Listener Questions #10

Daniel and Kelly answer questions about prions, playing music near a black hole, and medical maggots. 

See omnystudio.com/listener for privacy information.

Episode Transcript

Speaker 1 (00:05):
How do prions infect healthy proteins? Someone please ask about
Aunt Lion Queen's.

Speaker 2 (00:11):
What does a concert sound like near a black hole?
Can medical maggots help make a wound hole?

Speaker 1 (00:18):
Biology, physics, archaeology, forestry. We like medicine, so thank you chemistry.

Speaker 2 (00:25):
Do you have questions about particles or cats? We'll find
answers to all of that.

Speaker 1 (00:30):
Whatever questions keep you up at night. Daniel and Kelly's
answer will make it right.

Speaker 2 (00:34):
Welcome to another Listener Questions episode on Daniel and Kelly's
Extraordinary Universe. Him Daniel, I'm a particle physicist with a

(00:56):
growing interest in biology, and I love here feedback from
listeners about the new podcast format.

Speaker 1 (01:03):
Hello, I'm Kelly Wiener Smith. I study space and parasites.
I also love hearing from the listeners, and I'm excited
about the kind of creepy crawley stuff we're talking about today.

Speaker 2 (01:13):
I am too. There's so much about our natural world
which is amazing. Even if we don't understand quantum gravity
and how all the particle bits come together to make
this bizarre world, it's still totally worth studying. With so
many incredible, gooey mysteries and the.

Speaker 1 (01:27):
Non gooey mysteries are good too. I'm also becoming a
budding physics enthusiast. You gave me the other day a
pod in physics, and I'll take it.

Speaker 2 (01:37):
Yeah. It turns out people can be interested in physics
and in biology and and all sorts of crazy things
about our extraordinary universe. And I just wanted to read
a snippet from a listener who wrote to me and
encourage anybody out there to write to us questions at
Daniel and Kelly dot org. Send us your questions, send
us your feedback, send us your ideas, send us your
hopes and dreams, send us your love letters from fifth grade, whatever,

(01:58):
and we'd love hearing from you. Particular listener has a
long history with me and wrote that he originally quote
had the idea that I wouldn't be as interested in
a podcast that wasn't focused entirely on physics. How wrong
I was. I have found myself fascinated by the biology episodes,
especially the recent episodes on insulin and gender, and I
have to feel like I'm going along for the ride. Also,

(02:20):
like I didn't know how fascinating biology was, and so
I'm really grateful to get to explore all these topics.

Speaker 1 (02:25):
And I'm so grateful for everyone who's given the biology
a chance, everyone who sort of came for the physics
but is staying for the biology and hopefully is enjoying
it as well. And the listener mentioned the insulin episode.
We are super lucky to have Katrina Whitson coming for
a little guest appearance on the show again today. But yes,
I read that email too, and it absolutely made my month.

(02:48):
I love when we get emails like that.

Speaker 2 (02:49):
Me too. And also, you can't mention Katrino without referring
to all of her accolades. I know if you're aware
she's the Whites And Endowed Chair at the Whites And Institute.

Speaker 1 (02:57):
Oh my gosh, wow incredible. I have been dying to
get an adjunct position at the Whites And Research Institute.

Speaker 2 (03:05):
The review process is really strict. Yeah, a bunch of
snobs over there.

Speaker 1 (03:12):
I've met Katrina. I'm not sure about that. She seems
very nice.

Speaker 2 (03:15):
No, of course, we'd love to have you anyway. Today
we are talking about your questions about this extraordinary universe,
physics questions, black hole questions, weird protein questions. We'd love
to answer your question on the podcast. Please do right
to us questions at Danielankelly dot org. Again, if you
write to dot com, you'll be sending your message to

(03:36):
a very lovely couple who just got married, but that's
not us.

Speaker 1 (03:39):
Congratulations Daniel and Kelly. We wish you a beautiful forever together.

Speaker 2 (03:45):
And Daniel and Kelly dot com. If you guys have questions,
send them to us. We'd love to have you guys
on the podcast.

Speaker 1 (03:50):
Hey, Daniels and Kelly's.

Speaker 3 (03:53):
Well.

Speaker 1 (03:53):
Our first question today is an amazing question by Niall
about pry on or pre on. I don't know I'm
going to say it, however, you know it comes out
of my mouth at the time, but let's go ahead
and hear the question.

Speaker 3 (04:05):
Hi, Kelly and Daniel, my name is Nile, and I
have a question regarding preons and preon diseases. I understand
that preons are misfolded proteins that are capable of causing
significant damage to our nervous systems if we are exposed
to them. However, I am particularly interested in understanding why

(04:26):
preon diseases are infectious slash contagious. Specifically, I'm wondering what
causes our normal properly folded proteins to adopt the misfolded
preon structure when exposed to them, rather than just defaulting
to their correct structure. I would greatly appreciate any insight

(04:47):
you can provide on this topic. Thank you so much,
And I love the show.

Speaker 1 (04:51):
This is a fantastic question that I did not know
the answer to, and you'll see that by the end,
I spent five hours slamming my head against the lit
and eventually we called in someone smarter than either of us,
and that's where Katrina comes in. But let's back up
a little bit, all right, So how do diseases usually
replicate and transmit? So, if you have a bacterial infection,

(05:15):
like you've got a cold, the bacteria get into your
body and then those bacteria start making more and more
of themselves and they, you know, spread throughout your body.

Speaker 2 (05:23):
That's kind of creepy, right, You're being like colonized by
some malevolent force.

Speaker 1 (05:27):
It is pretty creepy. Yeah. And then if you get parasites,
like you know, the parasites that I love to talk
about so much, something like tapeworms or nematodes, what usually
happens there is every single infection you get is because
you have accidentally, for example, consumed an egg that was
in the environment. And so the way you get more
of those infections is you accidentally encounter and consume more

(05:49):
of those eggs. For viral infections, the way you get
more of those is that the virus injects some of
its genetic material.

Speaker 2 (05:57):
So gross, so gross.

