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Success in Failure

John Tisdale, Class of 1986

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John Tisdale ’86 pauses for a moment and looks up at the first slide of his PowerPoint presentation.

With a slight smile, he turns to the audience in the College’s new science center’s auditorium and says, “Today, I’m going to show you the highlights – the experiments that worked over the last 15 years. But there were at least a hundred that didn’t. Perhaps that’s the first and most important lesson.”

That lesson is about failure. Tisdale knows failure. He knows it in a way that few people do. In fact, he doesn’t shy away from it. As a scientist, he knows that failure is the surest path to discovery.

“Failures, of course, are frustrating at the moment they happen,” Tisdale admits, “but they lead to your success.”

And Tisdale’s success is something that has ramifications for the more than 2 million people worldwide suffering from sickle cell anemia.

Over the last two years, the work of Tisdale and his team at the National Institutes of Health in Bethseda, Md., along with other researchers, has garnered considerable attention, from The New England Journal of Medicine to NBC Nightly News. His team, of which he is the senior investigator, made a breakthrough in treating sickle cell disease through bone marrow transplants.

Rather than replacing all of the bone marrow through chemotherapy and radiation – which had been the traditional treatment – Tisdale’s team found that they could insert as little as 10 percent of new bone marrow from a matched donor, and this new bone marrow would eradicate the sickle cells. With this procedure, doctors now won’t have to employ the high doses of radiation and chemotherapy to make the new bone marrow take, meaning lower costs, a lot less medical support and fewer complications.

“Our patients have had a remarkable change in their lives,” Tisdale says of this new treatment. “They’re no longer being admitted to the hospital for frequent pain crises, and they’ve been able to stop chronic pain medications. They’ve been able to go back to school and work, get married and have children. Given these results, our regimen will likely have broad application to other nonmalignant diseases and can be performed at most transplant centers.”

The next hurdle for Tisdale’s team to clear: Make the procedure work for someone who has a half match – such as a parent, sibling or child – thereby greatly increasing the number of patients eligible for treatment.

The seeds of this discovery began nearly four decades ago when an 8-year-old Tisdale was seriously injured in a lawn mower accident. During his extended recovery, involving many procedures over several years, he marveled at his doctors’ expertise. “I aspired to do things that I saw people doing well,” Tisdale remembers. “And I saw how well they did medicine.”

But unlike many aspiring doctors, Tisdale wasn’t a straight-A student. It wasn’t until he came to the College and began studying chemistry that he gained the confidence to chase his boyhood dreams of becoming a doctor.

“In chemistry, you learn a set of rules and concepts, and then you get to apply them – it’s not memorization. For me, it just clicked. I realized I could be a student. I hadn’t really taken studying too seriously before. Growing up in Charleston, I cared more about waterskiing and cars – typical teenage stuff,” Tisdale recalls. “Can I do this? That was the real question for me. After the first year, I thought I could. It was hard, but I could do it.”

As a student, he worked and lived all four years at McAlister Funeral Home on Wentworth Street. Despite the macabre environment, it was the perfect place for a budding scientist to set up shop.

“I had this desk that was almost as big as a room,” Tisdale says, “and my chemistry buddies would come over. We would spread out our work and do P-Chem problem sets. Obviously, it was a big, quiet facility – and it allowed us to focus.”

That focus paved the way toward medical school and the fellowships that led to his career at the NIH, where he found that he had the “incessant curiosity” needed to sustain him as a researcher.

“But the hard part?” notes Tisdale: “Doing the same thing every day and not making progress. Until you stop and look at the big picture, you don’t know how far you’ve come.”

And looking at the slides of that presentation on treating sickle cell disease, Tisdale can smile, knowing he has come a long way.