0:01

My name's Marsha.

0:03

I lived in the UK, as you can tell

0:05

by my accent, and

0:08

I pad super cell for the longest

0:11

time I can remember.

0:15

My parents found out when I was about

0:18

six years old. My mom

0:21

knew she had the trade, but

0:23

my dad didn't know that he carried

0:26

the trade. And obviously my older sister

0:28

was born and she just

0:31

had a trade. So it was my mom was

0:33

like, okay, fine, and she got that from me. But

0:36

when I came about, I was

0:38

born with another sort of illness

0:41

on top of sickle cell, which is called the six

0:43

deficiency, so it kind

0:45

of mossed the

0:47

sickle cell. So over the many

0:50

years growing up, I was like becoming sick.

0:52

They couldn't quite work out. And

0:55

then it was when my younger.

0:56

Sister was born they said, you know, let's be tested

0:58

for sickle cell, and that's when they found

1:01

out that I had

1:03

the full blown disease. I

1:06

kind of understood I

1:09

had an illness much

1:11

later on.

1:12

I would say, when I was about

1:15

nine eight or nine.

1:17

Yes, I went to hospital appointments prior

1:19

to that, but it just didn't really sunking.

1:21

I kind of let my parents deal

1:24

with it all, like, okay, well you.

1:25

Manage my health.

1:27

I managed being a child and playing with my

1:29

friends and stuff like that.

1:30

I didn't really understand it too,

1:33

I think as I went later

1:35

on in my teenage years, when I went started going

1:37

to secondary school, that's when

1:40

I started taking more control over

1:43

my illness and saying, Okay, well, you

1:45

know, I have to eat right, I have to dress

1:47

right, I have to make sure I get enough

1:50

rest, and you know,

1:52

not overstress myself because I know

1:54

if I don't, these things can trigger

1:56

off a crisis and I can

1:59

be left out of school for like weeks

2:01

on end. And it was only when

2:04

I'm joined to sort of like be

2:06

positive choir that I actually

2:09

came out and a lot of my school

2:11

friends, I was like, do.

2:12

You know what?

2:13

I did not know?

2:14

You heard sicker celt I didn't know

2:16

how to explain it to them in a way, and

2:18

I didn't know how they would receive

2:21

me. I always think, like, you know, if I said

2:23

it, I would lose friends, which

2:25

I remember having a friend who said they didn't

2:27

want to be my friend because they.

2:29

Thought they could catch sickle cell if they

2:31

held.

2:31

My hand, And I was like,

2:34

it doesn't work that way unless you're born with it.

2:37

Does not work that way, So it

2:39

was very.

2:41

I shield myself just

2:43

so I wouldn't have to face that

2:46

negativity, and that hurt.

2:49

Later on my adult years.

2:51

I was like, you know what, if

2:53

you don't like me the way I am, then

2:55

that's fine.

2:56

Somebody else will. There's many people in this

2:58

world that will.

3:00

And I grew that confidence

3:03

and was able to mental

3:05

or talk toever teenager

3:08

girls and boys who were in my situation

3:10

to say, you know, don't let

3:12

super cells stop you from doing what you

3:15

want to do. When I do get in a

3:17

crisis and I'm in pain, the

3:19

best way to describe it it has

3:21

to be like when you get

3:23

a really bad cold and

3:25

you have eggs and pains and

3:28

all of your body hurts on

3:30

it ten times worse skill

3:32

than aches and pains. When you've got a cold and

3:35

you just want it to stop, and I've

3:38

had it's brought me to tears before

3:41

many times, and it's

3:43

brought me to the parts where I'm like, do

3:45

you know what, I don't want to be here on

3:47

this earth because I don't want experience

3:49

to pay.

3:50

Why do I have to go for it? You know?

3:52

Why?

3:53

Was I the unlucky one? And

3:56

I did kind of go.

3:57

For the fase of blaming my parents,

4:00

so to speak, saying, you know, you should have checked each

4:02

other before.

4:03

You had me, why didn't you do this?

4:05

And you know, your

4:07

mind starts thinking

4:10

loads of things of you know, I if

4:13

I wasn't here, would.

4:14

I be in a better place?

4:15

Or if I was born before my

4:17

sister, would I be in a better place?

4:19

And you just think many things.

4:23

Every day you wake up. You don't know if

4:25

it's going to be a good day, if it's

4:27

going to be a bad day. And I

4:29

think that affects your social

4:32

life as well, because you're

4:34

forever counseling on your friends.

4:37

And it's the same with relationships.

4:40

I've like broken up with

4:42

a lot of partners because they don't

4:44

understand the extent of sick of self

4:47

going into hospital that's our last

4:50

result on our mind.

4:52

We tend to not quite

4:54

going into the hospital, but we

4:57

like we want to try and treat it the best we

4:59

can at home. Sometimes we don't

5:01

like the hospitals because of the stigma

5:03

that we get. We get

5:05

looked upon as oh, we're drug

5:08

addicts or you know, we're

5:10

not really in pain, we're just he because

5:12

we need to fix, and it's like I

5:14

would don't want to be in hospital.

5:16

This is the last place I want to be.

5:19

Lucky enough, my family are amazing,

5:22

bless their hearts. I have snapped

5:24

up them many times, but

5:27

it's not the case that I mean to. It's

5:29

just a case of all

5:32

I can feel is this pain, and

5:34

I don't want to feel the pain anymore.

5:36

And I have apologized to them afterwards,

5:38

but now they kind of know my routine.

5:41

Not you know, when I say I'm in a crisis,

5:43

they don't answer silly questions.

5:45

They're just like pay.

5:47

Meds, heatpad or

5:49

hot bath or if it's

5:51

that bad, do you need to go to the hospital. And

5:54

obviously I've got a son who

5:56

is fantastic. I'll

5:59

call him a little Dr Quinn. The

6:01

minute you know, I say mummy's not feeling

6:03

very well.

6:04

He's on it.

6:05

With the pain meds, the hot cups of

6:07

tea, the hot water bottle,

6:10

everything you can think of to make to cheer me

6:12

up. He'll put my favorite movie on and cuddles

6:15

and there with me. So he is literally

6:18

amazing. But because it's just me

6:20

and him that lived together,

6:22

I feel like that sometimes he feels

6:25

his childhood got robbed in. Sometimes

6:27

he feels that he can't be a child because he

6:29

has to look after mummy and also

6:32

be himself, which is I knew was

6:34

quite hard. And I think that was the same

6:37

thing when I knew when I was going to have children.

6:39

You know what impact would

6:42

my health have on him?

6:44

And for me?

6:46

When I felt pregnant.

6:49

After my pregnancy, that's when my

6:51

sickle sell got worse. I had

6:54

a minor stroke. More things were

6:56

happening to my body where I

6:58

felt like it was deteriorating, and

7:00

I feel that that was not

7:03

made or where to me when

7:06

I was thinking about starting

7:08

a family. So I'm now going

7:10

over that hurdle of experience and things

7:12

where I feel that maybe

7:15

I could have been made more aware of

7:18

and given that option of

7:20

what to do. But nevertheless,

7:22

he's still a blessing and I loven't

7:25

pieces and I think

7:27

now that where I

7:30

joined to be positive choir, it's

7:32

a journey that you don't want to

7:34

end. Singing for Britain's

7:37

got talent, singing for

7:40

the Queen, Meghan, Prince

7:42

Harry, Prince William, everyone,

7:44

it was amazing.

7:46

It was like I was living a dream. I had to keep saying

7:48

pinch me. Somebody pinched me? Is that Megan over there?

7:51

No, So it

7:53

was absolutely amazing.

7:54

And the way since we've

7:56

come on that platform it's

7:59

gone.

7:59

Viral, I think it's got more awareness.

8:02

Everybody's starting to get involved and

8:04

starting to be more

8:06

clued up and taking notice

8:08

of what sickle cell is, and you

8:11

know how they can go around

8:13

helping to spread the awareness.

8:16

And I feel that it's.

8:17

A way that brings the community

8:19

together as well, because in the choir

8:22

there are many people who have

8:24

the illness and we share

8:27

our stories. We've got you know, everybody

8:29

experiences sucle cell differently, so

8:31

it's nice and where we've become like

8:34

a big unit and

8:36

we get to share it around

8:38

the world, which is amazing,

8:41

and we have a laugh, we

8:43

have a love and that's the main thing. Yes,

8:45

you have your down days, but also

8:47

you have your good days.

8:50

But everyone always says, you know, how is it You're

8:52

always smiling, And I think I

8:54

look at the positive that now

8:57

I don't see sickle cell as a burden

9:00

as I did before. I actually see

9:02

it as a gift and a blessing

9:04

to have because I can go out

9:06

and spread the word about six sol and

9:08

make friends. Yeah, I'm happy,

9:11

literally happy. I couldn't be

9:13

more happier.

9:17

So my name is Sheriff to sob them.

9:19

I was born in Kampala, Uganda, a small

9:21

East African country, and

9:25

I have scle cell disease. So

9:28

when I was born, my mom and dad

9:30

had a very love story. They

9:32

gave birth to the baby boy like all parents, so

9:35

very excited to have a baby boy. I

9:37

think after about four or five months after that, I

9:39

started to show up with I was very irritated.

9:41

I was alreadys crying and they told me I had

9:44

all the my social.

9:46

In hands and didn't know. They didn't know what was really going

9:48

on.

9:49

And my mom kept on going to different

9:51

health centers and until the time

9:54

one doctor did sugges said, no, what we need to do

9:56

a cyclo cell test to be able to find out if

9:58

this after has cell and and so

10:00

that was the change of their story because once

10:02

she told my dad, they actually broke

10:05

up and my dad left her because he's like,

10:07

no, I've not had any

10:09

child or cicle cell and in my family we don't have

10:11

sicosle business. So my

10:13

mom ended up having to raised me as a single

10:16

mother because my dad had left. During

10:18

that time, she was pretty scared about what's

10:20

going on. She didn't know what was going on because at that time

10:23

the ninety sicosa wasn't really a

10:25

very big thing. Most people who have cycle

10:27

cell To date in Uganda, we find that over ninety

10:30

percent of the babies who were born in shep was Sel

10:32

died before their fifth pack. So this is

10:35

mostly because we don't have a comprehensive

10:37

for a program that you're going to be diaganized

10:39

and go to Cico cell center and be

10:42

followed up to sell the care.

10:43

All that has not been there if it has started

10:46

to come up.

10:46

I think in the last one one or two three years we're

10:48

starting to see scosol the centers across the country

10:50

in Uganda. So during

10:53

that time when she was pretty long, pretty scared, she

10:56

named me to Suvida. So my second name

10:58

is Sheriff to Suvida to Subida means we

11:00

hope. So high institution with the names

11:02

with them was mostly because of the fact that she wanted

11:04

to have a way to always have

11:06

some hope in her heart. Because if everyone around

11:09

you is trying to say your baby's going to die, every

11:11

mom will preace care. But as a

11:13

child growing up, I really I didn't know what was

11:15

going on, yes, or have pain and cry and ask what's

11:17

going on? And my mom didn't

11:19

really have a wolf explaining it to me until I think

11:21

to my six or seven years.

11:24

But when I go to play and kids have come to

11:26

play, we'd say, they would say and

11:28

and I, which.

11:29

Means in my local anguage, you don't play with him. He's

11:31

sick.

11:32

So that that's why I start to realize that there's something

11:34

different about me. So that was

11:36

my kind of childhood experience. And this was

11:38

the case whereby I'll be on the pitch

11:40

trying to pick the ball and I feel pain

11:42

in my leg, feel pain in my hand, and

11:45

said and sometimes I just couldn't walk. My friends

11:47

would have to carry me home. I'd always

11:49

ask my mom, what's going on?

11:51

Why me? Why am I feeling like this? Why

11:53

I think?

11:53

I remember all the time after growing up, I asked her for

11:55

a knife slight that I could cut off my hand and

11:58

cut off my leg because it was bringing too much

12:00

pain for me. And they're like, no, we can't do that.

12:02

You can't just just can't just cut off the leg

12:05

because you took my pain. But

12:07

even then yes, I would feel very

12:09

stigmatized and feel very bad about it. And

12:11

when it went when he went to school, it was actually very

12:14

different as well at school because at school in

12:16

the rainy season, the extreme seasons,

12:19

or being pained and I couldn't go to school, so you missed

12:21

like two weeks or three weeks of school, and the teachers

12:23

to say, where has he been, and so

12:25

often my mom would have to explain, you know what he

12:27

has cycle, sell if he has missed, if he tells you

12:30

his hands are sick, he can't write, it's fine, you

12:32

have to understand.

12:32

But it was really hard for the teacher to understand because,

12:35

like I.

12:35

Said, this disease is most partly nothing

12:37

about like even the teachers like this kid has just

12:40

just has an excuse. Every time I want

12:42

him to come and drawn the blackboard, he's saying

12:45

his hand is hurting. You want him to be part

12:47

of the class activity, He's

12:49

saying he feels pain in his leg

12:51

and feels pain and there.

