E60: The 2021 Bestie Awards PLUS Jack Dorsey starts the Web3 Wars

Tiger Global turned late-stage venture investing into a near-automated machine: founders could submit one sheet of metrics and receive a term sheet within two days. The hosts said Tiger deployed roughly $15 billion in 2021 and built third-party data infrastructure to evaluate companies at extraordinary scale.

Microsoft Teams put enough pressure on Slack that Chamath Palihapitiya said Slack effectively had no choice but to sell to Salesforce. He cited that episode while praising Satya Nadella’s ability to turn Microsoft into a larger, more aggressive company without attracting the backlash facing other technology giants.

Coinbase’s decision to remove political activism from the workplace cost only about 5% of employees, according to David Sacks, and was followed by continued hiring and a major IPO. Sacks presented Brian Armstrong’s policy as evidence that a company could explicitly prioritize mission over internal politics without triggering the organizational collapse critics expected.

Sequoia’s new evergreen fund changed the venture model by allowing investors to remain exposed to successful companies instead of forcing conventional fund-style exits. After DoorDash, Airbnb, Snowflake and Unity created more than $300 billion in combined value, both Jason Calacanis and David Friedberg viewed the permanent-capital structure as a major competitive advantage.

The NFT boom was already producing extraordinary economic activity: OpenSea’s monthly volume reportedly jumped from $8 million in January to $3.46 billion in August 2021. Friedberg expected much of the speculation to end badly, but believed the underlying model could let artists, writers and musicians sell directly to audiences without surrendering large margins to intermediaries.

In-vivo CRISPR moved from theory toward medicine in 2021, with genetic material delivered directly into patients to suppress a toxic liver protein and produce modest vision improvements in inherited blindness. The important step was not merely editing cells in a laboratory, but getting the body itself to perform the genetic correction.

Chinese researchers demonstrated a synthetic system that used biological proteins outside plants to build starch, pointing toward food production with far less dependence on conventional agriculture. Friedberg considered the specific system less important than the broader possibility of combining atmospheric carbon, renewable electricity and engineered biology to manufacture food.

The hosts disclosed that serious internal conflict nearly fractured the podcast: one public feud was real, while a larger dispute happened privately and ultimately produced an NDA and operating agreement. Jason Calacanis said he and Chamath spent substantial time mediating between the others to keep the show together, making its relaxed on-air chemistry considerably harder-won than listeners knew.