A Shocking Medical Breakthrough Would Allow Anyone to Have a Biological Child
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
An emerging technology called in vitro gametogenesis would allow babies to be made from skin cells.
[Ed. Note: This is the third episode in our Moonshot series, which will explore four cutting-edge scientific developments that stand to fundamentally transform our world.]
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
Opioid prescription policies may hurt those in chronic pain
Guidelines aim to prevent opioid-related deaths by making it more challenging to get prescriptions, but they can also block access for those who desperately need them.
Tinu Abayomi-Paul works as a writer and activist, plus one unwanted job: Trying to fill her opioid prescription. She says that some pharmacists laugh and tell her that no one needs the amount of pain medication that she is seeking. Another pharmacist near her home in Venus, Tex., refused to fill more than seven days of a 30-day prescription.
To get a new prescription—partially filled opioid prescriptions can’t be dispensed later—Abayomi-Paul needed to return to her doctor’s office. But without her medication, she was having too much pain to travel there, much less return to the pharmacy. She rationed out the pills over several weeks, an agonizing compromise that left her unable to work, interact with her children, sleep restfully, or leave the house. “Don’t I deserve to do more than survive?” she says.
Abayomi-Paul’s pain results from a degenerative spine disorder, chronic lymphocytic leukemia, and more than a dozen other diagnoses and disabilities. She is part of a growing group of people with chronic pain who have been negatively impacted by the fallout from efforts to prevent opioid overdose deaths.
Guidelines for dispensing these pills are complicated because many opioids, like codeine, oxycodone, and morphine, are prescribed legally for pain. Yet, deaths from opioids have increased rapidly since 1999 and become a national emergency. Many of them, such as heroin, are used illegally. The CDC identified three surges in opioid use: an increase in opioid prescriptions in the ‘90s, a surge of heroin around 2010, and an influx of fentanyl and other powerful synthetic opioids in 2013.
As overdose deaths grew, so did public calls to address them, prompting the CDC to change its prescription guidelines in 2016. The new guidelines suggested limiting medication for acute pain to a seven-day supply, capping daily doses of morphine, and other restrictions. Some statistics suggest that these policies have worked; from 2016 to 2019, prescriptions for opiates fell 44 percent. Physicians also started progressively lowering opioid doses for patients, a practice called tapering. A study tracking nearly 100,000 Medicare subscribers on opioids found that about 13 percent of patients were tapering in 2012, and that number increased to about 23 percent by 2017.
But some physicians may be too aggressive with this tapering strategy. About one in four people had doses reduced by more than 10 percent per week, a rate faster than the CDC recommends. The approach left people like Abayomi-Paul without the medication they needed. Every year, Abayomi-Paul says, her prescriptions are harder to fill. David Brushwood, a pharmacy professor who specializes in policy and outcomes at the University of Florida in Gainesville, says opioid dosing isn’t one-size-fits-all. “Patients need to be taken care of individually, not based on what some government agency says they need,” he says.
‘This is not survivable’
Health policy and disability rights attorney Erin Gilmer advocated for people with pain, using her own experience with chronic pain and a host of medical conditions as a guidepost. She launched an advocacy website, Healthcare as a Human Right, and shared her struggles on Twitter: “This pain is more than anything I've endured before and I've already been through too much. Yet because it's not simply identified no one believes it's as bad as it is. This is not survivable.”
When her pain dramatically worsened midway through 2021, Gilmer’s posts grew ominous: “I keep thinking it can't possibly get worse but somehow every day is worse than the last.”
The CDC revised its guidelines in 2022 after criticisms that people with chronic pain were being undertreated, enduring dangerous withdrawal symptoms, and suffering psychological distress. (Long-term opioid use can cause physical dependency, an adaptive reaction that is different than the compulsive misuse associated with a substance use disorder.) It was too late for Gilmer. On July 7, 2021, the 38-year-old died by suicide.
Last August, an Ohio district court rulingset forth a new requirement for Walgreens, Walmart, and CVS pharmacists in two counties. These pharmacists must now document opioid prescriptions that are turned down, even for customers who have no previous purchases at that pharmacy, and they’re required to share this information with other locations in the same chain. None of the three pharmacies responded to an interview request from Leaps.org.
In a practice called red flagging, pharmacists may label a prescription suspicious for a variety of reasons, such as if a pharmacist observes an unusually high dose, a long distance from the patient’s home to the pharmacy, or cash payment. Pharmacists may question patients or prescribers to resolve red flags but, regardless of the explanation, they’re free to refuse to fill a prescription.