12:53

So that was another issue because of

12:55

my cycle.

12:55

So I had complications like

12:58

John this in my eyes and had the distant and prettish

13:00

all those things that made me

13:03

look more of an outlier like you don't. Yes,

13:05

you look like everyone else, but you your

13:07

eyes are pretty yellow. So that's the thing that you

13:09

have to explain everyone why your eyes yellow.

13:11

I didn't know how much to break it down, but

13:14

all I would say, yes, I have cicle said it is a blood disease.

13:16

That's all I would say.

13:16

And when I get sick, and we

13:18

had a school nuns, I would go and get careful the

13:21

nuns. So high school was was a bit was a

13:23

much better experience. So during

13:25

my second day and the university, I did get

13:27

sick, and I got sick and I missed I think

13:29

I missed almost three or four weeks of school. So

13:31

when everyone was asking why Sharif and I mean

13:33

and I didn't really do my disclosure. And that's the time I had

13:36

started to day, I was I was taking a very before woman.

13:38

And when I got to seek, I was in the hospital and

13:40

she tells me, you know what, I can't do with

13:43

you because of yoursical cell. I mean, I've never

13:45

seen myself with someone with That

13:48

was a tinning point for me. So that

13:50

that was my driving fact and now to make

13:53

a change in not only in my life but

13:55

in the life of all those people living so such

13:57

that they don't have to go through what had

13:59

gone to. So it was me, myself,

14:02

Ashoff, and two other people, Evelyn

14:05

and another guy's Aalim. We agreed to

14:07

create an organization called Scostal Network

14:09

You. It was the first cico cell and I profit

14:12

that we did register. Because of

14:14

my background and stigma

14:16

and experience, I had. One of the first projects

14:18

that implemented was having psycoso concer

14:20

training. When I looked at my background

14:24

of lavato science and the fact that in

14:26

our market you could have people test for HIV,

14:29

I thought myself and said, I think we should be able to test for cico

14:31

cell. We started out at all

14:33

our community events would have a team of lavaty

14:35

people to do the cicosol screening, our

14:37

counselors to do the you know have councilor cert

14:39

that people could understand what it means if you trade,

14:42

what it means if you if you have pico cell,

14:44

and a lot of those things. And after two years of this,

14:47

our local meanings of Health actually did

14:49

accept and adopt this program.

14:52

It's now been rolled out and several health

14:54

centers have these rapid co celf testing kids

14:56

and people know can be happy to access the cicosol

14:59

screen test whatever they are. So in Uganda,

15:01

we have a tribe called the Baganda.

15:03

Tribe makes up the biggest proportion of the population,

15:06

but we did have a local name for sicco cell.

15:08

And this is not only the Baganda, but most tribes

15:10

in Uganda do not actually do not actually have a

15:12

local name for sco cell. And the indicator

15:15

for this means that if you don't have the local name for something, it

15:17

means you're not talking about it. If you're not talking about

15:19

it, then then that explains all the stigma. So because

15:21

people don't talk about it is no name. But the biggest

15:23

one for me as the advocate is the fact that the

15:26

kingdom gave us a local name for sico cell. They

15:28

did say, now we pronounced that sico salling

15:30

that we just called Umbili. At least now

15:32

somebody who's uneducated, somebody

15:35

who had never been to school, can have a

15:37

word that they can not to mean sico

15:39

Cell, and that in a way helps us beat

15:41

the stigma because then people can be able to

15:44

talk about.

15:45

Their mother town.

15:47

Looking back on how the genius come from

15:49

the time when we introduced communitis Coroso

15:51

screening. From the time when we have a local

15:53

name to the fact that we have, we have not been able

15:55

to support the imaginence of so many Pico so nonprofities.

15:58

And for example, the time when we sarted, there

16:00

was only one nonprofit in Uganda working

16:02

on SIICO so called Circnstatation of Uganda.

16:05

Today, as I speak, seven years later, we have

16:07

over twenty five cb odds committey

16:09

best organization all working.

16:12

To CICO selling local communities.

16:14

I think in twenty nineteen I

16:16

decided know what I've been, I've been an advocate

16:18

for the past few years. I think I need to think

16:21

of something much engine that's a I fund. I thought

16:23

of coming back to grad school, and I decided

16:25

to come back to the US for my grad schools.

16:27

I came back.

16:27

I went to the University of Caansas

16:29

as a peach student. When

16:31

I came to the US, I was hearing a lot of this thing

16:33

of the raciore, the racial bias in terms

16:36

of Icosa, and it had actually never

16:38

happened to me until one time. I think it may I

16:40

go to the er. I had a lot of pain in my

16:42

I was actually very sick.

16:44

I had a lot of pain.

16:45

I spent the whole thing in the r they give me all the pain

16:47

made that I was still in pain. But guess what happened to

16:49

me? The er doctor says, you're

16:51

fine. We have checked everything very normal. So we can

16:54

admit to one of the kid driving factors

16:56

in terms of why even as advocates

16:59

living in the US, we need to come out and promote

17:01

more awareness and boscle soucers that

17:03

the doctors would have a more understanding.

17:05

I think one of the key in wantant aspects.

17:07

It's not it may not be so much of a big deal

17:09

in the US, but it's the big deal is where in the world That part

17:12

whereby people not understanding and accepting

17:14

scle celf having all these meats and

17:16

beliefs. So it still goes back to awareness

17:18

people and having understand that this is

17:21

like any other blood disease. If you can

17:23

take good care of yourself, if you can have a comprehence

17:25

you follow up, if you can do whatever we can do

17:27

to stay healthy, then I can leave like any

17:29

anybody else. I shouldn't worry about death. I shouldn't

17:32

worry that will not be able to meet my dreams.

17:35

My story started out because of a heat

17:37

break, because of the love sad love story

17:39

ended up being a sipo's advocate today. I was

17:41

able to find love, married to Sophia

17:44

and have two kids, Kneeman Shet, and

17:46

they're part of my support system to keep me healthy

17:48

and strong and going. So I

17:51

appreciate them and everyone who's supporting me.

17:53

Thank you.

18:37

Thank you so much Marcia and

18:39

Shurie for sharing your stories with us. We

18:42

really really appreciate it and

18:44

we want to tell you a bit more about

18:46

our amazing guests. Marcia

18:48

started her blog My Life was Sickle Cell in

18:50

twenty sixteen and has since been recognized

18:53

for her awareness raising efforts by appearing

18:55

on TV programs, radio shows,

18:57

newspapers, you name it. And

19:00

in her first hand she mentioned being a member of

19:02

the BE Positive Choir, which is a choir

19:04

made up of people with sickle cell disease or

19:06

those who have friends or family members

19:08

affected and the B Positive Choir

19:11

has made amazing strides in raising

19:13

awareness of sickle cell disease as well

19:15

as encouraging blood donations and

19:17

also, as you heard, they were on Britain

19:20

Scott Talent and performed

19:22

in front of the Royal Family, which is pretty dang

19:24

cool.

19:26

That's amazing. Our other

19:28

incredible guest, Sharif, has been instrumental

19:31

in a number of different advocacy and

19:33

outreach efforts which you heard a bit about

19:35

in his first hand including launching

19:38

the East Africa Sickle Cell Alliance, working

19:40

with the Pan African Sickle Cell Federation

19:43

International, and serving as

19:45

the first executive director of the Uganda

19:47

Sickle Cell Rescue Foundation.

19:49

That's incredible, so amazing.

19:51

Sharif's amazing advocacy and

19:53

outreach efforts have been recognized by many

19:55

organizations. In twenty seventeen,

19:58

he was named Amandela Washington Fellat through

20:00

the Young African Leaders Initiative. In

20:02

twenty eighteen, he became a Telemachus

20:04

Fellow under the Global Thinkers Forum, and

20:07

this year twenty twenty, he was named

20:09

the International Sickle Cell Advocate

20:11

of the Year.

20:13

No big deal, No big deal.

20:15

Oh and he's just casually also

20:17

getting his PhD studying quantitative

20:20

genetics at the University of Kansas, just

20:22

like.

20:22

Casually casually getting

20:24

a major degree. Right,

20:27

Oh my goodness, that's amazing. We

20:29

will provide links to both Marsha and Shreef's

20:32

websites and social media handles on our

20:34

website this Podcast will Kill You dot com

20:36

and in our show notes if you'd like to learn more

20:38

about these awesome humans and their work.

20:41

Yeah.

20:42

Hi, I'm Aaron Welsh and

20:44

I'm Erin Olman Updyke, and

20:46

this is this podcast will Kill You. This

20:49

week we are, as you may have guessed.

20:51

You might have figured it out by now covering

20:54

sickle cell disease. Yeah,

20:57

this is a big one.

20:58

Obviously, this is a huge one.

21:01

And we've been wanting to do this one for a while

21:04

and I'm very excited now that

21:06

we're finally doing it because there's

21:09

so much. There's so much to it.

21:11

Yeah. Absolutely, there's such

21:13

fascinating biology. I can't wait

21:15

to learn about the history. I have a feeling it's going to be

21:17

equal parts fascinating and infuriating.

21:20

That's my guess.

21:21

Oh why would say maybe not even

21:23

equal parts? I would say, oh, mostly infuriating.

21:27

Yeah awesome. Okay, there are some like you know,

21:29

shining moments, but yeah,

21:31

oh.

21:32

But I can tell you that there are some

21:34

very exciting things to talk about

21:36

in the current events section, for

21:38

which we had the pleasure of speaking

21:41

with a very special guest, doctor Meghan

21:43

Hawkstrasser, whose education

21:46

programs manager at Innovative Genomics

21:48

Institute in Berkeley.

21:50

It's incredible. I'm sure that you

21:52

may have heard the word crisper

21:55

or genome editing at some point and

21:58

been like, what the heck is that. Don't

22:00

worry, We're going to get into it

22:02

at least a little bit, and it's going

22:04

to make you so thrilled

22:06

and make you feel like you're living in the future.

22:09

It's thrilling. But before we get

22:11

into all of the thrilling things that we're going to talk about

22:13

today, erin what time is it?

22:15

I believe aarin that it is quarantine

22:18

any time.

22:19

You would be correct about that. What

22:21

are we drinking today?

22:23

We are drinking the Witten lovely.

22:27

Oh yes, And the Witten is named

22:29

for doctor Charles Witten, who,

22:32

among many other amazing accomplishments,

22:35

was the co founder of the Sickle

22:37

Cell Disease Association of America,

22:40

and he made amazing strides in raising

22:42

awareness of sickle cell throughout the

22:44

seventies and eighties and into

22:46

the nineties as well. And he also

22:49

initiated a lot of programs that

22:51

were designed to provide more

22:53

opportunities for those underrepresented

22:55

in medical fields to actually have medical

22:57

school as an opportunity. So we

23:00

wanted to name our quarantini in

23:02

the to honor this amazing human

23:04

in the tiniest possible way.

23:07

And to do so.

23:09

What is in this quarantini

23:11

exactly the witten

23:14

is strawberry infused tequila, which

23:16

is so good and also just

23:19

really easy to do.

23:20

Just takes patience and lime

23:23

juice and agave syrup.

23:25

Fabulous. We'll post the full recipe for

23:27

that quarantini as well as our non alcoholic

23:30

plus e verta on our website. This podcast

23:32

would kill you dot Com and all of our social

23:34

media channels, so make sure you're following us.

23:37

And we have one more piece of business

23:39

before we get into the

23:42

business of sickle Cell,

23:44

just.

23:44

A little one, which is a big news.

23:47

Actually we

23:49

have new merch, new merch.

23:52

We've been waiting. We're so excited.

23:55

We have some really fun cool things,

23:57

like we'll just drop a few little hints. You want

24:00

a hoodie, We got a hoodie.

24:01

Oh, we got some socks,

24:04

keep your toes warm.

24:07

Big shout out to Abigail Irvin Penner,

24:09

who's always incredible artwork is

24:11

featured on so many of these Honestly,

24:13

like I'm I'm in love.

24:15

I can't wait to be tpwky head

24:17

to toe baby, I mean literally head

24:20

to toe and for my SIPs.

24:22

Yeah. Okay, if you

24:24

would like to see this new merch, you

24:26

can head to this podcast will Kill You dot

24:29

com and click on the merch tab at the

24:31

top of the screen.

24:32

All right, is that all our business eron?

24:34

I believe so.

24:35

Well, then let's take a quick break and dive

24:38

straight into the biology.

24:39

Of sickle cell let's do it.

25:03

So, sickle cell disease

25:06

or sc D. I

25:08

think it's often taught as sickle

25:11

cell anemia, right, this like

25:13

one particular illness, but

25:15

in fact, sickle cell disease is a group

25:18

of disorders of red

25:20

blood cells, and

25:22

it's a genetic disease, which means it's inherited,

25:25

so it's caused by a mutation.

