Infections: Why We Need Them—Spare the Rot and Spoil the Child

This July Tuesday warms me as I walk to my truck. The air smells of pines and the sour seep from the feedlots to the east. A blue jay screams about how great it is to be a blue jay this morning. But today I don't care about blue jays. This morning, I'm watching the ants

Several small brown hills rise in the seams of my driveway. This happens every summer. Sometime in spring, the small clods push up, and the ants roll them into something that resembles finely ground tobacco. Small holes grant egress and ingress, and a steady stream of wasp waisted insects carve their own Silk Road, moving leaves, twigs, and bits of bologna from surface to cave.

On Saturdays, I try by various means to obliterate these mounds and to disperse their inhabitants. On Sundays, while I read the paper, both reappear. On Mondays, work takes my mind. On Tuesdays, I insist on taking time to study the ants.

This Tuesday, a regiment of small soldiers has strung out single-file across the driveway toward a rotting plum. A phalanx of black beads has swallowed the plum itself. From under the mound of plum-sucking ants, another line of workers makes its way directly back to the small brown mounds of earth in the cracks between the concrete of my driveway. I open the door to my pickup truck and drop my computer case in side. Then I walk back to where the ants have arrayed themselves. I pick up the plum with its beard of ants, and I move it a yard up the driveway. For a few minutes, everything is chaos. Ants string out from the plum in several directions. The ants leading the march from the hills begin to lash about lazily like the fronds of an underwater fern. Finally the two—the ants stringing from the plum and the ants lashing from the anthills—meet. There appears to be a brief conversation among the lead ants, cursing me, no doubt. Then the regiment realigns itself, locates the plum, and everything continues pretty much as before. Once again, I move the fruit, now more purple pulp than plum, and watch what happens. The earlier scene repeats itself—a few moments of disarray, then single-file order. Twice more I move the plum. Twice more the ants quickly move to solve the problem I have created for them.

Tired of this, and clearly no match for the ants' resolve, I change tactics. I isolate a single ant and, using a leaf, move her six feet from the others. At first, the ant seems totally confused, adrift. She makes some jagged back-and-forth movements, then she begins to circle. As the ant rotates, the circles widen, the size of a peanut, then an almond, then a pecan, then a golf ball, then a tennis ball, then a baseball, then a basketball. Until the orbiting ant at last bumps into a smell. The smell of purpose. Immediately, the lost one aligns herself with the smell and moves toward the plum, her reason for being reestablished.

I choose another one. This ant looks a little like my father—thin in the middle, a little larger behind, and committed. I move her away from the rest. Confusion. Circling. Community and purpose.

I pick one more—a female again, because all worker ants are females—and I carry her a full five yards from all the rest. She hesitates, suspecting a trick. Her legs lift and drop like she has never felt a concrete like this one. A stone at a time, she feels her way. She stops, lifts her head, seems to watch the sun. Then, abruptly, she begins moving in circles that grow even faster than the ones I've seen before. A moment, at most, and she disappears— another period in a long line of commas.

There are no rogue ants here. No one sets off on his or her own, even when forced to face the unknown. None like the dog Buck. No call from the fierce unknown or the pack that roams where no ant has wandered alone. Resistance is futile.

In fact, I realize, there truly is no individual ant here at all. There is only the colony. In a very real sense, there is no such thing as "ant," only "ants." The unit here in my driveway is the colony. No rugged individualists, no Daniel Boone, no Lewis, no Clark, not among ants. An ant without a colony is meaningless.

But that is not the first thing that comes to mind when a person looks at an anthill. We see what appear to be individual ants moving about doing various individual tasks—hauling leaves, tending eggs, rolling grains of sand, gathering bits of plum. Because most of it is buried, and because we're not used to thinking of living things in other ways, we don't see the colony. But it is there, and in one very real sense, it is all that is there.

The Fearsome Fate of the Uninfected

Without infection, terrible things happen.

Fruit flies, those annoying little things that buzz in and out of your ears while you are trying to lift a peach from your neighbor's tree, normally live a month or two. But uninfected fruit flies—and in particular fruit flies uninfected by bacteria—live, on average, 30 percent shorter lives. For a fruit fly that might mean a loss of ten or twenty days of life. But for you and me, that would translate to about twenty-seven fewer years of life—a noticeable difference, for flies and people.

