Jean Bennett knew that she had only one hour to convince the unsmiling committee of scientists that her research project was worth supporting.

A gentle wisp of a woman with long black hair tied back, Bennett thought she had found a technique that might eventually prevent the most common form of inherited blindness - retinitis pigmentosa (RP).

Speaking quickly and moving rapidly from point to point, she was seeking support from the University of Pennsylvania's Institute for Human Gene Therapy to use genetic techniques against a disease that affects more than 100,000 people in the United States alone.

Bennett, a Penn ophthalmologist, explained how she and her husband, eye surgeon Albert Maguire, had temporarily repaired the genetic defect in mice.

Normally, the animals are blind by the third week of life, said Bennett as she flashed a color slide of a sightless newborn mouse on the screen at the head of the conference table. But the animals she and Maguire treated were apparently still able to see at eight weeks.

After finishing her presentation, Bennett was bombarded with questions, mostly from institute director James M. Wilson.

Standing to leave for a meeting on another proposed gene therapy trial, Wilson said the final decision would be made the following month, after Bennett presented even more detailed information to the institute's executive committee.

Wilson and the committee were impressed with Bennett's presentation. What she had failed to make clear, however, was that few of the 100,000 RP patients had been screened to determine which genetic form of the disease they had.

In fact, only five people in the country were known to have the particular gene defect she was working on. It was questionable that the institute would embark on a human trial with so few subjects.

Bennett's head was spinning after her presentation to the committee last summer.

Only months earlier, she thought it would take another five years of work before she could treat patients, and here she was about to draw up specific plans for human trials.

Though more than 200 human gene therapy trials against 25 diseases have been approved throughout the world, this would be the first attempt to use the potentially revolutionary treatment against an eye disease.

Bennett knew that it was essential to get the institute's support.

Not only would the institute make the drug used in the trial - a complicated and time-consuming process - but it would also provide and care for the many animals needed for preclinical tests, get the drug-safety data required by the Food and Drug Administration before human trials can start, move the project through the complicated local and federal regulatory processes, draw up a budget, and help get money for the study.

Most scientists don't have the resources to do all these things, and Bennett was well aware of promising research projects languishing in university laboratories for want of such support.

As director of the institute, Wilson is forever pressing scientists like Bennett to think of ways of using gene therapy to treat the diseases in which they specialize.

Penn oncologists have just started human trials with a drug against mesothelioma, a rare cancer of tissue lining the chest wall and lungs.

A similar drug for brain cancer, which the institute also helped develop, is about to undergo human testing. A gene drug for a rare childhood liver disease - ornithine transcarbamylase (OTC) deficiency - is going through final regulatory reviews preparatory to human trials, which should begin in a few months.

And Wilson himself is in the middle of trials of a drug for the inherited lung disease cystic fibrosis.

Walking out into the bright afternoon sunlight with her husband and the third member of their team, noted RP specialist Samuel Jacobson, Bennett talked with the others about what now must be done to get ready for the next meeting.

Jacobson was as bewildered by the fast-moving events as was Bennett. Having joined the Penn faculty only a month earlier, he hadn't even finished unpacking his books.

It was the possibility of doing gene therapy research on RP that had attracted the shy, soft-spoken specialist to Philadelphia.

After having spent so many years with patients for whom he could do little, it was exciting for Jacobson to think that they might be on the verge of developing a treatment for this cruel disease.

Bennett, 40, and Maguire, 35, started experimenting with gene therapy in 1990, shortly after completing their medical training.

With practically no research money and working in a basement sink in the Beaumont Hospital in Royal Oak, Mich., the husband-and-wife team had few successes at first.

It wasn't until the summer of 1993, after Maguire became a surgeon at the Scheie Eye Institute and Bennett arrived at Penn, that things began to look up. Rather than working in a basement sink, she had use of the beautifully equipped labs in Scheie's F.M. Kirby Center of Molecular Ophthalmology.

And Wilson had just arrived at Penn, announcing that he was setting up the gene therapy institute and looking for projects. Having worked under him as a medical student when Wilson was an intern at Massachusetts General Hospital in Boston, Bennett sent Wilson an I-bet-you-don't-remember-me letter and a request for a get-together.

Wilson did remember her and was eager to talk about gene therapy. Huddling over a little wooden table in Wilson's office, the two spent an hour discussing the prospects of using it to treat eye disease.

Bennett explained how RP was actually many different genetic diseases, each caused by a defect in a different gene. Though probably dozens of genes are involved, most produce the same damage to the photoreceptor cells in the retina.

In humans, RP begins with poor night vision in childhood. The disease then strikes the periphery of the retina, covering photoreceptor cells with a black pigment that blocks light. The disease is named for these pigments.

As the damage slowly moves to the center of the retina, the patient develops tunnel vision that grows progressively narrow until the patient is completely blind, usually before the age of 50.

Bennett told Wilson that she thought the potential for treating RP with gene therapy was good because six RP genes had been identified.

She wanted to work with the gene that makes phosphodiesterase (PDE), an enzyme that helps turn light waves into neurological signals the brain can interpret. She wanted to work with PDE because some mice had defects in this gene, providing her animals with which to test the therapy.

Bennett wanted to inject viruses containing the PDE gene into the retina. The virus would infect the photoreceptor cells and deposit the PDE gene, which would start making the enzyme that RP patients lacked.

It was technically difficult since the eye of a newborn mouse is smaller than the tip of a ballpoint pen, but Maguire had no doubts that he could get the vector in.

Wilson was so impressed with Bennett's ideas and enthusiasm that he gave her the genetically altered viruses, or vectors, with which to experiment.

For two years, starting in the summer of 1993, the couple worked with Wilson's vectors, first testing them on photoreceptor cells in the test tube and then injecting them into the retina of mice. Since no one had ever done this before, there were many things to learn, such as when to treat the animals.

