Why do I Stress Eat?

Immunologist Clare Bryant answers...

Clare -  Yes, it's a really interesting emerging area. So, if you look at patients that have got severe depression, for example, what you find is, if you look in blood samples from these patients, they actually have elevated levels of inflammatory mediators. And in fact, you can look at different mouse models of depression and you can see that in those animals, you get the influx of immune cells into the brain, you can see increase in inflammatory mediators, and there seems to be a gathering body of evidence to suggest that. And it kind of makes sense because stressed people will produce cortisol. Cortisol dampens the immune system. So you can see how the immune system and the CNS works in balance. And also immune cells can actually modify regions of neurons called synapses, which is where neurons talk to each other. Immune cells can actually trim little areas of this off. So, you could see how there's a complex interplay between the immune cells and the neurons and that would then affect mood and mood disorders.

Chris -  And is that the basis of the observation that if you take, say an elderly person caring for another elderly person who describes that as very stressful or someone who is lonely and you find that in them, they tend to respond much less well to say a flu vaccine?

Clare - Presumably, yes. I mean, it all will kind of make a lot of sense, wouldn't it? That these kinds of interplays between efficiency of vaccination and what's happening within your brain and your mood would potentially affect how your immune system responds. But also in the elderly, we know that they are already in a state of heightened inflammation anyway, and that could also affect how a vaccine works. So I think it's, it's a very complex interplay of different systems.

Chris - And can that affect the progression of heart disease, James, and how fast arteries fur up, cause there's an inflammation part and parcel of that.

James - Very much so, Chris. Yeah, inflammation has long been recognized as probably the prime player, really, all the way along from very early vascular disease, very early hardening of the arteries, all the way through to triggering heart attacks. And hence stat in drugs. Probably half of the effect that they have is due to their anti inflammatory effect on the arteries.

Fran takes this question...

Fran - Yeah, that's a good question. A neutrino is a very, very light particle. It's one of the particles of the standard model, which means we're very sure it exists. It's produced in radioactive decays, and around a hundred trillion neutrinos pass through your body every second. But because they're so weakly interacting, they just go straight through you and you don't notice them. To detect even a handful of neutrinos we have to build huge and very, very sensitive detectors; but they're actually all around us, they come from the sun, they come from nuclear reactors, they were produced in the early universe... so they're just everywhere.

Chris - So are they actually part and parcel of an atom or, are they only produced when there's a radioactive event - an atom decays, for example, and then the particle whizzes off - and if the latter, what's their ultimate fate then?

Fran - They're only produced in a radioactive decay, as you say. When they're produced by the atom they whizz off. And they don't really have an ultimate fate. They just stream through the universe forever.

Chris - Does that mean the number of them is therefore, theoretically, permanently increasing indefinitely?

Fran - Yes, but space is expanding. So more and more are being produced, but they're also being diluted by the expansion of space.

Chris - But the number of neutrinos out there is going up all the time, through radioactive decay? And they're not going to turn into anything else, there's nothing else they can do, once they're a neutrino?

Fran - They do occasionally turn into other things in a process that's like the inverse of radioactive decay. I don't quite know how those two effects balance out. My guess would be that whenever a radioactive decay happens, some decays always produce a neutrino, whereas once the neutrino is there it's very rare for it to ever interact with anything. So my guess would be the total number of neutrinos is always increasing. But I'd have to go and check that to tell you for sure.

Clare Bryant answers...

Clare - Yeah, well that's the holy grail of any form of chemotherapy, which is a drug that will kill what you don't want but leave your healthy cells alone. So with bacteria it's relatively easy, because what you're aiming to do is to target something that's expressed by the bacteria, so some constituent of the bacterium that's not present in humans or animals. Bacteria for example... the classic example is penicillin. Bacteria have a very thick bacterial cell wall, which is made in a very unique way by a series of enzymes. And penicillin will actually target the enzymes that are in the bacterial cell walls. And those enzymes aren't present in humans or animals, so therefore you get a selective killing of the bacterium but you leave the mammalian cells alone.

Chris - Is that why we have a problem making good drugs for viruses? Because bacteria, being cells in their own right, are really different from our own tissue and cells; they're quite easy, relatively speaking, to find differences between them and us. Whereas viruses are part and parcel of us, when they infect us they're growing in our own cells, using all our own equipment; it's like they come in and hijack the premises, isn't it, and turn our factory into a virus factory instead. And therefore much harder to find a difference.

