Molecules Versus Malaria

            

          Malaria is very well known disease today, even though it is a disease that is no longer a problem in developed countries, it is still a very big problem in less developed countries. This disease that can be caused by four different types of microscopic parasites may have been one of the greatest reasons for human mortality of all time. This disease can be passed very fast and just one person can transmit it to hundreds of people and in the past this disease wasn’t just found in tropical areas, it was actually found in different parts of the world; temperate regions, coastal areas of England and Netherlands, Sweden, Finland, United States, Canada. The disease would develop wherever the anopheles mosquito would develop, because the disease was transmitted from person to person thanks to this mosquito.  The mosquito would eventually bit the infected person and the blood taken would be infected with the parasite. The parasite would then continue its life cycle in the mosquito’s gut and be transmitted to the next person that the mosquito decided to bite. The parasite now in the new victim would invade its blood stream and enter the red blood cells, which could then be available for another mosquito which would again perform the transmission process. Malaria was a world issue, affecting the rich and the poor, destroying populations and putting armies in danger due to its vulnerability to the mosquito. This disease continued a major issue worldwide even until to the twentieth century.  

            For centuries people looked for the cures for this disease, using different methods to control them and three specific molecules have shown to very important in this fight against Malaria. The first of these three molecules is quinine, an alkaloid molecule found in the barks of a tree from the Cinchona genus family, located high in the Andes, thousand feet above the sea level. A lot of stories tell who Europeans became aware of the antimalarial abilities of these barks, and the lifes that were coincidently saved thanks the quinine present in it. When the Jesuits became aware of this ability they started to import and sell this barks in big quantities throughout Europe, but in protestant England, they refused to use this medicine given by papists, being unpopular in the region. They preferably used another remedy produced and sold by Robert Talbor a secret formula that eventually was found out to contain the same bark as the one given by the Jesuits. However, even though it was a deceiving business, this saved the innumerous lifes of those who refused to use a medicine given by the catholic. With time and the big demand for the cinchona bark, there was a need for the understanding and production of the antimalarial molecule since the sources for this molecule could eventually be endangered. 

Due to this studies started to be done, in an attempt to better understand this miraculous molecule. In 1820, joseph Pelletier and Joseph Caventou were finally able to obtain and purify quinine from the cinchona bark, the active ingredient in this plant, but further production was met with only failures since only in the twentieth century did its structure become fully determined and understood.  Even without a synthetic method to produce quinine, people still needed it and the demand only increased with time and with the European colonizations, so people resorted to the cultivation of cinchona species in other countries, as to increase the supply as much as possible. This did not happen fast since the governments in Bolivia and other countries had forbidden the export of living cinchona plants, as to protect their profitable monopoly, but Charles Ledger was able to obtain some seed and sold them to the Dutch, which planted them in Java. The production of quinine was also very important for the outcome of the WWII, since the Japanese and German had taken on their power all the quinine supply for Europe, the Allied troops needed some other kind of supply that had antimalarial properties too. During this time chloroquine was produced using synthetic derivatives of the quinine molecule, and these had proven very safe and successful, but the development of malaria parasite resistant to these molecules created a decrease in its use. Quinine molecule was finally really synthesized in 2001 by Gilbert Stork that using a different quinoline derivative, carrying every step of the synthesis process themselves and repeating the processes four times to get rid of another very similar molecule always produced in the process, was then able to synthesize the first real quinine.  

            While chemists searched for the molecule, physicians were more worried about the disease itself, how it developed and how it was originated. It was understood that the blood cells of  the infected were different from the normal ones, and this because the merozoites from the parasite stay inside the blood cells continuously  producing spores, and from time to time break out of the host cells releasing the spores and causing the fever to spike. When later the cycle between parasite, mosquito, human was also eventually understood, people also started to see some more vulnerable moments in the cycle where it could be stopped. The first possibility was to kill the merozoites when they were in the liver or blood, and another way was to prevent the mosquito bites. This prevention of the mosquito was what made the molecule DDT, the Chlorocarbon compound, so important at this time, being this the initial most important use for the molecule. Eventually the improvement of public health and a drained of water and the use of this insecticide had made the rate of malaria greatly decrease during the early twentieth century in the develop countries.

            As for the less developed countries it is harder for them to afford these insecticide molecules or increase the public health related issues, and due to that the rate of malaria is still high in this areas. However the natural process of evolution named natural selection may be having a role in the natural fight and resistance to the parasite. In the Saharan area in Africa a disease named sickle-cell anemia, which is characterized by increased rigidity and sickle shape of the blood cells. Since this blood cells are more rigid they have a higher difficulty in going through the capillaries and may cause blockages, leaving muscle tissues without blood and oxygen which causes a strong pain and eventually anemia with the destruction of these sickle blood cells, by the body. This life threating disease is caused by a mutation in the protein molecule, hemoglobin that is found in blood cells, and which gives it its red color and ability to carry oxygen. People with this disease have a mutant production of hemoglobin, in which the sequence of aminoacids is different from the normal sequence of hemoglobin. In this cases the aminoacid Valine, substitutes the Glutamic acid position and this change is enough to produce the big change. Without the COOH group of glutamic acid, the hemoglobin molecule will be less soluble and will precipitate inside the red blood cells, changing the shape and decreasing the flexibility. The main point is that the people who carry this disease have the some sickling but not enough to compromise their life, and it was observed that the carriers have some kind of immunity to malaria. If this theory proves to be true, the carrier-people will have a higher chance to survive and reproduce and carry the gene, which with evolution may originate a human immunity to this disease.

            As the authors have shown malaria is a worldwide problem, something that affect all people and is still a problem today, and demonstrating all the historical events of the evolution of malaria and the impacts that certain molecules have had in history and our human survival completely demonstrates their importance. The molecules quinine and DDT have shown a deep effect on the world, saving innumerous lifes and making nations be able to have their eras of prosperity, and mutant hemoglobin has shown the potential of nature and a promising evolution. Today quinine and mutant hemoglobin are still important, quinine is still used as a medicine for malaria and other areas, and the hemoglobin is still making the change happen and slowly producing the change. However DDT, even though crucial in the past for the eradication of the mosquito, today is not as important due to the decrease of malaria in the developed country and its dangerous properties. This molecules may seem to be not as important today, because most of us don’t deal directly with malaria, however some of them as still as important and crucial to life as they were in the past.