As the risk of litigation has grown, so has finger-pointing, says Seth Whitelaw, a compliance consultant at Whitelaw Compliance Group in West Chester, PA, who advises drug, medical device, and biotech companies. Drugmakers accused in National Prescription Opioid Litigation (NPOL), a complex set of thousands of cases on opioid epidemic deaths, which includes the Ohio district case, have argued that they shouldn’t be responsible for the large supply of opiates and overdose deaths. Yet, prosecutors alleged that these pharmaceutical companies hid addiction and overdose risks when labeling opioids, while distributors and pharmacists failed to identify suspicious orders or scripts.
Patients and pharmacists fear red flags
The requirements that pharmacists document prescriptions they refuse to fill so far only apply to two counties in Ohio. But Brushwood fears they will spread because of this precedent, and because there’s no way for pharmacists to predict what new legislation is on the way. “There is no definition of a red flag, there are no lists of red flags. There is no instruction on what to do when a red flag is detected. There’s no guidance on how to document red flags. It is a standardless responsibility,” Brushwood says. This adds trepidation for pharmacists—and more hoops to jump through for patients.
“I went into the doctor one day here and she said, ‘I'm going to stop prescribing opioids to all my patients effective immediately,” Nicolson says.
“We now have about a dozen studies that show that actually ripping somebody off their medication increases their risk of overdose and suicide by three to five times, destabilizes their health and mental health, often requires some hospitalization or emergency care, and can cause heart attacks,” says Kate Nicolson, founder of the National Pain Advocacy Centerbased in Boulder, Colorado. “It can kill people.” Nicolson was in pain for decades due to a surgical injury to the nerves leading to her spinal cord before surgeries fixed the problem.
Another issue is that primary care offices may view opioid use as a reason to turn down new patients. In a 2021 study, secret shoppers called primary care clinics in nine states, identifying themselves as long-term opioid users. When callers said their opioids were discontinued because their former physician retired, as opposed to an unspecified reason, they were more likely to be offered an appointment. Even so, more than 40 percent were refused an appointment. The study authors say their findings suggest that some physicians may try to avoid treating people who use opioids.
Abayomi-Paul says red flagging has changed how she fills prescriptions. “Once I go to one place, I try to [continue] going to that same place because of the amount of records that I have and making sure my medications don’t conflict,” Abayomi-Paul says.
Nicolson moved to Colorado from Washington D.C. in 2015, before the CDC issued its 2016 guidelines. When the guidelines came out, she found the change to be shockingly abrupt. “I went into the doctor one day here and she said, ‘I'm going to stop prescribing opioids to all my patients effective immediately.’” Since then, she’s spoken with dozens of patients who have been red-flagged or simply haven’t been able to access pain medication.
Despite her expertise, Nicolson isn’t positive she could successfully fill an opioid prescription today even if she needed one. At this point, she’s not sure exactly what various pharmacies would view as a red flag. And she’s not confident that these red flags even work. “You can have very legitimate reasons for being 50 miles away or having to go to multiple pharmacies, given that there are drug shortages now, as well as someone refusing to fill [a prescription.] It doesn't mean that you’re necessarily ‘drug seeking.’”
While there’s no easy solution. Whitelaw says clarifying the role of pharmacists and physicians in patient access to opioids could help people get the medication they need. He is seeking policy changes that focus on the needs of people in pain more than the number of prescriptions filled. He also advocates standardizing the definition of red flags and procedures for resolving them. Still, there will never be a single policy that can be applied to all people, explains Brushwood, the University of Florida professor. “You have to make a decision about each individual prescription.”
A company uses AI to fight muscle loss and unhealthy aging
In December 2022, a company called BioAge Labs published findings on a drug that worked to prevent muscular atrophy, or the loss of muscle strength and mass, in older people.
There’s a growing need to slow down the aging process. The world’s population is getting older and, according to one estimate, 80 million Americans will be 65 or older by 2040. As we age, the risk of many chronic diseases goes up, from cancer to heart disease to Alzheimer’s.
BioAge Labs, a company based in California, is using genetic data to help people stay healthy for longer. CEO Kristen Fortney was inspired by the genetics of people who live long lives and resist many age-related diseases. In 2015, she started BioAge to study them and develop drug therapies based on the company’s learnings.
