Writing Samples

The Multiplicity of Microbes
by Valerie J. Brown
Published Autumn 1998 in Conservation Matters
http://www.clf.org/pubs/microbes.htm

Are plague and pestilence part of our future? Are we losing the war against the humble bacterium? Some experts think we will, unless we can match the microbe's versatility with new ways of looking at them.

Recently, an intriguing bacterium has come to the attention of some microbiologists. Burkholderia (Pseudomonas) cepacia was first described in 1949 as a rotter of onions. Sometime in the late 1970s, it surfaced as an opportunistic predator of people with cystic fibrosis (CF), causing serious lung and blood infections and a significant increase in death rates among CF patients.

At about the same time, agricultural biologists noticed that B. cepacia has amazing capabilities to attack blight in rapeseed, canola, and ginseng plants, as well as several other diseases in a number of other economically significant plants. Then environmental microbiologists noticed that B. cepacia can break down toxic chemicals such as chlorinated aromatics found in pesticides and herbicides. To top off its talents, B. cepacia has an enormous, mutation-prone genome and multiple antibiotic resistance.

The microbiologists involved in these studies only learned by chance about each other's activities a couple of years ago. Since then, experts from all sides, mediated by the EPA, have been trying to sort out the questions raised by the prospect of a known human pathogen coming into widespread, intentional industrial use.

The problem is a new twist in the old relationship between humans and microbes. B. cepacia is only one of a growing list of microbes that have, seemingly suddenly, turned from benign to threatening, from the conquered to the conquering. These microbes range from the terrifying hemorrhagic viruses such as Ebola to the mundane fungi responsible for athlete's foot. Old infectious diseases once thought defeated, such as malaria and tuberculosis, have also revived, sometimes in more dangerous forms. Add the alarming increase in antibiotic resistance among disease germs, and we have a very serious global threat.

Yet, terrifying as the prospect of worldwide plague is, the microbial situation is also revealing profound wonders about both human and planetary biology. Since Pasteur established the germ theory of disease in the late 19th century, humans have considered microbes enemies. The body is a battleground, the immune system an army, the doctor a commander-in-chief wielding powerful weapons, namely, antibiotics. When first introduced shortly after World War II, antibiotics were truly miracles, turning once-fatal bacterial infections into short-term inconveniences. By 1962, some 25,000 antibiotics had been developed and public health authorities assumed infectious diseases were a thing of the past.

Inherent failure

However, antibiotics contained the seeds of their own destruction. They would inevitably fail because of the ruthless law of natural selection, which forces a species to adapt to its environment or die. As soon as bacteria were exposed to antibiotics, they found ways to evade them. Even a weak ability to resist an antibiotic will give a microbe a better chance of surviving the flooding of its environment with a chemical that was toxic to it. Survivors have carte blanche to repopulate the devastated landscape, until they dominate the ecological niche and are impervious to the antibiotic. This problem is rapidly reaching crisis proportions with Staphylococcus aureus, which commonly infects hospital patients and of which a totally drug-resistant strain has now emerged.

Such resistance was observed very early in the antibiotic revolution, but its significance was lost in the wave of miraculous cures that followed. However, researchers soon noticed that antibiotic resistance was cropping up in microbes that had never been exposed to that drug. It turns out that both bacteria and viruses can share genetic material on a global scale, by swapping genes and trading smaller DNA snippets called plasmids and transposons. It's as if there's a microbial Internet distributing resistance capacity far and wide-even to microbes not known (so far) to be human pathogens.

The existence of this web is not equally astonishing to all microbiologists. While medical microbiologists tend to focus on particular types of bacteria that cause trouble for human beings, and think of them as individual species, microbial ecologists tend to think of bacteria as interconnected because, in principle, any bacterium may exchange genetic material with any other bacterium. In the words of microbiologist Lynn Margulis at the University of Massachusetts at Amherst, "This extreme genetic fluidity makes the concept of species meaningless."

Moreover, as Tufts University School of Medicine professor Dr. Stuart B. Levy has written, "Antibiotic usage has stimulated evolutionary changes that are unparalleled in recorded biologic history."This usage includes not only prescribed doses by physicians, but a vast international black market and the administration of antibiotics to more than six billion food animals and domestic pets in the U.S. each year. Levy can imagine a time when resistance factors have distributed so thoroughly in the global bacterial community that resistance is the norm rather than the exception. If that happens, plagues, or at least serious epidemics, are probably inevitable. As president of the Alliance for the Prudent Use of Antibiotics, Levy is working to increase international awareness of the problem and its potential solutions. (See box.)

