Carl Elliott
The Experiments a three-part documentary film series directed by Bosse Lindquist
The Experiments a three-part documentary film series directed by Bosse Lindquist
Dr. Paolo Macchiarini relaxes into a barber’s chair, leaning back to have his hair washed. “I am working for the university, and we are trying to create new organs,” he tells the barber, pausing to add an explanation: “Frankenstein.” Although Macchiarini, a transplant surgeon born in Switzerland to Italian parents, is fending off charges of research misconduct at his university, he appears untroubled, even carefree, in this scene from Bosse Lindquist’s documentary The Experiments.1 Knowing what lies ahead for him—dismissal, disgrace, manslaughter charges—it’s hard not to think of the beginning of Brian De Palma’s film The Untouchables, in which Robert De Niro, playing Al Capone, entertains questions from reporters as he gets a shave. Macchiarini is just as charming. As the barber finishes his work, Macchiarini breaks into a mischievous grin. “Perfect,” he says, clapping his hands in appreciation.
Few medical research scandals are as spectacular as Macchiarini’s. Five years ago he was a celebrity surgeon at the Karolinska Institute in Sweden, one of Europe’s premier medical centers, which awards the Nobel Prize in Physiology or Medicine. Macchiarini was implanting the world’s first artificial tracheas into patients—and by his account, doing it with great success. But soon there were murmurs about his methods. His patients appeared to be dying. In 2015 an external expert commissioned by the Karolinska Institute found him guilty of research misconduct. Yet the leaders of KI continued to defend Macchiarini and dismissed allegations by his critics, including four of his surgical colleagues. That defense ended in the early months of 2016, when Lindquist’s riveting three-part documentary was shown on Swedish television. The ensuing scandal not only led to the dismissal of Macchiarini and the senior leadership of the institute but also threatened the future of the Nobel Prize in Physiology or Medicine. Macchiarini’s dramatic rise began in 2008, when he performed a novel surgical procedure on Claudia Castillo, a young mother of two in Barcelona whose trachea had collapsed after a tuberculosis infection. Macchiarini took a trachea from a deceased donor, stripped it down to its cartilaginous structure, and seeded it with cells taken from Castillo’s bone marrow. The theory was that Castillo’s stem cells would attach themselves to the cadaveric trachea and transform into tracheal cells, making the trachea functional and eliminating the need for the immunosuppressant drugs that are necessary after transplants. A “milestone in medicine,” CNN proclaimed. Two years and several transplants later, Macchiarini got an offer to move to the Karolinska Institute.
“He was a very powerful and colorful person in many ways,” says Dr.
1Albert Bonniers Förlag in Sweden will also publish a book by Lindquist, based on his continued investigation of the issues surrounding Macchiarini, in September. Karl-Henrik Grinnemo in The Experiments. “Your chin just dropped and you just stood and absorbed it all and thought: ‘What an amazing person we have here!’” Grinnemo and Dr. Matthias Corbascio, both surgeons at KI, were asked to help Macchiarini set up a new transplantation unit. By that point, however, some of the earlier transplant patients were beginning to have problems, including the collapse of Claudia Castillo’s transplanted trachea. So Macchiarini proposed an even more audacious procedure. Instead of transplanting cadaveric tracheas, he would use a synthetic trachea made of plastic, manufactured by a scientist at University College London. His first patient was Andemariam Beyene, a thirty-six-year-old Eritrean graduate student with tracheal cancer who was studying in Iceland. Macchiarini claimed the situation was urgent. Harvard doctors had estimated that Beyene would die within six months, Macchiarini says in The Experiments. So in June 2011, after a long, difficult operation, Beyene got his synthetic trachea. “We all felt we had made history,” Grinnemo recalls. Soon after, Macchiarini and his colleagues published their results in The Lancet, one of the world’s most respected medical journals.
