by Sonia Shah
It is in light of selfish gene theory that sexual reproduction and death come to seem confounding, for neither sex nor death is a particularly efficient means of disseminating genes, given the alternatives.
Consider sexual reproduction. At one time, all life on the planet reproduced asexually (by cloning or other methods). There were no sexually reproducing creatures. But at some point in the history of evolution, sexual reproduction emerged. And yet, from the point of view of our genes, it was a vastly inferior strategy compared to other methods of reproduction. Organisms that clone themselves pass on 100 percent of their genes to their offspring. Sexual reproducers must not only partner up with another individual to reproduce, but both parents lose half of their genes in the bargain, for the resulting child inherits half of its genes from each parent.
To survive, the first sexually reproducing organisms would have had to outcompete the cloners, who dominated the resources and habitats of the planet. But how could they? In the 1970s, the evolutionary biologist William Hamilton created a computer model to simulate what that contest looked like. The simulation set up a population in which half of the individuals practiced cloning and half paired up and had sex. (Imagine a clan of all-female Amazons who replicate themselves without males, alongside a tribe of females who could reproduce only with the help of a male.) Everyone was equally subject to the kind of random deaths that befall populations in the wild, like being attacked by predators or frozen in an ice storm. The model then calculated the reproductive success of the two tribes, counting the number of offspring they each produced.
The cumulative effect of the two different reproductive strategies didn’t take long to reach its logical conclusion. Every time Hamilton ran the model, the sexual reproducers rapidly went extinct. Random deaths in the sexually reproducing tribe resulted in a disproportionate loss to the mating pool (as anyone who has tried to find a date after the age of forty can understand intuitively). Not so for the cloners, who maintained their vigorous rate of replication regardless of random losses. It didn’t matter that the offspring of the sexually reproducing tribe were more genetically diverse and therefore more resilient to long-term changes in the environment. The burden of random deaths was too immediate to allow those benefits to manifest themselves.
Thus sexual reproduction should have been an experiment that failed. And yet it didn’t. Eventually, the reproductive strategy of our most distant ancestors spread throughout the animal kingdom, including in us, many years later, in whom it became a central preoccupation.
It was Hamilton who offered a startling explanation that solved the mystery: sex evolved, he said, because of pathogens.
Sexual reproduction requires a profound genetic sacrifice, he noted, but the payback is that the offspring of sexual reproducers are genetically distinct from their parents. That was no big advantage in surviving hostile weather or predators, Hamilton observed, but it was a huge advantage in surviving pathogens. That’s because pathogens, unlike the weather or predators, refine their attacks upon us.
Imagine a pathogen that first strikes when you’re a baby. As you develop, the pathogen goes through hundreds of thousands of generations. By the time you’re an adult (if you’ve survived the ravages of the pathogen) and are ready to reproduce, the pathogen has become far better at attacking you than you are at defending yourself against it. While your genetic makeup has stayed the same, the pathogen’s has evolved.
But individuals who clone themselves provide pathogens exact replicas of the target they’ve already gotten so good at stalking. They endow their offspring with the worst possible chances of surviving the pathogen’s appetites. Much better, in that case, Hamilton theorized, to produce offspring that are genetically distinct from you, even if that means forsaking half of your own genes.
Scientists have shown how refined pathogens’ attacks become over time by experimentally transferring the pathogens of an old individual into a young one. One study cited by the evolutionary zoologist Matthew Ridley focused on long-lived Douglas fir trees, which are routinely attacked by scale insects. (Although scale insects are not microbes, they are disease-causing organisms just like microbial pathogens.) In the wild, old trees are more heavily infected than young ones. This is not because the old trees are weaker than the young ones, as one might think. The old are more heavily infested because their pathogens have had more time to adapt to them. When scientists transplanted the scale insects of an old tree onto a young tree, the young tree suffered the same heavy burden of disease as its elders. It’s easy to see how, with pathogens like that around, sexual reproduction would provide a better chance at survival than cloning.5
Since Hamilton first articulated his theory about pathogens and the evolution of sex, a large body of supportive evidence has accumulated. Biologists have found that species that practice both sexual and nonsexual reproduction will switch between the two depending on the presence of pathogens. When raised in a lab devoid of their usual pathogens, or in the presence of pathogens that are altered in such a way that they cannot evolve, the roundworm Caenorhabditis elegans will mostly replicate without sex. But when stalked by pathogens, it will reproduce sexually instead. In other experiments, scientists altered roundworms so that they cannot sexually reproduce. When they reared these worms with pathogens, the nematodes went extinct within twenty generations. In contrast, when they allowed roundworms to practice sexual reproduction, they survived alongside their pathogens indefinitely. Withstanding pathogens seems to require the special benefits provided by sexual reproduction.6
By forcing the evolution of sex, pathogens may have forced an additional adaptation: death. The notion that death is some optional thing that can “evolve” may seem counterintuitive. The idea that deterioration and death are inevitable is central to how most of us think about life. We think of the body as a kind of machine that inevitably wears out over time. Individual parts fail and the damage accumulates. Finally, after some critical threshold is passed, the entire machine stops working. Thus we say that nobody can “cheat death.” We even equate the word “aging,” which is simply the passing of time, with diminishment. (What we really mean is what biologists call “senescence,” a gradual deterioration of function that proceeds with the passing of time and ultimately leads to death.)
