Immune System

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this is the bbc

hello i'm brian cock and i'm robin it's and this week we are looking at health because brian and i are getting on a bit now unusually we are recording this show in early march because robin is doing a summer season at jodral bank with jim alkalili and the crankies

hopefully you are listening to this on a jet chair in fronton while eating a mivi because as we said we are basically breaking the laws of time.

This is March where we are speaking from and you are hopefully sitting there in the middle of the summer.

So let's find out if Brian, because this is a great moment for you, basically you listening to this currently know more than Brian Cox.

Because Brian knows nothing about what happened in March, April, May or June.

So you are wiser than him and let's find out, Brian, give us one of your March predictions and we'll find out if it's accurate in mid-summer.

I reckon that the anomalous magnetic moment of the muon will have been shown to be a five-sigma effect, signaling new physics beyond the standard model.

That's what I reckon.

I wonder where William Hill are on that one.

I'm not entirely sure, but yet again, Brian foils us by using a language very few understand.

Who knows if that became true or not?

We'll find out later if we read the right books.

Now, today we are talking about the human immune system.

How does it work?

Why does it go wrong?

And why is it still proving so difficult to understand?

Joining us today are an immunologist, a snail expert, and someone who has managed to survive survive near biblical plagues in an Australian jungle.

And they are Steve Jones.

I'm Professor of Genetics at University College London.

And in my view, the biggest medical breakthrough of the last few years is reading the human DNA from end to end and finding that we've got fewer genes than a tomato does.

Hi, my name's Dan Davis.

I'm from the University of Manchester.

I wrote two books about the immune system, including The Beautiful Cure.

My favourite ever medical breakthrough, I'm going back a bit, is the discovery of germs.

It's not obvious that we live in a world surrounded by germs, it was discovered.

And the fact that disease can be caused by germs leads to everything else.

So, clean drinking water, vaccination, antibiotics, all in a sense, stem from our understanding of that stems from our discovery of germs.

It's also vital to me because our misunderstanding of what causes disease.

We used to think it was bile, phlegm, and blood that was going wrong, or we used to think that God was punishing people, and in fact, non-Christians and Jews were killed for supposedly for causing disease.

So, the discovery of the fact that germs cause disease is by far the most important thing.

Yes.

My name is Shafi Khorsandi.

I am a comedian, an author, and a keen cyclist.

I have published 25 pop-up books about the immune system

and a

very bad liar.

My favourite scientific breakthrough is by one of my neighbours.

I live in a really friendly street and I know all of my neighbours.

And you know, when other people tell you about their job, you don't always listen.

I wasn't 100% sure what she did.

Turns out she's a consultant pediatrician, a professor, and really clever.

And she mentioned that something had happened at work, and she said she just mentioned,

I discovered a little jean.

She's very, very soft-spoken and sweet.

And I said, oh, that's lovely.

Have a pie.

And then I got on with the party.

The next day, she was all over the papers.

Manju Kurian, one of my neighbours, thank you, I taught her everything she knows.

She discovered a new genetic disorder which stops children walking and controlling their limbs.

And it's a single gene called the KMT2B.

Write that down.

And it prevents the other genes from performing as well as they could.

And because of my neighbour, have I mentioned she's my neighbour?

My neighbour's research team, millions of children are now going to be helped to be able to walk again, whereas before she'd come to my party, they could not.

And this is our panel.

Steve, sorry, before we start, this tomato thing, right?

So basically, the tomato is more complex than the human in terms of the coding.

Well, I mean, humans have got 23,000 working genes approximately, depending how you define a gene.

Tomatoes have got about 28,000.

So they're only a bit clever than we are.

What are they all for in a tomato?

Making tomatoes.

I don't know where you get to the shortcuts.

Why does the.

So, in terms of just information content, the genome of the tomato exceeds that of a human, or is most of it non-coding?

I mean, tomatoes do things we can't.

For example, if we lie in the sun,

we don't make oxygen, right?

So tomatoes photosynthesize, as they say.

They keep us alive, they make oxygen.

That's quite a difficult thing to do.

