Trial and Error - programme summary
It was the simplest idea but one with enormous potential.
If a gene is defective in the human body, just replace it with
one that works properly. Gene therapy would mean that genetic
disorders would become a thing of the past. Cancer would be
cured, as would cystic fibrosis and hundreds of other genetic
illnesses. Scientists were justifiably excited about the idea
but, this enthusiasm that would end up costing one young man
his life.
Jesse Gelsinger was born with a liver disorder, a rare
condition called ornithine transcarbamylase (OTC) deficiency
that stops the liver metabolising ammonia. People with the
disease can suffer from brain damage or coma. At its most
extreme the illness is fatal.
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"In 1998, Jesse was as healthy as I had ever known
him" |
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Paul Gelsinger, Jesse's
father |
Jesse was lucky, able to lead a fairly normal life although
he had a daily cocktail of drugs to control his condition.
Jesse wanted to help others. When he was offered a chance to
take part in a medical trial to test the safety of using gene
therapy for OTC deficiency, he was keen to participate. He
knew this was not a cure for his condition but that, by
volunteering he might be able to help others in the future.
Delivering a cure
Although the concept of gene therapy is simple, the
practice of administering the treatment is much more
difficult. In order to replace defective genes, doctors must
get working ones into the body and to the place where they are
needed.
Scientists had an ingenious solution to the problem. Hijack
one of our most deadly enemies - the virus. A virus infects a
human by inserting its harmful genes directly inside our
cells. Normally this causes damage to the cell making us sick,
but scientists were convinced they could tame this natural
ability. Replace the harmful genes with good ones, and the
virus would be the perfect delivery vehicle, or vector.
It was initially believed that a retrovirus would be the
best way of getting modified genes into the body. Most viruses
and cellular organisms store their genetic material as
deoxyribonucleic acid (DNA). Retroviruses use ribonucleic acid
(RNA) instead. Retroviruses combine their genetic material
with that of the host permanently, hence they can offer a
permanent cure.
Unfortunately trials using retroviruses had very little
success treating any illness other than one particular type of
blood disorder, severe combined immunodeficiency (SCID).
British doctors have recently used this technique to cure five
year old Rhys Evans with great success. Scientists realised
that if they wanted to treat organs in the body like the
heart, liver or lungs, they would have to find an alternative
way of delivering their treatment - retroviruses simply
couldn't get in.
The answer would come from respected scientist Dr James
Wilson, who had in 1992 set up the largest gene therapy centre
in the world. He proposed using the most common virus around:
the adenovirus, cause of the common cold. The adenovirus
seemed like a good choice because it is able to affect almost
every cell in the human body.
The trial
Wilson needed a disease to trial his adenovirus vector on,
and by chance set his sights on OTC deficiency, the disease
affecting Jesse Gelsinger. So in September 1998 Jesse and his
family were approached to participate in a trial. Jesse knew
that taking part was not going to cure his OTC but he was keen
to help because he knew that if successful he would have
played a part in curing thousands of diseases.
On 12 September 1999 Jesse arrived at the University of
Pennsylvania to begin the trial. One day later a member of
Wilson's team injected Jesse with the tame viral particles. He
was given the biggest adenovirus dose of any of the trial
participants. The doctors told Jesse to expect a small
reaction to the virus.
On the 14th when a nurse checked on Jesse she found that he
was slightly confused and jaundiced. Although they doubted
this was serious, the team wanted to be sure. The adenovirus
was supposed to be harmless but Jesse's body was behaving like
it was under attack. By the next day Jesse was in a coma.
Over the next two days Jesse's condition deteriorated until
on day five, Wilson's team of doctors delivered the
devastating news to his parents. Jesse had no brain activity,
his internal organs were shutting down. The doctors suggested
that Jesse be removed from life support. Jesse died at 2.30 pm
on 17 September.
Leaning the lessons
In the aftermath of Jesse's death, it emerged that vital
facts about the dangers of the vector had never been given to
the Gelsingers.
What chance of success is there now for gene therapy and at
what risk? For many people the dream of gene therapy is dead.
It is not the cure all that we dreamed of ten years ago but
instead it is a highly selective treatment for a very small
number of diseases. Gene therapy may still become an effective
treatment for thousands of people but this is no miracle
cure.
