Sex Sleep Eat Drink Dream (24 page)

Your spouse hasn't moved; you lie for a while and watch that free, even breathing with considerable envy. Both of you were exposed to the same party, the same child, the same bed and bathroom cup. Why are you the lucky one?

Take a close look at your life. Perhaps you're more vulnerable because you're suffering from chronic stress, which has been linked with greater susceptibility to rhinovirus-induced colds. Maybe you're short on protein or zinc or vitamin E, which can depress immunity. Or perhaps your overzealous immune response makes you more predisposed to suffer symptoms.

As Gwaltney has discovered, not everyone exposed to a virus—or even infected with it—experiences cold symptoms. When he and his team inoculated with rhinovirus a large group of healthy young adults who previously possessed no antibody to the virus, nearly all of them became infected. Yet only 75 percent went on to develop symptoms of a cold. Just what's going on in the one in four people who don't succumb remains a riddle. "There are some people who claim never to get colds," says Gwaltney. "My wife is one. It's pretty irritating. These people may not be making normal amounts of inflammatory mediators. If this is the case, there's an irony here. We know that cold symptoms are the result of the body's inflammatory response to a foreign invader. So people with more active immune systems may be more prone to developing cold symptoms than people with a less powerful immune response."

Apparently, you're one of the "active" set, so you get up to seek some medicinal assistance. In your bathroom cabinet may reside a crowd of cold remedies, each specifically designed to combat one symptom or another. The decongestants shrink that turbinate nasal tissue to relieve the stuffy feeling. Antihistamines suppress sneezing by acting on the histamine receptors in the sneeze center (where they also produce drowsiness). Ibuprofen helps to ease general malaise. If your shelves are empty of over-the-counter cough remedies-suppressors designed to sit on the tickle, demulcents to soothe it, and expectorants to loosen the phlegm—don't bother making a trip to the pharmacy. A major review of nonprescription cough medicines concluded there is little to recommend them.

Your medicine cabinet certainly holds no real cures for the common cold either; they simply don't exist. The search for one has led into many a stagnant backwater, though few match that of Thomas Jefferson. The great president is said to have counseled a friend to stave off colds as he did, by—of all things—every morning soaking his feet in cold water. A century later, a popular remedy for aborting a cold was to irrigate the nose twice a day with warm water and borax: "No syringe necessary; but by simply immersing the nose in a basin of water, and making forcible inspiratory and expiratory movements, holding the breath at the epiglottis, the nasal passages may be thoroughly irrigated." There are advantages to the syringe from the standpoint of neatness. But the treatment has no proven benefits, Gwaltney says, and may have inherent risks if the borax is contaminated with bacteria.

Modern efforts to cure the common cold have focused on magic bullets targeting a single symptom, but these provide only partial relief. Any really effective cure, argues Gwaltney, must tackle both the virus itself and the symptoms. For more than a decade, Gwaltney has been working on this combination antiviral, anti-inflammatory cold treatment. One such blend of interferon and ibuprofen he tested not long ago seemed promising: In a large group of people with full-blown colds, the team counted and weighed facial tissues from days two to five of their illness and found that the group treated with the combination therapy drug had dramatically reduced severity of sneezing, nasal obstruction, sore throat, cough, headache, and malaise; this group also had 71 percent less nasal fluid and reduced its tissue use by more than half. Treatment must take place early, though, for full benefit.

Gwaltney and others studying colds spend a lot of time measuring mucus. They collect used tissues after nose-blowing, count them and weigh them, then subtract from the total the weight of the same number of dry tissues. "Not particularly pleasant work," says Gwaltney. Nevertheless, measuring soggy tissues has yielded much hard information, including insights into the circadian nature of cold symptoms.

The nose, it turns out, runs by its own clock. Graphs of sneezing, stuffy nose, runny nose, and itchy nose, whether from cold or allergy, show a peak in the morning hours. Volunteers infected with cold and flu viruses use the most tissues in the morning, between 8 and 11
A.M.
(with sneezing at its heaviest around 8), and the fewest between 5 and 8
P.M
. Cough frequency, too, shows a marked circadian rhythm, peaking between noon and 6
P.M
. Most of us would probably fail a quiz on this. I feel certain that I cough more at night. But questionnaires suggest that people are not very good at estimating their own cough frequency; reliable counts can be captured only with tape recorders.

