Transcript of Bbc Documentary on the Death of Jesse Gelsinger

Trial and Error - programme transcript

BBC Two, Thursday, 27 February 2003

NARRATOR (DILLY BARLOW): This is the story of a beautiful idea.

NEWS MONTAGE: There was a historic medical first today... ...began a revolutionary new treatment... ...the first small step for the major revolution in medicine.

NARRATOR: It is the story of one of the greatest dreams in science: to cure every disease on the planet, but on this mountainside that dream died.

VOICE: ...was his bounty and his soul sincere...

NARRATOR: Sending one family on a journey into the dark heart of modern medicine.

PAUL GELSINGER: My son's death has been called a pothole in the road to gene therapy. His death was no pothole.

NARRATOR: This is an investigation into the medical miracle that never was, a miracle that crumbled into tragedy.

PAUL GELSINGER: Born on June 18th, 1981 Jesse Gelsinger was a real character in a lot of ways. Not having picked out a name for him prior to his birth, the name Jesse came to us three days later.

NARRATOR: Jesse was the Gelsinger's second son. It was a close, loving family and Jesse was growing up to be a lively, boisterous little boy.

PAUL GELSINGER: When he started talking it quickly became obvious that this was one kid that would speak his mind and crack everybody up.

NARRATOR: Jesse's dad, Paul, was working as an odd-job man in Tucson, Arizona. For the Gelsinger family life was good. Then, when Jesse was two years old, everything would change.

PAUL GELSINGER: On a Saturday morning Jesse got up at his normal time to watch cartoons and promptly fell back asleep. We couldn't rouse him, he wouldn't wake up.

NARRATOR: Paul rushed his unconscious son to the hospital. For no apparent reason his healthy young boy was now on the verge of death.

PAUL GELSINGER: He was in a first stage coma. We were very frightened. We didn't know what was wrong with him.

NARRATOR: The puzzled doctors battled to save Jesse unsure what was causing his illness, but they soon had the answer. Jesse was suffering from a genetic liver disease called OTC deficiency. It was often fatal.

PAUL GELSINGER: It's a very serious disorder, very rare. I knew that it could, it was a life-threatening condition, could result in brain damage.

NARRATOR: But for the Gelsinger family there was some hope. The doctors told Paul that if Jesse was carefully looked after he could survive and as Jesse grew up their optimism became even greater. A medical revolution had begun, a revolution that would offer the chance of a miracle. For the first time devastating genetic diseases, like OTC deficiency, cystic fibrosis and haemophilia would be cured. These plagues of human health would be wiped away. Leading the revolution was Dr. French Anderson.

DR FRENCH ANDERSON (USC Keck School of Medicine): Most people thought it was impossible the medical equivalent of putting an astronaut on the Moon.

NARRATOR: Dr. Anderson had a dream, a dream that if it worked could cure every disease on the planet. His dream was called gene therapy.

FRENCH ANDERSON: The basic idea of gene therapy is incredibly simple. It's like if you have a radio and there's a broken wire you go in and replace the broken wire and the radio works again. It's the same thing in a human patient. You have a, a broken gene and so you put in a normal gene, Cure the disease.

NARRATOR: Anderson's idea was so straightforward it was almost child-like. Simply identify the defective gene that causes a disease and then implant a working gene in its place. The only trick was to find a way of putting the gene into millions of defective cells.

FRENCH ANDERSON: There was so many things that had to be done that had never been done before to try to put a DNA molecule, a gene, into a human being in a safe and effective way.

NARRATOR: This problem of finding something to transport a healthy gene was all that stood between Anderson and medical history. They called it the vector problem. The solution scientists came up with was both strange and ingenious.

PROF DUSTY MILLER (Fred Hutchinson Cancer Research Center): The vector problem in gene therapy is how you take DNA and get that into cells. There's been a tremendous challenge to find the best vector, the ideal vector, the best vector, the ideal vector (REPEATED SEVERAL TIMES)...

