[Once] the germ theory of contagion finally caught on, it did so with a vengeance. Different types of bacteria were implicated in anthrax, gonorrhea, typhoid, and leprosy. Microbes, once amusing little anomalies, became demonized…. [They] became a virulent “other” to be destroyed.
—Lynn Margulis and Dorion Sagan, What Is Life?
It is worth considering that despite being smaller than one millionth of a meter long, microbes compromise fully 60 percent of the mass of life on the planet.
—Brad Spellberg, Rising Plague
There is a unique smell to hospitals, composed of equal parts illness, rubbing alcohol, fear, and hope. Few of us who have been in a hospital can forget that smell or the feelings it engenders. But underneath those memory-laden smells and feelings is the belief that in this place, this hospital, an army of men and women is fighting for our lives, working to bring us back from the brink of death. We have learned, been taught, know for a fact, that this army is winning the war against disease, that antibiotics have made an end to most bacterial diseases. It is a comforting belief. Unfortunately, what we “know” couldn’t be more wrong.
Late in 1993, as Newsweek’s Sharon Begley reported, infectious disease specialist Dr. Cynthia Gilbert entered the room of a long-term kidney patient. Her face was set in the mask that physicians have used for centuries when coming to pass sentence on their patients. The man was not fooled; he took it in in a glance. “You’re coming to tell me I’m dying,” he said.
She paused, then nodded curtly. “There’s just nothing we can do.”
They each paused then. One contemplating the end of life, the other the failure of her craft and the loss that goes with it.
Dr. Gilbert took a deep, painful breath. “I’m sorry,” she said.
The man said nothing; for what he was contemplating there were no words. His physician nodded sharply as if settling her mind. Then she turned and left him, facing once again the long hall filled with the smells of illness, rubbing alcohol, fear, and hope, and the questions for which she had no answer.
Her patient was going to die of something easily curable a few years earlier—an enterococcal bacterial infection. But this particular bacteria was now resistant to antibiotics; for 9 months she had tried every antibiotic in her arsenal. The man, weakened as he was by disease, could not fight off a bacteria impervious to pharmaceuticals. Several days later he succumbed to a massive infection of the blood and heart.
This outcome, inconceivable even a few decades earlier, is growing ever more common. Millions of people are contracting resistant infections every year in the United States, and hundreds of millions more are doing so around the globe. Increasingly, as the virulence and resistance of bacteria worsen, more of them are succumbing to formerly treatable diseases. Estimates of the dead and maimed rise every year with little hope in sight for their reduction.
The toll is mounting because the number of people infected by resistant bacteria is increasing, especially in places where the ill, the young or old, or the poor congregate, such as homeless shelters, inner cities, prisons, and child care centers. And the most dangerous place of all? Well, it’s your average hospital. For there is no place else on Earth where so many sick people congregate. No place else where so many pathogenic bacteria congregate. And there is no place else where the bacteria will experience such a multiplicity of antibiotics.
We face an uncertain future but it’s not widely understood just how this has come to pass.
You probably haven’t heard of Anne Miller; almost no one has. Nevertheless, when she died in 1999 at the age of 90, her obituary was published in the New York Times. Why did “the paper of record” publish the obituary of an obscure elderly woman? Well, because she was the first person to be saved by a very new, experimental drug—a drug that altered human history.
In March of 1942 Anne Sheafe Miller was in a hospital in New Haven, Connecticut, dying from pneumonia caused by a streptococcal infection. She was delirious, slipping in and out of consciousness, with a temperature near 107°F. Her doctors had tried everything they could think of, sulfa drugs and blood transfusions, and nothing had worked. But then someone remembered reading about a new, highly experimental drug. The doctors managed to get a small amount of it from a laboratory in New Jersey. Once they injected her with it, Anne’s temperature dropped to near normal overnight. The next day she was no longer delirious and within a few days she was sitting up, eating full meals, and chatting with her visitors. That moment changed our world. News of her miraculous recovery made headlines across the country. The pharmaceutical companies took note and began full production of the first “miracle” drug in existence. The drug? Penicillin.
In 1942 the world’s entire supply of penicillin was a mere 32 liters (its weight? about 64 pounds). By 1949, 156,000 pounds a year of penicillin and a new antibiotic, streptomycin (isolated from common soil fungi), were being produced. By 1999—in the United States alone—this figure had grown to an incredible 40 million pounds a year of scores of antibiotics for people, livestock, research, and agricultural plants. Ten years later some 60 million pounds per year of antibiotics were being used in the United States and scores of millions of pounds more by other countries around the world. Nearly 30 million pounds were being used in the United States solely on animals raised for human consumption. And those figures? That is per year. Year in, year out.
Epidemiologist and veterinarian Wendy Powell, of the Canadian Food Inspection Agency, comments that “in 1991, there were more than 50 penicillins, 70 cephalosporins, 12 tetracyclines, 8 aminoglycosides, 1 monobactam, 3 carbapenems, 9 macrolides, 2 new streptogramins and 3 dihydrofolate reductase inhibitors” on the market.1 Those numbers are even higher now.
Most people don’t realize it, but—these antibiotics? They never go away.
Antibiotics, in their pure or metabolized states, form a significant part of hospital waste streams. They are excreted in their millions of pounds from the millions of patients who visit hospitals each year. Expired antibiotics (sold or unsold, in their millions of pounds) are simply thrown into the garbage. Antibacterials, as disinfectants, and antibiotic remnants from various treatments also enter the hospital waste streams. All of the antibiotics that hospitals buy end up, one way or another, in the environment, usually in wastewater streams. They travel to treatment plants and pass relatively unchanged into the world’s water supplies.
American physicians outside of hospitals dispense an additional 260 million antibiotic prescriptions yearly, and those, too, are excreted into the environment. Adding to the antibiotic waste stream, pharmaceutical manufacturers discharge thousands of tons of spent mycelial and other antibiotic-related waste into the environment, much of it still containing antibiotic residues. Yearly, American factory farms dispense nearly 30 million pounds, or more, of antibiotics so that America’s food animals—primarily pigs, cattle, and chickens—will survive overcrowding (low levels of antibiotics also stimulate weight gain, increasing revenue). The millions of gallons of their excrement is funneled into waste lagoons, from where it flows relatively unchanged into local ecosystems. Open-range farm animals (as well as millions of other domesticated animals—mostly dogs and cats), deposit their antibiotic-laden feces directly onto the ground. Ninety-seven percent of the antibiotic kanamycin passes unchanged through animal gastrointestinal (GI) tracts onto the surface of the soil.
