How to tame a restless genome

Short pieces of DNA — jumping genes — can bounce from one place to another in our genomes. When too many DNA fragments move around, cancer, infertility, and other problems can arise. Cold Spring Harbor Laboratory (CSHL) Professor & HHMI Investigator Leemor Joshua-Tor and a research investigator in her lab, Jonathan Ipsaro, study how cells safeguard the genome’s integrity and immobilize these restless bits of DNA. They found that one of the jumping genes’ most needed resources may also be their greatest vulnerability.
The mammalian genome is full of genetic elements that have the potential to move from place to place. One type is an LTR retrotransposon (LTR). In normal cells, these elements don’t move much. But if something happens to allow them to move, say during sexual reproduction or in cancerous cells Joshua-Tor says:
“Sometimes they jump into very important spots, either genes themselves or in areas of the genome that is important for regulating genes.”
In this study, Joshua-Tor and Ipsaro examined a mouse protein called Asterix/Gtsf1 that immobilizes LTRs. To understand how this protein locks down LTRs, Ipsaro used several techniques, including cryo-EM, to take a closer look at the protein structure. Joshua-Tor says:
“Structure just informs us in many ways, like how things work. If you can see something, you have a way better idea of how it works.”
Ipsaro found Asterix/Gtsf1 binds directly to a particular class of RNA called transfer RNA (tRNA). tRNAs normally are part of the cell’s protein manufacturing machinery. LTRs have borrowed that part of the protein-making machinery to replicate their genetic material. Asterix/Gtsf1 overrides what the LTRs are trying to do by freezing the otherwise mobile element in place, shutting down their ability to move. Ipsaro says:
“It’s trying to copy and paste itself all over the genome. A part of it evolutionarily has depended on tRNA binding in order to replicate.”
Instead of freezing the entire genome, scientists think Asterix/Gtf1 is using tRNAs to suppress small specific regions, like LTRs. Researchers are trying to figure out how cells protect themselves against these and other types of mobile genetic elements. They hope that someday they might tame an overly restless genome, preventing new mutations in the germline and in tumors.
Story Source:
Materials provided by Cold Spring Harbor Laboratory. Original written by Luis Sandoval. Note: Content may be edited for style and length.

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Vaccinated Mothers Are Trying to Give Babies Antibodies via Breast Milk

