Where plants and large animals are concerned, evolutionary change is usually viewed as a gradual process unfolding over hundreds of thousands or millions of years. In microbiology, however, the impact of evolution can make itself felt in months, even weeks, and do so in a manner that directly affects the survival of larger species such as ourselves.
AIDS offers a dramatic example. Random mutation acted upon by natural selection enables HIV, the virus that causes AIDS, to rapidly neutralize the effectiveness of drugs designed to combat it.
How does evolution play a role? First, HIV's method of replicating itself introduces many variations very quickly, and the drugs themselves provide the powerful selective pressure.
The human immunodeficiency virus (HIV) has a relatively simple structure: a compact sequence of genetic code composed of RNA molecules (ribonucleic acid), accompanied by a powerful enzyme (reverse transcriptase), all packaged within a protective shell that can attach itself to the wall of specific living cells in the human body. Once an HIV virus bonds to a cell of the right type, its RNA and reverse transcriptase enzyme can pass through the cell wall into the cell's interior.
There, the viral RNA is able to transcribe itself into a comparable strand of DNA (deoxyribonucleic acid), using molecules already present in the cell for raw materials, and helped by the reverse transcriptase enzyme. The RNA transcription process is error prone, however, and here is where variation enters the picture. The new DNA version, including whatever changes have been introduced during copying, is moved into the cell's nucleus by the cell's own natural transport mechanisms. Once inside the nucleus, the alien DNA is incorporated into the cells own genes.
Now the cell's natural replication mechanisms take over. From the information stored in the alien DNA, multiple copies of the original viral RNA are manufactured, along with multiple copies of proteins and other molecules that are needed to build shells for the new viruses. These parts then begin to self-assemble inside the cell and bud from its walls to form complete new viruses, which travel through the body until they encounter more cells of the right type. Once they attach to those, the entire process is triggered all over again.
The power of evolution to drive this process is augmented by the huge numbers involved. Billions of new HIV viruses can be manufactured inside one human body in a single day. Each time a virus transcribes itself inside a new host T-cell, the chances are high that its copies will contain variations. While most of these variations will tend to render the next generation less fit to survive, a few will turn out to be beneficial, depending on the circumstances.
Those circumstances are produced by anti-viral drugs, which generally work by introducing molecules that interfere with one stage of the HIV transcription/replication process. Such interferences can greatly reduce the number of viral copies being produced inside an infected person at any one time, but the drugs can never completely eliminate the presence of the virus, or stop the replication process entirely. This is because the genes that manufacture the new viruses are embedded deep inside cells that the body cannot afford to lose. These cells, known as T-cells, are essential to the function of the human immune system. Drugs that might attack and kill T-cells would simply be doing what HIV itself already does. Once HIV begins to use a T cell to manufacture copies, the replication process eventually destroys that cell. And once enough T-cells are being destroyed on a daily basis that the body can no longer keep up with the loss by manufacturing new ones, the body's immune system begins to fail. The body then falls prey to opportunistic infections of many kinds, resulting in the varied symptoms of full-blown AIDS.
An anti-viral drug repeatedly introduced into an infected person's body will suppress the replication of all viruses vulnerable to it, but if mutation produces a new HIV variant that can withstand the drug's effects, that variant will thrive in the environment created by the drug, and will be able to colonize the majority of the host T-cells available. Over time this mutant variant of HIV will become dominant in the victim's body, and then, no matter how often the drug is taken or how much is given, it will no longer be able to repress the rapid replication of new viruses.
Two strategies have been developed by scientists to counteract the evolutionary pressures that help HIV defeat drugs designed to stop it. One is well established, the other highly experimental.
In the first approach, an HIV infected patient who has not yet developed drug resistance is given several anti-viral drugs at once, each affecting a different stage of the viral replication process, or the same stage in a different way. By introducing multiple medications into the body at the same time, the odds are lowered that any one viral mutation will introduce mechanisms that can defeat all the drugs at once. This multi-drug strategy, known as HAART (highly active antiretroviral therapy) was first introduced in 1996 and has been widely applied since.
The second approach is intended for patients who have already developed resistance to one or more anti-viral drugs. This strategy, named "Structured Treatment Interruption," capitalizes on the tendency of HIV to mutate very rapidly in order to regenerate the drug's effectiveness. Treatment with the drug is suspended for a period of time, removing the selective pressure inside the body that favors the development of resistance. During the hiatus, the body's viral load increases but different strains of the virus are likely to become dominant - strains that may be more vulnerable to the drug. The drug is then reintroduced. More information about the evolutionary implications of Structured Treatment Interruption is available in a second video from the Evolution Library.