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‘Bird Flu-Pocalypse’ Forces Hong Kong To Suspend Some Imports Of US Poultry Meat

‘Bird Flu-Pocalypse’ Forces Hong Kong To Suspend Some Imports Of US Poultry Meat

The recent spread of bird flu—also known as highly pathogenic…

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'Bird Flu-Pocalypse' Forces Hong Kong To Suspend Some Imports Of US Poultry Meat

The recent spread of bird flu—also known as highly pathogenic avian influenza, or HPAI— across several US states has been hyped by corporate media. Some journalists are quoting 'experts' who warn the bird flu pandemic could be '100 times worse' than Covid.' 

According to Bloomberg data, the story count in corporate media for all things "Bird Flu" last week hit a record high on data going back to 2014. 

The context here is crucial. Bird flu is not just a US issue anymore; it's 'going global,' and this is happening just before the US presidential elections in November.  

On Tuesday, Hong Kong's food safety authority published a memo stating, "Import of poultry meat and poultry products suspended in some areas of the United States." 

Here's the full memo from the Center for Food Safety (CFS) of the Food and Environmental Hygiene Department:

The Center for Food Safety (CFS) of the Food and Environmental Hygiene Department announced today (April 9) that in response to a notification from the World Organization for Animal Health regarding an outbreak of highly pathogenic H5N1 avian influenza in Ionia County, Michigan, and Parmer County, Texas, USA, The CFS immediately instructed the trade to suspend the import of poultry meat and poultry products (including poultry eggs) from the above-mentioned areas to protect public health in Hong Kong.

A spokesman for the CFS said that according to the Census and Statistics Department, Hong Kong imported about 37,770 tonnes of chilled and frozen poultry meat and about 83.84 million poultry eggs from the United States last year.

The spokesman said: "The CFS has contacted the US authorities regarding the incident and will continue to closely monitor information on the outbreak of avian influenza from the World Organization for Animal Health and relevant authorities, and will take appropriate actions in light of the development of the local epidemic."

If it's bird flu or whatever "Disease X" could possibly be, there appears to be a push to "intersect" some type of 'Covid crisis' before the 2024 US elections.

"They will surely try to run their "Disease X" ruse. But they have already lost the trust of the people they made war against in their own country. In which case, expect resistance among the un-sick," James Howard Kunstler penned in a note earlier this month.

Tyler Durden Tue, 04/09/2024 - 21:20

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“An Open-Minded Spirit No Longer Exists Within NPR” – NPR Veteran Excoriates Outlet Over Hunter, Russiagate Activism

"An Open-Minded Spirit No Longer Exists Within NPR" – NPR Veteran Excoriates Outlet Over Hunter, Russiagate Activism

Authored by Uri Berliner…

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"An Open-Minded Spirit No Longer Exists Within NPR" - NPR Veteran Excoriates Outlet Over Hunter, Russiagate Activism

Authored by Uri Berliner via The Free Press (emphasis ours),

You know the stereotype of the NPR listener: an EV-driving, Wordle-playing, tote bag–carrying coastal elite. It doesn’t precisely describe me, but it’s not far off. I’m Sarah Lawrence–educated, was raised by a lesbian peace activist mother, I drive a Subaru, and Spotify says my listening habits are most similar to people in Berkeley. 

I fit the NPR mold. I’ll cop to that.

So when I got a job here 25 years ago, I never looked back. As a senior editor on the business desk where news is always breaking, we’ve covered upheavals in the workplace, supermarket prices, social media, and AI. 

It’s true NPR has always had a liberal bent, but during most of my tenure here, an open-minded, curious culture prevailed. We were nerdy, but not knee-jerk, activist, or scolding. 

In recent years, however, that has changed. Today, those who listen to NPR or read its coverage online find something different: the distilled worldview of a very small segment of the U.S. population. 

If you are conservative, you will read this and say, duh, it’s always been this way.

But it hasn’t.

For decades, since its founding in 1970, a wide swath of America tuned in to NPR for reliable journalism and gorgeous audio pieces with birds singing in the Amazon. Millions came to us for conversations that exposed us to voices around the country and the world radically different from our own—engaging precisely because they were unguarded and unpredictable. No image generated more pride within NPR than the farmer listening to Morning Edition from his or her tractor at sunrise. 

Back in 2011, although NPR’s audience tilted a bit to the left, it still bore a resemblance to America at large. Twenty-six percent of listeners described themselves as conservative, 23 percent as middle of the road, and 37 percent as liberal.

By 2023, the picture was completely different: only 11 percent described themselves as very or somewhat conservative, 21 percent as middle of the road, and 67 percent of listeners said they were very or somewhat liberal. We weren’t just losing conservatives; we were also losing moderates and traditional liberals. 

