#188: Play the Hand You Are Dealt (Bret Weinstein & Heather Heying DarkHorse Livestream)
In this 188th in a series of live discussions with Bret Weinstein and Heather Heying (both PhDs in Biology), we discuss the state of the world through an evolutionary lens. In this episode we discuss medicine, scientific publishing, and just how bad things have gotten. The New England Journal of Medicine declined to publish a letter that would have provided valuable scientific context for a paper they recently published, and we discuss Bret’s reserve capacity hypothesis regarding the evo...
Hey folks, welcome to the Dark Horse Podcast live stream number, we should have talked about this before we went on air, number 189.
88.
88, right, 188, of course.
That makes sense, because of the last one being 187.
It does, it does, yeah.
Yes, I'm Dr. Brett Weinstein, you are Dr. Heather Hying.
We are going to confront some of the emerging phenomenology of things local to planet Earth.
Can you define phenomenology for me and everyone else?
Yes.
Really?
Well, yeah.
Phenomenology is like the set of related phenomena to some pattern of focus.
Okay.
The phenomenology surrounding, you know, the growth of your garden would involve soil nutrients.
It would involve sunlight.
It would involve systems impinging on.
Yeah.
Those things that are relevant to, I would say.
Ology makes it sound like it is a careful, scholarly discipline, but of course there's lots of ologies out there that sound like that and aren't anymore.
I happen to know that the study of phenomenology is the phenomenologyology, which is a subset of biology.
Is it?
Yes.
When we're talking about living systems.
Sure.
All right.
Here we are.
All right.
Big progress.
This is such big progress.
I think we might even be done.
Uh, you mean like finished?
Yeah, like cancelled.
Oh gosh, that's happened before.
Well, here we are.
You are watching or listening to us on any number of platforms, but if you are watching, consider coming over to Rumble and joining us there, subscribing to the channel there.
And if you're watching live, even if you're not watching live, but especially if you're watching live, come join us on Locals.
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We really encourage you to do that, and we'll talk more about other places to find us and reasons to join us and such at the end of the show.
But for now, we're going to do a Q&A after today's show, and you can ask questions at darkhorsesubmissions.com, and we're just going to talk to you about our three sponsors at the top of the hour.
Uh, which are Mindbloom, Sundays, and Paleo Valley this week.
So, without further ado... Totally.
With a cameo, I totally forgot to tell you, we were on the mainland yesterday, and, um... Yes, we were.
A guy stopped me.
Uh-huh.
Uh, his name was Chris, I believe, and he said he'd been holding on to a line forever, and he was going to deliver it in person.
He said, That our influence in the world was such that if we were a musical act, we would be called Relief Band, which is, of course, a sponsor that we have had for many years now.
In any case, so that happened.
That's a cameo, a cameo ad spot for a sponsor that we love.
And anyway, somebody mentioned them on the street.
Excellent.
Yes, there it is.
Trying to figure out when that might have happened, given that we were together most of the time.
Oh, when was that?
When did that happen?
I had just gotten off the... I will fill in the details for them.
I had just gotten off my motorcycle, which I had to take to the mainland to get the firmware updated by the dealer, who were the only people who could do it, in order that the bike would be able to go in reverse.
Yep, you got that right.
And I was there with you.
Taking our younger son to the mainland to get his firmware updated for the school year, also known as his clothing.
I think that's software.
I mean, if it's properly made.
No, no, no, no.
It's not firmware?
If it was hardware, it'd be scratchy.
You wouldn't want to wear it.
So, the better clothes have got to be software.
All right, this has not been that productive.
There are a bunch of people out there, a lot of them have already forgotten that it happened, but there are a certain number of people out there scratching their heads over a firmware update that requires you to take your bike to the mainland in order to go in reverse, but it's all true.
Yep, it is all true, and you can now go in reverse, apparently.
I can now go in reverse.
I mean, you could go in reverse, but now the bike will help.
Mmm.
Hey, you know, we had a cat once who used to beep when she went in reverse.
Yes.
Was that a she or a he?
It was a she.
Dude.
I mean, sometimes it's hard to tell.
I wonder how many people have a cat and have the wrong idea of what sex it is for its entire life and never get confirmation of the reality.
But no, in this case, that was a she.
That was a she.
Beep.
Beep.
Exactly.
Beep.
All right.
It's ad time.
Yep.
Are you going to start?
Of course I am.
Again, with the reading.
Yeah, again with the reading.
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It's pretty, pretty, pretty good to quote Larry David.
And you would know.
I would know.
I'm one of few who would know, but I do know.
Yes.
And, uh, yeah.
Pretty good.
In a pinch, it would work as trail mix for humans.
And if you didn't tell them, they'd be none the wiser.
They probably would.
No.
I don't think so.
No, really?
Okay.
Add a couple M&Ms.
Oh, then they would... I don't know that M&Ms is the right matching.
I think something more in the, uh, not quadrant.
Raisins.
Some raisins you'd get away with, something over nut-ward would be... Onward.
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Fantastic.
Fantastic.
I do love turmeric.
Turmeric.
It's a fine ingredient.
It tastes great.
Yeah, it does indeed.
You want to be careful about getting it out of your clothes.
Yes!
Well, unless you get it all over your clothes very evenly.
Or you're already wearing turmeric-colored clothes.
This is not going to be easy today, is it?
No, it's going to be tripping over words, but so be it.
We both want to talk about some stuff going on in medicine land, but not the usual stuff.
Not the usual.
Yeah.
You want to start?
Sure, why not?
So I wanted to give an update, and in light of that update, Paint a certain picture from a bit that we covered.
Jeez, it would be several months ago at this point.
It would be, I think, back in June.
In fact, we can figure out almost exactly when it was based on the publication.
Yeah, it was in June of 2023.
We covered the publication of a paper.
Zach, you want to show the paper?
The paper's title is Familial Clonal Hematopoiesis in Long-Telomere Syndrome by Du Bois and many other authors, Du Bois et al.
And we covered this paper because although it is independently fascinating, it is even more fascinating to us in light of the fact that it matches the prediction of the telomere hypothesis that I published with Debbie Cizik back in 2002.
That is a paper that many who listen to the podcast will know a whole bunch about.
It is a paper that argued that the evolutionary theory of senescence, and I used the word theory correctly there, this has now been borne out by many empirical results, but the evolutionary theory of senescence is a match for many of the mechanistic discoveries that have been made in gerontology, in the study of cancer, and elsewhere in biology of late.
And my point at the time that we covered it before was that actually this The paper completed the puzzle, that it shows that long telomeres are associated with the inheritance of a predisposition to malignant neoplasms, that is, cancers, which is an exact match for the hypothesis that I published with Debbie Cizek.
And that is a match for the fact, which has been known now for a couple decades, that short telomeres are associated with progeria syndromes.
Progeria syndromes being accelerated aging syndromes.
And the hypothesis that we published... Little boys that look like old men.
That is... It tends to be in men.
That is Hutchison-Gilford progeria, which is the most extreme of the progeria syndromes.
And it is almost always males.
And in those cases, these kids have Every pathology normally associated with aging save two, and the two are they don't get cognitive decline, they have the minds of children, everybody's sharp, and they don't get cancer.
So anyway, that is all a kind of interesting background.
But the point of this paper was made in isolation from most of that context.
The point of this new paper?
The point of this new paper, yeah, Du Bois et al.
did not mention any of the evolutionary context that creates this rather complete picture.
And so I thought it, oh go ahead, It is another example of something we've talked about repeatedly, which is to say the exclusive rise of empiricism over theory in much of what is passing for science.
If all you do is you go out and look for things to test without considering in advance what might be true and why and have a careful hypothesis going in and consider why things might be true at the systemic level, you end up, frankly, with, you know, at best, you end up with papers like this, which appear to be work that is well done at a technical level, but which is unframed in terms of any context in which it could be interpreted.
Which means you derive a small fraction of the power that you would get from the work.
So the work costs whatever it costs to do in terms of the time, the people who did it, the grants that went into it, the laboratory space, all of the materials.
That's some cost.
And then the question is, what did you get?
What's the return on investment?
Well, the return on investment goes through the roof if you place these things properly in their theoretical context, especially if you're dealing with a broad, powerful theory rather than a narrow and mundane one.
So in any case, in light of this, I thought the right thing to do, the right thing to do in normal by the normal academic rules and the right thing to do, logically speaking, was to submit a letter to the New England Journal of Medicine calling their attention to the theoretical context that had been missed.
