The Pharmaceutical Journal
Vol 275 No 7376 p644
19 November 2005

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Juggling risks and benefits more
Interactions emerge between biological clocks more
Radio-tracked rodent surprises researchers more
Keep singing and stay healthy more

Juggling risks and benefits

An editorial in Science for 30 September considers the significance of risk in actions over which decisions must be taken in modern societies. Choice of whether or not to take a particular line of action is usually decided after a comparison of possible or probable risks and benefits. If the latter prevail, a project goes forward. But things are in practice far more complicated. There may be alternative ways of gaining the same benefit and, in that event, the basis of choice must have reference to a comparison of the probable risks associated with the alternatives.

In industrialised democracies people and governments are usually averse to risk, and in legal and administrative circles greater safety is preferred to lesser, and definitions are vague, such as “reasonable certainty of no harm” or “adequate margin of safety”, whatever those phrases may mean. Making a decision on such grounds is difficult. In chlorinating water supplies, for instance, the risk of water-borne infection has to be balanced against the possible risk of producing carcinogenic derivatives of compounds present in the water.

In treating people with drugs, doses only slightly higher than those prescribed may produce toxic effects on the heart or other organs, and the chance of such an event must be borne in mind. Logically, over-the-counter analgesics and anti-inflammatory drugs can only be taken after assessing the risk.

Many developed nations have decided that the risks of nuclear power generation, which involves the chance of accident or illegal diversion and raises the question of how to dispose safely of waste, are unduly high. Other methods of obtaining energy are liable to promote global warming, with its many effects on tides, weather and crops, and so also involve risk.

Counteracting such risky behaviour has vastly enlarged the necessity to plan on a worldwide scale, not only considering effects upon our persons but also those with a much wider and more prolonged effect upon the face of the earth on which we depend.

None of the options we have is free from risk and we have to choose from imperfect alternatives.

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Interactions emerge between biological clocks

Biological clocks, or circadian rhythms, control behaviour and essential life processes, including eating, sleeping, seasonal migrations and cell proliferation. Some sort of time keeping is part of the fabric of life, and regulatory clocks vary over a wide range of dimensions, from the millisecond operations of neuronal activity to the seasonal changes shifting the amount of daylight during the year and prompting variations in our habits.

Timekeeping mechanisms have hitherto been considered in isolation, but unexpected interactions between clocks have emerged. These have been examined by Martha Gillette of Illinois and Terence Sejnowski of California in an article in Sciencefor 19 August.

Interesting questions about why life processes are subject to biological clocks involve genetic, cellular and molecular considerations. One that has been broadly studied is that of mitosis, regulating the dynamic process of eukaryotic cell division. Cells of different types and sizes are governed by different amounts of time in different parts of their cycle. Key proteins, the cyclins, undergo phosphorylation, proteolysis and spatial targeting as they progress.

Yeast cells show reductive and oxidative phases of metabolism, their replication being restricted to the reductive phase. It is not known whether their cell division and metabolic cycles are linked. Associated metabolic and mitotic oscillations have been observed in human cell cultures, so there may be similarities between the respective clocks. Moreover, yeast shows a high frequency oscillation synchronised with respiration phases.

Cycles of cell division and metabolism also appear to be co-ordinated with the familiar circadian pacemaker, an innate timekeeping mechanism governing the activity over roughly 24-hour intervals in an organism’s lifetime. In mammals the circadian clock is controlled by the suprachiasmic nucleus of the brain. Treatment of cultured mammalian cells with haem synchronises gene expression in the circadian clock — further evidence that this and the metabolic states are coupled in some way.

The most familiar timing system in organisms is the daily cycle of sleep and wakefulness. Studies of human sleep patterns and performance indicate that the sleep-wake cycle is regulated by dual brain mechanisms, the drive to sleep, increased with time spent awake and restorative during rest, and the circadian process in the suprachiasmic nucleus of the brain, which organises sleep and wakefulness in relation to night and day. Other brain regions may track time spent awake and also effects of food restriction. It is loss and restoration of brain energy stores that govern sleep homoeostasis, something attributable to gene regulation. Intensity of light plays a part in the cycle in many organisms.

There is a need to concentrate on the interrelationships between the many cyclical processes found in organisms and their interaction across a wide range of temporal and spatial scales, since natural clocks do not function in isolation.

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Radio-tracked rodent surprises researchers

Invasive rodents, particularly rats, have been observed to disrupt severely the ecosystems of confined territories such as islands. A paper by biologists in Auckland, New Zealand, published in Nature for 20 October, describes experiments using a free-ranging Norway rat (Rattus norvegicus). Rats can be eliminated from islands but often reinvade. At least 11 islands in New Zealand have been reinvaded by this rat species since 1980, and in the early stages elimination is difficult.

A group of uninhabited islands had been rat free for more than two years in 2004, but at the end of that year an adult male Norway rat was caught in a chocolate-baited trap and fitted with a radio collar, then released on an island beach after a DNA sample had been taken from its tail. It traversed the entire island for four weeks and then settled in a home range of about a hectare. After 10 weeks the radio signal was lost, but it was then regained on another island 400m away over a stretch of open water. The rat was caught 18 weeks after its release.

Norway rats can supposedly swim up to 500m, but this is the first record of one traversing hundreds of metres across open water. It illustrates that eliminating a single invading rat is extremely difficult, although when high density populations arise, competition for food and territory makes elimination easier.

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Keep singing and stay healthy

“The exercise of singing is delightful to Nature, and good to preserve the health of man. It doth strengthen all parts of the breast, and doth open the pipes.”

—William Byrd: ‘Psalms, sonnets and songs’ (1588)

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