In Breakthrough, William Pao ’86 shines a light on unsung medical heros.

When William Pao was 13 and attending Sidwell Friends, his father died of metastatic colon cancer. “I really did vow then to make a difference for patients,” he said at a Conversation With Friends event in April. He has more than lived up to that promise. Today, Pao, an oncologist and scientist, helps develop new cancer medications, and he has written a book about pioneers in medicine and drug discovery, Breakthrough: The Quest for Life-Changing Medicines.

To call Pao’s path, from Sidwell to author, “impressive” would be an understatement. After earning a bachelor’s degree from Harvard, Pao did a combined M.D. and Ph.d. in biology at Yale. From there, he studied internal medicine at NewYork-Presbyterian’s Weill Cornell Medical Center, did a medical oncology fellowship at Memorial Sloan Kettering, and worked at Vanderbilt University as a medical school professor and director of personalized cancer medicine. He was head of pharma research and early development at Roche and chief development officer at Pfizer before launching his own biotech firm, Revelio Therapeutics. Clearly, William Pao is a determined man.

It’s a necessary quality for a scientist in his field. Since its founding over a century ago, the FDA has approved roughly 1,800 medications. (More than 20,000 drugs are sanctioned for U.S. marketing; but to be labeled “FDA-approved,” rigorous testing is involved.) If 1,800 since 1906 seems low, consider the odds. There are 30 to 40 trillion cells in the human body, each with their “own signaling pathways, their own molecules, their own structures, their own biology that we still don’t fully understand,” Pao said. On top of that, there are 8 billion unique people on the planet who have to be able to tolerate any new medicines. Finding a molecule that doesn’t just have a medically significant effect on the human body but improves on billions of years of evolution and can get over the finish line at the FDA is seriously difficult. Pao has helped find 20 of them—20 approved medications that help cancer patients like his father.

And yet, when the world hears about new drugs, the names in the headlines are the pharmaceutical companies, universities, or maybe one or two scientists. But bringing medicine into the world is a years-long process with hundreds of authors. “The medicine doesn’t say anything about the scientists behind it,” Pao said. “I really wanted to highlight the unsung heroes of drug development.” To do that, his book, Breakthrough, explores the work behind eight pioneering medicines: from Tylenol, which was discovered by accident (it didn’t treat worms, but it brought down a fever), to Risdiplam, the first oral RNA-splicing modifier approved by the FDA.

All medications hew to what Pao calls a “central dogma”: DNA to RNA to protein. The DNA is a blueprint; the RNA has the sub-plans to make the protein; the protein is what affects the molecules inside cells. Scientists are essentially tricking cells into incorporating proteins in order to get them to behave differently. In the case of Risdiplam, the medicine targets the SMN2 gene, which produces the SMN protein, which helps keep spines healthy. Those with spinal muscular atrophy, often called “floppy baby syndrome,” don’t make enough SMN protein. Risdiplam tells the SMN2 gene to make more of it. The National Institutes of Health calls Risdiplam transformative. 

“These medicines don’t appear out of thin air,” Pao said. “They are 100 years in the making in terms of being able to build upon scientific knowledge over decades. Think about that the next time you take a pill.”

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To watch the full Conversation With Friends with William Pao, or to find other conversations, go to sidwell.edu/conversationwithfriends.