Speaker 1: My name's Marsha.
Speaker 2: I lived in the UK, as you can tell by
Speaker 2: my accent, and I pad super cell for the longest
Speaker 2: time I can remember.
Speaker 3: My parents found out when I was about six years old.
Speaker 3: My mom knew she had the trade, but my dad
Speaker 3: didn't know that he carried the trade. And obviously my
Speaker 3: older sister was born and she just had a trade.
Speaker 3: So it was my mom was like, okay, fine, and
Speaker 3: she got that from me. But when I came about,
Speaker 3: I was born with another sort of illness on top
Speaker 3: of sickle cell, which is called the six deficiency, so
Speaker 3: it kind of mossed the sickle cell. So over the
Speaker 3: many years growing up, I was like becoming sick.
Speaker 1: They couldn't quite work out. And then it was when
Speaker 1: my younger.
Speaker 3: Sister was born they said, you know, let's be tested
Speaker 3: for sickle cell, and that's when they found out that
Speaker 3: I had the full blown disease. I kind of understood
Speaker 3: I had an illness much later on.
Speaker 1: I would say, when I was about nine eight or nine.
Speaker 3: Yes, I went to hospital appointments prior to that, but
Speaker 3: it just didn't really sunking. I kind of let my
Speaker 3: parents deal with it all, like, okay, well you.
Speaker 4: Manage my health.
Speaker 1: I managed being a child and playing with my friends
Speaker 1: and stuff like that.
Speaker 3: I didn't really understand it too, I think as I
Speaker 3: went later on in my teenage years, when I went
Speaker 3: started going to secondary school, that's when I started taking
Speaker 3: more control over my illness and saying, Okay, well, you know,
Speaker 3: I have to eat right, I have to dress right,
Speaker 3: I have to make sure I get enough rest, and
Speaker 3: you know, not overstress myself because I know if I don't,
Speaker 3: these things can trigger off a crisis and I can
Speaker 3: be left out of school for like weeks on end.
Speaker 3: And it was only when I'm joined to sort of
Speaker 3: like be positive choir that I actually came out and
Speaker 3: a lot of my school friends, I was like, do.
Speaker 4: You know what?
Speaker 1: I did not know?
Speaker 3: You heard sicker celt I didn't know how to explain
Speaker 3: it to them in a way, and I didn't know
Speaker 3: how they would receive me. I always think, like, you know,
Speaker 3: if I said it, I would lose friends, which I
Speaker 3: remember having a friend who said they didn't want to
Speaker 3: be my friend because they.
Speaker 1: Thought they could catch sickle cell if they held.
Speaker 3: My hand, And I was like, it doesn't work that
Speaker 3: way unless you're born with it.
Speaker 1: Does not work that way, So it was very.
Speaker 3: I shield myself just so I wouldn't have to face
Speaker 3: that negativity, and that hurt.
Speaker 1: Later on my adult years.
Speaker 3: I was like, you know what, if you don't like
Speaker 3: me the way I am, then that's fine.
Speaker 1: Somebody else will. There's many people in this world that will.
Speaker 3: And I grew that confidence and was able to mental
Speaker 3: or talk toever teenager girls and boys who were in
Speaker 3: my situation to say, you know, don't let super cells
Speaker 3: stop you from doing what you want to do. When
Speaker 3: I do get in a crisis and I'm in pain,
Speaker 3: the best way to describe it it has to be
Speaker 3: like when you get a really bad cold and you
Speaker 3: have eggs and pains and all of your body hurts
Speaker 3: on it ten times worse skill than aches and pains.
Speaker 3: When you've got a cold and you just want it
Speaker 3: to stop, and I've had it's brought me to tears
Speaker 3: before many times, and it's brought me to the parts
Speaker 3: where I'm like, do you know what, I don't want
Speaker 3: to be here on this earth because I don't want
Speaker 3: experience to pay.
Speaker 1: Why do I have to go for it? You know?
Speaker 5: Why?
Speaker 1: Was I the unlucky one? And I did kind of go.
Speaker 3: For the fase of blaming my parents, so to speak, saying,
Speaker 3: you know, you should have checked each other before.
Speaker 1: You had me, why didn't you do this?
Speaker 3: And you know, your mind starts thinking loads of things
Speaker 3: of you know, I if I wasn't here, would.
Speaker 1: I be in a better place?
Speaker 3: Or if I was born before my sister, would I
Speaker 3: be in a better place?
Speaker 1: And you just think many things.
Speaker 3: Every day you wake up. You don't know if it's
Speaker 3: going to be a good day, if it's going to
Speaker 3: be a bad day. And I think that affects your
Speaker 3: social life as well, because you're forever counseling on your friends.
Speaker 1: And it's the same with relationships.
Speaker 3: I've like broken up with a lot of partners because
Speaker 3: they don't understand the extent of sick of self going
Speaker 3: into hospital that's our last result on our mind. We
Speaker 3: tend to not quite going into the hospital, but we
Speaker 3: like we want to try and treat it the best
Speaker 3: we can at home. Sometimes we don't like the hospitals
Speaker 3: because of the stigma that we get. We get looked
Speaker 3: upon as oh, we're drug addicts or you know, we're
Speaker 3: not really in pain, we're just he because we need
Speaker 3: to fix, and it's like I would don't want to
Speaker 3: be in hospital.
Speaker 1: This is the last place I want to be.
Speaker 3: Lucky enough, my family are amazing, bless their hearts. I
Speaker 3: have snapped up them many times, but it's not the
Speaker 3: case that I mean to. It's just a case of
Speaker 3: all I can feel is this pain, and I don't
Speaker 3: want to feel the pain anymore. And I have apologized
Speaker 3: to them afterwards, but now they kind of know my routine.
Speaker 3: Not you know, when I say I'm in a crisis,
Speaker 3: they don't answer silly questions.
Speaker 1: They're just like pay.
Speaker 3: Meds, heatpad or hot bath or if it's that bad,
Speaker 3: do you need to go to the hospital. And obviously
Speaker 3: I've got a son who is fantastic. I'll call him
Speaker 3: a little Dr Quinn. The minute you know, I say
Speaker 3: mummy's not feeling very well.
Speaker 1: He's on it.
Speaker 3: With the pain meds, the hot cups of tea, the
Speaker 3: hot water bottle, everything you can think of to make
Speaker 3: to cheer me up. He'll put my favorite movie on
Speaker 3: and cuddles and there with me. So he is literally amazing.
Speaker 3: But because it's just me and him that lived together,
Speaker 3: I feel like that sometimes he feels his childhood got
Speaker 3: robbed in. Sometimes he feels that he can't be a
Speaker 3: child because he has to look after mummy and also
Speaker 3: be himself, which is I knew was quite hard. And
Speaker 3: I think that was the same thing when I knew
Speaker 3: when I was going to have children. You know what
Speaker 3: impact would my health have on him?