Speaker 1 (05:59):
Yes, yeah, I know I hate viruses and bacteria, but
none of them are as bad as ticks. Ticks are
the worst. Yes, So they inject genetic material into your
own cells, hijack your cell's machinery, and your cell essentially
makes more viruses for the virus.

Speaker 2 (06:15):
All of these things have nucleic material, right, this DNA
or RNA or something, and all these things. People argue
about whether viruses are alive or not, but like they
have this code inside of them. That's what they all
have in common.

Speaker 1 (06:26):
Right, Yeah, that's right. And so when the first person
suggested that what's happening with what ended up being called
prion diseases is that it's actually a protein that is
essentially replicating, not by sort of copying itself using genetic
material like you would expect, but is essentially touching other
proteins and making those other proteins infectious. That was a

(06:51):
bit controversial for a while because that's not how we
usually see infections transmitting in any of the ways that
we sort of understand this.

Speaker 2 (06:57):
Are you underplaying it a little bit, a bit controvert, Like,
wasn't that sort of laughed out of the room for
a while, People are like, that's impossible.

Speaker 1 (07:04):
Yes, yes, no, we were all very skeptical. It took
a while for that to be widely accepted.

Speaker 2 (07:10):
And for those of us who are not biologists or biochemist,
remind us what you mean when you say protein. You're
using in a technical sense, not like chicken breasts or
tofu on top of your salad. When your server asks
if you'd like to add protein? You mean something about
the chemical structure, right.

Speaker 1 (07:25):
Yeah, so I mean chicken breast is made of proteins.
So your genetic code contains the information that your body
needs to make proteins. And proteins are strings of amino acids,
and they essentially make up all of your body, and
they help your chemical reactions happen, and they are ubiquitous, and.

Speaker 2 (07:43):
They're incredible little molecular machines. Right, they do stuff. They
come from the DNA and then they fold into these shapes.
They're like little robots, right, They're amazing. The engineering here
is just.

Speaker 1 (07:53):
Astounding, delicious in your salad and fantastic in your body.
So the listener to know about prions. So these are
protinaceous infectious particles, is the fancy way of sort of
saying it. And there's a couple different ways that proteins
can transmit disease. So one of them is that they're
sort of infectious in the way you might usually think

(08:14):
of infectious material. So, for example, if you eat meat
that has the mad cow prion in it, and you
consume that meat, that prion can then move around your
body and cause your proteins to become abnormal. So that's
infectious in a way that we sort of are used
to thinking about infectious material.

Speaker 2 (08:33):
And just to make sure I'm following, when you say
prion is a protinaceous infectious particle, it's still just a protein.
Is just like a weird protein in a particular shape, right,
It's not like it's turned into a particle the way
we talk about it.

Speaker 1 (08:45):
Oh yeah, no, forget the physics, man, forget the physics.
We're in bio world.

Speaker 2 (08:49):
Right now, I'm listening to biologists talk about particles, but
it has nothing to do with particles. That's great.

Speaker 1 (08:55):
I don't know whether particles in biology are more confusing
than particles in physics, but either we're gonna buddle through.

Speaker 2 (09:01):
All right. So you can get these in your body
and they can turn some of your proteins into preon's.
What's another way that you can get one of these
horrible diseases.

Speaker 1 (09:10):
Another way you can get one of these horrible diseases, unfortunately,
is if you end up with a mutation in your
own genes, and then your genetic code now produces a
protein that folds in a way it's not supposed to fold.
And usually when you get this heritable gene that has
this bad mutation, you don't start making these weird proteins
until you're a little bit older, like sixties or more.

(09:33):
Funny story, I was talking to a neighbor the other
day who said something to the effect of, oh, well,
when I'm talking to young people, they're not so interested
in this, And I was like, oh, I'm interested. And
then I realized that he didn't mean me exactly. He
could tell I was interested because I was one of
the old people, and he was talking about other people. Anyway.

Speaker 2 (09:49):
Did I ever tell you about the time I was
accidentally c seed on an email where they were looking
for a young ish professor to take on some roll
and somebody said whites and is he youngish anymore? I'm
not sure?

Speaker 1 (10:00):
And I was like, oh, nice. Oh I thought I
just had a little gray in my hair. And someone
told me I was rocking the salt and pepper look,
which was very nice. But that was the first time
I realized that I had transitioned to salt and pepper. Anyway,
you and I are aging, but hopefully we don't have
this mutation.

Speaker 2 (10:15):
All right, So this mutation just means that you produce
a protein through the normal mechanism of like DNA RNA protein,
But it's one of these bad proteins. Yes, you said
that it doesn't fold the way it's supposed to. Is
it that it doesn't fold the way the DNA tells
it to, or that it folds in a way that's damaging.

Speaker 1 (10:31):
It folds in a way that's damaging if you have
this mutation. Mutations often result in changes in an amino
acid in the sequence that makes up a protein, and
when you have a change in that amino acid, it
can change the shape of the protein. So the protein
might be doing what the genetic code told it to do,
but now it's folding up in a configuration that's bad

(10:52):
for you and can go and cause other proteins to
do it too.

Speaker 2 (10:55):
All right, So you can either get through from outside
the body or you can just have your genetic code
do these terrible things. Is that it or is there
another thing we have to worry about.

Speaker 1 (11:04):
The third way is what they call spontaneous. So you've
got proteins, and actually, something that I learned while doing
this research is that sometimes your proteins will change shape
and then go back to their normal shape. Wow, while
they're in your body, and it doesn't seem efficient, just
like be consistent, man, But so I guess sometimes they
will sort of get out of their configuration and when

(11:26):
they go back into their configuration, they don't go back correctly,
and so now they've got this bad shape. And once
you've got either the heritable or the spontaneous version of
these prions, they start to act infectious. So they go
around and they make other prions abnormally shaped as well.

Speaker 2 (11:44):
Weird. That's incredible that one protein can turn another protein bad.
It's like the bad influence protein.

Speaker 1 (11:50):
This spontaneous prion thing. This is like stay up at
night worrying about what all your proteins are doing. I'm
not worrying about my kids anymore. I'm worried about whether
or not my proteins are behaving. But I'm sure it's fine.

