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.]
WENDY SCHMIDT is a philanthropist and investor who has spent more than a dozen years creating innovative non-profit organizations to solve pressing global environmental and human rights issues. Recognizing the human dependence on sustaining and protecting our planet and its people, Wendy has built organizations that work to educate and advance an understanding of the critical interconnectivity between the land and the sea. Through a combination of grants and investments, Wendy's philanthropic work supports research and science, community organizations, promising leaders, and the development of innovative technologies. Wendy is president of The Schmidt Family Foundation, which she co-founded with her husband Eric in 2006. They also co-founded Schmidt Ocean Institute and Schmidt Futures.
Editors: The pandemic has altered the course of human history and the nature of our daily lives in equal measure. How has it affected the focus of your philanthropy across your organizations? Have any aspects of the crisis in particular been especially galvanizing as you considered where to concentrate your efforts?
Wendy: The COVID-19 pandemic has made the work of our philanthropy more relevant than ever. If anything, the circumstances of this time have validated the focus we have had for nearly 15 years. We support the need for universal access to clean, renewable energy, healthy food systems, and the dignity of human labor and self-determination in a world of interconnected living systems on land and in the Ocean we are only beginning to understand.
When you consider the disproportionate impact of the COVID-19 virus on people who are poorly paid, poorly housed, with poor nutrition and health care, and exposed to unsafe conditions in the workplace—you see clearly how the systems that have been defining how we live, what we eat, who gets healthcare and what impacts the environment around us—need to change.
"This moment has propelled broad movements toward open publication and open sharing of data and samples—something that has always been a core belief in how we support and advance science."
If the pandemic teaches us anything, we learn what resilience looks like, and the essential role for local small businesses including restaurants, farms and ranches, dairies and fish markets in the long term vitality of communities. There is resonance, local economic benefit, and also accountability in these smaller systems, with shorter supply chains and less vertical integration.
The consolidation of vertically integrated business operations for the sake of global efficiency reveals its essential weakness when supply chains break down and the failure to encourage local economic centers leads to intense systemic disruption and the possibility of collapse.
Editors: For scientists, one significant challenge has been figuring out how to continue research, if at all, during this time of isolation and distancing. Yet, your research vessel Falkor, of the Schmidt Ocean Institute, is still on its expedition exploring the Coral Sea Marine Park in Australia—except now there are no scientists onboard. What was the vessel up to before the pandemic hit? Can you tell us more about how they are continuing to conduct research from afar now and how that's going?
Wendy: We have been extremely fortunate at Schmidt Ocean Institute. When the pandemic hit in March, our research vessel, Falkor, was already months into a year-long program to research unexplored deep sea canyons around Australia and at the Great Barrier Reef. We were at sea, with an Australian science group aboard, carrying on with our mission of exploration, discovery and communication, when we happened upon what we believe to be the world's longest animal—a siphonophore about 150 feet long, spiraling out at a depth of about 2100 feet at the end of a deeper dive in the Ningaloo Canyon off Western Australia. It was the kind of wondrous creature we find so often when we conduct ROV dives in the world's Ocean.
For more than two months this year, Falkor was reportedly the only research vessel in the world carrying on active research at sea. Once we were able to dock and return the science party to shore, we resumed our program at sea offering a scheduled set of now land-based scientists in lockdown in Australia the opportunity to conduct research remotely, taking advantage of the vessel's ship to shore communications, high resolution cameras and live streaming video. It's a whole new world, and quite wonderful in its own way.
Editors: Normally, 10–15 scientists would be aboard such a vessel. Is "remote research" via advanced video technology here to stay? Are there any upsides to this "new normal"?
Wendy: Like all things pandemic, remote research is an adaptation for what would normally occur. Since we are putting safety of the crew and guest scientists at the forefront, we're working to build strong remote connections between our crew, land based scientists and the many robotic tools on board Falkor. There's no substitute for in person work, but what we've developed during the current cruise is a pretty good and productive alternative in a crisis. And what's important is that this critical scientific research into the deep sea is able to continue, despite the pandemic on land.
Editors: Speaking of marine expeditions, you've sponsored two XPRIZE competitions focused on ocean health. Do you think challenge prizes could fill gaps of the global COVID-19 response, for example, to manufacture more testing kits, accelerate the delivery of PPE, or incentivize other areas of need?
Wendy: One challenge we are currently facing is that innovations don't have the funding pathway to scale, so promising ideas by entrepreneurs, researchers, and even major companies are being developed too slowly. Challenge prizes help raise awareness for problems we are trying to solve and attract new people to help solve those problems by giving them a pathway to contribute.
