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Discovery science: intergenerational effects

Watch Professor Andrew Prentice explain how discovery science is important and how it has changed the way we think about health interventions we use.
ANDREW PRENTICE: So if you believe that we know everything about the human body, then you would say we don’t need any more discovery science. Let’s just get on and implement what we know. Let me give you examples of where we don’t know what’s going on. If I ask you what causes preeclampsia? What causes preterm birth? You might be able to give me some answers and you could give me partial answers, but you certainly wouldn’t know the vast majority of the causation. And if we don’t know the causes, we don’t know the solutions.
Now, let me switch track a little bit and give you a lovely– or to my mind– a lovely example of where lab science has really progressed our thinking. So I’m going to talk about iron deficiency anaemia in children. Now, the old view used to be that children were terribly badly designed to absorb iron and hence we needed to give them lots of iron in a very easily absorbable form. And we gave it in tablets or capsules, in a very unphysiological way. Now, the new science, once we’ve now discovered how iron is controlled, how the absorption of iron is controlled, tells us something quite different. It tells us the children are not badly designed to absorb iron.
They are actively trying to keep it out and they’re trying to keep it out because, if they take too much in, they’ll get infections which are likely to kill them. And furthermore, the iron that’s not absorbed affects the microbiota in the gut. So that’s just a little example of how science has completely changed the way that we think about a problem and, as a consequence, needs to completely change the interventions that we use. I find it very exciting to be at the sort of cutting edge of discovery science but, at the same time, making sure that we’re always directing that towards making a difference. What difference can we make?
What new bit of knowledge would be important for us to design another intervention? The Gates Foundation uses this wonderful phrase, distinguishing between nice to know, which a lot of discovery science, and need to know, what we actually need to know in order to make a difference? Now, let me give you one example from our recent work. We’ve been very excited to discover that a mother’s nutrition at the time of conception has a huge effect on the epigenome of her baby and hence of its health. Now, what do we mean by epigenome?
Epigenetics is the way that genes that we inherit from our parents are modified by chemical modifications, methyl groups, and these modifications tell the body how to read the genes. So, the genes don’t change but the way that they’re read, that they’re interpreted is changed. And what we’ve discovered is that women conceiving babies at the two different seasons of the year, the dry season versus the wet season, it has a huge difference on how their offspring’s genes are read and that has some effect on their health.
So, at the end of the day, we hope to be able to translate this into an intervention in mothers or this intervention would have to be given before conception, in fact, so that we could optimise the epigenome and, as a consequence, the health of the children. So that’s really exciting because it shows how discovery science could lead to a next generation of intervention that would really make a big difference. The question then of whether we have an inter-generational effect. In other words, could the nutrition of my parents and my grandparents, your parents, your grandparents, have an effect on you, is a big one, in many ways. Now, of course, to some extent, we have inter-generational effects.
Our parents influence us as to what we’re going to eat, our grandparents influence them as to how they live their lives and what they would eat. So that’s all known and, of course, we inherit these effects through families. What is much less known is whether this can occur biologically. Is there any information that can be laid into our genome, our genetic makeup, that would then be remembered across generations? And this is still very controversial but there’s quite a lot of emerging evidence to suggest that yes, this is possible.
The reason it’s controversial is that the epigenetic marks, so these are labels put down on DNA, that might carry some messages are mostly cleaned up as soon as the sperm meets the egg and fertilisation occurs. Then there’s a kind of wipe clean exercise. And so all these messages from the prior generation some people believe would be completely wiped. Now, the other camp believe that actually a lot of wiping occurs, but not all of it. And a substantial number of messages get through.
So we’re still at the point of discovery, where we’re not quite sure but we have a lot of evidence to suggest that yes, it is very possible that the environmental effects on our parents, our grandparents, our great grandparents are still influencing our health. And that, of course, is very important in terms of understanding how quickly we could achieve change within a single generation and also how we should go about that. So it may well be that, as we’re trying to move societies from being very poor at the moment, poor health outcomes, that it maybe we have to be patient and go generation by generation and not try to fix the whole issue here and now in a single generation.
If we try that, we might actually have adverse consequences.

How can discovery science contribute to the improvement of child health? If we don’t know the cause of a problem, we’re unlikely to know the solution to it either. This is how science has changed the way we think and the health interventions we use. In this step we focus on epigenetics, with Professor Andrew Prentice highlighting the potential intergenerational effects of nutrition on mothers and their children.

In thinking about discovery science, what would be nice for us to know, and what do we need to know in order to make a difference to child health? If you could choose anything, what new piece of biological information do you think would help us solve a particular problem that impacts upon child mortality and morbidity?

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Improving the Health of Women, Children and Adolescents: from Evidence to Action

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