Macchiarini, Paolo

In 2008, Professor Macchiarini, who led an international team of scientists, performed an operation at the University Hospital of Barcelona to transplant a trachea patient grown from her own stem cells on a disinfected donor cage in a bioreactor . In October 2009, another unique operation was performed - this time an organ was formed inside the patient's body without using a bioreactor.

In June 2011, Professor Macchiarini, in collaboration with Professor Alexander Saifalian from London University College , carried out the first operation on the transplantation of a human organ entirely grown in a laboratory. A 36-year-old African student living in Iceland was transplanted with a trachea, which biotechnologists were able to form also on the basis of his own stem cells, but on an artificial skeleton. In October 2011, a second such transplant was performed at the Karolinska University - a patient from the USA .

In December 2010, Professor Paolo Macchiarini, together with Russian transplantologists from the Petrovsky Research Center, conducted Russia's first tracheal transplantation according to his methodologies to a 25-year-old patient who suffered as a result of the accident. At that time, a depleted donor cage was used, however, it was assumed that the transplantations that were planned to be carried out in the future within the framework of a grant from the Government of the Russian Federation would use improved artificial nanocomposite frameworks. In July 2018, the patient died. This happened a month after a re-transplant of a trachea at the clinic of the First MSMU named after Sechenov in Moscow ^[4] .

Since 2011, he was the lead scientist of the project “Research of molecular mechanisms and new approaches in the field of regenerative medicine for the creation of airway and lung tissues”.

At the end of 2014, doctors from the Karolinska Institute accused Macchiarini of having embellished his achievements, described by him in seven scientific articles (six articles described the transplantation of artificial organs to people, one article was the transplant of an artificial esophagus to rats; six out of eight patients whom Macchiarini spent transplantation of artificial trachea, died ^[5] ). On this basis, a scientific investigation was launched against Macchiarini. Published in May 2015, the results of an independent examination, which was conducted by Bengt Gerdin, the chief surgeon of Uppsala University , confirmed that Macchiarini had falsified the results of his research and committed a scientific fraud ^{[6] [7]} . However, the Vice-Chancellor of the Karolinska Institute, Anders Hamsten, in August 2015 acquitted Macchiarini. According to Hamsten's wording, Macchiarini’s works “do not meet the high quality standards of this university,” but no scientific fraud was found in them ^[8] . In February 2016, Anders Hamsten resigned as vice-chancellor of the Karolinska Institute, admitting in his letter that he was biased during the investigation of Macchiarini’s activities in the summer of 2015, and that the results of this investigation should be corrected towards the recognition of the fact of scientific fraud on the part of Macchiarini ^{[ 9]} .

In January 2015, ^[10] Swedish television journalists began investigating the history of Professor Macchiarini’s patients who received bioengineering tracheas. The investigation took a year and a half. “We systematically searched for patients who received bioengineered trachea. We still don’t know if we’ve found everyone, because there was no single universal list, ”says one of the film’s authors, Johannes Valström ^[10] . A three-part documentary film with the general title “Experimenten” (Experiments) caused a scandal in medical circles and the public. In the course of this investigation, conducted at the signal of the doctors from the Karolinska Clinic (mainly Dr. Grinnemo), it was concluded that Macchiarini's operations with transplantation of an artificial trachea made of plastic were not experimentally tested, and therefore were not allowed to be performed on humans ^[10] . It is alleged that Macchiarini’s doctoral thesis allegedly contained fraudulent and unverified facts and deception. Macchiarini was acquitted in September 2015 ^[11] .

However, the investigation was resumed in January 2016 and expanded to reflect new facts. ^[12] In particular, it was found that Macchiarini distorted his biography, which served as the basis for obtaining the position of guest professor at the Karolinska University. ^[13] On June 25, 2018 Macchiarini and some of the co-authors of the articles were found guilty of fraud. Some articles were withdrawn ^{[14] [15]} .

