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Abstract
today. Sickle Disease is a recessive genetic disorder that worsens its host. Sickle Cell Disease,
however, provides immunity to Malaria. Carriers, individuals heterozygous for the Sickle Cell
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trait, demonstrate an immunity to Malaria without any of the other negative symptoms. This
provided immunity is the most effective solution, as proven by the selective advantage, to
Introduction
Sickle Cell disease is a genetic disorder that causes sickling of the cell. Patients with
Sickle Cell disease are inherently immune to Malaria. Malaria is a Plasmodium that acts similar
environments such as Africa. Several solutions have been proposed but none of the solutions that
have been implemented have been effective. Although certain experts have suggested solutions
such as the use of vaccines derived from dead P. Falciparum and the use of T cells to combat
cell genotype through the use of CRISPR and plasmids is the superior method for dealing with
Malaria.
Literature Review
Malaria is a Plasmodium that uses vectors, female mosquito contact with infected blood,
for transportation. As such, Malaria is not openly communicable from person to person and is
only transferable from mosquito to human (Gong, Parikh, & Rosenthal, 2013). Upon interaction
of a human with a female mosquito that possesses the Malaria Plasmodium, Malaria infiltrates
the red blood cells through diffusion in the cellular membrane. Malaria then interacts with the
genetic coding of the cell. Here, the Plasmodium acts as a parasite through inserting its own
DNA into the target host’s genome in order to transcribe and translate that section of DNA. This
will encode for proteins that allow for further reproducing of the Malaria protist (Gong, Parikh,
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& Rosenthal, 2013). In order to more effectively reproduce, the Malaria alters the cell’s cellular
peripheral clocks and SCH in order to alter its rhythm. This allows for the cell to work around
the clock and reproduce more of the Malaria protist (Animal activity around the clock with no
During reproduction and mitosis, the Malaria infected cell uses one’s bodily resources
through taking advantage of the cell cycle. The plasmodium uses Interphase to grow inside a
newly created cell. This new cell eventually matures, reproduces, and repeats the cycle again.
After the Malaria has reproduced enough, it ruptures the cell membrane. As the cell membrane is
vital in osmosis, diffusion, and maintaining the shape and organelles of the cell, the previous host
cell of the Malaria is killed after departure. The created Plasmodium then infects more red blood
After the stage of infestation of the red blood cells has been completed, the Malaria then
transports to the liver cells of the patients. Here, it undergoes the same process as with the red
blood cells. The killing of both red blood cells and liver cells accounts for all the symptoms of
Malaria including fever, halted glucose intake, headaches, and vomiting (Choby, Buechi,
Farrand, Skaar, & Barber, 2018). After these two phases are done, a vector interacts with the
blood of an infected patient. Doing so will cause the vector to transport the plasmodium. Here,
present in the short arm of the 11th chromosome. These mutations cause changes that result in
the improper construction of Heme iron and unoxygenated hemoglobin present. (Pishchany &
Skaar, 2012). Usually, in normal individuals, when under anaerobic conditions, hemoglobin
stacks up on top of each other in a cell. However, in sickle celled individuals, when under
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anaerobic conditions, hemoglobin is produced with binding and receptor parts. The receptor and
binding parts of the hemoglobin bind to each other causing the hemoglobin to line up. This
causes the cell to form a sickle shape and causes sickling in oxygen deprived environments
(Choby, 2019). This sickle shape of a cell results in decreased oxygen intake to the cell.
Symptoms of the disease on the organismal level derive from the sickle shape. They range from
clogging of blood vessels due to the immobility of shape to decreased energy due to less aerobic
respiration. However, on the cellular level, other than decreased oxygen intake, nothing else is
changed. Sickled Cells maintain the same constant circadian clock, peripheral clock, and SCH as
The decreased oxygen intake in Sickled cells due to the sickle shape results in choking of
the Plasmodium within Sickled cells. This is due to cellular respiration. All cells, including
Malaria infected cells, go through respiration. Cellular respiration is divided into four portions.
