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.]
Announcing "The Future of Science in America: The Election Issue"
As reviewed in The Washington Post, "Tomorrow's challenges in science and politics: Magazine offers in-depth takes on these U.S. issues":
"Is it time for a new way to help make adults more science-literate? What should the next president know about science? Could science help strengthen American democracy? "The Future of Science in America: The Election Issue" has answers. The free, online magazine is packed with interesting takes on how science can serve the common good. And just in time. This year has challenged leaders, researchers and the public with thorny scientific questions, from the coronavirus pandemic to widespread misinformation on scientific issues. The magazine is a collaboration of the Aspen Institute, a think tank that brings together a variety of public figures and private individuals to tackle thorny social issues, the digital science magazine Leapsmag and GOOD, a social impact company. It's packed with 15 in-depth articles about science with a view toward our campaign year."
The Future of Science in America: The Election Issue offers wide-ranging perspectives on challenges and opportunities for science as we elect our next national and local leaders. The fast-striking COVID-19 pandemic and the more slowly moving pandemic of climate change have brought into sharp focus how reliant we will be on science and public policy to work together to rescue us from crisis. Doing so will require cooperation between both political parties, as well as significant public trust in science as a beacon to light the path forward.
In spite of its unfortunate emergence as a flash point between two warring parties, we believe that science is the driving force for universal progress. No endeavor is more noble than the quest to rigorously understand our world and apply that knowledge to further human flourishing. This magazine aspires to promote roadmaps for science as a tool for health, a vehicle for progress, and a unifier of our nation.
This special issue is a collaboration among LeapsMag, the Aspen Institute Science & Society Program, and GOOD, with support from the Gordon and Betty Moore Foundation and the Rita Allen Foundation.
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TABLE OF CONTENTS:
- SCIENTISTS:
Award-Winning Scientists Offer Advice to the Next President of the United States - PUBLIC OPINION:
National Survey Reveals Americans' Most Important Scientific Priorities - GOVERNMENT:
The Nation's Science and Health Agencies Face a Credibility Crisis: Can Their Reputations Be Restored? - TELEVISION:
To Make Science Engaging, We Need a Sesame Street for Adults - IMMIGRATION:
Immigrant Scientists—and America's Edge—Face a Moment of Truth This Election - RACIAL JUSTICE:
Democratize the White Coat by Honoring Black, Indigenous, and People of Color in Science - EDUCATION:
I'm a Black, Genderqueer Medical Student: Here's My Hard-Won Wisdom for Students and Educational Institutions - TECHNOLOGY:
"Deep Fake" Video Technology Is Advancing Faster Than Our Policies Can Keep Up - VOTERS:
Mind the (Vote) Gap: Can We Get More STEM Students to the Polls? - EXPERTS:
Who Qualifies as an "Expert" and How Can We Decide Who Is Trustworthy? - SOCIAL MEDIA:
Why Your Brain Falls for Misinformation—And How to Avoid It - YOUTH:
Youth Climate Activists Expand Their Focus and Collaborate to Get Out the Vote - SUPREME COURT:
Abortions Before Fetal Viability Are Legal: Might Science and a Change on the Supreme Court Undermine That? - NAVAJO NATION:
An Environmental Scientist and an Educator Highlight Navajo Efforts to Balance Tradition with Scientific Priorities - CIVIC SCIENCE:
Want to Strengthen American Democracy? The Science of Collaboration Can Help
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.
Scientists Envision a Universal Coronavirus Vaccine
With several companies progressing through Phase III clinical trials, the much-awaited coronavirus vaccines may finally become reality within a few months.
But some scientists question whether these vaccines will produce a strong and long-lasting immunity, especially if they aren't efficient at mobilizing T-cells, the body's defense soldiers.
"When I look at those vaccines there are pitfalls in every one of them," says Deborah Fuller, professor of microbiology at the Washington University School of Medicine. "Some may induce only transient antibodies, some may not be very good at inducing T-cell responses, and others may not immunize the elderly very well."
