Researchers Behaving Badly: Known Frauds Are "the Tip of the Iceberg"
Last week, the whistleblowers in the Paolo Macchiarini affair at Sweden's Karolinska Institutet went on the record here to detail the retaliation they suffered for trying to expose a star surgeon's appalling research misconduct.
Scientific fraud of the type committed by Macchiarini is rare, but studies suggest that it's on the rise.
The whistleblowers had discovered that in six published papers, Macchiarini falsified data, lied about the condition of patients and circumvented ethical approvals. As a result, multiple patients suffered and died. But Karolinska turned a blind eye for years.
Scientific fraud of the type committed by Macchiarini is rare, but studies suggest that it's on the rise. Just this week, for example, Retraction Watch and STAT together broke the news that a Harvard Medical School cardiologist and stem cell researcher, Piero Anversa, falsified data in a whopping 31 papers, which now have to be retracted. Anversa had claimed that he could regenerate heart muscle by injecting bone marrow cells into damaged hearts, a result that no one has been able to duplicate.
A 2009 study published in the Public Library of Science (PLOS) found that about two percent of scientists admitted to committing fabrication, falsification or plagiarism in their work. That's a small number, but up to one third of scientists admit to committing "questionable research practices" that fall into a gray area between rigorous accuracy and outright fraud.
These dubious practices may include misrepresentations, research bias, and inaccurate interpretations of data. One common questionable research practice entails formulating a hypothesis after the research is done in order to claim a successful premise. Another highly questionable practice that can shape research is ghost-authoring by representatives of the pharmaceutical industry and other for-profit fields. Still another is gifting co-authorship to unqualified but powerful individuals who can advance one's career. Such practices can unfairly bolster a scientist's reputation and increase the likelihood of getting the work published.
The above percentages represent what scientists admit to doing themselves; when they evaluate the practices of their colleagues, the numbers jump dramatically. In a 2012 study published in the Journal of Research in Medical Sciences, researchers estimated that 14 percent of other scientists commit serious misconduct, while up to 72 percent engage in questionable practices. While these are only estimates, the problem is clearly not one of just a few bad apples.
In the PLOS study, Daniele Fanelli says that increasing evidence suggests the known frauds are "just the 'tip of the iceberg,' and that many cases are never discovered" because fraud is extremely hard to detect.
Essentially everyone wants to be associated with big breakthroughs, and they may overlook scientifically shaky foundations when a major advance is claimed.
In addition, it's likely that most cases of scientific misconduct go unreported because of the high price of whistleblowing. Those in the Macchiarini case showed extraordinary persistence in their multi-year campaign to stop his deadly trachea implants, while suffering serious damage to their careers. Such heroic efforts to unmask fraud are probably rare.
To make matters worse, there are numerous players in the scientific world who may be complicit in either committing misconduct or covering it up. These include not only primary researchers but co-authors, institutional executives, journal editors, and industry leaders. Essentially everyone wants to be associated with big breakthroughs, and they may overlook scientifically shaky foundations when a major advance is claimed.
Another part of the problem is that it's rare for students in science and medicine to receive an education in ethics. And studies have shown that older, more experienced and possibly jaded researchers are more likely to fudge results than their younger, more idealistic colleagues.
So, given the steep price that individuals and institutions pay for scientific misconduct, what compels them to go down that road in the first place? According to the JRMS study, individuals face intense pressures to publish and to attract grant money in order to secure teaching positions at universities. Once they have acquired positions, the pressure is on to keep the grants and publishing credits coming in order to obtain tenure, be appointed to positions on boards, and recruit flocks of graduate students to assist in research. And not to be underestimated is the human ego.
Paolo Macchiarini is an especially vivid example of a scientist seeking not only fortune, but fame. He liberally (and falsely) claimed powerful politicians and celebrities, even the Pope, as patients or admirers. He may be an extreme example, but we live in an age of celebrity scientists who bring huge amounts of grant money and high prestige to the institutions that employ them.
The media plays a significant role in both glorifying stars and unmasking frauds. In the Macchiarini scandal, the media first lifted him up, as in NBC's laudatory documentary, "A Leap of Faith," which painted him as a kind of miracle-worker, and then brought him down, as in the January 2016 documentary, "The Experiments," which chronicled the agonizing death of one of his patients.
Institutions can also play a crucial role in scientific fraud by putting more emphasis on the number and frequency of papers published than on their quality. The whole course of a scientist's career is profoundly affected by something called the h-index. This is a number based on both the frequency of papers published and how many times the papers are cited by other researchers. Raising one's ranking on the h-index becomes an overriding goal, sometimes eclipsing the kind of patient, time-consuming research that leads to true breakthroughs based on reliable results.
