Canada is Killing Itself

The country gave its citizens the right to die. Doctors are struggling to keep up with demand.

The euthanasia conference was held at a Sheraton. Some 300 Canadian professionals, most of them clinicians, had arrived for the annual event. There were lunch buffets and complimentary tote bags; attendees could look forward to a Friday-night social outing, with a DJ, at an event space above Par-Tee Putt in downtown Vancouver. “The most important thing,” one doctor told me, “is the networking.”

Which is to say that it might have been any other convention in Canada. Over the past decade, practitioners of euthanasia have become as familiar as orthodontists or plastic surgeons are with the mundane rituals of lanyards and drink tickets and It’s been so long s outside the ballroom of a four-star hotel. The difference is that, 10 years ago, what many of the attendees here do for work would have been considered homicide.

When Canada’s Parliament in 2016 legalized the practice of euthanasia—Medical Assistance in Dying, or MAID, as it’s formally called—it launched an open-ended medical experiment. One day, administering a lethal injection to a patient was against the law; the next, it was as legitimate as a tonsillectomy, but often with less of a wait. MAID now accounts for about one in 20 deaths in Canada—more than Alzheimer’s and diabetes combined—surpassing countries where assisted dying has been legal for far longer.

It is too soon to call euthanasia a lifestyle option in Canada, but from the outset it has proved a case study in momentum. MAID began as a practice limited to gravely ill patients who were already at the end of life. The law was then expanded to include people who were suffering from serious medical conditions but not facing imminent death. In two years, MAID will be made available to those suffering only from mental illness. Parliament has also recommended granting access to minors.

At the center of the world’s fastest-growing euthanasia regime is the concept of patient autonomy. Honoring a patient’s wishes is of course a core value in medicine. But here it has become paramount, allowing Canada’s MAID advocates to push for expansion in terms that brook no argument, refracted through the language of equality, access, and compassion. As Canada contends with ever-evolving claims on the right to die, the demand for euthanasia has begun to outstrip the capacity of clinicians to provide it.

There have been unintended consequences: Some Canadians who cannot afford to manage their illness have sought doctors to end their life. In certain situations, clinicians have faced impossible ethical dilemmas. At the same time, medical professionals who decided early on to reorient their career toward assisted death no longer feel compelled to tiptoe around the full, energetic extent of their devotion to MAID. Some clinicians in Canada have euthanized hundreds of patients.

The two-day conference in Vancouver was sponsored by a professional group called the Canadian Association of MAiD Assessors and Providers. Stefanie Green, a physician on Vancouver Island and one of the organization’s founders, told me how her decades as a maternity doctor had helped equip her for this new chapter in her career. In both fields, she explained, she was guiding a patient through an “essentially natural event”—the emotional and medical choreography “of the most important days in their life.” She continued the analogy: “I thought, Well, one is like delivering life into the world, and the other feels like transitioning and delivering life out.” And so Green does not refer to her MAID deaths only as “provisions”—the term for euthanasia that most clinicians have adopted. She also calls them “deliveries.”

Gord Gubitz, a neurologist from Nova Scotia, told me that people often ask him about the “stress” and “trauma” and “strife” of his work as a MAID provider. Isn’t it so emotionally draining? In fact, for him it is just the opposite. He finds euthanasia to be “energizing”—the “most meaningful work” of his career. “It’s a happy sad, right?” he explained. “It’s really sad that you were in so much pain. It is sad that your family is racked with grief. But we’re so happy you got what you wanted.”

Has Canada itself gotten what it wanted? Nine years after the legalization of assisted death, Canada’s leaders seem to regard MAID from a strange, almost anthropological remove: as if the future of euthanasia is no more within their control than the laws of physics; as if continued expansion is not a reality the government is choosing so much as conceding. This is the story of an ideology in motion, of what happens when a nation enshrines a right before reckoning with the totality of its logic. If autonomy in death is sacrosanct, is there anyone who shouldn’t be helped to die?

by Elaina Plott Calabro, The Atlantic | Read more:
Image: Johnny C.Y. Lam

Did Your Cancer Treatment Just Get Taken Away?

It starts with a little bump on your neck. You notice it when your hand brushes against it while you’re washing your hair, but at first you don’t pay it much attention. Then your spouse looks at your neck and asks you “What’s that?” It’s a little brown bump, maybe a mole. You think that maybe you should get it checked out by a dermatologist, but you forget to make an appointment, because work has just been so busy lately.

Then a few weeks later you look at the bump again, and it looks noticeably bigger. This time you call the dermatologist, but the soonest they can get you in is three weeks from now. By the time you’re in the doctor’s office, the bump is at least double the size it was when you noticed it. The doctor is tense and concerned, and he does a biopsy. Five days later you get the result over the phone: Melanoma.

“That’s cancer, right?” you ask, just to confirm, feeling something fall away in the pit of your stomach. “Yes,” the doctor’s assistant confirms. “That’s cancer.”

Cancer. The word is like the fall of an axe, cutting off the future you had imagined for yourself. Now instead, the days ahead are filled with surgeries, chemotherapy, radiation, CT scans, MRIs. You will never again entirely be free of the eternal gnawing fear of discovering that the cancer has spread. Your hair is going to fall out, you’re going to go under the knife, you’re going to be weak and sick. You’re going to to read everything there is to read about cancer, and it still won’t help. It may go into remission, or you may die, but your life will never read the same.

This story reflects the sad reality of life for millions of Americans. Cancer is the second most common cause of death, just barely behind heart disease, killing over 600,000 every year. And every year, almost 2 million Americans are diagnosed with new cases of cancer. Some kinds, like prostate cancer, are usually manageable; others, like pancreatic cancer and glioblastoma, are practically death sentences.