Generally, vaccines work by introducing an antigen into the body—either a dead or attenuated pathogen that can't replicate, or parts of the pathogen or its proteins, which the body will recognize as foreign. The pathogens or its parts are usually discovered by cells that chew up the intruders and present them to the immune system fighters, B- and T-cells—like a trespasser's mug shot to the police. In response, B-cells make antibodies to neutralize the virus, and a specialized "crew" called memory B-cells will remember the antigen. Meanwhile, an army of various T-cells attacks the pathogens as well as the cells these pathogens already infected. Special helper T-cells help stimulate B-cells to secrete antibodies and activate cytotoxic T-cells that release chemicals called inflammatory cytokines that kill pathogens and cells they infected.
"Each of these components of the immune system are important and orchestrated to talk to each other," says professor Larry Corey, who studies vaccines and infectious disease at Fred Hutch, a non-profit scientific research organization. "They optimize the assault of the human immune system on the complexity of the viral, bacterial, fungal and parasitic infections that live on our planet, to which we get exposed."
Despite their variety, coronaviruses share certain common proteins and other structural elements, Fuller explains, which the immune system can be trained to identify.
The current frontrunner vaccines aim to train our body to generate a sufficient amount of antibodies to neutralize the virus by shutting off its spike proteins before it enters our cells and begins to replicate. But a truly robust vaccine should also engender a strong response from T-cells, Fuller believes.
"Everyone focuses on the antibodies which block the virus, but it's not always 100 percent effective," she explains. "For example, if there are not enough titers or the antibody starts to wane, and the virus does get into the cells, the cells will become infected. At that point, the body needs to mount a robust T-cytotoxic response. The T-cells should find and recognize cells infected with the virus and eliminate these cells, and the virus with them."
Some of the frontrunner vaccine makers including Moderna, AstraZeneca and CanSino reported that they observed T-cell responses in their trials. Another company, BioNTech, based in Germany, also reported that their vaccine produced T-cell responses.
Fuller and her team are working on their own version of a coronavirus vaccine. In their recent study, the team managed to trigger a strong antibody and T-cell response in mice and primates. Moreover, the aging animals also produced a robust response, which would be important for the human elderly population.
But Fuller's team wants to engage T-cells further. She wants to try training T-cells to recognize not only SARV-CoV-2, but a range of different coronaviruses. Wild hosts, such as bats, carry many different types of coronaviruses, which may spill over onto humans, just like SARS, MERS and SARV-CoV-2 have. There are also four coronaviruses already endemic to humans. Cryptically named 229E, NL63, OC43, and HKU1, they were identified in the 1960s. And while they cause common colds and aren't considered particularly dangerous, the next coronavirus that jumps species may prove deadlier than the previous ones.
Despite their variety, coronaviruses share certain common proteins and other structural elements, Fuller explains, which the immune system can be trained to identify. "T-cells can recognize these shared sequences across multiple different types of coronaviruses," she explains, "so we have this vision for a universal coronavirus vaccine."
Paul Offit at Children's Hospitals in Philadelphia, who specializes in infectious diseases and vaccines, thinks it's a far shot at the moment. "I don't see that as something that is likely to happen, certainly not very soon," he says, adding that a universal flu vaccine has been tried for decades but is not available yet. We still don't know how the current frontrunner vaccines will perform. And until we know how efficient they are, wearing masks and keeping social distance are still important, he notes.
Corey says that while the universal coronavirus vaccine is not impossible, it is certainly not an easy feat. "It is a reasonably scientific hypothesis," he says, but one big challenge is that there are still many unknown coronaviruses so anticipating their structural elements is difficult. The structure of new viruses, particularly the recombinant ones that leap from wild hosts and carry bits and pieces of animal and human genetic material, can be hard to predict. "So whether you can make a vaccine that has universal T-cells to every coronavirus is also difficult to predict," Corey says. But, he adds, "I'm not being negative. I'm just saying that it's a formidable task."
Fuller is certainly up to the task and thinks it's worth the effort. "T-cells can cross-recognize different viruses within the same family," she says, so increasing their abilities to home in on a broader range of coronaviruses would help prevent future pandemics. "If that works, you're just going to take one [vaccine] and you'll have lifetime immunity," she says. "Not just against this coronavirus, but any future pandemic by a coronavirus."
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.