"I think we've gotten as close to scientific proof as you can get without actually using humans in experiments nobody could do or approve," said Dr. David Blask, a neuroendocrinologist at Bassett Research Institute in Cooperstown, N.Y., and lead author of one of the latest studies.In a paper published in December in the journal "Cancer Research," Blask and colleagues at Thomas Jefferson University in Philadelphia injected human breast cancer cells into genetically modified mice. Once the cancer cells had taken hold, the resulting tumors were transplanted into female rats, where the tumors continued to grow.
Researchers then collected blood samples from 12 healthy, premenopausal women. The blood samples were taken during the day, at night following two hours of complete darkness and at night following 90 minutes of exposure to bright, fluorescent lighting.
The blood was injected directly into the rat tumors, with markedly different consequences: Samples drawn from volunteers during the day or after bright light exposure, when blood levels of a key brain hormone called melatonin were lowest, stimulated tumor growth. Conversely, blood samples taken at night after total darkness, when melatonin levels were higher, significantly slowed tumor growth.
"The experiment clearly shows that melatonin suppression results in human breast cancer growth, at least in animal models," said Blask. "And it's been known for a while that light suppresses melatonin production in the brain. This data is about as close to cause-and-effect as you're going to get. The only way to nail it down further would be to put women under controlled lab conditions for years."
Melatonin is called "the hormone of darkness" because the pineal gland - a pea-sized body near the center of the brain - primarily produces it at night, peaking around 1 or 2 a.m.
There's good reason for the timing. During the day, when humans are most active, stress hormones like cortisol and adrenaline necessarily flood the body, pumping up body temperature, heart rate and other functions to maximize physical and mental abilities.
But constantly maintaining high levels of these hormones is unhealthy, akin to keeping an engine revving past the red line for long periods of time. Without respite, the engine will eventually break down.
Humans are no different. Their respite is night and sleep. As daylight fades, optic nerves signal the pineal gland to begin ramping up production of melatonin. The hormone serves as a sort of sedative, dialing down the body's blood chemistry so various systems can rest, recover and repair themselves for the next day. Melatonin is a powerful antioxidant, effectively erasing cellular and tissue damage caused by at least 60 degenerative conditions, among them Alzheimer's, heart disease and cancer.
In 1980, Alfred J. Lewy and colleagues at the National Institute of Mental Health made a significant discovery. They found that relatively brief exposure to bright light at night - just two hours - measurably reduced melatonin levels, interrupting or negating the body's period of rest and recovery.
Subsequent studies by Lewy and George C. Brainard, director of the Light Research Program at Jefferson Medical College in Philadelphia, found that the light didn't have to be particularly bright. As little as 1.3 lux of blue light, such as that emitted from fluorescent bulbs, noticeably reduced melatonin production.
(A lux is the amount of illumination cast by a single wax candle. A 40-watt light bulb produces about 50 lux; a comfortably dim living room measures around 100 lux.)
At the time of their discovery, few people suspected a link between artificial light and cancer. Indeed, bright light therapy became a popular treatment for Seasonal Affective Disorder, a form of depression linked to winter and reduced exposure to natural light.
One scientist who did wonder about negative consequences was Richard G. Stevens, then a cancer epidemiologist at Pacific Northwest Laboratories in Richland, Wash. In a brief 1987 note to Walter Willett, director of the Nurses' Health Study II, a long-term project tracking how women's health relates to diet, activity, genetics and other factors, Stevens proposed exploring whether nighttime illumination interrupted melatonin production enough to measurably increase the risk of cancer, particularly breast cancer which is greatly influenced by hormonal levels. Willet agreed.
The first evidence of this link, however, came from a statistical analysis conducted in 1991 by Robert A. Hahn of the federal Centers for Disease Control and Prevention. Hahn hypothesized that blind women - whose retinas could not detect changing light conditions and thus influence melatonin production - would be less likely to get breast cancer than sighted women.
Hahn surveyed the records of 11,700 women hospitalized for breast cancer between 1979 and 1987. His hypothesis held up: Blind women appeared to be only half as likely to develop breast cancer as sighted women.
As a control, Hahn also compared heart disease rates among sighted and blind women, assuming melatonin played no role in that ailment. Both groups had comparable incidence rates.