Now, there’s a common myth that cancer is an intractable disease that will never succumb to modern medicine. In 1971, President Richard Nixon launched the so-called “War on Cancer”; for many years, it was fashionable to say that cancer had won the war. But in fact, since around 1990, humanity has been making steady gains. Thanks to advances in early detection, screening, and various treatments, as well as the drop in smoking and a vaccine against a virus that causes cervical cancer, death rates have fallen at every age for almost every type of cancer. For a while this was masked by an increase in lung cancer from the smoking boom, but now that’s over too:

The problem is that since the population is growing steadily older, overall death rates are still higher than they were in Nixon’s day:

We’re delaying death from cancer, but not eliminating it.

In recent years, however, an explosion of new therapies has promised to accelerate our progress in treating the disease, changing the very nature of what it means to have cancer. The most promising of these are immunotherapies — medical techniques that use the body’s own immune system to attack cancer cells. And of those therapies, one of the most promising is mRNA vaccines.

Yes, mRNA vaccines — the same kind of technology that we used to vaccinate Americans against Covid during the pandemic. But it works a little differently. These mRNA cancer vaccines aren’t something that everyone takes in advance, to prevent themselves from getting cancer — instead, they’re a type of therapy that you take after you get diagnosed with the disease. Often, the vaccines are personalized, meaning that they develop a specific vaccine for your particular cancer.

mRNA vaccines, in combination with other therapies, promise to contain many cancers, turning them from a death sentence into a manageable, non-fatal disease. These vaccines are currently in development to fight all of the biggest killers: lung cancer, colon cancer, pancreatic cancer, breast cancer, and melanoma. They’re even being used against glioblastoma, the most aggressive and common type of brain cancer. There are even some tantalizing results suggesting that mRNA could soon be used to create a universal cancer therapy.

Imagine how the story I told at the top of this post would go in an age of highly effective mRNA therapies. Instead of being sentenced to years of gut-wrenching fear, possibly followed by an agonizing death, someone diagnosed with cancer would simply sigh and realize that they would have to spend a bunch of money on treatments for the foreseeable future. That is the world toward which science is taking us.

And yet now all of this is in danger. The MAGA movement, which now holds near-absolute political power in America, has gone to war against mRNA technology. RFK Jr., Trump’s Secretary of Health and Human Services and a prominent vaccine skeptics, just canceled a large amount of federal funding:

The Department of Health and Human Services (HHS) announced this week it is beginning a "coordinated wind-down" of federally funded mRNA vaccine development.

This includes terminating awards and contracts with pharmaceutical companies and universities and canceling 22 investment projects worth nearly $500 million. While some final-stage contracts will be allowed to be completed, no new mRNA-based projects will be initiated, the HHS said.

Officially, all of the cancelled funding is supposedly for mRNA vaccines for upper respiratory illness — basically, Covid and anything that looks remotely like Covid. So officially, cancer research isn’t being cancelled — yet. But cancer researchers are terrified that this move will derail their whole field, and with good reason. The chilling effect of this funding cancellation will cause a general loss of enthusiasm for the technology.

If you’re a researcher developing an mRNA treatment for lung cancer, how would you rate your chances of RFK Jr. approving your therapy for mass use when it has “mRNA” in the name? If you’re a private funding organization, do you really want to fund a technology that the government — and a large chunk of the American electorate — has an irrational vendetta against? What lab is going to want to allocate resources toward a field that’s marked for destruction? And what aspiring researcher is going to want to dedicate their career to it? (...)

So it’s very possible that thanks to RFK Jr., the Trump administration, and the MAGA movement writ large, cancer vaccines will not be available nearly as soon as it looked like they would just a few months ago. Eventually, the technology will be developed, with some combination of funding from Europe, China, private companies, and so on. But in the meantime, many people — including many Americans — will experience the nightmare of a traditional cancer diagnosis, like what I described at the top of this post.

Why is this happening? Why is the U.S. government attacking the technology that offers us the greatest chance to defeat one of humanity’s oldest and most terrible scourges?

It’s pretty easy to trace the reasons historically. During the pandemic, the antivax movement took over the American right — possibly because of fear of needles, possibly as a macho way to express bravery against the virus itself, possibly because of instinctive dread of modern technology or expert consensus or government recommendations. But whatever the reason, Trump — despite having authorized the project that created mRNA vaccines, and despite wanting to take some deserved credit for defeating Covid — was forced to accede to the wave of antivax sentiment, and to ally with it in order to win reelection in 2024. Part of that meant hiring RFK Jr. and putting him in charge of HHS — a political marriage of convenience.

But fundamentally, it’s hard to fathom just how America arrived at this juncture. We’ve certainly seen both sides of the U.S. political divide embrace blatant lies in order to express solidarity. For the right, the biggest lie was always that climate change isn’t happening, or isn’t caused by humans. Climate denial might seem like a lie without consequences — after all, the worst harms from climate change are going to arrive decades in the future. But because green energy technologies also happened to become cheap, the right-wing dogma that anything “green” is bad is causing the MAGA movement to oppose the cheapest and most reliable energy sources available:

Not having cheap energy is certainly bad. But dying of cancer? You’d think that would be a bridge too far, even for Trump’s followers. But recall how during the Covid pandemic, right-wing types died in droves because they refused to take the life-saving vaccine: 

by Noah Smith, Noahpinion |  Read more:

Image: OurWorldInData

Of Mice, Mechanisms, and Dementia

“The scientific paper is a ‘fraud’ that creates “a totally misleading narrative of the processes of thought that go into the making of scientific discoveries.”

This critique comes not from a conspiracist on the margins of science, but from Nobel laureate Sir Peter Medawar. A brilliant experimentalist whose work on immune tolerance laid the foundation for modern organ transplantation, Sir Peter understood both the power and the limitations of scientific communication.

Consider the familiar structure of a scientific paper: Introduction (background and hypothesis), Methods, Results, Discussion, Conclusion. This format implies that the work followed a clean, sequential progression: scientists identified a gap in knowledge, formulated a causal explanation, designed definitive experiments to fill the gap, evaluated compelling results, and most of the time, confirmed their hypothesis.