Speaker 1: And for me?
Speaker 3: When I felt pregnant. After my pregnancy, that's when my
Speaker 3: sickle sell got worse. I had a minor stroke. More
Speaker 3: things were happening to my body where I felt like
Speaker 3: it was deteriorating, and I feel that that was not
Speaker 3: made or where to me when I was thinking about
Speaker 3: starting a family. So I'm now going over that hurdle
Speaker 3: of experience and things where I feel that maybe I
Speaker 3: could have been made more aware of and given that
Speaker 3: option of what to do. But nevertheless, he's still a
Speaker 3: blessing and I loven't pieces and I think now that
Speaker 3: where I joined to be positive choir, it's a journey
Speaker 3: that you don't want to end. Singing for Britain's got talent,
Speaker 3: singing for the Queen, Meghan, Prince Harry, Prince William, everyone,
Speaker 3: it was amazing.
Speaker 1: It was like I was living a dream. I had
Speaker 1: to keep saying pinch me. Somebody pinched me? Is that
Speaker 1: Megan over there? No, So it was absolutely amazing.
Speaker 3: And the way since we've come on that platform it's gone.
Speaker 1: Viral, I think it's got more awareness.
Speaker 3: Everybody's starting to get involved and starting to be more
Speaker 3: clued up and taking notice of what sickle cell is,
Speaker 3: and you know how they can go around helping to
Speaker 3: spread the awareness.
Speaker 1: And I feel that it's.
Speaker 3: A way that brings the community together as well, because
Speaker 3: in the choir there are many people who have the
Speaker 3: illness and we share our stories. We've got you know,
Speaker 3: everybody experiences sucle cell differently, so it's nice and where
Speaker 3: we've become like a big unit and we get to
Speaker 3: share it around the world, which is amazing, and we
Speaker 3: have a laugh, we have a love and that's the
Speaker 3: main thing. Yes, you have your down days, but also
Speaker 3: you have your good days. But everyone always says, you know,
Speaker 3: how is it You're always smiling, And I think I
Speaker 3: look at the positive that now I don't see sickle
Speaker 3: cell as a burden as I did before. I actually
Speaker 3: see it as a gift and a blessing to have
Speaker 3: because I can go out and spread the word about
Speaker 3: six sol and make friends. Yeah, I'm happy, literally happy.
Speaker 3: I couldn't be more happier.
Speaker 4: So my name is Sheriff to sob them.
Speaker 6: I was born in Kampala, Uganda, a small East African country,
Speaker 6: and I have scle cell disease. So when I was born,
Speaker 6: my mom and dad had a very love story. They
Speaker 6: gave birth to the baby boy like all parents, so
Speaker 6: very excited to have a baby boy. I think after
Speaker 6: about four or five months after that, I started to
Speaker 6: show up with I was very irritated. I was alreadys
Speaker 6: crying and they told me I had all the my social.
Speaker 4: In hands and didn't know. They didn't know what was
Speaker 4: really going on.
Speaker 6: And my mom kept on going to different health centers
Speaker 6: and until the time one doctor did sugges said, no,
Speaker 6: what we need to do a cyclo cell test to
Speaker 6: be able to find out if this after has cell
Speaker 6: and and so that was the change of their story
Speaker 6: because once she told my dad, they actually broke up
Speaker 6: and my dad left her because he's like, no, I've
Speaker 6: not had any child or cicle cell and in my
Speaker 6: family we don't have sicosle business. So my mom ended
Speaker 6: up having to raised me as a single mother because
Speaker 6: my dad had left. During that time, she was pretty
Speaker 6: scared about what's going on. She didn't know what was
Speaker 6: going on because at that time the ninety sicosa wasn't
Speaker 6: really a very big thing. Most people who have cycle
Speaker 6: cell To date in Uganda, we find that over ninety
Speaker 6: percent of the babies who were born in shep was
Speaker 6: Sel died before their fifth pack. So this is mostly
Speaker 6: because we don't have a comprehensive for a program that
Speaker 6: you're going to be diaganized and go to Cico cell
Speaker 6: center and be followed up to sell the care.
Speaker 4: All that has not been there if it has started
Speaker 4: to come up.
Speaker 6: I think in the last one one or two three
Speaker 6: years we're starting to see scosol the centers across the
Speaker 6: country in Uganda. So during that time when she was
Speaker 6: pretty long, pretty scared, she named me to Suvida. So
Speaker 6: my second name is Sheriff to Suvida to Subida means
Speaker 6: we hope. So high institution with the names with them
Speaker 6: was mostly because of the fact that she wanted to
Speaker 6: have a way to always have some hope in her heart.
Speaker 6: Because if everyone around you is trying to say your
Speaker 6: baby's going to die, every mom will preace care. But
Speaker 6: as a child growing up, I really I didn't know
Speaker 6: what was going on, yes, or have pain and cry
Speaker 6: and ask what's going on? And my mom didn't really
Speaker 6: have a wolf explaining it to me until I think
Speaker 6: to my six or seven years. But when I go
Speaker 6: to play and kids have come to play, we'd say,
Speaker 6: they would say and and I, which.
Speaker 4: Means in my local anguage, you don't play with him.
Speaker 4: He's sick.
Speaker 6: So that that's why I start to realize that there's
Speaker 6: something different about me. So that was my kind of
Speaker 6: childhood experience. And this was the case whereby I'll be
Speaker 6: on the pitch trying to pick the ball and I
Speaker 6: feel pain in my leg, feel pain in my hand,
Speaker 6: and said and sometimes I just couldn't walk. My friends
Speaker 6: would have to carry me home. I'd always ask my mom,
Speaker 6: what's going on?
Speaker 4: Why me? Why am I feeling like this? Why I think?
Speaker 6: I remember all the time after growing up, I asked
Speaker 6: her for a knife slight that I could cut off
Speaker 6: my hand and cut off my leg because it was
Speaker 6: bringing too much pain for me. And they're like, no,
Speaker 6: we can't do that. You can't just just can't just
Speaker 6: cut off the leg because you took my pain. But
Speaker 6: even then yes, I would feel very stigmatized and feel
Speaker 6: very bad about it. And when it went when he
Speaker 6: went to school, it was actually very different as well
Speaker 6: at school because at school in the rainy season, the
Speaker 6: extreme seasons, or being pained and I couldn't go to school,
Speaker 6: so you missed like two weeks or three weeks of school,
Speaker 6: and the teachers to say, where has he been, and
Speaker 6: so often my mom would have to explain, you know
Speaker 6: what he has cycle, sell if he has missed, if
Speaker 6: he tells you his hands are sick, he can't write,
Speaker 6: it's fine, you have to understand.
Speaker 4: But it was really hard for the teacher to understand because,
Speaker 4: like I.
Speaker 6: Said, this disease is most partly nothing about like even
Speaker 6: the teachers like this kid has just just has an excuse.
