Watching him run and play, you would never know two-year-old James Machin is a haemophiliac. Because of a gene inherited from his mother, his blood lacks the clotting factor which normally keeps people from bleeding to death when they are injured. Not long ago, James would have faced a life of mollycoddling to prevent him injuring himself, and pain and progressive degeneration of his joints when, inevitably, he did fall or bump himself. But now, James will grow up going to school and playing sports like any normal boy, because Ireland is to become the first country in Europe to offer the latest in high-tech, safe medicine to all haemophiliacs.
The medicine itself, Factor VIII is nothing new: it was the miracle development of the 1960s, a blood product that supplied haemophiliacs with the clotting factor they needed. But as time went on, it became apparent that Factor VIII, too often containing infections, regularly harmed as it saved. But James's medication is different. Like all young Irish haemophiliacs, he is now being given Factor VIII cultivated in a laboratory, which eliminates the danger - and the fear - of contracting viruses from donor blood. Also, it is hoped that new research being conducted in this country into the gene which causes haemophilia could help bring about a cure. Beneath his clothes, James has a small, yellow "porta-cath" inserted into his chest. Twice a day his parents, Gillian and Robin, from Dublin, inject him painlessly with "recombinant" Factor VIII through the porta-cath. "It's meant that we haven't had to wrap him in cotton wool," says Gillian Machin. "We still have to watch him for bruises, swelling and joint damage, but he's full of life and energy and his life has no restrictions." At the National Children's Hospital in Harcourt Street in Dublin, Dr Owen Smith uses recombinant Factor VIII prophylaxis to turn severe haemophiliacs, like James, into moderate or mild cases. This preventive treatment eliminates the once inevitable long-term effects of haemophilia, such as crippling joint damage. The first generation of children treated in this way in Sweden has reached adulthood and is physically normal. "Fifteen years ago, these children with haemophilia were stigmatised. They were on crutches, in wheelchairs and many had fixed joints with pronounced limps. Today you wouldn't know a child with haemophilia to look at them," says Dr Smith.
If James had been born before 1985, he would by now almost certainly be infected with Hepatitis C and the chances are high that he would be also have been infected with HIV, the virus that causes AIDS.
Before 1989, the only source of Factor VIII was the plasma from donated blood. It took the blood of 2,000 donors to make a single 10ml vial of Factor VIII. Children and adults with haemophilia were exposed to the contaminants in the blood of 2,000 people each time they were injected. But James is lucky. Since his birth in 1995, he has been receiving recombinant Factor VIII produced artificially - from hamster kidney cells.
The Factor VIII gene was first cloned in 1985: then, it was discovered that it was possible to incorporate the gene into the DNA of the hamster kidney cell, whereupon the cell would start producing the Factor VIII protein. This "recombinant" Factor VIII is then purified and dried into a powder.
In 1989, recombinant Factor VIII began to be used in children born in the US and by 1995 in some children in the Republic. Because of its cost, children born before 1985 in Ireland were excluded. But - call it a guilty conscience, if you will - by the end of this year the Republic will become the first country in Europe treating 100 per cent of its haemophiliacs with recombinant Factor VIII rather than the plasma-derived form. Only 45 per cent of US haemophiliacs get recombinant Factor VIII and in the UK, an unevenly financed health service means that haemophiliacs get "Factor VIII by postcode", as one newspaper described it. In Canada, the proportion is more than 80 per cent.
Whatever its motivation, the Department of Health deserves praise for its decision to pay for recombinant Factor VIII: the cost is £36,000 to £72,000 for each patient, each year - about 25 per cent more than plasma-derived Factor VIII.
