Sexually transmitted pathogens take on secretive and even sinister strategies. The underlying reason is that people have sex with new partners less frequently than they come within sneezing or coughing distance. The sporadic opportunities for sexual transmission put sexually transmitted pathogens in a difficult situation. They have to stay viable within a person until the person has a new sexual partner. They have to persist in the face of an immune system that is superb at recognizing and destroying foreign invaders. Then they must be transmissible to the next sexual partner when the opportunity arises. And that is just to break even. To make a profit, the pathogens must meet these challenges for at least another round of partner change—the more rounds, the better their competitive advantage. Respiratory pathogens typically reproduce to the point of contagiousness and then get wiped out or at least sequestered by the immune system within a week or two. A sexually transmitted pathogen using such a strategy would be cut out of the competition. To evade this fate, sexually transmitted pathogens must employ sneaky tricks.

Sexually transmitted pathogens must act like criminals living in a town that is heavily patrolled by police. Like human criminals, they have developed a variety of strategies for evading recognition, surveillance, and capture. Because the immunological police soon become very familiar with their appearance, most sexually transmitted pathogens keep a low profile.

The bacteria that cause syphilis persist by stripping off many of the external molecules that would make them recognizable to the immune system. They are like criminals who sand off their fingerprints.

HIV impersonates a police officer, wrapping itself in the immune cell's own membrane when it buds off a cell. To stay ahead of the current mug shot, it frequently modifies its telltale features by mutating and recombining its genetic instructions—genetically engineered plastic surgery.

The bacteria that cause gonorrhea are quick-change artists, wearing different external molecules from day to day to avoid being tracked down after they are recognized. They also hide out away from the areas of most active surveillance, causing damage to the reproductive tract but not so much that it generates a sweeping immunological assault.

Herpes simplex viruses keep a low profile by hiding out in the neurons. There they are relatively safe because an immune system that destroys neurons could irreparably cripple the body. When a person is under stress, the viruses in the neurons break their latency and begin producing progeny, which migrate down the neuronal fibers. Presumably stress is an indication that it is a good time to break out of their hiding place—either to get out before something bad happens to the person, or to get out while the immune system may be less able to mount a defense. The tubelike fibers serve them as a kind of subway through which they can leave town without being detected by immune surveillance. The end of the line lies just below the skin. There the viruses disembark and cause the familiar herpes blister, which upon rupturing provides the viruses with their necessary exit. Then they wait for sexual contact to provide access to new bodies and new neurons. If contact occurs and viruses are transferred, the lucky viruses first infect the cells of mucus membranes, perhaps a cell of the cervix, where they multiply. Some are available for immediate transfer; others enter neuron fibers, migrating up them to reach the cells' nuclei, where they can continue their strategy for reaching sexual partners long into the future.

Human papillomaviruses are the organized criminals. They take over cells of the cervix, making them work for the new boss. Instead of obeying the normal rules of self-control that are necessary for each cell to fulfill its assigned role in the body's community, these cells sometimes develop into cancerous growths that spread at the expense of the law-abiding cells. The goal of the papillomavirus is not to create cancer, but to alter allegiances. In the precancerous state, the virus causes the cells to divide at a level that is too high for the good of the body; but that cellular reproduction is good for the virus because it can replicate along with the cells, with little exposure to immune surveillance. The cells are now working for the virus rather than the body, generating a subcommunity with allegiances that conflict with the interests of the larger community. The papillomaviruses are difficult to root out because these cells, being the body's own cells, provide the cover of an upstanding citizen. The viruses may eventually destroy the entire community, as the disregulated growth of an infected cell develops into a cancerous growth, but until the cancer takes its effect, the viruses get resources and turn profits with little exposure. By the time the cancer destroys the body, the papillomaviruses have moved on to infest new communities.

For these pathogens, the disease is not the goal of their activities. Rather, it is the cost of doing business. These outlaw strategies seem tenuous, yet sexually transmitted pathogens are very successful and pernicious in human populations. They are so successful because sex is so seductive. From an evolutionary viewpoint, sexually transmitted diseases are costly to a person, but the cost of no sex is higher. If a person were genetically programmed not to be interested in sex, those genetic instructions would disappear—in about one generation.