The Science of Discovery
Dr. Kenneth Cox and Ellery Woodward-Hartman
Two-year-old Ellery Woodward-Hartman had been gravely ill for months. Her liver was scarred with cirrhosis and she was badly jaundiced.
Conventional medical wisdom said a transplant was the best option for her rare liver-and-colon diagnosis — primary sclerosing cholangitis — though it came with no guarantees: The disease could re-invade and destroy a transplanted organ.
But Packard Children's gastroenterologist Kenneth Cox, MD, had another option: a drug therapy he had discovered by accident. In a handful of other children, regular doses of a powerful antibiotic had been found to resolve the symptoms of Ellery's disease. In late October 2005, his team offered the treatment to Ellery's parents, Lyn Woodward and Melissa Hartman.
"There's a line from Emily Dickinson: 'Hope is the thing with feathers,'" Melissa said. "I thought of that poem. It was such a relief."
Cox, who is also chief medical officer at Packard Children's, wasn't sure a child as sick as Ellery would benefit from the therapy; his other patients had mostly been at earlier stages of PSC illness. Maybe the antibiotic would give her a few months to get stronger before a transplant, he told Melissa and Lyn. Cox wrote the prescription and invited the family to the annual holiday party the liver transplant team holds for past and prospective patients, an effort to help acclimate them to the idea of a transplant.
An Accidental DiscoveryIt was because of an earlier patient's serendipitous colon infection that Cox could offer hope to children like Ellery.
In 1993, a 15-year-old boy came to Cox with a classic case of PSC. His colon was badly inflamed. A liver biopsy showed damage to his bile duct, the tube that carries newly manufactured bile out of the liver so that it can digest dietary fat. His obstructed duct trapped bile in the liver, leading to liver failure.
PSC is particularly frustrating because no one understands what triggers its chain of destruction. The disease leaves patients feeling severely unwell, with abdominal pain, itching, jaundice, poor appetite, deep fatigue, and malnourishment.On top of it all, in this case, the boy's colon was infected with an aggressive bacteria, Clostridium difficile. Although Cox had little to offer for the teen's other medical problems, he could treat the infection. He prescribed the antibiotic vancomycin.
And something very strange happened. The liver-disease symptoms vanished.
"At first I thought it was a coincidence," Cox said. Maybe he had misattributed symptoms of infection to liver disease, he thought. "But then I stopped the antibiotic, and the liver disease came back, even though the infection was gone."
So Cox gave a second round of vancomycin. Once again, the teenager's appetite returned, his pain disappeared and his liver test results normalized.
Cox tried vancomycin in several other PSC patients who had never had Clostridium difficile infections. These kids had been told they were untreatable, yet in many cases their liver symptoms disappeared.
Holiday SurpriseOn Dec. 3, 2005, a few weeks after Ellery began taking vancomycin, the little girl, her moms and her twin brother Robert arrived at the holiday party. It was a chance for liver-transplant families to have fun and offer each other mutual support. Ellery and her family were excited to see Cox and his pediatric gastroenterology fellow, Anca Safta, MD, who had provided much of Ellery's care. But the doctors were even more excited to see her.
"When we came in, Dr. Safta and Dr. Cox couldn't believe how well she looked," Lyn recalled. Ellery's jaundice had cleared up. Her belly, previously swollen with fluids that accumulated when her liver function was at its worst, was a healthy shape. She was still tiny in comparison to her twin – the liver disease stunted her growth – but she was more energetic than before.
That same month, the hospital’s transplant selection committee concluded Ellery didn't need a liver transplant.
Filling the Knowledge GapsCox is continuing his research on the effect of vancomycin on PSC. In 2008, he published clinical observations of 14 patients who received the drug. He's now collaborating with other scientists across the country to test possible explanations for how the drug works.
When Cox talks about vancomycin, he expresses a scientist's prudence: There are still many open questions, and he wants precise answers to fill the gaps in his knowledge.
But beneath his caution is a definite sense of excitement.
"Most discoveries come by careful observation. I feel lucky that I've made this observation," he said. "The remarkable part is, not only do the liver tests get better, but, also the children feel so much better. If you take a look at these children before and after therapy, they don't look like the same child."
And Ellery's family is thrilled. Five years after they got the best holiday surprise ever, their daughter is thriving. Though her liver still bears the scars of cirrhosis, her liver-function tests are now normal. Her growth has caught up to her brother's.
For Lyn and Melissa, perhaps the best outcome is the opportunity to watch Ellery enjoy ordinary childhood pleasures: drawing pictures every night before bed, taking lessons in gymnastics and going to karate classes.
"I can't even calculate what Dr. Cox has been able to do for Ellery," Lyn said. "We've had access to something amazing."