At What Point?

by MARKIE

I have to ask this question. When are people going to realize that there are bigger problems in the world than the petty things which our society seems to be focusing on lately? If foreign countries could read our headlines or watch our news coverage (cancel culture? What is that!), they would probably turn away in disgust. No matter your or my political beliefs, there are certain things happening right now that are simply outrageous.

Who cares about Mr. And Mrs. Potato Head? They are toys which help teach children motor skills. That’s it.

And why is Dr. Seuss under fire? He wrote books that rhymed, which are fun and entertaining for children. Nothing more.

Now I’m hearing words against another children’s book, curious George. Because it’s about a white man who has a monkey, and the word ‘monkey’ has been used by some as a racial slur against black people. News flash: a monkey is an animal. It’s not the author’s fault that some low class people have chosen to use that word as an offensive word against other people! At what point do we draw the line between what is, and is not, offensive? I would argue that we’re already past that point, because people are condemning this book in which the word ‘monkey’ is used in its original, correct context! Come on, America.

Why would anyone want to remove the police officer dog from Paw Patrol? It’s not only a cartoon, but the favorite cartoon of millions of children! This cartoon teaches children to respect our men and women in uniforms of all kinds. There is not only a police officer pup, but pups who represent construction, aerial rescue, coast guard, and others. The point is, are we going to boycott the construction pup because we’re fed up with having to take detours? Or the aerial rescue pup because it’s offensive to those who are scared of heights? Where does the madness end!

PAW PATROL

It is imperative that society stop swaying with the crowd, and know our own minds. And it is okay to go against the majority. Just because one or two people raise a stink about something does Not mean that the whole country needs to go into an uproar. Likewise, just because a group of people- even if it is the majority- agree on something, doesn’t mean it’s right.

In listing the above examples, I’ve noticed a common denominator: it sounds to me like it’s our children who are under attack! Because believe you me, they listen. And they hear all of this craziness. Children are extremely impressionable, and it is scary and confusing to them when the adult influences in their lives start talking about gender neutral toys and systemic racism, and asking them what sex they want to be . The list goes on!

Generations of people have grown up reading these books and playing with these toys. Think of it this way: everything is offensive to somebody, somewhere. You think I like having to press 2 for English when I live in America? No!

But I digress.

Like I always tell my stepdaughter when she’s frustrated with the rules: people are adults for the majority of their lives. Childhood is just a fraction of it, and she should try to enjoy being a kid while it lasts.

Let’s let our kids enjoy being kids, and stop taking away their innocence!

NOTHING SCANDALOUS ABOUT MATT GAETZ, AND THAT’S THE SCANDAL

This happens all the time.

by Jessica Wildfire

So…

Florida representative Matt Gaetz has been sleeping with 17-year-old girls and sharing private nudes of women with his pals in congress.

Here’s the thing:

No woman on earth is surprised.

We’re just pissed off.

The scandal is that it’s not a scandal. We’ve encountered worse than Matt Gaetz. I’ve watched 30-something men try to pick up 15-year-old girls at gas stations. There’s thousands of men out there who don’t care what’s right or wrong, just what they can get away with.

What’s surprising is that Matt Gaetz might actually face some consequences this time, but probably not severe enough to deter him. Like so many others, he’ll go right on doing the same thing he’s always done, and setting a low bar for men everywhere.

It’s almost a given.

This happens all the time.

The problem isn’t what Matt Gaetz did. It’s that what he did happens practically all the time.

Men learn early on how to pressure young women into all kinds of sexual acts, including nude photos they share with all their friends later, like it’s some trophy. When these teenage boys grow up into 40-year-old men, they still try to date women half their age.

It’s downright normal.

We let it happen, just slightly out of sight.

It’s not unusual for wealthy, powerful men to spend their free time grooming underage women for sexual service. It’s almost expected that some men will use their positions and privilege to lure young women into relationships. There’s no shortage of Hollywood celebrities and recording artists who’ve managed to get away with it for years.

Almost every single university has at least one professor who treats their graduate TAs like groupies, promising favors and career advancement in exchange for sex. Then they get bored and discard them. The woman winds up hurt, and often vilified.

Don’t believe me?

Ask around.

This happens all the time.

Here’s the simple truth about gender dynamics in America. Men are still allowed to destroy women’s lives.

Some treat it like a sport.

I know professors who’ve been assaulted in bathrooms where they work. Their own students have propositioned them for sex. I know professors who’ve had students expose themselves in classrooms.

When they report these crimes, they become the subject of an investigation into their credibility. The police meet with Human Resources to sit her down for recorded interviews that feel like interrogations. They cajole her into signing a transcript under penalty of perjury. They go through all of these steps before even questioning her attacker.

This is why so many women either don’t report sexual harassment or assault or retract their allegations.

They get intimidated.

This happens all the time.

I know students who’ve had to transfer to different universities because stalkers threatened their friends and family with a loaded gun, on top of terrorizing them on social media.

These universities often care more about the stalker’s rights than their victims. They hardly ever expel young men for the torture they inflict on women. They impose minimal penalties. Stuff like this has happened to me as well. Society teaches you it’s your fault. After forty years of calling out crimes like this, we still hear questions like, “What were you wearing?” and “Why were you walking on campus alone?”

Justice doesn’t happen for most women. It happens to them, on behalf of men who violate women and then portray themselves as victims whenever they finally get into trouble. The system teaches women that in order to go up against a white guy, they need a small army.

All too often, it’s a futile battle.

This happens all the time.

Nothing that bad will happen to Matt Gaetz.

Women will be shocked if he ever sees the inside of a prison cell. After all, we’re talking about the country that confirmed a supreme court judge days after an upstanding woman accused him of rape.

