Russia Puts Trophied NATO Vehicles From Ukraine on Display

Follow the latest developments in former President Donald Trump's criminal hush money trial in New York.

Humans have always been explorers. For better or worse, something in our collective makeup seems to push us to discover new things, understand the enigmatic, or reach past the limits of what we imagine is possible. Some people dream about what the cosmos could contain; scientists launch probes into space, and astronauts travel beyond Earth’s atmosphere. Others go on life-threatening quests, such as climbing the planet’s tallest peaks and diving into the sea’s deepest trenches, to tap into the wonder, fear, and awe that come from experiencing—and surviving—the places on Earth most hostile to human life.The six books below reflect on what drives our species to seek out the uncharted and unknown. In each, what propels an individual’s desire to expand their experiences differs; some stories follow people yearning for adventure or to set a record, while other protagonists turn to exploration when they want to run away from something. No matter where these books take us, whether they cover searching for life beyond our planet or diving miles deep into the ocean to discover ecosystems heretofore unknown, their pages bring readers along for the ride. Gallery Books Contact, by Carl SaganIn Sagan’s 1985 novel, the astronomer Ellie Arroway is the leader of a scientific endeavor called Project Argus, a network of radio telescopes that picks up a message from an extraterrestrial source. The missive includes blueprints to build a machine that can take a group of humans … somewhere. Sagan’s story weaves Ellie’s personal life, particularly her relationship with her parents, together with Earth’s many competing efforts to build (or destroy) a working version of this machine. Though the novel doesn’t shy away from humanity’s propensity to sow discord and violence, Sagan’s story has a through line of hope—Contact is ultimately about how people’s tendency to seek the unknowable can lead them to better understand themselves and others. By the end of the novel, Ellie—who has traveled to the stars and back—realizes that “for small creatures such as we the vastness is bearable only through love.” This message resonates nearly four decades later, as humans wade farther and farther into the galaxy. Doubleday The Underworld: Journeys to the Depths of the Ocean, by Susan CaseyFor all of humanity’s stargazing, the deepest trenches of Earth’s oceans remain relatively unexplored. Many people consider the sea “the earth’s haunted basement—sinister, shrouded in blackness, spewing molten rock and poisonous gases, a den of freaky beings and hoary specters—and they would rather stay upstairs,” Casey writes in her book about those who do seek to journey to the bottom of the sea, where “intraterrestrial” life thrives. Casey herself is one of those people, and in The Underworld, she showcases others whose vocations send them into the ocean’s depths. But the book isn’t only about humans: Equal time is given to the creatures that live down there—including animals that aquanauts have given flippant monikers to, such as assfish, snailfish, weirdfish, and rattails—and underwater natural phenomena, such as black smoker hydrothermal vents, chimneylike structures that spew a sulfide-rich “smoke” into the water. Through Casey’s research, interviews, and firsthand experience, readers journey to the abyssal and hadal zones of the ocean, which run 10,000 to 36,000 feet deep, and get to share the “alchemical mix of wonder and fear” the author finds there.Read: The Titanic sub and the draw of extreme tourism One World Lone Women, by Victor LaValleExploration isn’t always about running toward something—at times, it’s about running away from something else. Lone Women uses the trappings of the American West, a complicated, enduring cultural symbol of a supposedly untouched frontier, to delve into the human tendency to try to escape the past. It follows Adelaide Henry, a Black woman who leaves her family's California farm in 1915 under violent circumstances and lugs a mysterious trunk to Montana, where the U.S. government is offering free land to those who homestead there. The trunk’s undisclosed, possibly supernatural contents disturb Adelaide, and seem directly related to what she’s trying to leave behind. Over the course of the book, we see her failed attempt to shut that part of her past away as she tries to build a life in the brutal landscape of the Great Plains, a place that can destroy anyone who’s unprepared or without friends—or be a refuge for those looking to build a new home with space for the love, and suffering, that comes with living. Read: The ‘curious’ robots searching for the ocean’s secrets Vintage The River of Doubt: Theodore Roosevelt’s Darkest Journey, by Candice MillardTeddy Roosevelt lived his life by fighting his way through it, pummeling any hardships or setbacks with relentless action and an indomitable force of will. In 1912, he lost a presidential election that would have given him a third term. The defeat devastated him, and—as he was wont to do—he sought an endeavor that would put his mental and physical limits to the test. He decided on an expedition to an unmapped expanse of land in South America, which to North Americans represented an alluring, seemingly impenetrable wilderness. Once he landed in Brazil, he was persuaded to explore an Amazonian tributary ominously and aptly called the River of Doubt. “If it is necessary for me to leave my bones in South America, I am quite ready to do so,” he wrote. Roosevelt did, in fact, almost die on that trek. He and the men who accompanied him were, “for all their own experience and knowledge, vulnerable outsiders,” Millard writes. She goes on to describe how their hubris on that journey made them “clumsy, conspicuous prey” at the mercy of not only the Cinta Larga tribe, whose members shadowed them throughout and could have killed them easily if they’d decided to, but also the flora and fauna they knew little about. The River of Doubt is a riveting look at how exploration can be laden with arrogance and ignorance. Millard vividly recounts how Roosevelt brought both with him into the Amazon, and how much both cost him.Read: The difference between exploring and tourism Vintage Into the Wild, by Jon KrakauerIn April 1992, a 24-year-old man named Chris McCandless walked into the wilds three hours outside Fairbanks, Alaska, intent to live off the land without any modern conveniences. “I don’t want to know what time it is. I don’t want to know what day it is or where I am. None of that matters,” he told the man who dropped him off at the edge of the bush. McCandless never made it out—he died in the home he’d made in an abandoned bus sometime that August. His journey was reckless—he was unprepared in terms of both supplies and the knowledge of how to survive. His story, which Krakauer first recounted in an article for Outside magazine, angered many: How could McCandless have been so foolhardy? (Krakauer’s account also doesn’t capture all of his subject’s life: Chris’s sister Carine alleged years later that their parents had physically and mentally abused both children; they called her memoir “fictionalized.”) McCandless, however, was confounded by people passively staying within the confines of a civilization that he found crushing. Krakauer’s recounting of his final months is captivating, giving readers a window into McCandless’s mentality; it is a tragic portrait of a man whose urge to escape into nature was so strong and alluring that, decades later, the circumstances of his death have morphed into legend. William Morrow Seveneves, by Neal StephensonAt certain moments, the impetus to go somewhere new isn’t about gaining knowledge or traveling simply for the novelty: Sometimes, it’s the only way to survive. In Seveneves, the moon explodes, making Earth uninhabitable for humans. The bulk of the story centers on the 1,500 or so people who struggle in the aftermath of the disaster, living initially in ad hoc habitats built around the International Space Station. Most of them die in these first years, destroyed by mounting internal discord and by the struggle to gain the basic resources—water, air, food—required for life. Stephenson goes deep into the science of their attempts to make it, and the book will fire up anyone who, for example, wants to know in detail how humans might be able to capture water from a passing ice comet. Ultimately, only seven women able to bear children remain, and they later set up base in a cleft of the broken moon. Then, about two-thirds of the way through the book, the action leaps 5,000 years into the future, where a civilization with billions of genetically altered humans seeks to reclaim Earth. Stephenson’s considerable extrapolations about what humans—or their genetically altered future descendants—will do to survive make the novel a fun, philosophical, and surprisingly hopeful read.

