could explain his results. He called these variables A and B. In his notebook he noted, "a remarkable regularity appeared in the behavior of the 22 blood specimens examined. If one excludes the fetal placental blood, which did not produce agglutination..., in most cases the sera could be divided into three groups: In several cases (group A) the serum reacted on the corpuscles of another group (B), but not on those of group A, whereas the A corpuscles are again influenced in the same manner by serum B. In the third group (C) the serum agglutinates the corpuscles of A and B, while the C corpuscles are not affected by sera of A and B..... In ordinary speech, it can be said that in these cases at least two different kinds of agglutinins (antibodies) are present: some in A, others in B, and both together in C."
After studying his results, he proposed that agglutination was a real phenomenon and was caused by differences between the red cells of different people. We know these today as blood types. He proposed that there were three types of blood: A, B, and C, which he later called zero and was eventually renamed O. This explainded why sometimes transfusions worked wonderfully, and at other times led to disastrous, even fatal results. He detailed his results in a paper published in 1901. It was called Ueber Agglutinationserscheinungen normalen menschilchen Blutes." (Translated this means: On agglutination phenomenon of normal human blood.)
"The sera of healthy individuals not only have an agglutinating effect on animal red cells but also on human red cells from different individuals. It remains to be decided whether this phenomenon is due to individual differences or to the influence of injuries or bacterial infection."
"Since no observations whatever had been made in this direction, I selected the simplest experimental arrangements available and the material which offered the best prospects. Accordingly, my experiment consisted of causing the blood serum and erythrocytes (red blood cells) of different human subjects to react with one another."
"Moreover, my investigations show that the different sera do not act identically with respect to agglutination. If one believes, therefore, that they owe their agglutination ability to a kind of autoimmunization through resorption of cell constituents, then one must again assume individual differences to obtain the different sera."
His neighbor, a teenage boy who had befriended him, remembered his parting words, "Finish your studies and then go out into the great big world. And if you are ever in any trouble let me know, and I'll do my best to help."
About his work situation:
"If I am asked to make do with only a microscope I have to comply."
About his living conditions in New York:
"Just imagine. I can't even play the piano I managed to lay my hands on. It was my only form of relaxation, but the neighbors complained that I made such a noise they couldn't listen to the radio. So now I never touch it."
-Phil Levine, a colleague
"The line of least resistance was to embark on efforts to discover new bacteria, now that the methods of cultivation of bacteria were laid down by the discoveries of Pasteur and Koch. Those who took the line of least resistance did discover the pneumococcus, meningococcus..., but what else did they contribute to the medical sciences?"
"Now I found myself face to face with a tall, very slim, good-looking young man with brown hair and eyes, a moustache, and a rather sensual mouth. His movements were brisk, yet graceful. We had a brief conversation, in the course of which I was impressed by his extraordinary attraction and by his burning enthusiasm for research-work, despite the unpretentious modesty with which he spoke of it."
"He formulated precisely the relationships between cause and effect, and did not complicate what was still unknown by hypotheses. When he did introduce hypotheses, they were supported scientifically by experiments. He never claimed more than he was able to prove scientifically or could verify by his own experiments."
"Landsteiner had a mind that was by nature sharp-edged and rigorous, delighting in the exact. He read the higher mathematics for diversion, amused himself with problems in advanced algebra and calculus, and followed with zest each forward step in the new mathematical physics."
"Landsteiner's work dispelled any notion that might have once been held that there is absolute specificity in immune relations. Indeed, the structures of the many cross-reacting molecules uncovered in work from his laboratory were used to great advantage to illuminate how a ligand's [any molecule that binds to another] shape, size, and charge distribution affects the extent to which it is recognized by antibodies."
"For many years I had had no news of Landsteiner at all; but during a study-tour of America in 1929 I ran him to earth in his laboratory. I found him rather depressed and full of complaints about his work, especially about the regulations that apart from restricting his activities in certain fields bore no relation at all to the virtually unlimited scope of his own scientific ambitions."
Adriano Sturli, one of the doctors who donated blood for Landsteiner's blood group experiment, told an amusing story about Landsteiner: "Towards the end of 1901 I was asked by Landsteiner, with whom I had up to then only done some histological and bacteriological studies, whether I would like to join him in some serological studies and experiments (these would lead to the discovery of the fourth blood group AB). I agreed with alacrity, and thus had an opportunity of repeating all his experiments to his explicit satisfaction. I should add that the final studies started on the afternoon of 31 December 1901 and went on without a break until 8:30 PM. The two of us were quite alone in the Pathological Institute, now silent and deserted. These hours were a sort of tragicomedy for me, because I had naturally been itching for hours to join my friends and see the New Year in in style. However, Landsteiner was gently but firmly insistent, and kept me washing blood-corpuscles, mixing sera, centrifuging, saturating charcoal-powder with dyes, etc. under his supervision, with results that seemed to me amazing but to Landsteiner were self-evident. Eventually we took leave of one another, tired but still good friends, with a cordial ‘Happy New Year'."
