Is Alzheimer's Contagious?
The following is an excerpt from the new book Infectious Madness by Harriet A. Washington (Little, Brown, 2015).
We have met the enemy, and he is us.
— Pogo comic strip, 1971
Jeroen Raes glides onto the stage. Clad in a simple dark sweater but wearing confidence like an Armani suit, he glances at the overhead projection of his first slide before his gaze flits briefly in the direction of his audience. It doesn’t alight there; he’s unconcerned with eye contact.
“So you think you are human,” he begins.
Raes is giving a Brussels TED talk about his work as director of Flanders’s Vlaams Instituut voor Biotechnologie, or VIB, the Belgian research institute, and he tosses a dizzying array of numbers at us: “There are seven billion people on this planet,” he announces, and goes on to say that our bodies are home to ten times as many microbial cells as human cells. My attention begins to wander, because I’ve heard these numbers before. Except for one.
“You know how many microbes there are [on earth]? Five nonillion.”
Five nonillion? That’s a 5 followed by 30 zeros. There are, in other words, as many microbes living on this planet as there are stars in the universe — multiplied by five million.
It’s a good thing that the scientists in Paul de Kruif ’s Microbe Hunters didn’t know this. Even those irrepressible twentieth-century stalwarts might have despaired of exterminating their targeted pathogens had they known the size of the army arrayed against them. Instead, to a man — and they were all men — they were confident, even arrogant in their dominance. De Kruif presents them as conquering heroes of the microbial world, and his book is studded with martial metaphors, as are others of the genre — his Hunger Fighters and Han Zinsser’s Rats, Lice and History. The warlike tone is echoed in the work of evolutionary theorists like George C. Williams, who wrote, “Natural selection, albeit stupid, is a story of unending arms races, slaughter and suffering.”
Casting the evolutionary contest as a war to the death between humans and microbes has become a cliché, reflected in the ways we conceptualize and speak about illness. Man fights to annihilate pathogens and vanquish disease. Microbes, although versatile, often favor guerrilla warfare, invading by stealth, crippling or taking over their hosts’ immunological armies, and sapping their strength, blood, fluids, and resources before wiping them out. Patients “battle” cancer and drugs “suppress” infection in a scorched-earth arms race in which pathogens seek to eradicate their enemies by ever-harsher measures. And in this age of antibiotic-resistant organisms, we do the same to them. A type of bacterium has become drug resistant? Turn to a harsher antibiotic with a broader spectrum that will kill even more types — and render itself useless when bacteria become resistant to it too. Douse the environment, and yourself, for good measure, with the antimicrobial hand sanitizers that sprout on office walls, in restrooms, and inside handbags, although studies show that soap and water is more effective at keeping germs at bay without fostering dreaded resistant strains.
When we habitually describe contests between rival organisms as brute death matches, it helps such blunt and shortsighted approaches sound more rational and necessary than they are.
Influenced by Williams’s 1960 book Adaptation and Natural Selection, the 1976 bestseller The Selfish Gene by Richard Dawkins moved this conflict squarely into the genetic arena by proposing that it is our species’ genes, not our individual selves, that direct and profit from the battle for survival with the sole goal of propelling human genes into the next generation. We, apparently, are just along for the ride.
Dawkins’s gene-centered view of evolution recasts many instances of apparent altruism as ruthless strivings for absolute dominance. When the monkey shares his meager meal with his community, when a woman risks her life to free her trapped cousin from a burning building, when a gay man helps support and raise his niece, the altruism does not seem to improve the altruists’ fates. But, Dawkins argues, it is the gene that seeks immortality, so the more closely two individuals are genetically related, the more logical it is to behave selflessly. The fitness of the gene — that is, the extent to which it survives into the next generation — is the true measure of its evolutionary success, so saving the life of your relation, feeding your extended family from which you or your children will choose a mate, and ensuring that children who are genetically related to you survive all boost your genes’ evolutionary fitness and are therefore sound survival strategies for your genome.
But despite the sophistication of these arguments, Dawkins perpetuated the military Weltanschauung when he invested the gene with the same anthropomorphic selfishness.
The Microbes Within
What if this worldview is wrong, and human evolutionary survival depends on something other than killing the competition in order to usher our genes safely into the future? What if, despite the rampant sickness caused by pathogens, our myopic view of them causes us to see malevolent foreign invaders where there are none and encourages us to obliterate organisms when our future health demands a more nuanced approach?
And what if, as the Pogo epigraph above suggests, the enemy is not wholly external?
For we are mostly microbes, and this is what Raes meant by his intimation that you are not wholly human. The numbers he offered supply evidence.
One hundred trillion viruses, fungi, archaea, and protozoa — but mostly bacteria — call your intestines home, and your guests outnumber your human cells ten to one. A coat of many microbes covers your skin, eyes, genitals, and mouth, each bacterial genotype specializing in an area of the body. Microbial scientists call this the commensal microbiome, a bit of a misnomer because the adjective describes a relationship in which one organism benefits while the other is unaffected, and as we shall soon see, you and your fellow travelers affect each other in many ways, sometimes dramatically.
Staphylococci colonize the skin, Escherichia coli prefer the colon, and lactobacilli coat the vagina. And that’s just on the surface; ten thousand different species of organisms thickly populate your gut, the folded, invaginated, nine-meter expanse from your mouth through your stomach and anus. Just as our genes constitute our genomes, these creatures make up our microbiomes. But unlike genes, with their numerical constancy, the human microbiome is constantly changing in type and numbers. Its makeup varies in different sites of the body and often in different sites on the globe. It changes over a person’s lifetime and in relation to the host’s genes. And mental health changes with it.