That may be what makes the difference.

You know, when you said tomatoes can do things that we can't do, I immediately thought roll along a counter.

But then I thought, actually, if I had a counter big enough, I could probably roll.

So, my thought was none and void.

Well, originally, this was a show about immunology, but now it's going to be an examination of the salad bowl and its complexity.

But the interesting thing about tomatoes, how many times more tomatoes are eaten in the world now than were eaten in 1918?

100,000 times as many.

People didn't eat tomatoes until about the 1920s.

Occasionally, people, Thomas Jefferson ate one once.

It's in his diary, he didn't like it.

So we eat tomatoes, and it's a new habit.

So they're obviously smarter than we are.

Now, Dan, the lettuce, of course, has fascinated people since time began.

We'll come back to lettuce and tomatoes and cucumbers and possibly come quite later on.

But first of all, the immune system, can I talk about

when I cut my finger, for instance, or someone else cuts it for me,

that I presume, the healing process, what happens there, that that is my immune system in action.

Absolutely.

So that's true.

So when you cut your finger, then you're...

the cell, there's damage there, there's bacteria or other minuscule microbes in the air that might enter into that wound.

And that then triggers off this process of inflammation, which is the sort of redness and the tenderness and the swelling as cells rush in there and you'll have immune cells that have receptors on them on the surface of them that that would sense the presence of little microbes like bacteria or something and then some of those cells will be able to directly kill off the germs straight away and that is an instant reaction, a reflex action that's vital to keep you alive.

But as well as that, some of the cells there would grab some of the bacteria or other types of germs there, and it would then take samples of those germs back through the body, and it would show to yet other kinds of immune cells the types of germs that have just entered into that wound.

And then, immune cells that are best equipped to deal with that type of germ would then travel back out through blood to that place eventually, and that would kick-start a more specific kind of immune response.

So, you have so essentially you have a sort of instant reaction to the presence of germs, and you have a slightly more tailored response to germs that take some time to kick off.

So, the immune system is this very complex choreography of events that happen in the body, and it's essentially a very dynamic, multi-layered, fascinating system.

How do the immune system cells recognize the alien cells, if you like?

What happens for them to say, this is a threat, and therefore we're going to deal with it or take it back to the node?

That is essentially the crux of the whole immune system.

How does it decide what warrants an attack versus what should be just left alone?

So, there are many ways actually in which the immune system does that.

So, one of the ways it does that is immune cells have receptor proteins that protrude out from the surface of the cell.

And receptors tend to lock onto other molecules in the same way that sort of jigsaw pieces might fit together.

And then that would trigger an immune cell to respond.

And you have these receptor proteins that would, as an example, directly recognize the shape of a molecule that could only be present on the surface of a bacteria.

And so, these receptor molecules would detect the presence of

another molecular shape that signifies the presence of a bacteria, and then that would kick off an immune response.

On another level, the answer to your question would be that, in fact, another way in which this whole works out is, remember, I mentioned that cells would traffic move in the body to another place and they would present samples of what the germ is.

And then you have other kinds of immune cells that would recognize the samples of little components of the germ.

And the way that that works is literally the most amazing thing in immunology.

But I don't know if I'm talking too much.

Can I explain that?

No, no.

So the most amazing thing in immunology is something you should mention on this show.

Hey, but maybe not yet.

So let me just, so what happens?

No, it really is quite amazing, right?

So one way is that they have receptor proteins that directly lock onto things from, say, bacteria that can't have be from your body.

That's clear.

Another way that they work is that immune cells they have receptor molecules at their surface that are essentially randomly shaped tips at the end so as these immune cells develop they shuffle around some of their genes and edit the genes a little bit and then they put at the surface of them a receptor that has a randomly shaped tip so that means it could lock onto some other particular shape of a molecule that is a random shape, a particular one, but it's that each of the immune cells would lock onto something different.

Then what happens is any cell that happens to have a receptor that would stick to something from your own body is killed off.

So that means the cells that are let out into the blood are the ones that do not have a receptor that lock onto something made in your own body.