The cause of the scandal that erupted throughout Sweden and throughout the medical world, were the facts of the deaths of patients who Macchiarini implanted artificial larynx, trachea. Six out of eight patients for whom the surgeon transplanted the trachea died, including Julia Tuulik from Russia. Two other patients are on long-term treatment. ^{[16] [17] [18]} .

The documentary film shows the facts and videos taken by doctors who examined patients after surgery. On the website of the channel SVT 1 also posted short videos with documentary evidence of severe complications found in patients operated on Macchiarini. ^[19] At the same time, citations from Macchiarini’s article published a year after the first operation, where all the negative complications are not mentioned, are shown. The video shows that Macchiarini was personally present at one of the surveys, which did not detect the formation of epithelium and blood vessels in the patient, described in an article published by Macchiarini a few months later, showing documents from the doctors. Metal mesh-stents, introduced to the patient already 8 months after the operation, are shown. An article in the Lancet magazine instead writes about the formation of an “almost normal trachea” ^[20] . The Royal Swedish Academy of Sciences published a letter in the Lancet magazine, where the facts of silence about negative consequences, including the death of a patient, are brought to the attention of readers. ^[21]

According to the relatives of the first deceased patient, Macchiarini persuaded him to agree to the operation, referring to the successful results of experiments on pigs. In fact, such experiments were not conducted. SVT 1 also published an interview with a patient who, at the last moment, avoided a synthetic trachea transplantation in 2011. According to the patient and her doctor, Macchiarini claimed that she would live no more than a year without an operation. At the time of the interview, the patient lived for 5 years. ^[22]

On February 4, 2016, the Karolinska Institute announced that the labor contract with Macchiarini would not be renewed after its termination on November 30, 2016 due to the loss of trust in the administration. The reason for this decision in a statement of the Institute is a publication in the magazine “ Vanity Fair ” dated January 5, 2016, which states that Macchiarini indicated false information in a summary of his previous places of work and his titles in foreign scientific institutions. The press secretary of the Karolinska Institute Claes Keisu said that the documentary “Experiment” shown on Swedish SVT caused damage to the reputation of the Karolinska Institute in the eyes of the scientific community and the general public. In a letter to the editorial board of the journal Science , Klaes Keisu stated that Macchiarini had abused the reputation of the Karolinska Institute during his work in Krasnodar. The Macchiarini research team at the Karolinska Institute will be disbanded upon the decision of the management of this institution. After publication in the magazine “Vanity Fair” of January 5, 2016, many medical workers, politicians, journalists, law enforcement officers in the United States, Sweden and Italy began to find out how Macchiarini could be allowed to conduct such crucial operations in the United States and Europe, and whether criminal offenses are committed during their conduct ^{[23] [24] [25]} .

A joint statement by the press services of NII-KKB No. 1 and Kuban State Medical University, states that the information presented in the Swedish program is biased and distorts reality ^[26] . The facts of biographical distortions in official documents, omission of negative consequences and even death of patients are not commented on in this statement. The official website of Megagrant on February 23 is still reporting successful operations, keeping silent about the facts of complications and death of patients ^[27] .

The retired vice chancellor of the Karolinska Institute, Anders Hamsten, said that the film “The Experiment” and the journalists' attention to the problem caused by it helped to obtain new information concerning Macchiarini’s abuses. However, the doctors, who in 2014 caught Macchiarini in scientific fraud, reported that they had provided Hamsten, then, with all the necessary information that showed Macchiarini’s dishonesty. On February 11, 2016, the Royal Swedish Academy of Sciences stated that the conduct of a scientific investigation into the Macchiarini scientific fraud case should be transferred from the Karolinska Institute to the Central Scientific and Ethical Observatory of Sweden to ensure the impartiality of this investigation ^[28] .

The Secretary General of the Nobel Assembly and a member of the Nobel Committee on Physiology and Medicine at the Karolinska Institute Urban Lendal resigned in early February 2016 in order not to jeopardize the reputation of these bodies, since he was among the professors of the Karolinska Institute who in 2010 gave a recommendation to Macchiarini for his employment in this institute ^[29] .

