Genetic validation is the gold standard of biopharma. @bioio_tech's MOAT platform is the chemical validation for that genetic validation.

trump’s coders can’t code. Nobody is surprised.

Would be impressive if Bronny makes it in the NBA. Different kind of pressure than his dad but still a lot.

Best part about Web3 is no one region or institution is leading the way. You can *feel* Silicon Valley, Google, Harvard carrying no weight where we’re heading. /1

bench’s reaction hilarious

Key point:

Universities are basically FTX Run by ivy league “geniuses” who take poor peoples’ money to prop up their own worthless token (diploma), all the while making people believe it’s all about altruism

don’t always have to be the reply guy

👆the correct take on Buffett and Munger

DeSci is a generational idea it’s what The Science set out to do but because The Science had no good way to do incentives it has failed badly Adding liquidity via crypto is figuratively giving water to bring projects to life It’s such a small but significant difference that can change everything if we just do it

No wonder biotech lags behind software tech Biotech people have PhDs who prefer fancy over actual solutions Software can’t take over biotech soon enough

No amount of biohacks will overcome the physics behind mortality Diet, exercise, modern medicine is like the sun compared to all the stars in the galaxy. 1 out of billions Were *many* orders of magnitude off in making a difference in radical lifespan extension. Need to get a grip on the math on what it would take. Until then everyone is wasting their time

I feel like this is becoming a meme. Socially minded people realizing capitalism is much more fair than forced redistribution. One group doing the redistribution can never be as fair as an open market competition. That being said, like with sports it seems there will always be a tension on deciding the rules of the market. It’s good to have 2 sides debating the rules so one side can’t win too much. With one side wanting to add rules and the other side wanting to take away rules

@mikealfred’s relentless trolling of chart wizards is pretty funny. Such a simple joke but he lands it every time. It is too beautiful that crypto makes a mockery of how the world works while fixing it at the same time. Mockery is a far better solution than violence to fix the world

What has single cell RNAseq discovered?

If biotech people had 1/1000th the conviction that crypto people had we would be a lot farther

I feel like to get a social media account there should be a test of whether one can read graph axes

mRNA-LNPs are the therapeutic endgame. Let’s talk in 10 years.

Statins give you diabetes and Alzheimer’s but they lower your cholesterol…😵‍💫. I can’t think of a better example of Goodharts law

always good to put down the phone before making a hyperbole

basically what CS Lewis said

indirect wealth transfer - a short story boomers save real estate to leave their Gen x/z/millennial children real estate goes to zero because of fiat debasement fortunately, good for nothing children had bought “worthless” crypto which goes to infinity fate loves irony

if SEC really wanted to do its job, it would seem very easy to filter stock transactions by % gain, timing of investment relative price change, and amount earned, and to investigate those above some threshold the more gained, the more likely insider trading happened humans are predictable

HEY SCIENTISTS, do you know donating $1 to support research on @gitcoin will add up to big $$$? How? Gitcoin has "matching pools" where big donors will transform your small donation to $100s to $1000s. gitcoin.co/grants/explorer/?…. /1

Healthy weight commitment foundation run by the junkiest of junk food manufacturers? With the exception of a healthy lung foundation run by tobacco companies, I can’t think of a more cynical initiative

this won’t stop anything people always find ways around prohibitions Pelosi’s husband does all the trading

New paper by us in @ScienceTM. Congratulations to @LSurfactant and everyone that contributed. We identified a gene, ATRAID, that appears important for how people respond to bisphosphonates, which are common drugs for osteoporosis and cancer metastasis. stm.sciencemag.org/content/1…

I wish I would have realized this almost a decade ago when I tried doing crypto stuff (an OpenSea-like platform for research) at MIT and Harvard. Literally no one at these places cared. It was such an ostracizing experience. /2

In hindsight it makes perfect sense. Ivory Tower is ironically caught in innovator’s dilemma. Ironic because the theory was laid out by Harvard’s own @claychristensen /3 en.m.wikipedia.org/wiki/The_…

not ideal that the longevity conference circuit is just the same people over and over just in different cities what can we do differently?

