Breakthrough drugs aren't always driven by novel biological targets. Major successes like Humira or GLP-1s often succeeded through a superior modality (a humanized antibody) or a contrarian bet on a market (obesity). This shows that business and technical execution can be more critical than being the first to discover a biological mechanism.

Some individuals possess genetic variants, like FOXO3, that slow their biological clocks. The goal of emerging "gero-protectors" is not immortality but to replicate this advantage for everyone, slowing aging to compress frailty into a shorter period at the end of life and extend healthspan.

Progress in drug development often hides inside failures. A therapy that fails in one clinical trial can provide critical scientific learnings. One company leveraged insights from a failed study to redesign a subsequent trial, which was successful and led to the drug's approval.

A $2,000 preventative injection like a PCSK9 inhibitor sounds expensive. However, its cost is likely justified when calculated against the massive societal and individual expense of future medical bills, plus the economic value of additional healthy, productive years.

The Polygenic Index (PGI) summarizes thousands of minor genetic effects into a single predictive score for complex outcomes like educational attainment or heart disease. This 'age of genomic prediction' will radically alter social domains like insurance, education, and even embryo selection, creating profound ethical challenges.

Unlike using genetically identical mice, Gordian tests therapies in large, genetically varied animals. This variation mimics human patient diversity, helping identify drugs that are effective across different biological profiles and addressing patient heterogeneity, a primary cause of clinical trial failure.

Focusing solely on LDL is a mistake. Even individuals with a genetic mutation leading to lifelong low LDL levels can still have cardiovascular events if they have other unmanaged risk factors like metabolic syndrome, obesity, or diabetes, highlighting the need for a comprehensive approach.

Step Pharma's confidence in their drug's clean safety profile originated from studying a human population with a natural mutation in the CTPS1 gene. This real-world genetic data de-risked their therapeutic approach from the outset, guiding development towards a highly selective and safe inhibitor.

Universal cholesterol screening in young children acts as a trigger for cascade screening, where parents (often in their 30s) and grandparents (50s) are also tested. This uncovers and allows for treatment of familial hypercholesterolemia across three generations from a single pediatric test.