NARRATOR: Scientists like Dusty Miller decided to harness the power of our most ancient enemy, an enemy which specialises in infiltrating cells with deadly precision. The answer to the vector problem was to use a virus.

DUSTY MILLER: One way of thinking about our use of viruses for gene therapy is that we're really hijacking millions if not billions of years of evolutionary progress on the part of viruses.

NARRATOR: A virus infects a human by inserting its genes directly inside our cells. This can be deadly, but scientists like Miller were convinced they could tame this natural ability for good.

DUSTY MILLER: You've got defective genes in a person, you've got a virus that can transfer lots of genes very efficiently. Why not combine the two and use a virus in that way?

NARRATOR: The theory was they could remove all the dangerous genes in the virus. In their place they would put a healthy human gene. The virus would then carry this gene into a patient's defective cells. If it worked the dream of gene therapy would be brought to life.

DUSTY MILLER: So at the end of the day what we have here is basically a machine that we can use to transfer any desirable gene into a human cell with very high efficiency.

NARRATOR: Miller's team started working with the most promising type of virus: the retrovirus, a virus that can cause cancer. In animal experiments the retrovirus worked perfectly, but no one knew if it would work in a human. On September 14th 1990 French Anderson and his team decided to try out gene therapy for the very first time.

FRENCH ANDERSON: Many in the scientific community really thought that the whole trial was irresponsible, headline grabbing. There was enormous pressure on us. If anything had gone wrong we would have been crucified.

NARRATOR: The patient was Ashanti De Silva, a four-year-old girl born with a devastating genetic disorder, a disease called SCIDS, that left her with defective white blood cells and no ability to fight off even a minor infection..

FRENCH ANDERSON: And here is Ashi, four years and 11 days old, who at this point is perfectly calm, in fact Ashi was always calm, she was sort of like a Zen monk the whole time...

NARRATOR: Anderson's plan was to remove her defective blood cells and expose them to a retrovirus containing a healthy gene.

FRENCH ANDERSON: What we've done is to build a retrovirus in which the normal human gene is carried...

NARRATOR: After the virus had done its work, they then injected the corrected cells back into her.

FRENCH ANDERSON: ...but this is Ashi's hand and it's got about two teaspoons of the first genetically engineered cells ever put into a patient to treat a disease and so this was really the critical moment. I sat the whole time with a finger on her pulse. I never lost physical contact with her from beginning to end.

NARRATOR: Within months Anderson was convinced that the procedure had been a success. It seemed gene therapy was no longer just a dream. Here was living, breathing proof of its power.

NEWS MONTAGE: A four-year-old girl who made history here today will go home tomorrow... performed the first ever gene therapy procedure... ...first patient to receive gene therapy to treat a disease. Today's experiment at the National Institute...

NARRATOR: For people like Jesse Gelsinger the hope of a cure had arrived.

DUSTY MILLER: That initial gene therapy trial really broke the barriers, broke down the dam and really was, was a thing that got a lot of other gene therapy attempts going.

NARRATOR: The field of gene therapy exploded. Millions of dollars poured into the hottest new subject in science, but it wasn't just rare genetic diseases that suddenly seemed curable, it was everything. Dozens of genes were being discovered and linked to different diseases, diseases that affect everyone, like cancer, heart disease, AIDS and arthritis. Gene therapy promised to be the biggest advance that medicine had ever seen, but then doubts crept in because, apart from French Anderson's first experiment, no one else was being cured.

FRENCH ANDERSON: It wasn't until the mid-90s after several hundred clinical trials had been done, when we realised patients were not being helped, you know gene therapy was not working.

NARRATOR: What was not working was the retrovirus. The vector problem, the fundamental obstacle in the way of gene therapy, was back.

PROF INDER VERMA (The Salk Institute for Biological Studies): The concept of gene therapy was disarmingly simple, but when in reality the experiments were done it turned out that the delivery of a gene was not so easy.