Evolution - Beyond Darwin

In our antibiotic naivete, we have been influencing microbial evolution unconsciously. Now some scientists want to do it consciously. Amherst College evolutionary biologist Paul Ewald has been studying ways to make the cholera bacterium Vibrio cholerae less virulent by manipulating its environment. (Virulence is a measure of how strongly the germ overcomes the host's immune system and how sick the host gets. Antibiotic resistance does not necessarily increase virulence.) Ewald is taking advantage of the biological principle that the easier the access to a host, the more virulent the germ. That's especially true with waterborne diseases such as cholera. Because access via water is so easy, cholera can make its victims very sick and still move on to new ones. But if the water supply is clean, the microbe has trouble distributing itself. Therefore it makes its victims less sick so that it can stay inside them longer and be transmitted more frequently. As-yet unpublished work from his lab has, Ewald says, provided the strongest evidence that simply cleaning up a water supply not only reduces human exposure to the cholera germ, but makes the germ less virulent.

"Up till now, we've been looking at disease organisms as adversaries to be eradicated and we've locked ourselves into arms races with them,"Ewald says, "but this approach is quite different. It says, 'Let's realize that these organisms are evolving entities and use that knowledge to our advantage, so that we're not trying to eradicate them with weapons, but changing the environment and getting them to evolve toward benignity.'"

The evolutionary perspective shifts the way microorganisms and disease are conceptualized. Microbes are ubiquitous and ineradicable-it can even be said that humans inhabit the microbial web rather than vice versa. Human and microbial fates are inextricably intertwined. Interspecies relationshipsoccupy a spectrum, from mutualism to parasitism. (See graphic.) The organisms that make us sick are at the parasitic end of this spectrum."All we're trying to do is push our symbioses toward the mutualism side,"Ewald says. "If we can do anything to make sure that those organisms that are living inside us are very mild, we'll be better off. We can make something like a free live vaccine if we invest in efforts that will favor the mild organism."Ewald suggests that an evolutionary approach not only can make existing pathogens less virulent, but can "keep harmful organisms from emerging in the first place even if we haven't identified them."

The shifting grounds of relativity

The perspective is very promising, but not all microbes may respond to evolutionary nudging. And the human immune system is as complicated as the microbial web. Just deciding whether an organism is harmful has become difficult. John LiPuma, a pediatrician and microbiologist at Allegheny University of the Health Sciences in Philadelphia and a member of the International B. Cepacia Working Group, says, "In the past 20 years, [scientists] on the medical side have been changing our definition of a pathogen, mainly because of AIDS. The definition is relative and there are a number of populations in which a nonpathogen may in fact be pathogenic."People with cystic fibrosis are vulnerable to a simple onion blight, just as hospital patients weakened by other disease or surgery may not be able to fight off Staphylococcus aureus. Thus one person's benign companion may be another person's fatal germ. This relativity complicates the scientific and political struggles for solutions.

In order for promising microbes such as B. cepacia to be used safely, and for humans to stifle potential global epidemics, such solutions must be found. Now that we're beginning to understand just how little we really know, the task is both daunting and fascinating. Though LiPuma remains optimistic that the safe use of bacteria such as B. cepacia can be achieved, he cites the disastrous consequences to ecosystems of introduced species at the macro level. "Manipulating the micro environment and doing simple interventions will have effects that we can't even imagine,"he says.

The emerging picture of the microbial world raises more questions than it answers, and the antibiotic crisis proves once again that "we have met the enemy and he is us."Human behavior strongly encouraged the present situation, and human behavior must change, whether by modifying antibiotic use or manipulating microbial environments in other ways. To subvert the potential for global plague we must apply the very evolutionary principle that got us here-natural selection- in ways that benefit us rather than endanger us. Anything we can do to shift the relationship between the immune system and the microbial web from a fight to a dance will help us reach a new equilibrium.

ANTIBIOTIC DO'S AND DON'TS

DO recognize that microbes are everywhere, that most are benign or beneficial, and that we need to find a balance with them rather than try to kill them all, which is impossible.
DON'T ask your doctor to prescribe an antibiotic for a viral problem, such as a cold or the flu, because antibiotics don't work against viruses.
DO, if prescribed an antibiotic, always follow the instructions exactly and finish the complete course of treatment.
DON'T hoard antibiotics or give them to others, including your children or your cat.
DO wash raw fruits and vegetables thoroughly and make sure all meat you eat is completely cooked.
DON'T use antibacterial soaps and other products except around an immune system-compromised person.

[From "The Challenge of Antibiotic Resistance," by Stuart Levy, M.D., published in Scientific American, March 1998.]

To learn more about bacteria and their evolution, read:

The Antibiotic Paradox: How Miracle Drugs are Destroying the Miracle, by Stuart B. Levy, M.D., Plenum Press, 1992.

The Coming Plague: Newly Emerging Diseases in a World Out of Balance, by Laurie Garrett, Farrar, Straus & Giroux, 1994.

Slanted Truths: Essays on Gaia, Symbiosis and Evolution, by Lynn Margulis and Dorion Sagan, Springer-Verlag New York, Inc., 1997.

Valerie J. Brown is a freelance writer based in Portland, Oregon. She specializes in science, health, and social issues. She has written for a number of Pacific Northwest publications and contributes frequently to Environmental Health Perspectives and Columbia University's _21stC_. She is also a singer and songwriter.