David Jackson & Dr Ashley Jones, Kingís College London
Naked Scientist Graihagh Jackson is dunking her head in cold water in aid of science...
Graihagh - Remember the ice bucket challenge - I certainly do - my dad nominated me. I did it on holiday in Barcelona. The only thing we could find to put the water in though was this massive pottery urn. It seemed like a really good idea at 2am nonetheless.
Itís so heavyÖ fortunately though my brother was on hand to do the pouringÖ and my dad was there to laugh And, do you remember what it was in aid of? - a really debilitating condition called motor neuron disease, also known as amyotrophic lateral sclerosis or ALS in America. Although not a lot is known about the disease we do know that it affects nerve cells in the brain and spinal cord that control movement. So, as the disease progresses you become increasingly unable to move, to talk, to breathe, whilst maintaining all your cognitive functions.
Itís something my dad knows a bit about because one of his best friends Doug died from motor neuron disease.
David - Well, we were at Manchester University, in fact. We teamed up at the end of the first year and moved into a house, so there were seven of us at that stage. He stood out actually, so whereas we were perhaps your more typical student in terms of our interest in beer and the like, Doug was a man who preferred a gin and tonic so we were a pretty close knit group in fact.
And I suppose it was round about 2007 when it became clear, or rather Doug I should say, he had started to notice a certain slurring in his speech. He was referred to a specialist and he simply said he had an illness called motor neuron disease, and we realised that we were living on borrowed time. And, sure enough, over the course of the following three and a half years I think it was, he gradually became more and more disabled and certainly for the last two years he was in a wheelchair. And then around that time started to completely lose his power of speech and within a few months of that he was reduced to more or less being totally immobilised in fact.
He bore it with fantastic fortitude and genuine good humour right to the end. And the end was he inevitably fell ill of some other - in fact in this case it was a twisted gut problem but he was too weak and that was really the last that we saw of him.
He used to have a great collection of very wild coloured socks. In his Will, we were left one pair of socks each - we were the pallbearers at the funeral service and so we were requested to wear these coloured socks. And, in fact, ever since we have carried on having our Christmas lunches so now in his memory we attend those lunches wearing, in my case, bright green stripey socks that I was left. And, in fact, we always order a gin and tonic that we leave in the middle of the table in memory of him and, to be honest, after itís warmed up and thoroughly not very nice then we end up drinking it but we try and remember him as best we can.
He was a wonderful guy who left behind a very young family rather tragically and so far as illnesses go and my experience of illnesses, itís probably one of the worst Iíve ever seen in that sense. So the ice bucket challenge and any money thatís ever raised to that end is very well spent.
Graihagh - The ice bucket challenge raised more than a hundred million dollars, but that was over a year ago so whatís become of that money. Well, scientists like Ashley Jones were funded with the proceeds and theyíve discovered a slight variation in a gene - itís called NEK1.
Ashley - So NEK1 is multifunctional. There are three functions which are related to motor neuron disease - one is the development of cilia. Itís also involved in the regulation of mitochondria and involved in DNA repair.
Graihagh - So can I sort of think of it as a bit like the damage response unit of a cell basically - if something goes wrong it is there to repair?
Ashley - Yes very much, so itís regulation, keeping things in order and also if something goes wrong then it helps step in. So in a subgroup of motor neuron disease patients, there are small mutations within NEK1.
Graihagh - You can think of a mutation as an error in the code that creates you but sequencing thousands of these genes to find these errors is a pricey business and it was only made possible because ofÖ
Ashley - Ö things like the ice bucket challenge so we can extract genes from tens of thousands of people who suffer from motor neuron disease, and comparing their genomes with tens of thousands of those who do not suffer. And weíve seen in NEK1 that thereís an increased number of very rare, but damaging mutations within this gene which collectively contribute to motor neuron disease itself.
Graihagh - So was this found in all people who have motor neuron disease?
Ashley - Itís found in a subportion - around 3%.
Graihagh - Thatís not very many.
Ashley - On the face of it no, itís not. But actually what tends to happen with discoveries when genes associate or weíve found a genetic mutation, we are able then to look at similar genes that have similar function with NEK1, or have genes that interact with NEK1, and what we tend to find is that these are also dysregulated, sometimes we find mutations in these genes as well. So really, NEK1 is about shining a light upon a pathway function thatís going wrong in the cell.
Graihagh - Because really - correct me if Iím wrong - with things like motor neurons we really donít have any idea about how itís caused, how it progresses and, therefore, treatments really hard to pin down if you donít know any of these biological pathways?
Ashley - Absolutely. And another thing to add to that years down the line, we don't necessarily have to explain 100% of the genetic causation of motor neuron disease. We just need to know enough to make an effective therapy.
Graihagh - And this, I suppose, is step one in that effective therapy? Do you think this would have been possible without the ice bucket challenge?
Ashley - It would have been possible but it would have slowed it down. Gathering tens of thousand of genomes is very expensive and having that resource there has been paramount.