These portions consist of glycolysis, the Link Reaction, the Krebs Cycle, and oxidative
processes, and ready to be used, glycolysis begins. In glycolysis, a process that occurs in the
cytoplasm of the cell, a six-carbon glucose molecule is used to construct 2 PGAL molecules,
each consisting of 3 carbon. From here, these 2 PGAL molecules demonstrate reduction as an
electron is used to bind the positively charged NAD+ and positively charged H+, originally from
the 2 ATP molecules, to form NADH and two 1, 3 BPG molecules. From these 1,3 BPG
molecules, the 2 pyruvates needed for the link reaction is constructed. Continuing on to link
reaction, a process that occurs in the inner matrix of the mitochondria, the products of glycolysis
become the reactants of the Link Reaction with 2 pyruvates, a 3-carbon acid each, forming 2
Acetyl CoA, a 2-carbon molecule each. This is done when the Coenzyme A binds with the
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pyruvate, forming a molecule with differences in the amount of carbon. While this process is
occurring, 2 CO2 is released into the external environment, explaining the carbon difference
between the pyruvate and Acetyl CoA. The 2 acetyl CoA is then used for the next process, the
Krebs Cycle. The Krebs Cycle converts oxaloacetate produced in the cycle, 4 carbons each, into
transpire including the conversion of NAD to NADH and ADP and a phosphate group into ATP.
CO2 molecules are also released into the external environment. In oxidative phosphorylation, a
process that occurs in the inner membrane of the mitochondria, high potential electrons are
extracted from NADH and FADH2 to form NAD+ and FAD+. These high potential electrons,
the H+ and 2H+ from the NADH and FADH2 respectively, go through the electron transport
chain and allow for active transport, a process that requires energy to commence the movement
of molecules against the concentration gradient, to occur. During this process of active transport,
channel proteins transfer positively charged hydrogen inside of the intermembrane space. After
this, oxygen acts as an electron receiver (The contributions of respiration and glycolysis to
extracellular acid production, 2014). Oxygen receives the electrons from this transport chain, and
hydrogen and oxygen bond in order to produce water. The ATP synthase is another channel
protein that removes hydrogen ions from the intermembrane space to the mitochondrial matrix
and phosphorylates ADP to form ATP. During this process, 34 ATP and 6H2O is produced
(Gnaiger, Steinlechner-Maran, Méndez, Eberl, & Margreiter). If there is decreased oxygen intake
from sickling, there will not be enough reactants for glycolysis to occur. This leads to a chain
reaction in which future steps of cellular respiration do not occur either. Instead, however,
fermentation occurs producing drastically lowered ATP amounts (Variation in the link between
oxygen consumption and ATP production, and its relevance for animal performance). The
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amounts produced are so low cell reactions cannot be maintained. This kills the cell and anything
in it, including Malaria. This causes immunity from Malaria (INCREASED SICKLING OF
Now, there can be carriers of Sickle Cell as Sickle Cell is a recessive genotype. Carriers
can express no Sickle Cell Disease symptoms but possess the allele for Sickle Cell by being
heterozygous for Sickle Cell. Carriers or heterozygous patients do not experience regular
sickling in deoxygenated environment. Only partial sickling on cells with detected plasmodium.
This process occurs through hormone secretion and cell signaling (Liemburg-Apers, Willems,
Koopman, & Grefte, 2013). This is a great positive due to none of the negative symptoms of
Sickle Cell occurring in heterozygous individuals while they do experience the sickling
advantage of Malaria immunity. The viability of being heterozygous for Sickle Cell is
demonstrated through the natural selective advantage. Those with heterozygous Sickle Cell have
been rising in Malaria infested regions. This means they have been surviving and reproducing
more than those who are recessive or dominant for Sickle Cell (Ackerman, 2005). If this is
simulated in patients with Malaria, this would be the most effective solution as patients
demonstrate immunity to Malaria without having any negative symptoms of Sickle cell.
