The Mosquito Read online

  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 mercury-dipping environments below 50 degrees. Mosquitoes are generally at their prime health and peak performance in temperatures above 75 degrees. A direct heat of 105 degrees will boil mosquitoes to death. For temperate, nontropical zones, this means that mosquitoes are seasonal creatures with breeding, hatching, and biting taking place from spring through fall. Although never seeing the outside world, malaria needs to contend with both the short life span of the mosquito and temperature conditions to ensure replication. The time frame of malaria reproduction is dependent upon the temperature of the cold-blooded mosquito, which itself is dependent upon the temperature outside. The colder the mosquito, the more sluggish malaria reproduction becomes, eventually hitting a threshold. Between 60 and 70 degrees (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.

  In your case, you might have avoided this whole bloody malarial ordeal if you had decided on either a frigid or a blisteringly hot vacation destination, or elected not to brave the wilds during the mosquito’s peak campaigning season (in most temperate zones) of late spring to early fall. Alternatively, you could have opted out of your camping vacation altogether.

  In short, warmer climates can sustain year-round mosquito populations promoting endemic (chronic and ever-present) circulation of her diseases. Abnormally high temperatures from the effects of La Niña or El Niño can cause seasonal epidemics (a sudden outbreak of a disease that burns through populations before fading away) of mosquito-borne diseases in regions where they are generally absent or fleeting. Intervals of natural or artificially induced global warming also allow 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.

  The dinosaurs could not survive the meteoric crashing climate change, and they could not evolve quickly enough to outrun the onslaught of mosquito-borne disease. The tiny mosquito helped pave the way for their destruction, escorting in the evolutionary age of mammals, our hominid ancestors, and, eventually, modern Homo sapiens. As a survivor, she also set the table for her historic flight to global ascendancy. Unlike the dinosaurs, however, humans evolved to fight back. Through hasty natural selection, suits of hereditary immunological armor against the mosquito have been passed down through our Homo sapien family tree. Our DNA displays these genetically encoded keepsakes as reminders of the deadly and protracted war for survival our early ancestors fought against a merciless mosquito enemy.

  CHAPTER 2

  Survival of the Fittest: Fever Demons, Footballs, and Sickle Cell Safeties

  Ryan Clark Jr. was the epitome of health and in the prime of his life. As a starting safety in the National Football League (NFL), the thirty-one-year-old Clark was a famous, finely tuned professional athlete, lean and muscular at five feet eleven and 205 pounds. He was married to his high school sweetheart and had three beautiful young children. He had recently signed a lucrative new contract with the Pittsburgh Steelers to open the 2007 season. Life was good.

  Midway through the season, he and the Steelers headed to Denver to play the Broncos and lost in a heartbreaker—brought down by a last-minute field goal. A disheartened Clark boarded the plane for the long flight home. Just before takeoff, he experienced an acute stabbing pain under his left ribs. He was accustomed to the routine wear and tear and bumps and bruises on his body following a tough, physical football game. This, however, was something different, a piercing and wrenching pang he had never experienced before. “I called my wife and told her I didn’t think I was going to make it,” he remembered. “I’d never been in that much pain.” His concerned teammates and the Steelers medical staff acted quickly. The flight was immediately halted on the tarmac and Clark was rushed to a Denver hospital. A few days later, after being stabilized, Clark flew back home to Pittsburgh and was placed on injured reserve, although his doctors had not yet identified the cause of his puzzling symptoms.

  Over the next month, he had nightly teeth-chattering chills melting into fevers reaching 104 degrees. Clark lost forty pounds, transforming into a sickly skeleton of his former strapping self. One night, his pain was so severe, he was certain he was going to die. Clark recalls uttering a silent prayer, “God, if it’s my time, let my wife find a good husband. Let him not be as good-looking as me, but let him be a good guy. Take care of my family. Please forgive me for my sins. I’m ready.” He survived that terrifying night and eventually after another month of inconclusive medical examinations, his doctors finally intercepted the cause of his distress and agony. Clark was diagnosed with splenetic infarction—that is, the tissue death of his spleen. He was rushed into surgery and his rotting spleen and gall bladder were removed. The underlying cause of organ failure in such a healthy, young adult still needed to be isolated and identified.

