<p> Before the coming of penicillin and other antibiotics, bacterial
diseases simply ran their courses. Either the immune system
fought them off and the patient survived or the battle was lost.
But antibiotics changed the contest radically: they selectively
killed bacteria without harming the body's cells. For the first
time, potentially lethal infections could be stopped before
they got a foothold.
</p>
<p> Unfortunately, as Columbia University's Dr. Harold Neu observed
in the journal Science, "bacteria are cleverer than men." Just
as they have adapted to nearly every environmental niche on
the planet, they have now begun adjusting to a world laced with
antibiotics. It didn't take long. Just a year or two after penicillin
went into widespread use, the first resistant strain of staph
appeared. As other antibiotics came along, microbes found ways
to resist them as well, through changes in genetic makeup. In
some cases, for example, the bacteria gained the ability to
manufacture an enzyme that destroys the antibiotic.
</p>
<p> By now nearly every disease organism known to medicine has become
resistant to at least one antibiotic, and several are immune
to more than one. One of the most alarming things about the
cholera epidemic that has killed as many as 50,000 people in
Rwandan refugee camps is that it involves a strain of bacterium
that can't be treated with standard antibiotics. Relief agencies
had to scramble for the right medicines, which gave the disease
a head start in its lethal rampage.
</p>
<p> Tuberculosis, too, has learned how to outwit the doctors. TB
is an unusually tough microbe, so the standard therapy calls
for several antibiotics, given together over six months. The
length and complexity of the treatment have kept underdeveloped
nations from making much progress against even ordinary TB.
But now several strains have emerged in the U.S. and other developed
countries that can't be treated with common antibiotics.
</p>
<p> Even such seemingly prosaic but once deadly infections as staph
and strep have become much harder to treat as they've acquired
resistance to many standard antibiotics. Both microbes are commonly
transmitted from patient to patient in the cleanest of hospitals,
and they are usually cured routinely. But one strain of hospital-dwelling
staph can now be treated with only a single antibiotic--and
public health officials have no doubt that the germ will soon
become impervious to that one too. Hospitals could become very
dangerous places to go--and even more so if strep also develops
universal resistance.
</p>
<p> One of medicine's worst nightmares is the development of a drug-resistant
strain of severe invasive strep A, the infamous flesh-eating
bacteria. What appears to make this variant of strep such a
quick and vicious killer is that the bacterium itself is infected
with a virus, which spurs the germ to produce especially powerful
toxins. (It was severe, invasive strep A that killed Muppeteer
Jim Henson in 1990.) If strep A is on the rise, as some believe,
it will be dosed with antibiotics, and may well become resistant
to some or all of the drugs.
</p>
<p> Microbes' extraordinary ability to adapt, observes Harvard microbiologist
Fields, "is a fact of life. It's written into evolution." Indeed,
the end run that many organisms are making around modern antibiotics
is a textbook case of Darwin's theory in action (anti-evolutionists,
take note). In its simplest form, the theory states that new
traits will spontaneously appear in individual members of a
given species--in modern terms, mutations will arise in the
organisms' genetic material. Usually the traits will be either
useless or debilitating, but once in a while they'll confer
a survival advantage, allowing the individual to live longer
and bear more offspring. Over time, the new survival trait--camouflage stripes on a zebra, antibiotic resistance in a bacterium--will become more and more common in the population until
it's universal.
</p>
<p> The big difference between animals and bacteria is that a new
generation comes along every few years in large beasts--but
as often as every 20 minutes in microbes. That speeds up the
evolutionary process considerably. Germs have a second advantage
as well: they're a lot more promiscuous than people are. Even
though bacteria can reproduce asexually by splitting in two,
they often link up with other microbes of the same species or
even a different species. In those cases, the bacteria often
swap bits of genetic material (their DNA) before reproducing.
</p>
<p> They have many other ways of picking up genes as well. The DNA
can come from viruses, which have acquired it while infecting
other microbes. Some types of pneumococcus, which causes a form
of pneumonia, even indulge in a microbial version of necrophilia
by soaking up DNA that spills out of dead or dying bacteria.
This versatility means bacteria can acquire useful traits without
having to wait for mutations in the immediate family.
