Society Needs Regulations to Prevent Research Abuses
[Editor's Note: Our Big Moral Question this month is, "Do government regulations help or hurt the goal of responsible and timely scientific innovation?"]
Government regulations help more than hurt the goal of responsible and timely scientific innovation. Opponents might argue that without regulations, researchers would be free to do whatever they want. But without ethics and regulations, scientists have performed horrific experiments. In Nazi concentration camps, for instance, doctors forced prisoners to stay in the snow to see how long it took for these inmates to freeze to death. These researchers also removed prisoner's limbs in order to try to develop innovations to reconnect these body parts, but all the experiments failed.
Researchers in not only industry, but also academia have violated research participants' rights.
Due to these atrocities, after the war, the Nuremberg Tribunal established the first ethical guidelines for research, mandating that all study participants provide informed consent. Yet many researchers, including those in leading U.S. academic institutions and government agencies, failed to follow these dictates. The U.S. government, for instance, secretly infected Guatemalan men with syphilis in order to study the disease and experimented on soldiers, exposing them without consent to biological and chemical warfare agents. In the 1960s, researchers at New York's Willowbrook State School purposefully fed intellectually disabled children infected stool extracts with hepatitis to study the disease. In 1966, in the New England Journal of Medicine, Henry Beecher, a Harvard anesthesiologist, described 22 cases of unethical research published in the nation's leading medical journals, but were mostly conducted without informed consent, and at times harmed participants without offering them any benefit.
Despite heightened awareness and enhanced guidelines, abuses continued. Until a 1974 journalistic exposé, the U.S. government continued to fund the now-notorious Tuskegee syphilis study of infected poor African-American men in rural Alabama, refusing to offer these men penicillin when it became available as effective treatment for the disease.
In response, in 1974 Congress passed the National Research Act, establishing research ethics committees or Institutional Review Boards (IRBs), to guide scientists, allowing them to innovate while protecting study participants' rights. Routinely, IRBs now detect and prevent unethical studies from starting.
Still, even with these regulations, researchers have at times conducted unethical investigations. In 1999 at the Los Angeles Veterans Affairs Hospital, for example, a patient twice refused to participate in a study that would prolong his surgery. The researcher nonetheless proceeded to experiment on him anyway, using an electrical probe in the patient's heart to collect data.
Part of the problem and consequent need for regulations is that researchers have conflicts of interest and often do not recognize ethical challenges their research may pose.
Pharmaceutical company scandals, involving Avandia, and Neurontin and other drugs, raise added concerns. In marketing Vioxx, OxyContin, and tobacco, corporations have hidden findings that might undercut sales.
Regulations become increasingly critical as drug companies and the NIH conduct increasing amounts of research in the developing world. In 1996, Pfizer conducted a study of bacterial meningitis in Nigeria in which 11 children died. The families thus sued. Pfizer produced a Nigerian IRB approval letter, but the letter turned out to have been forged. No Nigerian IRB had ever approved the study. Fourteen years later, Wikileaks revealed that Pfizer had hired detectives to find evidence of corruption against the Nigerian Attorney General, to compel him to drop the lawsuit.
Researchers in not only industry, but also academia have violated research participants' rights. Arizona State University scientists wanted to investigate the genes of a Native American group, the Havasupai, who were concerned about their high rates of diabetes. The investigators also wanted to study the group's rates of schizophrenia, but feared that the tribe would oppose the study, given the stigma. Hence, these researchers decided to mislead the tribe, stating that the study was only about diabetes. The university's research ethics committee knew the scientists' plan to study schizophrenia, but approved the study, including the consent form, which did not mention any psychiatric diagnoses. The Havasupai gave blood samples, but later learned that the researchers published articles about the tribe's schizophrenia and alcoholism, and genetic origins in Asia (while the Havasupai believed they originated in the Grand Canyon, where they now lived, and which they thus argued they owned). A 2010 legal settlement required that the university return the blood samples to the tribe, which then destroyed them. Had the researchers instead worked with the tribe more respectfully, they could have advanced science in many ways.
Part of the problem and consequent need for regulations is that researchers have conflicts of interest and often do not recognize ethical challenges their research may pose.
