Reinforced skin for amputees, and could E.T. be an AI?

The Naked Scientists

The Naked Scientists Podcast

My dad works in B2B marketing.

He came by my school for career day and said he was a big ROAS man.

Then he told everyone how much he loved calculating his return on ad spend.

My friend's still laughing at me to this day.

Not everyone gets B2B, but with LinkedIn, you'll be able to reach people who do.

Get $100 credit on your next ad campaign.

Go to linkedin.com slash results to claim your credit.

That's linkedin.com slash results.

Terms and conditions apply.

LinkedIn, the place to be, to be.

All engine running.

Absolute genius.

Get this.

Welcome.

This is the show where we bring you science.

What that essentially means is...

Discovery.

Advances.

Questions.

Research.

Technology.

Unbelievable.

Without further ado, this is The Naked Scientist.

Hello, welcome to this week's Naked Scientist,

the show where we bring you the latest breakthroughs in science, technology, and medicine.

I'm Chris.

I'm Chris Smith.

Coming up, scientists uncover a way to help amputees to toughen up their skin

to make prostheses more comfortable.

Also, COVID mRNA jab pharmaceutical company Moderna

turn their attention to vaccines for MPOX.

Plus, the astronomer-oil Martin Rees on whether ET is really out there.

From Cambridge University's Institute of Continuing Education,

this is The Naked Scientist.

Paralympic runner Richard Whitehead recently told the BBC

that NHS prosthetics need to improve

to help produce Great Britain's next generation of elite athletes.

Richard, who's a double above-the-knee amputee,

was referring in part to the abrasiveness of uncomfortable prosthetics.

It's long been a problem for amputees

because limb stumps are often covered in much thinner skin

that can be pulled out.

It can be painfully abraded when they're inserted into prostheses.

But US scientists may have found a solution.

A team at Johns Hopkins Medical School

have been injecting connective tissue-producing cells

called fibroblasts,

which they collected from the skin

on weight-bearing parts of the body like the feet.

And they're showing that these can toughen up the tissue

in the new skin site where they're injected.

Now, it's early days,

but it does suggest that the approach can be used

to reinforce skin in places like the heart,

giving users a much easier ride, potentially.

Fiona Watt, who's director

of the European Molecular Biology Organisation,

has devoted her life to studying the skin,

and she's been very keenly following this development,

which she explained for us.

Every year, unfortunately,

a large number of people suffer an amputation.

And as you'll know from watching the Paralympics,

the quality, particularly of artificial limbs now,

is superb.

But the trouble is, if you think about your leg,

if you've had an amputation there,

what remains of your leg

is now in contact with the artificial limb.

And that part of your skin was not designed

to be weight-bearing in the same way as a foot, for example.

So what's interesting about this study

is the goal is to see

if you could convert skin

that isn't specialised to bear weight

to skin that can bear weight

and can fit a prosthesis.

So in other words, converting the skin

from like your chest or your arm

into that thick skin that you see on your palms and soles.

And the hope is that it would stop the pain

and the breakdown that happens of the skin

in amputees who have to wear a prosthetic limb

for a long time.

How are they trying

to do that?

And how does the thick weight-bearing skin

of a foot, for example,

differ from the skin

that someone will have over an amputation site?

The skin in all parts of our bodies has two layers.

There's the outer protective covering called the epidermis

and then the underlying,

what we call the connective tissue called the dermis.

And the dermis is full of specialised proteins

like collagens,

which,

provide bulk and strength if you like, to the skin.

And the skin on your palms and soles

is specialised for weight-bearing.

And if you look at your palms,

you can see that you've got fingerprints

and the fingerprints represent a way in which the epidermis,

the outer covering of the skin is specialised for grip

and to support weight, for example.

So in these specialised bits, regions of your body,

you've got a thicker epidermis than normal.

And also the underlying connective tissue is thicker and stronger.

Is it then a question of just reprogramming the skin

on, say, an amputation stump

to change its characteristics

so it looks more like a sole or a palm?

Or is it more involved than that?

No, I think you're absolutely right.

If you had some way in which you could just flick a switch

and change the programme from arm skin

into the sole of your foot, that would be fine.

But of course, we're talking about adults

rather than a process of development.

So different strategies are required.

So these scientists lined up some healthy volunteers.

Each volunteer agreed to have a small biopsy of skin

taken from the scalp or from the sole of the foot.

The scientists isolated cells from the skin.

And the particular kind of cell they were interested in

is a cell called a fibroblast

whose job is to make collagen.

So it's a connective tissue cell.

They've expanded them in the lab

and then they have injected them back into the same individual,

but this time injected it into the thigh.

And the question is, can those fibroblasts

from the different parts of the body

change the nature of the thigh skin

so that if it's sole fibroblasts, it looks thickened like sole?

And did that happen?

