Tue. Apr 23rd, 2019

"Who could have imagined that I would be tempted to lose my life?" | Science

"Who could have imagined that I would be tempted to lose my life?" | Science

He says Carlos López Otín that he felt "the happiest man in the world" until one day in the summer of 2017, when he became, in the blink of an eye, "the saddest man in the world." The professor of Biochemistry is one of the 10 European scientists with greater impact in the analysis of molecular secrets of cancer and aging. With his group from the University of Oviedo, he tells that he has deciphered the genome of hundreds of cancer patients, has discovered two new syndromes of accelerated aging and has found new genes that cause sudden death and hereditary melanoma. A decade ago, López Otín received from the hands of King Juan Carlos the National Research Award, endowed with 100,000 euros.

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However, remember, that day of the summer of 2017 "everything started to break". A colleague warned him that "someone" had dedicated himself to review the 450 scientific articles published throughout his career in search of irregularities. The PubPeer website, in which users comment on other people's scientific articles anonymously, was full of attacks against López Otín. For months, he defended himself against the accusations, repeating the experiments that were in doubt. But, at the beginning of June 2018, "a surprising infection" in his animal farm annihilated the more than 5,000 genetically modified mice designed by his team for years to study cancer and aging. "That same day in the afternoon I came to Madrid to the psychiatrist," he says. That June, the biochemist, born in Sabiñánigo (Huesca) in 1958, isolated himself from the world. The result is a book, Life in four letters (Paidós), in which López Otín tells his descent into hell and confesses that he considered the idea of ​​suicide.

Question. Do you write that Life in four letters It is a self-help book, but conceived in the first place to help its author. He says he felt "the happiest man in the world" and became "the saddest".

Answer. Yes, as is. I have lived very happy for almost 60 years. And, suddenly, everything staggers. Things happen that you do not imagine and that seem incredible to you, you do not understand anything. You say: but if all my life has been linear and with a social purpose. And everything has a banal explanation: minimal university envy. This starts up a machinery and you realize that today, in the current world, if someone wants to hurt and work it, it can destroy anyone's life. And then came the event of the bioterium and in one day we lost the future: all the genetically modified animals that were the basis of our work and many other laboratories in the world.

"I came to Madrid and the psychiatrist told me that I had to submit to total isolation"

P. What day was that?

R. One day of the first week of June 2018. That same day in the afternoon I came to Madrid to the psychiatrist. I had never had a disease of any kind, physical or mental or anything. But that day I felt that I had lost my ikigai, my purpose. I came and the psychiatrist told me that I had to submit to total isolation and proposed to enter a clinic. I told him that this was very strong for my mind and that I could have a discipline, as I have always had, maximum. And, under protection or continuous surveillance, I retired to my daughter's house in Mallorca and in 28 days I wrote the book. This is the story of this book. It arises from there, but tries to come to the conclusion that, in today's world, there is no possible defense against the damage that is amplified, without anyone asking you. And it reaches a level that is amplified so much that other people join and, then, you're completely lost. You also realize that you are not the first one that happens, but now it happens massively. And the answer is to ignore it completely -who want to withdraw an article, okay, I'll retire it tomorrow to see if you leave me alone- or commit suicide. I have studied in great detail who has committed suicide and why. This will be part, I hope, of another book, someday.

P. He tells in the book that one day in summer of 2017 "everything began to break". What happened that day?

R. Someone told me that in some social networks they had sent comments about some of our articles. Someone had spent a lot, a lot of time reviewing every last corner of our more than 450 scientific articles, to see what they could find. And they found nothing. Nothing serious. Not scientific No doubt. I am perhaps the most cited scientist in Spain and I am among the 10 most cited in Europe in our specialty. This indicates that all articles have been validated: they have thousands and thousands of citations. People who want to hurt can even invent things. All this I suffered, nothing different from what happens to other people, and I resisted. But the really serious thing was the loss of the mice. That is what definitely broke me.

P. He affirms in his book that he felt "very close to the breath of workplace harassment". What do you mean by workplace harassment? Did you suffer harassment inside the University of Oviedo?

R. Of course, this is studied: harassment based on looking for details of something that is wrong and amplifying them to make it look like your science is wrong. This, in 87% of the cases, arises from within and by problems in some internal promotion: someone who has not taken a place or things like that. What does workplace harassment mean? My purpose in the research was to devote myself to patients and to science. And, when someone harasses you, what you are looking for each day is to see what anonymous they are going to send you.

