Carly: Look at her little paw!

Leave it!

Maren: Ohhhh she’s going to bite the antenna I'm unsuccessfully trying to make friends with chicken because I want to see if I can get a reaction out of my immune system.

This is going against all my instincts here, and I am about to involve my face.

Oh, no.

Oh, yeah.

*Maren sneezes* She’s looking at me with such...

SNIFF.

I am feeling itchyyyy... *clears throat* *sneezes again* Carly: Oh, it’s happening!

I have so many questions, like why do I have this reaction, and Carly doesn’t?

Or, are my cat issues the same as something like a peanut allergy?

And how in the world is all of this connected to a failed experiment involving man-o-war venom and Prince Albert the first of Monaco?

Can you come be my friend?

...maybe not I am forlorn.

*sniffs* But let's start with the basics.

Why does something as innocent as cat hair make my body do something like this?

My nose is just... running down my face, that’s super pleasant.

And it's really just a case of mistaken identity.

If you have an environmental allergy like me, so an allergy to something like pollen or cat hair, here's how this goes down: When you were very first introduced to a thing, your body misidentified it as a pathogen, or something that could be harmful and maybe make you sick.

In response to this thing, which we’ll now call the allergen, your body produced a defensive molecule— it's a specific kind of antibody called IgE that's perfectly shaped to bind to the allergen.

So the next time you encounter the allergen out in the wild, your IgE antibodies are like, ‘oh my God, it's my time to shine, I was literally made for this.’ And they bind to the allergen.

And when your IgE binds to the allergen, that tells your immune cells to release histamine.

Along with other chemicals released during this response.

Histamine is what causes things like these itchy hives.

It dilates or expands your blood vessels, causing that flushing, itching, and swelling.

And the expansion of your blood vessels lowers your blood pressure, which can increase your heart rate In severe cases, this can cause dizziness or even fainting, and the swelling can even affect your airways, making it hard to breathe.

Not ideal.

That's the how.

What about the why?

Science has a couple of different theories, one of witch is: the hygiene hypothesis.

This is an older, outdated idea that we have allergies because we’re ‘too clean’ That we’re not being exposed to enough germs, and germs are what make our immune systems strong, so essentially, we have allergies because we’re not getting sick enough.

But the reality is.

What we call germs—or bacteria and viruses and other microbes that can make you sick—are pretty much just bad for you.

Like getting infected with something like the mumps or mono can actually lead to immune complications later on down the line, increasing your risk for things like allergies and autoimmune diseases.

This is why.

In science, we're moving away from the hygiene hypothesis and towards a newer, more accurate and updated idea called the Old Friends hypothesis.

The idea is that as the human immune system evolved, it was shaped by this really microbe rich environment around us in the dirt and our crops, on our animals.

And all of these harmless microbes are our old friends.

so when we were little and our immune systems were first forming, all of this microbial information acted as data, helping our developing immune systems accurately sort what was harmful from what wasn't.

in today's ultra clean day and age, way fewer of us live in direct contact with those harmless microbes This means that when our young immune systems are developing today, they have less microbial data to work with, so they get it wrong more often.

Like in my case, misidentifying cat hair as something harmful to mount an immune response to.

Now, that's just one of several modern ideas about the root cause of allergies.

Another one has to do with changes to our gut microbiome as we've adapted to our more modern lifestyle.

And another one really wowed me.

More on that later in the video.

But to come back to how a failed experiment made our modern understanding of the immune system possible in the first place... we need a little context.

It surprised me to learn that we have records of this understanding starting way back in 910 C.E., when Rhazes, who was widely regarded as one of the world's first medical experts, documented smallpox’s effect on the body.

He is one of the first to notice that if someone survived smallpox, they couldn't get sick again.

They became what we now call immune.

Fast forward to the 1540s, and Girolamo Fracastoro is the first to record the idea that it's tiny, transferable seed like entities that are responsible for making people sick, which was a pretty novel idea for his time.

Then, in the 1670s, Anthony van Leeuwenhoek is the first to actually observe microscopic life using his self-made microscope.

Like he actually sees the tiny stuff that, up until now, has been invisible to the human eye.

Then, in 1796, Edward Jenner, building on a long practice that came before him, developed what is widely regarded as the first official vaccine.

It defended people against smallpox, and by the 1870s, Louis Pasteur and Robert Koch are proving that it's germs, those little microorganisms that we can now see thanks to microscopes that are indeed the cause of disease— not bad air, or ill humors, or the wrath of the gods— and this cements germ theory in the history of medicine.

It also kicks off this whole era of vaccine development, where Pasteur goes on to develop vaccines for rabies, cholera in chickens and anthrax.

