How gene therapy overcame high-profile failures

Gene therapy pioneer Richard Jude Samulski remembers when he avoided the words “gene therapy.” In the mid-2000s, he told people he worked on “biological nanoparticles,” even attempting to trademark the term. “We felt that was the disguise we were going to have to wear to go forward,” recalls Samulski, a professor of pharmacology at the University of North Carolina at Chapel Hill Penyulingan.

The death of a teenager in a gene therapy clinical trial in 1999 and cases of leukemia in a trial soon after almost extinguished the field, which seeks to treat diseases at their roots by replacing or counteracting a malfunctioning gene. There were federal investigations, funding cuts and a lot of negative media attention. Yet a handful of researchers never stopped working, sometimes out of doggedness and sometimes because they couldn’t say no to desperate parents. “Everybody adapted to do what it took to keep going,” Samulski says.

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The gene therapy story has a happy ending. Today, the Alliance for Regenerative Medicine lists nine available gene therapies worldwide that have been approved by internationally recognized regulatory agencies, as well as more than 200 in advanced clinical trials. The field attracts billions of dollars in funding each year. But its tumultuous past reminds us that the course of medical innovation rarely runs smooth.

It all began more than half a century ago, with the discovery of molecular knives and a virus lurking in monkey cells.

Vectors and setbacks
In the 1960s, researchers identified proteins in bacteria that work like chemical knives to cut DNA into fragments. These “restriction enzymes” raised the amazing possibility that scientists could take DNA apart and put it back together. Then, in the 1970s, a virus called SV40, isolated from monkeys’ kidney cells, proved to be able to deliver genetic material into target cells.