So the ones that are traveling around are they all have randomly different shapes, but they do not lock onto something that's made in your own body.

So anything they do lock onto is definitely something that isn't from your body and that's another way in which they could detect disease.

And the really reason why that is wonderful is that you have to think that the immune system has to lock onto bacteria.

Okay, it has to lock onto particular germs.

But remember that, as Steve well knows, viruses and bacteria multiply incredibly fast.

So that's a familiar idea that you get the flu one year, the next year it's a different flu.

So your immune system has to be able to detect germs that have never existed before in the universe.

And the way that they do that is by making randomly shaped molecules, killing off the ones that would recognize stuff made in your body.

Now you have randomly shaped molecules able to detect stuff that's not part of you, not self, in the jargon.

And therefore, they could detect viruses that have never existed in the universe before.

Steve, Dan was just saying, you know, he's not going to dumb down, but as you were talking before when we were just in the green room, you were very interested in immunology when you first were going to be an academic, be a researcher, and then you looked at it and you went, oh my goodness, this is hard.

It is a very hard subject, is it?

Yes, it is.

It's mainly because it's a very complicated subject.

And there's an iron rule in biology, most of biology, certainly immunology, brain science.

The more you learn about something, the less you understand.

And that's not like physics, as Brian will tell you.

And

physics is actually dead simple, because the more you learn, the more you understand.

And that's a very

easy profession to follow.

So

many people become stand-up comics to get a bit of an intellectual challenge.

But biology isn't like that.

I remember when I was a student in Edinburgh in the dawn of time, I really did was very keen on immunology.

And I was completely baffled by it.

And I was baffled on two levels.

First of all, nobody had any idea what was going on.

The model of what was supposed to be happening was completely wrong.

The idea was that some bug would get into your bloodstream and would kind of instruct the body as to what antibodies, what defenses to make.

And that wasn't true.

That simply wasn't true.

But the thing that really struck me about the subject was, first of all, that everybody in the subject hates everybody else, right?

And reading Dan's book, it's clearly that's still true.

There are plenty of people who won't go to a scientific meeting if another scientist is at it, infantile or what, right?

And secondly, you have to learn

several new languages in order to cope with this thing.

IL-5, the cadirans, and I gave up, you know.

I mean, I could just about manage in English, but I certainly couldn't manage an immunospeak, so I worked on snails instead.

I almost feel we should go back to you, Dan.

That feels like that was the start of a fight there.

The glove was the Chappie.

Well, in fact, I'll ask, when you were out in the jungles,

did you find yourself, in terms of medicine and in terms of reaction to bizarre things there, did you find your immune system was pushed to the limit?

Not by plants and animals.

By the way, I'm just aware that a lot of people might not have seen I'm a celebrity, get me out of here.

If you haven't, it's sort of like the nation's finest minds in a confined space discussing mostly philosophy.

I did find that, so there was a creek, and we had to wash all our clothes and our bodies and our pots and pans in the same water.

And I kept thinking, what if there's a dead possum up the creek?

And then I got terribly ill one day

because, and everyone said, Oh, it's because of the germs in the creek, it's germs and creek.

And I thought, No, it's not, because two of the girls had gone on a trial where they had to eat disgusting things, and they told me about it.

And even someone telling me about something revolting they've eaten makes me ill.

And so I was just there going, No, it's not that, it's because she was telling me about this vomit plant that she ate, and now all I can think about is the vomit plant.

No, no, no, it's the bugs, it's the bugs in the water.

But I was like, Why isn't everybody ill then?

I wanted to be special, and they were telling me.

So, I truly believe that in there

you psychologically didn't get ill unless you wanted to just have a day where you can lie in your hammock and not talk to anyone, which is my case.

So, Dan, is that the idea of a psychosomatic that the immune system would make well

thoughts that just to thought that is that a possibility that there would be a reaction?

Yes, I'll answer for him, yes.

And she knows her neighbor's very clever.

Yes, your paper in the Lancet was great.

So,

well, it is certainly true that

your state of mind influences the immune system in the sense that, well, it's probably true that all different kinds of emotions influence your health and immune system, like laughing and and being violent, all these things probably influence the state of your immune system.