Such violations threaten to lower public trust in science, particularly among vulnerable groups that have historically been systemically mistreated, diminishing public and government support for research and for the National Institutes of Health, National Science Foundation and Centers for Disease Control, all of which conduct large numbers of studies.
Research that has failed to follow ethics has in fact impeded innovation.
In popular culture, myths of immoral science and technology--from Frankenstein to Big Brother and Dr. Strangelove--loom.
Admittedly, regulations involve inherent tradeoffs. Following certain rules can take time and effort. Certain regulations may in fact limit research that might potentially advance knowledge, but be grossly unethical. For instance, if our society's sole goal was to have scientists innovate as much as possible, we might let them stick needles into healthy people's brains to remove cells in return for cash that many vulnerable poor people might find desirable. But these studies would clearly pose major ethical problems.
Research that has failed to follow ethics has in fact impeded innovation. In 1999, the death of a young man, Jesse Gelsinger, in a gene therapy experiment in which the investigator was subsequently found to have major conflicts of interest, delayed innovations in the field of gene therapy research for years.
Without regulations, companies might market products that prove dangerous, leading to massive lawsuits that could also ultimately stifle further innovation within an industry.
The key question is not whether regulations help or hurt science alone, but whether they help or hurt science that is both "responsible and innovative."
We don't want "over-regulation." Rather, the right amount of regulations is needed – neither too much nor too little. Hence, policy makers in this area have developed regulations in fair and transparent ways and have also been working to reduce the burden on researchers – for instance, by allowing single IRBs to review multi-site studies, rather than having multiple IRBs do so, which can create obstacles.
In sum, society requires a proper balance of regulations to ensure ethical research, avoid abuses, and ultimately aid us all by promoting responsible innovation.
[Ed. Note: Check out the opposite viewpoint here, and follow LeapsMag on social media to share your perspective.]
Tapping into the Power of the Placebo Effect
When Wayne Jonas was in medical school 40 years ago, doctors would write out a prescription for placebos, spelling it out backwards in capital letters, O-B-E-C-A-L-P. The pharmacist would fill the prescription with a sugar pill, recalls Jonas, now director of integrative health programs at the Samueli Foundation. It fulfilled the patient's desire for the doctor to do something when perhaps no drug could help, and the sugar pills did no harm.
Today, that deception is seen as unethical. But time and time again, studies have shown that placebos can have real benefits. Now, researchers are trying to untangle the mysteries of placebo effect in an effort to better treat patients.
The use of placebos took off in the post-WWII period, when randomized controlled clinical trials became the gold standard for medical research. One group in a study would be treated with a placebo, a supposedly inert pill or procedure that would not affect normal healing and recovery, while another group in the study would receive an "active" component, most commonly a pill under investigation. Presumably, the group receiving the active treatment would have a better response and the difference from the placebo group would represent the efficacy of the drug being tested. That was the basis for drug approval by the U.S. Food and Drug Administration.
"Placebo responses were marginalized," says Ted Kaptchuk, director of the Program in Placebo Studies & Therapeutic Encounters at Harvard Medical School. "Doctors were taught they have to overcome it when they were thinking about using an effective drug."
But that began to change around the turn of the 21st century. The National Institutes of Health held a series of meetings to set a research agenda and fund studies to answer some basic questions, led by Jonas who was in charge of the office of alternative medicine at the time. "People spontaneously get better all the time," says Kaptchuk. The crucial question was, is the placebo effect real? Is it more than just spontaneous healing?
Brain mechanisms
A turning point came in 2001 in a paper in Science that showed physical evidence of the placebo effect. It used positron emission tomography (PET) scans to measure release patterns of dopamine — a chemical messenger involved in how we feel pleasure — in the brains of patients with Parkinson's disease. Surprisingly, the placebo activated the same patterns that were activated by Parkinson's drugs, such as levodopa. It proved the placebo effect was real; now the search was on to better understand and control it.
A key part of the effect can be the beliefs, expectations, context, and "rituals" of the encounter between doctor and patient. Belief by the doctor and patient that the treatment would work, and the formalized practices of administering the treatment can all contribute to a positive outcome.