Speaker 2 (12:02):
This is a whole fascinating area though. Protein folding. We
describe it as if it's like DNA RNA protein, but
it's very complicated.

Speaker 4 (12:09):
Right.

Speaker 2 (12:09):
You build this sequence of amino acids and when they fold,
they're like settling into a lower energy state. They're like
relaxing into it. And it's really hard to know what
that state is. You can look at the DNA code.
It's not easy to predict the configurations of proteins that
come out of that sequence. There was a huge result
recently alpha fold where people were able to predict these
things very well using AI. Really an incredible breakthrough. People

(12:32):
have been working on that for decades.

Speaker 1 (12:34):
Yeah, that is fantastic. Let's go into one real example.
Fritz Feld Jacob disease. So sorry about my pronunciation, apologize
ahead of time.

Speaker 2 (12:46):
I'm not even going to correct you because I enjoy
listening to your mispronunciations.

Speaker 1 (12:49):
Okay, do you know how to pronounce it correctly?

Speaker 2 (12:52):
I'm pretty sure it's quartz failed yakup disease, but I
like the way you said it.

Speaker 1 (12:55):
Oh okay, well thanks, I appreciate that.

Speaker 2 (12:57):
Especially like the way you like tiptoe through it in
a terrified.

Speaker 1 (13:02):
But from now on, it's CJD.

Speaker 2 (13:03):
Okay.

Speaker 1 (13:04):
So for CJD, what happens is that in older people
sometimes you sporadically get a protein that folds up incorrectly.
Now you've got this abnormal form. And I read a
bunch of papers that suggested that as various vertebrates age,
our proteins are sort of more likely to fold the
wrong way because aging is a real pain in the
rear end. And then in ten to fifteen percent of

(13:25):
the cases, this has to do with a genetic mutation
that's giving the protein essentially bad instructions, and every once
in a while, in a rare case, you can get
it transmitted. So, for example, if you get a cornea
transplant from somebody who has CJD, then you can get CJD.
So it's important to screen for this kind of stuff,
and so unfortunately, once you get it, we don't have

(13:46):
any treatment, and usually the symptoms get worse quite quickly
by the time the symptoms are identifiable, and according to
the CDC website, it causes a person's brain to break
down or stop working normally, which I'm sure we can
all is not a way we would like our brains
to be described.

Speaker 2 (14:02):
No, I do not want my brain to turn into
a smoothie.

Speaker 1 (14:04):
No, no me either. I think most people initially started
hearing about prions when they learned about bovine sponge of
worn and cephalopathy BS bad cow disease, and this showed
up in cows. Turns out cows were getting it from
one another because we were feeding cows cow parts. And yeah,
bad idea.

Speaker 2 (14:24):
Cannible cows annible cows, right.

Speaker 1 (14:26):
And you might remember from when we were feeding pigs
pig parts that that was bad for the transmission of
trick and ella. So in general, it seems like it's
a bad idea to feed animals animal parts, although I
do feed my chickens chickens sometimes. Oh I know, maybe
I'm asking for it.

Speaker 2 (14:41):
That's horrible. Yeah, there's something really creepy about that. I
don't know why I like chickens eating pork whatever, chickens
eating chickensoh.

Speaker 1 (14:49):
They don't seem to mind. They love the nuggies. They
love the chicken nuggies. All right?

Speaker 2 (14:55):
What kind of sauces do they like to like? The
dip it? Are they into the barbecue?

Speaker 1 (14:59):
No, they don't. We have the dexterity for that. I
don't know. If you've seen chicken claws, they're not real good.
They can scratch and that's about it.

Speaker 2 (15:05):
All right. So we know that getting these preons is bad.
You get these terrible diseases and they spread from body
to body, and even if you eat like meat that's
been cooked. We're used to like cooking something to kill it.
But if you cook a preon, is it then better?
Is it like denatured or can you still get it
from cooked meat? You know?

Speaker 1 (15:22):
As far as I can tell. One of the things
about these preons that is incredible is that they're really
resistant to things like cooking, and so you can cook
your burger and if it had bs, there's still some
chance that you could get it.

Speaker 2 (15:36):
I heard that even if you irradiate these things, like
zap them with radiation, they're super dup or robust, which
is one reason that they're able to spread from one
to the other. And so it's like really hard to
kill a preon. Like when they do brain surgery in hospitals,
they just throw away everything that touched the brain because
it might have a preon in it, and you do
not want that stuff to spread.

Speaker 1 (15:55):
We are so stink and lucky that preon diseases are
not more common. Thank your lucky stars everybody.

Speaker 2 (16:02):
So then let's get to the heart of the listener's question,
right he's asking about the fundamental mechanism, like how does
this happen? You were talking about one preon turning ou
a normal protein into another preon. Do we know how
that happens?

Speaker 1 (16:14):
If by we you mean Katrina, the answer is yes.
Let me quickly summarize the three problems that you need
to understand to understand prions. So, one, an abnormal protein
is made. This is pretty much what we've been talking about,
the various ways that you start getting these abnormal proteins.
Problem too, is that the prion starts causing more prion
proteins to be made, so it interacts with the healthy

(16:36):
proteins in the area and starts turning them into bad proteins.
And then problem three is that these proteins start clumping together,
and it's these clumps that start causing problems. So the
brain has trouble clearing these clumps out. So the listener
wanted to know the details for problem too. How does
one prion cause another protein to start misfolding and becoming

(16:57):
another one of these sort of infectious prions. And I
was so annoyed because I found so many papers, and
every paper was like, Okay, here's how we're gonna illustrate
how it works. And they were like, the normal protein
is a circle and the abnormal protein is a square,
and the circle becomes a square, and then the square
interacts with other circles and turns them into squares. And
I was like, that doesn't really explain what's happening.

Speaker 2 (17:20):
That's just a cartoon.

Speaker 1 (17:21):
It's just a cartoon. How does the circle turn the
squares in? Anyway? Eventually I threw my hands up and
we were so happy that we know a biochemist. And
so Daniel, go ahead and introduce your amazing wife.