  As athletes have known for decades, playing in Denver can be strenuous and exacting. The city sits 5,280 feet above sea level, and unlike their home-field opponents, visiting players are not acclimatized to the thin air. They struggle to catch a full breath and to provide enough oxygen to their working muscles, compounded by the physical exertion of professional competition. While a slight shortness of breath is anticipated, no one expects to die from a road trip to Denver’s Mile High Stadium.

  Unbelievably, Clark returned to football and a year later won the 2009 Super Bowl with the Steelers. His celebration was unfortunately cut short. Two weeks later, his twenty-seven-year-old sister-in-law died of a congenital blood disease. After thirteen years of NFL football, Clark retired in 2014 on his own terms. To understand what happened to Ryan Clark in Denver we need to travel back thousands of years into prehistory.

  Hooded and cloaked in his DNA at the time of his health crisis, Clark’s hereditary sickle cell trait, commonly called sickle cell anemia, triggered his near-death experience. As a genetic mutation of the red blood cells, sickle cell impedes the transport and delivery of oxygen to muscles and organs. In Denver’s oxygen-reduced atmosphere, and with its amplified demand by an elite athlete, Clark’s body tissues were starved of oxygen. His spleen and gall bladder simply shut down, and necrosis set in.

  Advanced by natural selection, sickle cell is a hereditary genetic mutation passed on precisely because it was originally a net benefit to the people who carried it. Yes, you read that correctly. The evolutionary design that nearly killed Ryan Clark was initially a lifesaving human genetic adaptation. Clark’s sickle cell, which first appeared in Africa 7,300 years ago in a female known to anthropologists as “Sickle Cell Eve,” is the most recent and well-known genetic response to falciparum malaria.

  This first appearance of sickle cell was a direct result of expansive agriculture encroaching on formerly undisturbed mosquito habitats. Roughly 8,000 years ago, pioneering Bantu farmers began concentrated yam and plantain cultivation. This pastoral intensification in West Central Africa along the Niger River delta, slashing south to the Congo River, awoke the mosquito from her isolated slumber. The consequences could hardly have been more catastrophic: Vampiric falciparum malaria was unleashed on its new human host. Within only 700 years, our immediate evolutionary counteroffensive, which bewildered the parasite, was to promote a random mutation of the hemoglobin—the cell became sickle (or crescent) shaped. Normally, healthy red blood cells are cast from a donut or oval template. The malaria parasite cannot latch on to the strange-shaped sickle cell.

  Children inheriting sickle cell from one parent and the norma
l gene from the other, known as sickle cell trait, of which Ryan Clark is a carrier, are blessed with 90% immunity from falciparum malaria. The downside (prior to modern medicine) was that the average life span of those carrying sickle cell trait was a brief twenty-three years. This would have been a great trade-off, however, in what anthropologists call our “ancestral environment,” where life spans were relatively short—twenty-three years is certainly long enough to pass on the trait to 50% of any offspring. In the modern era, however, this genetic interceptor and safety against falciparum malaria turns out to be a severe health impediment for modern NFL players, or anyone else who is a carrier and would like to live to the ripe old age of, say, twenty-four. The other downside within this Punnett square hereditary matrix is that 25% of offspring would receive no sickle cell and therefore no immunity, with the other 25% receiving two sickle cell genes. Those born with sickle cell from both parents, or sickle cell disease (which killed Ryan Clark’s sister-in-law two weeks after he hoisted the NFL championship Lombardi Trophy), inherit a death sentence, with the vast majority dying in infancy.

