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Science
by Pat Murphy & Paul Doherty

ALIENS INSIDE YOU

 
THIS IS NOT a column for the squeamish. We are going to tell you some stuff you may not want to know about the inner workings of your body.

Still with us? Okay. Don't say you weren't warned.

Your body is occupied by aliens. Nothing quite so over-the-top as the creatures in the 1979 movie Alien. Nor quite as personable as the aliens who used humans as hosts in Octavia Butler's Blood Child. These aliens have something in common with the Borg of Star Trek fame: you will be assimilated. In fact, you already have been.

These alien invaders—bacteria that have colonized your guts, your mouth, your skin, your sinuses and other parts of your body—outnumber your human cells ten to one. If you're like most people, about 100 trillion bacteria are living on your skin, in your saliva, and in your digestive tract.

Fantastic tales involving tiny aliens like these go way back. Edgar Allan Poe's The Masque of the Red Death (1842) might be considered the first that clearly fits in the fantasy genre and H. G. Wells's The Stolen Bacillus (1895) is an early example of a bacterial science fiction techno-thriller. (An anarchist steals what he thinks is a vial of cholera, intending to poison the water supply.) In more recent years, Greg Bear's Blood Music, Michael Crichton's Andromeda Strain, and Joan Slonczewski's Brain Plague feature microbes that cause no end of interesting fictional trouble.

In this column, we'll provide a crash course in the history of microbiology, which will probably match up nicely with what most people know about bacteria (basically something like "dangerous, icky, bad!"). We'll consider your guts and the glowing guts of zebrafish in an exploration of some of the unexpected ways these tiny aliens affect your health. We'll discuss whether you (yes, you!) are a warzone or an ecosystem. And we'll talk about how feces (yes, we mean poop) can be a valuable medical asset. Let's start where many a good science fiction tale begins: with a war against alien invaders.

And just to make sure we have your attention (and to further warn the squeamish among our readers), we'll let you know that bacteria make up between forty and sixty percent of human feces. If you want to put that in preschool terms, about half of what you poop is germs.
 

YOU ARE A WAR ZONE

For more than a hundred years, doctors have been waging war on these aliens living in your body.

For those among you who have forgotten the history of bacteriology, here's a Cliffs Notes version. In 1847, Hungarian obstetrician Ignaz Semmelweis noticed that patients attended by midwives who washed their hands were less likely to contract childbed fever than those attended by doctors who did not.

In 1855, doctor John Snow mapped the deaths in a cholera epidemic and realized that all the people who died of cholera had been drinking water from the Broad Street Pump. This led to the discovery that cholera was transmitted by contaminated water, evidence that supported what came to be called the germ theory of disease.

In 1876, German doctor Robert Koch determined in a series of experiments that a specific bacterium, Bacillus anthracis, caused anthrax. Koch developed techniques that led to the identification of the bacteria responsible for other diseases: tuberculosis (in 1882), cholera (in 1883), typhus (in 1880), tetanus (in 1884), and the Bubonic plague (in 1894). Working in Koch's lab, doctor Paul Ehrlich searched for what he called "magic bullets," chemicals that would kill specific microorganisms without harming the person infected with them. His first "magic bullet" was a drug marketed in 1910 as Salvarsan, which attacked the bacterium responsible for syphilis.

And all that leads us to Sir Alexander Fleming. Back in 1928, Sir Fleming noticed that mold Penicillium notatum could destroy colonies of Staphylococcus bacteria, an organism that can live harmlessly on your skin—and can cause pneumonia and other potentially lethal infections. Fleming's observation led to the development of penicillin, a life-saving antibiotic. In the early 1940s, large-scale production of penicillin began, marking the beginning of the era of antibiotics.

These days, any third grader can tell you that germs make you sick. To rid our bodies of those pesky germs, we wash our hands, use hand sanitizers, and demand antibiotics when we are under the weather. But to understand how these efforts to kill the aliens affect your health, we're going to consider your guts.
 

ULCERS AND ASTHMA

Consider the ulcer, an open sore in the stomach or small intestine. Until 1982, doctors were convinced that stress, spicy foods, and alcohol caused most ulcers, and they treated this problem with bland foods and bed rest. In 1982, doctors Barry Marshall and J. Robin Warren determined that ulcers in the stomach and small intestine were not caused by stress and poor diet, but rather by an infection of a bacterium called Helicobacter pylori. (Marshall was quite a dedicated researcher. Frustrated by the failure to infect lab animals with H. pylori, he downed a Petri dish full of the bacteria and gave himself gastritis, an inflammation of the stomach lining.)

