Sloppy Science Happens More Than You Think
The media loves to tout scientific breakthroughs, and few are as toutable – and in turn, have been as touted – as CRISPR. This method of targeted DNA excision was discovered in bacteria, which use it as an adaptive immune system to combat reinfection with a previously encountered virus.
Shouldn't the editors at a Nature journal know better than to have published an incorrect paper in the first place?
It is cool on so many levels: not only is the basic function fascinating, reminding us that we still have more to discover about even simple organisms that we thought we knew so well, but the ability it grants us to remove and replace any DNA of interest has almost limitless applications in both the lab and the clinic. As if that didn't make it sexy enough, add in a bicoastal, male-female, very public and relatively ugly patent battle, and the CRISPR story is irresistible.
And then last summer, a bombshell dropped. The prestigious journal Nature Methods published a paper in which the authors claimed that CRISPR could cause many unintended mutations, rendering it unfit for clinical use. Havoc duly ensued; stocks in CRISPR-based companies plummeted. Thankfully, the authors of the offending paper were responsible, good scientists; they reassessed, then recanted. Their attention- and headline- grabbing results were wrong, and they admitted as much, leading Nature Methods to formally retract the paper this spring.
How did this happen? Shouldn't the editors at a Nature journal know better than to have published this in the first place?
Alas, high-profile scientific journals publish misleading and downright false results fairly regularly. Some errors are unavoidable – that's how the scientific method works. Hypotheses and conclusions will invariably be overturned as new data becomes available and new technologies are developed that allow for deeper and deeper studies. That's supposed to happen. But that's not what we're talking about here. Nor are we talking about obvious offenses like outright plagiarism. We're talking about mistakes that are avoidable, and that still have serious ramifications.
The cultures of both industry and academia promote research that is poorly designed and even more poorly analyzed.
Two parties are responsible for a scientific publication, and thus two parties bear the blame when things go awry: the scientists who perform and submit the work, and the journals who publish it. Unfortunately, both are incentivized for speedy and flashy publications, and not necessarily for correct publications. It is hardly a surprise, then, that we end up with papers that are speedy and flashy – and not necessarily correct.
"Scientists don't lie and submit falsified data," said Andy Koff, a professor of Molecular Biology at Sloan Kettering Institute, the basic research arm of Memorial Sloan Kettering Cancer Center. Richard Harris, who wrote the book on scientific misconduct running the gamut from unconscious bias and ignorance to more malicious fraudulence, largely concurs (full disclosure: I reviewed the book here). "Scientists want to do good science and want to be recognized as such," he said. But even so, the cultures of both industry and academia promote research that is poorly designed and even more poorly analyzed. In Rigor Mortis: How Sloppy Science Creates Worthless Cures, Crushes Hope, and Wastes Millions, Harris describes how scientists must constantly publish in order to maintain their reputations and positions, to get grants and tenure and students. "They are disincentivized from doing that last extra experiment to prove their results," he said; it could prove too risky if it could cost them a publication.
Ivan Oransky and Adam Marcus founded Retraction Watch, a blog that tracks the retraction of scientific papers, in 2010. Oransky pointed out that blinded peer review – the pride and joy of the scientific publishing enterprise – is a large part of the problem. "Pre-publication peer review is still important, but we can't treat it like the only check on the system. Papers are being reviewed by non-experts, and reviewers are asked to review papers only tangentially related to their field. Moreover, most peer reviewers don't look at the underlying or raw data, even when it is available. How then can they tell if the analysis is flawed or the data is accurate?" he wondered.
Mistaken publications also erode the public's opinion of legitimate science, which is problematic since that opinion isn't especially high to begin with.
Koff agreed that anonymous peer review is valuable, but severely flawed. "Blinded review forces a collective view of importance," he said. "If an article disagrees with the reviewer's worldview, the article gets rejected or forced to adhere to that worldview – even if that means pushing the data someplace it shouldn't necessarily go." We have lost the scientific principle behind review, he thinks, which was to critically analyze a paper. But instead of challenging fundamental assumptions within a paper, reviewers now tend to just ask for more and more supplementary data. And don't get him started on editors. "Editors are supposed to arbitrate between reviewers and writers and they have completely abdicated this responsibility, at every journal. They do not judge, and that's a real failing."