But Not All Work and No Play
He would bring his beloved dog, Waldi, to work and let him sit under his desk. Around lunch time every day Waldi would start barking and Landsteiner would playfully reprimand him, "Waldi, you've not an atom of respect for science."
Patience is a Virtue
Not that Landsteiner was always dire. He still relished his lab, never losing his wit while there. The young scientists in his charge often rushed to conclusions. One day he said, "Is it not strange that I, who have so little time left, should be teaching patience to you, who have your life before you?"
Humble to the End
One evening in 1930 Philip Levine went to Landsteiner's apartment. He found the family placidly reading as usual. Levine was quite surprised, considering the news of the day. "What news?" Landsteiner's wife and son asked. Their looks told the story. Karl had told neither Helene nor Ernst what he had learned earlier that day, that he had been awarded the Nobel Prize in Medicine. Beginning in 1923, fourteen different nominators had put him up for the award for three different discoveries - his polio research, his immune system work, and his discovery of the blood groups. After 29 years, the committee finally granted him the award for his blood group work.
After being thoroughly immersed in chemistry, Landsteiner studied under a surgeon for a year, and then returned to Vienna University, to work under the tutelage of bacteriologist Max von Gruber. Born Jewish, Landsteiner had converted to Catholicism along with his mother when he was in college, well aware that only Catholics could be professors in the Austro-Hungarian Empire (he confirmed he was still Catholic almost 50 years later). Nevertheless, he was passed over for a routine job. Across the campus at the University's Institute of Pathological Anatomy was Anton Weichselbaum, a strict and severe bacteriologist, famous for discovering the bacterial cause of meningitis. Landsteiner approached him to be an unpaid assistant, was accepted, and immediately started experiments. They led to publishable findings, so after a year he applied for a paid job. The Erster Assistent (first or best assistant) at the institute, a powerful person in those days, wanted the same job and told Weichselbaum that he would leave if Landsteiner received the appointment. Weichselbaum went home and thought about it over night, then returned the next day and told him, "You can resign. I am appointing him." Humbled, the Erster Assistant abjured and stayed, and eventually became an admirer of Landsteiner.
Almost 4 million American receive a blood transfusion each year.
Americans donate approximately 12 million units of blood each year, which are processed and made into 20 million blood products.
Worldwide, there are about 890 million units of blood donated each year.
Almost half of the United States population has donated blood at some time. We can feel optimistic about humankind's compassion!
For more trivia about blood types click here. (link to blood type trivia)
The Science Behind the Discovery
Blood is essential to human life. This fact has been known throughout much of recorded history. It was apparent that significant blood loss from accidents, combat, or childbirth was fatal. However, no one had a good solution to the problem. People tried giving animal blood but this didn't seem to be a good solution as animals were not always available and it didn't work. James Blundell, a British physician said, "What is to be done in an emergency? A dog might come when you whistled, but the animal is small, a calf might have appeared fitter for the purpose, but then it had not been taught to walk properly up the stairs!". Distraught over so many mothers dying from childbirth hemorrhaging, he performed the first successful human to human blood transfusion in England and encouraged others to try it as well. But there were problems. Often after transfusion, the patient developed black urine, jaundice (yellowing of the skin and eyes due to liver failure), and then kidney failure. Many of the patients with the adverse reactions actually died. In 1848, a review of all known blood transfusions showed 18 out of 48 patients died. This stalled the practice of transfusion, as doctors were not willing to risk one in three patients dying.
In 1901, Karl Landsteiner came on the scene with a solution to this longstanding problem. He collected blood from himself and five of his co-workers at Vienna University's Institute of Pathological Anatomy. He then performed a beautifully designed elegant experiment, by mixing each person's red blood cells with the other people's serum. After many trials, and much study, he concluded that there were three types of blood. He named the different types A, B, and O. If cells from a person with one type of blood were mixed with the serum of another type, it triggered a phenomenon known as agglutination, or clumping. This reaction showed that blood could not be transfused to just anyone; it mattered what "type" or group the person belonged to. He immediately understood the importance of his discovery, noting in his paper, "Finally, it must be mentioned that the reported observations allow us to explain the variable results in therapeutic transfusions of human blood." This was a concept foreign to the current thinking of the day. No one at that time recognized that the immune system of the human body did anything other than fight germs. While this seems basic today, at the time Landsteiner was living, this was a much more difficult concept, since the immune system's functions were barely known. What he had found were actually what we call antigens today. They had no name at that time; they were given a name in 1908.