Speaker 6: Every time I want him to come and drawn the blackboard,
Speaker 6: he's saying his hand is hurting. You want him to
Speaker 6: be part of the class activity, He's saying he feels
Speaker 6: pain in his leg and feels pain and there.
Speaker 4: So that was another issue because of my cycle.
Speaker 6: So I had complications like John this in my eyes
Speaker 6: and had the distant and prettish all those things that
Speaker 6: made me look more of an outlier like you don't. Yes,
Speaker 6: you look like everyone else, but you your eyes are
Speaker 6: pretty yellow. So that's the thing that you have to
Speaker 6: explain everyone why your eyes yellow. I didn't know how
Speaker 6: much to break it down, but all I would say, yes,
Speaker 6: I have cicle said it is a blood disease.
Speaker 4: That's all I would say.
Speaker 6: And when I get sick, and we had a school nuns,
Speaker 6: I would go and get careful the nuns. So high
Speaker 6: school was was a bit was a much better experience.
Speaker 6: So during my second day and the university, I did
Speaker 6: get sick, and I got sick and I missed I
Speaker 6: think I missed almost three or four weeks of school.
Speaker 6: So when everyone was asking why Sharif and I mean
Speaker 6: and I didn't really do my disclosure. And that's the
Speaker 6: time I had started to day, I was I was
Speaker 6: taking a very before woman. And when I got to seek,
Speaker 6: I was in the hospital and she tells me, you
Speaker 6: know what, I can't do with you because of yoursical cell.
Speaker 6: I mean, I've never seen myself with someone with That
Speaker 6: was a tinning point for me. So that that was
Speaker 6: my driving fact and now to make a change in
Speaker 6: not only in my life but in the life of
Speaker 6: all those people living so such that they don't have
Speaker 6: to go through what had gone to. So it was me, myself, Ashoff,
Speaker 6: and two other people, Evelyn and another guy's Aalim. We
Speaker 6: agreed to create an organization called Scostal Network You. It
Speaker 6: was the first cico cell and I profit that we
Speaker 6: did register. Because of my background and stigma and experience,
Speaker 6: I had. One of the first projects that implemented was
Speaker 6: having psycoso concer training. When I looked at my background
Speaker 6: of lavato science and the fact that in our market
Speaker 6: you could have people test for HIV, I thought myself
Speaker 6: and said, I think we should be able to test
Speaker 6: for cico cell. We started out at all our community
Speaker 6: events would have a team of lavaty people to do
Speaker 6: the cicosol screening, our counselors to do the you know
Speaker 6: have councilor cert that people could understand what it means
Speaker 6: if you trade, what it means if you if you
Speaker 6: have pico cell, and a lot of those things. And
Speaker 6: after two years of this, our local meanings of Health
Speaker 6: actually did accept and adopt this program. It's now been
Speaker 6: rolled out and several health centers have these rapid co
Speaker 6: celf testing kids and people know can be happy to
Speaker 6: access the cicosol screen test whatever they are. So in Uganda,
Speaker 6: we have a tribe called the Baganda. Tribe makes up
Speaker 6: the biggest proportion of the population, but we did have
Speaker 6: a local name for sicco cell. And this is not
Speaker 6: only the Baganda, but most tribes in Uganda do not
Speaker 6: actually do not actually have a local name for sco cell.
Speaker 6: And the indicator for this means that if you don't
Speaker 6: have the local name for something, it means you're not
Speaker 6: talking about it. If you're not talking about it, then
Speaker 6: then that explains all the stigma. So because people don't
Speaker 6: talk about it is no name. But the biggest one
Speaker 6: for me as the advocate is the fact that the
Speaker 6: kingdom gave us a local name for sico cell. They
Speaker 6: did say, now we pronounced that sico salling that we
Speaker 6: just called Umbili. At least now somebody who's uneducated, somebody
Speaker 6: who had never been to school, can have a word
Speaker 6: that they can not to mean sico Cell, and that
Speaker 6: in a way helps us beat the stigma because then
Speaker 6: people can be able to talk about.
Speaker 4: Their mother town.
Speaker 6: Looking back on how the genius come from the time
Speaker 6: when we introduced communitis Coroso screening. From the time when
Speaker 6: we have a local name to the fact that we have,
Speaker 6: we have not been able to support the imaginence of
Speaker 6: so many Pico so nonprofities. And for example, the time
Speaker 6: when we sarted, there was only one nonprofit in Uganda
Speaker 6: working on SIICO so called Circnstatation of Uganda. Today, as
Speaker 6: I speak, seven years later, we have over twenty five
Speaker 6: cb odds committey best organization all working.
Speaker 4: To CICO selling local communities.
Speaker 6: I think in twenty nineteen I decided know what I've been,
Speaker 6: I've been an advocate for the past few years. I
Speaker 6: think I need to think of something much engine that's
Speaker 6: a I fund. I thought of coming back to grad school,
Speaker 6: and I decided to come back to the US for
Speaker 6: my grad schools.
Speaker 4: I came back.
Speaker 6: I went to the University of Caansas as a peach student.
Speaker 6: When I came to the US, I was hearing a
Speaker 6: lot of this thing of the raciore, the racial bias
Speaker 6: in terms of Icosa, and it had actually never happened
Speaker 6: to me until one time. I think it may I
Speaker 6: go to the er. I had a lot of pain
Speaker 6: in my I was actually very sick.
Speaker 4: I had a lot of pain.
Speaker 6: I spent the whole thing in the r they give
Speaker 6: me all the pain made that I was still in pain.
Speaker 6: But guess what happened to me? The er doctor says,
Speaker 6: you're fine. We have checked everything very normal. So we
Speaker 6: can admit to one of the kid driving factors in
Speaker 6: terms of why even as advocates living in the US,
Speaker 6: we need to come out and promote more awareness and
Speaker 6: boscle soucers that the doctors would have a more understanding.
Speaker 4: I think one of the key in wantant aspects.
Speaker 6: It's not it may not be so much of a
Speaker 6: big deal in the US, but it's the big deal
Speaker 6: is where in the world That part whereby people not
Speaker 6: understanding and accepting scle celf having all these meats and beliefs.
Speaker 6: So it still goes back to awareness people and having
Speaker 6: understand that this is like any other blood disease. If
Speaker 6: you can take good care of yourself, if you can
Speaker 6: have a comprehence you follow up, if you can do
Speaker 6: whatever we can do to stay healthy, then I can
Speaker 6: leave like any anybody else. I shouldn't worry about death.
Speaker 6: I shouldn't worry that will not be able to meet
Speaker 6: my dreams. My story started out because of a heat break,
Speaker 6: because of the love sad love story ended up being
Speaker 6: a sipo's advocate today. I was able to find love,
Speaker 6: married to Sophia and have two kids, Kneeman Shet, and
Speaker 6: they're part of my support system to keep me healthy
Speaker 6: and strong and going. So I appreciate them and everyone
Speaker 6: who's supporting me.