Clare - Yes, indeed. And this is the big issue with viruses, except that there are some unique viral target proteins, which is... then we use, for example, vaccination to generate an immune response, which will target a viral unique protein. It gets even more complicated with fungi, and then even further complicated with cancer, of course.

Cardiologist James Rudd takes this question...

James - Yes, it's a very good question, Chris. And I should say that around 200 heart transplants take place in the UK every year, but unfortunately over a thousand people a year die on the waiting list because they just can't get a suitable donated heart in time. Now the current method of taking hearts out of donors is that the heart is placed into an icebox where it is stored, and then the icebox is transported to the person who needs the new heart. Now the way of doing it using the icebox means that the heart stops beating because there isn't any blood supply. So the heart itself immediately starts to deteriorate and the heart cells die. It is cooled down using ice, so this offsets the deterioration to a certain extent, but still the heart needs to be implanted into the person within about three to four hours. So that limits the geographical range that hearts can travel from recipient to donor. There's a new technology which has been around just for a couple of years already called heart in a box. And that's a method of transporting donor hearts that allows them to survive up to eight hours outside the body. And the way it works, again it's a lunchbox-sized device, but this time the heart keeps beating once it's outside of the donor's body. It actually uses a similar technique to a heart-lung machine where the donor's own blood supplies the heart muscle with oxygen and glucose, and also immunosuppressant drugs which keep it beating and keep it in the best condition before it's implanted into the patient. And that can extend the time out to around eight hours. Machines are expensive, about 150,000 pounds, so they're not used in every case. But experts believe that that will increase the number of organs available by about 50%, so many more of those people on the transplant waiting list will hopefully get something in time.

Chris - I was also talking to the surgeons who do transplants of other offal organs, things like livers for example, kidneys; and they were testing devices so that you can rest an organ and give it a circulation for a while before you transplant it. And they were finding when they did this, they could get some organs to recover to a stage where you would then - have previously rejected them - you would then instead aacept them and say, "well that's good enough to transplant." And it would appear that instead of it having had a shock of having been taken out of a donor and then have the shock of going into a new patient, by resting it in a controlled environment for a little while beforehand, it enables it to regenerate a bit.

James - Yeah. I think that's very similar to the way that this is done. So organs that, we call them marginal organs, that might have been a little bit not good enough to be transplanted can now become available to a wider pool of people.

Chris - Yeah. Of course one other aspect of this is relevant to your field of immunology, Clare, and that's actually organ rejection, isn't it? Because one of the big challenges is finding organs that are a match. So when people talk about that, saying "I'm looking for a match", what do they actually mean by that?

Clare - So effectively what you're trying to do is to make sure that the organ matches the tissue in the immune environment of the patient to whom the organ is going to be donated. And so there are various ways you can do that. There are various molecules, you can look at different tissue types, and find somebody who's got an immune system and tissue that's as close to the immune system of the recipient as you possibly can. So that's why there are organ donor registers and so forth. So it's a central part. But what you also do is you put your patients on immunosuppressive drugs, which actually dampen down the immune system. So you're giving it the maximum chance, you have a tissue type that is closely matched between the donor and the recipient, but you also suppress the immune system so it doesn't attack the organ when it goes into the body.

Chris - There must be consequences of damping down the immune system like that though. Because we have an immune system for a reason.

Clare - Yeah, yeah. There are massive consequences. So the biggest problem is, well, one of the biggest problems is trying to protect your patients then from getting infection. So whereby a cold is normally something that one can fight off quite easily, if you're a patient on immunosuppressive drugs, particularly early on after a transplant when you're on particularly high doses, then you're at serious risk and you need to avoid people who've got colds and various other relatively harmless ailments to a greater degree. Because this can cause a serious, serious problem in these patients.

Chris - Why can't we reprogram the immune system to say... because it obviously had to learn in the first place that your heart is part of you, and to regard it as friendly; why have we not been able to reprogram the immune system to say, "James has kindly given you his heart, Clare, this is your friend. Don't reject it."

Clare - Yeah. We're moving towards being able to think about these things all the time, as we understand how 'foreign' and 'self' is seen within the body, and what the molecular biology behind those processes are. And we have processes such as gene transfer, gene editing, the CRISPR-Cas9 systems. They are all ways in which we can potentially change organs and change cells within organs such that they are more familiar to the immune system of the person that they're going into. But we're a long way from that at the moment.

Chris - Fran?

