The Fight Against Disease: A Strike Against Malaria

Malaria is an Epidemic

Malaria has been a growing problem in many third world countries, with mosquitos infecting an estimated 682,191 people a day in 2022. That is an increase of 5 million year over year from 2021. With the growing concern of how to stop this epidemic, researchers are looking at using a second-generation genetically attenuated parasite to create a "favorable immune induction profile and protective efficacy" response in humans infected with the virus. The trials show favorable results and it appears that the research is moving forward. This is great news, and to subdue any concerns, although the parasite does invade hepatocytes, it never reaches a blood stage infection due to the limitations placed on it via genetic modification. 

This is a great example of how genetic research can impact medicine and help save lives where other methods fall short. I'm excited to see where this goes, and if we can apply this to other parasite originated diseases. The next problem to work on in this case is a solution for those who have been previously infected, as this performs best in first infection cases, and sub optimally otherwise. Below is an important infographic relating to the study, easily digestible by those unfamiliar with the subject matter

.

Links:

https://www.nejm.org/doi/full/10.1056/NEJMoa2313892

https://www.nature.com/articles/s41541-024-00975-0

Suppressing Malaria-Carrying Mosquitos Through 'Gene Drives'

 Mosquitos are the primary carriers of the plasmodium parasite-- the source of the malaria disease. West Africa is notable for being a hotspot of malaria cases. A recently developed technology known as a "gene drive" has been considered to be a potential method of suppressing transmission of malaria, utilizing the natural process of a species' own inheritance as predicted by Mendelian genetics to control populations by altering the expression of genes related to disease transmission. In the last decade, advances in CRISPR technology have progressed gene drive research greatly. Though field trials have not yet been done, simulations and models can help predict how they might affect real populations. In the figure below, the effect of gene drive releases on west Africa's mosquito population shows that they are predicted to decrease in density over time, reducing the spread of malaria in the process. Of course, in real application of this technology, there are many more factors that will determine its effectiveness. However, these simulations show promise in this newly emerging phenomenon that may help combat against malaria.

https://www.nature.com/articles/s41467-024-53065-z#Bib1
https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2023

Genetic Engineering Can Suppress Population of Malaria-Transmitting Mosquitoes

 

    Recent studies and discoveries have allowed scientists to use genetic engineering in order to make female malaria-transmitting mosquitoes infertile, and therefore suppressing the population of these mosquitoes around the world. The lead researcher for this experiment calls it a “game-changer in bringing about malaria elimination”. This study, conducted at Imperial College London, Italy’s Polo Genomics Genetics and Biology, and the Liverpool School of Tropical Medicine, used “gene drive” technology for this study, which is a self-sustaining and fast-acting technology that can work simultaneously with other tools such as bed nets, vaccines, and insecticides. Using this type of technology, scientists are able to circumvent natural selection by inserting genetic instructions that are passed on through populations of mosquitoes, and in this particular case, that instruction is for infertility. This process is much quicker than if performed through regular selective breeding. This study also maps out the future effects of what can happen within 10 years of these self-destructive mosquitoes being released into the wild. “Gene drive” technology has been explored since 2003, but hit a bump in the road when researchers discovered that their gene drives vanished after a few generations due to mutations. This study identified a crucial sex determination gene, however, that is identical among these mosquitoes that are responsible for most of the malaria transmission in sub-Saharan Africa. The release of this gene drive into the population of malaria-transmitting mosquitoes can suppress the population size and potentially even rid the world of these mosquitoes.

Link to Study: https://www.nature.com/articles/s41467-021-24790-6?utm_medium=affiliate&utm_source=commission_junction&utm_campaign=3_nsn6445_deeplink_PID100093539&utm_content=deeplink

Link to Article: https://nypost.com/2021/07/29/genetic-engineering-may-eradicate-malaria-transmitting-mosquitoes/

Stopping Mosquitoes From Spreading Malaria

 

An article from eLife talks about altering a mosquito's genes so they spread antimalarial genes to the next generation, in the hopes of stopping mosquitoes, altogether, from spreading malaria. This study is using CRISPR-Cas9 gene-editing technology to make changes in mosquito genes. This will greatly reduce illnesses and deaths caused by malaria. Researchers are using genetically modified mosquitoes, which will be released into the environment and, eventually, will spread genes that will decrease mosquito populations or make them less likely to spread the malaria parasite. This article discusses, more in depth, about how genetically modified mosquitoes work. Testing is still being conducted, as of now, to make sure this is safe to release into the wild. 

Genetic Treatment to Malaria Growth in Mosquitoes

 

    Malaria is a parasitic disease, mainly transported into humans by over 30 species of mosquitoes. In 2019, 229 million people were infected with malaria and 409 thousand died. There are many antimalarial drugs on the market that can build up your immunity or fight the parasite itself. Children under 5 pose the greatest risk of dying to malaria, as 67% (274,000 deaths in 2019) of malaria deaths happen to them. Malaria has killed roughly 4-5% of anyone who has ever lived, making malaria one of the deadliest diseases ever. 