So when you put this population of foot fibroblasts,

so connective tissue making cells into the thigh,

do you get a sort of surrogate big toe on your thigh almost?

Does the skin change character as you would expect it would

if what you're saying is what happens?

Well, the skin does change character,

but unfortunately not as dramatically as you might have wished.

The evidence that it has changed came from measurements

like how resistant is the tissue?

Transplanted skin to different sorts of challenges.

And mainly it's evidence from taking a biopsy of the transplant site

and looking at molecular characteristics

which distinguish foot from scalp skin.

So this is absolutely not an off-the-shelf solution

for people who have amputations,

but it's very important because it's a step in the right direction.

How do they think?

Then you can optimise it because it shows that it might work

if we could make it work a bit better

and it will change the characteristic of the skin locally,

which would be ideal if you could thicken and toughen up

an amputation site skin.

Do they suggest how we might go about achieving that?

One of the things they showed in their study

was that if they take those cells in the dish

and subject them to pressure,

the foot cells respond differently to the scalp cells.

So one idea is...

One idea is that maybe if they had transplanted the cells

and subjected them to pressure,

which is what would happen in the stump of an amputee,

that might help the foot fibroblasts

to behave more like they were from the foot.

Do we have any insights into how they're sensing that

and then responding?

Because is it not possible if we can work that out,

we can just make cells from anywhere in the body pressure sensitive

so you don't have to do the transplant at all?

One thing that was shown many years ago,

which at the time I was really surprised by,

was that if you take fibroblasts from any body site,

you can show that they remember where they came from.

So that means that encoded in the DNA of the cell,

there is a memory that they came from the foot.

But I think to make skin,

you need a collaboration between the epidermis and the dermis

and probably stimulating the signal,

signaling molecules in the epidermis,

which help, for example, make the fingerprints on the palm,

would help as well.

So if you were to do this practically,

then would you, if you were performing an amputation on somebody,

would you go to the healthy limb that you're not amputating

and get the source of cells, these fibroblasts

that make the tough connective tissue

and have this memory that I am a foot cell,

would you get that from the healthy site

and then put that into the skin that you're fashioning,

the wound stump from,

so that it would kind of pre-endow that site

with the ability to become almost like a foot

and therefore it will be a better match for the prosthesis?

Yeah, I think it would be a very good idea.

I mean, you can isolate the cells,

you can grow them in culture

and you can store them for many years

so that you could give the stump time to heal

and then come in and help repair it.

There are many possibilities there.

Some great news.

That was Fiona Watt commenting on that new study

which is just out in the journal Science.

The pharmaceutical company Moderna,

who were responsible for one of the mRNA-based COVID jabs

that were developed and used during the pandemic,

have now gone on to use this same technology

to develop a new vaccine against the pox virus

that's causing the current outbreak of mpox

in the Democratic Republic of the Congo.

Yes, there are already vaccines against this emerging disease

but they're in short supply

and they're also more difficult

to update if the vaccine needs to change for some reason.

Indeed, UNICEF, which is the UN's children's agency,

recently issued an emergency tender

for the procurement of more mpox vaccines.

Galit Alter is Moderna's vice president of immunology research.

The current vaccine that we do have

that is licensed for global use,

this Genios vaccine,

does provide 100% protection against death

in the context of preclinical models

and has been shown in clinical trials

over the last few years

to provide protection also in humans

in reducing disease and pathology.

And so we do have an incredibly robust tool

currently out in the world

that is able to curb the potential threat

caused by the monkey pox virus.

I think the question that we're trying to ask here is,

you know, does this additional technology

that we now have

that can pivot and potentially create vaccines

in an accelerated timeline

that we know is safe

and that we know is highly immunogenic

and could potentially focus the response,

in a more deliberate way

because of the way that it trains the immune system,

could this technology help fill a gap

in our future response to monkey pox

or to other pandemic threats?

And so I think what we're trying to understand

is really how do we fit in the current world

where there is a particular vaccine out there

where we can potentially fill those needs

that might emerge with time

as this virus potentially spreads more aggressively

or changes with time.

How do you pick up the vaccine?

How do you pick what to put into your vaccine?

Because the way your vaccine works

is that you are taking the genetic code

that corresponds to a particular part of the virus.

So how do you pick that's the bit of the virus

we're going to put into the vaccine?

Well, that's a really important question.

And so I think the first thing I always try to explain

is that nothing we do is done in isolation.

Everything that we do in the context

of these pandemic threats

is done in collaboration with experts in the field

that have been studying these viruses

and that have been studying these viruses

for decades, you know, throughout their careers.

And so what we did really immediately

upon taking on this challenge for monkeypox

is to essentially create collaborations

with incredible figures in the pox viral world

who had been studying viruses

and understanding which particular components of the virus

are the most important targets

for protection against disease and infection.