NARRATOR: Virus scientists like Inder Verma found that the retrovirus just didn't work. In all the major human diseases it turned out to be useless.

INDER VERMA: Gene therapy wasn't working, the vectors were not right, so that, combined with a lack of success, gene therapy took a nosedive.

NARRATOR; The medical miracle had run aground.

INDER VERMA: What will be an ideal vector?

NARRATOR: If it was ever to fulfil its promise, someone would have to find a new, better vector.

INDER VERMA: ...will be the brain, the liver, lung...

NARRATOR: A vector that could cure everything. Then along came one man who thought he could crack the vector problem once and for all. Dr. Jim Wilson was one of gene therapy's brightest stars. In 1992 he set up the largest gene therapy centre in the world.

DR JIM WILSON (Interviewed in 1994): I'm the Director of an institute at the University of Pennsylvania that is attempting to develop gene therapies for many disorders.

DUSTY MILLER: Jim Wilson was one of the premier figures in, in gene therapy...

FRENCH ANDERSON: Jim Wilson was more than a rising star. He was already a star.

DUSTY MILLER: He had established a very large group...

INDER VERMA: Published good papers.

FRENCH ANDERSON: Superb scientist.

DUSTY MILLER: Really moving towards very effective gene therapy.

FRENCH ANDERSON: Present company excluded, he was the best person in the field.

NARRATOR: Wilson put a huge team of people into cracking the vector problem. It was widely thought that if anyone could do it it would be Wilson and Wilson's team thought they had the answer. The vector problem would be cracked by using the commonest virus of all - the adenovirus, the cause of the common cold.

DUSTY MILLER: Adenovirus vectors seemed like the magic bullet that people were wanting and it was thought by many groups that, including Jim Wilson's group, that these were the vectors of choice.

FRENCH ANDERSON: What made adenovirus so exciting is that adenovirus is a human virus and it, it can infect almost every cell in the body.

NARRATOR: It seemed the future of gene therapy was in Jim Wilson's hands. He had the best team, the most promising vector. All he had to do now was cure a disease. In the mid-90s he set his sights on a rare liver disease called OTC deficiency, the condition affecting Jesse Gelsinger.

PAUL GELSINGER: In September 1998 Jesse and I were made aware of a clinical trial being done at a renowned medical facility in Philadelphia. Jesse was as healthy as I'd ever known him to be, he had reached the maximum weight he'd ever been, he was, he was doing well. We were very pleased with Jesse and what he had become, what he was becoming.

NARRATOR: When Jesse and his father travelled to the local hospital they were told that the trial wouldn't cure his OTC. This first study was simply to test that the vector was safe, to try it on relatively healthy people like Jesse and make sure it had no side-effects. Nonetheless, Paul and Jesse were still keen to take part.

PAUL GELSINGER: They described the clinical trial as first phase safety study in the early stages. We were very excited that they were working on Jesse's disorder. It's such a rare disease and we were very enthusiastic about it.

NARRATOR: For the Gelsinger family it was simple. Jesse was doing an extraordinary thing: helping to find a cure for hundreds of diseases.

CAPTION: Sunday 12 September 1999.

NARRATOR: Within a year Jesse was on his way to Philadelphia. His family had stayed behind and would fly out to see him later in the week. Back in Tucson Jesse's step-mum Mickie was worrying about her boy leaving home for the first time.

MICKIE GELSINGER: I was proud, I was very proud for him. He was happy and he was excited and this was something he wanted to do. I think he saw this as his first big step into manhood.

NARRATOR: The night before the trial began Jesse called his parents.

PAUL GELSINGER: He was a little apprehensive. I tried to relax Jesse, I told him these guys knew more about his condition better than anybody on the planet.

MICKIE GELSINGER: It was safe, it was something he was just going to go through, go through some side-effects and then come home.