Democrats are concerned there isn't enough "energy" behind President Biden's re-election campaign to win him another term, according to a recent report.

ADAM ROSEINGLEWOOD, Calif. — There’s locker-room talk, and then there’s what the entire global Netflix subscriber base may have witnessed Sunday night.Seven-time Super Bowl champion quarterback Tom Brady allowed his former teammates, coach, owner, his longest on-field rival, a couple of celebrities and a pack of truly unleashed comedians go off on him in the largest-attended, longest-ever and most likely most-watched live broadcast of a comedy roast from the Kia Forum for the Netflix is A Joke Fest. The old Friars Club roasts in New York City may have gone longer and featured as much raunch back in the day, but none of those events were ever live streamed globally to a potential audience in the mega millions.Kevin Hart set the tone and the bar below the belt from the get-go as the roast’s host, saying this about the Forum’s previous sports dynasty owners of the 1980s Los Angeles Lakers. “They called this place Showtime because Jerry Buss used to show everybody his dick in this building,” Hart joked. “A lot of nasty shit has happened in this building … I wish I had a blacklight right now, I’d turn that bitch on now so y’all can see all the cum stains you sitting on in these nasty-ass seats.” He then cackled, adding: “Hahaha! That’s right. You better get comfortable being uncomfortable, baby!”Read more at The Daily Beast.

Judge Juan Merchan on Monday said he will consider a jail sentence for former President Trump if he continues to violate the gag order imposed upon him in his unprecedented criminal trial.

Jordan's King Abdullah II visited President Joe Biden at the White House for an informal meeting to discuss challenges facing the allies, like Israel's possible Rafah ground offensive.

Strong, long-lived tornadoes are possible in Oklahoma and Kansas on Monday as ingredients come together for a significant severe storm outbreak.

Former President Donald Trump's hush money trial continues in New York. Follow here for the latest live news updates, analysis and more.

The last episode of "Friends" aired on May 6, 2004, yet the appeal of the show is evident 20 years later in the popularity of these five New York City tourist attractions.

The announcement marked the latest disruption at a school roiled by weeks of pro-Palestinian protests and a police response that led to dozens of arrests.

"The legacy of it is incredible but it wasn’t great at the time."

Follow the Post’s live updates for the latest news, analysis and photos from the Trump trial in NYC.

Brendan McDermid/Pool/AFP via GettyDonald Trump has booked a one-way ticket to jail, and the judge overseeing his ongoing New York criminal trial on Monday said he’s ready to send him there at any moment.New York Supreme Court Justice Juan Merchan started the fourth week of Trump’s trial with a speech that’s more than a year in the making, explaining why he hasn’t yet thrown the politician into the slammer—making what he called his final warning to the former president.“I’ll find you in criminal contempt for the tenth time,” Merchan said in a stark tone. “It appears that the $1,000 fines are not serving as a deterrent. Therefore, going forward, this court will have to consider a jail sanction. Mr. Trump, it’s important to understand the last thing I was to do is put you in jail. You are the former president of the United States, and possibly the next one as well.”Read more at The Daily Beast.

Israel has issued a warning to the civilian population in the southern Gaza city of Rafah to leave, a sign of a possible ground invasion despite strong opposition from the U.S. and other allies. Israel says it's prepared for 100,000 people to move west to the al-Mawasi humanitarian camp.

Nearly two feet of rain fell in five days in southeast Texas, leading to hundreds of rescues over the weekend. It's the second largest amount of rain in a week since Hurricane Harvey in 2017.

