PREFACE

Beautiful hypothesis and an ugly little fact

Ken-Ichi HONMA
Editor-in-Chief
Hokkaido University Graduate School of Medicine, Sapporo, Japan

Twelve years have already passed since Sleep and Biological
Rhythms (SBR) was launched. Fortunately, the number of
submissions to SBR has rapidly increased in the past several
years. We have received a number of good manuscripts, far
more than we have been able to publish. For example, last
year (2014) 164 manuscripts were submitted from 25 coun-
tries. The most submissions came from Japan (40), Turkey
(28) and China (24). Since SBR is an official journal not only
of the Japanese Society of Sleep Research, but also of the
Asian Sleep Research Society, these figures are reasonable
and expectable. Furthermore, in 2014 we published six
Review Articles, 21 Original Articles, four Short Papers,
three Case Reports, two Letters to the Editor and one
Editorial. The acceptance rate is approximately 23%. The
5-Year Impact Factor was 1.035 in 2013. Recently, we
decided to increase the number of SBR pages from 320 to
400 per year with the aim of publishing more manuscripts.

SBR emphasizes the periodical aspect of sleep as implied
by the name of the journal. To understand sleep, we should
regard it not as a single physiological event, but as a
sequence of events, namely sleep and wakefulness. Sleep is
affected by the preceding wakefulness and succeeding
wakefulness is influenced by the preceding sleep. On the
other hand, a sleep and wakefulness cycle in mammals is
well known to be controlled by the circadian pacemaker
located in the hypothalamic suprachiasmatic nucleus. It was
more than 50 years ago that the sleep and wakefulness cycle
was found to spontaneously desynchronize from the circa-
dian body temperature rhythm, suggesting at least two
different oscillation mechanisms in humans (Aschoff,
1962). Under internal desynchronization, the sleep-wake
cycle showed either a shorter (approximately 17 h) or
longer (approximately 33 h) periodicity than the circadian
temperature rhythm (24.5 h). Several mechanisms have
been proposed to explain internal desynchronization.
Among them, the most beautiful hypothesis was formally
proposed some 30 years ago, called the two process model
(Daan et al. 1984). The hypothesis assumes two processes:
a self-sustained circadian process and an hour-glass pro-
cess, which is processed by something increasing monoto-

nously during wakefulness and declining exponentially
during sleep. The hour-glass process is often called a
homeostatic process. But in my opinion, the other terminol-
ogy may lead to misunderstanding, since we are still igno-
rant of the physiology which is controlled to be constant by
the homeostatic process. Regardless, the two process model
explains internal desynchronization, circabidian (approxi-
mately 48 h) rhythm and the relation between the time of
sleep deprivation and the length of following recovery sleep.
However, the two process hypothesis is still not supported
by biological experiments. One of the major reasons for the
present situation is a lack of an adequate animal model for
human sleep and wakefulness, which is characterized by
internal desynchronization, circabidian rhythm, non-photic
entrainment and consolidated sleep and wakefulness. These
characteristics are unique to humans and, to my knowledge,
have never been demonstrated in experimental animals
such as rats and mice except for non-photic entrainment by
feeding.

Methamphetamine, a central stimulant, is demonstrated
to mimic human sleep and wakefulness in terms of the
abovementioned four characteristics when chronically
administered by dissolving in drinking water in rats and
mice. The mechanism underlying methamphetamine-
induced internal desynchronization seems to be an inde-
pendent oscillator called Methamphetamine-induced
Oscillator (MAO) or Methamphetamine Sensitive Circa-
dian Oscillator (MASCO). Methamphetamine is a stimu-
lant of the central dopaminergic neurons. Recently,
circadian rhythms in the clock gene Per2 expression in the
several dopaminergic structures of the rat brain were
reported to be reorganized by methamphetamine and run
parallel with desynchronized behavior rhythms (Natsubori
et al. 2014). The findings support a two-oscillator model,
an alternative hypothesis for the human sleep-wake cycle,
which was proposed many years ago.

Hypotheses are useful to understand a complex phe-
nomenon with a simple principle and to make testable
predictions. But a tragedy is “a beautiful hypothesis slain by
an ugly little fact” (Thomas Henry Huxley).

bs_bs_banner

Sleep and Biological Rhythms 2015; 13: 195 doi:10.1111/sbr.12131

195© 2015 Japanese Society of Sleep Research