The Longevity Research Institute

A theme on this blog is “there isn’t enough good information.” Anti-aging research is worse than most topics at this, perhaps even worse than nutrition. There are several reasons for this: time/money requirements of research, the FDA’s focus on pathology rather than health, and science as a whole disincentives the kind of replication you need to truly trust a result. But there’s a new organization, the Longevity Research Institute, aiming to fill this gap. (Full disclosure: I’m on the board).

To run a longevity experiment, you have three choices: research something with a short life cycle (limited applicability to humans), research something with a long life cycle but track biomarkers instead of actual lifespan (risks goodharting the biomarker while not affecting or even hurting lifespan), or wait. Even a mouse experiment can take four years for your subjects to die. And the more successful your treatment, the longer (and thus more expensive) the experiment.

This would make lifespan-increasing treatments more expensive, but that’s hardly the end of the world. What could be more worth paying for than life? Unfortunately, the FDA takes another view. To get FDA approval, a drug must show effectiveness treating a specific disease, and aging is not considered a disease. This has been challenged recently, with the TAME trial, but has been a fact of life for a very long time and there’s no guarantee TAME will win the fight.

Finally, science in general is bad at replication. Repeated studies are necessary to have any confidence in a treatment, but glory goes to the original discoverers of a treatment and their funders, not to replicator three of ten. So we end up with a list of promising treatments that no one can trust because no one has any incentive to test them again.

All together, this leads to a lot of low-hanging fruit in longevity research; there’s a ton of promising molecules out there that only need money to be tested. The Longevity Research Institute aims to pick that fruit. It has a very targeted mission: take compounds already shown promising in at least one trial and fund replication trials where you actually wait to see how long the mouse lives. That’s it. Yes, it should worry you that this isn’t already being done.

The LRI is run by Sarah Constantin, who writes the blog this blog wants to be when it grows up. You can see her past work in e.g. treatment-resistant depression, STD transmission, and chronic fatigue syndrome. Because there are very few fixed costs (Sarah’s salary, some legal consulting) and studies are so expensive, there’s lots of room for more funding. You can see the LRI’s roadmap here and an initial list of promising compounds here. LRI’s first trial, of the synthetic pineal peptide epitalon, launched just last month.

For more information, you can follow the blog or Facebook group. If you feel so moved, you can donate to LRI here. I’m happy to talk to anyone considering donating (elizabeth-at-this-domain-name), and for larger amounts Sarah herself is available.

In Robert Kegan’s In Over Our Heads, he says “it is a poor school whose favorite students are the ones it does not have to teach.” (page 171). I get what he’s going for, but having lived it, I can also say it’s a poor school whose least favorite students are the ones it does not have to teach. It tends to lead to things like resentfully insisting you do have something to teach the student and forcing them to go through the motions of learning it, or standing in their way when they try to do something they’ll actually learn from. Or an intrusive focus on their personal life.

I feel like the whole concept of favorites is leading people astray here, which is a very Kegan thing to say.

Self Help Epistemic Spot Check Results

In a word: ¯\_(ツ)_/¯

I reviewed several self-help books with a wide range of scientific backing. For posterity:

Polyvagal Theory
The Tapping Solution/EFT
Full Catastrophe Living/Mindfulness
Exercise for Mood and Anxiety
A Guide to Better Movement
There were a few others I never published because I didn’t get very far into.

As a reminder, epistemic spot checks are checking a book’s early claims for truth/scientific validity/coherent modeling, to determine whether it’s worth continuing. After a few books I concluded that scientific backing didn’t seem that predictive of a book’s helpfulness, and started focusing on modeling. But that wasn’t predictive either.

I never officially decided to quit this project, but I can no longer get excited about checking out a new book, because nothing short of trying it seems to have any predictive ability of whether or not it is helpful. This leads me to believe that most of the effects are placebo effect, not in the sense of  “imagined” as people usually use the word, but in the sense that it’s your own brain doing most of the work, and people just have to try things until something clicks for them, starting with the cheapest. I find this answer deeply unsatisfying, but what are you gonna do?

 

Review: SOMA

I said I wanted to get this done while the game was still in a Humble Bundle, and technically I succeeded, but it turns out it doesn’t matter because I’m not going to recommend it.

SOMA was sold as “Like Amnesia but sci-fi and underwater” and I love all of those things, so I had very high hopes. Hopes that were dashed. I don’t know if my tastes have changed since I played Amnesia or SOMA just wasn’t as good, but I stopped playing two hours in.

If we’re assuming the former, the problem is I’ve played a lot of puzzle games since Amnesia and my standards have gone up. Both Amnesia and Portal have puzzles so you have something to do while running from monsters and…eh. I thought I was cheating myself by looking up solutions so often, but then I solved a few myself and there was still no sense of satisfaction. It’s more just testing what the environment will let you do until the problem somehow goes away.

I was intrigued enough by the story to look up the ending. If you’re looking for something with similar themes, less terror, and better puzzles, I strongly recommend The Swapper, which remains one of my favorite games of all time.

Manganese

In summary: Manganese is an essential nutrient and too much will kill you.

On one hand we have people exposed to manganese is the air from industrial processes. These people definitely get Parkinson’s like symptoms, and in the aggregate score lower on various intellectual tasks. Monkey infants on soy formula (which has more manganese than milk based formulas) had mild neurological effects, so you can take in enough from food alone to be dangerous.

On the other hand, manganese superoxide dismutase is the only thing keeping your mitochondria from melting, and it does several other things besides. So we can’t just throw up our hands and say “no more manganese”, we have to actually figure out a safe level.

The World Health Organization has set the No Observed Adverse Effects Level at 11mg/day, based on the observation that some humans naturally get that much through their diet. As mentioned previously, we know you can get manganese poisoning through food alone, so this is not very reassuring to me.

