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What to do when you fall ill


Cells continuously want to kill themselves
Martin Raff Scientist
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Let’s make it clear that the idea of cell death as suicide is not my idea. That was an idea that came in 1970s by these three cell pathologists who proposed that there’s a type of death that was a suicide, that cells had a death programme built into them, at least some cells, and that could be activated under certain circumstances. But the evidence that there really was a dedicated suicide or death programme built into cells came from studies… genetic studies in the worm that identified genes that did it. Until then, this idea that there was a suicide programme lay dormant.

So my contribution was this idea that, yes, cells have a built in suicide programme but it operates automatically by default and the… that that’s what cells really want to do. All the time they want to do that. The only reason they don’t is that other cells are saying, don’t do it, don’t kill yourself. That’s what was odd. Now, it turns out that some cells are saying, yes, kill yourself, kill yourself now, and other cells are saying, no, no, don’t do it. And each cell is getting signals saying do it and other signals saying don’t do it and are integrating these signals and deciding, live or die, and if the signal integration process comes up die, then they kill themselves by activating this death programme.

So I guess another contribution that we… we didn’t make many contributions to this field I should make absolutely clear, but one of them was the suggestion and evidence that this suicide programme is ready to go. All the components are there and ready to go. You don’t have to activate new genes and make new proteins. All of the death machinery is in place. That turns out to be true. Often you have to activate new genes and make new proteins to activate the death programme, but the death programme is in place. And the good news, slightly off tack, is that cancer cells have the death programme in place, too. No one has ever been able to find a cancer cell where this death programme has been disabled, it’s always there, which is surprising.

You would’ve thought that a cancer cell, as it evolves and acquires more mutations, would’ve inactivated the genes for this death programme because then they wouldn’t need signals to stay alive. They would automatically stay alive because they couldn’t kill themselves. You would think that would help in the progression of a cancer. So it’s not clear why it doesn’t work that way, but it’s very encouraging that cancer cells do have the death programme in place because now you could try to activate it to get them to kill themselves and, as I said, that’s how anti-cancer drugs generally work.   

[Q] And when you’re talking about development and the importance of cells, these programmes activate themselves or not activate, is that to do with development like why you have, I don't know, why you have five fingers and a thumb and so on, or…?

You’re asking a question about the role of death in development?

[Q] Yes.

Yes, so death does so many things in development. I mean, one, it does help sculpt bits of your body. So the cells between the developing digits kill themselves, that’s why you have fingers and toes. Cavities in organs can be built that way by the cells inside killing themselves. Mistakes, and mistakes are made all the time during development, are cleared by… by cells killing themselves. If cells don’t develop exactly right, in the right schedule, they kill themselves automatically and that’s very, very important. If you get rid of cell death in… in a mouse or a fly, the animal dies very early in development.

The worm is exceptional. You get rid of cell death in the worm and the worm lives a normal lifespan, but it only had 1,000 cells. It’s a very simple animal and cell… they’re not great, these worms, but they can live, whereas anything more complicated than a worm, such as a fly, you eliminate cell death and you don’t get very far in development. You need it for almost every aspect of development, or certainly many aspects of development. So it’s very, very important that… that cells can kill themselves when things go wrong because they go wrong a lot.

Martin Raff is a Canadian-born neurologist and research biologist who has made important contributions to immunology and cell development. He has a special interest in apoptosis, the phenomenon of cell death. Recently retired from his professorship at University College, London, these stories were recorded in 2000.

Listeners: Christopher Sykes

Christopher Sykes is a London-based television producer and director who has made a number of documentary films for BBC TV, Channel 4 and PBS.

Tags: cell death, cell suicide, apoptosis, programmed cell death, PCD, nematode, cancer, mutations, cancer drugs, C. elegans

Duration: 4 minutes, 24 seconds

Date story recorded: 2000

Date story went live: 13 July 2010