"I think the question of whether I cheated is so offensive"

P. Do you know who is the person posting the comments in PubPeer?

R. Clear.

P. And have you talked to that person?

R. No, because everyone told me that it was best to put up with it and not make it grow.

P. He wrote this book in June 2018. Six months later, in December, you retracted one of his scientific articles, published in the magazine Nature Cell Biology [Itwasaresearchinwhichhedescribedamoleculethat[eraunainvestigaciónenlaquedescribíaunamoléculaquedoubled life expectancy of mice with accelerated aging].

R. I have 450 articles. What happened to the one in Nature Cell Biology It has nothing to do with the book. It is a perfectly validated article that gave rise to great works published in magazines Cell and in Nature. In the case of that article, for a year they were harassing the students who had done it, for a matter derived from their work in another laboratory. They had not been in my laboratory for five years because of that. And they harassed them continuously. After a year of asking them for the data of the experiments, they did not find a triplicate of one of them. They had done the experiments more than five years ago and they were not tripled by one. The pressure was such that we decided to withdraw that job.

"Harassment networks put pressure on scientific journals with thousands and thousands of tweets"

P. In January 2019, it withdrew eight more studies, with minor failures, at the request of the magazine specialized Journal of Biological Chemistry. You have published 450 studies and have withdrawn or retracted nine of them. How would you explain to a reader the importance of this?

R. Any.

P. Have you ever cheated in your life?

R. Please, this is offensive. There is the answer that there was.[Halfahundredprestigiousscientists-suchasbiochemistry[Mediocentenardeprestigiososcientíficos—comolabioquímicaMargarita Salas, the geneticist Angel Carracedo and the exministra Cristina Garmendia- they wrote to the editors of Journal of Biological Chemistry to defend that the "anomalies" detected in the eight articles of López Otín did not invalidate their conclusions at all].

P. I also mean your team. Someone will be responsible.

R. And why were not detected in 20 years? It's insignificant. It's about talking about something that happened 20 years ago.

"I am not a believer, at all, but I have a lot of respect for believers"

P. Well, the withdrawal of the eight articles It was last January.

R. It is insignificant, irrelevant. All the experiments were repeated and sent to the journal. And hundreds of scientists have said that this no longer makes sense. Why is this happening? Because networks of harassment press the magazines with thousands and thousands of tweets, because they live on that. I find the question of whether I cheated so offensive ...

P. Someone would make mistakes, on purpose or not, perhaps to save time. [En el periodo en el que se publicaron los ocho artículos retirados, entre 2000 y 2007, había una carrera internacional para descubrir los genes relacionados con el cáncer].

R. I talked to everyone [los coautores]. No one told me that he had done it on purpose. Obviously, if there is an error, it is corrected and that's it.

P. My question is whether some of those minimal errors were committed with the will to save time and if you have identified the responsible person and talked to them.

R. Yeah sure. The people were identified, they talked about what happened. None is in the laboratory. This has done me a lot of harm, but what am I going to do, I have to assume it. In life come easy things, good things and difficult things. But this is irrelevant. The articles [retirados] They have been quoted thousands of times and we can publish them wherever we want. And, later, what am I going to do with the people? I say: "Hey, now suicidal, because you have made mistakes?".

"They could not find any big flaw in our studies, even though they would have loved it"

P. Absolutely.

R. Well, that's it. Hey, you made a mistake. Who has not made a mistake? What am I going to tell you? Well, I'm sorry. Why did not anyone notice? Because they are insignificant or undetectable errors. It is irrelevant. If they said that we have invented an experiment ... but they have not been able to find any big defect, even though they would have loved it. They could not.

P. You dedicate the book to your friend Juan Valcárcel, of the Genomic Regulation Center of Barcelona. He himself explained to this newspaper: "In the retired articles there are human errors and there are also attempts by some of the coauthors to aesthetically improve some figures". That's what Valcárcel said.

R. Clear.

P. So there was an attempt to embellish or gain time, win even two weeks to publish the results before, right? Simply that.

R. Yes.

Carlos López Otín, author of the book 'La vida en cuatro letras'.
Carlos López Otín, author of the book 'La vida en cuatro letras'.

P. How is it possible that there was an infection in your home? Do you know what happened?

R. No, I did not study it or study it. The main damage is in my mind, everything else does not matter to me.

P. Were they just his mice or those of the whole University of Oviedo?

R. No, 95% of that biotech is created by us. We seek financing ourselves, we build it and the vast majority, not to say everything there, is ours.

P. Do you think it was a natural infection?

R. I have no idea. I will not discuss it nor will I ever look at it.

P. But does he have the possibility that it was someone?

R. I'm not asking or interested.

P. You in the book tell that you evicted your family.

R. I was 17 years old and I was in college.

"I did not expect to be amazed at how far the levels of perversion of a few humans can reach now"

P. He says that it was because some businessmen did not pay their father. How did the eviction live?

R. I lived in Madrid, in Lavapiés. I lived it with distance. Later, when I grew up, I experienced it much worse, when I understood why my father had retired from the world. When this happened to him, a friend of his left him a flat, which is where they have lived all their lives. For 10 years he did not leave home. He died of Alzheimer's after 90 years. And this happened to him when he was 50 and something.