Snake wrangler Danielle Wall has become a celebrity in California’s high desert. But you’ll learn about more than snakes if you tag along.

Former PM of Israel Naftali Bennett discussed reports the Biden administration could "condition" ammunition aid to Israel on "Sunday Night in America."

Donald Trump’s ex-campaign manager Brad Parscale, who was the operative behind the ex-president’s election-winning Facebook ads in 2016, has debuted his own artificial intelligence platform. In a promotional video for the new platform, which Parscale claims will boost conservative campaigns, he touted “artificial intelligence that’s going to replace polling in the future across the country,”...

Columbia University said Monday they are altering their graduation plans after weeks of protests​ and turmoil on campus​.

"In honor of Tay Tay, let's take a look at the Chiefs' eras," Brady said. "Terrible for 50 years, good for five. Shake it off."

The bodies of three surfers, an American and two Australians who were found dead last week, have been identified. Authorities said evidence points to three suspects who appeared to have attacked the tourists after a carjacking attempt. The suspects are in custody.

“My name is Ron Burgundy. I am a very big deal but tonight is not about me. We are here to honor a champion of the gridiron, a great American, a father and a sexy man, a true patriot."

"Your puppy will give your older baby so many more years of life, just like a puppy again," one TikTok user wrote.

Tennis stars Stefanos Tsitipas and Paula Badosa broke up recently. The Spanish tennis star confirmed the split in a post on her Instagram Stories.

Termite had been living as a stray before he was hit by a car in a collision that saw him lose his sight and most of his hearing.

