Regenerative medicine has come a long way, baby
The field of regenerative medicine had a shaky start. In 2002, when news spread about the first cloned animal, Dolly the sheep, a raucous debate ensued. Scary headlines and organized opposition groups put pressure on government leaders, who responded by tightening restrictions on this type of research.
Fast forward to today, and regenerative medicine, which focuses on making unhealthy tissues and organs healthy again, is rewriting the code to healing many disorders, though it’s still young enough to be considered nascent. What started as one of the most controversial areas in medicine is now promising to transform it.
Progress in the lab has addressed previous concerns. Back in the early 2000s, some of the most fervent controversy centered around somatic cell nuclear transfer (SCNT), the process used by scientists to produce Dolly. There was fear that this technique could be used in humans, with possibly adverse effects, considering the many medical problems of the animals who had been cloned.
But today, scientists have discovered better approaches with fewer risks. Pioneers in the field are embracing new possibilities for cellular reprogramming, 3D organ printing, AI collaboration, and even growing organs in space. It could bring a new era of personalized medicine for longer, healthier lives - while potentially sparking new controversies.
Engineering tissues from amniotic fluids
Work in regenerative medicine seeks to reverse damage to organs and tissues by culling, modifying and replacing cells in the human body. Scientists in this field reach deep into the mechanisms of diseases and the breakdowns of cells, the little workhorses that perform all life-giving processes. If cells can’t do their jobs, they take whole organs and systems down with them. Regenerative medicine seeks to harness the power of healthy cells derived from stem cells to do the work that can literally restore patients to a state of health—by giving them healthy, functioning tissues and organs.
Modern-day regenerative medicine takes its origin from the 1998 isolation of human embryonic stem cells, first achieved by John Gearhart at Johns Hopkins University. Gearhart isolated the pluripotent cells that can differentiate into virtually every kind of cell in the human body. There was a raging controversy about the use of these cells in research because at that time they came exclusively from early-stage embryos or fetal tissue.
Back then, the highly controversial SCNT cells were the only way to produce genetically matched stem cells to treat patients. Since then, the picture has changed radically because other sources of highly versatile stem cells have been developed. Today, scientists can derive stem cells from amniotic fluid or reprogram patients’ skin cells back to an immature state, so they can differentiate into whatever types of cells the patient needs.
In the context of medical history, the field of regenerative medicine is progressing at a dizzying speed. But for those living with aggressive or chronic illnesses, it can seem that the wheels of medical progress grind slowly.
The ethical debate has been dialed back and, in the last few decades, the field has produced important innovations, spurring the development of whole new FDA processes and categories, says Anthony Atala, a bioengineer and director of the Wake Forest Institute for Regenerative Medicine. Atala and a large team of researchers have pioneered many of the first applications of 3D printed tissues and organs using cells developed from patients or those obtained from amniotic fluid or placentas.
His lab, considered to be the largest devoted to translational regenerative medicine, is currently working with 40 different engineered human tissues. Sixteen of them have been transplanted into patients. That includes skin, bladders, urethras, muscles, kidneys and vaginal organs, to name just a few.
These achievements are made possible by converging disciplines and technologies, such as cell therapies, bioengineering, gene editing, nanotechnology and 3D printing, to create living tissues and organs for human transplants. Atala is currently overseeing clinical trials to test the safety of tissues and organs engineered in the Wake Forest lab, a significant step toward FDA approval.
In the context of medical history, the field of regenerative medicine is progressing at a dizzying speed. But for those living with aggressive or chronic illnesses, it can seem that the wheels of medical progress grind slowly.
“It’s never fast enough,” Atala says. “We want to get new treatments into the clinic faster, but the reality is that you have to dot all your i’s and cross all your t’s—and rightly so, for the sake of patient safety. People want predictions, but you can never predict how much work it will take to go from conceptualization to utilization.”
As a surgeon, he also treats patients and is able to follow transplant recipients. “At the end of the day, the goal is to get these technologies into patients, and working with the patients is a very rewarding experience,” he says. Will the 3D printed organs ever outrun the shortage of donated organs? “That’s the hope,” Atala says, “but this technology won’t eliminate the need for them in our lifetime.”
