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Sergio Tufik: The sleep observer

A medical researcher who began to study the effects of sleep deprivation nearly 50 years ago eventually created one of the world's most productive sleep research teams

Léo Ramos Chaves

When Sergio Tufik finished medical school in 1972, he infuriated his father by announcing that he wanted to dedicate himself to scientific research instead of running his own hospital, in accordance with his father’s wishes. Later, failed experiments on the effects of marijuana pushed him into the study of sleep deprivation, which he helped prove has catastrophic effects on human health.

In 2009, in one round of his “Epidemiological Sleep Study” (EPISONO), he found that 32.9% of the city of São Paulo has sleep apnea (also known as obstructive sleep apnea syndrome), a chronic disease characterized by partial or total closure of the airway several times per night during sleep. In 2018, his group found that people with apnea had in common three small variations—called single nucleotide polymorphisms, or SNPs—in a particular gene. With this knowledge, it became possible to detect who might have this sleep disorder using DNA testing and begin treatment more quickly.

From 2001 to 2013, he coordinated the Center for Sleep Studies, one of the Research, Innovation, and Dissemination Centers (RIDC) supported by FAPESP. Although he retired in 2008 from the Federal University of São Paulo (UNIFESP), where he taught for almost 30 years, Tufik continues to head both the Sleep Institute and one of the most productive research groups in this field in the world. With 1,044 entries in the Scopus database, as of the end of January their work has been cited 28,666 times.

Imposing, with a strong, deep voice, Tufik is almost two meters tall, with an athletic build. During his undergraduate years at the School of Medical Sciences of Santa Casa de São Paulo, he played volleyball, competed in shot put, and was president of Atlética, the medical school’s sports association. He also began to exercise his entrepreneurial side during those years by translating and selling scientific articles to colleagues who couldn’t read English. He participated in the creation of the Workers’ Party (PT), served as city councilperson in the 1980s, and as if that weren’t enough, he also owned a video production company and an internet access provider, and is a shareholder in CDB, a clinical analysis laboratory.

Tufik was born in São Paulo, and has a son who is also a doctor. One morning in January he welcomed the Pesquisa FAPESP team to his office on the seventh floor of a building belonging to the Research Incentive Fund Association (AFIP), a private foundation he created during his doctoral studies in the late 1970s, which houses clinical analysis laboratories and the Sleep Institute. The place is busy around the clock. In the early evening, people begin arriving for polysomnography exams—about 100 per shift—which provide the foundations for sleep discoveries and for the recommendations Tufik gives on how to sleep better, presented in the following interview.

Age 73
Field of expertise
Sleep medicine
Federal University of Sao Paulo (UNIFESP)
Educational background
Undergraduate degree in medicine from the School of Medical Sciences of Santa Casa de São Paulo (1972), master’s degree in physiology from the University of São Paulo in Ribeirão Preto (1976), and a PhD in psychopharmacology from UNIFESP (1978)
Written works
1,357 scientific articles, 3 books as author, and 9 as coauthor

Have you and your team at the Sleep Institute seen any effect of the pandemic on people’s sleep?
Social isolation and the home office have changed people’s relationship with sleep a lot. They aren’t wasting time on transportation anymore, but other worries have increased. In 2020, my son, Sergio Brasil Tufik, interviewed 1,700 people across Brazil, from ages 18 to 93. More than half, 56%, claimed that their sleep had worsened; 39% didn’t notice any difference; and 9% saw their sleep improved. People reported their sleep had worsened because of worries, spending more time in front of TV or cell phone screens, and more time at home. There were a lot of complaints, such as taking a long time to fall asleep, feeling sick, and staying in bed longer than they would like. But this should all return to normal as the pandemic passes.

Do you sleep well?
I’m sleeping quite well. I usually sleep between six and seven hours, but in the last week I’ve been sleeping eight, I don’t know why. And I don’t snore, even though I have the body type to snore; I don’t have any apnea.

Is living in a city like São Paulo bad for sleep?
Absolutely. You can’t sleep well at night if you’re stressed or scared.

