Author: Alina Yang
Editors: Emily Yu
Artist: Helen Zhang
During the latter of the post-medieval era, commonly termed the Scientific Revolution, the emergence of modern medicine and mathematics brought a profound metamorphosis upon the longstanding Greek perception of the cosmos, which had endured for eons. Even amidst the magnificence of the Great Ages, surgical success, let alone blood transfusions, would have remained extremely scant compared to modern standards. Perhaps you’ve heard of bizarre medieval medical practices: iatromathematics (medical astrology), bloodletting (the draining of blood), or even the ritualistic release of birds to fly around the medical office to cure a “pestilential (disease-inducing) atmosphere”—which, of course, would be a miracle remedy for horrible illnesses. But were you aware that blood transfusions during this era were equally as eccentric? In 1667, two years after Richard Lower’s pioneering dog-to-dog transfusions, physician Jean-Baptiste Denis achieved a milestone with the first recorded successful blood transmission, transferring approximately 12 ounces of lamb blood to a fever-stricken man. This nonhuman-to-man transfer of blood became known as a xeno-transfusion. While his initial procedures yielded incomparable success, a fatality during the fourth attempt led to the prohibition of xeno-transfusions. Revelation of blood types awaited the dawn of the 20th century, revolutionizing our understanding of transfusion compatibility and human blood.
Throughout history, there was a common notion that all blood was the same. In 1900, Australian pathologist Karl Landsteiner pioneered the ABO categorization for blood types by attributing transfusion complications back to the interactions between antigens and antibodies. Landsteiner’s work identified three blood types: A, B, and C, later changed to O to stand for the German “Ohne,” meaning “null.” The fourth group, AB, was discovered a year later in 1901.
To understand the role of blood cell structure in determining blood type, we must differentiate between two components: the antigen and the antibody. The antigen in a red blood cell is attached to the membrane surface of the red blood cell, while antibodies are present in the plasma (the liquid part of blood, in which red blood cells are suspended). When foreign invaders such as bacteria or viruses infiltrate the body, white blood cells respond by producing antibodies to recognize, investigate, and potentially destroy antigens. Unlike regular antigens, sugar-based self-antigens are antigens in our red blood cells that do not elicit an immune response. It’s these particular antigens that determine one’s blood type. For example, if one has “A” antigens on the outside of the red blood cells and “B” antibodies in the plasma, they have type “A” blood, whereas type B individuals exhibit the opposite pattern. Individuals with type O blood lack specific antigens but possess both A and B antibodies in their plasma, hence Landsteiner’s decision to name this group after “Ohne.” Essentially, blood types are primarily determined by the antigens on the surface of red blood cells.
In medical consultations, we are often informed of our blood type being either positive or negative, a distinction governed by another set of antigens on the blood cell membrane—the protein-based Rh antigen, which determines the compatibility between mothers and their fetuses during pregnancy. In 1940, Karl Landsteiner and Alexander Wiener unveiled the Rhesus blood group system. This system fundamentally categorizes each blood type as either positive, denoting the presence of the Rh protein, or negative, indicating its absence. For instance, an individual with blood type "A positive" (A+) possesses both type A and Rh proteins on the surface of their red blood cells. Beyond mere classifications, the compatibility of blood types and Rh factors can mean the difference between life and death. Understanding our blood type is crucial as it influences various aspects of healthcare such as blood transfusions, organ transplants, and prenatal care.
As previously mentioned, the immune system is triggered by foreign antigens perceived as harmful. In cases of incompatible blood transfusions, the body fails to recognize the antigens in the donor blood, leading to activation of antibodies, or white blood cells, which attack. This defensive response results in the formation of clumps comprising antibodies and red blood cells, potentially culminating in the formation of large blood clots. These clots pose serious risks, including fatality, by obstructing blood flow—a condition known as thrombosis—and by increasing the likelihood of a heart attack or pulmonary embolism, the obstruction of blood flow to an artery of the lung. Thus, individuals with O- blood type are considered universal donors due to the absence of A, B, or Rh antigens on their red blood cells.
Conversely, those with AB+ blood types are considered universal recipients because they don’t possess any antibodies that will recognize type A or B surface molecules, or Rh antigens. Unfortunately, not everyone inherits these advantageous blood types. Statistics from the American Red Cross reveal that less than 4% of the US population shares this blood type, highlighting its rarity—a trait dictated by genetic inheritance.
Blood type is determined genetically, encoded by a single genetic locus known as the ABO locus, which has three alternative allelic forms: A, B, and O. The A allele codes for an enzyme that makes the A antigen, and the B allele codes for the enzyme that makes the B antigen. A third version of this gene, the O allele, codes for a protein that is not functional without surface molecules. Through inheritance, a child acquires one of the three alleles from each parent, leading to six potential genotypes and four distinct blood types. The Rh factors also follow a common pattern of Mendelian inheritance, following a similar pattern to the ABO blood group system but involving a single gene with two alleles: RhD (the dominant gene) and rh (the recessive gene). A child receives one allele from each parent, resulting in three possible genotypes: RhD/RhD (Rh+), RhD/rh (Rh+), and rh/rh (Rh-). As such, our genes reflect a complex interaction of alleles passed from parent to offspring, determining the intricacies of individual blood types and lineages.
The debate surrounding the origins of our blood types and the evolutionary trajectory of our species remains indefinite. Experts hypothesize that somewhere along the way it was in the human species' best interest to develop different blood types as a defense mechanism against deadly diseases—some studies have shown that certain ethnicities exhibit higher rates of specific blood types, whereas others possess lower frequencies of particular blood types. Yet, the underlying reasons for these variations remain largely unknown. While the exact genesis of humanity’s blood types remains shrouded in mystery, we possess a comprehensive understanding of blood type inheritance and transfusion. Modern researchers are working on turning any blood type into type O by using a naturally occurring enzyme that removes specific sugars from blood types A and B (which antigens are made of). This research holds the potential for a future where all blood types, including animal blood, could serve as universal donors, offering hope to patients worldwide and potentially saving millions of lives every year!
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