February 1997

Taking On the Common Cold

By Rex Graham

Colds researchers deleted the word "cure" from their lexicons in the early 1960s when they discovered that some 200 different viruses can cause colds-far too many to conquer with a vaccine, the conventional method of defeating an infectious disease. With the discovery of each new family of cold virus-rhinovirus, coronavirus, Coxsackie virus, adenovirus, respiratory syncytial virus, to name a few-researchers sank into a deeper funk. And as funding for common-cold research by the National Institutes of Health dwindled to its current level of $2 million per year, a mere 0.02 percent of its total budget, most researchers moved on to study influenza, herpes, AIDS, or other viral diseases.

But after years of low-profile research, biologists who remained dedicated to fighting the common cold believe they have homed in on a strategy both to stop cold viruses from replicating and to dampen the immune response that produces symptoms-together, the closest thing yet to a cure.

This optimistic scenario evolved in parallel with the gradual scientific unraveling of how the immune system reacts-or, more precisely, overreacts-when it encounters a cold virus. In fact, although cold viruses infect only about 1 percent of the epithelial cells that line the nasal passages (a mere pinprick compared with most other infectious viruses), they induce the immune system to launch a full-fledged attack that can result in the all-too-familiar congestion, runny nose, aches, and pains.

No one is sure why the immune system reacts so vigorously or why the resulting symptoms make us feel so lousy. But research shows that this aggressive response is present in vertebrates and invertebrates, suggesting that as humans evolved, the benefits of overkill outweighed the disadvantages.

In any case, viewing the immune system as part of the problem, rather than blaming only the viruses, is "the start of something new," says Jack M. Gwaltney, Jr., a professor of medicine at the University of Virginia School of Medicine who has pioneered treatments aimed at shutting down the body's runaway reaction to cold viruses. An important clue led Gwaltney and his colleagues to this novel theory: the knowledge that even though many different viruses cause colds, the body's reaction is almost the same for each one.

This response begins after virus-laden droplets, often from someone else's sneeze or cough, come in contact with nasal epithelial cells. In the case of rhinoviruses, a strain that causes most colds, the virus attaches to a receptor that coats the surface of the cells. This receptor, called intercellular adhesion molecule-1, or ICAM-1, is as slippery as silk to most of the natural world but is like Velcro to a rhinovirus.

Once the virus invades the nasal cells, the cholinergic nervous system-an early line of defense, so named because its signals are transmitted by a neurotransmitter molecule called acetylcholine-responds by triggering the secretion of a thin watery fluid through the mucous membranes to try to flush out the virus. When this happens, most people immediately sense they are coming down with something.