Flies without bacteria die sooner than infected flies. And the same is true for paramecia, termites, worms, mosquitoes, mice, rats, and, probably, human beings. Infection is as essential for life as a beating heart.

Why is that? What do these vermin do that we cannot live without?

Ultimately, the answer to that question is that all life on this planet relies on bacteria. Life must come to terms with bacteria, because bacteria are everywhere. And then there are fungi and viruses and parasites, the whole microscopic universe that we must contend with. Infection is now and always has been unavoidable. The only beings that have prospered on this planet have done so not because they learned to avoid infection but because they learned to thrive on infection.

Before men and women came along, no creature ever arrived in this world uninfected. It wasn't possible. Every space that any creature might occupy teemed with microscopic life. So, like the music of the spheres, infection had been humming along just beyond the range of human hearing for as long as there had been living things. No animal, no plant ever suffered from uninfection. No disease, no affliction, no syndrome ever arose naturally because an animal failed to become infected. No one noticed, but it was true all the same. It took the curiosity and the technical wizardry of human beings to create an uninfected soul.

Suddenly, we saw what we'd been missing all along.

Scientists created the first germ-free mice more than fifty years ago. It was as though they had opened Pandora's box.

From beneath the lopsided lid of that box, disease after disease rose, and hope followed none of them.

Unexpectedly, the cecum (the first part of the large intestine) in germ-free mice swelled up to several times its normal size. And in a few mice, the cecum became so large that the small intestine wrapped around itself, and the mice died. Just why a lack of bacteria causes cecal swelling isn't clear, but it is clear that these mice died from lack of infection.

After scientists found ways beyond the early afflictions of germ-free mice, illness after illness emerged.

Uninfected animals need more food and water than their infected counterparts. Germ-free rodents need one-third more water than normal rodents. We and other mammals need a lot of water for normal digestion. Much of that water is secreted by our stomachs and small intestines—as much as thirteen quarts per day. To keep us from dehydrating or being forced to drink thirteen quarts of water per day, the large intestine reabsorbs most of the water secreted by the stomach. Apparently, large intestines without bacteria don't absorb water nearly as well as intestines that are lousy with bacteria.

Germ-free mice need 30 percent more calories than normal mice. That's the equivalent of you or I eating four full meals a day instead of three. Thirty percent more fat, 30 percent more sugar, 30 percent more of most everything, just to keep up. Bacteria help us digest high-energy foods like complex sugars. Without microorganisms' help, all of these energy-rich sugars simply pass through us. To make up for that, animals without bacteria must consume a lot more simple sugars and fats.

Interestingly, even though germ-free mice ingest 30 percent more calories than infected mice, the germ-free mice have much lower levels of body fat. And when scientists returned the bacteria to germ-free mice, these mice underwent a 60 percent gain in body fat within fourteen days and often became insulin-resistant. This happens because gut bacteria accelerate absorption of sugars and their conversion to fat. Such a gain would have been a considerable gift for our ancestors who ate rarely and needed to store all the energy they could. It is less of a gift to modern humans who eat early and often. In fact, there is good evidence that the exact composition of our gut bacteria may be a major factor in predisposing some of us to obesity.

Mice without germs don't develop normal intestines. Uninfected intestines don't develop the same cell layers found in normal intestines. On top of that, the blood supply between the gut and the rest of the body doesn't form properly in these mice. Digested food fails to pass through the walls of these intestines. The mice that must live with these abnormalities often die from malnutrition.

Mice without germs don't develop functional immune systems. Germ-free rabbits fail to develop immune systems altogether. In rabbits, most immune development occurs in the intestines. Rabbit intestines without bacteria do nothing—no immunity, no digestion—nothing.

Germ-free rabbits are often overwhelmed by infections that a normal rabbit would never even notice. The lack of infection that these rabbits suffered as pups renders them defenseless as adults. And if you infect these rabbits as adults, you usually end up with a bloody mass of meat and fur. What they didn't get as pups, you cannot give them as doe or buck. Immunity depends on infection.