What I like most about this response is a willingness to admit one might be wrong. Few do this. We all need to do it more often

Y axis

Musk = Trump, look into Musk’s father:

Guy spends his many decades career scrutinizing investments and his wife outdoes him with a single Bitcoin purchase (hence the “We”) I love Jason on All-in but don’t think for a second this doesn’t dominate his psychology

creativity in crypto is much higher than in biotech A few explanations: 1. biotech people are too constraint by their training. PhD and MD training enforces overly codified rules of how things are. Some knowledge is critical but I think what makes someone be perceived as “good” in biotech still has too much overlap with what makes someone good in school - meaning, they are good at “guess what I’m thinking?” where the “I’m” is a human that gatekeeps in some way. What we need rather is people who can guess how nature works. This often requires a creativity to ignore what humans, especially those with the most reputation, think. Crypto people don’t necessarily have formal training. This can mean their brains are more free to possibilities. And not everyone in crypto is trying to save the world (e.g., dogecoin), which actually sometimes seems to make it more likely something impactful could result - fate loves irony. Per capita, I wouldn’t be surprised if Dogecoin has probably created more joy than SSRIs, considering SSRIs don’t work half the time. 2. The biotech ecosystem is like innovators dilemma in reverse where all the startups reinforce the incumbent, big pharma, rather than disrupting it. Whereas Crypto is the classic model disrupting banks and Wall Street. 3. It’s not financially and reputationally viable in biotech to work on something in the wilderness for a long time with no results whereas with crypto one can go to market much faster and care much less about reputation. The market creates the reputation Good news is crypto is coming to biotech, biotech could use more degens

Biotech will significantly improve when the digitizers take over Physicalists move too slowly and can only conceive of what’s possible based on their experience Digitizers are idealists, they use computers to explore what’s possible in vastly larger spaces than what one or a few brains can imagine Ultimately digitizers are taking over from the physicalists in all fields, eg., doctors/lawyers replaced by AI, but it’s been particularly slow in biotech - hence the (relatively) slow progress seems an unfortunate correlation is the larger the physicalists’ egos - the more they think they can outdo computers - the slower their field advances Of course physicalists will come at this post with “biology is hard” takes. Don’t be deterred. Technology takes time. Look at 10, 20, 30, 50 years is really nothing in what’s at stake here. If we’re talking life extension for hundreds of years do you really think if we leave it to the physicalists we will get there?

As bitcoin dematerializes the world, need to figure out real estate rules so our physical spaces aren’t completely trashed.

The irony of how much damage to our health the stress is of submitting grants to biomedical funding agencies

Biomedical researchers need to be better at math Gompertz law of mortality is an exponential This means factors compound to kill us your single target even if it is acting on an entire cell population won’t work for most diseases people care about. The effects don’t register on an exponential scale Below is gompertz equation Gompertz is base natural log, e =2.7 (like many natural phenomena) This means the mortality rate increases by a factor of 2.7 every 8 to 10 years of age (b = 8-10 in the US) This makes sense because the longer aging sets in the harder it is to successfully drug something Sure, stopping eating using GLP1 works but that’s just caloric restriction. Not a solution for significant lifespan extension Need to identify therapies that can make the exponent go to 0 such that e^0 = 1 Most therapies have a 5-20% effect, but what we need are 5000-20000% effects Let’s zoom out and think of the math needed

Biotech investors should reflect more on how YCombinator solved tech investing. Deep tech and shallow tech aren’t as different as people think. Both need people who execute. Neither need idea people. The ideas will emerge from getting the product to market. /1

diet and exercise will give an extra 5-20% healthspan and lifespan (could be 0% though because of error bars it should be obvious we will need much more radical approaches

Thanks for your Susan Collins concern.

Sounds like Elon, Jobs. Seems like many people’s agree/disagree meter has been turned off in this w*ke walk-on-karma-eggshells era. Good to turn it back on.

Single issue voting on crypto now is the best way to preserve your ability to vote however you want later

are we the same person

Great phrase: anarcho-tyranny

Don't fall for the trolling. He's trying to get thrown out so he can be a martyr before he goes up in flames due to Russia.

A Guide to DeSci, the Latest Web3 Movement | Future ⁦@vitadao⁩ ⁦@Molecule_dao⁩ ⁦@lab_dao⁩ ⁦@PsyDAO_⁩ mentioned thanks Sarah Hamburg! ⁦@Shamburgularara⁩ future.a16z.com/what-is-dece…

Another great episode of Unchained podcasts @laurashin @vladtenev Three use cases that developed world crypto skeptics need to realize 1) stablecoins - useful in developing world but will lower costs significantly on tradFi/trad banking in developed world too. Think no more 3% credit card transactions. That 3% makes a lot more possible. 2) software vs brick and mortar - people talk about AI replacing humans and buildings but crypto is also software that can replace lots of physical and human infrastructure, e.g., banks, clearing houses etc. In general crypto is much much cheaper that then trad system. Vlad cited that crypto business is 10x more profitable than equity business 3) token securities - speeds innovation by allowing anyone to fund startups. Currently one can’t invest in startups until they IPO and are multi $B. Crypto can enable much early investment at the $M or even less stage allowing more innovation to happen and more people capturing a 10-1000x ROI