Fran - So related to that, why is it that if a woman is pregnant, her body doesn't reject the baby as foreign tissue, but if the baby then grows up and donates an organ to her, that could still be rejected? What happens over that period? And could we use it to help?

Clare - Yeah, I mean there's quite a lot of changes that go on when somebody is pregnant. So they actually become semi-immunosuppressed and that helps to protect the baby. And of course a baby is not necessarily going to be a good donor for a mother because the baby has the father's DNA as well as the mother's DNA, so it depends how much of the mother's immune system and how much of the father's immune system, and the complex recombination, because the genes that are present in the father and mother in the immune system can also mix and match. So it's a complicated process.

Chris - It's also interesting that certain diseases of the immune system, autoimmune diseases, where the immune system attacks a tissue that it shouldn't do become much more common after a woman has had a baby. And people have pointed out that if you go hunting through a woman's body you can find, after she's been pregnant, examples of her baby's cells that have come out of the baby, gone round her bloodstream, and then taken up residence in certain tissues. For example the thyroid, people have done this showing if a woman has had a boy baby, there's no way she would ever have a Y-chromosome in her body. But after she's been pregnant you can find cells with Y-chromosomes in them in some of her tissues. And the suggestion is that after the baby is born and the immune system gears itself up to full strength again, then you get these autoimmune problems because all of a sudden the immune system starts to see these foreign cells sitting there in the host tissue that shouldn't be. And then you get a reaction.

Clare - Absolutely. And you've also reverted the hormonal status of the person, because things like progesterone are very, very - which is what's produced during pregnancy - is a fantastic immuno damper. And as soon as you bring oestrogen back in, which soups your immune system back up, then off you go and anything foreign is going to trigger a reaction. So yeah, it is very interesting.

Chris - The immune system's an amazing thing, isn't it? And it's one of those things we just don't have really much of an insight into really what it's really doing. We vaguely understand, at a sort of broad level, but we really don't understand the intricacies, do we yet?

Clare - One of the exciting things now is that we're really moving much, much further into understanding what the individual cells do and the plethora of cells, and there are different subtypes of sales, which makes life very complicated. But also as we look at patients of various rare diseases where they have to find mutation in different immune genes, then we're beginning to use that information to understand what the immune system does. But there is a long way to go.

Our expert panel  - Giles Yeo, Clare Bryant, James Rudd and Fran Chadha-Day - take on some fiendish quiz questions...

Chris - So James and Fran, you are going to be team one, and Clare and Giles, you are going to be team two. Round one is called scientific “oops”. So team one, that's James and Fran.

In the 1950's Noah McVicker and his brother, they worked at a soap company where they invented a clay based product that was for cleaning wallpaper to get the soot stains from cigarettes and coal-fired powers off of the walls, but the invention of wipe clean wallpaper unfortunately threatened to put pay to their invention until a nursery school teacher pointed out its potential and they turned it into. What do you think the answer is?

Fran - Well maybe it's something like Play-Doh?

James - I was going to say something like a whiteboard cleaner? Play-Doh is a good idea as well though. Nursery school 1950's. Yeah probably right, I reckon Play-Doh.

Chris - It is, very well done. It was indeed Play-Doh. Unfortunately, vinyl wallpaper threatened their industry, so they had to think outside the box and they took the soap out, put some colour in. The secret to the recipe remains intact. No one knows how they make it or how they give it that lovely smell, because I guarantee if I say Play-Doh, everyone can smell it. You can all smell it.

Fran - Definitely

Chris - You're all thinking of it.

James - Evocative.

Chris - Okay, well done. Well done to James and Fran. One point. Okay, Claire and Giles, it's your turn. Which of these inventions was not an accident? Laser pointers, microwave ovens or safety glass? What do you think?

Clare - Oh, what do you think?

Giles - I think it's going to be something like the safety glass. I bet you that was, that was done entirely, was not by accident.

Chris - Which one of these inventions was not an accident?

Clare - Yeah, yeah I kind of think...

Giles - I would go with safety glass.

Clare - Yeah. Safety glass. We are going with safety glass.

Chris - No, actually it's the laser pointer.

Clare - Interesting.

Chris - Microwaves turned up when, you might know the fairly famous story actually, the scientists noticed, he was working on radar and he had a microwave generator, a magnetron, on the desk in front of him. He had a chocolate bar in his pocket, and when he went to eat his chocolate bar it turned all gooey and realised that there was something coming out of this magnetron, which he was using for his radar experiments, which was very well absorbed.

Giles - That was microwaving him.