Harris laments the wasted time, effort, and resources that result when erroneous ideas take hold in a field, not to mention lives lost when drug discovery is predicated on basic science findings that end up being wrong. "When no one takes the time, care, and money to reproduce things, science isn't stopping – but it is slowing down," he noted. Mistaken publications also erode the public's opinion of legitimate science, which is problematic since that opinion isn't especially high to begin with.
Scientists and publishers don't only cause the problem, though – they may also provide the solution. Both camps are increasingly recognizing and dealing with the crisis. The self-proclaimed "data thugs" Nick Brown and James Heathers use pretty basic arithmetic to reveal statistical errors in papers. The microbiologist Elisabeth Bik scans the scientific literature for problematic images "in her free time." The psychologist Brian Nosek founded the Center for Open Science, a non-profit organization dedicated to promoting openness, integrity, and reproducibility in scientific research. The Nature family of journals – yes, the one responsible for the latest CRISPR fiasco – has its authors complete a checklist to combat irreproducibility, à la Atul Gawande. And Nature Communications, among other journals, uses transparent peer review, in which authors can opt to have the reviews of their manuscript published anonymously alongside the completed paper. This practice "shows people how the paper evolved," said Koff "and keeps the reviewer and editor accountable. Did the reviewer identify the major problems with the paper? Because there are always major problems with a paper."
When doctors couldn’t stop her daughter’s seizures, this mom earned a PhD and found a treatment herself.
Twenty-eight years ago, Tracy Dixon-Salazaar woke to the sound of her daughter, two-year-old Savannah, in the midst of a medical emergency.
“I entered [Savannah’s room] to see her tiny little body jerking about violently in her bed,” Tracy said in an interview. “I thought she was choking.” When she and her husband frantically called 911, the paramedic told them it was likely that Savannah had had a seizure—a term neither Tracy nor her husband had ever heard before.
Over the next several years, Savannah’s seizures continued and worsened. By age five Savannah was having seizures dozens of times each day, and her parents noticed significant developmental delays. Savannah was unable to use the restroom and functioned more like a toddler than a five-year-old.
Doctors were mystified: Tracy and her husband had no family history of seizures, and there was no event—such as an injury or infection—that could have caused them. Doctors were also confused as to why Savannah’s seizures were happening so frequently despite trying different seizure medications.
Doctors eventually diagnosed Savannah with Lennox-Gaustaut Syndrome, or LGS, an epilepsy disorder with no cure and a poor prognosis. People with LGS are often resistant to several kinds of anti-seizure medications, and often suffer from developmental delays and behavioral problems. People with LGS also have a higher chance of injury as well as a higher chance of sudden unexpected death (SUDEP) due to the frequent seizures. In about 70 percent of cases, LGS has an identifiable cause such as a brain injury or genetic syndrome. In about 30 percent of cases, however, the cause is unknown.
Watching her daughter struggle through repeated seizures was devastating to Tracy and the rest of the family.
“This disease, it comes into your life. It’s uninvited. It’s unannounced and it takes over every aspect of your daily life,” said Tracy in an interview with Today.com. “Plus it’s attacking the thing that is most precious to you—your kid.”
Desperate to find some answers, Tracy began combing the medical literature for information about epilepsy and LGS. She enrolled in college courses to better understand the papers she was reading.
“Ironically, I thought I needed to go to college to take English classes to understand these papers—but soon learned it wasn’t English classes I needed, It was science,” Tracy said. When she took her first college science course, Tracy says, she “fell in love with the subject.”
Tracy was now a caregiver to Savannah, who continued to have hundreds of seizures a month, as well as a full-time student, studying late into the night and while her kids were at school, using classwork as “an outlet for the pain.”
“I couldn’t help my daughter,” Tracy said. “Studying was something I could do.”