Powerful white men almost never pay for what they do to women. At worst, they lose a job and then find a different one. It’ll be no surprise that Matt Gaetz resigns his congressional seat and then winds up hosting a show on Fox News. He’ll probably make more money that way. No, white men often don’t suffer consequences for their actions.

The women do.

Every time a woman outs her rapist, she’s likely to receive death threats. She loses friends and colleagues. She has to relocate.

Suddenly, she’s toxic.

In America, rape isn’t a crime.

Allowing yourself to get raped, or making up a rape story, that’s what people are worried about.

This happens all the time.

Matt Gaetz isn’t a surprise.

He’s a republican.

If there’s one thing you can always count on republicans for, it’s a sustained assault on women’s rights.

The last president was a republican who openly bragged about using his celebrity status as a license to grope women. In this mind, letting a wealthy and powerful man grab them counted as consent. He’s been accused of sexual assault by 26 different women, with zero consequences. His daughter ran a sham organization that pretended to promote women entrepreneurs, but it was really just a giant publicity stunt.

He was pals with Jeffrey Epstein, a man who almost got away with running an actual underage prostitution ring.

Republicans have rejected legislation designed to pay women fair salaries or provide them with mandatory maternity leave. They’ve managed to shadow ban abortion in virtual every red state. Most recently, they voted against a bill meant to protect women against violence, literally in the midst of headline stories about violence against women.

They don’t care about women’s rights, just how they can use women as props to sell merchandise and spread fake news.

Even women in the republican party don’t care about women. They care about the power and prestige they get from throwing everyone else under the bus. They pretend to represent progress, when they only represent their own selfish, short-sighted interests.

So that’s how things go with republicans. Honestly, it would be surprising if one of them did care.

This happens all the time.

Women have learned to expect half of the men they meet to be something along the lines of Matt Gaetz. If given the opportunity, they’ll seduce 17-year-old girls (or traffic them) and then brag about it.

They’ll boast about their sexual conquests, even when they use power and money to coerce younger women into sleeping with them. They’ll interrupt women’s daily lives in order to hit on them. They’ll act like paying women unsolicited compliments is a favor.

They’ll pay women lower salaries and wages because they truly think women do inferior work. They’ll defend stalkers and rapists, and put women on trial for telling the truth, simply because it challenges the established order. They’ll scrutinize women’s achievements.

They’ll use their status as husbands and fathers to defend themselves, and it makes the rest of us shudder to think about what it must be like to live under their daily oppression.

No, not all men act like this. But half of them do.

So…

The most important thing you need to know about Matt Gaetz is that he’s not a scandal, not even close.

HE’S TYPICAL.

AMERICA IS A DEEPLY UNWELL SOCIETY


Going Back to “Normal” In a Broken Society Was Never Going to Be Good Enough
by umair haque

The picture above (missing for this post).
Kids are pretending to die in an “active shooter drill,” as men with guns pretend to kill them. I bring it up because America’s had another shooting. That’s two in two weeks. That’s six so far this year. Things are going back to normal, my friends tell me. I don’t want to say what I think back to them: normal in America was already dystopian. And now, perhaps, you see the flaw in the logic of “things can just go back to normal.”


America is a deeply unwell society. What was “normal” — before the overt fascism of the Trump years? School shootings and mass murders. Kids having to pretend to die as masked men burst in and shot them with blanks — “active shooter drills.” Can you imagine what it does to a kid to have to pretend to be shot? To die? Then there was the “student debt,” the “medical bankruptcy,” people begging strangers online for money to pay for bills. All that was normal.


But a society like that is not normal. It’s just that all that has been normalised in America. What is all “that,” though? I want to explain it in a different way to you.


When my European friends visit America, or live there, or when I return to America, having lived so long in Europe, what strikes us is this. How mean and cruel and brutal American life is. American culture is. In Spain and France, friends — or just strangers — will greet each other with kisses and an embrace. That’s not some kind of pointless anecdote. There is real human warmth in these cultures. In America, it seems to have gone missing entirely.


Nobody is really friendly in America. I know they think they are, but they’re not. Americans don’t seem to know what is to be gentle, warm, kind. Hug and kiss an American and they’d probably think you were crazy, or maybe try to shoot you. Go to the store, the airport, school — anywhere — and simple social interactions are bizarre, dehumanizing, alienated things of people barking orders at each other. To Canadians, Europeans, Asians — literally the whole world — this way of being is deeply bizarre.
You can feel anger and rage pulsing through America like a shockwave. If you’ve lived elsewhere.

Nobody will be nice to anyone, really, kind, gentle, warm. It’s exhausting, wearying, depressing, if you can sense it. Americans have mostly lived no other way, so they can’t. But if you have — it shakes you. The aggression and hostility of American life is omnipresent — literally everywhere, inescapable, ubiquitous. At school, at the workplace, at the university — thanks frats — at the office, in church. There is nowhere you can go in American life to escape the shockwave of aggression surging through it.


Why do I bring all that up? Am I just condemning Americans? Of course not. I am diagnosing a certain kind of social illness. Rage.


It’s true that guns are a big problem, and I’d never want you to think that I’m not on the side of gun control. Of course I am. But beneath the surface of guns, there is a culture of omnipresent aggression, brutality, cruelty. That has resulted in a culture of rage.


Where do you see the culture of rage? Where don’t you? Turn on the cable news, and you’ll see talking heads screaming at each other. American pop culture is movies about death on an epic scale and video games where people just kill each other. Am I saying movies and video games are to “blame” for mass shootings? Of course not. But I am saying so much rage and anger and violence are signs of a deeply unwell society. In a very precise and technical and formal way.


What is it that makes American so angry, so aggressive, so hostile, so cruel? Why is it that that’s the very first thing anyone not from America notices — and why the world, for example, rolls its eyes at American tourists?