And what they had learned over those decades of research

that they had been conducting in the laboratory,

in their environment,

in their animal models,

was that just four surface proteins

that sit on the outside of the virus

is really all you need to attack with an immune response

in order to prevent the virus

from gaining entry into human cells.

And what we focused on then for the next year or so,

really in the laboratory,

is working to design these particular proteins

so they could express effectively

off of our vaccine technology,

this genetic code that we essentially deliver

to the immune system,

to essentially make sure

that when the immune system sees these proteins,

they see them in a context

that is absolutely perfect to raise immune responses.

So we took these designer proteins

that we expressed off of our genetic vaccines.

We delivered them into mice.

We then challenged these animals to the monkeypox virus.

And what we were surprised and elated to see

was that this novel technology was able to raise responses

and essentially control the virus with an exquisite capacity,

both limiting the ability,

of the virus to cause death,

but also really helping to diminish the amount of disease

that these viruses can cause within these animal models.

And when you put this into the body,

or an experimental mouse, for example,

does it make antibodies

against those bits of the surface of the virus?

Or does it make white blood cells, T cells,

that can hit virally infected cells?

Or does it do both?

The beauty of the Moderna mRNA vaccine technology

is that we are able to raise

both these white blood cell responses

that are critically important

for helping the immune system

to make many, many antibodies

that can both block the virus

from infecting a future cell,

but also to recognize the virus

when it's floating around

and rapidly clear it from the system,

preventing it from causing

any further infection or disease.

What's the longevity of the response like?

Because we know that with things like the existing vaccinia

based vaccines,

the old fashioned way that Edward Jenner would recognize,

those tend to be lifelong,

those protective effects.

Do you think you'll get lifelong protection

with this Moderna construct?

Or do you think we'll be going back

giving people boosters?

That's a really important question.

With the mRNA vaccines,

what we saw in the COVID-19 pandemic

is that we saw these very robust immune responses

that did decline to some level.

But if you look at some of these long-term studies

that were done,

in large populations of vaccine individuals,

what we saw is that this technology

really is generating immune responses

that can last for a very, very long time.

But also importantly,

this technology also raises those white blood cells

that you mentioned,

that essentially live for very long periods of time,

constantly surveying our body

for potential entry of a pathogen.

And so we have this long-term immunity built in,

really both through these white blood cell responses,

as well as by antibodies that we hope that this,

this novel vaccine technology can help to serve

or to fill the gaps for other technologies

that are out there.

How long is it going to take you to get this to market?

So you've got something that's regulator approved

that could be deployed into the field?

Because obviously the crisis we're having is now,

and we need this sort of solution now.

Right.

So it's important to just mention

that this vaccine has not been approved by regulators.

We're right now in the middle of a phase one,

phase two trial.

And in those trials,

our goal is,

to go into healthy populations and ask,

are these vaccines safe?

With that data,

understanding that whether we are inducing

robust immune responses,

as well as seeing that these vaccines

are incredibly well tolerated at a population level,

gives us the essential information that we need then

to make decisions about how we can move forward

in the context of a licensure trial

or commercial deployment.

Let's hope they get it over the line.

Gallet Alter there from Moderna.

And that study on the new vaccine

has just come out in the journal Cell.

The Naked Scientist podcast

is produced in association with Spitfire.

Cost-effective voice, internet,

and IP engineering services for UK businesses.

Find out how Spitfire can empower your company

at spitfire.co.uk.

Music in the programme is sponsored by Epidemic Sound.

Perfect music for audio and video productions.

You're listening to The Naked,

Kid Scientist with me, Chris Smith.

Still to come,

Astronomer Royal Martin Rees

on whether ET really is out there or not.

But first, an international study has found

that one in four patients in a vegetative

or minimally conscious state

are actually able to follow instructions

and perform cognitive tasks.

The research was carried out

on a large cohort of patients,

including 100 in Cambridge.

Emmanuel Stamatakis from the University of Cambridge

is part of the study,

and he's been telling me about it.

Emmanuel Stamatakis,

We put these people in an MRI scanner,

or we fitted what we call an EEG cup.

It looks like a hairnet with sensors on it,

on their head,

and we measured activity in their brain.

Now, the activity was in response

to something we asked them to do.

So we asked them to think they're playing tennis

for about 30 seconds,

and then we asked them to stop,

and then we asked them to play tennis again

or move their hand.

Imagine they're moving their hand.

So 30 seconds on, 30 seconds off.

We then do a mathematical analysis

of this data,

and we see which part of the brain

they use to think they're moving.

And if they respond to this task,

it means, first of all,

they understand language,

they understand the instruction,

they can retain the instruction,

they have what we call working memory,

and they can do the task.

They can imagine they're moving.

So a very complex set of skills

is required to carry out this task.