For a long time there wasn’t much clarity about the functions of sleep. And how is it today?
There is nothing we spend more time on than sleeping—one-third, sometimes half of our lives. Until a few decades ago, there was no way to study sleep, because there’s no point in simply sitting next to someone who is sleeping. When polysomnography [an exam that records variations in breathing, heart rate, brain activity, and other parameters during sleep] became possible in the 1970s, we began to observe what’s happening with people while they sleep. At that time, I was one of the pioneers of sleep research in Brazil.

How did you start?
I came from USP [University of São Paulo] in Ribeirão Preto to do my doctorate at UNIFESP with Elisaldo Carlini [1930–2020]. He had me study the effects of marijuana on the brains of rodents, a very daring subject for the late 1970s. We were trying to discover the cellular receptor for marijuana in the brain. We were using Delta-9-THC, one of the compounds in marijuana, which is a hallucinogen. Carlini would deprive the mice of food, we would give them marijuana and they would fight. Then he started to deprive the animals of sleep, treated them with marijuana, and again the animals fought. We had found an animal model to study the action of marijuana. Sleeping as much as they wanted, but with marijuana, the animals were catatonic. Without sleep and with marijuana, they fought.

We train soccer teams, using melatonin and intense light to reduce the effect of time zones

What was the effect of marijuana on the animals’ brains?
We didn’t know. We thought that sleep deprivation changed brain receptors and marijuana activated them in such a way that the animals got into fights. Then we said: “Let’s block the effect of marijuana and learn which receptor is involved.” We were really excited. I no longer treated the animals with sleep deprivation, but with haloperidol, a dopamine-system blocker used for schizophrenic attacks. By blocking dopamine receptors, haloperidol stimulates cells to produce more receptors. Then I removed the haloperidol, gave them apomorphine and the mice fought. I gave them marijuana, and they went into total catatonia. Carlini got really upset; we hadn’t discovered what the receptor was, so he temporarily stopped working with marijuana and my thesis went down the tubes. I told him: “I’m going to study sleep deprivation, because I’ve already seen that it increases the effect of apomorphine and causes fights.” He got really angry and replied: “Do what you want!” So I started studying sleep back in 1976, because marijuana research didn’t work out. And I really got excited about sleep, because there was almost no research in this field, there weren’t any associations, no congresses, not even disease classifications. The first classification of sleeping disorders was in 1979. I soon made an interesting discovery, and I was invited to a world congress of psychiatry in Finland, which had a section on sleep. I felt great, I wasn’t even 30 years old yet.

What did you discover?
I found that sleep deprivation increased the sensitivity of dopaminergic neurons. With deprivation, when apomorphine was given the animals fought; without sleep deprivation, they didn’t fight. Sleep changed the status of the receptor. Sleep deprivation does many things, this was just the first. It changes everything, it’s terrible. After that, I studied the effect on the brain’s serotonin receptors and all the other neurotransmitters. Today I tell students: “When a disaster occurs in your life, it may be for the best and something better will come along.” It was like that for me. After the convention in Finland, my reputation grew. We held our first congress here in São Paulo, with the best sleep specialists from the United States, and we formed the Brazilian Sleep Society. And the research has kept growing. I recently found out that our group produces the most sleep research in the world. I was very impressed. It’s because I managed to assemble a real dream team, with good leaders. Monica Andersen publishes a lot. Lia Rita Bittencourt, from the clinical section, who is now the dean of Research at UNIFESP, also produced a lot. And Marco Túlio de Mello has gone to the Federal University of Minas Gerais to work with sports medicine, something he was already doing here.

Does sleep affect sport performance?
Completely. Since the late 1990s, the Sleep Institute has been preparing paraplegic athletes for the Paralympics and they’ve won in almost every sport. Now we’re also training soccer teams to reduce the effect of time zones. São Paulo had help from the Sleep Institute to minimize the effects of the time difference in the 2005 Club World Cup, in Japan, and we won the world championship. Of course I’m from São Paulo, and [soccer team] Corinthians also contracted the Institute, and then won the Club World Cup in 2012. As of last year, Santos and Palmeiras didn’t hire us and lost…