An open-minded spirit no longer exists within NPR, and now, predictably, we don’t have an audience that reflects America. 

That wouldn’t be a problem for an openly polemical news outlet serving a niche audience. But for NPR, which purports to consider all things, it’s devastating both for its journalism and its business model.

*  *  *

Like many unfortunate things, the rise of advocacy took off with Donald Trump. As in many newsrooms, his election in 2016 was greeted at NPR with a mixture of disbelief, anger, and despair. (Just to note, I eagerly voted against Trump twice but felt we were obliged to cover him fairly.) But what began as tough, straightforward coverage of a belligerent, truth-impaired president veered toward efforts to damage or topple Trump’s presidency. 

Persistent rumors that the Trump campaign colluded with Russia over the election became the catnip that drove reporting. At NPR, we hitched our wagon to Trump’s most visible antagonist, Representative Adam Schiff. 

Schiff, who was the top Democrat on the House Intelligence Committee, became NPR’s guiding hand, its ever-present muse. By my count, NPR hosts interviewed Schiff 25 times about Trump and Russia. During many of those conversations, Schiff alluded to purported evidence of collusion. The Schiff talking points became the drumbeat of NPR news reports.

But when the Mueller report found no credible evidence of collusion, NPR’s coverage was notably sparse. Russiagate quietly faded from our programming. 

It is one thing to swing and miss on a major story. Unfortunately, it happens. You follow the wrong leads, you get misled by sources you trusted, you’re emotionally invested in a narrative, and bits of circumstantial evidence never add up. It’s bad to blow a big story. 

What’s worse is to pretend it never happened, to move on with no mea culpas, no self-reflection. Especially when you expect high standards of transparency from public figures and institutions, but don’t practice those standards yourself. That’s what shatters trust and engenders cynicism about the media. 

Russiagate was not NPR’s only miscue.

In October 2020, the New York Post published the explosive report about the laptop Hunter Biden abandoned at a Delaware computer shop containing emails about his sordid business dealings. With the election only weeks away, NPR turned a blind eye. Here’s how NPR’s managing editor for news at the time explained the thinking: “We don’t want to waste our time on stories that are not really stories, and we don’t want to waste the listeners’ and readers’ time on stories that are just pure distractions.” 

But it wasn’t a pure distraction, or a product of Russian disinformation, as dozens of former and current intelligence officials suggested. The laptop did belong to Hunter Biden. Its contents revealed his connection to the corrupt world of multimillion-dollar influence peddling and its possible implications for his father.

The laptop was newsworthy. But the timeless journalistic instinct of following a hot story lead was being squelched. During a meeting with colleagues, I listened as one of NPR’s best and most fair-minded journalists said it was good we weren’t following the laptop story because it could help Trump. 

When the essential facts of the Post’s reporting were confirmed and the emails verified independently about a year and a half later, we could have fessed up to our misjudgment. But, like Russia collusion, we didn’t make the hard choice of transparency. 

Politics also intruded into NPR’s Covid coverage, most notably in reporting on the origin of the pandemic. One of the most dismal aspects of Covid journalism is how quickly it defaulted to ideological story lines. For example, there was Team Natural Origin—supporting the hypothesis that the virus came from a wild animal market in Wuhan, China. And on the other side, Team Lab Leak, leaning into the idea that the virus escaped from a Wuhan lab. 

The lab leak theory came in for rough treatment almost immediately, dismissed as racist or a right-wing conspiracy theory. Anthony Fauci and former NIH head Francis Collins, representing the public health establishment, were its most notable critics. And that was enough for NPR. We became fervent members of Team Natural Origin, even declaring that the lab leak had been debunked by scientists. 

But that wasn’t the case.

When word first broke of a mysterious virus in Wuhan, a number of leading virologists immediately suspected it could have leaked from a lab there conducting experiments on bat coronaviruses. This was in January 2020, during calmer moments before a global pandemic had been declared, and before fear spread and politics intruded. 

Reporting on a possible lab leak soon became radioactive. Fauci and Collins apparently encouraged the March publication of an influential scientific paper known as “The Proximal Origin of SARS-CoV-2.” Its authors wrote they didn’t believe “any type of laboratory-based scenario is plausible.” 

But the lab leak hypothesis wouldn’t die. And understandably so. In private, even some of the scientists who penned the article dismissing it sounded a different tune. One of the authors, Andrew Rambaut, an evolutionary biologist from Edinburgh University, wrote to his colleagues, “I literally swivel day by day thinking it is a lab escape or natural.”

Over the course of the pandemic, a number of investigative journalists made compelling, if not conclusive, cases for the lab leak. But at NPR, we weren’t about to swivel or even tiptoe away from the insistence with which we backed the natural origin story. We didn’t budge when the Energy Department—the federal agency with the most expertise about laboratories and biological research—concluded, albeit with low confidence, that a lab leak was the most likely explanation for the emergence of the virus.