Real lab work rarely follows such a clear path. Biological research is filled with what Medawar describes lovingly as “messing about”: false starts, starting in the middle, unexpected results, reformulated hypotheses, and intriguing accidental findings. The published paper ignores the mess in favour of the illusion of structure and discipline. It offers an ideal version of what might have happened rather than a confession of what did.

The polish serves a purpose. It makes complex work accessible (at least if you work in the same or a similar field!). It allows researchers to build upon new findings.

But the contrived omissions can also play upon even the most well-regarded scientist’s susceptibility to the seduction of story. As Christophe Bernard, Director of Research at the Institute of Systems Neuroscience (Marseilles, Fr.) recently explained,

“when we are reading a paper, we tend to follow the reasoning and logic of the authors, and if the argumentation is nicely laid out, it is difficult to pause, take a step back, and try to get an overall picture.”

Our minds travel the narrative path laid out for us, making it harder to spot potential flaws in logic or alternative interpretations of the data, and making conclusions feel far more definitive than they often are.

Medawar’s framing is my compass when I do deep dives into major discoveries in translational neuroscience. I approach papers with a dual vision. First, what is actually presented? But second, and often more importantly, what is not shown? How was the work likely done in reality? What alternatives were tried but not reported? What assumptions guided the experimental design? What other interpretations might fit the data if the results are not as convincing or cohesive as argued?

And what are the consequences for scientific progress?

In the case of Alzheimer’s research, they appear to be stark: thirty years of prioritizing an incomplete model of the disease’s causes; billions of corporate, government, and foundation dollars spent pursuing a narrow path to drug development; the relative exclusion of alternative hypotheses from funding opportunities and attention; and little progress toward disease-modifying treatments or a cure.

The incomplete Alzheimer’s model I’m referring to is the amyloid cascade hypothesis, which proposes that Alzheimer’s is the outcome of protein processing gone awry in the brain, leading to the production of plaques that trigger a cascade of other pathological changes, ultimately causing the cognitive decline we recognize as the disease. Amyloid work continues to dominate the research and drug development landscape, giving the hypothesis the aura of settled fact.

However, cracks are showing in this façade. In 2021, the FDA granted accelerated approval to aducanumab (Aduhelm), an anti-amyloid drug developed by Biogen, despite scant evidence that it meaningfully altered the course of cognitive decline. The decision to approve, made over near-unanimous opposition from the agency’s advisory panel, exposed growing tensions between regulatory optimism and scientific rigor. Medicare’s subsequent decision to restrict coverage to clinical trials, and Biogen’s quiet withdrawal of the drug from broader marketing efforts in 2024, made the disconnect impossible to ignore.

Meanwhile, a deeper fissure emerged: an investigation by Science unearthed evidence of data fabrication surrounding research on Aβ*56, a purported toxic amyloid-beta oligomer once hailed as a breakthrough target for disease-modifying therapy. Research results that had been seen as a promising pivot in the evolution of the amyloid cascade hypothesis, a new hope for rescuing the theory after repeated clinical failures, now appears to have been largely a sham. Treating Alzheimer’s by targeting amyloid plaques may have been a null path from the start.

When the cracks run that deep, it’s worth going back to the origin story—a landmark 1995 paper by Games et al., featured on the cover of Nature under the headline “A mouse model for Alzheimer’s.” It announced what was hailed as a breakthrough: the first genetically engineered mouse designed to mimic key features of the disease.

In what follows, I argue that the seeds of today’s failures were visible from the beginning if one looks carefully. I approach this review not as an Alzheimer’s researcher with a rival theory, but as a molecular neuroscientist interested in how fields sometimes converge around alluring but unstable ideas. Foundational papers deserve special scrutiny because they become the bedrock for decades of research. When that bedrock slips beneath us, it tells a cautionary story: about the power of narrative, the comfort of consensus, and the dangers of devotion without durable evidence. It also reminds us that while science is ultimately self-correcting, correction can be glacial when careers and reputations are staked on fragile ground.

The Rise of the Amyloid Hypothesis

In the early 1990s, a new idea began to dominate Alzheimer’s research: the amyloid cascade hypothesis.

First proposed by Hardy and Higgins in a 1992 Science perspective, the hypothesis suggested a clear sequence of disease-precipitating events: protein processing goes awry in the brain → beta-amyloid (Aβ) accumulates → plaques form → plaques trigger a cascade of downstream events, including neurofibrillary tangles, inflammation, synaptic loss, neuronal death, resulting in observable cognitive decline.

The hypothesis was compelling for several reasons. First, the discovery of the enzymatic steps by which amyloid precursor protein (APP) is processed into Aβ offered multiple potential intervention points—ideal for pharmaceutical drug development.

Second, the hypothesis was backed by powerful genetic evidence. Mutations in the APP gene on chromosome 21 were associated with early-onset Alzheimer’s. The case grew stronger with the observation that more than 50% of individuals with Down syndrome, who carry an extra copy of chromosome 21 (and thus extra APP), develop Alzheimer’s-like pathology by age 40.

Thus, like any robust causal theory, the amyloid cascade hypothesis offered explicit, testable predictions. As Hardy and Higgins outlined, if amyloid truly initiates the Alzheimer’s cascade, then genetically engineering mice to produce human amyloid should trigger the full sequence of events: plaques first, then tangles, synapse loss, and neuronal death, then cognitive decline. And the sequentiality matters: amyloid accumulation should precede other pathological features. At the time, this was a thrilling possibility.

Pharmaceutical companies were especially eager: if the hypothesis proved correct, stopping amyloid should stop the disease. The field awaited the first transgenic mouse studies with enormous anticipation.

How—with Unlimited Time and Money and a Little Scientific Despair—to Make a Transgenic Mouse

“Mouse Model Made” was the boastful headline to the independent, introductory commentary Nature solicited to accompany the 1995 Games paper’s unveiling of the first transgenic mouse set to “answer the needs” of Alzheimer’s research. The scientific argument over whether amyloid caused Alzheimer’s had been “settle[d]” by the Games paper, “perhaps for good.”

