by Rob Dunn
In this telling, the loss of the primate version of sialic acid is an ancient adaptation that is no longer useful now that we have been colonized by gorilla malaria (or, in a few lucky places on Earth, escaped malaria altogether). It may be that evolving a broken sialic acid gene allowed humans to escape a number of pathogens at once, at least for a while.19 But this escape left us with overreactive immune systems, which, when combined with poorly designed coronary arteries, diets rich in mammal meat, sedentary lifestyles, smoking, and other risk factors, began to clog arteries and kill us. The combination of these historical weaknesses, though, did not begin to kill humans with great frequency until relatively recently, for the simple reason that humans didn’t live long enough.
Modern apes live just fifteen to thirty years in the wild.20 Six million years ago, when our ancestors diverged from the ancestors of chimps, they probably lived no more than thirty short and brutish years, punctuated by episodes of eating fruit, fleeing from leopards, mating, and then, postmating, savoring some more fruit. Every so often, an individual might live much longer, but rarely. Inferring what happened between six million years ago and today is the difficult part.
Our best guess as to the life expectancy of early humans comes from studies of hunter-gatherers alive today, who tend to live around forty years (on average—such reconstructions always focus on averages), and we can infer that at some point in the transition from chimplike ape to hunter-gatherer human, our species gained some twenty or so years. Human life expectancy hovered around forty years through most of the nine hundred thousand years of hunter-gatherdom. If there is a natural human longevity, this is it: about forty. Then, as humans began to farm, life expectancies appear to have changed again; they seem to have decreased slightly.21 The royal mummies in the Egyptian Horus study, for example, had an average age of just thirty-eight years. No telling how long the average Joe lived, though everything we know about the long history of haves and have-nots suggests it is likely to have been fewer years. It was not until the 1800s that human life expectancies began to creep up into the fifties and then sixties and then seventies, and even, in recent decades, the eighties, at least in developed countries. In much of the world, a sixty-year-old is still an ancient.
Focusing on averages skews our understanding of these transitions to some extent. Averages include infant mortality, and one of the biggest shifts through time has been a progressive decrease in infant mortality (which removes many of the data points where life expectancy is less than one year from the averages). But even once infant deaths are taken out of the picture, human longevity generally increased through time. This means that, as time went on, more individuals were at risk of heart disease, even if nothing else about their lifestyles or biology changed. Today, heart disease and strokes (as well as cancers) tend to kill humans only when they are older than thirty-five. Until two hundred years ago, humans were usually killed by disease, predator, or mishap before their hearts and blood vessels had a chance to fail. The Egyptians, for example, do appear to have suffered greatly from heart disease, but very few of them—Queen Meryet-Amun being an interesting potential exception—lived long enough for heart disease to kill them. Human bodies have not had a chance to evolve a response to the overreactivity of their immune systems, and the more successful the medical treatments of immune disorders (including heart disease) are, the less likely it is that they ever will.
The Varkis continue to try to understand this story; many more details will probably emerge, but the generality seems likely to remain: we have atherosclerosis in part because our immune systems react to the LDL in our blood. Our immune systems are more aggressive than those of other primates because we were (and, in much of the world, still are) plagued by an unusually high diversity of pathogens, including pathogens deadly enough to cause an alteration in our genes. As a result, any lifestyle that provides more cholesterol in LDL in the blood also provides more substrate for the immune system to attack. By contrast, any lifestyle that increases HDL will decrease LDL, reducing what can be attacked.
The consumption of foods rich in antioxidants reduces the proportion of LDL molecules that are damaged by age, oxidized, and then attacked; anything that heightens immune reactivity makes attacks more eager and problematic. Smoking, as I’ve mentioned, triggers inflammation and an immune response, and it constricts arteries. There are a diversity of ways in which inflammation, cholesterol levels, the relative abundance of different types of lipoproteins, and the oxidation of lipoproteins influence the risk of atherosclerosis, and there are probably many more contributing elements that we don’t yet know about. Already, there are more factors involved than Ancel Keys or Akira Endo could have possibly imagined, factors influenced by our modern behavior as well as our ancient evolutionary history and our relationships with other species.
Take, for example, the ecology of teeth. Modern mouths are susceptible to tooth decay and gingivitis due to oral pathogens such as Streptococcus mutans and Porphyromonas gingivalis. But this, it turns out, is a relatively new state of affairs. Studies of the plaque on the teeth of ancient mummies—one of the few places where the DNA of ancient human-associated bacterial species can be determined with any certainty—have revealed at least two major transitions in oral ecology, both related to carbohydrate consumption. First, when humans switched from hunter-gatherer diets to the mealy foods of agricultural diets, gingivitis bacteria in their mouths increased. This increase led to more inflammation, more gingivitis. Second, over the past two hundred years, industrialization of the production of sugar, and its subsequent increase in human diets, has led to a reduction in the number of kinds of bacteria in the mouth. Sugar has favored the dominance of a few bad-news forms of oral bacteria, including Streptococcus mutans and its kin, which cause dental caries. These changes might not seem to have anything to do with the heart, but they do. Chronic gingivitis and tooth decay make the immune system more active, leading it to produce more and more macrophages, which must travel through the blood. In traveling through the blood, these macrophages meet up with the cholesterol in LDL, which they attack. In other words, the changes in human diets over the past twelve thousand years affect the cardiovascular system even when those changes involve areas far removed from the heart.22
The proportion of individuals with evidence of atherosclerosis in at least one artery. Estimates for mummies are minimum estimates because not all arteries are visible in most mummies. Data are from The Lancet 381, no. 9873 (April 6–12, 2013): 1211–12.