“Half of your stool is not leftover food. It is microbial biomass,” Lita Proctor, program director of the Human Microbiome Project, told the New York Times. We are so much larger than our microbial hangers-on that they contribute only an extra five or six pounds of body weight, but like unemployed houseguests, you can never get rid of them.
Our wealth of internal life should not surprise us. In sheer numbers, microbes rule the world: every teaspoon of seawater contains five million bacteria and fifty million viruses, which are the most numerous “living” things in the sea, a summit they reached by infecting other organisms, including bacteria.
Yet size and census counts matter less to our mental health than the microbiome’s astonishing power to keep a person healthy — or ill — and guide the immune system’s development. Embedded within the walls of your gut’s microbial rain forest is a web that has a thousand times more neurons than your brain. This neural web of cells, dubbed the enteric nervous system, or ENS, weighs twice what your brain does and deploys neurotransmitters that communicate with the brain.
The ENS influences your mind as well as your body. It first does so by globally shaping the development of the immune system, 80 percent of whose cells reside in your gut. By so guiding the immune system, the ENS determines your reaction to microbes’ behavior and how the interplay of the immune system and microbes affects your health, both physical and mental. But evidence from human studies suggests that the ENS is also directly connected to some specific mental disorders, including depression, autism, and possibly chronic fatigue syndrome. This explains why electrical stimulation of the vagus nerve, for example, is a treatment for depression. “I’m always by profession a skeptic,” Dr. Emeran Mayer, professor of medicine and psychiatry at the University of California, Los Angeles, told NPR, “But I do believe that our gut microbes affect what goes on in our brains.”
Semantics shape conception, so in order to understand how the enteric microbes and the ENS direct the formation of our immune systems, it helps if we take off the verbal blinders. The warlike metaphors of which science is so fond distort our view and limit our ability to express what is happening, as a type of “war cam” disregards mutualism, symbiosis, and the many benefits that microbes impart. Martial language fosters a myopia that shrouds the true nature of our intimate relations with some bacteria.
Rather than mounting direct attacks on the body’s immune system and brain, as the traditional language of battling and vanquishing microbes assumes, the internal microbiome subtly shapes and directs immune responses and, therefore, health and behaviors. Despite our big, complex brains, our single-celled passengers have a disquieting ability to manipulate us. And although this can evoke discomfort, it can also be a good thing.
Passengers is not quite the correct term. Most of the human bacterial complement has lived and evolved with our species for more than eight hundred million years, and some have melded so intimately with our bodies that they literally have become us.
For example, each human cell contains critically important organelles called mitochondria. They process food into energy rich adenosine triphosphate, or ATP, molecules, whose high-energy bonds provide 90 percent of the fuel that we need to function. A mitochondrion is an endosymbiont (from the Greek words for “within,” “together,” and “living”), an organism that lives within the cell or body of another organism.
Widely accepted endosymbiotic theory holds that eons ago, these mitochondria were free-living bacteria that found it in their evolutionary interests to move into human cells permanently. As they became an essential part of us, we benefited as well, from those high-energy ATP bonds. There is plenty of evidence of mitochondria’s bacterial origins: mitochondria reproduce by dividing, as bacteria do, and they have even retained their own thirty-seven genes contained in the circular single-stranded molecule of DNA that is typical of free-living bacteria but that we now count among our human genes. More than thirteen diseases are caused by mutations in these mitochondrial genes, including forms of diabetes and deafness that are inherited through our mothers, but eliminating mitochondria is not an option, because we cannot survive without them.
There are many other types of relationships between us as hosts and our resident microbes that are often broadly characterized as symbiosis or commensalism, describing a relationship in which at least one of the organisms benefits. In mutualism, both organisms benefit.
We are home to other endosymbionts. We need the stomach bacteria that stimulate our immune-system development, digest our fibrous foods, and unlock nutrients like isothiocyanate, which protects against cancer and is extracted from the broccoli we eat. Microbes neutralize external pathogens, like the ingested bacteria that cause food poisoning. We need the resident microbes that make vitamins such as biotin, vitamin K, and vitamin D, and we may even need Helicobacter pylori, which causes ulcers and stomach cancers but seems to sometimes protect against obesity. Bacteria also are necessary for metabolizing drugs, and how much of some medications, like the heart drug digoxin, reaches a person’s bloodstream depends on which bacteria are in his microbiome.
No wonder microbial scientists are wont to refer to the organisms in the microbiome as our “friends.” Jeroen Raes’s work at VIB12 includes experiments that show how anxiety behavior and exploratory behavior in mice are determined by what flora they have, and Dr. Ramnik Joseph Xavier, director of the Center for the Study of Inflammatory Bowel Disease at Harvard Medical School, agrees. Xavier points out that we rely on microbes for the folic acid that is essential to health and necessary to prevent birth defects. He warns against using probiotic supplements to do this job, because they introduce too few microbes and are not within the intestines’ carefully curated right balance: “Bacteria survive and do better when they are with their friends.”
Raes and his team divined the numbers he bandies about by using techniques unknown to the twentieth-century microbe hunters. They extracted DNA from the microbes in our internal rain forest using automated sequencing machines to determine how many and what kinds of microbes are resident in both healthy and diseased guts. They then assessed what these microbes’ genes did, because microbes other than mitochondria have genes too, a lot of them. When a European Union consortium assessed the genomes of 124 people, it found that the microbes within each individual harbor 3.3 million different genes, dwarfing the mere 25,000 in the human genome.
What, then, does it mean to speak of the human genome when we carry millions more bacterial genes than Homo sapiens genes? And if we speak of the medical fortunes of a selfish gene, can we separate our species’ genes from those of the microbial multitudes that have evolved with us so closely and for so long that we now cannot live without them?