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CHAPTER 1
THE END OF ANTIBIOTICS
[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 memoryladen 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.
The Antibiotic Age
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. 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."
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." 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.
The Limits of Antibiotics
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." 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." 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."
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."
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." 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."
The End of Miracle Drugs
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 ITLβITL-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 Rise of Bacterial Resistance
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."
(Continues…)
Excerpted from "Herbal Antibiotics"
by .
Copyright © 2012 Stephen Buhner.
Excerpted by permission of Storey Publishing.
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