Mosquito-EEE

These tiny pests adapt so successfully to changing conditions that they have become humankind’s deadliest predator. We might soon be able to eradicate them – but should we?

We are at war with the mosquito. A swarming and consuming army of 110tn enemy mosquitoes patrols every inch of the globe except for Antarctica, Iceland and a handful of French Polynesian micro-islands. The biting female warrior of this droning insect population is armed with at least 15 lethal and debilitating biological weapons, to be used against 7.7 billion humans deploying suspect and often self-detrimental defensive capabilities.

In fact, our defence budget for personal shields, sprays and other means of deterring her unrelenting raids is $11bn (£8.8bn) a year, and rising rapidly. And yet her deadly offensive campaigns and crimes against humanity continue with reckless abandon. While our counterattacks are reducing the number of casualties she perpetrates – malaria deaths in particular are declining rapidly – the mosquito remains the deadliest hunter of human beings on the planet.

Taking a broad range of estimates into account, since 2000, the average annual number of human deaths caused by the mosquito was around 2 million. Humans came in a distant second at 475,000, followed by snakes (50,000), dogs and sandflies (25,000 each), the tsetse fly, and the assassin or kissing bug (10,000 each). The fierce killers of lore and Hollywood celebrity were much further down our list. The crocodile was ranked 10th, with 1,000 annual deaths. Next on the list were hippos with 500, and elephants and lions with 100 fatalities each. The much-slandered shark and wolf shared 15th position, killing an average of 10 people per annum.

Yet the mosquito does not directly harm anyone. It is the toxic and highly evolved diseases she transmits that cause an endless barrage of desolation and death. Without her, however, these sinister pathogens could not be transferred or vectored to humans, nor could they continue their cyclical contagion. In fact, without her, these diseases would not exist at all.

Our immune systems are finely tuned to our local environments. Mosquitoes do not respect international borders. Marching armies, inquisitive explorers and land-hungry colonists brought new diseases to distant lands, but were also brought to their knees by micro-organisms in the foreign lands they intended to conquer. As the mosquito transformed the landscapes of civilisation, humans were unwittingly required to respond to her universal projection of power. After all, the truth is that, more than any other external participant, the mosquito, as our deadliest predator, drove the events of human history to create our present reality.

It has been one of the most universally recognisable and aggravating sounds on Earth for 190m years – the whine of a mosquito. After a long day of walking while camping with your family or friends, you quickly shower, settle into your lawn chair, open an ice-cold beer and exhale a deep, contented sigh. Before you can enjoy your first satisfying swig, however, you hear that all-too-familiar sound, signalling the approach of your soon-to-be tormentors.

It is nearing dusk, her favourite time to feed. Although you heard her droning arrival, she gently lands on your ankle without detection, as she usually bites close to the ground. It is always a female, by the way. She conducts a tender, probing, 10-second reconnaissance, looking for a prime blood vessel. With her backside in the air, she steadies her crosshairs and zeros in with six sophisticated needles. She inserts two serrated mandible cutting blades (much like an electric carving knife, with two blades shifting back and forth), and saws into your skin, while two other retractors open a passage for the proboscis, a hypodermic syringe that emerges from its protective sheath. With this straw she starts to suck out 3-5 mg of your blood, immediately excreting its water while condensing its 20% protein content.

All the while, a sixth needle is pumping in saliva that contains an anticoagulant, preventing your blood from clotting at the puncture site. This shortens her feeding time, lessening the likelihood that you feel her penetration and splat her across your ankle. The anticoagulant causes an allergic reaction, leaving an itchy bump as her parting gift. The mosquito bite is an intricate and innovative feeding ritual required for reproduction. She needs your blood to grow and mature her eggs.