But senescence and death are not inevitable facets of life. There are examples of immortality all around us. Microbes live forever. Trees don’t deteriorate with time. On the contrary, as they age they get stronger and more fertile. For microbes and many plants, immortality is the rule, not the exception. There are even some animals that don’t age: clams and lobsters, for example. Death, for them, is caused solely by external factors, not internal ones.
One way the human body is distinctly different from a machine is that it can repair itself. After we exercise, we repair ourselves from the damage we’ve inflicted to our muscles. When our bones are broken or skin ruptured, we grow new bone tissue and new skin. (There are even reports of people regrowing severed fingers.)7 Our cells have a wide range of ways they repair themselves from insult. Other animals have this capacity to self-repair. Worms rebuild their severed wriggling bodies. Starfish regrow their arms. Lizards regrow their tails. Such repairs actually make us stronger, not weaker.
Scientists have found that far from being an inherently inevitable process, senescence is controlled by particular genes, variously called “suicide genes” or “death genes.” Their job is to progressively turn off the processes of self-repair that keep our bodies in good condition. They’re like a host switching off the lights at the end of a party. It happens at a certain time, no matter what.8
The discovery of these genes dates back to the 1970s, when scientists found that removing certain glands from a female octopus could postpone her otherwise inevitable death. Normally, a female octopus will stop eating and die, like clockwork, ten days after she finishes tending her eggs. But surgically removing the glands that control maturation and breeding resulted in an octopus
that behaved quite differently. After laying her eggs, she resumed eating and survived for another six months.9 Scientists have similarly pinpointed genes with no known purpose other than to trigger deterioration and death in worms and flies. When those genes are experimentally inactivated, death is delayed. The worms and flies live on.10
So far, it seems unlikely that genes with such singular purpose will be found in people. More likely, suicide genes in humans play a number of different roles, both beneficial and detrimental. Genes that control inflammation may protect us from wounds and infections when we’re young, but then go suicidal and start attacking healthy cells. The conditions that trigger these abrupt about-faces have yet to be pinpointed, but for obvious reasons they are the focus of much zealously followed research conducted by antiaging scientists.11
The discovery of suicide genes begs the same question that sex does. How would such genes have ever evolved? The programmed death such genes cause is a loser compared to the alternative. In a straight evolutionary contest, individuals encumbered by suicide genes, collapsing halfway to the finish line while their rivals surge ahead, would surely lose. There would have had to have been some immediate payback to compensate for such a heavy debility.
That payback, according to what’s called the “adaptive theory of aging,” is protection against species-leveling pandemics. Immortality undoubtedly has its perks, but there are also significant drawbacks. One is that immortal species tend to rapidly expand their numbers to the limits of whatever resources are available in the environment. That leaves them vulnerable to catastrophic events, like famines and pandemics, which can strike them in one fell swoop, killing everyone all at once.
We know that catastrophic events like this happened in the past with some frequency. After all, 99.9 percent of all the species that have evolved on Earth are now extinct. Those of us who remain today are the few survivors on our volatile planet. How did we do it? Immortal species, like microbes, were probably resilient against catastrophic famine and pandemics because they also practiced cloning. That meant that even a pandemic that wiped out 99.9 percent of their population wouldn’t force them into extinction, for a small number of survivors could rebuild their numbers. But the odds for any immortal, sexually reproducing species would have been grim. One group of conservation biologists estimated the minimum population size required for most sexually reproducing animal species to remain viable to be around five thousand.12 Others put the range between five hundred and fifty thousand, depending on the species. Any pandemic (or famine) that wiped out more than that number would extinguish a sexually reproducing species forever.13
The adaptive theory of aging posits that this was the context in which suicide genes evolved. The scenario would have gone something like this. Imagine two competing groups of sexually reproducing organisms. In one group, all are immortal. In the other, suicide genes have emerged and so some individuals slowly age and die. The first group is like a dense forest; the second is like a regularly culled one. When the pandemic arrives, the former group will fare as poorly as the dense forest does in a forest fire. The latter group will be more likely to survive, allowing suicide genes to spread.
Suicide genes obviously don’t protect us entirely from the risk of famine and pandemic. But because individuals in our groups regularly age and die, “a little bit at a time,” as the antiaging researcher Joshua Mitteldorf puts it, the risk that those events will cause an extinction is much lower. We age and die, Mitteldorf contends, as a sacrifice to pandemics.14
Both Hamilton’s theory about the evolution of sex and the adaptive theory of aging are versions of what’s called the “Red Queen Hypothesis,” which has revolutionized modern biology. It’s named after a scene in Lewis Carroll’s Through the Looking Glass. Alice collapses to the ground after a vigorous bout of running with the Red Queen, only to find they’d made no progress at all. “You’d generally get to somewhere else,” Alice says, “if you ran very fast for a long time, as we’ve been doing.” The Red Queen explains the logic of why they did not: “Now, here, you see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!”
