In Part 1 we discussed chronobiology, the study of internal biological clocks, and outlined its development as a distinct scientific discipline.
1 We now describe some of the current research under way in this field.
In Figure 1 a historiograph showing a microhistory of the field since 1978 gives a clear indication of the increase in chronobiology research. Although it may appear that there has been a decline in research from 1985 to 1986, this is really just a consolidation; a glance at Table 1, which lists several 1986 Science Citation Index/Social Sciences Citation Index research fronts on chronobiology, shows that research on various aspects of biological rhythms continues at roughly the same pace it has for the past few years. The multidimensional-scaling map in Figure 2 shows the relationship between these fronts.
As is evident from the titles of these fronts, work in chronobiology is currently focusing not so much on how biological rhythms function but on how they malfunction. Many concern the consequences of rhythms that do not properly respond to or are out of phase with their synchronizers. One of these is the largest front in Table 1, entitled’ ‘Photoperiodic regulation of affective disorders and depression” (#86-0940). It is associated with 42 core papers and 338 published (citing) papers. Among the core papers are six articles by Colin S. Pitlendrigh, Stanford University, Califomia,2-7 and two by Jurgen Aschoff, professor of physiology and director, Max Planck Institute for Behavioral Physiology, Seewiesen uber Stamberg, Federaf Republic of Germany (FRG). 8-9
Front #86-0940 deals with the effects of light and temperature on biological rhythms in various organisms and how these environmental factors can both cause and be used to treat sleep disorders, depression, and other affective disorders. For instance, two core papers by Charles A. Czeisler, Laboratory of Human Chronophysiology, Department of Neurology, Montefiore Hospital, Bronx, New York, and the Sleep Research Center, Stanford University School of Medicine, and colleagues report the results of studies on the relationship between circadian rhythms and human sleep. 10.11 Incidentally, Czeisler and his work were featured in a recent National Geographic article on sleep. 12
One of the core papers, published in 1980, shows that the duration of sleep and episodes such as the rapid-eye-movement (dreaming) phases were correlated with body temperature rhythms and not with the length of prior wakefulness. 10 The other, published two years later, discusses the effects that rotating shift work has on sleep and health. Czeisler and colleagues found that work schedules that continually violate the circadian rhythms of workers reduce worker productivity, job satisfaction, and subjective health estimates and increase persomel turnover; work schedules that are in harmony with workers’ circadian rhythms produce the opposite effects. 1I
Another biological function that has been found to have a circadian rhythm in mammrds is the secretion of melatonin, a hormone produced by the pineal gland that causes the pigment melanin to be concentrated in certain cells. Under normal conditions, melatonin secretion takes place almost exclusively during the nighttime hours and persists in a 24-hour rhythm even in constant darkness. The first report of an endogenously generated rhythm in the regulation of melatonin production was made by David C. Klein and Joan L. Weller in 1970, when they were at the Section on Physiological Controls, Laboratory of Biomedical Sciences, National Institute of Child Health and Human Development, Bethesda, Maryland. 13 This classic work has been cited over 465 times since then. In his Citation Classic commentary, which appears in this issue of Current Conlents /Life Sciences, Klein notes that “the report has been frequently cited in part because it indicated that the [N-acetyltransferase activity that regulates melatonin production] was driven by an endogenous clock. ” 14
In a core paper published in 1980, Alfred J. Lewy, then of the Clinical Psychobiology Branch, National Institute of Mental Herdth (NIMH), Bethesda, and colleagues found that bright artificial light suppresses the cycle of melatortin secretion in six normal human subjects, just as artificial light of less intensity does in other mammals.15 This also established “that the human response to light is qualitatively similar to that of other mammals.”
Another intriguing effect of bright artificial light is its role in the treatment of seasonal affective disorder (SAD), a recurrent depression that appears and disappears at the same time each year. In another paper that is core to front #86-0940, Lewy, currently of the Department of Psychiatry, Sleep and Mood Disorders Laboratory, Oregon Health Sciences University, Portland, and some of the colleagues he worked with in the melatonin study collaborated with Norman E. Rosenthal, NIMH, and others on a paper describing SAD and some preliminary results of the use of light in treating the condition. 16
They studied 29 patients who suffered from depressions that were marked by overeating, oversleeping, a craving for carbohydrates, a decrease in physical activity, and difficulties at work and in interpersonal relationships. These depressions recurred each year at the same time (as summer changed to autumn) and improved at the same time each year (in the spring). Interestingly, depressed patients responded to traveling north or south in the winter traveling south caused an amelioration in their symptoms, while traveling north exacerbated them. The authors conclude that the patients’ illnesses were related to environmental factors—specifically, the number of daylight hours. They speculate that SAD may be a “pathologic manifestation of an [ancestral] seasonal rhythm, ” pointing out several similarities between patients suffering from SAD and hibernation in animals, such as increased sleep and appetite, decreased activity, weight gain, and change in food preference. 16 Hibernation will be the subject of a future essay.
