{"id":177534,"date":"2015-03-23T16:52:13","date_gmt":"2015-03-23T19:52:13","guid":{"rendered":"http:\/\/revistapesquisa.fapesp.br\/?p=177534"},"modified":"2015-04-23T17:03:37","modified_gmt":"2015-04-23T20:03:37","slug":"etelvino-jose-henriques-bechara-on-fireflies-and-mental-illnesses","status":"publish","type":"post","link":"https:\/\/revistapesquisa.fapesp.br\/en\/etelvino-jose-henriques-bechara-on-fireflies-and-mental-illnesses\/","title":{"rendered":"Etelvino Jos\u00e9 Henriques Bechara: On fireflies and mental illnesses"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-177543 alignright\" src=\"http:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-1_229.jpg\" alt=\"\" width=\"290\" height=\"388\" srcset=\"https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-1_229.jpg 290w, https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-1_229-120x161.jpg 120w, https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-1_229-250x334.jpg 250w\" sizes=\"auto, (max-width: 290px) 100vw, 290px\" \/><span class=\"media-credits-inline\">L\u00c9O RAMOS<\/span>While awaiting the response to his request for reinstatement to the University of S\u00e3o Paulo Chemistry Institute (IQ-USP), Etelvino Bechara said he had been without a laboratory, money with which to pursue research and students with whom to divvy up the work.\u00a0 Despite all that, he never stopped exploring the paths that opened before him \u2013 ever since leaving Capara\u00f3, the small town in Minas Gerais State where he was born and learned to read and write with adults at night school under lantern light.\u00a0 On a day in early February\u00a0 many years later, he was making final revisions to an article the journal <em>Science<\/em> would publish two weeks later that showed how extremely reactive chemical compounds known as free radicals\u00a0 \u2013 in this case formed out of the fragmentation of skin pigment, melanin \u2013contribute to continued damage to DNA, even after hours of direct exposure to sunlight (<em>see the report on page 62<\/em>).<\/p>\n<table class=\"tabela_interna\" border=\"0\" align=\"left\">\n<tbody>\n<tr>\n<td><strong>Age:<\/strong><\/td>\n<\/tr>\n<tr>\n<td>70<\/td>\n<\/tr>\n<tr>\n<td><strong>Specialty:<\/strong><\/td>\n<\/tr>\n<tr>\n<td>Chemi- and bioluminescence; free radicals<\/td>\n<\/tr>\n<tr>\n<td><strong>Education:<\/strong><\/td>\n<\/tr>\n<tr>\n<td>Chemistry Institute (IQ) of the University of S\u00e3o Paulo (undergraduate and PhD), Johns Hopkins University and Harvard University (post-doc)<\/td>\n<\/tr>\n<tr>\n<td><strong>Institutions:<\/strong><\/td>\n<\/tr>\n<tr>\n<td>USP Chemistry Institute (1971-2008), Federal University of S\u00e3o Paulo (2008-14)<\/td>\n<\/tr>\n<tr>\n<td><strong>Scientific production:<\/strong><\/td>\n<\/tr>\n<tr>\n<td>175 scientific papers, 1 book and 10 chapters in books<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>Bechara has been working on free radicals since pursuing his PhD\u00a0 under the orientation of Italian chemist Giuseppe Cilento, a preeminent figure in science at USP during the 1970s.\u00a0 Bechara was gradually able to determine that free radicals took part in fascinating biological phenomena, such as the glowing termite mounds of the Emas National Park in Brazil\u2019s Goi\u00e1s State, as well as helping cause or aggravate several diseases.\u00a0 \u201cI\u2019m inspired by the things I read in the newspapers or in conversations with people,\u201d he says.\u00a0 His fascination with the unknown led him to engage in or follow the field work at Vila Parisi, in the city of Cubat\u00e3o, one of the most polluted places in the world during the 1970s, then in psychiatric hospitals, shoe and car battery factories and, most recently, at a rehabilitation center for troubled teens in Bauru, in inland S\u00e3o Paulo State where he was able to associate lead poisoning \u2013 again by means of free radicals \u2013 with mental issues.<\/p>\n<p>A father to four and grandfather to four, Bechara taught at USP for 37 years, coordinated the planning and implementation of undergraduate and graduate courses at the Diadema campus of the Federal University of S\u00e3o Paulo (Unifesp) and was obligated to retire from public service when he turned 70 in December 2014.\u00a0 Now, he plans to return to USP as a senior professor so he can continue to do research and enjoy the company of colleagues and students.\u00a0 Bechara is the first name of his Lebanese maternal grandfather who arrived in Brazil in 1905.\u00a0 Henriques comes from his Portuguese father.<\/p>\n<p>In looking back over his personal and professional history in the office of his spacious apartment in S\u00e3o Paulo\u2019s Lapa neighborhood, where through the windows he can see the buildings and trees of USP\u2019s main campus in the distance, surrounded by his collection of paintings from popular artists, acquired during his travels, the first thing to come to his mind was an old teacher, Ilza Campos Sad.<\/p>\n<p><strong>Who was Ilza Sad?