Multiple studies show that there are antibodies in a vaccinated mother’s milk. This has led some women to try to restart breastfeeding and others to share milk with friends’ children.As soon as Courtney Lynn Koltes returned home from her first Covid-19 vaccine appointment, she pulled out a breast pump. She had quit breastfeeding her daughter about two months earlier because of a medication conflict. But she was off those pills, and she had recently stumbled across research suggesting that antibodies from a vaccinated mother could be passed to her baby through milk.Getting the milk flowing again — a process known as relactation — would not be easy. She planned to pump on every odd-numbered hour from 7 a.m. to 11 p.m. But Ms. Koltes and her husband were eager to finally introduce their 4-month-old daughter to family members, and with children not yet eligible for vaccination, she was willing to try.“I am starting to see very slow progress, so it is all worth it if it means I can protect her,” Ms. Koltes, who lives in Orange County, Calif., said last week — nine days after receiving her first dose of the Pfizer-BioNTech vaccine.Partly because it’s so physically taxing, relactation is not common. (Medication is often also involved.) But over the past few weeks, online forums focused on relactation have been swarmed with newly vaccinated mothers like Ms. Koltes. Some had stopped breastfeeding their children more than a year earlier.“I’m glad I’m not the only one here trying to relactate for this reason!” one woman wrote in a lively thread in a private Facebook group.“Go team vaccine!” another wrote.In stark contrast, other parenting and breastfeeding forums have been simmering with worries that breast milk from a newly vaccinated mother could be dangerous. It’s not only vaccine skeptics who have been encouraging those fears, which researchers say are unfounded: Some pediatricians and vaccine administrators have been urging nursing mothers to dump their milk after they are vaccinated.So which is it? Is breast milk from a vaccinated person a sort of elixir capable of staving off Covid? And if so, are the newly vaccinated mothers sneaking breast milk into older children’s cereal or sharing their extra milk with friends’ babies onto something? Or should nursing mothers hold off on getting vaccinated?The answer, six researchers agreed, is that newly vaccinated mothers are right to feel as if they have a new superpower. Multiple studies show that their antibodies generated after vaccination can, indeed, be passed through breast milk. As with so much to do with the coronavirus, more research would be beneficial. But there is no concrete reason for new mothers to hold off on getting vaccinated or to dump out their breast milk, they said.Does ‘vaccinated breast milk’ contain antibodies?Yes, study after study shows it does contain antibodies. How exactly these antibodies protect the infant from Covid is not yet clear.Rebecca Powell, left, and her research team have collected breast milk samples for analysis at their Mount Sinai hospital lab.James Estrin/The New York TimesIn the first nine months of the pandemic, around 116 million babies were born worldwide, according to Unicef estimates. This left researchers scrambling to answer a critical question: Could the virus be transmitted through breast milk? Some people assumed it could. But as several groups of researchers tested the milk, they found no traces of virus, only antibodies — suggesting that drinking the milk could protect babies from infection.The next big question for breast milk researchers was whether the protective benefits of a Covid vaccine could be similarly passed to babies. None of the vaccine trials included pregnant or breastfeeding women, so researchers had to find lactating women who qualified for the first vaccine rollout.Through a Facebook group, Rebecca Powell, a human milk immunologist at the Icahn School of Medicine at Mount Sinai in Manhattan, found hundreds of doctors and nurses willing to periodically share their breast milk. In her most recent study, which has not been formally published, she analyzed the milk of six women who had received the Pfizer-BioNTech vaccine and four who had received the Moderna vaccine, 14 days after the women had received their second shots. She found significant numbers of one particular antibody, called IgG, in all of them. Other researchers have had similar results.“There is reason to be excited,” said Dr. Kathryn Gray, a maternal fetal medicine specialist at Brigham and Women’s Hospital in Boston, who has conducted similar studies. “We’d presume that could confer some level of protection.”But how do we know for sure? One way to test this — exposing those babies to the virus — is, of course, unethical. Instead, some researchers have tried to answer the question by studying the antibodies’ properties. Are they neutralizing, meaning they prevent the virus from infecting human cells?In a draft of a small study, one Israeli researcher found that they were. “Breast milk has the capacity to prevent viral dissemination and block the ability of the virus to infect host cells that will result in illness,” Yariv Wine, an applied immunologist at Tel Aviv University, wrote in an email.Research is too premature for vaccinated mothers who are breastfeeding to act as if their babies can’t get infected, however, said Dr. Kirsi Jarvinen-Seppo, the chief of pediatric allergy and immunology at the University of Rochester Medical Center. Dr. Jarvinen-Seppo has been conducting similar studies. “There is no direct evidence that the Covid antibodies in breast milk are protecting the infant — only pieces of evidence suggesting that could be the case,” she said.How long might protection last?As long as the baby is consuming the antibody-containing breast milk.Destiny Burgess’s twins were born prematurely. Ms. Burgess and her husband are back at work in Asheville, N.C. One of their older children is in kindergarten. Two are in day care. All of that makes Ms. Burgess worried for her now 3-month-old babies.When a vaccinated friend offered to share some of her milk with the twins, she accepted.“I feel like I have this newfound superpower,” that friend, Olivia de Soria, said. Along with feeding her own 4-month-old and sneaking a bit of her milk into her 3-year-old’s chocolate milk, Ms. de Soria is now sharing her milk with five other families.“They can’t get the shot, so this is giving me a little peace of mind,” said Ms. Burgess. She does wonder, though, how much “vaccinated milk” would be needed to make a dent.The unsatisfying answer is that it’s not clear. What researchers agree on is that a baby who consumes breast milk all day long is more likely to be protected than one who gets just an occasional drop e. But none scoffed at the idea of giving a bit to older children if it’s not a hassle.They also agree that breast milk’s protective benefits work more like a pill that you must take every day than a shot that lasts a decade. This short-term defense — known as “passive protection” — may only last hours or days from the baby’s last “dose,” Dr. Powell said.“It’s not the same as the baby getting vaccinated,” she added.That means “as soon as you stop feeding that breast milk, there is no protection — period,” said Antti Seppo, another breast milk researcher at the University of Rochester Medical Center. Dr. Seppo also found that it took about two weeks after the first shot for the antibodies to show up in the milk and that they peaked after the second shot.How do we know ‘vaccinated breast milk’ is safe?Researchers say they know enough about how vaccines generally affect breast milk not to be concerned.Multiple researchers involved in research on breast milk and the Covid vaccine offered slight variations of the same opinion. “There is no reason to think there is anything about this vaccine that would cause it to be harmful, and there’s reason to believe it would be beneficial,” said Christina Chambers, co-director of the Center for Better Beginnings at the University of California, San Diego.So why are parenting forums brimming with anecdotes about pediatricians telling mothers to wait to get vaccinated until their baby is older or to dump their milk after vaccination? Mostly because lactating mothers were not included in vaccine trials, so researchers have not been able to concretely study risks.But researchers’ confidence that breast milk from Covid-19-vaccinated mothers is safe comes from what is known broadly about how vaccines work.“Unlike pregnancy, where there are theoretical safety concerns, there really aren’t concerns about lactation and vaccination,” said Dr. Kathryn Gray, a maternal fetal medicine specialist at Brigham and Women’s Hospital in Boston.Both the Moderna and the Pfizer-BioNTech products are mRNA vaccines. “The ingredients in the vaccine are mRNA molecules that have a short lifetime and have no way of making their way into milk,” Dr. Seppo said.So is relactation really worth all the effort?Maybe not, one initially enthusiastic mother decides.Nearly two weeks in, Ms. Koltes of Orange County was managing to pump only a few drops of breast milk each session. An email exchange with her pediatrician reinforced that she could not be sure — even if she got the milk flowing — that allowing unmasked, unvaccinated relatives to hold her daughter was safe. She applauded other women having more success with relactation. But for her, that was it.“It does feel like a weight is lifted,” she said of quitting her rigorous pumping schedule. Now all that’s left to do is wait for an actual vaccine for her daughter, she said. Both Pfizer and Moderna have recently begun testing their vaccines on babies as young as 6 months old.