New methods are out of this world
Jeanne Loring, another pioneer in the field and director of the Center for Regenerative Medicine at Scripps Research Institute in San Diego, says that investment in regenerative medicine is not only paying off, but is leading to truly personalized medicine, one of the holy grails of modern science.
This is because a patient’s own skin cells can be reprogrammed to become replacements for various malfunctioning cells causing incurable diseases, such as diabetes, heart disease, macular degeneration and Parkinson’s. If the cells are obtained from a source other than the patient, they can be rejected by the immune system. This means that patients need lifelong immunosuppression, which isn’t ideal. “With Covid,” says Loring, “I became acutely aware of the dangers of immunosuppression.” Using the patient’s own cells eliminates that problem.
Microgravity conditions make it easier for the cells to form three-dimensional structures, which could more easily lead to the growing of whole organs. In fact, Loring's own cells have been sent to the ISS for study.
Loring has a special interest in neurons, or brain cells that can be developed by manipulating cells found in the skin. She is looking to eventually treat Parkinson’s disease using them. The manipulated cells produce dopamine, the critical hormone or neurotransmitter lacking in the brains of patients. A company she founded plans to start a Phase I clinical trial using cell therapies for Parkinson’s soon, she says.
This is the culmination of many years of basic research on her part, some of it on her own cells. In 2007, Loring had her own cells reprogrammed, so there’s a cell line that carries her DNA. “They’re just like embryonic stem cells, but personal,” she said.
Loring has another special interest—sending immature cells into space to be studied at the International Space Station. There, microgravity conditions make it easier for the cells to form three-dimensional structures, which could more easily lead to the growing of whole organs. In fact, her own cells have been sent to the ISS for study. “My colleagues and I have completed four missions at the space station,” she says. “The last cells came down last August. They were my own cells reprogrammed into pluripotent cells in 2009. No one else can say that,” she adds.
Future controversies and tipping points
Although the original SCNT debate has calmed down, more controversies may arise, Loring thinks.
One of them could concern growing synthetic embryos. The embryos are ultimately derived from embryonic stem cells, and it’s not clear to what stage these embryos can or will be grown in an artificial uterus—another recent invention. The science, so far done only in animals, is still new and has not been widely publicized but, eventually, “People will notice the production of synthetic embryos and growing them in an artificial uterus,” Loring says. It’s likely to incite many of the same reactions as the use of embryonic stem cells.
Bernard Siegel, the founder and director of the Regenerative Medicine Foundation and executive director of the newly formed Healthspan Action Coalition (HSAC), believes that stem cell science is rapidly approaching tipping point and changing all of medical science. (For disclosure, I do consulting work for HSAC). Siegel says that regenerative medicine has become a new pillar of medicine that has recently been fast-tracked by new technology.
Artificial intelligence is speeding up discoveries and the convergence of key disciplines, as demonstrated in Atala’s lab, which is creating complex new medical products that replace the body’s natural parts. Just as importantly, those parts are genetically matched and pose no risk of rejection.
These new technologies must be regulated, which can be a challenge, Siegel notes. “Cell therapies represent a challenge to the existing regulatory structure, including payment, reimbursement and infrastructure issues that 20 years ago, didn’t exist.” Now the FDA and other agencies are faced with this revolution, and they’re just beginning to adapt.
Siegel cited the 2021 FDA Modernization Act as a major step. The Act allows drug developers to use alternatives to animal testing in investigating the safety and efficacy of new compounds, loosening the agency’s requirement for extensive animal testing before a new drug can move into clinical trials. The Act is a recognition of the profound effect that cultured human cells are having on research. Being able to test drugs using actual human cells promises to be far safer and more accurate in predicting how they will act in the human body, and could accelerate drug development.
Siegel, a longtime veteran and founding father of several health advocacy organizations, believes this work helped bring cell therapies to people sooner rather than later. His new focus, through the HSAC, is to leverage regenerative medicine into extending not just the lifespan but the worldwide human healthspan, the period of life lived with health and vigor. “When you look at the HSAC as a tree,” asks Siegel, “what are the roots of that tree? Stem cell science and the huge ecosystem it has created.” The study of human aging is another root to the tree that has potential to lengthen healthspans.