Germ-free mice get inflammatory bowel diseases—diseases like Crohn's disease and ulcerative colitis in humans—that normal mice never have. It seems that intestinal bacteria and other microorganisms normally suppress gut inflammation and keep it at an acceptable level.

This suppression allows us humans to maintain a flourishing layer of germs in our intestines without destructive inflammation. From an immunologist's point of view, this is very nearly a miracle. Normally, bacteria light and stoke the coals that burn beneath inflammation (think of strep and staph and influenza). But not in the gut or on the skin. In the gut and on the skin, bacteria somehow strike the chords that signal the fragile harmony between infection, inflammation, and immunity—a piece as intricate as a Bach fugue.

Uninfected mice must be fed vitamins and other nutrients that infected mice make themselves. The bacteria that normally haunt the halls of our intestines give us something we cannot do without.

And mice without germs are much more prone to allergies than normal mice. Under certain conditions, injection of ovalbumin (the major protein in egg whites) causes mice to become allergic to ovalbumin. But if these same mice are first infected with mycobacteria--a particular type of small bacteria—and then injected with ovalbumin, the mice don't develop allergies.

The list goes on. Mice and rabbits without bacteria and fungi and parasites live pitiful lives.

How is it that infection does so much good?

First, the microorganisms themselves create some of the good. Bacteria chew large sugars into smaller ones that we mammals can absorb. Bacteria produce vitamin K as well as many other nutrients that we cannot make on our own. Vitamin K helps blood clot—a fairly significant human endeavor.

Sugars and vitamins. Nutrients, enzymes, and the keys that unlock our potential. Bacteria feed us.

But the greatest good that comes from infection does not come directly from the products of the bacteria themselves. The greatest good comes from the ways the bacteria manipulate us. Most of the effects that bacteria have on animals, including humans, result from bacteria taking control of host genes. That's right. The bacteria that live inside of us have learned to manipulate our genes—bacteria control some of the most intimate and elemental pieces of us.

The effects of intestinal bacteria on absorption, intestinal development, immune development, prevention of infections, the formation of intestinal blood vessels, and water absorption all result from bacterial control of host (human) genes. Bacteria control hundreds of our genes, maybe more. Humans have only about thirty thousand genes total. Bacterial regulation of at least a few hundred of those genes represents a pretty significant concession of command to another species. We may imagine that we are the ones who direct our destinies. But we should not be so quick to discount the billions upon billions of others who live within our border

Nor should we fail to recognize the potential of these tireless workers to organize their vast numbers for singular purposes.

The bacteria inside of us do not simply wander about as individual germs trying to think of something useful to do. They get organized. When individual bacteria attach to intestines or mouths and then multiply, the germs change. As the bacteria spread, they begin to form thick sheets called biofilms. When the biofilms form, the bacteria undergo dramatic genetic changes and produce many products that are not produced by the same bacteria outside of biofilms. Inside of biofilms, bacteria differentiate, become individuals with individual needs and skills. Some of the germs collect into mushroomlike stalks, others secrete thick polymers that surround and protect the biofilm. Then channels open for water and nutrients, and DNA molecules (genes) pass from bacterium to bacterium. In place of a million or a billion individuals, one thing appears, spread across living human tissues—a single entity with a single purpose. A multicellular being swapping stories and genes and proteins and sugars, with itself and with us.

Then a most remarkable event occurs: The bacteria begin to speak among themselves using complex chemicals. This process is called quorum sensing, and it controls many of the functions of bacteria in biofilms.

One striking example of the power of quorum sensing happens in squid. Euprymna scolopes is a pink-and-brown mottled squid about the size of your hand. E. scolopes thrives near the Hawaiian Islands. Unlike most of its relatives, these squid live in fairly shallow waters near beaches. The squid hunt and feed at night. Because the water where they live is so shallow, a full or partly full moon causes these squid to cast shadows in the sand as they squirt across the shoals. The moving shadows attract predators, predators with a taste for E. scolopes.