Cornelia Li for Vox Why are more and more older people spending their dying years behind bars? In late 2018, Richard Washington sent a memo to the US Court of Appeals for the Ninth Circuit with the subject line “Notice I am being killed.” The 64-year-old man, who decades earlier was convicted on armed robbery charges, was serving a 63-year prison sentence in Arizona. In his letter, he alleged that the Department of Corrections was refusing to give him medication for his various health issues, which included diabetes, hypertension, and hepatitis C. Because of the lack of treatment, Washington wrote, “My greatest fear is that I’m going to die more sooner than later.” About six weeks later, he was dead. In state after state, prison systems have long been plagued by inadequate health care, resulting in the spread of treatable diseases and, in many cases, preventable deaths behind bars. But a key demographic trend threatens to make that problem even worse: Over the last several decades, America’s prison population has been rapidly aging, and, as in Washington’s case, prisoners’ health needs have become more significant as a result. People who were 55 years old or older made up about 3 percent of the US prison population in 1991; by 2021, they accounted for 15 percent. The total number of older prisoners is also steadily growing, with no signs of abatement: In 2020, there were about 166,000 incarcerated people aged 55 years or older; that number grew to about 178,000 in 2021 and 186,000 in 2022. The graying of America’s incarcerated population is effectively turning the US prison system into a de facto nursing home, leaving hundreds of thousands of older people in its care each year. The result is skyrocketing costs: The Bureau of Prisons’ health care spending on federal inmates rose from $978 million in 2009 to $1.34 billion in 2016, and various state governments have seen similar increases. Still, conditions in American prisons continue to be detrimental to people’s health and often lead to accelerated aging. Prisoners, for example, are much more likely to exhibit signs of cognitive decline, including dementia, at an earlier age than the general population, and one study found that a 59-year-old in prison has the same morbidity rate — that is, how often people get a disease — as a nonincarcerated 75-year-old. “We have facilities that aren’t considered humane,” said Lauren-Brooke Eisen, a senior director at the Brennan Center for Justice. “They’re not places for elderly people who have dementia and diabetes and maybe walkers or wheelchairs.” All of this raises both a moral and practical policy question that lawmakers have to face: Why are we forcing older people to spend their dying years in prison when they can get better care elsewhere? People aren’t just aging behind bars; police are locking up the elderly One of the explanations for the aging prison population is simple: Since the 1970s and the age of mass incarceration — when the American prison population ballooned and gave the United States the distinction of imprisoning more people than any other country in the world — people have been aging behind bars. The other explanation, however, is less obvious: Older people have been getting arrested at higher rates than they used to. In 1991, for example, people who were 55 years of age or older made up only 2 percent of adults who were arrested; by 2021, they made up 8 percent, according to the Prison Policy Initiative, a Massachusetts-based nonprofit that does criminal justice research and advocacy. The Marshall Project also found a similar pattern: Between 2000 and 2020, there was nearly a 30 percent increase in the number of arrests of people over 65, despite the overall number of arrests dropping by nearly 40 percent. That spike is especially surprising because people tend to age out of crime: Recidivism rates for older people are significantly lower than they are for younger people. According to a 2017 report by the United States Sentencing Commission that tracked people for eight years after they were released from prison, nearly 68 percent of people who were under 21 at the time of their release were rearrested. By contrast, just over 13 percent of people over 65 were rearrested. So why are arrests among older people suddenly on the rise? The resurging trend across many American cities and states to further criminalize poverty and impose harsher punishments for petty crimes, including things like shoplifting, is partly to blame because the groups of people who become common targets for police are getting older. “People who are unhoused and people suffering from mental health disorders and substance use disorders are also aging,” said Mike Wessler, the communications director at the Prison Policy Initiative. “If you look across the country right now, we’re obviously seeing efforts to ramp up policing of people who are unhoused, people with untreated mental health disorders, people with substance use disorder. So it’s almost a certainty that in the coming years we are probably going to see this problem get worse.” People experiencing cognitive decline, including those suffering from dementia, can also be especially vulnerable during interactions with police. Henry Hart, a 76-year-old with dementia in Maryland, for example, was arrested when he had what his daughter described as a mental breakdown. During the incident, Hart had grown agitated and hit her, and when she called for paramedics to take him to the hospital, police showed up at the scene instead. Officers ultimately arrested him for assault despite his family members’ pleas. After spending time in jail, Hart’s condition seemed to get notably worse, according to his daughter. “As Maryland’s population ages, experts fear that police will encounter people with dementia more often and without recognizing the condition or knowing how to respond to it,” Baltimore Sun reporters Angela Roberts and Cassidy Jensen wrote. “Arrest or jail time can be especially harmful to people with dementia, given their mental and physical vulnerability, experts say.” There’s also evidence that beefing up law enforcement has had a negative impact on older people. While younger people have become less likely to be arrested for drug-related crimes than in the past, arrests of older people for drug-related offenses have spiked. Between 2000 and 2018, for example, drug-related arrests of people over the age of 50 rose by 92 percent — the fastest increase out of any age group. And while substance use disorder among older people is on the rise, addressing the problem through stricter law enforcement is not a practical solution. “It’s a heck of a lot easier to order the National Guard to go stand on subway platforms than it is to figure out how to expand mental health treatment in the state; than to figure out how to address substance use disorders in the state; than to figure out how to address the housing crisis in the state,” Wessler said. The consequences of an aging prison population Studies have shown that incarcerated people have signs of aging at a faster rate than others as a result of prison conditions, and that each year in prison can shave years off of someone’s life. “Health care behind bars is bad even in the best scenarios,” Wessler said. “And that’s kind of by design in a lot of respects: Prisons are not places that are therapeutic or designed to heal; they are places that are designed to punish.” Infectious diseases tend to disproportionately affect prisoners compared to the general population, and the Covid pandemic in particular showed why prisons are especially dangerous for older people. Deaths of inmates rose by nearly 50 percent in the first year of the pandemic, and while mortality rates increased for prisoners across all ages, older people saw the highest surge in mortality. By contrast, among the general population, it was younger people who saw the highest increase in death rates. From a public policy standpoint, the aging prison population is a failure on multiple fronts. Most importantly, prisons cause people to age more quickly and die prematurely. After all, while so-called “natural” deaths — that is, death from disease or old age — make up the vast majority of deaths behind bars, they often receive little scrutiny despite the fact that many of them have been found to be the result of medical neglect. But it’s also costing states a lot of money — money that is clearly not well spent. In Texas, for example, the state’s prison health care costs increased by more than $250 million between 2012 and 2019, although the prison population actually decreased by 3 percent during that time. The state’s prison population aged 55 or older, on the other hand, had increased by 65 percent during that same period, according to data reviewed by the Texas Tribune. Some lawmakers have noted this is unsustainable. As former state Sen. John Whitmire told the Tribune, “Nobody’s tougher on crime than me, but once you’ve incarcerated a guy past the point that he’s a threat to anybody, I’d like to save that $500,000 to put him in a nursing home as a condition of parole, take that money, and spend it on either other public safety efforts or prison costs.” The system as it is, in other words, isn’t benefiting anyone. It’s both deadlier and more financially costly. And from a moral standpoint, it’s hard for a society to defend these outcomes. “Do we morally think that it is good to have people spend their dying years behind bars, especially for drug crimes from the ’80s and ’90s?” Wessler said. “That strikes me as morally wrong in addition to being bad public policy.” Tougher penalties turn into de facto death sentences In many ways, America’s aging prisons are the expected end result of the tough-on-crime approaches and surge in arrests of the 1980s and 1990s. A study by researchers at the the State University of New York at Albany, the University of Pennsylvania, and the RAND Corporation, found that young people who were locked up in the 1990s spent more time behind bars than any other generation, in large part because of tougher and longer sentences, higher recidivism rates, and escalating punishments for people who are rearrested. And that generation is now aging behind bars, unlikely to ever come out of prison. “These extreme sentence lengths paired with narrow release mechanisms — meaning fewer ways to actually leave the system — led to this huge crisis of older adults in American prisons,” Eisen, from the Brennan Center, said. “Because what you had is more people coming in, people staying for longer, and then fewer avenues for release because of mandatory minimums, because of three strikes [laws], because of life without parole.” While many older people in prison today are being sent there for petty crimes, it’s also true that many others, particularly those serving longer sentences, have been convicted of serious crimes. But regardless of what a person is guilty of, the fate of a death behind bars — which can be the result of inadequate medical care and botched treatments — could itself be seen as a cruel punishment, especially when people no longer pose a threat to society. Take, for example, the case of Walter Jordan, another elderly Arizona prisoner whose story is eerily similar to Richard Washington’s. Jordan, a 67-year-old man who was convicted of first-degree murder and kidnapping, was serving a life sentence. In a memo he wrote to a federal judge in 2017, he alleged that the state’s Department of Corrections and its private health care contractor had delayed his treatment for skin cancer. The memo was, in his words, a “notice of impending death.” Jordan wrote that he was in pain and suffering from memory loss. He alleged that other prisoners were also being denied care, and he wrote that as a result of his delayed treatment, he would be “lucky to be alive for 30 days.” Jordan was right: Just over a week later, he was dead. A physician who reviewed his case found that Jordan could have survived had he received adequate care. The situation was “horrific,” the physician wrote. “He suffered excruciating needless pain from cancer that was not appropriately managed in the months prior to his death.” There are more humane approaches. States and the federal government can start, for example, by expanding eligibility for compassionate release, which truncates sentences but tends to be reserved for people with terminal illnesses. Parole — which can sometimes have unintended consequences including strict rules that often result in parolees being sent back to prison — can also be especially beneficial to elderly prisoners who can get better health care outside of prison. And yet, tough-on-crime laws like those recently passed in Louisiana are making it harder for prisoners to be eligible for parole. Governors can also make use of their pardon powers and commute sentences for older prisoners who have shown signs of rehabilitation. And instead of readopting a tough-on-crime approach that will likely result in more arrests of older people, states and the federal government can support social safety net programs that would lift older people out of poverty and homelessness, reducing their odds of being arrested in the first place. America’s jail and prison population peaked in 2008, when more than 2.3 million people were behind bars. And while it has mostly declined since then — especially during Covid, when many prisoners were released as the virus ravaged prisons — it has recently been ticking back up. “We have far too many people in our prisons,” Eisen said. One of the fastest ways to address that problem is to release older people, who generally don’t pose a public safety risk. “This is a population that shouldn’t be behind bars.” But until lawmakers acknowledge that the current prison system is failing some of the most vulnerable people in its care, cases like Washington’s or Jordan’s will become all the more common. And more and more people who are now serving time in an American prison will slowly come to learn that their punishment has morphed into a death sentence.

