“In Missing Microbes, Martin Blaser sounds [an] alarm. He patiently and thoroughly builds a compelling case that the threat of antibiotic overuse goes far beyond resistant infections.”—Nature
Renowned microbiologist Dr. Martin J. Blaser invites us into the wilds of the human microbiome, where for hundreds of thousands of years bacterial and human cells have existed in a peaceful symbiosis that is responsible for the equilibrium and health of our bodies. Now this invisible Eden is under assault from our overreliance on medical advances including antibiotics and caesarian sections, threatening the extinction of our irreplaceable microbes and leading to severe health consequences.
Taking us into the lab to recount his groundbreaking studies, Blaser not only provides elegant support for his theory, he guides us to what we can do to avoid even more catastrophic health problems in the future.
“Missing Microbes is science writing at its very best—crisply argued and beautifully written, with stunning insights about the human microbiome and workable solutions to an urgent global crisis.”—David M. Oshinsky, author of the Pulitzer Prize-winning Polio: An American Story
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About the Author
Dr. Martin Blaser has studied the role of bacteria in human disease for over 30 years. He is the director of the Human Microbiome Program at NYU. He founded the Bellevue Literary Review and has been written about in newspapers including The New Yorker, Nature, The New York Times, The Washington Post, and The Wall Street Journal. His more than 100 media appearances include The Today Show, GMA, NPR, the BBC, The O’Reilly Factor, and CNN. He lives in New York City.
Read an Excerpt
How the Overuse of Antibiotics is Fueling our Modern Plagues
By Martin J. Blaser
Henry Holt and CompanyCopyright © 2014 Martin Blaser
All rights reserved.
I never knew two of my father's sisters. In the little town where they were born, early in the last century, they didn't see their second birthdays. They had high fevers, and I am not sure what else. The situation was so dire that my grandfather went to the prayer house and changed his daughters' names to fool the angel of death. He did this for each girl. It did no good.
In 1850, one in four American babies died before his or her first birthday. Lethal epidemics swept through crowded cities, as people were packed into dark, dirty rooms with fetid air and no running water. Familiar scourges included cholera, pneumonia, scarlet fever, diphtheria, whooping cough, tuberculosis, and smallpox.
Today, only six in every thousand infants in the United States are expected to die before age one — a remarkable improvement. Over the past century and a half, our nation and other countries in the developed world have been getting healthier. Chalk it up to improved sanitation, rat control, clean drinking water, pasteurized milk, childhood vaccinations, modern medical procedures including anesthesia, and, of course, nearly seventy years of antibiotics.
In today's world, children grow up without the deformed bones caused by lack of vitamin D or "cloudy" sinuses from infections. Nearly all women survive childbirth. Eighty-year-olds, once consigned to the veranda, are swatting tennis balls, often with the help of a metal hip joint.
Yet recently, just within the past few decades, amid all of these medical advances, something has gone terribly wrong. In many different ways we appear to be getting sicker. You can see the headlines every day. We are suffering from a mysterious array of what I call "modern plagues": obesity, childhood diabetes, asthma, hay fever, food allergies, esophageal reflux and cancer, celiac disease, Crohn's disease, ulcerative colitis, autism, eczema. In all likelihood you or someone in your family or someone you know is afflicted. Unlike most lethal plagues of the past that struck relatively fast and hard, these are chronic conditions that diminish and degrade their victims' quality of life for decades.
The most visible of these plagues is obesity, defined in terms of the body mass index (BMI), which expresses the relationship between a person's height and weight. People of healthy weight have a BMI between 20 and 25. Those whose BMI is between 25 and 30 are overweight. Everyone with a BMI over 30 is obese. Barack Obama has a BMI of about 23. The BMIs of most U.S. presidents have been under 27, except for that of William Howard Taft, who once got stuck in the White House bathtub. He had a BMI of 42.