  While it now seems inconceivable, in areas of Africa that were devastated by unremitting falciparum malaria, the death toll from sickle cell resulted from an advantage, or alternatively was an acceptable cost, for survival, compared to what must have been apocalyptic rates of malarial mortality. Despite the influx of sickle cell, the preadult death rate prior to 1500 was upwards of 55% in sub-Saharan Africa.

  Given that sickle cell both gives and takes away life, it was a hasty and imperfect evolutionary response to mosquito-borne malaria. What it reveals, though, is the sheer scale of the threat falciparum malaria posed to early humans and by extension our very existence: It was arguably the paramount evolutionary survival pressure on our species. It is almost as if the biological architect of our selective genetic sequencing implicitly understood, “There is no time for research and clinical trials. Hurry up and make a quick fix to ensure the survival of our species. We will worry about the rest later.” Desperate times called for desperate measures.

  The genetic distribution of sickle cell shadowed the spread of humans, mosquitoes, and malaria in and out of Africa. Today, there are about 50–60 million carriers of sickle cell worldwide, with 80% still living in its birthplace, sub-Saharan Africa. Regionally, there are pockets in Africa, the Middle East, and South Asia where upwards of 40% of the population harbor the sickle cell gene. The modern global diffusion of sickle cell is a hereditary reminder of our deadly and protracted war with the mosquito.

  One in twelve, or 4.2 million, African Americans currently possess the sickle cell trait, creating a safety issue for the National Football League, in which 70% of its players are potential carriers. With Clark’s terrifying and perilous experience, the league finally was provided the scare and the impetus to study sickle cell. It was quickly discovered that other players were also genetic receivers of this ancient guard against falciparum malaria. Each year a handful of competitors, like Ryan Clark, are unable to participate at the high-altitude stadium of the Denver Broncos because they possess the sickle cell trait. “The good thing is people are living longer and being a lot more productive,” Clark told reporters in 2015. “People are starting to understand sickle cell a little bit more. People have gained the knowledge to know how to take care of themselves.”

  He created the charity organization Ryan Clark’s Cure League in 2012 to raise awareness and research about sickle cell. The former All-Pro, Super Bowl champion now makes the rounds giving frequent lectures and making guest appearances to discuss the disease and educate his audiences about its deep-rooted, mosquito-reared human history. While Clark’s northern home of Pittsburgh is hardly a malarial mecca, one of his three children inherited the sickle cell trait, a living legacy of their African ancestors’ fierce fight for survival against the mosquito and of the long trajectory of her genetic impact across time. The mosquito and her pathogens, which are at least 165 million years old, have hitchhiked on board our wild evolutionary ride.

  In this primal lopsided battle, however, the mosquito and her malarial parasite have had the overwhelming advantage. She had millions of years’ head start on the journey of evolution and natural selection. The malaria parasite, for instance, began its life as a form of aquatic algae 600 to 800 million years ago, and still contains vestiges of photosynthesis machinery. As we evolved, these viruses and parasites, eager for new outlets, met our challenge and adapted to ensure their survival. Thankfully, for us, Lucy and her successive hominid offspring managed to outlast the onslaught of mosquito-borne diseases.* To safeguard our own species, we fought back through natural selection, giving rise to a series of genetically encoded antimalarial armors, including sickle cell. These immunological defenses are all human evolutionary survival responses to inescapable and menacing malaria exposure.

  In this never-ending cyclical war for survival linking man and mosquito we retaliated by way of genetic malaria-shielding mutations of our red blood cells. Approximately 10% of humans have inherited some degree of genetic protection against the two most common and deadly types of the five human malaria plasmodia: vivax and falciparum. There is a catch, however. These malarial screens, as revealed by Ryan Clark’s sickle cell, also carry serious, sometimes fatal, health-related penalties.