There’s a significant impediment to maximizing CRISPR’s potential for developing novel therapies: the lack of diversity in genetics research. | Paige Vickers/Vox; Getty Images The genetic data that underpins CRISPR has a big diversity problem. Medicine has entered a new era in which scientists have the tools to change human genetics directly, creating the potential to treat or even permanently cure diseases by editing a few strands of troublesome DNA. And CRISPR, the gene-editing technology whose creators won the Nobel Prize for Chemistry in 2020, is the face of this new normal. CRISPR’s novel harnessing of bacterial proteins to target disease-carrying genes has reshaped medical research over the past decade. While gene-editing itself has been around for more than 30 years, scientists can use CRISPR to edit genomes faster, cheaper, and more precisely than they could with previous gene-editing methods. The method’s novel harnessing of bacterial proteins to target disease-carrying genes has reshaped medical research over the past decade. As a result, investigators have gained far more control over where a gene gets inserted and when it gets turned on. That in turn has opened the door to a new class of better gene therapies — treatments that modify or replace people’s genes to stop a disease. Last December, the US Food and Drug Administration approved the first-ever CRISPR-based therapy, designed to treat sickle cell disease. In February, the treatment, called Casgevy, gained approval from the European Commission as well. It joins the dozen or so pre-CRISPR gene therapies that are already available to patients. But there’s a significant impediment to maximizing CRISPR’s potential for developing novel therapies: the lack of diversity in genetics research. For decades, gene therapy has been defined by both its enormous therapeutic potential, and by the limitations imposed by our imprecise knowledge of human genetics. Even as gene-editing methods, including CRISPR, have become more sophisticated over the years, the data in the genetic databases and biobanks that scientists use to find and develop new treatments are still riddled with biases that could exclude communities of color from enjoying the full benefits of innovations like CRISPR. Unless that gap is closed, CRISPR’s promise won’t be fully fulfilled. Gaps in research Developing effective gene therapies depends on growing our knowledge of the human genome. Data on genes and their correlation with disease have already changed the way cancer researchers think about how to design drugs, and which patients to match with which drug. Scientists have long known that certain genetic mutations that disrupt regular cell functions can cause cancer to develop, and they have tailored drugs to neutralize those mutations. Genetic sequencing technology has sped that progress, allowing researchers to analyze the genetics of tumor samples from cancer patients after they’ve participated in clinical trials to understand why some individuals respond better than others to a drug. In a clinical trial of the colorectal cancer drug cetuximab, investigators found retrospectively that tumors with a mutation in the KRAS gene (which helps govern cell growth) did not respond to treatment. As a result, clinicians are now asked to confirm that patients do not have the mutation in the KRAS gene before they prescribe that particular drug. New drugs have been developed to target those mutations in the KRAS gene. It’s a step-by-step process from the discovery of these disease-related genes to the crafting of drugs that neutralize them. With CRISPR now available to them, many researchers believe that they can speed this process up. The technology is based on — and named after — a unique feature in the bacterial immune system that the organism uses to defend itself against viruses. CRISPR is found naturally in bacteria: It’s short for Clustered Regularly Interspaced Short Palindromic Repeats, and it functions like a mugshot database for bacteria, containing snippets of genetic code from foreign viruses that have tried to invade in the past. When new infections occur, the bacteria deploys RNA segments that scan for viral DNA that matches the mugshots. Special proteins are then dispatched to chop the virus up and neutralize it. Jonathan Wiggs/The Boston Globe via Getty Images The headquarters at CRISPR Therapeutics, which received the first FDA approval for a treatment that uses the CRISPR gene-editing technology. To develop CRISPR into a biotech platform, this protein-RNA complex was adapted from bacteria and inserted into human and animal cells, where it proved similarly effective at searching for and snipping strands of DNA. Using CRISPR in humans requires a few adjustments. Scientists have to teach the system to search through human DNA, which means that it will need a different “mugshot database” than what the bacteria originally needed. Critical to harnessing this natural process is artificial RNA, known as a guide RNA. These guide RNAs are designed to match genes found in humans. In theory, these guide RNAs search for and find a specific DNA sequence associated with a specific disease. The special protein attached to the guide RNA then acts like molecular scissors to cut the problematic gene. CRISPR’s therapeutic potential was evident in the breakthrough sickle cell treatment approved by the FDA late last year. What made sickle cell such an attractive target is not just that it affects around 20 million people or more worldwide, but that it is caused by a mutation in a single gene, which makes it simpler to study than a disease caused by multiple mutations. Sickle cell is one of the most common disorders worldwide that is caused by a mutation in a single gene. It was also the first to be characterized at a genetic level, making it a promising candidate for gene therapy. In sickle cell disease, a genetic mutation distorts the shape of a person’s hemoglobin, which is the protein that helps red blood cells carry and deliver oxygen from the lungs to tissues throughout the body. For people with sickle cell disease, their red blood cells look like “sickles” instead of the normal discs. As a result, they can get caught in blood vessels, blocking blood flow and causing issues like pain, strokes, infections, and death. Since the 1990s, clinicians have observed that sickle cell patients with higher levels of fetal hemoglobin tend to live longer. A series of genome-wide association studies from 2008 pointed to the BCL11A gene as a possible target for therapeutics. These association studies establish the relationships between specific genes and diseases, identifying candidates for CRISPR gene editing. Casgevy’s new CRISPR-derived treatment targets a gene called BCL11A. Inactivating this gene stops the mutated form of hemoglobin from being made and increases the production of normal non-sickled fetal hemoglobin, which people usually stop making after birth. Out of the 45 patients who have received Casgevy since the start of the trials, 28 of the 29 eligible patients who have stayed on long enough to have their results analyzed reported that they have been free of severe pain crises. Once the treatment moves out of clinical settings, its exact effects can vary. And if the