For hundreds of millions of years, parasites have been shaping the evolution of our ancestors, and in the past ten thousand years they have not stopped. Malaria alone has done strange, profound things to our bodies. The hemoglobin that Plasmodium devours is made up of two pairs of chains, called alpha and beta, and each kind of chain is built according to instructions in our genes. We carry two genes for alpha chains—one inherited from our fathers, one from our mothers—and the same goes for the beta chains. If a mutation appears in any of those hemoglobin genes, it can damage a person’s blood. One sort of mutation in the beta chain causes a hereditary disease called sickle cell anemia. In this condition, hemoglobin can’t hold its shape if it’s not clamped around oxygen. Without it, the defective hemoglobin collapses into needle-shaped clumps, which then turn the cell itself into a sickle shape. The sickle cells snag in small capillaries, and the blood can no longer supply as much oxygen to the body. People who inherit only one copy of this defective beta chain gene can get by on the hemoglobin made by the remaining normal copy. But people who receive two copies of the bad gene make nothing but defective hemoglobin, and they’re usually dead by the time they’re thirty.
A person who dies of sickle cell anemia is less likely to pass on the defective gene, and that means that the disease should be exceedingly rare. But it’s not—one in four hundred American blacks has sickle cell anemia, and one in ten carries a single copy of the defective gene. The only reason the gene stays in such high circulation is that it also happens to be a defense against malaria. The needle-shaped clumps of hemoglobin don’t only threaten a blood cell; they can also impale the parasite inside. And as a sickle cell collapses, it lose its ability to pump in potassium, an element Plasmodium depends on. You need only one copy of the gene in order to enjoy this protection. The lives saved from malaria by single copies of the gene balance off the ones lost when people get two copies of the gene and die. As a result, people whose ancestors lived in many places where malaria has been intense—throughout much of Asia, Africa, and the Mediterranean—carry the gene at high levels.
Sickle cell anemia is actually just one of several blood disorders created in the fight between humans and malaria. In Southeast Asia, for example, you can find people whose blood cells have walls that are so rigid they can’t slip through capillaries. Called ovalocytosis, this disorder follows the same genetic rules as sickle cell anemia: it’s mild if a person only inherits the defective gene from one parent, but severe if both parents pass it on—so severe, in fact, that a baby with two genes will almost always die before it’s born. But ovalocytosis also makes red blood cells less hospitable to Plasmodium. Their membranes become so stiff that the parasite has a hard time pushing its way inside, and their rigidity seems to harm its ability to pump in chemicals such as phosphates and sulphates that the parasite needs to survive.
Humans have probably been fighting malaria with these sorts of changes to the blood for thousands of years, but the evidence is hard to come by. One of the few clear signs from antiquity is a condition called thalassemia, another defect of hemoglobin. People with thalassemia make the ingredients of their hemoglobin in the wrong amounts. Their genes produce too many or too few of the chains, and once the full hemoglobin molecules have been assembled from them, extra chains are left over. These end up binding together into clumps, which can wreak havoc inside a blood cell. They can grab an oxygen molecule the way normal hemoglobin can, but they can’t completely enclose it. Oxygen is a dangerously charismatic element; it can carry a powerful charge that attracts other molecules in the cell. They pull the oxygen out of the defective hemoglobin clumps and carry it away. As the oxygen roams the cell, it can react with still other molecules, wrecking them in the process.
People with severe forms of thalassemia usually die before birth, but in milder forms they can survive, although often suffering from anemia. The body of a person with thalassemia may try to compensate for its defective blood cells by making more blood in the bone marrow. The marrow swells up as a result and can spread into the surrounding bone, interfering with its growth. People with thalassemia can end up with distinctively deformed skeletons—curved, stunted arm and leg bones. And archaeologists in Israel have found bones with these deformities dating back eight thousand years.
Thalassemia has lingered for so long—and has become the most common blood disorder on Earth in that time—because it helps fight malaria. If you look at a map of a malaria-prone country like New Guinea, the rates of thalassemia match up closely with the prevalence of the parasite. While a severe form of thalassemia may kill, a milder case saves. Researchers suspect that the defective hemoglobin in a red blood cell makes life worse for the parasite inside than for the host. The loose hemoglobin strands grab oxygen, which slips free and can then damage Plasmodium. The parasites don’t seem to have any way of repairing themselves, so they can’t grow properly. When Plasmodium finally emerges from a red blood cell, it’s deformed and sluggish, and it can’t invade new cells. As a result, people with thalassemia who get malaria tend to have mild cases rather than fatal ones.
These blood disorders may do more against malaria than make life hard for the parasites. They may provide a natural vaccination program for children. Children who are bitten by a Plasmodium-laden mosquito for the first time reach a turning point in their lives: Will their naive immune systems be able to recognize the parasite and fight it off before it kills them? Stunting the growth of parasites—whether by thalassemia, ovalocytosis, or sickle cell anemia—gives the immune system more time to get beyond Plasmodium’s evasions, recognize it, and mount a response. These mild cases of malaria immunize children to malaria and let them live to adulthood.
Given how much parasites have shaped the human body, it’s tempting to wonder whether they’ve shaped human nature. Do women choose men for their parasite-proof immune systems the way a hen chooses a rooster? In 1990, a biologist named Bobbi Low at the University of Michigan reviewed the marriage systems in cultures plagued with parasites such as blood flukes, Leishmania, and trypanosomes. She found that the heavier a culture’s parasite load, the more likely the men were to have multiple wives or concubines. You might expect that sort of result from Hamilton and Zuk’s theory, since healthy men would be so highly valued in parasite-burdened places that many women would marry each one. How would women judge men for signs of parasite-proof immune systems? Men don’t have roosters’ combs, but they do have thick beards and broad shoulders, both of which are dependent on testosterone. The signs might not be visible either—a huge amount of communication goes on between people by odor that scientists haven’t begun to decode.