What’s immediately apparent to anyone from elsewhere is that Americans have reduced each other to commodities. In Europe or Canada, life is completely different. Schools are not just little arenas of violence, where kids are encouraged to compete brutally, for sports trophies or grades. The result is that there is less bullying — and far, far less violence like school shootings. The workplace isn’t like a prison — a place you have to go to have healthcare and retirement — because of course everyone already has those basics. University isn’t dominated by the stupidity and ignorance and violence of fraternities. Profit isn’t the sole motive of every aspect of human existence.


I could go on endlessly. The point is this. Take the example of going to the store. In America, you can go to the same Starbucks forever — and never know a thing about anyone who ever works there or goes there. That would violate a social norm. In Europe, you can’t not be friends with people, at least if you go to your neighbourhood bistro or cafe. That would violate the norm. American life is completely atomized, and because it is atomized, it has been dehumanized. What does that lead to?


America is a society that has undergone an almost complete process of social disintegration. Social bonds are almost entirely nonexistent anymore. Way back in the 90s, sociologist James Putnam began documenting this startling collapse of social bonds, in his famous Bowling Alone. In Holland, the number of people who think that most people can be trusted is almost 70%.

In America, it’s half that: just 35%. And that almost certainly overstates the number, because people tend to be polite in surveys.


Think about that for a second. Just three people out of every ten in America trust the rest. But can you blame them? I can’t.


Think about American life for a second. What is it, if we really think about it? It’s an endless war, a battle, a life-and-death contest, that you have to wake up and engage in day after day, every day, your whole life long, just to have the basics. Want healthcare? Want a tiny bit of money? Want to be able to have a place to live and pay the bills? Then you have to go out there and compete with everyone else for a “job.” That means, in plain English, some morsel of pointless work, whose only real purpose is to make billionaires richer. And you don’t even get a fair share of that.


American life is a bitter, bruising, endless life-and-death contest. For things that people in every other rich country, and plenty of poor ones, simply give each other. Healthcare, medicine, retirement, education, income, housing, transportation, utilities. Americans have to compete with everyone else just to have a tiny, tiny share of those things. And if they don’t compete, they don’t get them, which means they’re left to die. If they can’t compete, or if they don’t win this game, even on some tiny level, again, they’re left to die.


Existence itself has become a battle in America. So who can blame Americans for not trusting each other? They are made to regard each other as adversaries, enemies, competitors, rivals. For the basics of life, whether money, food, water, or shelter. That is the way America is “institutionally structured,” which is a fancy way of saying “set up.”


But turning life into an endless life and death contest for the basics, where if you lose, you die — it has a price. When you’re forced to regard everyone else as an enemy, rival, competitor, adversary — they can’t also be your friend. Ally. Partner.


Sure, you can pretend they are — with that weird fake plastic mean smile Americans are famous for. But that’s just a game of make-believe. Americans are made to regard each other was enemies, so, unfortunately, they can’t be friends.


That is why America has undergone a process of social disintegration. That is why it feels so bleak and brutal and cruel. It’s why when someone like me or my European or Canadian friends visit or move, they feel alienated, weirded out, estranged. Nobody’s genuinely friendly, and everybody’s angry and cruel all the time, and strangest of all, they don’t know it.


What my Canadian and European friends are baffled by is this. Why do Americans live this way? All the things they’re made to compete with each other for aren’t really in short supply. They are just kept in a condition of artificial scarcity. There’s no real shortage of houses, or money, or work. It’s just that these things are kept artificially scarce, by America’s weird, failed systems. Hedge funds buy entire neighbourhoods and demolish houses — while Americans go homeless. Billionaires like Bezos and Zuck have all the money — while the average American lives pay check to pay check and dies in debt, just like a neo-serf. There’s no shortage of insulin — it’s just made cruelly, fatally unaffordable because corporations need to perpetually jack up their profits, into infinity.


Americans are made to live the way they do — a bleak, brutal existence of competition and adversariality — because their failed systems make them. In that way, America’s worse than the Soviet Union right now. The Soviet Union really did have shortages of basics. America doesn’t. Americans live this way — in a state of perpetual competition for the basics — because that’s the way they’ve been told is a good and just and noble way to live.


But it isn’t. The theory is false — the theory being more or less all of American economics, which basically says if we give people the basics, they’ll turn lazy and mean and violent and stupid. Not having the basics is what’s made Americans violent and foolish. Why? Because the price has been to destroy social bonds.


That might not sound like a big deal to you — “the destruction of social bonds” — but let me assure you, there’s little greater calamity a society can suffer. What is it called when I begin to distrust you? Regard you as an enemy? Someone who has to be vanquished?
Hate.


America’s culture of rage has produced a hateful society. American society is so full of hate, it leaves the rest of us, who’ve lived elsewhere, exhausted and depressed, and plenty of Americans too. What do I mean by that? Do you really need more “evidence”? Weren’t the Trump years enough? How about two mass shooting in two weeks?


The first one, in Atlanta, was at the intersection of many kinds of hate — minority women were targeted. American life is permeated by rage and hate. And it spills over into violence. Real violence, like mass murder. All the time, over and over again.


And all that is because, at root, Americans live in a failed society, a failed state. Where artificial scarcities are used to control them. To force them into attitudes where everyone must everyone else’s competitor, adversary, enemy, not ally, friend, partner. Hence, America strikes the rest of the world — where friendship and warmth are norms, but in America brutality and cruelty are — as profoundly ugly and backwards and bizarre. It is.