<br \/>\n<\/strong>She was a wonderful middle school teacher I had at a public school in Manhua\u00e7u, in inland Minas Gerais State, on the Esp\u00edrito Santo state line.\u00a0 Mrs. Sad taught science and geography and it is to her I attribute my interest in nature and man instilled through our human geography and economics classes, taught in such a natural way; collecting cans to make a still and building small objects out of wood to demonstrate the laws of physics.\u00a0 She was so spectacular that she organized a news show called <em>A hora do estudante<\/em> (Student hour) on the city\u2019s radio station, and for one hour, we would talk to residents about literature, science, everything.\u00a0 It was the first time I\u2019d been awakened to the world.\u00a0 Later, I traveled a lot and always sent her postcards from wherever I was, telling her what I was doing.\u00a0 She established the Casa de Cultura in Manhua\u00e7u and they told me that she would display all the postcards I\u2019d sent her there.\u00a0 Prior to that, when I finished middle school, I stopped studying because there was no high school in the city.\u00a0 I\u2019d do an accounting course at night.\u00a0 A year later, in 1961, I passed the entrance exam for the agriculture course in Vi\u00e7osa\u00a0 [Minas Gerais State].\u00a0 It was full-time.\u00a0 I was lucky because the professors were also from the federal university, at the time, the Rural University of the state of Minas Gerais, now the Federal University of Vi\u00e7osa.\u00a0 My family had already moved to S\u00e3o Paulo.\u00a0 I had four brothers who each had their own jobs and contributed to the family.\u00a0 When I came as well, I worked as a peon in a chemistry laboratory at a factory in Ermelino Matarazzo.\u00a0 Lucky for me, my boss in the laboratory, Alexander Dubson, had been a professor at universities in Moscow, Rome and Peking.\u00a0 When he saw how interested I was, he took me on as a student, which allowed him to vent all his frustration about no longer being a professor and having to work in industry, and he taught me a lot of chemistry.\u00a0 In the beginning, I was in charge of quality control, but two months after I got there, with his help, I started researching methods that the factory could use to analyze sulphuric acid and other raw materials used to make cellophane paper.\u00a0 When I left the factory, I began the chemistry program at USP.\u00a0 In 1965, it was still on Alameda Glete in downtown S\u00e3o Paulo, and then, from 1966 to 1968, it was at the Chemistry Institute on the Main Campus.<\/p>\n<div id=\"attachment_177545\" style=\"max-width: 310px\" class=\"wp-caption alignright\"><a href=\"http:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-Bechara_229.jpg\"><img loading=\"lazy\" decoding=\"async\" class=\"size-medium wp-image-177545\" src=\"http:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-Bechara_229-300x208.jpg\" alt=\"At his graduation in Vi\u00e7osa, 1963 (Bechara is third from the left). Below, at Harvard, in 1974\" width=\"300\" height=\"208\" \/><p class=\"wp-caption-text\"><span class=\"media-credits-inline\">personal archives<\/span><\/a> At his graduation in Vi\u00e7osa, 1963 (<em>Bechara is third from the left<\/em>).<span class=\"media-credits\">personal archives<\/span><\/p><\/div>\n<p><strong>What was the program like?<em><br \/>\n<\/em><\/strong>It was wonderful and it prepared me for a variety of things.\u00a0 I fell in love with organic chemistry, I think because of my background, I\u2019d always loved natural history, I had a collection of crystals and I also liked botany, zoology and chemistry.\u00a0 At that time, I\u2019d heard a lot about Giuseppe Cilento, the internationally famous professor.\u00a0 He had done his post-doc at Harvard, and was better known abroad than in Brazil.\u00a0 I gave up organic chemistry and decided to do my PhD with him because at the time, in the late 1960s, there was a mini-revolution taking place in science.\u00a0 They were attempting to understand the mechanisms behind the formation of ATP [adenosine triphosphate] in the respiratory chain.\u00a0 It was a huge mystery.\u00a0 How does what we eat become ATP, the energy in our bodies? If we want to contract a muscle, think or do anything, we use ATP.\u00a0 It\u2019s our energy currency.\u00a0 It was a hot topic, I was very excited about it and I asked to do my PhD with him.<\/p>\n<p><strong>How did it go with Cilento?<em><br \/>\n<\/em><\/strong>It was kind of complicated.\u00a0 During the chemistry course, which was full-time, I even had classes on Saturday mornings.\u00a0 I had to earn money so I taught in the guild course in the School of Philosophy, then on the <em>Equipe Vestibular <\/em>[Entrance Exam Team] and was a student activist from the Trotsky party, the 4<sup>th<\/sup> International.\u00a0 I was president of the academic center and ended up getting arrested in the Ibi\u00fana congress in 1967 and prosecuted by the Second Army.