25:28

But as we'll see, it's not just one

25:30

single mutation, and there's not just one

25:32

single manifestation. So

25:35

we're going to start from the very beginning

25:37

before we even get into sickle cell disease

25:39

itself and talk about blood.

25:42

Cool.

25:43

Yes, okay, we've talked about blood

25:45

before a little bit.

25:46

We have, but we've never talked

25:48

about this.

25:52

We have talked about when we talked about blood

25:54

hepatitis. C Oh.

25:56

Yeah, this is a totally different blood discussion.

25:58

Okay, okay,

26:01

So what we're going to talk specifically about

26:03

is in our red blood cells,

26:06

the protein that is actually responsible

26:09

for carrying oxygen, and that protein

26:11

is hemoglobin. Okay. So,

26:15

hemoglobin is a protein that's made

26:17

up of four polypeptides,

26:19

two pairs of polypeptides,

26:22

and these four polypeptides or

26:24

strings of amino acids form

26:26

the protein that's in our red

26:29

blood cells that actually carries oxygen,

26:31

which obviously our tissues need in order

26:34

to survive. So in

26:36

most adult red blood

26:38

cells, hemoglobin is made up

26:41

of two alpha chains

26:44

alphas, and two beta

26:46

chains. So alpha, alpha, beta,

26:48

beta, Okay, sounds good.

26:51

Now, we also have some other forms

26:53

of hemoglobin, like you can have two

26:55

alpha chains and two delta

26:57

chains. That's another kind of adult hemoglobin.

27:02

And then in a fetus before

27:05

we are born, the majority

27:07

of our hemoglobin is actually two alpha

27:10

chains and two gamma chains,

27:12

and that's called fetal hemoglobin.

27:15

Why great questions, So glad you

27:17

asked. So you know how

27:20

fetuses are grown inside

27:23

and all of their blood comes from

27:25

mom right, So that means

27:27

that all of the blood that a fetus is getting is already

27:29

partially deoxygenated. It

27:31

doesn't have as much oxygen as

27:33

the blood in our bloodstream

27:35

because we're breathing in air. So

27:38

because of that, fetal hemoglobin

27:40

has to actually bind oxygen

27:43

more tightly than adult hemoglobin

27:45

because it has to be able to get all of that

27:48

oxygen out of mom's blood. Does that make

27:50

sense? Okay? Now

27:52

remember that because it's going to become

27:55

very important in our discussion of sickle

27:57

cell later. Okay, Okay,

28:00

So now we understand

28:02

hemoglobin inside

28:04

normal adult red blood cells. So what does that

28:07

mean for sickle cell disease? Why did I tell you all?

28:09

That?

28:09

Turns out that sickle cell disease

28:13

is produced by a single

28:16

amino acid change

28:19

if anyone cares, it's a glutamic acid

28:21

to a vailian that in

28:24

that beta hemoglobin chain. Okay,

28:27

So it's a single mutation

28:30

in beta hemoglobin that

28:33

results in what's called like sickled

28:36

beta hemoglobin, so hbs

28:38

instead of hb A for adult.

28:41

That is the change that if

28:44

you have two copies

28:46

of that mutated beta globin gene,

28:48

you have sickle cell anemia,

28:51

the disease caused by two

28:54

copies of these sickle cell genes.

28:57

So what happens if you have these

29:00

sickle cell versions of beta

29:02

hemoglobin, Well,

29:05

what happens is that in your red

29:08

blood cells at low

29:10

oxygen concentrations, like

29:12

low overall oxygen concentrations

29:14

in your blood, the hemoglobin

29:17

forms a polymer. So multiple

29:21

subunits, like multiple little globules

29:24

of hemoglobin protein will link

29:26

together inside the red blood cell

29:28

and form a linear chain.

29:30

Like a little string of beads, like.

29:32

A little string of beads exactly. And

29:34

this becomes rigid and

29:36

causes a deformation in the

29:38

whole red blood cell so that it kind

29:41

of sucks in on itself and becomes sickle

29:43

shaped or like a crescent moon shaped.

29:46

So a normal adult red

29:48

blood cell, even a fetal red blood

29:50

cell, is shaped kind of like a doughnut,

29:53

like the you know the things

29:55

you go down the lazy river in those like inflatable

29:58

tubes with like the in the

30:00

middle so your butt doesn't fall through.

30:02

Oh, I've never had one that had the mesh, but sure.

30:05

The fancy version. Okay, So that's

30:07

kind of what a normal red blood cell looks like. So

30:10

when you have two copies of this

30:12

sickle cell beta hemoglobin gene,

30:14

all of your hemoglobins line up in

30:17

the red blood cell and cicicle it so

30:19

instead of that nice donut, you have

30:22

a C shaped red blood cell. And

30:24

that is kind of the core

30:28

problem that results from

30:31

two copies of this sickle cell

30:33

gene. But how is that like?

30:35

Okay, it's just a different shape of your red

30:38

blood cell. Why is that so bad? So

30:41

these sickled cells are very rigid,

30:43

okay. Normal red blood cells are

30:45

kind of like an inflatable

30:47

donut. They're kind of squishy and squashy,

30:50

okay, So as they move through

30:52

your blood vessels through from

30:54

larger vessels to smaller vessels like your

30:56

capillaries, they can squash and deform

30:59

and scoot through small vessels and

31:01

then pop back out on the other side. Sickled

31:04

cells are more rigid, so they can't

31:06

do that as well. So

31:08

what happens is these cells can start

31:11

to get stuck, especially in small

31:13

vessels. Okay, but

31:16

it's not just the rigidness

31:19

of the sickled red

31:22

blood cells. So it turns

31:24

out that once a red blood cell sickles

31:26

like this, they're also literally

31:29

stickier, like proteins on the outside

31:31

of them become more sticky,

31:34

so that they get stuck to the walls

31:36

of your vessels, and

31:39

they get stuck to other like

31:41

white blood cells and things that are rolling

31:43

along in your vessels. Okay,

31:46

and imagine what happens if you

31:48

have a bunch of cells starting to stick

31:51

to one another inside of your.

31:52

Blood vessels, or you get a blood clot.

31:54

You're gonna get a blood clot exactly, and

31:56

so kind of the hallmark of

31:59

sickle cells that we'll talk a little

32:01

bit more about in a minute when we talk about the symptoms

32:04

are what's called vasoeclusive crises.

32:06

So you literally have occlusion

32:09

or blockage of your vessels

32:11

small vessels like capillaries, but

32:13

even larger vessels like in your brain,

32:16

leading to stroke.

32:17

That sounds terrible.

32:19

It's not great, that's for sure.

32:22

And there's more. Okay, So now

32:24

we know that these sickled cells, they get more

32:27

sticky, they can get stuck in places. But on

32:29

top of that, so red

32:31

blood cells only sickle at lower

32:33

oxygen concentrations. Okay,

32:35

So for the most part, in your arteries, even

32:38

if you have sickle cell disease, your red

32:40

blood cells are going to be in normal shape. It's

32:42

not until you reach the capillaries or

32:44

the veins where oxygen concentration

32:47

is lower that these

32:49

the hemoglobin will form those chains

32:52

and then cause the red blood cell to sickle.

32:54

But this is reversible, but there's

32:56

two problems with it. First of all,

32:59

this tends to happen in microvessels

33:02

like your capillaries and small veins,

33:05

because that's where both

33:07

oxygen concentration is low

33:10

and you have slow flow,

33:13

so the red blood cells in there for a

33:15

long time comparatively,

33:18

and so those two things combined lead to sickling.

33:21

And in small vessels, if you sickle

33:23

and you get stuck, then you can block those

33:26

small vessels directly.

33:27

Gotcha.

33:28

Now, another thing happens over

33:30

time, this constant sickling

33:33

and unsickling. Sickling and unsickling

33:36

causes damage to the red blood cell

33:38

membrane itself, so like the outer shell

33:40

of the red blood cell, and this

33:42

can cause an irreversible

33:44

sickling. So now it's just stuck sickled

33:47

all the time. And those sickled

33:49

cells in particular are very

33:51

very sticky, so that can

33:54

cause sticking on the inside of vessel

33:56

walls. And to white blood cells

33:58

in larger vessels, which can eventually

34:00

lead to blockage of even larger vessels,

34:03

not just small ones.

34:05

Right, and it seems like the white blood

34:07

cell thing then will play a role in immune

34:10

system function.

34:11

Oh, you're so accurate,

34:13

Aerin, here's a question.

34:15

Yeah, and maybe it's jumping the gun, but your

34:18

body, as we talked about

34:20

in the hepatitis C episode, your body makes

34:23

a lot, like makes new red blood

34:25

cells very frequently, and

34:27

so what does it do, like

34:30

does it attack the sickled

34:33

cells in any way, or like what is their

34:35

lifespan?

34:36

I'm so glad that you asked, Aaron. It's totally jumping

34:38

the gun, but it's the perfect question.

34:40

I love it.

34:41

So yeah, okay, I'm

34:43

going to answer that question in a couple parts. Okay,

34:46

So, first of all, you're right that white blood

34:48

cells and things play a big role. And overall,

34:51

even though this is technically a disease

34:53

of just red blood cells, right, it's just

34:55

hemoglobe and being messed up, it's

34:58

not just a disease that affects

35:00

your red blood cells. Overall, there's

35:02

an increase in inflammation and inflammatory

35:05

state in sickle cell disease

35:08

and the more inflammation. So

35:10

the higher people's leukocyte counts

35:12

or white blood cell counts, the worse

35:14

off their disease tends to be. And as

35:16

we'll see, there's huge variation in disease

35:19

severity, and that's one factor that plays

35:21

a role. Now in terms of how

35:23

long these blood cells last, that's a perfect

35:25

question to ask. A normal,

35:27

healthy red blood cell has a lifespan

35:30

of about one hundred and twenty days. In

35:32

someone with sickle cell disease, that lifespan

35:34

is reduced by over seventy five percent.

35:38

So some estimates that I saw were the life

35:40

span of a red blood cell in a person

35:42

with sickle cell disease, so that's two

35:44

copies of that sickle cell gene is

35:46

about sixteen days.

35:48

Oh wow. And so even

35:51

if your body is producing blood,

35:53

it's not enough to make up for the loss.

35:57

Oh you're getting the perfect yes,

36:00

hundred percent. So there's two

36:02

ways that you get anemia. One, like you said,

36:04

you just can't make enough because you

36:07

need to constantly make more red blood

36:09

cells and more red blood cells. But on top

36:11

of that, as those cells sickle and

36:13

unsickle and become damaged, that

36:15

leads to hemolysis. So red

36:18

blood cells actually breaking open

36:20

within your vasculature. So not

36:22

only can you have anemia from lack of production,

36:25

you can also have a hemolytic anemia.

36:28

So breaking open those red blood cells,

36:31

now, that leads to even

36:33

more problems because when you burst

36:35

open red blood cells, all that hemoglobin

36:38

that's inside those red blood cells is

36:40

now released into the blood stream, and

36:42

this causes like a whole host

36:45

of biochemistry reactions I'm

36:47

not going to get into, but one thing that it

36:49

does is it scavenges up

36:51

all of the nitric oxide, which

36:53

is an important molecule that helps

36:56

with things like vasodilation. So

36:59

as your hemoglobin sucks up all

37:02

that nitric oxide, now you have increased

37:04

vasoconstriction as well as

37:07

damage to like the epithelium of

37:10

the lining of your blood vessels, which

37:12

causes even more stickiness. Okay,

37:14

so it's like these horrible feedback

37:17

loop, if that makes sense, where

37:19

you have smaller vessels because

37:21

you have less nitric oxide, you

37:23

have damage to the

37:26

inner layer, which increases the

37:28

stickiness, you have inflammation.

37:30

So there's white blood cells rolling around picking

37:33

things up, and it's

37:35

it's bad. It's a mess. Okay.

37:37

Yeah, that's like a from one,

37:40

I mean no acid substitution. This

37:43

systemic these systemic

37:45

problems.

37:46

Isn't that it's fascinating

37:48

that you can have so many effects

37:51

from one single and I mean it's

37:53

a single nucleotide. It's a single base

37:55

pair change.

37:56

Right right, It's wow,

37:58

yeah, man.

38:00

Okay, So let's talk about what these symptoms then

38:02

look like. So now we know like what's happening

38:04

in your blood vessels, and it kind of all boils

38:06

down to like increased inflammation and

38:09

blocking your vessels. Okay,

38:12

so I said this already, but the main complication

38:15

are these vasoeclusive crises,

38:18

and so these can manifest, as you

38:20

can probably imagine, in so many different ways

38:22

depending on what vessels are getting blocked

38:24

up. Okay, So in

38:27

small children, especially tiny babies

38:29

like under the age of two, the most

38:31

common presentation is

38:35

when the small blood vessels in their

38:37

hands and feet get clogged up. This

38:40

causes swelling of the hands

38:42

and the feet, and this is really really

38:44

painful as well, because you're literally blocking

38:47

blood flow to your hands and feet. And

38:49

so in small babies

38:52

that for example, didn't have

38:54

a newborn screen done, so they didn't

38:56

know their parents maybe didn't know that they

38:58

had sickle cell anemia. This is a really

39:00

common way that they would come into the emergency

39:03

room and be identified as having sickle cell

39:05

anemia.

