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Feature

Stem cell research: time for a dose of realism

BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j443 (Published 31 January 2017) Cite this as: BMJ 2017;356:j443
  1. Michael Brooks, science journalist, London, UK
  1. mb{at}michaelbrooks.org

After the fall from grace of Paolo Macchiarini, whose artificial trachea transplants ended in the death of several patients, Michael Brooks asks whether there has been too much hype around stem cell therapy and what can realistically be achieved

Martin Birchall’s profile on the University College London website reads, “In 2008, with Prof Macchiarini, I co-led the team which performed the world's first stem cell based organ transplant.” It’s a claim that the professor of laryngology might wish to remove during the next edit of his CV.1

Between June 2011 and July 2013 Paolo Macchiarini inserted stem cell derived tracheal transplants into three patients at the Karolinska University Hospital in Sweden. The transplants caused serious complications that proved fatal in two cases, and the ethics of the surgery have been seriously criticised in several investigations and inquiries. After a great deal of external pressure, the Karolinska Institute eventually terminated Macchiarini’s employment and several senior staff resigned.

Macchiarini maintains that he and his team acted properly. However, the implications of the case go far beyond his employer’s reputation. UCL has launched an investigation into its own links with the Macchiarini affair, and Birchall is feeling the taint of association. “It most definitely has affected me,” he says.

Watch the hype

The slew of negative publicity has come at a critical time for stem cell research. The field has also been criticised for hyping results. A study led by Tim Caulfield of the University of Alberta, Canada, showed that 70% of newspaper articles about stem cell research claim that clinical applications are “just around the corner,” “in the near future,” or “within 5 to 10 years or sooner.”2 “That’s lightning fast and almost certainly impossible,” Caulfield says.

This is not simply a problem of media hype. In a surprisingly large number of cases, the source of these unrealistic expectations can be traced back to the scientists themselves. “There’s lots of evidence that press releases from institutions have hype language in them,” Caulfield says. “There has even been some interesting evidence suggesting that hype language has been increasing in peer reviewed literature.” A recent International Society for Stem Cell Research report calls for stem cell researchers and their institutions to work harder to keep claims and aspirations grounded in reality.3

The hype has arisen in part because, as a 2015 review put it, “considerable investment has been made in preclinical research and clinical trials, but as yet there is only a modicum of success.”4 Although many projects are in phase II and III clinical trials (fig 1), positive results remain elusive, and maintaining patient and funder confidence is difficult.

Figure1

Fig 1 Most of the 315 clinical trials for mesenchymal stem cell treatments in the National Institutes for Health database are early stage4

Another source of false hope arises from the fact that stem cell therapy is a huge and diverse field. Parts of it, such as the clinics that treat sports stars and celebrities with unlicensed therapies and make grandiose claims for their efficacy, are entirely unproved. But even the reputable work is mired in uncertainty.

In 2015, for example, researchers reported the results of treatment for multiple sclerosis called autologous haematopoietic stem cell transplantation.5 Newspaper headlines talked of cures that had patients dependent on wheelchairs “dancing, walking, and running again.”6

But the treatment involved aggressive chemotherapy that relatively few people with multiple sclerosis would tolerate. Perhaps, even more importantly, there was no control group to account for spontaneous remission.

Better trials

The University of Birmingham’s Philip Newsome is working to show the importance of comparison against a control group. He and his collaborators conducted large randomised trials of stem cell based liver regeneration therapies. Initial small scale studies had produced promising results.7 However, Newsome’s as yet unpublished results are disappointing. “We didn’t see any effect,” he says.

Such rigorous clinical trials will be vital to the future of stem cell therapies, Newsome says. Birchall agrees—especially within his own area, which has been plagued by “right to try” cases that offer few insights for future experiments. “There is merit in tissue engineering but it’s yet to find its place,” he says. “And unless we do properly constructed ethically approved phase I and II clinical trials, we won’t get to know where its place is.”

All these uncertainties, combined with the pressure to get results, mean that everyone must proceed with caution and remain vigilant against fraud, according to Steve Bloor, chief executive of stem cell research company Videregen. “Nobody in this business can afford to be complacent,” he says.

Videregen is running an EU funded trial of stem cell seeded trachea replacements that looks— superficially, at least—similar to what Macchiarini was doing.8 Bloor insists the procedures are very different but acknowledges that the Karolinska debacle will have an effect on their work. “In September we implemented a review to make sure we were completely compliant with all the regulations. It’s given us extra work to do, but it’s only right that we do that.”

For Alan Trounson of the Hudson Institute in Victoria, Australia, regulation is not enough. Leaders in the field must be vigilant, policing people and procedures from a position at the laboratory bench. “Fame and fortune is seductive and stem cells is one of those areas which can provide this,” he says. But he adds that regulating against poor practice is difficult: “Lab heads must be deeply embedded in the lab” to become aware of potential misconduct.

A further problem is that recognising and dealing with cases like Macchiarini’s involves swallowing pride—something that the Karolinska Institute, by its own admission, was reluctant to do. According to the institute’s internal investigation, part of its problem was being seen as a leading institution: this, the report warned, is something that “entails a risk of inadequacies and shortcomings not coming to light.”

Birchall suggests that, with thousands of techniques now in phase I and II clinical trials, and hundreds in phase III trials, it is the turn of funding bodies to swallow their pride. The Macchiarini debacle means they need to re-examine what they fund, the evidence base for it, and their monitoring procedures. “There are lessons to be learnt,” Birchall says.

For Caulfield, that re-evaluation should include a dose of realism; there might be some avenues that are simply not worth pursuing. “There’s a presumption that if we keep pushing resources into a field the breakthroughs are going to come,” he says. “But maybe the science isn’t there. There’s a finite amount of research resources, and they should be distributed based on good science, not on hype.”

In the end, the Macchiarini affair might have a silver lining for stem cell research as a whole. “I believe the field will move on with a little more care—we certainly need to,” Trounson says.

Footnotes

  • Competing interests: I have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

  • Provenance and peer review: Commissioned; not externally peer reviewed.

References

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