Now, my feeling was...
Just once again, the New England Journal of Medicine being the publication, being the journal where this paper was published.
Where this paper was published, and I forgot to mention, the New England Journal of Medicine, when they published the familial hematopoiesis paper by Dubois et al., also published an editorial on it describing the importance of this paper.
So the reason that that matters is that the New England Journal of Medicine thought this a significant enough piece of work that they actually did a commentary on what it meant in the same issue.
But still missing the evolutionary context.
Still missing the evolutionary context.
So, if you think about this, I, as a person from an adjacent field, evolutionary biology, who knows the evolutionary context, providing that context to the New England Journal of Medicine, this should be a win for everybody.
I get to point out the context.
The authors of the paper get to have that context placed historically around their paper, which increases the importance of the paper.
The New England Journal of Medicine gets to take a victory lap because the paper it published is even more important than it had realized at first.
It's wins across the board.
So I did submit a letter.
I submitted a letter, and letters are a form of academic publication.
They are very tightly regulated in terms of length and format.
You are, in this case, allowed only five references, and it had a very short word limit.
So I wrote my letter and showed it to a number of people, and then I submitted it.
And I wanted to read that letter so people can get a sense for what the New England Journal of Medicine was looking at.
Can I show it?
Yeah, why don't you show it.
I said in this letter, Science produces explanatory theories when predictive hypotheses withstand rigorous tests.
In showing that long telomeres promote life-shortening pathologies including cancer, Dubois et al.
have made an important discovery, even more significant because it matches predictions of the reserve capacity hypothesis which Cizek and I elucidated in 2002.
Dubois et al.
were apparently unaware they had tested our model and in so doing completed a classic series of insights beginning with Medawar in 1952 and Williams in 1957.
With their contribution, we now have a unified mechanistic and Darwinian explanation for why we grow old.
The force of natural selection decreases with age, creating a trade-off between longevity and youthful vigor.
In vertebrates, this trade-off manifests as a telomere-mediated balance between tumor suppression and tissue repair.
Runaway somatic cell lines are arrested at their hayflake limits.
So that's the letter.
And I recently got word that the New England Journal of Medicine wasn't interested in it.
They did not send it out for review.
They declared it dead at the editorial stage.
the letter, and I recently got word that the New England Journal of Medicine wasn't interested in it.
They did not send it out for review.
They declared it dead at the editorial stage, and I want to now show you the note that they sent me.
They said, Dear Mr. Weinstein, I am sorry that we will not be able to publish your recent letter to the editor regarding the Armanios article of 29th June 2023.
The space available for correspondence is very limited, and we may use our judgment to present a representative selection of material received.
Many worthwhile communications must be declined for lack of space.
Thank you for your interest in the journal.
Sincerely, etc.
All right.
That is... Is Armanios the final author?
I believe so.
The note that they sent is pure boilerplate, and it is meant to read as pure boilerplate.
The idea is you didn't even rise to the level of our interest.
This is not worth a note that was penned specifically.
Which is, if you think about it, rather odd.
I sent them a note, which would take very little space to publish, that increased the power of what they had already published and commented on, and they were not interested in the historical context.
And we can speculate about why that is.
But I thought, in light of the fact that they we're not interested in publishing this, that I would cover what the story that is now complete looks like, because really it's an amazing moment that we can now say, we're not speculating, it's not, there is a hypothesis that says,
we now have substantial empirical demonstration that we now have substantial empirical demonstration that illustrates that this long pattern of hypothesis and discovery, starting in 1952, is actually correct, and it gives us a simple answer to the question, why do we grow feeble and it gives us a simple answer to the question, why do we grow feeble and inefficient with
All right, so to lay this out, what Peter Medawar said in 1952, he actually, this is an interesting piece of history, He delivered a talk.
It was not even a paper, and it wasn't a paper in the sense of a talk delivered at a conference either.
He delivered a public speech that was titled, An Unsolved Problem in Biology.
Now Peter Medawar was a British biologist.
He ultimately won a Nobel Prize for his work on immunological graft rejection.
He's the guy who discovered why it is that if we take an organ from somebody who's a blood type match and we install it in another person, it is very likely to be rejected by the body and why you need a very close match at the major histocompatibility complex to get a graft not to be rejected.
But anyway, he delivered a public talk called An Unsolved Problem in Biology, which is now largely lost to history.
I had to work fairly hard to dig up a copy of it.
But in any case, he laid out a case for why it is that aging or senescence should evolve.
And his case, this is back in 1952, involved a thought experiment which was about a Some number of test tubes that arrived at a laboratory.
You know, like a thousand test tubes arrived in a package at a laboratory.
And then the question is how many of those test tubes Would still be around a year in, five years in, a decade in, 20 years in.
And you can imagine that these test tubes, which are no worse on their fifth year in service or their 10th year in service than they were when they were first delivered, would still diminish in number over time.
That you could graph how many test tubes would be left At a X number of years out, and that there would be a number of years out at which no test tubes would be left, just because there is some rate of breakage of test tubes, or loss of test tubes, that would eventually get rid of all of them.
And so what Medawar, in this public talk, where his real point was not about senescence, his real point was, here's how you address a problem we haven't solved.
So this was just a demonstration of how logic works in biology, and in so doing he solved an important piece of the puzzle.
So what he said was, If you take an object that does not degrade with age, like test tubes, and you look at the rate of attrition...
What you discover is that you get fewer and fewer of them left, independent of aging.
And then he reasoned that were there then characteristics of test tubes that affected them badly at some point in the future, that those impacts, the farther in the future they existed, would be less and less significant because fewer and fewer test tubes would be around to experience them.
And by less significant, you mean under less selective pressure.
Right.
Because there are fewer test tubes around to experience them.
Right.
So, for example, let's say you had a condition in which a test tube would spontaneously disintegrate 300 years after it was minted.
Well, virtually no test tube would ever disintegrate by this mechanism, because virtually no test tube makes it 300 years.
So, the point is, what's the cost of such a pathology?
It's virtually zero.
So, his point was, selection sees late life less clearly than it sees early life, and therefore You ought to get pathologies very late in life that are too far removed from selection's ability to do anything about them for selection to fix it.
And on the one hand, I will argue that this is sufficient, that this single point of Medawar's is sufficient to explain senescence.
But it does not work for the senescence that we see.
Because the fact is, selection, we begin to degrade very early in life.
We actually begin to degrade upon reaching reproductive maturity.
And so that's too early for the weakness of selection to explain the process.
So, 1952, Peter Medawar lays out his case for selection getting weaker the deeper into the lifespan one gets.
It is sufficient to explain some pattern of senescence, but it is not sufficient to explain the pattern of senescence that we actually see in animals.
So it isn't very many years.
1952, Peter Medawar lays that out.
George Williams, who we knew, we'd never met Metawar, but we knew George Williams, puts the second piece of the evolutionary puzzle together.
And over in laboratory space, when these guys are mentioned, they're very often mentioned as if they said the same thing, which they didn't.
Williams built on Metawar.
And what he said was that trade-offs were at the heart of this process because his point, and we didn't know that much about the genome back when Williams said this in 1957.
So he was insightful enough that what he said stood up, even though his mechanistic understanding was crude.
What he said was, genes will tend to do more than one thing.
That the weakness of selection for late-life processes comes into play when you have a gene that does something good for you early in life at some cost late in life, because the early-life benefit counts more than the late-life harm for the reasons that Medawar laid out.
And so what he said is there would be a balance between youthful vigor and longevity and that selection would have to deal with these things based on important characteristics like how much risk were you at?
Because according to Medawar, the more risk you are at from things that have nothing to do with how old you are, the less likely you are to make it to an advanced age at which you would experience some pathology.
So if you're a mouse living in an environment in which there are lots of raptors and you're not likely to make it five years, senescence or no, because a raptor is likely to pick you off, And the benefits of being a particularly effective mouse when you're young far outweigh the ability to live to an advanced age, which you're not going to get to anyway.
So Williams lays...
Yeah, go ahead.
Just to restate some of what you've already said, the observation that genes will tend to do more than one thing is called pleiotropy.
And generally speaking, certainly until Williams, but I think since and almost universally, It is understood that yes, a gene may do X and Y, and isn't that interesting?