So far, this fits nicely with the accepted medical approach to disease: H. pylori causes ulcers, so the solution is to find the magic bullet that will kill H. pylori. Research by Marshall and Warren led to the realization that ulcers could be treated with antibiotics that wiped out H. pylori. No bacteria; no ulcer. In 1996, the Food and Drug Administration approved the first antibiotic for treatment of ulcers. The medical establishment recognized H. pylori as the cause of ulcers, and the consensus was: the only good H. pylori was a dead H. pylori.

But of course, as Paul likes to say, it's more complicated than that. Today, H. pylori happily resides in the stomachs of at least half the world's population. But only fifteen percent of those people develop ulcers.

And recent research indicates that H. pylori is not all bad. As the presence of H. pylori in the human gut has declined, the rates of chronic inflammatory diseases like asthma, allergies, and inflammatory bowel disease have gone up. Research at the University of Michigan indicates that H. pylori affects the response of the immune system. The bacterium causes certain immune cells to stop producing inflammation-causing molecules called cytokines, which have been identified as the first step in the onset of immune responses in which the body attacks its own cells and tissues.
 

GLOWING FISH GUTS

Our relationship with the aliens in our guts isn't simple. They've been with us for hundreds of thousands of years—and the same organisms that help us can hurt us as well.

For another example of the complex interactions of your body and its alien invaders, we'll tell you about a recent study of bacteria of the phylum Firmicutes in the intestines of zebrafish. The researchers at the University of North Carolina chose to study zebrafish because the young fish are pretty much transparent. Specifically, they studied two different groups of fish—one raised in a sterile environment free of any gut bacteria, and the other with the normal populations of microbes in its guts. They fed both groups specially formulated fatty acids that glowed because they had been tagged with a fluorescent dye.

The glowing guts of the zebrafish with the normal microbe population revealed that the presence of microbes increased the fat absorbed from food. The microbes responsible for the increased absorption, researchers realized, were bacteria of the phylum Firmicutes. Not only did the Firmicutes help the fish absorb fat, the presence of fat in the food also affected the microbe populations—the more fat, the more microbes.

Studies of mice showed a similar effect. Rodents fed a fattier diet gained weight and had larger populations of Firmicutes in their guts. When researchers transferred Firmicutes from the intestines of the fat mice to the intestines of normal mice fed on a normal diet, the normal mice absorbed more fat, even though their diet hadn't changed.

You can, of course, question what's going on here. Are the Firmicutes helping the fish and mice get more nourishment from the food they eat? Are they reproducing like mad to try to grab as much nourishment as they can for themselves? Maybe both—but in either case, the microbes are having a significant effect on how the fish and mice make use of the food they eat.

The presence of Firmicutes lets us extract more calories from food. For those of us who are trying to lose some weight, that's interesting news. Traditionally, doctors stress three key factors in weight loss: diet, exercise, and your genes. This research adds one more factor to the big three. The types and balance of microbes in your gut can push you toward gaining weight or losing it. Being a science fiction reader, we're sure you're already considering the next step: can we manipulate these microbe populations—and eat more fat without absorbing the calories? No answers on that just yet.
 

AN UNMENTIONABLE TRANSPLANT THAT WE MENTION

All this brings us to the experience of a friend of ours who came out of a hospital stay afflicted with Clostridium difficile, also known as C. difficile or C. diff. This bacterium usually afflicts older adults (our friend is ninety) and causes symptoms ranging from severe diarrhea to life-threatening inflammation of the colon. It is resistant to antibiotics and, in fact, often occurs after a patient is treated with antibiotics. Apparently the antibiotics wipe out the other bacteria in the gut, leaving the territory open, and C. diff moves in.

Our friend suffered from C. diff for months, and nothing seemed to help—until she tried a treatment called a fecal transplant. It is just what it sounds like. A healthy donor provides a stool sample—yes, we're talking poop, not a three-legged seat. The stool is screened for parasites and specific health problems, and then is transplanted into the intestine of the patient using a colonoscope, or a nasogastric tube at the high-tech end of the spectrum, or an enema bag at the low-tech end.

Reintroduced into the intestine, the gut bacteria from the healthy donor re-establish themselves, doing battle with C. diff and, more often than not, winning. It took many months for our friend to find a doctor willing to provide the fecal transplant, a therapy not yet generally accepted, but once she received the transplant, she was quickly cured.
 

