Antibiotic resistance: Gene mutations or natural selection?

When a certain antibiotic fails to mop up an infection, a common statement is “Oh no! The bacteria have mutated once again!” Over time, large populations of bacteria have clearly developed resistance to a variety of antibiotics, but is antibiotic resistance really the result of gene mutations?

A mutation is a change in an organism’s normal gene sequence. Such changes occur when a cell makes a mechanical mistake as it copies a gene or when a sequence of information gets deleted, inserted, or transposed (turned end for end). Chemicals and radiation of certain kinds are known to cause harm to organisms’ genes. Agents which increase the rate of mutation are referred to as mutagens. When a mutation occurs, the normal genetic code of the organism is altered. The genetic information encoded in its cells is held on double stranded molecules called deoxyribonucleic acid (DNA). Although DNA is classified as an acid because of its chemical structure, it is more importantly a highly ordered biological molecule—much more complex than other organic molecules such as methane or ethanol. Whereas methane and ethanol repeat the same simple chemical sequence again and again, DNA contains a code much like the sentences of a written language encoded by letters. However, the genetic code contains only four characters. The sequence of characters within the DNA molecule provides the specific instructions for building proteins. Proteins are biological machines which allow the living cell to function; they are highly complex in their shapes. If the DNA code is slightly altered, the result is a protein of non-functional shape. Since protein structure is organized on at least three different levels, even if a mutation were to code for a superior protein structure, other profitable chance mutations would need to occur at the same time in order to produce structural changes at other levels to accommodate any critical positive changes. For a beneficial functional change, not only would the right random mutation need to occur, but in order to be beneficial, many other unlikely random mutations would need to occur at the same time. If all of these unlikely events did not occur simultaneously, none of them would be functional; in fact, such changes, though possibly beneficial collectively, would, in isolation, only drain the organism’s energy. The principle of irreducible complexity holds that the probability of unlikely events occurring simultaneously makes an overall beneficial result extremely unlikely—even when allowing millions or billions of years for the various unlikely events to occur at the same time. Thus, the now popular notion and claim that mutations cause any advantage of fitness is highly suspect and rests on a complete lack of observational evidence.

Rather than gene mutations, natural selection seems a more plausible explanation for antibiotic resistance. Natural selection is a readily observable and clearly understood biological principle, which holds that environmental factors select for the reproduction of individuals that are adept to the particular environmental conditions at hand. Neither is it contested that all sizeable populations exhibit great variation within their respective gene pools. Selective pressure on bacterial populations by weak administration of antibiotics has been detected within as few as one thousand bacterial generations. Many modern biology textbooks claim that bacteria evolve at a much faster rate than other organisms based on the fact that generations can double their numbers within minutes. Here, the term evolve presumes a natural increase in information and its complexity rather than simple selection of pre-existing information. Moreover, the conclusion that bacteria evolve faster than larger organisms is based on the assumption that evolution is occurring in the first place, and there is no observational evidence that it is. Even if bacteria were to have evolved over billions or millions of years to reach their present state of existence, how could random-chance mutations, over mere decades or years, produce the complex bacterial structures to alter metabolic pathways and redesign cell wall construction, which would be necessary to combat the tactics of antibiotics.

In summary, while all would agree that bacteria, like other organisms, undergo mutations, the connection between mutations and antibiotic resistance is highly suspect. Natural selection, on the other hand, is a readily observable scientific phenomenon. Thus, instead of assuming that mutations cause antibiotic resistance, it may be more accurate to conclude that selection of genetically resistant bacteria has occurred. There is no reason to doubt that all of the genes for resistance have been ever-present within the gene pool.

Dr. W. Daniel Bacon
Via email