‘fate loves irony’ - @elonmusk doubly ironically said about doge. /4

Incoming technical analysis: @BioProtocol gonna blow through the U

biotech stocks can be shitcoins for the same reason crypto tokens can be shitcoins- insiders/team dumps on retail because there is no product biotech people are not inherently better than crypto people. You could argue they are often worse because biotech generally has a good reputation with the public unlike cypto People investing in either space need to DYOR and invest in something real. This is much easier said then done. It is deep tech where the results are unknownable to everyone including the founders. It's much higher risk than a SAAS company even one with only a few customers Traditionally in biotech there's no customers until the very end several years down the road when the drug has been nearly completely derisked. Big institutions like pharma are super conservative and won't jump in until then This is where crypto can change the game for biotech. Liquidity as provided by @vitadao @Molecule_dao @pumpdotscience etc allows the market to decide from day 1. Like we saw with Polymarket and the presidential election, if something 1) has alot money on it 2) by a decentralized group of people 3) where few people hold large % and 4) key data is shared early and often publicly - it's probably a good bet. Contrast that with biotech stocks. Only #1 is true. Just like a shitcoin

Read the bottom of everything a PhD has published. “This has implications for x, y,z (e.g., cancer therapy).” Its always for someone else to figure out. Need more of this 👇

Google can’t turn around unless they pull an Elon and fire 80% of the team

This is super cool. PubMed is posting preprints that referenced their NIH funding. Thanks to all contributors! @labdao @WUSTLmed @bnfinck @KMccommis @bioio_tech @Niklas_TR pubmed.ncbi.nlm.nih.gov/3671… 1/

@sama said he thinks AI can make $1B one person companies, so here's my idea: What if we reverse engineer Gompertz law of mortality? Introducing RAGE therapeutics (Reverse Anti-Gompertz Engineered) Gompertz is a exponential curve that says our probability of death increases exponentially as we age

It shows how power works that this guy gets 6 years but those in charge of 2008 financial collapse or 2016 election get zero time or a few months.

Crypto maximalism 🤝 life expectancy maximalism.

Good thread with concrete evidence. In summary, making election about morality rather than normal stuff like taxes is how to get more Dems to vote. Need to ensure more Dems vote b/c Reps voting will be unchanged.

“Is Target-Based Drug Discovery Efficient? Discovery and “Off-Target” Mechanisms of All Drugs?” important recent article by @arash4sadri on what I agree is the main flaw of how the vast majority of drug discovery is done today pubs.acs.org/doi/10.1021/acs… (full text preprint - osf.io/preprints/osf/bxwcr) tldr: the "target-based" approach - based on "hitting" a single protein (gene) - remains the dominant drug discovery approach for decades despite discovering less than 10% of all drugs on top of this, only a fraction of the 10% target a single protein. the mechanism of action (MoA) of those 10% is often polypharmacy - hitting multiple targets and often what are discarded as "off-targets" thus, so much effort is spent on the target-based approach and yet it produces so few drugs the waste is so large it’s been documented by @JackScannell13 and is derisively known as “Eroom’s law” - which states it takes longer and costs more to develop drugs each year. current estimates are nearing a decade of time and costing > $1B per new drug back to the article: target-based drug discovery contrasts with the much more successful approach of phenotypic screening, which has discovered 90% of all drugs. famous examples include aspirin, penicillin, and for the longevity folks - metformin, bisphosphonates (see further below), and others some background on target-based vs. phenotypic screening: one can think of target-based as gene-centric. another way it's been described is "rational" drug design. this implies it is irrational to design a drug any other way 🤔. it has become the dominant mode because often people start with a disease and try to find a cause. The general approach is as follows: disease->target->drug. this makes sense but is overly reductionist as we and Arash argue. another way of saying this is that researchers have strong biases at each step in going from disease->target->drug in contrast to target-based, phenotypic screening can be thought of as drug-centric. Arash makes several arguments based on information theory on why target-based is inferior to phenotypic screening, but the bottom line is phenotypic screening’s cause-and-effect is much more tractable still the problem with phenotypic screening is one doesn't know how the drug has the good effects it does. thus, there is no path to improve the starting drug. and one needs this both to make a better drug but also to build intellectual property around it such that one has enough incentive to pursue the hard and expensive work of getting the drug to the market @bioio_tech we think we’ve developed the best of both worlds with our MOAT (mechanism of action technologies) platform. our approach combines phenotypic screening and target identification in a single experiment how? we start with a drug that has the desired phenotype of interest (e.g., it's already a proven anti-diabetic) and we do genome-wide screening using gene editing technologies such as CRISPR to identify which of the 20,000 genes most strongly interact with the drug. once our screen tells us the MoA, from there we do unbiased screening to identify which parts of which protein(s) in the MoA pathway the drug hits. this puts us in a great position to improve the starting molecule once we know exactly which protein(s) it hits and where. lastly, once we have the new and improved drug and the MoA we can do further unbiased screening to find what disease(s) the new drug works best on so, MOAT reverses the traditional disease->target->drug process. and because we use unbiased approaches at each step from drug->target->disease, there’s much less build up of sunk costs for further reading, we have a case study involving a famous class of aging (osteoporosis) drugs called bisphosphonates. PMID: 29745899, 32434850, 30033366. science.org/doi/10.1126/scit…. see also @JSheltzer's work where his team tackles the topic in cancer, where the problem is arguably most serious. science.org/doi/10.1126/scit… Arash makes several other interesting arguments on the inefficiencies of how drug discovery happens today, such as that most biotech and pharma happens in siloed overly specialized teams, so please check out the article h/t to @GolatoTyler for highlighting the original article in @vitadao’s Discord: discord.gg/vitadao. side note to all the biotech people out there: there’s lots of alpha like this in various DeSci Discords