CAPTION: Monday 13 September

NARRATOR: On 13th September the trial began. Jesse was the 18th and last patient. At 3.30pm one of Jim Wilson's team injected Jesse with 38 trillion viral particles. It was the biggest dose of vector anyone had received in the trial. The doctors told Jesse to expect a small reaction, such as fever and 'flu-like symptoms.

PAUL GELSINGER: I received a call late in the evening from Jesse. He wasn't feeling well, he was starting to have the side-effects from this treatment.

MICKIE GELSINGER: And I said are you feeling nauseous and he goes a little bit, I'm feeling out of sorts and I said you know it's going to get a little bit worse, be prepared. He says yeah I know, I just don't like it.

NARRATOR: As Jesse went to sleep that night the virus surged through his body. The medical team watched. At this stage everything seemed to be going to plan, but there were some things that Jesse didn't know. In this trial there was much more than just a medical breakthrough at stake. There was also, potentially, a great deal of money. Five years before Jesse's trial began Wilson and some colleagues had set up Genovo, a biotech company. Its purpose was to market any successful treatments he developed.

FRENCH ANDERSON: Anyone who was doing serious clinical trials really had to have ties with pharmaceutical industry, biotech industry.

DUSTY MILLER: To get a gene therapy product approved for use in people takes millions, hundreds of millions of dollars.

FRENCH ANDERSON: Where the question comes is at what point does one have so much financial interest in a company that it starts to, to sway your scientific thinking.

NARRATOR: By the time the trial began, Genovo had attracted over $30 million of investment. It made Wilson's team one of the best backed in the field. If the trial worked there was every chance that Wilson would become a very wealthy man.

CAPTION: Tuesday 14 September 6:00 am

NARRATOR: Early the next morning a nurse checked on Jesse. He seemed a little disoriented and jaundiced. A doctor was called to examine him. It seemed like nothing serious but they wanted to be certain.

PAUL GELSINGER: I received a phone call from the doctor in charge. He indicated that they were seeing a side-effect that they had not seen to date. I was a little alarmed at that point.

NARRATOR: Something unexpected was happening. The virus was supposed to be harmless, but Jesse's entire body was reacting as if it was under attack.

PAUL GELSINGER: He was going into a coma. I told the doctor I will be on my plane this evening, I will be there first thing in the morning. I didn't know enough, I didn't know what was going on.

NARRATOR: Paul certainly didn't know that this wasn't the first time there'd be problems with the adenovirus. Seven years earlier Jim Wilson had wanted to use it to treat another genetic disease, cystic fibrosis.

JIM WILSON (1994 Interview): I view cystic fibrosis as being on the point right now addressing all of the tough issues...

NARRATOR: Many people believed that this was an ideal candidate for gene therapy.

JIM WILSON (1994 Interview):'s really remarkable the progress we've made in cystic fibrosis has really paved the way towards the development...

NARRATOR: But as Wilson geared up for his trial it became clear that all was not well. In a study in New York another group of scientists sprayed the virus into patients' lungs. Within days one person had developed a severe chest infection and the trial was halted.

FRENCH ANDERSON: The side-effects that were occurring in some of the patients certainly in retrospect one can say oh, there's a red flag, you know. We should have realised.

JIM WILSON (1994 Interview): And it did worry us because this is not what we want to see in patients.

NARRATOR: The adenovirus seemed too dangerous to use, but Jim Wilson had other ideas. He worked on removing what he thought were the dangerous parts of the virus.

JIM WILSON (1994 Interview): Renders it incapable of causing many of the potential side-effects.

NARRATOR: By 1995 he was convinced he'd tamed the virus. He believed the vector he was using on Jesse was safe.

CAPTION: Wednesday 15 September

NARRATOR: Two days after the trial began Jesse's father, Paul, arrived in Philadelphia.