Instead, we introduced our coverage of that development on February 28, 2023, by asserting confidently that “the scientific evidence overwhelmingly points to a natural origin for the virus.” 

When a colleague on our science desk was asked why they were so dismissive of the lab leak theory, the response was odd. The colleague compared it to the Bush administration’s unfounded argument that Iraq possessed weapons of mass destruction, apparently meaning we won’t get fooled again. But these two events were not even remotely related. Again, politics were blotting out the curiosity and independence that ought to have been driving our work. 

Uri Berliner near his home in Washington, D.C., on April 5, 2024. (Photo by Pete Kiehart for The Free Press)

I’m offering three examples of widely followed stories where I believe we faltered. Our coverage is out there in the public domain. Anyone can read or listen for themselves and make their own judgment. But to truly understand how independent journalism suffered at NPR, you need to step inside the organization.

You need to start with former CEO John Lansing. Lansing came to NPR in 2019 from the federally funded agency that oversees Voice of America. Like others who have served in the top job at NPR, he was hired primarily to raise money and to ensure good working relations with hundreds of member stations that acquire NPR’s programming. 

After working mostly behind the scenes, Lansing became a more visible and forceful figure after the killing of George Floyd in May 2020. It was an anguished time in the newsroom, personally and professionally so for NPR staffers. Floyd’s murder, captured on video, changed both the conversation and the daily operations at NPR. 

Given the circumstances of Floyd’s death, it would have been an ideal moment to tackle a difficult question: Is America, as progressive activists claim, beset by systemic racism in the 2020s—in law enforcement, education, housing, and elsewhere? We happen to have a very powerful tool for answering such questions: journalism. Journalism that lets evidence lead the way. 

But the message from the top was very different. America’s infestation with systemic racism was declared loud and clear: it was a given. Our mission was to change it.

“When it comes to identifying and ending systemic racism,” Lansing wrote in a companywide article, “we can be agents of change. Listening and deep reflection are necessary but not enough. They must be followed by constructive and meaningful steps forward. I will hold myself accountable for this.”

And we were told that NPR itself was part of the problem. In confessional language he said the leaders of public media, “starting with me—must be aware of how we ourselves have benefited from white privilege in our careers. We must understand the unconscious bias we bring to our work and interactions. And we must commit ourselves—body and soul—to profound changes in ourselves and our institutions.”

He declared that diversity—on our staff and in our audience—was the overriding mission, the “North Star” of the organization. Phrases like “that’s part of the North Star” became part of meetings and more casual conversation.

Race and identity became paramount in nearly every aspect of the workplace. Journalists were required to ask everyone we interviewed their race, gender, and ethnicity (among other questions), and had to enter it in a centralized tracking system. We were given unconscious bias training sessions. A growing DEI staff offered regular meetings imploring us to “start talking about race.” Monthly dialogues were offered for “women of color” and “men of color.” Nonbinary people of color were included, too. 

These initiatives, bolstered by a $1 million grant from the NPR Foundation, came from management, from the top down. Crucially, they were in sync culturally with what was happening at the grassroots—among producers, reporters, and other staffers. Most visible was a burgeoning number of employee resource (or affinity) groups based on identity.

They included MGIPOC (Marginalized Genders and Intersex People of Color mentorship program); Mi Gente (Latinx employees at NPR); NPR Noir (black employees at NPR); Southwest Asians and North Africans at NPR; Ummah (for Muslim-identifying employees); Women, Gender-Expansive, and Transgender People in Technology Throughout Public Media; Khevre (Jewish heritage and culture at NPR); and NPR Pride (LGBTQIA employees at NPR).

All this reflected a broader movement in the culture of people clustering together based on ideology or a characteristic of birth. If, as NPR’s internal website suggested, the groups were simply a “great way to meet like-minded colleagues” and “help new employees feel included,” it would have been one thing. 

But the role and standing of affinity groups, including those outside NPR, were more than that. They became a priority for NPR’s union, SAG-AFTRA—an item in collective bargaining. The current contract, in a section on DEI, requires NPR management to “keep up to date with current language and style guidance from journalism affinity groups” and to inform employees if language differs from the diktats of those groups. In such a case, the dispute could go before the DEI Accountability Committee.

In essence, this means the NPR union, of which I am a dues-paying member, has ensured that advocacy groups are given a seat at the table in determining the terms and vocabulary of our news coverage. 

Conflicts between workers and bosses, between labor and management, are common in workplaces. NPR has had its share. But what’s notable is the extent to which people at every level of NPR have comfortably coalesced around the progressive worldview. 

And this, I believe, is the most damaging development at NPR: the absence of viewpoint diversity. 

