Podcast notes – Matthew Walker on the power of sleep (Farnam Street podcast)

Matthew Walker – Power of Sleep
Shane Farnam’s Knowledge Project

Very dangerous to stay in bed a long time while awake, because brain then associates wakefulness with bed
Go somewhere else, read, relax
You wouldn’t sit at dining table waiting to get hungry

Caffeine
Benefits of coffee are similar to benefits of sleep, but it’s not the caffeine, it’s the coffee BEAN bc it provides majority of daily antioxidants
Health benefits are similar with decaffeinated coffee
Keeps you awake (5-6 hour half life)
Caffeine accumulates over time
Not only can caffeine make it harder to fall asleep, but it can wake you up during sleep cycles
It can also decrease deep sleep from 20-40%

Alcohol
Helps you sleep but due to its sedative properties – it’s not healthy
Can spike your nervous system, produces sleep fragmentation (wake up multiple times)
Alcohol reduces REM sleep and growth hormone production
REM is good for creativity and emotional stability and hormone production
Even one glass of wine in evening can measurably impact sleep

Insomnia
4 types (eg, sleep onset insomnia, sleep maintenance insomnia)
Chronic grade insomnia – consistent symptoms for 3 months
Causes?
-30% heritable (genetic)
-stress & anxiety
-excess caffeine
-physical pain
Common cause of insomnia is hyper arousal – hyper alert nervous system (fight or flight branch) – the “tired & wired” phenotype
First line treatment is CBT (cognitive behavioral therapy) – benefits last longer than eg sleeping pills
1. if you’re awake, don’t stay in bed
2. don’t get anxious / angry, re-appraise and just tell yourself you’ll rest in bed, relax, even if you don’t fall asleep
3. constrain bed times (eg, instead of spending 2 hours tossing and turning, go to bed 2 hours later) – increase sleep efficiency. Longer you’re awake, the more sleep pressure there is. Teaches brain to become hungry for sleep

Temperature
A key regulator of sleep
Hunter gatherers fall asleep a few hours after sunset, and before sunrise (not at sunrise) when the temperature begins rising
When you feel most sleepy – your core body temp is dropping the fastest (1 deg C)
During sleep onset, blood swells to hands, face, feet – so paradoxically you’re warming up to fall asleep
Warming hands & feet can help you fall asleep
Mammals don’t have hair on hands and feet because it’s designed to radiate and release heat
That’s why hot baths and hot showers help – it’s because your extremities are hot, and your core body temp plummets (!)
As you approach waking up, your body temp rises
Part of why coffee helps is because it warms the body in the morning

Quantified self / Oura rings
He tracks with Oura ring and is advisor for them
Orthosomnia – anxiety about improving sleep that it’s self-defeating, becomes mal-adaptive
Sometimes the reports have placebo effect – if tracker tells you you had bad sleep, it can affect your cognitive performance
The best sleep tracker is the one you use consistently
Useful metrics
sleep efficiency is most important (90%+ is good)
-balance of REM and non-REM sleep
-sleep latency (how long it takes you to fall asleep) – need a balance, if fall asleep too fast then you probably have a lot of sleep debt

His blog addressing questions and criticisms:
https://sleepdiplomat.wordpress.com/

Made claim that lack of sleep doubles risk of cancer (should have been “certain kinds of cancer”)

3 things that ensure bad sleep: Caffeine, Alcohol, and Nicotine
Importance of mental health – anxiety and stress

Sleep chronotypes – are you morning type or evening type?
Everyone has their own 24 hour Circadian rhythm – individual variation in peak and trough
Important to match chronotype with bedtime – eg, if you naturally sleep and wake late, then don’t force yourself to sleep and wake early

If you’ve had a bad night of sleep, don’t change your habits the next day eg, sleep earlier, drink more caffeine, take a nap
Keep a consistent routine

Importance of a wind-down routine – just like for kids
eg, shower, meditation, light stretching

If you nap, nap before 1pm, and keep them brief (10-15 mins)

Don’t count sheep – it’s a myth
Can make you take longer to sleep
What does work – take yourself on a mental journey (like a mental hike, a mental bike ride) – take mind off itself
Don’t look at the clock! It’s not your friend

Podcast notes – Reshma Shetty (Ginkgo Bioworks founder) on Exponential View

Ginkgo Bioworks – automating biotech / synthetic bio

Podcast: Azeem Azhar’s Exponential View
Guest: Reshma Shetty – cofounder; compsci training; Ginkgo started as MIT grad student project
What if we can program cells the way we program computers?