Then, in the 1880s and 1890s, Ilya Metchnikoff was the first to discover specific immune cells in the human body that defend against microorganisms.

and Emil Behring and Paul Ehrlich discover antibodies or molecules produced by those immune cells that identify and defend against foreign substances.

And these discoveries mark the dawn of the modern era of understanding that we have our immune systems today.

Donc nous voila maintenant a Paris, et notre experience raté You and me in Paris!

Oh my gosh!

It's like Mary-Kate and Ashley film vibes ‘Adventure in Paris’ In the first couple of years of the 1900s, two important scientists, Charlotte Shea and Paul Porter, were invited by Prince Albert, the first of Monaco to attend a cruise on his yacht called the Princess Alice.

This might sound kind of weird, but Prince Albert was actually a huge proponent of science.

He even founded the Institute of Oceanography in Monaco, of which there is a branch here in Paris, and I don't know about you, but if I were a prince and had endless time and money and resources, I would probably also spend it just like...doing science stuff.

But I'm also a nerd, so.

And speaking of oceans...the Portuguese man-o-war looks a lot like jellyfish, but weirdly is not a jellyfish and has a very powerful shape and Richet and Portier want to know more about what makes its sting so sting-y.

And this is relevant to allergies and to the building behind me.

I promise.

Because this is where they keep the archives of the experiments that Richet and Portier were doing on their science cruise.

Now, sadly, they weren't able to film inside the archives, but.

We were allowed in to take pictures, and I actually got to hold this notebook in my hands, it’s over 120 years old.

It also made me feel a lot better about how messy my lab notebooks are.

let's look at it on the big screen, because this is where they're recording their notes about all the experiments they're doing to find out more about the toxin while they're on the cruise, using animals like frogs, pigeons and ducks.

But when the cruise ends and they have to go back to Paris, they still want to take it a step further and actually create a vaccine for this toxin.

Because remember, we're still in that vaccine creation craze era where once people have figured out that you can actually induce immunity on purpose every time they find something that can be detrimental to the human body, somebody is out there trying to make a vaccine to help defend against it.

They start working with the closely related sea anemone toxin instead of man-o-war toxin because that's easier to find in the middle of Paris.

And this is where it starts to get pretty sad, because the animal they're trying to induce immunity in is dogs.

The idea was to inject the dogs with a very small initial dose of the toxin, slowly injecting higher and higher doses over time until the dogs had developed immunity.

But instead, when injected with just the second dose, all of the dogs collapsed and died within minutes.

This was very unexpected.

They knew from previous experiments— —again, very sad that it took a relatively large amount of the toxin to kill a dog, and that it did so pretty slowly and gradually.

because these deaths are so sudden, and they're in reaction to such a smaller amount of the toxin that would normally take to kill the dogs Richet and Portier conclude there must be something else going on here.

And that something else must be the immune system.

Richet and Portier gave this sudden and violent reaction a name.

They called it aphlyaxis, but they later changed it to anaphylaxis because they thought that sounded better.

But they still think that this is intrinsically a property of the toxin, it’s because the toxin is toxic.

And it's not until years later when another experiment observes the exact same deadly reaction in response to a totally harmless substance that everybody starts to put these pieces together, that it's not the actual substance itself that is deadly, but it's the immune system's reaction to it.

So even though Richet and Portier were wrong about the mechanism, their failed experiment is the big kick off for the groundbreaking realization that has shaped modern allergy science, which is that your own immune system can kill you.

Now, I would be extremely remiss if at this point, I didn't note that while Charles Richet has been called the father of modern allergy science for this discovery— he went on to win the Nobel Prize for his work in anaphylaxis and he became the president of the French Academy of Sciences— He was also the president of the French Society of Eugenics, and he tried to use science to uphold this discriminatory beliefs.

He was also a massive, on-the-record racist, and on a much less serious note, he also devoutly believed in the supernatural, spent many years hunting for ghosts, and is actually the one who coined the word ectoplasm.

So.

We’ve focused on his experiments specifically to keep things simple, and also because it was a big milestone in the field and a very interesting failure, but I want to be really clear here that no one person can or should be held up as the sole discoverer of something, not only because it's never just the one person that gets us somewhere in science, but also just because someone had one good idea or contributed something to science doesn't mean that all of their other ideas had merit.

No.

With that in mind.

over the past century, there's been a huge rise in allergies of all kinds, including those to foods.

It's actually estimated that now about 8% of all schoolchildren in the U.S. have some kind of food allergy.

And I am so excited because we are about to talk to one of the main scientists who is absolutely key to figuring out that the whole way we've been thinking about and preventing and treating food allergies was pretty much completely wrong up until like ten years ago.