Speaker 2 (17:36):
That's right, Katrina actually has a PhD in biochemistry protein
folding DNA all this kind of interaction. She did her
PhD on like how proteins cut DNA and interact with it.
So she like has her head around all of this stuff.
So I asked her, Hey, can you explain to us
how this actually happens? How two proteins come together and
both end up bad? Like why don't they both end

(17:56):
up good? You know, all these arguments are like template this,
template that, Like why did they both end up bad?
So I asked her on the cash last night, and
here's what she had to say. Hey, Katrina, so how
does a prion turn another protein into a preon?

Speaker 5 (18:10):
So proteins are just these chains of amino acids, and
each block has different likeness for water, like some of
them like to be near water, some of them hate water.
The balance of those things forces the protein into a
certain shape, so each protein makes a really unique shape. However,

(18:31):
some proteins have more than one stable state, so they
might be happy in a slightly different shape. And what
preons do is they force the protein into an alternative shape.

Speaker 2 (18:44):
I think that's the bit we want to dig into.
When two proteins come near each other, why does the
preon force the good one into a preon shape rather
than the good one, forcing the preon into a good shape,
why does the preon win?

Speaker 5 (18:57):
And that shape is usually one that's a little hard
to get itself out of, so they get stuck in
that direction. So basically, if a protein forms the preon shape,
which it usually does at a lower rate than the
healthy correct shape, but if that happens, then when another
healthy protein gets near it, it gets peer pressured essentially

(19:18):
into forming that alternative but like disastrous and like disease
forming alternative shape. This happens for certain sequences of proteins,
and they often have repeat zones in them that are
like making it easier for them to collapse into this

(19:40):
unhealthy state. And so I can think of a couple
cases of proteins that misfold where it's driven by having
these like repeat zones. So that would mean that when
the healthy protein touches the preon protein, imagine a lego
clicking into a lego, it like clicks it together and
forces it into this unhealth the alternative but stable state.

(20:03):
All of the proteins are not like one hundred percent
folded all the time. They're kind of like wiggling around
a bit, and it makes it so they can kind
of like explore which shape they're going to sit at,
and the preon shape is harder to get out of.
Once you get collapsed into that preon state, you're like
a goopy mess.

Speaker 2 (20:20):
So the two come together, but the good protein is
still flexible about its actual shape, while the preon is
stuck into this deep local minimum. It's very stable configuration.

Speaker 5 (20:30):
Yes exactly, And so if you get stuck in that
deep local minimum, it's harder to get back out of it,
and if another protein gets nearby, it gets tempted into
that goopy minimum. And molecularly, what I mean is that
a region of the misfolded of the bad shape that
the preon is forming will have mirrored sites, like it'll

(20:53):
have interactions with the other healthy protein that will force
it into that shape, and then it stays there because
it's a local minimum that's hard to get out of.

Speaker 2 (21:05):
I see. So it's true that when the two proteins
sort of try to fit together, they're more likely to
end up similar. But the bad one, the preon one,
is harder to pull out of than the normal one
is to pull into the bad state, and so they
both end up in the bad state.

Speaker 5 (21:21):
That's my understanding.

Speaker 2 (21:23):
So my takeaway from this is that it relates to
the conversation we were having earlier about how proteins fold. But
it's not easy to predict, like how a protein is
going to fold, and it turns out sometimes they can
fold in multiple different ways. And the preons are special
and weird because they're like a very strong fold, like
it's hard to get them back out of that. For
people who like to think about optimization and minimum it's
like a very deep local minima. They're stuck in it

(21:45):
and it's extraordinarily hard to get them out, which is
why cooking or radiation will not bust these guys. And
if you have a preon meets a non preon, then
it's much more likely they both end up as preons
because it's harder to get the preon out of the
preon configuration than it is to the normal protein out
of its normal configuration.

Speaker 1 (22:02):
Yeah, and to build on that a little, often, when
your body ends up with a protein that's shaped the
wrong way, you send in what are called proteases, and
they essentially break the protein into pieces that are easier
to clean up and remove from the body. But these
proteases can't get into these clumps or into these abnormally
folded proteins, and so rather than getting cleared out, they

(22:23):
remain and they start clumping and they cause problems.

Speaker 2 (22:26):
Amazing. Biology is incredible. What boggles my mind is all
this stuff is happening all the time, and it mostly
just works. I go about my day, I drink coffee,
I think about particles, and inside all these little proteins
and these molecular machines are doing their thing. Thank you,
little biology particles.

Speaker 1 (22:42):
When you work great, We thank you. But understanding how
proteins get abnormal and start clumping up is important, we
think for understanding neurodegenerative diseases because sort of similar things
happen where proteins start accumulating and clumping and causing problems.
So you've got amyloid beta in TAO for Alzheimer's disease,
alphas and nucleon for Parkinson's disease, and huntington for Huntington's disease.

(23:06):
So sort of understanding what's happening here is a very
active research field.

Speaker 2 (23:10):
All right, well, thank you for sending this question. In
NIL it turns out to be a perfect union of
our interests because not only is it biology and does
it have the word particle involvement it. We also had
to bring in Katrina sob.

Speaker 1 (23:21):
Bum and the whole whitesn Research Institute with the adjunct
faculty included.

Speaker 2 (23:28):
That's right, Well, let's hear from Nile if we answered
his question or just confused him further.

Speaker 3 (23:34):
Hi, Kelly and Daniel, thank you for this response. You
definitely answered my question. I think the most surprising revelation
for me is that the reason prions are infectious has
more to do with chemistry and the molecular structure of
proteins rather than some other sort of active biological process.

(23:54):
It was a really interesting discussion and super enlightening, although
I do have to agree with Kelly that now knowing
there's such a thing as spontaneous prem formation, this will
keep me up at night. Thank you again.

Speaker 2 (24:25):
Okay, we're back and we are answering questions today from
listeners who think deeply about the nature of space and
time and whether their brain is infected by the meat
they eat. So now we have a question from Owen
and his daughter about concerts near black holes.

Speaker 6 (24:41):
Hi, Daniel and Kelly, I was curious my daughter plays violin,
and if.