In some ways, the commentary’s bravado seemed warranted. Why? Because in the mid-’90s, creating a transgenic mouse was a multi-stage, treacherous gauntlet of molecular biology. Every step carried an uncomfortably high chance of failure. If this mouse, developed by Athena Neurosciences (a small Bay Area pharmaceutical company) was valid, it was an extraordinary technical achievement portending a revolution in Alzheimer’s care.

First Rule of Making a Transgenic Mouse: Don’t Talk About How You Made a Transgenic Mouse

How did Athena pull it off? Hard to say! What's most remarkable about the Games paper is what's not there. Scan through the methods section and you'll find virtually none of the painstaking effort required to build the Alzheimer’s mouse. Back in the ‘90s, creating a transgenic mouse took years of work, countless failed attempts, and extraordinary technical skill. In the Games paper, this effort is compressed into a few sparse sentences describing which gene and promoter (nearby gene instruction code) the research team used to make the mouse. The actual details are relegated to scientific meta-narrative—knowledge that exists only in lab notebooks, daily conversations between scientists, and the muscle memory of researchers who perform these techniques thousands of times.

The thin description wasn’t atypical for a publication from this era. Difficult experimental methods were often encapsulated in the single phrase "steps were carried out according to standard procedures," with citations to entire books on sub-cloning techniques or reference to the venerable Manipulating the Mouse Embryo: A Laboratory Manual (We all have this on our bookshelf, yes?) The idea that there were reliable "standard procedures" that could ensure success was farcical—an understatement that other scientists understand as code for "we spent years getting this to work; good luck figuring it out ;)."

So, as an appreciation of what it takes to make progress on the frontiers of science, here is approximately what’s involved.

Prerequisites: Dexterity, Glassblowing, and Zen Mastery

Do you have what it takes to master transgenic mouse creation? Well, do you have the dexterity of a neurosurgeon? Because you’ll be micro-manipulating fragile embryos with the care of someone defusing a bomb—except the bomb is smaller than a grain of sand, and you need to keep it alive. Have you trained in glass-blowing? Hope so, because you’ll need to handcraft your own micropipettes so you can balance an embryo on the pipette tip. Yes, really.

And most importantly, do you sincerely believe that outcomes are irrelevant, and only the endless, repetitive journey matters? If so, congratulations! You may already be a Zen master, which will come in handy when you’re objectively failing your boss’s expectations every single day for what feels like an eternity. Success, when it finally comes, will be indistinguishable from sheer, dumb luck, but the stochastic randomness won’t stop you from searching frantically through your copious notes to see if you can pinpoint the variable that made it finally work!

Let’s go a little deeper so we can understand why the Games team's achievement was considered so monumental—and why almost everyone viewed the results in the best possible light.

by Anonymous, Astral Codex Ten |  Read more:

Image: via

GLP-1s Are Quietly Killing Your Cravings (and Maybe Your Bad Habits Too)

What happens when you can actually watch sugar cravings disappear from someone's brain? — You've probably heard people talking about 'food noise’. It’s that persistent, nagging voice in your head that keeps whispering about donuts, pizza, or cookies.

For many struggling with obesity, this chronic craving for sugar and fat feels like a voice you just can't mute.

But when people begin taking GLP-1 medications, it's as though someone finally found the volume knob and dialled it down to zero. The experience is something like an instantaneous liberation, so surreal and dramatic it almost feels like magic.

Recently, a good friend described starting tirzepatide this way:

"Bro, my food noise just vanished. Gone. Poof. I finally had the freedom to think about other things. And my shopping basket changed overnight. I actually wanted leafy greens and sweet potato. Sweet potato! Do you know how crazy that is?”

Stories like my friend's are piling up everywhere. So what's actually happening inside the brain when food noise just... stops?

When the brain says no

We've known for a while that GLP-1 meds like semaglutide dial down cravings, but now we've got visual proof of it actually happening in the brain.

A groundbreaking randomized controlled trial just published in Nature Medicine, used functional MRI (fMRI) scans to watch people's brains in real-time as they looked at images of high calorie, high sugar foods (think pizza, cakes, burgers etc) while taking tirzepatide, liraglutide, or a placebo.

Average brain activity shown on scans at the start of the study (baseline) and after three weeks of treatment (week 3). Bright colours (red and yellow) indicate higher brain activation in areas linked to cravings and reward when participants viewed images of high-fat, high-sugar foods.

Average brain activity shown on scans at the start of the study (baseline) and after three weeks of treatment (week 3). Bright colours (red and yellow) indicate higher brain activation in areas linked to cravings and reward when participants viewed images of high-fat, high-sugar foods.

After just three weeks on tirzepatide, the brain regions that light up when we see junk food went quiet. The areas responsible for cravings and reward anticipation (like the cingulate gyrus and medial frontal gyrus) showed roughly 170 % to 220 % less activation than they did on placebo, meaning these brain regions actually went into suppression. (...)

You’d think a drug like this would just crush hunger everywhere, like a sledgehammer smashing through a wall. Nope. Tirzepatide works more like an elite sniper perched on a rooftop, laser focused and zeroing in on your strongest cravings for high calorie, high sugary crap and picking them off with precision.

Amazingly, it leaves your appetite for fresh salads, crisp veggies, and sweet raspberries untouched.

Cravings for healthier foods (fruits and vegetables) remained virtually unchanged

The $1.2 Billion Question

Now, let’s zoom out for a second. What happens if millions of us suddenly lose that intense urge for soda, chips, or those wonderful chocolate chip cookies from subway (my fave)?

Agricultural economist Brian E. Roe calculated that even moderate levels of adoption of GLP-1s, say 10% among overweight people and 20% among those with obesity, would lead to a 3% drop in total calorie demand in the U.S.

That translates to around 20 billion fewer calories eaten daily and $1.2 billion less spent each week on food and drinks.