E. scolopes has solved this problem with talking bacteria. Vibrio fischeri, a marine bacterium, grows in high-density biofilms within specialized organs on the underside of E. scolopes. And when V. fischeri achieves a high enough density within the squid, quorum sensing causes all the bacteria to emit light.

As the glow blossoms, the shadows that swim beneath the squid vanish. Predators become confused and drift off in search of easier prey.

E. scolopes and V. fischeri, though they have different names, are a single creature. Neither is anything without the other. And in the end, it is the bacteria and the stories they spread among themselves that save them all.

Inside humans and other mammals, biofilms don't generally light up our lives, but they do help us to survive. We are only beginning to understand all the ways bacteria use biofilms and quorum sensing. Some bacteria use quorum sensing to develop into pathogenic (disease-causing) organisms in humans. Other bacteria use quorum sensing to interact with and control host cells. And still other bacteria use quorum sensing to produce antibiotic factors that protect us from more dangerous infections. Inside of biofilms, bacteria begin to look more like multicellular organisms, more like us. And, at the same time, humans begin to look more like complex mixtures of animal and bacteria— multi- and single-celled beings that speak to one another and choose paths that neither could have walked alone.

The Miracle in the Dirt: The Hygiene Hypothesis

In the 1990s, Erika von Mutius began a study of the children of reunified Germany. Dr. Mutius, a pediatrician, had taken an interest in childhood asthma and allergies and the origins of these diseases. The reunification of East and West Germany gave her the opportunity to compare children who had grown up in relatively clean and healthful environments (West Germany) with children who had grown up under dirtier and less healthful conditions (East Germany). Dr. Mutius had fully expected that the children of East Germany would have more as well as more severe allergies and asthma. What she found was just the opposite. The children who had grown up under the dirtiest conditions had the fewest allergies and asthmas.

Allergies and asthmas are inappropriate immune responses against innocuous environmental elements—like pollen. It isn't clear why some people develop allergies and others don't. Part of the cause appears to be genetic. Dr. Mutius's work with the German children suggested that there was a major environmental factor as well. But the nature of that environmental factor remained cloudy. In later work, Dr Mutius studied children on farms and compared them to children living in more urban settings. Children who drank fresh milk from the farm and who had regular contact with farm animals were more than ten times less likely to have asthma and more than four times less likely to have hay fever (a common allergy). She and her coworkers concluded, "Long-term and early-life exposure to stables and farm milk induces a strong protective effect against development of asthma [and] hay fever. . . ." No negative effects of farm life were identified.

Dr. Mutius has gone on to show that similar differences in childhood exposures to infections may explain the differences in the rates of asthmas and allergies among children in China.

Very recently Dr. Mutius and other investigators found that childhood exposure to bacteria, particularly a group called gram-negative bacteria, correlates inversely with the frequency of asthmas among school-age children in Austria, Germany, and Switzerland. Specifically, these researchers measured the levels of endotoxin (a product of gram-negative bacteria) in the mattresses of European school-age children. They found that the higher the levels of endotoxin in children's mattresses, the lower the incidence of asthma. The more bacteria the children had been exposed to, the healthier they were. Similarly, investigators in Boston, Massachusetts, collected dust samples from infants' bedroom floors, mattresses, parents' beds, family rooms, and kitchens. The Boston researchers' findings correlated directly with those of Dr. Mutius. New England children exposed to higher levels of endotoxin during the first one to three months of life were much less likely to develop eczema than children in cleaner environments. Eczema, like allergies and asthma, arises when the immune system overreacts. Again, early frequent exposure to bacteria made children healthier and immune systems wiser. Absence of bacteria made things worse.

A group in France further investigated the connection between infection and immunity by giving nursing infants either normal baby formula or fermented baby formula. The fermented milk contained much higher levels of Bifidobacteria than the normal infant formula. When these researchers later immunized the children with polio vaccine, the infants fed the fermented formula regularly produced better immune responses against the poliovirus. The additional bacteria somehow helped these infants develop stronger immune systems that produced higher levels of protection against polio.

Clearly, in humans as well as rodents, bacterial infection is essential to the proper development of the immune system. Without it, we fail to protect ourselves, or worse, we turn on ourselves.