Speaker 7: Thank you.
Speaker 8: Thank you so much Marcia and Shurie for sharing your
Speaker 8: stories with us. We really really appreciate it and we
Speaker 8: want to tell you a bit more about our amazing guests.
Speaker 8: Marcia started her blog My Life was Sickle Cell in
Speaker 8: twenty sixteen and has since been recognized for her awareness
Speaker 8: raising efforts by appearing on TV programs, radio shows, newspapers,
Speaker 8: you name it. And in her first hand she mentioned
Speaker 8: being a member of the BE Positive Choir, which is
Speaker 8: a choir made up of people with sickle cell disease
Speaker 8: or those who have friends or family members affected and
Speaker 8: the B Positive Choir has made amazing strides in raising
Speaker 8: awareness of sickle cell disease as well as encouraging blood
Speaker 8: donations and also, as you heard, they were on Britain
Speaker 8: Scott Talent and performed in front of the Royal Family,
Speaker 8: which is pretty dang cool.
Speaker 9: That's amazing. Our other incredible guest, Sharif, has been instrumental
Speaker 9: in a number of different advocacy and outreach efforts which
Speaker 9: you heard a bit about in his first hand including
Speaker 9: launching the East Africa Sickle Cell Alliance, working with the
Speaker 9: Pan African Sickle Cell Federation International, and serving as the
Speaker 9: first executive director of the Uganda Sickle Cell Rescue Foundation.
Speaker 8: That's incredible, so amazing.
Speaker 9: Sharif's amazing advocacy and outreach efforts have been recognized by
Speaker 9: many organizations. In twenty seventeen, he was named Amandela Washington
Speaker 9: Fellat through the Young African Leaders Initiative. In twenty eighteen,
Speaker 9: he became a Telemachus Fellow under the Global Thinkers Forum,
Speaker 9: and this year twenty twenty, he was named the International
Speaker 9: Sickle Cell Advocate of the Year.
Speaker 8: No big deal, No big deal.
Speaker 9: Oh and he's just casually also getting his PhD studying
Speaker 9: quantitative genetics at the University of Kansas, just like.
Speaker 8: Casually casually getting a major degree. Right, Oh my goodness,
Speaker 8: that's amazing. We will provide links to both Marsha and
Speaker 8: Shreef's websites and social media handles on our website this
Speaker 8: Podcast will Kill You dot com and in our show
Speaker 8: notes if you'd like to learn more about these awesome
Speaker 8: humans and their work.
Speaker 9: Yeah.
Speaker 8: Hi, I'm Aaron Welsh and I'm Erin Olman Updyke, and
Speaker 8: this is this podcast will Kill You. This week we are,
Speaker 8: as you may have guessed.
Speaker 9: You might have figured it out by now covering sickle
Speaker 9: cell disease. Yeah, this is a big one.
Speaker 8: Obviously, this is a huge one. And we've been wanting
Speaker 8: to do this one for a while and I'm very
Speaker 8: excited now that we're finally doing it because there's so much.
Speaker 8: There's so much to it.
Speaker 9: Yeah. Absolutely, there's such fascinating biology. I can't wait to
Speaker 9: learn about the history. I have a feeling it's going
Speaker 9: to be equal parts fascinating and infuriating. That's my guess.
Speaker 8: Oh why would say maybe not even equal parts? I
Speaker 8: would say, oh, mostly infuriating. Yeah awesome. Okay, there are
Speaker 8: some like you know, shining moments, but yeah, oh.
Speaker 9: But I can tell you that there are some very
Speaker 9: exciting things to talk about in the current events section,
Speaker 9: for which we had the pleasure of speaking with a
Speaker 9: very special guest, doctor Meghan Hawkstrasser, whose education programs manager
Speaker 9: at Innovative Genomics Institute in Berkeley.
Speaker 8: It's incredible. I'm sure that you may have heard the
Speaker 8: word crisper or genome editing at some point and been like,
Speaker 8: what the heck is that. Don't worry, We're going to
Speaker 8: get into it at least a little bit, and it's
Speaker 8: going to make you so thrilled and make you feel
Speaker 8: like you're living in the future.
Speaker 9: It's thrilling. But before we get into all of the
Speaker 9: thrilling things that we're going to talk about today, erin
Speaker 9: what time is it?
Speaker 8: I believe aarin that it is quarantine any time.
Speaker 9: You would be correct about that. What are we drinking today?
Speaker 8: We are drinking the Witten lovely. Oh yes, And the
Speaker 8: Witten is named for doctor Charles Witten, who, among many
Speaker 8: other amazing accomplishments, was the co founder of the Sickle
Speaker 8: Cell Disease Association of America, and he made amazing strides
Speaker 8: in raising awareness of sickle cell throughout the seventies and
Speaker 8: eighties and into the nineties as well. And he also
Speaker 8: initiated a lot of programs that were designed to provide
Speaker 8: more opportunities for those underrepresented in medical fields to actually
Speaker 8: have medical school as an opportunity. So we wanted to
Speaker 8: name our quarantini in the to honor this amazing human
Speaker 8: in the tiniest possible way.
Speaker 9: And to do so.
Speaker 10: What is in this quarantini exactly the witten is strawberry
Speaker 10: infused tequila, which is so good and also just really
Speaker 10: easy to do.
Speaker 8: Just takes patience and lime juice and agave syrup.
Speaker 9: Fabulous. We'll post the full recipe for that quarantini as
Speaker 9: well as our non alcoholic plus e verta on our website.
Speaker 9: This podcast would kill you dot Com and all of
Speaker 9: our social media channels, so make sure you're following us.
Speaker 8: And we have one more piece of business before we
Speaker 8: get into the business of sickle Cell, just.
Speaker 9: A little one, which is a big news.
Speaker 8: Actually we have new merch, new merch.
Speaker 9: We've been waiting. We're so excited.
Speaker 8: We have some really fun cool things, like we'll just
Speaker 8: drop a few little hints. You want a hoodie, We
Speaker 8: got a hoodie.
Speaker 10: Oh, we got some socks, keep your toes warm.
Speaker 8: Big shout out to Abigail Irvin Penner, who's always incredible
Speaker 8: artwork is featured on so many of these Honestly, like
Speaker 8: I'm I'm in love.
Speaker 9: I can't wait to be tpwky head to toe baby,
Speaker 9: I mean literally head to toe and for my SIPs.
Speaker 8: Yeah. Okay, if you would like to see this new merch,
Speaker 8: you can head to this podcast will Kill You dot
Speaker 8: com and click on the merch tab at the top
Speaker 8: of the screen.
Speaker 9: All right, is that all our business eron?
Speaker 8: I believe so.