Maybe we would prefer X to Y, and we don't necessarily want to encourage both things by promoting the expression of that gene, but it's pleiotropic, so what are you going to do?
And so his observation that early life effects from a gene that also have late life effects, which are negative, has a unique name associated with that kind of pleiotropy, which is antagonistic pleiotropy.
Antagonistic pleiotropy, yep.
Just to fill in some of the vocabulary here.
Yep, and please do that because this will be far clearer if we do it that way.
Okay, so Williams lays out this theoretical model.
It has lots of interesting implications, which are proven by biologists, field biologists, who studied populations of creatures.
They showed that similar creatures, for example, Ostad, a former lion tamer, Showed that possums living on islands where their predators are greatly reduced in number Have greater longevity when taken into the lab.
So he showed that William's William's intuition about creatures that live in safer environments having their longevity extended by selection was true.
Also laid out in Williams' paper was the fact that creatures that have a defense against predation would tend to outlive similar creatures that don't.
So for example, if you compare rodents to birds, flighted birds of a similar size, size tends to correlate with longevity.
The bigger an animal you are, the longer you tend to live.
But things that are flighted, if we're actually better... Between species, not within species.
Between species.
So if you compare, for example, Shrews to bats.
Shrews and bats are not very distantly related, but bats have picked up flight, and that means that they can fly away from danger in a way that a shrew can't.
The bats are disproportionately long-lived, and some are very shockingly long-lived.
There are small bats who've been recovered after three decades in the wild.
That's a kind of longevity that would be unheard of in something like a shrew.
So anyway, there are lots of things about Williams' paper that clearly are borne out by indirect evidence.
But the odd thing about his paper, he lays out this mechanism, and as Heather points out, the prediction of this paper is that the genome should be full of genes that do something good for you early in life at some late-life cost.
And at the point that I started working on this in the very late 90s, Not a single such gene had ever been found.
We knew that the effect that Williams had described was real because we could see it in the pattern of aging, but the genes weren't.
They weren't in evidence anywhere we could see them.
So that was a head-scratcher.
And that is where, you know, some of you will know that my dissertation was on trade-offs.
That's the thing that I have chosen to specialize on and that my belief is that trade-offs actually allow us to answer lots of questions that we can't answer otherwise.
This is where I got the idea.
I looked at Williams' elegant paper and I said, oh, this is a very powerful style of thinking and it doesn't stop with senescence.
So I sort of picked up what he had done and did some new stuff with it.
But all right, so we've got Williams says, selection decreases with age because lots of creatures just for reasons of accident and disease and whatever, you don't get to an advanced age and therefore you don't suffer as much from things that happen late in life.
Williams says... Medawar said that first thing.
Sorry, yes.
Medawar said that first thing.
Williams says it actually has to be trade-offs which explains why we start aging or we start senescing so early in life.
Williams also said some other really interesting things like that senescence was a self-exacerbating problem.
That once the selection decides to allow you to grow more feeble with age, it makes the likelihood of you getting picked off by a predator or getting felled by a disease worse, which means the likelihood of you getting to an advanced age gets worse.
And so the point is, once you start senescing, the bias towards early life grows.
It's a positive feedback, which is a pretty neat mechanism to find there.
Unfortunate, but neat.
Yeah, unfortunate but neat.
And you know, we can talk about creatures that don't have the prerequisites for this pattern.
We'll do that another day.
But it's not that this is the only way to exist, is to be a creature and to grow feeble and inefficient with age.
There are other ways to structure a creature.
And in fact, if you don't have a segregated germline, the whole picture is different.
That means if you don't have separate cells that make gametes... Yeah, so you could be a cedar and this won't happen to you.
Yes, and you know, depending upon what you're doing, it might be as good a deal.
Mobility isn't as good.
Mobility isn't as good.
Flammability is higher.
Yeah, it's not good.
Trade-offs everywhere.
I'm not sure that is well.
I'll have to think of it off camera.
But okay, so Williams delivers this update to Medawar in 1957.
We all know it's true, or decades after, because it's been demonstrated indirectly.
The genes that he suggested would be found were never found.
That was weird, which I thought was like, huh.
What are we doing wrong?
And now we get to where the laboratory folks start to make insights.
And the the key one early here is a guy named Lenny Hayflick.
Lenny Hayflick is still around.
Lenny Hayflick He showed that the long-standing belief of laboratory biologists that cells would go on dividing forever if you gave them the right conditions was not true for somatic cells from vertebrates like us.
He showed that if you give cells, I think he used chicken cells, if you give chicken cells, you know, A nice habitat.
You know, decorations on the walls.
You give them all the stuff that a cell culture could want, that those cells go on dividing for some time, and then they just stop.
Though they are evidently healthy.
So that, wasn't understood why that happened.
Despite the decorations.
Despite the hospitable habitat.
They just stopped dividing.
And so anyway, he called this the Hay Flick Limit.
AFLIC limits are known to differ between... Did he call it that?
Or was it called that?
I think it was called that.
Yeah, I don't... He's not the kind of guy who would have named it that.
But anyway, so that's an interesting result and obviously it has a potential implication here because cell division is necessary for defense of the body, repair, maintenance, all of those things, and the fact that cells won't keep doing it Obviously could be related to why we fail to repair ourselves so that ultimately we die from the collapse of one organ or another.
Now, he did that before telomeres and telomerase were understood.
Telomeres are these repetitive sequences at the ends of chromosomes.
They don't code for proteins.
They're not genes in that sense.
They are genetic material, but they are not genes.
They don't produce... the code is meaningless.
It's just a simple repeated sequence.
But it...
...produces a cap on the ends of chromosomes, which is often described as protecting the ends of chromosomes from the repair machinery that looks for frayed ends and fixes them.
They exist in a loop, actually, where the DNA comes back and inserts one of the two strands, inserts into one of the double-stranded places, so you get this thing called a D-loop.
And that D-loop shrinks every time a cell divides under normal circumstances.
Every time a human cell divides, it loses a little bit of telomere, which is often described as, you know, the incomplete replication of the chromosome.
And I think of it as like a train that can't reach the very end of the track at the station because there's a bumper there, right?
There's a bumper.
And so the train wheels... Or like a zipper.
Yeah, a zipper, any one of these things, where something at the very end of the line prevents the replication enzymes from seeing the very end of the chromosome.
Now, that's not a fatal condition.
Biology has, since our yeast-like ancestors, had the ability to add more telomere.
So it could just swap in some extra telomere for the part at the end of the line that it can't see.
But it doesn't under normal circumstances.
It allows the telomere to grow shorter with each cell division.
And that opens the question of whether or not the shortening of telomeres underlies Hayflick's limit, the limit where cells refuse to divide anymore, whether that limit underlies the senescence of the body that we fail to maintain whether that limit underlies the senescence of the body that we fail to maintain and repair ourselves because So, So anyway, that was an open question.
Is that the mechanism of the Hayflick limit?
We now know that it is.
And I should say Carol Greider and Elizabeth Blackburn elucidated the nature of the telomerase enzyme, a very interesting enzyme that allows telomere to be added either in a reproductive part of the process, in the production of gametes, or in cells where a Hafez limit is not tolerated.
This enzyme, which is mostly protein, as all enzymes are, which has an RNA template built into it, it's a very special enzyme, actually can add telomere DNA to the ends of chromosomes.
Okay, that's a lot of background.
And the thing that's put me on the trail here I knew all of the Hayflick limit stuff, the possibility that telomeres were involved, but I heard a lecture by a student in a cancer lab in which he reported that cancers were effectively all known to have an active version of the enzyme telomerase, where normal somatic cells, the cells of the body, not the germline, have their telomerase enzymes shut off.
They're not present.
And so he was describing the excitement over in the world of people studying cancer that maybe this enzyme, which is active in all cancers, all we've got to do is turn it off and we've cured cancer.
And I knew that folks over in the world of gerontology were interested in turning on the very same enzyme because it potentially could revive these cell lines that refuse to divide and halt the aging process.
And so you've got two groups of laboratory scientists Both think they're going to cure one of the major causes of death for people, but they want to do exactly the inverse thing.
And they weren't talking to each other.
And I looked at this and I said, huh.
Williams, I know, Williams has said that you're going to have genes that do something very good for you early in life, at some cost late in life.
And he called this antagonistic pleiotropy and that that was going to be the underlying explanation for senescence.
And I said, well, maybe the problem is the word gene.