Please don’t feel singled out. She bites everyone. There is absolutely no truth to the persistent myths that mosquitoes fancy females over males, that they prefer blonds and redheads over those with darker hair, or that the darker or more leathery your skin, the safer you are from her bite. It is true, however, that she does play favourites and feasts on some more than others. Blood type O seems to be the vintage of choice over types A and B, or their blend. People with blood type O get bitten twice as often as those with type A, with type B falling somewhere in between. (Disney/Pixar must have done their homework when portraying a tipsy mosquito ordering a “Bloody Mary, O-positive” in the 1998 movie A Bug’s Life.)

Those who have higher natural levels of certain chemicals in their skin, particularly lactic acid, also seem to be more attractive. From these elements, she can analyse which blood type you are. These are the same chemicals that determine an individual’s level of skin bacteria and unique body odour. While you may offend others and perhaps yourself, in this case, being pungently rancid is a good thing, for it increases bacterial levels on the skin, which makes you less alluring to mosquitoes – except for stinky feet, which emit a bacterium that is a mosquito aphrodisiac. The mosquito is also enticed by deodorants, perfumes, soap and other applied fragrances.

She also has an affinity for beer drinkers. Wearing bright colours is also not a wise choice, since she hunts by both sight and smell – the latter depending chiefly on the amount of carbon dioxide exhaled by the potential target. So all your thrashing and huffing and puffing only magnetises mosquitoes and puts you at greater risk. She can smell carbon dioxide from 200 feet away. When you exercise, you emit more carbon dioxide through frequency of breath and output. You also sweat, releasing those appetising chemicals, primarily lactic acid, that invite the mosquito’s attention. Lastly, your body temperature rises – an easily identifiable heat signature. On average, pregnant women suffer twice as many bites, as they respire 20% more carbon dioxide, and have a marginally elevated body temperature. This is bad news for the mother and the foetus when it comes to infection from Zika and malaria.

Unlike their female counterparts, male mosquitoes do not bite. Their world revolves around two things: nectar and sex. Like other flying insects, when they are ready to mate, male mosquitoes assemble over a prominent feature in the landscape – from chimneys to antennas to trees to people. Many of us grumble and flail in frustration as that dogged cloud of bugs droning over our heads shadows us when we walk, refusing to disperse. Take it as a compliment. Male mosquitoes have graced you with the honour of being a “swarm marker”.

Mosquito swarms have been photographed extending 1,000 feet into the air, resembling a tornado funnel cloud. With the cocksure males stubbornly assembled over your head, females will fly into their horde to find a suitable mate. While males will mate frequently in a lifetime, one dose of sperm is all the female needs to produce numerous batches of offspring. She stores the sperm and dispenses them piecemeal for each separate birthing of eggs. Her short moment of passion has provided one of the two necessary components for procreation. The only ingredient missing is your blood.

Back at the campsite, you have just finished your strenuous hike, and proceed to the shower, where you lather up with soap and shampoo. After drying off, you apply body spray and deodorant before finally putting on your bright red-and-blue beachwear.

It is nearing dusk – dinnertime for the Anopheles mosquito. You have done everything in your power to lure a famished female of the species. Having just mated in a swarming frenzy of eager male suitors, she willingly takes the bait and makes off with a few drops of your blood – a blood meal three times her own body weight. She quickly finds the nearest vertical surface and, with the aid of gravity, continues to evacuate the water from your blood. Using this concentrated blood, she will develop her eggs over the next few days. She then deposits roughly 200 floating eggs on the surface of a small pool of water that has collected on a crushed beer can that was overlooked during cleanup as you and your party headed home. She always lays her eggs in water, although she does not need much. From a pond or stream to a minuscule puddle in the bottom of an old container, used tire or backyard toy, any will suffice.

Our mosquito will continue to bite and lay eggs during her one-to-three-week lifespan. While she can fly up to two miles, she rarely ranges more than 400 metres from her birthplace. Although it takes a few days longer in cool weather, given the high temperatures, her eggs hatch into wiggling, water-bound worms within two or three days. Skimming the water for food, they quickly turn into upside-down, comma-shaped tumbling caterpillars who breathe through two “trumpets” protruding from their water-exposed buttocks. A few days later, a protective encasement splits and healthy adult mosquitoes take flight, with a new generation of succubus females ready to feed. This maturation to adulthood takes roughly one week.

