Chronobiologist and Nobel Laureate in Medicine Michael Rosbash: ‘Lack of sunlight during the day is worse than electric lighting at night’

The Earth had been spinning on its axis for a billion years when the first living beings appeared. Since then, we have adapted to alternate between light and darkness. Geneticist and chronobiologist Michael Rosbash, 79, a professor at Brandeis University in Massachusetts and a researcher at the Howard Hughes Medical Institute in Maryland, reminded us of that fact in his acceptance speech for the 2017 Nobel Prize in Medicine. The award, which he shares with his friend and collaborator Jeffrey C. Hall and Michael W. Young, recognized their contribution to deciphering the molecular gears of the biological clock that controls our circadian rhythms. From the Latin circa, “around” and dies, “day,” circadian rhythms are the 24-hour changes in our physiology that synchronize with the day-night cycle and modulate when we are hungry, sleepy, want sex and have asthma attacks or a fever in the afternoon.

Bacteria, plants and biomedical research’s most popular insect, the Drosophila melanogaster or fruit fly—the basis of Rosbash’s findings—also have biological clocks. On November 13, wearing a tie with Santiago Ramón y Cajal’s neuronal designs, the chronobiologist gave a lecture for young researchers, at the Madrid hospital named for the Spanish Nobel Prize winner, now celebrating two decades of its research foundation (FIBioHRC). The event took place within the framework of the Nobel Prize Inspiration Initiative and in collaboration with the AstraZeneca Foundation, which arranged this interview with EL PAÍS in a nearby hotel.

Question. During your Nobel Prize acceptance speech, you mentioned that 50% of our genes were regulated by circadian rhythms, but in your talk you said that it is at least 70%?

Answer. I have updated the figure due to new research done over the past six years. The 50% figure came from research in rodents, but in 2019 there was a large study done on baboons, the first in primates, and [the figure] went to 70%.

Q. How did you become interested in chronobiology?

A. [It began] almost 50 years ago, through my friend Jeffrey C. Hall, who also started as a professor at my university. He was already working on fly neurogenetics and knew about circadian rhythms. I had laboratory expertise that could be useful for his research. I suggested that we collaborate and see if that would go anywhere.

Q. And you two have made it this far.

A. To my surprise [smiles].

Q. You have forged your career with basic research, which is sometimes undervalued. How would you encourage young researchers to explore it and institutions or companies to fund it?

A. I tell young researchers that I hope they do something interesting and that they like it. Public funding agencies face the biggest challenge, because basic research is the foundation for applied research; it is very short-sighted to try to short-circuit the process by going directly to something translational. It is politically convenient because the public understands if you say you are going to cure Alzheimer’s, but if the foundations do not exist, it is money wasted. On the other hand, the pharmaceutical and biotech industries are very good at applied science. They make money and, when they see an opportunity, they go for it. I think public research organizations should focus on basic science, and industry should focus on applied science.

Q. What links the circadian rhythms of flies, which have 100,000 neurons, and those of people, who have 86 billion?

A. The basic process of keeping time. What happens in neurons is the same, although mammals have a larger number. From there, we try to use these neurons as a window into more general questions about brain science and behavior.

Q. For example?

A. Wiring. The general question is how animal brains carry out behavioral programs, how behavior works. Of course, a fruit fly performs simpler behaviors than we do and [is] simpler to investigate. So what is the program that enables complex behavior? We are making progress in appreciating how complex the circuits are at the anatomical level, even in the fly brain. It all has to do with the wiring, how the circuitry is designed to carry out a behavioral program.

Q. One of the things that flies and privileged people have in common is napping and sleeping at night. What is the biological purpose of sleep and of these intermediate pauses during the day?

A. We do not know. Memories are consolidated during sleep and neuronal morphology is modified during sleep. All that happens, but I do not think that is the major purpose of sleep. We do not know what fly and human sleep, for example, have in common. My guess is that it is related to metabolism, such as recharging ATP [adenosine triphosphate, a key energy molecule in cells]. The brain is the largest consumer of ATP; perhaps there is a metabolic need for recharging.