One idea might be for philanthropy to pair prizes and challenges with an "advanced market commitment" where the government commits to a purchase order for the innovation if it meets a certain test. That could be deeply impactful for areas like PPE and the production of testing kits.
Editors: COVID-19 testing, especially, has been sorely needed, here in the U.S. and in developing countries as well as low-income communities. That's why we're so intrigued by your Schmidt Science Fellows grantee Hal Holmes and his work to repurpose a new DNA technology to create a portable, mobile test for COVID-19. Can you tell us about that work and how you are supporting it?
Wendy: Our work with Conservation X Labs began years ago when our foundation was the first to support their efforts to develop a handheld DNA barcode sensor to help detect illegally imported and mislabeled seafood and timber products. The device was developed by Hal Holmes, who became one of our Schmidt Science Fellows and is the technical lead on the project, working closely with Conservation X Labs co-founders Alex Deghan and Paul Bunje. Now, with COVID-19, Hal and team have worked with another Schmidt Science Fellow, Fahim Farzardfard, to repurpose the technology—which requires no continuous power source, special training, or a lab—to serve as a mobile testing device for the virus.
The work is going very well, manufacturing is being organized, and distribution agreements with hospitals and government agencies are underway. You could see this device in use within a few months and have testing results within hours instead of days. It could be especially useful in low-income communities and developing countries where access to testing is challenging.
Editors: How is Schmidt Futures involved in the development of information platforms that will offer productive solutions?
Wendy: In addition to the work I've mentioned, we've also funded the development of tech-enabled tools that can help the medical community be better prepared for the ongoing spike of COVID cases. For example, we funded EdX and Learning Agency to develop an online training to help increase the number of medical professionals who can operate ventilators. The first course is being offered by Harvard University, and so far, over 220,000 medical professionals have enrolled. We have also invested in informational platforms that make it easier to contain the spread of the disease, such as our work with Recidiviz to model the impact of COVID-19 in prisons and outline policy steps states could take to limit the spread.
Information platforms can also play a big part pushing forward scientific research into the virus. For example, we've funded the UC Santa Cruz Virus Browser, which allows researchers to examine each piece of the virus and see the proteins it creates, the interactions in the host cell, and — most importantly — almost everything the recent scientific literature has to say about that stretch of the molecule.
Editors: The scale of research collaboration and the speed of innovation today seem unprecedented. The whole science world has turned its attention to combating the pandemic. What positive big-picture trends do you think or hope will persist once the crisis eventually abates?
Wendy: As in many areas, the COVID crisis has accelerated trends in the scientific world that were already well underway. For instance, this moment has propelled broad movements toward open publication and open sharing of data and samples—something that has always been a core belief in how we support and advance science.
We believe collaboration is an essential ingredient for progress in all areas. Early in this pandemic, Schmidt Futures held a virtual gathering of 160 people across 70 organizations in philanthropy, government, and business interested in accelerating research and response to the virus, and thought at the time, it's pretty amazing this kind of thing doesn't go all the time. We are obviously going to go farther together than on our own...
My husband, Eric, has observed that in the past two months, we've all catapulted 10 years forward in our use of technology, so there are trends already underway that are likely accelerated and will become part of the fabric of the post-COVID world—like working remotely; online learning; increased online shopping, even for groceries; telemedicine; increasing use of AI to create smarter delivery systems for healthcare and many other applications in a world that has grown more virtual overnight.
"Our deepest hope is that out of these alarming and uncertain times will come a renewed appreciation for the tools of science, as they help humans to navigate a world of interconnected living systems, of which viruses are a large part."
We fully expect these trends to continue and expand across the sciences, sped up by the pressures of the health crisis. Schmidt Ocean Institute and Schmidt Futures have been pressing in these directions for years, so we are pleased to see the expansions that should help more scientists work productively, together.
Editors: Trying to find the good amid a horrible crisis, are there any other new horizons in science, philanthropy, and/or your own work that could transform our world for the better that you'd like to share?
Wendy: Our deepest hope is that out of these alarming and uncertain times will come a renewed appreciation for the tools of science, as they help humans to navigate a world of interconnected living systems, of which viruses are a large part. The more we investigate the Ocean, the more we look deeply into what lies in our soils and beneath them, the more we realize we do not know, and moreover, how vulnerable humanity is to the forces of the natural world.
Philanthropy has an important role to play in influencing how people perceive our place in the world and understand the impact of human activity on the rest of the planet. I believe it's philanthropy's role to take risks, to invest early in innovative technologies, to lead where governments and industry aren't ready to go yet. We're fortunate at this time to be able to help those working on tools to better diagnose and treat the virus, and to invest in those working to improve information systems, so citizens and policy makers can make better decisions that can reduce impacts on families and institutions.
