Evolution and Disease - Antibiotics in Action

Evolution and Disease

When we mention the word “evolution” we often think of land mammals evolving into whales, ape-like creatures evolving into modern humans, or as some paleontologists propose, dinosaurs evolving into birds. That is, we think of changes that happened long ago in organisms. But evolution didn't just happen way-back-when. It happens today. What's more, it doesn't just happen to large animals. Evolution continues to happen to some of the smallest, simplest, and most primitive creatures on earth. Bacteria evolve and are evolving today. This can be both good and bad.

But before we can talk about why the evolution of bacteria is both good and bad, let's take a look at how evolution works. Evolution operates by what we call natural selection. Selection is something that farmers and animal breeders do to breed the best animals they can. For example, if a dog breeder wants to breed good sled dogs, he or she will select only the dogs that enjoy pulling sleds, and only allow those dogs to mate. This will ensure that the next generation of puppies will all enjoy pulling sleds. Likewise, a farmer will only breed those cows that produce lots of milk, ensuring that the next generation of cows will all give lots of milk as well.

Natural selection is similar, but it happens without the help of people. It is a result of two things: mutations and evolutionary pressures, and the next few paragraphs will help explain what these terms mean.

Each time an organism reproduces, its DNA is copied and passed along to the next generation. But the copying isn't always perfect, and changes occur whenever the DNA is copied. These changes are called mutations, and they happen at random. They happen every time an organism reproduces, so in a way we're all mutants.

Sometimes the mutations don't cause any change in the organism whatsoever. Other times, the mutation causes a harmful change in the organism. Still other times, the mutation causes a helpful change in the organism. For example, let's say two eagles have a brood of little baby eaglets. Let's suppose that due to a random mutation, one of the eaglets has poor eyesight. Since eagles need to see very well to fly and to hunt, this poor eagle may not survive long enough to reproduce. Now let's also suppose that another eaglet in the same brood has, due to a random mutation, better eyesight than any eagle has ever had. This eagle may be able to fly and hunt more effectively than all the other eagles around it. It may thrive and produce lots of offspring. After a few generations, the eagle with poor eyesight will have left few if any descendants, and the eagle with great eyesight will have left many descendants. So after a few generations, there will be lots of eagles with great eyesight, and few with poor eyesight. In fact, this is what we observe. Eagles have very good eyesight, and this is why we say a person who can see well has an “eagle eye.”

This is natural selection at work. The need to see well for flying and hunting is what we call an example of an evolutionary pressure. This evolutionary pressure “weeded out” the eagle that couldn't see well, and allowed only eagles with good vision to survive and reproduce. In the same way that farmers select only the animals with desirable traits, nature “selects” only those organisms with what it takes to survive.

Over time, the evolutionary pressures may change. For example, the climate of a place may change, or new predators or prey may be introduced to an environment. When this happens, the rules change, and what it takes to survive will change. Nature will begin to “select” for different traits. Then organisms will change and adapt, as the random mutations that are helpful in the new order of things become selected for. For example, if a lake dries up, a random mutation that allows a fish to survive out of water will be selected for, whereas it wouldn't have been before the lake dried up. Changes in the environment then lead to changes in organisms. This is why land mammals became whales, why early hominids became modern humans, and why dinosaurs may have evolved into birds.

But what about those little bacteria? What evolutionary pressures are there on bacteria to evolve? Antibiotics are one evolutionary pressure that humans are placing on bacteria. Antibiotics sometimes manage to only kill the more susceptible bacteria. The surviving bacteria survive because they can resist antibiotics. The surviving bacteria then reproduce, producing a new generation of bacteria, all of which are resistant to today's antibiotics. This is not good, because it makes infectious diseases harder to fight. (You can read more about this at Bugs Fighting Back: Basics of Bacterial Resistance.)

