Is Red Tape Depriving Patients of Life-Altering Therapies?
Rich Mancuso suffered from herpes for most of his adult life. The 49-year-old New Jersey resident was miserable. He had at least two to three outbreaks every month with painful and unsightly sores on his face and in his eyes, yet the drugs he took to control the disease had terrible side effects--agonizing headaches and severe stomach disturbances.
Last week, the FDA launched a criminal investigation to determine whether the biotech behind the vaccine had violated regulations.
So in 2016, he took an unusual step: he was flown to St. Kitt's, an island in the West Indies, where he participated in a clinical trial of a herpes vaccine, and received three injections of the experimental therapeutic during separate visits to the island. Within a year, his outbreaks stopped. "Nothing else worked," says Mancuso, who feels like he's gotten his life back. "And I've tried everything on the planet."
Mancuso was one of twenty genital herpes sufferers who were given the experimental vaccine in tests conducted on the Caribbean island and in hotel rooms near the campus of Southern Illinois University in Springfield where the vaccine's developer, microbiologist William Halford, was on the faculty. But these tests were conducted under the radar, without the approval or safety oversight of the Food and Drug Administration or an institutional review board (IRB), which routinely monitor human clinical trials of experimental drugs to make sure participants are protected.
Last week, the FDA launched a criminal investigation to determine whether anyone from SIU or Rational Vaccines, the biotech behind the vaccine, had violated regulations by aiding Halford's research. The SIU scientist was a microbiologist, not a medical doctor, which means that volunteers were not only injected with an unsanctioned experimental treatment but there wasn't even routine medical oversight.
On one side are scientists and government regulators with legitimate safety concerns....On the other are desperate patients and a dying scientist willing to go rogue in a foreign country.
Halford, who was stricken with a rare form of a nasal cancer, reportedly bypassed regulatory rules because the clock was ticking and he wanted to speed this potentially life-altering therapeutic to patients. "There was no way he had enough time to raise $100 million to test the drugs in the U.S.," says Mancuso, who became friends with Halford before he died in June of 2017 at age 48. "He knew if he didn't do something, his work would just die and no one would benefit. This was the only way."
But was it the only way? Once the truth about the trial came to light, public health officials in St. Kitt's disavowed the trial, saying they had not been notified that it was happening, and Southern Illinois University's medical school launched an investigation that ultimately led to the resignation of three employees, including a faculty member, a graduate student and Halford's widow. Investors in Rational Vaccines, including maverick Silicon Valley billionaire Peter Thiel, demanded that all FDA rules must be followed in future tests.
"Trials have to yield data that can be submitted to the FDA, which means certain requirements have to be met," says Jeffrey Kahn, a bioethicist at Johns Hopkins University in Baltimore. "These were renegade researchers who exposed people to unnecessary risks, which was hugely irresponsible. I don't know what they expected to do with the research. It was a waste of money and generated data that can't be used because no regulator would accept it."
But this story illuminates both sides of a thorny issue. On one side are scientists and government regulators with legitimate safety concerns who want to protect volunteers from very real risks—people have died even in closely monitored clinical trials. On the other, are desperate patients and a dying scientist willing to go rogue in a foreign country where there is far less regulatory scrutiny. "It's a balancing act," says Jennifer Miller, a medical ethicist at New York University and president of Bioethics International. "You really need to protect participants but you also want access to safe therapies."
"Safety is important, but being too cautious kills people, too—allowing them to just die without intervention seems to be the biggest harm."
This requirement—that tests show a drug is safe and effective before it can win regulatory approval--dates back to 1962, when the sedative thalidomide was shown to have caused thousands of birth defects in Europe. But clinical trials can be costly and often proceed at a glacial pace. Typically, companies shell out more than $2.5 billion over the course of the decade it normally takes to shepherd a new treatment through the three phases of testing before it wins FDA approval, according to a 2014 study by the Tufts Center for the Study of Drug Development. Yet only 11.8 percent of experimental therapies entering clinical tests eventually cross the finish line.
The upshot is that millions can suffer and thousands of people may die awaiting approvals for life saving drugs, according to Elizabeth Parrish, the founder and CEO of BioViva, a Seattle-based biotech that aims to provide data collection platforms to scientists doing overseas tests. "Going offshore to places where it's legal to take a therapeutic can created expedited routes for patients to get therapies for which there is a high level of need," she says. "Safety is important, but being too cautious kills people, too—allowing them to just die without intervention seems to be the biggest harm."