</p>
<p> The process is even faster with antibiotic resistance than it
is for other traits because the drugs wipe out the resistant
bacterium's competition. Microbes that would ordinarily have
to fight their fellows for space and nourishment suddenly find
the way clear to multiply. Says Dr. George Curlin of the National
Institute of Allergy and Infectious Diseases: "The more you
use antibiotics, the more rapidly Mother Nature adapts to them."
</p>
<p> Human behavior just makes the situation worse. Patients frequently
stop taking antibiotics when their symptoms go away but before
an infection is entirely cleared up. That suppresses susceptible
microbes but allows partially resistant ones to flourish. People
with viral infections sometimes demand antibiotics, even though
the drugs are useless against viruses. This, too, weeds out
whatever susceptible bacteria are lurking in their bodies and
promotes the growth of their hardier brethren. In many countries,
antibiotics are available over the counter, which lets patients
diagnose and dose themselves, often inappropriately. And high-tech
farmers have learned that mixing low doses of antibiotics into
cattle feed makes the animals grow larger. (Reason: energy they
would otherwise put into fighting infections goes into gaining
weight instead.) Bacteria in the cattle become resistant to
the drugs, and when people drink milk or eat meat, this immunity
may be transferred to human bacteria.
</p>
<p> Because microbial infections keep finding ways to outsmart antibiotics,
doctors are convinced that vaccines are a better way to combat
bacterial disease. A vaccine is usually made from a harmless
fragment of microbe that trains the body's immune system to
recognize and fight the real thing. Each person's immune system
is chemically different from everyone else's, so it's very difficult
for a bacterium to develop a shield that offers universal protection.
Diphtheria and tetanus can be prevented by vaccines if they
are used properly. A vaccine against the pneumococcus bacterium
has recently come out of the lab as well, and scientists expect
to test one that targets streptococcus A within a year.
</p>
<p> VIRUSES
</p>
<p> Unlike bacteria and protozoans, which are full-fledged living
cells, capable of taking in nourishment and reproducing on their
own, viruses are only half alive at best. They consist of little
more than a shell of protein and a bit of genetic material (DNA
or its chemical cousin RNA), which contains instructions for
making more viruses--but no machinery to do the job. In order
to reproduce, a virus has to invade a cell, co-opting the cell's
own DNA to create a virus factory. The cell--in an animal,
a plant or even a bacterium--can be physically destroyed by
the viruses it is now helplessly producing. Or it may die as
the accumulation of viruses interferes with its ability to take
in food.
</p>
<p> It is by killing individual cells in the body's all-important
immune system that the AIDS virus wreaks its terrible havoc.
The virus itself isn't deadly, but it leaves the body defenseless
against all sorts of diseases that are. Other viruses, like
Ebola, kill immune cells too, but very quickly; the dead cells
form massive, deadly blood clots. Still others, hantavirus,
for example, trigger a powerful reaction in which immune cells
attack both the invading virus and the host's healthy cells.
</p>
<p> Unlike bacteria and protozoans, viruses are tough to fight once
an infection starts. Most things that will kill a virus will
also harm its host cells; thus there are only a few antiviral
drugs in existence. Medicine's great weapon against viruses
has always been the preventive vaccine. Starting with smallpox
in the late 1700s, diseases including rabies, polio, measles
and influenza were all tamed by immunization.
</p>
<p> But new viruses keep arising to challenge the vaccine makers.
They may have gone undetected for centuries, inhabiting animal
populations that have no contact with mankind. If people eventually
encounter the animals--by settling a new part of the rain
forest, for example--the virus can have the opportunity to
infect a different sort of host.
</p>
<p> Scientists believe Ebola virus made just that kind of jump,
from monkeys into humans; so did other African viruses such
as Marburg and the mysterious X that broke out in Sudan. And
many more are likely to emerge. "In the Brazilian rain forest,"
says Dr. Robert Shope, a Yale epidemiologist, "we know of at
least 50 different viruses that have the capacity of making
people sick. There are probably hundreds more that we haven't
found yet."
