Genetic therapy: a bitter price for progress?
By Andrew Freeway (with thanks to Journal of American Medical Association JAMA)
First the infant, Wilco, had a deadly immune disease. Genetic therapy was applied. But now he has got leukemia. All over the world scientists and policymakers are struggling with this dilemma: can we continue the research and development of this 'successful' genetic therapy or do we have to stop it now?
This spring Wilco was the hero of the French science. The Dutch toddler, with his photo genetic blond hair, blue eyes and snub nose was covering the front page of all French newspapers. He even appeared in a fundraising TV-spot.
This public display was due to the glorious success of an experimental form of genetic therapy. Wilco was born and diagnosed from birth with the fatal hereditary immune disease SCID. He received this experimental therapy when he was only 1 month old; the therapy made it possible that he was still alive at an age of 3 years old.
This October, only half a year after the big media exposure, the tide is going out. Wilco, who was treated by the Parisian children's hospital Necker-Enfants Malades, was diagnosed with leukemia. The responsible professor Alain Fischer was hoping that the leukemia was a spontaneous disease, just bad luck. But after some detailed DNA-analyses he had to conclude that the leukemia was prompted by the genetic therapy that saved the boy's life in the first place. A personal drama for little Wilco and his parents: kept alive only to get leukemia! But also a big damper for the scientists; the genetic therapy was, till now, the only working therapy to defeat SCID.
Ethical dilemma
But Wilco's leukemia is also responsible for a major scientific and ethical dilemma. We now have to cope with the remarkable phenomena that someone contracted a life threatening disease through an experimental therapy that saved his life. Without the therapy Wilco would have died some time ago, but this therapy could mean that he will die soon as well. Is such a risk acceptable? And can the research continue or is a moratorium necessary?
For an answer we first have to look at the necessity of the therapy. Boys with SCID - girls are never affected - are missing an essential part of their immune system, the so-called T-cells and killer cells. Therefore they have hardly any resistance against viruses and bacteria. Not so long ago boys with SCID mostly died before they became 1 year old. The 'boy-in-the-bubble' is a famous example of a boy who had SCID and got older. Only after the introduction of bone marrow transplantations it became possible for these boys to reach the age of 65. But the side effects of this therapy were enormous and in many cases the transplantations did not work.
The French genetic therapy is based on the fact that SCID is caused by only one defective gene. Due to this defect the body is not developing T-cells and killer cells. Building a copy of a good working gene into the bone marrow of the patient, so it was thought, could repair the defective gene. Bone marrow cells are the incubator of all killer cells. With the introduction of the new gene the missing killer cells could still be developed in the patient's body.
10 of 11 boys have no complications thus far
When the theory was put into practice a miracle occurred. Eleven boys have been treated and 10 of them are now blessed with a good working immune system. The constant fear of infection is over and everything went without any complication.
But Wilco's leukemia became the hitch in this new approach. One of the healing new cells had nestled itself in a very unfortunate spot in Wilco's hereditary characters, the so-called LMO2-gene. A gene that was involved in developing new blood cells and that could create havoc if it became overactive. That is why these kinds of genes are called 'oncogene'.
The other 10 boys are still doing fine. But since there is a chance that also one of these boys will have this gene or another oncogene being infected by the therapy, they will be tested every 6 months. The question that has to be answered is clear: can other boys being treated with this genetic therapy or is the risk too high? The answer will be of great importance, and not only for boys with SCID. All other genetic engineering will be the subject of this decision.
Some countries putting this research on hold
Anticipating this difficult ethical debate, France, Germany and the United States have decided to put this research on hold. Only the United Kingdom will go forward using the argument that the parents of the boys and their physicians are well able to judge for themselves if they want to accept the risk. It is very likely that the United States will eventually follow this approach since the FDA have decided that putting the therapy on hold is too drastic a step to take.
And what about little Wilco? Since he is only 3 years old he hardly knows what is going on. He will receive the standard treatment for leukemia that probably gives him a reasonable chance of surviving the next 5 years. But since no one ever got leukemia due to genetic therapy it is not clear if the standard treatment will work. Time will tell, but progress can have a very high price.
(source Trouw)
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