HPRF researcher's life work on "human time clock" is making a difference of night and day

Erhard Haus, MD, PhD, has studied the effect of circadian rhythms on animals, including humans, since the 1950s. Photo by Kent Flemmer

Night-shift workers seem to shoulder more than their fair share of physical and social burdens. They don't get to enjoy the dark, uninterrupted peace that most of us do when we sleep at night. When they try to sleep during the day, telephones and doorbells ring, lawnmowers and garbage trucks motor on, and the sun rudely shines through the cracks in their window shades.

Even their own bodies rebel against this schedule -- particularly if they alternate working during the day. Disruptions in the body's normal pattern of exposure to light and dark have been associated with breast, prostate, colon and endometrial cancer; obesity; diabetes; heart disease; immune system suppression; cholesterol anomalies; and high blood pressure.

The body's backlash against the disruptions of these patterns -- commonly referred to as circadian rhythms -- is a large part of HPRF researcher Erhard Haus's life's work. Just as some scientists study the effect of the moon on ocean waves, Haus and his colleagues study chronobiology. This field focuses on the effect of daily and yearly cycles on animals (including humans) and how they adapt to the rhythms of the sun.

Haus, a pathologist with an MD and a PhD, believes that more attention should be paid to developing shift work schedules that cause the least amount of harm. But many more questions need to be answered before researchers can identify just what an optimal shift pattern would look like. "I think the whole shift work problem is very important," says Haus, who is also professor of laboratory medicine and pathology at the University of Minnesota. "Cancer is just one aspect."

More than just a phase

At 84, Haus holds a 60% appointment at Regions Hospital in St. Paul, where he supervises the autopsy and toxicology service and is engaged in continuation of his medical research, as he has since 1969.

To say he is devoted to his work might seem an understatement to those who know him. For example, he has been taking and recording his blood pressure five times a day since 1971 for collaborative research on the relationship between long-term blood pressure changes and circadian and circannual (yearly) rhythms. For 30 years, he logged detailed records of his circadian temperature rhythms and blood pressures across time zones and post-flight during frequent transcontinental trips.

His work in the human time structure, Haus hopes, will lead to its wider application in both diagnosing and treating disease and in creating healthier work schedules for shift workers. Up to 20% of workers in industrialized countries (up to 30% in the health care field) are engaged in night or shift work. Those who regularly travel across several time zones (for example, airplane crews) also stand to benefit.

Research has shown that sleep deprivation doesn't have to be extreme or prolonged to negatively affect health. Even partial sleep deprivation (for example, being able to sleep only 4 hours a night) can cause problems. Researchers believe that these changes are related partially to the secretion or suppression of the "sleep hormone," melatonin, which is, to a large extent, regulated by the exposure to light.

Many more potential ramifications of shift work remain to be explored. For example, do the babies of pregnant shift workers suffer health consequences? Are some people more sensitive to circadian rhythm disruptions than others? Does taking prescription medication at night affect their efficacy or side effects? These are the type of questions that keep researchers like Haus -- if not up at night -- coming to the office in the morning.

Studying shift workers over the length of time needed to see meaningful results, though, is expensive and logistically difficult. Although scientists have used results from larger studies such as the Nurses Health Study, research on the relationship of circadian disruption and cancer has been dominated by animal models. Still, he says, studies that led to optimization of shift schedules would be enormously interesting to both workers and their employers.

Getting into the (circadian) rhythm

Haus's story starts in Vienna, Austria, where he lived until his family moved to Tyrol, in western Austria, when he was 19 years old. During World War II, the family's ancestral home in Slovenia was taken over first by Germans, then by the Communists. The family's home in Innsbruck was then pillaged by French troops. "They jointly liberated us of pretty much everything we had," he says.

Haus remained in Austria to earn his MD and do his residency in internal medicine at the University of Innsbruck. There, he met Franz Halberg, a Romanian-born physician a few years his senior and assistant professor of the university who was studying chronobiology.