They thought the sooner the better since the disease quickly blinded the rodents, so they injected the mice immediately after birth. But the mothers kept eating their young because they had been touched by humans.

This didn't happen when the scientists waited until the animals were four days old - still enough time to start treatment since the disease didn't start destroying the retina until one week after birth.

RP blinds mice so quickly that Bennett would have been happy to slow down the process by even a few days. She wasn't prepared for what happened. The therapy prevented the disease, at least temporarily.

Normally by the second week of life, RP has extensively damaged the eye, covering the entire retina with black specks of pigment. But the photoreceptors that had taken up PDE genes were still clear one month after birth.

It wasn't until the fifth week that specks began to appear, apparently because - for unknown reasons - the transplanted genes stopped working. Total destruction of the treated area didn't occur until after the eighth week.

Bennett found the results "amazing" and wondered if the treatment would last longer in humans afflicted with a less virulent form of RP.

Bennett didn't immediately tell Wilson about the results. Instead, she spent three months doing more studies to make sure that the data were solid. She still wasn't ready to say anything when Wilson's office called, requesting an update on her work, last July. With little comment, she sent slides showing the treated and untreated retina.

Two days later, she received a handwritten note from Wilson asking her to call him.

"This is spectacular," he said when she phoned.

A few weeks later, Bennett found herself standing before the institute's research and development committee and talking about human trials.

As the date for the executive committee meeting approached, Wilson huddled with Bennett, Maguire and Jacobson and pressed them with questions about the incidence of the disease.

Wilson wanted to know how hard it would be to recruit patients for the trial.

Bennett pointed out that Jacobson was a national authority on RP, with a large number of patients who came to him from all over the world.

But how many have the PDE defect?

That's difficult to say, Maguire said because the precise genetic defect usually can't be identified with a routine eye exam. That requires costly lab studies, which most ophthalmologists don't bother with since all forms of RP are incurable.

Only a small percentage of RP patients have been identified as having the PDE defect, Jacobson said. How many? Wilson wanted to know.

They knew of five.

Wilson was shocked.

Couldn't they go after a different form of RP with more identified patients, he asked.

Maguire said that more patients were known to have the form of RP called choroideremia, because it can be picked up with routine eye exams, but that no animals were known to have it.

Bennett thought it was essential to test out prospective treatments on animals before going to humans, so they had to do PDE.

Wilson didn't want to abandon the project. He was impressed with Bennett's animal studies and considered diseases of the eye, which is easier to reach than other organs, ideal for gene therapy.

He wanted Penn and his institute to lead this research, but he did not want to spend hundreds of thousands of dollars preparing for a clinical trial without the assurance of test subjects.

The meeting with Wilson ended on an uncertain note. Bennett could see that Wilson was having serious doubts. If he didn't want to do it, it was unlikely that the executive committee would approve the project.

For the next several days, Wilson mulled over what to do. It was clear to him that if the only goal was to find an effective treatment for PDE, he would oppose the project because the payoff in new knowledge would be too limited.

But Bennett's PDE animal work proved that gene replacement can slow down RP. If it worked with PDE, Wilson asked, why wouldn't it work with choroideremia?

There was another argument for proceeding: Regardless of what form of RP was ultimately chosen for treatment, the surgical procedure and vector would be the same; only the gene carried by the vector would be different. With the exception of animal testing, all the time-consuming preparatory work would be the same.

And the need to know how to deliver these genes was growing. Six RP genes had already been identified, and probably many more would be found in coming months. It was important, Wilson thought, to know what was the best vector to use in eye diseases, what was the best dose, and how to deliver it.

It was not clear at all that the project should be abandoned.

Maguire and Jacobson were sitting at the conference table with members of the executive committee when Bennett rushed in a few minutes late. She immediately went to the head of the table and started her presentation.

Recapping much of the material presented at the earlier meeting, she said that, as they moved ahead with their preparations, they and other laboratories would be screening blood to find more patients with PDE.

Alan Davis, director of the institute's vector laboratory, said five vectors would be studied to see which was best suited for delivering genes to eyes.

Eric Wheeldon, who ran the institute's animal facility, said 50 mice, 160 rats and four monkeys would be used to test the different vectors before one was put into humans.

Jennifer Dennin, the institute's administrative coordinator, had priced out all the things that would go into the study and estimated that it would cost $330,000 to prepare for the human trial.

The executive committee - composed of Wilson and five other researchers from Penn, the Wistar Institute and Children's Seashore House - asked several questions and thanked the scientists for coming.

Bennett, Maguire and Jacobson spent the next two weeks anxiously awaiting word from the institute. Every afternoon, Maguire and Jacobson would call Bennett to see if she had heard anything.

Finally, Bennett received the letter from Wilson. The committee had agreed to support planning for human trials of a drug against retinitis pigmentosa.

The emphasis would be on finding the best vector to deliver genes to the retina and determining the maximum safe drug dose.

Though Bennett intended to push ahead with the PDE work, Wilson wasn't so sure that this would be the RP gene defect finally chosen.

Whatever it was, he wanted everything to be in place so they could go to human trials as soon as it was chosen. A lot of momentum had been built up, and Wilson had no intention of losing it.

Through the fall, Bennett and her colleagues moved quickly to prepare for the animal studies.

They arranged for the institute's vector lab to make viruses for pilot studies. They asked the institute's animal facility to get and house the animals.

Bennett started assembling the human PDE gene for insertion into the vectors that would be used in the human trials.

And scientists at the University of Iowa, which has the largest RP screening laboratory in the world, were asked to start looking for PDE patients.

Finally, everything was in place. The first of the animal studies started last month. And the list of PDE patients has grown to 12.