YOUR SECRET PETS

In our research for this column, we ran across many researchers who implied or said outright that medicine needed to take a different view of our relationship with bacteria. As our friend discovered, relying on antibiotics to combat infection has its limits. The late 1900s and early 2000s were apparently the "golden age of antibiotics" and that golden age is ending.

Superbugs like C. diff are nothing new. Almost immediately after the introduction of penicillin, some strains of staphylococci bacteria were identified as resistant to the new medicine. But back then, researchers were busy finding and developing many new types of antibiotics—sulfonamides or sulfa drugs, streptomycin, chloramphenicol, and tetracycline. If a strain of bacteria was resistant to one antibiotic, another might be effective. Unfortunately, the pace of antibiotic development slowed in the 1980s and '90s.

Fast forward to today. About seventy percent of the bacteria that cause infections in hospitals are resistant to at least one commonly used antibiotic, and some are resistant to all approved antibiotics. There are antibiotic-resistant strains of tuberculosis, pneumonia, septicemia, gonorrhea, and childhood ear infections. It seems that the genes that make a bacterium resistant to an antibiotic can be swapped between strains of bacteria and even between species of bacteria. And that spells trouble for us humans.

At least, it spells trouble if we insist on viewing the relationship between the human body and the bacteria inside it as a war. If that's how we think about it, we're definitely in danger of losing.

But is this really a war? As any science fiction reader can tell you, not all aliens are bad. Sure, bacteria can make you sick. But they can also keep you well. As our friend with C. diff realized, treating a bacterial infection with an antibiotic is a scorched-earth approach. You do in the bad guys—but you may wipe out the good guys, too—leaving territory open for the bad guys to take over.

Rather than thinking of the bacteria in your guts as invaders, you could try thinking of them as your secret pets. There are, after all, about three pounds of them—about the weight of a large guinea pig. Some of them—like species of Bacteroides, Lactobacillus species that ferment yogurt, cheese, pickles, and other foods and the Bifidobacteria—are reckoned to be good guys, breaking down certain complex molecules and giving your body a chance to extract some of the nutrition these molecules contain. Others—like the species of Clostridium responsible for botulism and tetanus and the varieties of Escherichia coli (familiarly known as E. coli) responsible for nasty varieties of food poisoning—are generally reckoned to be bad guys. But with an estimated five hundred different species of bacteria in your colon competing for nutritional resources, it's not that simple.
 

YOU ARE AN ECOSYSTEM

In recent years, some doctors, biologists, and medical researchers have started talking about the "human microbiome," the collection of bacterial passengers that you (and every other human being) carry around every day. Rather than thinking of the body as a war zone between bacteria and human cells, they are thinking of it more like an organic farm, where many crops grow and the success of one may help suppress the growth of another. Some use words like "stewardship" or talk about how the practice of medicine should be less like fighting a war and more like managing a park. If you are an ecosystem, your health depends on keeping that ecosystem in balance.

That could involve adding to the bacteria in your system—the good bugs known as probiotics. It could involve developing therapies that target specific bacteria—such as phage therapy, which makes use of viruses that prey on bacteria. (These viruses, known as bacteriophages, target specific strains of bacteria, making it possible to kill some strains without harming the others.)

This new view of bacteria has led to reevaluation of a bit of your body formerly considered useless—your appendix. This worm-shaped tube attached to the large intestine is best known for getting infected and removed. But now that researchers have developed a bit of respect for the good bugs in your guts, some hypothesize that the appendix acts as a storehouse for gut bacteria. When bouts of diarrhea clear beneficial bacteria from the colon, the appendix supplies the bacteria needed to repopulate your guts. This theory implies that the appendix would help protect people from the overpopulation of troublesome bacteria like C. diff. In fact, one study indicates that people with intact appendices are much less likely to experience recurrent C. diff infections.

Science fiction often deals with good intentions gone awry—alien species misunderstood, technological advances with unintended consequences, thoughtful experiments that lead to terrible results. The most interesting moments in science and society are those when the right course seems totally obvious (kill the alien invaders!)—and turns out to be totally wrong-headed (not all the invaders!).
 

__________________________________

Paul Doherty works at The Exploratorium, San Francisco's museum of science, art, and human perception—where science and science fiction meet. For more on Paul's work and his latest adventures, visit www.exo.net/~pauld. Pat Murphy used to work at the Exploratorium, but now she works at Klutz (www.klutz.com), a publisher of how-to books for kids. You can find out more about Pat's work at her newly refurbished website at www.brazenhussies.net/Murphy.

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