March 22, 2016 Macchiarini was dismissed from the Karolinska Institute for committing acts incompatible with work in this scientific institution. He did not admit his guilt and promised to appeal this decision ^[30] .

In June 2016, a criminal investigation was launched against Macchiarini, with the prospect of being charged with the unintentional murder of two patients ^[31] . On October 12, 2017, the Swedish Prosecutor's Office announced the results of a preliminary investigation into the death of three patients of Paolo Macchiarini, who received plastic tracheas in the Karolinska clinic in 2011—2013. The charges were dropped. ^[32]

In 2013, Macchiarini met a 49-year-old TV journalist named Benita Alexander. The TV journalist was shooting a film about the scientific success of Macchiarini, the film was shot in a positive way. Later, however, Alexander admitted the fact of violation of ethics by a journalist, as she began a roaring affair with Macchiarini during the filming of the film. The film was nominated for the prestigious Emmy Award. Macchiarini made a strong impression on her, because he claimed that Barack Obama, Bill Clinton and Hilary Clinton were his friends, that he was the Pope's personal doctor and belongs to the secret VIP club of surgeons doing operations for the presidents, the Pope and other prominent political figures. According to Alexander, for Christmas 2013, Macchiarini made her a marriage proposal. The couple set a wedding for July 2015, while Macchiarini promised his bride that they would be married by the Pope, and among the guests would be Russian President Vladimir Putin, US President Barack Obama with his wife, Bill and Hilary Clinton, as well as former French President Nicolas Sarkozy However, she suspected something was wrong and hired a private detective to find out the details of her fiance's life. Soon, the detective told her that Macchiarini was a poor man living in Barcelona, ​​and that he had been married for 30 years. After that, Alexander broke off relations with Macchiarini ^{[33] [34]} . In February 2018, the premiere of Benita Alexander’s documentary about Paolo Macchiarini’s film “He lied about everything” took place. The Russian version of the film has the name “A scam in a white coat” ^[35] .

In February 2010, Paolo Macchiarini traveled to Russia for the first time, arriving in Moscow at the invitation of the Russian Foundation for the Extension of Life Scientific Research Support Foundation and the personal assistance of journalist Elena Kokurina, the wife of Academician of the Russian Academy of Sciences Svyatoslav Medvedev , who later became the coordinator and researcher of Megagrant. During this visit, Macchiarini held a master class in regenerative medicine in the building of the Presidium of the Russian Academy of Medical Sciences, gave a lecture for students of the Moscow Medical Academy. I. Sechenov "Bionics in medicine of the future" and took part in the discussion about the prospects of growing organs for transplantation at a meeting with scientific journalists. The scientific meeting at the Presidium of the Russian Academy of Medical Sciences was opened by the President of the Russian Academy of Medical Sciences, Professor M. I. Davydov, and was chaired by the Academician of the Russian Academy of Medical Sciences M. I. Perelman ^[36] .

At the end of 2011, Paolo Macchiarini created on the basis of the Kuban State Medical University a laboratory of regenerative medicine within the framework of the development of a megagrant in the amount of 150 million rubles. This amount was allocated for 2011-2013 with a possible extension of 1-2 years and became unprecedented for Russian science. The conditions of the competition stipulated that Kuban State Medical University will provide co-financing of the project in the amount of 43 million rubles from extra-budgetary funds. The rector of Kuban State Medical University Sergey Alekseenko said that the victory of his university in the megagrant competition was achieved due to the presence of a good clinical base - Regional Clinical Hospital No. 1. However, some interested persons expressed the opinion that the decisive factor was the administrative resource in the form of support from the governor of Krasnodar Region Alexandra Tkacheva . Paolo Macchiarini, commenting on this project in an interview with the Russian magazine Expert, said that Western scientists criticized such projects, and that in one of the articles in the journal Nature, Russia called a country of corruption in which nothing can be done according to the law. However, Macchiarini reassured critics of such projects, saying that specialists from Kuban Medical University drew up a study protocol with his participation and held a meeting with a woman who could become the first candidate for artificial trachea transplantation. At the same time, Macchiarini argued that Russian specialists are capable of acting under a formal protocol and there is no need for illegal activities to implement this project. Macchiarini identified three criteria for the success of this project: 1) if the laboratory of regenerative medicine begins to operate; 2) if all clinical activities meet the criteria of bioethics ; 3) if within two years there will be several operations on transplantation of artificial trachea. At the same time, Macchiarini expressed his conviction that it was necessary to actively implement bioethics in the field of medical research ^[37] .