Speaker 3 (24:47):
She were to take a trip to a really deep.

Speaker 6 (24:49):
Gravitational well like close to a black hole or a
neutron star, and recorded herself playing violin and then brought
the recording back with the time dilation cause a key change,
would it make the frequency higher or lower? Or when
we played it back here on Earth would it be
the same.

Speaker 1 (25:06):
Wow, that is a fantastic question. All right, let's start
by talking about what is time dilation?

Speaker 2 (25:14):
Yeah, time dilation one of my favorite topics and very
confusing aspects of special relativity. And one thing that's really
important to understand about it is that there are two
types of time dilation that work differently. It's important to
keep them separate, especially for this question. One is the
one we hear about a lot when you're like in
a rocket ship moving fast. And this is velocity based

(25:35):
time dilation, which you can summarize very easily just by
saying moving clocks run slow. So if Kelly has a
clock in her ship and she's moving very fast relative
to me, I see her clock moving, so I see
her clock going slow. Kelly doesn't see her clock moving,
it's right in front of her. She sees it running
at the normal time, and that's the right time. I mean,

(25:56):
it's east coast time, which is whatever I prefer, best
coast time.

Speaker 1 (25:59):
I think a world runs up East coast time, my friends.
But all right, moving on.

Speaker 2 (26:03):
That might be true, Yeah, that might be true. High
But the cool thing about this kind of time dilation
is that it's symmetrical. Right. I see Kelly's clock is
running slow because I see her moving quickly, but she
sees my clock moving, which means she sees my clock
running slowly. So we both see the other person's clock
is running slower than ours. So it's symmetric, which is beautiful,

(26:24):
but it also feels contradictory because you have this instinct
to say, hold on a second, whose clock is really
running slower? Right? Because our accounts are discrepant, And the
answer is there's no single true answer. There is no authority,
there's no single clock in the universe. Both of our
accounts are correct, and you can't actually link it together
into a complete understanding. It's just that everybody sees things

(26:44):
differently from different perspectives.

Speaker 1 (26:46):
Okay, all right, so now we've got our minds wrapped
around velocity based time dilation. What is the other kind.

Speaker 2 (26:53):
The other kind is gravity. You don't have to be
moving fast to have your clock run slow. You just
have to be near a massive object like the movie
Interstellar where they land on Miller's planet, which is super
duper massive. When you're in space that's curved, time runs slower. So,
for example, if you're standing on the surface of the Earth,
your clock will run slower than a clock that's in
orbit or run the Earth, or out in deep space

(27:15):
where there's less curvature. You're further from masses, so your
clocks run faster.

Speaker 1 (27:20):
So your clock would run much slower on Jupiter relative
to Earth.

Speaker 2 (27:23):
Yes, exactly, And it would run much slower on the
surface of the Sun, and much much slower near the
event horizon of a black hole. And the amazing thing
about this one is that it's not symmetric. Everybody can
agree on it. Like if I'm in orbit with the
clock and Kelly's on the surface of the Earth or
the clock, we will both agree that her clock is
running slower. I see her clock running slower, she sees

(27:44):
my clock running faster. This is the only time in
relativity when you can see something speed up. Mostly you're
just seeing time slow down, But with gravitational time dilation,
you can see things speeding up. So if you stand
near the edge of a black hole, for example, you
see the time in the to the universe go faster,
and like fast forwards you to the future.

Speaker 1 (28:03):
So if you could live near a black hole, could
you live forever? Is this what biologists have been looking for?

Speaker 2 (28:09):
Your time would still run normally, right, so you would
still live eighty years or whatever in your time that
might last eighty thousand years or eighty million years in
the outside universe. So it's a way, definitely to fast
forward to the future, but not to live infinitely long.

Speaker 1 (28:22):
Physics keeps disappointing.

Speaker 2 (28:24):
Sorry on, Okay, So those are the two kinds of
time dilation that we need to understand to answer Owen's
question about a daughter with a violin. But this one
more piece we need, which is red shifting. Right. All
this changing of time has consequences, like it changes how
long things seem to be, because it affects when people
measure the front and the back. And we can dig

(28:45):
into the details of length contraction another time. But if
you change the way clocks run, you also change the
frequency of waves. Right, the wave length of a wave. So,
for example, if light is admitted to you by an
object that's moving away really really fast, it lengthens the
wavelength of that light. It red shifts it. So things

(29:06):
that are moving away from you get red shifted, things
that are near black holes get red shifted. One way
to think about it is that it's just all about
time dilation. Clocks are slowed down and so the waves
get slower and redder. If you'll watch a spaceship approach
a black hole, it's not going to look normal to you.
It's going to get redder and redder and redder, and
then eventually become invisible.

Speaker 1 (29:26):
We're near a black hole, so we're talking about gravity dilation,
and we are thinking about waves because sound is a wave,
and we've just established that waves get spread out near
a black hole because of the gravity dilation. Okay, I'm
on the same page.

Speaker 2 (29:43):
Let's get to Owen's question, but there's a few versions here.
Imagine that Owen is far away from the black hole
and his daughter is near the black hole, and she's
playing the violin and he's watching and he's listening. So
what's going to happen, Well, her time is going to
be slowed down for him. So he's going to see
her or moving and thinking and drinking and breathing in
slow motion, and the light and sound that come from

(30:06):
her will have longer wavelengths. So he will watch a
video and he will see her moving in slow motion,
and all the light will be redder than it normally is.
If it's really dilated, it'll be invisible. It won't be
in the visible spectrum anymore, and it'll happen slower, so
the key will be lower and be like in the
old days when your tape deck is running out of
battery and everything zones low.

Speaker 1 (30:28):
You said, key is key the same thing as frequency.
These music words go past me.

Speaker 2 (30:33):
Ooh, I'm so not an expert in that. But the
wavelength will get longer and the frequency will go down,
which I think means a lower key.

Speaker 1 (30:40):
Okay, that's how I imagine whale sound.