In short, the American continent, like much of the world, is literally awash in antibiotics. And as physician and researcher Stuart Levy remarks, many of these antibiotics are not easily biodegradable. “They can remain intact in the environment unless they are destroyed by high temperatures or other physical damage such as ultraviolet light from the sun. As active antibiotics they continue to kill off susceptible bacteria with which they have contact.”2
In an extremely short period of geologic time, the earth has been saturated with hundreds of millions of tons of nonbiodegradable, often biologically unique pharmaceuticals designed to kill bacteria. Many antibiotics (whose name literally means “against life”) do not discriminate in their activity but kill broad groups of diverse bacteria whenever they are used. The worldwide environmental dumping over the past 65 years of such huge quantities of synthetic antibiotics has initiated the most pervasive impacts on the earth’s bacterial underpinnings since oxygen-generating bacteria supplanted methanogens 2.5 billion years ago. It has, as Levy comments, “stimulated evolutionary changes that are unparalleled in recorded biologic history.”3 In the short run this means the emergence of unique pathogenic bacteria in human, animal, and agricultural crop populations. In the long run it means the emergence of infectious disease epidemics more deadly than any in human history.
Perhaps no technological advance has been more widely advertised and capitalized upon than the development of antibiotics. It is routinely lauded as one of the primary accomplishments of the application of science and modern medicine in Western culture—the success of the scientific method over the uninformed medicine of the past.
The excitement over the discovery and successful use of antibiotics in medicine was so strong in the late 1950s and early 1960s that many physicians, including my great-uncle Lee Burney, then surgeon general of the United States, and my grandfather David Cox, president of the Kentucky Medical Association, jointly proclaimed the end for all time of epidemic disease. A 1963 comment by the Australian physician Sir F. Macfarlane Burnet, a Nobel laureate, is typical. By the end of the twentieth century, he said, humanity would see the “virtual elimination of infectious disease as a significant factor in societal life.”4
Seven years later, one of my great-uncle’s successors, Surgeon General William Stewart, testified to Congress that “it was time to close the book on infectious diseases.”5 Smallpox was being eradicated and polio vaccines were showing astonishing success in preventing infection in millions of people in the United States, Africa, and Europe. Tuberculosis and malaria, it was predicted, would be gone by the year 2000. With satisfaction David Moreau observed in an article in Vogue magazine that “the chemotherapeutic revolution [had] reduced nearly all non-viral disease to the significance of a bad cold.”6
They couldn’t have been more wrong.
In spite of Moreau’s optimism, when his article appeared in 1976, infectious disease was already on the rise. By 1997 it had become so bad that three million people a year in the United States were being admitted to hospitals with difficult-to-treat, antibiotic-resistant, bacterial infections. The Centers for Disease Control (CDC) estimated in 2002 that another 1.7 million were becoming infected while visiting hospitals and 100,000 were estimated to be dying after contracting a resistant infection in a hospital.
“To reiterate,” says Brad Spellberg of the Infectious Diseases Society of America, “these people come into the hospital for a heart attack, or cancer, or trauma after a car accident, or to have elective surgery, or with some other medical problem and then ended up dying of infection that they picked up in the hospital…. The number of people who die from hospital-acquired infections is unquestionably much higher now, and is almost certainly more than 100,000 per year in the United States alone.”7
This would make hospital-acquired resistant infections, by conservative estimates, the fourth leading cause of death in the United States. And that doesn’t even include the death toll from infectious diseases in general, the same infectious diseases that were going to be eradicated by the year 2000. R. L. Berkelman and J. M. Hughes commented in 1993 in the Annals of Internal Medicine that “the stark reality is that infectious diseases are the leading cause of death worldwide and remain the leading cause of illness and death in the United States.”8 Pathologist and researcher Marc Lappé went even further, declaring in his book When Antibiotics Fail, “The period once euphemistically called the Age of Miracle Drugs is dead.”9
Though penicillin was discovered in 1929, it was only with World War II that it was commercially developed and it wasn’t until after the war that its use became routine. Those were heady days. It seemed science could do anything. New antibiotics were being discovered daily; the arsenal of medicine seemed overwhelming. In the euphoria of the moment no one heeded the few voices raising concerns. Among them, ironically enough, was Alexander Fleming, the discoverer of penicillin. Dr. Fleming noted as early as 1929 in the British Journal of Experimental Pathology that numerous bacteria were already resistant to the drug he had discovered, and in a 1945 New York Times interview, he warned that improper use of penicillin would inevitably lead to the development of resistant bacteria. Fleming’s observations were prescient. At the time of his interview just 14 percent of Staphylococcus aureus bacteria were resistant to penicillin; by 1953, as the use of penicillin became widespread, 64 percent to 80 percent of the bacteria had become resistant and resistance to tetracycline and erythromycin was also being reported. (In 1995 an incredible 95 percent of staph was resistant to penicillin.) By 1960 resistant staph had become the most common source of hospital-acquired infections worldwide. So physicians began to use methicillin, a beta-lactam antibiotic that they found to be effective against penicillin-resistant strains. Methicillin-resistant staph (MRSA) emerged within a year. The first severe outbreak in hospitals occurred in the United States in 1968—a mere 8 years later. Eventually MRSA strains resistant to all clinically available antibiotics except the glycopeptides (vancomycin and teicoplanin) emerged. And by 1999, 54 years after the commercial production of antibiotics, the first staph strain resistant to all clinical antibiotics had infected its first three people.
Originally limited to patients in hospitals (the primary breeding ground for such bacteria), by the 1970s resistant strains had begun appearing outside hospitals. Now they are common throughout the world’s population. In 2002 I saw my first resistant staph infection outside a hospital setting. Now (2011) every month brings an e-mail or call from someone with another.