Leverage software and automation

Started in a compsci + AI lab instead of a bio lab

Goal was not to discover but to ENGINEER biology

Engineering is about design – to make something, tangible discipline
Biology is fundamentally about discovery

We’re good at engineering at cell level, can do a little at organism level, but no idea how to do it at ecosystem level yet

McKinsey – Bioeconomy opportunity is multi-trillion

Ginkgo is a platform company helping other companies engineer cells
As platform, more customers = more benefits to all customers (more data, knowledge, programs)
Many partnerships – equity, cash, flexible depending on customer

First question is technical feasibility – can it be done?
Second is financial
Third is “caring” – not values neutral (eg, internal staff diversity)

Example – Motif food company (learning from Impossible Burger, which added heme protein to make their burger taste more like meat)
Motif are the food science experts, Ginkgo provides an “R&D engine” and innovation, they formulate and commercialize

Example – Sim Logic – metabolic disease, could we supplement patients’ metabolism with an engineered microbe?
A new therapeutic modality

Cell programming isn’t that different from other engineering disciplines:
DESIGN – BUILD – TEST – LEARN
Involves a lot of research into prior art, lessons from nature

Designing DNA sequences for each functionality, writing in DNA instead of code

Most folks on their team focus on architecture and “how to do it”
Then a specialized team that turns specs into DNA
They do many thousands of designs and test them all

Biological design today is a search problem
Very large search space – DNA combos are effectively unlimited
Nature has given a lot of clues

Many methods of design: Machine learning; Nature; Evolution; Simulation

Evolution is a powerful tool they can use
Generate a lot of diversity, and let the best cells replicate and win

No silver bullet tech – not even CRISPR

How to scale – similar process to brewing beer using engineered bacteria, fermentation -> harvesting -> purification

Ginkgo does design and process and how to scale
there are CMOs that can help manufacture (contract manufacturing orgs)

Best microbe isn’t always the most productive, but the one that can do it most reliably at scale
Microbes that can produce even with variation in environment and manufacturing conditions

Cells take time to grow – presents a fundamental limit to speed
Parallelizing helps

Miniaturization?
Helpful to reduce costs, and can be faster

Work with customers to share IP, re-use for future projects and across portfolio

Seeing more and more bio startups

IPO in Sept 2021 – surprised how well the story has resonated

Moonshot dream app?
Terraforming Mars (!)

Podcast notes: David Sinclair on the science of looking younger (Longevity Podcast)

David Sinclair – Science of looking younger
Co-host Matthew LaPlante

We’ve evolved to have children up to ~30yo – after that risks increase
Infertile ~40yo – menopause – lots of physical changes
Estrogen + progesterone / HRT treatment can be beneficial
Most women don’t know their baseline levels especially during menstrual cycles

Truth to “you’re as old as you look” – subjective physical appearance is correlated with longevity

Importance of skin health
Skin is body’s largest organ
Simple skin test – palm on table, pinch back of hand, skin should return to place in <2 seconds when young – by 40s to 50s it’s <10 seconds
Problem of epidermal thinning – menopausal women, older men
Bruising, ripping, tearing – becomes life or death especially when older
Health of skin cells is very correlated with measured biological age

Skin is full of dying cells (senescent cells)
The dying cells secrete bad chemicals, and if you kill these cells it can improve health

Prevention –
Avoid UV light
Wear sunscreen – 10-20 mins of sun can be good but don’t overdo it
Other bad things – smoking, alcohol, processed foods

Cures / Treatments –
Collagen supplements (jury still out on benefits, but likely no harm)
Vitamin C
Retin A / Retinol (short-term benefits, but unclear on long-term)
Anti oxidants (literature is not good for longevity, except resveratrol in certain applications)
HA (hyaluronic acid)
Botox – very effective at reducing wrinkles for 6-9 months; it’s cosmetic not medical

Nails
Rate of nail growth is good indicator of aging
Decreases 0.5% per year

Hair loss
It’s strongly genetic – 600 genes involved – carried on X-chromosome
Hair follicles shrink with age
Treatments – RetinA; Rogaine; Propecia
Laser treatment has proven benefit (low laser light therapy) – likely causes hormesis and rejuvenates stem cells – similar to how infra saunas are growing in popularity

Gray hair as evolutionary indicator of experience, status – stress can induce it, and gray hair is reversible (especially in early stages)
Believes there will be products to naturally restore hair color before long

Hair starts growing in wrong places as you get older
Likely due to gene expression going awry