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Biologists create better method to culture cells for testing drug toxicity

When a new drug is being developed, the first question is, “Does it work?” The second question is, “Does it do harm?” No matter how effective a therapy is, if it harms the patient in the process, it has little value.
Doctoral student Robert Skolik and Associate Professor Michael Menze, Ph.D., in the Department of Biology at the University of Louisville, have found a way to make cell cultures respond more closely to normal cells, allowing drugs to be screened for toxicity earlier in the research timeline.
The vast majority of cells used for biomedical research are derived from cancer tissues stored in biorepositories. They are cheap to maintain, easy to grow and multiply quickly. Specifically, liver cancer cells are desirable for testing the toxicity of drugs for any number of diseases.
“You like to use liver cells because this is the organ that would detoxify whatever drug for whatever treatment you are testing,” Menze said. “When new drugs are being developed for diabetes or another disease, one of the concerns is whether they are toxic to the liver.”
The cells do come with limitations, however. Since they are cancer cells, they may not be as sensitive to toxins as normal cells, so they may not reveal issues with toxicity that can appear much later in the drug testing process.
Skolik and Menze have discovered that by changing two components of the media used to culture the cells, they can make liver cancer cells behave more like normal liver cells. Rather than using standard serum containing glucose, they used serum from which the glucose had been removed using dialysis and added galactose — a different form of sugar — to the media. The tumor cells metabolize galactose at a much slower rate than glucose. This changes the metabolism of the cells making them behave more like normal liver cells.

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Parkinson's, cancer, type 2 diabetes share a key element that drives disease

When cells are stressed, chemical alarms go off, setting in motion a flurry of activity that protects the cell’s most important players. During the rush, a protein called Parkin hurries to protect the mitochondria, the power stations that generate energy for the cell. Now Salk researchers have discovered a direct link between a master sensor of cell stress and Parkin itself. The same pathway is also tied to type 2 diabetes and cancer, which could open a new avenue for treating all three diseases.
“Our findings represent the earliest step in Parkin’s alarm response that anyone’s ever found by a long shot. All the other known biochemical events happen at one hour; we’ve now found something that happens within five minutes,” says Professor Reuben Shaw, director of the NCI-designated Salk Cancer Center and senior author of the new work, detailed in Science Advances on April 7, 2021. “Decoding this major step in the way cells dispose of defective mitochondria has implications for a number of diseases.”
Parkin’s job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson’s disease, making the protein unable to clear away damaged mitochondria. While scientists have known for some time that Parkin somehow senses mitochondrial stress and initiates the process of mitophagy, no one understood exactly how Parkin was first sensing problems with the mitochondria — Parkin somehow knew to migrate to the mitochondria after mitochondrial damage, but there was no known signal to Parkin until after it arrived there.
Shaw’s lab, which is well known for their work in the fields of metabolism and cancer, spent years intensely researching how the cell regulates a more general process of cellular cleaning and recycling called autophagy. About ten years ago, they discovered that an enzyme called AMPK, which is highly sensitive to cellular stress of many kinds, including mitochondrial damage, controls autophagy by activating an enzyme called ULK1.
Following that discovery, Shaw and graduate student Portia Lombardo began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit. They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants — first AMPK, then ULK1, then Parkin — was so surprising that Shaw could scarcely believe it.
To confirm the findings were correct, the team used mass spectrometry to reveal precisely where ULK1 was attaching a phosphate group to Parkin. They found that it landed in a new region other researchers had recently found to be critical for Parkin activation but hadn’t known why. A postdoctoral fellow in Shaw’s lab, Chien-Min Hung, then did precise biochemical studies to prove each aspect of the timeline and delineated which proteins were doing what, and where. Shaw’s research now begins to explain this key first step in Parkin activation, which Shaw hypothesizes may serve as a “heads-up” signal from AMPK down the chain of command through ULK1 to Parkin to go check out the mitochondria after a first wave of incoming damage, and, if necessary, trigger destruction of those mitochondria that are too gravely damaged to regain function.
The findings have wide-ranging implications. AMPK, the central sensor of the cell’s metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, as established by Shaw in prior work, and it is activated by a type 2 diabetes drug called metformin. Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever “anti-aging” therapeutics in clinical trials.
“The big takeaway for me is that metabolism and changes in the health of your mitochondria are critical in cancer, they’re critical in diabetes, and they’re critical in neurodegenerative diseases,” says Shaw, who holds the William R. Brody Chair. “Our finding says that a diabetes drug that activates AMPK, which we previously showed can suppress cancer, may also help restore function in patients with neurodegenerative disease. That’s because the general mechanisms that underpin the health of the cells in our bodies are way more integrated than anyone could have ever imagined.”
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Materials provided by Salk Institute. Note: Content may be edited for style and length.

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New test to study language development in youth with Down syndrome

Expressive language sampling (ELS) is a useful tool for measuring communication development in youth with Down syndrome, a new multi-site study has found.
The study, co-led by Angela Thurman and Leonard Abbeduto from the UC Davis MIND Institute and the Department of Psychiatry and Behavioral Sciences, focused on language as an outcome measure to detect meaningful changes in communication skills of individuals with Down syndrome. It successfully tested and validated ELS as a reliable set of procedures for collecting, measuring and analyzing the spoken language of participants interacting in a naturalistic setting.
Down syndrome and language delays
Down syndrome is the leading genetic cause of intellectual disability. Approximately one in every 700 babies in the United States is born with Down syndrome. Individuals with Down syndrome frequently have speech and language delays that might severely affect their independence and successful community inclusion.
“Interventions leading to improvements in language would have great impacts on the quality of life of individuals with Down syndrome,” said Abbeduto, director of the UC Davis MIND Institute, professor of psychiatry and behavioral sciences and senior author of the study. “To develop and evaluate such interventions, we need a validated measurement tool and ELS provides that.”
The ELS procedure
During the ELS procedure, researchers collect samples of participants’ speech during two types of natural interactions: conversation and narration.