Illnesses of many types are affected by the body's biologic rhythms. As Michael Smolensky, a chronobiologist at the University of Texas, suggests, the daily fluctuations in such ailments as allergies, hypertension, gout, and asthma may be so pronounced that testing for them at the wrong time of day can mean false results. To diagnose an allergy, for example, doctors rely heavily on skin tests. But as Smolensky points out, the skin's response to histamine and to the allergens in house dust and pollen is most pronounced in the evening, just before bedtime, when few doctors schedule appointments. Blood pressure runs higher in the afternoon, so morning diagnostic tests can underestimate the severity of hypertension. A patient may be diagnosed as normal by one physician he sees in the morning and as hypertensive by another who sees him in the afternoon.

If rhythm is as critical a factor in sickness as it is in health, it would seem common sense for doctors to pay close attention to the timing of not only diagnostic tests but also drug treatments. Unfortunately, surveys suggest that many physicians are still unconvinced that circadian rhythms are an important aspect of disease or therapy. This is a problem, say chronobiologists, because the body may process the same dose of a drug in different ways depending on the time of day.

Though direct evidence of circadian modulation of drug action is rare, one groundbreaking study in 2006 showed that in mice, at least, the circadian clock drives rhythms in the genes that allow the body to respond to drugs and other foreign substances. Mice with normal clocks cleared their bodies of the drug pentobarbital much faster at night than during the day. Mice with mutated clocks had severe deficits in clearing the drug from their systems at all times of day. They also experienced more toxic side effects to two chemotherapeutic agents.

Research in humans suggests similar circadian effects. One study shows that anesthesia for dentistry lasts longer in the afternoon than in the morning: Lidocaine taken between 1
P.M.
and 3
P.M.
relieved dental pain for three times longer than it did early in the morning. On the other hand, a 2006 report showed that patients who undergo anesthesia for surgery in the afternoon suffer more pain and postoperative nausea and vomiting than those who receive the drugs and have their procedures in the morning. This may result from errors in the delivery of the anesthesia because of physician fatigue, but it may also be rooted in the way the body handles a particular drug at a particular time of day.

The pace at which drugs work in the body—the way they're absorbed, metabolized, and excreted—is shaped by circadian rhythms in a variety of body functions. The daily rise and fall of different hormones affect drug absorption. The rhythmic nature of stomach activity (emptying faster by day, more slowly by night) means that some drugs taken by mouth before bed may move into the bloodstream more slowly. Medications taken late in the day are in general more rapidly destroyed by the body because higher body temperature speeds the chemical reactions the body uses to detoxify a foreign substance. Such time-of-day effects have been documented for more than a hundred drugs.

The goal in timing the delivery of medication, says the chronobiologist Russell Foster, should be to balance what the body does to the drug with what the drug does to the body. This is especially true with cancer drugs, where timing can mean the difference between life and death.

***

About twenty-five years ago, my mother underwent courses of radiation and chemotherapy for cervical cancer. The case was an extremely aggressive one: She was diagnosed in February and died in July. In the early days of her treatment, she suffered nausea and loss of appetite. I tried to entice her to eat by offering her small portions of her favorite foods, a perfectly seared bratwurst or cheese from the new gourmet shop down the street, even brownies laced with hashish, which has been known to relieve nausea. Nothing worked. My mother's intestinal distress resulted from the lethal effect of the highly toxic chemotherapy drugs on the swiftly dividing cells lining her gastrointestinal tract.

The aim in cancer treatment is to kill tumor cells without killing normal cells. Many anticancer drugs are designed to destroy only cells that divide rapidly. Since cancer cells multiply at a faster pace than most normal cells (every six to twelve hours, versus every twenty-four hours), they're preferentially destroyed. But chemotherapeutic drugs are imprecise weapons. They strike not just their intended target but also innocent bystanders, the normal, healthy cells in the body that also happen to divide quickly, such as the cells in the bone marrow, hair follicles, and in the lining of the digestive tract. This is what causes the side effects of the therapy—anemia, hair loss, and gastrointestinal upset. The toxicity of these drugs limits how much and how often they can be taken.