Quite a while ago,

I remember a colleague of yours,

Adrian Owen, came on.

He was a professor at the University of Glasgow.

And he said,

to actually some dramatic fanfare,

that people who were regarded

as completely cut off from the world

could communicate in this way.

They asked people to imagine

giving someone a tour around their house

versus, as you say, playing tennis,

and they could see the different activations

in their brain.

And they concluded these people

were responding meaningfully,

and that perhaps people we'd regarded

as unconscious are not as unconscious

as we thought.

So what's the question you've asked next then?

How have you built,

on that study from nearly 20 years ago?

So that original study

was carried out in a handful of patients.

Now we're having a group of 350 patients.

The data from which was acquired

from all over the world,

mostly Northeast US, Paris,

Liège in Belgium, Cambridge.

So this is the biggest group of patients

we have ever looked at

to understand whether there is

residual cognitive function.

And what fraction,

of people who are in that state,

have this residual cognitive function then,

based on these big numbers

you've now looked at?

So, so far,

studies with a lot smaller numbers

suggested 10% to 20%

could respond to this task.

For the first time,

with this group of 350 people,

we found out that a quarter

can respond to these tasks.

That's a big number,

and it's alarming in a number of ways,

because what this means is that

people who we had,

looked after,

but perhaps regarded as

not really there with us,

are probably listening to a lot of

what's being said around them,

and they're thinking,

and they would probably love to communicate,

but they can't.

Absolutely.

This discovery, this research,

presents us with a huge number

of ethical considerations.

You mentioned one of them yourself.

Should we have this discussion

around these patients?

Should we try to perhaps

harness what we've discovered

and work towards some means

of communication,

communication?

Because you can use this

almost like a yes-no answer system,

can't you?

Nod for yes,

shake your head for no,

because you can ask them questions,

look at the brain response,

and this means you can have

an albeit limited,

but a conversation with these people

for the first time.

Absolutely.

The task you mentioned earlier,

if one imagines one is playing tennis,

the area of the brain you use

is quite high in the brain.

If you imagine you're wandering

around the rooms of your house,

the area of the brain

that responds to this

is quite low in the brain,

so we have two distinct areas.

So yes, in a way,

we can use that kind of task

to respond yes or no.

At the same time,

with functional imaging,

what we can do these days

is what we call decode

pictures we look at.

So we can look at brainwaves

and decide,

well, a computer can decide

what kind of picture

you're looking at.

So I don't think

it's going to be very far

before we can advance this

to speech and language.

Have you had

some meaningful conversations

with people in this study,

the participants?

As in, apart from just asking them

yes or no type things,

have you begun to elicit

information from them

that gives you some kind of insight

into what it's like

to be in their situation?

No, at Cambridge we haven't.

I think we will need to,

again, going back

to the ethical implications of this,

request ethical approval

before we start doing

something like this.

But this kind of result

may open the way

to that kind of study.

Does it also open

the door to better rehabilitation?

Because when someone hurts their leg,

we give them physiotherapy,

we exercise the damaged leg

and we restore movement and so on.

If someone's regarded

as in a persistent vegetative state,

there's nothing happening neurologically,

we thought,

therefore we didn't exercise the brain.

Have we missed an opportunity

to rehabilitate them?

Could we now reopen that door

and restore better function

for those people?

There are two directions

that research is going on

on that particular front.

We have published work

two years ago

using, again, functional MRI

suggesting that dopaminergic drugs

may be a way forward

with this kind of patient.

These are the same drugs

that we give to people

with Parkinson's disease.

They mimic the action of dopamine.

Absolutely.

At the same time,

there is a huge revolution

in a way happening

with what we call neurostimulation,

stimulating the brain with ultrasound

or with magnetic waves,

non-invasive techniques

and invasive techniques

where neurosurgeons implant electrons.

And we're starting to understand

better what unconsciousness means.

So I think the future is bright

for this kind of patient.

You've dwelled on the ethics

a couple of times.

One of the things that's immediately

coming to the front of my mind

is that we sometimes,

unfortunately in medicine,

find ourselves in a situation

where we have to make a decision

about whether to carry on

treating someone.

And very often people look at a person

who's in a position like this

and they say,

well, we don't think

there's any prospect of recovery

and that influences the decision.

Is that going to change then

off the back of what you've found?

I think it should change.

I think we have established

that we have technology

that at least in cases

where patients are responsive

can give us additional information

than what we have currently,

than what medics

who take those decisions consider.

I think, again,

in the very near future,

we should see changes

in this kind of consideration.

Emmanuel Stamatakis there

and that study has just been published

in the New England Journal of Medicine.

Now, earlier this summer,

the Astronomer Royal, Martin Rees,

delivered a wonderful virtual lecture

to the Starmer Science Conference

in Bratislava.

It was about whether we're alone

in the universe.

It was so good that we thought