Speaker 9: Well, then let's take a quick break and dive straight
Speaker 9: into the biology.
Speaker 8: Of sickle cell let's do it.
Speaker 9: So, sickle cell disease or sc D. I think it's
Speaker 9: often taught as sickle cell anemia, right, this like one
Speaker 9: particular illness, but in fact, sickle cell disease is a
Speaker 9: group of disorders of red blood cells, and it's a
Speaker 9: genetic disease, which means it's inherited, so it's caused by
Speaker 9: a mutation. But as we'll see, it's not just one
Speaker 9: single mutation, and there's not just one single manifestation. So
Speaker 9: we're going to start from the very beginning before we
Speaker 9: even get into sickle cell disease itself and talk about blood.
Speaker 4: Cool.
Speaker 8: Yes, okay, we've talked about blood before a little bit.
Speaker 9: We have, but we've never talked about this.
Speaker 8: We have talked about when we talked about blood hepatitis.
Speaker 8: C Oh.
Speaker 9: Yeah, this is a totally different blood discussion. Okay, okay,
Speaker 9: So what we're going to talk specifically about is in
Speaker 9: our red blood cells, the protein that is actually responsible
Speaker 9: for carrying oxygen, and that protein is hemoglobin. Okay. So,
Speaker 9: hemoglobin is a protein that's made up of four polypeptides,
Speaker 9: two pairs of polypeptides, and these four polypeptides or strings
Speaker 9: of amino acids form the protein that's in our red
Speaker 9: blood cells that actually carries oxygen, which obviously our tissues
Speaker 9: need in order to survive. So in most adult red
Speaker 9: blood cells, hemoglobin is made up of two alpha chains alphas,
Speaker 9: and two beta chains. So alpha, alpha, beta, beta, Okay,
Speaker 9: sounds good. Now, we also have some other forms of hemoglobin,
Speaker 9: like you can have two alpha chains and two delta chains.
Speaker 9: That's another kind of adult hemoglobin. And then in a
Speaker 9: fetus before we are born, the majority of our hemoglobin
Speaker 9: is actually two alpha chains and two gamma chains, and
Speaker 9: that's called fetal hemoglobin. Why great questions, So glad you asked.
Speaker 9: So you know how fetuses are grown inside and all
Speaker 9: of their blood comes from mom right, So that means
Speaker 9: that all of the blood that a fetus is getting
Speaker 9: is already partially deoxygenated. It doesn't have as much oxygen
Speaker 9: as the blood in our bloodstream because we're breathing in air.
Speaker 9: So because of that, fetal hemoglobin has to actually bind
Speaker 9: oxygen more tightly than adult hemoglobin because it has to
Speaker 9: be able to get all of that oxygen out of
Speaker 9: mom's blood. Does that make sense? Okay? Now remember that
Speaker 9: because it's going to become very important in our discussion
Speaker 9: of sickle cell later. Okay, Okay, So now we understand
Speaker 9: hemoglobin inside normal adult red blood cells. So what does
Speaker 9: that mean for sickle cell disease? Why did I tell
Speaker 9: you all?
Speaker 3: That?
Speaker 9: Turns out that sickle cell disease is produced by a
Speaker 9: single amino acid change if anyone cares, it's a glutamic
Speaker 9: acid to a vailian that in that beta hemoglobin chain. Okay,
Speaker 9: So it's a single mutation in beta hemoglobin that results
Speaker 9: in what's called like sickled beta hemoglobin, so hbs instead
Speaker 9: of hb A for adult. That is the change that
Speaker 9: if you have two copies of that mutated beta globin gene,
Speaker 9: you have sickle cell anemia, the disease caused by two
Speaker 9: copies of these sickle cell genes. So what happens if
Speaker 9: you have these sickle cell versions of beta hemoglobin, Well,
Speaker 9: what happens is that in your red blood cells at
Speaker 9: low oxygen concentrations, like low overall oxygen concentrations in your blood,
Speaker 9: the hemoglobin forms a polymer. So multiple subunits, like multiple
Speaker 9: little globules of hemoglobin protein will link together inside the
Speaker 9: red blood cell and form a linear chain.
Speaker 8: Like a little string of beads, like.
Speaker 9: A little string of beads exactly. And this becomes rigid
Speaker 9: and causes a deformation in the whole red blood cell
Speaker 9: so that it kind of sucks in on itself and
Speaker 9: becomes sickle shaped or like a crescent moon shaped. So
Speaker 9: a normal adult red blood cell, even a fetal red
Speaker 9: blood cell, is shaped kind of like a doughnut, like
Speaker 9: the you know the things you go down the lazy
Speaker 9: river in those like inflatable tubes with like the in
Speaker 9: the middle so your butt doesn't fall through.
Speaker 8: Oh, I've never had one that had the mesh, but sure.
Speaker 9: The fancy version. Okay, So that's kind of what a
Speaker 9: normal red blood cell looks like. So when you have
Speaker 9: two copies of this sickle cell beta hemoglobin gene, all
Speaker 9: of your hemoglobins line up in the red blood cell
Speaker 9: and cicicle it so instead of that nice donut, you
Speaker 9: have a C shaped red blood cell. And that is
Speaker 9: kind of the core problem that results from two copies
Speaker 9: of this sickle cell gene. But how is that like? Okay,
Speaker 9: it's just a different shape of your red blood cell.
Speaker 9: Why is that so bad? So these sickled cells are
Speaker 9: very rigid, okay. Normal red blood cells are kind of
Speaker 9: like an inflatable donut. They're kind of squishy and squashy, okay,
Speaker 9: So as they move through your blood vessels through from
Speaker 9: larger vessels to smaller vessels like your capillaries, they can
Speaker 9: squash and deform and scoot through small vessels and then
Speaker 9: pop back out on the other side. Sickled cells are
Speaker 9: more rigid, so they can't do that as well. So
Speaker 9: what happens is these cells can start to get stuck,
Speaker 9: especially in small vessels. Okay, but it's not just the
Speaker 9: rigidness of the sickled red blood cells. So it turns
Speaker 9: out that once a red blood cell sickles like this,
Speaker 9: they're also literally stickier, like proteins on the outside of
Speaker 9: them become more sticky, so that they get stuck to
Speaker 9: the walls of your vessels, and they get stuck to
Speaker 9: other like white blood cells and things that are rolling
Speaker 9: along in your vessels. Okay, and imagine what happens if
Speaker 9: you have a bunch of cells starting to stick to
Speaker 9: one another inside of your.
Speaker 8: Blood vessels, or you get a blood clot.
Speaker 9: You're gonna get a blood clot exactly, and so kind
Speaker 9: of the hallmark of sickle cells that we'll talk a
Speaker 9: little bit more about in a minute when we talk
Speaker 9: about the symptoms are what's called vasoeclusive crises. So you
Speaker 9: literally have occlusion or blockage of your vessels small vessels
Speaker 9: like capillaries, but even larger vessels like in your brain,
Speaker 9: leading to stroke.
