It was time to try it on people.

In the family

Giuseppe Ferraro noticed, when his firstborn son was 5 months old, that the baby didn't seem bothered by bright lights. In fact, he looked straight at them.

Eventually, Ferraro learned that his son had LCA.

His vision had been impaired since birth, and it would become steadily worse.

There was no cure.

Four years later, the Ferraros had twins. Sadly, Tommaso and Josalinda were born with the same mutation.

Tommaso grew up and got a job as a dispatcher for the forest service, where a government-appointed guide helps him get around. Josalinda got married and began to raise two children. Both could see a little bit out of one eye, especially in bright sunlight. But under normal interior lighting, their vision was just about zero.

Through doctors in Naples, they heard that scientists in Philadelphia were working on an experiment that might help them.

Tommaso and Josalinda were 26. The trial was limited to those 27 and under; any older, and the retina would likely be beyond rescue.

Tommaso was a little hesitant when he heard that a needle would be inserted into his right eye. And, the doctors warned him, his eye could become inflamed. The corrective genes, borne by the viruses, might not take hold. And his brain - starved of visual information for decades - might have trouble making sense of the new signals coming from his rejuvenated eye.

Yet the doctors seemed confident not only that the procedure was safe - but that he might even regain some vision.

He and his twin sister agreed to try it. They booked flights to Philadelphia.

Using viruses

Since scientists began trying gene therapy on humans in 1990, there have been hundreds of trials on thousands of patients, but scant success. There are some promising signs in treating hemophilia. In France, 10 children were cured of the immune disorder known as the "bubble boy disease." But three of them later developed leukemia.

And in 1999 at Penn, in the case that haunts the field, Arizona teenager Jesse Gelsinger had a fatal immune reaction after he was injected with genetic material to treat a metabolic disorder.

In that trial, as in most cases, scientists had delivered their corrective genes by piggybacking them on an agent that is extremely effective at invading human cells: the virus.

But the virus has another ability that is not so welcome: It hijacks the cell's machinery and makes copies of itself. Those copies, in turn, seek out and invade other cells. These modified cells can attract the attention of the patient's immune system, which attempts to snuff them out - thus defeating the whole purpose.

In Gelsinger's case, the problem was far more severe. Scientists used an agent called an adenovirus that had been stripped of its ability to replicate, yet his immune system became lethally overstimulated.