Helicobacter pylori is a bacterium that appears commonly among the normal flora of the human gut. The exact function of H. pylori is unknown, but there is solid evidence that this bacterium plays a role in the development of peptic ulcers. Nevertheless, a study performed in Britain indicates that when H. pylori is intentionally eliminated from people's intestines, there are several negative consequences, including changes that could lead to increased appetite, weight gain, and esophageal reflux. When the stomach or small intestine is compromised—by, say, too much aspirin—H. pylori causes ulcers. But without H. pylori, appetites may change, weight gain may follow, or the acids of the stomach may move into the esophagus, where they can do incredible damage.

Every year nearly twenty-five hundred children in the United States contract acute lymphoblastic leukemia, or ALL. ALL is the most common cancer of children, accounting for nearly 25 percent of all cancers diagnosed in children. When this cancer develops, a few white blood cell precursors take over the bone marrow. Normally, the bone marrow produces all of the many types of cells of the blood—red blood cells, lymphocytes, platelets, monocytes, eosinophils, basophils, neutrophils, and so on. As ALL develops, the bone marrow is forced to produce only a few types of white blood cells, and these white blood cells are rushed into production so quickly that most are completely nonfunctional. Children with ALL become anemic and thrombocytopenic (there are too few platelets in the blood). Platelets play a big role in repairing damaged blood vessels. So these children bruise and hemorrhage very easily. They are unusually susceptible to infections, especially bacterial infections. Without treatment, nearly all would die.

We know very little about the causes of ALL. Genes are clearly part of it. ALL tends to run in families and involves damaged chromosomes (deletions, inversions, etc.). There are also environmental factors that contribute.

Very recently, researchers in the United Kingdom have provided convincing evidence that one of the environmental factors that increase the risk of ALL is lack of early childhood infection. These investigators compared two large groups of children, ages two to fourteen. One group had attended day care, the other had not. The researchers looked for any relationship between how early the children had attended day care and their likelihood of developing ALL. They found that the earlier the children attended day care (less than three months of age), the less likely they were to develop leukemia. Early childhood exposure to other children reduces the risk of at least this form of cancer.

We know that immune systems don't develop properly in uninfected or underinfected mammals. And there is evidence that ALL, like some other human leukemias, develops after a viral infection, Children in day care come in contact with a large array of infectious microorganisms during critical periods of immune development. Children who remain at home, especially children in small families, encounter many fewer infectious agents. Because of this difference in the frequency and breadth of infection, it seems likely that the immune systems of these two groups of children develop differently. Such differences could make the underinfected group more susceptible to infection by leukemia-causing viruses, or the immune systems of underinfected children might respond against an infectious virus and then lose control. Since the working cells of the immune system are white blood cells, lack of control during an immune response could lead to dramatic expansion of white blood cells, just like that seen in ALL. Either way, children who encounter fewer unrelated children (infections) during the first few months of life are more likely to develop childhood leukemias. One more strike against sterility.

Allergies, asthma, obesity, inflammation, leukemia—the consequences of good clean living. We humans are complicated creatures.

But we like simple ways of looking at things. After Pasteur showed what anthrax could do to cattle and to humans, bacteria and all the other microscopic vermin became the enemy. After all, along the way, we saw what syphilis, plague, tularemia (named for Tulare County, California, this disease causes terrible ulcers in people's lungs and is one of the most infectious diseases known), and brucellosis (a bacterium that causes abortions in cattle and swine and fatalities in humans) could do. Diseases, we reasoned, especially infectious diseases, are bad. So when Fleming finally brought penicillin to the public in the late 1940s, it seemed a miracle. And as surely as any other miracle, it would have saved my uncle Henry's life, just as it saved thousands of lives, especially among children. We were overjoyed, and rightly so. This was our first and greatest victory in the treatment of infectious diseases. But in our joy, we may have gone too far.

Because of our first successes, and because of our lack of understanding about how bacteria weave the magic that they do, we were all only too eager to start spreading antibiotics everywhere.