Maybe it's not a gene.
Maybe it's a mechanism that does this, which would have all of the same theoretical consequences that Williams laid out, but it's not a gene in the sense it doesn't code for protein.
Okay, so that allowed me and Deborah Cizek to put together a model in which we showed all of the evidence that would link these things together.
The theoretical explanation, Hayflick's laboratory insight, what little was known about progeria syndromes at the time, and we put together this paper.
Actually, maybe, Heather, you should show it, if you can show your screen.
So I can do it?
Not showing up.
Okay, well, while Zach is working on that puzzle, the paper was called, The Reserve Capacity Hypothesis, Evolutionary Origins, and Modern Implications of the Trade-off Between Tumor Suppression and Tissue Repair.
All right, we should be able to show it now.
No, I think so.
All right, we're giving it a second.
Published in Experimental Gerontology in 2002.
Published in Experimental Gerontology in 2002.
And there it is on your screen.
Okay, so this paper laid out a bunch of the framework.
I wonder if we should read the abstract.
What do you think?
Perhaps.
Maybe you'll do better.
Okay.
Given where it is.
Again, the abstract of Brett and Debussy's 2002 paper published in Experimental Gerontology in 2002.
I already said that.
Antagonistic Pleiotropy, the evolutionary theory of senescence, posits that age-related somatic decline is the inevitable late-life byproduct of adaptations that increase fitness in early life.
That concept, coupled with recent findings in oncology and gerontology, provides the foundation for an integrative theory of vertebrate senescence that reconciles aspects of the accumulated damage, metabolic rate, and oxidative stress models.
We hypothesize that 1.
In vertebrates, a telomeric failsafe inhibits tumor formation by limiting cellular proliferation.
Two, the same system results in the progressive degradation of tissue function with age.
Three, again these are the distinct hypotheses of Brett and Debbie in this paper.
Three, these patterns are manifestations of an evolved antagonistic pleiotropy in which extrinsic causes of mortality favor a species optimal balance between tumor suppression and tissue repair.
Four.
With that trade-off as a fundamental constraint, selection adjusts telomere lengths.
Longer telomeres increasing the capacity for repair, shorter telomeres increasing tumor resistance.
5.
In environments where extrinsically induced mortality is frequent, selection against senescence is comparatively weak as few individuals live long enough to suffer a substantial phenotypic decline.
The weaker the selection against senescence, the further the optimal balance point moves toward shorter telomeres and increased tumor suppression.
The stronger the selection against senescence, the farther the optimal balance point moves toward longer telomeres, increasing the capacity for tissue repair, slowing senescence, and elevating tumor risks.
6.
In iteroparous organisms, that is organisms that expect to have multiple reproductive events in their lifetime, in iteroparous organisms selection tends to coordinate rates of senescence between tissues such that no one organ generally limits lifespan.
A subsidiary hypothesis argues that senescent decline is the combined effect of 1. uncompensated cellular attrition and 2. increasing histological entropy.
Entropy increases due to a loss of the intratissue positional information that normally regulates cell fate and function.
Informational loss is subject to positive feedback, producing the ever-accelerating pattern of senescence characteristic of iteroperous vertebrates.
Though telomere erosion begins early in development, the onset of senescence should, on average, be deferred to the species' typical age of first reproduction.
The balance point at which selection on this tradeoff should allow exhaustion of replicative capacity to overtake some cell lines.
We observe the captive rodent breeding protocols, designed to increase reproductive output, simultaneously exert strong selection against reproductive senescence and virtually eliminate selection that would otherwise favor tumor suppression.
This appears to have greatly elongated the telomeres of laboratory mice.
With their telomeric fail-safe effectively disabled, these animals are unreliable models of normal senescence and tumor formation.
Safety tests employing these animals likely overestimate cancer risks and underestimate tissue damage and consequent accelerated senescence.
That just that last sentence, safety tests, is a reference to drug safety testing.
Yep.
Drug safety testing.
Why are drug safety tests constantly failing to find the damage that these drugs will do?
Here it is in this paper in 2002.
Right, so this would account for patterns exactly like we saw with things like Biox, Fenfen, Zeldain, Erythromycin, where you think a drug is safe and then it turns out to do damage, and the damage that we notice is heart damage.
Now, you will find this pattern familiar.
Why heart damage?
It's presumably because the heart has a very low capacity to repair and its failure is utterly conspicuous.
So when young people die from heart failure, we notice.
So it's not that it does heart failure.
We predict that all of these things do body-wide damage, but we notice it in the heart and so we come to think of it as heart failure.
All right.
Yeah, it's not that it doesn't do heart damage, it's that we can more easily see the heart damage, and so that is what gets recorded.
Right.
The damage that will kill you in your heart might be unnoticeable if it was done in your liver, where you have a tremendous amount of capacity to replace damaged tissue.
Right.
Okay, so what we have here I want to note one thing.
There is a piece of this, I very much regret how we named it in this article, because the world had not yet, or the biological world, had not yet woken up to the full importance of the molecular epigenetic findings that were coming to light.
And so what we call histological entropy should have been called epigenetic entropy.
I believe that this is a very important fact that we predict this and I believe we are correct about it in this paper that the degradation of the body is in part about the fact that the body is very well organized when it is young at the end of maturation it is very well organized and then a derangement occurs that isn't the same entropy that we talk about physically
What it is, is a loss of information about what cell belongs where, so that tissues become less well organized and less effective at doing all the things that they do.
But so it's both.
Like, you know that I think the term histological entropy is brilliant.
I think it's excellent.
And your epigenetic entropy may better define the causal thing that's going on, but it manifests.
Like, every human who ages experiences this histological entropy.
Where, you know, we end up with color, with spots where we didn't have them before, with, you know, less... things that were, you know, beautiful and clean are no longer as beautiful and... Hairs out of place.
Right.
So that is, that manifestation of perhaps the epigenetic entropy inside is a kind of histological entropy.
Right.
The reason I regret it is not that there's anything wrong with the term.
I think it's a perfectly, you know, in a world in which people didn't have biases, it would be a fine, a fine descriptor.
The problem is, it's because we didn't use the term epigenetic People assume that this is yet another version of entropy overtakes the body, which is in some sense not false, but it is not simple entropy that overtakes the body.
It is entropy that overtakes the body because of Hayflick limits, which are built around telomeres, etc.
In any case, I believe that this is a topic on which David Sinclair has been very active.
He is, in many ways, all about the loss of information.
But he doesn't cite this work, and I don't know why that is, but it may be because the term did not bring it into the right circles.
I don't, and presumably many of our audience do not know who you're talking about.
David Sinclair is a senescence researcher.
He's also been a Joe Rogan guest, which is probably where people will know him from.
But anyway, histological entropy, I believe, is an important subsidiary hypothesis here that will ultimately be borne out if anybody ever notices that it was proposed in this paper.
But leave that, be that as it may, I think the important point is that it took generations of biologists to figure out why we senesce.
This is a question that occurs to every biologist and certainly every biologist since Darwin has wondered about it in evolutionary terms.
Is it a failure of evolution?
Is it a product of evolution?
There are lots of bad hypotheses like Oh, we age so we don't, you know, the old don't out-compete the young in the pursuit of food.
There's lots of nonsense in this realm.
And the ability to now tell a complete story, and mind you, I do fault the laboratory scientists for not Thinking deeply about the evolutionary side of the puzzle, but I also fault the evolutionary folks for not typically wanting to get too deeply into mechanism.
The thing that I think Debbie Ciesek and I did right was we said, look, this is neither a mechanistic question nor an evolutionary question.
It is inherently both, as all questions will be.
And the ability now to tell a story that doesn't shortchange one side, you tell just a mechanistic story of, you know, telomeres and Hayflick limits, but it also tells a story about creatures living in environments where extrinsic causes of mortality are either High, in which case senescence will be profound or low, in which case it will be delayed, right?
That is a much richer story and it wasn't something that anybody could do alone.
It literally goes back to 1952 and a beautifully named talk by Peter Medawar in which he tried to show people how you solve a problem in biology, right?
What's the answer?
Well, you start here, and then it takes decades of various people's work to actually complete that story.
And so I just want to end here by reading again the end of the letter, which the New England Journal of Medicine did not want to publish.
Not of sufficient interest, I would think.
Right, not of sufficient interest, right.
It says, with their contribution, that is Du Bois et al., we now have a unified mechanistic and Darwinian explanation for why we grow old.
