The evidence is clear: Jesse Gelsinger died from a medical experiment led by James Wilson.
At 18, Gelsinger was confronting a rare metabolic disorder, and Wilson, a biotechnology pioneer, held out hope with an unproven treatment that was supposed to rewrite the young man’s DNA. Instead, the therapy killed him.
Gelsinger’s death, in 1999, sent the fledgling field of gene therapy into a decade-long funk in the U.S. Almost overnight, an area with seemingly limitless medical and commercial promise was tainted.
Which is why what is happening now might seem so surprising.
After years of worry and doubt, gene therapy -- in effect, using genes as medicine -- is exploding across the white-hot biotech scene. And at the center of it all is none other than James Wilson.
It’s a remarkable turn of events for Wilson, whose career was derailed 16 years ago. Drug giants from Bayer AG to a spinoff of Baxter International Inc. have followed scientific trails he blazed. Venture capitalists are staking hundreds of millions on gene-therapy start-ups, including two associated with Wilson. On the U.S. stock market, a dozen different gene-therapy companies like Juno Therapeutics Inc., Bluebird Bio Inc. and Spark Therapeutics Inc. are worth a combined $20 billion.
Wilson, 60, says he’s still haunted by what happened to Gelsinger, whose mild form of the rare condition was posing no imminent threat of death when the trial began.
Crossing to Safety
“I think about him almost every day,” Wilson says. He agreed to a five-year ban from overseeing clinical trials in settling a U.S. Justice Department investigation; he didn’t admit to allegations and said his conduct was lawful. Federal investigators claimed he’d failed to stop the trial when safety problems arose and didn’t warn patients of all the risks.
Wilson says he accepts responsibility for mistakes made during the 1999 trial, which he oversaw at the University of Pennsylvania. He also says Gelsinger didn’t die in vain. Following his lethal gene therapy, researchers did a “real pivot” toward finding safer treatments, Wilson says.
The geneticist’s rebound is no less remarkable for Gelsinger’s father, Paul. He says Wilson is after fortune and fame in this potentially lucrative corner of science.
“He’s an entrepreneur first, a research scientist second and a physician last,” Paul Gelsinger says. “For him to use Jesse’s name in promoting his endeavors is offensive to Jesse’s memory and to us, his family.”
Jesse Gelsinger had a rare genetic mutation that affected his liver and caused life-threatening levels of ammonia to build up in his blood.
In Wilson’s trial, Gelsinger was infused with healthy copies of a gene via a weakened cold virus. Within hours, his immune system rebelled. Four days later, he was dead.
Wilson and the university subsequently settled a lawsuit filed by the Gelsinger family, the terms of which were confidential. Penn also paid more than $500,000 to settle U.S. investigations into the incident. The university didn’t admit to wrongdoing and also said it acted lawfully.
After Gelsinger died, Wilson’s research funding dried up and his lab staff shrunk to 50 from 250.
“I was a pariah,” he says.
Looking for safer ways to deliver genes, Wilson found new funding from a predecessor of GlaxoSmithKline Plc and started researching viruses not linked to diseases. He eventually found the most promising types not in humans but in monkeys.
Wilson’s team used one of the monkey viruses to transfer a gene that prompts blue coloration into the livers of mice. He had a eureka moment when a colleague showed him cross sections of the livers -- all of them dappled with blue.
“It was stunning. Every cell in the liver had taken up the new gene,” Wilson says. “This is when I knew this is a game changer.”
One of the new virus discoveries was used to treat Derek Houser, a hemophiliac who suffered from spontaneous internal bleeding in his joints. The painful episodes often made walking impossible without crutches.
Houser received an experimental infusion of blood-clotting genes in 2012 carried by an AAV8 virus discovered in Wilson’s lab. The bleeding and swelling stopped as if a switch had been flipped, Houser says.
“It is a night and day difference,” says Houser, 36, who was given the treatment at St. Jude Children’s Research Hospital in Memphis. “It has completely changed the quality of my life.” Baxalta Inc., a recent spinoff from Baxter, is testing a related therapy that combines AAV8 with a more potent version of the clotting gene.
Aware of the previous damage to his reputation, Wilson says he’s sharing the new viral vectors with as many researchers as possible outside University of Pennsylvania labs, to maximize chances for drug developments.
“We were being criticized and we were being ostracized,” Wilson says. “We were going to give it to everyone.”
Penn now has agreements permitting more than 3,000 researchers at 900 universities and other institutions in 32 countries to use its viruses for non-commercial experimentation.
After one of Wilson’s supporters at GlaxoSmithKline left the drug company in 2006, the company’s interest waned. That paved the way for Wilson to start Regenxbio Inc., which swapped commercial rights to the discoveries from Glaxo for a stake in the new venture.
Wilson’s technology “is pretty transformative” says Matt McPherron, managing director at Brookside Capital, a hedge fund backing Regenxbio. “It solved the main issue about safety.”
One gene treatment Wilson is working on now targets Gelsinger’s rare disorder, which can kill infants within months in severe forms.
Wilson devised a two-dose treatment that has kept mice with the disorder alive for at least 18 months, well into their adulthood. Dimension Therapeutics Inc., the other company Wilson co-founded, has said it hopes to begin human trials in the disease next year. Wilson has stakes of less than 5 percent in both Dimension and Regenxbio, each of which has raised over $100 million.
Gene therapy still confronts hurdles, including concerns about safety. Despite investor excitement, no gene-therapy drug has yet been approved in the U.S.
Still, Wilson said the technology is substantially better than it was 16 years ago and he is certain that safe, successful treatments will be found.
“There is absolutely no doubt in my mind,” he said.
Read this next:
- Gene Therapy for Immune Disorder Lasts 9 Years, Studies Show
- Spark Surges in IPO as $1 Million Prices Fuel Gene Therapy
- Money Flows Again to Gene-Therapy Drugs Investors Once Shunned