2023-12-01 04:20:00
The Earth had been spinning on its axis for billions of years when the first living beings appeared. Since then, we have adapted to alternating between light and darkness. The geneticist and chronobiologist Michael Rosbash (Kansas City, USA, 79 years old), professor at Brandeis University in Massachusetts and researcher at the Howard Hughes Medical Institute in Maryland, remembered it during his acceptance speech for the Nobel Prize in Medicine 2017. The award, shared with his friend and collaborator Jeffrey C. Hall and Michael W. Young, recognized his contribution to deciphering the molecular gears of the biological clock that controls circadian rhythms. From the Latin circa, “around” and dies, “day”, they are the changes that our physiology experiences during 24 hours when synchronized with the day-night cycle and that modulate when we are hungry, sleepy, want to have sex, asthma attacks or The fever increases in the followingnoon.
Bacteria, plants and the most popular insect in biomedical research, Drosophila melanogaster or fruit fly, the basis of Rosbash’s findings, also have clocks. On November 13, this scientist gave a lecture to young researchers wearing a tie with neuronal designs by Santiago Ramón y Cajal, at the Madrid hospital of the same name as the Spanish Nobel Prize winner, which is celebrating two decades of its research foundation (FIBioHRC). It occurred within the framework of the Nobel Prize Inspiration Initiative and in collaboration with the AstraZeneca Foundation, who arranged this interview with EL PAÍS in a nearby hotel.
Ask. During his Nobel acceptance speech, he mentioned that 50% of our genes were regulated by circadian rhythms, but in his talk he said that it is at least 70%…
Answer. I have updated the figure due to new research carried out in these 6 years. The 50% came from research in rodents, but in 2019 there was a large study done in baboons, the first in primates, and it rose to 70%.
Q. How did you become interested in chronobiology?
A. Almost fifty 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 regarding circadian rhythms. I had laboratory technical knowledge that might be useful for his research. I suggested that we collaborate and see if it went anywhere.
Q. And they came here.
A. To my surprise [sonríe].
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Q. You have built your career on basic research, which is sometimes underappreciated. 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. The biggest challenge is for public funding organizations because basic research is the basis of applied research and it is very short-sighted to try to short-circuit the process by going directly to something translational. It’s politically expedient because the public understands if you say you’re going to cure Alzheimer’s, but if the foundation doesn’t exist, it’s wasted money. On the other hand, the pharmaceutical and biotechnology industries deal very well with applied science. They make money and when they see an opportunity, they go for it. I believe that public research organizations should focus on basic science, and industry on applied science.
Q. What links the circadian rhythms of flies, with 100,000 neurons, and those of people, with 86,000 million?
A. The basic process of keeping time. What happens in neurons is the same, although mammals have a greater number. From there, we try to use these neurons as a window into broader questions regarding brain science and behavior.
Q. For example?
A. The wiring. The general question is how animal brains carry out behavioral programs, how behavior works. Of course, a fruit fly performs behaviors that are simpler than us and simpler to investigate. So what is the program that allows complex behavior? We are making progress in appreciating how complex the circuits are at an anatomical level, even in the fly brain. It all has to do with the wiring, how the circuit is designed to carry out a behavioral program.
Nobel Prize in Medicine Michael Rosbash, wearing a tie with neuronal designs by Santiago Ramón y Cajal.Jaime Villanueva
Q. One of those that flies and privileged people share is taking a nap and at night. What is the biological purpose of sleep and those intermediate breaks during the day?
A. We don’t know. Memories are consolidated by sleeping and neuronal morphology is modified with sleep. All that happens, but I think it is not the deep purpose of sleep. We do not know what there is in common, for example, between the fly’s dream and the human dream. My guess is that it is related to metabolism, like ATP recharging [adenosín trifosfato, molécula clave para la obtención de energía en las células]. The brain is the largest consumer of ATP, perhaps there is a metabolic need for recharging.
Q. Our internal clock has a natural cycle of 24 hours and a quarter. After millions of years here, why isn’t it set to 24 hours and we need to synchronize daily?
A. It is not known in humans, but there is information from other animals. Some, like sheep and rodents, are seasonal in reproductive terms. Their physiology changes with the season and seasons are identified by the length of the day. To monitor their reproductive physiology, they compare their clock lag to the length of the photoperiod, the length of daylight, which varies throughout the year. That is, they use it as a measuring device, although this is partly speculative.
Q. How does electric light, which we even take to bed through 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 electrical lighting is far inferior to sunlight. In fact, according to recent research, the 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 carried out in Colorado on people who camp in nature for a couple of weeks shows 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. These 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., instantly half the audience is snoring. This does not happen with well-rested individuals. It’s a totally sleep-deprived culture.
Q. You said that you take your statins at night, when they are most effective. The time also influences the effectiveness or adverse effects of antihypertensives, corticosteroids or chemotherapy. Should I change the way I prescribe them?
A. The short answer is yes. The deeper question is, like almost everything in pharmacology and in life, what is the cost-benefit ratio. For society, doctors or the pharmaceutical industry, what is gained versus what is lost by taking this into account? It has proven better to give chemotherapy for some cancers at 3 a.m., but people don’t want to work at that time. Until very convincing research is published, there will not be substantial changes because there is a lot of inertia in everything we do.
Q. According to the WHO cancer agency (IARC), working shifts or at night 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 it very rigorously, you can avoid most problems because your body does not know what day and night are. What matters is how much light comes in and when you eat. If there is no light and you keep the room dark during the eight hours of sleep, you are not interrupted and you do not eat during that period, your body does not notice the difference. The problem is interacting with your family, with the rest of the world.
Q. Why snack at night? increases the risk of obesity and metabolic syndrome?
A. It is not well known. One hypothesis has to do with our DNA damage repair systems, which are regulated by the circadian clock. Food contains a mix 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 time, our repair systems are not prepared to eliminate. There is also speculation that the largest epidemic of epithelial cancers, such as colon cancer, in the United States, is due to this reason.
Q. Is this related to time-restricted feeding? [time-restricted feeding]which follows the pattern of light and dark?
A. This diet is not very 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 isn’t too difficult or painful and it makes sense, why not do it?
Q. Juan Antonio Madrid, one of the pioneers of chronobiology in Spain, asks this question for you: Would it be possible to address the chronodisruption that comes with aging by manipulating the molecular clock with drugs?
A. I think so. Elderly flies have the same sleep pattern as older people, a fragmented sleep: the first four hours, sleep is solid and then frequent awakenings begin. In young people, sleep also becomes lighter following a few hours, but not so much that they wake up. It is not very well understood why it happens. To some extent, this returns to the previous question, what is sleep for? The two things are almost certainly related.
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