rom the air we breathe to the food we eat to the ground and floors we walk on, bacteria
are everywhere. They are the true masters of the Earth, among whom we survive, perhaps,
more precariously than we care to admit. This point was forcibly hammered home in the
1330s, when the bacillus Pasteurella pestis, a.k.a. the
bubonic plague or Black Death,
wiped out a third of the population of Europe. Today, the Plague is common in
rodents throughout the world, but human cases are rare (only 10-15 cases per
year in the United States, and 1,000-3,000 per year worldwide), and with a mortality
rate of only 14% given prompt antibiotic treatment, human plague deaths are
rarer still.
Much of the credit for this goes to Scottish microbiologist Alexander Fleming,
who in 1928, through a combination of blind luck and poor experimental hygiene,
discovered a mold--Penicillium notatum--which was capable of killing off bacteria.
This was actually not the world's first antibiotic; since ancient times, physicians
have sped the healing of wounds with honey and spiderwebs and various herbal pastes
and poultices, including molds. But penicillin was the first such drug to be
studied closely, industrially refined, concentrated and pressed into edible
tablets for the bodywide treatment of infection.
This idea was not widely implemented at first, but when World War II began
presenting Allied doctors with wounded men by the thousands upon thousands,
the survival benefits of oral antibiotic treatment quickly became apparent;
penicillin-filled soldiers were able to stave off infection as never before,
healing more quickly and more completely than even the doctors themselves could
believe. Penicillin was hailed as a wonder drug, and the age of antibiotics was
born.
War breeds medicine's new weapon
Soon, researchers were isolating, synthesizing and mass-producing the
bacteria-killing substances from all the age-old remedies and more, adding
weapons like erythromycin and tetracycline (1952) to the armories of 20th-century
medicine. Which was a good thing, because penicillin turned out to
be poisonous only to Gram-positive bacteria--those with a thick layer of
the substance peptidoglycan in their outer wall. Infectious agents such as
Mycobacterium tuberculosis--the cause of the progressive lung disease
tuberculosis--were not affected by it at any dose. But as the latter
half of the 20th Century unfolded, antibiotics specific to every major
bacterial pathogen were found, and dread diseases such as tuberculosis,
cholera and bubonic plague all but vanished from the developed world.
Bacterial infection, a source of mortal terror since before the dawn of
civilization, was suddenly demoted to the level of mere inconvenience.
Moreover, many of the antibiotics discovered were "broad-spectrum"
treatments, capable of killing off virtually any bacterium at all,
often with few if any side effects in human beings.
That turned out to be a good thing, too, because bacteria, the most metabolically
inventive organisms on the planet, have had nearly four billion years' experience in
adapting to chemically unfriendly environments. Since it takes an average bacterium
only about 20 minutes to reproduce itself, as opposed to years or decades for
higher animals, bacteria are capable of evolving hundreds of thousands of times
faster. If evolution were a footrace, bacteria would be circling the entire
Earth in the time it took the rest of us to circle the block. And the presence
of poisons in the environment turns out to be an ideal driver of natural selection,
because the weak die off quickly, while the strong--the resistant--may hang
on long enough to reproduce, passing their slightly better genes along to an
exponentially growing family of descendants. Then the weaker descendants die
off, while their superior siblings survive. ... Whatever doesn't kill you makes
you stronger, yeah. Rapidly.
Bacteria have another trick, too: unlike higher animals, they're able to
share and trade ring-shaped DNA segments called plasmids--the genetic equivalent
of software plug-ins or card game booster packs, which contain important new talents,
such as the ability to metabolize a dangerous substance. And with surprising altruism,
even bacteria of different species can and do help each other out this way, so doctors
began to find that if some hapless patient quit taking his medicine before an infection
was 100% cured, he not only incubated a strain of resistant microbes inside his own
body, but sometimes wound up educating the unrelated strains inhabiting his home,
office, car and family.
By the 1960s, we began to hear rumors of penicillin-resistant strains of syphilis
and gonorrhea--diseases often acquired and treated in secret, away from medical
scrutiny. Soon, though, other illnesses were showing similar signs of trouble.
Of course, any genetic trait requires time and energy to support, so these
resistances often vanished when a new class of drugs were brought to bear.