Speaker 2 (30:45):
But he's not asking about that scenario. He's asking about
what happens if a recording is made near the black hole. Right,
So now let's do another scenario. Let's say Owen is
next to the black hole, also with his daughter. Right,
she's next to the black hole. She's playing the violin
he's there right next to her, what does he see?
Everything looks normal to him because she experiences it normally
and he's there with her. So yes, somebody far away

(31:08):
will see them both in slow motion, but from their perspective,
everything is happening normally. The outside universe is fast forwarding.
So if he's there with her, everything seems normal.

Speaker 1 (31:18):
Okay, But what if they're recording it?

Speaker 2 (31:21):
Yeah? Right? I love these versions of the questions. So
if instead of Owen, you have Owen's video camera and
it's there with her, and it takes a video of
what's happening near the black hole, it's going to record
what Owen would have seen, which is a normally occurring
violin performance. Right, You then take the video somewhere else.
The video hasn't changed. You play it back on your

(31:41):
TV at home. You're going to just play back a
normal recording, and so everything is going to look normal
on the video because it was taken near the black hole,
where everything seems normal to the people near the black hole.

Speaker 1 (31:52):
Now, are you sure that's right? Because that sort of
matches my intuition, which usually means it's wrong. So because
I'm really good at this, But all right, I'll go
with it.

Speaker 2 (32:01):
There are other weirder versions of this question, you know,
that depend on exactly how the information is encoded. Like
we're talking about literally sending waves from the black hole
and interpreting them literally. If instead you have computers and
they're coming this in binary, then they can avoid the
time dilation effects. There's some subtle wrinkles there if you've
word the question differently, But the way he asked it,

(32:23):
the answer is that the concert would appear normal if
it was filmed near the performers.

Speaker 1 (32:28):
Okay, well, let's go ahead and see what Owen thinks
of this answer and if there's any follow up questions.

Speaker 3 (32:33):
Wow, thanks for answering my question. You guys, you know
I think you nailed it.

Speaker 2 (32:38):
Thank you so much.

Speaker 1 (32:55):
All Right, so we wrapped up a question that was
beautiful playing music in deep space near a black hole,
and now we are descending into the depths of biology
to discuss magots. All right, what does Jonathan want to
know about maggots?

Speaker 4 (33:13):
Hi, Kelly, I remember reading about medical maggots five or
ten years ago. As I recall, it was an experimental
procedure back then, but showed real promise in the fight
against drug resistant bacteria? Where are we today on this
Can I stop worrying about superbugs now? Thanks?

Speaker 2 (33:28):
I thought we had already reached maximum grossness on this episode.
I didn't realize we were just in the foothills of
grossness and now we're climbing to the peak.

Speaker 1 (33:35):
Oh, Daniel, we have just begun.

Speaker 2 (33:41):
All right, take us there, Kelly. What do we need
to know about medical maggots?

Speaker 1 (33:45):
All right? So, apparently for centuries, folks have realized that
if you find maggots in someone's wounds, those people with
maggots in their wounds tend to have faster healing wounds
than people who don't have maggots in their wounds. So
you might be thinking it would be better to not
have maggots in my wounds, But if you want your

(34:05):
wound to heal quickly, apparently it would be good to
have it. And this bit of disgusting wisdom was known
by Genghis Khan, the Mayans, and other indigenous peoples, according
to videos I watched on YouTube from reputable sources like
the BBC.

Speaker 2 (34:21):
You know, I think that's incredible because I think it's
often included as like things we did before we really
understood science, you know, leeches and maggots and drilling holes
in people's heads and praying to the gods and whatever.
But actually this is another example of sort of pre
modern science experimental understanding. Right, you're saying, people like looked
at the data and they're like, maggots are gross, but

(34:42):
they do seem to help people. Maybe we should use maggots.
I mean, isn't that scientific. Isn't that hypothesis forming and
drawing conclusions from data.

Speaker 1 (34:49):
Well, so my understanding is that for a long time
folks noticed that there seems to be this association, but
they might not have had control over, for example, the
fly life cycle to be ab to purposefully infect people
with maggots. The first documented instance of someone purposefully placing
maggots in someone's wound was in the American Civil War.

(35:10):
And you know, can you imagine being the first person
where someone's like, no, really, these maggots are gonna do
you wonders.

Speaker 2 (35:17):
But and this is gonna be great for a biology
podcast in a couple hundred years.

Speaker 1 (35:20):
Trust us, that's right. It'll all be worth it when
Kelly and Danie'll get to gross out over there.

Speaker 2 (35:26):
Here's the big payoff, all right, that's right.

Speaker 1 (35:28):
And then an orthopedic surgeon in World War One named
William Behar started applying maggots to wounds that wouldn't heal
at Johns Hopkins University for a patient community of children. Wow,
And from that, medical maggots kind of took off. In
the nineteen thirties, you get medical maggots that are very
common in America, Canada, Europe. Hospitals open in sectories so

(35:52):
that they can have medical maggots on hand whenever you
need them, and you can order them from a company
called Surgical Maggots out of Pearl River, New York.

Speaker 2 (36:01):
And so other than looking gross and being gross, what
are these maggots doing in these wounds?

Speaker 1 (36:07):
So the first thing they're doing that's helpful is what's
called debridement. So essentially they are removing the dead and
dying tissue in the wound. So they are secreting and
excreting stuff that starts breaking down the dead tissue and
it makes it into sort of like a slurry. And
then the maggots suck up that slurry.

Speaker 2 (36:27):
Yeah, yam, yum yum yum, yeh yum yum. Yes, I'm
trying to get into this I'm like, let's go the
non gross route. Let's just like really marinate in the biology.

Speaker 1 (36:36):
Ganny. You No, I love the attitude and I appreciate
the energy and the motivation you bring to these discussions.
You're really trying and I like that.

Speaker 2 (36:43):
Yeah, I'm like, let's get a nice big ice cube.
We'll have like a you know, a slurry cocktail. This
sounds fantastic. You can get into anything, So start.