Conditioning can be another important component in generating a response, as Pavlov demonstrated more than a century ago in his experiments with dogs. They were trained with a bell prior to feeding such that they would begin to salivate in anticipation at the sound of a bell even with no food present.
Translating that to humans, studies with pain medications and sleeping aids showed that patients who had a positive response with a certain dose of those medications could have the same response if the doses was reduced and a dummy pill substituted, even to the point where there was no longer any active ingredient.
Researchers think placebo treatments can work particularly well in helping people deal with pain and psychological disorders.
Those types of studies troubled Kaptchuk because they often relied on deception; patients weren't told they were receiving a placebo, or at best there was a possibility that they might be randomized to receive a placebo. He believed the placebo effect could work even if patients were told upfront that they were going to receive a placebo. More than a dozen so call "open-label placebo" studies across numerous medical conditions, by Kaptchuk and others, have shown that you don't have to lie to patients for a placebo to work.
Jonas likes to tell the story of a patient who used methotrexate, a potent immunosuppressant, to control her rheumatoid arthritis. She was planning a long trip and didn't want to be bothered with the injections and monitoring required in using the drug, So she began to drink a powerful herbal extract of anise, a licorice flavor that she hated, prior to each injection. She reduced the amount of methotrexate over a period of months and finally stopped, but continued to drink the anise. That process had conditioned her body "to alter her immune function and her autoimmunity" as if she were taking the drug, much like Pavlov's dogs had been trained. She has not taken methotrexate for more than a year.
An intriguing paper published in May 2021 found that mild, non-invasive electric stimulation to the brain could not only boost the placebo effect on pain but also reduce the "nocebo" effect — when patients report a negative effect to a sham treatment. While the work is very preliminary, it may open the door to directly manipulating these responses.
Researchers think placebo treatments can work particularly well in helping people deal with pain and psychological disorders, areas where drugs often are of little help. Still, placebos aren't a cure and only a portion of patients experience a placebo effect.
Nocebo
If medicine were a soap opera, the nocebo would be the evil twin of the placebo. It's what happens when patients have adverse side effects because of the expectation that they will. It's commonly seem when patients claims to experience pain or gastric distress that can occur with a drug even when they've received a placebo. The side effects were either imagined or caused by something else.
"Up to 97% of reported pharmaceutical side effects are not caused by the drug itself but rather by nocebo effects and symptom misattribution," according to one 2019 paper.
One way to reduce a nocebo response is to simply not tell patients that specific side effects might occur. An example is a liver biopsy, in which a large-gauge needle is used to extract a tissue sample for examination. Those told ahead of time that they might experience some pain were more likely to report pain and greater pain than those who weren't offered this information.
Interestingly, a nocebo response plays out in the hippocampus, a part of the brain that is never activated in a placebo response. "I think what we are dealing with with nocebo is anxiety," says Kaptchuk, but he acknowledges that others disagree.
Distraction may be another way to minimize the nocebo effect. Pediatricians are using virtual reality (VR) to engage children and distract them during routine procedures such as blood draws and changing wound dressings, and burn patients of all ages have found relief with specially created VRs.
Treatment response
Jonas argues that what we commonly call the placebo effect is misnamed and leading us astray. "The fact is people heal and that inherent healing capacity is both powerful and influenced by mental, social, and contextual factors that are embedded in every medical encounter since the idea of treatment began," he wrote in a 2019 article in the journal Frontiers in Psychiatry. "Our understanding of healing and ability to enhance it will be accelerated if we stop using the term 'placebo response' and call it what it is—the meaning response, and its special application in medicine called the healing response."
He cites evidence that "only 15% to 20% of the healing of an individual or a population comes from health care. The rest—nearly 80%—comes from other factors rarely addressed in the health care system: behavioral and lifestyle choices that people make in their daily life."
To better align treatments and maximize their effectiveness, Jonas has created HOPE (Healing Oriented Practices & Environments) Note, "a patient-guided process designed to identify the patient's values and goals in their life and for healing." Essentially, it seeks to make clear to both doctor and patient what the patient's goals are in seeking treatment. In an extreme example of terminal cancer, some patients may choose to extend life despite the often brutal treatments, while others might prefer to optimize quality of life in the remaining time that they have. It builds on practices already taught in medical schools. Jonas believes doctors and patients can use tools like these to maximize the treatment response and achieve better outcomes.