*  *  *

There’s an unspoken consensus about the stories we should pursue and how they should be framed. It’s frictionless—one story after another about instances of supposed racism, transphobia, signs of the climate apocalypse, Israel doing something bad, and the dire threat of Republican policies. It’s almost like an assembly line. 

The mindset prevails in choices about language. In a document called NPR Transgender Coverage Guidance—disseminated by news management—we’re asked to avoid the term biological sex. (The editorial guidance was prepared with the help of a former staffer of the National Center for Transgender Equality.) The mindset animates bizarre stories—on how The Beatles and bird names are racially problematic, and others that are alarmingly divisive; justifying looting, with claims that fears about crime are racist; and suggesting that Asian Americans who oppose affirmative action have been manipulated by white conservatives.

More recently, we have approached the Israel-Hamas war and its spillover onto streets and campuses through the “intersectional” lens that has jumped from the faculty lounge to newsrooms. Oppressor versus oppressed. That’s meant highlighting the suffering of Palestinians at almost every turn while downplaying the atrocities of October 7, overlooking how Hamas intentionally puts Palestinian civilians in peril, and giving little weight to the explosion of antisemitic hate around the world. 

For nearly all my career, working at NPR has been a source of great pride. It’s a privilege to work in the newsroom at a crown jewel of American journalism. My colleagues are congenial and hardworking. 

I can’t count the number of times I would meet someone, describe what I do, and they’d say, “I love NPR!” 

And they wouldn’t stop there. They would mention their favorite host or one of those “driveway moments” where a story was so good you’d stay in your car until it finished.

It still happens, but often now the trajectory of the conversation is different. After the initial “I love NPR,” there’s a pause and a person will acknowledge, “I don’t listen as much as I used to.” Or, with some chagrin: “What’s happening there? Why is NPR telling me what to think?”

In recent years I’ve struggled to answer that question. Concerned by the lack of viewpoint diversity, I looked at voter registration for our newsroom. In D.C., where NPR is headquartered and many of us live, I found 87 registered Democrats working in editorial positions and zero Republicans. None. 

So on May 3, 2021, I presented the findings at an all-hands editorial staff meeting. When I suggested we had a diversity problem with a score of 87 Democrats and zero Republicans, the response wasn’t hostile. It was worse. It was met with profound indifference. I got a few messages from surprised, curious colleagues. But the messages were of the “oh wow, that’s weird” variety, as if the lopsided tally was a random anomaly rather than a critical failure of our diversity North Star. 

In a follow-up email exchange, a top NPR news executive told me that she had been “skewered” for bringing up diversity of thought when she arrived at NPR. So, she said, “I want to be careful how we discuss this publicly.”

For years, I have been persistent. When I believe our coverage has gone off the rails, I have written regular emails to top news leaders, sometimes even having one-on-one sessions with them. On March 10, 2022, I wrote to a top news executive about the numerous times we described the controversial education bill in Florida as the “Don’t Say Gay” bill when it didn’t even use the word gay. I pushed to set the record straight, and wrote another time to ask why we keep using that word that many Hispanics hate—Latinx. On March 31, 2022, I was invited to a managers’ meeting to present my observations.

Throughout these exchanges, no one has ever trashed me. That’s not the NPR way. People are polite. But nothing changes. So I’ve become a visible wrong-thinker at a place I love. It’s uncomfortable, sometimes heartbreaking.

Even so, out of frustration, on November 6, 2022, I wrote to the captain of ship North Star—CEO John Lansing—about the lack of viewpoint diversity and asked if we could have a conversation about it. I got no response, so I followed up four days later. He said he would appreciate hearing my perspective and copied his assistant to set up a meeting. On December 15, the morning of the meeting, Lansing’s assistant wrote back to cancel our conversation because he was under the weather. She said he was looking forward to chatting and a new meeting invitation would be sent. But it never came.

I won’t speculate about why our meeting never happened. Being CEO of NPR is a demanding job with lots of constituents and headaches to deal with. But what’s indisputable is that no one in a C-suite or upper management position has chosen to deal with the lack of viewpoint diversity at NPR and how that affects our journalism. 

Which is a shame. Because for all the emphasis on our North Star, NPR’s news audience in recent years has become less diverse, not more so. Back in 2011, our audience leaned a bit to the left but roughly reflected America politically; now, the audience is cramped into a smaller, progressive silo. 

Despite all the resources we’d devoted to building up our news audience among blacks and Hispanics, the numbers have barely budged. In 2023, according to our demographic research, 6 percent of our news audience was black, far short of the overall U.S. adult population, which is 14.4 percent black. And Hispanics were only 7 percent, compared to the overall Hispanic adult population, around 19 percent. Our news audience doesn’t come close to reflecting America. It’s overwhelmingly white and progressive, and clustered around coastal cities and college towns.