This rate of resistance development was supposed to be impossible. Evolutionary biologists had insisted that evolution in bacteria (as in all species) could come only from spontaneous, usable mutations that occur with an extremely low frequency (from one out of every 10 million to one out of every 10 billion mutations) in each generation. That bacteria could generate significant resistance to antibiotics in only 35 years was considered impossible. That the human species could be facing the end of antibiotics only 60 years after their introduction was ludicrous. But in fact, bacteria are showing extremely sophisticated responses to the human “war” on disease.
The thing that so many people missed, including my ancestors, is that all life on Earth is highly intelligent and very, very adaptable. Bacteria are the oldest forms of life on this planet and they have learned very, very well how to respond to threats to their well-being. Among those threats are the thousands if not millions of antibacterial substances that have existed as long as life itself.
One of the crucial understandings that those early researchers ignored, though tremendously obvious now (only hubris could have hidden it so long), is that the world is filled with antibacterial substances, most produced by other bacteria, as well as fungi and plants. Bacteria, to survive, learned how to respond to those substances a very long time ago. Or as Steven Projan of Wyeth Research puts it, bacteria “are the oldest of living organisms and thus have been subject to three billion years of evolution in harsh environments and therefore have been selected to withstand chemical assault.”10
What makes the problem even more egregious is that most of the antibiotics originally developed by human beings came from fungi, fungi that bacteria had encountered a very long time ago. Given those circumstances, of course there were going to be problems with our antibiotics. Perhaps, perhaps, if our antibiotic use had been restrained, the problems would have been minor. But it hasn’t been; the amount of pure antibiotics being dumped into the environment is unprecedented in evolutionary history. And that has had tremendous impacts on the bacterial communities of Earth, and the bacteria have set about solving the problem they face very methodically. Just like us, they want to survive, and just like us, they are very adaptable. In fact, they are much more adaptable than we ever will be.
As soon as a bacterium encounters an antibiotic, it begins to generate possible responses. This takes time, usually a number of bacterial generations. But bacteria live a lot more quickly than we do; a new generation can occur every 20 minutes for many species. This is some 500,000 times faster than us. And during that quickened time scale, bacteria have found a lot of different ways to respond to our antibiotics.
Bacteria can decrease the amount of the antibiotic that gets inside them. Antimicrobials, in most instances, need to enter bacterial cells in order to kill them—they need to negotiate the cell envelope that surrounds the bacteria. Some do this by taking advantage of the normal influx of materials that must go into the bacterial cells daily in order for them to live. In other words, they sneak in by attaching themselves to nutrients of one sort or another or even appear to be a necessary nutrient so that the bacteria take them up.
To avoid this infiltration the bacteria alter the permeability of their cell membranes, often by altering the structure of the doorways that let outside substances into the cell. This makes it harder, or impossible, for antibiotics to sneak in—essentially keeping the level of the drug below that needed to affect the bacteria.
Bacteria can alter their internal structure so that the intended target of the antibiotic won’t be affected by it. As David Hooper at the Division of Infectious Diseases at Massachusetts General Hospital puts it, “Resistance by the general mechanisms of target modification can be brought about, however, by a remarkable variety of specific means, which have been exploited by different clinically important bacteria. The modification mechanism often results in an altered structure of the original drug target structure that binds the drug poorly or not at all.”11
In other words, they change the structure of their bodies so specifically that the parts of themselves that would be affected by the antibiotics aren’t. The antibiotic enters the cell, but it just doesn’t do anything.
Bacteria can degrade or destroy the antibiotic, even if it gets inside them, by creating antibiotic-specific inactivation or disabling compounds—often these are enzymes such as extended-spectrum beta-lactamases (ESBLs). As Harry Taber of the New York Department of Health puts it, “It is not surprising to find, then, that antibiotic inactivating enzymes are found in the [cell] envelope: β-lactamases and aminoglycoside-modifying enzymes are examples.”12
The newest member of this group is NDM-1, New Delhi metallo-beta-lactamase. NDM-1 is a kind of ESBL but much more problematical than any known so far because it is potently active against carbapenem antibiotics, a class of beta-lactams that were previously resistant to ESBL deactivation. NDM-1 is carried on plasmids and transfers easily to a wide range of bacteria. “The frightening thing about this,” says Timothy Walsh, a professor of microbiology and antibiotic resistance at Cardiff University in the UK, is that “it appears to be spreading fast.”13
Bacteria can remove antibiotics from their cells as fast as they enter them using something called an efflux pump. Essentially they create a kind of sump pump that will pump out exactly the things they want pumped out. There are a variety of efflux pumps in all bacteria, each coded for particular substances. Some efflux pumps act on only a single substance, while others (multidrug efflux pumps) can pump out a wide range of compounds. Often the compounds have very little in common with each other; no one yet understands why one pump can act on so many different kinds of substances.
But when one of those substances is identified by a bacterium, the pump kicks in, the drug goes out. Researchers have commented that these “pumps can recognize and extrude positive-, negative-, or neutral-charged molecules, substances as hydrophobic as organic solvents and lipids, and compounds as hydrophilic as aminoglycoside antibiotics.”14
Bacteria have, over long evolutionary time, created a wide range of pump types in order to protect themselves from the millions of antimicrobial substances that exist in the world. There are five main forms:
• The major facilitator superfamily (MFS)
• The APT-binding cassette superfamily (ABC)
• The small multidrug resistance family (SMR)
• The resistance-nodulation-cell division superfamily (RND)
• The multi-antimicrobial extrusion protein family (MATE)
Most Gram-positive bacteria use MFS as their primary efflux mechanism. Most Gram-negative bacteria use RND. These pumps have a wide variety of purposes, among them the protection of the organism from things like bile salts and stomach acids, which, in their own way, act much like antimicrobials on pathogenic bacteria.
Sometimes bacteria learn how to live and prosper in antimicrobial environments, such as the cleaning solutions in hospitals. As one journal article put it, “Contamination, mainly by Gram-negative bacteria, was found in 10 freshly prepared solutions and in 21 of 22 at discard.”15 Sometimes, they even learn to use the antibiotics for food.
