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Hi friends 👋,

Happy Friday and welcome back to our 101st Weekly Dose of Optimism.

We hope you had a lovely Fourth of July and are keeping the patriotic vibes up heading into the weekend. Coming out of what was an admittedly pretty demoralizing presidential debate last week, it’s been fun to watch folks rally around what makes this country so special in the first place over the last week. The general mood I’ve picked up has been “Yeah, politically this is a shit show but America is absolutely humming right now — the economy, entrepreneurism, culture — so let’s celebrate that.” At least that’s been my little corner of the internet during this holiday week.

Let’s get to it.

(1) Approval of Newest Alzheimer’s Drug Will Accelerate New Era of Treatment

Peter Loftus for The Wall Street Journal

With the arrival of Lilly’s Kisunla, Alzheimer’s care could become more like treatment of cancer and rheumatoid arthritis and their regular infusions.

Eli Lilly’s is world’s largest drugmaker by market value, and it is using that heft to bring to market a newly FDA-approved Alzheimer’s drugs. The drug, Kisunla, is not an Alzheimer’s cure, but it has been proven to moderately slow cognitive decline, and could lead to patients living independently for longer periods of time.

Kisunla is not the first Alzheimer’s drug to hit the market in recent times. Biogen’s Leqembi became commercially available last year, but has been off to a slow start with only a few thousand patients having started treatment so far. Biogen was slow to work the drug into health system procedures and the drug has relatively low awareness.

This is where Eli Lilly comes in. The company has a market cap 26x that of Biogen. It has the resources to build awareness and work its Alzheimer’s drug into the healthcare system, in a way that Biogen simply can’t at this point. That’s good news for the six million American’s that currently suffer from Alzheimer’s disease, and even better news for the ~one million of those folks that could benefit from a drug like Kisunla today.

(2) Continuous neural control of a bionic limb restores biomimetic gait after amputation

Song et al in Nature

In a cohort of seven leg amputees, the interface is shown to augment residual muscle afferents by 18% of biologically intact values. Compared with a matched amputee cohort without the afferent augmentation, the maximum neuroprosthetic walking speed is increased by 41%, enabling equivalent peak speeds to persons without leg amputation. Our results suggest that even a small augmentation of residual muscle afferents restores biomimetic gait under continuous neuromodulation in individuals with leg amputation.

This new research is certainly a step in the direct direction for amputees.

A team of MIT researchers have developed a bionic leg controlled by the brain and spinal cord, which enables amputees to walk nearly as fast as non-amputees. The device uses a small computer to boost signals from the remaining muscles in the amputated leg, letting the user control the bionic leg with their thoughts and natural muscle movements. This makes the prosthesis move more like a real limb.

In clinical trials, participants with this technology walked 41% faster than those with standard robotic legs and demonstrated better balance and mobility. Said another way, these guys would absolutely smoke Oscar Pistorius on the track (Yes, Oscar Pistorius is a terrible dude and yes, I have some Olympic fever right now.)

These bionic legs are currently in clinical trials, but should be made available for military and general population usage over the next few years.

(3) Perforation-type anchors inspired by skin ligament for robotic face covered with living skin

Kawai et al in Cell Reports Physical Science

In this study, we develop and characterize perforation-type anchors inspired by the structure of skin ligaments as a technique to effectively adhere skin equivalents to robotic surfaces. To showcase the versatility of perforation-type anchors in three-dimensional (3D) coverage applications, we cover a 3D facial mold with intricate surface structure with skin equivalent using perforation-type anchors. Furthermore, we construct a robotic face covered with dermis equivalent, capable of expressing smiles, with actuation through perforation-type anchors.

Will man become machine before machine becomes man?

A team of researchers from The University of Tokyo have developed a “skin-equivalent” that can anchor to a robotic surface, in a similar way to how skin attached to a human body. Essentially, they’ve given robots very human-like faces. And the early result is about as creepy as it sounds :)

As creepy as this first iteration might be, this is ultimately a good thing. Whether you like it or not, the world is going to be filled with humanoid robots over the next couple of years — in your factories, in your homes, in your restaurants, etc. And if they’re going to be performing human tasks and be displaying human mannerisms and manners, then I want to interact with them in a similar way to how I interact with humans. Faces go along way in making that possible.

Plus……well…never mind…

(4) The elemental foe

Noah Smith for Noahpinion

But our intelligence has given us an opportunity not afforded to other animals — the chance to conceive of our species as a single team, fighting not individually but as an army united against the implacable, elemental foe of poverty and desolation. It is our highest task to push that foe ever backward, to build out the fortress of industrial modernity, to reclaim the Earth for the safety and comfort of beings that think and feel. The Earth, and eventually, all the other places as well.

God, I freaking love that chart. Up there with my top 5 favorite charts.

Noah Smith used the chart in his recent essay to show just how long humans lived in abject poverty and just how recently we’ve been able to breakthrough in the fight against, what he describes as, the elemental foe.