Rosenthal and colleagues have continued their research into SAD and light therapy and have arrived at several important tindings. Concerning melatonin secretion, for example, Rosenthal and colleagues showed that while melatonin plays some role in the symptoms of SAD as well as in treatment of the condition, changes in the level of melatonin secretion are neither sufficient to cause SAD nor to relieve it. 17 Thus, according to Rosenthal and colleagues, the efficacy of phototherapy for SAD may not depend on how successfully it changes the pattern of melatonin secretion. 18 They also suggest that timing the application of phototherapy during a certain parl of the day may not be critical to the success of the treatment, 18 although Lewy and colleagues found that phototherapy during the morning was more effextive than the same therapy applied during the evening. 19Rosenthal and colleagues have sdso shown that the antidepressant effects of light appear to be mediated by the eyes rather than the skinzo and are not dependent on extending the length of the day.21
A front related to #86-0940 is entitled “Circadian pawmaker in pregnancy and depression” (#86-783 1). It deals with some of the physiologic aspects of circadian rhythms and their relationship to various biologicrd functions. It has 108 citing papers and 7 core papers, of which 4 are by Pittendrigh. Thrw are part of a five-part analysis of circadian rhythms in nocturnal rodents, published with coauthor Serge Daan, Zoological Laboratory, Groningen State University, The Netherlands .22-24 The other reviews various properties of free-running circadian rhythms and environmental cues that force these cycles into the rhythm of the 24-hour Iightdark cycIe.’25 Also core to this front is a review by psychologists Benjamin Rusak, Drdhousie University, Halifax, Nova Scotia, Canada, and Irving Zucker, University of California, Berkeiey, on the neurological basis for biological rhythms in various animals. 26 This classic paper has been cited over 450 times.
The biological rhythms of animals are also the focus of the front entitled’ ‘Thermoregulation and photoregulation effects on animal energetic” (#86-1226), with 94 papers published in 1986. Among the 12 core papers for this front is a 1970 article by Aschoff and H. Pohl, Max Planck Institute for Behavioral Physiology.27 It discusses circadian rhythms in the metabolic rate of warm-blooded organisms. A core paper by zoologists Robert C. Lasiewski, UCLA, and William R. Dawson, University of Michigan, Ann Arbor, also discusses rhythmic variations in metabolic rate-specifically, in birds-and relates these to variations in body weight .’28
A smafler front concerned with the mechanisms of biological rhythms in animals is called “Cellular circadian clocks” (#86-8092). It has 23 citing papers and 3 core papers-one by Pittendrigh on the internal clock that controls emergence from the pupal stage in fruit flies29 and the other two by Hans-Georg Schweiger, Max Pkutck Institute for Cell Biology, Heidelberg, FRG.30, 31 Schweiger coauthored one with Manfred Schweiger, Institute for Biochemistry, Innsbruck University, Austria, on the functioning of the biological rhythms of rmicellular organisms at the molecular level. 30 The other, coauthored with P. Dehm and S. Berger, Max Planck Institute for Cell Biology, discusses the conditions under which Acetahdatira cells grow best in culture. 31 The front entitled “Circadian seasonal variations of venous blood components in humans and mice” (#86-64 16) has 2 core papers and 26 citing papers. One of the core papers, by Erhard Haus and colleagues, Department of Pathology, St. Paul-Ramsey Medical Center, St. Paul, Minnesota, deals with the effects of biological rhythms on the components of the circulatory and immune systems. 32 The other, by Walter Nelson and Franz Halberg, Chronobiology Laboratories, Department of Laboratory Medicine and Pathology, University of Mimesota, and colleagues, reviews various methods for measuring the period of biological rhythrns.33
Answers to all your Biology Questions