I can’t think of any other society where rage and hate are as normal as they are in America, because people are made to compete, controlled by artificial scarcities — to the point that they are driven mad by them. Remember, we humans are deeply social beings. If we don’t have sociality — we begin to lose our marbles. And that is what appears to have happened to Americans. Not having sociality — true sociality — in society anymore, warmth, gentleness, friendship, has created the illusion that brutality, cruelty, selfishness, materialism, objectification, commodification, treating everyone else like something to be dominated, abused, acquired, discarded, are all normal. They’re normal in America, sure, but they’re not normal at all.


And when a society normalises dehumanization, brutality, cruelty, selfishness, isn’t it obvious to see how things like mass killings become, well, everyday events?


America’s a deeply unwell society. Americans still don’t really grasp it. They don’t feel how abnormal it is to live in a society where aggression and hostility are the only things that exist, because the only way people are allowed to regard each other are as rivals and enemies. All that’s normal in America.

But that, my friends, is why going back to “normal”

was never going to be good enough.

CONCERNS OF LIPID NANOPARTICLE CARRYING MRNA VACCINE INTO THE BRAIN: WHAT TO MAKE OF IT?

Detailing the arguments for and against this concern with input from experts.

by Shin Jie Yong

We are all-in into vaccinating as many people as possible against Covid-19, with mRNA vaccines at the forefront. So, we might as well go all-in into understanding the little intricacies of how mRNA vaccine encapsulated by lipid nanoparticles (LNPs) might interact with delicate cell types — such as neurons in the brain — that a few experts have raised.

Before going further, the conclusion herein is that the actual risk of SARS-CoV-2 infection or Covid-19 largely outweighs the hypothetical risks of the LNP-encapsulated mRNA vaccine. But there are still a few concerns left unanswered, which deserve more transparency.

Current vaccines rely on spike protein

Nearly all the vaccine candidates for Covid-19 — such as the mRNA, DNA, viral vector, recombinant protein, viral-like particles, and peptide-based vaccines — rely on the SARS-CoV-2 spike protein to induce immunity.

The Pfizer-BioNTech and Moderna mRNA vaccines consist of an mRNA genetic material encased within LNPs that can fuse with muscle and immune cells upon injection. The released mRNA then instructs the cells to make spike proteins, which are expressed on the cell surface to trigger various aspects of the immune system.

The AstraZeneca-Oxford and Johnson & Johnson adenoviral vector vaccines use a harmless modified adenovirus to deliver DNA into the cell to make SARS-CoV-2 spike proteins to induce immunity.

The Novavax peptide-based or protein subunit vaccine uses purified spike proteins of SARS-CoV-2 to induce immunity.

The Sinovac and Sinopharm inactivated vaccines use dead SARS-CoV-2 virions with the spike proteins intact to induce immunity.

While these vaccines all rely on the SARS-CoV-2 spike proteins to train the immune system in one way or another, only the mRNA vaccines use the innovative LNP technology to deliver the mRNA into cells.

For simplicity, the spike protein mentioned from hereon belongs to SARS-CoV-2, the coronavirus that causes Covid-19.

Lipid nanoparticles (LNPs) hypothetical risks

The mRNA vaccine is injected intramuscularly through the arm. This method is preferred because large muscle cells have high vascularity, so the injected biomaterial can easily reach the systemic bloodstream and lymphatic system.


LNPs fuse with and enter mammalian cells easily. As mentioned, the Pfizer-BioNTech and Moderna mRNA vaccines use LNPs to encapsulate the mRNA genetic material for more efficient cell delivery.

Thus, the combined intramuscular injection and LNP technology would enable the mRNA vaccine to reach a broad range of cell types. The mRNA might even reach delicate cells or places that we don’t want them to, such as neurons in the brain or spinal cord.

In fact, LNPs are often used to overcome the problem of the BBB blocking medical drugs from entering the brain. Given that the BBB and blood-spinal cord barrier are lipid-soluble, the LNP-encapsulated mRNA vaccine might be able to enter the brain and spinal cord.

As a result, brain cells that express the spike protein might be marked as foreign by the immune system. For example, cytotoxic T-cells, which kill virus-infected and cancerous cells, might see the spike protein-expressing brain cells as a threat. Unlike muscle cells and many other cell types, neurons in the brain rarely regenerate.

Jacob Wes Ulm, MD, Ph.D., a geneticist, explained this concern in detail in a letter to the British Medical Journal, as well as in a public comment to an article about mRNA vaccines on January 2021:

…it seems that they [mRNA vaccines] can enter a much broader tissue range compared to even attenuated virus vaccines…And since the mRNA vaccines would induce SARS-CoV-2 viral spike protein expression, that seems to mean that people who get the mRNA vaccines are going to have a much greater range of cells and tissues vulnerable to cytotoxic [T-cell] attack…with side effects that may not manifest for years (with cumulative damage and chronic inflammation).

“This is where the picture gets aggravatingly murky,” Dr. Ulm added, mentioning that there seems to be no comprehensive data on the cellular localization — i.e., which types of cells the biomaterial enters— of the LNPs used by Pfizer-BioNTech and Moderna.

Although there have been past studies on the cellular localization of LNPs (more on this below), different LNP formulations would enter different cell types, Dr. Ulm stated, so “we don’t know where in the body they’re going,” adding that:

The nightmare scenario would be if e.g. the mRNA vaccines’ lipid nanoparticles are, indeed, crossing the BBB and getting endocytosed into critical glial cells, like oligodendrocytes, or even worse, into neurons themselves in the brain and spinal cord, putting a bullseye on these critical cells for cytotoxic [T-cells].

In fact, one 2017 study vaccinated mice against influenza viruses with LNP-encapsulated mRNA vaccine. While the mRNA vaccine immunizes the mice, the study found traces of the mRNA in the brain at 0.4 ng/ml. However, the amount of mRNA found in the muscle injection site, proximal lymph nodes, distal lymph nodes, and spleen were much larger at 5680, 2120, 117, and 87 ng/ml, respectively.