So we humans have actually made some bacteria tougher to kill by our attempts to fight them. But some scientists have wondered that if we can place evolutionary pressures on bacteria to make them tougher, could we also use evolutionary pressure to make bacteria less harmful? Many harmless bacteria are living in the bodies of every human being. Could we use evolutionary pressure to turn our most dreaded pathogens into equally harmless bacteria?

Some say it's possible. To see just how, let's look at a disease called cholera. Cholera is not a pleasant sickness to have. It causes massive diarrhea and vomiting, and this sometimes leads to death from dehydration. The bacterium that causes cholera, Vibrio cholerae, is spread by drinking contaminated water. Needless to say, cholera is found most often in places without modern water treatment and poor sanitation: the world's developing nations.

Recent research by Andrew Camilli and cowokers at Boston's Tufts University has shown that V. cholerae taken from the stools of cholera patients is hundreds of times more virulent that the V. cholerae cultured in the laboratory. The reasons for this are not known, but Camilli's team has found that there are at least ten genes that are inactive in laboratory-cultured V. cholerae, but are active and functioning in the V. cholerae grown inside the intestines of a mouse.

This means that scientists can try to design vaccines that work by inactivating some or all those ten genes somehow. But it also means that we can take another approach to fighting cholera. If V. cholerae becomes virulent in people's intestines, then it would be a good idea to keep V. cholerae out of people's intestines! How do we do this? The best way is with good water treatment to make sure that the water people drink doesn't have V. cholerae living in it, and to provide good sanitation, that is, flushing toilets and sewage treatment, so that the feces of people sick with cholera doesn't infect the drinking water supply.

This is not a new idea. In fact, it was used first in North America and western Europe in the late 1800s, and virtually wiped out cholera in the developed world. It's still considered the best way to fight cholera. But for decades, scientists thought we were only protecting ourselves by keeping the nasty V. cholerae out of our bodies when we cleaned up our drinking water. Now we are learning that in places where a clean water supply ensures that V. cholerae is kept out of people's intestines, the V. cholerae that lives in untreated water is in fact much less potent.

Have we applied an evolutionary pressure on V. cholerae to make it less virulent, simply by cleaning up our drinking water supply? Possibly, though we can't say for certain at this point. But it raises a question: If we can tame V. cholerae, what about other pathogens?

It might be possible. For example, some have speculated that promiscuity has allowed sexually tranmitted diseases such as HIV/AIDS to become more deadly. If a person is monagomous, the disease is forced to keep the host alive for many years in order to spread. Meanwhile, if a person has many partners, the disease can kill its host quickly, as it will soon be spread to other hosts, the reasoning goes. If this speculation is correct, then monagomy would be one way of exerting an evolutionary pressure on a sexually transmitted microbe to become less virulent.

It may well be that the simple means of preventing disease that we've known about for years also may help make diseases less dangerous. While this facet of evolutionary science is still in its infancy, it does offer hope in our fight against disease. This is a battle we once thought was won, but now seems to be flaring up again thanks to antibiotic-resistant bacteria. But the new emerging knowledge tells us something we've known for a long time: Antibiotics are just part of our defense against disease, and they must be used carefully and in conjunction with good disease prevention techniques to bring about long-term security from disease.
For more information, at other Web Sites...

The Alliance for the Prudent Use of Antibiotics (APUA) — official site with information for patients and health care professionals.
Charles F. Chandler — a biographical sketch, part of Chemical Achievers from the Chemical Heritage Foudnation.
Cholera Needs Guts to Survive — from Nature Science Update.
Evolution: A Journey into Where We're From and Where We're Going — companion site to the PBS series, featuring content on the evolution of antibiotic resistance under the heading “survival.”
The Rise of Antibiotic-Resistant Infections — from FDA Consumer, September 1995, published by the U.S. Food and Drug Administration.

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Reference

“The Evolutionary Arms Race” — Part 4 of the PBS series Evolution, produced by Richard Hutton, 2001.

Copyright ©2002 The Chemical Heritage Foundation