Didac Carmona talking about his work at FameLab 2012 ©

Cheltenham Festivals

Didac Carmona, winner of FameLab 2012, talks to Eva Vlckova about his research and why your cells dying keeps you alive.

This article has been republished with thanks to Czech LN Daily where it was originally published. It is a shortened version of the original interview by Eva Vlckova. The original full length article (in Czech) can be found here,  (in English) here.

You study the suicidal behaviour of cells. Can you explain that further? 

It’s an inbuilt suicidal programme that our cells have. When they are old, damaged or when they mutate, e.g. after being exposed to chemicals or harmful radiation, they can pose a risk to our body. That’s why they commit suicide. So they don’t harm us and the immune system can remove them from our body. Billions of cells die like this every day and are replaced by new ones, which is great news!

What happens when this mechanism fails?

Then dangerous cells continue to grow, multiply and can create a tumour. On the other side of the coin, there are cells that die even though they shouldn’t. If this happens to nerve cells in the brain it can lead to neurodegenerative diseases, like Alzheimer’s or Parkinson’s. We’re searching for ways to save cells that shouldn’t be dying, and vice versa, we’re trying to kill the ones that should be dying, but refuse to do so.

What does this search look like in practice?

We test natural substances contained for example in tea, coffee, wine or chocolate. For now we are concentrating on substances that could save useful cells from suicide – that is after all a little easier than targeting specifically cancerous cells. If we want to force them to commit suicide we have to first ensure that the healthy cells aren’t dying alongside them.

How do you choose substances for testing?

We looked within a specific group of substances which includes thousands of compounds and chose a few hundred that are representative based on their chemical structure. We also get inspiration from traditional Chinese medicine and other things that have been tested over the centuries. This tells us which natural substances can contain something interesting worth investigating. I should probably mention that we always start our testing on yeast. They are very primitive cells, but many of the processes taking place within them can also be found in human cells.

But yeast is an independent organism, whereas human cells are a part of a bigger organism...

That’s a good point, but Professor Frank Madeo, with whom I have been working for many years, discovered that even yeast cells have a cell death programme. They communicate with each other and commit suicide. They’re actually clones, because a yeast community comes from one cell, so they have the same hereditary information. Thus, it makes sense that at one point some of them sacrifice themselves to benefit the rest of the community – so they don’t consume their nutrients and so on.

And it turns out that a lot of the things we see in yeast also work in fruit flies, worms and even cultivated human cells. That doesn’t cease to fascinate me.

Have you already found a substance that could serve as a cure?

We have a couple of substances that are showing promise, but we are still at the beginning. The journey from discovery to a cure is very long. For example you have to discover any side effects, those are usually tested on mice first and so on. So, we aren’t that close to a pill. I’m not saying it’s going to take 50 years, but perhaps 10. And during that time anything can happen, because cell death is a very complex process.

Once you find such a substance, is it going to be better to manufacture it in the form of pills, or to advise people to eat more of the foods that contain it?

If we find a substance like that and if we know that it is contained, for example, in cranberries, then I would say it is good to eat more cranberries...

Is a suitable food palette the answer to the question of why people in Asian cultures live longer than we in Europe do? 

This is just my personal opinion, but I think it can be related. However, there are other reasons. For example, one of the things known to prolong life is restricting calories. All big religions that have survived to this day have periods of lent. It’s possible to assume that there is something about fasting. It had already been tried out on mice in the 30’s, but in recent years it has been rediscovered. When you lower your calorie intake and regularly fast – for example one day you eat whatever you fancy and the next day you don’t eat anything at all – it has a positive effect on your health. Two different studies were conducted on monkeys. One showed that life is prolonged by doing this and the other concluded that it won’t prolong life, but rather the period during which the individual remains healthy.

Do we know the molecular mechanisms that cause this?

We are also working on that in my lab and we think that one of the mechanisms is the so-called autophagy, aka cells eating themselves. During their life cells collect a lot of waste inside.  When you let them starve they start looking for food and this forces them to clean up their insides. They destroy excessive and potentially toxic substances by turning them into new building blocks like amino acids.

We are trying to identify substances that would kick-start this mechanism. For example in 2009 our lab published a paper, according to which this process can be started by a substance called spermidine. 

Does that mean we could have it in a pill and mimic our body starving?

Exactly. That’s one of our dreams. We have to be pragmatic – everyone knows that fatty foods, smoking and excessive alcohol consumption is bad for your health, but many continue to do those things. I would say it’s our nature. It would be wonderful to have something that would simulate starving. Personally I would take such a pill.