Not everyone was convinced. The bluntest critic of the procedure was Dr. Pierre Delaere, a professor of respiratory surgery at Katholieke Universiteit Leuven. According to Delaere, there was no scientific research to suggest that a synthetic trachea would work. “You don’t have to be a doctor to know that a synthetic trachea cannot transform into a living trachea by applying bone marrow on it,” he says. Delaere felt that it was only a matter of time before the patients died. “If I had the option of a synthetic trachea or a firing squad,” he says, “I’d choose the last option because it would be the least painful form of execution.” Delaere tried repeatedly to alert authorities at the Karolinska Institute of the dangers to their patients, but his warnings were dismissed.
Shortly after the operation on Beyene, surgeons at University College London tried implanting a synthetic trachea in Keziah Shorten, a nineteenyear-old woman into whom Macchiarini had transplanted a cadaveric trachea, which had eventually failed. She died six months later. At KI Macchiarini implanted a synthetic trachea in Christopher Lyles, a thirty-yearold man from Maryland with tracheal cancer. He lived only five months. The third patient at KI to get a synthetic trachea from Macchiarini was Yesim Cetir, a university student from Turkey whose trachea had been severely damaged in a botched operation. Cetir lived for five more years, but keeping her alive required constant care: repeated bronchoscopies to clear her airways, dialysis, ECMO (an artificial lung), a second synthetic trachea, the removal
of her esophagus, and multiple organ transplants. She died at Temple University in March 2017.
A more cautious surgeon would have slowed down. Macchiarini accelerated. Rather than continue with cancer patients like Beyene and Lyles, he decided to try the synthetic trachea as an elective procedure in patients who were in relatively good health. This was an astonishing choice. The procedure had never even been tested in animals. Yet Russian authorities gave him permission to start a formal clinical trial in Russia. Casting around for potential candidates, Macchiarini and his team invited people to send videos explaining why they should be chosen, like applicants for a reality television show. The winner was Julia Tuulik, a young teacher and former dancer in St. Petersburg. Although she was healthy, a car accident had left her with a tracheostomy, and in order to speak, she had to cover the opening with her hand. She hoped the surgery would let her sing to her son. Accompanied by a German film crew, Macchiarini gave Tuulik a synthetic trachea in June 2012 at Kuban State University in Krasnodar, Russia. A few days later, the two appeared together at a triumphant press conference. Tuulik’s condition began to deteriorate, however, shortly after the procedure. “She had bouts of coughing, lasting for hours, and she could barely breathe,” her husband says in The Experiments. Macchiarini replaced the synthetic trachea with a second one, but it didn’t work either. “It smelled of rotting flesh,” Tuulik’s mother says. Tuulik lived for less than two and a half years. As Lindquist investigated Tuulik’s death, he obtained access to stunning unedited film footage from the German production crew. One scene showed Macchiarini in the spring of 2012, shortly after the death of Christopher Lyles, walking on a beach and speaking on his cell phone with David Green of Harvard Biosciences, the manufacturer of a “bioreactor” used to grow stem cells for the synthetic trachea. Macchiarini confesses that the synthetic tracheas are faulty. “Listen, what happens is that the [trachea] scaffolds dry out,” Macchiarini says. Yet only a few weeks later, he will implant that same kind of synthetic trachea in Tuulik.
A second conversation is even more alarming. Macchiarini has just arrived at the Kuban State University medical center when he is approached by a thoracic surgeon wearing blue scrubs who asks: “Do you know about the problem?” All three of the available synthetic tracheas are defective, the surgeon explains. One is too short, another has holes, and a third is unstable. Yet Macchiarini barely hesitates. Rather than postponing the surgery, he decides to proceed with the short trachea without telling Tuulik. “We know this material is very safe,” David Green tells Tuulik as she perches on the side of her bed. “You’re in very good hands . . . . Paolo is the best surgeon in the world.” “I know,” Tuulik replies, nodding gratefully.