What does this mean for our epidemic past and future? According to classic natural selection theory, as articulated in 1859 by Charles Darwin and as taught in high school biology classes around the world, pathogens and their victims adapt to each other over time, evolving toward a less fractious relationship. The Red Queen Hypothesis says otherwise. For every adaptation on the part of one species, it holds, there’s a counteradaptation on the part of its rival. What that means is that pathogens and their victims don’t evolve toward greater harmony: they evolve increasingly sophisticated attacks on each other. They’re like spouses in a bad marriage. They run “very fast and for a long time,” but they don’t “get to somewhere else.”
And that leads to the same conclusion as arguments about the nature of microbes and the immune system and the evolution of sex and death. That is, that the relationship between pathogens and their victims does not evolve toward greater accommodation. On the contrary, it’s a continuous battle in which each side evolves increasingly more sophisticated ways to crack the other’s defenses.
This suggests that epidemics are not necessarily contingent on specific historic conditions at all. Even in the absence of canals and planes and slums and factory farms, pathogens and their hosts are locked in an endless cycle of epidemics. Far from being historical anomalies, epidemics are a natural feature of life in a microbial world.
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These theories about sex, death, and pathogens were not formulated to reveal the extent of our long entanglement with pathogens. They were attempts to resolve theoretical problems in natural selection, the cornerstone theory of modern biology. But strange patterns in our genes, and the way geneticists and other scientists have tried to understand what they mean, support their theoretical claims.
One of those strange patterns has to do with the nature of genetic diversity among us. Colloquially, we say that each of us is “genetically unique,” but that’s actually not accurate. In fact, we all have the same genes. Each of us has genes that tell the body how to build a nose or how to shape an ear, for example. (A gene is simply a specific segment of DNA where instructions for specific traits are stored.) What we have among us are different variants of the same gene, for the sequence of chemicals in that segment varies from individual to individual. Your variant, for example, may call for an attached earlobe and mine for a hanging one.
Sex and mutations introduce new variants and combinations into our genomes at a regular clip. But it’s a messy process with no direction. It’s like blindly throwing a wrench at a bicycle. Most of the time, new variants are downright unhelpful. The genome is degraded by the variant just as the bicycle would be. Sometimes, the variant is neutral and there’s no noticeable effect at all. Very rarely, a random variant will happen to coincide with events that make it useful. Over time, unhelpful genetic variants are methodically weeded out while the beneficial ones come to dominate. And so, when geneticists compare the genomes of a bunch of different people at a given moment in time, they expect to find a certain degree of genetic variation, but not a huge amount.
And yet, when geneticists zoom in to one part of the genome, they find a singular anomaly. It’s the part of the genome where certain pathogen-recognition genes lie. These genes provide instructions for building what are called human leukocyte antigens (HLA), proteins that signal to the immune system when a cell has been infected. (They do this by binding to a fragment of the pathogen and displaying it on the surface of the cell, like a flag.) On this one part of the genome, we’ve maintained a huge number of variants among us. Our HLA or pathogen-recognition genes are more diverse, in fact, than any other part of the genome, by two orders of magnitude. So far, more than twelve thousand variants have been discovered.
There are two possible explanations for it. Either each
of those twelve thousand variants is neutral and thus the variation is meaningless—which is hard to believe given the sheer number of variants—or some powerful force has reversed the normal pressures that reduce variation, making it somehow advantageous for us to maintain a vast library of old genetic variants.
That force may be pathogens causing repeated cycles of epidemics. To cause repeated epidemics in the same population, a pathogen must switch between different strains to evade detection, like a thief using different disguises to repeatedly rob the same bank. Retaining a large number of pathogen-detection genes among us ensures that there’ll always be a few individuals who can suss out the latest disguise. Each pathogen-detection gene variant thus neither fully dies out nor sweeps into dominance. We carry them around with us, like a treasure chest full of specialized detection tools handed down from generation to generation.15
What’s more, we’ve been doing this for millennia. We have a lot of old genes in our genomes, genes for useful traits like eyes and brains and backbones, which we share with other species. Our pathogen-recognition genes are on par with these. Some of the pathogen-recognition genes embedded in modern people’s genomes are 30 million years old. They’ve survived among us even as we’ve split off into different species multiple times. That suggests that pathogens have been cyclically causing epidemics, dying down, then lashing out again for geological eons.16
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Our genomes also contain clues about a specific pandemic in our past. This one struck the hominid line (of which Homo sapiens are the sole survivors) around 2 million years ago. The evidence lies in a gene that controls the production of a particular compound called a sialic acid. Over the course of three hundred thousand years—a heartbeat in evolutionary time—every individual who produced this sialic acid died out or failed to reproduce, leaving behind only those who didn’t produce the sialic acid, because they had variant of the gene that inactivated it.