There have been other suggested solutions to the Malaria pandemic that have been
demonstrated as not effective. Beginning with the first one, one suggested solution is Vector
control through elimination of vector populations or destruction of breeding nests. Though this
would control the transportation of Malaria, there would be negative effects that would follow
including trophic cascade in both the predator and prey levels (Long & Hoffman, 2002). This is
therefore not an effective solution. For the second one, another suggested solution is pesticide
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use in recreational and residential areas to prevent exposure to vector and therefore Malaria.
Though this would again control the transportation of Malaria, there would be negative effects
on the human population as there is a demonstrated connection between these pesticides and
cancer. This is therefore not an effective solution. For the third solution, a suggested solution is
vaccination through use of dead p. Falciparum. This has been recorded to have provided
immunity for 10 months (Long & Hoffman, 2002). Though this solution has provided immunity
for these 10 months, this solution would not ultimately be effective long term as Malaria would
naturally select allowing plasmodium strains to become immune to the vaccination. This would
therefore not be an effective solution. Simulating a heterozygous Sickle cell environment does
not cause trophic cascade, does not harm the human population, and cannot be adapted to due to
that are heterozygous for Sickle Cell is the most effective solution. This simulate can be
administered through the use of plasmids and CRISPR. Plasmids are untangled, circular portions
of DNA within bacteria. They provide a sufficient “canvas” through removal, genome
plasmid, genomes can be edited with that particular DNA. Implementation of new DNA through
complementary tRNA anticodons, and translation of mRNA into polypeptides and proteins to
influence phenotype. Implementation of these plasmids can be done through the use of CRISPR.
CRISPR can be used by specifying a targeting sequence within the RNA in order to efficiently
edit a genome (Ran, 2013). CRISPR is an effective editing tool for several reasonings. Firstly,
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CRISPR is easily customizable due to change in oligos. Secondly, CRISPR possesses Cleavage
Pattern, mutations in the nuclease allowing for nicking and verification. Thirdly, CRISPR has the
ability to target multiple sections at one. Fourthly, CRISPR contains HDR, a structure possessing
the power of mammalian repair assists, which is made more reliable through Double nicking in
Cas 9 which prevents error (Doudna & Charpentier, 2014). Fifthly, the Programmable sequence
specific endonuclease within CRISPR are really helpful for particular binds to membrane
proteins allowing different simulation of DNA or direct editing allowing for amazing efficiency
(Development and Applications of CRISPR-Cas9 for Genome Engineering, 2014). Sixthly, the
DNA oligonucleotides present allow for preciseness with use of CRISPR (Development and
Applications of CRISPR-Cas9 for Genome Engineering, 2014). These benefits make plasmids
through the use of CRISPR the most effective way to implement the most effective solution of a
Data Collection
Meta-analysis is the data collection strategy that was picked for this paper. Originally,
experimental data collection was going to be used to compile data that would be able to prove
the thesis. Practically, carrying out experiments or studies of populations to get the data that is
required would be impossible to do with the resources present. So instead of carrying out
experiments or studies, Data was compiled from a multitude of studies and experiments in order
to accomplish the same goal of supporting the thesis and proving the side of the argument argued
by the paper. There were other particular reasons why Meta-analysis was picked over the other
data collection strategies. Firstly, experimental data collection would not work for the reason
given above. Observational data collection was not picked as once again resources are not
sufficient enough for one to observe Sickle Cell and Malaria and collect data based on those
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observations. Data collection based on questionnaires, surveys, and interviews was not picked
because the collection of opinions of a population will not prove the thesis nor argument.
INCREASED Example of
PARASITISED Malaria.
ES AS
MECHANISM
OF
RESISTANCE
AGAINST
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MALARIA IN
THE SICKLE-
CELL TRAIT.
14 February
1970
Total 200 Total 290 were not equal were not equal
participants. participants.
Adjusted Adjusted
Total(1000) Total(583)
Plasmodium. generation.
With M2B1,
throughout the
whole
experiment (40
days) no
individuals were
diagnosed with
the strain.