In 1990, about 12 percent of Americans were obese. By 2010, the national average was above 30 percent. Next time you go to an airport terminal, supermarket, or mall, look around and see for yourself. The obesity epidemic is not just a U.S. problem; it's global. As of 2008, according to the World Health Organization (WHO), 1.5 billion adults were overweight; of these, over 200 million men and nearly 300 million women qualified as obese. Many of these people live in developing countries that we associate more with famine than with overeating.
These figures are alarming, but the really shocking fact is that this accumulation of global human body fat has been accelerating not over the course of a few centuries but in a mere two decades. Yet fat- and sugar-rich foods, so often blamed for all the extra pounds, have been ubiquitous for a good deal longer than that, at least in the developed world, and the new generations of overweight people in the third world have not suddenly adopted a Kentucky-fried American-style diet. Epidemiologic studies have shown that high caloric intake, while definitely not helpful, is not sufficient to explain the distribution or course of the worldwide obesity epidemic.
At the same time, the autoimmune form of diabetes that begins in childhood and requires insulin injections (juvenile or Type 1 diabetes) has been doubling in incidence about every twenty years across the industrialized world. In Finland, where record keeping is meticulous, the incidence has risen 550 percent since 1950. This increase is not because we are detecting Type 1 diabetes more readily. Before insulin was discovered in the 1920s, the disease was always fatal. Nowadays, with adequate treatment, most children survive. But the disease itself has not changed; something in us has changed. Type 1 diabetes is also striking younger children. The average age of diagnosis used to be about nine. Now it is around six, and some children are becoming diabetic when they are three.
The recent rise in asthma, a chronic inflammation of the airways, is similarly alarming. One in twelve people (about 25 million or 8 percent of the U.S. population) had asthma in 2009, compared with one in fourteen a decade earlier. Ten percent of American children suffer wheezing, breathlessness, chest tightness, and coughing; black children have it worst: one in six has the disease. Their rate increased by 50 percent from 2001 through 2009. But the rise in asthma has not spared any ethnicity; the rates were initially different in various groups, and all have been rising.
Asthma is often triggered by something in the environment such as tobacco smoke, mold, air pollution, cockroach leavings, colds, and flu. Once an attack begins, asthmatics gasp for air and, without quick medication, are rushed to emergency rooms. Even with the best care, they can die, as did the son of a physician colleague. No economic or social class has been spared.
Food allergies are everywhere. A generation ago, peanut allergies were extremely rare. Now, if you stroll through any preschool, you will see walls plastered with "nut-free zone" bulletins. More and more children suffer immune responses to proteins in foods, not just in nuts but in milk, eggs, soy, fish, fruits — you name it, someone is allergic to it. Celiac disease, an allergy to gluten, the main protein in wheat flour, is rampant. Ten percent of children suffer from hay fever. Eczema, a chronic skin inflammation, affects more than 15 percent of children and 2 percent of adults in the United States. In industrialized nations, the number of kids with eczema has tripled in the past thirty years.
These disorders suggest that our children are experiencing levels of immune dysfunction never seen before, as well as conditions such as autism, a much discussed and debated modern plague that is a focus of my laboratory. Nor are adults escaping their own share of modern plagues. The incidence of inflammatory bowel disease, including Crohn's and ulcerative colitis, is rising, wherever we look.
When I was a medical student, esophageal reflux, which causes heartburn, was uncommon. But the ailment has exploded in these past forty years, and the cancer it leads to, adenocarcinoma of the esophagus, is the most rapidly increasing cancer in the United States and everywhere else it has been tracked, and is a particularly nasty problem for Caucasian men.
* * *
Why are all of these maladies rapidly rising at the same time across the developed world and spilling over into the developing world as it becomes more Westernized? Can it be a mere coincidence? If there are ten of these modern plagues, are there ten separate causes? That seems unlikely.
Or could there be one underlying cause fueling all these parallel increases? A single cause is easier to grasp; it is simpler, more parsimonious. But what cause could be grand enough to encompass asthma, obesity, esophageal reflux, juvenile diabetes, and allergies to specific foods, among all of the others? Eating too many calories could explain obesity but not asthma; many of the children who suffer from asthma are slim. Air pollution could explain asthma but not food allergies.