  First appearing in the African population roughly 97,000 years ago, red blood cell Duffy antigen negativity, or simply Duffy negativity, was the inaugural human genetic response to the scourge of vivax malaria. The vivax parasite uses the antigen receptor on the hemoglobin molecule as a gateway to invade our red blood cells (like a shuttle docking at a space station or a sperm entering an egg). The absence of this antigen, that is, Duffy negativity, closes the portal, denying the parasite entrance to the red blood cell. Currently, an astonishing 97% of West and Central Africans carry the mutation for Duffy negativity, making them impervious to vivax and knowlesi infection. Some communities, such as the Pygmy, are effectively 100% Duffy negative. While Duffy negativity was the first of the four genetic human malaria responses to arise, it was the last to be scientifically unmasked. Despite this shorter research life, a few negative health correlations have been detected. Current studies have revealed a higher predisposition to asthma, pneumonia, and various cancers in those with Duffy negativity. Even more alarming is that Duffy negativity also increases the susceptibility to HIV infection by 40%.

  As both man and malaria ventured out of Africa, isolated and pocketed populations developed their own genetic answers to the malaria question. Thalassemia, which is an abnormal production or mutation of the hemoglobin, reduces the risk of vivax malaria by 50%. Today, thalassemia occurs in roughly 3% of the global population and is particularly prevalent among peoples from southern Europe, the Middle East, and North Africa. Historically, malaria had a firm grip on this Mediterranean expanse, which led to another fascinating genetic mutation to combat the far more lethal falciparum strain.

  Identified in the early 1950s, and usually called G6PDD (an abbreviation for the tongue-twisting mouthful of Glucose-6-phosphate dehydrogenase deficiency), this modification robs red blood cells of an enzyme that protects the cell against oxygen-raiding substances known as oxidants. Antioxidants in trendy “superfoods” that include blueberries, broccoli, kale, spinach, and pomegranate, combat oxidants by promoting the healthy oxygen maintenance and transport capacity of our red blood cells. Similar to thalassemia, G6PDD offers partial immunity to malaria but not near-complete immunity as do Duffy negativity and sickle cell. Carriers do not show any negative symptoms unless their red blood cells are exposed to a trigger, prompting what has been called “Baghdad Fever” for centuries, which has a range of symptoms, from lethargy, fever, and nausea, to death on rare occasions.

  Unfortunately, the triggers include antimalarial drugs such as quinine, chloroquine, and primaquine. M*A*S*H aficionados may well remember the episode where Corporal Klinger develops a serious illness after being presc
ribed primaquine. Given Klinger’s Lebanese ancestry, this is cinematically accurate, for G6PDD primarily affects those of Mediterranean and North African origin. The most common trigger is fava beans, which is why the condition is commonly known as favism. As a precaution, it became customary across the Mediterranean world to cook fava beans with rosemary, cinnamon, nutmeg, garlic, onion, basil, or cloves, all of which dull the effects of favism and soften its symptomatic blow. In fact, the famed Greek philosopher and mathematician Pythagoras was warning his people of the dangers of eating fava beans in the sixth century BCE.

  The final resistance to malaria in our defensive arsenal, enlisted alongside Duffy negativity, thalassemia, G6PDD, and sickle cell, is repeated infection, commonly labeled “seasoning.” Those who suffer chronic malarial infections build up a marginal tolerance to the parasite, producing milder symptoms with each infection, while nullifying the risk of death. I hardly suggest that this is a positive or pleasant inoculation strategy, but in areas with rampant malaria rates, it might be argued that the more you suffer, the less you suffer. “Seasoning” will be an important ingredient in our story. Local seasoning to mosquito-borne disease was a critical factor during the wars of colonization and liberation in the Americas in the shadows of the Columbian Exchange. The origins of both malaria and our various evolutionary shields against it occurred in Africa. The longer association of Africans with mosquito-borne diseases and their corresponding full or partial acquired immunities bent by natural selection would have severe repercussions during the dark days of slavery.