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.]
We Pioneered a Technology to Save Millions of Poor Children, But a Worldwide Smear Campaign Has Blocked It
In a few weeks it will be 20 years that we three have been working together. Our project has been independently praised as one of the most influential of all projects of the last 50 years.
Two of us figured out how to make rice produce a source of vitamin A, and the rice becomes a golden color instead of white.
The project's objectives have been admired by some and vilified by others. It has directly involved teams of highly motivated people from a handful of nations, from both the private and public sector. A book, dedicated to the three of us, has been written about our work. Nevertheless, success has, so far, eluded us all. The story of our thwarted efforts is a tragedy that we hope will soon – finally – reach a milestone of potentially profound significance for humanity.
So, what have we been working on, and why haven't we succeeded yet?
Food: everybody needs it, and many are fortunate enough to have enough, even too much of it. Food is a highly emotional subject on every continent and in every culture. For a healthy life our food has to provide energy, as well as, in very small amounts, minerals and vitamins. A varied diet, easily achieved and common in industrialised countries, provides everything.
But poor people in countries where rice is grown often eat little else. White rice only provides energy: no minerals or vitamins. And the lack of one of the vitamins, vitamin A, is responsible for killing around 4,500 poor children every day. Lack of vitamin A is the biggest killer of children, and also the main cause of irreversible childhood blindness.
Our project is about fixing this one dietary deficiency – vitamin A – in this one crop – rice – for this one group of people. It is a huge group though: half of the world's population live by eating a lot of rice every day. Two of us (PB & IP) figured out how to make rice produce a source of vitamin A, and the rice becomes a golden color instead of white. The source is beta-carotene, which the human body converts to vitamin A. Beta-carotene is what makes carrots orange. Our rice is called "Golden Rice."
The technology has been donated to assist those rice eaters who suffer from vitamin A deficiency ('VAD') so that Golden Rice will cost no more than white rice, there will be no restrictions on the small farmers who grow it, and nothing extra to pay for the additional nutrition. Very small amounts of beta-carotene will contribute to alleviation of VAD, and even the earliest version of Golden Rice – which had smaller amounts than today's Golden Rice - would have helped. So far, though, no small farmer has been allowed to grow it. What happened?
To create Golden Rice, it was necessary to precisely add two genes to the 30,000 genes normally present in rice plants. One of the genes is from maize, also known as corn, and the other from a commonly eaten soil bacterium. The only difference from white rice is that Golden Rice contains beta-carotene.
It has been proven to be safe to man and the environment, and consumption of only small quantities of Golden Rice will combat VAD, with no chance of overdosing. All current Golden Rice results from one introduction of these two genes in 2004. But the use of that method – once, 15 years ago - means that Golden Rice is a 'GMO' ('genetically modified organism'). The enzymes used in the manufacture of bread, cheese, beer and wine, and the insulin which diabetics take to keep them alive, are all made from GMOs too.
The first GMO crops were created by agri-business companies. Suspicion of the technology and suspicion of commercial motivations merged, only for crop (but not enzymes or pharmaceutical) applications of GMO technology. Activists motivated by these suspicions were successful in getting the 'precautionary principle' incorporated in an international treaty which has been ratified by 166 countries and the European Union – The Cartagena Protocol.
The equivalent of 13 jumbo jets full of children crashes into the ground every day and kills them all, because of vitamin A deficiency.
This protocol is the basis of national rules governing the introduction of GMO crops in every signatory country. Government regulators in, and for, each country must agree before a GMO crop can be 'registered' to be allowed to be used by the public in that country. Currently regulatory decisions to allow Golden Rice release are being considered in Bangladesh and the Philippines.
The Cartagena Protocol obliges the regulators in each country to consider all possible risks, and to take no account of any possible benefits. Because the anti-gmo-activists' initial concerns were principally about the environment, the responsibility for governments' regulation for GMO crops – even for Golden Rice, a public health project delivered through agriculture – usually rests with the Ministry of the Environment, not the Ministry of Health or the Ministry of Agriculture.
Activists discovered, before Golden Rice was created, that inducing fear of GMO food crops from 'multinational agribusinesses' was very good for generating donations from a public that was largely illiterate about food technology and production. And this source of emotionally charged donations would cease if Golden Rice was proven to save sight and lives, because Golden Rice represented the opposite of all the tropes used in anti-GMO campaigns.
Golden Rice is created to deliver a consumer benefit, it is not for profit – to multinational agribusiness or anyone else; the technology originated in the public sector and is being delivered through the public sector. It is entirely altruistic in its motivations; which activists find impossible to accept. So, the activists believed, suspicion against Golden Rice had to be amplified, Golden Rice had to be stopped: "If we lose the Golden Rice battle, we lose the GMO war."
Activism continues to this day. And any Environment Ministry, with no responsibility for public health or agriculture, and of course an interest in avoiding controversy about its regulatory decisions, is vulnerable to such activism.
The anti-GMO crop campaigns, and especially anti-Golden Rice campaigns, have been extraordinarily effective. If so much regulation by governments is required, surely there must be something to be suspicious about: 'There is no smoke without fire'. The suspicion pervades research institutions and universities, the publishers of scientific journals and The World Health Organisation, and UNICEF: even the most scientifically literate are fearful of entanglement in activist-stoked public controversy.
The equivalent of 13 jumbo jets full of children crashes into the ground every day and kills them all, because of VAD. Yet the solution of Golden Rice, developed by national scientists in the counties where VAD is endemic, is ignored because of fear of controversy, and because poor children's deaths can be ignored without controversy.
Perhaps more controversy lies in not taking scientifically based regulatory decisions than in taking them.
The tide is turning, however. 151 Nobel Laureates, a very significant proportion of all Nobel Laureates, have called on the UN, governments of the world, and Greenpeace to cease their unfounded vilification of GMO crops in general and Golden Rice in particular. A recent Golden Rice article commented, "What shocks me is that some activists continue to misrepresent the truth about the rice. The cynic in me expects profit-driven multinationals to behave unethically, but I want to think that those voluntarily campaigning on issues they care about have higher standards."
The recently published book has exposed the frustrating saga in simple detail. And the publicity from all the above is perhaps starting to change the balance of where controversy lies. Perhaps more controversy lies in not taking scientifically based regulatory decisions than in taking them.
But until they are taken, while there continues a chance of frustrating the objectives of the Golden Rice project, the antagonism will continue. And despite a solution so close at hand, VAD-induced death and blindness, and the misery of affected families, will continue also.
© The Authors 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver applies to the data made available in this article, unless otherwise stated.
[Ed. Note: This is the third episode in our Moonshot series, which will explore four cutting-edge scientific developments that stand to fundamentally transform our world.]
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.