Universities also create a high-pressured environment that encourages scientists to cut corners. They, too, place a heavy emphasis on attracting large monetary grants and accruing fame and prestige. This can lead them, just as it led Karolinska, to protect a star scientist's sloppy or questionable research. According to Dr. Andrew Rosenberg, who is director of the Center for Science and Democracy at the U.S.-based Union of Concerned Scientists, "Karolinska defended its investment in an individual as opposed to the long-term health of the institution. People were dying, and they should have outsourced the investigation from the very beginning."
Having institutions investigate their own practices is a conflict of interest from the get-go, says Rosenberg.
Scientists, universities, and research institutions are also not immune to fads. "Hot" subjects attract grant money and confer prestige, incentivizing scientists to shift their research priorities in a direction that garners more grants. This can mean neglecting the scientist's true area of expertise and interests in favor of a subject that's more likely to attract grant money. In Macchiarini's case, he was allegedly at the forefront of the currently sexy field of regenerative medicine -- a field in which Karolinska was making a huge investment.
The relative scarcity of resources intensifies the already significant pressure on scientists. They may want to publish results rapidly, since they face many competitors for limited grant money, academic positions, students, and influence. The scarcity means that a great many researchers will fail while only a few succeed. Once again, the temptation may be to rush research and to show it in the most positive light possible, even if it means fudging or exaggerating results.
Though the pressures facing scientists are very real, the problem of misconduct is not inevitable.
Intense competition can have a perverse effect on researchers, according to a 2007 study in the journal Science of Engineering and Ethics. Not only does it place undue pressure on scientists to succeed, it frequently leads to the withholding of information from colleagues, which undermines a system in which new discoveries build on the previous work of others. Researchers may feel compelled to withhold their results because of the pressure to be the first to publish. The study's authors propose that more investment in basic research from governments could alleviate some of these competitive pressures.
Scientific journals, although they play a part in publishing flawed science, can't be expected to investigate cases of suspected fraud, says the German science blogger Leonid Schneider. Schneider's writings helped to expose the Macchiarini affair.
"They just basically wait for someone to retract problematic papers," he says.
He also notes that, while American scientists can go to the Office of Research Integrity to report misconduct, whistleblowers in Europe have no external authority to whom they can appeal to investigate cases of fraud.
"They have to go to their employer, who has a vested interest in covering up cases of misconduct," he says.
Science is increasingly international. Major studies can include collaborators from several different countries, and he suggests there should be an international body accessible to all researchers that will investigate suspected fraud.
Ultimately, says Rosenberg, the scientific system must incorporate trust. "You trust co-authors when you write a paper, and peer reviewers at journals trust that scientists at research institutions like Karolinska are acting with integrity."
Without trust, the whole system falls apart. It's the trust of the public, an elusive asset once it has been betrayed, that science depends upon for its very existence. Scientific research is overwhelmingly financed by tax dollars, and the need for the goodwill of the public is more than an abstraction.
The Macchiarini affair raises a profound question of trust and responsibility: Should multiple co-authors be held responsible for a lead author's misconduct?
Karolinska apparently believes so. When the institution at last owned up to the scandal, it vindictively found Karl Henrik-Grinnemo, one of the whistleblowers, guilty of scientific misconduct as well. It also designated two other whistleblowers as "blameworthy" for their roles as co-authors of the papers on which Macchiarini was the lead author.
As a result, the whistleblowers' reputations and employment prospects have become collateral damage. Accusations of research misconduct can be a career killer. Research grants dry up, employment opportunities evaporate, publishing becomes next to impossible, and collaborators vanish into thin air.
Grinnemo contends that co-authors should only be responsible for their discrete contributions, not for the data supplied by others.
"Different aspects of a paper are highly specialized," he says, "and that's why you have multiple authors. You cannot go through every single bit of data because you don't understand all the parts of the article."
This is especially true in multidisciplinary, translational research, where there are sometimes 20 or more authors. "You have to trust co-authors, and if you find something wrong you have to notify all co-authors. But you couldn't go through everything or it would take years to publish an article," says Grinnemo.
Though the pressures facing scientists are very real, the problem of misconduct is not inevitable. Along with increased support from governments and industry, a change in academic culture that emphasizes quality over quantity of published studies could help encourage meritorious research.
But beyond that, trust will always play a role when numerous specialists unite to achieve a common goal: the accumulation of knowledge that will promote human health, wealth, and well-being.
