The documentary opens with the controversial announcement by Chinese researcher He Jiankui in 2018, who claimed to have created the first gene-edited babies. This event triggered widespread condemnation and highlighted the ethical complexities surrounding gene editing. The narrator emphasizes that this moment ushered in a new era where humans can control and change their genes, but also poses immense promises and perils.

Dr. Wendy Chung, a gene hunter at Columbia University Medical Center, dedicates her work to over 5,000 rare diseases. She works closely with affected families, like the Rosens, whose daughter Susannah suffers from a rare degenerative condition caused by a KIF1A gene mutation. Dr. Chung's personal tragedy fuels her passion to make a difference in the lives of her patients, serving as a 'Sherpa' in their long and challenging journey.

The film traces the historical understanding of heredity, from ancient Greek theories to the 19th century. Early beliefs included Pythagoras's mystical vapors and Aristotle's concept of inherited information. The concept of preformationism, where a tiny, complete person exists within sperm or egg, was prevalent. This eventually gave way to a need for a new theory to explain how traits are inherited and how human interventions could improve breeding. This search led to Gregor Mendel's groundbreaking experiments with pea plants, where he discovered the elemental and unchangeable nature of inherited information, paving the way for the concept of genes.

Thomas Hunt Morgan, initially skeptical of genetics, used fruit flies in his 'Fly Room' to prove Mendel's theories and advance the understanding of heredity. By tracking mutations, like white-eyed flies, he discovered that genes are physical objects arranged like 'beads on a string' along chromosomes. His student, Alfred Sturtevant, then used this data to invent genetic mapping, showing the relative locations of genes on chromosomes.

Dr. Chung, driven by her personal experiences, has become a dedicated advocate for her patients. The urgency of Susannah's condition, caused by the KIF1A mutation, highlights the immediate need for treatment. As her condition worsens, Luke Rosen's family embarks on campaigns like 'We Need a Mouse' to generate awareness and funding for research into a mouse model for KIF1A, a crucial step in developing potential therapies.

The documentary takes a stark turn to discuss the problematic history of eugenics, a pseudo-science championed by Francis Galton, Darwin's cousin. The idea of 'improving' the human race gained traction in early 20th-century America, leading to forced sterilization laws for those deemed 'unfit.' This ideology was later embraced and horrifyingly escalated by Nazi Germany under Adolf Hitler, where eugenics provided a justification for genocide, illustrating the dangers of misusing scientific knowledge to control human heredity.

Erwin Schrödinger, a physicist, theorized that life's instructions must be encoded on genes as a 'code-script.' This led to the pivotal question of what chemical compound carries this genetic information. While proteins were initially favored, Oswald Avery's experiments pointed to DNA, the 'stupid molecule' with only four chemical components (A, T, C, G). James Watson and Francis Crick, using Rosalind Franklin's Photo 51 without her explicit permission, famously deciphered DNA's double helix structure, revealing how genetic information is stored and replicated. Their discovery, which earned them a Nobel Prize (Franklin had passed away), revolutionized biology, explaining how genetic information translates into life.

The discovery of DNA's structure opened new questions about how it translates into life. Scientists later discovered the 'Central Dogma' of biology: DNA to RNA to protein. RNA copies genetic information from DNA to create functional proteins. Further research by Sydney Brenner and Marshall Nirenberg confirmed that sets of three DNA bases ('codons') specify 21 different amino acids, which in turn combine to form all proteins in our bodies. This universal genetic code, shared by all life forms, established a fundamental understanding of life's mechanisms.

The story of Leonore Wexler and her daughters, Nancy and Alice, highlights the devastating impact of Huntington's disease, a progressive and fatal neurological disorder. Nancy Wexler, despite having no formal genetics training, embarked on a personal quest to find the gene responsible for Huntington's. She used the concept of genetic mapping with 'markers' – small spelling differences in DNA – to narrow down the search.

Nancy Wexler's relentless search led her to a remote village in Venezuela, where a large, intergenerational family was heavily affected by Huntington's. Through meticulous collection of blood and skin samples and constructing a vast family tree, her team, led by Dr. David Botstein, was able to correlate genetic markers with the disease. This breakthrough led to the discovery of the mutated gene on chromosome 4, which contained a repeating 'CAG' sequence, causing the devastating symptoms of Huntington's. This discovery, though not a cure, enabled testing for the disease, presenting agonizing choices for affected families.

The ability to test for Huntington's disease raised profound ethical questions. Nancy Wexler chose not to be tested, preferring to live with ambiguity rather than the certainty of a devastating diagnosis without a cure. The Allen family in the UK illustrates a similar dilemma. Jenny, one of eight siblings at risk, decides to get tested, driven by the hope of future treatments and the desire to be a beacon for her family. Her emotional journey highlights the personal stakes involved in genetic testing.

The success in understanding DNA's code ignited the ambition to edit it. Paul Berg's experiments in the 1970s, using bacterial enzymes to cut and paste DNA from different species, marked the birth of recombinant DNA technology. This ability to combine DNA from two different life forms, a process Berg called 'recombinant DNA,' was a monumental step, turning scientists into 'engineers' of life. This revolutionary technology led to a moratorium on certain experiments due to safety concerns, culminating in the Asilomar Conference which set guidelines for safe research.

The controversy surrounding genetic engineering paved the way for its commercial application. Bob Swanson and Herb Boyer founded Genentech, a pioneering biotechnology company. Their first success was using recombinant DNA to produce insulin, a life-saving drug, on an industrial scale. This marked the beginning of a multi-billion dollar biotech industry, producing drugs for various diseases and fundamentally changing medicine.

Luke Rosen continues his tireless advocacy for Susannah, attending conferences with Dr. Chung to find solutions for KIF1A. At one conference, a new compound for Huntington's disease shows promising results, offering a glimmer of hope. Pete Allen, a Huntington's patient, experiences significant improvements on this new drug. This successful clinical trial inspires hope that similar treatments can be developed for other rare genetic diseases, including Susannah's KIF1A. The documentary concludes with the profound sentiment that for the first time, a light can be seen at the end of the tunnel for many families afflicted by genetic conditions.