The force of natural selection decreases with age, creating a trade-off between longevity and youthful vigor.
In vertebrates, this trade-off manifests as a telomere-mediated balance between tumor suppression and tissue repair.
Runaway somatic cell lines are arrested at their hayflick limits, that is cancers.
But the aging body is condemned to degrade beginning at reproductive maturity due to the incomplete and increasingly chaotic replacement of lost cells.
That is now a one paragraph description of why vertebrates grow feeble with age.
And it's very elegant and it took, you know, what, 70 years?
That's a pretty interesting story and shame on the New England Journal of Medicine for not being interested in telling it.
Either not being imaginative enough to understand it, or being so petty about wanting to be territorial here that they didn't even want to do the authors of Du Bois et al.' 's paper the service of putting their work in proper historical context.
Poor shame.
Poor shame.
Well, maybe the American Medical Association is doing better.
Let's hope so.
Turns out not.
Let's talk about uterine transplants for a bit.
Wow.
Yeah.
OK.
Uterine transplants.
Well, there are some number of baby girls born without uteruses.
And there are, of course, many high-tech and newfangled ways of helping people with reduced fertility get fertility.
Of course, there are ancient ways of dealing with this.
Adoption is not limited to humans.
It is found in other species as well.
Um, but, uh, you know, everyone will be familiar with, uh, interventions like IVF and such, and, um, you know, we know people who have benefited from such interventions, and they, you know, they do raise, uh, ethical questions, but, uh, but it's, it is not, you know, it has become somewhat common in some milieus, uh, for it to be understood that some number of people, in part because, uh,
You know, upper middle class educated people are often waiting a fairly long time to start families, that there will be assistance in having kids.
And being, you know, utterly without a uterus is, of course, a rather giant barrier.
And it seems like it might be too much of a barrier.
But as it turns out, there have been some Some successful attempts to do uterine transplants in women.
It's very new.
It's mostly unsuccessful.
It requires a lot of other systems to be functional.
Wait, wait.
Question.
Yes?
A question you may not know the answer to, but successful uterine transplants, does that mean That transplanted uteruses, I don't know that that's how you pluralize that, but let's just say it is.
Probably uteri, but I don't know.
I would think it would be uteri, but neither you nor I know if it's uteri.
No, no we don't.
No we don't.
Is there at least one case, I will be surprised if there is, in which a transplanted uterus without surgical intervention resulted in a healthy vaginal birth of a child?
What do you mean by surgical intervention?
Because obviously the entire thing is rather surgical.
Right, but I will be less impressed if a cesarean section is necessary to birth.
That seems much more likely.
Let me read to you a bit from this paper called The History Behind Successful Uterine Transplantation in Humans.
Okay.
Published in an article called, I don't know what JBRA stands for here, but Assisted Reproduction in 2017.
You can show my screen here.
By a bunch of researchers in Mexico and Europe.
Excuse me, from the abstract.
Twenty-five UTX, uterine transplant procedures, have been performed in humans.
This is as of publication in 2017.
The first two cases were unsuccessful, but established the need for rigorous research to improve success rates.
As a result of a controlled clinical study under a strictly designed research protocol, nine subsequent uterine transplant procedures have resulted in six healthy live births, the first of them in 2014.
Further, failed uterine transplant procedures have been performed in China, Czech Republic, Brazil, Germany, and the United States, most of which used living donors.
Albeit still an experimental procedure, uterine transplant is the first potential alternative for the treatment of absolute uterine factor infertility, which is to say just not having them mostly.
Okay, so let me read just a little bit from the introduction.
The clinical field of tissue transplantation now includes uterine transplants.
It has its peculiarities, however.
It is a transitory procedure that does not necessarily save a life in danger, which we normally think of with regard to transplants, right?
But instead improves quality of life and offers women anatomically or functionally unable to bear children the possibility of becoming mothers and giving birth to healthy infants.
Hysterectomy is indicated after parity mainly to avoid the risks secondary to long-term immunosuppression.
That is critical, right?
Okay, so I'm shocked that this works at all and ever.
There have apparently been some successes, and I assume it's C-section, but I don't remember.
I didn't look carefully, right?
But it's not permanent.
You don't get a uterus and then live with that uterus for your entire life.
The point is to be able to bring a baby to term in your own body and to avoid things like donors and surrogacy, which have a whole other set of ethical problems associated with them, right?
And psychological problems.
But then, after a successful birth, the idea is to have that uterus removed so that you don't have to continue to be on immunosuppressive drugs and such.
And so, just one more thing from the introduction.
This is just the same thing.
Once parity has been achieved, that is to say, once a birth has successfully happened from a gestation that occurred in that uterus, the uterus is surgically removed to allow the suspension of immunosuppressants, thus minimizing long-term side effects.
This is so fascinating.
Yeah.
Can I just have my screen back?
Go on.
A couple of things.
One, very interesting tie-in with Peter Medawar, because it is the rejection of even a well-matched uterus, which causes the leaving of the newly installed uterus in place, too costly to contemplate.
Nowhere in this so far have I heard anybody, so if you put in a uterus and you have to use immunosuppressive drugs to reduce the likelihood of graft rejection, The baby is going to live in that uterus until... In the body of a woman who is taking immunosuppressant drugs.
Right.
What is the effect of that?
That is an obvious question.
Absolutely.
And I think just to put this in proper context, this is another case where the terminology Leads you to the wrong model.
Just as we have vaccines that aren't vaccines.
Yes, they look a lot like vaccines, they're administered like a vaccine, but actually they turn your cells into a vaccine in the case of an mRNA so-called vaccine.
Here you've got a transplant.
That is the temporary placement of a uterus inside of the body so that a person can experience some of the normal processes that go along with pregnancy, but that uterus is then going to be taken out after the pregnancy is over.
It is the temporary placement of a uterus into Into a woman which is not a transplant.
I've never heard of a transplant before that's temporary Maybe there are examples, but I would argue that that's that actually deserves a different term that's a that's a temporary thing and There is a question.
I mean look I certainly have sympathy for a woman who can't give birth because of a compromised or absent uterus on the other hand there is a question about something do you really in order to have the natural experience of pregnancy rather than for example adopting a child This is a very highly medicalized and unnatural process.
It sure is.
I wish I knew the answer to your question, but I assume that it's just going to be C-sections.
Now that I've heard what I've heard, I will bet dollars to donuts.
There are a lot of C-section babies out there, and cesarean sections have saved the lives of countless mothers and babies.
But it's not as good as vaginal birth, it's just not.
It doesn't impart the same information, largely immune, that vaginal birth does.
And that's just one of the things that we can see that is going to be difficult here.
And of course, all of this assumes that everything else about the woman, the mother-to-be into whom the uterus is being transplanted, is functional, and that she has all of the other systems that are necessary, right?
So just one more...
Brief thing from the discussion section of this paper 2017 on the status of uterine transplants in humans.
Uterine transplantation is a temporary process in which the recipient undergoes a process of adapting to a received uterus, followed by treatments to achieve pregnancy through IVF, Which ultimately bring a child into the world in the shortest time possible to allow the removal of the uterus.
The recipient has to go through a process that brings with it a new phase of understanding pain over the loss and readaptation.
So there's an additional, you know, much as women who have had hysterectomies Often, and I've spoken to some, I know some, have experienced great loss, even those who felt that they were already beyond their childbearing years.
Giving up some part of your body, especially if it is associated with a particular way of being that you know has contributed to how you are in the world, can provide a significant kind of loss.
And if you have been able to receive an organ that you have then gestated a child in, and that child is now in the world and is going to be your child forever.
And then you have to give up the organ that allowed it, that is going to take, as they say, a new phase of understanding, pain over the loss and re-adaptation.
So all sorts of unintended consequences as a result of this technology, right?
So on the same topic, it seems very, I mean, humans are unique in the sense of having, or almost unique in the sense of having menopause, where you have these organs which are sidelined after some where you have these organs which are sidelined after some stage of life.
Because humans are almost unique in having this, and it's really a couple of other creatures in which they're candidates.
I think elephants and orcas.
But the idea that this tissue remains there, inert, is not resorbed.
Likely that tissue is still doing things and the question of what its endocrinological impact is and therefore what the loss of it is and what impacts that has are significant.
Now a person who doesn't have a uterus or had to have it removed because of a pathology would be in that circumstance anyway, but One does have to ask the question.