underlying data set doesn’t reflect the diversity of the patient population, the gene therapies derived from them might not work the same for every person. The nuances of genetics Sickle cell disease as the first benefactor of CRISPR therapy makes sense because it’s a relatively simple disorder that has been studied for a long time. The genetic mutation causing it was found in 1956. But ironically, the same population that could benefit most from Casgvey may miss out on the full benefits of future breakthrough treatments. Scientists developing CRISPR treatments depend on what’s known as a reference genome, which is meant to be a composite representation of a “normal” human genome that can be used to identify genes of interest to target for treating a disease. However, most of the available reference genomes are representative of white Europeans. That’s a problem because not everybody’s DNA is identical: Recent sequencing of African genomes shows that they have 10 percent more DNA than the standard reference genome available to researchers. Researchers have theorized that this is because most modern humans came out of Africa. As populations diverged and reconcentrated, genetic bottlenecks happened, which resulted in a loss of genetic variation compared to the original population. Most genome-wide association studies are also biased in the same way: They have a lot of data from white people and not a lot from people of color. So while those studies can help identify genes of importance that could lead to effective treatments for the population whose genes make up the majority of the reference data — i.e., white people — the same treatments may not work as well for other nonwhite populations. “Broadly, there’s been an issue with human genetics research — there’s been a major under-representation of people of African ancestry, both in the US and elsewhere,” said Sarah Tishkoff, professor of genetics and biology at the University of Pennsylvania. “Without including these diverse populations, we’re missing out on that knowledge that could perhaps result in better therapeutics or better diagnostics.” Even in the case of the notorious breast cancer gene BRCA1, where a single gene mutation can have a serious clinical impact and is associated with an increased risk of developing cancer, underlying mutations within the gene “tend to differ in people of different ancestries,” Tishkoff said. These differences, whether large or small, can matter. Although the vast majority of human genomes are the same, a small fraction of the letters making up our genes can differ from person to person and from population to population, with potentially significant medical implications. Sometimes during sequencing, genetic variations of “unknown significance” appear. These variants could be clinically important, but because of the lack of diversity in previous research populations, no one has studied them closely enough to understand their impact. “If all the research is being done in people of predominantly European ancestry, you’re only going to find those variants,” Tishkoff said. Tammy Ljungblad/The Kansas City Star/Tribune News Service via Getty Images A patient receives treatment for sickle-cell disease in 2018, prior to the FDA’s approval in late 2023 of a new CRISPR-based therapy for the condition. Those limitations affect scientists up and down the developmental pipeline. For researchers using CRISPR technology in preclinical work, the lack of diversity in the genome databases can make it harder to identify the possible negative effect of such genetic variation on the treatments they’re developing. Sean Misek, a postdoctoral researcher at the Broad Institute of MIT and Harvard, started developing a project with the goal of investigating the differences in the genetic patterns of tumors from patients of European descent compared to patients of African descent. CRISPR has become a versatile tool. Not only can it be used for treatments, but it can also be used for diagnostics and basic research. He and his colleagues intended to use CRISPR to screen for those differences because it can evaluate the effects of multiple genes at once, as opposed to the traditional method of testing one gene at a time. “We know individuals of different ancestry groups have different overall clinical responses to cancer treatments,” Misek said. “Individuals of recent African descent, for example, have worse outcomes than individuals of European descent, which is a problem that we were interested in trying to understand more.” What they encountered instead was a roadblock. When Misek’s team tried to design CRISPR guides, they found that their guides matched the genomes in the cells of people with European and East Asian ancestry, whose samples made up most of the reference genome, but not on cells from people of South Asian or African ancestry, who are far less represented in databases. In combination with other data biases in cancer research, the guide RNA mismatch has made it more difficult to investigate the tumor biology of non-European patients. Genetic variations across ancestry groups not only affect whether CRISPR technology works at all, but they can also lead to unforeseen side effects when the tool makes cuts in places outside of the intended genetic target. Such side effects of “off-target” gene edits could theoretically include cancer. “A big part of developing CRISPR therapy is trying to figure out if there are off-targets. Where? And if they exist, do they matter?” said Daniel Bauer, an attending physician at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. To better predict potential off-target edits, Bauer collaborated with Luca Pinello, associate professor at Massachusetts General Hospital and Harvard Medical School, who had helped develop a tool called CRISPRme that makes projections based on personal and population-level variations in genetics. To test it, they examined the guide RNA being used for sickle cell disease treatment, and found an off-target edit almost exclusively present in cells donated by a patient of African ancestry. It is currently unclear if this off-target edit detected by the CRISPRme tool has any negative consequences. When the FDA approved the sickle-cell therapy in December 2023, regulators required a post-marketing study to look into off-target effects. Any off-target edits affecting a person’s blood should be easily detected in the blood cells, and drawing blood is easier to do than collecting cells from an internal organ, for example. The genetic variant where the off-target effect occurred can be found in approximately every 1 in 10 people with African ancestry. “The fact that we actually were able to find a donor who carried this variant was kind of luck,” Bauer said. “If the cells we were using were only of European ancestry, it would’ve been even harder to find.” “Most of these [off-target] effects probably won’t cause any problems,” he said. “But I think we also have these great technologies, so that’s part of our responsibility to look as carefully as we can.” To CRISPR or not to CRISPR These issues recur again and again as investigators hunt for novel treatments. Katalin Susztak, professor of medicine and genetics at the University of Pennsylvania, thinks one promising