In other words, companies like Coca-Cola, Kellogg's, and Nestlé, who’ve built sprawling empires by tapping directly into the very cravings we've just seen silenced on MRI, may soon face an existential threat.

Some innovative companies, however, have already started adapting.

Smoothie King sensed the winds shifting first, cleverly rolling out high-protein, GLP-1-friendly shakes to capture the health-aware consumer.

Expect other fast-moving brands to dive headfirst into a wave of products customized specifically for people freed from the constant grip of food cravings.

The rest will need to pivot quickly or risk fading into oblivion.

GLP-1s as Impulse Dampeners

But tirzepatide might be doing something even more profound than silencing food noise. The same study suggests it's actually rewiring impulse control in the brain itself.

The researchers measured impulsiveness using the Barratt Impulsiveness Scale, a validated psychological tool that captures everyday impulsive tendencies like “acting without thinking” or “struggling to resist urges.”

After 3-6 weeks of tirzepatide treatment, participants reported feeling significantly less impulsive than those who received the placebo.

They reported feeling calmer, more in control, and far less prone to snap decisions or irresistible urges.

This is important when you consider that impulsivity is the engine behind pretty much every self-destructive habit out there. Whether you're talking binge-drinking, gambling, chain-smoking or falling into the black hole of substance abuse.

If GLP-1 meds can dial down the noisy circuits in our brains screaming 'just do it!', we might be staring down the barrel of an entirely new way of treating addiction and it’s devastating consequences.

Just imagine a world (to borrow from John Lennon) with fewer overdose headlines, calmer Friday nights in emergency rooms, shrinking gambling debts, maybe even drops in domestic violence and incarceration rates.

Researchers are taking this seriously.

Major clinical trials already underway are testing whether GLP-1 meds might quiet the destructive impulses behind addiction itself. If they're right, we're looking at something much bigger (and far more important) than just weight loss.

by Ashwin Sharma, MD, GLP-1 Digest |  Read more:

Image: GPT/GLP-1 Digest Illustration; Nature Medicine

[ed. See also: How GLP-1s Are Breaking Life Insurance; and, Why are GLP1 drugs good for everything?]

May 18, 2025: Big Bad Billionaire Bill

AKA: Medicaid Death Watch

Tonight, late on a Sunday night, the House Budget Committee passed what Republicans are calling their “Big, Beautiful Bill” to enact Trump’s agenda although it had failed on Friday when far-right Republicans voted against it, complaining it did not make deep enough cuts to social programs.

The vote tonight was a strict party line vote, with 16 Democrats voting against the measure, 17 Republicans voting for it, and 4 far right Republicans voting “present.” House speaker Mike Johnson (R-LA) said there would be “minor modifications” to the measure; Representative Chip Roy (R-TX) wrote on X that those changes include new work requirements for Medicaid and cuts to green energy subsidies.

And so the bill moves forward.

In The Bulwark today, Jonathan Cohn noted that Republicans are in a tearing hurry to push that Big, Beautiful Bill through Congress before most of us can get a handle on what’s in it. Just a week ago, Cohn notes, there was still no specific language in the measure. Republican leaders didn’t release the piece of the massive bill that would cut Medicaid until last Sunday night and then announced the Committee on Energy and Commerce would take it up not even a full two days later, on Tuesday, before the nonpartisan Congressional Budget Office could produce a detailed analysis of the cost of the proposals. The committee markup happened in a 26-hour marathon in which the parts about Medicaid happened in the middle of the night. And now, the bill moves forward in an unusual meeting late on a Sunday night. (...)

Cohn explains that Medicaid cuts are extremely unpopular, and the Republicans hope to jam those cuts through by claiming they are cutting “waste, fraud, and abuse” without leaving enough time for scrutiny. Cohn points out that if they are truly interested in savings, they could turn instead to the privatized part of Medicare, Medicare Advantage. The Congressional Budget Office estimates that cutting overpayments to Medicare Advantage when private insurers “upcode” care to place patients in a higher risk bracket, could save more than $1 trillion over the next decade.

Instead of saving money, the Big, Beautiful Bill actually blows the budget deficit wide open by extending the 2017 tax cuts for the wealthy and corporations. The Congressional Budget Office estimates that those extensions would cost at least $4.6 trillion over the next ten years. And while the tax cuts would go into effect immediately, the cuts to Medicaid are currently scheduled not to hit until 2029, enabling the Republicans to avoid voter fury over them in the midterms and the 2028 election. [ed. emphasis added]

The prospect of that debt explosion led Moody’s on Friday to downgrade U.S. credit for the first time since 1917, following Fitch, which downgraded the U.S. rating in 2023, and Standard & Poor’s, which did so back in 2011. “If the 2017 Tax Cuts and Jobs Act is extended, which is our base case,” Moody’s explained, “it will add around $4 trillion to the federal fiscal primary (excluding interest payments) deficit over the next decade. As a result, we expect federal deficits to widen, reaching nearly 9% of GDP by 2035, up from 6.4% in 2024, driven mainly by increased interest payments on debt, rising entitlement spending and relatively low revenue generation.” (...)

The continuing Republican insistence that spending is out of control does not reflect reality. In fact, discretionary spending has fallen more than 40% in the past 50 years as a percentage of gross domestic product, from 11% to 6.3%. What has driven rising deficits are the George W. Bush and Donald Trump tax cuts, which had added $8 trillion and $1.7 trillion, respectively, to the debt by the end of the 2023 fiscal year.

But rather than permit those tax cuts to expire— or even to roll them back— the Republicans continue to insist Americans are overtaxed. In fact, the U.S. is far below the average of the 37 other nations in the Organization for Economic Cooperation and Development, an intergovernmental forum of democracies with market economies, in its tax levies. According to a report by the Center for American Progress in 2023, if the U.S. taxed at the average OECD level, over ten years it would have an additional $26 trillion in revenue. If the U.S. taxed at the average of European Union nations, it would have an additional $36 trillion. (...)