\u00a0 When I started my graduate work, I looked up Cilento. He said that they had information about me that prevented him from accepting me as his student.\u00a0 But I had been one of his best students.\u00a0 That\u2019s how he was; he wanted folks who worked hard, got results through good projects and in excellent papers.\u00a0 He didn\u2019t care about the rest.\u00a0 He accepted me as a student but only on the condition that I refrained from talking about politics in the laboratory.\u00a0 I sealed the deal with him immediately and fulfilled my commitment.\u00a0 I never talked politics in the laboratory although I continued to be very active.<\/p>\n<p><strong>Doing what?<em><br \/>\n<\/em><\/strong>My house was an apparatus [a place that housed clandestine political groups during the dictatorship] and I helped hide people, carry documents, whatever was needed.\u00a0 I was arrested by the Oban [Operation Bandeirantes], and spent a day in jail.\u00a0 I don\u2019t know how I convinced the guy in charge at the time that my business was really science.\u00a0 I depended upon science for my survival.\u00a0 During that entire time I had to help support my father, who was a tailor, and my mother, a housewife.\u00a0 At the time to me, being a Brazilian citizen\u00a0 meant working against the dictatorship, against obscurantism, and against violence and torture.\u00a0 Even at the university I never ran away from a fight.<\/p>\n<p><strong>And the research with Cilento?<br \/>\n<\/strong>In 1969 I began working with him on oxygen and light, two topics that still haunt me. That\u2019s when Alberto Carvalho da Silva, scientific director of FAPESP at that time, signed my first grant. My PhD work began with a study on ATP synthesis in the respiratory chain.\u00a0 Cilento said that there was enormous pressure all over the world to understand how ATP was formed in the mitochondria, one of the compartments of a cell.\u00a0 I worked on one of the three approaches, the so-called chemical hypothesis, which held that during metabolism, compounds rich in energy are formed, but it didn\u2019t\u00a0 solve all the problems because the energy-rich compounds that were proposed were unstable in water and couldn\u2019t be isolated, and all of the experiment models in the laboratory were conducted in aqueous solution so there was no chance of forming ATP because the compound would be destroyed by the water.\u00a0 What was Cilento\u2019s suggestion?\u00a0 Conduct the operation in a non-aqueous solution, in pyridine.\u00a0 When I used pyridine, I was able to synthesize 26% of ATP, without mitochondria or anything.\u00a0 Cilento had warned me that the project was very difficult and that it was being tested all over the world.\u00a0 He would always say that he would rather give a good student a hard project than a good one.\u00a0 He kept tabs on things, but it ran the risk of not working out, but it didn\u2019t matter.\u00a0 I had worked with him for one whole year on a similar hypothesis and ended up throwing all the data in the garbage because it didn\u2019t work.\u00a0 At that time, one did research to prove one\u2019s ideas, generate new knowledge and, if that happened, we could publish the paper in a good journal. We weren\u2019t doing the study just to publish, but instead, to generate new knowledge \u2013 publication would be an outcome of the research process.\u00a0 In 1971, I was hired as teaching assistant at USP and the following year, after defending my dissertation, I became an assistant professor and shared the laboratory with Cilento until he died in 1994.\u00a0 The research on ATP led me to the superoxide radical, which then led me to the free radicals.<\/p>\n<p><strong>How did this connection come about?<em><br \/>\n<\/em><\/strong>At the time I was describing the ATP synthesis reaction, I had to talk about a free radical called superoxide.\u00a0 The findings could only be explained if the superoxide had been involved.\u00a0 But there was no reagent; there was no way to test the hypothesis. It was in 1969 when Irwin Fridovich at Duke University first described the superoxide dismutase enzyme.\u00a0 Superoxide dismutase destroys superoxide, but we had no way of preparing that enzyme.\u00a0 How did we deal with the problem? Cilento invited Vincent Massey, of the University of Michigan in Ann Arbor to spend some time at USP.\u00a0 He was one of the greats in the field of flavins, participants in the respiratory chain.\u00a0 He came in 1971 and taught me how to prepare superoxide dismutase.\u00a0 We made it from oxblood.\u00a0 We got six pails of oxblood from a slaughterhouse in Osasco, took it to the laboratory and prepared several milligrams of the pure enzyme. The enzyme was known to build up copper in the cell membranes.\u00a0 Copper is very toxic, but its ability to destroy the free radical superoxide was only explained by Fridovich. Up to that point, talking about free radicals in cells was taboo, because they are generally highly reactive.\u00a0 How could one even imagine that the body was making its own free radicals?