But the only thing that scientists unambiguously agree on is that stress influences your immune system.

And that is well studied, and it comes down to the particular hormone cortisol, which is elevated in times of stress.

All different kinds of stress, from you know, being on a radio program with you guys to losing a job, or all these different

kinds of stresses elevate cortisol.

Why did you link being on this show with losing a job?

Yeah, it's only happened to about 10% of the academics.

So all different kinds of stresses leads to changes in this hormone cortisol.

But cortisol levels also change just simply by day and night because it's a hormone that increases in blood to sort of give your body a response to a change.

So just waking up in the morning, your cortisol levels are increased.

And cortisol levels directly dampen the activity of your immune system.

That's clearly understood.

Whether or not that's just a sort of of byproduct of the fact that your you know changes in cortisol are there to do certain sort of channel the energy use of the body into doing something like a flight or flight response and just a consequence of that dampens your immune system or whether it's there's some specific reason why dampening your immune system is a good thing to do when you're about to change your activity no one quite knows but it's stress undoubtedly affects the immune system.

But this is the difficult bit.

So if you then think that, okay, so then practices that reduce stress, which might be whatever yoga, Tai Chi, mindfulness, colouring in, anything, anything, to know whether that improves your immune system or your ability to fight infections, that's not really proven.

So, it is proven that your immune system is affected by stress, but it's not actually proven that practices that reduce stress directly help you find infection.

The reasons why that's not proven is it's actually really, really difficult to do the experiments, essentially.

So, experiments have been done where you would say take people that do Tai Chi and people that don't and see what happens if they then get a vaccine.

But the problem with that kind of experiment is you've already taken people that do Tai Chi and people that don't you haven't.

So you might have selected for the type of person that does Tai Chi.

You haven't just told a group of people you do Tai Chi you don't.

Even if you did that, it's not a fair comparison because doing Tai Chi versus not doing Tai Chi, you're not giving the, there's also the social factor of being in a group doing an activity and you haven't done a fair comparison.

Even if you did that, then the way that you assess whether or not their immune system responds well to a vaccine is that they have certain blood components, more antibody, let's say, in their blood

for one group versus the other.

But that really can't tell you whether they would actually do better in a reinfection because it's not ethically possible to say, Here's a bunch of people, you do Tai Chi, you don't, then we're going to give you a really bad disease and see what happens.

So you can't really.

So the experiments are actually just really quite difficult.

You're right, Steve.

This is chaos.

I can see why you went into snails instead.

I'm dying to ask you something, right?

Because for about five or six years of my life, I went through phenomenal stress continuously.

And now I'm not.

I'm all like Zen.

So, if that stress was going to kill me, would it have already done so?

Or has my body stored that and it's going to floor me in a yoga session?

I think it is clear that sort of a chronic level of stress during that period would be detrimental to various health things, but I don't think it's clear as to whether, you know, once the stress has stopped, everything would bounce back.

I mean, if it's down to corticoff levels, they fluctuate rapidly, very quickly, so you would be back to a normal level.

So I think you're doing fine, Shappy.

But okay, just one more question.

I'm so sorry, but it's not very often I get to sit next to Dan Stroke Daniel.

Okay, so when I was 14, I got the flu.

And I was so ill, I couldn't believe I was so ill.

I was really ill, and I swore to myself that I would never, ever, ever get flu again, and I haven't.

Is that because I'm really strong-minded, or is it because I eat lots of blueberries?

No one knows the answer to that.

Thank you.

But there is an important kind of well, sorry, is this on blueberries or Tai Chi?

It is true that there's a difference in each of our abilities to deal with the flu.

So it is true that there's a variability in our genes.

So Steve mentioned there's 23,000 genes in the human genome, and they're roughly the same.

Your genes will be roughly the same in mine, but 0.1% of our genes will be different.

And actually, most people might think that the genes will be different between us might relate to hair colour, eye colour, skin colour, anything like that.

But that is not true.

The big difference in our genes are in our immune system.