How do you prepare athletes?
When we move across time zones, we have to adapt quickly, otherwise our performance won’t be at the same level. Soccer players, for example, need to be in top form to face the big European clubs. Brazilians arrive for games on other continents like zombies, then are required to perform at an hour when their bodies say they should be sleeping. With melatonin and bright light, an intense light, we make them quickly synchronize their circadian rhythm—their sleep schedule—with the place where they’re going to play. If they’re going from here to Japan, we reverse the cycle of light and dark, because it’s day here and night there. It takes two weeks for a person to adapt naturally. With melatonin and bright light, we do it in two days. Melatonin is a hormone that synchronizes biological rhythms. It’s produced in the pineal gland when it gets dark. It was said to have many other functions, but that doesn’t seem to be the case. In the old days, when our activities were regulated only by the sun, the cycle was simple. When daylight arrived, melatonin levels would drop and a person would wake up. When the sun went down, melatonin increased and sleep would come. With artificial light we ended this natural cycle because at night people are home with the lights on—and using televisions, computers, and cell phones. The excess of light at night messed with sleep and people started to have a lot of insomnia.

Those who have apnea are more at risk of having cardiovascular problems. What appears first is hypertension

With all the scientific production, how is your group seen in other countries?
There is still bias and envy. A few years ago, I was in a multicenter group to study apnea genetics, SAGIC [the Sleep Apnea Global Interdisciplinary Consortium]. I felt mistreated by the other researchers. I had a very good idea, to study the extremes. In general, the more overweight and older the person, the more apnea you see. I thought differently, about comparing the least expected situations. I wanted to take a look at the overweight, old man, without apnea, on the one hand, and on the other, a young, thin person with apnea. So we could see, for example, what leads a thin, young woman—who would normally have less apnea than men—to develop apnea, and why the obese, old, male, contrary to what would be expected, doesn’t have apnea. I passed the idea on to the group, and the project went forward. However, when the papers started to come out, my name—which should have appeared last on the list of authors since I proposed the experiment—was in the middle, in a place of lesser importance. They said it was the rule, but they actually made up a rule. So I left the group, but in the end I made the biggest discovery about apnea.

What was that?
We followed a group of people at EPISONO, in the city of São Paulo, and we found that people with apnea, all of them, have three SNPs in a specific gene. It was difficult to get published, because the peer reviewers who analyzed the scientific article didn’t believe the results, but we managed. It came out in 2018 in Sleep Medicine. It’s an important work because now we can do genetic testing, see if a person has all three SNPs and is more likely to develop apnea, and begin preventive treatment with diet and exercise. The first thing that apnea causes is cardiovascular problems. When I announced this relationship between apnea and heart problems, I was publicly criticized, but today it’s more than proven. Those who snore and have apnea are at greater risk of having a cardiovascular problem. What appears first is hypertension, followed by arrhythmia. If a person has 60 apneas per hour, breathing stops once per minute and puts a strain on the cardiovascular system. We weren’t first to observe this, but we have several works in this area.

How has this knowledge been used to prevent apnea?
It was applied immediately. If a person has had apnea for only a short time, it’s possible to prevent the onset of hypertension with the use of CPAP [a device used when sleeping, which pumps air to prevent airway obstruction; the acronym stands for continuous positive airway pressure]. I received a lot of help from physiologist Eduardo Moacyr Krieger. I was his student at USP in Ribeirão Preto. I made the biggest discoveries about hypertension and apnea there with him. When it began being used back in the 1980s, CPAP was a huge device; today it’s a small box that insufflates air, opens the airways and allows you to breathe normally during sleep. It ends apnea. There are people who adapt right away to CPAP and wake up the next day jumping around, happy, because sleeping better improves sexual performance; it improves everything. But others suffer, they don’t adapt, they want to have surgery; but apnea surgery doesn’t work. At EPISONO, using polysomnography exams, we found that one-third of the population of the city of São Paulo had apnea. A group from Harvard University had published an article in the New England Journal of Medicine in 1994, indicating that the prevalence of apnea in the population was between 2% to 4%. Imagine, completely wrong. The Harvard researchers didn’t bring people in to do polysomnography and made their conclusions based only on the evaluation of a group of workers who snored. Our study was complimented by everyone.