PAUL GELSINGER: It's a very helpless feeling knowing your kid is in serious trouble and you're a continent away. My plane got into Philly at 8 o'clock a.m. Arriving at the hospital at 8.30 I immediately went to find Jesse.

NARRATOR: Paul arrived at the surgical intensive care unit to find Jesse hooked up to a ventilator and in a coma.

PAUL GELSINGER: I dressed in scrubs with gloves and a mask because of the isolation requirement due to the virus status and went in to see Jesse. I'd wanted to go and see if I could rouse him. There was absolutely no response.

NARRATOR: As Paul sat with his unconscious son, Wilson's team desperately tried to work out what had gone wrong. Why had he reacted so violently to the vector? Could the reaction have been predicted? For one man the answer was yes. Five years earlier Dr. Robert Erickson had considered getting the trial stopped.

DR ROBERT ERICKSON (University of Arizona): When I was initially given the OTC protocol I was very negative about it because of questions of toxicity of the adenovirus.

NARRATOR: Erickson was on the government committee in charge of ensuring that the trial was safe. He was alarmed at evidence that showed that an earlier form of the vector had been deadly.

ROBERT ERICKSON: The adenovirus that was being tried was one with toxicity enough to have killed a baboon.

NARRATOR: On this evidence Erickson's committee were prepared to halt the trial, but Jim Wilson argued that it was the earlier version of the virus that had been lethal. He said he had modified the virus to make it less dangerous.

ROBERT ERICKSON: Jim Wilson's reputation was very important for my coming around to voting to approve the protocol. I had known Jim, followed his career for over a decade at that point.

NARRATOR: Wilson's argument won the day. Erickson changed his mind and the trial was given the green light.

CAPTION: Thursday 16 September 1:00 am

VOICE: If the hurricane remains on its now expected course and at its current strength the area where it makes landfall will be struck by a storm surge of anywhere from ten...

NARRATOR: In the early hours of Thursday morning a hurricane struck Philadelphia. As Jesse lay critically ill in hospital, Paul phoned his wife.

MICKIE GELSINGER: I get a call and he says get on a plane Mickie, he's going down, it doesn't look good.

PAUL GELSINGER: His lungs were failing. Indicated to me that it looked like he might have only a 10% chance of survival.

MICKIE GELSINGER: I couldn't think that things could get worse. I always was hopeful that it was OK, he was going to get better, he was going to come home.

CAPTION: 8:00 am

NARRATOR: After travelling through the night Mickie arrived in Philadelphia and went straight to the hospital.

MICKIE GELSINGER: And everyone there, all the staff, everybody was quiet, stepped out of our way. I think they were in shock too because...


MICKIE GELSINGER: ...this wasn't anything they had expected and it was unbelievable. This boy, this young boy who at one time was such a little boy. His, he had, he had swollen, his whole body had swollen, he was unrecognisable. It, it just was heartbreaking.

PAUL GELSINGER: I couldn't recognise Jesse. He was so swollen. It had, he was so swollen it had swollen his eyes shut.

MICKIE GELSINGER: And you were just standing there and thinking can't believe this, this is your son and what have they done to him.

PAUL GELSINGER: It was shocking, it was not something I ever want to witness again.

CAPTION: Friday 17 September 8:30 am

PAUL GELSINGER: We awoke early in the morning to go see Jesse. We walked over there about 8 o'clock in the morning.

MICKIE GELSINGER: And we were led to this little conference room, small conference room and two doctors walked in and, and sat down and told us that the bad news was that they found no - how did they put it? - there was no activity in his brain.

PAUL GELSINGER: That all his vital organs were shutting down, that they wanted to shut off life-support.

MICKIE GELSINGER: And they walked out of the room. That's it? So, so I guess that's when it hit, that it was going to end, his life was going to end, this 18-year-old boy because he was doing the nice thing, the good thing. He was so proud of it.

CAPTION: 2:28 pm

MICKIE GELSINGER: And the chaplain said a prayer and then he looked at us and...