At the beginning of the twenty-first century, we have a list of antibacterial drugs as long as our arms. On top of that, we have antifungal, antiviral, and antiparasitic drugs that would drop a billion bugs in an instant. To that we've added antibiotic crib mattresses, countertops, dinnerware, hand soaps, deodorants, mouthwashes, toothpastes, shampoos, toilet cleaners, dish soaps, cleaning sprays, aerosols, powders, scrubbers, toothbrushes, and towelettes. We give antibiotics to our cows and pigs and chickens like there was no tomorrow. Ignoring our four billion years of history with bacteria, we have tried and continue to try to push the bugs out of our lives. And we nearly have.

But not without consequences. Between 1980 and 2005, the number of Americans with asthma rose from 6.7 million to 17.3 million. And the frequency of asthma continues to rise faster than that of any other disease in the United States. By 2020, it is estimated that the number of people with asthma in the United States will nearly double, to 29 million.

Beyond the simple increase in numbers, there are some interesting trends in these increases. The level of parents' education correlates directly with the incidence of allergies. That is, the more educated the parents, the more likely the children are to suffer from allergies. And non-Hispanic white children are more likely than Hispanic children to have had allergies. Which suggests that with money, like education, the more you have the more likely it is that your kids will have allergies.

Though some might consider allergies and asthma as a fair trade-off for infectious diseases, it isn't the use of antibiotics in the treatment of infectious diseases that has led us to our present state. It is the overuse of antibiotics—drugs that we have spread like insulation to deafen us against the threat of infectious diseases—that has brought us to where we now stand.

Life and Death and Bacteria

Greg LeMond was once the greatest U.S. cyclist, and before he was done, he was the first non-European to win the Tour de France. Eventually, he won it three times—in 1986, 1989, and 1990. LeMond also won cycling's world championship twice—in 1983 and 1989. Blue-eyed and blond, LeMond was wildly popular with American cyclists, and even the French seemed enamored with him. After three victories in the Tour, American cyclists were beside themselves with joy. But in 1991, LeMond began to falter. That year, even though he wore the leader's yellow jersey briefly during the race, he finished seventh in the tour. In 1992, LeMond failed to finish the race. And finally, in 1994, he announced his retirement from competitive cycling. In the space of two years, LeMond had gone from cycling's greatest athlete to noncompetitive. But it wasn't exactly his fault. A part of him had failed, a part that most athletes give no thought to whatsoever.

The bacteria that cover our skin, our noses, our intestines, and our tracheae are not the only bacteria that we humans need if we are to survive. We also need bacteria inside every one of our cells.

Mammalian cells are eukaryotic cells, meaning they have cellular organelles—little membrane-wrapped structures—inside of them. These include, among others, the Golgi apparatus where proteins are festooned with sugars and directed to their final destinations; the endoplasmic reticulum where proteins are made; the nucleus where the chromosomes work their magic; endosomes where things are assembled, disassembled, eaten, and excreted; and mitochondria. The last of these, the mitochondria, are small peanut-shaped organelles found in varying numbers inside all of our cells. Mitochondria are the source of most of the energy it takes to be a human being. Mitochondria are like little machines that extract enormous amounts of energy from fats and sugars and make that energy into a chemical called adenosine triphosphate (ATP), the stuff of life. Every action that distinguishes a living human being from a dead human being is dependent on ATP. ATP comes from mitochondria. Amazingly, mitochondria are bacteria.

These little bits of us are the descendants of free-living bacteria that long ago moved inside eukaryotic cells. Like all other bacteria, mitochondria have no internal membranes. Mitochondria have their own DNA, but no nucleus, also like all other bacteria. And mitochondria divide when their environment is right, not when their host cell divides. Mitochondria are the living remnants of bacteria tucked away inside every one of our cells. Without these bacteria, we would not be human. Bacteria fuel every human action.

Today, mitochondria's nearest living relatives appear to be Rickettsia Prowazekii. This is the bacterium that causes typhus, the disease that killed Anne Frank and thousands of others in Nazi concentration camps.

Billions of years ago, the bacteria that would one day become mitochondria were ingested by, infected, or in some other way inserted themselves inside of the primitive ancestors of eukaryotic cells. But instead of destroying one another, these two cells struck a bargain— energy for food. The arrangement was novel by all current standards, but it appealed to both parties. The bacteria found an unlimited supply of food and in return they provided a nearly unlimited amount of energy to their hosts. The face of evolution changed forever.