It isn’t long before Tuulik realizes what is happening. As she recovers from her surgery, The Experiments shows Macchiarini and the Russian surgeons huddled around her bed in a critical care unit. They are looking at the results of a bronchoscopy, which indicate that the synthetic trachea has folded over. The surgeons seem worried. After some discussion, however, Macchiarini tells Tuulik that the trachea is working perfectly. When she begins to weep, an older Russian surgeon berates her. “Stop crying!” he says. “Remember that the wounds in a winner heal quicker.”
Only days after the surgery on Tuulik, Macchiarini tried again with Alexander Zozulya, who, like Tuuilik, had a tracheostomy. He died after twenty months. Next came the first child recipient: Hannah Warren in Peoria, Illinois. Within three months she was dead. In January 2014, Andemariam Beyene died. It was the alleged “success” of Beyene’s implant that justified the later procedures, yet in The Experiments Macchiarini appears to take the death in stride. On a ferry trip, he meets an old friend and surgical colleague from Turkey, Cengiz Gebitekin, who explains to Lindquist how important it is for a surgeon to be cautious. “The best surgeon knows when not to operate,” says Gebitekin, turning to Macchiarini for agreement. Macchiarini does not look up from his phone.
As
Macchiarini was traveling the world performing experimental implants, the task of keeping the patients in Sweden alive fell to his colleagues at Karolinska University Hospital. When they compared what they were seeing clinically to what Macchiarini
had published, they saw that his deception extended to his scientific articles. “Apart from the fact that what was written in the articles was inaccurate, manipulated or embellished, the most important information, the worst part, had consistently been left out,” Matthias Corbascio says. Macchiarini had exaggerated the dire condition of his patients to justify experimental surgery, then distorted the record to claim success. Five and half months after the surgery on Beyene, Macchiarini had published a paper in The Lancet describing Beyene’s airway as open and the synthetic trachea lined with healthy new tissue. In reality, the airway was so near to closing up that surgeons had to insert stents to keep it open. In addition, an alarming fistula had developed. Later, an autopsy revealed only inflammation and dead tissue. The synthetic trachea was so loose that it could simply be lifted out of Beyene’s neck by hand. In 2013, four whistleblowers—Corbascio, Thomas Fux, Karl-Henrik Grinnemo, and Oscar Simonson— began a series of futile efforts to warn Karolinska Institute leaders. “The mere thought of these plastic tracheas still being implanted in patients terrifies me,” Grinnemo says. Again and again the whistleblowers met with institutional officials and followed up in writing, providing documented evidence of research fraud and abuse. Nothing worked. Instead, the whistleblowers suffered swift retaliation. Officials threatened them with dismissal and even reported them to the police. Macchiarini and his protégé, Philipp Jungebluth, filed a complaint against Grinnemo, alleging that he had stolen their work. In the summer of 2014, as Karolinska officials were stonewalling the whistleblowers, Macchiarini implanted his eighth synthetic trachea in Russia, causing life-threatening complications for the recipient.
In late November 2014, Karolinska officials finally agreed to an external investigation. But when Dr. Bengt Gerdin, a professor emeritus of surgery at Uppsala University, delivered a highly critical report corroborating most of the whistleblowers’ claims, the Karolinska Institute simply overruled him. In August 2015, four solemn Karolinska officials filed into a conference room. Macchiarini was “not guilty” of research misconduct, Vice-Chancellor Anders Hamsten told the assembled reporters; he still had “the trust of the Karolinska Institute.” The Lancet applauded the decision with an editorial titled “Paolo Macchiarini Is Not Guilty of Scientific Misconduct.”
In The Experiments, Hamsten gives Lindquist an on-camera interview about the decision. The contrast between the two men is striking. Blonde and distinguished-looking, Hamsten is wearing a dark business suit and a bright yellow tie. Lindquist, modest and unassuming, is dressed in a gray flannel shirt. But the impeccably dressed vice-chancellor is incapable of answering the simplest questions. When Lindquist presses him to defend the false claims in Macchiarini’s Lancet paper, Hamsten stammers and professes ignorance with an apologetic smile, as if he expects to be forgiven. It becomes clear that the vice-chancellor has personally exonerated Macchiarini of wrongdoing in a case about which he knows virtually nothing.