So with the current Big, Beautiful Bill, we are looking at a massive transfer of wealth from ordinary Americans to those at the top of American society. The Democratic Women’s Caucus has dubbed the measure the “Big Bad Billionaire Bill.” (...)

Speaker Johnson hopes to pass the bill through the House of Representatives by this Friday, before Memorial Day weekend.

by Heather Cox Richardson, Letters from an American |  Read more:

Image: Speaker of the House Mike Johnson (R-La.). Bill Clark/CQ-Roll Call, Inc via Getty Images

[ed. See also: How to Take Medicaid from Millions of Americans, in Less Than 72 Hours (The Bulwark); Who Changed and America Has Become Trump's Battered Wife (Slack Tide); and, State-by-State Data on Health Insurance Losses from Medicaid, ACA Cuts (Joint Economic Committee).

Over 13 Million to Lose Health Insurance Under GOP Plan

The House leadership late Sunday released the GOP’s plan for cutting health care spending to pay for tax breaks for the rich and large corporations. It whacks both Medicaid and the expanded subsidies that make individual plans sold on the Obamacare exchanges affordable.

While they pitched their plan as a modest program designed to appeal to Republican moderates, there is no way they can generate more than $700 billion in savings without making major cuts to both programs.

Mainstream media coverage is aiding and abetting the subterfuge. “Republicans Propose Paring Medicaid Coverage but Steer Clear of Deeper Cuts,” the New York Times online headline read this morning. “House bill includes work requirements but not deeper reductions some fiscal hawks demanded,” the subhead in the Wall Street Journal read.

Using Congresstional Budget Office estimates, Democrats on Capitol Hill immediately released an analysis that showed 4.2 million people will lose Obamacare coverage over the next decade under the plan. It is largely due to expiration of the expanded premium tax credits passed in 2022 that made the plans affordable for millions.

Another estimated 1.8 million people will lose coverage through new rules making it harder to enroll. The bill calls for shortening the enrollment period, demands more income verification paperwork and excludes non-citizens from the program.

The Medicaid cuts would go deeper, driving an estimated 7.7 million people from the rolls. The GOP bill includes a moratorium on Biden-era rules for streamlining the enrollment process; an 80-hour monthly work requirement (unless you’re a student or pregnant); a monthly redetermination process for eligibility; and denies enrollment to non-citizens without “satisfactory immigration status.” The latter provision eliminates so-called dreamers (Deferred Action for Childhood Arrivals) from qualifying for the program.

Very few people on Medicaid are able-boded, working age adults who are unemployed. Work requirements are not designed to help them find work; they are meant to drive people from the rolls through increased paperwork for the already employed, which is more than half of all working age recipients.

The combined effects of those changes will drive the uninsured rate back into double digits — possibly as high as one in every eight Americans.

There’s more. The proposal, which will be marked up in the House tomorrow, eliminates the 90% federal match for the nine states that have yet to expand Medicaid under the Affordable Care Act, which allows individuals earning up to 138% of the federal poverty line to qualify for the program. It also gives states the right to impose up to a $35 co-pay for every service (capped at 5% of income), which will discourage many people from signing up and discourage those already in the program from seeking health care when they need it.

Little room to lose votes

With narrow majorities in both houses, the Trump-loyal GOP leadership can’t afford to lose many votes. It’s questionable whether the proposed plan will mollify Republican representatives in swing districts or Senators from conservative states that have come around to embracing Obamacare’s health coverage expansion.

On the same day the House plan was released, Sen. Josh Hawley (R-Mo.) wrote on the op-ed page of the New York Times that “slashing health insurance for the working poor … is both morally wrong and politically suicidal.” In August 2020, Missouri voted by a 53% to 47% margin to enshrine expanding Medicaid under Obamacare in its state constitution over the objections of the state’s GOP leadership. (...)

In true GOP fashion, there are several provisions in the bill aimed at appeasing corporate lobbyists and their employers. The bill repeals the rule passed by the Biden administration that requires minimum staff-to-patient ratios in the nation’s nursing homes. It also reins in the middleman charges that pharmacy benefit managers lard onto prescription drug costs. It allows insurance companies to deny future coverage to anyone who once fell behind on their exchange plan premiums. And it further delays cuts in the extra payments some hospitals receive for serving a disproportionate share of the poor.

What’s noticeably absent from the bill is any effort to limit insurance companies’ upcoding in Medicare Advantage plans, which costs taxpayers as much as $80 billion a year. Simply paying MA plans the same amount as their members would cost had they remained in traditional Medicare would save more money over the next decade than all the provisions in the bill released Sunday combined.

by Merrill Goozner, GoozNews | Read more:
Image: KFF

[ed. Think homelessness is bad now?]

The Future of Silk

The invention of the hypodermic needle in 1844 brought major benefits ​to the practice of medicine, but ran headlong into an unexpected quirk of human nature. It turns out that millions of people feel an instinctive horror at the thought of receiving an injection – at least ten percent of the US adult population and 25 percent of children, according to one estimate. This common phobia partly explains the widespread reluctance to receive vaccinations against Covid-19, a reluctance which has led to tens of thousands of unnecessary deaths.

But a company in Cambridge, Massachusetts, called Vaxess Technologies plans to sidestep this common fear by abandoning stainless steel needles and switching to silk.

Vaxess is testing a skin patch covered in dozens of microneedles made of silk protein and infused with influenza vaccine. Each needle is barely visible to the naked eye and just long enough to pierce the outer layer of skin. A user sticks the patch on his arm, waits five minutes, then throws it away. Left behind are the silk microneedles, which painlessly dissolve over the next two weeks, releasing the vaccine all the while.

The silk protein acts as a preservative, so there’s no need to keep it on ice at a doctor’s office. ‘It’s similar to what happens when you freeze something,’ said Vaxess founder and chief executive Michael Schrader. ‘It’s room-temperature freezing.’ In testing, Vaxess found that flu vaccines stored in a silk patch at room temperature remained viable three years later.