From all we know, this isn't likely to be the last pandemic the world will see. It's been said that a crisis comes before change, and we would hope that we can play a role in furthering the work to build systems that are resilient—in information, energy, agriculture and in all the ways we work, recreate, and use the precious resources of our planet.
[This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online.]
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
[Editor's Note: Welcome to Leaps of the Past, a new monthly column that spotlights the fascinating backstory behind a medical or scientific breakthrough from history.]
------
Until about 40 years ago, ulcers were a mysterious – and sometimes deadly – ailment. Found in a person's stomach lining or intestine, ulcers are small sores that cause a variety of painful symptoms, such as vomiting, a burning or aching sensation, internal bleeding and stomach obstruction. Patients with ulcers suffered for years without a cure and sometimes even needed their stomachs completely removed to rid them from pain.
"To gastroenterologists, the concept of a germ causing ulcers was like saying the Earth is flat."
In the early 1980s, the majority of scientists thought that ulcers were caused by stress or poor diet. But a handful of scientists had a different theory: They believed that ulcers were caused by a corkscrew-shaped bacterium called Helicobacter pylori, or H. pylori for short. Robin Warren, a pathologist, and Barry Marshall, an internist, were the two pioneers of this theory, and the two teamed up to study H. pylori at the Royal Perth Hospital in 1981.
The pair started off by trying to culture the bacteria in the stomachs of patients with gastritis, an inflammation of the stomach lining and a precursor to developing an ulcer. Initially, the microbiologists involved in their clinical trial found no trace of the bacteria from patient samples – but after a few weeks, the microbiologists discovered that their lab techs had been throwing away the cultures before H. pylori could grow. "After that, we let the cultures grow longer and found 13 patients with duodenal ulcer," said Marshall in a later interview. "All of them had the bacteria."
Marshall and Warren also cultured H. pylori in the stomachs of patients with stomach cancer. They observed that "everybody with stomach cancer developed it on a background of gastritis. Whenever we found a person without Helicobacter, we couldn't find gastritis either." Marshall and Warren were convinced that H. pylori not only caused gastritis and peptic ulcers, but stomach cancer as well.
But when the team presented their findings at an annual meeting of the Royal Australasian College of Physicians in Perth, they were mostly met with skepticism. "To gastroenterologists, the concept of a germ causing ulcers was like saying the Earth is flat," Marshall said. "The idea was too weird."
Warren started treating his gastritis patients with antibiotics with great success – but other internists remained doubtful, continuing to treat their patients with antacids instead. Making matters more complicated, neither Warren nor Marshall could readily test their theory, since the pair only had lab mice at their disposal and H. pylori infects only humans and non-human primates, such as rhesus monkeys.
So Marshall took an unconventional approach. First, he underwent two tests to get a baseline reading of his stomach, which showed no presence of H. pylori. Then, Marshall took some H. pylori bacteria from a petri dish, mixed it with beef extract to create a broth, and gulped it down. If his theory was correct, a second gastric biopsy would show that his stomach was overrun with H. pylori bacteria, and a second endoscopy would show a painfully inflamed stomach – gastritis.
Less than a week later, Marshall started feeling sick. "I expected to develop an asymptomatic infection," he later said in an interview published in the Canadian Journal of Gastroenterology. "… [but] after five days, I started to have bloating and fullness after the evening meal, and my appetite decreased. My breath was bad and I vomited clear watery liquid, without acid, each morning."
At his wife's urging, Marshall started on a regimen of antibiotics to kill off the burgeoning bacteria, so a follow-up biopsy showed no signs of H. pylori. A follow-up endoscopy, however, showed "severe active gastritis" along with epithelial damage. This was the smoking gun other clinicians needed to believe that H. pylori caused gastritis and stomach cancer. When they began to treat their gastritis patients with antibiotics, the rate of peptic ulcers in the Australian population diminished by 70 percent.
Today, antibiotics are the standard of care for anyone afflicted with gastritis.
In 2005, Marshall and Warren were awarded the Nobel Prize in Physiology or Medicine for their discovery of H. Pylori and its role in developing gastritis and peptic ulcers. "Thanks to the pioneering discovery by Marshall and Warren, peptic ulcer disease is no longer a chronic, frequently disabling condition, but a disease that can be cured by a short regimen of antibiotics and acid secretion inhibitors," the Nobel Prize Committee said.
Today, antibiotics are the standard of care for anyone afflicted with gastritis – and stomach cancer has been significantly reduced in the Western world.