    Recently researchers from the Imperial College of London published a journal about their findings on genetically editing Anopheles gambiae mosquitoes' genes to inhibit the development of the malaria parasite within them. The researchers were able to make healthy mosquitoes that couldn't infect others with malaria. They then bred the mosquitoes and their spawn also were healthy without the malaria parasite developing within them. The researchers are currently looking to test the gene edited mosquitoes in the field as a way to prevent malaria, but that may be a long ways away. I think if we can conclude there are no dangers to the environment, mosquitoes or the people getting bit, this could be the end of malaria, and prevent millions of more deaths to malaria.

Links:

https://www.genengnews.com/news/curbing-malarias-spread-by-genetic-engineering/

https://elifesciences.org/articles/58791

https://www.who.int/news-room/fact-sheets/detail/malaria

How malaria parasites hide from the human immune system

 Erin Garcia de Jesus outlines malaria parasites in the human immune system in this article. Malaria parasites hide out in the human body by keeping the cells they infect from clinging  to blood vessels. They do this during Africa's dry season since mosquitos are scarce so the parasites have a hard time spreading. Silvia Portugal her colleagues did experiments on dry season and wet season parasites and they found that blood cells infected with malaria use certain proteins to adhere to blood vessels. There is a loss of stickiness  and this  could be because of two things: Either because the parasite makes fewer of these proteins or because the  proteins are different in some way.  Parasitologist Abdirahman Abdi says  that to narrow down which genes may be affecting stickiness researchers might need to compare genetic activity in parasites at the same stage. It's crazy to think that malaria can actually hide itself in the human body, undetected. Scientists findings help researchers better understand how these parasites turn on and off their genes during the wet and dry seasons so more tests can be conducted. 

This gives extensive information about malaria, it's diagnosis, treatment, etc.

 Malaria Hides in Human Immune System

During the dry season in Africa, the parasites that carry malaria have to find a new host since mosquitos are scarce during this time period. The parasites have developed a way to keep their cells from attaching to the blood vessels. By doing this, the blood will circulate the infected cells out and help malaria stay in the body unaffected and the hosts will have less severe symptoms. The way malaria parasites work is by attaching proteins they make to blood vessels and they don't go to the spleen where blood gets circulated. They studied the difference between the parasites that were found during the dry season and the other seasons and found several differences. The ones in dry season behaved differently and weren't sticking due to the different genes turned on and off. The differences found were that 1131 genes were on during the dry season that is off during the wet season. These studies show that the parasites will alter its genes to make itself more sticky during the wet season and less during the dry season. There is still more research to be done to specifically find out if the genes being switched is for the stickiness of the cells.

How malaria parasites hide from the human immune system

According to ScienceNews, an article by Erin Garcia de Jesus, malaria parasites hide in the human body by keeping the cells they infect from clinging to blood vessels. By doing this, "infected cells get removed from circulation and parasite levels in the body remain low, making people less sick and allowing the parasite to persist undetected." This is why symptoms tend to wane during the dry season. This has been successful for the malaria parasite as it produces proteins and make them stick to the blood vessels so they won't be carried to the spleen. Researchers took samples to see if the gene was turned on or off from asymptomatic people in the dry season as well as symptomatic people in the wet season. "they saw that 1,607 genes had distinct seasonal patterns. In the dry season, 1,131 genes were turned on that were off in wet-season parasites. Another 476 were turned off in dry-season parasites, suggesting that when the wet season ends, P. falciparum may alter its genetics to make red blood cells less sticky." The one thing researchers are uncertain about is what genes are involved in the shift. I think this article was very interesting. First of all, this article is very recent and I think it's interesting to see how malaria parasites are able to hide in the human body and that researchers have just discovered this. As well as the fact that they are able to alter their genes which I had no idea they were capable of doing!

The Fight Against Malaria

In any hot and humid environment, a person can run come into contact with many flying insects, particularly with mosquitos. These pesky insects cause havoc from this bites, causing itches, and even sickness. Mosquitoes, however, have been known transmit and infect many with Malaria.

The disease, however, has been genetically identified. Scientists used piggyBac - transposon insertional mutagenesis to identify the genes that were associated with malaria. Parasites carrying malaria can now be readily identified and can potentially be treatable. Such a step can be help patients who are in dire straits when dealing with the diseases. Still, drug resistance is still a major problem, but using such a gene technique can allow for even better drug resistance and at the source. 

Link to main Article

Link to Research on Malaria Gene

How One Child's Sickle Cell Mutation Helped Protect the World from Malaria

Recently a study conducted by the Center of Research on Genomics and Global Health, a part of the National Institutes of Health looked into how humans obtained sickle cell anemia. This genetic mutation alters ones hemoglobin which is the molecule on the red blood cell that moves oxygen throughout the body. Roughly 7,300 years ago in Africa, scientists have found that if a person had two copies of a mutated hemoglobin gene led to the sickle cell shape attributed to the name, sickle cell anemia. However, researchers were left in a, "genetic mystery," onto why this mutation never died off. It was discovered that if a person had one mutated hemoglobin gene this allowed that individual to survive the mosquito transmitted disease, malaria, a wide spread disease in Africa at the time. Essentially, if an individual had only one copy of this allele they were safe however, if one was to have two copies of this allele, their blood cells would be defective and clog the blood vessels in the body. This discovery led researchers to believe that the development of sickle cell anemia is linked to human survival of malaria.