Parrish herself was frustrated with the slow pace of gene therapy trials; scientists worried about the risks associated with fixing mutant DNA. To prove a point, she traveled to a clinic in Colombia in 2015 where she was injected with two gene therapies that aim to improve muscle function and lengthen telomeres, the caps on the end of chromosomes that are linked to aging and genetic diseases. Six months later, the therapy seemed to have worked—her muscle mass had increased and her telomeres had grown by 9 percent, the equivalent of turning back 20 years of aging, according to her own account. Yet the treatments are still unavailable here in the U.S.
In the past decade, Latin American countries like Columbia, and Mexico in particular, have become an increasingly attractive test destination for multi-national drug companies and biotechs because of less red tape.
In the past decade, Latin American countries like Columbia, and Mexico in particular, have become an increasingly attractive test destination for multi-national drug companies and biotechs because of less red tape around testing emerging new science, like gene therapies or stem cells. Plus, clinical trials are cheaper to conduct, it's easier to recruit volunteers, especially ones who are treatment naïve, and these human tests can reveal whether local populations actually respond to a particular therapy. "We do have an exhaustive framework for running clinical trials that are aligned with international requirements," says Ernesto Albaga, an attorney with Hogan Lovells in Mexico City who specializes in the life sciences. "But our environment is still not as stringent as it is in other places, like the U.S."
The fact is American researchers are increasingly testing experimental drugs outside of the U.S., although virtually all of them are monitored by local scientists who serve as co-investigators. In 2017 alone, more than 86 percent of experimental drugs seeking FDA approval have been tested, at least in part, in foreign countries, like Mexico, China, Russia, Poland and South Africa, according to an analysis by STAT. However, in places without strict oversight, such as Russia and Georgia, results may be fraudulent, according to one 2017 report in the New England Journal of Medicine. And in developing countries, the poor can become guinea pigs. In the early 2000s, for example, a test in Uganda of an AIDS drug resulted in thousands of unreported serious adverse reactions and 14 deaths; in India, eight volunteers died during a test of the anti-clotting drug, Streptokinase—and test subjects didn't even know they were part of a clinical trials.
Still, "the world is changing," concludes Dr. Jennifer Miller of NYU. "We need to figure out how to get safe and effective drugs to patients more quickly without sacrificing too much protection."
Is there a robot nanny in your child's future?
From ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. Copyright © 2024 by the author and reprinted by permission of St. Martin’s Publishing Group.
Could the use of robots take some of the workload off teachers, add engagement among students, and ultimately invigorate learning by taking it to a new level that is more consonant with the everyday experiences of young people? Do robots have the potential to become full-fledged educators and further push human teachers out of the profession? The preponderance of opinion on this subject is that, just as AI and medical technology are not going to eliminate doctors, robot teachers will never replace human teachers. Rather, they will change the job of teaching.
A 2017 study led by Google executive James Manyika suggested that skills like creativity, emotional intelligence, and communication will always be needed in the classroom and that robots aren’t likely to provide them at the same level that humans naturally do. But robot teachers do bring advantages, such as a depth of subject knowledge that teachers can’t match, and they’re great for student engagement.
The teacher and robot can complement each other in new ways, with the teacher facilitating interactions between robots and students. So far, this is the case with teaching “assistants” being adopted now in China, Japan, the U.S., and Europe. In this scenario, the robot (usually the SoftBank child-size robot NAO) is a tool for teaching mainly science, technology, engineering, and math (the STEM subjects), but the teacher is very involved in planning, overseeing, and evaluating progress. The students get an entertaining and enriched learning experience, and some of the teaching load is taken off the teacher. At least, that’s what researchers have been able to observe so far.
To be sure, there are some powerful arguments for having robots in the classroom. A not-to-be-underestimated one is that robots “speak the language” of today’s children, who have been steeped in technology since birth. These children are adept at navigating a media-rich environment that is highly visual and interactive. They are plugged into the Internet 24-7. They consume music, games, and huge numbers of videos on a weekly basis. They expect to be dazzled because they are used to being dazzled by more and more spectacular displays of digital artistry. Education has to compete with social media and the entertainment vehicles of students’ everyday lives.