Speaker 8: That sounds terrible.
Speaker 9: It's not great, that's for sure. And there's more. Okay,
Speaker 9: So now we know that these sickled cells, they get
Speaker 9: more sticky, they can get stuck in places. But on
Speaker 9: top of that, so red blood cells only sickle at
Speaker 9: lower oxygen concentrations. Okay, So for the most part, in
Speaker 9: your arteries, even if you have sickle cell disease, your
Speaker 9: red blood cells are going to be in normal shape.
Speaker 9: It's not until you reach the capillaries or the veins
Speaker 9: where oxygen concentration is lower that these the hemoglobin will
Speaker 9: form those chains and then cause the red blood cell
Speaker 9: to sickle. But this is reversible, but there's two problems
Speaker 9: with it. First of all, this tends to happen in
Speaker 9: microvessels like your capillaries and small veins, because that's where
Speaker 9: both oxygen concentration is low and you have slow flow,
Speaker 9: so the red blood cells in there for a long
Speaker 9: time comparatively, and so those two things combined lead to sickling.
Speaker 9: And in small vessels, if you sickle and you get stuck,
Speaker 9: then you can block those small vessels directly.
Speaker 8: Gotcha.
Speaker 9: Now, another thing happens over time, this constant sickling and unsickling.
Speaker 9: Sickling and unsickling causes damage to the red blood cell
Speaker 9: membrane itself, so like the outer shell of the red
Speaker 9: blood cell, and this can cause an irreversible sickling. So
Speaker 9: now it's just stuck sickled all the time. And those
Speaker 9: sickled cells in particular are very very sticky, so that
Speaker 9: can cause sticking on the inside of vessel walls. And
Speaker 9: to white blood cells in larger vessels, which can eventually
Speaker 9: lead to blockage of even larger vessels, not just small ones.
Speaker 8: Right, and it seems like the white blood cell thing
Speaker 8: then will play a role in immune system function.
Speaker 9: Oh, you're so accurate, Aerin, here's a question.
Speaker 8: Yeah, and maybe it's jumping the gun, but your body,
Speaker 8: as we talked about in the hepatitis C episode, your
Speaker 8: body makes a lot, like makes new red blood cells
Speaker 8: very frequently, and so what does it do, like does
Speaker 8: it attack the sickled cells in any way, or like
Speaker 8: what is their lifespan?
Speaker 9: I'm so glad that you asked, Aaron. It's totally jumping
Speaker 9: the gun, but it's the perfect question.
Speaker 8: I love it.
Speaker 9: So yeah, okay, I'm going to answer that question in
Speaker 9: a couple parts. Okay, So, first of all, you're right
Speaker 9: that white blood cells and things play a big role.
Speaker 9: And overall, even though this is technically a disease of
Speaker 9: just red blood cells, right, it's just hemoglobe and being
Speaker 9: messed up, it's not just a disease that affects your
Speaker 9: red blood cells. Overall, there's an increase in inflammation and
Speaker 9: inflammatory state in sickle cell disease and the more inflammation.
Speaker 9: So the higher people's leukocyte counts or white blood cell counts,
Speaker 9: the worse off their disease tends to be. And as
Speaker 9: we'll see, there's huge variation in disease severity, and that's
Speaker 9: one factor that plays a role. Now in terms of
Speaker 9: how long these blood cells last, that's a perfect question
Speaker 9: to ask. A normal, healthy red blood cell has a
Speaker 9: lifespan of about one hundred and twenty days. In someone
Speaker 9: with sickle cell disease, that lifespan is reduced by over
Speaker 9: seventy five percent. So some estimates that I saw were
Speaker 9: the life span of a red blood cell in a
Speaker 9: person with sickle cell disease, so that's two copies of
Speaker 9: that sickle cell gene is about sixteen days.
Speaker 8: Oh wow. And so even if your body is producing blood,
Speaker 8: it's not enough to make up for the loss.
Speaker 9: Oh you're getting the perfect yes, hundred percent. So there's
Speaker 9: two ways that you get anemia. One, like you said,
Speaker 9: you just can't make enough because you need to constantly
Speaker 9: make more red blood cells and more red blood cells.
Speaker 9: But on top of that, as those cells sickle and
Speaker 9: unsickle and become damaged, that leads to hemolysis. So red
Speaker 9: blood cells actually breaking open within your vasculature. So not
Speaker 9: only can you have anemia from lack of production, you
Speaker 9: can also have a hemolytic anemia. So breaking open those
Speaker 9: red blood cells, now, that leads to even more problems
Speaker 9: because when you burst open red blood cells, all that
Speaker 9: hemoglobin that's inside those red blood cells is now released
Speaker 9: into the blood stream, and this causes like a whole
Speaker 9: host of biochemistry reactions I'm not going to get into,
Speaker 9: but one thing that it does is it scavenges up
Speaker 9: all of the nitric oxide, which is an important molecule
Speaker 9: that helps with things like vasodilation. So as your hemoglobin
Speaker 9: sucks up all that nitric oxide, now you have increased
Speaker 9: vasoconstriction as well as damage to like the epithelium of
Speaker 9: the lining of your blood vessels, which causes even more stickiness. Okay,
Speaker 9: so it's like these horrible feedback loop, if that makes sense,
Speaker 9: where you have smaller vessels because you have less nitric oxide,
Speaker 9: you have damage to the inner layer, which increases the stickiness,
Speaker 9: you have inflammation. So there's white blood cells rolling around
Speaker 9: picking things up, and it's it's bad. It's a mess. Okay.
Speaker 8: Yeah, that's like a from one, I mean no acid substitution.
Speaker 8: This systemic these systemic problems.
Speaker 9: Isn't that it's fascinating that you can have so many
Speaker 9: effects from one single and I mean it's a single nucleotide.
Speaker 9: It's a single base pair change.
Speaker 8: Right right, It's wow, yeah, man.
Speaker 9: Okay, So let's talk about what these symptoms then look like.
Speaker 9: So now we know like what's happening in your blood vessels,
Speaker 9: and it kind of all boils down to like increased
Speaker 9: inflammation and blocking your vessels. Okay, so I said this already,
Speaker 9: but the main complication are these vasoeclusive crises, and so
Speaker 9: these can manifest, as you can probably imagine, in so
Speaker 9: many different ways depending on what vessels are getting blocked up. Okay,
Speaker 9: So in small children, especially tiny babies like under the
Speaker 9: age of two, the most common presentation is when the
Speaker 9: small blood vessels in their hands and feet get clogged up.