These are perilous times for news organizations. Last year, NPR laid off or bought out 10 percent of its staff and canceled four podcasts following a slump in advertising revenue. Our radio audience is dwindling and our podcast downloads are down from 2020. The digital stories on our website rarely have national impact. They aren’t conversation starters. Our competitive advantage in audio—where for years NPR had no peer—is vanishing. There are plenty of informative and entertaining podcasts to choose from. 

Even within our diminished audience, there’s evidence of trouble at the most basic level: trust. 

In February, our audience insights team sent an email proudly announcing that we had a higher trustworthy score than CNN or The New York Times. But the research from Harris Poll is hardly reassuring. It found that “3-in-10 audience members familiar with NPR said they associate NPR with the characteristic ‘trustworthy.’ ” Only in a world where media credibility has completely imploded would a 3-in-10 trustworthy score be something to boast about. 

With declining ratings, sorry levels of trust, and an audience that has become less diverse over time, the trajectory for NPR is not promising. Two paths seem clear. We can keep doing what we’re doing, hoping it will all work out. Or we could start over, with the basic building blocks of journalism. We could face up to where we’ve gone wrong. News organizations don’t go in for that kind of reckoning. But there’s a good reason for NPR to be the first: we’re the ones with the word public in our name. 

Despite our missteps at NPR, defunding isn’t the answer. As the country becomes more fractured, there’s still a need for a public institution where stories are told and viewpoints exchanged in good faith. Defunding, as a rebuke from Congress, wouldn’t change the journalism at NPR. That needs to come from within.

A few weeks ago, NPR welcomed a new CEO, Katherine Maher, who’s been a leader in tech. She doesn’t have a news background, which could be an asset given where things stand. I’ll be rooting for her. It’s a tough job. Her first rule could be simple enough: don’t tell people how to think. It could even be the new North Star.

Uri Berliner is a senior business editor and reporter at NPR. His work has been recognized with a Peabody Award, a Loeb Award, an Edward R. Murrow Award, and a Society of Professional Journalists New America Award, among others. Follow him on X (formerly Twitter) @uberliner.

Tyler Durden Tue, 04/09/2024 - 13:50

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Organoids Stand Out as Stand Ins in Drug Development

Organoids may make the truest tissue models. But what makes the truest organoids? An answer to that question was suggested in a review article that appeared…

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Organoids may make the truest tissue models. But what makes the truest organoids? An answer to that question was suggested in a review article that appeared 10 years ago,1 just a few years after organoids began incorporating induced pluripotent stem cells. Today, the review article’s main point is as apt as ever: “Organoids are derived from pluripotent stem cells or isolated organ progenitors that differentiate to form an organ-like tissue exhibiting multiple cell types that self-organize to form a structure not unlike the organ in vivo. … Because organoids can be grown from human stem cells and from patient-derived induced pluripotent stem cells, they have the potential to model human development and disease. Furthermore, they have potential for drug testing and even future organ replacement strategies.”

Organoids of this sort can mirror the genotype and phenotype of real tissues. Indeed, this capability has been demonstrated in the creation of organoids that mimic different tissues, such as tissues of the brain, gut, and lung. Also, there are immune organoids, or lymphoid tissue models. (Alternatively, the term “immune organoids” may refer to tissue models of any type that incorporate a functional immune system.)

Organoid development has been accelerating thanks to the introduction of commercial technologies. For example, there are extracellular matrix gels that, in the words supplied by the review, allow organoids to “self-organize through cell sorting out and stem cell lineage commitment in a spatially defined manner to recapitulate organization of different organ cell types.” Also, there are technologies that combine organoids with microfluidic systems, which can provide sophisticated microenvironments for recapitulating body organs.

Such technologies are enabling the modeling of rare diseases and tumors. Also, they are encouraging developers and regulators to position organoids as alternatives to animal models in drug testing. It should come as no surprise, then, that organoids represent a market with enormous growth potential. According to a market research study issued in 2023 by Insight Partners, the organoid market will register an annual growth rate of 22% in the coming years and reach a value of $12 billion by 2030.

Mini organs on scaffolds

“Organoids have become increasingly popular as tissue models since they can retain the genetic and phenotypic heterogeneity of the original tissue,” reports Hilary Sherman, senior applications scientist, Corning Life Sciences. “This concept has become invaluable for cancer research, where we know that individuals with similar cancers can respond very differently to drugs. Additionally, organoid models can be developed more quickly and cheaply than animal models.”

Sherman notes that organoids can model diseases that are a result of multiple or varied mutations. Indeed, organoids can model complex genetic diseases such as cancer. If organoids incorporate patient-specific mutations, individualized modeling is possible. Such modeling could be used to determine which drugs would be most suitable for individual patients.

