The heroes of the cystic fibrosis fight

In 1999, a Microsoft colleague named Paul Flessner approached me with a personal request: Would I be willing to help fund the development of new drugs for cystic fibrosis, an awful lung disease that affects about 30,000 people—including more than 10,000 children—in the U.S. and about 70,000 people worldwide?

Ten years after the discovery of the gene implicated in CF, researchers still had not produced any medical breakthroughs for CF patients, and Paul was concerned that time was running short for his sons. So he asked me to support an effort by a small startup called Aurora Biosciences to screen up to 10,000 chemical compounds a day in an effort to find ones that might help CF patients; at the time, typical screening methods allowed for testing just a few chemical compounds a day.

The whole project was untried and risky. But my dad, who was helping Melinda and me with our early philanthropic efforts, and I reasoned that philanthropists should be willing to take big risks like this, and so we decided to provide $20 million of the $47 million needed to launch this research project.

This pathbreaking work led, over two decades, to several very effective CF medicines, including drugs marketed with the names Kalydeco, Orkambi, and Trikafta. For many CF patients, these medicines produce the kind of miraculous “Lazarus effect” that I would see when I visited with AIDS patients taking cocktails of antiretroviral medicines. In fact, Paul recently sent me a video of one of his sons, a software engineer in his early 30s, running at an altitude of 7,500 feet. “For both boys, it’s like not having CF anymore,” he wrote. “Since Trikafta, one of the boys has stopped taking all of the antibiotics he used to control infections and stopped all airway-clearance therapy. It is a huge new liberty for him.”

Through Paul, I’ve been able to follow the big milestones in this success story. But now, thanks to a new book called Breath from Salt, I understand a lot more about all the people who made these breakthroughs possible, including many thousands of physicians, scientists, statisticians, engineers, patients, advocates, donors, and entrepreneurs.

Breath from Salt is not for everyone. It’s long and sometimes feels overly detailed; I suspect the author, Bijal P. Trivedi, felt obliged to include all of the people she interviewed, even if they played minor roles. But given my interest in the process of discovery and my connection to this specific effort, I couldn’t put the book down.

The book is reminiscent of Tracy Kidder’s 1981 book Soul of a New Machine, which documents the creation of a powerful new computer, because Trivedi leads you on a tour through the ups and downs of the discovery process. She gives it life-and-death urgency and emotion. In fact, I was surprised to learn that she doesn’t have a family connection to CF.

Among the heroes Trivedi profiles is the O’Donnell family, who live near Boston. In 1974, Kathy and Joe O’Donnell had their first child, Joey. Unfortunately, Joey inherited CF mutations from both of his parents, which meant he got the disease. Like all CF patients, Joey could not produce healthy copies of the protein we all need to maintain the balance of salt and water on surfaces in our bodies, such as the surface of the lung. That meant his tiny lungs would fill with thick, sticky mucus, reducing his lung capacity and making him highly susceptible to dangerous infections.

Joe and Kathy knew that many CF patients didn’t make it past adolescence. But they simply would not give up on Joey. They found outstanding healthcare providers, spent months on end in hospitals, and dedicated hours of every day to clapping on Joey’s chest to help free mucus from his airway. Even with Kathy and Joe’s significant resources, their son died at age 12.

Joe, who had grown up in a tough neighborhood but had gone on to become a very successful businessman, found purpose in leading huge fundraising campaigns to spur CF drug discovery. Without his own financial contributions, fundraising prowess, and business acumen, there’s no way that CF patients would have the treatments they have today. Joe helped raise money for drugs that would have worked for his son, but the book makes it clear that that wasn’t his motivation. He did it for all children with CF.

The second hero of this story is the Cystic Fibrosis Foundation and its three generations of leaders. Given that CF is an orphan disease that affects only a small slice of the population, it’s remarkable to me that this organization grew to become one of the biggest and most powerful players among disease-research charities. I was impressed by the courage of the foundation leaders who made the controversial decision to place almost all their chips on scientific research and to build sophisticated patient registries to facilitate clinical trials. I also admired the creative “venture philanthropy” approaches the CF Foundation used to fund drug discovery.

The third group of heroes is the CF researchers who kept building the knowledge necessary to produce these drugs, such as the San Diego-based team that started with Aurora and now work for a company called Vertex. Breath from Salt shows us their passion for their work, the ways they fought to protect it even when it wasn’t paying financial dividends, and the remarkable scientific breakthroughs they pioneered.

It was touching to learn about emotional moments in the process, such as when Fred Van Goor, one of the leaders of the San Diego team, heard the results of the clinical trial on the drug combination he’d helped to create. “Hearing how the patients’ lungs responded to this new medicine, how dramatically it opened them up, made [him weep]. Van Goor was unprepared for the pent-up emotions that had been swirling in him for the past 18 years, and for how desperately he’d wanted those treatments to work.”

The final group of heroes are compassionate caregivers, including parents, who fought to keep CF children alive when they had few tools for doing so. This list includes not just senior physicians like Joey’s doctor at Massachusetts General Hospital but also unsung heroes like a physical therapist who grew very close to Joey and so many other children while working with them every day to help them keep their lungs as healthy as possible.

Breath from Salt is an inspiring book. It’s a testament to what’s possible when passionate leaders help to harness the unique strengths of philanthropy, nonprofits, government, academia, biotechs, big pharma, and medical providers. Given the remarkable pace of innovation in the biosciences, I know there will be more success stories like this in the coming years.