For the first two episodes of The Experiments, Macchiarini appears as a quiet, rather inscrutable presence: selfconfident, polite, unruffled by failure. But in the third, when Lindquist finally confronts him with hard questions in an interview, he turns contemptuous. He sneers, dodges, and turns Lindquist’s questions back on him. “And your profession is?” he asks Lindquist with a selfsatisfied smile. “You are a producer, a TV producer, right?” He shrugs. “How can you possibly understand the details of a medical evaluation?” It is as if a disguise has been shed, finally revealing the face beneath the mask.
In
January 2016, six months after Hamsten declared his trust in Macchiarini, an article by Adam Ciralsky in Vanity Fair laid out a brazen story of intrigue and deception. A year and a half earlier, NBC News had profiled Macchiarini in a fawning, Emmy-nominated special called A Leap of Faith. During the production Macchiarini had become romantically involved with Benita Alexander, an NBC producer, to whom he soon proposed. By that point, Macchiarini was such a celebrity that it didn’t seem far-fetched when he began to announce elaborate wedding plans. According to Vanity Fair, he told Alexander that the ceremony would take place at the Apostolic Palace of Castel Gandolfo, where Pope Francis would officiate. Andrea Bocelli would sing. Guests would include Vladimir Putin, Russell Crowe, Elton John, John Legend, and Kenny Rogers—not to mention the Obamas, the Sarkozys, and the Clintons. Macchiarini and Alexander sent out engraved wedding invitations sheathed in lambskin.2
Two months before the wedding, Alexander got an e-mail from a friend with the subject line “The Pope.” It linked to an article stating that Pope Francis would be in South America at the same time as the wedding. With that, the charade fell apart. Aided by a private investigator, Alexander learned that virtually every detail Macchiarini had provided about the wedding was false. The pope had no idea who Macchiarini was. Andrea Bocelli would not be performing. According to a public records search, Macchiarini was still married to his wife of nearly thirty years. Further investigation suggested that he had fabricated a number of items on his CV, claiming degrees he did not have and positions he had never held.
Shortly after the article in Vanity Fair, The Experiments aired on Swedish television. Public reaction was swift and fierce. Macchiarini was fired in March, and then indicted for involuntary manslaughter. Institutional leaders lost their positions, including the chancellor of the Swedish university system, Harriet Wallberg-Henriksson, for her part in hiring and defending Macchiarini. Scholars began to question the legitimacy of a Nobel Prize awarded by an institution capable of such deception. It has been decades since a work of investigative reporting on a medical research scandal has produced such dramatic consequences. The Experiments unfolds with the narrative drama of a crime movie. Lindquist repeatedly exposes his subject’s lies simply by showing the visual evidence: video
2Benita Alexander also tells this story in her new documentary, He Lied About Everything, on the Investigation Discovery network. footage from bronchoscopies, firsthand testimony from the whistleblowers, conversations filmed as they occurred in clinics and hospital rooms. When the family members of the victims speak to Lindquist, the pain in their voices is raw. What permitted such a medical disaster? The media have relentlessly hyped stem cells as a miracle cure for any number of life-threatening conditions. Desperate patients and their families make for easy targets. The blessing of the Karolinska Institute gave the experimental procedures an air of authority, and by invoking “compassionate use” for dying patients, institutional officials allowed Macchiarini to avoid the ethical review that would ordinarily have accompanied a research study. As long as the trachea implants appeared to be successful, plenty of international colleagues were happy to collaborate with Macchiarini as coauthors on his publications. Macchiarini was even savvy enough to partner with a bioethicist, New York University’s Arthur Caplan, with whom he published three articles. (To his credit, Caplan has called for the papers to be retracted.) More than anything else, the Macchiarini affair should be seen as a failure of institutional leadership. It is not simply that Karolinska officials dismissed credible warnings for years. It is not even that they dismissed warnings by four of their own surgeons who had direct, firsthand knowledge of the wrongdoing and whose claims were corroborated by the institute’s handpicked expert. It is that they attempted to punish and intimidate those surgeons, who were trying to protect the lives of research subjects. Grinnemo was forced to work under a cloud of suspicion for three years before he was finally cleared of the false charges of research misconduct that had been brought against him. That the four whistleblowers persisted in the face of such pressure is a testament to their moral courage and tenacity.