Poverty, as Smith sees is, is the natural state of humanity. It’s all humans knew for the the first ~1800 years after Christ was born and for the hundreds of thousands of years before Christ was born. It is our natural state. Only in the last couple of hundreds years have we been able to start rising above poverty, thanks to industrial modernity. Industrial modernity is the result of industrial development and technological progress, and it has transformed societies with unprecedented economic growth and a result lifted billions of people out of abject poverty already.

Much of the fight against poverty has been waged in the last couple of decades, and if things are to continue on as projected, much of the remaining fight will be won in the coming decades. China’s industrialization lifted a billion people out of abject poverty towards the end of the 20th century and beginning of the 21st century. And India’s ongoing industrialization and modernization should lift another billion people out of poverty over the coming decades.

But that elemental foe is never out of the fight. Even rich societies are just a few hard blows away from spiraling back into it — a massive food shortage, or supply chain issue, or catastrophic event. So we must keep on fighting, keep on building industry, and keep on advancing technology. We’re fighting against the natural state of things, and that requires continuous effort and continuous growth.

(5) A molecular glue degrader of the WIZ transcription factor for fetal hemoglobin induction

Ting et al in Science

Sickle cell disease (SCD) is a prevalent, life-threatening condition attributable to a heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) can ameliorate disease complications and has been intently pursued. However, safe and effective small-molecule inducers of HbF remain elusive. We report the discovery of dWIZ-1 and dWIZ-2, molecular glue degraders of the WIZ transcription factor that robustly induce HbF in erythroblasts.

We may soon have a globally accesible, oral treatment for sickle cell diseases, thanks to the discovery of “WIZ degraders.” Sickle cell disease (SCD) is a genetic disorder that causes red blood cells to become misshapen and break down, leading to severe pain, anemia, and organ damage that affects millions of people worldwide. In the U.S., approximately 100,000 people — mostly Black people — suffer from the disease.

WIZ is a protein that normally helps regulate the production of fetal hemoglobin, but in this context, it acts as a blocker that prevents the production of fetal hemoglobin. By targeting and breaking down WIZ, researchers can increase fetal hemoglobin levels to help treat sickle cell disease. Targeted protein degraders, like dWIZ-1 and dWIZ-2 help modulate gene control factors by selectively breaking down specific proteins that regulate gene activity, allowing scientists to adjust gene expression levels.

Last year, the FDA approved Casgevy, a CRISPR-based therapy for sickle cell anemia, but this new approach would allow patients to simply take a pill. Given these molecular glue degraders were just discovered, we’re likely at least a few years out from commercialization as potential new therapeutics go through trials and approval phases, but the discovery is an important step in developing a universally effective and accessible treatment for SCD.

(Bonus) The American Millennium + Updating Views on Immigration

Early this week, Packy dropped The American Millennium. The basic premise of the essay is that America is in a much better place — economically, geopolitically, and relatively — than it’s perceived to be. The narrative does not match the reality. Despite the headlines and admittedly frustrating way that the country operates, America enjoys extreme strength and will continue to enjoy it over the coming generations. That’s because America’s still-vibrant entrepreneurial spirit is stronger than its bureaucratic drag.

Packy argued that America is the first Capitalist Empire, which is how it’s become as strong as it is and why it may be more resilient and enduring than the empires that came before it. The way America was set up means that it, and specifically its most enterprising citizens, can come up with solutions to whatever problems arise. Against the backdrop of the 4th of July and a bleak presidential debate, it’s worth the read.

Speaking of narrative not matching reality, Tyler Cowen recently argued that we need to update our views on immigration. In short, his view on immigration is that, despite increased public opposition and political backlash, the practical benefits of immigration remain positive, but some countries may need to adopt tougher policies to manage these political consequences.

Our family came here as immigrants from Ireland and Italy. No one wanted the Irish and Italians here. They stole jobs from Americans, committed crimes, drank too much, were generally unintelligent, and maybe worst of all, they were Catholic. Stores hung up “Irish need not apply” signs. Many Americans believed Irish and Italian immigrants wouldn’t be able to assimilate, that they wouldn’t adopt American customs or values. And here we are, a few generations later, as American as apple pie.

Today, despite all of the hoopla around immigration, the data actually supports modest positive wage effects, lower crime rates despite higher immigrant populations, positive fiscal contributions from immigrants, significant contributions to post-pandemic recovery, and evidence of assimilation among Latino voters.

Tyler writes, “So we shouldn’t talk down immigration per se. Instead we should try to combat excess negativism in many spheres of life.” Amen.

Change is always hard, but in my view, these two ideas hold true across the course of American history:

• Capitalism and democracy are good

• Immigration is never popular and usually long-term positive

Take it from the Gipper (h/t @pitdesi).

Have a great weekend y’all. Thanks to Eight Sleep for sponsoring!

We’ll be back in your inbox on Tuesday.

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Thanks for reading,

Packy + Dan