P. You also say that you would have liked to save your father's suffering. What do you think of the current debate on euthanasia and dignified death?

R. I would like each person to have the opportunity to decide what is best for her, for her environment or for her family. And I absolutely respect the opposing positions. This is discussed a lot in my classes: maximum respect for everything. But I would not want anyone to impose what I have to do with my life, although I respect who thinks backwards. I'm not a believer, not at all, but among my best friends, Sammy Basso for example, there are some who are extraordinarily believers. There are more believers than non-believers and I have a lot of respect for them. And, of course, I have a high sense of human spirituality.

P. The transcendence of the one that speaks in the book?

R. No, not transcendence. I do not feel transcendent at all. Transcendence for me is that you are here and you can transcend to another dimension or to the future. Spirituality, for me, is that while I'm here I like to have deep feelings, but focused on the human species.

P. You affirm that you are not a believer and suggest it several times in the book. He writes: "It also does not seem that it obeys the intelligent purpose of an intelligent designer the fact that thousands of children with diseases caused by hereditary genetic defects come to the world every day." You had a social genomics clinic on Fridays. He will have seen everything.

"In my case, the social support has been so extraordinary that I think it's exaggerated"

R. Of everything. Worst. Who was there? Who could not be helped in any other way in the conventional sites. What could we do? We had an experience that, at the time, was unique in Spain: the ability to study genomes very deeply, with programs that we developed in the laboratory and with pencil and paper. Once we had all the possible data through computer techniques, we passed to the human eye, which I believe is fundamental to solve problems that machines have not yet been able to solve. Most of the lab's successes in this regard have been to combine the most advanced technologies in the world with the human eye. By the way, the social genomics query could not be maintained because I was not there anymore. All are complexities.

P. Will not he take it back?

R. I do not know. Now I try to survive, simply. I try to rebuild the lab in the first place. I have my classes and there is some work that we are trying to carry out. Sammy's[BassoayoungItalianbiologistof23yearswho[Bassounjovenbiólogoitalianode23añosquesuffers an accelerated aging]It was the best example, because for me it was the culmination of my scientific career. I do not think I can do a job that combines so important science with humanism: knowing that one of my students has also been a patient who has benefited from the studies in a way that has allowed him to survive, study and come to work on your own illness. And publish an article of maximum impact, because it is the first time that a genetic disease systemic disease was successfully made. And that Sammy is a co-author of this work seems to me to close a definitive circle in my life. It coincided with all these catastrophes and we took it forward.

P. The publication of that article in the magazine Nature Medicine It served as a stimulus.

R. Very much. I did not know if we could get the job done. We put all the effort of recomposition after the hecatomb. Now we will have to recover the research lines one by one and start doing the experiments. We will need five years to return to the starting point.

P. How is it to undertake the task?

R. Well, I try to recompose myself. I'm completely misplaced. I'm confused Using a quote from Chesterton that comes to my mind now, "I will grow old for everything except amazement." I always interpreted it in positive. I like to be amazed at the new, to learn new things. My students know that my classes are based on education in amazement, in amazement of the keys of life and explanation in molecular terms. Based on that, I'm still amazed. What I did not expect is to be amazed at how far the levels of perversion of a few humans can now reach. And this has me confused, absolutely baffled. I am, of course, on medical treatment.

"If they do this to me, what will not they do to defenseless people or maybe they do not have talents?"

P. Speak in the book of kintsukuroi, the ancient Japanese art of recomposing the broken leaving golden scars in sight. Your book also leaves scars in sight.

R. Yes absolutely. I do not care about anything, because I hope others learn from this. Thanks to these things coming out in the media in the end, many students who have been harassed have come to show me their solidarity and to tell me their cases.

P. In his book, depression floats.

R. More than depression is disappointment. Deep disappointment My life, although it is hard to believe or imagine it, has been dedicated to society, 100%. We have received thousands of messages in the laboratory, from all segments of society. From the most important you can imagine to the most anonymous people. And this is what really amazed me, because normally these stories end with the social stoning of a person, as in the case of José Baselga [theSpanishoncologistwhoinSeptember2018resignedfromthemedicaldirectorateoftheMemorialSloanKetteringCancerCenterinNewYorkafterthediary[eloncólogoespañolqueenseptiembrede2018renuncióaladirecciónmédicadelCentroOncológicoMemorialSloanKetteringdeNuevaYorkdespuésdequeeldiarioThe New York Times will reveal that he had not made public payments received from large pharmaceutical multinationals]. In my case, the social support has been so extraordinary that I think it's an exaggeration. I have not searched or talked to anyone. My only interlocutor with the world has been Juan Valcárcel. He, at the same time that I developed my illness, serious disappointment, he developed a lymphoma. We said to each other: "I will help you to heal you". And we try. He has healed and I have not. But I hope to heal.

