With our 30th birthdays on the horizon my best friend and I decided to make a bucket list. As the months ticked by one thing on my list stood out – blood donation. I must admit I feel slightly ashamed that, peering over the horizon of the big 30, I’m yet to give blood, especially since both my mum and maternal grandmother donated so regularly in their youth that they were given awards. My grandmother always told me she felt compelled to donate since she had a relatively rare blood type*. She also told me that the reason my mother was an only child was because of an incompatibility between my mother’s blood, which was positive for a blood factor, and her own, which was negative (https://en.wikipedia.org/wiki/Rh_disease). This got me thinking – how many blood types are there, and why do they exist? How is it that the blood flowing through my veins and yours can be made of the same basic elements and yet be so different?
All human blood consists of the same fundamental components – red blood cells, white blood cells, plasma and platelets. Of these, it is the red blood cells that give the blood it’s identity or ‘type’. The surface of red blood cells is covered with molecules, and the presence or absence of a particular molecule determines which blood group you belong to. The principal blood grouping system used for humans is the ABO system which categorizes people into one of four groups – A, B, AB, or O on the basis of the presence or absence of a particular antigen. An antigen is a molecule capable of producing an immune response only when it does not originate from within your own body. For example, a person with type B blood who has the B antigen on their red cells could not receive blood from a person of blood type A, since the A antigens on this donor’s blood would be foreign to the type-B recipient’s body and would therefore cause an immune response. People with blood type B have the B antigen on their red cells whilst type A people have the A antigen. If you belong to AB, your red cells have both A and B antigen types and if you are group O you have neither A nor B. This basic grouping can be expanded to 8 groups when another important factor ‘Rh’ is considered. The Rh antigen can either be present (+) or absent (-), so if like my grandmother you have A- blood it means that your red cells have A antigens and are negative for the Rh factor.
At first glance categorizing blood into different types may seem like an academic exercise or a scientific curiosity but it has serious real world consequences. In the 1800s many doctors noted the seemingly unnecessary loss of life from blood loss; however few were brave enough to attempt transfusions. This reluctance stemmed from earlier attempts at transfusion in the 1600s in which animal blood was transfused into human patients. Most of these attempts ended in disaster and by the late 1600s animal blood transfusions were not only banned in both Britain and France but also condemned by the Vatican. However, after watching another female patient die from haemorrhaging during childbirth, the British obstetrician James Blundell resolved to find a solution. He thought back to the earlier transfusion attempts and correctly guessed that humans should only receive human blood. Unfortunately, what he didn’t realise was that any given human can only receive blood from certain other compatible humans. Blundell tried but with mixed success, and by the late 19th century blood transfusion was still regarded as a risky and dubious procedure that was largely shunned by the medical establishment.
Finally in 1900, the Austrian doctor Karl Landsteiner made a breakthrough discovery. For years, it had been noted that if you mixed patients’ blood together in test tubes, it sometimes formed clumps. However, since the blood was usually taken from people who were already ill, doctors simply assumed that clumping was caused by the patient’s illness and this curiosity was ignored. Landsteiner was the first to wonder what happened if the blood of healthy individuals was mixed together. Immediately he noticed that some mixtures of healthy blood clumped too. He set out to investigate this clumping pattern with a simple experiment. He took blood samples from the members of his lab (including himself) and separated each sample into red blood cells and plasma. Systematically, he combined the plasma of one person with the red cells of another and noted if it clumped. By working through each combination he sorted the individuals into three groups which he arbitrarily named A, B, and C (later renamed O). He noted that if two individuals belonged to the same group, mixing plasma from one with red blood cells of the other didn’t lead to clumping- the blood remained healthy and liquid. However, if blood from an individual in group A was mixed with a sample from an individual in group B (or vice versa) the blood would clump together. Group O individuals behaved differently. Landsteiner found that both A and B blood cells clumped when added to O plasma, however he could add A or B plasma to O red blood cells without clumping. We now know that this is because red blood cells express antigenic molecules on their surface. If an individual is given blood of the ‘wrong’ type (i.e. one that expresses a different antigen to the host’s blood) the person’s immune system notices that the transfused blood is foreign and attacks it, causing potentially fatal blood clots. Our knowledge of different blood types means that we can now make safe blood transfusions from one human to another thereby saving countless lives. In recognition of this fundamental discovery, Karl Landsteiner was awarded the Nobel Prize in Physiology or Medicine for his research in 1930.
Since Landsteiner’s work, scientists have developed ever more powerful tools for studying blood types. However, despite increasingly detailed knowledge of the genes and molecules expressed by different blood groups, it’s still unclear why different types exist at all. In an effort to understand the origins of blood types, researchers have turned to genetic analysis. The ABO gene is the gene responsible for producing the antigens expressed on the surface of our red blood cells. By comparing the human gene to other primates, researchers have found that blood groups are extremely old – both humans and gibbons have variants of A and B blood types and those variants come from a common ancestor around 20 million years ago.
The endurance of blood groups though millions of years of evolution has led many researchers to think that there could be an adaptive advantage to having different types. The most popular hypothesis for the existence of blood types is that they developed during our ancestors’ battles with disease. For example, if a pathogen exploited common antigens as a way of infecting its host, then individuals with rarer blood types may have had a survival advantage. In support of this, several studies have linked different disease vulnerabilities to different blood groups. For example, people with type O blood are more protected against severe types of malaria than people type A blood, and type O blood is more common in Africa and other parts of the world that have a high prevalence of malaria. This is suggestive of malaria being the selective force behind the development of type O blood.
As I sign up for my first blood donation appointment I think back to everything I’ve learnt about blood types. I’m eager to find out what my blood type is and what that might mean about the history of my ancestors, and the disease challenges they’ve faced. Most of all though I’m excited to continue my family’s tradition and contribute to one of the humankind’s greatest medical advancements.
Post by: Michaela Loft
*A- which is only present in ~7% of caucasians.