Authors: Nathan Wolfe
During the time that our own ancestors went through their microbial cleansing, their ape cousins continued to hunt and accumulate novel microbes. They also maintained microbes that would have been lost in our own lineage. From a human perspective, the ape lineages served as a repository for the agents we’d lose—a microbial Noah’s ark of sorts, preserving the bugs that would disappear from our own bloodlines. These great ape
2
repositories would collide with expanding human populations many centuries later, leading to the emergence of some of our most important human diseases.
* * *
Perhaps the single most devastating infectious disease that afflicts humans today is malaria.
3
Spread by mosquitoes, it is estimated to kill a staggering two million people each year. Malaria has had such a profound impact on humanity that our own genes maintain its legacy in the form of sickle cell disease. Sickle cell, a genetic disease, exists because its carriers are protected from malaria. Protection was so important that natural selection maintained it despite the debilitating disease that appears in approximately 25 percent of the offspring of couples that each carry the gene. People who are afflicted with sickle cell have their origins almost exclusively in one of the world’s most intensely malaria affected areas—west central Africa.
My interest in malaria is both personal and professional. During my time working in malaria-infested areas of Southeast Asia and central Africa, I was infected by it on three separate occasions. On the last of those occasions, I almost died. The first two times I’d had malaria were both in regions where malaria was common. I’d exhibited all the typical symptoms—severe neck ache (similar to how you’d feel if you slept in a strained position) followed by intense fever and profuse sweating. On each of my first two bouts, I simply went to a local doctor and received a quick diagnosis and treatment. While the pain and illness were miserable, they both resolved reasonably quickly.
I was in complete denial at the time I had my third round with this deadly disease. I wasn’t in the tropics; I was in Baltimore! I had returned from Cameroon to do research at Johns Hopkins University, and I had very different symptoms, led by intense abdominal pain. I must have also had fever since I remember complaining to friends who were putting me up in their local bed and breakfast that my room was too cold. These new symptoms and the fact that I’d left Africa many weeks earlier fed my denial that this could possibly be malaria. I finally realized I needed urgent care while sitting half delirious in a tub of scalding water and watching the overflow hit the floor of my friends’ bathroom. Although I recovered after a few days in the hospital, the illness brought home for me the huge impact that this disease has on the millions of people who are regularly sickened by it.
My professional interest in malaria had started much earlier. As a doctoral student studying the malaria of orangutans in Borneo, I’d had the good fortune to spend a year working with some of the world’s foremost experts on malaria evolution at the CDC in Atlanta. There I had the luxury of spending afternoons with Bill Collins, perhaps the world’s greatest expert on the malaria parasites of primates, discussing how malaria might have originated. Among the prominent themes of our chats was the importance of wild apes.
At the time, we knew that wild apes had a number of seemingly distinct malaria parasites. One of them was particularly intriguing.
Plasmodium reichenowi
was named after a famous German parasitologist, Eduard Reichenow, who had first documented the parasites in chimpanzees and gorillas in central Africa. Reichenow and his contemporaries saw a number of these particular parasites, collector’s items for the German researcher, and correctly identified them through examination by microscope as closely related to our own
Plasmodium falciparum
. In the 1990s, during my time at the CDC, molecular techniques were paving the way to detailed examination of these parasites, allowing us to compare them accurately to our own parasites and providing much greater evolutionary resolution than a microscope could ever offer. Sadly, all of the parasites of Reichenow’s time had been lost, and all that remained was a single lone specimen.
Initial work with this lone
P. reichenowi
parasite showed that in fact it was the closest of the many primate malarias to our own deadly human malaria,
P. falciparum
. Yet with only a single specimen, it remained impossible to say much about the origins of these parasites. Perhaps, long ago, the common ancestor had a parasite that over millions of years had gradually evolved into distinct lineages of
P. reichenowi
and
P. falciparum
, a hypothesis favored by some at the time. Or perhaps the ape parasite simply resulted from the transmission of the common human parasite to wild apes at some point in fairly recent evolutionary history. A third possibility, neglected by most considering the huge number of humans and the incredible proliferation of
P. falciparum
among them compared to the existence of only a few dozen known parasites in apes, was that perhaps
P. falciparum
was in fact an ape parasite that had moved over to human populations.
Bill and I understood that to truly address the evolutionary history of these parasites we’d need to get more samples from wild apes, ideally many. As a young doctoral student, I was ambitious yet still naïve about the difficulties associated with getting these kinds of samples. But I promised Bill I’d do it and set about planning ways to sample apes in the wild.
Unbeknownst to me at the time, I was about to be called away by my soon-to-be postdoctoral mentor Don Burke to conduct research in Cameroon. I was unaware at the time that I’d spend nearly five years establishing a long-term infectious-disease-monitoring site there in Cameroon. Eventually, though, I did follow through on my promise to Bill and got those ape samples. Ultimately, in collaboration with sanctuaries in Cameroon that helped to provide homes to orphan chimpanzees, we discovered that ape malaria parasites were not as uncommon as people had suspected. By teaming up with Fabian Leendertz, a veterinary virologist who had done similar work in the Ivory Coast, molecular parasitologist Steve Rich, and the legendary evolutionary biologist Francisco Ayala, we took an important step toward cracking the origin of this disease.
Together we were able to compare the genes in hundreds of human
P. falciparum
samples that already existed with around eight new
P. reichenowi
specimens from chimpanzees in locations throughout west Africa. The genetic comparison surprised us all. Amazingly, we found that the entire diversity of
P. falciparum
(the human malaria) was dwarfed by the diversity of the handful of
P. reichenowi
chimpanzee parasites we’d managed to uncover. This discovery told us that the most compelling explanation for
P. falciparum
was that it had been an ape parasite and only jumped over to humans through a bite by some confused mosquito, sometime after our split with the chimpanzee lineage. Human malaria had, in fact, originated in wild apes. In the years that followed our work, a number of researchers documented more and more of the parasites in wild apes.