Article: https://www.nytimes.com/2018/03/08/health/sickle-cell-mutation.html
Original Study: http://www.cell.com/ajhg/fulltext/S0002-9297(18)30048-X

Potential Danger of Gene Drive Research

  

Could this Be Malaria’s Achilles Heel?

Researchers at the Instituto de Medicina Molecular have discovered that the Plasmodium parasite, which is the cause of malaria, defends itself by replicating inside its host’s liver cells. Replicating inside the host’s liver allows the parasite to infect red blood cells and cause potentially deadly symptoms. Symptoms of malaria in humans include fever, chills, and a flu-like illness (cdc.gov).

Portuguese researchers have recently discovered that the Plasmodium parasite is resistant to autophagy, a cellular defense mechanism. However, the resistance to autophagy all hinges on the presence of UIS3, a protein which binds to another protein, LC3. When UIS3 is bound to LC3, a shield protects the Plasmodium parasite from autophagy, leaving the parasite free to replicate inside the liver of its host. However, parasites that lack the UIS3 protein do not have this protective shield, and can be eliminated by the host. Therefore, the UIS3 protein could potentially become a target for protection against the malaria parasite.

I think that this development in genetics could help so many people in the future. If a malaria vaccination or cure that renders the UIS3 protein inoperable could be developed, many lives will be saved. According to the CDC, 429,000 people died of malaria in 2015 alone. It would be amazing to see a combatant for malaria come out of this genetic discovery, especially now that drug resistance is becoming an issue.

Could This Be Malaria's Achilles Heel?

Information on Malaria from the CDC

Gene Drive, The Most Powerful and Alarming New Tool In the Science World Today

There is recent study on the extension of CRISPR with a system called gene drive, that uses CRISPR as a stepping stone. CRISPR gene drive is one of the most powerful and alarming new tool in the science world today. Some researchers though of what if CRISPR inserted not only on the new gene but also a machinery that does the cutting and pasting. In other words, CRISPR also copied and pasted itself. The result will be a perpetual motion machine for gene editing.  CRISPR gene drive created by a scientist name Esvelt, which guarantees that a trait will get passed on, but if it is used in the germline cells, it will automatically copy and paste the new gene into both chromosomes of every single individual. It is like a global search and replace, or in science terms, it makes a heterozygous trait homozygous instead. 

There is a research using the gene drive to create mosquitoes carrying anti-malaria gene. The result given, the Mendelian genetics says when a male and a female mate, their baby inherits half of its DNA from each parent. As a result, if the original mosquito was aa and the new mosquito is aB, where B is the anti-malarial gene, the babies should come out in four permutations: aa, aB, aa, Ba. Instead, with the new gene drive, they all came out aB. Biologically, that should not even be possible. However, CRISPR gene drive make it completely possible for any researchers to achieve this miracle. 

Personally, this new tool is pretty alarming. CRISPR is fascinating enough, but with new add-on feature, an entire population's genome can be change very rapidly, especially with a fast reproductive cycle that the mosquitoes have. This can lead to an earlier evolution than just solely depend on mutation slowly introduce to a population or any other effects on the population.

Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913862/

http://www.pnas.org/content/112/49/E6736.abstract

Possibility of Wiping Out Malaria and Other Diseases with the CRISPR

What if it was possible to wipe out a disease that has caused so many lives to perish? Futurism magazine reports 584,000 people have died and 200 million have suffered from malaria in 2013. Evolutionary ecologist James Collins from Arizona State University believes scientists have the technology to wipe out the gene in mosquitoes that carry the malaria parasite using the gene editing technique, CRISPR (clustered regularly interspaced short palindromic repeats). Specifically, the tool “gene drive”, it will increase the probability of a certain gene being inherited. Unlike in normal sexual reproduction where the offspring would inherit a random half of genes from each parent, this modified offspring would only receive genes the scientist chooses. Ensuring that the disease is completely eradicated in that population and for all generations to come.

Altering genes has uplifted controversies throughout the world. What gives scientists the right to alter another organism? There is always a possibility for error, such as an organism escaping the laboratory. What if this error occurs affects us all? Kevin Esvelt, a researcher at Wyss Institute rebuttals concerns explaining that any premature revealing to the outside world could be reversed with putting the same organism with altered genes out into the world. This would then cause the new genes to be inherited rather than the genes of the accidentally released organism.

I can understand why some would think using the CRISPR goes against nature, but if it is used to help millions of people I believe that the world should embrace it. There are obviously risks that must be taken, for example it should be placed in the right hands and used for good. We do not need someone getting ahold of this type of technology to spread diseases throughout animals or people.

http://www.sciencetimes.com/articles/9131/20170222/controversial-crispr-can-alter-and-wipe-out-malaria.htm

https://futurism.com/crispr-gives-us-the-power-to-end-diseases-and-remake-species/