Let's say that you temporarily... I'm using the term... Maybe I should not use the term install.
You implant a uterus in a woman who doesn't have one.
She is then presumably... Egg is then implanted.
A fertilized egg is implanted, an embryo.
I don't know.
is implanted, the pregnancy proceeds, a cesarean section happens, the uterus is removed.
My guess is that this is not going to trigger normal lactation either.
That would be my guess.
And that that's one...
I don't know.
I'm not certain of that.
Okay.
Yeah, there's so many, of course, just to think endocrinologically, which is not all of it, but there's so many hormonal triggers and associations with pregnancy and just the things I'm thinking of at but there's so many hormonal triggers and associations with pregnancy and just the things I'm thinking of at the moment, other than the estrogens and progesterone, but prolactin and oxytocin and, gosh, others, luteinizing
I don't...
The...
I also don't know anything about what prompts birth.
Do uterine contractions prompt a c-section here?
One of the reasons I think that c-sections aren't as beneficial to babies as vaginal birth is that what leads up to vaginal birth is the body preparing to have a baby that needs to be fed outside of the body as opposed to inside the body.
And so there is a certain, you know, the letdown of milk and, you know, all of these things that happen are triggered from inside the body.
And, you know, a C-section, just like as also like a scheduled vaginal delivery, won't tend to be, the body will not tend to be as prepared as it would be if the body was in charge, as opposed to a doctor.
Yeah, I agree with that.
I predict that this doesn't result in normal lactation.
There's also a question about the things like antibiotics and other compounds that will be used to make these two surgeries that are, you know, book-ending pregnancy.
To make that work, there's a question about whether or not that stuff ends up in the breast milk, if there even is breast milk.
So again, my overall impression is I have lots of sympathy for women who find themselves reproductively incapable for whatever reason, but that this sounds like, yes, there are people who are so desperate to have gone through pregnancy
That they will do virtually anything and so the demand here is very high that does not make this wise and it this is so Highly technological and medical that the idea that it is done so that you can have the natural experience of pregnancy How natural is that?
Okay There's more Okay How about uterine transplants for trans women?
I was afraid you were headed there.
First definitions.
I increasingly do not like the term trans woman and trans man.
Because while it seemed a kindness and a kind of respect, it of course has been weaponized.
And now you have all sorts of people saying, it's just type of woman, just type of woman.
Well, no, no, it's not.
So I just Googled, duck, duck, goad, trans woman definition, just to see.
Yeah.
And so what I have, just from the American Heritage Dictionary, Is trans woman noun one a transgender person who lives as a woman?
I would say a transgender man who lives as a woman, but okay.
Our second definition, a male to female transgender or transsexual person.
Okay, good.
Wikipedia, however.
I remember Wikipedia.
Yes.
Wikipedia, a trans woman is a woman who was assigned male at birth.
Trans women have a female gender identity and may experience gender dysphoria.
Gender dysphoria may be treated with gender affirming care.
Gender affirming care may include social and medical transition.
Do you remember when Wikipedia was good?
Oh, man, that was great.
So that's insane.
Wikipedia is wrong.
That's not what a trans woman is.
But that's what we are being led to believe, and that's what something like half the country is at least pretending to believe when they say trans women.
Okay, so that is what I mean now when I am saying, what about uterine transplants for trans women?
That's men who are living as women.
Should they be allowed to get uterine transplants?
Yes, you have a comment?
Well, no is the answer.
And no is the answer because children have to be primary in all of this.
And there is no way that the brave new world represented by... I mean, effectively, you are transplanting a
uterus you are using a trans woman that is a man living as a woman you are using that person's blood to keep alive a uterus from somebody else that The thing is so, there's nothing natural about this.
Okay, well, the American Medical Association's Journal of Ethics feels differently.
The American Medical Association.
Yeah, here we go.
Yeah.
June 2023.
Hey, the same, yeah, the same month, The New England Journal of Medicine published that important research, albeit untethered to any theoretical considerations that we talked about in the first half of today's episode.
Here it is, the AMA, American Medical Association's Journal of Ethics, in June 2023, published what it identifies right up front as a peer-reviewed article called, Should Uterus Transplantation for Trans Women and Trans Men Be Subsidized?
Here we go.
From the introduction.
Costs of uterus transplantation.
Gestation of a child following uterus transplantation in cisgender women with absolute uterine infertility factor has proved successful in the United States.
The reference that they give there, incidentally, is the paper that I was just reading from.
So that is a weak version of successful, but let's take that at face value for the moment.
Given the success of uterine transplantation that relies on both living and deceased donors, not at the same time, they're talking about different situations, but okay, interest in the procedure is likely to extend beyond cisgender women.
Among those likely to be interested in uterine transplants are trans women who want to gestate their own children, trans women who want uterus transplants to consolidate their identities but not to gestate children, Some trans men who want to gestate their own children, and cis men wanting to gestate children of their own.
I will continue, so that you can have time to respond.
And this was published... Two months ago.
In June, not April.
All right, yeah.
With regard to trans women who want to gestate children, Even though there has been no uterus transplant to date in trans women that we know of, some clinicians have maintained that there are no absolute barriers in anatomy, hormones, and obstetric considerations that would rule out the possibility of successful uterine transplant in trans women.
Trans women wanting to gestate children can plausibly justify subsidy of uterine transplants on a number of grounds, as mentioned above.
Trans women lack a trait, the ability to bear children, that may cause them to experience psychological dissonance in a way that undermines their health and well-being.
The lack of uterus also closes off the prospect of gestating a child in a way that is available to women as a class.
It follows that lack of uterus is an obstacle to full participation in the social goods attached to women's identity.
So too is the fact that you're not a woman.
That's going to get in the way of participating in womanhood.
It just is.
I'm going to read that one sentence that struck me a lot and then I'm going to go on a little bit and then... Trans women lack a trait, the ability to bear children, that may cause them to experience psychological dissonance in a way that undermines their health and well-being.
And the next sentence is particularly nasty too.
The lack of a uterus also closes off the prospect of gestating a child in a way that is available to women as a class.
So one thing that emerges from this, one of many things that emerges from this, is that people need to stop looking to medical intervention to solve their socio-psychological problems.
You should get a grip.
Like, seriously, get a grip.
Go outside, do something real, learn a skill, eat real food, move your body, anything.
Get a grip, not a uterus.
This is insane!
Okay, trans women who want to consolidate identity.
So this is an article in the American Medical Association's Journal of Ethics on why insurance companies should consider paying for uterine transplants in all sorts of people who aren't actually women.
Including cis men who are women, but the re- well, we'll get there, but oh my god.
Okay.
Trans women who want to consolidate identity.
Some, but not all, of this rationale also applies to trans women who want uterine transplants not to have a child, but to consolidate their identity.
They may experience dissonance at not having a uterus, but in this case, uterine transplant is not sought to remedy lack of access to the goods, the goods, of gestation and childbearing.
I will remind the viewers and the listeners, that this is inherently a temporary process.
It is removed after parity is achieved, after birth happens, because it's not a long-term sustainable solution to anything because of the immunosuppressive drugs that you have to be on as a result of having someone else's uterus in your body.
I would point out that there are two other issues here.
Oh, there are so many other issues.
Okay.
Now, before we get to the trans men, yes, go on.
Well, I just want to, I just want to point out these uteri.
Sure.
Come from somewhere.
They are either going to come from actual women.
And of course, this is a document about the ethics of this process.
And so.
Some of them are coming from trans men who have decided they don't need their uteri.
In fact, they have to get rid of it in order to fully realize their whatever they said.
Yeah.
Yeah.
OK, well, let's put it this way.
But it's also there's also cadaver donors.
Well, cadaver donors.
But it sounded like from the first paper that you read that that was not as likely to function.
Um, the cases, um, there have been successful cases, um, from, not cadaver, from the two successful cases that I can think of that I know in my head were actually living mother to daughter.
Yeah.
And I think another one was another family member for immunosuppressed reasons.
But in the case of a so-called trans woman, Are we going to get into a situation where women are going to be paid to surrender their uteruses, and therefore if uteruses are important to being a woman, some woman is giving up some amount of woman-ness in order for some guy to pretend to be a woman?
Yeah, you thought surrogacy was bad.
Right.
This is next level insane.
Then we're going to get into, okay, suppose That these are going to be cadaver uteruses.
