On Individual Differences in Human Blood

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On Individual Differences in Human Blood

The Discovery of Blood Groups

Lecture

Date: December 11, 1930

Source: Nobel Lectures, Physiology or Medicine 1922–1941. Amsterdam: Elsevier, 1965. Also available online at 〈http://nobelprize.org/medicine/laureates/1930/landsteiner-lecture.html〉 (accessed May 10, 2005).

About the Author: Karl Landsteiner (1868–1943) was an Austrian physician. After completing a medical degree he worked in biochemistry, investigating the composition of blood ash. He later became interested in immunology and antibodies. Landsteiner contributed significantly to pathological anatomy and immunology, working on polio and the immunology of syphilis. However, it was his lifetime work on blood groups, antigens, and antibodies that brought him fame and the Nobel Prize in Physiology or Medicine in 1930. Landsteiner did subsequent work on blood groups in New York City where he moved after leaving Vienna.

INTRODUCTION

The Nobel Prize recognizes the most significant achievements in various areas of science. The work recognized by the Nobel Committee has to be highly significant to the scientific community. Scientists awarded the prize must deliver a public lecture on the topic for which they are recognized.

The discovery of the blood groups by Karl Landsteiner in 1901 was very important because it explained why transfusions between different individuals are sometimes successful and sometimes not successful. Unsuccessful transfusions resulted in patients' deaths due to hemolysis (blood cell destruction).

In the years prior to Landsteiner's discovery, numerous trials transfusing blood from person to person and from animals to people were carried out. The first recorded successful blood transfusion was performed by James Blundell in 1818. However, a number of later attempts failed, and the reasons for these failures remained unknown until the beginning of the twentieth century.

Blood is composed of red blood cells (erythrocytes), white blood cells, platelets, and plasma. When blood is spun in a centrifuge, a clear, sticky fluid called serum separates from the red blood cells. Serum was shown to have the ability to induce clustering of the red blood cells, and Landsteiner's studies focused on identifying why this clustering of red blood cells occurred.

Landsteiner discovered that the reaction between two blood types involved antibodies. In his Nobel Prize lecture, he described the research results that led to the discovery of blood groups and attributed the differences among blood groups to non-protein components on the surface of the red blood cells. His lecture also suggested possible practical uses of the blood groups in medicine and forensic science. The use of blood groups in transfusions, as he recommended, became routine during the First World War (1914–1918).

PRIMARY SOURCE

… 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 of different human subjects to react with one another.

The result was only to some extent as expected. With many samples there was no perceptible alteration, in other words the result was exactly the same if the blood cells had been mixed with their own serum, but frequently a phenomenon known as agglutination—in which the serum causes the cells of the alien individual to group into clusters—occurred.

The surprising thing was that agglutination, when it occurred at all, was just as pronounced as the already familiar reactions which take place during the interaction between serum and cells of different animal species, whereas in the other cases there seemed to be no difference between the bloods of different persons. First of all, therefore, it was necessary to consider whether the physiological differences discovered between individuals were in fact those which were being sought and whether the phenomena, although observed in the case of blood of healthy persons, might not be due to endured illness. It soon became clear, however, that the reactions follow a pattern which is valid for the blood of all humans…. Basically, in fact, there are four different types of human blood, the so-called blood groups. The number of the groups follows from the fact that the erythrocytes evidently contain substances (isoagglutinogens) with two different structures, of which both may be absent, or one or both present, in the erythrocytes of a person. This alone would still not explain the reactions; the active substances of the sera, the isoagglutinins, must also be present in a specific distribution. This is actually the case, since every serum contains those agglutinins which react with the agglutinogens not present in the cells—a remarkable phenomenon, the cause of which is not yet known for certain….

… I—working in conjunction with Levine—obtained significant results by using special immune sera which had been produced by injecting human blood into rabbits; these results led to the discovery of three new agglutinable factors present in all four groups…. In addition it was shown that weak iso-reactions (Unger, Guthrie et al.; Jones and glynn; Landsteiner and Levine), which do not follow the group rule and which vary in their specificity, are more common than had previously been assumed—irregular reactions, which can indeed easily be distinguished from the typical ones and which in no way affect the validity of the rule of the four blood groups….