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Blood test for depression, bipolar disorder

Worldwide, 1 in 4 people will suffer from a depressive episode in their lifetime.
While current diagnosis and treatment approaches are largely trial and error, a breakthrough study by Indiana University School of Medicine researchers sheds new light on the biological basis of mood disorders, and offers a promising blood test aimed at a precision medicine approach to treatment.
Led by Alexander B. Niculescu, MD, PhD, Professor of Psychiatry at IU School of Medicine, the study was published today in the high impact journal Molecular Psychiatry . The work builds on previous research conducted by Niculescu and his colleagues into blood biomarkers that track suicidality as well as pain, post-traumatic stress disorder and Alzheimer’s disease.
“We have pioneered the area of precision medicine in psychiatry over the last two decades, particularly over the last 10 years. This study represents a current state-of-the-art outcome of our efforts,” said Niculescu. “This is part of our effort to bring psychiatry from the 19th century into the 21st century. To help it become like other contemporary fields such as oncology. Ultimately, the mission is to save and improve lives.”
The team’s work describes the development of a blood test, composed of RNA biomarkers, that can distinguish how severe a patient’s depression is, the risk of them developing severe depression in the future, and the risk of future bipolar disorder (manic-depressive illness). The test also informs tailored medication choices for patients.
This comprehensive study took place over four years, with over 300 participants recruited primarily from the patient population at the Richard L. Roudebush VA Medical Center in Indianapolis. The team used a careful four-step approach of discovery, prioritization, validation and testing.

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For Him, the Delight Is in the Digging

Patrick Radden Keefe has investigated human smuggling, government espionage and the Northern Ireland conflict. With “Empire of Pain,” he takes on the Sackler family and the opioid crisis.Patrick Radden Keefe has always been interested in secrets.“I think I have an almost childlike suggestibility where if you tell me you know a secret and you won’t tell, I’m going to do everything I can to figure out what that secret is,” he said in a video interview from his home in Westchester County, N.Y.But if you’ve ever read something Keefe, 44, has written, you may already sense that he has a passion for unearthing what’s hidden. In his 2009 book, “The Snakehead,” he reported on a human smuggling operation run out of New York’s Chinatown, untangling the web of the enterprise and highlighting its victims and its perpetrators. In his 2019 best-seller, “Say Nothing,” he dove into the decades-long sectarian conflict in Northern Ireland, particularly the mystery surrounding Jean McConville, a young mother who was kidnapped from her home in 1972.Now he’s back with a new book, “Empire of Pain,” out from Doubleday on Tuesday, that examines the opioid crisis. It’s a byzantine topic, but Keefe focuses on the Sackler family, which owns Purdue Pharma, the maker of OxyContin.“I didn’t want to write an opioid crisis book per se,” Keefe said. “The hope is that a certain kind of reader will be interested in this book, primarily as a story about a great American dynasty, and what I would argue is the corruption of a great American dynasty.”In a statement, a lawyer for Raymond Sackler’s family, Daniel S. Connolly, said, “Documents being released in Purdue’s bankruptcy now demonstrate that Sackler family members who served on Purdue’s board of directors acted ethically and lawfully.” A representative for members of Mortimer Sackler’s family said, “Our focus is on concluding a resolution that will provide help to people and communities in need, rather than on this book.”Like the tales in his books, the saga of how Keefe came to write about the Sacklers is anything but simple. In the 2010s, he was reporting on El Chapo, and wrote about the drug lord for The New York Times Magazine in 2012 and The New Yorker in 2014.During his research, he noticed the uptick in heroin usage in the United States. As he learned more about soaring opioid abuse, he stumbled on the Sackler name. He had heard of the family because the name is displayed at the Metropolitan Museum of Art, but he didn’t know much about them.So he began reporting. His first article about the Sacklers and the opioid crisis was published in The New Yorker in 2017. In 2018, Maura Healey, the attorney general of Massachusetts, sued Purdue Pharma, and in January 2019, court filings from the lawsuit were released. Sitting in his home office, Keefe read the documents and tweeted what he found.The documents gave him what he felt he needed to transform his reporting into a compelling book. “It was important for me to include the point of view of the Sacklers, even if they wouldn’t talk to me,” he said. “The stories the Sacklers tell themselves are really important.”In his statement, Connolly said Keefe “has refused to correct errors in his past reporting and also blatantly violated journalistic ethics by refusing to meet with representatives for the Sackler family during the reporting of his book.” In response, Daniel Novack, a lawyer for Doubleday, said, “Representatives for members of the Raymond and Mortimer Sackler family have attempted to disrupt this book from the outset with legal threats and unfounded attacks on Mr. Keefe’s professionalism. They refused to be interviewed or to substantively engage with Mr. Keefe’s request for comment.”By the time Keefe was ready to begin writing “Empire of Pain,” he was busy promoting “Say Nothing” and working on a Cold War podcast, “Wind of Change,” while also on staff at The New Yorker. Then the coronavirus pandemic struck, and cleared his calendar. “There was nothing left to do but write the damn book,” he said.He spent much of last year working on it while sitting on his bed, because he didn’t have access to his desk at work, and his wife, Justyna Gudzowska, a lawyer, was using their home office.Keefe working on “Empire of Pain” from his home during Covid lockdown.Justyna GudzowskaKeefe grew up as the oldest of three siblings in Boston. His mother was a philosophy professor at the University of Massachusetts, Boston, and his father worked in state government before becoming a real estate developer. He studied history at Columbia, followed by a master’s degree in international studies from Cambridge and a second master’s in new media and informations systems from the London School of Economics. When he returned to the United States, he enrolled in law school at Yale.Throughout his studies, he was pitching stories to The New Yorker and other publications, but he wasn’t getting assignments. (He framed a 1998 rejection letter from The New Yorker and hung it in his home office.) Eventually, Keefe took a year off from law school and worked on “Chatter,” a book about government eavesdropping, on a New York Public Library fellowship that was directed by the biographer Jean Strouse.“He just tunneled in and really worked,” Strouse said of Keefe. “He just finds these great, complicated stories and dives in.”She became a mentor, and Keefe began writing for The New York Review of Books, Slate and Legal Affairs. But he still wasn’t sure if he could be a full-time writer. He returned to Yale, finished his degree and in 2005 started studying for the New York bar exam. In the process, he became fascinated by the trial of Sister Ping, a woman accused of smuggling in Chinatown. Once again, he pitched The New Yorker. This time, Daniel Zalewski, the features director, said yes.“There is, I think, a prosecutorial zeal to his work,” Zalewski said. He has been Keefe’s primary editor ever since.“When he walks in my office door and begins to tell me something he’s excited about, it’s incredibly infectious,” Zalewski added. “He kind of chuckles to himself constantly, not because he’s self-impressed but because the story is delighting him so much.”Still, Keefe juggled writing and other jobs, including at the progressive think tank the Century Foundation and the Pentagon, before he was hired full-time at The New Yorker in 2012. Those experiences helped his reporting, he said. “I love legal documents, probably more than the next reporter.”Law school also “demystified the law for me a little bit. So when I get a threatening legal letter, I’m not as easily terrified,” he said. Even before he began working on “Empire of Pain,” he received such letters from a lawyer for the Sacklers.The pressure made him more determined to finish the book, he said. But he knows its ending may be unrewarding for readers. There’s no neat conclusion. Litigation over the opioid crisis is still ongoing, and Purdue Pharma filed for bankruptcy protection in 2019. But for Keefe, his book is a step.“The small thing that I can do is tell the story that is hopefully rigorous and compelling and creates a record for people who want to know what really happened,” he said. “And a kind of record that the family, as much as they might try, cannot really expunge. That’s not the accountability anybody wants, but it’s not nothing.”Follow New York Times Books on Facebook, Twitter and Instagram, sign up for our newsletter or our literary calendar. And listen to us on the Book Review podcast.