Eating too many simple carbohydrates increases heart disease by increasing oral microbes (as well as triglycerides). Meat-eating contributes to atherosclerosis in more ways than just those noted by the Varkis. As Keys observed, eating meat high in saturated fats affects the levels of LDL and HDL in the blood, though the degree to which this happens is genetically dependent and the subject of great debate. But meat-eating also increases inflammation, because the sialic acid in nonhuman animal meat triggers the response of the immune system (perversely, this means that the one kind of meat that can be eaten without incurring the chronic wrath of one’s immune system is human meat. Cannibals might be expected to be at a slightly reduced risk of atherosclerosis). Finally, a recent study has shown that individuals who eat red meat tend to have different bacteria in their guts; these may be the kinds of bacteria that cause problems. Red meat and eggs both contain the compound choline (as well as other compounds related to choline). Choline is necessary for all animals (and its absence in the diet can cause heart problems). However, some bacteria found in the guts of meat-eaters turn choline into another compound, trimethylamine, the presence of which increases the formation of atherosclerotic plaques.
The effects of all these factors depend on genes associated with cholesterol, inflammation, and even a predisposition to certain bacteria. This makes it clear that while we humans might be able to decrease atherosclerosis and heart disease, doing so is complicated. Our modern heart problems are not simply the result of eating
the wrong foods but of living long lives in bodies built for shorter ones. Our bodies are complex, filled with thousands of species and influenced by many more. Our bodies have evolved to escape pathogens long enough to make children, no matter what that escape costs us in old age or in other contexts. Our bodies have life expectancies shaped by the realities of human history, not our hopes for the future. Nowhere, it turns out, is this clearer than in the rate of our hearts.
17
Escaping the Laws of Nature
We repair ourselves—we parry every blow, and all in the service of keeping the gyroscope of life spinning smoothly.
—SHERWIN B. NULAND, THE WISDOM OF THE BODY
In medieval Christianity, God was said to inhabit the heart, taking notes on its inner walls. To some, this writing was literal.1 The heart was a muscular parchment on which the Almighty scribbled vigorously, recording each furtive glance, each generous or ungenerous thought. A long life would fill the heart with stories by which one’s worth could be fairly judged. With time, the heart was seen in sufficient detail for men to realize there were no notes inside. To the extent that our stories are recorded in our bodies, we tend to think the records can be found in our brains. The brain does indeed record our actions to memory, albeit via chemistry. But among one group of scientists, a group that has taken an entirely different perspective on our tickers, the heart is still a record of our fates in this life rather than the next.
You can probably think of many things the heart rate says about us. The heart’s pounding and thumping enthusiasm speaks of fear, of love and lust, of how much one exercises, of the lives of one’s ancestors, of one’s diet. Some scientists argue that it also speaks of our demise—or, rather, a comparison of the human heart to those of other animals does.
These scientists study what is called scaling (also referred to, even more obscurely, as allometry), a field concerned with understanding the relationships of different features of organisms as they grow or evolve. Scaling tells us how big dinosaurs would have been able to get without collapsing under their own weight and why plant-eaters tend to be bigger than predators. It also tells us how tall the tallest trees can grow and how densely trees (or cells) can live. Many of the phenomena that scaling purports to explain are straightforward and well understood. Although life is inscrutably diverse and complex, scaling reminds us that such complexities tend to obey the universal demands made by physical laws. Nobody gets away from gravity or momentum.
The laws of scaling are said to follow those of physics, and so perhaps it is appropriate that one of the most ambitious and reaching allometricians, Geoffrey West, spent most of his career as a physicist at the Los Alamos National Laboratory, the research center established to develop the Manhattan Project. West worked on the theoretical physics of protons and neutrons at Los Alamos from 1976 until 1993, when the $11 billion necessary to build the Superconducting Super Collider in Texas, where he had planned to do his future research, failed to fully materialize. West was fifty-three. He could have taken it a little easy and drifted into retirement, but instead, he decided to try something new. He had done what he could with protons and neutrons; he wanted to explain life, including the bustle of human life in cities and the bustle of blood in the heart. He eventually went to work at the Santa Fe Institute, where he was given a big space in which to do his job, which was to think.
