Are we the generation to eliminate one of the biggest killers in human history?

Health, Pharmaceuticals, Science 2017-04-24

April 25th marks World Malaria Day, a day dedicated to promoting the global efforts to understand and control Malaria – one of the biggest killers in human history. A disease so deadly, some researchers believe it may be responsible for the deaths of almost half of all people who have ever lived.

Caused by different forms of the Plasmodium parasite, there are four types of this life-threatening disease of varying severities. In its most serious form it can affect the kidneys and brain, causing anaemia, coma and death. Malaria is present in over 90 countries and roughly half of the population is currently at risk of catching the disease, with the greatest burden being in the least developed areas where there is very limited access to life-saving preventions, diagnoses and treatments.

Malaria Infographic

How is malaria spread?

It is quite fitting that this lethal disease is transmitted to people through the deadliest animal on the planet – the mosquito. The Mosquito itself does not benefit from transmitting the malaria parasite, it is merely the disease vector – but, having survived for hundreds of millennia, with a population in the trillions and the ability to lay hundreds of eggs at a time, it’s an organism that certainly makes a very effective carrier.

A mosquito bite is simply the beginning of the process for the plasmodium sporozoites (an immature form of the parasite), which have accumulated in the mosquitos’ salivary glands, ready to be released into your body once your skin has been penetrated. This is where the human infection begins, and the sporozoites parasitize the liver, where they appear dormant as they mature and multiply to merozoites. The cells they inhabit eventually erupt and the merozoites are released into the bloodstream, cunningly disguising themselves with the liver cell membranes to avoid an immune attack. This is where they begin their second assault, causing red blood cells to erupt and release toxins that stimulate an immune response – it is this that leads you to experience flu-like symptoms such as fever. In severe cases, if the blood-brain barrier is breached, this can lead to a coma, neurological damage or even death.

The current situation

There have been large-scale efforts to eradicate malaria in the last 75 years. For example, during the WHO’s anti-malarial campaign in the 1950s and 60s DDT was used which, at the time, was hailed as kryptonite to mosquitoes. Bill Gates has famously stated that the world’s fight against malaria is one of the greatest success stories in the history of human health, and yes, over the last couple of decades there certainly has been a significant decline in the global burden of malaria. In fact, since 2000, almost 60 countries have seen a drop of at least 75% in new malaria cases, contributing to a 37% drop globally. However, the 2016 WHO report shows that in 2015 alone more than 400,000 people died of malaria and 214 million were infected. So, the job is far from finished.

Target Malaria – a new approach

There have been remarkable advances in gene-editing technologies in recent years, so one of the main focuses in malaria research lies in exploring different strategies to reduce or modify the populations of Anopheles mosquitoes; specifically, the three species in this genus that are responsible for most of the malaria transmission in Africa. Target Malaria is a not-for-profit research consortium that aims to develop and share technology for malaria control. Their focus is reducing the number of the deadliest malaria-transmitting mosquitoes in Africa – Anopheles gambiae. Specifically, they are interested in targeting female mosquitoes, as these are the only ones that bite, and this is an effective approach to control population size. Target Malaria are investigating the potential of using nuclease enzymes, that cut specific sequences of DNA, to modify mosquito genes. By changing certain genes, malarial resistance, female infertility and almost exclusively male offspring can be induced. The researchers are inserting genes that code for these enzymes into mosquito eggs, with the hope of affecting their reproduction. An example of this research involves nucleases that cut the X chromosome while males are making their sperm, resulting in mainly male offspring. Alongside this, researchers are also investigating how to disrupt the fertility of female mosquitoes to reduce the number of offspring, as well as engineering mosquitoes that are unable to transmit malaria.

These scientists are utilising a method called ‘gene drive’, a powerful emerging technology that is able to override genetic rules to ensure all offspring acquire a trait, as opposed to just, half as would normally be the case, allowing the trait to be spread extremely quickly.

Burkina Faso

Nowhere are the devastating effects of malaria as obvious as in sub-Saharan Africa, where hundreds of thousands fall victim each year, making up 90% of the total mortality count for the disease. Target Malaria researchers are currently working in Mali, Uganda and Burkina Faso with Bana, a small village in Burkina Faso, having the potential to be the site of a revolutionary genetic experiment. At Imperial College London, gene drive mosquitoes are being designed to have reduced female offspring or the inability to reproduce in general, and are then planned to be released into the wild in Bana. Their hope is that this would nearly eradicate Anopheles gambiae, to a point sufficient to prevent malaria transmission.

So what are we waiting for?

For one thing, the communities need to be prepared for the release. Firstly, there needs to be education, not just regarding genetic engineering and the impact the release will have, but also basic genetics – which may be a challenge in a community where there is no equivalent term, even for the word gene. Additionally, there are still years before scientists will be able to fully develop test gene drive mosquitoes in this manner.

If an experiment of this type is successful in the future, not only could this essentially eradicate malaria, but it could also pave the way for eliminating other mosquito-borne diseases such as dengue fever or even other insect-transmitted diseases like Lyme disease. However, humans have never before changed the genetic code of a free-living organism on this scale and released it into the wild. This genetic-engineering technology is very powerful and definitely needs to be treated as such. But, with millions dying and suffering at the hands of malaria each year, should we look to do this sooner rather than later?

What do you think? Could we be the generation that ends one of the oldest and deadliest diseases in human history? Tweet me your thoughts @PranikaAtNotch.