Hilary Sherman
Corning Life Sciences

Organoids can be assembled or allowed to self-assemble. In either case, they are typically cultured with specific growth factors and extracellular matrix proteins. This approach was pioneered in 2009, when researchers generated the first 3D organoid culture from adult stem cells.2 They used Corning Matrigel Matrix, a solubilized basement membrane preparation. Rich in extracellular matrix proteins such as laminin and collagen, Matrigel Matrix is used to produce hydrogels that support organ/tissue architectures. Sherman comments, “Corning Matrigel Matrix is considered the gold standard hydrogel for organoid applications.”

Corning also provides the Matribot bioprinter. It is designed to print with temperature-sensitive inks, such as inks containing Matrigel matrix or collagen. “Due to the bioprinter’s temperature-controlled print head, Matrigel Matrix/organoid ink solutions can easily be dispensed into microplates,” Sherman notes. “Often, organoid assays are conducted by dispensing small droplets of Matrigel Matrix/organoid solutions onto microplates.”

“I foresee the continued development of more complex organoid models that will continue to better recapitulate what is happening in vivo,” Sherman declares. “For me, a major accomplishment would be for organoids to completely replace animal testing.”

Corning Matribot bioprinter
The Corning Matribot bioprinter dispenses and prints with Corning Matrigel matrix, collagen, and other temperature-sensitive hydrogels without the need for cold blocks, ice buckets, or a cold room. The device can also be used to bioprint with hydrogels that need ambient temperature, such as alginate-based bioinks.

Multiple modalities

“[Organoids] have been harnessed for a multitude of purposes,” says Dan Rocca, PhD, research leader, Charles River Laboratories. “Brain organoids, for instance, have been used not only to understand early brain development in humans, but also to study how it may have been different in our Neanderthal cousins. Lung organoids have been used to test novel antivirals against SARS-CoV-2 during the pandemic. Tumor organoids, originating from a number of tissue-restricted primary cancers, have been used to help us to reveal how therapeutics impact tumor growth.”

Rocca observes that organoids “better mimic the complexity and heterogeneity of human tumors compared to cell lines isolated from tumor biopsies and support a personalized medicine approach.” Another advantage of organoids, Rocca points out, is that they can be used to help us reduce the number of animals used in drug development.

Dan Rocca, PhD
Dan Rocca, PhD
Charles River Laboratories

However, Rocca says one current challenge is that many organoids represent an early developmental state of an organ and can often form in an inside-out manner that doesn’t always reflect the mature tissue. “They lack vascularization and relevant microenvironments, plus their cross-talk with other organs is limited,” he points out. “These problems need to be carefully considered when interpreting findings from drug screens,
for example.”

Louise Brackenbury, PhD, science director, Charles River Laboratories, indicates that most of the company’s initial organoid focus is on “generating tissue-specific safety/toxicity models to better predict downstream clinical liabilities and de-risk discovery programs early, but they can also be used for mechanism-of-action studies and for efficacy testing.”

Louise Brackenbury, PhD
Louise Brackenbury, PhD
Charles River Laboratories

Brackenbury reports that gut organoids are the most developed organoid capability within the company: “They offer better predictivity following infection with enteroviruses and allow efficient and robust screening of antivirals.”

“Alongside this,” she continues, “our immune organoids have proven suitable for testing novel immunomodulators in B-cell recall responses, which we quantify by determining antibody production. Naïve responses to novel antigens, such as Ebola glycoprotein, are detectable in some donors, suggesting it may be a suitable platform in which to determine the immunogenicity of vaccine candidates in a fully ‘human’ system.”

Looking into future possibilities of the technology, Rocca projects, “A measure of great success of the technology would be to use organoids as therapeutic tools, instead of just models. The ability to expand scalable ‘organs’ in vitro and functionally transplant these into patients to ameliorate tissue defects would be a boon for regenerative medicine.”

Large-scale production

“The top three issues I see in organoid R&D today are scalability, reproducibility, and the ability to reflect genetic diversity,” states Shantanu Dhamija, PhD, vice president, strategy and innovation, Molecular Devices, an operating company of Danaher Corporation. He believes that solving these problems will require working in collaboration with others.

Shantanu Dhamija, PhD
Shantanu Dhamija, PhD
Molecular Devices

“Organoid research is a team sport where collaborations are key,” Dhamija stresses. “Under Danaher’s Beacon program, we identify leading innovators in the field to fund product-driven pioneering scientific research. The latest Beacon program with Cincinnati Children’s Hospital Medical Center focuses on preclinical drug safety issues and major causes of drug failure in clinical trials.”