Chris - That was microwaving him but more importantly, microwaving and melting the chocolate bar. So the microwave was directly informed accidentally by that experiment. The other one was safety glass, which you chose and actually safety glass was a scientific accident. Someone dropped a whole beaker that they were working on, which was full of cellulose nitrate. When the beaker hit the ground, it didn't smash. It cracked a bit, but it remained intact. And that's because the inside of the glass had got coated with whatever the cellulose nitrate was doing and then they realised the concept of making safety glasses, which could absorb impacts and not break. The laser pointer wasn't the accident. Right, so that's nul point for you there i'm afraid so far. Round two. Now this is called 'Pound for Pound', this round. Okay, so back to James and Fran. Pound for pound, printer ink is the most expensive liquid in the world. What do you think? True or false?

Fran - What about, like, molten gold or something though?

James - Does it have to be liquid at room temperature?

Chris - Oh, it's not a trick question in that respect. No, it's a liquid.

Fran - Or something like liquid helium?

James - Yeah. I have bought some printer ink recently and it is frighteningly expensive.

Chris - Set you back a bit?

Fran - Yeah. I mean maybe there's something in the pound for pound. Yeah, my instinct is that it's false, but I'm not 100% sure. Like, maybe there's just not much printer ink in the thing that you buy, so it's ends up being. What do you think?

James - It's only a few mills I think, per cartridge. So i'd say yes. It's such a ridiculous question, it must be true.

Fran - Okay, let's just say true.

Chris - You know what? You're not going to get this. Yes, and Giles is shaking. He's going, yes, yes, in with a chance! But the answer is actually the most expensive liquid is scorpion venom. The death stalker scorpion. The death stalker scorpion is the most dangerous scorpion on the planet. It's venom is also the most expensive liquid on the Earth. It's 6 million pounds per litre. 100 quid will get you a droplet smaller than the grain of sugar.

James - Wow.

Fran - Why do people want to buy it?

Chris - Ah well, you see a lot of these things, Claire would probably tell you, because a lot of these things are neuro-active, because they're very fast acting, they very, very precisely target very specific elements of the nervous system. So, scientists are really interested in them as potential leads for drugs and other therapeutics, and also ways to unpick how the nervous system works. So they're actually very valuable commodities, also other venoms from snakes and so on as well are in demand.

Clare - And of course you need to develop anti-venoms to protect you if you get bitten by one of these things.

Chris - True. Printer ink, since James, you said you're a bit out of pocket recently. You felt the sting of that. Since we're talking about the scorpions. Printer ink, a competitive 3000 pounds a litre, so still exorbitantly expensive.

James - Wow, I am in the wrong business I think.

Chris - Right, so we are level pegging now, almost. Okay. So if you get this right, you can equalise. You ready Giles and Clare? True or false, anti-matter is the most expensive substance on Earth to make?

Clare - What do you think Giles? I've got no idea.

Giles - I've got no idea, can we even make anti-matter? Isn't that an Avengers story line in terms of that?

Clare - The physicist is not helping here, you know, she's just not really supporting is she?

Chris - Do you notice how we divided the teams quite carefully apportioned to the questions?

Giles - Okay. Assuming they can make anti-matter, you probably only get some nano-particle. So I would say let's go with true.

Clare - It's got to be worth a shot.

Chris - You're going to go true.

Giles - Yes.

Chris - All right. You are going true and true is...

Giles - So you can make anti-matter!

Chris - Oh yes. If you go to, well Fran you can probably tell someone, if you go to to Addenbrooke's hospital and have a pet scan, a positron emission tomography scan, you actually are using the effects of anti-matter in order to scan someone. That's correct, would you concur?

Fran - Yeah, absolutely.

Chris - Yup. According to various sources, because it's so difficult to make, the price tag is a hefty 18 billion pounds per gram, but yep, We can make anti-matter. Level pegging, one-all, back to Fran and James. Round three, a question of numbers. Okay, here we go. This will test whether you were paying attention in the head and neck lectures when you were at medical school. James, how many teeth form a complete set of milk teeth in a child? Is it 20, 28 or 30? What do you think Fran and James?

Fran - I just do not know. 20 feels too low - I feel like I remember having more than 20 teeth.

Chris - You have now.

James - Yeah, I think it is 20.

Fran - OK, right, you should know, so we'll go with your answer.

James - Medical school was a long time ago.

Chris - You are right.

Chris - 20 is the number of milk teeth. It did seem surprising, so it was five in each quadrant - so five on the right upper five on the right lower and vice versa. Adults have, do you know how many adults have?