Another compelling argument for teaching robots is that they help prepare students for the technological realities they will encounter in the real world when robots will be ubiquitous. From childhood on, they will be interacting and collaborating with robots in every sphere of their lives from the jobs they do to dealing with retail robots and helper robots in the home. Including robots in the classroom is one way of making sure that children of all socioeconomic backgrounds will be better prepared for a highly automated age, when successfully using robots will be as essential as reading and writing. We’ve already crossed this threshold with computers and smartphones.
Students need multimedia entertainment with their teaching. This is something robots can provide through their ability to connect to the Internet and act as a centralized host to videos, music, and games. Children also need interaction, something robots can deliver up to a point, but which humans can surpass. The education of a child is not just intended to make them technologically functional in a wired world, it’s to help them grow in intellectual, creative, social, and emotional ways. When considered through this perspective, it opens the door to questions concerning just how far robots should go. Robots don’t just teach and engage children; they’re designed to tug at their heartstrings.
It’s no coincidence that many toy makers and manufacturers are designing cute robots that look and behave like real children or animals, says Turkle. “When they make eye contact and gesture toward us, they predispose us to view them as thinking and caring,” she has written in The Washington Post. “They are designed to be cute, to provide a nurturing response” from the child. As mentioned previously, this nurturing experience is a powerful vehicle for drawing children in and promoting strong attachment. But should children really love their robots?
ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold (January 9, 2024).
St. Martin’s Publishing Group
The problem, once again, is that a child can be lulled into thinking that she’s in an actual relationship, when a robot can’t possibly love her back. If adults have these vulnerabilities, what might such asymmetrical relationships do to the emotional development of a small child? Turkle notes that while we tend to ascribe a mind and emotions to a socially interactive robot, “simulated thinking may be thinking, but simulated feeling is never feeling, and simulated love is never love.”
Always a consideration is the fact that in the first few years of life, a child’s brain is undergoing rapid growth and development that will form the foundation of their lifelong emotional health. These formative experiences are literally shaping the child’s brain, their expectations, and their view of the world and their place in it. In Alone Together, Turkle asks: What are we saying to children about their importance to us when we’re willing to outsource their care to a robot? A child might be superficially entertained by the robot while his self-esteem is systematically undermined.
Research has emerged showing that there are clear downsides to child-robot relationships.
Still, in the case of robot nannies in the home, is active, playful engagement with a robot for a few hours a day any more harmful than several hours in front of a TV or with an iPad? Some, like Xiong, regard interacting with a robot as better than mere passive entertainment. iPal’s manufacturers say that their robot can’t replace parents or teachers and is best used by three- to eight-year-olds after school, while they wait for their parents to get off work. But as robots become ever-more sophisticated, they’re expected to perform more of the tasks of day-to-day care and to be much more emotionally advanced. There is no question children will form deep attachments to some of them. And research has emerged showing that there are clear downsides to child-robot relationships.
Some studies, performed by Turkle and fellow MIT colleague Cynthia Breazeal, have revealed a darker side to the child-robot bond. Turkle has reported extensively on these studies in The Washington Post and in her book Alone Together. Most children love robots, but some act out their inner bully on the hapless machines, hitting and kicking them and otherwise trying to hurt them. The trouble is that the robot can’t fight back, teaching children that they can bully and abuse without consequences. As in any other robot relationship, such harmful behavior could carry over into the child’s human relationships.
And, ironically, it turns out that communicative machines don’t actually teach kids good communication skills. It’s well known that parent-child communication in the first three years of life sets the stage for a very young child’s intellectual and academic success. Verbal back-and-forth with parents and care-givers is like fuel for a child’s growing brain. One article that examined several types of play and their effect on children’s communication skills, published in JAMA Pediatrics in 2015, showed that babies who played with electronic toys—like the popular robot dog Aibo—show a decrease in both the quantity and quality of their language skills.
Anna V. Sosa of the Child Speech and Language Lab at Northern Arizona University studied twenty-six ten- to sixteen- month-old infants to compare the growth of their language skills after they played with three types of toys: electronic toys like a baby laptop and talking farm; traditional toys like wooden puzzles and building blocks; and books read aloud by their parents. The play that produced the most growth in verbal ability was having books read to them by a caregiver, followed by play with traditional toys. Language gains after playing with electronic toys came dead last. This form of play involved the least use of adult words, the least conversational turntaking, and the least verbalizations from the children. While the study sample was small, it’s not hard to extrapolate that no electronic toy or even more abled robot could supply the intimate responsiveness of a parent reading stories to a child, explaining new words, answering the child’s questions, and modeling the kind of back- and-forth interaction that promotes empathy and reciprocity in relationships.