That said, this is also consistent with what the European Medicines Agency’s (EMA) assessment report of the Moderna mRNA vaccine has reported:

Low levels of mRNA could be detected in all examined tissues except the kidney [in rats]. This included heart, lung, testis, and also brain tissues, indicating that the mRNA/LNP platform crossed the blood/brain barrier, although to very low levels (2–4% of the plasma level).


Therefore, these reports suggest that the LNPs can carry bits of the mRNA vaccine into the brain.

But we still don’t know what would happen after the mRNA vaccine enters the brain (more on this below).
Notably, for the Pfizer-BioNTech mRNA vaccine, the assessment report by the U.K. government is a bit vague, stating that:

Information regarding the potential distribution of the test articles to sites other than the injection site following IM [intramuscular] administration has been provided and is under review as part of the ongoing rolling assessment.

Last month, I received an email from Goh Kiang Hua, MD, a consultant general surgeon, asking if I’ve come across any scientific data on what happens to the cell that makes and expresses the spike proteins upon receiving the mRNA vaccines.

I couldn’t find such any, except for the abovementioned EMA’s report that I found posted in an mRNA discussion google group that William Steward, Ph.D., founded.

Dr. Ulm couldn’t either, publicly commenting that:

I used to work in gene therapy and recall how we’d obsess on tissue tropism for our vectors before considering clinical trials, so I’m bewildered that this information seems almost absent for an almost entirely new vaccine modality…Without knowing more about the specific LNP formulations and their cellular and tissue trafficking patterns, we just can’t say much of anything with certainty.

Note that tissue tropism or trafficking patterns mean which tissue or cell types the biological material might enter, similar to cellular localization.

The surgeon then mentioned cases of immune thrombocytopenia — a life-threatening blood clot or platelet disorder — occurring shortly after mRNA vaccination. While no causative link has been confirmed, he considered that maybe the LNPs had carried the mRNA vaccine into the megakaryocytes (platelet-producing cells) in the bone marrow. The megakaryocytes then express the spike protein, only to be marked for destruction by cytotoxic T-cells. Platelets then become deficient, causing thrombocytopenia. Of course, he emphasized that these are just speculations.

This may be an ‘off-target effect’ of mRNA vaccines. For example, a literature review published in Pharmaceutics in January 2020 stated:

Cell-specific delivery of mRNA would be beneficial for the development of mRNA-based therapeutics. This can enhance the delivery of mRNA molecules to the targeted cells and hence reduce the required mRNA dose, as well as reducing potential off-target effects.

Overall, I see that many experts have raised hypothetical concerns of where and which cell types the LNPs might carry the mRNA vaccine into. Depending on where the mRNA ended up, the subsequent mRNA-induced spike protein expression might possibly trigger biological reactions we don’t want.

For more context about this issue, the British Medical Journal (BMJ) has also covered it last week, featuring Dr. Ulm’s concerns on the cellular localization of LNPs.

Screenshot of an article published in the British Medical Journal (BMJ) on 10th March 2021.

Why it might not be a problem
A few past studies have investigated the cellular localization of LNPs carrying an mRNA that encodes luciferase, a protein detectable via imaging scan. With this method, researchers can visually see where or which cell types the LNPs had carried the mRNA into. In a word, the luciferase visualization is a proxy for mRNA cellular localization.

A 2015 study administered LNP-encapsulated mRNA into mice via various routes. The intramuscular route is one of the most effective ones, resulting in mRNA localization mostly in the liver and, to a lesser extent, the muscles, spleen, and lungs. The mRNA-induced luciferase protein expression peaked at about 5-hour and declined thereafter.

A 2017 study injected LNP-encapsulated mRNA vaccine into mice and found that the mRNA disseminated mostly into the muscles, lymph nodes, spleen, and liver. But this study also found traces of mRNA in the heart, bone marrow, kidney, lung, stomach, rectum, intestines, testes, and brain. The mRNA-induced protein expression peaked at about 6-hour.

A 2019 study injected LNP-encapsulated mRNA vaccine into macaque monkeys intramuscularly. The mRNA ended up entering the liver the most, followed by the spleen and muscles. The luciferase protein expression only lasted about 8 hours and then declined.

A 2021 study administered LNP-encapsulated mRNA vaccine into mice via various routes, including intramuscularly. Scanning the mice’s body revealed some degree of luciferase expression. While specific body parts were not mentioned, the brain didn’t appear to be one of the areas the mRNA entered. The mRNA-induced protein expression was highest within the first 24 hours and mostly gone by day 6.

Nevertheless, whether the LNP formulation of Pfizer-BioNTech and Moderna mRNA vaccines is the same as these studies remains unknown.

But we can see a trend in these studies — that intramuscular LNPs injection tends to deliver the mRNA into the muscles, liver, spleen, and lymph nodes. This cellular localization pattern is also consistent with the EMA’s assessment report of the Moderna mRNA vaccine, although they also found tiny mRNA traces in other cell types, such as the heart and brain.

Thus, we can be assured that the brain is most likely not the main tissue or organ that the Pfizer-BioNTech’s and Moderna’s LNPs enter.

In a detailed post in the mRNA discussion google group, Dr. Goh reasoned that the mRNA vaccine is unlikely to reach the brain from the arm injection site owing to the many obstacles along the way.

The mRNA vaccine would have to first escape from the densely packed muscle cells at the injection site into the lymphatic system and bloodstream. And living cells present throughout such route could take up the mRNA vaccine anytime. “Along the way, especially in the capillary beds of the lungs where the blood flow is slow, the LNPs face multiple hurdles as the whole route is lined by living cells,” he explained.