Subsequent work by my collaborators Beatrice Hahn and Martine Peeters (the same scientists who have done work on SIV evolution) has shown that the malaria parasites infecting wild apes are even more diverse than our study indicated. They have shown that the ape parasites most closely related to human
P. falciparum
exist in wild gorillas, rather than chimpanzees. How these parasites have been maintained among wild apes and whether or not they’ve moved back and forth between chimpanzees and gorillas remain questions for future studies. Either way, there is no longer any doubt that human
P. falciparum
moved from wild apes into humans and not in the opposite direction.
* * *
That malaria crossed from a wild ape into humans makes great sense when viewed from the perspective of the evolution of our lineage. The microbial cleansing that resulted from habitat change, cooking, and population bottlenecks among our own ancestors had cleared our microbial slate, decreasing the diversity of microbes that were present before. Perhaps the many years with leaner microbial repertories had also decreased selective pressure on the many innate mechanisms that we have to fight against infectious diseases, effectively robbing us of some of our protective disease-fighting tactics.
In more recent times, as our population sizes began to increase, wild ape diseases, some of which we’d lost millions of years earlier, had the potential to infect us again. When these diseases reentered humans, they acted on us like uniquely suited novel agents. Malaria was not the sole microbe to make the leap from apes to modern humans, and the stories of others, like HIV, tell a strikingly similar tale. The loss of microbial diversity in our early ancestors and the resulting decrease in their genetic defenses would make us susceptible to the microbial repositories that our ape cousins maintained during our own microbial cleansing. While we continued to change as a species, yet another part of the stage would be set for the brewing viral storm.
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CHURN, CHURN, CHURN
The oysters were excellent, but the company was even more striking. As I sat in the small Parisian bistro with a tray of fresh shellfish, I savored the taste of the ocean. But the more powerful memory of that day was of another patron of the restaurant. At the table next to me sat an impeccably put together Frenchwoman. Her bag, skirt, and socks all matched—not exactly, but just enough to notice. Her dining companion sat to her right—a miniature poodle, sitting on the chair and drinking water from a bowl on the table. Pieces of his meal—chicken I think—fell over the side of his plate, mingling with the crumbs from his owner’s bread.
Dogs play an important role in the lives of many people around the world. I had stopped only briefly in Paris on the way home from a month-long trip conducting research in Asia and Africa. It might have been the jet lag, but my recollection of the event could only be described as surreal. During my trip I’d spent time in a part of Borneo where people eat dog, including on at least one occasion my unsuspecting self. I’d also visited Muslim areas of the Malay Peninsula, where devout people won’t even touch dogs because of religious beliefs. And I’d spent time in central Africa, where I’d seen local hunters work with their small, silent basenji hunting dogs—dogs that lived on their own but in exchange for scraps followed hunters into the forests, helping them catch their prey. In the United States, many people treat dogs as members of their families, paying large fees for medical expenses and mourning for them when they die. Sitting on the beach near my home in San Francisco, it would be hard for me to spend an hour without seeing someone kiss his or her pet dog on the mouth. Watching that woman in Paris sharing a meal with her dog solidified just how linked we are to these animals.
* * *
The close relationships we have with dogs, whether as companions, work animals, dinner guests, or a source of food, should not surprise us. Dogs play a special role in human history. If we were to compile the “greatest hits
”
of human evolution, hunting and cooking would certainly make the cut. Language and the capacity to walk on two feet would also be on the list. But central among our species’ critical historical events is domestication—and dogs were the first in a long line of plants and animals that our ancestors tamed.
The capacity to domesticate plants and animals underlies much of what we now think of as being human. To imagine a world without domestication, we’d have to spend time with one of the few dozen human populations on the planet that still practice hunting and gathering lifestyles, groups like the Baka and Bakoli, the so-called pygmies, living in central Africa that I have worked with for years, or the Aché that live in South America. For these groups of people, there is no bread, no rice, no cheese. There is no agriculture, and therefore the many rituals of our planet’s major traditions, including the harvest and planting pilgrimages and their associated festivals, are entirely absent—no holidays such as Ramadan, Easter, or Thanksgiving. There is no wool, no cotton, only textiles made from wild tree bark or grasses and the skins from hunted animals.
These hunter-gatherer populations have complex histories, and many of them lived at some point with some form of agriculture before returning to a foraging lifestyle. Yet they provide us with interesting clues on what the lives of our ancestors looked like before the advent of widespread domestication.
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Among the traits hunter-gatherer populations share are small population sizes and a nomadic lifestyle. As we’ll see, these traits have an important impact on keeping the microbial repertoires of these populations at low levels.
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The first human foray into domestication came with modification of wolves into the canines we know today. Archaeological and DNA evidence suggests that populations in the Middle East and east Asia began domesticating gray wolves as early as thirty thousand years ago, turning them into guard dogs and work animals as well as using them for food and fur. The early history of dog domestication is still unclear. One hypothesis is that wolves followed humans, scavenging off of their kills, and over time became dependent on humans, a dependency that set the stage for their later domestication. But no matter how it began, by fourteen thousand years ago dogs played an integral role in human life and culture. In some archaeological sites in Israel, humans and dogs were even buried together. These early dogs would have resembled modern-day basenjis, the silent hunting dogs preferred by the central African hunters with whom I work.
Occurring around twelve thousand years before we would domesticate anything else, the domestication of the dog was an early precursor to what would follow. Around ten to twelve thousand years ago, a
domestication revolution
occurred in earnest, starting with sheep and rye and then followed by a diverse group of other plants and animals.