Resistance To Drugs And Poisons

When antibiotics were first introduced in the 1940s, everyone thought that they would finally solve the problem of infectious disease caused by bacteria. The drugs worked so well that nearly everyone with tuberculosis, strep throat, or pneumonia could be cured with a couple of simple injections or a vial of pills. But we forgot about natural selection. Given their huge population sizes and short generation times—features that make bacteria ideal for studies of evolution in the lab—the chance of a mutation producing antibiotic resistance is high. And those bacteria that are resistant to a drug will be those that survive, leaving behind genetically identical offspring that are also drug-resistant. Eventually the effectiveness of the drug wanes, and once again we have a medical problem. This has become a severe crisis for some diseases. There are now strains of tuberculosis bacteria, for example, that have evolved resistance to every drug doctors have used against them. After a long period of cures and medical optimism, TB is once again becoming a fatal disease.

This is natural selection, pure and simple. Everyone knows about drug resistance, but it's not often realized that this is about the best example we have of selection in action. (Had this phenomenon existed in Darwin's time, he would certainly have made it a centerpiece of The Origin.) It is a widespread belief that drug resistance occurs because somehow the patients themselves change in a way that makes the drug less effective. But this is wrong: resistance comes from evolution of the microbe, not habituation of patients to the drugs.

Another prime example of selection is resistance to penicillin. When it was introduced in the early 1940s, penicillin was a miracle drug, especially effective at curing infections caused by the bacteria Staphylococcus aureus ("staph"). In 1941, the drug could wipe out every strain of staph in the world. Now, seventy years later, more than 95 percent of staph strains are resistant to penicillin. What happened was that mutations occurred in individual bacteria that gave them the ability to destroy the drug, and of course these mutations spread worldwide. In response, the drug industry came up with a new antibiotic, methicillin, but even that is now becoming useless due to newer mutations. In both cases, scientists have identified the precise changes in the bacterial DNA that conferred drug resistance.

Viruses, the smallest form of evolvable life, have also evolved resistance to antiviral drugs, most notably AZT (azidothymidine), designed to prevent the HIV virus from replicating in an infected body. Evolution even occurs within the body of a single patient, since the virus mutates at a furious pace, eventually producing resistance and rendering AZT ineffective. Now we keep AIDS at bay with a daily three-drug cocktail, and if history is any guide, this too will eventually stop working.

The evolution of resistance creates an arms race between humans and microorganisms, in which the winners are not just bacteria but also the pharmaceutical industry, which constantly devises new drugs to overcome the waning effectiveness of old ones. But fortunately there are some spectacular cases of microorganisms that haven't succeeded in evolving resistance. (We must remember that the theory of evolution doesn't predict that everything will evolve: if the right mutations can't or don't arise, evolution won't happen.) One form of Streptococcus, for example, causes "strep throat," a common infection in children. These bacteria have failed to evolve even the slightest resistance to penicillin, which remains the treatment of choice. And, unlike the influenza virus, the polio and measles viruses have not evolved resistance to the vaccines that have now been used for over fifty years.

Still other species have adapted via selection to human-caused changes in their environment. Insects have become resistant to DDT and other pesticides, plants have adapted to herbicides, and fungi, worms, and algae have evolved resistance to heavy metals that have polluted their environment. There almost always seem to be a few individuals with lucky mutations that allow them to survive and reproduce, quickly evolving a sensitive population into a resistant one. We can then make a reasonable inference: when a population encounters a stress that doesn't come from humans, such as a change in salinity, temperature, or rainfall, natural selection will often produce an adaptive response.

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