All-In PodcastE35: Biogen's controversial Alzheimer's drug approval, the billionaire space race, Bitcoin & more
CHAPTERS
- 0:00 – 2:38
Besties banter: early start, Chamath in Europe, and climate whiplash
The episode opens with playful ribbing about camera angles and the brutal Saturday-morning start time. Chamath checks in from Europe, showing off his surroundings and describing extreme day-to-day weather swings as a visceral example of climate change.
- •Cold open jokes about Jacob’s camera proximity and the early recording time
- •Chamath’s remote setup and “castle”/cathedral ceiling banter
- •Quick travel update: London’s rapid temperature and rain shifts
- •Climate change framed as something Europeans “feel every day”
- •Roundtable roll call: Sacks and Friedberg introduced
- 2:38 – 6:04
Biogen’s Alzheimer’s drug approved despite advisory backlash: what the drug is
Jason tees up the controversial FDA approval of Biogen’s aducanumab, highlighting resignations and the high annual price. Friedberg explains the science: it’s a monoclonal antibody designed to clear amyloid plaque, a target whose causal role in Alzheimer’s remains unproven.
- •FDA approves Biogen’s aducanumab; advisory committee voted against
- •Three advisory members resign; concerns about modest efficacy
- •Drug is a monoclonal antibody (“-mab”) aimed at amyloid plaque
- •Amyloid hypothesis explained as plausible but not proven causality
- •Clinical results vs placebo described as underwhelming overall
- 6:04 – 14:51
Efficacy slicing, accelerated approvals, and the pricing controversy ($56K/year)
The group digs into how Biogen revived a previously shelved program by emphasizing outcomes in high-dose subgroups. They debate whether low-risk but low-evidence drugs should be approved, and how pricing is justified even when manufacturing costs are low.
- •Biogen re-files using high-dose subgroup showing ~23% slower decline
- •Debate over correlation vs causation and mixed cognitive endpoints
- •Manufacturing cost vs list price: “$5 to make” vs ~$56,000/year claimed
- •Ethics of monetizing ‘hope’ when payers shoulder costs
- •FDA’s role vs physicians’ role in interpreting labels and evidence
- 14:51 – 26:44
Medicare Part B incentives and the ‘lottery ticket’ problem in healthcare economics
Chamath and Friedberg outline how Medicare Part B reimbursement can create perverse incentives, including physician markups tied to drug price. The conversation broadens into systemic issues: fragmented agency jurisdiction and how socialized payment pools can fuel medical inflation.
- •Medicare Part B: physicians allegedly earn a % of drug price (bad incentive)
- •Copays and who ultimately bears cost across insurers/taxpayers
- •Inter-agency mismatch: FDA approves, CMS pays—Congress doesn’t fix system
- •Friedberg’s ‘lottery ticket’ framing: upside for patients, diffuse cost burden
- •Sacks favors provisional access for terminal diseases with revisiting later
- 26:44 – 32:56
Bezos, Branson, and risk: should billionaires fly the first human missions?
The besties pivot to Jeff Bezos flying on Blue Origin’s first crewed flight, comparing safety narratives across Blue Origin, SpaceX, and Virgin Galactic. They debate whether historical mishaps inform current risk, and whether it’s a smart brand move or needless danger.
- •Bezos announces he’ll fly with his brother; auction seat climbs in price
- •Jason frames ‘risk of ruin’ using past flight failures; Friedberg pushes back on stats misuse
- •Discussion of first-crewed-flight risk vs tested systems and safety confidence
- •Sacks calls it an unnecessary ‘brain fart’ and suggests VR instead
- •Speculation Bezos goes full-time/CEO at Blue Origin after the flight
- 32:56 – 35:06
Why space is a government-success story: contracts, competition, and innovation spillovers
The conversation reframes space as a model of effective government intervention via milestone-based contracting rather than direct development. They compare modern private-sector execution to the costly Space Shuttle era and argue this dynamic could spark a new industrial age.
- •Government contracts as incentives that seed private R&D (SpaceX example)
- •Privatization vs shuttle program: cost and risk tradeoffs
- •Space as the next industrial platform, analogous to semiconductor spillovers from Apollo
- •Sacks supports ‘fund the goal, contract the delivery’ rather than building in-house
- •Discussion of applying this model to other areas (manufacturing, infrastructure)
- 35:06 – 42:55
Owning vs dominating space: military ‘high ground’ debate and escalating geopolitics
Jason argues the West must dominate space to prevent authoritarian advantage; Chamath disputes the idea of ‘owning’ space while Sacks emphasizes military realities. The segment turns to space-based weapons concepts and the strategic importance of orbital superiority.
- •Jason’s thesis: democracies can’t cede space advantage to rivals
- •Chamath: space is too vast to ‘own,’ but strategic positions matter
- •Sacks: warfare history favors the high ground; future artillery could be space-based
- •Examples discussed: anti-satellite attacks, kinetic ‘rods from God’ concept
- •Tension between innovation and future regulatory constraints (ITAR, restrictions)
- 42:55 – 51:47
Back-to-office policies at Big Tech: supervision, culture, and onboarding at scale
The besties survey Apple, Amazon, Google, Twitter, and Meta policies converging on hybrid work. Sacks argues remote work exposes management’s inability to detect low performers, while Chamath highlights onboarding as the unsolved challenge for large organizations.