In early February, the organizations launched a multiyear collaboration specifically aiming to improve liver organoid technology as a drug toxicity screening solution. The project will employ technology from Molecular Devices, such as the company’s new CellXpress.ai Automated Cell Culture System. Dhamija says this is “an artificial intelligence–enabled solution for the streamlined, reliable, and reproducible production of organoids at scale.”

Dhamija notes that more than 20% of all clinical trials fail due to liver toxicity. “Despite extensive and multifaceted safety testing for pharmaceuticals, drug-induced liver injury (DILI) remains a major challenge,” he continues. “It is not reliably predicted by current in vitro models, such as immortalized cell lines or primary cells. However, liver organoids represent more highly complex, multicellular, and physiologically relevant models capable of predicting individual patient reactions to therapeutics.”

Large-scale production has been a major challenge impeding the advance of organoids into this arena. “Due to their complexity, liver organoids have been harder to produce at scale with sufficient genetic diversity for accurate analyses,” Dhamija explains. “With our new systems, we can enable the creation of more diverse liver organoids at scale. This allows better patient stratification and higher reproducibility in clinical trials.”

organoids
This image from Molecular Devices shows HepG2 cells in organoid cultures before (top row) and after (bottom row) treatment with different compounds. Left: control (no treatment). Middle: haloperidol. Right: rotenone. Differences in viability are apparent.

Better together

Cellular models often can lack the complexity and sophistication necessary for accurate translation to human physiology and disease. Emulate places combinations of human organoids and/or other cell subsets on a chip to mirror organ responses more exactly. “The chips are agnostic to the cell,” says Lorna Ewart, PhD, the company’s CSO. Cell subsets can be organoids, cell lines, primary cells, or stem cells. “The benefit of an organoid,” she note, “is that it recapitulates epithelial biology.”

Lorna Ewart
Lorna Ewart, PhD
Emulate

Emulate’s chip system includes an upper and a lower channel separated by a porous membrane coated with a tissue-specific extracellular matrix. To create the intestinal chip, the company begins by establishing epithelial-like organoids from endoscopic biopsies of healthy adults. These are then dissociated and seeded into the chip’s top channel. Primary microvascular endothelial cells are added to the bottom channel.

“We include an endothelial cell because communication between the epithelium and endothelium is very important,” Ewart elaborates. “We also include a cyclic stretch to emulate in vivo peristaltic motions.” Two examples of the company’s Organ-Chips that employ organoids are the Colon Intestine-Chip and the Duodenum Intestine-Chip.

Ewart reports, “We have found that when tissue-specific microenvironments are recreated, biological processes related to intestinal maturation are enhanced.” Following growth and differentiation of the cells, the intestinal chip can be utilized for drug testing, studies of inflammation, studies of tumor invasion, and other applications.

The combination of organoids and organ chips can provide the best of both worlds. “The organoid cell cultures are more complex because they have the epithelial cells, and the cell communication avenues and microenvironments allow the cells to behave as if they were inside the human body,” Ewart says. “We are leveraging the strength of both technologies.”

Emulate is also engaged in a broader narrative of building a framework to help people understand the predictive value that Organ-Chip models can generate. “More published examples of Organ-Chip characterization are required to drive wider adoption in the pharmaceutical industry and to gain acceptance by regulatory bodies,” Ewart notes.

To that end, Ewart and Daniel Levner, PhD, Emulate’s CTO, co-authored a paper that detailed workflows for the practical use of the company’s Liver-Chip.3 In another paper, Ewart and colleagues discussed the Liver-Chip’s value in predictive toxicology.4 They argued that the platform would allow manufacturers to bring safer, more effective medicines to market in less time and at lower costs.

Ewart notes that the predictive toxicology paper ranks in the top 1% of research articles of a similar age in the field. “For a scientist, that is tremendous,” she declares. “It indicates that the information is well received, widely read, and frequently referenced!”

Ewart says that Emulate’s work is particularly relevant in light of the FDA Modernization Act 2.0. Passed in 2022, the act eliminates the requirement for mandatory animal testing before a drug can begin Phase I trials. Alternatives such as cell-based assays are now acceptable, paving the way for the use of organoids. Additionally, a further update, version 3.0, is currently being considered.

Future directions

Finally, it just may be true that the future of organoid R&D is out of this world! NASA’s Expedition 71 astronauts will be conducting organoid research aboard the International Space Station’s microgravity laboratory. Although organoids have been examined in space before, the organoids that will be part of Expedition 71 will be the first organoids in space to incorporate induced pluripotent stem cells from Alzheimer’s patients. Experiments with these organoids may provide insights into mechanisms of aging, potentially identify new targets involved in neurodegenerative diseases, and help accelerate drug discovery.