And that would be one reason why you may recover from the flu in three days and I might take four days because of the difference in our immune system genes.

So we do have different innate abilities to deal with different kinds of illnesses.

So yes to blueberries.

Now, Steve.

Steve, let me say there's one gene which is very important in the immune system and then a few other things too, which four of the people on this panel share and one doesn't.

And that's the gene that makes you male, okay?

And the gene that makes you male, of course, makes testosterone.

And one of the strange things that testosterone does, and it's a steroid hormone like cortisol, is it actually suppresses the immune system.

So that men are actually on average less good at dealing with infections than women are.

So in an evolutionary sense, what do we know?

Because that's interesting, because evolution works on the evolution of the world.

It is interesting.

I mean, I have to say that as an evolutionist, which is basically what I am, I hate it when we say we are as a species, we are as individuals very different.

And the thing which is interesting, you know, we are pretty different from each other, but we're much less different from each other,

both in the general level and in the immune system, than let's say chimpanzees are, okay, because we are, as a species, very, very homogeneous and boring.

The amount of difference between the world's most sophisticated nation, France, needless to say, and

shall we say, whatever, Papua New Guinea,

people look quite different, but the amount of overall difference, including in the immune system between those two groups, is much less than the difference between two groups of chimpanzees living 100 miles apart in West Africa.

And that's because we went through a tiny little population bottleneck, which removed a lot of diversity, including immune system diversity.

So we are different, but we're not as different as we'd like to congratulate ourselves as being.

We're basically the boring primate.

What do we know about the evolution of the immune system?

Well, one thing which is certainly about the evolution of the immune system is that it did not evolve to make life difficult for transplant surgeons, okay?

People tend to think, oh, the bloody immune system.

It didn't do it for that, and it might not even have evolved only to deal with

infectious disease, because there are plenty of creatures that make the chemical clues which are in the immune system,

they make it not in in the blood, but they're another useful fluid, which is the urine.

Now, when I was a lad, I was, of course, a nerd,

and I used to keep mice.

And my mother used to get furious about this because of the stink.

Mice smell, if you've ever been into a mouse house, I don't recommend it, it's awful.

And the reason they smell is that they're courting with their urine.

And they're producing chemical cues in the urine, which are cues of

identity.

And if you take a pregnant female laboratory mouse and you put her in a cage and you bring in another male which was genetically different from her, she will actually absorb her fetuses and mate with this other male.

If you bring in a male which is the same as her, she won't do that.

So she prefers to mate with the male who is different.

And that's cued for in the scent of genes, which are very like some of the immune genes in the urine.

Now you might think, well, you know, humans might do that.

And in Dan's book, there's a lot about sniffing t-shirts.

So, you know, you get, can you you identify this person's t-shirt?

I've done that with students over the years, and I've highly

correctional, I've got students to do it to each other over the years.

And we've got only one highly significant result, which is that men wash less often than women.

My dad found a live mouse in his fridge the other day, and it turned out he'd been using the drip tray as a urinal.

And he won't get rid of the fridge.

This isn't going to make the edit.

I just thought I'd tell you.

He said that really stinks that room, and I found one mouse stuck behind the fridge, which he worked out.

He said that's a short-tailed vole.

He hasn't got a clean house, but he's got very good mouse recognition.

Anyway, sorry, so

Shappi was talking about going into the jungle, and there's the idea.

I think we all expect that if we go to somewhere that we're not familiar with, in particular, we're going to live in a jungle for weeks, then we might well get ill.

And on the other side, there's the, I remember when I was growing up and my granddad always used to say to me, just eat some soil, it'll make you stronger, you know, like that.

Don't wash those carrots, just eat them.

Is there any sense in which being exposed to

a different country, different foods, just germs strengthens the immune response?

Or is that one of those kind of old wives' tales?

That is a fascinating area.