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Lessons Learned About Substance Use Disorders During the COVID-19 Pandemic

Every spring, I and my colleague Dr. Nora Volkow, Director of NIH’s National Institute on Drug Abuse (NIDA), join with leaders across the country in the Rx Drug Abuse and Heroin Summit. Our role is to discuss NIH’s continued progress in tackling our nation’s opioid crisis. Because of the continued threat of COVID-19 pandemic, we joined in virtually for the second year in a row.

While the demands of the pandemic have been challenging for everyone, biomedical researchers have remained hard at work to address the opioid crisis. Among the many ways that NIH is supporting these efforts is through its Helping to End Addiction Long-Term (HEAL) Initiative, which is directing more than $1.5 billion to researchers and communities across the country.

Here’s a condensed transcript of our April 6th video dialogue, which focused on the impact of the COVID-19 pandemic on people struggling with substance use disorders and those who are trying to help them.

Collins: What have we learned so far through HEAL? Well, one thing HEAL is doing is tackling the need for pain treatments that help people avoid the risks of opioids. This research has uncovered new targets and therapeutics for different types of pain, including neuropathic, post-surgical, osteoarthritic, and chemotherapy induced. We’re testing implanted devices, such as electrodes and non-invasive nerve stimulation; and looking at complementary and integrative approaches, such as phone-based physical therapy for low back pain.

Through HEAL, we’ve launched a first-in-human test of a vaccine to protect against the harmful effects of opioids, including relapse and overdose. We’re also testing a tool that provides pharmacists with a validated opioid use disorder risk measure. The goal is to identify better who’s at high risk for opioid addiction and to determine what kind of early intervention could be put in place.

Despite COVID, many clinical studies are now recruiting participants. This includes family-based prevention programs, culturally tailored interventions for hard-hit American Indian populations, and interventions that address social inequities, such as lack of housing.

We are also making progress on the truly heart-breaking problem of babies born dependent on opioids. HEAL has launched a study to test the effectiveness of a new approach to care that measures the severity of a baby’s withdrawal, based on their ability to eat, sleep, and be consoled. This approach helps provide appropriate treatment for these infants, without the use of medication when possible. We’re also developing novel technologies to help treat neonatal opioid withdrawal syndrome, including a gently vibrating hospital bassinet pad that’s received breakthrough device designation from the FDA.

2020 was an extraordinary year that was tragic in so many ways, including lives lost and economic disasters that have fallen upon families. The resilience and ingenuity of the scientific community has been impressive. Quick pivoting has resulted in some gains through research, maybe you could even call them silver linings in the midst of this terrible storm.

Nora, what’s been at the forefront of your mind as we’ve watched things unfold?

Volkow: When we did this one year ago, we didn’t know what to expect. Obviously, we were concerned that the stressors associated with a pandemic, with unknowns, are factors that have been recognized for many years to increase drug use. Unfortunately, what we’ve seen is an increase in drug use of all types across the country.

We have seen an exacerbation of the opioid epidemic, as evidenced by the number of people who have died. Already, in the 12 months ending in July 2020, there was a 24 percent increase in mortality from overdoses. Within those numbers, there was close to a 50 percent increase in mortality associated with fentanyl. We’re also seeing an increase, not just in deaths from fentanyl and other synthetic opioids, but in deaths from stimulant drugs, like cocaine and methamphetamine. And the largest increases have been very much driven by drug combinations.

