A globe-trotting Paolo Macchiarini once epitomized the excitement around pioneering uses for stem cells in medicine. The Italian regenerative scientist and surgeon's goal was to use stem cells to create replacement organs for the terminally ill. And only a few years ago, there were indications that he'd found a way.
Except that his patients kept dying.
So after nine headline-grabbing operations in Sweden, Russia, Britain, and the United States in which most of his patients died after receiving artificial tracheas made from plastic and coated with stem cells, Macchiarini became the focus of media and peer criticism so strong that he was dismissed by his most prestigious employer.
The Karolinska Institute in Stockholm fired him in March for breaching its "fundamental values" and damaging its reputation. Three months later, in June, Swedish police opened an investigation -- which is continuing -- into whether he might have committed involuntary manslaughter.
Meanwhile, despite the ongoing criticism of his record in Europe, Macchiarini continues to lead a research team in bioengineering and regenerative medicine at the University of Kazan, on the banks of the Volga River in Tatarstan, about 800 kilometers east of Moscow.
But there are signs his welcome in Russia may be running out. Today, Macchiarini is restricted purely to research activities in a country that previously allowed him to perform four artificial trachea transplants.
"The grant that Paolo Macchiarini has for work at Kazan Federal University is exclusively for preclinical studies and applies to creating tissue-esophageal structures to replace damaged organs in test nonhuman primates," university spokeswoman Natalia Darashkevich told RFE/RL's Russian Service recently.
Working With Baboons
The restriction to preclinical studies means Macchiarini conducts research that might later be applicable in organ transplants for humans but that he is not operating on human patients. Instead, he is working with baboons.
He also no longer works with tracheas, commonly known as windpipes, but with a different organ, the esophagus, and he no longer pursues the difficult goal of using synthetic materials for the "scaffold," or base structure, of the replacement organ. Instead, he is restricted to using biological tissues, which have been studied by researchers far longer than synthetics such as plastic, and are widely seen as a less challenging substrate on which to grow stem cells.
Roman Deev, the director of science at the Human Stem Cells Institute in Moscow, a leading Russian biotech company, has followed Macchiarini's work in Russia for many years. He told RFE/RL that the surgeon's existing grant from the Russian Science Foundation, which funds his work at Kazan Federal University, automatically expires in 2018.
Deev expressed skepticism that Macchiarini would get another research grant in Russia. "I don't consider [his work now] as something on the front line of real science," he said.
Paolo Macchiarini carrying out the world's first transplant of a synthetic trachea or windpipe on Andemariam Teklesenbet Beyene in Stockholm in 2011. The patient later died in 2014.
That is a long way from Macchiarini's early work in Russia in the late 2000s, when he was a rapidly rising star in his field. Macchiarini was initially brought to the country by Russian businessman Mikhail Batin, an enthusiastic promoter of life-extension technologies and the founder of the Science for Life Extension foundation.
Batin invited Macchiarini to perform a trachea transplant in Russia using not a synthetic trachea but one from a human cadaver. The recipient was a 26-year-old woman from neighboring Kazakhstan named Zhadrya Iglikova, whose own trachea had been seriously injured in a car accident four years earlier.
The operation took place in Russia in December 2010 and was initially celebrated by Russian media as a success. Russia's Channel One quoted Iglikova as saying afterward that she was looking forward to going back to work after rehabilitation. But then she dropped out of sight until a TV crew from Swedish national broadcaster SVT interviewed her parents in mid-2016 for a three-part documentary aired by the BBC on Macchiarini titled Fatal Experiments: The Downfall Of A Supersurgeon. The parents told the broadcaster that their daughter was unable to speak or stand and only left their home to visit health facilities.
Just six months after his first operation in Russia, Macchiarini performed his first synthetic trachea transplant in Sweden. That operation, in June 2011, propelled the surgeon to the height of fame and then to the depths of notoriety as he initially claimed full success but, 2 1/2 years later, the patient Andemariam Beyene died when the plastic trachea came loose because the stem cells had failed to fix it to his throat.
In the meantime, Macchiarini went on to perform four more synthetic-trachea transplants in Russia. His other patients were Yulia Tuulik and Aleksandr Zozulya, who died within two years of their 2012 operations; Jordanian citizen Sadiq Kanaan, who died after his operation in 2013; and Dmitry Onogda, who survived the implant in 2014 and its subsequent removal.
Paolo Macchiarini with Chris Lyle, another patient on whom he performed a trachea transplant in Stockholm in 2011. Lyles died a few months later.
Throughout his controversial career, Macchiarini has rejected any suggestions of misconduct.
"I always believed that my operation is able to help the patient," he told RFE/RL in a written response to questions about his activities.
Macchiarini also said that data he received on his patients' postoperative condition justified optimism about their progress.
"None of the reports that I had from the patients' clinicians contained information that was unexpected and concerning, and none of the clinicians raised any urgent or unresolvable issues until the very last days of the first patient's life," he wrote.
Macchiarini added that he had responded in detail to peer criticism and that "my responses to all the accusations made so far are publicly available."
As Macchiarini carries out research in Russia, he continues to come under pressure from scientists in Sweden, including former colleagues, who criticize his work.
Courageous Or Irresponsible?
In October, the editors of the respected online scientific journal, Nature Communications, appended an "Expression Of Concern" to a research report by Macchiarini and co-authors published in April 2014. The editors' note said that an investigation conducted on behalf of the Karolinska Institute had raised concerns regarding the accuracy of some of the data in the report.
In December, a group of Swedish doctors published a petition asking Russian authorities to conduct an investigation into Macchiarini's activities in Russia in light of allegations about his work in Sweden. The petition was handed to Moscow's ambassador to Stockholm but has yet to receive a response.
Still, it remains to be seen whether the criticism will realize its goal of ending Macchiarini's research career. That appears to depend on whether he is offered any new grants in Russia or elsewhere in the future.
As to whether Maccharini's once-revolutionary goal of using synthetic organs combined with stem cells as made-to-order replacement parts for humans will one day be reached, some experts say they are confident it will.
But some of them also argue that it will not be through the former superstar scientist's working methods.
"Further progress is possible, but in science you cannot move forward with giant leaps -- you need to go by small steps," Bengdt Gerdin, a retired professor of surgery at the University of Uppsala who suggested Maccharini had "relied on chance" in his research, told RFE/RL. "Can I call it courage? Perhaps this is a form of courage that borders on irresponsibility."
Based on reporting by RFE/RL's Russian Service correspondent Sergei Dobrynin. Written by Charles Recknagel