Speaker 9: This causes swelling of the hands and the feet, and
Speaker 9: this is really really painful as well, because you're literally
Speaker 9: blocking blood flow to your hands and feet. And so
Speaker 9: in small babies that for example, didn't have a newborn
Speaker 9: screen done, so they didn't know their parents maybe didn't
Speaker 9: know that they had sickle cell anemia. This is a
Speaker 9: really common way that they would come into the emergency
Speaker 9: room and be identified as having sickle cell anemia.
Speaker 8: Okay, is there a treatment for that aspect of it
Speaker 8: or is it?
Speaker 9: So we'll talk about treatment more later, but for the
Speaker 9: for the most part, not really Okay, yeah, God yeah, okay.
Speaker 9: So then as you can imagine, as you get older,
Speaker 9: these pain crises, these vasoeclusive crises, just kind of keep happening,
Speaker 9: and they can happen almost anywhere. So it's very common
Speaker 9: for people to come in with massive, massive amounts of
Speaker 9: pain without any kind of you can't see anything wrong
Speaker 9: with them because it's these tiny blood vessels in your
Speaker 9: abdomen or your legs, in your arms, anywhere that get
Speaker 9: clogged up. This causes a huge amount of pain. If
Speaker 9: you imagine, like a heart attack happens when you have
Speaker 9: a blockage of blood flow to your heart. Heart attacks
Speaker 9: are extremely painful. This is happening in small vessels throughout
Speaker 9: somebody's body during a sickle cell crisis. This is a
Speaker 9: disease that is I think often very misunderstood, and the
Speaker 9: pain I think can be minimized by people because it's
Speaker 9: not visible it's another kind of disease, like we've talked
Speaker 9: about before, where you don't look sick necessarily, and so
Speaker 9: I think it's really important to get across just how
Speaker 9: debilitating the pain associated with these can be.
Speaker 8: It's funny that you're using the phrases invisible and visible,
Speaker 8: because I that's like, that's my theme, and when I
Speaker 8: talk about the history.
Speaker 9: Of it, Yeah, yeah, it's really it's bad. Okay. So
Speaker 9: then you also can have additional symptoms or sort of
Speaker 9: more specific symptoms, depending on where you have these blockages.
Speaker 9: It can happen in people that have a penis, it
Speaker 9: can happen and you can get what's called priapism, which
Speaker 9: is a long lasting and very painful erection. If it
Speaker 9: happens in the blood vessels under your skin, especially in
Speaker 9: your legs, which is really common, it can cause chronic ulcers,
Speaker 9: so open wounds on your legs that are unable to
Speaker 9: heal because they're not getting good blood flow over time.
Speaker 9: If it happens in your eyes, it can lead to
Speaker 9: blindness because the vessels in your retina become blocked. God,
Speaker 9: it can happen in your bones, and this is very
Speaker 9: serious because your bones are also alive. They need blood flow,
Speaker 9: So when you block off the vessels to your bones,
Speaker 9: you get what's called a vascular necrosis. So that means
Speaker 9: tissue death because of lack of blood flow. So your
Speaker 9: bone marrow will literally die. Oh my god, yep, So
Speaker 9: that's pretty bad as you can imagine. That can also
Speaker 9: lead you susceptible to like osteomyelitis, which is infection of
Speaker 9: your bone, like a bacterial infection of your bone, because
Speaker 9: you don't have good blood flow to that bone. It
Speaker 9: can happen in your spleen, which is very common, and
Speaker 9: with your spleen kind of two different things can happen,
Speaker 9: so you can have like an what's called an acute
Speaker 9: splenic crisis. So all of a sudden your spleen, like
Speaker 9: blood flow to your spleen gets blocked. This can cause
Speaker 9: your spleen to enlarge very rapidly, and that can kill you,
Speaker 9: like right, that alone can kill you. Your spleen is
Speaker 9: an organ where a ton of blood flows through it
Speaker 9: because it's a lymphatic organ, so all of your white
Speaker 9: blood cells kind of hang out in your spleen and
Speaker 9: are responsible for like gobbling up bacteria and cleaning your bloodstream.
Speaker 9: Of infection. Okay, so because it has such huge volumes
Speaker 9: of blood, if you block that blood flow, then you
Speaker 9: can die just from that alone. But it can also happen,
Speaker 9: and it commonly does happen where over time, small vessels
Speaker 9: get blocked little by little in your spleen, leading to
Speaker 9: long term death of your spleen. What's called auto infection, right,
Speaker 9: so that a person, even though they have a spleen
Speaker 9: in their body, it's essentially non functional. It's like you
Speaker 9: removed it. So that leaves you very susceptible to infection,
Speaker 9: especially bacterial infections, because you don't have a spleen to
Speaker 9: take care of all those bacteria. So it's very common
Speaker 9: for people, especially young children, to die not from sickle
Speaker 9: cell anemia or sickle cell disease itself, but from an
Speaker 9: overwhelming bacterial infection because their spleen is nonfunctional. God, another
Speaker 9: really horrible outcome would be stroke. And this is actually
Speaker 9: what is so tragic is that stroke is very common
Speaker 9: in young kids with sickle cell anemia. And so that's
Speaker 9: essentially not just from small vessels being blocked, but from
Speaker 9: larger blood vessels in your brain that get blocked, and
Speaker 9: then overall the most common cause of death and the
Speaker 9: second most common cause of emergency room visit for someone
Speaker 9: with sickle cell anemia at least in this country, is
Speaker 9: what's called acute chest syndrome or ACS. And this is
Speaker 9: when you essentially get those crises in your lungs.
Speaker 8: Oh my god.
Speaker 9: Yeah. And what is awful and also very interesting about
Speaker 9: ACS is that the trigger for that can be almost anything,
Speaker 9: So it doesn't necessarily start with just these sickled cells
Speaker 9: blocking blood vessels. It can be a viral infection that
Speaker 9: causes inflammation that then triggers all these events. It could
Speaker 9: be an asthma attack, because you can have asthma and
Speaker 9: sickle cell that triggers all of these events. It can
Speaker 9: be fat embolism because if you have, for example, necrosis
Speaker 9: of your bones, your bone marrow is full of fat,
Speaker 9: little pieces of that fat can break off and travel
Speaker 9: to your lungs, and then those little emboli they're called,
Speaker 9: can cause a blockage that can then trigger all these
Speaker 9: downstream effects. So a cute chest syndrum ACS is it's
Speaker 9: basically a triad of extreme chest pain infiltrates so fluid
Speaker 9: and junk all over your lungs and then what's called
Speaker 9: arterial hypoxemia, So not able to get oxygen in your
Speaker 9: arteries because of all this fluid and junk in your lungs.
Speaker 9: It's horrible, it's really really awful. So yeah, that's kind
Speaker 9: of the overall symptom picture of what happens with sickle
Speaker 9: cell anemia or sickle cell disease.
Speaker 8: And so these happen, like you talked about, these tend
Speaker 8: to happen at different stages of someone's life. So what,
Speaker 8: like why is that? Is it just a matter of
Speaker 8: like your body growing and like certain things growing at
Speaker 8: certain times more Like, yeah, it's.