So, we have the perfect storm. We have people stressed to their limits by decreases in the economy, the loss of jobs, the death of loved ones. On the other hand, we see dealers taking the opportunity to bring in drugs such as synthetic opioids and synthetic stimulants and distribute them to a much wider extent than previously seen.

Collins: On top of that, people are at risk of getting sick from COVID-19. What have we learned about the risks of coronavirus illness for people who use drugs?

Volkow: It is a double whammy. When you look at the electronic health records about the outcomes of people diagnosed with substance use disorders, you consistently see an increased risk for getting infected with COVID-19. And if you look at those who get infected, you observe a significantly increased risk of dying from COVID.

What’s driving this vulnerability? One factor is the pharmacological effects of these drugs. Basically, all of the drugs of abuse that result in addiction, notably opioids, damage the cardiopulmonary system. Some also damage the immune system. And we know that individuals who have any disruption of cardiovascular health, pulmonary health, immune function, or metabolism are at higher risk of getting infected with COVID-19 and having adverse outcomes.

But there’s another factor that’s as important—one that’s very tractable. It is the way in which our society has dealt with substance use disorders: not actually treating them as a disease that requires intervention and support for recovery. The stigmatization of individuals with addiction, the lack of access to treatment, the social isolation, have all created havoc by making these individuals so much more vulnerable to get infected with COVID-19.

They will not go to a doctor. They don’t want to be stigmatized. They need to go out into the streets to get access to the drugs. Many times, they don’t have a choice of what drugs to take because they cannot afford anything except what’s offered to them. So, many, especially those who are minorities, end up homeless or in jails or prison. Even before COVID, we knew that prisons and jails are places where infections can transmit extraordinary rapidly. You could see this was going to result in very negative outcomes for this group of individuals.

Collins: Nora, tell us more about the trends contributing to the current crisis. Maybe three or four years ago, what was going straight up was opioid use, especially heroin. Then, fentanyl started coming up very fast and that has continued. Now, we are seeing more stimulants and mixing of different types of drugs. What is the basis for this?

Volkow: At the beginning of the opiate pandemic, mortality was mainly associated with white Americans, many in rural or semi-suburban areas of the Appalachian states and in New Mexico and Arizona. That has shifted. The highest increase in mortality from opioids, predominantly driven by fentanyl, is now among Black Americans. They’ve had very, very high rates of mortality during the COVID pandemic. And when you look at mortality from methamphetamine, it’s chilling to realize that the risk of dying from methamphetamine overdose is 12-fold higher among American Indians and Alaskan Natives than other groups. This should make us pause to think about what’s driving these terrible racial disparities.

As for drug combinations, many deaths from methamphetamine or cocaine—an estimated 50 percent—are linked to these stimulant drugs being combined with fentanyl or heroin. Dealers are lacing these non-opioid drugs with cheaper, yet potent, opioids to make a larger profit. Someone who’s addicted to a stimulant drug like cocaine or methamphetamine is not tolerant to opioids, which means they are going to be at high risk of overdose if they get a stimulant drug that’s laced with an opioid like fentanyl. That’s been contributing to the sharp rise in mortality from non-opioid drugs.

Collins: I’m glad you raised the issue of health disparities. 2020 will go down as a year in which our nation had to focus on three public health crises at once. The first is the crisis of opioid use disorder and rising mortality from use of other drugs. The second is COVID-19. And the third is the realization, although the problem has been there all along, that health disparities continue to shorten the lives of far too many people.

The latter crisis has little to do with biology, but everything to do with the way in which our society still is afflicted by structural racism. We at NIH are looking at this circumstance, realizing that our own health disparities research agenda needs to be rethought. We have not fully incorporated all the factors that play out in health inequities and racial inequities in our country.

You were also talking about how stimulants have become more widespread. What about treatments for people with stimulant use disorders?

Volkow: For opioid addiction, we’re lucky because we have very effective medications: methadone, buprenorphine, naltrexone. On top of that, we have naloxone, Narcan, that if administered on time, can save the life of a person who has overdosed.

We don’t have any FDA-approved medication for methamphetamine addiction, and we don’t have any overdose reversal for methamphetamine. At the beginning of this year, we funded a large clinical trial aimed at investigating the benefits of the combination of two medications that were already approved as anti-depressants and for the treatment of smoking cessation and alcoholism. It found this combination significantly inhibits the urge to take drugs and therefore helps people stay away from use of methamphetamine. Now, we want to replicate these findings, and to tie that replication study in with guidelines from the FDA on what is needed to approve our new indication for these medications. Why? Because then insurance can cover it, and that will increase the likelihood that people will get treated.

Another exciting possibility is a monoclonal antibody against methamphetamine that’s in Phase 2 clinical trials. If someone comes into the emergency room with an overdose of a combination of opioid and methamphetamine, naloxone often will not work. But this monoclonal antibody with naloxone may offer a greater likelihood of success.Another thing that’s promising is that investigators have been able to modify monoclonal antibodies so they stay in the bloodstream for a longer time. That means we may someday be able to use this passive immunization approach as a treatment for methamphetamine addiction.

Collins: That’s good to hear. Speaking of progress, is there any you want to point to within HEAL?

Volkow: There’s a lot of excitement surrounding medication development. We’re interested in developing antidotes that will be more effective in reversing overdose deaths from fentanyl. We’re also interested in providing longer lasting medications for treatment of opioid use disorders, which would improve the likelihood of patients being protected from overdoses.