So I just, you know, that comes around this general idea of it's been called the hygiene hypothesis, where sort of exposure to germs might somehow train your immune system and it actually comes from I think it's David Strachan in 1989 he studied I think 17,000 children followed what happened to them what allergies they got and he came across the idea that children that had many older siblings were much less likely to get allergies and that led to him thinking that maybe it's to do with the because if you have older children you're more likely to get exposed to germs and infections they have it led to this idea essentially that if you're exposed to lots of germs at a younger age, it might stop you getting allergies.

And so that comes to this so-called hygiene hypothesis, exposed to some sort of dirty environment and would become too hygienic.

So, folks, it is important to realize that it's not about the hygiene at the level of washing and stuff.

There's no evidence that not having a bath or shower is going to help you.

But there is evidence that somehow this does pan out.

So, if you look, the best studies are really done with these small farming communities in North America, the Amish and Hutterites, the small isolated communities.

And the Amish communities live closer to the animals, closer to where the animals live, and the sheds.

And the Hutterites have a slightly different structure of their farm, so they're further away.

And the Amish communities that live nearer to animals get much less allergies than the Hutterite communities.

I think the Hutterites get about four times more likely to get asthma, I think, is the right sort of statistic.

It then turns out that if you take dust from Amish communities and the dust particles from their houses would contain the types of germs that they're exposed to, and you give mice those dust particles, the mice are much less likely to get the symptoms of asthma.

So that was published in the New England Journal of Medicine 2016.

That is pretty good, amazing evidence actually, that something about the germs you're exposed to as kids would influence how your immune system develops.

But it's not quite yet a medical breakthrough in the sense that we know how to deal with allergies because we don't really quite understand how that works.

We've got to the point where there's definitely something in it, but we're not at the point where I know how to take that knowledge and create a new medicine from it because we don't really understand how those bacteria somehow influence.

It's probably something to do with the way that your microbiome develops.

So the many bacteria that live on you and in you that are not part of you but do benefit you in some way.

Probably that shift in microbiome happens due to the germs you're exposed to as kids, and somehow that trains your immune system.

But it's not quite there for a medical breakthrough.

Yeah, both those groups you mentioned are interesting for related reasons.

The Hutterites and the Amish are both what we call religious isolates.

They're groups of people who came to the United States in the 18th or even the 17th century because they were being persecuted in Europe.

And of course, like many people in that situation, as soon as they got to the United States, they started persecuting people themselves who didn't belong to their community.

The Hutterites, there are very few of them.

There are Amish, there are enormous numbers of them.

But both those groups have specific

genetic diseases of their own.

But the Hutteroites are famous because some years ago, it turned out that lots of the women in the Hutterite community who wanted to get pregnant would get pregnant but couldn't finish,

couldn't continue the pregnancy.

It was spontaneous, they had spontaneous abortion.

And a woman called Carol Ober, I think her name was, went to study them, and she found that this arose much more often when women were marrying somebody or people were marrying who inadvertently they didn't know that they were close relatives and if you got beyond a certain level of relatedness then you couldn't complete a pregnancy and that's actually true in mice and other creatures too that there is a kind of level of what's sometimes called optimal outbreeding you know some people say you should always you should you're best to marry your second cousin um whether that's a good idea or not i don't know but that's another aspect of the immune system it's it's an outbreeding system you know We have an enormously strong taboo against mating with brothers and sisters.

Whether that's genetic or not, we don't know.

But other animals have it too.

So we've got a system which is outbreeding.

John Barbaroni once came up with a very useful phrase: everybody should try everything once except for incest and folk dancing.

He was right.

People shouldn't try incest.

People shouldn't try it, and it's partly for

immunological reasons.

You need to have quite a lot of immunological diversity to complete a pregnancy.

I can do a simple experiment to show how similar we all are.

This is radio and not television, so you can't see it.

But if you'd like to shake the hand of the person to your left.

See, they're doing it.

Gingerly, they're doing it.

For half of you, for half of you, I have just introduced you to your fifth cousin.

And

that shows how closely related we are.

Is that an optimal breeding proposition?

I've just set it up.

I've been trying desperately to get something.

I think that's just specific to infinite monkey cage audience, right?

That's not in general.