“If the LNPs survive the journey so far, the next stage is equally if not more treacherous.” The mRNA vaccine then has to resist tremendous force as the heart pumps blood throughout the body. “If the LNPs disintegrate from the turbulence, the mRNAs will be rapidly destroyed by ribonucleases,” he said. But, “those that remain intact will be sent to the WHOLE body.” Still, he further cautioned that “the structural integrity of these LNPs after being expelled from the [heart’s] left ventricle is doubtful.”

That said, here is where the brain or other organs might encounter the LNPs.

However, the brain is shielded by the BBB. So, even if the LNPs are about to enter the brain, the BBB cells could take up the mRNA vaccine, and the spike protein production might just be limited to the BBB.

Assuming the mRNA vaccine crossed the BBB successfully and entered the brain, we still don’t know what might happen after that.


Maybe the mRNA gets degraded once it enters the brain. Maybe the neurons will take up the mRNA and express spike protein on its surface, triggering cytotoxic T-cell attacks. But this is further assuming, Dr. Goh pointed out, that the T-cells would also cross the BBB. In fact, T-cell trafficking into the brain is highly regulated to prevent unwanted inflammation, so it’s not easy for T-cells to cross the BBB. The next question would be if such neuronal injury is severe enough to trigger diseases. Maybe the neuronal injury is just a little stressor that may not be detrimental health-wise.

Still, one could argue that immune cells in the brain, like microglia, might attack neurons that take up the mRNA vaccine. We know mRNA vaccine activates T-cells, but whether brain immune cells are also activated has not been studied.

It’s also worthy to note that mRNA doesn’t stay in the cell for long; it’s gone after being translated into proteins. Indeed, studies studying mRNA vaccine — in the bulleted points above — show that the mRNA-induced protein expression peaks within a few hours and then declined sharply, lasting only for a few days. As T-cells belong to the adaptive immune system, they take about 7–15 days to activate.

Dr. Goh further reminded us that participants in phase I clinical trial are still being followed up closely for nearly a year now. “This is probably the most closely watched vaccine roll-up ever in the history of vaccinology,” he stated. “To date, thankfully, there has been no signal of any long-term issues of concern.”

What to make of all this?
Overall, authorities and pharmaceutical companies may want to provide more transparency on the hypothetical concern of LNPs carrying the mRNA vaccine into areas we don’t want them to.
However, if such concerns are legitimate, it’s hard to imagine that health authorities and pharma have overlooked them. The more likely scenario may be that such concerns were considered but deemed of low concern for reasons discussed above.

Ultimately, human organ systems are complex. Theories or hypotheses alone do not always translate to the real biological phenomenon. We have seen far too many times that in vitro (test tube or cell culture) and in vivo (animal) study results failed to be replicated in humans. And these in vitro and in vivo studies are usually based on theories or hypotheses that scientists wanted to test out.

Lastly, we must also weigh the LNP mRNA vaccine’s hypothetical risks against the coronavirus’s actual threats. Not only is Covid-19 life-threatening among the vulnerable populations — such as older adults, people of color, and people with underlying medical conditions — but long-Covid or post-Covid syndrome is another serious threat to the young and fit.

Steve Pascolo, Ph.D., co-founder of CureVac, is one of the earliest researchers to advocate for mRNA vaccines’ potential in 2004. He also has an impressive publishing record on mRNA vaccines and was kind enough to respond to my email inquiring about this topic. Dr. Pascolo admits that some cells that take up the mRNA and express spike proteins on their surface might get destroyed by cytotoxic T-cells.

But he added:
…that is what happens to a much higher grade and in all organs when we get infected by SARS-CoV-2…or vaccinated with live viral vaccines…With the mRNA vaccine (30 micrograms in the muscle) the eventual destruction of cells by CD8 [cytotoxic T-cells] would always be very minor compared to what happens in infection when the viruses infect virtually all cells in all organs and the immune system is fully activated to get rid of it…”

Thus, the mere 30 micrograms of mRNA vaccine injected intramuscularly pale in comparison to the actual virus infection in the capacity to trigger cytotoxic T-cell attacks in the brain or elsewhere. And yes, SARS-CoV-2 is capable of invading the brain and many other organs.

Indeed, experts in the mRNA discussion google group who first raised the hypothetical risks of LNP-encapsulated mRNA vaccines are still pro-vaccine, agreeing that SARS-CoV-2 or Covid-19 is the larger threat.

To conclude, this article doesn’t intend to undermine the mRNA vaccine but to better understand its subtle intricacies that might be important. Hopefully, there will be more research on this matter. If at all such concern is an issue, which is unlikely, we could still find ways to circumvent it.

If not, then we can safely dismiss one worry we have.

Either way, it’s worth knowing.

CAN YOU STILL TRANSMIT COVID-19 AFTER VACCINATION?


By Zaria Gorvett – guest post

There’s no evidence that any of the current Covid-19 vaccines can completely stop people from being infected – and this has implications for our prospects of achieving herd immunity.

It was 17 June 2009. An 11-year-old boy returned to the US from the UK – and inadvertently brought something with him. Later that week, while attending a religious education programme in Sullivan County, New York, he developed a mysterious swelling of his salivary glands. He had mumps, a respiratory infection spread by contact with droplets in the air.

Meanwhile, the religious course continued. The 400 children in attendance spent hours each day engaging in prolonged face-to-face contact – specifically, a kind of Orthodox Jewish education involving facing a study partner, a chavrusa, across a narrow table, while analysing and debating text from the Talmud. By the time the programme ended, 22 others had been infected, along with three adults.

As the students went back to their homes, the virus spread to Brooklyn and Rockland County, then on to Ocean County and Orange County. In all, the outbreak lasted a year, and at least 3,502 people developed the disease.