\u00a0 It would be suicide, but it demonstrated that this enzyme was in the tissues and, since its specific purpose is to destroy these free radicals, it demonstrated that the body made free radicals.\u00a0 Now we know that free radicals are part of the body\u2019s normal metabolism although they can be toxic and can trigger disease when produced in excess.\u00a0 During a follow-up stage, Cilento began to realize that many free radical reactions were chemiluminescent \u2013 they emitted light.\u00a0 The energy was converted into photons instead of heat.\u00a0 I worked with him on some of these reactions.\u00a0 At the time, one of the major authorities in chemiluminescence was Emil White, of Johns Hopkins University.\u00a0 Cilento and White thought that these reactions that emitted light could transmit energy to other molecules and thus perform photochemistry without light, in essence, photochemistry in the dark.\u00a0 In 1974, they proposed various substances that through the action of enzymes could generate an excited product in just the same way as light.\u00a0 This way, there could be a typically photochemical reaction in a plant\u2019s roots as well as in the body\u2019s liver that receives no light.<\/p>\n<div id=\"attachment_177546\" style=\"max-width: 300px\" class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-177546\" src=\"http:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-3_229.jpg\" alt=\"At Harvard, in 1974\" width=\"290\" height=\"423\" srcset=\"https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-3_229.jpg 290w, https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-3_229-120x175.jpg 120w, https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-3_229-250x365.jpg 250w\" sizes=\"auto, (max-width: 290px) 100vw, 290px\" \/><p class=\"wp-caption-text\"><span class=\"media-credits-inline\">Personal archives<\/span>At Harvard, in 1974<span class=\"media-credits\">Personal archives<\/span><\/p><\/div>\n<p><strong>Were these enzymes already known or just hypothetical?<em><br \/>\n<\/em><\/strong>That\u2019s where Cilento comes in. He described how some enzymes called peroxidases could do this.\u00a0 I began to study these reactions with him, using horseradish peroxidase. Horseradish is like a radish, a Japanese condiment.\u00a0 Later, in the 1990s, I did important work on photochemistry in the dark with Alicia Kowaltowski and Anibal Vercesi. We demonstrated that degradation of the mitochondria caused by phosphate occurs from the formation of highly reactive forms of oxygen called triplet carbonyl compounds.\u00a0 They have to do with chemiluminescence.\u00a0 Then, in 2014, Paolo Di Mascio and I published a paper with PhD student Camila Mano, demonstrating <em>in vitro<\/em> that this excited species, besides emitting light and performing photochemistry, was able to convert energy into oxygen, forming highly reactive singlet oxygen, which is associated with cell and tissue damage. Cilento would be happy to see this research.<\/p>\n<p><strong>Tell us about your work with glowing termite mounds.\u00a0 How did that start?<br \/>\n<\/strong>When I was at Harvard, from June 1975 to May 1976 working with chemiluminescence, some researchers there just couldn\u2019t get over the fact that I didn\u2019t know Cleide Costa from the USP Zoology Museum who had studied the glowing termite mounds of Goi\u00e1s.\u00a0 When I got back to Brazil in 1976, I looked her up.\u00a0 She was very excited and said that she would help me.\u00a0 Paulo Vanzolini, Museum director, authorized me to use the museum\u2019s facilities to conduct my research.\u00a0 I started working at the Emas National Park. I got there \u2013 there were poachers, a landing strip and the park was deserted. I helped get the park some media attention; I gave interviews about the termite mounds that appeared in the <em>Folha de S.Paulo<\/em> and <em>Estad\u00e3o<\/em>, <em>Fant\u00e1stico<\/em>, <em>Globo Rural <\/em>and <em>Globo Ci\u00eancia <\/em>newspapers.\u00a0 Bioluminescence is nothing more than chemiluminescence, but it occurs inside the firefly catalyzed by an enzyme known as luciferase, which is a peroxidase.\u00a0 When I went there the first time, I fell in love with the fireflies, which reminded me of my childhood in Capara\u00f3, where I was born. We had no toys so we played with fireflies and beetles. Capara\u00f3 was a small town; it didn\u2019t even have 1,000 residents.\u00a0 Early on, I kept the fireflies at the Zoology Museum, but then the research expanded so much that I had to set up a bioluminescence laboratory at the Chemistry Institute.\u00a0 That\u2019s were Vadim Viviani, who still works with fireflies at the Federal University of S\u00e3o Carlos [UFSCar], on the Sorocaba campus, came from.\u00a0 As a matter of fact, I\u2019ve always tried to advise and instruct people to be better than I was.\u00a0 And I always told them that they shouldn\u2019t be afraid when faced with strange or challenging possibilities that appeared in their paths.\u00a0 They have to open a lot of doors to see opportunities and make choices.