Breakthrough by William Pao Review – The Drugs Work | Science and nature books

'A A lot of creativity goes into developing new drugs, and most of it is seen and appreciated by only a small handful of people.” This is partly what inspired William Pao, an oncologist turned pharmaceutical executive, to write “Breakthrough.”, It tells the stories of some of the most important discoveries in modern medicine.

Like many in the drug discovery field, Pao has his own story about a family illness. When he was 13, his father died suddenly of colon cancer – an event that his family found to be a “catastrophic shock.” It charted his course: “After my father’s death, I vowed to dedicate my life to making a difference for patients like him,” he writes.

Pao's career included positions at Memorial Sloan-Kettering Cancer Center in New York, Vanderbilt University, Pfizer and Roche. But breakthrough is not a memoir. Nor is it explicitly a defense of “Big Pharma.” Instead, it focuses on the innovative achievements of determined researchers working to develop treatments for devastating diseases.

The diseases are well known – lung cancer, breast cancer, sickle cell anemia, hemophilia, AIDS and Covid-19. The chemistry, less so: Pao begins gently with a useful, clear introduction to DNA, mRNA, and peptides before launching into chapter-by-chapter case studies of drug development.

Most of these breakthroughs are the result of careful experiments with microscopic particles. But pure luck also plays a role. Take the discovery of paracetamol, for example. Its precursor, a drug called acetanilide, was originally manufactured and marketed (as antifebrin) by a German paint manufacturer. Antifebrin was the product of a complete accident after a pharmacist mistakenly administered a completely different compound to a patient expecting treatment for worms. This could have ended in disaster, but instead had the effect of lowering his fever. And while many types of innovation require a thorough understanding of the properties of antibodies, kinase inhibitors, and the like, sometimes a little improvisation helps. At some point, a group of spinal muscular atrophy researchers who didn't have specialized equipment found a way to transform an old Coke machine into a custom-made device for storing and loading refrigerated sample plates.

A highlight of the book is Pao's account of the development of antiviral drugs against Covid-19 – a process carried out via video call as researchers gathered in their makeshift home offices to review the molecular structure of the most promising compound “and decide which one.” Parts to be used” to be kept and what to be thrown away”. It was one of the fastest successes in the history of drug development. Despite everything that went wrong in the pandemic response, it's worth enjoying what went right.

“Much of what we do in pharmaceutical research seems to go nowhere and can look like a failure,” Pao writes. But “everything we learn and discover, especially in a well-connected ecosystem with good institutional memory and data sharing, has the potential to be important at a later date.” At the top of this ecosystem, of course, are individuals – often tenacious and brilliant. Pao brings them to life in his pen portraits: A young man who reads “The Double Helix,” James Watson's account of the discovery of DNA, is inspired to pursue a career in gene editing. An aspiring doctor who witnesses the rapid deterioration – and death – of a patient due to sickle cell anemia ends up working to cure it. A little girl whose father is dying of lung cancer and who is inspired to study biology by walks in the forest with her grandfather develops new treatment options for therapy-resistant breast cancer.

In the end, the victories are theirs. But as Breakthrough makes clear, we all owe much to the “slow, incremental, and seemingly meandering innovation of dedicated scientists around the world, driven by curiosity and a thirst for knowledge and solutions.”