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.]
As a type 2 diabetic, Michael Snyder has long been interested in how blood sugar levels vary from one person to another in response to the same food, and whether a more personalized approach to nutrition could help tackle the rapidly cascading levels of diabetes and obesity in much of the western world.
Eight years ago, Snyder, who directs the Center for Genomics and Personalized Medicine at Stanford University, decided to put his theories to the test. In the 2000s continuous glucose monitoring, or CGM, had begun to revolutionize the lives of diabetics, both type 1 and type 2. Using spherical sensors which sit on the upper arm or abdomen – with tiny wires that pierce the skin – the technology allowed patients to gain real-time updates on their blood sugar levels, transmitted directly to their phone.
It gave Snyder an idea for his research at Stanford. Applying the same technology to a group of apparently healthy people, and looking for ‘spikes’ or sudden surges in blood sugar known as hyperglycemia, could provide a means of observing how their bodies reacted to an array of foods.
“We discovered that different foods spike people differently,” he says. “Some people spike to pasta, others to bread, others to bananas, and so on. It’s very personalized and our feeling was that building programs around these devices could be extremely powerful for better managing people’s glucose.”
Unbeknown to Snyder at the time, thousands of miles away, a group of Israeli scientists at the Weizmann Institute of Science were doing exactly the same experiments. In 2015, they published a landmark paper which used CGM to track the blood sugar levels of 800 people over several days, showing that the biological response to identical foods can vary wildly. Like Snyder, they theorized that giving people a greater understanding of their own glucose responses, so they spend more time in the normal range, may reduce the prevalence of type 2 diabetes.
The commercial potential of such apps is clear, but the underlying science continues to generate intriguing findings.
“At the moment 33 percent of the U.S. population is pre-diabetic, and 70 percent of those pre-diabetics will become diabetic,” says Snyder. “Those numbers are going up, so it’s pretty clear we need to do something about it.”
Fast forward to 2022,and both teams have converted their ideas into subscription-based dietary apps which use artificial intelligence to offer data-informed nutritional and lifestyle recommendations. Snyder’s spinoff, January AI, combines CGM information with heart rate, sleep, and activity data to advise on foods to avoid and the best times to exercise. DayTwo–a start-up which utilizes the findings of Weizmann Institute of Science–obtains microbiome information by sequencing stool samples, and combines this with blood glucose data to rate ‘good’ and ‘bad’ foods for a particular person.
“CGMs can be used to devise personalized diets,” says Eran Elinav, an immunology professor and microbiota researcher at the Weizmann Institute of Science in addition to serving as a scientific consultant for DayTwo. “However, this process can be cumbersome. Therefore, in our lab we created an algorithm, based on data acquired from a big cohort of people, which can accurately predict post-meal glucose responses on a personal basis.”
The commercial potential of such apps is clear. DayTwo, who market their product to corporate employers and health insurers rather than individual consumers, recently raised $37 million in funding. But the underlying science continues to generate intriguing findings.
Last year, Elinav and colleagues published a study on 225 individuals with pre-diabetes which found that they achieved better blood sugar control when they followed a personalized diet based on DayTwo’s recommendations, compared to a Mediterranean diet. The journal Cell just released a new paper from Snyder’s group which shows that different types of fibre benefit people in different ways.
“The idea is you hear different fibres are good for you,” says Snyder. “But if you look at fibres they’re all over the map—it’s like saying all animals are the same. The responses are very individual. For a lot of people [a type of fibre called] arabinoxylan clearly reduced cholesterol while the fibre inulin had no effect. But in some people, it was the complete opposite.”
Eight years ago, Stanford's Michael Snyder began studying how continuous glucose monitors could be used by patients to gain real-time updates on their blood sugar levels, transmitted directly to their phone.
The Snyder Lab, Stanford Medicine
Because of studies like these, interest in precision nutrition approaches has exploded in recent years. In January, the National Institutes of Health announced that they are spending $170 million on a five year, multi-center initiative which aims to develop algorithms based on a whole range of data sources from blood sugar to sleep, exercise, stress, microbiome and even genomic information which can help predict which diets are most suitable for a particular individual.
“There's so many different factors which influence what you put into your mouth but also what happens to different types of nutrients and how that ultimately affects your health, which means you can’t have a one-size-fits-all set of nutritional guidelines for everyone,” says Bruce Y. Lee, professor of health policy and management at the City University of New York Graduate School of Public Health.
With the falling costs of genomic sequencing, other precision nutrition clinical trials are choosing to look at whether our genomes alone can yield key information about what our diets should look like, an emerging field of research known as nutrigenomics.