How has EPISONO progressed?
When planning the first survey, I saw that the initial task was to take a snapshot of sleep disturbances. We started in 1986 with a small number of participants, conducting questionnaires to verify the most frequent problems, then we followed this group from decade to decade, more or less like the Demographic Census. In the third edition of the study, in 2007, we brought in 1,101 participants between the ages of 20 and 80 to sleep at the Sleep Institute for a night to undergo polysomnography. This group was a representative sample of the city of São Paulo. In addition to polysomnography, we collected blood samples and conducted RNA analyses and a series of tests and evaluations, which included detailed questionnaires. Nobody had ever done that. Our drivers would pick people up at home and take them back in the morning. This is how I demonstrated that 33% of the population of the city of São Paulo has apnea. The average is 40% in men and 26% in women. The problem increases with age. It starts with a frequency of 7% in the 20–29 age group. Among women, it appears later, around age 50, after menopause, because female hormones protect them from apnea. By their later years, the frequency for women is equal to the men’s. After age 70, 80% of men and women have apnea.

We discovered 33% of the city of São Paulo has apnea. The average is 40% in men and 26% in women

Is apnea the biggest sleep problem?
The two biggest are sleep apnea and insomnia, with much more insomnia in women and more sleep apnea in men. Apnea is worse, because the person stops breathing and loses sleep, but not in insomnia, only sleep is lost. But complaints about the three types of insomnia, namely, difficulty initiating sleep or maintaining sleep and early awakening, were also high, reaching 30%. Look how it’s grown over the last three decades [pointing to graphs on a big screen on the wall next to his desk], because of increased violence, stress, and traffic.

Do physicians in other specialties respond well to studies on the effects of sleep deprivation? One study years ago from your group showed the interference of sleep disorders on metabolism. Do endocrinologists today recognize sleep as a problem?
Endocrinologists and immunologists were easier to convince, with studies, which just keep coming out. The cardiologists took the longest, but at the most recent sleep congresses I made a presentation just for them, and it filled up. And they’ve started asking for polysomnography exams. Instead of treating hypertension, which is the clinical manifestation, they treat apnea, which is the cause. The problem is that the private health insurance system pays for polysomnography, but not for the CPAP device, which is the treatment. Polysomnography is an expensive test. In addition to the equipment, there are the hospitality fees, because people spend the night here. When José Serra was Minister of Health [1998 to 2002], we were able to include treatment for apnea in the SUS [Unified Health System] coverage. I even constructed a building to serve SUS patients next door, but later stopped using it. At the time, SUS paid just over R$100, which was already low, and they didn’t adjust it over the following years. You can’t do a polysomnography for R$100. Here we try to do them from between R$500 and R$700. The Hospital das Clínicas at USP still does them [at the original rate]. And SUS also doesn’t provide CPAP.

Sleep disorders are a public health problem, aren’t they?
Apnea alone affects 33% of the population. That’s millions of people. The other problems are rarer. For example, narcolepsy [a disorder marked by sudden attacks of sleep, even after a good night’s rest] affects less than 1% of people, but it’s serious because the individual may be driving and suddenly fall asleep, or could be in the middle of conversation and go in and out of sleep from one moment to the next. It’s easy to treat with medication. Luiz Roberto Barradas Barata [1953–2010] was the São Paulo State Secretary of Health [from 2003 to 2010], and at that time he was helping to structure a public policy to treat sleep disorders. We wanted to treat at least the severe cases of apnea, but he died suddenly of a heart attack, and the project didn’t progress any further.

How do doctors typically learn about sleep disorders?
UNIFESP created a separate discipline, Biology and Sleep Medicine, but most medical schools treat these disorders within pulmonology or neurology. Neuro dominates the polysomnography, while pulmonology focuses on apnea. Sleep Medicine still isn’t well established in the Brazilian medical curriculum, but at least within these disciplines, sleep is talked about. There is already a medical residency in the field, the next step is for it to become a specialty, but it takes time. We have to train people. I’ve trained a lot of people, around 3,000 doctors, who opened sleep laboratories all over the country.