When scientists analysed what had happened, they suggested that the chavrusa style of learning might have allowed for “particularly efficient transmission of mumps virus”. What might seem most surprising in this case is that the accidental super-spreader had received a full course of the MMR (measles, mumps and rubella) vaccine. It’s likely that he did have some immunity – like the other vaccinated children, he developed relatively mild symptoms with no complications – but he was still able to carry the virus and transmit it to others.

In fact, most vaccines don’t fully protect against infection, even if they can block symptoms from appearing. As a result, vaccinated people can unknowingly carry and spread pathogens. Occasionally, they can even start epidemics.

“EFFECTIVE” OR “STERILISING” IMMUNITY

There are two main types of immunity you can achieve with vaccines. One is so-called “effective” immunity, which can prevent a pathogen from causing serious disease, but can’t stop it from entering the body or making more copies of itself. The other is “sterilising immunity”, which can thwart infections entirely, and even prevent asymptomatic cases. The latter is the aspiration of all vaccine research, but surprisingly rarely achieved.

Take meningitis as an example. For the kind caused by the bacteria Neisseria meningitidis, there are many vaccines available for the tens of different strains. The three given in the US – MCV4, MPSV4 and MenB – can together prevent 85-90% of disease cases. However, several have been shown to still allow people to “carry” the bacteria involved.

They can hide out in the nose or the back of the throat, from where they are able to infect others via sneezing, coughing, kissing, or sharing cigarettes or utensils. In one study of university students in the United Kingdom, the vaccine had no effect on the proportion of people harbouring the pathogen four weeks later.

“Two meningitis vaccines can have two very different effects on whether you can spread the disease,” says Keith Neal, professor emeritus of epidemiology at the University of Nottingham. “But only a minority of those people who get the germ go down with meningitis [in well-vaccinated communities] because they have immunity to it.”

It’s also possible to be infected with pertussis, hepatitis B, mumps, and (often, but not always) influenza, regardless of whether you have been vaccinated – though all these immunisations are highly effective at preventing people from developing serious symptoms or needing to be hospitalised.

HOW STERILISING IMMUNITY WORKS

While effective immunity is usually provided by a combination of white blood cells – such as B and T cells – along with antibodies, sterilising immunity is typically all about the latter. In particular, it relies on neutralising antibodies, which defend the body from pathogens by sticking to their outer surface and preventing them from interacting with their intended targets, such as the cells that line the nose, throat or lungs.

In the case of Covid-19, neutralising antibodies that recognise the virus bind to the spike protein on its surface, which it uses to enter cells. To achieve sterilising immunity, vaccines must stimulate enough of these antibodies to catch any virus particles entering the body and immediately disarm them.

WHAT TYPE OF IMMUNITY DO THE COVID-19 VACCINES PROVIDE?

“In a nutshell we don’t know, because they’re too new,” says Neal.

So far, the available Covid-19 vaccines have not been judged primarily on their ability to prevent transmission – though this is now being evaluated as a secondary endpoint for many of them. Instead, their efficacy was assessed by whether they could prevent symptoms from developing. “This means that we set our targets kind of pragmatically,” says Danny Altmann, professor of immunology at Imperial College London.

Israel had already vaccinated more than half of its citizens by the end of January, making it a useful place to study how the vaccines affect transmission (Credit: Getty Images)
Israel had already vaccinated more than half of its citizens by the end of January, making it a useful place to study how the vaccines affect transmission (Credit: Getty Images)

Scientists already know that the antibodies people develop after natural infections with Covid-19 don’t always prevent them from being reinfected. One study of British healthcare workers found that 17% of those who had antibodies already when the study began – presumably from a first infection – caught it a second time. Around 66% of these cases were asymptomatic, but it’s thought that you don’t need to have symptoms to be at risk of passing the virus on to others.

“For a virus like this, I almost think that’s asking too much of a vaccine,” says Altmann. “It’s really, really hard to do.”

Happily, this isn’t quite the end of the story.

There are some early hints that certain vaccines might be able to reduce transmission, even if they can’t eliminate it entirely. One way it might do this is by reducing the number of viral particles in people’s bodies. “It is quite likely that if the vaccines are making people less ill, they are producing less virus, and therefore will be less infectious, but that’s just a theory,” says Neal.

Sterilising immunity is also notoriously tricky to prove.

Since most clinical trials didn’t check whether the vaccines were preventing transmission, scientists are currently looking to see whether they are having an impact on infection rates in places where they have already been widely distributed. In the UK, you might expect that outbreaks in care homes – where vaccination efforts are being prioritised – would become less frequent, if the vaccines were having an effect.

But this is problematic. “There are two factors,” says Neal. “We’ve got lockdowns and a vaccine. So, it’s actually quite difficult to separate them out. Is it the vaccine? Is it the lockdown, or more likely a combination of both?”

Here’s what we know so far about the current vaccines’ ability to halt transmission. (But first – to avoid confusion, information about their ability to prevent symptoms or protect people from disease has not been included.)

OXFORD-ASTRAZENECA

Back in July last year, a study testing the efficacy of this vaccine in rhesus macaques – which have similar lung physiology to humans – provided some promising results. It found that while the monkeys were protected from serious illness, it did not prevent them from becoming infected with Covid-19 in the first place. Vaccinated monkeys were as likely to become infected as the unvaccinated ones, though they did have fewer viral particles in their lungs than the unvaccinated group.

The authors noted that their results suggested that the vaccine might not prevent the transmission of the virus, “however, it could significantly reduce illness”.

Fast-forward to the phase III trials in humans, and the picture becomes a little more complicated. Unusually, the Oxford-AstraZeneca vaccine didn’t just involve injecting the participants with two doses of either the new vaccine or a placebo – in this case, the meningitis vaccine – and then following up to see if they had developed any symptoms several weeks later. This trial also involved the additional step of asking them to complete a nose and throat swab each week, to test for asymptomatic infections.