The leaders of the Karolinska Institute would like to put the controversy behind them, as would many in the research community. By September 2016, the journal Nature was already praising the Karolinska for its “exemplary approach to the scandal.” Yet more than two years after The Experiments aired, it is far from clear that its problems have been fixed. Many of the officials who tried to cover up the scandal remain employees of the institute, and despite demands for their resignations, Anders Hamsten and Harriet Wallberg are still members of the Nobel Assembly. The hospital hired a new chief executive in 2014, but a recent survey put his approval rating at 3 percent. While two external investigations of the scandal have produced official reports criticizing the way the Macchiarini affair was handled, neither investigation really penetrated to the heart of the matter. An investigation led by Sten Heckscher, a former judge and government minister, concentrated most of its attention on the faulty procedures behind the hiring of Macchiarini. It declined to call for the resignation of institutional leaders, and inexplicably cleared the Karolinska Institute of responsibility for the disastrous procedures that Macchiarini and his team performed in Russia. Kjell Asplund, professor emeritus in medicine at Umeå University, led a more comprehensive investigation of the Karolinska Hospital, yet even that investigation failed to address the scandal’s most glaring question. What permitted so many institutional officials to dismiss the credible, documented warnings raised by the surgeons with the most knowledge of Macchiarini’s patients? Most importantly, neither report recommended compensating the families of the victims for their suffering. So far, those families have received nothing. In a more recent and thorough Icelandic investigation into the death of Andemariam Beyene, reviewers commissioned by the University of Iceland noted with surprise that Karolinska University Hospital had still not even contacted Beyene’s widow to review its liability for the mistakes that led to his death. What will happen to Macchiarini is also unclear. In October 2017, Swedish prosecutors dropped their involuntary manslaughter charges against him, saying that they were unable to prove any crime had been committed. Shortly afterward, Macchiarini claimed victory in a televised interview and said he would be doing surgery the next day in New York. But at the end of October, Sweden’s Central Ethics Review Board found evidence of scientific misconduct in six of Macchiarini’s synthetic trachea transplantation articles and called for their retraction. Macchiarini has also lost funding for his experimental procedures in Russia. In December, the Swedish Public Prosecution Authority announced that it would review the decision to drop the involuntary manslaughter charges after discovering evidence of potential bias in the earlier decision. Over the past two years, neither the Karolinska Institute nor the hospital has done anything to make amends with the whistleblowers they tried to silence. Kim Sjölund, the press officer for the Karolinska University Hospital, says the hospital has “no plans for an official apology.” Dr. Karin Dahlman-Wright, the pro-vice-chancellor of KI, says that she gave a public apology in a press conference last year and does not plan to do anything more. But none of the whistleblowers has any memory of that apology. Two of the four have left the institute for positions at Uppsala University.
When institutional leaders respond in this way, it sends a powerful message to employees. It says that loyalty to the institution comes before the welfare of patients, and that anyone else who speaks out will be treated like the whistleblowers. Until that message changes, it is hard to be optimistic about reform. According to Grinnemo and Simonson, the culture at the Karolinska Institute and the hospital is now even worse than it was before the scandal. Grinnemo told me in an email: “No one dares to report anything.”