Speaker 1 (36:51):
Having themed drinks for some of these episodes, or themed
meals like pasta for the parasite episodes. All Right, the
stuff that if they release that starts breaking down the
dead tissue tends to leave the living tissue alone. And
so if you have a wound that's got a combination
of dead and living tissue and you'd like to remove
the dead stuff so you can specifically start working with

(37:12):
helping the living stuff to recover. These are pretty helpful.
They do it in sort of surgically precise ways, it seem,
so that's benefit one. Benefit two is that some of
the stuff that they're excreting and secreting has antimicrobial properties,
so it's killing some of the bacteria that could be
infecting the wounds. And while they're slurping that stuff up.

(37:33):
They're also consuming the bacteria that could be infecting a wound,
and you have like a thousand yard stare right now.

Speaker 2 (37:41):
I'm just wondering, like why maggots would do this, Like
I mostly see maggots in garbage or whatever. That they
didn't evolve in garbage, right, They must have evolved like
eating feces and rotting carcasses and stuff. Is that why
they're good at this? Because they evolved basically eating dead
flesh or near dead flesh.

Speaker 1 (37:59):
So the horror truth is that there's lots of flies
in this world, and they have lots of different life cycles,
and so the carrion flies, what happens is that the
mom comes along and she lays her eggs in dead tissue,
and those eggs hatch and you get maggots that have
to go through a couple different life cycles. And those

(38:19):
maggots are competing with the bacteria who want to break
down the dead stuff, and in some cases those bacteria
release toxins that might not be good for the maggots.
And so being able to consume the bacteria is good
because you're accidentally going to consume some of them anyway,
but also killing some of them remove some of the
competitors in your food.

Speaker 2 (38:39):
So this is exactly what they evolved to do, right
to I'll compete the bacteria and to eat all the
dead stuff. Why don't they also eat the living flesh? Like,
why do they leave that alone? That's awfully convenient.

Speaker 1 (38:49):
I'm going to preface this with I'm spitballing because you
asked me lots of great questions. I don't necessarily always
know the answers too, So my first guess is that
mostly what these guys are doing is the moms are
laying their eggs on stuff that is like totally dead,
totally dead, and every once in a while they opportunistically
find an open wound with some dead skin and they

(39:11):
lay their eggs in there too, And so they are
specialists on the dead stuff and are less interested in
the living stuff. There's also a bit of a trade
off I think between being able to infect and break
down living tissue which has like an immune response and
might try to fight back, versus just going after dead
tissue which isn't going to fight back. That's my best guess.

Speaker 2 (39:34):
Yeah, all right, so they're lazy. They don't want to
work hard. They just go for the easy dead stuff,
and that amazingly works perfectly for our use case.

Speaker 1 (39:41):
Right, yeah, and I mean I hate dipterance. So they
go through a couple stages in the dead stuff. They
have a wandering phase where they fall off of the
dead thing and then bury underground, and that's thought to
maybe help them avoid drying out or keep them safe
from predators. So, like you know, crows will go around
and they'll find dead insects in carcasses and eat them up,
so they kind of and then they hatch as adults

(40:01):
and they go off to complete their life cycle. Okay,
so that's all kind of complicated, So you can imagine
that growing flies in a lab could be a little complicated,
especially if you want to make sure that when you
grow those flies they're grown under sterile conditions. So you
don't want flies walking around on some dead, infected roadkill

(40:23):
and then getting added to your wound because that would
be pretty gross. So while this was popular in the
nineteen thirties, it was difficult to you know, cheaply provide
maggots for wound debreadment and to find ways to contain them.
So you definitely don't want your leg maggots or your
foot wound maggots to escape. And then now they're like

(40:46):
free in the hospital and they can like go and
spread whatever diseases you had on your foot to somebody else.
And it's also gross to have flies around, so it
was kind of a pain. It was expensive because.

Speaker 2 (40:56):
The magots literally sprout wings and try to fly around.
That's what they do. They'd call them flies, right, So that's.

Speaker 1 (41:02):
Yeah, that's right, that's right. They're going through their insect stages.
They transform it or metamorphose into adults. And yeah, then
they go when they fly around and they're super gross.

Speaker 2 (41:10):
Does that mean that if you have a wound with
maggots on it, there's some like container that captures the flies.
Then you have like dead flies on your wound you
have to clean off all the time.

Speaker 1 (41:18):
We're going to get there. I was looking on the
website of companies who grow medical maggots. But I'm almost there.
I'm almost there, I promise. So in the nineteen forties,
antibiotics become widespread, and you know, quite frankly, if I
had the choice between someone sprinkling maggots on my legs
or giving me you know penicillin medication I can pop

(41:39):
in my mouth. I'm going to go for the penicillin.

Speaker 2 (41:41):
But is that just because of the size. Like you
can see maggots and they seem gross because penicilla is
like a fungus and it's like also growing and attacking
the bacteria. If the fungus was like bigger, if you
had like mushrooms growing out of your wound, would that
be as gross as maggots.

Speaker 1 (41:54):
Well, they're not like spreading fungus like you spread butter
on a piece of bread, like onto your leg.

Speaker 2 (42:02):
I'm thinking of marmite now, I'm like, mmm yum.

Speaker 5 (42:05):
Yeah.

Speaker 1 (42:06):
Sometimes it's like a pill that you take WHIRLI or
you know, maybe it could be like a cream or something.
But you know, the maggots they escape sometimes you can
feel them moving around, and you know, I get that
it's gross.

Speaker 2 (42:18):
We should have a whole episode on the biology of grossness,
like why do we think some things are gross and
other things? Where does that come from? Anyway back to maggots.

Speaker 1 (42:26):
So that would involve a lot of evolutionary psychology. I
think I'm totally down for tackling that. But so in
the nineteen forties, antibiotics come along, that solves a bunch
of the problems. Maggots fall out of favor because they
were kind of a pain in the rear. End. In
the nineteen eighties nineteen nineties, antibiotic resistance starts becoming a
big problem. People have non healing wounds and it's starting
to get harder and harder to kill the bacterial infections

(42:47):
that are in those wounds. So medical maggots come back
in style, and in two thousand and four, the Food
and Drug Administration in the United States actually approves maggots
as a medical device to treat things like diabetic foot
ulcers that won't heal. And there's also some evidence that
for some sort of limb issues, maggots can help with

(43:07):
debridement and help with antimicrobial stuff, and in some cases
people can keep their limbs because of what a great
job the maggots did.

