CHAPTERS
Colossal Biosciences: What a de-extinction company actually does
Joe and Ben open with Ben’s role as CEO/cofounder of Colossal Biosciences and what “de-extinction and species preservation” means. They frame the work as real-world Jurassic Park—then immediately pivot to how the science differs from movie fantasy.
How Ben met George Church and why mammoths became the first target
Ben recounts a call with synthetic biology pioneer George Church that unexpectedly spiraled into a mammoth-focused plan. He explains why mammoths were the logical starting project and how viral attention expanded Colossal’s scope to other extinct species.
The mammoth workflow: ancient DNA recovery, AI assembly, and reference genomes
Ben walks through the de-extinction pipeline: finding degraded ancient DNA, assembling fragments, and comparing genomes to living relatives. He emphasizes that the hardest parts are computational—AI, mapping, and building reliable reference genomes that often don’t exist.
Mammoths weren’t that long ago: extinction timing and Wrangel Island theories
They zoom in on mammoth history, highlighting how recently the last mammoths lived and discussing competing extinction hypotheses. Wrangel Island becomes the focal point for bottlenecks, inbreeding, and possible freshwater shortages.
Elephants up close: behavior, intelligence, and ethical discomfort with riding them
Joe and Ben digress into elephant behavior, herd dynamics, and personal experiences interacting with them. The conversation touches on animal intelligence and the ethical tension of tourism practices like riding elephants.
Museum basements, permafrost expeditions, and the ‘miracle pup’ thylacine genome
Ben describes the real-world scavenger hunt: expeditions to retrieve specimens and deep museum archive searches. He shares standout examples from thylacine work—unexpected preserved samples enabling near-complete genomes and revealing how under-inventoried museum holdings can be.
Thylacine sightings, Papua New Guinea ‘singing dogs,’ and separating myth from data
Joe asks about alleged thylacine sightings; Ben explains why his team doesn’t buy them after extensive sampling and camera trapping. The discussion detours into Papua New Guinea singing dogs and how cryptid-style narratives complicate real conservation science.
Synthetic biology basics: bridging genome gaps with precision edits and phenotype targeting
They clarify how de-extinction doesn’t require a perfect ancient genome. Ben explains modern editing: from CRISPR to nucleotide-level changes, synthesizing DNA blocks, and focusing edits on phenotype-driving regions rather than rewriting everything.
Woolly mice: multiplex edits, off-target screening, and public obsession
Ben details Colossal’s woolly mouse proof-of-concept: editing multiple genes at once, verifying safety, and demonstrating end-to-end capability. The conversation covers why it mattered scientifically, how viral it became, and how they manage breeding, care, and display requests.
Why dire wolves: indigenous partnerships, wolf conservation, and finding usable dire wolf DNA
Ben explains how conversations with MHA Nation and the red wolf crisis helped shape the dire wolf project. He walks through the key scientific breakthrough: leveraging a tooth and a skull’s petrous bone to reach high genome coverage necessary for reconstruction.
‘You made a dire wolf’: revealing Romulus, Remus, and Khaleesi and how they’re raised
Joe reacts to photos and videos of the first dire wolf pups and their rapid growth. Ben describes their secure 2,000-acre preserve, veterinary oversight, vaccines, diet plans, and the early emergence of hunting behaviors and unexpected physical traits like mane-like fur.
Backlash, ‘playing God,’ and the politics of science vs. publish-or-perish
They discuss criticism from journalists and academics, shifting goalposts, and philosophical objections about what counts as a ‘real’ species. Ben argues the company’s integrated, systems-level approach and conservation focus contrasts with academic incentives and institutional inertia.
Red wolf genetic rescue: cloning from blood and frustration with bureaucracy
Ben introduces Hope, the first cloned red wolf, and describes creating multiple individuals from different genetic lines. He emphasizes a major conservation leap—non-invasive cloning from blood-derived cells—and contrasts supportive vs. obstructive government responses to rapid innovation.
Scaling limits, artificial wombs, and the ethical line around humans
The conversation broadens to where de-extinction should stop, why keystone and human-caused extinctions matter most, and how artificial wombs could transform endangered species recovery. They confront future social/ethical implications, especially if ex-utero gestation ever reached humans.
Rewilding realities: stakeholder working groups and predator-prey ecosystem effects
Ben describes how Colossal plans for rewilding long before animals exist by forming working groups with governments, landowners, and indigenous communities. They discuss lessons from wolf reintroductions, the need for measured ecology, and how Tasmania planning includes even logging stakeholders.
Tasmania deep dive: thylacine ecology, devils’ cancer, invasive cats, and engineering cane-toad resistance
They explore how reintroducing a top predator could reshape Tasmania’s ecosystem, potentially reducing disease spread in Tasmanian devils by removing sick individuals. The chapter ends with a concrete conservation-genetics example: a single-letter edit conferring massive cane-toad toxin resistance, with plans to help quolls and other marsupials.