Halberg coined the term "circadian" to refer to the roughly 24-hour cycle of biochemical, physiological and behavioral processes. "I first thought he was working with grasshoppers [cicadas]," Haus quips.

In 1959, Haus wrote his first review article on chronobiology (Endocrine System and Blood, in the German Handbook of Hematology). "And I swore I would never do that again," he says with a smile. He followed Halberg to the University of Minnesota in 1958, where he completed a residency in pathology and earned his PhD in 1970. Halberg later founded the University's Halberg Chronobiology Center, where he still works at age 92.

In 1966, Haus began working at what was then known as the St. Paul-Ramsey Medical Center, which later became Regions Hospital. Over the years, he built an academic pathology residency program that trained 52 residents; the program was discontinued when the medical center merged with HealthPartners. He was head of pathology at the hospital for 35 years, from 1969 to 2004.

In 1971, medical technologist Linda Sackett-Lundeen applied for a position in his lab. Intimidated and struggling to decipher scientific terms delivered in Haus's Austrian accent, "I didn't understand a word he said, so I just kept saying 'yes'," she jokes. "And I'm still saying that."

Across time zones

The role of shift work in health is well-known but not always acknowledged in the United States, Haus says. Socialist countries such as those in Scandinavia are more aware and proactive. In Denmark, for example, female shift workers who develop breast cancer after at least 20 years of shift work receive workers compensation if they have no other risk factors for breast cancer. Of course, this presents difficulty in practice, as there's no way to know for certain whether a particular malignancy is related to shift work, he says.

In Brazil, where he flew to study shift work at the Sao Paolo Institute of Public Health, he discovered that shift workers were given three hours to take a nap. While research has shown that naps benefit productivity, they were a confounding factor when attempting to extrapolate the results to other countries, Haus says.

His international travel schedule has slowed somewhat, but he keeps publishing and giving presentations all over the world on health problems related to chronobiology and mechanisms of cancer development in shift work. At the International Agency for Research on Cancer in Lyon, France, where he has lectured (In addition to English and German, he's fluent in French and can read Italian, Spanish, Dutch and Scandinavian languages), he was part of a working group in 2007 exploring the carcinogenicity of shift work, painting and firefighting. The resulting report was covered widely in newspapers and on television. Always self-deprecating, "I found myself very knowledgeable about painting and firefighting," he jokes.

Haus has always excelled at balancing his clinical and research roles, according to HPRF Executive Director Andrew Nelson, MPH. "He has contributed personal discoveries as well as led a field of research internationally in chronobiology," he says. "He is now transitioning to concentrate on research full-time and continue to provide his gifts to a body of work that impacts our daily lives."

Doesn't miss a beat

Haus and his wife, Geraldine, have nine children and "a growing herd" of 25 grandchildren, who often spend summer days swimming at their home on the St. Croix River in Scandia. Family photos from as recently as the Fourth of July line the shelves in his office, along with a photo of Haus grimacing in jest and a caption reading "Beware of dog" in French.

Haus straps on his skis regularly despite having an artificial hip that was implanted in 1979 and that, by his surgeon's account, should have deteriorated long ago. Sackett-Lundeen, who says the Haus family must carry a gene that codes for "no fear," can't say enough good things about him. "Dr. Haus is one of the fairest people," she says. "He includes everyone and gives everyone credit."

Currently, he is collaborating with researchers at Emory University in Atlanta on the role of melatonin receptors in breast cancer. Other research focuses on the chronobiology of drug actions and the role of hormones in chronobiology. He still has data that he has yet to analyze and publish, such as his flight temperature and blood pressure data.

When musing about the future, Haus says he would like to go to the International Society of Chronobiology meeting in India in 2012, but it's expensive, and it happens to be where, in his travels, he picked up the echinococcal cyst that still resides in his liver. "We live together in peaceful coexistence," he says, apparently untroubled by the parasite. "Actually, it's probably dead, because it's partially calcified."

So then, where, one might ask, is he going next? He doesn't miss a beat: "Home," he says.