History of Sickle Cell Disease

The fatal disease of sickle cell is a disease that directly affects the hemoglobin. This disease was first documented in American in 1910 but has been known to been around since the late 1600s (History 2013). The discovery of this disease was also accompanied by the hypothesis that sickle cell anemia and malaria are linked and what the relationship between the two exactly is. As well as the complex relationship between sickle cell anemia and malaria. sickle cell anemia had many discoveries that followed the study of the disease itself. In this paper the importance of sickle cell anemia will be explained as well as the historical landmarks that made the discovery of this disease such an eye opener to medicine. In 1904 a young dental student by the name of Walter Clement Noel was admitted to the Chicago Presbyterian Hospital for severe anemia. Noel was of African decent from a wealthy family that lived in Grenada. Ernest Edward Irons was the doctor that exam Noel and put into his notes that Noels hemoglobin was, “Peculiar elongated and sickle-shaped. Noel was reinstated in the hospital a couple of times before returning to Grenada and opening a dentistry. Unfortunately, Noel died just twelve years in 1916 of pneumonia (History 2013). James B. Herrick, Irons supervising physician, wrote a paper in the Archives of Internal Medicine that was published in 1910 about the first known case of sickle cell disease. This was the first case in the United States that had been reported but strange blood smears of pear shaped hemoglobin was found in African literature in the 1870s. Because of the extremely high infant mortality rate researchers never really payed high attention to these strange blood smears until the discovery of Herrick and Irons (Winter). So what exactly is sickle cell anemia, it is a mutation in the hemoglobin gene that causes atypical hemoglobin molecules that have been named hemoglobin S. These hemoglobin S molecules can reshape the red blood cell to look like a C shape or a crescent shape. Because of the S or crescent you can imagine that in places that wind a lot like your intestines or brain the hemoglobin S molecules may catch onto each other and cause extreme pain from causing stagnation or blocking the flow of blood or Qi in TCM terms. Other signs of sickle cell is low blood cell count which in turn makes sickle cell turn into sickle cell anemia. Repeated infections is also a symptom of this disease and these signs and symptoms generally start in childhood (Genetics 2018). Sickle cell anemia is such a devastating disease because it can eventually lead to organ failure from oxygen deprivation to that organ. When the hemoglobin is in a crescent shape it cannot carry oxygen like how it is designed to do. Another problem is the crescent shape of the hemoglobin is not flexible and, as stated above, can get caught on each other causing blockage in small blood vessels which also disrupts the blood flow to organs. When Irons and Herrick discovered this in 1910 many mysterious and unexplained deaths started to make sense to more and more scientist and doctors and of course further research was accomplished. In 1927 two men named Hahn and Gillespie discovered that the sickle shape of the hemoglobin meant that there was a depletion of oxygen in the cell that was making it into this crescent shape. At first the two men were very excited because it was one more thing they knew about the disease but then were later disappointed when patients would come with the character trait of the sickle shaped hemoglobin but did not have the disease. This condition was named the, “sickle trait. ” This “sickle trait ” was further researched and in the late 1940s and early 1950s explanations started to arise. Reasons why some patients only had the “sickle trait ” verses the actual disease was explained as patients with the sickle trait were heterozygous, carry two different allele, where as patients with the actual disease were homozygous, carried two of the same sickle cell gene. This study was shown in 1949 when two papers interdependently came out one written by Col. E. A. Beet and the there by Dr. James V. Neel (Winters). The papers explain that the sickle cell disease is hereditary and that is how it is passed on generation after generation. As well as these two journals that were published in 1949, Linus Pauling and his colleague Dr. Harvey Itano started to test theories and demonstrate how sickle cell is actually a result of a genetic abnormality that takes place in the red blood cell itself. Two years later in 1951 they were able to prove this theory that hemoglobin had a different structure in patients with sickle cell disease rather than patients without sickle cell disease. Dr. Pauling termed this, “molecular disease” for certain disease that actually interrupt the chemical compound of their specific structure (History 2013). This led to thousands of diseases of molecular based genetic disease such as cystic fibrosis, hemochromatosis, and marfan syndrome just to name a few. In the early 1970s a doctor by the name of Charles F. Whitten realized that people with sickle cell disease had limited resources as far as medical and