Antibiotics

It is obvious that the human immune system has been involved in a type of arms race against many pathogens that have been scourges upon mankind since the beginning of history. Arms races against pathogens, either specific types or simply pathogens in general, could account for the stunning complexity of the immune system we see today. The introduction of antibiotics as a supplement to the basic human immune system has led to easily observable evolutionary changes in the fast-mutating population of bacteria.

Antibiotics are one of the most important twentieth-century inventions, and they have saved countless lives from otherwise generally fatal diseases. However, their use (and abuse) has helped to foster their own ineffectiveness against the bacterial population. When antibiotics were first introduced, they doubtless seemed like wonder drugs that could cure all diseases caused by bacteria. Penicillin was the first discovered, as an element of fungal natural defense against bacteria. Scientists rapidly isolated other compounds with similar properties from additional fungi as well as from other organisms. They refined, purified, synthesized, and sometimes altered or combined these compounds for use against different types and classes of bacteria. This explosion in human defenses against bacteria surely led to a drastic decrease in the bacterial population as a whole.

The bacteria were not in any danger, however. They are quick to grow and reproduce, and they lack many of the "genetic proofreading" mechanisms possessed by humans and other higher organisms. In addition, many bacteria can share genetic information by transferring short loops of genetic material called plasmids between different bacterial organisms or different species, which are sometimes widely different. Even before the introduction of antibiotics for human use, some bacteria held antibiotic-resistance genes, presumably as adaptations against the antibiotics in nature.

Preexisting resistance genes, ease of mutation, and exchange of genetic material was a recipe for breeding antibiotic resistance, especially in a time when antibiotics were routinely fed to livestock en masse, prescribed even for non-bacterial infections, demanded by housewives to treat their sick children, and prescribed by doctors unaware of the dangers. Added to the volatile mix was the fact that people commonly stopped taking their medicine after they began to feel better, instead of finishing the full prescription; this is one of the best ways to breed resistant organisms.

As could be predicted, bacteria began to exchange their antibiotic-resistance genes among each other in the form of easily transferable plasmids. New mutations also sprang up quickly, and existing resistance genes were improved due to natural selection. The ubiquity of antibiotics worked in the bacteria's favor, because they drugs would decimate all but the hardiest and most resistant bacteria in any population. These few survivors would then enjoy a bonanza of feeding, growth, and reproduction, which led to new infections and more doses of antibiotics, which again weeded out the less-adapted, and so on in a vicious cycle. The result was that bacteria quickly evolved resistance to the mainstays of the antibiotic arsenal, and consequently newer drugs were introduced, to which the bacteria then adapted further. The ultimate result of this evolution is that bacteria are now being noted that are resistant to all known antibiotics, including "last-resort" drugs and even synthetic drugs. This last implies gradual refinement of spontaneous mutations, since bacteria could not have had preexisting genes for resistance to synthetic compounds.

Resistance in Viruses

Bacteria are not the only organisms that evolve rapidly in response to human intervention. Viruses, the simplest of all organisms - composed just a genome of RNA or DNA and a protein coat - also respond to drugs by evolving resistance. In general, an antiviral drug attacks the conformation of the virus' protein coat in some way, thereby disabling its ability to infect cells. Viruses respond with alterations of the conformation of their protein coat, so that the drugs no longer work against the new shape or structure. Viruses are especially rapid mutators because they entirely lack any proofreading mechanisms, and because of their incredibly large populations. In RNA viruses, called retroviruses, the enzymes they use to transcribe RNA into DNA is relatively "sloppy" and adds another rich source of mutations.

One excellent example of virus mutation is provided by HIV. This virus, a retrovirus, commonly evolves so quickly that the strain originally present in an infected person could be entirely different from the strain isolated after the person's death. The human immune system is overwhelmed, not only because the virus targets immune cells specifically, but also because of the extremely high mutation rate. As soon as defenses have been constructed against one strain, the virus simply mutates and the defenses become useless. In experimental-drug trials, compounds that initially were highly successful later waned in their success because the viruses in one individual had evolved resistance to the drug. This incredible mutation rate is one extremely important factor in our difficulty in containing the virus: vaccines or drugs are very difficult to create, because they virus quickly mutates and renders them useless. Even worse, such drugs and vaccines are unlikely to be effective against the entire population of viruses at once, because they exhibit such vast diversity.

The New Arms Race

For the vast majority of human existence, the arms race has been between pathogenic adaptations and human adaptations. Now, since they introduction of antibiotics, a new type of arms race has begun: a race between pathogenic adaptations and human ingenuity. This battle, which pits the forces of natural selection against the intelligence natural selection helped to create, is unprecedented in evolutionary history. The results - and the battle itself - are sure to be fascinating and instructive.

The Immune System: Simulation

A virtual experiment in which you can design your own antibodies and test them against simulated viruses! This simulation is an excellent demonstration of the operation of the immune system, and it gives you an opportunity to take clonal selection into your own hands. Try the Viruses and Antibodies simulation now!

Notes

The term "arms race" is commonly used in relation to the ideas presented here, but was first encountered in Richard Dawkins' book The Extended Phenotype. The concepts and examples used in the text are original.

Links and References

The following links and references will be useful in the study of arms races in nature and the problem of antibiotic resistance.

• Books
  • The Extended Phenotype by Richard Dawkins

• Websites
  • The Challenge of Antibiotic Resistance
  • Center for Science in the Public Interest - Antibiotic-Resistance Project
  • Emerging Antibiotic Resistance
  • Understanding Drug Resistance

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