\u00a0 They have to be bold.<\/p>\n<p><strong>How do glowing termite mounds work?<em><br \/>\n<\/em><\/strong>Fireflies take over the termite mound and develop a network of tunnels that are independent form the termite chambers and tunnels.\u00a0 This network is dug out around 1-10 cm from the surface of the termite mound.\u00a0 When it rains, firefly larvae stick their heads and bright thoraxes out of windows in the hill that are open to the outside, attracting insects.\u00a0 Now during the rainy season, at dusk, there is a cloud, a swarm of insects that hovers around the termite mound and emits a green light.\u00a0 The light comes from the tiny green points of each larva lantern.\u00a0 Each termite hill has 200 to 300 larvae.\u00a0 It\u2019s like a Christmas tree, and there are hundreds of termite hills.\u00a0 The insects attract scorpions, centipedes and frogs, which in turn attract owls and other nocturnal birds. They defecate near the termite mound and disperse seeds from which plants grow.\u00a0 With roots nearby, armadillos and rodents come next.\u00a0 Because there are termites and ants, anteaters are also attracted.\u00a0 The termite mound is like a huge hotel that serves a nightly banquet to a variety of guests.<\/p>\n<p><strong>Do the termites get anything out of this?<em><br \/>\n<\/em><\/strong>That\u2019s a great question that has not yet been answered.\u00a0 We have to remember that termites form a caste society: queen, king, workers and soldiers.\u00a0 Soldier termites are very aggressive and don\u2019t allow any other species to come near, but they don\u2019t attack the firefly larvae that live in independent spaces.\u00a0 Quite the contrary.\u00a0 The larvae\u2019s preferred prey is the termite because the adult termite also flies in that cloud of insects. Each larva can get about 10-12 termites a night.\u00a0 When we made the mold of a termite mound by injecting polystyrene into the tunnels, we saw that the larvae had constructed a dining room 1 centimeter away from the surface.\u00a0 When they take a bite, they regurgitate the digestive liquid, which we already studied with Walter Terra of the Chemistry Institute. Like spiders, firefly larvae bite and pre-digest their prey; digestion is external.\u00a0 Then they feed off that soup that is already prepared, as they\u2019ve already broken the larger molecules down to smaller ones.<\/p>\n<p><strong>Did you destroy the park\u2019s termite mounds?<em><br \/>\n<\/em><\/strong>No! We preserved the Emas National Park precisely because we had to open up the termite mounds to collect the larvae.\u00a0 We worked at the Santo Ant\u00f4nio farm, located at the crossroads of the states of Mato Grosso, Mato Grosso do Sul and Goi\u00e1s, near the park, and we stayed at a little hotel in Costa Rica, in the state of Mato Grosso do Sul. The woods around the farm disappeared. All the termite mounds were knocked down to plant soybean.\u00a0 A graduate student from the School of Architecture and Urban Studies at USP and I did the design for an advanced laboratory for studying bioluminescence, with researchers from several fields, but there needed to be a counterpart, which had to be local, and the farm\u2019s owner would not allow it.\u00a0 I appealed to Congress, the tourism departments, and the governments of nearby cities but never got any support or any response.\u00a0 I did what I could, but was unsuccessful.<\/p>\n<p><strong>Are there other glowing termite mounds in Brazil?<br \/>\n<\/strong>A few, very few. There are still a few glowing termite mounds in the region, in thickets of palm.\u00a0 My former student Vadim Viviani, who is now a professor at UFSCar in Sorocaba, is starting a research study on glowing termite mounds in Amazon Rainforest clearings.<\/p>\n<div id=\"attachment_177547\" style=\"max-width: 300px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-177547\" src=\"http:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-4_229.jpg\" alt=\"In 2003, in the Manhua\u00e7u classroom where he had studied many years before\" width=\"290\" height=\"216\" srcset=\"https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-4_229.jpg 290w, https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-4_229-120x89.jpg 120w, https:\/\/revistapesquisa.fapesp.br\/wp-content\/uploads\/2015\/04\/022-029_Entrevista-4_229-250x186.jpg 250w\" sizes=\"auto, (max-width: 290px) 100vw, 290px\" \/><p class=\"wp-caption-text\"><span class=\"media-credits-inline\">personal archives<\/span>In 2003, in the Manhua\u00e7u classroom where he had studied many years before<span class=\"media-credits\">personal archives<\/span><\/p><\/div>\n<p><strong>In 1978, you went to Vila Parisi, in Cubat\u00e3o. Why?<em><br \/>\n<\/em><\/strong>It was for a side study on free radicals that came along after I got back from Harvard.\u00a0 Some of my colleagues criticize me because I go from one thing to the next and do a lot of things at the same time, but that\u2019s just my style.