Once a bacterium develops a method for countering an antibiotic, it systematically begins to pass the knowledge on to other bacteria at an extremely rapid rate. Under the pressure of antibiotics, bacteria are interacting with as many other forms and numbers of bacteria as they can. In fact, bacteria are communicating across bacterial species lines, something they were never known to do before the advent of commercial antibiotics. The first thing they share is resistance information and they do this in a number of different ways.
Bacteria encode several different kinds of plasmids, essentially chromosome-independent DNA strands, each of which contains resistance information, and they pass these on to other bacteria. Plasmids are highly mobile genetic strands and are widely exchanged throughout the bacterial world. Aminoglycosides, for example, some of the most potent antibacterials known, were originally isolated from actinomycetes, a type of bacteria. Those bacteria created and used aminoglycosides themselves to kill invading or competing bacteria, but the aminoglycosides could also kill actinomycetes, so the actinomycetes also created something to deactivate aminoglycosides and they stored that information on plasmids inside themselves. All resistance to aminoglycosides worldwide, including in Pseudomonas and Acinetobacter organisms, has come from those ancient plasmids created by the actinomycetes. Once aminoglycosides began to be promiscuously prescribed by the medical community, the actinomycetes released the plasmids like a puff of dandelion seeds on the wind.
Bacteria use transposons, unique movable segments of DNA that are a normal component of their genome. Sometimes called “jumping genes,” transposons easily move between chromosomes and plasmids. They are readily integrated into DNA structures, and when they are, the genetic makeup, and hence the physical form of the organism, is altered. Bacteria use transposons to transfer a significant amount of resistance information and often release them in free form into the environment to be taken up later by other bacteria.
They use integrons as well, a type of DNA sequence that integrates into the genome structure at specific sites. Integrons are especially active in the transfer of both resistance and virulence information.
Bacterial viruses, or bacteriophages, also help transfer resistance information between different bacteria. It is now known that instead of making only copies of themselves when they reproduce, bacteriophages take up and make copies of host chromosome segments that contain resistance information, which are then transferred to newly infected bacteria. In other words, the viruses that infect bacteria (they get colds, too) teach them how to be resistant to antibiotics.
Bacteria can share resistance information directly or simply extrude it from their cells, allowing it to be picked up later by other roving bacteria. They often experiment, combining resistance information from multiple sources in unique ways that increase resistance, generate new resistance pathways, or even stimulate resistance to antibiotics that they have never encountered before. Even bacteria in hibernating or moribund states will share whatever information on resistance they have with any bacteria that encounter them. When bacteria take up any encoded information on resistance, they weave it into their own DNA, and this acquired resistance becomes a genetic trait that can be passed on to their descendants forever—distressingly Lamarckian. Researchers have noted that the rise of resistance over the past 50 years has had a one-to-one correlation to the production and use of antibiotics and that resistance mechanisms are not just passed on to other bacteria but are conserved within species.
Antibiotics, ultimately and regrettably for us, have actions similar to pheromones; they act as chemical attractants and literally pull bacteria to them. Once in the presence of an antibiotic, a bacterium’s learning rate immediately increases by several orders of magnitude. Tetracycline, in even extremely low doses—in fact, especially in low doses—stimulates from one hundred to one thousand times the transfer, mobilization, and movement of transposons and plasmids. (Treatment of acne and fattening of industrial farm animals, by the way, generally involves low doses of tetracycline, often over years.) Wendy Powell comments that “this means that in times of stress, predicated by the presence of antibiotics, the antibiotics themselves promote the exchange of plasmids, which may contain resistance genes.”16
The fairly recent discovery that all of the water supplies in the industrialized countries are contaminated with minute amounts of antibiotics (from their excretion into water supplies) means that bacteria everywhere are experiencing low doses of antibiotics all the time. This exposure is exponentially driving resistance learning; the more antibiotics that go into the water, the faster the bacteria learn.
What is more, as bacteria gain resistance, they pass that knowledge on to all forms of bacteria they meet. They are not competing with each other for resources, as standard evolutionary theory predicted, but rather promiscuously cooperating in the sharing of survival information. “More surprising,” one research group commented, “is the apparent movement of genes, such as tetQ and ermB between members of the normal microflora of humans and animals, populations of bacteria that differ in species composition.”17 Anaerobic and aerobic, Gram-positive and Gram-negative, spirochetes and plasmodial parasites, all are exchanging resistance information—something that, prior to antibiotic usage, was never known to occur (and contributing to a growing recognition that nature may not be red in tooth and claw but much more mutualistic and interdependently connected than formerly supposed). The recognition, long delayed by incorrect assumptions about the nature of the genome, is now widespread—genetic structures in all organisms are not static but fluid, sometimes along a wide range. Barbara McClintock, who early recognized the existence of transposons, noted in her 1983 Nobel lecture that the genome “is a highly sensitive organ of the cell, that in times of stress can initiate its own restructuring and renovation.”22 She noted as well that the instructions for how the genotype reassembled came from not only the organism but the environment itself. The greater the stress, the more fluid and specific the action of the genome in responding to it.
Research, new since the first edition of this book, has borne out McClintock’s observations with a vengeance. The genome of an organism is stored in its DNA. It turns out that antibiotics often damage bacterial DNA through boosting production of free-radical oxygen molecules inside the bacteria. In other words this highly flexible organ of the cell is partially corrupted by antibiotics. Once that occurs the organism immediately begins repairing the damage. The bacteria begins to reweave the DNA, including the genomic structure encoded within it. Part of the data that informs those repair processes is the factors that caused the damage. So the bacteria literally restructure the genome in such a way as to counteract the damaging event. And since the damaging event is the antibiotic creation of free radicals, the bacteria develop resistance to all antibiotics that create free radicals.
Resistant bacteria tend to specialize in what part of the body they infect. Enterococcus, Pseudomonas, Staphylococcus, and Klebsiella bacteria take advantage of surgical procedures to infect surgical wounds or patients’ blood in hospitals.
