Leading Edge
with Geoff Watts 
Geoff Watts: Roger Highfield,Roger you've been listening to that,do your sympathies lie with the threats or reassurances side of the argument? Do you lie awake at night about PCBs? 

Roger Highfield : It's a very difficult problem and you need a two - pronged attack on that problem,you need epidemiology.We heard reference to these big prospective studies,and there you want to establish a link between exposure to some chemical and say low sperm counts,and that's not that easy,and then maybe to help things along you might do something called a meta-analysis,where you bundle together lots and lots of studies and then see if they're all pointing the same way.Then the other prong of the attack is toxicology,you have to show what's going on at the molecular level.You have to see whether a chemical is mimicking the action of Oestrogen,the female sex hormone,or in some way blocking the action of Testosterone,the male sex hormone,and then you have to back that with animals,and there are traps with each approach.Epidemiology gives you false association.So you could do a study of 10,000 Chinese and find a link between testicular cancer and silk underwear,but that could be because only individuals who can afford silk underwear could afford a 100 cigarette -a - day habit! 
You might find your meta-analysis is bogged down,because scientists won't bother to report studies that don't show any associations,so that biases the data,and equally you might find a chemical that has a shape and and electronic properties of a sex hormone in a detailed toxicological study won't actually get through the body to the place where it's going to have any effect.So you've got to out these things together and there are some very big cautionary tales.Only last week David Lewis of the Environmental Protection Agency in the States told us that we've completely neglected one huge factor,which is whether these environmental pollutants come in right-handed or left-handed forms [Ref: Video BB10:RI Lecture {Man in the Mirror};[Media 1] Focus 1 {Thalidomide}],and that completely changes the way the body reacts towards them,and indeed the way that they're broken down in the environment.So because we don't know that,we're actually....all these enormous data bases on environmental pollutants are fundamentally flawed,so it's a big difficult problem. 

Geoff Watts: That takes us on to the more quite general point,I suppose about science stories that we hear in the newspapers,watch on television,even hear on radio.We can't always take them at face value can we? Because there's so many vested interests behind them? 

Roger Highfield : Absolutely,I mean I think there are two problems here.First of all the agenda of journalists is you know,I write stories on a daily basis and actually it can take decades for this kind of complicated problem to really show all the kind of nuances and all the details and subtleties,so we lurch from headline to headline,and secondly I think environmental groups are just as ruthless as big business when it comes to over playing the significance of a certain study,and so people like me are sort of piggy-in- the -middle,we're trying to make sense of a lot of complicated information and we get very aggressive campaigns from green groups,just as much as we get very sort of aggressive campaigns telling us that all chemicals are safe from industry groups.It's very hard to sort of see away through all this information. 

Geoff Watts: Worth remembering when one reads the stories.Thanks very much Roger. 

Geoff Watts: Now,like begats like,goes the old proverb,and never more so you might think,than when the organisms doing the begatting are genetically identical.One woman though,along with a nest of Australian mice would dispute that view. 

Emma Whitelaw : These mice are genetically identical to one another,but they display different coat colours.There are, within a litter of genetically identical individuals,some yellow,some are completely grey and some have a mottled appearance of yellow and grey patches,and every mouse has actually got a unique coat colour and unique patches. 

Geoff Watts: That was Emma Whitelaw of the department of biochemistry at the University of Sydney, writing in the latest issue of the journal "Nature: Genetics",Dr Whitelaw describes the appearance of her Technicolor mice as a product of what's called "epigenetic inheritance".The information which determines the structure,function and appearance of any organism is carried in its genes,long molecules of DNA,wrapped up into sausage-like packages,called chromosomes.All other things being equal,mice which have the same genes,will all look the same,but other things may not be equal,says Dr Whitelaw.Scattered along the length of the DNA molecule are chunks of protein which can mask certain genes.In other words prevent a cell getting access to the information those genes contain.To use a homely metaphor,you and I might both have the same size tins of the same nice yellow paint,but if only one of us can get the lid off,only one of us will end up with nice yellow walls.If Dr Whitelaw's mice really are the product of this extra influence,this epigenetic inheritance,they're probably not alone.There's evidence of it operating in yeast,fruit flies,various plants,and even humans. 

Emma Whitelaw : It's known,for example,in genetically identical twins that there are many physical traits which differ between genetically identical twins,such as their tendency,for example,to display genetic diseases.There can be one member of a pair of twins who suffers from a genetic disease,but the other member of the pair does not suffer from that disease.There are also rather more obvious ones,like eye colour,you can have one member of the twin having blue eyes,and another member having hazel eyes [One might ask how genetically identical they are under such circumstances-LB].I suppose a pure geneticist,who was not prepared to accept the idea of epigenetic inheritance might say that these differences were the result of differences in the environment that these two twins experienced at some stage in their life,or their early development.But really,for things like eye colour,it's seems rather hard to believe. 