Bugs which had learned to live with penicillin would generally succumb to
something stronger like tetracycline, which also gave the penicillin a
chance to "rest" while its enemies forgot about it. For a while, it seemed
this drug rotation strategy might keep the world healthy forever.
Alas, evolution is smarter than that. In order to survive and reproduce, bacteria
rely on a series of metabolic tools and processes--their internal life-support
systems, their metabolism. Antibiotics operate by disrupting these. Any break
in the metabolic chain will suffice to kill off an infection, and every family of
antibiotics targets a different life support process, so it seems reasonable to
suppose that no single bacterium could be immune to everything. But at heart these
processes are all molecular: an enzyme breaks down sugar molecules for energy,
another brings together amino acids to form a protein, and so on. All of this
is made possible by tiny molecular motors called efflux pumps, which dot the surface
of a bacterium's outer membrane, and which carefully and constantly control the
critter's internal chemistry. Food, water and electrolytes are passed inside
for the grand construction project that will let the cell reproduce and divide,
while toxins and waste products are pumped out.
The supergerms deliver a stalemate
By the early 1990s, the phenomenon of multiple drug resistance was well documented;
some bacteria were immune not only to antibiotics from wildly different families, but
to new drug families they had never been exposed to in the first place! The bacteria
had done an end-run around our defenses; they had simply increased the number of
efflux pumps in their membranes, and were getting rid of everything they didn't
immediately need or want inside them. By 1997, doctors were seeing their final
defensive lines crumble, as enemy staph and strep bacteria--ubiquitous sources
of human infection--began to overcome vancomycin. That's the broadest and most
powerful antibiotic known, and is toxic enough to humans that it had long been
reserved as a drug of last resort. For the first time in nearly half a century,
the developed world faced bacterial infections that were literally incurable.
And that was three and four years ago.
Not to be alarmist, but this is no longer a science fictional scenario.
This is no longer an issue we can push off into some indefinite future. In the past
few years, our farms and hospitals--ostensibly civilization's life support
centers--have become the spawning grounds of supergerms, which are immune
to every treatment we can throw at them. Our prisons and homeless shelters are
even worse, and countries like Russia, which have fallen on hard times, can now
boast tuberculosis and other deadly-again diseases as their largest export
commodity. According to the Centers for Disease Control, almost 70,000 Americans
died of bacterial infection in 1998, and last year's age-adjusted rates were up
4.8% for septicemia, and roughly 2.3% for pneumonia. If you haven't known or
heard of someone who's died this way, chances are you soon will.
That's the bad news. The good news is that there are simple things you can do to
protect yourself. Staying out of the hospital is a good first step; outpatient care
is usually a fine alternative. Also, use antibiotics only and exactly as prescribed
by your doctor, and throw away those silly antibacterial hand soaps; unless you're
scrubbing in for surgery, their health benefits are entirely negative. On
a more subtle note, U.S. factory-farming practices are increasingly churning
out meat products contaminated with resistant bacteria. When was the last time
you felt safe eating raw eggs or undercooked meat? Organic produce isn't
really that much more expensive, and may prove substantially safer in the long
run. Ask a victim of Mad Cow Disease! Also, support for strong public health
programs should be seen as a medical issue, rather than a political one on
the illusory liberal-conservative scale.
The other good news is that antibiotic research, after years of slumber, has
reawakened with several promising lines of attack, including new drugs which target
and shut down the efflux pumps themselves. And as 20th-century style drug research
(a.k.a. "the bug juice lottery") gives way to medicines designed from the molecular
level up, we'll almost certainly discover new Achilles heels in the machineries of
bacterial life, and also new ways to immunize our own bodies. The golden age may
yet be restored.
For a while, anyway; given the speed of evolution and the ubiquity of bacteria
in our environment, this is a war we can stalemate, but never win.
Wil McCarthy is a rocket guidance engineer, robot designer, science fiction author
and occasional aquanaut. He has contributed to three interplanetary spacecraft, five
communication and weather satellites, a line of landmine-clearing robots, and some
other "really cool stuff" he can't tell us about. His short fiction has graced the
pages of Analog,
Asimov's, Science Fiction Age and other major publications, and his
novel-length works include Aggressor Six, the New York Times Notable
Bloom, and The Collapsium.