Many theories have been proposed to explain each disorder: lack of sleep makes you fat; vaccines lead to autism; genetically engineered wheat strains are toxic to the human gut; and so on.
The most popular explanation for the rise in childhood illness is the so-called hygiene hypothesis. The idea is that modern plagues are happening because we have made our world too clean. The result is that our children's immune systems have become quiescent and are therefore prone to false alarms and friendly fire. A lot of parents these days try to ramp up their kids' immune systems by exposing them to pets, farm animals, and barnyards or better still by allowing them to eat dirt.
I beg to differ. To me, such exposures are largely irrelevant to our health. The microbes present in dirt have evolved for soil, not for us. The microbes in our pets and farm animals also are not deeply rooted in our human evolution. The hygiene hypothesis, as I will show you, has been misinterpreted.
Rather we need to look closely at the microorganisms that make a living in and on our bodies, massive assemblages of competing and cooperating microbes known collectively as the microbiome. In ecology, biome refers to the sets of plants and animals in a community such as a jungle, forest, or coral reef. An enormous diversity of species, large and small, interact to form complex webs of mutual support. When a keystone species disappears or goes extinct the ecology suffers. It can even collapse.
Each of us hosts a similarly diverse ecology of microbes that has coevolved with our species over millennia. They thrive in the mouth, gut, nasal passages, ear canal, and on the skin. In women, they coat the vagina. The microbes that constitute your microbiome are generally acquired early in life; surprisingly, by the age of three, the populations within children resemble those of adults. Together, they play a critical role in your immunity as well as your ability to combat disease. In short, it is your microbiome that keeps you healthy. And parts of it are disappearing.
The reasons for this disaster are all around you, including overuse of antibiotics in humans and animals, Cesarian sections, and the widespread use of sanitizers and antiseptics, to name just a few. While antibiotic resistance is a huge problem — old killers like tuberculosis are increasingly resistant and making a comeback — there now seem to be separate ones, affecting people with such scourges as Clostridium difficile (C. diff), bacteria of the digestive tract resistant to multiple antibiotics, a potential danger in the hospital, and a spreading pathogen, methicillin-resistant Staphylococcus aureus (MRSA), which can be acquired anywhere. The selective pressure of antibiotic use is clearly increasing their presence.
But as terrible as these resistant pathogens are, the loss of diversity within our microbiome is far more pernicious. Its loss changes development itself, affecting our metabolism, immunity, and cognition.
I have called this process the "disappearing microbiota." It's a funny term that does not immediately roll off your tongue, but I believe it is correct. For a number of reasons, we are losing our ancient microbes. This quandary is the central theme of this book. The loss of microbial diversity on and within our bodies is exacting a terrible price. I predict it will be worse in the future. Just as the internal combustion engine, the splitting of the atom, and pesticides all have had unanticipated effects, so too does the abuse of antibiotics and other medical or quasi-medical practices (e.g., sanitizer use).
An even worse scenario is headed our way if we don't change our behavior. It is one so bleak, like a blizzard roaring over a frozen landscape, that I call it "antibiotic winter." I don't want the babies of the future to end up like my poor aunts. That is why I am sounding an alarm.
* * *
My personal journey toward the realization that our friendly microbes are in trouble began on July 9, 1977. I remember the date because it was the first time I heard the name of a microbe, Campylobacter, that literally set my life's research into motion. I was a newly minted fellow in infectious diseases at the University of Colorado Medical Center in Denver.
That morning I was asked to see a thirty-three-year-old patient who had come to the hospital a few days earlier. He had been suffering from a high fever and was confused. A spinal tap confirmed that he had meningitis, a serious inflammation of the nervous system. His doctors sent samples of his blood and spinal fluid to the culture lab to determine whether the cause was a bacterial infection and, if so, to find out what kind of bacterium it was. While those tests were pending, they started him on antibiotics anyway because he looked quite ill. They believed that he needed big doses of antibiotics immediately or he would die. They were correct.