Dr.

Lack: Hello, Maren, how are you?

Maren: Hi, Doctor Lack I'm good.

It's so nice to actually meet you.

It's a pleasure to meet you.

So...happy to answer your questions.

There's been a rise in eczema in the last 20, 30 years that parallels the rise in food allergies there were a number of publications showing the close association between early onset eczema and the development of food allergies.

So to continue exploring this link, Gideon and his colleagues conducted a study.

They looked at 640 babies between four and 11 months of age and who were at high risk of developing a peanut allergy.

High risk, meaning they had eczema and already had developed an egg allergy.

These babies were divided into two groups.

one group, received regular peanut snacks in some form, and one group avoided it altogether.

At five years old, those who had avoided peanut products had a ten fold higher rate of peanut allergy than those who didn't.

But what in the world does eczema have to do with peanut allergies?

What is the border of our body?

Our skin?

It's our skin.

Exactly.

And the skin is actually a major part of the immune system.

It's prevents it's our first line of defense.

Exactly.

In eczema there's an inflammatory response in the skin, which means that skin becomes more permeable and it allows penetration of molecules.

if you think about it, a parent is eating peanut butter, well, not giving it to their seven month-old baby.

but is kissing the baby, touching the baby with little bits of peanut butter and the baby's got a bit of eczema on the face, those molecules penetrate through the skin and the body thinks it's an invading parasite.

Because it's coming through the skin.

Exactly.

So so we think of the the gastrointestinal tract as a digestive tract.

but also the immune cells in the lining of the gut, all food molecules that enter early in life have to be processed in these immune centers that decide, gosh, this is coming in the right way.

This is friend, not foe: tolerate it.

So it's the mode of entry.

The mode of entry, it's the mode of exposure.

If you're exposed to peanut through the skin in the first place without any GI exposure, you're set up for developing peanut allergies.

It's about the skin.

That's crazy.

And we always assumed that, well, eating peanuts causes peanut allergic reaction.

Therefore don't give it to babies on the level of other peanuts and that’s a logical fallacy.

it became very clear that if you introduce peanuts and subsequently also in other studies, eg especially very early on in the first six months of life, you will protect to a very large degree against these food allergies.

So a total 180.

A total flip, yeah.

Our way of thinking has changed both in terms of prevention and in terms of treatment.

and this this very important phenomenon, oral tolerance induction, which I believe is a very powerful tool where you give tiny milligram doses in increasing amounts to a child who already has peanut allergy...

So trying to retrain that immune response... And that will retrain response system.

Sure.

So in in moderation, the trigger can also be the treatment.

Correct.

Okay, so Gideon and his colleagues totally changed the game for how we think about and prevent and treat allergies like peanut allergies.

But I was just really struck by this whole skin connection.

I had no idea.

And I keep thinking that if eczema is one of the potentially main root causes of issues like peanut allergy, then what are we doing about the eczema?

So Claudia, what is this magnificent creature?

It looks like a friendly little dinosaur.

Yeah, it's a giraffe!

Well, this is an air filtration device.

So what happens is room air is taken in at the bottom.

There's a big filter in there, that filter filters out pretty much all the particles that are in the room.

So that's any particle— that can be pollutants, that can be allergens, that can be whatever, some of them we don't even know what they are— it filters out solid particles of all sizes.

Wow.

And then it comes up here and then it falls out, displacing the particle laden- air.

So what you're breathing in is clean.

And the idea behind that in relation to helping eczema, what's the relationship?

Yeah.

So a lot of people who have eczema, especially if it's more severe or long lasting eczema, will have some form of environmental allergies.

So if you take them away, what we hope will happen overnight and what we think happens overnight is that it gives the immune system a bit of a rest.

I would say for many of my patients, if we can take the edge off and take 20% away of what's going on, in particular, we can improve sleep.

So that that makes an enormous difference for them Sleep is probably the worst affected thing with eczema, my god And in this study to know whether or not the device is working, we're using a number of methods: some of them are looking at how intact your skin is, what's going on in your skin quality of life questionnaires... another test that we can do is, is to check for how leaky your skin is.

that little probe measures transepidermal water loss.

And so in someone with eczema, would that be high?

That's right Why do you think that is?

I don't know, we've got dry skin.

Because the barrier is not intact.

And what happens when the barrier is not intact?

You evaporate.

That's right.

Well, the water evaporates.

You guys, I will no longer exist soon... Can we prevent eczema from happening?