No more need for a ‘cold chain’, the costly network of refrigerators ​between manufacturing plants and medical clinics required by so many vaccines. Indeed, there’d be no need to get vaccinated at a clinic at all. Patients could vaccinate themselves.

‘We would mail you a patch,’ said Schrader. ‘It looks like a nicotine patch, only much smaller. You wear the patch for five minutes, then take it off and throw it away.’

Having completed a successful phase one clinical trial of the silk patches in late 2022, Schrader hopes to bring them to market by 2028.

It’s hardly the sort of product we’d usually associate with silk, the tough, luxurious, and luminous fabric that has delighted people for at least 5,000 years. But silk is proving to be far more valuable than its early Chinese cultivators could have imagined.

Much of what we now understand about silk was discovered at Silklab, ​a branch of the department of engineering at Tufts University in Medford, a suburb of Boston. Here a visitor encounters silken lenses that project words and images when bathed in laser light; surgical gloves coated in silk that display a warning if they’ve been contaminated with pathogens; tiny silken screws that are strong enough to repair a broken bone, only to dissolve entirely once the injury is healed.

For Silklab director Fiorenzo Omenetto, silk is not a fashion statement. It’s a set of microscopic Lego blocks that he and his colleagues are pulling apart and reassembling into an array of unexpected products.

‘We make everything,’ said Omenetto. ‘We make plastics, we make edible electronics, we make coatings for food.’

Silk isn’t everything at Silklab. Omenetto and his colleagues experiment with a variety of similar molecules, known as structural proteins. They’re found all over the place, shaping and strengthening plant and animal ​tissues. There’s the keratin in hair, collagen that holds our organs together, and more.

But for Omenetto, silk comes first. And his team has found an array of new uses for a fiber that humans have been cultivating for millennia.

Legend has it that the wife of the Yellow Emperor, who reigned around 2700 BC, was sipping hot tea under a mulberry tree when the cocoon of a silkworm fell into her cup. The hot liquid dissolved the cocoon’s sticky coating and caused the silk underneath to unravel, revealing its extraordinary beauty and strength. Then again, Chinese archeologists in 2017 found traces of silk in the soil under bodies in tombs 8,500 years old. The traces could be wild silk, but they could also suggest that sericulture – silk farming – may have begun much earlier.

A gray moth called Bombyx mori is the source of the silk. Centuries of selective breeding have created moths that reproduce at an exceptional rate – up to eight generations per year, compared to just three for wild silk moths. Domestication has wrought other changes; their wings are so stubby that the moths can barely fly, and the female moths are born already fat with as many as 500 eggs ready for immediate fertilization by a male.

In about ten days, the eggs hatch into silkworms, tiny caterpillars that are only about two or three millimeters in size. They mature quickly; given proper care, the worms will grow to 10,000 times their birth weight in about a month.

Theirs is a monotonous diet – they eat only the leaves of mulberry trees, and quite a lot of them. The recipe for one pound of silk: start with about 3,000 worms, gradually add 220 pounds of clean, fresh mulberry leaves, and wait about a month.

That’s when the silkworms begin to spew forth the cocoons that will shield them from harm as they develop into moths. The silk emerges from two glands called spinnerets located near the worm’s jaws. The stuff is almost entirely made of a protein called fibroin. The worm emits two streams of fibroin, then coats them in a gooey protein called sericin.

For up to three days, the silkworm’s head weaves back and forth as it wraps itself in silk. The finished cocoon is no bigger than a chocolate-​covered almond, yet its silk forms a continuous thread a kilometer long.

To get at the silk, humans boil the cocoons, killing the worm inside and stripping away the sericin. Then the silk fiber is unspooled.

The stuff is stronger than a steel wire of equal thickness, stronger even than the Kevlar fibers found in bullet-resistant vests. In fact, one of the first such vests, developed by Chicago Catholic priest Casimer Zeglen in 1897, was woven of silk. It worked, too.

Spider silk is actually stronger than that produced by silkworms. But nobody’s been able to successfully domesticate spiders, which have an unfortunate habit of eating one another. Happily, silkworms have been getting along well with humans and one another for quite a few centuries. (...)

One Silklab spinoff, Boston-based Mori, has raised over $82 million in investment capital, and has begun signing contracts with food distributors for a product that turns silk into a food preservative.

Keeping meats and vegetables flavorful is largely a matter of keeping oxygen and bacteria out and moisture in. A plastic wrapper can accomplish this, but supermarkets aren’t going to wrap each apple or banana. Apart from the cost and inconvenience, it would generate vast amounts of plastic waste.

But in 2016, Omenetto and Kaplan joined with Benedetto Marelli, an associate professor at the Massachusetts Institute of Technology, to demonstrate that merely dipping the food in a solution of silk and water leaves behind a film that holds in moisture and keeps out air and bacteria. ​On average, fruit and vegetables coated in silk protein can remain fresh at room temperature for one week longer than unwrapped food. And unlike plastic wrap, there’s no waste. It’s not even necessary to wash off the silk coating; it’s flavorless, nontoxic, and biodegradable. (...)

Today’s skin care ingredients are mostly synthetic compounds supplied by petrochemical companies. Not dangerous in themselves, the manufacture of these synthetics often involves the use of toxins like cyanide and heavy metals. Besides, many of these chemicals eventually end up in our food and water.

‘We don’t necessarily know if they’re biodegradable,’ Altman said. ‘We don’t know where they end up.’

Altman and Lacouture’s new company, Evolved by Nature, developed a version of silk protein that substitutes for claudin, a different protein that occurs naturally in human skin. Over time, claudin tends to erode, making our skin more vulnerable to moisture loss. Evolved by Nature’s skin barrier is designed to deliver a dose of silk protein to fill in the gaps. (...)

But Altman said skin care is only the beginning. Silk protein, he said, makes an excellent substitute for petrochemical coatings used in a vast array of products.