Bacteria, viruses and parasites, along with worms and fungi, have triggered untold misery, and have commanded the course of human history. Why have these pathogens evolved to exterminate their hosts? If we can set aside our bias for a moment, we can see that these microbes have journeyed through the natural selection voyage just as we have. This is why they still make us sick and are so difficult to eradicate. You may be puzzled: it seems self-defeating and detrimental to kill your host. The disease kills us, yes, but the symptoms of the disease are ways in which the microbe conscripts us to help it spread and reproduce. It is dazzlingly clever, when you stop to think about it. Generally, germs guarantee their contagion and replication prior to killing their hosts. Some, like the salmonella “food poisoning” bacteria and various worms, wait to be ingested – that is, one animal eating another animal.

There is a wide range of waterborne transmitters, including giardia, cholera, typhoid, dysentery and hepatitis. Others, including the common cold, the 24-hour flu and true influenza, are passed on through coughing and sneezing. Some, such as smallpox, are transferred directly or indirectly by lesions, open sores, contaminated objects or coughing. My personal favourites – strictly from an evolutionary standpoint, of course – are those that covertly ensure their reproduction while we intimately ensure our own. These include the full gamut of microbes that trigger sexually transmitted diseases. Many sinister pathogens are passed from mother to foetus in utero.

Others that germinate typhus, bubonic plague, Chagas and trypanosomiasis (African sleeping sickness) catch a free ride provided by a vector (an organism that transmits disease) such as fleas, mites, flies, ticks and mosquitoes. To maximise their chances of survival, many germs use a combination of more than one method. The diverse collection of symptoms, or modes of transference, assembled by micro-organisms helps them effectively procreate and ensures the existence of their species. These germs fight for their survival just as much as we do, and stay an evolutionary step ahead of us as they continue to morph and shape-shift to circumvent our best means of extermination.

To understand the stealthy, sprawling influence of the mosquito on history and humanity, it is first necessary to appreciate the animal itself, and the diseases it transmits. According to a quotation erroneously attributed to Charles Darwin: “It is not the strongest of the species that survives, nor the most intelligent that survives. It is the one that is most adaptable to change.” Regardless of the origin of this passage, the mosquito and its diseases – most notably malaria parasites – are the quintessential example of the point it is making. They are masters of evolutionary adaptation. Mosquitoes can evolve and adapt to their changing environments within a few generations.

During the Blitz of 1940-41, for example, as German bombs rained down on London, isolated populations of Culex mosquitoes were confined to the air-raid tunnel shelters of the London Underground, along with the city’s resilient citizens. These trapped mosquitoes quickly adapted to feed on mice, rats and humans instead of birds, and are now a species distinct from their above-ground parental ancestors.

What should have taken thousands of years of evolution was accomplished in less than 100. “In another 100 years,” jokes Richard Jones, former president of the British Entomological and Natural History Society, “there may be separate Circle line, Metropolitan line and Jubilee line mosquito species in the tunnels below London.”

While the mosquito is miraculously adaptable, it is also a purely narcissistic creature. Unlike other insects, it does not pollinate plants in any meaningful way, or aerate the soil, or ingest waste. Contrary to popular belief, the mosquito does not even serve as an indispensable food source for any other animal. She has no purpose other than to propagate her species, and perhaps to kill humans. As the apex predator throughout our odyssey, it appears that her role in our relationship is to act as a countermeasure against uncontrolled human population growth.

Throughout our existence, the mosquito’s toxic twins of malaria and yellow fever have been the prevailing agents of death and historical change, playing the role of antagonists in the protracted chronological war between man and mosquito.