The most comprehensive source I found on this was this thread on the soylent message boards (they cite several of the same things I did above, all correctly, so I trust their work ). According to their sources, most adults already eat enough Manganese to meet the RDA. I don’t want to put too much stock in the RDA, because neither I nor they could find out how the FDA (or the Linus Pauling Institute) set it. However even if you accept the number, if people are already getting it through diet, and too much is toxic, it doesn’t belong in a multivitamin.

This is worrisome enough to me that I’m tossing my multivitamin and focusing on getting individual missing nutrients through specific supplements (if anyone knows of a balanced B supplement, please let me know). It’s not so bad I’m tossing my protein/vitamin powder, because it has a lower volume of manganese and I don’t eat much at a time- however when it’s gone, I’ll probably switch to a straight protein powder.

 

The Supply Chain Game

When you hear “supply chain”, your first thought is probably not “let’s base a leisure activity around that.” But the world is so big and game development is so cheap now that that this does not stop there being more video games than I can play that cater to my taste in complicated supply chains. If you happen to share those tastes, here are some games to try:

Colonization: Built off the Civilization 4 engine. You build cities near resources on the map, which you can harvest using units of various skill levels, which can then be processed into various goods, again by units of various skill levels. Theoretically you need to build liberty so you can declare war against your colonial power, but I always quit before that stage, because why would I spent time on war when there are supply chains to build. You have to move goods between cities (for processing and selling to the mainland) manually, which makes this my low-thought comfort game.

Anno (1404): This is a whole series based on both trading and supply chains. I would say they made it just for me but there is a combat section :(. I’ve only played Anno 1404, supposedly the best of the series. Anno 2070 is set in post-apocolyptic water world, which seems like it’s even more for me, but it has annoying Ubisoft DRM so I’ve never actually played it. Anyway, the mechanics. James Recommends does a better job explaining than I will, but it is a video, so I will try anyway.

You start on an island that has all the resources you need to keep your peons alive, which you provide by building resource extractors (apple farms) and processing plants (cider mills). As you make them happy they evolve into better people, enabling you to tax them more and build new buildings. Which is good, because these better people have more demands for making them happy. Complicated demands.

For example, Patricians want books, which requires a printing house. Books need indigo (which requires a sufficiently large Oriental settlement on an island fertile for indigo) and paper, which requires a paper mill, which requires lumber input, which comes from a lumberjack hut. Oh and paper mills can only be built on rivers, so you might have to find an island just for that. That’s not too bad. But you also have to build the printing house, which requires glass. Glass comes from a glass smelter, which needs quartz (which requires a higher level Oriental settlement and a quartz quarry) and potash, which comes from a glassworks building that runs on trees.

Put more graphically

What is most unique about Anno is that your resources are limited to the island they were farmed/created on, and if you want them on a different island you have to move them with ships.

Unlike every other game I can think of, Anno lacks a staffing mechanic. All buildings come fully staffed, even if there’s no housing on their island (and there are reasons you generally concentrate your housing on two islands). Housing is essentially a tax farm, with which you get money to build more buildings. I think the purpose of combat here is to create something for you to spend money on that is not more buildings, which is fine, but it involves more strategery and uncertainty than I feel like dealing with in my leisure time. Luckily, Anno lets you turn off pirates and rivals completely so I can build my little anthill uninterrupted.

Tropico: I think I’ve played Tropico 1, 3, and 4, which is enough to say they’re all the same and it doesn’t really matter which one you get.* In Tropico you are the Presidente of a banana republic, and have goals like “build a kickass diversified economy” and… I didn’t commit the others to memory. I think one involves a Swiss bank account?

Tropico’s production supply chains are much simpler than Anno’s, barely more complicated than Civilization’s.  Raw material -> processed good -> ship off the island for money. But it does have a nifty education mechanic. Different buildings require employees of different genders and education levels. You can’t simply overeducate your workforce, because being underemployed makes people dissatisfied and inclines them towards regime change. You could rig the election or kill them, but that has other consequences. You can give them makework, but that gets expensive, especially if you give them makework as teachers and professors and create more education.

Tropico has no combat mechanic, unless you count peasant revolt, which I don’t because it can be averted with good enough supply chains.

 

*I picked up Tropico 5 in the latest Humble Jumbo Bundle, which is around until 4/3, but I’m trying to finish Soma in time to review it while the latest Humble Indie Bundle is up, so I haven’t actually tried it. I assume it’s like the last 4 but with more DLC.

Can History be Moved?

When it comes to history, I lean towards “trends and forces” over the “great man” theory. I’d like to test this. Do you have recommendations for people or especially specific media that would challenge my view?

Some clarifying examples:

– Neither Sabin nor Salk get credit for curing polio, because if one of them hadn’t the other one would have, and if neither had someone else would have. Obviously developing the vaccine faster was a big deal for the kids who would otherwise have caught polio in 1956, but it’s not changing the trajectory of the world.

– Robert Moses may count as a Great Man because he locked NYC into a car-based equilibrium that people are unable to break to this day. In general I think “moved world to a different equilibrium” is going to be a common pattern among people who change the world.

– Dictators killing a bunch of their own people doesn’t count, the effect is too local.

– There’s a reasonable argument John Wilkes Booth counts because Lincoln would plausibly have handled Reconstruction much better than Johnson. But if I learned there were many planned attempts on Lincoln’s life and estimate at least one would have succeeded, Booth would no longer count.

– To the best of my knowledge, whoever started the American civil war doesn’t count, because that was pretty clearly going to happen. But both Grant and Lee do count, because who won the war mattered and there weren’t equally skilled replacement generals. We know this because the north tried 400 people before Grant.