Q. Our internal clock has a natural 24-and-a-quarter-hour cycle. After millions of years here, why is it not set to 24 hours, and we have to synchronize daily?

A. For humans, we don’t know, but there is information from other animals. Some, like sheep and rodents, are seasonal in terms of reproduction. Their physiology changes with the season, and the seasons are determined by the length of the day. To control their reproductive physiology, they compare the offset of their clocks with the length of the photoperiod, the amount of daylight, which varies throughout the year. That is, they use it as a measuring device, although this [explanation] is partly speculative.

Q. How does electric light, which we even take to bed with us with our screens, contribute to chronodisruption?

A. It is a problem, but it is difficult to estimate its severity. We are exposed to too much light at night and not enough during the day because indoor electric lighting is far inferior to sunlight. In fact, according to recent research, a lack of sunlight during the day is even worse than the presence of light at night. Many cases of sleep problems are cured by addressing these environmental factors.

On the other hand, research conducted in Colorado on people who camp out in nature for a couple of weeks found that they sleep better, go to bed when it gets dark and wake up earlier. There are also studies in Brazil comparing those who stayed in the jungle with those who moved to the city. They are like us, they sleep worse, they go to bed later; you can immediately see the change in pattern. All of them, like you and me, are slightly sleep deprived. If the lights go out in a seminar room at 4 p.m., half the audience is snoring right away. That does not happen with well-rested individuals. It’s a totally sleep-deprived culture.

Q. You said you take your statins at night, when they are most effective. The time of day also influences the efficacy or adverse effects of antihypertensives, corticosteroids and chemotherapy. Should we change the way they are prescribed?

A. The short answer is yes. The more important question—as with almost everything in pharmacology and in life—is what is the cost-benefit analysis? For society, physicians and the pharmaceutical industry, what is gained versus what is lost by taking this into account? Giving chemotherapy for some cancers at 3 a.m. has worked better, but people don’t want to work at that hour. Until very convincing research is published, there is not going to be a significant change because there is so much inertia in everything we do.

Q. According to the WHO cancer agency (IARC), shift work or night work is potentially carcinogenic. What would you advise people with those jobs?

A. The trick is to pretend that night is day and vice versa. If you do this very rigorously, you can avoid most problems because your body doesn’t know what is day and what is night. What matters is how much light comes in and when you eat. If there is no light and you keep the room dark for eight hours of sleep, you are not interrupted and you don’t eat during that period, your body doesn’t know the difference. The problem is interacting with your family, with the rest of the world.

Q. Why does snacking at night increase the risk of obesity and metabolic syndrome?

A. We don’t really understand why. One hypothesis has to do with our DNA damage repair systems, which are regulated by the circadian clock. Food contains a mixture of nutrients and toxins. Plants produce toxins to avoid being eaten, such as psoralen, which is abundant in celery. Snacking at night introduces toxins that, at that hour, our repair systems are not ready to eliminate. There is also speculation that the major epidemic of epithelial cancers, such as colon cancer, in the U.S. is because of this.

Q. Is this related to time-restricted feeding, which follows the pattern of light and dark?

A. That diet is not much different from avoiding snacking at night. No one knows why these patterns are beneficial, but metabolism changes depending on the time of day, so eating food in sync with circadian metabolic processes makes sense. If something is not too difficult or painful and it makes sense, why not do it?

Q. Juan Antonio Madrid, one of the pioneers of chronobiology in Spain, poses this question to you: Would it be possible to address the chronodisruption that comes with aging by manipulating the molecular clock with drugs?

A. I think so. Older flies have the same sleep pattern as older people, fragmented sleep: in the first four hours, sleep is solid and then they start waking up frequently. In young people, sleep also becomes lighter after a few hours, but not so much that they wake up. Why this happens is not well understood. To some extent, this goes back to the previous question, what is sleep for? The two things are almost certainly related.

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