According to these results, published in January 2021, the vaccine was 59% effective at preventing infections in those who received a half dose, followed by a standard dose – a group that also happened to be younger than the average for the study overall. However, among those who received two full doses, that figure dropped to just 4%. The research did not look at whether the vaccine had any impact on the number of viral particles in the patients’ lungs.

The authors explained that while the reduction in the number of infections – and therefore the potential for transmission – in the half-dose group was promising, further data was needed to confirm the findings.

The latest development is a new paper published in pre-print on 1 February, which revealed the results of a further month of studying the trial participants. The researchers found that the vaccine cut the number of cases with detectable virus by 67% after a single standard dose, and wrote that this shows “the potential for a substantial reduction in transmission”.

PFIZER-BIONTECH

There isn’t yet any conclusive evidence that the Pfizer-BioNTech vaccine can prevent people from being infected with the coronavirus – and therefore halt its spread. But there are some early signs that it might.

In early January, the chief executive of Pfizer, Albert Bourla, said animal studies found that it provided significant protection from transferring the virus, though this hasn’t been proven in humans.

Then a small Israeli survey found that, out of 102 medical staff who had received two doses of the vaccine, only two had developed “low” amounts of antibodies. The other 98% had more antibodies than people who had been infected with Covid-19. The results were released via a press release, which quotes the head of the study speculating that these powerful immune responses were likely to prevent people from becoming carriers or spreading the disease.

However, there are a number of reasons to be cautious about interpreting these results, such as the small sample size and the fact that the research was not published in a peer-reviewed journal.

More recently, the Israeli Ministry of Health (MoH) looked at the health records of a million people in the country, and found that – a week after being fully vaccinated – just 317 people out of 715,425 tested positive for the coronavirus.

Again, this was not a clinical trial – there was no unvaccinated control group, and the effect could be down to something else, such as the impact of a lockdown imposed in December. But the infection rate was considerably lower than elsewhere (0.04%, while it’s estimated that 1.87% of people in England had the virus in the week ending 23 January).

A study by the nation’s domestic healthcare provider – Maccabi Healthcare Services – found similarly encouraging results. Out of 163,000 people given a full course of the vaccine, just 31 were infected, compared to 6,500 infections in an equivalent group of unvaccinated people.

MODERNA

Though the Moderna trial did not look specifically at whether the vaccine can prevent transmission, participants were checked for Covid-19 infection before they received their first and second doses – meaning it was possible to compare the rates of infection in these groups. In all, 14 people tested positive after having one shot, verses 38 who had received a placebo.

This suggests that the vaccine might be able to prevent two-thirds of asymptomatic cases after one shot. However, there were limitations to this provisional research – the number of people who tested positive was small, so the estimate may not be entirely accurate. It was published in a briefing submitted to the FDA, and has not yet been peer-reviewed.

NOVAVAX

The vaccine hasn’t yet been approved for use anywhere in the world – and like the others, it has not yet been comprehensively shown to prevent infections or transmission in humans.

But back in November, some early results got scientists excited.

The company revealed that it prevented the virus spreading entirely during studies in rhesus macaques, when they were given a high enough dose. These results put it in an exclusive club of vaccines that are able to prevent asymptomatic transmission completely in other primates – seen as a promising sign, because they have similar respiratory physiology to humans.

Now scientists are waiting to find out if the vaccine can achieve sterilising immunity in vaccinated humans, too.

INCOMPLETE HERD IMMUNITY

Unfortunately, the ability of the vaccines to prevent transmission won’t just have an effect on how long social distancing rules need to be followed – it will also have an impact on herd immunity.

“If the vaccines don’t completely stop transmission, it will increase the amount of people we need to vaccinate to truly cross the herd immunity thresholds and drive down cases to somewhere near zero,” says Michael Head, a senior research fellow in global health at the University of Southampton. He explains that it’s not yet clear what the herd immunity threshold is, because it hasn’t been reached either through natural infection or through vaccination.

Herd immunity is the indirect protection from an infectious disease that populations acquire when enough people are immune. The threshold needed to achieve it depends on many different factors, such as the reproduction number of the virus, or “R” – the number of further people infected by each carrier – which itself varies widely. Some factors that affect the latter include where in the world you live, the variant involved, and the conditions on the ground, such as lockdowns.

This means that, even when scientists do know more, there will be no set threshold for herd immunity that works everywhere – but it’s possible to estimate roughly what it might be.

For example, one calculation suggests that for a vaccine that totally eliminates transmission, 60-72% of the population would need to have it, in order to accomplish complete herd immunity. But if the vaccine’s effectiveness were 80%, between 75 and 90% of people need to have it.

This is potentially higher than the vaccination ambitions of many countries. The UK is aiming to immunise every adult by September, which equates to around 51m out 67.5m people – 75% of the population in total. That’s assuming that every adult in the country is willing to be vaccinated, and healthy enough to be eligible.

However, most scientists aren’t expecting to eliminate the virus entirely. For the moment, the goal is to reduce its transmission as much as possible. “Even if you vaccinate, you’ve still got a fairly large number of susceptible people there,” says Head. “So, we will still see outbreaks happen. I think they would be fairly localised, but they would still cause concern and cause a burden of disease”.

Some scientists argue that the emphasis on preventing transmission is a red herring, because once enough people have been vaccinated, it doesn’t matter if they are still able to spread the virus – everyone will have immunity.

However, it may prove crucial for those who are unable to be vaccinated, for example because they are pregnant, too young, or too unwell.

Until we have an answer, perhaps we should all keep in mind the story of the 11-year-old boy with mumps – and act as though we haven’t been vaccinated, even if we have.

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