This time last year, baby Rhys Evans was struck down with pneumonia and needed a ventilator to breathe. Suffering from a rare inherited disorder that had robbed him of a working immune system, Rhys had to live in an ultra-sterile hospital room cut off from the outside world.
Today, the 18-month-old toddler is like any other little boy of his age – full of mischief and fun, with an insatiable desire to run around whenever he can. He lives at home and shows no signs he was once so ill.
Doctors at Great Ormond Street Hospital said yesterday that Rhys was living proof that gene therapy works. Some went so far as to say he has been cured – the first gene therapy patient to receive that accolade in Britain, and only the second gene therapy "cure" worldwide.
"We're very pleased to announce the successful cure of the first patient in the UK by gene therapy," said Professor Christine Kinnon, director of the Centre of Gene Therapy for Childhood Diseases at the Institute of Child Health in London, who collaborated on treatment.
It is rare for doctors to use the "c" word. Cures are meant to be permanent and, although Rhys shows every sign he is now normal, there is still a risk he may relapse, making him once again vulnerable to the opportunistic infections that strike someone with a compromised immune system.
Indeed, Adrian Thrasher, the consultant paediatric immunologist at the Great Ormond Street Hospital, who carried out the treatment was more cautious. "I'd like to say that Rhys is cured but we can't say that," he said.
"Rhys will be followed up for years and years. Only in the long term will we really be able to compare what we've done to Rhys with our other patients who've been through more conventional transplant procedures."
The first signs that something was wrong with Rhys came four months after his birth at about the time when his mother, Marie, began to stop breastfeeding. A series of chest infections turned into severe pneumonia, which led to 10 days in an oxygen tent before he was put on a ventilator. After a series of tests, the problem was finally identified. Rhys had acquired a defective gene on the x-chromosome – inherited from his mother. It meant he could not produce the vital lymphocytes – a type of white blood cell – essential for his immune system.
Medically, the condition is called x-linked severe combined immunodeficiency (XSCID). The more popular name is "baby in the bubble" syndrome, because of the sterile plastic spheres used to protect some babies with the disorder.
An analysis of Rhys's blood showed the few lymphocytes he possessed came from his mother and the supply had been cut off when breastfeeding ended.
Marie Evans, 31, remembers the pit of despair she and her husband faced knowing their little boy was so ill. She said yesterday: "Life was a bit of a rollercoaster. One day we could be up and the other day we could be down."
Mark, her husband, gave up his job to care for Rhys and he suffered badly from depression and anxiety. Mr Evans said: "If you'd seen how bad he was. He was skin and bone, too weak to hold his head up."
When Rhys regained enough strength, he was transferred from hospital in south Wales to a sterile room at Great Ormond Street. Doctors soon began the search for a bone marrow donor. It was the one source of hope for Rhys who did not have a brother or sister to act as a tissue-matched donor. For the past 20 years bone marrow transplants have been an effective treatment for disorders of the blood and immune system. But without a suitable match, a transplant was impossible.
Mrs Evans said: "We were told one day there wasn't a match in the UK, we looked worldwide and we were told there was an American donor and the next day we were given the opportunity of gene therapy."
The first stage of the operation was simple enough. Under a general anaesthetic, doctors extracted bone marrow cells from Rhys and froze them.
They genetically engineered a mouse retrovirus – a type of virus with a natural capacity to inject genetic material into the chromosomes of a cell – so that it possessed a healthy copy of the human "gamma c" gene that Rhys lacked.
Scientists connected a bag containing the genetically modified virus to a bag of Rhys's bone marrow. The hope was that the virus would mingle with the bone marrow cells and inject the healthy gene into the stem cells.
Mingling completed, the doctors then transfused the marrow back into Rhys last summer in a painless procedure similar to a blood transfusion. There was then an agonising period when both parents and doctors waited to see whether it had worked.
By Christmas, Rhys was showing signs of getting well. Two months later, his lymphocyte count shot up to almost normal levels. For the first time in his life, Rhys was able to start mixing with other children and playing outdoors.
Dr Thrasher said: "Rhys has a normal immune system, he's thriving, he's normal. We were enormously relieved. We were ecstatic. We've been working on gene therapy for many years in the laboratory and it's great to be able to take that work into the clinic and see some therapeutic success."
The first gene therapy trial took place in the US in September 1990. Since then about 500 trials worldwide have been done, with little success. Although there are risks with gene therapy, Dr Thrasher believes it is safer than conventional bone marrow transplants, which often involve chemotherapy.
A second 10-month-old child with SCID also underwent gene therapy at Great Ormond Street four months ago. The patient is doing even better than Rhys at a comparable stage.
Dr Thrasher said: "The procedure is incredibly safe. We've seen no side-effects at all in either of the patients. The risk of cancer resulting from conventional chemotherapy is probably a lot higher." He said Great Ormond Street had applied to the Gene Therapy Advisory Committee for permission to conduct further trials on other conditions. "In principle, it means we can extend this type of therapy to other blood diseases and that's going to be hugely important for many of our patients who don't have bone marrow donors," he said.
Disorders and diseases that could be tackled
Mucopolysaccharide diseases: These affect one in every 25,000 babies and are caused by genetic defects resulting in missing enzymes. Waste products build up inside cells, causing progressive physical and sometimes mental deterioration. Children with the disease usually die at a young age and at present there is no cure.
Chronic granulomatous disorder: Simple inherited defects involving just one gene cause this dangerous blood disorder. Children are vulnerable to pneumonia, bone infections and abscesses on vital organs. Gene therapy trials are to begin soon at Great Ormond Street hospital.
Cystic Fibrosis: The most common genetic disorder of north Europeans. A single gene defect causes a build-up of sticky mucus in the airways of the lungs. Children have to undergo hours of physiotherapy. Scientists have already begun trials to replace the defective gene using a genetically modified cold virus, but this has proved to be difficult.
Haemophilia: One of the most studied genetic diseases, it famously affected the royal families of Europe. It is caused by the lack of blood-clotting factors that control bleeding and bruising. Gene therapy trials in the US have begun with the first few patients producing healthy amounts of the missing clotting factors. The Royal Free hospital in London has considered a similar trial.
Primary immunodeficiencies: These affect the immune system. More than 80 diseases have been identified; the most complex are the severe combined immunodeficiencies (SCIDs), a variety of which afflicts Rhys Evans.Reuse content