The young man on Albert Maguire's operating table had a big red mark stamped on the right side of his forehead.

The mark told the surgeon just where to insert his needle: straight into the patient's right eye.

Maguire didn't really need the reminder. He and his wife, molecular geneticist Jean Bennett, had been focusing on this moment for months - in truth, for decades.

The patient was blind. Maguire's hair-thin needle traveled through the "white" of his eye, all the way back to his badly scarred retina, where it would deliver billions of genetically modified viruses. Each virus carried a single gene: the recipe to produce a crucial enzyme that his eye was unable to make on its own.

Within weeks, beyond what anyone had predicted, the experiment worked. The young man and two other patients began to regain some vision.

The results, reported online today by the New England Journal of Medicine, represent a dramatic advance in the field known as gene therapy, a field marked by sparkling - yet so far largely unfulfilled - promise.

The three patients, treated in a joint effort by the University of Pennsylvania and Children's Hospital of Philadelphia, remain legally blind. But there are indications that the procedure may work even better in children, and the lessons could one day apply to other forms of inherited blindness.

"This Philadelphia trial is exceptionally exciting," said Savio Woo, a gene-therapy specialist at the Mount Sinai School of Medicine who was not involved with the study. "It's absolutely remarkable."

The Inquirer followed the trial over eight months under the agreement that it would not print an account until the research was published in an academic journal.

The official goal of the surgery was to make sure such an injection was safe; no one promised the young man, who had flown from Italy for the experimental treatment, that he would see any better.

But luck was on his side.

Bennett and Maguire set the date of the surgery for Thursday, Dec. 13.

To them, it was just another day on the calendar. But to the Italian clinicians assisting in the operation, it was auspicious.

The 13th is the feast day of Santa Lucia, patron saint of the blind.

A 'simple problem'

Jean Bennett and Albert Maguire first talked about the eye idea as they were finishing up Harvard medical school in the mid-1980s - she exploring the fledgling field of genetics, he learning to be a surgeon.

The two had hit it off in neuroanatomy class. They were lab partners on the day they had to dissect a human brain.

After they cut the brain in half, Maguire took Bennett's hand and put it on top of the hypothalamus.

"I want to show you my favorite organ," he said, reminding her that it is sometimes called the "pleasure center."

Not missing a beat, she responded:

"That's my second-favorite organ."

They were married two years later.

It was 1985. Still in school, Maguire was working in a lab that specialized in retinal degeneration, and he knew that many such diseases were the result of a single defective gene. With the practical, fix-it approach common to those in the surgical profession, Maguire wondered if matters could be addressed in the operating room.

"I thought: 'Simple problem: fix gene, fix disease,' " he said.

Of all the body's organs, the eye is one of the most accessible. So he asked his wife, who already had a Ph.D. in biology: Was it possible to inject a corrective gene?

Sure, she said - in theory. Researchers had been talking for years about the goal of inserting genes into living tissue.

Except that no one had identified any of the genes that cause retinal disease.

"Had I actually known how difficult and complex the problem really was, I probably would have dismissed the idea immediately," he says now. "Jean has a more long-term view and didn't tell me."

The two did a stint at Yale, where Bennett had grown up, the daughter of a famous physicist who co-invented the gas laser.

Later, Maguire interviewed for a fellowship with Robert Machemer, a pioneer in retinal surgery, and eagerly told him what he and his wife were trying to do. The response was not good.