It turns out that staph bacteria need the iron that occurs naturally in blood cells, and the organisms prefer one kind of blood—ours. Anyplace where human blood is widely available, staph organisms congregate in large numbers. Staphylococcus organisms are “the leading cause of pus-forming skin and soft tissue infections, the leading cause of infectious heart disease, the number one hospital acquired infection, and one of the four leading causes of food-borne illness.”23 And the organisms keep learning.
Effluent streams from cities, filled with excreted antibiotics and resistant staph organisms, flow into the seas surrounding cities. Resistant staph is endemic in all oceans abutting land masses—and the adjoining beaches. It also learned how to transmit itself from person to person during sex. Welcome to the newest STD.
Haemophilus, Pseudomonas, Staphylococcus, Klebsiella, and Streptococcus infect lung tissue, many times gaining access by hitching a ride on infected breathing tubes, oh-so-carefully inserted into patients by hospital staff. The bacteria cause pneumonia, often untreatable, in elderly patients in hospitals and nursing homes. Once known as the old person’s friend (because it, relatively gently, eased the old into death), pneumonia was significantly reduced through antibiotic use but is now making a comeback as a leading cause of death in the elderly.
Pseudomonas and Klebsiella, traveling into urinary passageways on nurse-inserted catheters, initiate serious or intransigent urinary tract infections in many patients. They also gain entry into female nurses’ urinary tracts through poor hygiene, where they rapidly mutate under the pressure of the free antibiotics dispensed to such hospital personnel. (Most nurses’ and physicians’ hands are covered in resistant bacteria whether they wash or not—hand disinfection and hand washing are not the same thing.)
Haemophilus and Streptococcus initiate serious ear infections (sometimes leading to meningitis) in pediatric wards, which multiple rounds of antibiotics often fail to cure. These organisms can also cause debilitating infections of the GI tract accompanied by severe, unremitting diarrhea. And they are not alone in this. One of the newer, more dangerous infectious organisms of the GI tract is Clostridium difficile. As the Infectious Diseases Society of America reports, “The rate of infections caused by Clostridium difficile in U.S. hospitals doubled between 2000 and 2003. Outbreaks of severe C. difficile disease among hospital patients and clusters of unusually severe C. difficile disease among previously low-risk patients have been reported from multiple states. Many of the changes in the behavior of this infection appear due to the spread of an epidemic strain of C. difficile with increased virulence and increased resistance to commonly used fluoroquinolone antimicrobials.”24
According to the CDC, there were four times as many deaths from this disease in 2004 as there were in 1999. The organism has become so difficult to treat with antibiotics that Western doctors are turning to a new treatment: fecal transplants. Yes, you heard that right, they put someone else’s poop into your bowel in hopes that a healthy bowel population might just reestablish itself. The new poop is fed into the body through a tube in the patient’s nose. (This is modern medicine.)
Tuberculosis (TB) is increasingly resistant and is spreading in inner cities, homeless shelters, and prisons. About two billion people worldwide are thought to have latent TB, about one in three people. Two hundred million of those will become infectious (15 million in the United States) while three million a year will die. About 80 percent of those infected show some signs of antibiotic resistance. Two percent, or 40 million people worldwide, currently have an untreatable, resistant strain. TB is, in fact, becoming so difficult to treat that older approaches, such as surgical removal of the diseased lung, are sometimes being utilized.
Gonorrhea has reemerged with a potent resistance it learned in brothels in Vietnam among prostitutes who were regularly given daily courses of antibiotics. It now causes 700,000 infections in the United States each year. Malaria, spread by mosquitos and once considered only a disease of the tropics, kills one million people a year worldwide and is resistant to pharmaceuticals over 85 percent of the time.
Cholera has also learned resistance to a number of antibiotics through improper dosing by physicians. Even more telling, it has learned resistance to the primary drug used to kill it in the wild—chlorine. Chlorine, though naturally present in the ecosystem, rarely exists in pure form. Generally, it is chemically bonded to something else, as in such things as table salt (sodium chloride). Industrial production is around 50 million pounds a year of chemically pure chlorine. It is used in products such as organochlorines (e.g., the PVCs used in medicine) and, commonly, in water supplies as an antimicrobial disinfectant. Both cholera and E. coli have developed resistance to chlorine as a result. Dangerous in and of itself but more so because E. coli, exposed to such large numbers of antibiotics in the human GI tract, is one of the principal bacteria that learns resistance and passes it on. This information exchange is especially easy with other types of GI tract bacteria, especially if they are Gram-negative, which cholera is. In 2000, when the first documented outbreak of simultaneous infection by enterotoxigenic E. coli and cholera occurred in India, both were resistant organisms.
Cholera lives in water, usually near human settlements, in a quiescent state between epidemics. During these lulls cholera encounters not only chlorine but the scores of other antibiotics that flow in sublethal doses into nearly all water supplies on Earth. Resistance determinants are widely shared between multiple serotypes of cholera. Like all pathogenic bacteria, the resistance curve of cholera organisms is exponential. In 1992, only 35 percent of cholera O1 serotypes were resistant to ampicillin. By 1997, 100 percent were.
Cholera epidemics tend to emerge in human populations when the fecal content of waste streams from population centers is high. The organisms follow the effluent upstream, seeking its source. They usually find it.
Antimicrobial pressure has caused E. coli, not normally pathogenic, to also develop unexpected virulence capacities in such forms as the potentially deadly E. coli O157:H7. Epidemiologists now know, through genetic markers, that it was taught its virulence by Shigella bacteria. Researcher and physician Marguerite Neill, a specialist in infectious medicine, observes that judicious reflection on the meaning of this finding suggests a larger significance—that E. coli O157:H7 is a messenger, bringing an unwelcome message that “in mankind’s battle to conquer infectious diseases, the opposing army is being replenished with fresh replacements.”25
Hospitals, where large numbers of pathogenic bacteria and antibiotics come into frequent contact, give bacteria the most opportunity to develop resistance and virulence. Researchers examining the effluent streams from hospitals have found them to contain exceptionally large numbers of resistant bacteria as well as large amounts of excreted antibiotics. These antibiotics and resistant bacteria flow into the environment and spread everywhere. As Julie Gerberding of the Centers for Disease Control comments, “Once restricted to hospitals, where seriously ill patients are exposed to constant infusions of drugs, these [resistant bacteria] are now being found in the community.”26
The prodigious production of antibacterial soaps that end up going into the water are stimulating resistance among many classes of bacteria as well. Even though resistance dynamics were well understood long before antibacterial soaps were allowed on the market, under pressure from corporations they were still allowed in the United States. And like all other antibacterial substances, they have begun to confer unique forms of resistance on the planet’s bacteria. The fear of microbes, so thoroughly leveraged by television advertising, has only hastened the resistance problem. The Centers for Disease Control in Atlanta, Georgia, found that the average amount of the antibacterial component of such soaps, triclosan, increased in Americans’ urine by 42 percent between 2003 and 2006. Studies have shown that the chemical encourages bacterial resistance and that it disrupts hormone levels in regular users. Triclosan is common in many toothpastes, in nearly all antibacterial soaps, and even on knives and cutting boards.