The Justice Community Opioid Innovation Network (JCOIN) is another HEAL landmark project. It involves a network of researchers that is working with judges and with the workers in jail and prison systems responsible for taking care of individuals with substance use disorders. Through this network, we’ve been able to start to harmonize practices. One thing that’s been transformative in the jail and prison system has been the embracing of telehealth. In the past, telehealth was not much of a reality in jails and prisons because of the fear of it could lead to communications that could perhaps be considered dangerous. That’s changed due to COVID-19. Now, telehealth is providing access to treatment for individuals in jail and prison, many of them with substance use disorders.

Also, because of COVID, many nonviolent individuals in jails and prisons were released. This gives us an opportunity to evaluate how best to help such individuals achieve recovery from substance use disorders. Hopefully we can generate data to show that there are much more effective strategies than incarceration for dealing with substance use disorders.

The HEALing Communities Study, involves Massachusetts, New York, Ohio, and Kentucky—four of the states with the highest rates of mortality from overdoses from the inception of the opioid epidemic. By implementing a battery of interventions for which there is evidence of benefit, this ambitious study set out to decrease overdose mortality by 40 percent in two years. Then, came COVID and turned everything upside down. Still, because we consolidated interactions between agencies, we’ve been able to apply support systems more efficiently in those communities in ways that have been very, very reinforcing. Obviously, there’ve been delays in implementation of interventions that require in-person interactions or that involve hospital emergency departments, which have been saturated with COVID patients.

We’ve learned a lot in the process. I may be too optimistic, but I do believe that we can stay on goal.

Collins: Now, I’d like to transition to a few questions from people who subscribe to the HEAL website. Announced at this meeting three years ago, the HEAL Initiative involves research participants and patients and stakeholders—especially people who have lived experience with pain, addiction, or both.

Let’s get to the first question: “What is NIH doing through HEAL to address the stigma that prevents people who need opioid medications for treatment from getting them?”

Volkow: A crucial question. As we look at the issue of stigma, we need to recognize that there are structural issues in how our society is prioritizing the importance of substance use disorders and the investments devoted to them. And we need to recognize that substance use disorder doesn’t exist in isolation; it is frequently comorbid with mental illness.

We need to listen. Some of the issues that we believe are most problematic are not. We need to empower these communities to speak up and help them do so. This is probably one of the most important things that we can do in terms of addressing stigma for addiction.

Collins: Absolutely. The HEAL Initiative has a number of projects that are focusing on stigma and coming up with tools to help reduce this. And here’s our second question: “In small communities, how can we provide more access to medications for opioid use disorder?”

Volkow: One project funded through HEAL was to evaluate the effectiveness of community pharmacies for delivering buprenorphine to individuals with opioid use disorder. The results show that patients receiving buprenorphine through community pharmacies in rural areas had as good outcomes as patients being treated by specialized clinicians on site.Another change that’s made things easier is that in March 2020, the DEA relaxed its rules on how a physician can prescribe buprenorphine. In the past, you needed to go physically to see a doctor. Now, the DEA allows a patient to be initiated on buprenorphine through telehealth, and that’s opened the possibility of greater access to treatment in rural communities.

My perspective is let’s look at innovative ways of solving problems. Because the technology is changing in so many ways and so rapidly, let’s take advantage of it.

Collins: Totally with you on that. If there’s a silver lining to COVID-19, it’s that we’ve been forced to take stock of the ways we’ve been doing things. We will learn from this pandemic and change the way we approach so many things in health and medicine as a result. Certainly, opioid use disorder ought to be very high on that list. Let’s move on to another question: “What is the HEAL initiative doing to promote prevention of opioid use?”

Volkow: This is where the HEAL initiative is aiming to provide alternative treatments for the management of pain that reduce the risk of addiction.

Then there’s the issue of prevention in people who start to take opioids because they either want to get high or escape. With the COVID pandemic, we’ve seen increases in anxiety and in depression. Those are factors that can put a teenager or young adult on a trajectory for higher risk of substance use disorders.

So, what is HEAL doing? There is prevention research specifically targeted, for example, at the transition from adolescence to young adulthood. That is the period of greatest vulnerability of uptake of opioids, or drugs of misuse. We’re also targeting minority groups that may be at very, very high risk. We want to be able to understand the factors that make them more vulnerable to tailor prevention interventions more effectively.

Collins: Today, we’ve shared some of the issues that NIH is wrestling with in its efforts to address the crisis of opioid misuse and overdose, as well as other drugs that are now very much part of the challenge. To learn more, go to the HEAL website. You can also send us your thoughts through the HEAL Idea Exchange.

These developments give me hope in the wake of a very difficult year. Clearly, we still have the capacity to work together, we are resilient, and we are determined to put an end to our nation’s opioid crisis.

Volkow: Francis, I want to thank you for your incredible leadership and your support. I hope the COVID pandemic will bring forth a more equitable system, in which all people are given the chance for resilience that maximizes their life, happiness, and productivity. I think science is an extraordinary tool to help us do that.

Links:

Video: The 2021 Rx Drug Abuse & Heroin Summit: Francis Collins with Nora Volkow (NIH)

COVID-19 Research (NIH)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

HEAL Idea Exchange (NIH)

National Institute on Drug Abuse (NIH)

Rx Drug Abuse & Heroin Summit, A 2021 Virtual Experience

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Pharmacist says get vaccinated despite brother's death

A pharmacist whose brother died after having the AstraZeneca vaccine has told the BBC she still feels strongly that people should continue have their jabs. Alison Astles’ brother Neil, 59, died of a blood clot on the brain on Sunday, after having the vaccination on 17 March.She said he was “extraordinarily unlucky” and that “more lives will be saved by people having the vaccine than not.”