We would love to say that we can, but I don't think we're particularly successful.

yes, if we could prevent eczema, I think we would be able to prevent quite a bit of food allergy, not all of it, but quite a bit...We are, we have a study open where we are working on training computer software, machine learning algorithms to accurately score eczema severity from digital images because we find that patients, especially children who can't advocate for themselves, are often out in the community untreated that's worse if they have darker skin, So the eczema on it's study looks to train this computer software to accurately severity score eczema and all skin tones.

It's about access and early access to the right treatments.

So I firmly believe that treating eczema early is incredibly important to help prevent food allergy.

It's incredibly important for the baby's development and quality of life the family's quality of life, you know, eczema doesn't kill you, but eczema can take your life away.

Yeah.

Ooh.

Okay.

We've covered a lot in this one.

From the old friends hypothesis to the eczema connection.

And I hope that all of it, from Richet and Portier’s failed experiment to Gideon and his colleagues’ work which has turned our understanding of food allergies completely on its head, shows you that science is always still a work in progress.

We're still figuring so much of it out, especially when it comes to something as complex as the immune system.

And we always have to be open to incorporating new information to help inform how things like our solutions will evolve into the future.

isn’t that right, Chicken?

and, yknow...maybe if I had wanted to avoid this kind of misery when touching cats I probably should have grown up on a farm or something.

Anyway!

Thanks for watching.

Bye.

isn’t that right,Chicken?

to film inside the archives, but.

Do.

You.

You.

You.

You.

You.

You.

You.

You.

You you you you.

You you you.

You you you.

Me.

You you you.

You you.

It surprised me to learn that we have records of this understanding starting way back in 910 C.E., when Rosi's was widely regarded as one of the world's first medical experts, documented smallpox, its effect on the body.

He is one of the first to notice that if someone survived smallpox, they couldn't get sick again.

They became what we now call immune.

Fast forward to the 1540s, and Girolamo Oro is the first to record the idea that it's tiny, transferable seed like entities that are responsible for making people sick.

Which was a pretty novel idea for his time.

Then in the 1670s, Anthony van Leeuwenhoek is the first to actually observe microscopic life, using his self-made microscope.

Like he actually sees the tiny stuff that up until now has been invisible to the human eye.

then in 1796, Edward Jenner, building on a long practice that came before him, developed what is widely regarded as the first official vaccine.

It defended people against smallpox, And by the 1870s, Louis Pasteur and Robert Cork are proving that it's germs, those little microorganisms that we can now see thanks to microscopes that are indeed the cause of disease, not bad air or ill humors, or the wrath of the gods.

And this cements germ theory in the history of medicine.

Then, in the 1880s and 1890s, Elias nCoV is the first to discover specific immune cells in the human body that react to microorganisms.

and Emile Baring and Paul Ear like discover antibodies or molecules produced by those immune cells that identify and defend against foreign substances And this is truly the dawn of a new era.

Now, when you think about the training, the immune system, food desensitization or oral immunotherapy, it's also called you want to start with a dose that doesn't give symptoms and then gradually you build up and this building up takes many months as many visits.

at the moment we know that we cannot cure food allergy.

So one way of describing is we want to reach a state of sustained non responsiveness, which just means you're not having lots of reactions.

So what we've got here is a selection of nuts and sesame paste that are ready for food challenges.

we start with a small dose.

So starting out with some almond butter, for example, we've got this one here, which is tiny.

20 minutes later, if everything is fine, you go to the next dose.

All these doses are determined by international protocols.

So then we've got a big blob.

And 20 minutes later, you go to those three, 20 minutes later, those four, and then 20 minutes later, assuming everything's good, you go to dose five.

So that would be the top dose for almond.

my passion really and my my research work is in the field of eczema and allergies.

you know, early onset eczema is a significant risk factor for the development of food allergies because we know that really exposure to a food should happen through the gut and not through the skin and eczema is incredibly distressing.

It's hugely itchy.

You can't sleep.

Their whole body image issues, eczema doesn't kill you, but eczema can take your life away.

I'm passionate about working on that.

So what am I doing?

Two things.

One, we are we have a study open where we are working on training, computer software, machine learning algorithms to accurately score eczema severity from digital images because we find that patients, especially children who can't advocate for themselves, are often out in the community untreated that's worse if they have darker skin, So the eczema on it's study looks to train this computer software to accurately severity, score eczema and all skin tones.

that will help people get treatment in the first place.

And then we're looking at, okay, well, what treatments do we have?

it's creams, creams, schemes, ointments, ointments, greasy stuff.

You know, But for most of the patients I see and I obviously look after a sort of cohort that is particularly bad, that is not enough.

So the research that we do is looking at environmental exposure and does controlling what happens to you exposure at home in bed where you spend of course, a lot of your time, a lot of your life is spent in bed sleeping.