In 1980, though, he opened up the journal Science and suddenly understood how doctors might someday cure Lesch-Nyhan, along with thousands of other genetic disorders that had once seemed incurable. Two Stanford biologists, Richard Mulligan and Paul Berg, had figured out a way to transplant genes into cells, effectively rewriting their DNA. The phrase gene therapy had been floating around medical circles for decades, but Wilson realized that its time had come. As soon as he finished his degrees, he and his wife moved to Boston so he could learn about gene transplantation from Mulligan, now at MIT. After nearly three years under Mulligans tutelage, he headed back to Michigan to set up his own lab.

The first disease that Wilson targeted was called familial hypercholesterolemia, in which the patient lacks the gene that produces receptors for grabbing bad cholesterol, or LDL, from the blood, which the liver normally filters out. Vessels become so badly clogged that many sufferers have heart attacks in their forties and fifties, and sometimes even before age 30.

Wilson figured out how to make a vector to attack the conditiona virus with a working version of the gene loaded on it. He first tested it on a type of rabbit genetically prone to high levels of LDL, and the gene therapy lowered those levels considerably. For a human trial in 1992, he and his colleagues chose a 28-year-old woman from Canada. Surgeons removed part of her liver, and then Wilson and his colleagues infected its cells with the virus, which delivered a working version of the defective gene. Finally, Wilson and his colleagues injected those cells back into the womans liver, where they took hold and grew. The womans LDL levels dropped by 23 percent.

The result, published in 1994, was a milestone in the young field. GENE EXPERIMENT TO REVERSE INHERITED DISEASE IS WORKING, The New York Times reported, noting that Wilsons paper was the first to report any therapeutic benefits of human gene therapy. Thanks to this study and others, the FDA gave the green light to more clinical trials every year, jumping from zero in 1989 to 91 in 1999. Universities set up gene therapy programs to stake a claim in the new field.

One of those was the Institute for Human Gene Therapy at the University of Pennsylvania. At age 38, Wilson became the institutes head, overseeing a staff that soon grew to more than 200. They launched new clinical trials, including a sequel to Wilsons study on familial hypercholesterolemia and on another genetic disorder in the liver: OTCD. Wilson now wanted to take the surgery out of gene therapy, so he and his colleagues searched the scientific literature for a virus that could seek out liver cells in the body.

They settled on a virus known as an adenovirus. Adenoviruses are best known for causing the common cold, but other scientists had found that they were very good at delivering genes into cells. Everything seemed to be moving forward nicelyuntil Jesse Gelsinger checked into Childrens Hospital of Philadelphia.

Read the rest here:
The Fall and Rise of Gene Therapy

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