A few years later, Finnish scientists repeated Hahn's study with similar results. A Swedish study compared cancer incidence among 13,000 visually impaired people and 1,600 men and women who were completely unable to detect light. The visually impaired had cancer rates similar to the general population; the profoundly blind experienced only 70 percent of that cancer risk.
In 2001, data from the second Nurses' Health Study provided even more compelling evidence. Eva Schernhammer of Brigham and Women's Hospital in Boston surveyed cancer rates among longtime nurses working nights. She found that nurses who worked graveyard shifts for 30 years were an astounding 36 percent more likely to develop breast cancer than their day-shift counterparts. Nurses who worked nights occasionally had an 8 percent elevated risk of breast cancer. Another study in 2004 reported a 48 percent rise in breast cancer among women who typically worked at night.
Late last year, Stevens, now at the University of Connecticut Health Center, published a multiyear study with Finnish colleagues that found breast cancer is less common in women who sleep more than nine hours per night than those who do not. The researchers wrote that women who consistently slept nine hours or more per night had less than one-third the risk of developing breast cancer than those who slept seven or eight hours per night.
Sleep, though, is not the key; darkness is. "You don't have to be asleep for melatonin production to increase," said Stevens. "It just has to be dark."
While these studies are dramatic and troubling, no scientist is claiming to have established an absolute causal connection between artificial light and cancer. Cancer risk is affected by many factors: genetics, age and behavior among them. Schernhammer, for example, has conducted research that suggests obesity and heavy smoking reduce melatonin production. And numerous known and unknown chemicals in the environment can skew one's blood chemistry, impacting the immune system and perhaps diminishing cancer defenses.
One thing that does seem obvious, though, is that chronic disruption of the body's circadian clock - its cycle of wakefulness and sleep - is harmful.
"You can see the effects of disruption in animal models," said Mark Rea, a professor of cognitive science and director of Rensselaer Polytechnic Institute's Lighting Research Center. "If you put rodents in perpetual jet lag, where they're not getting enough rest, they develop gastrointestinal and cardiovascular problems. They get cancer. Mortality increases."
Something similar occurs with people. Chronic sleep disruption and loss are associated with numerous ailments and diseases, from obesity and diabetes to mental illness. People who work nights (and thus are more likely to get fewer hours of deep, restful sleep) are typically more susceptible to stress disorders, stomach ulcers, depression, heart disease and a weakened immune system. Blast believes his research may extend to other cancers, such as prostate, and is seeking funding to explore the possible connection.
But what to do? Since the debut of electrical light, human waking hours have been extended an average 13 percent. It's hard to avoid the light.
Synthetic melatonin supplements may be part of the solution, but maybe not. They are promoted as over-the-counter sleep aids, but Stevens and others note there is no broadly accepted empirical proof they actually work as advertised.
"I wouldn't recommend them, not at this time," Stevens said. "People forget or don't realize they're taking a serious hormone, and that no one knows the long-term effect of doing so. These supplements spike melatonin levels in the blood way higher than normal, and unless you're taking them at 1 in the morning, they can actually disrupt the circadian system."
Rea at Rensselaer urges caution and common sense. "People are talking about light in very loose terms. We know a lot about light in relation to vision, but we're just beginning to understand how radiant energy affects the retinal and circadian systems. We don't yet know exactly what kind of light does what to the body or how much exposure you must have."
Indeed. While there appears to be a substantial association between extensive, long-term exposure to nighttime light and breast cancer, the link is far less certain for shorter, more occasional exposure to nighttime light. For example, reading late at night, watching TV and sleeping in a less-than-completely dark room may all reduce nighttime melatonin levels, but whether the consequences are health-threatening hasn't been conclusively answered.
"What about turning on the bathroom light at night?" asked Stevens. "There's a good chance that it suppresses melatonin production, but maybe not significantly. And there are good reasons for being able to see what you're doing."
Stevens and others say the most prudent course of action is simply to get plenty of sunlight exposure during the day - most Americans don't - but also an extended period of true darkness at night.
"It doesn't hurt to make your bedroom as dark as possible," said Stevens. "If you need a night light, get one that's very dim or reddish. Red wavelengths seem to have less effect on melatonin production than white or blue."