These circumstances have increased the rate of resistance in bacteria exponentially. In 1999, 95 percent of E. coli was susceptible to ciprofloxacin but that had dropped to 60 percent by 2006; Acinetobacter susceptibility decreased by 70 percent in just 4 years; 36 percent of Staphylococcus organisms were resistant in 1992 but by 2003 64 percent were—the usual exponential learning curves. But these are only part of the story.
The use of antibiotics by factory farms and wide antibiotic use by veterinarians for our pets has created a similar bacterial evolution in fast-forward. At least half, if not more, of all antibiotics used in the United States goes to huge factory farm operations. This has generated tremendously potent and quick resistance in a large range of bacteria. As reporter Brandon Keim comments, “Much of it is used to treat diseases spread by industrial husbandry practices, or simply to accelerate growth. As a result, farms have become giant petri dishes for superbugs, especially multidrug-resistant Staphylococcus aureus or MRSA, which kills 20,000 Americans every year—more than AIDS.”27
Nicols Fox comments in her exposé of the problem in her book Spoiled: The Dangerous Truth About a Food Chain Gone Haywire:
The conditions under which [farm animals were] raised presented all the conditions for infection and disease: the animals were closely confined; subjected to stress; often fed contaminated food and water; exposed to vectors (flies, mice, rats) that could carry contaminants from one flock to another; bedded on filth-collecting litter; and given antibiotics (which, ironically, made them more vulnerable to disease) to encourage growth as well as ward off other infections…. Every condition that predisposed the spread of disease from animal to human actually worsened. Farming became more intensive, slaughtering became more mechanical and faster, products were processed in even more massive lots, and distribution became wider.28
As with human diseases, pathogenic animal bacteria have specialized: E. coli O157:H7 in beef, Salmonella in chicken eggs, Campylobacter in chickens, Listeria in deli meat. (And there are others such as Cyclospora, Cryptosporidium, and Yersinia). Like the resistant bacteria emerging from our hospitals, bacteria from factory farms spread quickly into the wider world. And while factory farm owners deny their practices have anything to do with the problem, the only place where antibiotic-resistant organisms genetically identical to those from factory farming operations don’t yet seem to exist is in indigenous animals in the northern arctic regions.
One of the early pioneers in antibiotic resistance is Stuart Levy, a professor who runs the Levy Lab at the Center for Adaptation Genetics and Drug Resistance at Tufts University School of Medicine. To trace the flow into the environment of resistant bacteria from farming operations, he took six groups of chickens and placed them 50 to a cage. Four cages were in a barn, two just outside. Half the chickens received food containing subtherapeutic doses of oxytetracycline. The feces of all the chickens as well as the farm family living nearby and farm families in the neighborhood were examined weekly. Within 24 to 36 hours of eating the first batch of antibiotic-containing food, the feces of the dosed chickens showed E. coli–resistant bacteria. Soon the undosed chickens also showed E. coli that were resistant to tetracycline. But even more remarkable, by the end of 3 months, the E. coli of all chickens were also resistant to ampicillin, streptomycin, and sulfonamides even though they had never been fed these drugs. Still more startling: At the end of 5 months, the feces of the nearby farm family (who had had no contact with the chickens) contained E. coli resistant to tetracycline. By the sixth month their E. coli were also resistant to five other antibiotics. A similar but longer study in Germany found that this resistance eventually moved into the surrounding community—taking a little over 2 years.
Salmonella, which is now genetically lodged in the ovaries (and hence the eggs that come from them) of many agribusiness chickens, can survive refrigeration, boiling, basting, and frying. To kill salmonella bacteria the egg must be fried hard or boiled for 9 minutes or longer. Listeria in deli meat can survive refrigeration. E. coli can now live in both orange juice and apple juice—two acidic mediums that previously killed it. And a recent study (2011) found that nearly 50 percent of all store-bought meat and poultry tested were contaminated with staph, and over half the bacteria tested were resistant strains. Lance Price, the lead author of the study, remarked, “The fact that drug-resistant S. aureus was so prevalent, and likely came from the food animals themselves, is troubling.”29
These food-borne bacteria are moving with greater frequency into the human food chain and human populations. There were 23 recalls by the U.S. FDA in 2010 for contamination from Salmonella, Listeria, Clostridium, E. coli, and Bacillus organisms.
Recent research has found that one of the main vectors for the spread of resistant organisms into the general community is flies. At minimum, over 30,000 flies will visit a poultry farming operation within any 6-week period. Researchers who studied groups of flies from such operations found them to be infected with exactly the same genetic variants of resistant bacteria as those found in the poultry wastes the flies were feeding on. This same phenomenon occurs at all large-animal factory farms, with both cattle and pigs.
The growth rate of resistance and virulence is so fast that 15 years ago Stuart Levy observed, “Some analysts warn of present-day scenarios in which infectious antibiotic-resistant bacteria devastate whole human populations…. This situation raises the staggering possibility that a time will come when antibiotics as a mode of therapy will only be a fact of historic interest.”30 To people such as David Livermore, MD, at the Antibiotic Resistance Monitoring and Reference Laboratory in London, it has now gone much further. “It is,” he says, “naive to think we can win.”31
In the first edition of this book I noted that bacteria are, in fact, learning resistance to new antibiotics in only a few years instead of the decades that it took previously. At the time of this second edition, that span has lessened to 6 months to a year. As infectious disease specialist Brad Spellberg has commented, “Resistance is inevitable.”