39:06

Okay, is there a treatment

39:08

for that aspect of it or is it?

39:11

So we'll talk about treatment more

39:13

later, but for the for the most

39:15

part, not really

39:18

Okay, yeah, God yeah,

39:22

okay. So then as you can imagine,

39:24

as you get older, these

39:27

pain crises, these vasoeclusive

39:30

crises, just kind of keep happening, and they

39:32

can happen almost anywhere.

39:35

So it's very common for people

39:37

to come in with massive, massive

39:40

amounts of pain without any

39:42

kind of you can't see

39:44

anything wrong with them because it's

39:46

these tiny blood vessels in your

39:48

abdomen or your legs, in your

39:51

arms, anywhere that get

39:53

clogged up. This causes a huge

39:55

amount of pain. If you imagine, like a

39:57

heart attack happens when

39:59

you have a blockage of blood

40:01

flow to your heart. Heart attacks are extremely

40:04

painful. This is happening in

40:06

small vessels throughout somebody's body

40:08

during a sickle cell crisis. This

40:11

is a disease that is I think

40:13

often very misunderstood, and

40:16

the pain I think

40:18

can be minimized by people

40:21

because it's not visible it's another

40:23

kind of disease, like we've talked about before, where you

40:26

don't look sick necessarily,

40:29

and so I think it's really important to get across just

40:31

how debilitating the pain associated

40:34

with these can be.

40:36

It's funny that you're using the phrases

40:38

invisible and visible, because I that's

40:41

like, that's my theme, and when

40:43

I talk about the history.

40:44

Of it, Yeah, yeah, it's really it's

40:47

bad. Okay. So

40:49

then you also can have additional

40:52

symptoms or sort of more specific symptoms,

40:54

depending on where you have

40:57

these blockages. It

40:59

can happen in people that have a penis,

41:01

it can happen and you can get what's

41:03

called priapism, which is a long lasting

41:06

and very painful erection. If

41:09

it happens in the blood

41:11

vessels under your skin, especially in your legs,

41:13

which is really common, it can cause chronic ulcers,

41:16

so open wounds on your legs that

41:19

are unable to heal because they're

41:21

not getting good blood flow over time. If

41:24

it happens in your eyes, it

41:26

can lead to blindness because

41:28

the vessels in your retina become

41:31

blocked. God, it

41:34

can happen in your bones, and

41:36

this is very serious because

41:40

your bones are also

41:42

alive. They need blood flow, So when

41:44

you block off the vessels to your bones,

41:47

you get what's called a vascular

41:49

necrosis. So that means tissue

41:51

death because of lack of blood flow.

41:54

So your bone marrow will literally die.

41:56

Oh my god, yep, So

41:59

that's pretty bad as you can imagine. That

42:01

can also lead you susceptible to like

42:04

osteomyelitis, which is infection

42:06

of your bone, like a bacterial

42:09

infection of your bone, because you don't have good

42:11

blood flow to that bone.

42:14

It can happen in your spleen, which

42:16

is very common, and with your spleen

42:19

kind of two different things can happen, so

42:21

you can have like an what's called an

42:23

acute splenic crisis. So

42:26

all of a sudden your spleen, like

42:29

blood flow to your spleen gets blocked. This

42:31

can cause your spleen to enlarge

42:33

very rapidly, and that can kill

42:36

you, like right, that alone

42:38

can kill you. Your spleen is

42:41

an organ where a ton

42:43

of blood flows through it because it's a lymphatic

42:46

organ, so all of your white blood cells kind of

42:48

hang out in your spleen and are responsible

42:51

for like gobbling up bacteria and

42:53

cleaning your bloodstream. Of infection.

42:55

Okay, so because it has

42:58

such huge volumes of blood, if

43:00

you block that blood flow, then

43:02

you can die just from that alone.

43:05

But it can also happen, and it

43:07

commonly does happen where over time, small

43:10

vessels get blocked little

43:12

by little in your spleen, leading

43:15

to long term death of your spleen.

43:18

What's called auto infection, right,

43:21

so that a person, even though they have

43:23

a spleen in their body, it's essentially

43:25

non functional. It's like you removed

43:27

it. So that leaves

43:30

you very susceptible to infection,

43:32

especially bacterial infections, because you don't

43:34

have a spleen to take care of all those

43:36

bacteria. So it's very

43:38

common for people, especially young children,

43:42

to die not from

43:44

sickle cell anemia or sickle cell disease

43:46

itself, but from an overwhelming

43:48

bacterial infection because their spleen

43:51

is nonfunctional. God,

43:53

another really horrible outcome

43:56

would be stroke. And

43:58

this is actually what is

44:00

so tragic is that stroke is

44:03

very common in young kids with

44:05

sickle cell anemia. And

44:09

so that's essentially not

44:11

just from small vessels being blocked,

44:13

but from larger blood vessels in your brain

44:15

that get blocked, and then

44:18

overall the most common

44:20

cause of death and the second

44:22

most common cause of emergency

44:25

room visit for someone with sickle cell anemia

44:28

at least in this country, is what's called

44:30

acute chest syndrome or ACS.

44:33

And this is when you essentially get those crises

44:36

in your lungs.

44:38

Oh my god.

44:39

Yeah. And what is

44:41

awful and also very interesting about

44:44

ACS is that the trigger

44:46

for that can be almost anything, So

44:49

it doesn't necessarily start with just

44:51

these sickled cells blocking blood

44:54

vessels. It can be a viral infection

44:56

that causes inflammation that then triggers

44:59

all these events. It could be

45:01

an asthma attack, because you can have

45:03

asthma and sickle cell that

45:05

triggers all of these events. It

45:08

can be fat embolism

45:10

because if you have, for

45:12

example, necrosis of your bones, your

45:15

bone marrow is full of fat, little

45:17

pieces of that fat can break off and travel

45:19

to your lungs, and then those little

45:22

emboli they're called, can cause

45:24

a blockage that can then trigger all

45:26

these downstream effects. So

45:29

a cute chest syndrum ACS is it's

45:32

basically a triad of extreme

45:35

chest pain infiltrates

45:37

so fluid and junk all over

45:39

your lungs and then what's

45:41

called arterial hypoxemia, So

45:44

not able to get oxygen in your arteries

45:47

because of all this fluid and junk in your

45:49

lungs. It's horrible, it's really really

45:51

awful. So

45:55

yeah, that's kind of the

45:57

overall symptom picture of

46:00

what happens with sickle cell anemia

46:02

or sickle cell disease.

46:04

And so these happen,

46:06

like you talked about, these tend to happen

46:08

at different stages of someone's

46:10

life. So what, like why

46:13

is that? Is it just a matter of like

46:15

your body growing and like certain

46:18

things growing at certain times

46:20

more Like, yeah, it's.

46:22

It's a really good question. It's not. I don't

46:24

fully know, but it is the case

46:26

that people tend to present differently

46:28

at different ages. So like in very

46:31

young kids, the first presentation

46:34

might be that hand and foot swelling

46:36

right in like a very young baby. As

46:38

they get older, especially under five,

46:41

it's very common to have bacterial

46:43

infections that can end up

46:46

becoming very serious. Then

46:48

at a certain age, stroke is

46:50

a common manifestation. And

46:52

then after that these pain crises

46:55

and acute chest syndrome, right

46:58

gosh, yeah, and then on top of that,

47:00

like we said, kind of already you have kind

47:02

of chronic anemia, so not enough

47:05

red blood cells, this homolysis, which

47:07

leads to fatigue, it leads

47:09

to jaundice. You can have gallstones

47:12

very commonly because of all this hemoglobin

47:15

in your bloodstream. It can cause the formation of

47:17

gallstones. So you can have huge pain

47:19

from that. It's it's

47:22

very bad. Kidney failure is really

47:24

common. If you block the kidneys

47:27

the bloodstream to your kidneys, you can have kidney

47:29

failure. That's really common. I mean, it's it's everything, I

47:31

meanwhere your blood flows.

47:33

Yeah, exactly.

47:35

And what I also want to mention that

47:38

I think is often glossed over is the

47:41

huge amount of mental and behavioral health

47:43

complications from this. Depression and anxiety

47:46

are very very high among people

47:48

living with sickle cell because they

47:50

have chronic pain. Not

47:54

only are they living with chronic pain, not

47:56

only do they have a reduced life expectancy,

47:59

they're frequently in the emergency room, they're

48:01

frequently being hospitalized. That's a massive

48:03

amount of financial cost that's incurred.

48:06

And on top of that, there's a long standing

48:08

history of medical professionals not

48:11

believing or not taking seriously

48:13

the pain that you're in. So,

48:17

yeah, this is a very it's

48:19

a single mutation that

48:22

leads to so very

48:24

many complications.

48:27

Oh yeah, oh yeah, yeah.

48:31

Well is it a single mutation

48:33

at bench there's my transition. Okay,

48:38

So all of that is kind of the description

48:40

of sickle cell anemia, which is

48:42

when you have two copies

48:44

of that mutated beta

48:47

globin gene, so that you have messed

48:49

up hemoglobin. That's not the

48:51

only way that you can have sickle cell disease.

48:55

There are a number of other

48:58

mutations that can result

49:00

in sickle cell disease that is usually

49:03

less severe than sickle cell anemia,

49:06

although in some cases it's almost as severe.

49:08

So if you have one

49:11

copy of the sickle

49:13

like HBS, that sickle cell allele,

49:16

and then you have one copy of a

49:18

beta thallasmia allele. So

49:21

beta thallasemia is something most people might have

49:23

heard of, or thallasmia maybe you've heard of.

49:26

This is another entirely separate

49:28

mutation of your beta globin gene.

49:31

Right, you can have one copy of HBS

49:34

and one copy of beta thallasmia, then

49:37

you kind of have thallasmia and you

49:39

kind of have sickle cell disease. You have like a

49:41

combination of both. So typically

49:43

your symptoms aren't going to be as severe as

49:46

someone with two copies of sickle cell,

49:49

but you're still going to have some of that. You can still

49:51

have some cells that stickle essentially, Okay,

49:54

gotcha. Yeah, there's another gene

49:57

called HBC that's like another

49:59

form of sickle cell, so you can be HBS

50:02

HBC. That's a whole

50:04

nother one. There's another

50:06

type of thallacemia called alpha

50:08

thallasmia, So that's where those alpha

50:11

polypeptides are messed up rather than the betas

50:13

in your hemoglobin, and

50:16

that typically leads to actually like a

50:18

less severe form of sickle

50:20

cell anemia or of sickle cell disease.

50:23

Why, like, what's the difference between the alpha

50:25

and the beta that it would be a different.

50:27

So it's actually this is very complicated,

50:29

but it's actually because instead of only two copies

50:32

of alpha, we have four

50:34

copies of alpha. So if you have just

50:36

one mutation, you still have three good copies.

50:39

Gotcha.

50:40

So what's I think really important to

50:42

kind of that? It's a good question. I'm glad you asked that,

50:44

Aaron, because what's important about this is

50:46

that if you have one copy

50:48

of this HBS, this sickle cell

50:50

a wheel you're still gonna make

50:53

that kind of messed up beta

50:56

hemoglobin, but you'll make

50:58

enough normal that you won't

51:00

have these sickling events. Okay,

51:04

you make enough normal hemoglobin

51:06

that they can't form those chains

51:08

and sickle unless you have

51:11

like extremely low oxygen

51:15

concentrations. Okay, So in

51:17

rare instances you can still get sickling,

51:19

but in general it's going to be a lot less. It's

51:22

not going to be nearly as many of your red blood

51:24

cells. If you have two copies,

51:26

all you make is a messed up beta

51:28

hemoglobin. Okay, So all

51:30

of your red blood cells have this messed

51:33

up hemoglobin okay.

51:34

Right, And this is where, like the language

51:37

around it is so important

51:39

to remember, like the difference between

51:41

sickle cell disease, sickle cell trait,

51:44

and sickle cell anemia exactly, And

51:46

that's led to a lot of confusion. Yeah,

51:48

in the history of it as all talk about.

51:51

Yeah, and so sickle cell trait would be if you

51:53

have one copy of HBS and one

51:55

copy of a normal HbA

51:58

or normal adult hemoglobin right

52:01

right, Oh gosh,

52:04

So yeah, Okay, I think that's

52:06

all about those types

52:08

of things. What

52:10

else do you want to know about the biology. Arin, I've got

52:13

more for you.

52:16

Well, I want to know about treatments.

52:18

Okay, let's talk about it.

52:20

It's not great, Okay.

52:22

There are some good things. So

52:25

remember how, especially for young

52:27

kids, most common cause of like death

52:29

is overwhelming bacterial infection. So

52:33

in many countries in the world,

52:35

we now screen for sickle cell

52:38

disease in newborns,

52:41

and if you identify somebody with sickle

52:43

cell disease, you can start treating them prophylactically

52:46

so before they ever get sick with penicillin.