Summing up the potential of the field, Hans Clevers, MD, PhD, a pioneer in organoid research and head of Roche’s Pharma Research and Early Development (pRED) notes in a blog post5 that “One can implement human organoids at every step of the way—from target identification and target validation through preclinical safety and efficacy to stratification in clinical trials.” He foresees that organoid technology “might not only revolutionize the way we do research and develop medicines, but also [enable the discovery of] completely new molecules for devastating diseases.”

 

References

1. Lancaster MA, Knoblich JA. Organogenesis in a dish: Modeling development and disease using organoid technologies. Science 2014; 345(6194): 1247125.

2. Sato T, Vries RG, Snippert HJ, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 2009; 459(7244): 262–265.

3. Levner D, Ewart L. Integrating Liver-Chip data into pharmaceutical decision-making processes. Expert Opin. Drug Discov. 2023; 18(12): 1313–1320.

4. Ewart L, Athanasia Apostolou A, Briggs SA, et al. Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology. Commun. Med. 2022; 2(154): 1–16.

5. Roche launches the Institute of Human Biology to pioneer new approaches for drug discovery and development. Modeling the Future blog. Published May 4, 2023. Accessed March 1, 2024.

The post Organoids Stand Out as Stand Ins in Drug Development appeared first on GEN - Genetic Engineering and Biotechnology News.

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FDA Finally Takes Down Ivermectin Posts After Settlement

FDA Finally Takes Down Ivermectin Posts After Settlement

Authored by Zachary Stieber via The Epoch Times (emphasis ours),

Social media posts…

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FDA Finally Takes Down Ivermectin Posts After Settlement

Authored by Zachary Stieber via The Epoch Times (emphasis ours),

Social media posts urging people not to take ivermectin as a treatment for COVID-19 have been taken down by the U.S. Food and Drug Administration (FDA).

The FDA removed posts from X (formerly Twitter), Facebook, Instagram, and LinkedIn that stated: “You are not a horse. You are not a cow. Seriously y'all. Stop it.”

The posts had remained up even after the regulatory agency agreed to take them down as part of a settlement in a legal case brought by doctors who said the posts wrongly interfered with their practice of medicine.

The March 21 settlement said the FDA would take down specific posts within 21 days. The posts were made in August 2021.

The FDA has also deleted the following posts:

  • An Aug. 21, 2021, Instagram post that said: “You are not a horse. Stop it with the #ivermectin. It’s not authorized for treating #COVID.”

  • An April 26, 2022, Twitter post that said: “Hold your horses ya'll. Ivermectin may be trending, but it still isn’t authorized or approved to treat COVID-19.”

The posts directed people to an FDA webpage titled, “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19.” The page itself acknowledged that the FDA has approved ivermectin for some uses but said “taking a drug for an unapproved use can be very dangerous” and “currently available data do not show ivermectin is effective against COVID-19.”

The agency pointed to a database of clinical trials testing ivermectin against COVID-19; some of the trials showed the drug works against the illness.

Doctors commonly prescribe FDA-approved drugs for a range of purposes, including some outside the scope of approval. The practice is known as off-label prescription.

The FDA’s ivermectin posts gained tremendous traction across social media and news outlets, prompting internal excitement, emails obtained by The Epoch Times showed. Millions of people saw the posts. “That was great! Even I saw it!” Dr. Janet Woodcock, the agency’s acting commissioner at the time, said in one missive.

The FDA has not alerted its followers on social media that it removed the posts.

2022, celebrated the development.

The case “sets an important legal precedent which should deter them from attempting this stunt again anytime soon,” she wrote on X. In another post, she said that “the terms we were asking for were met when we agreed to settle” and “we were not optimistic about what we would get in discovery.”

But while the posts and page have been removed, the FDA has created a new page about ivermectin and COVID-19.

Published on April 5, it states: “One of the U.S. Food and Drug Administration’s jobs is to carefully evaluate the scientific data on a drug to be sure that it is both safe and effective for a particular use. There continues to be interest in a drug called ivermectin for the prevention or treatment of COVID-19 in humans. The FDA has not authorized or approved ivermectin for use in preventing or treating COVID-19 in humans or animals.”

The page repeats the statement that “the FDA has determined that currently available clinical trial data do not demonstrate that ivermectin is effective against COVID 19 in humans,” but lacks the link to the database showing mixed results from trials.

The page also says that “health care professionals may choose to prescribe or use an approved human drug for an unapproved use when they judge that the unapproved use is medically appropriate for an individual patient.”

An FDA spokesperson previously told The Epoch Times that the settlement was not an admission of a violation of law or any other wrongdoing.

FDA has not changed its position that currently available clinical trial data do not demonstrate that ivermectin is effective against COVID-19,“ the spokesperson said. ”The agency has not authorized or approved ivermectin for use in preventing or treating COVID-19.”

Tyler Durden Mon, 04/08/2024 - 22:20

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