hey all, @gitcoin's GR13 Funding Round for longevity and other important causes is now live. Please share and consider donating. @LifespanIO has a handy guide on how to donate. lifespan.io/news/new-gitcoin…

Excited to share our latest "Cell Fitness Is An Omniphenotype". We argue cell fitness is a biological hash function that enables interoperability of biomedical data. biorxiv.org/content/10.1101/…

I’m continually blown away that otherwise intelligent people make price predictions on things. They are always wrong.

The longevity field should consider *heart rate variability (HRV)* as a key biomarker: 1) HRV decreases are seen across major aging related diseases in both mice and humans (cancer, diabetes, alzheimer's), suggesting that therapeutics to increase HRV would be bona fide gerotherapies aka "pipeline-in-a-pill" 2) HRV is a much faster predictor of lifespan extension than waiting for mice to die, suggesting that HRV could be a better "target" compared with individual genes in drug development perplexity.ai/search/does-hr…

I just funded 12 grants on @gitcoin gitcoin.co/grants/cart/bulk-…

because strawmanning such as your tweet used to not be eagerly upvoted

love all the research talk on @HairDAO_ ‘s Discord scientists and biohackers need more places like this reddit and other web2 only allow alignment of time, DAOs are superior because they allow alignment of time and money

I would totally pay for a “finish my paper” service. Decentralized grad student paper finishing service. I have 4 manuscripts I have no time for. Can someone in DeSci build plz?

Hey journal editors, I know you're having trouble getting reviewers. DM me. We @vitadao can help. We will pay them.

Tarun doing the same FUD that other trads have done. We’ve heard it before. Default to “it’s a scam unless I’m involved”. Bio people are particularly good at “appeal to my authority” logical fallacy. You can help build. Insults don’t work.

.pptx too. This is easy way to see which of your images are huge and jacking up your presentation file size.

Be skeptical of the single solution

Dear DeSci

I just voted on The Longevist (VDP-75) The Longevist will be an on-chain overlay journal of aging research where every quarter a large body of longevity KOL (key opinion leaders) will vote on the top preprints 1/3 snapshot.org/#/vote.vitadao.… @vitadao @SnapshotLabs

Cool study but not surprising. Knocking out many genes in many different tissues of the body would confer resistance to metformin, even low dose. Genes are in highly interconnected pathways and metformin has likely many targets. The MoAs for most drugs are dramatically oversimplified. Internalize this and you will restore yourself to sanity.

VDP-53 The Longevity Decentralized Review (TLDR) - Uber for peer review service ⁦@vitadao⁩ Please provide feedback. gov.vitadao.com/t/vdp-53-the…

Midwest started the culture change for a change Maybe related, football took over basketball in the same way

housekeeping gene basically means “highly expressed gene that changes in levels less than my favorite gene does such that when I normalize by the housekeeping gene it exaggerates the importance of my favorite gene”

Please follow @scienceman2023 He’s helped @vitadao in too many ways to count. Just an all around boss 💪. Very grateful to work with him 🙏

@vitadao would fund this. Feel free to DM me about it.