Though resistance in the bacteria affecting people and farm animals has been the most publicized and studied, these bacteria are not confined to people or their food animals. They move freely in the ecosystem and among species. Newer research has found that seagulls, and other birds, not only humans, are spreading resistant bacteria throughout the world. As Dr. Jeffrey Fisher, in his book The Plague Makers, notes:
The resistant bacteria that result from this reckless practice do not stay confined to the animals from which they develop. There are no “cow bacteria” or “pig bacteria” or “chicken bacteria.” In terms of the microbial world, we humans along with the rest of the animal kingdom are part of one giant ecosystem. The same resistant bacteria that grow in the intestinal tract of a cow or pig can, and do, eventually end up in our bodies.32
This is especially true if antibiotics flow into water. This promotes the transmission of resistant traits throughout the environment because bacterial growth is high wherever water-related biofilms occur: on the surface of water, on stones in water, and in the sediment of ponds, rivers, and oceans. Antibiotics given to fish contact all these regions, as does the antibiotic-rich effluent from factory farms and human waste treatment facilities. Resistance transfers in these biofilm regions from domestic to wild bacteria and it tends to persist in these natural ecosystems.
Researchers Christian Daughton and Thomas Ternes report that “a number of stream surveys documented the significant prevalence of native bacteria that display resistance to a wide array of antibiotics including vancomycin. Isolates from wild geese near Chicago, Illinois, are reported to be resistant to ampicillin, tetracycline, penicillin, and erythromycin.”33 Researchers have found 16 antibiotics commonly present in groundwater/surface waters that are detectable in the microgram-per-liter range. Some researchers report that these antibiotic compounds are showing genotoxicity; that is, they are affecting the integrity of genetic structures in other life-forms. Daughton and Ternes comment that this is indeed cause for concern, as the bacteria never seem to forget what has been done to them:
Indeed, the rampant, widespread (and sometimes indiscriminate) use of antibiotics, coupled with their subsequent release into the environment, is the leading proposed cause of accelerated spreading resistance among bacterial pathogens, which is exacerbated by the fact that resistance is maintained even in the absence of continued selective pressure (an irreversible occurrence). Sufficiently high concentrations could also have acute effects on bacteria. Such exposures could easily lead to altered microbial community structures in nature and thereby affect the higher food chain.34
Salmon, catfish, and trout—all raised commercially—are heavily dosed with antibiotics and other drugs, which are often blended into their food. As the food gets wet, the antibiotics begin to leach into the water. Commercial salmon, unlike catfish and trout, are raised in the open sea in pens, speeding the flow of antibacterials throughout the oceans. Because of crowded conditions, the 55 million pounds of commercial U.S. salmon are frequently dosed with antibiotics for long periods of time—about 150 pounds of antibiotic per acre of salmon. Stuart Levy comments:
Since they are deposited in the water, [antibiotics] can be picked up easily by other marine animals. Tetracycline is not rapidly degraded in fish. Thus, it is excreted in its active state in feces and deposited on the sea floor. Here, too, it remains relatively stable, out of direct sunlight, which can degrade it. Consequently, the ecological effect of this antibacterial agent in the sea is the same as it is in land animals: the long-term selection of resistant and multi-resistant bacteria in salmon and other marine life.35
Plant communities and soil are also exposed to direct antibiotic use, not just through effluent flows. To treat infections in mono-cropped fields, especially while attacking fire blight in apple and pear orchards, antibiotics such as streptomycin are sometimes sprayed in heavy doses directly on crops. In the United States, between 40,000 and 50,000 pounds of tetracycline and streptomycin are sprayed on fruit trees every year (1 pound of tetracycline will treat 450 people). This kills not only bacteria on the plants but all susceptible bacteria in the soil itself with cascading effects on soil integrity and health. While spraying allows potent doses of streptomycin to directly enter the ecosystem, other antibiotics, like oxytetracycline, are sometimes injected, much as they are with people, directly into larger plants’ trunks and roots. Not surprisingly, resistant pathogenic plant bacteria have been found in soil and plant communities wherever such practices occur. The bacterial transposon developed by leaf blight during resistance acquisition has been found in seven wild bacterial species in the soil. All these bacteria now have resistance to the streptomycin normally produced by the soil fungi in the region. This same dynamic has also been found occurring in the soil under wheat plants. The application or spread of antibiotic effluents in the environment is promoting resistance impacts in natural soil communities among wild bacteria, thus interfering with the normal balance of the soil biota. Agricultural practices such as liming fields and industrial heavy-metal pollution have been found, as well, to increase the density of resistant pathogens in the soil. Researchers have also started to insert bacterial resistance factors directly into the genetic structure of some plants (e.g., sugar beets), and these resistance factors have also been found to move into ecosystem bacteria.
The immense production of antibacterial substances once found only in minute quantities in the environment—substances produced by soil fungi, bacteria, or plants to protect their territorial integrity—has begun to affect the life cycle of bacteria and thousands of other organisms in the ecosystem and subsequently is affecting the health of the soil and the planet itself.
We have, as Mark Lappé remarked in The End of Antibiotics, “let our profligate use of antibiotics reshape the evolution of the microbial world and wrest any hope of safe management from us.”
Bacteria are not our enemies, as some scientists have postulated, nor a dangerous life-form bent on sickening mankind, as so many television commercials would have us believe. They are our ancestors and we are very much alike; we both metabolize fats, vitamins, sugars, and proteins. Lynn Margulis comments succinctly, “The more balanced view of microbe as colleague and ancestor remains almost unexpressed. Our culture ignores the hard-won fact that these disease ‘agents,’ these ‘germs,’ also germinated all life. Our ancestors, the germs, were bacteria.”36 Bacteria are not germs but the germinators—and fabric—of all life on Earth. In declaring war on them, we declared war on the underlying living structure of the planet, on all life-forms we can see, on ourselves.