</p>
<p> Viruses like Ebola and X are scary, but they're too deadly to
be much of a threat to the world. Their victims don't have much
of a chance to infect others before dying. In contrast, HIV,
the AIDS virus--which may have come from African primates
as early as the 1950s--is a more subtle killing machine, and
thus more of an evolutionary success. An infected person will
typically carry HIV for years before symptoms appear. Thus,
even though HIV doesn't move easily from one human to another,
it has many chances to try. Since the first cases were reported
in the late 1970s, HIV has spread around the world to kill perhaps
a million people and infect an estimated 17 million.
</p>
<p> It isn't just new viruses that have doctors worried. Perhaps
the most ominous prospect of all is a virulent strain of influenza.
Even garden-variety flu can be deadly to the very old, the very
young and those with weak immune systems. But every so often,
a highly lethal strain emerges--usually from domesticated
swine in Asia. Unlike HIV, flu moves through the air and is
highly contagious. The last killer strain showed up in 1918
and claimed 20 million lives--more than all the combat deaths
in World War I. And that was before global air travel; the next
outbreak could be even more devastating.
</p>
<p> Vaccines should, in theory, work just as well for new varieties
of disease as they do for old ones. In practice, they often
don't. An HIV vaccine has proved difficult to develop because
the virus is prone to rapid mutations. These don't affect its
deadliness but do change its chemistry enough to keep the immune
system from recognizing the pathogen.
</p>
<p> Creating a vaccine for each strain of flu isn't exactly simple
either. "First," says Yale's Shope, "we have to discover something
new is happening. Then we have to find a manufacturer willing
to make a vaccine. Then the experts have to meet and decide
what goes into the vaccine. Then the factory has to find enough
hens' eggs in which to grow the vaccine. There are just a lot
of logistical concerns."
</p>
<p> People are partly to blame for letting new viruses enter human
populations. Says Dr. Peter Jahrling, senior research scientist
at the U.S. Army Medical Research Institute of Infectious Diseases:
"If you're a monkey imported from the Philippines, your first
stop when you hit this country is a quarantine facility. If
you're a free-ranging adult human being, you just go through
the metal detector and you're on your way."
</p>
<p> Sometimes environmental changes help microbes move from animals
to humans. Lyme disease, a bacterial infection, was largely
confined to deer and wild mice until people began converting
farmland into wooded suburbs--which provided equally good
habitats for the animals and the bacteria-infested ticks they
carry and also brought them into contact with large numbers
of people. The mice that transmit the hantavirus often take
refuge in farmers' fields, barns and even homes. Air-conditioning
ducts create a perfect breeding ground for Legionnaires' disease
bacteria. Irrigation ditches and piles of discarded tires are
ideal nesting spots for the Aedes aegypti mosquito, carrier
of dengue and yellow fevers; imported used tires have already
brought the Asian tiger mosquito, also a carrier of dengue,
into the U.S.
</p>
<p> Clearly there is no way to prevent human exposure to microbes.
But the risks can be reduced. To minimize bacterial resistance,
for example, doctors can be stingier with antibiotics. "We've
been careless," says Dr. Robert Daum, a University of Chicago
pediatrician. "Every childhood fever does not require antibiotics."
Nor does a healthy farm animal.
</p>
<p> Most important is increased vigilance by public-health authorities.
The faster a new microbe can be identified and its transmission
slowed, the less likely a small outbreak will turn into an epidemic.
Unfortunately, the trend has been in the other direction. "Even
in the U.S.," says Thomson Prentice of the World Health Organization
in Geneva, "disease-monitoring expertise has been lost, either
through cost-cutting or reduced diligence. If some of the edge
has been lost in the U.S., just imagine how poorer countries
have reacted."
</p>
<p> American health officials are convinced that their information-gathering
network must be strengthened. That has begun to happen under
a new program that will, among other things, increase the surveillance
of new microbes and educate both health workers and the public
about how to deal with emerging diseases.
</p>
<p> An all-out effort to monitor diseases, vaccinate susceptible
groups, improve health conditions around the world, develop
new drugs and get information to the public would be enormously
expensive. But the price of doing nothing may be measured in
millions of lost lives. Doctors are still hopeful but no longer
overconfident. "I do believe that we're intelligent enough to
keep ahead of things," says epidemiologist Shope. Nonetheless,
neither he nor any of his colleagues will ever again be foolish
enough to declare victory in the war against the microbes.