P. His friend Valcárcel said that questioning the professional and human integrity of López Otín "is as if someone wanted to question the discovery of Columbus because he did not adequately supervise the berthing of the fleet in the port of La Gomera on the way to America."

R. I did not read it. You know what your life is and what you have done, that's why the question has hurt me so [de si alguna vez en mi vida he hecho trampas]. I am a person who works in a very small place, which becomes the most considered Spanish scientist, it is like that, without ever having gone anywhere, without inviting people to visit you in [grandes centros como] the CNIO or the CNIC, nothing. In a very low profile. I have never been a director of anything, I have only been with my students and with the people who have needed me. And this everyone knows. I have lectured a week throughout my professional life and I have gone on to give none. Any. I have gone from answering 200 messages a day to not answering any. The bulk was 200 social messages, from people who wanted me to talk to a school or tell me that their son was dying. When you have a life dedicated to that, I'm not depressed, I'm disappointed with the world. If they do this to me, what will they not do to defenseless people or maybe they do not have talents? Why do I go ahead? Because, for a series of social talents, for social commitment, I dedicated my whole life to helping others. And then, people, when they see this, they say: "But what are they doing to this guy? But this is unheard of!"

P. Do you think that the scientific system is being perverted with the pressure to publish articles in magazines? With the call publish or perish (publishes or dies), researchers have a lot of pressure and can speed up braking.

R. Most problems [detectados en nuestros artículos] They are very ancient and are due to the enormous degree of craftsmanship that was in some places, especially in the smallest. In the most [laboratorios] Large ones had photographic cabinets. I believe that the problems are others. These things do not improve science at all. Do you know how many have committed suicide for these things?

P. How many?

R. I'm not going to talk about that because I want to write it.

"I know how the genomes are repaired and I would like to know how the soul is repaired"

P. In his book he says: "In recent times I would not have minded sharing with Jeremiah de Saint-Amour, the character of Love in the times of cholera, some incense of gold cyanide. "

R. No, how will I care?

P. There is about 3,600 suicides a year only in Spain. Do you think that little is said about it? In the book you suggest that it can happen to anyone.

R. This book puts many things on the table, but many. Each page has a message, each music. An absolutely profound and delicate message. Who could have imagined that I might be tempted to lose my life when it is, for me, the most important thing? I have fought for my life and for thousands of people. We have deciphered thousands of cancer genomes, especially. But every case of illness that I have known is a lesson in humanity. And I have dedicated myself fully, convincing the whole world that life is the best, that we have to fight for it. I have thousands of examples. And, suddenly, I lost my sense, my purpose, my ikigai, which is a beautiful Japanese word.

P. What would you say to a person who is considering committing suicide right now?

R. To be rebuilt, to practice the five tips for happiness [que doy en mi libro]. The first is the most important for everyone, not only for those who want to commit suicide, but also for those who feel envious of the next person and can not stand it: to recognize imperfection. I have also written the book so that scientists understand that molecular biology provides answers. I make a parallel between the repair of the genomes, which is one of the crucial moments to defend ourselves from aging and cancer, and the repair of the soul. I know how genomes are repaired, I have discovered genes for repair of genomes, and I would like to know how the soul is repaired. And this may have a molecular substrate. We must accept imperfection. If we were perfect, we would still be microbes. We are imperfect, let's accept it. We are not worth everything, we do not have gifts for everything. Rafa Nadal is one of my heroes. I enjoy it. I do not know how to play tennis, but I enjoy that someone else can play tennis. Enjoy the world. The world is full of special things. Why do a few insist on bothering others? The goal of his life is to bother. How much have these people had to suffer so that the only objective of their life is to demolish others? That is what I want to point out: how far can human suffering go, not only what one is capable of resisting, but that of others who have suffered so much that what they want is for others to suffer as well, instead of rebuilding themselves. And, in the end, notice how easy it is to change loneliness for happiness, with a gene editing[LópezOtínfinisheshisbookwiththephotographofacopyof[LópezOtínterminasulibroconlafotografíadeunejemplardeOne hundred years of loneliness dedicated, in which Gabriel García Márquez crosses out the word "solitude" and replaces it with "happiness for Carlos"].


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