52:48

So these kids get penicillin just every

52:50

day for like the first five years of their life.

52:53

So that has reduced the death rate to like

52:56

less than three percent compared to over twenty

52:58

five percent.

53:00

That's great.

53:00

So that's great. Vaccinating babies

53:04

is massively helpful in preventing

53:06

overwhelming infection because we have

53:08

vaccines for a lot of the things that commonly

53:11

cause infection in these kids.

53:15

But beyond that, so that's kind of like

53:17

we can prevent kids from dying at

53:19

a very young age from sickle cell

53:22

but beyond that, we really have cruddy

53:25

treatment for sickle cell disease and sickle

53:27

cell anemia. If somebody

53:29

comes in with one of these acute crises

53:32

of pain. There's not much more to do besides

53:34

pain control, which I'm sure you'll

53:36

talk more about later. Is like, yeah,

53:40

the problems, so many problems. You

53:43

can give transfusions, so

53:46

you can do an exchange transfusion where you

53:48

take out their blood and give them new

53:51

blood essentially, so that can decrease

53:53

the amount of sickled cells in their blood, which

53:55

can be very helpful. But

53:57

the only actual treatment

54:00

like drug that we have is hydroxyurea,

54:04

which this is so fascinating.

54:06

We have no idea how

54:09

it does this, but what

54:11

it does is it increases the amount

54:13

of that fetal hemoglobin,

54:16

that gamma hemoglobin. I

54:18

see your confused.

54:19

Face, Saran, Yeah, how

54:22

why? Why is how okay?

54:24

How can we have a.

54:25

Normal amount Do we have, like any amount

54:27

of gamma hemoglobin just circulating

54:29

at any given time?

54:30

Yes? So okay and great

54:33

question. Potentially yes.

54:36

And there's massive amounts of variation

54:38

in how much fetal hemoglobin a non

54:41

sickle cell disease person produces,

54:43

and even within someone with sickle cell

54:46

disease, how much fetal hemoglobin

54:48

they have correlates

54:50

to how severe their disease is. So the more fetal

54:53

hemoglobin, the less severe

54:55

their disease tends to be. So

54:57

giving somebody hydroxyurea in

55:00

increases the production of fetal

55:02

hemoglobin, decreases the severity

55:05

of disease.

55:07

That's fascinating, fascinating,

55:09

And I have a question, Okay, do

55:12

you know is there any

55:14

sort of elevational or altitudinal

55:17

gradient in terms of like, let's

55:19

say, if populations whose ancestral history

55:21

has been mostly like high

55:23

elevation, do they produce more

55:26

gamma hemoglobin than those lower

55:28

elevations.

55:29

That's such a good question, and I can't remember.

55:32

That is such a good questionnairein I can't

55:34

remember. I

55:36

don't know if people tend to have higher fetal hemoglobin,

55:39

but there are certainly adaptations in

55:41

populations that have lived for a long time at high

55:43

altitudes where their hemoglobin has

55:45

a higher affinity so it binds tighter

55:47

to oxygen the way that fetal

55:50

hemoglobin does the same way.

55:52

Interesting.

55:52

Yeah, there's there's so much more

55:55

to that whole, like the whole oxygen

55:57

thing and altitude

56:00

get into it.

56:00

But I know, I mean, there's we

56:02

really should do like an episode on blood

56:05

ooh, because I also

56:07

want to talk about blood groups at some point.

56:09

Oh, I know we've never done that. That would be super fun.

56:12

I'd love to talk about blood even more. Okay,

56:15

people will be experts by then because we did

56:17

it in hepatitis and now we're doing hemoglobin.

56:20

It's cool.

56:22

Okay.

56:23

So that's hydroxyurea. So that

56:25

is considered a disease modifying

56:27

agent. It's the only one we have because it actually

56:30

improves your

56:33

functioning essentially by increasing

56:35

the amount of fetal hemoglobin. But

56:38

the only cure, and I'm going to

56:40

put that in air quotes, is

56:43

bone met or chansplant.

56:45

But that has its own suite of problems.

56:47

Absolutely always does. Yeah,

56:50

So it has to be, you know, a perfectly

56:52

or very well matched donor, which is very

56:55

difficult to find. It

56:57

requires that you wipe out somebody's entire

57:00

bone marrow first, which leads them

57:02

very susceptible to infection. Then

57:04

once you put in the new bone marrow,

57:07

you can have auto rejection, et

57:09

cetera. And so because

57:12

the severity of sickle cell disease

57:14

and sickle cell anemia is so it

57:17

ranges so much, transplants

57:19

are not generally done except in very severe

57:21

cases, and even then only in high

57:24

income countries like the US or the UK.

57:26

So it's very rare essentially,

57:28

which is problematic

57:30

since that's the only curative treatment

57:33

that we.

57:33

Have, right, and it's like curative

57:36

is in like gets done

57:38

forever.

57:39

Like you're if yeah, as long as your body doesn't

57:41

reject it, then yes you have you

57:43

have brand new bone marrows, so you no longer

57:45

make these sickled cells. You could still

57:47

pass that on, right, You would still

57:50

be able to if you had a kid, they could

57:52

have either sickle cell trait or

57:54

sickle cell anemia because but

57:57

but yeah, you would be cured. Yeah.

58:01

I think that's all

58:03

the major things I wanted to talk about for the biology.

58:07

Okay, gosh,

58:10

this is a big one.

58:11

It's a big one, Aaron.

58:14

Where did this come from? Why

58:16

does anyone have to live with sickle cell disease?

58:19

And what the heck is up with this mutation?

58:22

Tell me about it, Okay, as

58:24

soon as we take a short break. Okay,

58:55

So to tell

58:57

the history of sickle cell trait and

59:00

sickle cell anemia. For

59:02

this, I'm going to concentrate primarily on

59:04

the HB S form,

59:06

not talk about thalacmia. This is just about

59:08

sickle cell anemia and sickle cell trait. I

59:11

think that the best place to start is in

59:13

the name itself, because,

59:16

aside from being one of my favorite things

59:18

to learn about and talk about for any

59:20

disease, it can also be incredibly

59:23

revealing, especially in the case

59:25

of sickle cell because the

59:28

name tells us not only what those

59:30

who named it saw and what was important

59:33

to them in describing this disease, but

59:35

it also makes us consider what

59:37

discovery is like, what does discovery

59:40

mean, and how often that term is

59:42

misapplied to something that could

59:45

more accurately be called a development.

59:47

Ooh.

59:49

So, when

59:51

the term sickle cell anemia was first used

59:53

by Western medicine in nineteen twenty

59:55

two, named by doctor Verna

59:58

Reem Mason, the medical

1:00:00

field was still in the midst of

1:00:02

this big rush of new technology

1:00:05

and new theories and new hypotheses

1:00:07

that led to enormous leaps forward in

1:00:09

the understanding of disease, both

1:00:12

infectious and non infectious,

1:00:15

and with huge improvements in microscopic,

1:00:19

surgical and other medical

1:00:21

tools, physicians could now

1:00:23

get a much more detailed look at what was

1:00:25

going on inside the human body, and

1:00:28

among other things, this led to a shift

1:00:30

in how diagnoses were made so

1:00:33

previously doctors may

1:00:35

have had to rely solely on symptoms

1:00:37

of disease as described by the patient, but

1:00:40

with these new tools, it allowed for

1:00:43

measurements and observation. So

1:00:45

the art of medicine was becoming a science,

1:00:47

and this is something that we've kind of talked

1:00:49

about before. Yeah,

1:00:52

And the vast increase in

1:00:54

knowledge of medicine

1:00:56

and the human body also changed

1:00:59

the medical field in terms of specialization

1:01:02

because with the volume of

1:01:05

information that was growing day by

1:01:07

day, it was nearly impossible for

1:01:09

one person to learn it all and

1:01:11

retain it all, and

1:01:13

so there was not only the capacity,

1:01:16

but also the need for specialists in

1:01:18

certain fields. Okay, interesting,

1:01:21

and so both of these shifts were enormously

1:01:23

beneficial to the people being treated because

1:01:26

with an accurate diagnosis, you had

1:01:28

a greater chance of getting appropriate treatment

1:01:30

and care. But there

1:01:32

were also some unintended consequences.

1:01:36

So in some ways, medicine became

1:01:38

more about the body and less about the

1:01:40

person, and the

1:01:42

heightened attention paid to measurements

1:01:45

or direct observation could sometimes take

1:01:47

away from the experience of the person

1:01:49

receiving treatment, and this is

1:01:51

reflected in the naming of sickle

1:01:53

cell anemia.

1:01:56

As you mentioned, The term sickle

1:01:58

cell describes the shape of the

1:02:00

affected cells, which is a direct

1:02:02

result of the mutated allele, and

1:02:04

it was given that name by the physicians who

1:02:06

first observed these types of cells under

1:02:08

a microscope. But the

1:02:11

condition, the experience of sickle

1:02:13

cell anemia had been known long

1:02:15

before the nineteen hundreds, thousands

1:02:18

of years before, and people

1:02:20

who lived in areas of high prevalence,

1:02:23

notably in parts of Africa, had names

1:02:25

for the disease as well.

1:02:28

And I have a list of these names,

1:02:30

but I don't want to butcher them

1:02:33

entirely. But one of the commonalities

1:02:35

of these names is that they have sort

1:02:38

of this onomatapia, this

1:02:40

automatapoetic like rhythm

1:02:42

to them, And that's because

1:02:45

it represented the repetitive,

1:02:47

gnawing pain of sickle cell anemia rather

1:02:49

than the cellular morphology, right.

1:02:52

So it's like a description of what people were going

1:02:54

through, not just exactly this what

1:02:56

the cell looks like, exactly fascinating.

1:02:59

And there was also another name that was reported

1:03:01

in the African medical literature in the late eighteen

1:03:04

hundreds. It was a term

1:03:07

agwanges, meaning children

1:03:09

who come and go, which is in reference

1:03:11

to the high childhood mortality. Yeah,

1:03:14

and so yeah, these names describe someone's

1:03:16

experience with the disease and perhaps

1:03:19

how they would define it, rather

1:03:21

than a cellular observation which was completely

1:03:24

removed from the experience. I mean,

1:03:26

if you think about it, if you have sickle cell anemia,

1:03:28

you are probably familiar with these extremely

1:03:31

painful episodes characteristic of the disease,

1:03:34

but you may have never seen your own sickle

1:03:36

shaped cells under a microscope. Right,

1:03:39

So I just think that was a very yeah.

1:03:42

Oh, I love that, Aaron. That's so

1:03:44

so interesting and important, and

1:03:46

I don't think I ever would have thought about about

1:03:48

it, quite honestly.

1:03:49

Well, and this is not my observation,

1:03:51

this is something I've read in a book, but I

1:03:54

think it also it did make me think about other

1:03:56

diseases that we have talked about. And you

1:03:58

know, there is a lot of me in a name, whether

1:04:00

it's a specific to a location and we've talked

1:04:03

about the issues with that, and or

1:04:05

whether it's these this very clinical, detached

1:04:08

way, objective way of looking at

1:04:10

a condition. And

1:04:13

I think that. I mean, there are some other ones that

1:04:15

have that are more about the experience

1:04:17

itself, like Dengey, I remember, may

1:04:20

have some link to the painful

1:04:22

bone breaking sensation.

1:04:25

But yeah, it's a.

1:04:27

That's very interesting.

1:04:28

It's interesting.

1:04:29

Yeah.

1:04:30

And also, as the author

1:04:33

of one of the books I read pointed out,

1:04:36

the sharp contrast between the visible,

1:04:38

the sickle shaped cells, and the invisible

1:04:41

the excruciating pain endured

1:04:44

in the various names of sickle cell anemia.

1:04:46

In many ways, it mirrors

1:04:49

the history of the disease, particularly throughout

1:04:51

the twentieth and twenty first centuries in

1:04:54

the US. Oh Okay,

1:04:57

So, though there were some brief

1:05:00

descriptions of what was likely sickle

1:05:02

cell anemia since the eighteen hundreds the

1:05:04

mid eighteen hundreds, the first clinical

1:05:06

description of the disease was made in nineteen

1:05:08

oh four by the University of Chicago

1:05:10

physician James Herrick, who

1:05:13

reported quote peculiar elongated

1:05:15

and sickle shaped red blood corpuscles

1:05:18

in a twenty year old patient

1:05:21

of his named Walter Clement Nole,

1:05:23

who was originally from Grenada and

1:05:25

the only person of African descent

1:05:28

to be accepted into the Chicago College of

1:05:30

Dental Surgery that year.

1:05:31

Wow.

1:05:32

Yeah, so Noel had some I

1:05:35

don't know if it's Noel or Nol. So I'm just saying Noel.