candidate for a future CRISPR therapy is a standout gene for kidney disease: APOL1. Researchers identified the gene when they looked into kidney disease risk in African Americans. While genome-wide association studies turned up thousands of distinct genes increasing risk for people of European ancestry, in African Americans, this single gene was responsible for “3 to 5 times higher risk of kidney disease in patients,” said Susztak. The APOL1 variant is common among African Americans because it protects people from developing African sleeping sickness, which is spread by the Tsetse fly present across much of the continent. This is similar to the story of the sickle cell mutation, which can protect people from malaria. “The variant is maybe only 5,000 years old, so this variant has not arisen in Europe, Asia, or anywhere else. Just in West Africa,” Susztak said. “But because of the slave trades, West Africans were brought to the United States, so millions of people in the United States have this variant.” The variant also predisposes people to develop cardiovascular disease, high blood pressure, and COVID-related disease, “which maybe explains why there was an increased incidence of deaths in African Americans during COVID than in Europeans,” Susztak said. “APOL1 is potentially a very interesting target [for CRISPR] because the disease association is strong.” A CRISPR treatment for kidney disease is currently being investigated, but using the tool comes with complications. Cutting the APOL1 gene would set off an immune response, Susztak noted, so they will have to somehow prevent undesirable side effects, or find a related, but editable gene, like they did with sickle cell. An alternative RNA-based strategy utilizing CRISPR is also in the works. DNA needs to be transcribed into a messenger RNA sequence first before it can be turned into proteins. Instead of permanently altering the genome, RNA editing alters the sequence of RNAs, which can then change what proteins are produced. The effects are less permanent, however, lasting for a few months instead of forever — which can be advantageous for treating temporary medical conditions. And it may turn out that gene therapy is simply not the right approach to the problem. Sometimes, a more conventional approach still works best. Susztak said that a small molecule drug developed by Vertex — which works similarly to most drugs except special classes like gene therapies or biologics — to inhibit the function of the APOL1 protein has enjoyed positive results in early clinical trials. An outlook on the future of CRISPR Even with these limitations, more CRISPR treatments are coming down the pike. As of early last year, more than 200 people have been treated with experimental CRISPR therapies for cancers, blood disorders, infections, and more. In the developmental pipeline is a CRISPR-based therapeutic from Intellia Therapeutics that treats transthyretin amyloidosis, a rare condition affecting the function of the heart tissues and nerves. The drug has performed well in early trials and is now recruiting participants for a Phase III study. Another CRISPR drug from Intellia for hereditary angioedema, a condition that causes severe swelling throughout the body, is slated to enter Phase III later this year. As the CRISPR boom continues, some research groups are slowly improving the diversity of their genetic sources. The All of Us program from the National Institutes of Health, which aims to find the biological, environmental, and lifestyle factors that contribute to health, has analyzed 245,000 genomes to date, over 40 percent of which came from participants who were not of European ancestry. They found new genetic markers for diabetes that have never been identified before. Then there’s the Human Pangenome project, which aims to create a reference genome that captures more global diversity. The first draft of its proposal was released last May. Another project called the PAGE study, funded by the National Human Genome Research Institute and the National Institute on Minority Health and Health Disparities, is working to include more ancestrally diverse populations in genome-wide association studies. Getty Images/Westend61 New projects are underway to gather genetic data from underrepresented people and improve scientists’ ability to develop effective CRISPR therapies. But at the current pace, experts predict that it will take years to reach parity in our genetic databases. And the scientific community must also build trust with the communities it’s trying to help. The US has a murky history with medical ethics, especially around race. Take the Tuskegee experiment that charted the progression of syphilis in Black American men while hiding the true purpose of the study from the participants and withholding their ability to seek treatment when it became available, or the controversy over Henrietta Lacks’ cervical cells, which were taken and used in research without her consent. Those are just two prominent historical abuses that have eroded trust between minority communities and the country’s medical system, Tishkoff said. That history has made it more difficult to collect samples from marginalized communities and add them to these critical data sets. Where the research is being done, where the clinical trials are being held, as well as who’s doing the research, can all have an impact on which patients participate. The Human Genetics & Genomics Workforce Survey Report published by the American Society of Human Genetics in 2022 found that 67 percent of the genomic workforce identified as white. Add in the financial burden of developing new treatments when using a reference genome, or a pre-made biobank from past efforts to collect and organize a large volume of biological samples, saves time and costs. In the race to bring CRISPR treatments to market, those shortcuts offered valuable efficiency to drug makers. What this means is that the “first-generation” of CRISPR therapeutics might therefore be blunter instruments than they might otherwise be. However, if improvements can be made to make sure the source genomes reflect a wider range of people, Pinello believes that later generations of CRISPR will be more personalized and therefore more effective for more people. Finding the genes and making drugs that work is, of course, momentous — but ultimately, that’s only half the battle. The other worry physicians like Susztak have is whether patients will be able to afford and access these innovative treatments. There is still an overwhelming racial disparity in clinical trial enrollment. Studies have found that people of color are more likely to suffer from chronic illness and underuse medications like insulin compared to their white counterparts. Gene therapies easily rack up price tags in the millions, and insurance companies, including the Centers for Medicare and Medicaid Services, are still trying to figure out how to pay for them. “Because it’s the pharmaceutical industry, if they don’t turn around profit, if they cannot test the drug, or if people are unwilling to take it, then this inequity is going to be worsened,” said Susztak. “We are essentially going to be creating something that makes things worse even though we are trying to help.”