Another example
with people
without Sickle
Cell is present
B4. In 8 days, 2
people were
diagnosed with
this strain. In 10
days, 50 people
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were diagnosed
In 12 days, 100
people were
diagnosed with
this strain. On
contrary, with
people with
one was
diagnosed with
the duration of
the study
Beginning with results, results from study 1 demonstrate the idea that individuals
diagnosed with a heterozygous sickle cell genotype experience increased sickling in cells
infested with the Malaria Parasite. This data is not surprising as the mechanism in which cells
sickle support the results of this data. The results were caused by this mechanism. Upon
stimulation through Malaria infiltration, for heterozygous individuals, hormone proteins are
released that interact with the cellular membrane of cells with detected plasmodium infiltration.
The interaction acts as a promoter and causes sickling. This supports the data. Alone, the results
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mean nearly nothing to my research question. Support with the upcoming studies alongside the
results of this study demonstrate how Sickle Cell is a superior solution to the Malaria argument.
Continuing on with the results from study 2, the results from study 2 demonstrate that Sickle Cell
provides near perfect immunity to all strains of Malaria as demonstrated through non induced
sickle cell patients being diagnosed for Malaria much more than sickle cell patients. This is also
demonstrated through study 4 with different severities of Malaria. In general, sickle cell patients
demonstrate almost perfect immunity to all severities of Malaria. Study 4 and 2 were not
surprising as the scientific mechanism with Sickle Cell Disease supports these findings. The
results are as a result of the characteristics of Sickle Cell. As a result of the shape of sickled cells,
less oxygen is provided to these cells. In Malaria infected cells, this decrease in oxygen causes
the death of the plasmodium. This results in immunity as demonstrated in the data. Here is where
the results of study 1 come into play. As the results of study 2 and 4 determined that sickling of a
patient’s cells provide immunity and study 1 determined that malaria induced cells are sickled at
a greater degree, the conclusion from these 3 studies is that Sickle Cell focuses Malaria induced
cells with increased sickling, kills these cells with decreased oxygen, and provides almost perfect
immunity to the Plasmodium. This supports the thesis and the argument that stimulating a
heterozygous sickle cell environment is the superior solution. Finally, the results of study 3
determine that younger generations when compared with older generations exhibit increase
genotypic features incorporating heterozygous sickle cell traits. This was not surprising as it
makes sense according to the mechanism of evolution and natural selection. A trait that makes an
organism better fit for an environment will result in the more fit organism surviving at a greater
rate than the less fit organisms. This will eventually result in the population with this fit trait
increasing due to the increased rate of survival. Based on this reasoning, since those with
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heterozygous sickle cell are surviving at greater rates than those that do not have heterozygous
sickle cell and therefore increasing in population, heterozygous sickle cell must make the human
organism more fit for a Malaria environment. This supports the thesis and the argument through
demonstrating stimulating Sickle Cell is an effective method to dealing with Malaria. Study 3’s
results ultimately combine with the results of study 1,2, and 4 and ultimately, support the
argument.
The limitations of the data collection, meta-analysis, derive from the point that articles
are not specifically suited for each other and are distinctive in their own manner. This makes it
difficult to connect all of them. If this were to be done again, articles would be found that were
even better suited for each other in order to connect them even more.
These results ultimately support the thesis and argument which states implementing a
Sickle Cell environment would be the superior way to deal with Malaria. This may warrant
future research into the topic and allow for a possible cure to the disease through genome editing.
The new knowledge that can be extrapolated from the results include implementing a Sickle Cell
Conclusions
Throughout the years, possible solutions have arrived to solve the argument of the
Malaria endemic. Ultimately, they are not as viable for use as a solution to the Plasmodium as
Sickle Cell immunity is, due to the negative effects they result in. Studies have also
demonstrated heterozygous Sickle Cell as a near perfect method for immunity to Malaria.
Simulating a heterozygous Sickle Cell environment is the superior method to deal with Malaria
and a practical one with implementation through bacterial plasmids and the Cas9 CRISPR
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mechanism. Now that there is a method, the people can make the world a Malaria free place.
Now, the people must voice their opinion and change public policy.
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