The team works with special biobanks that have been collecting blood samples and health data from individuals for up to 45 years. Using artificial intelligence, BioAge is able to find the distinctive molecular features that distinguish those who have healthy longevity from those who don’t.
In December 2022, BioAge published findings on a drug that worked to prevent muscular atrophy, or the loss of muscle strength and mass, in older people. Much of the research on aging has been in worms and mice, but BioAge is focused on human data, Fortney says. “This boosts our chances of developing drugs that will be safe and effective in human patients.”
How it works
With assistance from AI, BioAge measures more than 100,000 molecules in each blood sample, looking at proteins, RNA and metabolites, or small molecules that are produced through chemical processes. The company uses many techniques to identify these molecules, some of which convert the molecules into charged atoms and then separating them according to their weight and charge. The resulting data is very complex, with many thousands of data points from patients being followed over the decades.
BioAge validates its targets by examining whether a pathway going awry is actually linked to the development of diseases, based on the company’s analysis of biobank health records and blood samples. The team uses AI and machine learning to identify these pathways, and the key proteins in the unhealthy pathways become their main drug targets. “The approach taken by BioAge is an excellent example of how we can harness the power of big data and advances in AI technology to identify new drugs and therapeutic targets,” says Lorna Harries, a professor of molecular genetics at the University of Exeter Medical School.
Martin Borch Jensen is the founder of Gordian Biotechnology, a company focused on using gene therapy to treat aging. He says BioAge’s use of AI allows them to speed up the process of finding promising drug candidates. However, it remains a challenge to separate pathologies from aspects of the natural aging process that aren’t necessarily bad. “Some of the changes are likely protective responses to things going wrong,” Jensen says. “Their data doesn’t…distinguish that so they’ll need to validate and be clever.”
Developing a drug for muscle loss
BioAge decided to focus on muscular atrophy because it affects many elderly people, making it difficult to perform everyday activities and increasing the risk of falls. Using the biobank samples, the team modeled different pathways that looked like they could improve muscle health. They found that people who had faster walking speeds, better grip strength and lived longer had higher levels of a protein called apelin.
Apelin is a peptide, or a small protein, that circulates in the blood. It is involved in the process by which exercise increases and preserves muscle mass. BioAge wondered if they could prevent muscular atrophy by increasing the amount of signaling in the apelin pathway. Instead of the long process of designing a drug, they decided to repurpose an existing drug made by another biotech company. This company, called Amgen, had explored the drug as a way to treat heart failure. It didn’t end up working for that purpose, but BioAge took note that the drug did seem to activate the apelin pathway.
BioAge tested its new, repurposed drug, BGE-105, and, in a phase 1 clinical trial, it protected subjects from getting muscular atrophy compared to a placebo group that didn’t receive the drug. Healthy volunteers over age 65 received infusions of the drug during 10 days spent in bed, as if they were on bed rest while recovering from an illness or injury; the elderly are especially vulnerable to muscle loss in this situation. The 11 people taking BGE-105 showed a 100 percent improvement in thigh circumference compared to 10 people taking the placebo. Ultrasound observations also revealed that the group taking the durg had enhanced muscle quality and a 73 percent increase in muscle thickness. One volunteer taking BGE-105 did have muscle loss compared to the the placebo group.
Heather Whitson, the director of the Duke University Centre for the study of aging and human development, says that, overall, the results are encouraging. “The clinical findings so far support the premise that AI can help us sort through enormous amounts of data and identify the most promising points for beneficial interventions.”
More studies are needed to find out which patients benefit the most and whether there are side effects. “I think further studies will answer more questions,” Whitson says, noting that BGE-105 was designed to enhance only one aspect of physiology associated with exercise, muscle strength. But exercise itself has many other benefits on mood, sleep, bones and glucose metabolism. “We don’t know whether BGE-105 will impact these other outcomes,” she says.
The future
BioAge is planning phase 2 trials for muscular atrophy in patients with obesity and those who have been hospitalized in an intensive care unit. Using the data from biobanks, they’ve also developed another drug, BGE-100, to treat chronic inflammation in the brain, a condition that can worsen with age and contributes to neurodegenerative diseases. The team is currently testing the drug in animals to assess its effects and find the right dose.
BioAge envisions that its drugs will have broader implications for health than treating any one specific disease. “Ultimately, we hope to pioneer a paradigm shift in healthcare, from treatment to prevention, by targeting the root causes of aging itself,” Fortney says. “We foresee a future where healthy longevity is within reach for all.”