Much of the medical profession has been resistant to these approaches. Part of that is simply tradition and limited data on their effectiveness, but another very real factor is the billing process for how they are reimbursed. Jonas says a new medical billing code added this year gives doctors another way to be compensated for the extra time and effort that a more holistic approach to medicine may initially require. Other moves away from fee-for-service payments to bundling and payment for outcomes, and the integrated care provided by the Veterans Affairs, Kaiser Permanente and other groups offer longer term hope for the future of approaches that might enhance the healing response.
This article was first published by Leaps.org on July 7, 2021.
New tech helps people of all ages stay social
In March, Sonja Bauman, 39, used an online platform called Papa, which offers “family on demand,” to meet Mariela Florez, an 83-year-old retiree. Despite living with her adult children, Florez was bored and lonely when they left for work, and her recoveries from a stroke and broken hip were going slowly. That's when Bauman began visiting twice per week. They take walks, strengthening Florez’s hip, and play games like Connect Four for mental stimulation. “It’s very important for me so I don’t feel lonely all day long,” said Florez. Her memories, blurred by the stroke, are gradually returning.
Papa is one of a growing number of tech approaches that are bringing together people of all ages. In addition to platforms like Papa that connect people in real life, other startups use virtual reality and video, with some of them focusing especially on deepening social connections between the generations — relationships that support the health of older and younger people alike. “I enjoy seeing Mariela as much as she enjoys seeing me,” Bauman said.
Connecting in real life
Telehealth expert Andrew Parker founded Papa in 2017 to improve the health outcomes of older adults and families. Seniors can meet people — some their grandkids’ age — for healthy activities, while working parents find retirees to watch their children. These “Papa Pals” are provided as a benefit through Medicare, Medicaid and some employer health plans.
In 2020, Papa connected Bauman, the 39-year-old Floridian, with another woman in her mid-70s who lives alone and has very limited mobility. Bauman began driving her to doctor’s appointments and helping her with chores around the house. “When I’m not there, she doesn’t leave her apartment,” said Bauman. The two have gone to the gym together, and they walk slowly through the neighborhood, chatting so it feels less like exercise.
Parker was driven to start Papa by the problem of social isolation among seniors, exacerbated by the pandemic, but he believes users of all ages can benefit. “Many of our Pals feel more comfortable opening up with older members than their same-aged friends,” he said.
Other platforms aim for similar, in-person connections. Generation Tech unites teens with seniors for technology training. And Mon Ami, which provides case management software for aging and disability service providers, has an app that connects isolated older people with college-age volunteers.
Making new connections through video
Several new sites match you with strangers for real-time video chatting on various topics, such as finding common ground on political issues. Other video platforms focus on intergenerational connections.
S. Jay Olshansky, a gerontology professor at the University of Illinois-Chicago, recalls the first time he saw Hyunseung Lee, an 11-year-old from Seoul, through his computer screen. The kid was shy, but Olshansky, 67, encouraged him to ask questions. “Turns out, he was thirsting for this kind of interaction.”
They’d connected through Eldera, a platform that pairs mentors age 60 and up with mentees, using an algorithm, for video conversations. “The time and wisdom of older adults is the most important natural resource we can give future generations,” said Dana Griffin, Eldera's CEO. “Connecting through a screen is the opposite of social media.”
In weekly meetings, Olshansky noticed Lee’s unique interest in math. “There’s something special in you,” Olshansky told him. “How do we bring it to the surface?” He suggested Lee write a book on his favorite subject, and the preteen ran with it, cranking out 70 pages in two weeks. Lee has published his love letter to theorems on Amazon.