The test results revealed a slow-growing bacterium identified as Campylobacter fetus, an organism that no one at the hospital had ever heard of. That's why I was called. On the job for nine whole days, I was supposed to know the answers.
Campylobacter organisms are a genus of spiral-shaped bacteria. Like that of so many tiny corkscrews, their helical shape helps them penetrate the gelatin-like mucus that lines the gastrointestinal tract. But why the odd species name fetus? (In biology, each organism is identified first by the name of its genus, in this case Campylobacter, and then by its species, in this case fetus. Each genus has many species and subspecies. Humans are Homo sapiens: of the genus Homo and the species sapiens.) Digging into the medical literature, I discovered that the microbe had this strange name because it affected pregnant sheep and cattle, causing them to abort. It rarely infected humans. How our patient got infected was a mystery. He was a city man, a musician.
Once we knew the organism, we tailored an appropriate antibiotic treatment, and the patient recovered in a couple of weeks. Meanwhile, I was scheduled to give a talk at a clinical conference and decided I would speak about Campylobacter. What could be better than talking about a rare infection that no one knew anything about? My own ignorance as a novice would go undetected.
In reading more about Campylobacter fetus, I soon learned it has a cousin, Campylobacter jejuni. (The jejunum is part of the small intestine.) The literature, scanty as it was, suggested that people infected by C. fetus usually have bloodstream infections, whereas those invaded by C. jejuni tend to have diarrheal illnesses. Here were two nearly identical organisms with very different effects on the body. Why would one Campylobacter stay trapped in the gut, where it kind of belonged, while the other escaped like a ninja into the bloodstream? I was hooked.
Over the next several years, moving from academia to the Centers for Disease Control and back to academia (University of Colorado and Vanderbilt), I became an expert in C. fetus, my "favorite" bacterium, and discovered some secrets about its Houdini-like nature.
In this respect, C. fetus played an early role in the evolution of my disappearing microbiome hypothesis by teaching me fundamental lessons about how bacteria can persist in their hosts. Yes, they cause disease but, as I later came to appreciate more fully, there also are bacteria that live in us, using a variety of similar tools to escape our immune system. They usually don't harm us; rather, they protect us. I learned that bacteria employ countless tricks, honed from millions of years of trial and error, to do their business, which might either help or hurt their hosts, depending on the circumstances. I will discuss this concept in depth.
C. fetus in particular taught me about stealth — how microorganisms acquire means of escaping host defenses. While 99.9 percent of all bacteria, including C. jejuni, are killed by factors found in blood, C. fetus glides into the bloodstream by donning a kind of "cloak of invisibility." Even so, it can be trapped by the cells within a heathy liver. But if it is not cleared from the blood in someone with an injured liver (I later learned that the patient whom I'd seen earlier was a severe alcoholic), meningitis can result.
While I was working on C. fetus and C. jejuni in the early 1980s, a new relative of Campylobacter was discovered in, of all places, the stomach. Dubbed "gastric campylobacter-like organism" or GCLO (we now call it Helicobacter pylori), it turned out to possess a bag of tricks that, in Jekyll and Hyde fashion, can do us harm or protect us from harm. I have been chasing this organism for the past twenty-eight years, for I believe, and hope to prove, that it is the bellwether that can help solve the puzzle of our modern plagues.
Excerpted from Missing Microbes by Martin J. Blaser. Copyright © 2014 Martin Blaser. Excerpted by permission of Henry Holt and Company.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
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Table of Contents
1. Modern Plagues 1?
2. Our Microbial Planet 12?
3. The Human Microbiome 22?
4. The Rise of Pathogens 40?
5. The Wonder Drugs 50?
6. The Overuse of Antibiotics 64?
7. The Modern Farmer 79?
8. Mother and Child 87?
9. A Forgotten World 104?
10. Heartburn 123?
11. Trouble Breathing 130?
12. Taller 144?
13. ... and Fatter 152?
14. Modern Plagues Revisited 167?
15. Antibiotic Winter 185?
16. Solutions 199