\u00a0 I pursue what interests me, not necessarily what\u2019s in style.\u00a0 Vila Parisi caught the world\u2019s attention and Cubat\u00e3o was considered to be the most polluted city in the world during the 1970s.\u00a0\u00a0 I had read in the paper that Paulo Naum, a biologist at the S\u00e3o Paulo State University (Unesp) in S\u00e3o Jos\u00e9 do Rio Preto, had measured high levels of methemoglobin in the blood of residents of Vila Parisi. Methemoglobin is hemoglobin that does not contain iron 2, but iron 3, which is oxidized and unable to carry oxygen, which is bad. It was not easy to collect blood samples from the residents of that location to do the analyses.\u00a0 It was Marisa Medeiros who was able to collect it as part of her master\u2019s work.\u00a0 We went there and I gave a talk in the parish hall. I explained what we wanted to do and asked for everyone\u2019s cooperation with us.\u00a0 All the people we worked with, people from Cubat\u00e3o, workers from the Saturn battery factory, the boys from Febem, now the Funda\u00e7\u00e3o Casa; we explained what we were doing and asked for their consent.\u00a0 It was also a question of respect and ethics.\u00a0 People need to know why they are donating blood and how it will be used.\u00a0 By comparing Cubat\u00e3o with two nearby locations that were not polluted &#8211; Mogi das Cruzes and S\u00e3o Jos\u00e9 do Rio Preto \u2013 we saw that there was a link between air pollution and methemoglobin.\u00a0 I called Naum because he had discovered methemoglobin and I thought I knew the reason behind this.\u00a0 I thought that if methemoglobin were present, there would have to be superoxide as well.<\/p>\n<p><strong>Why?<em><br \/>\n<\/em><\/strong>In the presence of some pollutants, iron 2 from hemoglobin converts electrons to oxygen, resulting in iron 3+, and releases superoxide.\u00a0 In order to protect the individual, superoxide causes the formation of superoxide dismutase, which helps the body prevent potential damage caused by an excess of superoxide.\u00a0 It is an adaptive body response.\u00a0 In 1976 we published the findings together in the journal <em>Archives of Environment Health<\/em>. We no longer refer to superoxide as toxic \u00a0because we\u2019ve seen that it can have other functions such as fertilization of eggs by sperm as well as fighting bacteria.<\/p>\n<p><strong>Afterwards you started to study diseases caused by free radicals, right?<br \/>\n<\/strong>I began to get interested in the pathology of free radicals in the 1980s.\u00a0 I\u2019d already had a genuine sense of the importance of free radicals because oxygen has two major ways of reacting. It reacts either through free radicals or through electronic excitation, the so-called singlet oxygen, energized.\u00a0 What energizes oxygen are dyes for example.\u00a0 You take a labial herpes or a mycosis and add some\u00a0 gentian violet or methylene blue.\u00a0 The dye absorbs the sunlight, becomes stimulated and converts this energy to the oxygen, forming electronically excited singlet oxygen. It is very reactive and damages the DNA, causing immediate cell death. I then began to see what health damage could be caused by free radicals.\u00a0 My inspiration came from Adolf Michelson of the Institute of Physical and Chemical Biology in Paris, who had already written several papers showing the toxic role of oxygen in numerous diseases, especially psychiatric disorders such as schizophrenia, paranoia and bipolar disorder.\u00a0 Michelson spent some time with me in Brazil and I became very excited about his work, especially with mental disorders.\u00a0 I thought that we could perhaps conduct some research on other mental illnesses that had not yet been studied.\u00a0 I thought about acute intermittent porphyria, a genetic disease that generally manifests itself in women after adolescence, causing very strong abdominal pain, psychiatric changes and even hallucinations.\u00a0 That was the subject of the master\u2019s work of Marisa Medeiros and the first study by a group of Brazilians associating free radicals and porphyria, published in the journal <em>Clinical Chemistry<\/em> in 1982.<\/p>\n<p><strong>Why porphyria?<br \/>\n<\/strong>Because of a physician colleague of mine from the Hospital das Cl\u00ednicas at USP, Paulo Marchiori, who came by my laboratory and worked with inactive porphyrias, which are diseases associated with the hemoglobin metabolism in the blood.\u00a0 Michelson had never worked with this.\u00a0 Since Michelson\u2019s data on schizophrenia and bipolar disorder were very generic, they reflected quite a heterogeneous sampling, so I suggested to my doctoral student at the time, Dulcineia Abdalla, that we study this further.\u00a0 We collected blood from people with schizophrenia being treated at the Hospital das Cl\u00ednicas as well as from those with bipolar disorder at the Juquery Psychiatric Hospital and did a systematic study.\u00a0 We came up with the hypothesis that a specific compound, hydroxydopamine, is what was involved with the neurological changes of schizophrenia and bipolar disorder.