"Alright, alright, alright," Kardashian said as she attempted to calm the audience.

The criminal hush money trial continues for its fourth week in New York City. Follow Newsweek's live blog for the latest updates.

More than 25 million people are under the threat of severe storms from Dallas, Texas to Sioux Falls, South Dakota. CNN Meteorologist Derek Van Dam reports on the latest.

Ben Affleck's appearance at Netflix's Tom Brady roast was judged, with one fan saying, "Ben Affleck’s face lift looks insane."

Steward Health Care, the struggling hospital group that owns hospitals in Massachusetts, Texas, Florida and other states, announced Monday that it is filing for bankruptcy.

"Pull it together and stand with other women," Marcil told "stupid, transparent (jealous)" Instagram trolls. "We are still the minorities."

Dangerous impacts from the heat are expected to peak on Wednesday.

Many Americans convicted of drug crimes do not have access to SNAP benefits currently.

Columbia University is canceling its university-wide commencement ceremony on May 15 after weeks of disruptive and violent anti-Israel protests on campus, officials at the Ivy League school said Monday.Instead, the university is opting for “smaller-scale, school-based celebrations.” “We have decided to make the centerpiece of our commencement activities our class days and school-level ceremonies, where students are...

Hormel Foods says potentially contaminated products were shipped to Publix and Dollar Tree distribution warehouses.

The University of Mississippi NAACP chapter has called for the expulsion of the "primary perpetrators of racist remarks."

After years of delays, Boeing is set to launch its Starliner spacecraft with a crew for the first time Monday. The test flight will carry two astronauts to the International Space Station.

Caitlin Ochs/ReutersColumbia is canceling its university-wide commencement ceremony later this month and will instead proceed with “smaller-scale, school-based celebrations,” officials said Monday, after several weeks of turmoil on campus amid protests around Israel’s war in Gaza.In a statement, the Ivy League school said “Class Days and school-level ceremonies, where students are honored individually alongside their peers,” would form the “centerpiece” of commencement activities “rather than the University-wide ceremony that is scheduled for May 15.” It added that it would be focusing resources on ensuring that the ceremonies are kept “safe, respectful, and running smoothly.”The decision comes after weeks of tension between pro-Palestinian activists and school officials that have seen demonstrators suspended and even arrested in police crackdowns. The encampment that sprang up at the New York City campus has inspired activists to launch similar protest campaigns at other schools around the U.S. and internationally.Read more at The Daily Beast.

The Kansas City Chiefs tight end spent Sunday night at American Express' Carbone Beach alongside race winner Lando Norris.

The opening weekend of the high school baseball playoffs was filled with top performances by ace pitchers.

The seven-time Super Bowl-winning quarterback caught multiple jabs during his Netflix roast that aired Sunday night for leaving Bridget Moynahan while she was pregnant in 2006.

Houston Texans legend and five-time First-team All-Pro defensive end J.J. Watt is open to a return to the NFL.

As more older workers retire, a tough labor market and a limited number of candidates means leaders will need to get creative to attract qualified candidates.

After her bathroom got clogged, visitors must now dig a hole in the garden if they need to go, Ivy Bloom, 23, tells Newsweek

Hispanic and Black Americans both reported more stress with applications than white Americans.

Elizabeth Pipko, a 28-year-old born-and-bred Manhattanite, told The Post she’s happy to trade her signature “New York uniform of dark black” for red, white and blue as she helps the rebranded RNC try to re-elect the former president in November.