Professor Emeritus Bo Risberg, a recognized expert in the field of bioethics, called the actions of Macchiarini and the Karolinska Institute, leading to the unjustified death of patients, “ethical Chernobyl”. ^[38] Harsh statements condemning Macchiarini were made by several well-known professors, including Nobel laureate Arvid Karlsson ^[39] .

In June 2012, a young Russian woman, Yulia Tuulik, who lived with a tracheostomy after an accident, in the Krasnodar Regional Clinical Hospital No. 1 under the guidance of Macchiarini, an artificial trachea was implanted. In October 2013, the patient died. Yulia Tuulik's mother reported that the death of her daughter was painful and before her onset, there were external signs of rotting processes in her body. Некоторые медики высказали мнение, что без проведения данной операции Юлия Туулик могла прожить ещё не один десяток лет. Первый заместитель главного врача Краснодарской краевой клинической больницы № 1 Игорь Поляков в фильме шведского телевидения SVT «Эксперимент» объяснил согласие российских медиков участвовать в данном проекте тем, что он проводился под вывеской Каролинского института. По словам Полякова, «это было возбуждение, это примерно, как человека в космос запустить» ^[40] .

В феврале 2016 года Маккиарини заявил о своей невиновности в смерти Юлии Туулик, а также о необоснованности других обвинений в его адрес. При этом он назвал Россию одной из немногих стран, где неукоснительно соблюдаются все этические и регуляторные принципы. Он сообщил, что средства мегагранта закончились, и российские специалисты под руководством Маккиарини в Центре регенеративной медицины в Кубанском медицинском университете в Краснодаре продолжили работу по другому гранту — над созданием пищевода ^[41] .

The press services of the Scientific Research Institute-KKB No. 1 and the Kuban State Medical University, responsible for conducting an operation on a Russian patient, called the charges baseless ^[26] . In February 2016, Roszdravnadzor launched an inspection of NII-KKB No. 1 in connection with the Macchiarini scandal, during which it promised to monitor the observance of citizens' rights in the field of health care, the implementation of procedures and standards for medical care and the provision of medical care to patients . As a result of the audit, it was revealed that Paolo Macchiarini did not pass the procedure for admitting medical activities to people in Russia who received medical education abroad ^[42] . In December 2016, the doctors of the Karolinska clinic in a petition addressed to the rector of the Karolinska Institute, the Russian ambassador to Sweden, as well as to the Russian competent authorities, demanded to investigate Macchiarini’s activities in Russia ^[43] . April 12, 2017 The Anti-Corruption Policy Center of the Yabloko party appealed to Olga Vasilieva, Minister of Education and Science, to conduct a megagrant spending test obtained by Paolo Macchiarini ^[42] .

In September 2016 ^[44] it became known that Macchiarini was appointed head of the laboratory "Bioengineering and Regenerative Medicine" of the Kazan Federal University , after media interest from the media began ^{[45], the} photo of the Italian doctor disappeared from the University website from the section "Priority areas", in other sections of which the photo of the surgeon with the staff of his laboratory remained intact ^[46] The grant received by Macchiarini from the Russian Science Foundation assumes preclinical studies and is carried out on e creating a tissue-engineering construction of the esophagus to replace the damaged organ with models of lower primates ^[47] . In March 2017, it became known that the grant of the Russian National Fund was not renewed ^[42] . On April 20, 2017, the Directorate of the KFU International Competitiveness Program decided to close the project under the leadership of Paolo Macchiarini, and he will soon leave the university ^{[42] [48]} .

