Thank you very much.
Thank you for asking me to be part of this important meeting.
My main interest started when I was about to become a medical student and heard, of course, of the Distillers action in the U.K. when the story of the thalidomide problem first broke. Thalidomide was in fact the start of the discipline that I've worked in since 1980, namely pharmacovigilance.
Pharmacovigilance is a discipline that looks for problems with medicines and tries to establish a causal link between a medicine and the harm. The difficulty is how to establish causation. That was the difficulty that faced the investigators in the early days in Germany and in the U.K. It's a real problem because, given the extreme disability caused or thought to be caused by thalidomide, what they were tasked with was, how do you decide on what is caused by thalidomide?
They were actually seeing individuals and trying to work out what was the causative link between thalidomide and a variety of defects. They put together what we would call a “syndrome of defects”, which they were sure—or pretty sure—followed the exposure to thalidomide. Knowledge of the exposure was a critical factor. The first point I must make is that it isn't just being exposed to thalidomide: it's being exposed at a critical time, during the first three months while the baby is forming essential organs. That is a critical factor in the cause-and-effect situation: to know exactly when the drug was taken by the mother.
The second thing is that the thalidomide syndrome was rare. Therefore, each expert at the time would see perhaps a maximum of 200 patients. Indeed, in the research I'll talk about shortly, we have been able to have only around about 200 people who we're sure took thalidomide during those early three months of pregnancy, so therefore we could be as sure as we possibly could be that there was a cause-and-effect relationship.
That work was done a long time ago. Things have moved on since then. It's important to note that there's a kind of gap. We do know that thalidomide is still being used for inflammatory diseases and cancer, but that usually means that it's not given to women of child-bearing age.
It is used in the treatment of leprosy to counteract the negative effects of Dapsone, and therefore it is given to some young people. In Brazil, for example, we know there are about 400 women who have had children with the obvious features of thalidomide exposure. The trouble is that we haven't been able to look at them closely because they're in rural areas and the facilities haven't been made available for us to update our knowledge.
I was asked by The Thalidomide Trust in the U.K. if I would help them bring together a meeting of experts within the WHO umbrella to see what we could firmly state about the cause-and-effect relationship between thalidomide and congenital defects. The short answer is that we were only really able to confirm for sure what was thought all those years ago.
There is research, and it was actually all presented at a meeting, about the way in which the thalidomide-type drugs might affect a growing embryo, and it's in all sorts of ways. Unfortunately, that is only experimental work, and we're left with a feeling that there might be more. There is some excellent work going on, but as I say, we don't have anything that goes from the experimental work in animals and other models to what happens in human beings who are exposed now.
There is a final thing I want to say by way of introduction. When the thalidomide embryopathy was first discovered, it was thought that it was going to be unique because it was so rare. People were saying that it only occurs with thalidomide, that it doesn't occur naturally. Since then, we've found that unfortunately there are genetic reasons that similar limb reduction and other defects can occur because of a family history of genetic problems. That makes it very difficult.
I think I would prefer to answer questions, but I want to mention one thing. We have worked out a “decision tree” way of making a diagnosis of the conditions that might be caused by thalidomide in a human being, based on this historic evidence and based on Europeans. It really only confirms the very limited views that we have about the effects that are well known to be caused by thalidomide.
We haven't been able to say any more. Indeed, what we have been able to say is that some of the conditions where thalidomide has been a possible cause have in fact been explained by other genetic problems. Genetic testing is a key issue.
As I say, I think I would prefer to answer questions.