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.]
Pregnant and Breastfeeding Women Might Have a New Reason to Ditch Artificial Sweeteners
Women considering pregnancy might have another reason to drop artificial sweeteners from their diet, if a new study of mice proves to apply to humans as well. It highlights "yet another potential health impact of zero-calorie sweeteners," according to lead author Stephanie Olivier-Van Stichelen.
The discovery was serendipitous, not part of the original study.
It found that commonly used artificial sweeteners consumed by female mice transfer to pups in the womb and later through milk, harming their development. The sweeteners affected the composition of bacteria in the gut of the pups, making them more vulnerable to developing diabetes, and greatly reduced the liver's capacity to neutralize toxins.
The discovery was serendipitous, not part of the original study, says John Hanover, the senior author and a cell biologist at the NIH National Institute of Diabetes and Digestive and Kidney Diseases. The main study looked at how a high sugar diet in the mother turns genes on and off in the developing offspring.
It compared them with mothers fed a low sugar diet, replacing sugar with a mix of sucralose and acesulfame-K (AK), two non-nutrient artificial sugars that are already used extensively in our food products and thought to be safe.
While the artificial sweeteners had little effect on the mothers, the trace amounts that were transferred through the placenta and milk had a profound effect on the pups. Hanover believes the molecules are changing gene expression during a crucial, short period of development.
"Somewhat to our surprise, we saw in the pups a really dramatic change in the microbiome" of those whose mothers were fed the artificial sweeteners, Hanover told leapsmag. "It looked like the neonates were much, much more sensitive than their mothers to the sucralose and AK." The unexpected discovery led them to publish a separate paper.
"The protective microbe Akkermansia was largely missing, and we saw a pretty dramatic shift in the ratio of two bacteria that are normally associated with metabolic disease," a precursor to diabetes, he explains. Akkermansia is a bacteria that feeds on mucus in the gut and helps remodel the tissue to an adult state over the first several months of life in a mouse. A similar process takes several years in humans, as the infant is weaned off of breast milk as the primary food source.
The good news is the body seems to remove these artificial sweeteners fairly quickly, probably within a week.
Another problem the researchers saw in the animals was "a particularly striking change in the metabolism of the detoxification systems" in the liver, says Hanover. A healthy liver is dark red, but a high dose of the artificial sweeteners turned it white, "which is a sign of massive problems."
The study was conducted in mice and Hanover cautions the findings may not apply to humans. "But in general, the microbiome changes that one sees in the rodent model mimics what we see in humans...[and] the genes that are turned on in the mouse and the human are very similar."
Hanover acknowledges the quantity of artificial sweeteners used in the study is on the high end of human consumption, roughly the equivalent of 20 cans of diet soda a day. But the sweeteners are so ubiquitous in consumer products, from foods to lipstick, and often not even mentioned on the label, that it is difficult to measure just how much a person consumes every day.
The good news is the body seems to remove these artificial sweeteners fairly quickly, probably within a week. Until further studies provide a clearer picture, women who want to err on the side of caution can choose to reduce if not eliminate their exposure to artificial sweeteners during pregnancy and breastfeeding.
NASA Has the Technology to Save Us From an Asteroid Strike, But Congress Won’t Fund It
At the biannual Planetary Defense Conference earlier this year, NASA ran a simulation of an asteroid slamming into the center of Manhattan.
For several millennia now, we've been lucky, but our luck won't hold out forever.
The gathering of astronomers, planetary scientists, and FEMA disaster-response experts attempted a number of interventions that might be possible within a time window of eight years, the given warning period before impact.
Catastrophic asteroid crashes are not without precedent, and scientists say it's only a matter of time before another one occurs—that is, if we do nothing to prevent it. It's believed that a huge asteroid crash off the coast of Mexico's Yucatan Peninsula created a worldwide disaster that helped to speed the extinction of the dinosaurs 65 million years ago.
In 1908, a meteoroid less than 300 feet in diameter exploded in the air over the Tunguska region of Siberia, creating a shockwave that leveled trees for hundreds of square miles. It's a matter of sheer luck it didn't hit a major population center, where human casualties could have been enormous.
For several millennia now, we've been lucky, but our luck won't hold out forever. There are millions of asteroids circulating about in our solar system, some of them hundreds of miles across, and although the odds of a massive one crashing to Earth in the near future is statistically low, the devastation could be apocalyptic.
Back at the conference, the experts tried sending several spacecrafts to knock the asteroid off-course by slamming into it. They considered blasting it with nuclear weapons. They even considered painting it white so it absorbed less of the sun's energy, hoping that would shift the asteroid's trajectory. In the simulations, all of the interventions failed and the giant space rock crashed into Manhattan, killing 1.3 million people in a massive explosion that was 1,000 times more powerful than the Hiroshima bomb.
NEOCam is designed, tested, and ready to build, but the project is currently frozen because of a $40 million gap in NASA funding.
Given more time, the scientists said, they might have succeeded in preventing the disaster. However, with today's asteroid-hunting telescopes, it's not likely we would have more warning. Our current telescopes are not powerful enough to detect all the near-earth asteroids, nor are they positioned well enough for sufficient detection. As recently as last week, for example, an asteroid traveling 15 miles a second narrowly missed crashing into the Earth, and it was only noticed several days in advance.
Now for the good news: There is a new technology that could buy us the time we need, says MIT planetary sciences professor Richard P. Binzel and colleagues who attended the conference. The Near-Earth Object Camera, or NEOCam, designed by NASA's Jet Propulsion Laboratory, would detect more than 90 percent of nearby objects that are 420 feet across or larger, according to Binzel.
The powerful infrared telescope is designed to sit within the L1 Lagrange point, a stable location in space where the gravitational pulls of the Earth and the sun cancel each other out. From there, large space bodies could be detected early enough to give scientists decades of warning when an asteroid is heading for Earth. NEOCam is designed, tested, and ready to build, but the project is currently frozen because of a $40 million gap in NASA funding.
The status of NEOCam, according to Binzel, is a case-study in short-sightedness and a lack of leadership. Congress needs to raise NASA's Planetary Defense budget from its current $160 million to $200 million to get the telescope built and launched into space, a goal that would seem eminently doable within the strictures of 2020's $4.75 trillion government budget. But Binzel describes a current deadlock between NASA, Congress, and the Office of Management and Budget as a "cosmic game of chicken."
If we don't use our technology to defend the planet, "it would be the most epic failure in the history of science."
In an excruciatingly budget-conscious atmosphere, "No one wants to stick their neck out and take adult responsibility" for getting the funding allocated that would unfreeze the project, says Binzel. But, he adds, "We have a moral obligation to act."
NEOCam would not only spot the overwhelming majority of asteroids in Earth's vicinity, it would determine their size and pinpoint exactly where they are likely to strike the Earth. And it would allow us decades to act, according to Binzel. Repeated ramming by an international armada of specialized spacecraft could slightly change the trajectory of an asteroid, he says. Changing the trajectory only a tiny bit, given the scale of millions of miles and several decades for the course change to take effect, could cause an asteroid to miss the Earth altogether.
"So far we've been relying on luck," says Binzel, "but luck is not a plan." Now that we have the technology to discover what's careening through our space neighborhood, it's our ethical duty to deploy it. If we don't use our technology to gain the knowledge we need to defend the planet, Binzel concludes, "it would be the most epic failure in the history of science."
Should Congress green light the $40 million budget for the new asteroid-hunting telescope? @NASA #NASA #astroid— leapsmag (@leapsmag) 1564681293.0