Following that fateful mosquito bite, the miscreant malaria parasite will mutate and reproduce inside your liver for one to two weeks, during which time you will show no symptoms. A toxic army of this new mutated form will then explode out of your liver and invade your bloodstream. The parasites attach to your red blood cells, penetrate the outer defences, and feast on the haemoglobin within. Inside the cell, they undergo another metamorphosis and reproductive cycle. Engorged blood cells eventually burst, spewing both a duplicate form, which marches forward to attack fresh red blood cells and also a new “asexual” form that relaxedly floats in your bloodstream, waiting for mosquito transportation.

The parasite is a shape-shifter, and it is precisely this genetic flexibility that makes it so difficult to eradicate or suppress with drugs or vaccines. You are now gravely ill with an orderly, clockwork progression of chills followed by a mercury-driving fever that may touch 41C. This full-blown cyclical malarial episode has you in its firm grip, and you are at the mercy of the parasite. Lying prostrate and agonisingly helpless on sweat-soaked sheets, you twitch and fumble, curse and moan. You look down and notice that your spleen and liver are visibly enlarged, your skin has the yellowing patina of jaundice and you vomit sporadically. Your fever will relapse at precise intervals with each new burst and invasion of the parasite from your blood cells. The fever then subsides while the parasite eats and reproduces inside new blood cells.

The parasite uses sophisticated signalling to synchronise its sequencing, and this entire cycle adheres to a very strict schedule. The new asexual form transmits a chemical “bite me” signal in our blood, significantly boosting the chances of being picked up by a mosquito from an infected human to complete the reproductive cycle. Inside the stomach of the mosquito, these cells mutate once more, into both male and female varieties. They quickly mate, producing threadlike offspring that make their way out of the gut and into the salivary glands of the mosquito. Within the saliva glands, the malaria parasite shrewdly manipulates the mosquito to bite more frequently by suppressing the production of her anticoagulant and thus minimising her blood intake during a single feeding. This forces her to bite more frequently to get her required fill. In doing so, the malaria parasite ensures that it maximises its rate and range of transfer, its procreation and its survival.

Temperature is an important element for both mosquito reproduction and the life cycle of malaria. Given their symbiotic relationship, they are also both climate-sensitive. In colder temperatures, it takes longer for mosquito eggs to mature and hatch. Mosquitoes are also cold-blooded and, unlike mammals, cannot regulate their own body temperatures. They simply cannot survive in environments below 10C. Mosquitoes are generally at their prime health and peak performance in temperatures above 23C.

A direct heat of 40C degrees will boil mosquitoes to death. For temperate, non-tropical zones, this means that mosquitoes are seasonal creatures with breeding, hatching and biting taking place from spring through autumn. Although never seeing the outside world, malaria needs to contend with both the short lifespan of the mosquito and temperature conditions to ensure replication. The timeframe of malaria reproduction is dependent on the temperature of the cold-blooded mosquito, which itself is dependent on the temperature outside. The colder the mosquito, the more sluggish malaria reproduction becomes, eventually hitting a threshold. Between 15C and 21C (depending on the type of malaria), the reproductive cycle of the parasite can take up to a month, exceeding the average life span of the mosquito. By then, she is long dead, and brings malaria down with her.

Warmer climates can sustain year-round mosquito populations, promoting endemic circulation of her diseases. Abnormally high temperatures can cause seasonal epidemics of mosquito-borne diseases in regions where they are generally absent or fleeting. Global warming also allows the mosquito and her diseases to broaden their topographical range. As temperatures rise, disease-carrying species, usually confined to southern regions and lower altitudes, creep north and into higher elevations.

Since a breakthrough discovery by a team led by the biochemist Dr Jennifer Doudna at the University of California, Berkeley in 2012, the revolutionary gene-editing innovation known as Crispr has shocked the world and altered our preconceived notions about our planet and our place on it.