Think he did. West is a mathematical thinker, the sort of character who appears in movies but seems unlikely in the real world. Yet he exists. He is a tall, thin, angular man, all elbows and knees, with untended silver-gray hair and a beard and mustache of the same color. He reaches his arms out, hands open, as he talks, and his weedy eyebrows rise as he makes a point or ponders. He thinks. He talks. He writes equations and codes models. The son of a professional gambler and a dressmaker, he tries to weave beautiful ideas by playing the odds. He uses mathematics to see aspects of the functioning of the universe that others have missed. He is drawn to elegantly simple explanations for complex real-world problems, and he uses equations to describe where mere words fail. In doing so, he is always “onto something,” the next clear view of some muddied problem. The possibility of the next clear view, like the possibility of climbing the next big hill, is great enough to sublimate many ordinary necessities. West gets by, when he is working, on a diet of nuts and tea. He can’t be bothered to deal with more. Maybe, as he told one journalist, he is allergic to food. Just as likely, he is allergic to worrying about mundane things when the next equation or analysis might explain something as central as the function of cities or, better yet, the human heart. As he told that same reporter, he wants “to find the rules that govern everything.”2
The work West has become best known for is the study, begun in 2003, of how humans live and act in cities. West had the idea that much of the raucous detail in cities, detail that seemed whimsical, the pure art of living, was predictable, in the way that, as a general rule, the behavior of neutrons are. Sure, an individual neutron or person might make wild deviations from the expected, but collectively, the behaviors of humans and neutrons are predictable, he believed. West thought that if he knew the size and demands of a particular city, he could predict its necessary infrastructure as well as its major human features. The people in a city need resources, and these needs are dependent on the number and density of people; they must, in the terminology of the field, scale with them. As a result, West thought, the relationship between the demand for these resources and the size of the population must obey certain rules, since roads can only be so wide, bodies require a certain amount of food, and buildings need a certain amount of energy. But what if there were also rules for how population size influenced not just what humans needed but also what they did, rules that governed, for example, where art and innovation thrived? If so, the study of these relationships might explain apparently diverse and unconnected things across geography and history: how many miles of road there would be in a city of 150,000 people, how many hot-dog vendors, how many robberies and of what type, but also how much artistic and scientific innovation would exist. From simple mathematical rules, an entire circus of particulars can emerge, or at least that is what West hoped. He hoped he could weave all of the beauty of human creation into math.
To test whether the features of cities were predictable, West collected data on cities. He considered anything that might be predictable, anything that might depend on the “how many” and “how dense” of our living ways. He and his team gathered data like magpies collecting shiny pebbles, avidly and somewhat indiscriminately. They would look at any features of cities they could find information on. Whole fields already considered how cities worked—urban planning, architecture, landscape design. West’s team was large and included experts in multiple fields, but they would ignore these fields. West’s team would build on physics and biological scaling rather than on the work of the thousands of individuals who had spent their lives studying cities.3 It was an act of arrogance suitable to a man who sometimes compared his own efforts to those of Galileo.
Amazingly, after years of gathering and modeling, it has all worked out to West’s great satisfaction. He can, he thinks, explain cities, and his explanation steadily becomes more useful, since each generation is ever more urban and so ever more subject to West’s laws. If you tell him the size and population of a city, he will predict for you the surface area of its roads, the number of gas stations, the scope of the sewage system, and then also its human phenomena, such as the pace of innovation. But the interesting thing is not just that he can predict these features, but that each of these features relates to the size of a city in a slightly different way. The resources a city needs (gas, food, and so on) decrease on a per capita basis as the size of a city increases (bigger cities are progressively more efficient; the slope is less than 1), but the innovation a city engenders shows the opposite pattern: it increases on a per capita basis as cities become larger (the slope is greater than 1). In short, the bigger the city, the
greater its efficiency and innovation; the more art and the less gas.
One should be skeptical of anyone who attempts to explain modern human life with a few equations, but West thinks he and his collaborators have solved the city. Many argue with the details of West’s models and approach. He trades, they say, accuracy for comprehensiveness. West’s equations have a sweeping simplicity that is frustrating to those in the detail-rich trenches.4 His models do an okay job of accounting for many features of the world rather than a great job of predicting or understanding any particular feature. Others suggest the interesting things about West’s models are not where they work, but where they fail, where cities violate his laws. But cities are not the only realm West has considered. He actually started with the study of human bodies and human longevity; in some tellings, this is part of why he began to study scaling in the first place. He was thinking about his own death. West comes from a long line of working-class men who die young, and he had begun to consider the possibility that his own death might not be far off. He wondered about his heart, a heart that, in its beating, was not so unlike the throbbing center of Los Angeles or New York. He wanted to know when it would stop, when he would die, when any of us would die, and why. In hearts, West saw physical laws in action. In hearts, he found what he described as “the single most pervasive theme underlying all biological diversity,” all life—namely, death.