Shabby, can I ask you, does it make you sometimes when I hear the two things that I'm particularly taken for this so far is I love the fact that there are certain things that we know work, but we don't seem to really understand them, right?

And the other one is when you get phrases like, we collected some dust from the Amish and then gave them some mice.

There's something rather wonderful about the ingenuity of immunology, isn't there?

I think it's wonderful that people are getting on with it, like and learning all this stuff and then like telling us about it.

Sometimes I worry that it's best not to know certain things because I have a tendency to panic about stuff.

I went on a date with a guy who couldn't see and when he was a child and someone threw a snowball at him, had dog poo in it, and he caught a disease and he lost his sight, right?

That that means my my children are not allowed to enjoy themselves.

The more that we understand, I mean, obviously, as you've said, it's a it's a cutting-edge science, and we're learning more every day.

Can you foresee a time when we understand the immune system to the point where we can,

first of all, eliminate most diseases, we really understand how it works, but also, I suppose, the most feared diseases or disease, probably cancer, for example.

Does the immune system play a role in that?

And can you see a time when we can really begin to think of eliminating that disease?

It was actually once thought that your immune system could not detect cancer because there's not like a bacteria or a virus or some kind of germ that's obviously not part of your body that your immune system could be trained to look at.

It's your own cells that have just gone a bit awry.

But then it did turn out, once research was more research was done, and the mutations that make a cell cancer do make slightly different shapes of proteins.

and so your immune system can detect cancer.

From that understanding,

we're at the point now where there are, I mean, I don't think it's overhyped, we are in the state where we are at a point where there's a revolution in medicine because we do have a lot of new drugs that work by boosting your immune system's response to cancer.

So

one of the ways in which that happens came about by scientists looking at a receptor, a protein on the surface of an immune cell and no one knew what it did.

So scientists investigate what does this receptor do?

Turns out that that a particular receptor on immune cells was acted as a break.

So it switched off the activity of your immune system.

And that's because when you get infected with say flu, your immune system has to kick off.

Cells able to attack the flu have to multiply and deal with the flu.

But once you've killed off the virus, your immune system has to come back to a normal resting level.

You can't be in this continuous state of fighting flu when the flu's done.

Your immune system has to switch off.

So these receptor molecules on immune cells acted as breaks.

They switch off your immune response after you've been infected with flu, switch it off, go back to a resting state.

That led to the idea that what if you had something like cancer where you need a long-lasting ongoing immune response, what happens if the immune system is switching itself off after a while, like it would do with a flu virus, but now it's switching itself off when you've got cancer and you don't want that.

So that led to the idea of blocking the breaks on the immune system.

You switch off the switching off signal and now you can boost your immune system to fight off cancer.

And that is a revolutionary idea and it's proved to be successful for certain types of cancer.

About 20% of patients with skin cancer, for example, do respond to that kind of therapy.

But the big deal, the reason why that's really exciting is that for a few patients, it doesn't just help them live a few months more, it actually really does make them live for, you know, using the word cure is difficult, but they can, there are patients that have been around for sort of 10 years after,

you know, seemingly having the chances of living six months being very difficult.

So, these types of medicines are amazing.

Now, the reason why I'm saying it's not an overhype to say it's a revolution is because that opens the door now because actually there are loads of ways in which you could try to boost the immune system.

We're not short of ideas.

There are 20 different types of breaks on the immune system, and we can try blocking each of them in turn, use them in block them in combination, use them in combination with other kinds of drugs, the normal chemotherapies and other cancer drugs.

So there is a huge number of ways in which we could use the immune system to fight off cancer.

Steve, as an evolutionist,

however wonderful immunology becomes, however many diseases that we manage to conquer, is the point that the diseases will continue to evolve and they will find new ways of trumping us.

Yes, they will.

I mean it's an evolutionary race between ourselves and the diseases.

And, you know, we constantly get new diseases, things like HIV, things like Zika.

They come from, nearly all of them come from animals, domestic animals,

most of them.

I quite often go to Sydney and in the botanic gardens in Sydney, which is the most

beautiful gardens, there are big, big trees, big eucalyptuses, with bats hanging in them.