The pages of many widely read magazines and journals are currently consumed by the topic of Crispr and mosquitoes. First successfully used in 2013, Crispr is a procedure that snips out a section of DNA sequencing from a gene and replaces it with another desired one, permanently altering a genome, quickly, cheaply, and accurately.

The Bill and Melinda Gates Foundation has been funding research into mosquito-borne diseases since its creation in 2000. In 2016 it made investments in Crispr mosquito research totalling $75m. “Our investments in mosquito control,” said the foundation, “include nontraditional biological and genetic approaches as well as new chemical interventions aimed at depleting or incapacitating disease-transmitting mosquito populations.” These genetic approaches include the use of Crispr machinery to eradicate mosquito-borne diseases, most notably malaria.

The strategic goal of the Gates Foundation is the extermination of malaria and other mosquito-borne diseases; it is not to bring the mosquito – which is harmless when flying solo, untethered from a hitchhiking micro-organism – to the brink of extinction. Of the more than 3,500 mosquito species, only a few hundred are capable of vectoring disease. Prefabricated, genetically modified mosquitoes rendered incapable of harbouring the parasite (a hereditary trait passed down their bloodline) might just end the timeless scourge of malaria. But, as Doudna and the Gates Foundation are aware, gene-swapping technology also has the potential to unleash darker, more sinister genetic blueprints with dangerous possibilities. Crispr research is a global phenomenon, and neither Doudna nor the foundation has a monopoly on its limitless designs, its instruments of implementation or its operational execution.

It has been dubbed the “extinction drive”, as this is precisely what it can accomplish – the extermination of mosquitoes by way of genetic sterilisation. This theory has been floating around the scientific community since the 1960s. Crispr can now put these principles into practice. To be fair, the mosquito altered our DNA in the form of sickle cell and other genetic malarial safeguards; perhaps it is time to return the favour. Male mosquitoes that have been genetically modified with domineering “selfish genes” using Crispr are released into mosquito zones to breed with females to produce stillborn, infertile or only male offspring. The mosquito would be extinct in one or two generations. With this war-winning weapon, humanity would never again have to fear the bite of a mosquito. We would awaken to a brave new world, one without mosquito-borne disease.

An alternative is simply to make mosquitos harmless, a strategy supported and funded by the Gates Foundation. With “gene drive” technology, Gates explained in October 2018, “essentially, scientists could introduce a gene into a mosquito population that would either suppress the population – or prevent it from spreading malaria. For decades, it was difficult to test this idea. But with the discovery of Crispr, the research became a lot easier. And just last month, a team from the research consortium Target Malaria announced that they had completed studies where mosquito populations were fully suppressed. To be clear: the test was only in a series of laboratory cages filled with 600 mosquitoes each. But it is a promising start.”

Dr Anthony James, a molecular geneticist at the University of California, Irvine, Crispr’d a species of Anopheles mosquito to make it incapable of spreading malaria, by eliminating the parasites as they are processed through the mosquito’s salivary gland. “We added a small package of genes,” explains James, “that allows the mosquitoes to function as they always have, except for one slight change” – they can no longer harbour the malaria parasite.

The Aedes breed is more difficult to tackle, since it transmits a handful of diseases that include yellow fever, Zika, West Nile, chikungunya, Mayaro, dengue and other encephalitides. “What you need to do is engineer a gene drive that makes the insects sterile,” James said of the Aedes breed. “It doesn’t make sense to build a mosquito resistant to Zika if it could still transmit dengue and other diseases.”

We have valid, although yet unknown, reasons to be careful what we wish for. If we eradicate disease-vectoring mosquito species, would other mosquito species or insects simply fill the ecological niche? What effect would eliminating mosquitoes have on nature’s biological equilibrium? What would happen if we exterminate species that play an essential but unrecognised role in our ecosystem? We are just beginning to ask these morally fraught and biologically ambiguous questions, and for now, no one really knows the answers.

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