James - 32?

Chris - Yep, adults have 32, assuming the wisdom teeth come through. So your eights are your wisdom teeth. So 32 teeth in total in an adult. So in the lead so far, let's see if you can equalise, over to Giles and Clare. You have got to stay in this just to stay in the game. What's the chance of having twins in a pregnancy? Any twins. Okay, either identical or non-identical and this is a natural pregnancy, It's not assisted conception. Is it one in 75, one in 150, or one in 300?

Clare - Wow.

Giles - This will be have to be a guess, for some reason I remember the number one in 150, but it could be because I was imagining things.

Clare - Well, it's relatively rare isn't it?

Giles - It is relatively rare.

Clare - Yeah. So one in 150 or one in 300?

Giles - Oh goodness.

Clare - You've actually remembered a number, so maybe we should just go with that.

Giles - And if we lose?

Clare - I'll let you off, Giles. It's all right. It's not the end of the world if we lose this quiz.

Chris - So what you choosing?

Giles - One in 150.

Chris - I'm really sorry. It's actually one in 75. It's 1.33% and it's quite interesting. You can remember this because twins, non-identical twins, one in 75; triplets, one in 75 squared times; and identical twins, much rarer still, 0.3% of pregnancies. So you didn't get the point. So I think this week's winners, therefore are James and Fran. Give them a round of applause. You win a prize beyond price. That's this week's Naked Scientists big brain of the week award. So very well done to you. They look a bit miserable that you beat them.

Cardiologist James Rudd answers...

James - Well, it's really all down to the fact that pig hearts are very similar to the size of human hearts. And let's talk about heart valves for a little bit. There are four heart valves in everybody's heart. And their job is to make sure that the blood flows the right way through the heart. And the valves can become diseased and damaged and they can either be too narrowed down so the blood doesn't flow properly, or they can become leaky. So the blood flows back where it shouldn't be. And so what happens is we can use pig heart valves which are specially treated. It takes about four weeks to actually prepare a pig heart valve to go into a patient.

Chris- So we would actually take the native valve from the pig heart?

James-Indeed, native valve comes out of the pig heart. It's treated with glutaraldehyde which completely sterilizes the valve, removes some of the immunological triggers that might cause people to reject it, and it's then placed in a kind of a strut which is suitable for sewing into a patient.

Chris- And do they substitute like for like, so the valve that you were talking about, the aortic valve earlier that you're interested in with that furring up and becoming narrowed in patients and you can spot that with your radioactive toothpaste, would it be a pig aortic valve in place of a human valve? Would it be a pig mitral valve in place of a human mitral valve? Would you go anatomically like for like?

James- Yes, you do indeed. And as I say, it really boils down to the fact that pigs and humans have roughly the same size heart.

Giles- Where are we with actually genetically modifying pigs or the heart so that we actually remove the immunological problems?

James- So in humans we're nowhere near, but there have been some experiments done where pigs have been modified and then their hearts have been transplanted to other species, which I think chimpanzees and the chimpanzees have stayed alive for about a year. So I think we're on the road to that. There are clearly perhaps ethical concerns that we need to think about before we take that last jump of xenotransplantation. But pig valves have certainly served as well for the last 40 years.

Chris- I spoke to Professor George Church from Harvard, who's a pioneer of a lot of this genomic technology earlier this year. And one of the things that he did was to work out where all of these viruses that loiter in the genome of all animals actually, but where they all are in pigs. Because one worry is when you take a heart from a pig and put it into a person, because they'd be immunosuppressed as we were discussing earlier, if any of these viruses reawaken, they would then be growing in the face of a, of a new body without any kind of immune response to tackle them and that could have all kinds of consequences. So he's gone through and found where in the genome these things are lurking and they've removed them. And this is obviously a step towards making these things safer. But as you say, we're not quite there yet with the whole question of how to stop the immune system still regarding this as pig, not human.

James- Yeah indeed. And with the heart valves, as I say, we actually blast the valve tissue itself with very strong detergent under high pressure and high temperature to kill any kind of immune signal.

Chris- Does it regrow new cells? Human cells of the recipient over that tissue then over time, so it's like road resurfacing, but then you grow a layer of your own cells. So over time you don't see pig tissue, you see human tissue.

James- Exactly. Yeah. It takes about three or four months to do that completely. So patients need to be on anticoagulant drugs for the first few months, but afterwards they can stop that. Once the valve has been endothelialised, we call it.