The ASPIRE-DNA clinical trial at Imperial College London is aiming to see whether particular genetic variants can be used to classify individuals into two groups, those who are more glucose sensitive to fat and those who are more sensitive to carbohydrates. By following a tailored diet based on these sensitivities, the trial aims to see whether it can prevent people with pre-diabetes from developing the disease.
But while much hope is riding on these trials, even precision nutrition advocates caution that the field remains in the very earliest of stages. Lars-Oliver Klotz, professor of nutrigenomics at Friedrich-Schiller-University in Jena, Germany, says that while the overall goal is to identify means of avoiding nutrition-related diseases, genomic data alone is unlikely to be sufficient to prevent obesity and type 2 diabetes.
“Genome data is rather simple to acquire these days as sequencing techniques have dramatically advanced in recent years,” he says. “However, the predictive value of just genome sequencing is too low in the case of obesity and prediabetes.”
Others say that while genomic data can yield useful information in terms of how different people metabolize different types of fat and specific nutrients such as B vitamins, there is a need for more research before it can be utilized in an algorithm for making dietary recommendations.
“I think it’s a little early,” says Eileen Gibney, a professor at University College Dublin. “We’ve identified a limited number of gene-nutrient interactions so far, but we need more randomized control trials of people with different genetic profiles on the same diet, to see whether they respond differently, and if that can be explained by their genetic differences.”
Some start-ups have already come unstuck for promising too much, or pushing recommendations which are not based on scientifically rigorous trials. The world of precision nutrition apps was dubbed a ‘Wild West’ by some commentators after the founders of uBiome – a start-up which offered nutritional recommendations based on information obtained from sequencing stool samples –were charged with fraud last year. The weight-loss app Noom, which was valued at $3.7 billion in May 2021, has been criticized on Twitter by a number of users who claimed that its recommendations have led to them developed eating disorders.
With precision nutrition apps marketing their technology at healthy individuals, question marks have also been raised about the value which can be gained through non-diabetics monitoring their blood sugar through CGM. While some small studies have found that wearing a CGM can make overweight or obese individuals more motivated to exercise, there is still a lack of conclusive evidence showing that this translates to improved health.
However, independent researchers remain intrigued by the technology, and say that the wealth of data generated through such apps could be used to help further stratify the different types of people who become at risk of developing type 2 diabetes.
“CGM not only enables a longer sampling time for capturing glucose levels, but will also capture lifestyle factors,” says Robert Wagner, a diabetes researcher at University Hospital Düsseldorf. “It is probable that it can be used to identify many clusters of prediabetic metabolism and predict the risk of diabetes and its complications, but maybe also specific cardiometabolic risk constellations. However, we still don’t know which forms of diabetes can be prevented by such approaches and how feasible and long-lasting such self-feedback dietary modifications are.”
Snyder himself has now been wearing a CGM for eight years, and he credits the insights it provides with helping him to manage his own diabetes. “My CGM still gives me novel insights into what foods and behaviors affect my glucose levels,” he says.
He is now looking to run clinical trials with his group at Stanford to see whether following a precision nutrition approach based on CGM and microbiome data, combined with other health information, can be used to reverse signs of pre-diabetes. If it proves successful, January AI may look to incorporate microbiome data in future.
“Ultimately, what I want to do is be able take people’s poop samples, maybe a blood draw, and say, ‘Alright, based on these parameters, this is what I think is going to spike you,’ and then have a CGM to test that out,” he says. “Getting very predictive about this, so right from the get go, you can have people better manage their health and then use the glucose monitor to help follow that.”
Luckily, two college freshmen at the Rotterdam School of Management, Erasmus University, were naïve enough to take their bicycles to the scrapyard. In a previous stroke of fortune, the freshmen, Adrian Goosses and Michael Widmann, had been assigned as roommates and had quickly hit it off. Now they were looking for a cool recycling project for their first semester “strategic entrepreneurship” course—maybe they could turn old tires into comfortable lounge chairs, they thought.
“Everybody gets around by bike in Rotterdam,” says Goosses, now 32, from his home in Cologne, Germany. “The tires were way too heavy and cumbersome to transport by bike,” Widmann chimes in via Zoom from Bolzano, Italy, where he lives.
Sifting through the car trash for something handier led the two students to an idea that has since flourished: Could the airbag and seatbelts from a banged up compact car be salvaged and turned into a sustainable backpack? The size of the airbag was already a natural fit. The seatbelts made perfect shoulder straps. After returning from the scrapyard, “We stitched the prototype together by hand with a needle and yarn,” says Goosses. “Yet we didn’t even know how to sew!”
Much to their surprise, their classmates responded with so much enthusiasm to their “trash bag” concept that it convinced the two innovators to keep going. Every semester, they improved the prototype further. With the help of YouTube videos, they taught themselves how to sew. Because modern electric sewing machines had a difficult time breaking through the tough nylon of the airbags, Goosses and Widmann went to a second-hand shop and purchased an ancient Singer from 1880 for 10 Euros. They dyed the first airbags in a saucepan in the garden outside of the apartment they shared.