In August 2017, Macchiarini’s megagrant report for the first half of 2014 was published on the website of the patient human rights organization CIRCARE, which mentions an operation performed in Krasnodar to a 6-month-old child as a preparatory stage for tracheal transplantation ^[10] .

• Macchiarini, P., Fontanini, G., Squartini, F., Angeletti, CA, & Hardin, MJ (1992). Relation of neovascularization to metastasis of non-small-cell lung cancer. The Lancet , 340 (8812), 145–146. doi: 10.1016 / 0140-6736 (92) 93217-B
• Macchiarini P, Dartevelle P. (1994). Tracheal Transplantation: Unlock The Door? Acta Biomedica . 65; 51-58. PMID 7717036
• Macchiarini, P., Jungebluth, P., Go, T., Asnaghi, MA, Rees, LE, Cogan, TA, ... & Dickinson, SC (2008). Clinical transplantation of a tissue-engineered airway. The Lancet , 372 (9655), 2023-2030. doi: 10.1016 / S0140-6736 (08) 61598-6
• Birchall, M., & Macchiarini, P. (2008). Airway transplantation: a debate worth having ?. Transplantation , 85 (8), 1075-1080. doi: 10.1097 / TP.0b013e31816a10e4
• Go, T., Jungebluth, P., Baiguero, S., Asnaghi, A., Martorell, J., Ostertag, H., ... & Macchiarini, P. (2010). Both cell epithelial cells and mesenchymal stem cell-derived chondrocytes contribute to the survival of a tissue-engineered airway transplants in pigs. The Journal of thoracic and cardiovascular surgery , 139 (2), 437-443. doi: 10.1016 / j.jtcvs.2009.10.002
• Jungebluth, P., Luedde, M., Ferrer, E., Luedde, T., Vucur, M., Peinado, VI, ... & Haag, J. (2011). Mesenchymal stem cells restore lung function by recruiting resident and nonresident proteins. Cell transplantation , 20 (10), 1561-1574. doi: 10.3727 / 096368910X557254
• Jungebluth, P., Alici, E., Baiguera, S., Blomberg, P., Bozóky, B., Crowley, C., ... & Hermanson, O. (2011). Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. The Lancet , 378 (9808), 1997–2004. doi: 10.1016 / S0140-6736 (11) 61715-7 - withdrawn .
• Fishman, JM, De Coppi, P., Elliott, MJ, Atala, A., Birchall, MA, & Macchiarini, P. (2011). Airway tissue engineering. Expert opinion on biological therapy , 11 (12), 1623-1635. doi: 10.1517 / 14712598.2011.623696
• Badylak, SF, Weiss, DJ, Caplan, A., & Macchiarini, P. (2012). Engineered whole organs and complex tissues. The Lancet , 379 (9819), 943-952. doi: 10.1016 / S0140-6736 (12) 60073-7 - withdrawn .
• Jungebluth, P., & Macchiarini, P. (2014). Airway transplantation. Thoracic surgery clinics , 24 (1), 97-106. doi: 10.1016 / j.thorsurg.2013.09.005 - withdrawn .
• Taylor, DA, Caplan, AL, & Macchiarini, P. (2014). Ethics of bioengineering organs and tissues. Expert opinion on biological therapy , 14 (7), 879. doi: 10.1517 / 14712598.2014.915308
• Sebastian Sjöqvist, Paolo Macchiarini, et al. Experimental orthotopic transplantation of a tissue-engineered esophagus in rats, Nature Communications 8, 15077 (2017) - withdrawn .