This sort of relationship is called symbiotic, two different living things inhabiting the same space. And when one of the beings is inside of the other, it is called an endosymbiotic relationship. The one who lives within is called an endosymbiont. Bacteria are endosymbionts that play a big part in our lives.

They also play a big part in our deaths. Besides providing most of the energy we need to be humans, mitochondria regulate how we develop inside our mothers and whether our adult cells live or die. As a human fetus forms, some of its cells must die to allow for normal development. For example, at about week nine of human development, the hands and feet of the fetus look like paddles, because the toes and fingers are webbed. As fetal development continues, the cells that form the webs die. The death of these cells allows for the continued development of normal fingers and toes. The timing for this event is critical. If the cells of the web die too early, fingers and toes don't develop fully. If the cells of the web die too late or not at all, the infant is born with webbed hands or feet or both. The mitochondria inside the cells of the web determine when these cells die.

Similarly, throughout our adult lives, most cells of our bodies must periodically die and be replaced by new cells. The balance between these two events—cell death and cell division—is critical. If cells die too slowly, a person will soon have enough skin or liver for two people, then four, or worse, cancer. If cells die too quickly, organs atrophy and people die. Mitochondria and their products regulate the rate of cell death throughout our lives. And it now appears that just how mitochondria do this also determines just how long and how well we live.

As a child, Greg LeMond made a list of three things he wished to do. The first was to win the Tour de France. The second was to win a World Cycling Championship. The last was to win the Olympic Men's Pro Road Race.

In 1980, LeMond made the Olympic cycling team but never got the chance to compete, because that year, the Americans boycotted the Moscow Olympics. His professional status kept him from competing later in his career.

In 1983, LeMond won the first of two world championships. In 1986, he won his first Tour de France. His star looked very bright. But in 1987, he was accidentally shot in the back by his brother-in-law while the two men were hunting. LeMond underwent emergency surgery to remove pellets from his liver, his kidneys, his lung, and his intestines. But even af ter surgery, at least two lead pellets remained in the lining of his heart, and nearly thirty pellets were never removed from the muscles of his back. Nevertheless, in 1989, Greg LeMond overcame all of that and again won the Tour de France. His wounds and the remnants of the shotgun blast could not stand for long between LeMond and the sport he loved most.

But in 1992, for the first time ever, LeMond couldn't finish the Tour de France. It wasn't because of the shotgun pellets. His legs just wouldn't push him up the big hills any longer. And it wasn't because of lack of training or effort. Instead, LeMond was suffering from a disease called mitochondrial myopathy—muscle weakness caused by inadequate energy output from his mitochondria.

We still don't know much about this disease, but one thing was clear even then. When LeMond's bacteria began to fail, he was powerless to change his fate. The mitochondria that had carried him to the pinnacles of cycling were failing him now. The energy that drove his feet through pedal stroke after pedal stroke up Mont Ventoux couldn't do it even one more time. In 1994, LeMond quit the race he loved and retired to Minnesota.

None of us is a single thing, a person apart, an island, a hermit, or a lone wolf. We are orchestras of individuals. And in every race we run, every thought we form, every human victory or defeat, each player has a part.

So too for these ants, strewn across my driveway this morning. The eggs, the queen, the caves filled with drones, and caches of food are rarely seen. But they are there. Without them the rest is meaningless. And though there is a queen, she never gives an order. Nor does anyone else. Yet ants never want for direction. They may be without minds, but they are not mindless

We are no different. Upon and beneath the surface of our skins, a colony of workers toils continuously. With no apparent connection to our brains, part of us goes about its business tirelessly and mindlessly as ants. We are oceanfuls of life. We are, each of us, as numerous as the stars. No human ever acted alone.

I think at last of Howard Hughes, the great aviator and billionaire who ended his days huddled in a hotel room because of an obsessive fear of infection. No ant would be so foolish. Our salvation doesn't lie between the sterile sheets of a sanitized room. As every ant knows instinctively, it lies instead in the dirt beneath our feet.