Can you become a donor that forbids the installing of your uterus into a trans woman?
It's transphobic, right?
Exactly.
And so the point is then there's going to be some legal question about whether or not you are allowed to be specific about to whom your organs go and presumably you can't.
And so this is going to cause organ donation to dry up.
Yep.
I mean, sure, the whole thing is so bonkers and over.
It's not like, you know, it masquerades as a magic wand that's going to allow you to experience this sacred piece of being a woman.
And the point is, no, this is so heavily medicalized that there's nothing natural about it.
Except that it even works for real women.
Right.
Exactly.
OK, one more bit from this paper.
With regard to who, besides women, might be eligible for uterine transplants.
Trans men who want to gestate children after gender-affirming surgery.
So before I read the rest of this, let me just unpack that.
Yeah, please do, because I'm working.
I can't get it.
This is women who've decided they're actually men and who have had so-called bottom surgery that removes their functional female reproductive parts and maybe installs some totally non-functional male parts out of the skin on their arm, whatever.
Having thought about it more, decided that yeah, they still apparently, by this language, do believe themselves to be men, that is trans men, but they also want to gestate a child, because that's what men do.
Trans men who want to gestate children after gender-affirming surgery.
This is not detransitioners.
Right.
This is trans men who want to gestate children after gender-affirming surgery.
Trans men start life with female-typical bodies, but modify their bodies to align with male-typical traits to varying degrees.
Some trans men have children prior to any body modifications that interfere with gestation.
Others do not, and have their uterus removed to conform their bodies to a certain gender ideal.
Some trans men have transitioned in gender but retained their uterus and gestated children.
This precedent triggered interest in uterine transplants among trans men, especially if they did not retain their uterus or store gametes prior to their transition.
What is the word especially doing there?
What is any of this doing here?
Yeah.
Um...
This is so beyond simultaneously narcissistic at the individual level and apocalyptic at the societal level.
It is apocalyptic narcissism.
May I have my screen back for a second?
It's even worse than that.
Whoa.
Yeah.
Do you have comments before I go to even worse than that?
Yeah, there's something about this that I increasingly regard transhumanism as a kind of techno-utopian mental disorder.
Yep, 100%.
And the point is, one of the principles of maturation, one of the things that you are supposed to pick up as you become a human being, I mean, let's face it, you are getting used to all sorts of craziness to be a human being.
Yes, you are a fish who has taken to land and your ancestors spent a lot of time as primates swinging through the trees.
Right, so you have this weird set of baggage and then okay You're a person and you're a person and you can use language to convey things or to manipulate or you have all of the things that language does part of becoming a person is Reconciling yourself to what you are and playing the hand you've been dealt if you don't like that hand you can work to better yourself to upgrade it but the idea of
Of dragging medicine into tailoring you or tailoring you enough that at a cocktail party you can claim to be something and there is some medical justification for using the terms you're using.
It's nonsense.
How much happier are people who do this actually going to be?
Of course plastic surgery is the same thing, right?
Bigger boobs, tighter jawline, skin light.
I mean, Michael Jackson was, you know, was doing this constantly as well in, you know, in a different domain.
And, okay, you look like your version of a more perfect ideal.
And now what?
Like, now you know that you couldn't get there on your own?
Like, to what end?
Right.
To what end?
And the fact is, if you... Look, we have a world that's badly structured.
Developmentally, it's a mess.
And it causes lots and lots of people to be deeply dissatisfied, which is not their fault.
That is the fault of us having structured the world that they were born into badly.
And we should fix it.
If you are such a person, you are born into this crazy world and development leaves you totally unsatisfied with what you are so you want a total redo, what are the chances that the redo that you get the medical establishment to provide you for money is actually going to satisfy you?
What is the chances that the problem isn't that you are constitutionally unsatisfied and unsatisfiable and that you're going to be as unsatisfied with the thing you land as, as the thing you started off as?
The chances are extremely high.
So why is modern medicine pretending that that's not even a question?
Oh, you think you'll be happier when you have X?
How many myths do we have in which people do we not have a proverb?
Be careful what you wish for.
Right?
People used to know that you needed to be careful what you wished for because you might not be as happy with it if you got it as you think you will be.
Grass is always greener.
The grass is always greener, that whole thing.
And so somebody at the very least needs to study this madness and discover whether or not it results in satisfied people or people who Get to these places compromised in themselves and still feel about as they did, which that's the cruel trick that's being played on kids.
Kids are being told, hey, that thing that you desperately want, you can have it.
And then, of course, the kid is going to learn after they've lost their reproductive capacity.
Their ability to have a proper sex life They're gonna discover.
Oh, that was a lie told to you by adults who should have known better, but there was money at stake Yeah, it didn't know better usually Okay, so you know how, luckily we have never been in these fields, but you know how a lot of professional fields require for you to stay in good standing that you get continuing education credits?
So if you go back and look at this paper that I've just been reading from the American Medical Association Journal of Ethics, Right below the abstract, it says the American Medical Association designates this journal-based CME activity for a maximum of one AMA PRA Category 1 credit available through AMA EdHub.
Physicians should claim only the credit commensurate with the extent of their participation in the activity.
I looked at that and went, that's a lot of acronyms I don't recognize.
But I suspect, and it turns out I was right, that what that's referring to is the American Medical Association's PRA credit system, which demonstrates a physician has participated in continuing medical education activities that meet the requirements of state medical boards, medical specialty societies, specialty boards, hospital, medical staffs, the joint commission, insurance groups, and others.
And there is a quiz that you can take based on this article that I've just been reading to you, and if you pass, you get some continuing medical credits from the AMA.
Now, I took this quiz and I passed it, but I'm going to show you the first of five, and you only have to get four of these questions right.
The first of five questions in this quiz.
Just to demonstrate what it is that you need to stay in good standing with, for instance, your state medical board, your medical specialty society, your specialty boards, your hospital medical staffs, your insurance companies, etc.
Okay?
Hand me my screen for a second so I can find it here, Zach.
I told you it was even worse than that.
Okay, hold on, let me find this.
Okay, so yeah, here we are.
You can show this is the continuing medical education version of this article.
They have, in case the article was just too complex for you, they've supplied an outline and then you can actually take the quiz.
And you know they have author affiliations over here and again the title of the article that you can demonstrate your complete knowledge of in order to get continuing medical education credits through the AMA is Should Uterus Transplantation for Trans Women and Trans Men be Subsidized?
The first question of five on the quiz is... Which of the following is true about uterus transplantation in trans women?
A. Anatomy serves as a barrier to doing so.
B. Hormones make uterus transplantation in trans women impossible.
C. Obstetric considerations have produced poor results.
D. No uterus transplant has been performed in a trans woman.
Obviously, at least one correct answer to this question is A. Anatomy serves as a barrier to doing so.
I, however, long skilled in taking tests and gaming such systems, knew exactly what they were looking for, because it is also true that D, no uterus transplant has been performed in a trans woman.
And that is, of course, the only correct answer that they will accept for this quiz.
Which you would be very well aware of if you had read the outline, considerably provided by the AMA, in order for you to gain, as a physician, your continuing medical education credits.
And one more time, my screen, if I might, I just want to show off that I did indeed pass.
Here we go.
You can show this.
This certifies that I successfully completed this journal-based continuing medical education activity.
Should uterus transplantation for trans women and trans men be subsidized?
If I had a state medical board or insurance company or anything that I needed to report my continuing medical education credits to, I could use this to demonstrate that I am in full current standing and I have been keeping up on my medical education and I really know what's going on now.
So you can trust me, patients, with everything you need because I have passed this quiz.
Well, you weren't kidding about it's worse than that.
That is unbelievable.
I mean, it is obviously a medical version of the social credit score method for controlling behavior.
I can't even figure out how you phrase The obvious indoctrination of doctors so that they are on board with things that are clearly a violation of the Hippocratic Oath and almost certainly in practice Nuremberg To be fair, why should we?
But to be fair, I don't know how many ways that you can earn your continuing medical education credits.
- Sure. - So like there's, I do not suspect that most doctors are being funneled through this particular thing, but it doesn't matter.
It doesn't make any difference.
What they are doing is they are causing a belief system that is radical and highly suspect to become commonplace by teaching it as if it were factual and then testing you on it for a credit that you need.
In which you have to answer the wrong way in order to pass.
You have to deny, what was the question again?