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Most experts acknowledge that robots can be valuable educational tools. But they can’t make a child feel truly loved, validated, and valued. That’s the job of parents, and when parents abdicate this responsibility, it’s not only the child who misses out on one of life’s most profound experiences.
We really don’t know how the tech-savvy children of today will ultimately process their attachments to robots and whether they will be excessively predisposed to choosing robot companionship over that of humans. It’s possible their techno literacy will draw for them a bold line between real life and a quasi-imaginary history with a robot. But it will be decades before we see long-term studies culminating in sufficient data to help scientists, and the rest of us, to parse out the effects of a lifetime spent with robots.
This is an excerpt from ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. The book will be published on January 9, 2024.
Story by Big Think
In rare cases, a woman’s heart can start to fail in the months before or after giving birth. The all-important muscle weakens as its chambers enlarge, reducing the amount of blood pumped with each beat. Peripartum cardiomyopathy can threaten the lives of both mother and child. Viral illness, nutritional deficiency, the bodily stress of pregnancy, or an abnormal immune response could all play a role, but the causes aren’t concretely known.
If there is a silver lining to peripartum cardiomyopathy, it’s that it is perhaps the most survivable form of heart failure. A remarkable 50% of women recover spontaneously. And there’s an even more remarkable explanation for that glowing statistic: The fetus‘ stem cells migrate to the heart and regenerate the beleaguered muscle. In essence, the developing or recently born child saves its mother’s life.
Saving mama
While this process has not been observed directly in humans, it has been witnessed in mice. In a 2015 study, researchers tracked stem cells from fetal mice as they traveled to mothers’ damaged cardiac cells and integrated themselves into hearts.
Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Scientists also have spotted cells from the fetus within the hearts of human mothers, as well as countless other places inside the body, including the skin, spleen, liver, brain, lung, kidney, thyroid, lymph nodes, salivary glands, gallbladder, and intestine. These cells essentially get everywhere. While most are eliminated by the immune system during pregnancy, some can persist for an incredibly long time — up to three decades after childbirth.
This integration of the fetus’ cells into the mother’s body has been given a name: fetal microchimerism. The process appears to start between the fourth and sixth week of gestation in humans. Scientists are actively trying to suss out its purpose. Fetal stem cells, which can differentiate into all sorts of specialized cells, appear to target areas of injury. So their role in healing seems apparent. Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Sending cells into the mother’s body may also prime her immune system to grow more tolerant of the developing fetus. Successful pregnancy requires that the immune system not see the fetus as an interloper and thus dispatch cells to attack it.
Fetal microchimerism
But fetal microchimerism might not be entirely beneficial. Greater concentrations of the cells have been associated with various autoimmune diseases such as lupus, Sjogren’s syndrome, and even multiple sclerosis. After all, they are foreign cells living in the mother’s body, so it’s possible that they might trigger subtle, yet constant inflammation. Fetal cells also have been linked to cancer, although it isn’t clear whether they abet or hinder the disease.
A team of Spanish scientists summarized the apparent give and take of fetal microchimerism in a 2022 review article. “On the one hand, fetal microchimerism could be a source of progenitor cells with a beneficial effect on the mother’s health by intervening in tissue repair, angiogenesis, or neurogenesis. On the other hand, fetal microchimerism might have a detrimental function by activating the immune response and contributing to autoimmune diseases,” they wrote.
Regardless of a fetus’ cells net effect, their existence alone is intriguing. In a paper published earlier this year, University of London biologist Francisco Úbeda and University of Western Ontario mathematical biologist Geoff Wild noted that these cells might very well persist within mothers for life.
“Therefore, throughout their reproductive lives, mothers accumulate fetal cells from each of their past pregnancies including those resulting in miscarriages. Furthermore, mothers inherit, from their own mothers, a pool of cells contributed by all fetuses carried by their mothers, often referred to as grandmaternal microchimerism.”
So every mother may carry within her literal pieces of her ancestors.