And people like to sit underneath these trees.

I wouldn't sit underneath those trees.

These bats can fly 5,000 kilometers and quite a lot of new diseases have come from bats we now know.

So the answer is yes, the bats are going to get us in the end.

There's so much more that because one of my favorite we wanted to find out more about why if you have one virus you this is

homework later homework.

And it's very interesting.

The fascinating thing is a very interesting thing.

I'll throw it to you done which is the intriguing thing, we don't really think about this.

If you've got one virus, you don't normally have another.

So if you have one ailment, you don't normally have two running at the same time.

Which somehow just oh well of course we don't, but why?

What have we found out from that fact that we, if you have one virus, you don't normally have another one running through you at the same time?

Right, right.

So, that is a really amazing story.

So, it was it was just anecdotally noted actually originally, like you just said, that if you happen to be infected with one virus, you don't get another virus.

It turns out that's also true within with cells in a dish.

If you give them one virus, then they can't easily be infected with another virus.

Two scientists,

Lindemann and Isaacs, in working in Mill Hill, North London, not too far from here, were investigating that.

Why is it that when you infect cells with one virus, you can't easily infect them with another virus?

It turns out that what happens is almost any cell in your body can detect in itself when it's been infected with a virus and it starts secreting a particular protein molecule called interferon.

They named it interferon because they thought biology needed something like you know bosons and gluons and muons, right?

Absolutely does.

It's about time.

And so they named it interferon, this stuff that would be secreted by cells when they were infected with a virus, and then that would trigger essentially a complicated genetic response.

Lots of genes get activated by interferon and that is a kind of ant it triggers an antiviral response in your cells.

So that would stop other viruses being infected.

But the story is actually quite complex and difficult.

There were initially people didn't believe them at all.

Lots of other scientists said, oh, yeah, it's not interferon, it's the misinterpreton, because they wouldn't believe them.

And the experiments were difficult because you have to, you know, it was quite hard to prove that something is coming out of a cell and stopping a virus infecting it.

They thought it was just, they couldn't isolate the protein for a very, very long time.

And Isaac, one of the people who discovered that, died very young, I think about 45 from a brain hemorrhage.

And it wasn't really entirely established by the time he died that it was all necessarily proved true.

So it's quite a difficult story.

I mean, all scientists die with things still to work out.

That's the tragedy of being a scientist.

But for him, it was very difficult, I think.

And it's a wonderful story, actually.

All us non-scientists going, oh, I'm fine dying.

I've finished.

Oh, I've done everything I needed to do.

So,

Brian, for those reasons we should say, we recorded this two days after Brian turned 50.

Turn 50?

But he cannot he's so young looking.

Yes, he is, really 50.

And we asked our audience, what do you think is the secret to Brian's everlasting youth?

So, let's find out.

Steve Simpson believes it's a lie.

He's 25 but had a very hard paper round.

This says rubbing in Dara O'Brien's scalp oil.

It is true that most of your co-presenters look a lot older than they really are and you look younger as if you've made a machine to steal our souls.

Well this one here it says hanging out with Robin Ince.

I am very it's it's the way it's the disco's I do.

Robin is his picture of Dorian Gray.

They just keep on going.

Sam Smith.

I'll get you yet.

Shappy, you've got some as well.

Yes, Lee Grayson says, Well, he gets at least eight hours a night of uninterrupted dereeming.

Tim Hopgood says, Higgs Botox.

So,

thank you very much to our guests, Steve Jones, Daniel Davis, and Chappie Corsandi.

Now,

next week.

next week, in the tradition of recording at a different time period to when it will be broadcast, we are recording in January 1974.

And we'll be asking, will Ted Heath's government survive into the spring?

Will ABBA win the Eurovision Song Contest?

And should we remain in the common market in next year's June referendum?

That's if your machine works, to be quite honest.

It was making an awful noise.

I've heard Jim Alcleally was trying to go back to Blackpool 1982 to see the crankies.

He is obsessed.

Anyway, thank you very much for listening.

Goodbye.

Hi, this is Lauren Laverne.

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