The stuff’s everywhere, Altman said. ‘There’s a layer on your glasses. There’s a coating on a trillion dollars of textiles produced every year. In every house, architectural surfaces. In every car, on every piece of leather.’

His company’s future product road map includes custom silk protein for coating fabrics and leather. Because it’s not a medical application, these coatings needn’t be made of the finest silk. Altman said his company could thrive on silk producers’ leftover scraps. ‘Evolved by Nature could generate a billion dollars in revenue’, he said, ‘and never use anything but the trash of the sericulture industry.’

by Hiawatha Bray, Works in Progress |  Read more:

Images: Wikimedia; Library of Congress

Shingles Vaccine Could Help Stave Off Dementia

According to a study that followed more than 280,000 people in Wales, older adults who received a vaccine against shingles were 20 percent less likely to develop dementia in the seven years that followed vaccination than those who did not receive the vaccine.

This could be a big deal. There are very few, if any, treatments that can prevent or slow down dementia, beyond good lifestyle habits like getting enough sleep and exercise. The possibility that a known, inexpensive vaccine could offer real protection is enormously meaningful. We have good reason to be confident in the findings: While this study is perhaps the most prominent to show the protective effects of the shingles vaccine, other studies of the vaccine have come to similar conclusions.

Beyond the promise of preventive treatment, the new study adds further evidence to a growing body of research raising the possibility that we have been thinking about neurodegenerative diseases like dementia and Alzheimer’s all wrong. It’s possible these horrible conditions are caused by a virus — and if that’s the case, eliminating the virus could be enough to prevent or treat the diseases.

How the study worked

To understand why the new shingles vaccine study is such a big deal, it helps to know a little bit about how medical studies are carried out. (...)

The new study... took advantage of a quirk in Welsh health policy to do something better. Beginning on September 1, 2013, anyone in Wales who was 79 became eligible to receive a free shingles vaccine. (Those who were younger than 79 would become eligible once they turned that age.) But anyone who was 80 or older was not eligible on the grounds that the vaccine is less effective for the very old.

The result was what is known as a “natural experiment.” In effect, Wales had created two groups that were essentially the same — save for the fact that one group received the shingles vaccine and one group did not.

The researchers looked at the health records of the more than 280,000 adults who were 71 to 88 years old at the start of the vaccination program and did not have dementia. They focused on a group that was just on the dividing line: those who turned 80 just before September 1, 2013, and thus were eligible for the vaccine, and those born just after that date, who weren’t. Then, they simply looked at what happened to them.

By 2020, seven years after the vaccination program began, about one in eight older adults, who by that time were 86 and 87, had developed dementia. But the group that had received the shingles vaccine were 20 percent less likely to be diagnosed with the disease. Because the researchers could find no other confounding factors that might explain the difference — like years of education or other vaccines or health conditions like diabetes — they were confident the shingles vaccine was the difference maker.

A new paradigm in dementia research?

As Paul Harrison, a professor of psychiatry at the University of Oxford who was not involved in the study, told the New York Times, the research indicates that the shingles vaccine appears to have “some of the strongest potential protective effects against dementia that we know of that are potentially usable in practice.”

But this is a vaccine originally designed to prevent shingles. Why does it also appear to help with dementia?

Scientists theorize it could be related to inflammation. Shingles, or herpes zoster, is caused by the same virus responsible for chickenpox, which lies dormant in nerve cells after an initial infection and can reawaken decades later, causing painful rashes.

That reactivation creates intense inflammation around nerve cells, and chronic inflammation is increasingly recognized as a major factor in cognitive deterioration. By preventing shingles, the vaccine could indirectly protect against the neural inflammation associated with dementia.

What about the amyloid and tau protein plaques that tend to be found in the brains of people suffering from Alzheimer’s, which have long been thought of as the primary cause of the disease? It’s possible that these may actually be the body’s response to an underlying infection. That could help explain why treatments that directly target those plaques have been largely ineffective — because they weren’t targeting the real causes.

by Bryan Walsh, Vox |  Read more:

Image: H. Rick Bamman/ZUMA Wire/Alamy Live News

[ed. See also: Shingles Vaccine Can Decrease Risk of Dementia, Study Finds (NYT):]

***

“If you’re reducing the risk of dementia by 20 percent, that’s quite important in a public health context, given that we don’t really have much else at the moment that slows down the onset of dementia,” said Dr. Paul Harrison, a professor of psychiatry at Oxford. (...)

Several previous studies have suggested that shingles vaccinations might reduce dementia risk, but most could not exclude the possibility that people who get vaccinated might have other dementia-protective characteristics, like healthier lifestyles, better diets or more years of education.

The new study ruled out many of those factors. (...)

They also examined medical records for possible differences between the vaccinated and unvaccinated. They evaluated whether unvaccinated people received more diagnoses of dementia simply because they visited doctors more frequently, and whether they took more medications that could increase dementia risk.

“They do a pretty good job at that,” said Dr. Jena, who wrote a commentary about the study for Nature. “They look at almost 200 medications that have been shown to be at least associated with elevated Alzheimer’s risk.”

He said, “They go through a lot of effort to figure out whether or not there might be other things that are timed with that age cutoff, any other medical policy changes, and that doesn’t seem to be it.”

The study involved an older form of shingles vaccine, Zostavax, which contains a modified version of the live virus. It has since been discontinued in the United States and some other countries because its protection against shingles wanes over time. The new vaccine, Shingrix, which contains an inactivated portion of the virus, is more effective and lasting, research shows.

A study last year by Dr. Harrison and colleagues suggested that Shingrix may be more protective against dementia than the older vaccine. Based on another “natural experiment,” the 2017 shift in the United States from Zostavax to Shingrix, it found that over six years, people who had received the new vaccine had fewer dementia diagnoses than those who got the old one. Of the people diagnosed with dementia, those who received the new vaccine had nearly six months more time before developing the condition than people who received the old vaccine.