\u00a0 To test the hypothesis, we performed intrathecal injections of a substance that uses dopamine to form hydroxydopamine, the neurotoxin in rats.\u00a0 We saw that the blood was biochemically similar to the blood we had seen in people suffering from schizophrenia as well as bipolar disorder.\u00a0 Superoxide dismutase, catalase and glutathione peroxidase, the three enzymes that control the toxicity of oxygen, were formed. The study ended there.\u00a0 Abdalla was hired in the School of Pharmacy and changed her line of research, but later groups from other countries proved our hypothesis in several scientific papers.\u00a0 Later we were alerted to the fact that individuals exposed to lead could also experience behavior disturbances, including hallucinations.\u00a0 Lead poisoning is a type of acquired porphyria.\u00a0 I started reading in <em>Folha de S.Paulo<\/em> and in <em>Estad\u00e3o<\/em> about the poisoning experienced by shoemakers in shoe factories in Franca [state of S\u00e3o Paulo]. Shoemakers hold onto the lead pins in their mouth using their teeth, and become contaminated.\u00a0 I also read about lead poisoning at Saturn, a car battery factory in Sorocaba, and received support from Fiesp-Sesi and Fundacentro to test the involvement of free radicals in the health of the workers.\u00a0 The study on lead contamination took me 20 years, because it dates back to the biochemistry study, clarifying reaction mechanisms and following workers in porcelain, electrical wire and car battery factories.\u00a0 It all has to do with free radicals.<\/p>\n<p><strong>In 2002, you said that you were interested in antioxidant therapy that could mitigate the effects of free radicals on the body.\u00a0 What happened?<br \/>\n<\/strong>That was way off. Soon after discovering superoxide dismutase and confirming that the superoxide radical was produced in the cells, there was a veritable boom of studies exploring the so-called toxic activity of oxygen.\u00a0 A lot of researchers, including me, started to test the production of superoxide in various situations: in Vila Parisi, lead poisoning, schizophrenia, and porphyrias.\u00a0 We proposed the use of superoxide dismutase for Peyronie disease, cancer, Crohn\u2019s disease, mental illnesses and several other things.\u00a0 Afterwards we saw <em>in vitro<\/em> that vitamins and other compounds also had the potential to control the level of these free radicals. Vitamin E, vitamin C, carotene, N-acetyl cysteine, a huge number of natural and synthetic substances \u2014they would act as enzymes although less effectively, destroying the free radicals.<\/p>\n<p><strong>Some physicians took advantage of this, right?<br \/>\n<\/strong>The medical community went bug-eyed and said:\u00a0 \u201cLet\u2019s give megadoses of these substances so we can cure and prevent diseases.\u201d The problem is that Brazilian physicians, unlike those in the United States and Europe, don\u2019t have a lot of training in biochemistry.\u00a0 Suddenly, there were a bunch of physicians taking two-day courses on how to use antioxidants.\u00a0 You began to see what\u2019s known as orthomolecular medicine, which started to be adopted by medical experts who would even inject dymethyl sulfoxide into joints.\u00a0 It was ridiculous.\u00a0 It was a very easy field in which to see the proliferation of dishonest professionals.\u00a0 One of these, in Rio de Janeiro, distributed dismutase superoxide pills for oral use.\u00a0 Now, if the enzyme is a protein, when it gets to the stomach, it can only be hydrolyzed.\u00a0 My colleagues from USP and I got excited and joined a group of physicians in an association of orthomolecular medicine, but then we saw that most of them only wanted to make money.\u00a0 How many vitamins should we give out? They were not even a little concerned about learning the molecular bases of the diseases.\u00a0 We pulled out, mainly because we saw that the superoxide wasn\u2019t necessarily toxic \u2013 it\u2019s actually needed for many functions in the body.\u00a0 The problem is overdosing, and it\u2019s not just about the diseases involving oxidative stress.\u00a0 I recently helped \u00c1lvaro Pereira, one of the editors of the show <em>Fant\u00e1stico<\/em>, to expose some of these physicians.<\/p>\n<p><strong>One of your recent research studies dealt with lead poisoning in children and teenagers.<em><br \/>\n<\/em><\/strong>It was a study that began at Febem, today known as the Funda\u00e7\u00e3o Casa, and ended in a Bauru neighborhood, next to the Ajax factory that had contaminated the entire region with lead. The student who sought me out to propose the research, Kelly Kaneshiro Olympio, is a dentist who graduated from Bauru and is today a professor in the School of Public Health at USP.\u00a0 She\u2019d heard about my work with lead poisoning.\u00a0 I agreed to do it and we formed a partnership with Professor Wanda Ghunter, at [the School of] Public Health, and Pedro de Oliveira, an analytical chemist at the USP Chemistry Institute.