[Correction: An earlier version of this story mistakenly credited The New York Times with breaking the news of the Anversa retractions, rather than Retraction Watch and STAT, which jointly published the exclusive on October 14th. The piece in the Times ran on October 15th. We regret the error.]
Twice a day, morning and night, I use a neti pot to send a warm saltwater solution coursing through one nostril and out the other to flush out debris and pathogens. I started many years ago because of sinus congestion and infections and it has greatly reduced those problems. Along with vaccination when it became available, it seems to have helped with protecting me from developing Covid-19 symptoms despite being of an age and weight that puts me squarely at risk.
Now that supposition of protection has been backed up with evidence from a solidly designed randomized clinical trial. It found that irrigating your sinuses twice a day with a simple saltwater solution can lead to an 8.5-fold reduction in hospitalization from Covid-19. The study is another example of recent research that points to easy and inexpensive ways to help protect yourself and help control the epidemic.
Amy Baxter, the physician researcher behind the study at Augusta University, Medical College of Georgia, began the study in 2020, before a vaccine or monoclonal antibodies became available to counter the virus. She wanted to be able to offer another line of defense for people with limited access to healthcare.
The nasal cavity is the front door that the SARS-CoV-2 virus typically uses to enter the body, latching on to the ACE2 receptors on cells lining those tissue compartments to establish infection. Once the virus replicates here, infection spreads into the lungs and often other parts of the body, including the brain and gut. Some studies have shown that a mouthwash could reduce the viral load, but any effect on disease progression was less clear. Baxter reasoned that reducing the amount of virus in the nose might give the immune system a better chance to react and control that growth before it got out of hand.
She decided to test this approach in patients who had just tested positive for Covid-19, were over 55 years of age, and often had other risk factors for developing serious symptoms. It was the quickest and easiest way to get results. A traditional prevention study would have required many more volunteers, taken a longer period of follow up, and cost money she did not have.
The trial enrolled 79 participants within 24 hours of testing positive for Covid-19, and they agreed to follow the regimen of twice daily nasal irrigation. They were followed for 28 days. One patient was hospitalized; a 1.27% rate compared with 11% in a national sample control group of similar age people who tested positive for Covid-19. Patients who strictly adhered to nasal irrigation had fewer, shorter and less severe symptoms than people in the study who missed some of their saline rinses.
Baxter initially made the results of her clinical trial available as a preprint in the summer of 2021 and was dismayed when many of the comments were from anti-vaxxers who argued this was a reason why you did not need to get vaccinated. That was not her intent.
There are several mechanisms that explain why warm saltwater is so effective. First and most obvious is the physical force of the water that sweeps away debris just as a rainstorm sends trash into a street gutter and down a storm drain. It also lubricates the cilia, small hair-like structures whose job it is to move detritus away from cells for expulsion. Cilia are rich in ACE2 receptors and keeping them moving makes it harder for the virus to latch on to the receptors.
It turns out the saline has a direct effect on the virus itself. SARS-CoV-2 becomes activated when an enzyme called furin snips off part of its molecular structure, which allows the virus to grab on to the ACE2 receptor, but saline inhibits this process. Once inside a cell the virus replicates best in a low salt environment, but nasal cells absorb salt from the irrigation, which further slows viral replication, says Baxter.
Finally, “salt improves the jellification of liquid, it makes better and stickier mucus so that you can get those virus out,” she explains, lamenting, “Nobody cares about snot. I do now.”
She initially made the results of her clinical trial available as a preprint in the summer of 2021 and was dismayed when many of the comments were from anti-vaxxers who argued this was a reason why you did not need to get vaccinated. That was not her intent. Two journals rejected the paper, and Baxter believes getting caught up in the polarizing politics of Covid-19 was an important part of the reason why. She says that editors “didn't want to be associated with something that was being used by anti-vaxxers.” She strongly supports vaccination but realizes that additional and alternative approaches also are needed.
Premeasured packets of saline are inexpensive and can be purchased at any drug store. They are safe to use several times a day. Say you’re vaccinated but were in a situation where you fear you might have been exposed to SARS-CoV-2; an extra irrigation will clear out your sinuses and may reduce the risk of that possible exposure.
Baxter plans no further study in this area. She is returning to her primary research focus, which is pain control and reducing opioid use, but she hopes that others will expand on what she had done.
Podcast: The Friday Five Weekly Roundup in Health Research
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- A pill to prevent lung cancer?
- Ancient wisdom about Neti pots could pay off for Covid
- Breakthrough for precision medicine and obesity
- How to refreeze the north and south poles
- The connection between taking multivitamin pills and brain health