Pauling and Sickle Cell Anemia
The First Condition Described as a Molecular Disease
A summary of the research of Linus Pauling's Team in 1949 which led to his coining the term "Molecular Disease"
Sickle cell anemia is a life-threatening, inherited condition that is usually found in people of African descent. It is an affliction in the blood in which the red blood cells of sufferers, instead of being circular in shape, bend into a crescent or sickle shape when they are oxygenated. These sickle-shaped cells can get stuck in the narrower blood vessels, blocking the flow of blood. Symptoms include those normally associated with anemia such as fatigue, shortness of breath and paleness, they also include pain in body organs or joints and eye problems.
Linus Pauling
This article concerns the discovery by Linus Pauling and his team in the late 1940s that sickle cell anemia is a molecular disease, opening the door to the understanding and treatment of many conditions on a molecular level.
Hemoglobin
Pauling was an inorganic chemist at the California Institute of Technology or Caltech. He was studying the structures of complicated large molecules and had chosen hemoglobin to investigate. Hemoglobin is the protein in the red blood cells, containing iron, which binds to oxygen molecules to transport them around the body. He spent several years studying the structure of the protein molecules that made up hemoglobin and how oxygen binds to it.
Different Structures
Particularly important was their discovery that when oxygen binds to hemoglobin (oxyhemoglobin) it does not have magnetic properties, but when the oxygen is removed magnetic properties are measured. They suggested that this was because the iron atom binds covalently to the rest of the molecule in oxyhemoglobin but with ionic bonds in hemoglobin.
Sickle Cell Anemia
His studies proved useful in 1945 when he heard about sickle cell anemia. He later claimed that when he heard about the condition he understood what was happening in “two seconds”. The fact that the sickling occurs in oxygenated blood implied that it was caused by hemoglobin which changes structure so dramatically when it binds to oxygen.
Electrophoresis
Pauling's team used a new method called “electrophoresis” to show that the hemoglobin in sickle-cell sufferers was different to “normal” hemoglobin. Electrophoresis essentially uses an electric current to separate substances with different ionic charges. It was used in this case to show that the sickle cell hemoglobin has more positive charges than normal hemoglobin.
Molecular Disease
What was the use of this discovery? Essentially what Linus Pauling and his team showed was that sickle cell anemia was caused by a small difference in the molecular structure of one type of protein. The structure of hemoglobin was determined by the sequence in the DNA of the sufferer so it was a genetically caused molecular disease. This was a huge stride forward in the study of disease and genetics.
Sources:
"Its in the Blood! A Documetary History of Linus PAuling, Hemoglobin and Sickle Cell Anemia", http://osulibrary.oregonstate.edu/specialcollections/coll/pauling/blood/index.html
"Genetic Disease Profile: Sickle Cell Anemia", http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/sca.shtml
