Geoff Woods and Alva Chen, University of Cambridge
A group of extremely rare individuals, who canít feel pain, have helped scientists to uncover an important gene - catchily called PRDM12 - that controls the formation of pain nerves in the developing body, and also their function in the adult nervous system. The discovery was made by Alva Chen and her colleague, Geoff Woods. They told Chris Smith about the breakthrough...
Geoff - For a long time, weíve been studying people who donít feel any pain. Either they're born not feeling pain or over the course of the first couple of years of life, they'd lose the ability to feel pain. And weíve been very surprised that no one researches this area and weíve been trying to find people with the condition and then find the genetic basis of their condition.
Chris - When you say they donít feel pain, are we saying they could literally put their hand in boiling water and they wouldnít know?
Geoff - Yes, that's quite right because they have senses such as touch and temperature sensation, but they wouldnít know when hot water was becoming painfully and dangerously hot. They'd just think it was hot water.
Chris - What do they think about that experience? They must know itís abnormal.
Geoff - They learn itís abnormal because everyone is so worried about their behaviours and the fact that they get damaged which they eventually realise is dangerous to their well-being. But for quite a while, they're completely perplexed by why everyone else is upset and can't put their hands in places they can put their hands, fall over and not hurt themselves. And so, there's a time where they're extremely clumsy because theyíll just bash into things, fall over and not care. And they suddenly get it that other people feel pain and theyíve got to pretend to feel pain and emphasise that other people feel pain.
Chris - Alva, how many patients did you study?
Alva - We studied over 160 patients and we compared their genetic component to 20,000.
Chris - I see. So, you have this group of people who have this trait. They donít have the pain. You're comparing them letter by letter genetically with a very, very large group of people from the general population to see if there are differences in the people who have the syndrome that keep coming up that are not present in the big group of normal people.
Alva - Yes, essentially. So, weíre comparing the genetic sequence of the affected patient to the healthy individual and found that a gene called PRDM 12, they all have mutation in this gene.
Chris - That has the effect of damaging or altering the way the gene works.
Alva - The mutations in the gene certainly damage the protein that is produced.
Chris - So, it can't do its job properly. Jeff, what are the implications of what you found?
Geoff - PRDM 12 is quite extraordinary in that itís the most specific gene for pain neurons that yet has been found. Itís not expressed in any other type of cell. If you can work out what itís doing and either augment it or block it, you should have a pain-specific treatment. The next feature of the gene which is exciting is that itís involved in the early development of pain neurons. Then its expression decreases and then it comes back again on in mature pain neurons. So, that would make you feel that it must have a postnatal role, either in making pain neurons healthy or in supressing pain. And so, the next role Alva will be involved with is trying to find out what is the role of this gene postnatally in normal people and in people with pain. Now, if itís involved in programming genes in pain neurons which was essential for their function, if you could block that process, maybe you could either deactivate the pain neuron or you can make a pain neuron become healthy or in fact, you could shut off a pain neuron by control of this. So, there's potential here for treating painful conditions arising from extremely rare people who donít feel pain.