What happens to you, happens in very early life. If you’re very anaemic, if your spleens come out, it’s coming down there, and it’s coming down very fast, and extraordinarily fast in some of these children. Once you seem to get past that, then everything seems to slow up. So we wondered obviously why, and one of the things we decided to look at, was the way these children respond to anaemia, by, and of course, anaemia response is partly through the red cells shifting its oxygen affinity, and partly through the kidneys then getting a hypoxia signal to produce more erythropoietin and once that’s all done, then the old heart starts to bang in, and so we’d done all that, well, we’ve done two of those things– we’ve not yet, we are now looking at the hearts of these people compared with age match controls but, the interesting thing is that, is the erythropoietin response. So if one looked at them, one’s got duplicate, triplicate examples over time, the first observation was totally surprising to me, that, that age and haemoglobin are independent variables for erythropoietin response. And then if you start to draw erythropoietin response curves at different haemoglobin levels, they seem to be age dependent. So if you’ve got five grams of haemoglobin at the age of two years, on average your erythropoietin response will be much higher than if you’ve got five grams of haemoglobin at five years, and that’s the thing that’s just seen the light of day in the PNAS. Now, that was really fascinating, but then the question was, well, is this something that’s just due to thalassemia, some quirk of the disease? It’s not, nothing to do with foetal haemoglobin, we know that, but, so we went back to Papua New Guinea, where we’d been doing a study of alpha thalassemia response to malaria, and did exactly the same measurements, and fairly exactly the same thing, that there is an age-dependent effect on your response to profound anaemia, and that the younger you are, the greater the EPO response. So, in terms of thalassemia, that’s making us wonder now, well maybe in these slightly milder forms like E thalassemia, we could possibly start attempting to do what you might call transient transfusion. If we could see those, see them through those developmental phases of maximum response, could we stop it? And so, we have stopped transfusing quite a number of these children that have got older now, but that would be quite anecdotal. They’ve stayed off, they’ve grown well, they’ve developed well, but one has to now do this in a proper, controlled kind of way, I think.