Hyunseung Lee, age 11, of Korea, and U.S. college professor Jay Olshanksy, 67, discuss math, strategy and Hyunsung's budding career as a book author during their video chats through a platform called Eldera. (Photo by Dana Palmer/Eldera)
Lee’s parents told Olshansky that their son has become more assertive — a recurring theme, Griffin said. “Confidence is the number one thing parents tell us about.” Since Eldera’s inception last year, the number of mentors has grown exponentially. Even so, Griffin said the waitlist for mentors typically numbers 200 kids.
Another site, Big and Mini, hosts video interactions between seniors and young adults; about 10,000 active users have joined since 2019, said co-founder Aditi Merchant.
Users often bring the benefits of their video interactions to their real-world relationships. Olshansky views Lee as an older version of his grandkids. “Eldera teaches me how to interact with them.” Lee, high on confidence, began instructing his classmates in math. Griffin noted that a group of Eldera mentors in Memphis, who met initially on Eldera, now take walks together in-person to trade ideas for helping each other’s Eldera kids solve problems in their schools and communities.
“We’ve evolved into a community for older adults who want to give back to the world,” said Griffin. Other new tools for connection take the form of virtual reality apps.
Connecting in virtual reality
During pandemic isolation, record numbers of people bought devices for virtual and augmented reality. Such gadgets can convince you that you’re hanging out with friends, even if they’re in another hemisphere. Lifelike simulations from miles away could be especially useful for meaningful interactions between people of different generations, since they’re often geographically segregated.
VR’s benefits require further study, but users report less social isolation and depression, according to MIT research. The immersive, 3-D experience is more compelling than FaceTime or Zoom. “It’s like the difference between a phone call and video call,” said Rick Robinson, Vice President of AARP’s Innovation Labs.
“When VR is designed right, the medium disappears,” said Jeremy Bailenson of Stanford.
Dana Pierce, a 56-year-old government employee in Indiana, got Meta's VR headset in May, 2021, thinking she’d enjoy it more than a new laptop. After many virtual group tours of exotic destinations, she has no regrets. Her adventures occur on Alcove, an app made by Robinson’s Innovation Labs. He co-created it with VR-company Rendever and sought input from people over age 50 to tailor it to their interests. “I’m an introvert,” said Pierce. “I’ve been more socially active since getting my headset than I am in real life.”
Tagging along with her to places like Paris are avatars representing real people around the world. She’s gotten to know VR users in their 70s, 80s and 90s, as well as younger people and some her own age. One is a new friend she plays chess with in relaxing nature settings. Another is her oldest son. He lives 90 minutes away but, earlier this year, Pierce welcomed him and his girlfriend to her virtual house on Alcove. They chatted in the living room decorated with family photos uploaded by Pierce. Then they took out a boat to go VR fishing — because why not — until 2 a.m.
“When VR is designed right, the medium disappears,” said Jeremy Bailenson, a communications professor who directs Stanford’s Virtual Human Interaction Lab. He’s teaching a class of 175 students entirely in VR. After months of covid isolation, the first time the class met, “there was a big catharsis. It really feels like you’re in a big crowd.” Like-minded people meet in VR for events such as comedy shows and creative writing meetups, while the Swedish pop group ABBA has performed this year as digital versions of themselves (“ABBA-tars”) during a virtual concert tour.
Karen Fingerman, a psychologist and director of the Texas Aging and Longevity Center at the University of Texas-Austin, supports the idea of VR for social connection, though she added that some people need it more than others. Hospitals and assisted-living facilities are using products such as Penumbra’s REAL I-Series and MyndVR to bring VR excursions to isolated patients and seniors. “If you’re in a bed or facility, this gives you something to talk about,” said Gita Barry, Penumbra’s executive vice president.
Pierce uses it on most days. She may see another adult son, who lives with her, less often as a result. But VR helps her manage real-world stressors, more than escaping them. After a long workday, she visits her back porch on Alcove, which overlooks a pond. “It’s my little retreat,” she said. “VR improves my mood. It’s added a lot to my life.”
Some seniors are using more than one technology. Olshansky and Lee discuss strategy while playing Internet chess. And Olshansky recently began using VR. He sees his sister, who lives far away, in a virtual beach house. “It’d be a great way to interact with Hyunseung,” he said. “I should get him a headset.”
A version of this article first appeared in The Washington Post on December 3, 2021.