Regenerative medicine has come a long way, baby
After a cloned baby sheep, what started as one of the most controversial areas in medicine is now promising to transform it.
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.”
Podcast: The Friday Five weekly roundup in health research
Scientists have designed a phone app that could alert consumers to high levels of cancer-causing chemicals, Yale researchers revive organs in dead pigs, and more in this week's Friday Five.
The Friday Five covers five stories in health research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Listen to the Episode
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Covered in this week's Friday Five:
- A new blood test for cancer
- Patches of bacteria can use your sweat to power electronic devices
- Researchers revive organs of dead pigs
- Phone apps detects cancer-causing chemicals in foods
- Stem cells generate "synthetic placentas" in mice
Plus, an honorable mention for early research involving vitamin K and Alzheimer's
The limits of digital privacy are becoming clearer in the post-Dobbs era, as a wide range of data sources can reveal online and offline activities, including whether a woman seeks an abortion.
Since the recent reversal of Roe v. Wade — the landmark decision establishing a constitutional right to abortion — the vulnerabilities of reproductive health data and various other information stored on digital devices or shared through the Web have risen to the forefront.
Menstrual period tracking apps are an example of how technologies that collect information from users could be weaponized against abortions seekers. The apps, which help tens of millions of users in the U.S. predict when they’re ovulating, may provide evidence that leads to criminal prosecution in states with abortion bans, says Anton T. Dahbura, executive director of the Johns Hopkins University Information Security Institute. In states where abortion is outlawed, “it’s probably best to not use a period tracker,” he says.
Following the Dobbs v. Jackson ruling in late June that overturned Roe, even women who suffered a miscarriage could be suspected of having an abortion in some cases. While using these apps in anonymous mode may appear more secure, “data is notoriously difficult to perfectly anonymize,” Dahbura says. “Whether the data are stored on the user’s device or in the cloud, there are ways to connect that data to the user.”
Completely concealing one’s tracks in cyberspace poses enormous challenges. Digital forensics can take advantage of technology such as GPS apps, security cameras, license plate trackers, credit card transactions and bank records to reconstruct a person’s activities,” Dahbura says. “Abortion service providers are also in a world of risk for similar reasons.”
Practicing “good cyber hygiene” is essential. That’s particularly true in states where private citizens may be rewarded for reporting on women they suspect of having an abortion, such as Texas, which passed a so-called bounty hunter law last fall. To help guard against hacking, Dahbura suggests using strong passwords and two-factor authentication when possible while remaining on alert for phishing scams on email or texts.
Another option for safeguarding privacy is to avoid such apps entirely, but that choice will depend on an individual’s analysis of the risks and benefits, says Leah Fowler, research assistant professor at the University of Houston Law Center, Health Law & Policy Institute.
“These apps are popular because people find them helpful and convenient, so I hesitate to tell anyone to get rid of something they like without more concrete evidence of its nefarious uses,” she says. “I also hate the idea that asking anyone capable of becoming pregnant to opt out of all or part of the digital economy could ever be a viable solution. That’s an enormous policy failure. We have to do better than that.”
The potential universe of abortion-relevant data can include information from a variety of fitness and other biometric trackers, text and social media chat records, call details, purchase histories and medical insurance records.
Instead, Fowler recommends that concerned consumers read the terms of service and privacy policies of the apps they’re using. If some of the terms are unclear, she suggests emailing customer service with questions until the answers are satisfactory. It’s also wise for consumers to research products that meet their specific needs and find out whether other women have raised concerns about specific apps. Users interested in more privacy may want to switch to an app that stores data locally, meaning the data stays on your device, or does not use third-party tracking, so the app-maker is the only company with access to it, she says.
Period tracking apps can be useful for those on fertility journeys, making it easier to store information digitally than on paper charts. But users may want to factor in whether they live in a state with an anti-abortion stance and run the risk of legal issues due to a potential data breach, says Carmel Shachar, executive director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard Law School.