PAUL GELSINGER: then I nodded to the doctors that it was time. Dr. Raper stepped in with a stethoscope. He turned off the machines. Within a minute Dr. Raper put his stethoscope on Jesse's chest.

MICKIE GELSINGER: And it was over. That was it. No turning back. Your kid is gone.

FRENCH ANDERSON: When I heard that he had died it was, it was absolutely overwhelming.

INDER VERMA: Immediately my heart sank.

FRENCH ANDERSON: How could this have happened? I presume that some mistake must have been made.

NEWS MONTAGE: ...also on the health watch medical detectives have now concluded that an 18-year-old is the first known person ever to die of gene therapy. Jesse Gelsinger... ...Jesse Gelsinger was 18 when he died last... ...this is a very, very serious... ...18-year-old Jesse Gelsinger died...

NARRATOR: The trial at Penn was halted and the government immediately launched an inquiry.

NEWS MONTAGE: ., that cold virus killed him. ...death of 18-year-old Jesse...

NARRATOR: For a brief while gene therapy labs across the USA were shut down and their practices examined.

NEWS MONTAGE: ...administration... ...University of Pennsylvania researchers did not disclose... ...outcry...

NARRATOR: By January 2000 the government had completed its first report.

NEWS MONTAGE: ...reaction... ...I would say this is a straightforward conflict of interest... ...nearly 700 serious adverse reactions... ...committee investigating... ...moratorium on all...

NARRATOR: And its findings about Jesse's case would shock the scientific world.

VOICE: ...death led to Washington hearings on how closely gene therapy experiments are...

NARRATOR: The investigators discovered that Wilson's team had not reported three crucial pieces of information about the trial.

JIM WILSON: But in particular we're here today to talk about the circumstances that led to the death of Jesse Gelsinger.

NARRATOR: Before Jesse was injected, they had modified the virus to make it less dangerous, but tests, even with this new vector, led to the death of two monkeys. It suggested a significant danger to humans, but Wilson's team never reported this.

JIM WILSON: ....come up was whether we had fully disclosed all of the animal data...

NARRATOR: Instead they modified the virus again.

JIM WILSON: ...repeated is to pass them along...

NARRATOR: It also emerged that Jesse was not the first patient to suffer adverse reactions to the virus. Earlier in the trial several patients had shown dangerous side-effects when injected with a lower dose than Jesse. According to guidelines, the trial should have been stopped immediately. Wilson's team didn't report this either. Finally, it emerged that there were questions about Jesse Gelsinger even participating in the trial. His OTC was flaring up at the time he arrived in Philadelphia. It should have ruled him out from taking part, but again it wasn't reported.

JIM WILSON: ...prior to this trial did we in any way expect to see what we saw in Jesse Gelsinger?

NARRATOR: Instead, the investigators learnt that Jesse Gelsinger, one of the weakest patients in the trial,. was given the biggest dose of virus. All of Wilson's clinical research was stopped. For the field of gene therapy the impact was devastating.

INDER VERMA: There were many stop signs and they shield have been followed and the trials should have stopped earlier and I think rightfully so for that Jim Wilson and his colleagues in the Institute of Human Gene Therapy is guilty of those practices.

NARRATOR: It didn't take long for the news to reach Paul Gelsinger.

PAUL GELSINGER: I was in shock. I cried for an hour and realising that, that these men had failed Jesse, the very men themselves who I had trusted, who had said they wanted me to be a part of their team.

NARRATOR: Paul Gelsinger now wanted to know why? Why had the animal deaths not been reported, why had the safety signs been ignored and why had these eminent doctors given the biggest dose of virus to such a weak patient?

PAUL GELSINGER: They were bending the rules all along and we had no awareness of this. I had nowhere to turn but legal counsel at that point.

NARRATOR: The man that Paul went to was Alan Milstein, successful but low profile lawyer in the suburbs of Philadelphia.