Hey @vitadao community, What do you think about us funding the following DCT (decentralized clinical trial)? h/t @vincentweisser 1/ 🧵

Our latest: 1) provides potential mechanism of action for Chloroquine involving inhibition of sphingolipid initiating enzyme, serine palmitoyltransferase 2) suggests sphingolipids are key host factors for diverse pathogens incl. potentially SARS-CoV biorxiv.org/content/10.1101/…

Always good to assume people don’t believe the extreme interpretation of what they say Being mad at the extreme interpretation only harms the ones who believe it

Don’t discriminate based on skin color but rest of your message stands.

I just funded 8 @vitadao curated longevity grants on @gitcoin gitcoin.co/grants/cart/bulk-… One has to have DAI and ETH to use @zksync checkout to minimize fees. Web3 user experience could use some improvements to go more mainstream, but pretty impressive everyone! Thanks Gitcoin!

Just tweeting this post I wrote so I can pin it, would be grateful for any feedback 🙏 Thanks @SiMaclennan for bringing the graphic to life! vitadao.medium.com/public-he…

I just voted on the VitaDAO 2024-2025 Mandate proposal to in the next two years: ☑️ launch 10 IPTs ☑️ fund $10M of commercializable research ☑️ generate $1M in revenue via the member portal ☑️ make VitaDAO a top 100 crypto community ☑️ grow the treasury by $15M snapshot.org/#/vote.vitadao.… @vitadao #Snapshot

Banks say crypto is risky because banks themselves are risky Banks legally hold almost 0% of our deposits, such that if there is a bank run the whole system crashes So much worse than crypto Bank bailouts make the problem worse. At least crypto wiping people out teaches the right lesson

What happened in the Alzheimer’s field with amyloid beta is not an isolated incident. Other areas of research have similar stories.

THANK YOU again so much to @biogerontology @ScheibyeKnudsen @Dr_Bischof, Daniela Janina Bakula, Polly Firs, @MaxUnfried, and many others. @ARDD_Meeting (Aging Research & Drug Development) is an incredible event. Great city and venue, great research and innovation on many fronts. Very grateful to attend to learn about everyone’s exciting work! Sponsors like @InSilicoMeds @vitadao @Molecule_dao and many others play a huge role in making this a top notch event through their financial and human resources support. Super inspiring!!! Very few must attends but this is one.

The FDA not requiring a clinical endpoint to approve Alzheimer’s drugs opens the door for longevity drugs.👌

Great work. Respect.

I applaud @LEVfoundation for tackling lifespan per se. There’s a lot talk about identifying lifespan extending therapies but most of us aren’t actually doing it. Also for being transparent with the data. Real-time public data should be how things are done. @pumpdotscience and @vitadao with @artan_bio @vitaFAST are also doing real-time, so kudos to all there. Two comments/suggestions for LEVF’s upcoming lifespan trials, RMR2: 1) it’s great that LEVF's next round of treatments are focused on adding back functionality. Aging is about deficits (e.g., bone, muscle loss, loss of immune diversity). Thus, it’s exactly the wrong thing that most drugs are inhibitors. Two wrongs don’t make a right. More drugs need to be designed to activate rather than inhibit. 2) RMR2’s four interventions seem solid and they will be combined to see if there is any additive effect. According to Gompertz-Makeham law of mortality (probability of death rises exponentially with age), additive combos will likely not be sufficient. Exponents are multiplication, so we need multiplicative i.e., synergistic treatments to affect lifespan. To find needle-in-haystack synergistic treatments, IMO one needs to test in a more systematic, unbiased fashion before testing in vivo. ln vivo experiments will take a long time to play out. It would be better to find optimal drugs and their combinations in a more scaled time efficient way, e.g., vitro/in silico, before deciding what to put in animals. This is what I'm proposing with our Synthetic Vitality ("combo drugs") project for @vitadao. Please go vote. Voting is live now until tonight. Thank you. snapshot.org/#/s:vote.vitada…

Longevity seems a good candidate to satisfy the full definition of Network State, which includes physical territory. Longevists want physical environments conducive to good health. Clean water and air, healthy fresh food, low crime, etc.

love the question by @NateHindman on how serious vs. unserious should science and DeSci should be. As someone who's been in tradSci for a long time Science is way too serious currently DeSci will naturally get more serious as the stakes raise. No need to force it

should be the norm everywhere

Another banger. “Make no mistake, the 2024 vote split broke into People Who Believe What Their TV Tells Them vs. People Who Look Shit Up On The Internet.”

Biotech investing has much more in common with crypto investing than most people realize. They’re both 99% YOLO, 1% logic. I’m taking no questions.

Schedule of events is now live at ⁦@LongevitySummit⁩ huge thanks to ⁦@DrGlorioso⁩ ⁦@longevitySF⁩ for organizing! Looking forward to being there and presenting our ⁦@vitadao⁩ funded project! longevitysummit.io/schedule-…