You have to deny that anatomy serves as a barrier to uterus transplantation for men who happen to think they're women.
Right.
You have to not notice that that is an obviously correct answer.
And how many times do you say lies before you start to believe them?
Well, that's just the thing.
Here is at least one of the punchlines of it's worse than that in this case.
Yeah.
How did we get to a place where virtually the entirety of modern medicine, the medical schools, the hospitals, the doctors, the nurses, were all saying false things about the safety and effectiveness of treatments?
Well, this is the system they live in.
And that system, in that system, this is not going to strike people as wildly beyond the pale.
This is somehow Normal.
Yep.
And it creates... Why are we so obsessed with this?
Why do we care?
Why do we care so much?
This is also of a piece with, when we covered McNeil and Fenton's Yeah, the cheap trick in which efficacy was simulated through a mathematical, a statistical artifact.
COVID vaccine efficacy was simulated through an experimental design artifact.
Paper after paper that had been peer-reviewed and nobody caught it and our point was actually peer-reviewed clearly doesn't exist because if it didn't catch this then it couldn't have caught anything.
What's it catching?
Right, so the point is, okay, that's the academic side.
This is the medical side.
You have pure medical nonsense being taught and then tested as if it were factually insightful and a required bit of knowledge in order to practice.
This is madness.
Yes it is.
You absolutely do not want a doctor, the only doctor who passed that test that you want is one who knew they were lying in order to pass it, who knew they were gaming the system.
Any doctor who thought that they were actually participating in continuing education and responded correctly is not a doctor that you want dealing with your medical issues.
That's right.
So that's the world we're living in.
And what it means is you want, the only things that make any sense are going to be off-label.
You want the things that were reviewed by peers in a bar, gave you a hard time about stuff in your study, and got you to fix it in a bar.
You don't want it peer-reviewed at some journal that believes nonsense.
That's not going to work.
It's going to be counterproductive.
You don't want doctors who went through continuing education in silliness like this.
You want doctors who... Who care enough about it to... I mean, I think the bar thing is actually important here.
It doesn't need to be a bar, but you want people who care deeply enough about the scientific process and about medicine and about what it is that they've chosen to dedicate their lives to, that they continue to talk about it when they're not literally being paid to do so.
This is in their minds.
Are you a scientist after 5pm?
Well, yes.
Those of us who think this way, it is a way of being.
It is not something that stops at the office door and the paycheck.
And, you know, I think peer review has become, just like these continuing medical education credits, just like, well, I just got to tick the box, tick the box.
Okay, what do I have to do today?
I'm going to pick up milk at the grocery store.
I got to get my CMEs.
Like, it's meaningless.
And it's just one more thing in a list of meaningless events that everyone is doing.
And like, to the degree that some number of doctors had real passion and compassion when they began their work, this will kill it.
This will destroy it.
It will destroy it.
I'm reminded, I can't remember the name of the guy, but there was a registered nurse during early in COVID who was reporting that patients that he was in charge of, He knew very well that the treatment they were being given required that they be gotten up and out of bed and walked around because they were going to drown in their own fluids if they were left sitting and they were forbidden to do it.
And I remember him saying, I cannot participate in this anymore.
I cannot be in charge of these patients where I know the right thing to do for them, and I'm not allowed to do it.
And I have to watch them die.
And he quit.
And I think the point is, okay, what world does that leave us?
Where the people who didn't quit are the last people you would want in charge of your care, but it's all you're going to have available to you.
And there has to be some sort of, you know, you now have, I guess we're the off-label scientists.
Oh yeah.
You know, we'll review papers right here on Dark Horse, right?
Is that peer review?
Well, I don't know.
If you're up to it, I guess it is.
But, you know, you don't want something that's been reviewed by people who didn't spot the cheap trick, right?
Those people are not qualified.
Whatever their degree says, and doctors who Pass a test like this and didn't know that they were lying in order to pass it, aren't doctors that you want in charge of your health?
It's just insane.
Nope.
That's all true.
That's all true.
So, sorry to have blown your mind like that.
Yeah, you know, it did actually throw me, because you think you know how ridiculous things get, and the fact is, okay, uterine transplants, if you think about it, of course, should such a thing be medically possible, then of course it will be dragged into this trans madness.
But the idea of the AMA, this isn't some fringe practice, this is the AMA signing onto it wholesale.
And then creating quizzes and continuing medical education as a way to what?
Fund themselves as a way to justify their continued existence.
Yeah.
So you did succeed in putting me back on my heels where I thought I was pretty well versed in this space.
I did not see the AMA leading the charge here.
Yeah.
Well, there it is.
More than halfway through 2023.
Who knows what comes next?
Or whether we get to the end of 2023.
I hope so.
I hope we do.
I hope we do.
I think that about does it.
That about does it.
All right.
I think that about does it, but we will be back.
So we are going to spend a couple minutes telling you about places to find us and things to look for and such, but we will be back about 15 minutes after we stop with our live Q&A, where you can ask questions at darkhorsesubmissions.com.
And let's see, we've got lots of things to talk about.
Please subscribe to the channel on Rumble, and please consider joining us at Locals.
So at Locals, you get the watch parties with our live streams.
You get all the guest episodes, and Brett's doing a lot of them now.
They're two, three, four a month at this point.
And when they are released, they're released on Locals a day before they're released anywhere else to our Locals community only on Saturdays and then a day later.
Our Local supporters, thank you Zach, our Local supporters on Saturday and then a day later to Rumble and Spotify and YouTube and everywhere else.
And we also, this month, are going to start doing our private Q&A instead of at my Patreon.
We're going to be doing that for our supporters on Locals.
And the Discord integration is going to be up and running before the end of the month, hopefully.
Maybe.
Okay.
Oh, we're working on that.
Let's see.
Oh, at Natural Selections this week, I wrote about a near-miss that I had with a truck.
I was on my bicycle.
It was a pickup truck and I wrote about rules of the road and what it is to be an experienced bicyclist on the road, sharing the road with drivers, most of whom haven't spent time on bikes, but also talked about theory of mind and And a bit about, I didn't specify this in the piece, but you and I went back to that same place later that day.
We were driving into town and I asked you to drive us back through that from the opposite direction.
And we went a couple of times because it struck me that In this place where I had been following all of the rules and because I am a skilled bicyclist, I did not get flattened by a truck that turned in front of me, as it should not have.
Coming up from the other direction in a truck, as we were, I saw that the visibility was not as good as I had thought it was.
And so I too did not have as complete a model of the theory of mind of the driver there as I should have.
Not, you know, again, She was in the wrong, and I was not, but who's in the wrong, who's in the right isn't a complete description of how it is that you have to be maneuvering around spaces, right?
You also have to really, really try to put yourself in the head of other people, and not just what they know, which is where I spent a lot of the piece.
Like, okay, most drivers don't know how to bike.
They don't never bike with, you know, they've never biked on roads, really.
But even more important, and really more human and more basic, is what can they see?
Like, what can they actually see?
What do they know about the spirit of the environment that is different from what you see?
And as anyone who's ever hiked knows, especially if you've gone to the backcountry and you've known that you need to sort of keep checking back so that you know what things look like in both directions, you can be in a particular spot looking this way and things look totally different if you just turn 180 degrees.
Right, and so the same is true when you're in traffic.
So check that out.
That's Rules of the Road at Natural Selections this week.
We've got stuff at the store.
We're going to have some new stuff at the store soon.
You just proposed a new piece of merchandise.
But we've got Dark Horse merch, PsyOp Until Proven Otherwise, Epic Tabby, lots of good stuff there.
We've got the book.
We've still got our Patreons.
You've got these fantastic monthly meetings that you're running on yours.
Yeah, and the Discord server, which is currently at our Patreons, we're going to be moving it into the Discord, into locals as soon as we can.
Lots of great conversation there, so we encourage you to join us there as well.
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Check them out.
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Please subscribe, share, like, and talk with people about what you're hearing here, and about where you too can pick up your Continuing Medical Education credits if you need them.
It's easy.
It's not hard at all.
You can do that without any effort at all.
Continuing medical indoctrination credit.
Yeah, they don't put that I in there, but it belongs in there.
Yeah.
Okay, so again, we'll be back in in a bit with a Q&A and then of course we'll be back next week, same time, Wednesdays at 1130 Pacific with another live stream.
Until we see you next, be good to the ones you love, eat good food, and get outside.