One of the few naturally sterile places on Earth is a woman’s womb, and the gestation period prior to birth is the only time any human body is bacteria free. At birth, assuming it is a healthy one, the baby is immediately placed on the mother’s chest near the nipple. As the first movements toward bonding are taking place, the bacteria that live on the mother’s skin began to colonize her baby’s body. When the infant begins to nurse, the interior of the baby’s intestinal tract is colonized—from the skin around the nipple and the milk itself—and these bacteria are crucially important. Nursing introduces lactobacilli and other bacteria such as Bifidobacterium bifidus into the intestinal tract of newborns. This has significant effects on their health. Lactobacillus acidophilus bacteria create important vitamins and nutrients such as B1, B2, B3, B12, and folic acid in the intestinal tract. They help digest food and they also secrete natural antibiotic substances such as acidophilin, various organic acids, and peroxides that help prevent bacterial infections.
One to two pounds of our adult body weight comes from our coevolutionary bacteria. The bacteria that colonize us as infants have an ancient, coevolutionary relationship with human beings; they are an integral part of our species’ development and our body ecology. They are in fact our first line of defense against disease.
The skin of our bodies and the mucosal systems of our sinus passages and intestinal tracts are to bacteria much like fresh fertile black soil is to plants. Plow up the soil, disturbing the plants that grow there, and even if you don’t plant anything, the soil will soon be covered with a profusion of new plant growth. The same thing occurs in our bodies if our bacterial ecology is disturbed, as it often is, by antibiotics.
The bacteria that colonize our bodies are friendly, mutualistic bacteria. They take up all the space on and in our bodies on which bacteria can grow. By so doing, they leave no room for other, less benign bacteria to live. But the relationship goes beyond this. All of our coevolutionary bacteria generate antibiotic substances that kill off other, less friendly bacteria. The Streptococcus bacteria that normally live in our throats produce large quantities of antibacterial substances that are specifically active against the Streptococcus pyogenes bacteria that cause strep throat.
Regular exposure to pathogenic bacteria as we are growing teaches our bodies and our symbiotic bacteria how to respond most effectively to disease organisms. This produces much higher levels of health in later life. Research continually finds that children who are “protected” from bacteria by keeping them in exceptionally clean environments where they are constantly exposed to antibacterial soaps and wipes are not in fact healthier but much sicker overall than children not so protected. The constant exposure to a world filled with bacteria, the world out of which we emerged as a species, in fact stimulates the immune health of all of us as we grow. We actually need to come into contact with the microorganisms of the world to be healthy.
The truth is, we live in an ancient, healthy symbiosis with bacterial, viral, and microfaunal colonizers. Our bodies are much like the soil of the earth, covered inside and out with a broad diversity of microfauna providing an interdependent complex of support services. When we become ill, our symbiotic relationship with the healthy bacteria and other microfauna—our body ecology—is disturbed. The underlying factor that disrupts the body ecology is the illness, not the pathogenic bacteria that take advantage of it to occupy body sites. Antibiotics do not cure disease, they simply kill off opportunistic bacteria. Without the body’s ability to restore a healthy ecology, people die anyway. More than any other disease, AIDS has taught us the limitations of antibiotics and the bacterial model of disease. Irrespective of the quantities of antibiotics used, when AIDS patients’ bodies can no longer reestablish their internal ecology they die. As Marc Lappé says, “It is the body which ultimately controls infections, not chemicals. Without underlying immunity, drugs are meaningless.”37 Ironically, as many public health historians now know, the major decreases in human mortality and disease proclaimed to be brought about by antibiotics were due more, in fact, to better public hygiene.
Because they kill off so much of the internal symbiotic microfauna along with pathogenic bacteria, antibiotics create significant changes in human microfaunal ecology and makeup. The appearance of many diseases new to humankind such as certain nutrient deficiencies, candida overgrowth, certain chronic infections, allergies, and chronic immune suppression are now being directly linked to the distorted internal landscape antibiotics cause. Marc Lappé comments:
Lincomycin eliminates virtually all of the bacteria that require oxygen, while neomycin and kanamycin decrease the number of oxygen-requiring germs and gram-positive anaerobic ones, leading to overgrowth of Candida albicans and Staphylococcus aureus. Polymyxin can reduce native E. coli to the point of extinction, leaving the terrain open for staph and strep organisms. Erythromycin has a similar favorable effect on streptococci, while bacitracin and damycin, by contrast, appear to favor the growth of Clostridium difficile.38
And it is not just humans that have coevolutionary bacterial partners but all plant, insect, and animal life. When these other life-forms encounter antibiotics, their interior and exterior ecologies are disturbed as well.
If bacteria had not learned how to develop resistance, all life on Earth, including humans, would already have died. When we try to kill all disease organisms on this planet, ultimately, we are acting to kill ourselves.
The situation is dire and there are solutions, but they are not easy ones. As David Livermore has said, “A lot of modern medicine would become impossible if we lost our ability to treat infections.”39 Routine surgeries would no longer be routine but nearly impossible to perform safely. Infectious diseases would regularly become epidemic, sweeping through whole communities. The use of quarantine, rare now, would become common. Mortality among the old and the very young would rise tremendously. An entire world view, commonly accepted by most people in Western countries, would begin to crumble. It would be (medically speaking), for all practical purposes, 1928 again.
In the first edition of this book, I, as many others have done, urged people to give up using antibiotics unless there were a serious threat of death or disability if they did not. (I also thought real estate in Nevada might be a good investment.) More than a decade later, it is clear that antibiotics are not going to be used any less and in fact are being used at far greater rates than they were 15 years ago. The human species, as a group, has never really been known for doing the sensible thing before it is too late. We will stop using antibiotics only when they truly fail to work. And even then most of the people in the Western world will still try to hold on to them and our fatally flawed approach to bacterial disease.
But for those who clearly understand what the word “exponential” means, who want to truly empower themselves and their families and prepare for the time that is so quickly approaching us, there are options.
You can take control over your own health and health care. You can prepare. You can learn to use herbal medicines to heal yourself from disease. And you can learn what to do if you find that one day you need to know how to treat a resistant infection.
The rest of this book is designed to help you do just that.