Speaker 2 (43:15):
So people are still using maggots today.

Speaker 1 (43:16):
Yeah, no, So maggots are making a comeback.

Speaker 2 (43:18):
Amazing.

Speaker 1 (43:19):
They're not incredibly widely used, and based on the surveys
that I read, that is mostly from what everybody calls
the quote yuck factor end quote, And I totally get that.
Apparently like, sometimes you can feel them moving around a little,
but mostly what they're doing is moving around in dead tissues,
so you don't usually feel it a lot. But here's

(43:39):
what happens. They sprinkle some little maggots they're like a
couple millimeters long in the wound, and then they have
really fancy bandages that cover up the wound and keep
the maggots in the wound and don't let them get out.
There's a company called Monarch Labs, for example, that sells

(44:00):
the Maggot Megapack, maggot t shirts and the le Flap
du jore case dressing.

Speaker 2 (44:08):
So.

Speaker 1 (44:11):
It contains the maggots while still letting the maggots breathe.
And what happens is the maggots spend a couple days
in their larval form going around eating dead tissue, and
then when they get to the stage where they would
usually fall off and try to bury themselves in the soil,
you remove the dressing, you collect all of the maggots,
and then you just take them away. And the maggots

(44:32):
have cleaned off the dead tissue, they have fought some
of the bacterial infections, and there's fairly good evidence that
actually outcomes are pretty good. Here's where some of the
nuances of biology come in, because the answer is never clear.
Some studies do find that the maggots do less well
against particular species of bacteria. Sometimes the results are contradictory

(44:56):
between studies, suggesting that you don't always get consistent results
for obvious reasons. Pharmaceutical companies are trying to figure out
if you can not have the maggots but still have
the antimicrobial properties. So they're trying to understand what kind
of compounds the maggots are secreting and excreting. And there
is a drug called seratusin which was it sounds like

(45:19):
derived from maggot secretions excretions, and it inhibits twelve strains
of MRSA, which is that multi antibiotic resistance Staphylococcus aureus.
Was that right?

Speaker 2 (45:31):
Sounds right?

Speaker 1 (45:32):
Yeah? Nice?

Speaker 2 (45:33):
Is there some tech bro out there making like tiny
robotic maggots that like walk around and eat dead flesh
and ooze out this.

Speaker 1 (45:39):
Medicine maybe eventually, who knows what the future holds mag bots.

Speaker 2 (45:44):
That's a billion dollar idea right there.

Speaker 1 (45:46):
Somebody call me, yeah, well you should patent it while
you're ahead. So there's other kinds of compounds that have
been secreted that help with different kinds of bacteria. So
folks are working on this, and there have been some
studies on wounds in children that we're having difficulties sort
of healing up, and they had multi drug resistant pseudomonous
originosa in them, and they had been treated with things

(46:09):
like antibiotics, but the bacteria were resistant, and they treated
the kids with maggots, and the maggots really did seem
to help. They still did some other follow up treatments,
but the maggots seemed to be like the thing that
helps these diseases turn the corner, and after thirty four days,
these infections no longer had bacteria.

Speaker 2 (46:25):
Bo. Yeah, amazing, good job maggots.

Speaker 1 (46:27):
Yeah. But so our listener wanted to know if they
can stop worrying about superbugs because we're all going to
be using maggots. There's a couple problems with that. So,
first of all, maggots tend to be used for a
pretty narrow range of problems. So diabetic foot ulcers, pressure
ulcers basically wounds on the exterior of your body that

(46:47):
are having trouble healing, and we have problems with antibiotic
resistant bacteria insider a body two And you know, drinking
a slurry of maggots isn't going to help us with that.

Speaker 2 (46:57):
And it's super weird to have maggots like eating a
wound on the outside of your body. I can't imagine
having maggots that crawl around inside you.

Speaker 1 (47:03):
I don't think they'd survive for very long, but you'd
feel them wiggling to their death and it would be unpleasant.

Speaker 2 (47:08):
Yeah.

Speaker 1 (47:08):
I also imagine that if we started using maggots to
the same extent that we use some of our current antibiotics,
it wouldn't surprise me if resistance arose to whatever the
maggots were producing as well. And so I don't think
this is a panacea, but it is a solution that
seems to be working pretty well for certain types of
non healing wounds.

Speaker 2 (47:27):
Amazing. It's incredible how many times evolution has found the
answer to a problem that we have. You know, it's
just like, give it a billion years and so many mutations,
they will explore the whole landscape and find an incredible solution.

Speaker 1 (47:41):
Yes, this field is called Darwinian medicine. I believe where
you go to nature for some answers. I found a
doctor named doctor Ronald Sherman, and I loved reading his
papers because he was so excited about the maggots. So
I want to wrap this up on a quote from
the conclusion of one of his two thousand and nine papers.
He said, medicinal maggots are as precise in their debreedment

(48:04):
as a highly skilled microsurgeon, as attentive to their host
wounds as the most dedicated wounds care nurse. It is
no wonder that they have found their way into the
hearts and wounds of so many.

Speaker 2 (48:19):
So hearts and wounds is the title of his autobiography.

Speaker 1 (48:23):
Yes, thank you for your enthusiasm, doctor Sherman, and let's
go ahead and reconnect with Jonathan and see if we've
answered his questions.

Speaker 4 (48:31):
Yes, indeed, you have answered my questions. Thank you. It
looks like what was old is new once again.

Speaker 2 (48:36):
All right, thank you very much everybody for sending in
your questions. We'd love to hear your questions on the pod.
Please don't be shy. Send them to us to questions
at Danielankelly dot org.

Speaker 1 (48:45):
Can't wait to hear from you. Daniel and Kelly's extraordinary
Universe is produced by Iheartreading. We would love to hear
from you.

Speaker 2 (49:00):
Really would. We want to know what questions you have
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Speaker 1 (49:05):
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