Twelve years later, Tracy had earned a PhD in neurobiology.
After her post-doctoral training, Tracy started working at a lab that explored the genetics of epilepsy. Savannah’s doctors hadn’t found a genetic cause for her seizures, so Tracy decided to sequence her genome again to check for other abnormalities—and what she found was life-changing.
Tracy discovered that Savannah had a calcium channel mutation, meaning that too much calcium was passing through Savannah’s neural pathways, leading to seizures. The information made sense to Tracy: Anti-seizure medications often leech calcium from a person’s bones. When doctors had prescribed Savannah calcium supplements in the past to counteract these effects, her seizures had gotten worse every time she took the medication. Tracy took her discovery to Savannah’s doctor, who agreed to prescribe her a calcium blocker.
The change in Savannah was almost immediate.
Within two weeks, Savannah’s seizures had decreased by 95 percent. Once on a daily seven-drug regimen, she was soon weaned to just four, and then three. Amazingly, Tracy started to notice changes in Savannah’s personality and development, too.
“She just exploded in her personality and her talking and her walking and her potty training and oh my gosh she is just so sassy,” Tracy said in an interview.
Since starting the calcium blocker eleven years ago, Savannah has continued to make enormous strides. Though still unable to read or write, Savannah enjoys puzzles and social media. She’s “obsessed” with boys, says Tracy. And while Tracy suspects she’ll never be able to live independently, she and her daughter can now share more “normal” moments—something she never anticipated at the start of Savannah’s journey with LGS. While preparing for an event, Savannah helped Tracy get ready.
“We picked out a dress and it was the first time in our lives that we did something normal as a mother and a daughter,” she said. “It was pretty cool.”
A sleek, four-foot tall white robot glides across a cafe storefront in Tokyo’s Nihonbashi district, holding a two-tiered serving tray full of tea sandwiches and pastries. The cafe’s patrons smile and say thanks as they take the tray—but it’s not the robot they’re thanking. Instead, the patrons are talking to the person controlling the robot—a restaurant employee who operates the avatar from the comfort of their home.
It’s a typical scene at DAWN, short for Diverse Avatar Working Network—a cafe that launched in Tokyo six years ago as an experimental pop-up and quickly became an overnight success. Today, the cafe is a permanent fixture in Nihonbashi, staffing roughly 60 remote workers who control the robots remotely and communicate to customers via a built-in microphone.
More than just a creative idea, however, DAWN is being hailed as a life-changing opportunity. The workers who control the robots remotely (known as “pilots”) all have disabilities that limit their ability to move around freely and travel outside their homes. Worldwide, an estimated 16 percent of the global population lives with a significant disability—and according to the World Health Organization, these disabilities give rise to other problems, such as exclusion from education, unemployment, and poverty.
These are all problems that Kentaro Yoshifuji, founder and CEO of Ory Laboratory, which supplies the robot servers at DAWN, is looking to correct. Yoshifuji, who was bedridden for several years in high school due to an undisclosed health problem, launched the company to help enable people who are house-bound or bedridden to more fully participate in society, as well as end the loneliness, isolation, and feelings of worthlessness that can sometimes go hand-in-hand with being disabled.
“It’s heartbreaking to think that [people with disabilities] feel they are a burden to society, or that they fear their families suffer by caring for them,” said Yoshifuji in an interview in 2020. “We are dedicating ourselves to providing workable, technology-based solutions. That is our purpose.”
Shota Kuwahara, a DAWN employee with muscular dystrophy. Ory Labs, Inc.
Wanting to connect with others and feel useful is a common sentiment that’s shared by the workers at DAWN. Marianne, a mother of two who lives near Mt. Fuji, Japan, is functionally disabled due to chronic pain and fatigue. Working at DAWN has allowed Marianne to provide for her family as well as help alleviate her loneliness and grief.Shota, Kuwahara, a DAWN employee with muscular dystrophy, agrees. "There are many difficulties in my daily life, but I believe my life has a purpose and is not being wasted," he says. "Being useful, able to help other people, even feeling needed by others, is so motivational."