educational and made it a point to satisfy these peoples needs. Because of Dr. Whitten the Sickle Cell Disease Association of America (SCDAA) was created. He started this organization by simply taking an interest and having empathy towards patients that he saw and understanding that to overcome a disease you have to understand it and be smarter than the disease (History 2013). Because of the renowned research made by these scientist other facts about hemoglobin and molecular diseases were discovered. Because sickle cell anemia is a disease in where the red blood cell is disformed scientist discovered that there can be such molecular diseases that can lead to haemoblobinopathies (Luzzatto 2012). Hemoglobinopathy can better be defined as all genetic diseases of specifically hemoglobin. It was unknown before this discovery that diseases could take such a role on hemoglobin and actually inhibit its function. Different types of anemia were discovered because of this such as aplastic anemia, autoimmune hemolytic anemia and iron deficiency anemia. Once sickle cell started to get more and more research behind it scientist started to study the structural components of hemoglobin. It was then understood why the three-dimensional shape had different character traits when the hemoglobin was oxygenated or not. One of the main jobs of hemoglobin is to bind to oxygen and transport it to the desired tissue. Whether that be organ tissue, muscle tissue, etc. every tissue needs oxygen in order to survive. As stated above, tissues that receive lack of oxygen are in trouble of shut down which, as well know as medical professionals, once one organ starts to shut down they all start to shut down as well. This is one of the ways that makes sickle cell disease so dangerous because of the lack of oxygen flow to the body (Luzzatto 2012). One of the most major discoveries about sickle cell anemia was the genetic compound that accompanies the disease. The make up of the sickle cell disease as discussed earlier is a homogenous disease whereas carriers have a heterozygous trait. The discovery of this allowed researchers to start to wonder if other unexplained illnesses could be from genetic compounds as well. It was clear after continuous research and laboratory experiments that parents can have a direct affect on what their child will carry verses what their child with actually contract (Winters). There are some non-life threatening disorders such as poor vision but there are also fatal genetic disorders such as cystic fibrosis and breast cancer. As well as lack of oxygen to tissues, infections, and reduced number of red blood cells, research also shows that sickle cell disease can be especially detrimental if combined with infectious diseases, specifically malaria and salmonella. J B S Haldane had a theory that people who are composed of different genetic make ups would be at different risk of mortality when confronted with an infection disease or parasitic organism. He then theorized that this could especially be the case in malaria since it was see in many cases with people who had the sickle cell genetic make up. The first person to test this theory was A C Allison who showed through his research that the S gene was in high concentration of people who had contracted malaria, and even more surprising that patients that only had were carries of the gene seemed to have more of a protective gene against malaria. Further research depicted carriers of the S gene do get malaria but they tend to have lower numbers of parasitized red blood cells (Luzzatto 2012). Generally, malaria episodes can be taken care of but since malaria is an infectious disease of the blood the combination of sickle cell anemia and malaria can be extremely dangerous. Because of the reasons is because that the disease of malaria will make the anemia of sickle cell anemia worse (Protective 2018). This can make the anemia so bad that it is possible to be life threatening if not taken care of. Another way that malaria can directly affect the patient is making the patient extremely susceptible to pain to the point in which it is unbearable (Luzzatto 2012). Sickle cell is a genetic disease where the hemoglobin molecule is crescent shaped, brittle, and inflexible. The disease dates all the way back to the late 1600s but there was not any papers published about this disease till the year of 1910. The discovery and research of sickle cell disease led to the further discovery of genetic diseases. Specifically, scientist figured out through studying this genetic disease that there can be carriers of genetic diseases verses actually contracting the disease. Many infections such as salmonella and malaria have also been studied with this disease. Sickle Cell disease is an extremely dangerous disease that can have a detrimental affect on a persons life. The average person with sickle cell anemia lives till they are 42-47. Although life expectancy as well as vitality of life has increased, a great thanks to Dr. Whitten, there is so much more that needs to be understood about not only this genetic disease but all genetic diseases so as practitioners of medicine we can do our best to prevent and help patients overcome them.