Geoff Watts: I don't know if you're familiar with the work of an epidemiologist,who works in Southampton in this country,called David Barker,but he has put forward the idea that many of our adult health characteristics are affected by our experiences in early life,while we're in the womb...... 

Emma Whitelaw : Yes. 

Geoff Watts: ...is it possible that some of what he is describing,as the effects of the environment in the womb,might be also explained by..as an epigenetic phenomenon on the kind of explanation you're putting forward? 

Emma Whitelaw : Yes.Yes,and I think his work is extremely interesting.I heard somebody talk about it in fact in Sydney,about six months ago,and I said....at the end of the talk,I talked to him about the possibility of epigenetics as being an explanation for this,and although he didn't mention it at all in the talk,he said that they were just employing somebody to actually study the epigenetic state of some of the genes that they thought were associated with the physical traits that they were measuring.So they too,were beginning to be interested in this as an angle and an explanation for their work. 

Geoff Watts: Can you conceive of any biological advantages that might explain why this whole system had appeared in the first place? Does it have any positive virtues from the point of view of the organism? 

Emma Whitelaw : Some people believe that the reason that the silencing,epigenetic silencing mechanisms first arose in organisms,was to suppress or silence foreign genetic information that invades the genome,and tries to take over. 

Geoff Watts: A kind of defence mechanism? 

Emma Whitelaw : Yes,a defence mechanism,exactly.the kinds of genes which display these effects appear to be controlled by neighbouring bits of DNA called retroviruses.Now retroviruses are organisms in their own right that invade the genome,and in a way take over the genome.It's like an infection. 

Geoff Watts: An example would be what? 

Emma Whitelaw : Something like AIDS. 

Geoff Watts: Right HIV? 

Emma Whitelaw : HIV. 

Geoff Watts: Any particular reason you think we are beginning to get to grips with this now? Because after all we've been ,you know - for 20-30 years -a fair idea about the molecular basis of inheritance? 

Emma Whitelaw : Well,one of the reasons that we're beginning to see these events now,is because we're doing experiments in which we add bits of DNA back to genome,and these experiments are sometimes called genetic modification,genetic engineering.All of this involves adding DNA molecules back to the genome of a living organism,whether it be a plant or a mouse,and of course,if you're talking about a human,that kind of experiment is called gene therapy.But the observation that scientists have made,when trying to do these experiments is that frequently the genetic information that we add to the genome of an organism is silenced,and it's been really a puzzle why,when we put a perfectly good bit of DNA,in terms of its sequence,the sequence information was perfect,we would put it into a mouse and it would be silent,and this is tremendously frustrating to scientists who would like to achieve gene therapy,such that the gene is on at all time. 

Geoff Watts: If Emma Whitelaw is right,it really is bad news for gene therapy.Transplant surgeons already have to use immuno -suppressant drugs,to overcome the bodies tiresome habit of rejecting donor organs.In attempting to introduce new genes the molecular physicians of the future may have to do something similar,to develop what I suppose you could call epigenetico-suppressant drugs,though if they do I hope they find a simpler name. 
Roger does any of this undermine Darwin's Theory of Natural Selection,do you think? Because it is after all,slightly different from the basis of hereditary that we normally think of in terms of Darwinism? 
[[Belief 1] AOL-QA2] 

Roger Highfield : I don't think it does undermine Darwinian ideas at all.But certainly there's evidence that these epigenetic mutations could be more common than we think,and that's certainly something that Enrico Cohen of the John Innes Centre in Norwich has found in rather lovely studies of flower mutants. 

Geoff Watts: What sort of plants has he been looking at? 

Roger Highfield : Well,there's one very nice piece of work he did on a mutant flower that actually baffled the great Lineaus,the father of taxonomy,so this is a mystery that goes back 250 years and Lineaus was presented with a variant of common Toadflax,and Toadflax looks a bit like a Snapdragon, but when you saw this mutant,it actually had five identical flowers,and he called it Poloria (sp?),which is the Greek for monster,because it rather shook some of his beliefs,and in a rather nice study Enrico Cohen and his team,found that the reason you got these poloric flowers a defect in a gene which controls flower symmetry [Ref: I.Stewart "Nature's Numbers"],but this wasn't a conventional defect,it was an epigenetic one,and it turns out that the DNA for that particular gene had been decorated with chemical modifications,something called Methyl groups,and it turns out that during cell division,this Methylated DNA can be transmitted,so this silenced trait is passed on.But his conclusion of all this work was that these kind of Methylation effects are perhaps much more common in nature than we think, and could be responsible for all sorts of funny effects out there. 

Geoff Watts: Roger thanks.Roger Highfield of the Telegraph.That's all.In next weeks programme the last of the present series,I'll be joined by a panel of scientists eager to talk about money,science funding in other words.Who pays? Who spends? What on? And have we got the formula right?