… The praecipitin reactions—mentioned at the beginning of this lecture—which revealed the species difference between proteins gave rise to the view that the substrates of all serological reactions were proteins or substances closely related to them. At first this view was shaken by the study of blood antigens. The solubility of specific substances in organic solvents and in particular the investigation into heterogenetic sheep's blood antigen,… from which a substance specifically binding but not acting directly as an antigen can be separated by extraction with alcohol, led me to the view that the constituents of many cell antigens are not protein-like substances and only as a result of uniting with proteins become antigens, which are appropriately called "complex antigens." This theory was strongly supported by the fact that I was able to restore the antigen action of the specific substance by mixing with protein-containing solutions….

One practical application of the group characteristics which immediately suggested itself was the distinguishing between human blood stains for forensic purposes….

To a far greater extent the group reactions have been used in forensic medicine for the purpose of establishing paternity. The possibility of arriving at decisions in such cases rests on the studies of the hereditary transmission of the blood groups; the principal factural results in this field we owe to the work of von Dungern and Hirszfeld. As a result of their research it became established that both agglutinogens A and B are dominant hereditary characteristics and that transmission of these characteristics follows Mendel's laws….

More important to practical medicine is the use of blood-group reaction in transfusions….

The first blood transfusion in which the agglutinin reaction was taken into account was carried out by Ottenberg, but it was only during the emergencies of the Great War that the method of transfusion with serological selection of donor was widely adopted—a method which has since remained the normal practice….

… It should only be mentioned that it is not absolutely necessary to use blood of the same group, but that in stead of this, blood of group O for instance,… can also be used…. Use of blood from so-called "universal donors" belonging to group O can be of great value in emergency cases and for recipients belonging to the rare blood groups….

SIGNIFICANCE

The discovery of ABO blood groups initiated a new era in medicine as successful blood transfusions became possible. After the First World War, transfusions became a standard procedure whenever a patient's injuries caused extensive bleeding or a patient required transfusion due to an illness. Typing the blood before a transfusion has virtually eliminated transfusion-associated complications.

In his lecture, Landsteiner mentioned another phenomenon—newborn hemolytic anemia—that he studied with Levine. This type of anemia was shown to have a hereditary basis. At about the same time, another scientist discovered that antibodies raised against Rhesus monkey erythrocytes in rabbits reacted with 85 percent of human samples. These studies led Landsteiner and his colleagues to describe the Rh blood factor. In contrast to blood groups, the Rh factor is only described as positive or negative.

The Rh factor was discovered to cause hemolytic anemia only in cases in which an Rh negative mother and an Rh positive father produced an Rh positive baby. During pregnancy, fetal blood crosses the placenta enters the mother's circulation. As a result of this mixing of maternal and fetal blood, antibodies directed against the baby's red blood cells are slowly generated. But, hemolytic anemia of the newborn can be prevented by giving the Rh immunoglobulin to pregnant women who are Rh negative. This prevents development of antibodies in later stages of pregnancy.

Therefore, when a patient is given a blood transfusion, the blood that she receives must be compatible not only with her ABO blood group, but also with her Rh factor. The most commonly used blood for transfusions is type O and Rh negative. The advantage of type O blood is that its erythrocytes lack both A and B antigens, and thus type O blood cannot be precipitated by anti-A or anti-B antibodies. On the other hand, individuals with type AB can receive blood from any donor, since they have neither anti-A or anti-B antibodies in their blood.

Due to uneven distribution of the blood types within a population, blood banks play an important public health role by storing blood donated by volunteers for later use.

The use of blood groups in paternity testing was also suggested by Landsteiner. However, blood groups cannot be used to identify the father, but only to exclude a man as the potential father. This is due to the fact that an individual with type A blood can be either homozygous (AA, carrying two identical blood group gene types), or heterozygous (AO, carrying two different blood group gene types). A person with either of the genotypes will have type A blood. This same pattern is true for blood group B as well.

Currently there are 26 different blood groups known.