\u00a0 Olympio carried around a portable office and she would remove tiny samples of enamel from the patient, treating the teeth on the spot.\u00a0 In return, she would do a dental cleaning and oral health diagnostic on the volunteer.\u00a0 Our sampling began to snowball.\u00a0\u00a0 We asked if anyone knew of anyone living in the area around the Ajax factory, and people started coming to us.\u00a0 Olympio examined around 400 children and adolescents.\u00a0 We found high levels of lead and attempted to relate it to aggressive behavior compared to individuals who had low levels of lead.\u00a0 We used a validated questionnaire that eliminated factors that could affect the outcome, such as family problems or complicated personal histories, and we established a hierarchy of behaviors, ranging from mild to medium to severe and the frequency with which they were committed.\u00a0 These behaviors ranged from bullying to murder. We were able to show that adolescents who had been exposed to lead during their early childhood had a higher probability of developing changes in their behavior. It was a study that combined biochemistry and behavior and it was published in the journal <em>Neurotoxicology and Teratology <\/em>in 2009.<\/p>\n<p><strong>And did anything change in Bauru?<em><br \/>\n<\/em><\/strong>No, things have remained just the same.\u00a0 Despite getting authorization from the Febem supervisor and the then-attorney general, the local director prevented us from completing the study.\u00a0 To this day, I don\u2019t understand why. At Olympio\u2019s dissertation defense, a lawyer talked about the judicial branch\u2019s discomfort in dealing with this issue, or issues like that of Chambinho who killed that young couple [Liane Friedenbach and her boyfriend]. If you show that the boy had been poisoned by lead and had brain abnormalities as a result, how do you deal with this problem in the legal realm?\u00a0 As a scientist, I think that what we cannot do is hide the findings of scientific studies.\u00a0 All the papers end with a warning about this poisoning.\u00a0 Even birthday candles with little stars have lead as do some phytotherapic compounds, game meat, ceramic or welded utensils.\u00a0 Wall paint continues to have lead and we have to teach people about how to prevent lead poisoning because once the damage is done, especially brain damage, there is no going back.<\/p>\n<p><strong>How did you put together your collection of paintings?<em><br \/>\n<\/em><\/strong>On trips to collect fireflies, I met painters and starting collecting paintings.\u00a0 Some I received as gifts and others I purchased.\u00a0 Even back in the 1960s when I took part in protests as a student leader, running away from the police, I\u2019d take refuge in Embu das Artes, a city in the greater S\u00e3o Paulo metropolitan area. There I met Solano Trindade, the sculptor Assis and several painters from the area. As I traveled, I added to my collection.\u00a0 I ended up with 90 primitive and <em>na\u00eff <\/em>paintings. When I found the work by Isabel de Jesus, I thought it was by Chagall; so beautiful. I told her about the glowing termite mounds, which she had never seen, but she did a painting for me.\u00a0 It shows the termite mound, and each little point is a firefly larva.\u00a0 Earwigs, scorpions, and spiders are all feeding there, as are an owl and some strange animals, because Isabel de Jesus is famous all over the world for her surrealism.\u00a0 When I told her I was sad to see all of the creatures dried up, she did another painting, which is of the Emas National Park Fire.\u00a0 She is so sensitive, she didn\u2019t paint them all burned but rather just looking down.\u00a0 She lives in Franco da Rocha, not far from S\u00e3o Paulo.<\/p>\n","protected":false},"excerpt":{"rendered":"Chemist investigated highly reactive compounds, the free radicals","protected":false},"author":17,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[161],"tags":[210,259,224,258],"coauthors":[5968],"class_list":["post-177534","post","type-post","status-publish","format-standard","hentry","category-interview","tag-cellular-biology","tag-chemistry","tag-ecology","tag-psychiatry"],"acf":[],"_links":{"self":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/177534","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/users\/17"}],"replies":[{"embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/comments?post=177534"}],"version-history":[{"count":0,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/posts\/177534\/revisions"}],"wp:attachment":[{"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/media?parent=177534"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/categories?post=177534"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/tags?post=177534"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/revistapesquisa.fapesp.br\/en\/wp-json\/wp\/v2\/coauthors?post=177534"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}