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Crémieux Profile picture
@cremieuxrecueil
Jul 17 • 9 tweets • 4 min read • Read on X
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It's so good to see more gene therapies getting worked on.

This one is particularly amazing because it's effectively a one-shot, permanent Exenatide—making humans produce a version of the compound in Gila monster venom like lifelong Ozempic!

But is it safe?

Probably! Short🧵 Image
In the picture I posted above, you can see the effects of having variants that increase the effect of the gene GLP1R.

This was relevant when I was discussing compositional effects of GLP-1RAs. As you can see, bodyfat *percentage* declines with higher natural GLP-1R agonism.
I went ahead and checked the effects of the same SNPs and an extended set of SNPs on the effects of GLP1R on colorectal cancer risk.

It seemed to reduce it (pic is an excerpt from one of my subscriber-only posts). Image
But the thing here is exendin-4, which has a synthetic analog in the early GLP-1RA exenatide. It shows 53% sequence identity with human GLP-1, but with a glycine substitution and 9 extra amino acid residues on its C-terminus, for stability.

So it's not exactly what I targeted.
But it is highly similar, and the differences should not make it have many different phenotypic effects.

That said, exendin-4 has been associated in preclinical data with reduced incidence of various types of cancers. Image
Image
Image
As far as I can tell, exenatide has the same cancer risk profile as the newer, stronger GLP-1RAs like semaglutide and tirzepatide, it's just weaker.

So, it should come with a reduced risk of several obesity-associated cancers like GLP-1RAs in general seem to be. Image
It might also come with increased odds of survival for certain types of cancer. Image
Since this stuff should have the same safety profile as the drug itself, it's likely just as safe.

And that means, it's likely safe. But not only is it likely safe, it's likely effective and protective.

I'm reasonably certain that this gene therapy will deliver major benefits.
Sources:

ec.bioscientifica.com/view/journals/…

link.springer.com/article/10.100…

diabetesjournals.org/diabetes/artic…

jamanetwork.com/journals/jaman…

gynecologiconcology-online.net/article/S0090-…

Also: liebertpub.com/doi/10.1089/di…

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More from @cremieuxrecueil

Crémieux Profile picture
Jul 12
This is not true, but remember:

Premodern society was hyper-violent by modern standards.

Almost half the fighting-aged males in late Neolithic Europe showed skeletal evidence of violence and at least 10% died from it.

For comparison, the 2022 U.S. homicide rate was 7.5/100k. Image
This isn't even the most violent prehistoric society, it's one of the more peaceful ones known. Image
Communist states have killed a lot of people historically, but they had nothing on non-state societies.

I cannot recommend trying out any sort of statelessness, let alone communism.

Image
Read 4 tweets
Crémieux Profile picture
Jul 11
There is no reason to keep pit bull type dogs legal, but there is plenty of reason to ban them.

They are extremely disproportionately likely to bite and to kill. Keeping them around serves no purpose. Image
Pit bull owners are disproportionately likely to be mentally ill, to have criminal records, to be low-income and poorly-educated, etc.

But this doesn't explain the breed's issues. Even when they were not the premiere fighters, they dominated injury stats

It's also worth noting that, despite not being the most common type of dog in New York City, pit bulls still commit the largest share of the dog bites: Image
Read 4 tweets
Crémieux Profile picture
Jul 10
Though the policy is harmful, the overwhelming majority of Americans support capping rent increases.

Americans overwhelmingly support many bad policies🧵 Image
Americans strongly support raising the minimum wage considerably. Image
In earlier years, support for tariffs was higher.

Now it's still quite high, and if you ask the question in certain ways support goes up or down.

Ask about China and you get majority support. Image
Read 12 tweets
Crémieux Profile picture
Jul 9
The Atlantic was once a credible news outlet.

One of their best pieces came out 99 years ago, written by "A Woman Resident in Russia".

It describes the chaos that followed the Communists destroying the institution of marriage.

Let's read about the Soviets ruining marriage🧵Image
"To clear the family out of the accumulated dust of the ages we had to give it a good shakeup, and we did."

Russia boasted it had no illegitimate children. True. They eliminated the "illegitimate" category. Image
"Men took to changing wives" and 300,000 abandoned children resulted. Image
Read 18 tweets
Crémieux Profile picture
Jul 2
I've seen people mentioning that Europe's heat-related death issue is larger than American gun violence—true!

But people neglect saying how many heat-related deaths America has.

Approximately 1% of what Europe does even though America is hotter and Americans are less healthy! Image
Those factors mean Americans are more at-risk for heat-related deaths, even after accounting for Europe being a little older than America.

So let's be clear:

Europeans die from heat at relatively high rates; Americans survive it with technology. Image
Image
What technology?

It's the terraforming technology of air conditioning.

Install A/C and the heat-related deaths will mostly disappear, if Europe can keep their grid operational. Image
Read 7 tweets
Crémieux Profile picture
Jul 2
What happens when scholars get canceled?

They end up publishing fewer papers and they receive fewer citations.

In other words, scientific productivity falls🧵 Image
Tons of scholars have been cancelled in recent years.

That is, they've received professional backlash for expressing views that people deem "controversial, unpopular, or misaligned with prevailing norms." Image
Cancellations happen outside of academia, but it's very bad in it.

Large portions of the academy dislike the freedom of speech. Many of those free speech opponents have high agency and the clout to cause material harm to people they dislike = particularly bad cancel culture. Image
Read 13 tweets

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