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Online Scammers Have a New Offer For You: Vaccine Cards

Hundreds of sellers are offering false and stolen vaccine cards, as businesses and states weigh proof of vaccinations for getting people back to work and play.SAN FRANCISCO — On Etsy, eBay, Facebook and Twitter, little rectangular slips of paper started showing up for sale in late January. Printed on card stock, they measured three-by-four inches and featured crisp black lettering. Sellers listed them for $20 to $60 each, with a discount on bundles of three or more. Laminated ones cost extra.All were forgeries or falsified copies of the Centers for Disease Control and Prevention vaccination cards, which are given to people who have been inoculated against Covid-19 in the United States.“We found hundreds of online stores selling the cards, potentially thousands were sold,” said Saoud Khalifah, the founder of FakeSpot, which offers tools to detect fake listings and reviews online.The coronavirus has made opportunists out of many people, like those who hoarded bottles of hand sanitizer at the start of the pandemic or those who cheated recipients out of their stimulus checks. Now online scammers have latched onto the latest profit-making initiative: the little white cards that provide proof of shots.Online stores offering counterfeit or stolen vaccine cards have mushroomed in recent weeks, Mr. Khalifah said. The efforts are far from hidden, with Facebook pages named “vax-cards” and eBay listings with “blank vaccine cards” openly hawking the items.A screenshot of a “vax cards” page on  Facebook. Selling fake vaccination cards could break federal laws that forbid copying the C.D.C. logo, legal experts said. If the cards were stolen and filled out with false numbers and dates, they could also violate identity theft laws, they said.But profiteers have pressed ahead as demand for the cards has grown from anti-vaccine activists and other groups. Airlines and other companies have recently said they may require proof of Covid-19 immunization so that people can safely travel or attend events.The cards may also become central to “vaccine passports,” which offer digital proof of vaccinations. Some tech companies developing vaccine passports ask people to upload copies of their C.D.C. cards. Los Angeles also recently began using the C.D.C. cards for its own digital proof of immunization.Last week, 45 state attorneys general banded together to call on Twitter, Shopify and eBay to stop the sale of false and stolen vaccine cards. The officials said they were monitoring the activity and were concerned that unvaccinated people would misuse the cards to attend large events, potentially spreading the virus and prolonging the pandemic.“We’re seeing a huge market for these false cards online,” said Josh Shapiro, Pennsylvania’s attorney general, whose office has investigated fraud related to the virus. “This is a dangerous practice that undermines public health.”The C.D.C. said it was “aware of cases of fraud regarding counterfeit Covid-19 vaccine cards.” It asked people not to share images of their personal information or vaccine cards on social media.Facebook, Twitter, eBay, Shopify and Etsy said that the sale of fake vaccine cards violated their rules and that they were removing posts that advertised the items.The C.D.C. introduced the vaccination cards in December, describing them as the “simplest” way to keep track of Covid-19 shots. By January, sales of false vaccine cards started picking up, Mr. Khalifah said. Many people found the cards were easy to forge from samples available online. Authentic cards were also stolen by pharmacists from their workplaces and put up for sale, he said.Many people who bought the cards were opposed to the Covid-19 vaccines, Mr. Khalifah said. In some anti-vaccine groups on Facebook, people have publicly boasted about getting the cards.“My body my choice,” wrote one commenter in a Facebook post last month. Another person replied, “can’t wait to get mine too, lol.”Other buyers want to use the cards to trick pharmacists into giving them a vaccine, Mr. Khalifah said. Because some of the vaccines are two-shot regimens, people can enter a false date for a first inoculation on the card, which makes it appear as if they need a second dose soon. Some pharmacies and state vaccination sites have prioritized people due for their second shots.The tweet linked to a now-defunct Etsy shop that sold fake vaccine cards. One Etsy seller, who declined to be identified, said she had sold dozens of fake vaccine cards for $20 each recently. She justified her actions by saying she was helping people evade a “tyrannical government.” She added that she did not plan to get inoculated.Vaccine proponents say they have been troubled by the proliferation of forged and stolen cards. To hold those people accountable, Savannah Sparks, a pharmacist in Biloxi, Miss., began posting videos on TikTok last month naming the sellers of falsified vaccine cards.In one video, Ms. Sparks explained how she had tracked down the name of a pharmacy technician in Illinois who had nabbed several cards for herself and her husband and then posted about it online. The pharmacy technician had not disclosed her identity, but had linked the post to her social media accounts, where she used her real name. The video has 1.2 million views.“It made me so mad that a pharmacist was using her access and position this way,” Ms. Sparks said. The video drew the attention of the Illinois Pharmacists Association, which said it reported the video to a state board for further investigation.Ms. Sparks said her work had drawn detractors and vaccine opponents, who have threatened her and posted her home phone number and address online. But she was undeterred.“They should be first in line advocating for people to get vaccinated,” she said of pharmacists. “Instead, they’re trying to use their positions to spread fear and help people circumvent getting the vaccine.”Mr. Shapiro, the Pennsylvania attorney general, said in addition to violating federal copyright laws, the sale of counterfeit and stolen cards most likely broke civil and consumer protection laws that mandate that an item can be used as advertised. The cards could also violate state laws regarding impersonation, he said.“We want to see them stop immediately,” Mr. Shapiro said of the fraudsters. “And we want to see the companies take serious and immediate action.”

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