ALAN MILSTEIN (Lawyer): Paul comes in. He was still quite emotional. He was just coming to the point of realising that the Penn doctors had committed a terrible wrong.

NARRATOR: For 20 years Alan Milstein specialised in commercial law. Gene therapy was completely new to him.

ALAN MILSTEIN: I certainly knew very little about gene therapy. This was going to be quite a learning process for me.

NARRATOR: Milstein promised Gelsinger that he would answer one question, the one question Paul wanted to understand more than any other: why; why did Wilson's team break so many rules; why did a simple safety study go so wrong?

ALAN MILSTEIN: What troubled me from the start was what motivated Wilson and his team to do the things that they did, what explanation was that these were second or third-rate scientists at a second or third-rate institution and they really didn't know how to properly go about doing what they were doing. That I immediately rejected. These were top, top scientists.

NARRATOR: Milstein's inquiries next led him to Genovo and Jim Wilson's financial commitments. Was it greed that had motivated him?

ALAN MILSTEIN: Everything I learned about Jim Wilson suggested that this wasn't a man motivated by money. Money wasn't his god. His god was gene therapy.

NARRATOR: It appeared money alone could not explain what Wilson's team had done. Milstein was sure there had to be another, more convincing reason.

ALAN MILSTEIN: There were a lot of unanswered questions throughout this process.

NARRATOR: Gradually Milstein began to construct a theory, a theory that seemed to explain everything about Jesse's death.

ALAN MILSTEIN: You have to start back with the original design of this study.

NARRATOR: A few months before Jesse signed up, Wilson's team had made an apparently small but crucial change to the trial. By the time Jesse volunteered it was no longer just about safety. They wanted to see something more. The aim of the trial now was to see if Wilson's approach to gene therapy could ever actually help a patient.

ALAN MILSTEIN: They wanted not just to find that the dose was safe but that it works, which would have been a startling discovery.

NARRATOR: The problem Wilson's team faced was that most of those involved in the trial had a very mild form of OTC deficiency and none of them had shown any results, but Milstein believed that there was one patient left that could have allowed them to succeed. In the medical archives was a report on a unique case of OTC, on a four-year-old boy like no other in the world. That boy was Jesse Gelsinger.

ALAN MILSTEIN: He was someone that presented new possibilities for the scientists in this experiment.

NARRATOR: Jesse's condition made him unlike any other patient. Half his liver cells were normal, but the other half had the severest type of OTC deficiency, so severe it made him the most likely patient in the trial to respond to gene therapy.

ALAN MILSTEIN: He was a unique guinea pig. There was no guinea pig like it.

NARRATOR: Suddenly it all seemed to make sense: why Wilson's team ignored their own stop signs; ignored the animal deaths; above all else why they took so many risks. It seemed that Jesse provided Wilson's team with the ultimate opportunity: to be the first to unlock the full potential of gene therapy.

ALAN MILSTEIN: Rightly or wrongly, Paul believes that he led his son into this and that's a horrible burden for any father to carry.

NARRATOR: No one can ever be certain why Jesse Gelsinger died. With no comment from Wilson and his team, Milstein's theory will remain just that. On the top of Mount Wrightson Paul Gelsinger and his family said goodbye to Jesse.

PAUL GELSINGER: We spoke about Jesse and his life, what he was like, the character that he had and then we cast Jesse's ashes to the wind and I can look to this mountain any time and I can remember. I will not ever be able to forget this.

CAPTIONS: Jim Wilson has been banned from conducting trials on human patients. The University of Pennsylvania settled out of court with the Gelsinger family for an undisclosed sum.

NARRATOR: In the 12 years since French Anderson's first experiment only a handful of children have been cured with gene therapy. All had the same rare blood disorder. Two of these children have now developed leukaemia as a direct result of the vector. Even these successful genre therapy trials have now been halted. Gene therapy remains as elusive as ever.