Who were you inspired by?
In Ribeirão Preto, the neurophysiologist Miguel Covian [1913–1992] and Krieger. Covian was my master’s advisor. I learned from him how to do science. He was a philosopher, a being from another planet. At night, we would get together just to talk about philosophy, to reflect on the Universe. Krieger is more entrepreneurial. Carlini, here at UNIFESP, was super daring. We were always very active politically. I participated in the creation of the PT [Worker’s Party] and was a city councilor. Then I walked away from it. I used to make all the PT’s videos because I had a film production company.

To sleep well, you have to reduce stress. You don’t have to suffer so much from life’s problems

Where does the name Tufik come from?
It’s my Lebanese grandfather’s name. Our family names are all wrong. My great-grandfather’s name was José Kalil Sawaya. He named my grandfather Tufik José Kalil, using his own name as a surname. Then my grandfather used his name as my father’s surname, Brasil Tufik. All the Lebanese do this in Brazil, I don’t know why. We’ve continued on with Tufik, which isn’t actually a last name, it’s a first name.

The entrepreneurial gene must come from your family.
It comes from the Lebanese. My father was an entrepreneur. He started with a store, then he opened a bar and worked in construction. He wasn’t an engineer, but he designed the plans himself. When I graduated from medicine, he wanted to open a hospital for me. I said I wanted to do science and he got really angry. He said I would be a “barnabas,” which at that time was what you called a civil servant who didn’t really work, but later he saw that I started doing other things as well.

You once said that you created AFIP because you didn’t want to be a beggar scientist.
In the past, UNIFESP researchers had funding problems. At FAPESP they said: “You’re federal, look to the CNPq [National Council for Scientific and Technological Development] or CAPES [Coordination for the Improvement of Higher Education Personnel].” When I arrived at CAPES and CNPq, they said the exact opposite: “But you’re from São Paulo, go to FAPESP.” So in 1976, I was 28 years old and still a doctoral student when I recognized this problem and thought: “I’m going to start a nonprofit organization to bring in money for research.” We started doing private polysomnography exams. The first thing I did was to give a salary boost to the lab technicians so that they would stay after 5 p.m. and we wouldn’t miss out on any experiments. We would set up a lab to do research and later dismantled it. I thought: “I’m going to stop this; I can’t stand to keep doing it this way anymore. I’ll leave it working, get a few jobs and when a study comes in, we’ll do it.” I created AFIP, a private foundation linked to UNIFESP. Today AFIP has 50 laboratories and performs six million tests per month, mostly for SUS. We do one to two million tests per month for the city of São Paulo and from two to three million for the state. I have 3,600 employees. What was supposed to just provide a little help has grown and is now in nine states. With the money that comes in, I pay employees to work in the Department of Psychobiology at UNIFESP and donate space and supplies. The Sleep Institute and this building are owned by AFIP.

Even with the funding problems at UNIFESP, you got approval and coordinated the Sleep Studies Center for ten years, supported by FAPESP.
Yes, and it was very productive. I don’t know why they didn’t renew for another ten years, I was really upset, because everything was going well. The center was where Marco Túlio de Mello discovered that 48% of professional drivers, from a sample of 400, were still tired and sleepy when it was time to drive again, which increased the risk of accidents. Based on this data, we were able to change transportation legislation, which now includes an assessment of sleep disorders among the criteria for obtaining a professional driver’s license. After evaluating almost 8,000 people, we also observed that people who work night shifts gained five to six kilograms during their first year and 0.8 to 1.2 kg per year after that. They eat more high-calorie food because they’re awake, when they should be eating only lighter foods, in addition to exercising.

One very practical question: how can we sleep better?
You have to understand your body. If you’re overweight, you have to lose weight. If you don’t exercise, you need to— those things no one likes to hear when they go to the doctor. You also have to dim the light at night for your melatonin level to start rising so you’ll sleep. Mainly, you have to reduce stress. You don’t have to suffer so much from life’s problems. If you’re too on edge, you’ll wear yourself out or attack other people, and then the problems will only increase. You have to focus on the problem and solve it if possible. If you can’t, it’s best to forget about it. Otherwise, sleep will really abandon you.

Read the Pesquisa FAPESP articles about sleep research