“By the time we graduated, we had a presentable prototype and a business plan,” Goosses says.
Despite their progress, Goosses and Widmann are up against a problem that’s immense: Cars are notoriously difficult to recycle because many parts are considered toxic waste.
It’s an example of “upcycling,” when you spot a potential new use in something that’s been trashed, shelved or otherwise retired. The approach has received increasing attention and support from the U.S. Environmental Protection Agency and others to boost sustainability in all kinds of areas, from fashion (where even luxury brands like Balenciaga or Coach repurpose vintage clothing and bags) to architecture, where reusing wood, steel and bricks significantly reduces a building’s carbon footprint.
In addition to helping the planet, those who do it well can make a living from it. These days, Goosses and Widmann own a flourishing company: Airpaq. A crowdfunding campaign in 2017 yielded 70,000 Euros to get them started. Since then, they have upcycled 80,000 airbags, 100,000 seatbelts and 28,000 belt buckles – the equivalent of 60 tons of car trash.
For the successful upcycling, they received the 2021 German Design Award and, earlier this year, the renowned German Sustainability Award. The jurors evaluating the product commented that the startup “convinced us not only because of their uncompromising quality and functionality but also because of their ecological and ethical values….How well the startup translates upcycling and green fashion into an urban lifestyle brand is impressive.”
Despite their progress, Goosses and Widmann are up against a problem that’s immense: Cars are notoriously difficult to recycle because many parts are considered toxic waste. Therefore, up to 25% of vehicle scraps get shredded every year in Germany alone, the equivalent of over 501,000 tons. Because airbags and seatbelts are nearly indestructible, they are costly to recycle and almost always end up in landfills. Given that airbags and seatbelts save lives, they are subject to stringent security regulations, and manufacturers have a sky-high reject rate. “If a tiny filament protrudes somewhere, the manufacturer will throw out the entire output,” Widmann explains.
The nearly indestructible qualities that make this material very difficult to recycle render it an excellent resource for backpacks. “The material is so durable, you almost cannot tear it,” Goosses adds and demonstrates with a hard tug that even when the material already has a hole, it won’t rip it further. The material is also water repellent and extremely light.
The antique Singer is still in their Cologne headquarters but only as decoration. Their company with 12 employees is producing 500 backpacks and fanny packs every week in Romania, where the parts are professionally cut by laser, dyed and sewed. Airpaq still procures the belt buckles at scrapyards but they get most of the airbags directly from the reject pile of a nearby airbag producer. “We process the materials where they are produced,” Goosses explains. Only about 15 miles lie between one of Europe’s biggest airbag manufacturers and the Airpaq seamsters in Romania.
Co-founders Adrian Goosses and Michael Widmann demonstrate their company's equation: airbag plus seatbelt equals a backpack that's durable and eco-friendly.
Airpaq
The founders are aware that with price tags ranging from 100 to 160 Euro - a cost that reflects their intensive production process - Airpaq’s bags are hardly competitive. After all, anybody can buy a discount backpack for a fraction of the cost. So they recently added fanny packs for 30 Euro to their product line. Goosses and Widmann know they will need to lower their prices in the long run if they want to expand. Among other things, they didn’t pay themselves salaries during the first two years after founding the company.
Money-making isn’t their only objective. “Of course, it would be cheaper if we did what almost all textile producers do and move production to Asia,” Goosses says. That wasn’t an option for him. “Ship trash to Vietnam and let seamsters sew it together for cheap? No way, that would be anything but sustainable,” he says.
Michael Widmann’s family was already operating a textile production in Romania, mainly producing thin, elastic sports fashion. The family allowed Widmann and Goosses to produce their first professional prototypes there, but then the two youngsters had to buy their own machines, acquire the necessary knowhow, and hire their staff. They both moved to Romania for six months “to get to know the people behind the machines.” The founders emphasize that they pay fair wages, use eco-certified dyes and clean their own wastewater. “Normal production uses five to six liters of water per kilo material,” Widmann explains. “We only need a fraction because we massage the dye into the material by hand: 100 ml water for washing and dying per kilo.”
However, every time they return to the scrapyard, the abundance of trash sparks new ideas. “When you see how much material ends up there…” Widmann says, shaking his head without finishing the sentence. Goosses picks up the train of thought: “We want to make upcycling the new standard. You just have to be creative to get upcycling into the mainstream.”
And maybe they’ll return to their roots and finally find an idea for the tires after all. “One could turn the rubber into soles for comfortable shoes,” Widmann thinks out loud.