A common way to visualize the antigens on the surface of red blood cells today is a tree. You can think of different shape trees sticking out of the surface of the cell. The different "trees" are really different proteins or sugars. Every red cell has many, many antigens on its surfaces. If our immune system comes across an antigen it isn't familiar with, it produces an antibody to it. An antibody is produced to destroy foreign invaders and keep our body healthy. An antibody will attack the antigen, often destroying the cell in the process. Sometimes this is done by agglutination, which will release the contents of the cell as well.
Landsteiner also realized another use for his discovery, one that we all depend upon today for entertainment. He suggested that blood types could be used forensically. So, actually, Landsteiner was the discoverer of CSI's technology. He also suggested that it could be used for paternity testing. Where would the legal profession be today without forensics and paternity testing???
When Landsteiner first published his paper, there was almost no reaction from the scientific community. Realizing how important it was, he repeated his discovery that transfusion reactions stemmed from blood group incompatibility in another scientific publication. Finally, in 1907, Reuben Ottenberg carried out blood group compatibility testing at Mount Sinai Hospital in New York City. He observed that group O individuals could be used as universal donors. This started the use of limited transfusions. But, until 1913, only about 50 transfusions a year took place in New York City hospitals.
One of the main problems to overcome in making transfusion a routine procedure was that blood clots rather quickly when taken out of people. The methods used to get around this were rather crude. Initially, they tried attaching people arteries together so the blood would flow directly from one person to another. This was rather brutal and also there was no way to tell how much blood was transferred. In 1914, Dr. Richard Lewisohn, again at Mt. Sinai Hospital, discovered that adding sodium citrate could prevent blood from clotting. This dramatically changed transfusion, as it no longer was a surgical procedure. Blood could simply be drained into a container, and then a measured amount could be transfused.
The injuries from World War I caused an American lieutenant, Oswald Hope Robertson, serving as a surgeon on the Western Front, to build the first blood bank. This was rapidly put into use on a wide scale, and tens of thousands of transfusions were performed from 1914 to 1918. British medical history books declared blood transfusion "the most important medical development of the war." After this, transfusions became a normal hospital procedure. Landsteiner noted this in a letter he wrote to a colleague, "I was very glad to have your pretty card: thank you very much...the isoagglutinins we were working on are highly thought of in America, where an immense number of transfusions are performed, the blood-group determined in every case..." In 1932, the first civilian blood bank in the world was established in Leningrad, Russia. Bernard Fantus coined the term "blood bank" and the first one established in the U.S. was in Chicago in 1937. Blood Banks then sprang up in cities world wide.
Now, blood transfusion is amazingly safe. Fatal transfusion reactions only occur about once in 250,000 transfusions. Compare this to 1 in 3 before Landsteiner discovered blood groups and you see how far we have come. About half of current transfusion reactions are due to error - incorrect screening or clerical error (giving the blood to the wrong person). The risk of getting Hepatitis B from a transfusion is about one in 250,000 as well. The risk of getting HIV from a transfusion has dropped dramatically from the 1990's, after improved testing was developed and implemented. Now the risk is about one in two million.
So, from where blood transfusion started to today we now have:
The Greatest Life-Saving Medical Advance in History!
Transfusions are at the heart of critical care, saving lives due to trauma caused by automobile wrecks (needing up to 50 units of blood), burns (up to 20 units), and other accidents. A unit of blood is about one pint. In the United States, blood is obtained by blood banks set up to collect blood, type it, test it, and deliver it. It is obtained from healthy donors and is entirely voluntary. Other major uses of blood are for organ transplants (up to 30 units), heart surgery (up to 6 units), and other surgeries. James Blundell, the 19th century obstetrician, would be happy as well. In the developing world, where maternal hemorrhaging after childbirth is still common, transfusions are vital to saving new mother's lives. Blood can also be transformed into at least 25 different specific blood products used in medicine, such as platelets to aid in clotting, gamma globulins to increase immune activity, and plasma for trauma patients. Donating blood is one of the most charitable and beneficial gifts a person can give another person.