Francis Lévi believes that
when
people receive anticancer treatment is at least as important as what they receive in determining whether the treatment will be successful or dangerously toxic. Lévi, a physician who studies circadian interactions with cancer at the Hôpital Paul Brousse near Paris, belongs to a growing group of researchers who believe that timing is critical to successful cancer treatment.

Most cancer patients still receive chemotherapy at times that are convenient for the hospital staff. But more and more studies by Lévi and others are showing that giving cancer drugs at carefully selected times of day can maximize their therapeutic effects and minimize their toxic side effects.

The key is understanding the distinct timing of cell division in cancer cells and normal cells. Take lymphoma. Cells in certain kinds of lymphoma tend to divide between 9 and 10
P.M.,
the cells in the gut lining at around 7
A.M.,
and those in the bone marrow near noon. William Hrushesky, a pioneer researcher in chronotherapy at the University of South Carolina School of Medicine, has found that the cells lining the gut proliferate twenty-three times as much during day as they do at night. So a chemotherapeutic agent that's known to damage the gut and bone marrow might be expected to be less toxic—and more effective against lymphoma cells—if given in the nighttime hours.

More than two decades ago, Hrushesky published a study on the timing of chemotherapy in forty-one women with ovarian cancer. Women on one schedule developed only half the negative side effects as women on another schedule. According to Hrushesky, every measure of toxicity was lowered several-fold depending on what time of day the drugs were given. "Those women who received the drugs at least damaging times of day also had a fourfold better chance of surviving five years," says Hrushesky. "This shows that human cancer susceptibility to chemotherapy depends on the time of day these drugs are received."

More recently, Francis Levi has had similar success treating advanced colorectal cancer with a drug called oxaliplatin. In one study, Levi found that when the drug was delivered in a conventional, steady dose, tumors were reduced by 30 percent; with chronotherapy, by 51 percent. "And," adds Levi, "the most effective therapy was also the least toxic one," with less severe side effects.

How common is the practice among oncologists of carefully timing the delivery of cancer drugs? "Ten or fifteen years ago, most people thought we came from another planet," says Levi. "They're listening now, but it's a slow process of acceptance."

Fretting about whether the well-timed delivery of cancer drugs might have saved my mother—or at least eased her discomfort—is the sort of speculation that keeps me up at night, cold or no cold.

It's midnight, day's official close. If you're like me, you would give anything to slip into the gray shadowland of sleep. We delight in thresholds, but not if the crossing is protracted. Think of the painful lag Brick feels in
Cat on a Hot Tin Roof
as he waits for that booze-induced "click" that ushers him into welcome oblivion; think of the intolerable waiting of adolescence, as Theodore Roethke calls it, "a longing for another place and time, another condition"; think of this, the long, fitful effort to fall asleep. Normally I drop off easily as soon as my husband switches off the light, as if there's a cable linking his lamp with my brain. But some nights, circumstances conspire against it: indigestion, a cold, or just a mind buzzing in circles like some heat-maddened fly.

Anxiety and stress are, in fact, among the chief reasons people have trouble getting to sleep. There are medications, of course, including a whole new generation of "gentle" somnolents. But experts say that sleeping pills of any kind derange normal sleep. The best strategy is good "sleep hygiene": going to bed at a regular time, covering your clock, not exercising late at night. It also may help to limit demanding mental work and, perhaps, to heed the advice of Robert Burton, "Hear sweet Musick ... or read some pleasant Author" and hope for a quick crossing over.

12. SLEEP

T
HE ITALIANS CALL IT
dormiveglia;
the Germans,
einschlafen.
But the English language possesses no single, really expressive word for the passage into sleep. I don't know why this is so. Perhaps for the same reason that we have a perfectly good word for birthday but none for life's other bookend. Perhaps it reflects the significance our culture ascribes to its perceived moments of importance.