The day yields to the night

The day yields to the night (published in Italian in Osservatore Romano Oct 7 2017)

The day yields to the night, action to rest. According to the wisdom of the Bible, and of many other religions, God has made both: the earth, which turns on itself and around the sun, and organisms, which receive and respond to the light of the sun and to the changing seasons. It is difficult to sleep on full moon nights. To face the day, one needs to mobilize new energy and, in winter, certain animals change colour of the hair or hibernate. The biological sciences have dealt with these phenomena for a long time but it is only in the last decades that the underlying molecular mechanisms have been elucidated. The 2017 Nobel Prize for Medicine and Physiology has been a recognition of the discoveries that have been made in this field with implications of general importance that, as we will say later, link the biology of circadian rhythms to the risk and therapy of tumours. They may perhaps be interest also to those who care of other things and who alternate, as recommended to the monks of many centuries ago, “orare” with “laborare” (prayers with deeds).

A fundamental characteristic of biological systems is that they are extremely complex and “robust”, i.e. able to maintain a dynamic balance and adapt to changes in the surrounding environment. Each organism is a system of systems (nervous, digestive, etc.), each relatively autonomous but co-regulated with others. The brain is an organ of primary importance for the response to the oscillation of the day and night, but so is the liver that presides over the intake and conversion of nutrients and elimination of harmful substances. Hormones play an essential role in coordinating the functioning of organs in an organism, including the response to changes of the day and the night.

The fundamental unit of biological systems is the cell. Cells activated by light – not just those of the eye – transmit a signal that is translated, encoded and re-encoded by innumerable other cells in mutual communication. Even within the same cell, there are multiple “systems” of molecules with different functions, each system relatively independent of the other, but all in some way synchronized. One of these systems presides over the cyclical changes that take place in the different hours of a day, even in cells isolated and studied separately from the organism they come from. It can be said that every cell has an internal clock able to count the hours and it is like in an orchestra, where the beating of time is necessary for the development of the various movements. Together with the so-called “circadian rhythm”, another very important oscillatory system is that of the “cell cycle”, with well-regulated time periods that allow a cell to double its size and then divide. It is thus that a cell can generate two daughter cells, with either identical or different destiny and with a differentiated specialization that can lead, in the end, to “programmed death”.

An essential feature of systemic oscillators, in biology as in engineering, is that they are based on “negative feedback control mechanisms”: a certain signal induces a response that can eventually turn off the starting signal. It’s like when a lamp is turned on in a room where there is someone who is waken up, who turns off the switch to go back to sleep. At the level of the circadian rhythm, the bulbs that are turned on and off are a small group of genes, units of information “written” with a four-letter alphabet in the linear sequence of the DNA. The genes contain the instructions necessary for the production of the corresponding proteins, the main functional units of the cell. It is the proteins themselves that can read and translate the information encoded by genes and decide whether to induce (turn on) or suppress (turn off) this or that other gene. This year’s Nobel Prize for Medicine has been awarded to pioneers who have identified the genes responsible for the circadian rhythm in a humble organism, a fruit fly which has become famous thanks to many studies of classical genetics, Drosophila. These genes have names that suggest well their function, such as period and clock. These same genes and corresponding proteins, with only some minor modifications, work in human cells and there are genetic sleep disorders, such as the familial advanced sleep phase syndrome (FASP), which are due to mutations similar to those that alter the circadian rhythm of bugs.

The cyclic rhythm in response to the variations of day and night, and of the different length of days and the seasons, is not limited to flies or higher organisms, but is also found in plants, fungi and bacteria. The types of genes involved are different but the fundamental principle is always the same : that of light bulbs that are turned on and off. Even among bacteria, it has been shown that populations that adapt best to changes of light have the upper hand over others. Thus, one can speak of “convergent evolution“, where, from a different starting point, completely different organisms and biological systems converge towards the same type of organization and response.

While all these are fascinating topics for scientists, what kind of interest and practical importance can they have for “normal” people who do not want to know about science? Jet lag is a well-known consequence of the alterations of the normal circadian rhythm due to time zone changes with air travel. Less known are the higher cancer risk for night workers and the different response to chemotherapy that cancer patients can have if the drugs are given at different hours of the day or night. The specific mechanisms remain to be defined, but in both cases there are reasons to imply the biological clock. Finally, to those who are taken by so many thoughts and anxiety bouts, which wake them up in the middle of the night, one can suggest to turn to the Psalterium Gallicanum with confidence. Is it possible that, with the ancient singing and meditations that accompany the various hours of the day and night, even our own biological clock can be resynchronized with that of the universe?