1:05:39

Noel had some ulcers on his leg

1:05:41

and described painful episodes

1:05:43

and other symptoms of anemia, and

1:05:46

so Herrick drew some blood and gave it to his

1:05:48

interurn named Ernest Irons to check

1:05:50

it out, and Irons made the

1:05:52

actual observation like that

1:05:55

description, but Herrick reported

1:05:57

his findings at a conference in nineteen

1:05:59

ten, and then Irons was

1:06:02

given no credit as per USh

1:06:04

as per usan And

1:06:06

although Walter Clement Knole recovered

1:06:09

from his illness after his visit to Herrick,

1:06:11

he did die at a young age

1:06:13

at thirty two of pneumonia

1:06:16

twelve years after that visit. And

1:06:18

this first description of sickle cell anemia

1:06:21

was closely followed by many others

1:06:23

who noted that it primarily affected

1:06:25

black Americans of African descent. These

1:06:28

were all American physicians, and that complications

1:06:31

arising from the condition often led

1:06:33

to death at an early age. And

1:06:35

despite these warning bells going hey,

1:06:38

we have a serious disease here on our hands.

1:06:40

Maybe we should learn more about it and how

1:06:42

to treat it, sickle cell anemia remained

1:06:45

largely invisible for a couple of decades

1:06:47

before finally gaining some recognition in the nineteen

1:06:50

thirties. Wow. Okay,

1:06:52

so why was sickle

1:06:54

cell anemia obscured

1:06:56

for so long? I think

1:06:59

many reasons. Yeah.

1:07:03

Part of it was the

1:07:05

pre antibiotic high prevalence

1:07:07

of acute infectious diseases, and also

1:07:09

pre vaccine, some of which

1:07:11

mimicked the symptoms of sickle celenemia,

1:07:14

such as malaria, and made it more difficult

1:07:16

to see this disease underneath.

1:07:19

And when antibiotics, vaccines,

1:07:22

and infectious disease control policies

1:07:24

were implemented in the

1:07:26

early decades of the twentieth century, other

1:07:29

chronic diseases became much more visible.

1:07:32

So it was like kids were just getting sick and

1:07:34

dying from sickle cell anemia before

1:07:36

they knew that it was because of sickle cell anemia

1:07:39

exactly. Okay, that makes sense exactly.

1:07:42

But of course, the other

1:07:45

enormous component was the inherent racism

1:07:47

in medicine.

1:07:48

Yeah.

1:07:49

Higher rates of disease, higher infant

1:07:51

mortality, and lower life expectancies

1:07:53

overall in Black Americans compared to

1:07:55

white Americans was dismissed

1:07:58

by the vast majority of those in the medical field,

1:08:00

which of course were primarily white,

1:08:03

as either evidence for a biological

1:08:05

basis of race or they

1:08:07

said, oh, that this is just indicating

1:08:10

that, you know, there's large,

1:08:12

widespread ignorance of medical practices.

1:08:15

Oh and essentially

1:08:17

the fact that Black Americans faced

1:08:19

worse health outcomes was seen as

1:08:22

normal, as an inevitability.

1:08:24

I would say, unfortunately, that still

1:08:26

is the bias in medicine.

1:08:28

Oh yeah, oh yeah, yeah. And

1:08:31

this false concept

1:08:33

of racial superiority in biology is so

1:08:35

longstanding and insidious

1:08:38

and is still, like we talked about,

1:08:40

very present today in medicine. So,

1:08:43

following the American Civil War, some opponents

1:08:46

of emancipation claimed that the black

1:08:48

race would die out and that the high rates of disease

1:08:50

and poverty among black

1:08:52

people were evidence that enslavement was

1:08:55

a good thing. And these

1:08:57

paternalistic beliefs bled

1:08:59

into policy policies

1:09:01

which were designed to uphold these divisions

1:09:04

of class and privilege and prevent any

1:09:06

movements across those invisible but

1:09:08

very real lines. In

1:09:10

addition, there was the bigger issue of how

1:09:13

risks of disease overall were perceived.

1:09:15

So in much of the American South, for instance, discussions

1:09:18

about disease were framed as

1:09:20

the dangers posed by black

1:09:22

people, rather than the dangers the

1:09:25

diseases posed to black people.

1:09:27

Wow.

1:09:28

So this is something that, like I've talked about before

1:09:30

in the context of syphilis, to berculosis,

1:09:33

hookworm, and so on. So high

1:09:35

rates of disease among black people were not

1:09:37

seen as worrisome because they were directly

1:09:40

damaging the health and shortening

1:09:43

life expectancy of black people. It was more, oh,

1:09:45

well, we don't want white people to get sick

1:09:47

from black people. So that is where the

1:09:49

focus primarily was.

1:09:52

How can we prevent white people from getting sick

1:09:54

with what the black people have? Exactly

1:09:56

yeah, exactly yeah.

1:10:00

And this shaped policy and attitudes toward

1:10:02

public health and access to health care. Basically,

1:10:05

the only way a public health policy was

1:10:08

going to be enacted or research funds

1:10:10

awarded was if the disease affected

1:10:12

or threatened to affect white Americans

1:10:14

in some way, okay.

1:10:17

And so when antibiotics and vaccines became

1:10:19

more widely available throughout the nineteen thirties

1:10:21

and forties, the widespread prevalence

1:10:24

of chronic diseases such as sickle cell

1:10:26

anemia was revealed. At

1:10:30

the same time, the commodification

1:10:32

of health and people's bodies had

1:10:34

really ramped up. And

1:10:36

what I mean by that is that basically,

1:10:39

alongside the medical developments of the

1:10:41

late nineteenth century and early twentieth

1:10:43

century, people's health and

1:10:46

bodies began to be assigned a monetary

1:10:48

value. How much did this procedure

1:10:50

cost, how much did that medicine cost,

1:10:53

how much did someone's poor health limit

1:10:55

their productive output?

1:10:57

Disability adjusted life years and yep.

1:11:00

Right.

1:11:01

The medical profession contributed

1:11:03

to this, not just through the exchange

1:11:05

of money for treatment, but also

1:11:07

by assigning intrinsic values

1:11:09

to certain conditions. People

1:11:12

with rarer diseases were seen as valuable

1:11:14

to the medical profession. Hospitals

1:11:17

in poverty stricken, densely populated

1:11:19

urban areas were considered to be great

1:11:21

places to get experience in training

1:11:23

as a medical student, and

1:11:26

the term clinical material was frequently

1:11:28

used as a way to

1:11:31

even further remove the

1:11:33

person from the medical experience,

1:11:36

as in whatever general hospitals

1:11:38

supplied an adequate amount of clinical

1:11:40

material to train students at not one,

1:11:42

but two medical schools.

1:11:44

I'm sorry, so that means clinical material meaning

1:11:47

humans? Humans?

1:11:48

Yeah, humans, or like different

1:11:51

cases or like different surgeries.

1:11:53

I mean, and this is like still,

1:11:56

this is still today.

1:11:57

People.

1:11:58

It's very much like, oh, you should do

1:12:00

you should you get experience there because you're

1:12:02

likely to see more of these diseases.

1:12:05

The amount of times I heard, oh, we've got really

1:12:07

interesting pathology at this residency

1:12:10

program, I'm like, Wow, that's horrible

1:12:13

for the people in that area, but yeah,

1:12:15

yeah.

1:12:17

And employers also played

1:12:19

a large role and continue to play

1:12:21

a large role in the commodification of

1:12:23

health. Maximize profits and productivity

1:12:26

by ensuring that your employees are well

1:12:28

enough to work, and of course, if your

1:12:30

health can't be improved, consider dropping them.

1:12:33

Against this backdrop of this

1:12:36

enormous growth of medical knowledge, reduction

1:12:38

of infectious disease, and commodification

1:12:40

of health and disease awareness

1:12:43

of sickle cell anemia rose greatly,

1:12:46

and in the coming decades this fame

1:12:48

would grow to become in some ways a double

1:12:50

edged sword. So on the one

1:12:53

hand, the adoption of sickle cell anemia

1:12:55

throughout the nineteen fifties, sixties

1:12:58

seventies as a cause by many

1:13:00

social groups and the increase in research

1:13:02

funding for it led to a great deal

1:13:04

of important knowledge being gained and

1:13:07

in a raising awareness overall. Researchers

1:13:10

fascinated by the puzzle that the disease posed

1:13:13

not necessarily by the people experiencing

1:13:16

the disease, they

1:13:18

had uncovered that certain conditions

1:13:20

like low oxygen and high acidity could

1:13:23

induce sickling of cells, and they had

1:13:25

also observed that sickling could also result

1:13:27

in people who did not have the disease

1:13:29

but were relatives of those that did. In

1:13:32

nineteen forty nine, two papers published

1:13:35

nearly simultaneously by doctor James

1:13:37

Neil and Colonel ea Beat presented

1:13:40

the hypothesis that the disease was

1:13:42

an autosomal recessive trait, meaning

1:13:45

that it was inherited, and like

1:13:47

you said, the two copies were required for

1:13:49

disease to be present. I

1:13:51

also want to note that,

1:13:53

once again discovery versus development,

1:13:56

that the inheritability of

1:13:58

sickle cell anemia had long recognized

1:14:00

in some groups where the disease was especially

1:14:03

prevalent, such as among certain populations

1:14:05

in GHANAA makes sense. Yeah.

1:14:08

And also in nineteen forty nine, doctor

1:14:10

Harvey Etano and doctor Linus Pauling

1:14:12

demonstrated that the sickling was caused

1:14:15

by an abnormality in the hemoglobin

1:14:17

molecule, prompting them to call

1:14:20

it a molecular disease. I think it might

1:14:22

actually be the first disease described

1:14:24

as a molecular disease. A few

1:14:26

years later, the individual amino acid

1:14:28

substitution leading to the structural change

1:14:30

in hemoglobin was identified, teaching

1:14:33

researchers that that single mutation

1:14:36

could be responsible for this whole suite

1:14:38

of systemic effects on the body.

1:14:40

Yeah, which is pretty incredible.

1:14:42

Oh yeah. But a huge shift

1:14:44

in the notion or representation of sickle

1:14:47

cell trait or that sickle cell that

1:14:49

mutated allele as a disease condition

1:14:51

came about with the hypothesis first

1:14:54

floated in like the mid nineteen forties that

1:14:56

the sickle cell trait so again, one

1:14:58

copy of that mutated actually

1:15:01

provided a level of protection against

1:15:03

the falciparum malaria parasite,

1:15:07

giving insight into why the

1:15:09

allele was present at relatively high

1:15:11

rates despite its deliterious effects.

1:15:15

And so this is an example of what is

1:15:17

called a balanced polymorphism. And

1:15:20

this turned the the dichotomy

1:15:22

or this long standing dogma of normal

1:15:25

equals good and abnormal equals bad

1:15:28

on its head.

1:15:28

Yeah, it's why the term normal is

1:15:31

stupid.

1:15:32

Yeah, it's it's

1:15:35

yeah, it's it's inadequate.

1:15:37

It doesn't, it doesn't. I mean, what is normal?

1:15:40

Like it?

1:15:40

That's not it? And sometimes

1:15:42

it's hard, like I'm like, I don't I don't know what other word

1:15:45

to use, but that it's not a good word.

1:15:48

I know, because we need to improve our vocabulary.

1:15:51

Yeah for that. So,

1:15:55

but these these scientific breakthroughs,

1:15:57

particularly in its labeling as

1:16:00

a molecular disease, and all the

1:16:02

hype that that generated, it

1:16:04

got a lot of researchers super excited

1:16:08

to jump on the sickle cell train, which

1:16:10

was also pulled forward

1:16:13

by the increasing interconnectedness of hospitals,

1:16:15

research institutions, public health departments,

1:16:18

and outreach groups. And

1:16:20

this wealth of new information about the nature

1:16:22

of sickle cell trait and sickle cell anemia

1:16:25

did not, though necessarily,

1:16:27

translate directly into lives

1:16:29

saved, because in much of

1:16:31

the South, racial segregation still

1:16:33

prohibited Black Americans from seeking

1:16:36

care at the highest funded

1:16:38

hospitals, which were of course

1:16:40

white only.

1:16:41

Yeah wow.

1:16:43

In addition, and here comes the

1:16:46

other side of that double edged sword.

1:16:48

Despite these advancements in the understanding

1:16:50

of the disease outside

1:16:52

of academia, such as

1:16:54

in political discussions or debates,

1:16:57

clear knowledge about the exact nature

1:16:59

of cell anemia lagged far

1:17:01

behind, especially in understanding

1:17:03

the difference between sickle cell trait and

1:17:06

sickle cell anemia. For

1:17:08

instance, during World War Two, a

1:17:11

controversial debate arose

1:17:14

about whether sickle cell trait, so

1:17:16

having the one copy posed a

1:17:18

threat to the health of soldiers who

1:17:20

had the trait, in other words, posed a

1:17:22

threat to war efforts. Oh gosh, suddenly

1:17:26

this disease that had been invisible for so long

1:17:28

was now visible and could be used to discriminate

1:17:31

against those with the disease or

1:17:33

even just the trait. After

1:17:36

four people in the Marine Corps with sickle cell trait

1:17:38

died after a training exercise at a high

1:17:40

elevation, strict limits

1:17:42

were placed on whether those with sickle cell trait

1:17:45

could become pilots either in

1:17:47

the armed forces or commercial airlines,

1:17:49

or hold other positions. So not

1:17:52

just in armed forces, so there was like a

1:17:55

huge, huge restrictions

1:17:57

placed on that, but also in other

1:17:59

parts of the workforce, so like flight attendants.

