Signal Hill FEATURE | Unknown Unknowns
Nov 4, 2025
Lio Wong, writer and cognitive scientist who narrates a first-person search for answers about starting testosterone. Andy Perfors, cognitive science professor and mentor who reflects on living with ambiguity after coming out as trans. They explore parsing limited medical evidence, ‘theoretical risk’ in guidelines, personal experiments with hormones, and choosing lived experience amid scientific uncertainty.
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Why Guidelines Call Cancer Risk Theoretical
- Scientific guidelines often state mechanisms (like aromatization of testosterone to estrogen) without resolving whether those mechanisms produce real long-term harms.
- Lio Wong reads UCSF guidance that calls a plausible pathway a "theoretical risk" because lifetime outcomes haven't been measured.
Sleepless Literature Rabbit Hole
- Lio repeatedly re-reads the same papers hoping for clarity and alternates between hope and panic.
- He describes the exercise as hopeful and paranoid, rereading studies at 3 a.m. in Rotterdam.
Everyday Reasoning Mirrors Formal Science
- Human cognition routinely makes reasonable decisions from sparse, noisy data; lab decision tasks mirror everyday uncertainty.
- Lio cites his advisor Josh: we keep figuring out beliefs using only sparse noisy data of an uncertain world.