Born: June 14, 1868
Died: June 26, 1943
Homes: Vienna, Austria; Zurich, Switzerland; New York, New York
He was once passed over for a routine job at Vienna University so he sought a more amenable workplace and moved on to an unpaid assistant's job for Anton Weichselbaum at the Institute of Pathological Anatomy. After working unpaid for a year, he published some of his findings and received a paying job there performing daily autopsies. While working there, he kept up with the current scientific happenings and performed research, including his landmark investigation of blood incompatibility in 1901. Finally, in 1908, he was able to advance by taking a position in the Department of Pathology at the Imperial Wilhelmina Hospital in Vienna. This relieved him of his autopsy duty and freed him to do research. Soon after beginning this job, his mother, whom he was very close to, died. A few years later, he began dating Helene Wlasto and they married in 1916. He was 48 and she was 36. They had one son, Ernst Karl. The family continued to live in Austria until the conditions from the war were so bad that the family emigrated to Holland, where he did routine lab work, and autopsies. He still continued his research in his spare time. Finally, after two years of this, he was invited to join the Rockefeller Institute in America. He arrived in the US in 1923 and lived in New York City over a butcher shop on Madison Avenue. He continued to work there until his retirement in 1939. He was allowed to keep his lab however, and continued his research, publishing another 28 papers. He died of a heart attack in 1943. His wife died later that same year of cancer.
Landsteiner's Other Research
Landsteiner was a researcher at heart and contributed to many other facets of medical discovery as well. He helped make diagnosis of Syphyllis much easier by developing dark field illumination - a way of visualizing the bacteria on a dark background under the microscope. He furnished much of the basic knowledge about polio that helped lay the groundwork for the development of the vaccine. He discovered it was caused by a virus, not a bacteria. He introduced a technique to preserve the virus in glycerin so it could be studied. He developed a blood test for it and demonstrated how to transfer it to monkeys, which also was instrumental in the development of a vaccine. He worked on allergies as an immune reaction as well. He discovered more blood groups besides the ABO system. He discovered the M, N, and P groups, and the Rh factor which is designated by the positive or negative sign you see after blood types. Rh factor incompatibility used to cause the death of many babies - an Rh negative mother's immune system reacts with Rh positive blood of her infant.
Landsteiner is considered the father of Immunology and with good reason. He overturned the simplistic thinking about the immune system. He wrote a book on it titled the Specificity of the Serologic Reactions, which was considered a classic. In it he detailed the mechanism of allergy, infection resistance, hypersensitivity diseases, immune complex diseases, tissue transplantation problems, and immune mechanisms. He once showed up at a lecture of Linus Pauling at Cornell, and Dr. Pauling stated that in the following four days he received the world's greatest course in immunology by Dr. Landsteiner. He truly was a genius.
Timeline of Landsteiner's Life
June 14, 1868 - Born in Vienna, Austria
Philip Levine worked with him on the MNP blood groups.
Alex Wiener, Philip Levine, and R.E. Stetson worked with him on the Rh factor.
Speiser, Paul. Karl Landsteiner, the discoverer of the blood-groups and a pioneer in the field of immunology: Biography of a Nobel Prize winner of the Vienna Medical School. Hollinek, 1975. (Not a normal narrative biography, but a great book that collects a few anecdotes from those who knew him, along with a short description of some of his work. It has many good photographs. Paperback. Out of print.)
Heidelberger, Michael. Karl Landsteiner: June 14, 1868-June 26, 1943 (Biographical memoirs / National Academy of Sciences). Columbia University Press, 1969.
Woodward, Billy, Shurkin, Joel and Gordon, Debra. Scientists Greater than Einstein: The Biggest Lifesavers of the Twentith Century. Linden Publishing, 2009.
Karl Landsteiner received the Nobel Prize in medicine in 1930
Landsteiner published 346 academic papers. The blood group paper that revolutionized medicine is:
Landsteiner, K, 1901. Ueber Agglutinationserscheinungen normalen menschlichen Blutes. (Translation: On agglutination phenomena of normal human blood). In Papers of Human Genetics, ed. S.H. Boyer, 27-31. Englewood Cliffs, NJ: Prentice-Hall.
Links to Information on the Science
Normal 0 A short biographical sketch of Karl Landsteiner.
Facts about blood
Explanation of antigens
More details of Karl Landsteiner's research
This is a good site by the American Red Cross which explains the basics of blood groups and transfusion medicine.
PBS also has a nice website which gives lots of important information about blood, transfusions, and blood banking.
A history of transfusion
Explanation of blood components
The nobel prize website Landsteiner biography