1:18:02

There was a lot of issues with health

1:18:04

insurance carriers dropping people who

1:18:07

were found to have sickle cell trait or

1:18:09

sickle cell anemia.

1:18:10

Oh my god.

1:18:13

And so these restrictions were

1:18:15

instances of racial discrimination, since

1:18:17

the overwhelming majority of those forbidden

1:18:20

from entering the armed forces, for instance, due

1:18:22

to sickle cell trait were black, and

1:18:24

class action lawsuits led

1:18:27

to the removal of some of these restrictions,

1:18:29

but only decades after they were first put in

1:18:31

place.

1:18:31

Oh my god.

1:18:32

But of course, just because restrictions

1:18:34

are gone does not mean the racial discrimination and

1:18:37

the workplace was gone. And

1:18:39

whether it was because the parent of a child with

1:18:42

sickle cell anemia was more likely to miswork

1:18:44

or if they themselves were affected, there

1:18:46

was simply no shortage of ways for people

1:18:48

to be discriminated against.

1:18:52

Into the nineteen sixties and nineteen

1:18:54

seventies, sickle cell trait and sickle cell

1:18:56

anemia moved or was pulled

1:18:59

even for into the spotlight in

1:19:02

academic circles. Sickle cell became the focus

1:19:05

of narratives that interwove of biology,

1:19:07

anthropology, and history to explain

1:19:10

whatever story was the goal of the

1:19:12

author, and these narratives were

1:19:14

sometimes criticized for their tendency to make

1:19:17

sweeping generalizations about

1:19:19

entire groups of people or entire places,

1:19:23

or for forcing the facts to fit the

1:19:25

story, making it sort of a just so story.

1:19:28

Other researchers finally began talking about

1:19:30

how sickle cell disease and inadequate

1:19:33

medical care may lead to poverty

1:19:35

rather than poverty being the cause of disease

1:19:37

and ill health, and understanding

1:19:40

the more of the cycle of poverty

1:19:43

and access to healthcare. And

1:19:45

in the socio political sphere, sickle cell

1:19:47

disease took on new meaning during the civil

1:19:50

rights movement of the nineteen sixties. It

1:19:52

was held by some civil rights groups to be

1:19:55

symbolic of the long standing invisible

1:19:57

or ignored pain and suffering experience

1:20:00

by so many who had long been racially

1:20:02

discriminated against and whose

1:20:04

access to healthcare had always been restricted.

1:20:08

Despite the increased awareness of sickle

1:20:10

cell, it's still lagged behind

1:20:12

other genetic diseases in terms

1:20:15

of funding, particularly those that disproportionately

1:20:17

affected white people, such as cystic fibrosis.

1:20:20

Oh yeah, So, For example, in nineteen

1:20:22

sixty seven, there were roughly the same

1:20:25

new number of cases of cystic fibrosis

1:20:27

and sickle cell anemia, but the difference

1:20:30

in funding from volunteer organizations

1:20:33

was staggering. For

1:20:35

cystic fibrosis, these organizations

1:20:37

raised one point nine million dollars,

1:20:40

and for sickle cell that number was fifty

1:20:43

thousand. Uh.

1:20:45

Do you want some current numbers or do you want me to tell

1:20:47

you those later?

1:20:48

Because tell me those later but I'm yeah,

1:20:50

I'm sure that they're not any better at all. Yep,

1:20:52

yep. But there

1:20:55

was a lot of charitable work

1:20:57

being done and awareness

1:20:59

efforts that were made. So the

1:21:01

Black Panther Party, among other groups, organized

1:21:04

and created a massive network of healthcare

1:21:06

centers across the country where one

1:21:08

of the goals was to raise sickle cell awareness

1:21:11

and funding. Doctor

1:21:13

Charles Witten, for whom our drink is named,

1:21:16

started the Sickle Cell Detection and Information

1:21:18

Center in Detroit in nineteen seventy one and

1:21:21

also helped found the Sickle Cell Disease

1:21:23

Association of America, which

1:21:25

has been instrumental not

1:21:27

only in their educational efforts, but also

1:21:30

in assisting families who have been impacted

1:21:32

by sickle cell disease. And

1:21:34

also he did a lot of work in terms of lowering barriers

1:21:37

for people who were underrepresented in medicine

1:21:39

to be able to go

1:21:41

to medical school and have that as an option.

1:21:45

Federal funds also poured in as

1:21:47

Nixon signed into law the Sickle Cell

1:21:49

Anemia Control Act in nineteen seventy

1:21:52

two, and so this act included

1:21:55

increased funds for research as

1:21:57

well as healthcare for those impacted.

1:21:59

It also required genetic

1:22:01

screening to be voluntary rather than

1:22:04

mandatory, which had

1:22:06

been a huge issue previously

1:22:08

because that just like paved the way for

1:22:11

discrimination, and

1:22:14

it also included support for reproductive

1:22:16

counseling. And

1:22:19

during the seventies our understanding

1:22:21

of the disease itself became more nuanced

1:22:23

as well. So first, new research

1:22:25

about the possible origins of the allele showed

1:22:28

that it likely emerged in four

1:22:30

different mutational events between

1:22:33

seventy one hundred and fifty thousand years

1:22:35

ago, three events that

1:22:37

took place in Africa and a fourth that took place

1:22:39

in either Saudi Arabia or Central India.

1:22:42

This allele emerged in different places

1:22:44

around the world, it's not just from one origin

1:22:47

event. Secondly, there was

1:22:49

the growing awareness of other hemoglobin disorders

1:22:52

and the fact that sickle cell trade was found

1:22:54

in non black people as well, which

1:22:56

threw some complexity into the discussion.

1:22:59

In the seventies, representation

1:23:02

of sickle cell anemia and popular media

1:23:04

also increased, as characters

1:23:06

with the disease were featured in a couple of movies

1:23:08

or TV episodes, and magazines

1:23:11

featured articles about the condition. But

1:23:14

once again, here comes the other side

1:23:16

of that double edged sword. Yeah,

1:23:19

The prominence of sickle cell anemia and

1:23:21

political discussions of this time meant

1:23:23

that some politicians felt as

1:23:26

though they could use the disease to symbolize

1:23:28

whatever they wanted to in

1:23:30

order to drive their own narrative about race

1:23:32

relations in the US, and

1:23:34

sometimes it was used. Sometimes that was used

1:23:37

to bring about real positive change, but

1:23:39

other times it was twisted to halt

1:23:41

forward progress. Let's take genetic

1:23:44

screening and reproductive counseling as an

1:23:46

example. Okay, the

1:23:48

push for genetic screening for sickle cell anemia

1:23:50

and sickle cell trait came at a time

1:23:53

when genetic screening in general

1:23:55

had greatly increased, and

1:23:57

when discussion of reproductive rights was at

1:23:59

the forefront, especially issues of

1:24:01

birth control and abortion. Genetic

1:24:04

screening to look for sickle cell trait or

1:24:06

sickle cell anemia, although it

1:24:08

was helpful in terms of getting people the medical

1:24:11

attention that they may need, it often

1:24:13

did an inadequate job of

1:24:16

explaining what exactly the difference

1:24:18

between sickle cell trait and sickle cell anemia

1:24:21

was. And this inadequate

1:24:23

explanation may have been unintentional

1:24:26

or intentional at times. It appears

1:24:29

so people who had the trait just

1:24:32

one copy of the allele, were often openly

1:24:34

discouraged from having children

1:24:37

and urged to have abortions or undergo

1:24:39

sterilization procedures

1:24:41

that were sometimes made free as an incentive.

1:24:44

Uh yeah.

1:24:47

And then the concept of mandatory screening

1:24:49

for this and other genetic disorders

1:24:52

was floated, and Linus Pauling,

1:24:54

the Nobel Prize winner and whose name I mentioned

1:24:56

earlier as being the scientist yep,

1:24:59

he suggests, did that everyone

1:25:01

who had the sickle cell trait should have it tattooed

1:25:04

on their forehead so that when they see

1:25:06

another person with the tattoo, they can avoid

1:25:08

falling in love and wanting to have children with

1:25:11

them. What mm hmmm

1:25:14

mm hmm.

1:25:15

Oh.

1:25:19

And these acts, these

1:25:21

discussions, of course, resulted

1:25:24

in accusations of restricting

1:25:26

black fertility, racial genocide, and

1:25:28

new eugenics. And rightfully, so.

1:25:31

Yeah, that's what sounds like to

1:25:33

me.

1:25:33

Oh yeah, And this misleading

1:25:36

reproductive counseling for sickle cell was

1:25:38

just one way that reproductive

1:25:40

restrictions were intentionally or forcefully

1:25:43

placed upon Black people. I

1:25:46

really recommend Killing the Black Body by

1:25:48

Dorothy Roberts to read more about that topic.

1:25:52

And so, before wrapping

1:25:54

up with the history of sickle cell in the nineteen

1:25:56

eighties and nineteen nineties. I want

1:25:58

to read a quote by the author of Dyeing in the City

1:26:00

of the Blues that I think does a really good

1:26:02

job of summing up the nineteen seventies

1:26:04

and sickle cell perfectly. The

1:26:07

story of sickle cell disease in the early nineteen

1:26:09

seventies also revealed the ways

1:26:11

in which the political process both channeled

1:26:14

and deflected the popular activism

1:26:16

of the time. It was a time

1:26:18

of grudging recognition of the black experience,

1:26:21

but it proved difficult to translate that awareness

1:26:24

directly into health policy without

1:26:26

creating enormous new, stigmatizing

1:26:28

burdens for Black Americans and without

1:26:30

fostering growing cynicism about racial

1:26:33

politics. Yep, yep.

1:26:36

And so that brings us to the nineteen eighties

1:26:38

and nineteen nineties. I don't want to step

1:26:41

on your toes too much, Aaron, about

1:26:43

whatever you're going to talk about. So I'm just going to go over

1:26:46

a few big developments or patterns

1:26:48

that emerge during this time with regard to sickle

1:26:50

cell that I

1:26:52

have a feeling you'll talk more about.

1:26:54

Okay, let's see.

1:26:56

Yeah, So, as you

1:26:58

mentioned pain management is a huge

1:27:00

component of sickle cell anemia, and

1:27:03

the sympathy for people with sickle

1:27:05

cell that seemed characteristic of

1:27:08

the nineteen sixties and nineteen seventies

1:27:10

kind of gave way to this disturbing trend

1:27:13

of cynicism and stigma.

1:27:16

More and more healthcare providers seem to

1:27:18

simply not believe that people with sickle

1:27:20

cell anemia were experiencing a true

1:27:22

painful episode, and

1:27:24

there were increasing reports of healthcare

1:27:27

providers accusing their sickle cell anemia

1:27:29

patients of faking it, of

1:27:31

exhibiting drug seeking behavior and

1:27:33

correspondingly limiting the pain medication

1:27:35

prescribed. And earlier,

1:27:38

when you talked about the different timeline of

1:27:40

when at different ages you experience

1:27:43

you're more likely to experience one symptom over another,

1:27:46

that the increase in

1:27:48

painful episodes in late adolescents

1:27:51

and early adulthood is something

1:27:53

that also made

1:27:55

this whole made this whole thing worse. They were like,

1:27:57

oh, well, you're a young adult, you're just seeking drugs,

1:28:00

not going to give you any Oh my god, And

1:28:02

this is you know, this is despite

1:28:04

the fact that there was research indicating

1:28:06

that this wasn't going on, that

1:28:08

people with sickle cell anemia were just as worried

1:28:11

about their own, you know, narcotic consumption

1:28:13

or pain medication consumption as

1:28:16

as anyone else. And it was it's

1:28:19

just like it didn't seem to

1:28:21

make a difference. Yeah, it's like it

1:28:23

seemed to be like this this belief that

1:28:25

became so embraced

1:28:27

and like so difficult to get rid of.

1:28:29

It's so frustrating that in so many papers

1:28:31

that you read, it's still something that is

1:28:33

mentioned like, oh, you often have

1:28:35

to use opioids to treat pain, which

1:28:38

can lead to addiction. It's like that's true

1:28:40

in anyone. And there's no higher rates

1:28:42

of opioid addiction in people with sickle cellinemia

1:28:45

than in the general population, Like there just

1:28:47

isn't. So it's it's infuriating

1:28:49

that you'd be like withholding treatment

1:28:51

that is necessary.

1:28:53

Ough.

