Links #25
New drugs and ending heart disease, population peaking sooner than we thought, and more.
1.
Lots of recent, promising results on therapies for cardiovascular disease (CVD):
Verve therapeutics has promising initial results from a gene therapy trial to permanently lower LDL-C.
Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk
Oral Muvalaplin for Lowering of Lipoprotein(a): A Randomized Clinical Trial
An Oral PCSK9 Inhibitor for Treatment of Hypercholesterolemia: The PURSUIT Randomized Trial
Mentioned in links #23: Lepodisiran — A Long-Duration Small Interfering RNA Targeting Lipoprotein(a)
I also just finished Outlive by Peter Attia1 which convinced me that along with the breakthroughs above, we already have great medications for addressing heart disease.
What’s shocking is that every adult is already forming fatty plaques in their arteries. Our medical system waits decades until you have a full-blown heart condition before treating you with these drugs. But these drugs prevent the growth of plaques!
From page 131: “[a]s Peter Libby, one of the leading authorities on cardiovascular disease, and colleagues wrote in Nature Reviews in 2019, ‘Atherosclerosis probably would not occur [emphasis mine2] in the absence of LDL-C concentrations in excess of physiological needs (on the order of 10 to 20 mg/dl).’”
This is why we need to Reclassify the Statin, because early and aggressive prevention can eliminate the biggest killer in developed countries. To be sure, some heart disease comes from aging of the cardiovascular system. Solving that would require some sort of anti-aging intervention to rejuvenate or replace vascular tissue.
If we solve cardiovascular disease, dementia may fall as well. Attia discusses evidence that dementia is related to vascular problems and an energy deficit in the brain. There’s also tantalizing evidence that neural tissue will last as long as the body supporting it.
In a world without heart disease, cancer and systemic aging may be the last barriers to living indefinitely.
Related:
My favorite links on health
A newish CPR technique
Exciting case study of patient with Type-1 diabetes receiving stem cell therapy. Appears to have cured her diabetes. Caveats that we don’t know how repeatable or expensive this might end up being.
EDIT: If GLP-1 Drugs Are Good For Everything, Should We All Be on Them?. GLP-1 inhibitors cure even more stuff now.
2.
Simple low-dimensional computations explain variability in neuronal activity. Big if true. Suggests that simulating the brain may be simpler than we expect.
I also think there’s a substantial chance that information processing in the brain comes from aggregation of neural signals rather than individual neurons:
Beyond dimension reduction: Stable electric fields emerge from and allow representational drift
Cortical columns as A Fundamental Unit Of Intelligence. Neurons organizing into groups with consistent behavior coincides with the idea that the brain might be easy to simulate.
If individual neurons are easy to simulate and organize into larger functional units, scanning our brains may be easier than we thought. Validating this hypothesis will still require lots of detailed connectomics and neural simulation.
Related:
Logan Thrasher Collins has a great list of papers in neuroscience, connectomics, and nanotech.
3.
Important point before discussing demographic decline: demographic decline is a solvable problem, it does not justify draconian policies. Freedom comes first.
The Demographic Future of Humanity is an eye-opening presentation from Jesús Fernández-Villaverde. The UN population projections are wildly optimistic and at odds with their own data. Fernández-Villaverde believes population will peak in 2055 only slightly above the population today.
Looking at his numbers and the chart below from John Burn-Murdoch, it seems that the UN low fertility scenario is the best projection of our demographic destiny. Though we don’t really know where the fall in fertility will level out.
One interesting point from the presentation is that many countries have bad data collection; the UN is probably overstating their population. That means the true fertility rate is higher than we think. Consider also that cohort fertility suggests a smaller shortfall from replacement rates.
Among the other causes of fertility decline, Finishing education and fertility makes the case that couples wait until they finish their education to have kids. Rising educational requirements and attainment cause people to delay having kids. Starting a family in your 30’s makes it harder to reach the number of kids you want due to lower fertility at higher ages.
Everything else
36 questions that lead to love by Arthur Aron. Not really about “love” per se but good questions to ask anyone you want to know better.
Lewis signaling game is a neat way to model how language developed and how we might coordinate with minds different than our own.
The fruit fly of organizational decision-making
Could AI Save Us From Making Hard Choices About the Budget?. A dramatic productivity boost from AI reduces US debt plus service costs by about one third. Some countries see their debt problems worsen. Regardless, assuming a speculative technology will fix our debt seems like a bad choice. We have straightforward ways to address this today.
The Outsize Impact of AI Logistics
Scaling Collapse Reveals Universal Dynamics in Compute-Optimally Trained Neural Networks. “We show that despite the complex interactions between architecture, training algorithms, and data, compute-optimally trained models exhibit a remarkably precise universality. Specifically, loss curves from models of varying sizes collapse onto a single universal curve when training compute and loss are normalized to unity at the end of training.” We’re getting a better understanding of scaling and the thermodynamics of AI. If all approaches scale at a similar rate, that means data is the key bottleneck for AI.
MIT.nano Seminar Series: Chad Mirkin. Depositing arrays of nano droplets with dissolved metals and evaporating them can make arrays of nanoparticles with different compositions. Accelerates the search for new catalysts.
Primary investigation on Ram-Rotor Detonation Engine. A new type of rotating detonation engine that might make for more powerful rockets and planes.
The war in Ukraine has sparked a revolution in off-the-grid clean energy. Renewables and batteries aren’t only cheaper, they are more resilient and easier to replace.
Scapegoating the Algorithm a good review about how engagement, misinformation, and polarization actually works.
I highly recommend the chapters on heart disease and exercise
"mine” in this case being Attia’s emphasis.