Consumers’ risks extend beyond period tracking apps in the post-Roe v. Wade era. “Anything that creates digital breadcrumbs to your reproductive choices and conduct could raise concerns — for example, googling ‘abortion providers near me’ or texting your best friend that you are pregnant but do not want to be,” Shachar says. Women also could incriminate themselves by bringing their phones, which may record geolocation data, to the clinic with them.
The potential universe of abortion-relevant data can include information from a variety of fitness and other biometric trackers, text and social media chat records, call details, purchase histories and medical insurance records, says Rebecca Wexler, faculty co-director of the Berkeley Center for Law & Technology. “These data sources can reveal a pregnant person’s decision to seek or obtain an abortion, as well as reveal a healthcare provider’s provision of abortion services and anyone else’s provision of abortion assistance,” she says.
In some situations, people or companies could inadvertently expose themselves to risk after posting on social media with offers of places for abortion seekers to stay after traveling from states with bans. They could be liable for aiding and abetting abortion. At this point, it’s unclear whether states that ban abortion will try to prosecute residents who seek abortions in other states without bans.
Another possibility is that a woman seeking an abortion will be prosecuted based not only on her phone’s data, but also on the data that law enforcement finds on someone else’s device or a shared computer. As a result, “people in one household may find themselves at odds with each other,” says K Royal, faculty fellow at the Center for Law, Science, and Innovation at Arizona State University’s Sandra Day O'Connor College of Law. “This is a very delicate situation.”
Individuals and corporate executives should research their options before leaving a digital footprint. “Guard your privacy carefully, whether you are seeking help or you are seeking to help someone,” Royal says. While she has come across recommendations from other experts who suggest carrying a second phone that is harder to link a person’s identity for certain online activities, “it’s not practical on a general basis.”
The privacy of this health data isn’t fully protected by the law because period trackers, texting services and other apps are not healthcare providers — and as a result, there’s no prohibition on sharing the information with a third party under the Health Insurance Portability and Accountability Act of 1996, says Florencia Marotta-Wurgler, a professor who specializes in online consumer contracts and data privacy at the NYU School of Law.
“So, as long as there is valid consent, then it’s fair game unless you say that it violates the reasonable expectations of consumers,” she says. “But this is pretty unchartered territory at the moment.”
As states implement laws granting anyone the power to report suspected or known pregnancies to law enforcement, anti-choice activists are purchasing reproductive health data from companies that make period apps, says Rebecca Herold, chief executive officer of Privacy & Security Brainiacs in Des Moines, Iowa, and a member of the Emerging Trends Working Group at ISACA, an association focused on information technology governance. They could also buy data on search histories and make it available in places like Texas for “bounty hunters” to find out which women have searched for information about abortions.
Some groups are creating their own apps described as providing general medical information on subjects such as pregnancy health. But they are “ultimately intended to ‘catch’ women” — to identify those who are probably pregnant and dissuade them from having an abortion, to launch harassment campaigns against them, or to report them to law enforcement, anti-choice groups and others in states where such prenatal medical care procedures are now restricted or prohibited, Herold says.
In addition to privacy concerns, the reversal of Roe v. Wade raises censorship issues. Facebook and Instagram have started to remove or flag content, particularly as it relates to providing the abortion pill, says Michael Kleinman, director of the Silicon Valley Initiative at Amnesty International USA, a global organization that promotes human rights.
Facebook and Instagram have rules that forbid private citizens from buying, selling or giving away pharmaceuticals, including the abortion pill, according to a social media post by a communications director for Meta, which owns both platforms. In the same post, though, the Meta official noted that the company’s enforcement of this rule has been “incorrect” in some cases.
“It’s terrifying to think that arbitrary decisions by these platforms can dramatically limit the ability of people to access critical reproductive rights information,” Kleinman says. However, he adds, “as it currently stands, the platforms make unilateral decisions about what reproductive rights information they allow and what information they take down.”