1:28:54

Yeah, well, and there's also there was also something

1:28:56

that was mentioned in this book about how there was

1:28:58

research indicating that opioid

1:29:00

addictions starting from hospital

1:29:03

treatments or medical treatments is extraordinarily

1:29:06

low. That is not the way that the vast

1:29:08

majority of opioid addictions begin. And

1:29:10

so but despite all this, this

1:29:13

enormous bias still remains and this is

1:29:15

I mean, this is a larger

1:29:17

issue. Yeah, the invisibility

1:29:19

of pain in medicine.

1:29:22

We can't measure it, and I think

1:29:24

that that makes people trust

1:29:26

it less, trust the person less.

1:29:28

And it sort of goes back to what I was saying earlier

1:29:30

about how like medicine became more about the body

1:29:33

and measurements and these things that you could,

1:29:35

you know, you could put on a chart.

1:29:37

Then it became about the person's

1:29:40

experience itself.

1:29:41

Yeah.

1:29:41

So yeah, yeah,

1:29:43

but you know, in this context, what

1:29:45

this meant, this this increasing

1:29:48

you know, disbelief, was

1:29:50

that people with sickle cell anemia were at

1:29:53

renewed risk for their pain,

1:29:55

their experience to once again be neglected,

1:29:59

ignored, and made invisible.

1:30:02

And this persists today.

1:30:05

This issue and

1:30:07

these decades also brought the

1:30:09

promise of many different therapies for sickle

1:30:12

cell anemia, such as hydroxyurea

1:30:14

as you mentioned, and bone mirror transplantation, which

1:30:18

didn't necessarily uphold

1:30:21

the shiny promises that had been made about

1:30:23

them in their first introduction. But

1:30:26

I'm really hopeful to hear more

1:30:28

about new approaches.

1:30:31

But I want to end now again

1:30:33

with another quote, again from

1:30:35

Keith Wailu. The author of Dying in the City

1:30:37

of the Blues. For liberals,

1:30:40

moderates, and conservatives alike, the history

1:30:42

of neglect and the disease's chronic, painful

1:30:45

character seemed to reflect White America's

1:30:47

neglect and misunderstanding of black health concerns

1:30:50

and demanded attention. The disease

1:30:52

became a multipurpose metaphor a proxy

1:30:55

in social, economic, and political debates

1:30:57

about a wide range of seemingly unrelated

1:30:59

issues. Ye okay,

1:31:01

erin, bring me up to speed on what's

1:31:03

going on with sickle cell today.

1:31:05

Okay, let's take a quick

1:31:08

break first, all

1:31:41

right, So we'll

1:31:44

talk first about numbers,

1:31:47

how many people are being affected

1:31:49

by sickle cell in

1:31:51

the US and in the world today, and

1:31:53

then we'll touch a little bit more on why

1:31:56

that is and the malaria connection, because

1:31:58

I do think that's a really interesting part of the story.

1:32:01

And then we'll talk about current research.

1:32:04

Does that sound good?

1:32:05

Sounds great?

1:32:06

Okay? So we'll talk

1:32:08

first about the US and then globally.

1:32:13

So in the US, newborn

1:32:15

screening is conducted since two thousand and six

1:32:17

or two thousand and seven across the board in all

1:32:19

states plus Puerto Rico, and the US Virgin Islands,

1:32:23

so we know the rates of sickle

1:32:25

cell allele in the population. So

1:32:28

one copy having one copy of the sickle

1:32:30

cell trait okay. So

1:32:33

overall in the US in twenty

1:32:35

ten, the incidence was fifteen

1:32:38

per one thousand babies born trait

1:32:41

trait okay. But this

1:32:43

is a huge range, from seventy

1:32:45

three per one thousand among black

1:32:48

newborns to

1:32:50

two per one thousand

1:32:52

in Asian, Native, Hawaiian and Pacific

1:32:54

Islander newborns, three

1:32:57

in white babies, and seven

1:33:00

per one thousand in Hispanic newborns.

1:33:03

And this is voluntary or mandatory

1:33:06

screening.

1:33:06

So newborn screening is generally it's

1:33:09

universal. I think it is

1:33:11

possible to opt out of it, but

1:33:14

in general it's universal and kind

1:33:16

of recommended. I think most of the time they

1:33:20

don't want to let you leave the hospital without newborn

1:33:22

screening because it doesn't

1:33:24

only screen for sickle cell. This screen's for a whole

1:33:26

bunch of different We talked about

1:33:29

this in the cystic fibrosis episode

1:33:31

as well, right right, because

1:33:33

you're also identifying then those newborns

1:33:36

with sickle cell anemia. But what's interesting

1:33:38

is that it's actually hard to get a number

1:33:40

on the number of babies in

1:33:42

the US born with sickle cell anemia,

1:33:45

which I think is interesting. So let's talk about the

1:33:47

whole globe. How many people are born every

1:33:49

year with sickle cell anemia globally.

1:33:53

Estimates are about three hundred

1:33:55

thousand, just over three hundred thousand babies

1:33:58

born every year with sickle cell

1:34:00

anemia.

1:34:01

That's a huge number.

1:34:03

It's a massive number, and

1:34:05

I want to point out that that number is

1:34:08

the number of babies born with sickle

1:34:11

cell HBSS.

1:34:14

But remember that there are other ways

1:34:16

that you can have sickle cell anemia, right.

1:34:18

You could have it with one copy of HBS

1:34:21

and one copy of beta thalacemia. You

1:34:24

could have it with one copy of HBS

1:34:26

and one copy of HBC. Those

1:34:30

aren't included in that estimate of three

1:34:32

hundred thousand. So it's

1:34:34

thought that that total number accounts for about

1:34:36

seventy percent of the total amount of sickle

1:34:39

cell disease, so that whole range

1:34:41

of clinical disease worldwide.

1:34:45

And it's also estimated that

1:34:47

about half of these babies worldwide

1:34:50

are born in Nigeria, the

1:34:52

Democratic Republic of Congo, and

1:34:54

India, and

1:34:57

that in many parts of Sub

1:34:59

Saharan Africa, sickle

1:35:01

cell anemia might be responsible

1:35:04

for as much as six percent

1:35:06

of all childhood mortality.

1:35:09

Six percent, Oh my god,

1:35:11

just from sickle cell anemia. Because in

1:35:14

many places, in many parts of the world,

1:35:17

under five mortality from sickle cell anemia,

1:35:20

so dying before your fifth birthday can be

1:35:22

as high as fifty to ninety

1:35:24

percent, which is atrocious.

1:35:27

Wow.

1:35:28

Yeah, wow, yeah

1:35:32

yeah. And that's because if

1:35:34

babies aren't identified by newborn

1:35:36

screening, then they don't receive

1:35:39

penicillin prophylaxis, or they

1:35:41

don't receive adequate vaccinations,

1:35:43

then it's very common that they will die from

1:35:46

overwhelming infection before they turn

1:35:48

five. So that's why

1:35:50

newborn screening is so important and

1:35:52

has been so helpful. Like it's

1:35:54

only worth screening if you can do something

1:35:56

about it, right, So we screen for things that we

1:35:58

can prevent death

1:36:01

if we identify them early. And so that's

1:36:03

what we can do with newborn screening.

1:36:05

Yeah, I think it's just been It's like

1:36:07

I mean, and this is in general. Newborn

1:36:09

screening or any kind of genetic screening

1:36:12

is such a touchy issue because it

1:36:14

can so easily lead to you know, who

1:36:17

has that information and how can I use it against

1:36:19

you absolutely.

1:36:21

I mean, plus it gets into so many things

1:36:23

of So if you identify a newborn

1:36:25

with a genetic trait, that

1:36:28

had to come from either mom or

1:36:30

dad, right, so now

1:36:32

you know that either mom or dad has this. Maybe

1:36:34

they didn't want to know that. Like, there's a whole the

1:36:37

ethics of all of that is wide

1:36:39

ranging and more than we can talk about in this episode.

1:36:42

Yes, but identifying babies

1:36:44

with sickle cell anemia prevents them from dying,

1:36:47

So in that way it's extremely important

1:36:49

and helpful. But despite

1:36:51

the fact that this is a very common

1:36:54

disease and a very common trait

1:36:56

among the population, like

1:36:59

you said, funding discrepancies remain,

1:37:02

which is why to date we have only

1:37:05

one disease modifying treatment,

1:37:08

that is hydroxyurea. So

1:37:10

I want to talk I want to give some more specific numbers.

1:37:13

You mentioned them from I think the sixties and seventies,

1:37:16

so let's talk about the last decade,

1:37:18

from two thousand and eight to twenty eighteen.

1:37:20

Is that I was hoping you would do this.

1:37:22

This paper just came out in March of this year. So

1:37:26

we'll compare federal funding per

1:37:29

person between cystic fibrosis,

1:37:31

which we did an episode on and sickle

1:37:34

cell disease. So, cystic fibrosis is another

1:37:36

genetic disorder. It's also identified

1:37:38

on newborn screens. It's also like

1:37:40

the most common genetic disorder among white

1:37:42

babies. So compared

1:37:45

with cystic fibrosis,

1:37:48

per person with the disease. In

1:37:50

the US, cystic fibrosis received

1:37:52

two thousand, eight hundred dollars

1:37:55

in federal funding compared

1:37:57

to eight hundred for sickle cell.

1:38:00

Wow, that's two thousand dollars

1:38:02

more. And it's even worse if you look

1:38:04

at charitable foundation expenditures

1:38:07

cystic fibrosis seven

1:38:09

thousand, six hundred dollars

1:38:12

per person with cystic fibrosis

1:38:14

compared to one hundred.

1:38:16

Oh my god, oh my for sickle

1:38:18

cell.

1:38:20

Which I mean this directly leads

1:38:23

to a discrepancy in the

1:38:25

number of new drug approvals. In

1:38:27

that same time period, four new drugs were

1:38:29

approved for cystic fibrosis, one for

1:38:32

sickle cell.

1:38:33

I mean, it just it just trickles down and down

1:38:35

and down. Like you have the research

1:38:38

money, you have treatment accessibility,

1:38:40

you have new treatments being developed, you have healthcare,

1:38:43

access to healthcare, like all of these different components

1:38:46

to it, which is yeah.

1:38:48

And so to put like a specific number two

1:38:50

on the difference in terms of overall

1:38:52

prevalence of sickle cell versus

1:38:55

cystic fibrosis in the US. This paper

1:38:57

reported the US birth rate of stickle

1:38:59

cell disease is one

1:39:01

in three hundred and sixty five black

1:39:04

babies. For cystic

1:39:07

fibrosis, it's one. It's very

1:39:09

high. That's scary high. For cystic

1:39:12

fibrosis. It's one in twenty

1:39:14

five hundred white babies, which

1:39:17

is also you could say, very high, but

1:39:20

one in three sixty five is a lot higher.

1:39:23

But yeah, when you when you put the numbers side

1:39:25

by side, it is very I

1:39:28

mean, it's not surprising, but it is appalling

1:39:30

that I know there's such unequal support,

1:39:33

yeah, funds.

1:39:34

And so I think it kind of leads

1:39:36

to a really important question about

1:39:39

why is it that this is such a prevalent

1:39:41

disease. Because a lot of times when we have genetic

1:39:43

diseases that are recessive,

1:39:46

so you have to have two copies of that allele

1:39:50

in theory evolutionarily that

1:39:52

that allele that mutation should die

1:39:54

out right if it's so bad that if

1:39:57

you have two copies of it you end up dying before

1:39:59

the age of five, You're not going to be

1:40:01

reproducing, so you're not going to be passing on that

1:40:03

allele. So why is it at such high

1:40:05

prevalence in the black

1:40:07

population. Here's

1:40:10

why, or at least what

1:40:12

we think. It

1:40:15

turns out that if you have one copy

1:40:17

of this allele, it's very protective

1:40:19

against dying from malaria.

1:40:23

It's very protective against infection

1:40:26

severe infection with Plasmodium

1:40:28

falciparum malaria. So

1:40:31

in regions where Plasmodium falciparum

1:40:33

malaria, so that one species of malaria

1:40:35

is very very prevalent, the

1:40:38

prevalence of this specific

1:40:40

mutation is also very prevalent.

1:40:43

What I think is so interesting is like this

1:40:46

has been kind of an epidemial. We've shown this epidemiologically

1:40:49

in so many many studies

1:40:52

just how massive the protection is. But

1:40:55

there's still not a clear molecular

1:40:57

answer as to how one

1:41:00

copy of this allele protects you against

1:41:03

dying from malaria. Overall,

1:41:05

it seems like if you have some of

1:41:07

that HBS beta

1:41:10

hemoglobin, then your

1:41:12

cells can eventually sickle, and then

1:41:14

those cells that are infected

1:41:16

with plasmodium, the plasmodium doesn't

1:41:19

replicate, so essentially malaria can't

1:41:21

grow as well in those cells for

1:41:24

like a number of different reasons that we still

1:41:26

don't fully understand.

1:41:27

Right, But it's it's only in the cells that have