Eunuchs – no testes – live 14-19 years longer than the normal man (!)
In a study of 81 eunuchs, 3 became centenarians (100x greater rate than baseline)
Smaller people live longer too

All cells have fundamental same causes of aging, and similar treatment pathways

“If you keep yourself looking good, you’ll probably live longer too”

Podcast notes: Crypto whale Tetranode on Bankless

Ethereum whale Tetranode on “how to become a whale”

What is a Tetranode?
Quake game reference

Played Starcraft a lot growing up

Calls himself a “retired software engineer” but still works 100 hours/week
It’s a compulsion, doesn’t feel like work

First 4 years of crypto he just hodled – built discipline

Initially crypto community on reddit, moved to Twitter

Eventually bought a house with crypto gains but still drives a Toyota

Several levels of wealth
1. When poor, just want more money
2. Make millions – self-retirement, freedom
3. Then you wanna make others rich

Early investor in FunFair but held through crash, learned the importance of execution

For investments, he wants to know he can be the biggest customer – so he can help / influence

Measures his wealth in ETH
“hardest money on Earth”

Why bullish ETH in early days?
Angry that bitcoin didn’t scale (during block wars)
Started buying ETH at Kraken listing in 2015

Why not alt L1s?
None of them really solve the scalability trilemma – just make different tradeoffs
At his scale, security issues become greater

Experimented with Fantom and BSC – but bridge UX wasn’t good, and bridges are dangerous for larger transfer sizes

Why does decentralization matter?
The consequences are fat-tailed – eg, censorship resistance
Centralization adds risk – eg, Binance regulatory risk, and CZ keyman risk

Don’t do buybacks – causes a project’s treasury to bleed and doesn’t help project in long-run

What he values: Large addressable market; How the product helps his own needs

Farmers he respects
-@Pleyuh
-@DegenSpartan

How does Tetranode move markets?
Either through online influence or direct market actions
He’s not a true market maker like 3AC

Info asymmetry exists even in Ethereum – its value should surpass Bitcoin based on activity and fees alone

Better to make own judgments early than wait to be validated later (when your alpha is gone)
Trust your tuition to make the call

How are whale games played?
With smaller investments he can control the market and will do things like liquidating short sellers
In a few whale rooms where they can collab to make those decisions

Nowadays he makes money by #1 Farming and #2 Being advisor for new projects
How he helps: Tokenomics advice; Market making; Marketing

His favorite projects (Infinity Gauntlet)
-Dopex (highest conviction) – his most used L2 app
-Redacted + Olympus (partners)
-Fei + Rari
-Rocket Pool (only decentralized staking pool)
-Curve (tokenomics is among best)

Governance doesn’t really work in 2022 – voting isn’t binding, controlled by a few large hodlers – it’s more “decentralization theater”
Profit sharing is more effective (eg, Curve)

1/3 of his portfolio is on L2
Lending market is a weakness currently, need more uptime assurances
Ideal L2 has fast withdrawal time
ZKSync is holy grail but no generalized EVM compatibility yet

In long run, ZKP is end game (because open source)

Podcast notes: Founders of NFT marketplace OBJKT on Kevin Rose’s podcast

Guests: objkt founders (3)
Source: https://www.proof.xyz/objkt-and-its-path-to-the-largest-nft-marketplace-on-tezos/#play

objkt is an NFT marketplace on the Tezos blockchain
the founders met on Twitter

HEN (Hic et nunc) came before objkt and was the biggest Tezos NFT marketplace
HEN loads data directly from blockchain so it’s sometimes slow / not stable
Felt HEN was missing ability to make offers and doing auctions
objkt built those features, and started to grow

Tezos’s NFT standard is FA1.2 or FA2 (compared to Ethereum erc721 and 1155)
objkt supports these standards and has indexer to read from Tezos blockchain and display in their marketplace

objkt recently launched NFT minting
wants to add push and email notifications – need good filters so it doesn’t overwhelm very active artists and collectors

Kevin: Tezos more green, more indie vibes, big collector, but worried about Tezos scalability, every time there’s a major NFT launch, Tezos blockchain has problems
when HEN marketplace went down, artists and collectors were worried their NFT data would disappear

right now all objkt data on IPFS
have human curator for home page
will add more algorithmic curation, a feed for artists and collectors you follow

what about social features?
won’t add comments anytime soon, happen already on Twitter / Discord

governance token / DAO?
“at some point…but not rushing anything”
all of it still experimental – can’t really ship fast and nail it later