The revolutionary science underlying the extension of the healthspan needs to be available to the whole world, Siegel says. “We need to take all these roots and come up with a way to improve the life of all mankind,” he says. “Everyone should be able to take advantage of this promising new world.”
Social isolation. Strange pathogens outside. Strategic resource planning. Our Earthbound pandemic-driven social distancing could be mistaken for adapting to another, foreign planet. After all, we're donning all our protective apparel to go on an airplane or to the grocery store, nevertheless to just open our front door. Perhaps this is training for the world galactic visionaries Elon Musk, Jeff Bezos, and Richard Branson see in our future.
"There are parallels to the individual psychological experience, but from an operational standpoint, it is too different."
Ready to go live on Mars or something? Not so fast, experts say. The experience of shelter in place isn't parallel to being a space settler, or even an astronaut.
"Certain aspects are similar, but still, honestly, there are too many differences to say it preps us," says Angelo Vermeulen, co-founder of the art-science collective SEADS (Space Ecologies Art and Design) Network. In 2013, he served as a NASA crew commander for a four-month Mars-on-Earth mission, isolated in a geometric biodome with five others. "There are parallels to the individual psychological experience, but from an operational standpoint, it is too different. You don't need a spacesuit, aren't threatened by a thin atmosphere or worried about being overpowered by radiation."
Outside threats aside, we have a bigger experience gap: Most of us didn't see this pandemic coming and weren't trained to survive the current new normal. NASA astronauts get at least two years of basic training. We received none. Intergalactic explorers understand gravity, air pressure, and other important criteria based on decades of space knowledge. Alternatively, new novel coronavirus data is coming in real time, changing the threats, precautions, and needs dramatically. Things feel a little different when you're winging it.
Lastly, with respect to Apollo 13, space travelers have a timeline for when their experience will be over. There are mishaps, challenges and adjustments, but every well-supported journeyperson leaves Earth with an agenda (and a team back home to help keep them on track).
The pandemic, on the other hand, has no definitive end. It is unclear when a reliable vaccine will be readily available. It is also not known how long we should shelter-in-place, as pulling the trigger too early could bring another wave of illness. We are missing definitive milestones, which, Vermeulen says, would make our isolation experience easier to navigate. "When you're on a mission, the end date is always on the horizon. You can celebrate the midpoint and check off major milestones, which helps."
Also, unlike a kid pretending to be in a rocket, most of us didn't dream of one day being socially isolated for an indeterminate amount of time. "If you're ambitious and working in the field, then it is your goal in life to experience [space and the related isolation]," he says. "With the pandemic, though, nobody chose to do this."
[Editor's Note: This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online.]
Neil deGrasse Tyson Wants Celebrities to Promote Scientists
"President Kennedy was the first president to not wear a hat. Have you seen men wearing hats since then?" Neil deGrasse Tyson, one of the world's few astrophysicists with a household name, asks on the phone from his car. Well, no. "If I wear some cowboy hats, it's because it's the outfit, it's not because that's my standard equipment when I leave the home."
"We have classes on 100 things and none of them are on the ability to distinguish what is true and what is not."
But Tyson, who speaks in methodically reasoned paragraphs with lots of semi-rhetorical questions to make sure we're all still listening, isn't really making a point about Mad Men-era men's clothing trends. "Should a president influence fashion?" he says. "I think people sometimes don't know the full power they have over other people. So, that's the first prong in this comment. My second prong is, why would anyone take medical advice from a politician?"
Days before our conversation, news broke that President Trump said he was taking hydroxychloroquine, which he had hyped for months as a surefire magical cure for COVID-19 — the science just hadn't caught up to his predictions. But the science never did catch up; instead, it went the opposite direction, showing that hydroxychloroquine, when used to treat COVID-19 patients, actually led to an increased risk of death.
Alarm spread swiftly around the globe as experts cast the president's professed self-medicating as illogical and dangerous. However, it was just one of a series of wild pieces of medical advice espoused by Trump from his mighty pulpit, like that, hey, maybe disinfectants could cure people when injected into their bodies. (That also leads to death.)