It was one Dr Judith Pool who in 1964 found a treatment to replace the traditional treatment for haemophilia - massive transfusions of plasma. She found plasma frozen and then thawed separated into a slurry and a clear fluid. The slurry, which she called "cryo-precipitate", contained high levels of Factor VIII in a smaller volume than ordinary plasma. Parents took the frozen vials home and if the child began to bleed, they thawed the contents and injected them into the child. Children with haemophilia were freed from the hospital and could be independent and go to school. Cryo-precipitate seemed a miracle in itself but there was a high price to pay. By the late 1970s, one of the great medical tragedies of this century began to unfold. Haemophiliacs started to show abnormal liver function as a result of Hepatitis C. In 1982, the first haemophiliac was diagnosed with HIV infection. In the early 1980s the horrifying truth emerged that the entire plasma pool used to make Factor VIII and its successor, Factor IX in North America and Europe was contaminated with HIV and Hepatitis C.
By 1985, almost everybody who been treated regularly with Factor VIII concentrates had been contaminated - either with HIV and Hepatitis C, or with Hepatitis C alone. In the Republic, the toll included 120 haemophiliacs infected with both HIV and Hepatitis C, 45 of who are still living. Two hundred children and adults were infected with Hepatitis C alone.
Since 1985, various agents have been used to fight Hepatitis C and HIV in plasma, but there are other viruses which cannot be killed with heat or chemical methods. These include Hepatitis A and the parvovirus, which can cause bone marrow failure.
Recombinant Factor VIII - and recombinant Factor IX, due to become available in the spring of 1998 - eliminates these risks.
But more can be done. Dr Smith has asked the Minister for Health, Brian Cowen, to bring in a "haemophilia comprehensive care programme", a one-stop shop for haemophiliacs where doctors, nurses, social workers, physiotherapists and orthopaedic consultants would be based in one unit to be called the National Centre for Inherited Bleeding and Clotting Disorders. As well as haemophilia, the unit would also treat and research other blood disorders affecting more than 1,000 Irish people. Dr Smith thinks that this new unit could be based only at either St James's Hospital or the new Adelaide and Meath Hospital incorporating the National Children's Hospital at Tallaght in Co Dublin. He estimates the cost at £1.2 million.
One of the unit's most important functions would be to offer genetic counselling to affected families. It still happens that some parents discover they have a haemophiliac child on the delivery table - a far-from-ideal time to prevent possible complications, since babies with haemophilia should be delivered without forceps or by Caesarean section, to prevent serious brain haemorrhage.
Already, some young Irish women with haemophilia in their families are receiving genetic counselling at St James's, where a team of four scientists is studying the genetic basis of the disease. Haemophilia affects only males, but the genetic defect is passed from fathers to daughters and from daughters to sons. There is a simple blood test to tell a woman whether she is a carrier. Then, if she decides to have children, her obstetrician can opt for a Caesarean birth. There is also the possibility that the foetus could be treated with Factor VIII in the womb or soon after birth. The earlier the baby is treated, the less likely he is to develop "inhibitors", or antibodies, to Factor VIII. At St James's Hospital, the team is trying to find out why a particular haemophilia gene mutation predisposes a sufferer to make Factor VIII or IX inhibitors (antibodies). James, for instance, has developed inhibitors to Factor VIII - which means that when he bleeds, he has to be treated with recombinant Factor VIIa: it is hoped, meanwhile, that the twicedaily injections of recombinant Factor VIII will persuade his body to tolerate the treatment so that he no longer produces the inhibitor.
This process has already been successful for one Irish child in James's situation - but by the time it worked, when he was six, his treatment had cost the State £1 million. "If we can get them earlier then we can use less Factor to tolerise them," Dr Smith says.
Dr Smith believes that, with proper funding from the Department of Health, the Republic could be the first country in Europe to have gene therapy for its haemophiliacs. "Having recombinant Factor VIII without the unit to back it up is like having a Formula One racing car with a 70-year-old granny driving it, or having a Jacques Villeneuve without the pit stop people. The time has come for us to have a truly comprehensive haemophilia care centre. This community has been decimated and deserves the best available care," he says. For James, the future looks bright. For James's grandchildren, haemophilia will be cured before birth. The horrors it has brought - from fatal bleeding in the 1880s to AIDS in the 1980s - will belong to the medical history books.