- •Hybrid norms emerging: 3 days in-office / 2 remote at multiple companies
- •Sacks: petitions and internal activism at Apple; management ‘caves’ and creates a loop
- •Remote work makes top performers better but lets low performers hide
- •Chamath: onboarding new hires remotely is the biggest gap
- •Friedberg: hybrid meetings create awkwardness and coordination conflicts
- 51:47 – 56:49
Measuring productivity in distributed teams: Slack workflows, hubs, and ‘TPS report’ jokes
They move from philosophy to tactics: Sacks endorses hubs for certain functions, while Friedberg notes measurable productivity gains in remote claims/customer service. Jason describes simple start-of-day/end-of-day reporting in Slack to clarify accountability.
- •Hubs vs fully remote: call centers and measurable jobs discussed
- •Friedberg: Metromile remote shift increased throughput per employee
- •Jason’s SOD/EOD/EOW Slack practice to set intent and document outputs
- •Remote work framed as manageable with systems and measurement
- •Salesforce positions Slack as the anchor product for distributed work (marketing + strategy)
- 56:49 – 57:41
Real estate and housing crunch: office vacancies, institutional buyers, and NIMBY constraints
The discussion connects hybrid work to commercial vacancies (especially in San Francisco) and juxtaposes that with a nationwide housing shortage. They argue the core driver is supply restrictions and permitting/NIMBYism, which institutional capital exploits by bidding up homes.
- •San Francisco office vacancy cited (millions of square feet) alongside housing crisis
- •Institutional buyers (hedge funds, platforms) bidding up single-family homes
- •Sacks: bipartisan populist backlash brewing; California proposes extreme subsidies
- •Root cause: building is too hard—zoning, approvals, NIMBYism limits supply
- •Jason: modular/factory-built housing could help if regulation allows it
- 57:41 – 1:05:01
Inflation ‘head fake’ and macro crosscurrents: breakevens, QE, and tech deflation
Chamath argues inflation fears may be overstated, citing falling 10-year breakevens and the likelihood that supply will respond once builders regain confidence. Sacks counters with the macro tug-of-war: inflationary fiscal/monetary policy versus long-run technological deflation.
- •Chamath: 10-year breakeven as market inflation gauge; recent softening noted
- •Short-term CPI spikes vs longer-term normalization thesis
- •Housing supply response depends on rate/inflation expectations
- •Sacks: government debt + ongoing QE are concerning for inflation and rates
- •Framework: tech-driven deflation vs government-set-price sectors (healthcare, education)
- 1:05:01 – 1:15:58
ProPublica IRS leak and billionaire taxes: income vs wealth, borrowing against assets, and deductions
The besties react to ProPublica’s leaked tax data, focusing on both the privacy breach and the public misunderstanding of how income taxation works. They explain why unrealized gains aren’t taxed, how wealthy individuals borrow against assets, and how interest deductibility can amplify advantages.
- •ProPublica leak of returns: story is as much about the breach as the tax outcomes
- •Core concept: US taxes recognized income, not annual unrealized asset appreciation
- •Wealthy ‘live on credit’ via margin loans; consumption taxes still apply on spending
- •Chamath: interest deductibility can further ‘pervert’ incentives when borrowing to invest
- •Sacks: leverage carries liquidation risk when collateral falls; not a free lunch
- 1:15:58 – 1:22:33
Bitcoin conference ‘toxicity’ and online tribalism: maximalism, cult dynamics, and status anxiety
Jason describes the Miami Bitcoin conference’s strict maximalist posture and argues it’s evolving into “toxicity” that repels newcomers. The group broadens into why online communities harden into tribes, tying it to frustration, status signaling, and social media-driven desire.
- •Conference rule: don’t mention other cryptocurrencies; stage stunts (Dogecoin shirts)
- •Jason: maximalism becomes toxicity—attack critics to defend the ‘one true’ coin
- •Sacks counters: Jason also denounces many crypto projects; debate over moral panic
- •Chamath: frustrated young men find belonging, then stop thinking independently
- •Fight Club quote used to frame generational anger; Instagram amplifies comparison
- 1:22:33 – 1:31:40
Meritocracy vs diversity: Snowflake CEO apology, speech chill, and ‘losing the script’ vs global competition
They dissect Snowflake CEO Frank Slootman’s comments prioritizing performance and the backlash that prompted an apology. The segment becomes a critique of shallow discourse, a call for honest debate, and a recurring comparison to China’s 9-9-6 work culture and strategic focus (including nuclear energy).
- •Snowflake CEO: diversity matters but ‘best person for the job’ comes first; backlash ensues
- •Apology seen as proof CEOs can’t speak candidly without punishment
- •Chamath: society struggles to hold two truths; example: nuclear power is clean/safe yet opposed by parts of environmental movement
- •Sacks: real equality requires school reform/choice; critics focus on easier targets
- •Theme: US domestic priorities misaligned with long-term competition with China
- 1:31:40 – 1:35:36
Science corner finale: induced pluripotent stem cells and the road to human cloning
The episode closes with Friedberg’s “mind blown” science segment explaining induced pluripotent stem cells (iPSCs) and the theoretical path from a body cell to an egg cell and potentially a clone. The besties riff on the implications—clone armies, alternate careers, and sci-fi ethical dilemmas—before signing off.
- •iPSCs: reprogramming adult cells back into stem-like state (Yamanaka factors)
- •Conceptual pathway: cell → iPSC → egg cell; induce division without fertilization (theoretical for mammals)
- •Potential future: cloning from a hair/skin cell within decades (speculative)
- •Humorous debate: would you befriend or destroy your clone; ‘clone wars’ jokes
- •Wrap-up and farewell banter from the besties