But people do take medical advice from politicians. An Arizona man afraid of COVID-19 died after consuming chloroquine phosphate, which he and his wife had sitting on the back of a shelf after using it to treat koi fish for parasites. The pandemic has exposed many weaknesses in the feedback loop of society, government, the media, and science, including the difficulty of seeding accurate medical information with the masses. Many on the left and right decry a broken political and news media system, but Tyson believes the problem isn't mega-influencers like Trump. Rather it's the general public's desire to take their advice on complex topics – like the science of virology – that such influencers know nothing about.
Tyson's not upset with the public, who follow Trump's advice. "As an educator, I can't get angry with you," he says. Or even Trump himself. "Trump was elected by 60 million people, right? So, you could say all you want about Trump, kick him out of office, whatever. [There's] still the 60 million fellow Americans who walk among us who voted for him. So, what are you going to do with them?"
Tyson also isn't upset with Facebook, Twitter, and other social platforms that serve as today's biggest conduits for misinformation. After all, in the realm of modern media's history, these networks are tadpoles. "As an educator and as a scientist, I'm leaning towards, let's figure out a way to train people in school to not fall victim to false information, and how to judge what is likely to be false relative to what is likely to be true. And that's hard, but you and I have never had a class in that, have we? We've had biology classes, we've had English lit, we've had classes on Shakespeare — we have classes on 100 things and none of them are on the ability to distinguish what is true and what is not."
This is why Tyson himself doesn't engage in Trump bashing on his social feeds, but does try to get people to differentiate factual science from fake news. "I feel responsibility to participate in the enlightenment of culture and of civilization, because I have that access," says Tyson, who has 13.9M followers on Twitter, 1.2M on Instagram, and 4.2M on Facebook. He doesn't tell his followers not to inject themselves with Clorox ("no one likes being told what to do"), but tries to get them to visualize a pandemic's impact by comparing it to, say, a throng of rabbits.
"Left unchecked, 1,000 rabbits in 5 years, become 7-billion, the human population of the World. After 15 years, a 'land-ocean' of rabbits fills to one-kilometer depth across all of Earth's continents. Viruses can reproduce waaaay faster than Rabbits," he tweeted on April 6, after much of the nation had locked down to slow the pandemic's spread. For added viral impact, he attached a photo of an adorable, perhaps appropriately scared-looking, white bunny.
Of course, not all celebrities message responsibly.
Tyson is a rare scientist-turned-celebrity. His appeal isn't acting in movies or singing dance-pop anthems (if only). Rather, his life's work is making science fun and interesting to as many people as possible through his best-selling books on astrophysics and his directorship of the planetarium at the American Museum of Natural History in New York. His longstanding place in popular culture is an exception, not the rule.
And he believes his fellow celebrities, actors and pop music stars and internet influencers, should aid the public's quest for accurate scientific information. And in order to do that, they must point their followers to experts and organizations who know what they're talking about. "It could be to a website, it could be to a talk that was given. I would say that that's where the responsibility lies if you control the interests of a million people," he says.
One example of this is Lady Gaga's March 14 Instagram of herself on her couch with her three dogs with the caption, "So I talked to some doctors and scientists. It's not the easiest for everyone right now but the kindest/healthiest thing we can do is self-quarantine and not hang out with people over 65 and in large groups. I wish I could see my parents and grandmas right now but it's much safer to not so I don't get them sick in case I have it. I'm hanging at home with my dogs." (All the celebrities here in this article are my references, not Tyson's, who does not call out specific people.)
Of course, not all celebrities message responsibly. Jessica Biel and Jenny McCarthy have faced scorn for public stances against vaccines. Gwyneth Paltrow and her media brand GOOP have faced backlash for promoting homeopathic treatments with no basis in science.
"The New Age Movement is a cultural idea, it has nothing to do with religion, has nothing to do with politics, and it's people who were rejecting objectively established science in part or in total because they have a belief system that they want to attach to it, okay? This is how you get the homeopathic remedies," says Tyson. "That's why science exists, so that we don't have to base decisions on belief systems."
[Editor's Note: This article was originally published on June 8th, 2020 as part of a standalone magazine called GOOD10: The Pandemic Issue. Produced as a partnership among LeapsMag, The Aspen Institute, and GOOD, the magazine is available for free online.]