Speaker 9: It's a really good question. It's not. I don't fully know,
Speaker 9: but it is the case that people tend to present
Speaker 9: differently at different ages. So like in very young kids,
Speaker 9: the first presentation might be that hand and foot swelling
Speaker 9: right in like a very young baby. As they get older,
Speaker 9: especially under five, it's very common to have bacterial infections
Speaker 9: that can end up becoming very serious. Then at a
Speaker 9: certain age, stroke is a common manifestation. And then after
Speaker 9: that these pain crises and acute chest syndrome, right gosh, yeah,
Speaker 9: and then on top of that, like we said, kind
Speaker 9: of already you have kind of chronic anemia, so not
Speaker 9: enough red blood cells, this homolysis, which leads to fatigue,
Speaker 9: it leads to jaundice. You can have gallstones very commonly
Speaker 9: because of all this hemoglobin in your bloodstream. It can
Speaker 9: cause the formation of gallstones. So you can have huge
Speaker 9: pain from that. It's it's very bad. Kidney failure is
Speaker 9: really common. If you block the kidneys the bloodstream to
Speaker 9: your kidneys, you can have kidney failure. That's really common.
Speaker 9: I mean, it's it's everything, I meanwhere your blood flows.
Speaker 8: Yeah, exactly.
Speaker 9: And what I also want to mention that I think
Speaker 9: is often glossed over is the huge amount of mental
Speaker 9: and behavioral health complications from this. Depression and anxiety are
Speaker 9: very very high among people living with sickle cell because
Speaker 9: they have chronic pain. Not only are they living with
Speaker 9: chronic pain, not only do they have a reduced life expectancy,
Speaker 9: they're frequently in the emergency room, they're frequently being hospitalized.
Speaker 9: That's a massive amount of financial cost that's incurred. And
Speaker 9: on top of that, there's a long standing history of
Speaker 9: medical professionals not believing or not taking seriously the pain
Speaker 9: that you're in. So, yeah, this is a very it's
Speaker 9: a single mutation that leads to so very many complications.
Speaker 8: Oh yeah, oh yeah, yeah.
Speaker 9: Well is it a single mutation at bench there's my transition. Okay,
Speaker 9: So all of that is kind of the description of
Speaker 9: sickle cell anemia, which is when you have two copies
Speaker 9: of that mutated beta globin gene, so that you have
Speaker 9: messed up hemoglobin. That's not the only way that you
Speaker 9: can have sickle cell disease. There are a number of
Speaker 9: other mutations that can result in sickle cell disease that
Speaker 9: is usually less severe than sickle cell anemia, although in
Speaker 9: some cases it's almost as severe. So if you have
Speaker 9: one copy of the sickle like HBS, that sickle cell allele,
Speaker 9: and then you have one copy of a beta thallasmia allele.
Speaker 9: So beta thallasemia is something most people might have heard of,
Speaker 9: or thallasmia maybe you've heard of. This is another entirely
Speaker 9: separate mutation of your beta globin gene. Right, you can
Speaker 9: have one copy of HBS and one copy of beta thallasmia,
Speaker 9: then you kind of have thallasmia and you kind of
Speaker 9: have sickle cell disease. You have like a combination of both.
Speaker 9: So typically your symptoms aren't going to be as severe
Speaker 9: as someone with two copies of sickle cell, but you're
Speaker 9: still going to have some of that. You can still
Speaker 9: have some cells that stickle essentially, Okay, gotcha. Yeah, there's
Speaker 9: another gene called HBC that's like another form of sickle cell,
Speaker 9: so you can be HBS HBC. That's a whole nother one.
Speaker 9: There's another type of thallacemia called alpha thallasmia, So that's
Speaker 9: where those alpha polypeptides are messed up rather than the
Speaker 9: betas in your hemoglobin, and that typically leads to actually
Speaker 9: like a less severe form of sickle cell anemia or
Speaker 9: of sickle cell disease.
Speaker 8: Why, like, what's the difference between the alpha and the
Speaker 8: beta that it would be a different.
Speaker 9: So it's actually this is very complicated, but it's actually
Speaker 9: because instead of only two copies of alpha, we have
Speaker 9: four copies of alpha. So if you have just one mutation,
Speaker 9: you still have three good copies.
Speaker 8: Gotcha.
Speaker 9: So what's I think really important to kind of that?
Speaker 9: It's a good question. I'm glad you asked that, Aaron,
Speaker 9: because what's important about this is that if you have
Speaker 9: one copy of this HBS, this sickle cell a wheel
Speaker 9: you're still gonna make that kind of messed up beta hemoglobin,
Speaker 9: but you'll make enough normal that you won't have these
Speaker 9: sickling events. Okay, you make enough normal hemoglobin that they
Speaker 9: can't form those chains and sickle unless you have like
Speaker 9: extremely low oxygen concentrations. Okay, So in rare instances you
Speaker 9: can still get sickling, but in general it's going to
Speaker 9: be a lot less. It's not going to be nearly
Speaker 9: as many of your red blood cells. If you have
Speaker 9: two copies, all you make is a messed up beta hemoglobin. Okay,
Speaker 9: So all of your red blood cells have this messed
Speaker 9: up hemoglobin okay.
Speaker 8: Right, And this is where, like the language around it
Speaker 8: is so important to remember, like the difference between sickle
Speaker 8: cell disease, sickle cell trait, and sickle cell anemia exactly,
Speaker 8: And that's led to a lot of confusion. Yeah, in
Speaker 8: the history of it as all talk about.
Speaker 9: Yeah, and so sickle cell trait would be if you
Speaker 9: have one copy of HBS and one copy of a
Speaker 9: normal HbA or normal adult hemoglobin right right, Oh gosh,
Speaker 9: So yeah, Okay, I think that's all about those types
Speaker 9: of things. What else do you want to know about
Speaker 9: the biology. Arin, I've got more for you.
Speaker 8: Well, I want to know about treatments.
Speaker 9: Okay, let's talk about it.
Speaker 8: It's not great, Okay.
Speaker 9: There are some good things. So remember how, especially for
Speaker 9: young kids, most common cause of like death is overwhelming
Speaker 9: bacterial infection. So in many countries in the world, we
Speaker 9: now screen for sickle cell disease in newborns, and if
Speaker 9: you identify somebody with sickle cell disease, you can start
Speaker 9: treating them prophylactically so before they ever get sick with penicillin.
Speaker 9: So these kids get penicillin just every day for like
Speaker 9: the first five years of their life. So that has
Speaker 9: reduced the death rate to like less than three percent
Speaker 9: compared to over twenty five percent.
Speaker 8: That's great.
Speaker 9: So that's great. Vaccinating babies is massively helpful in preventing
Speaker 9: overwhelming infection because we have vaccines for a lot of
Speaker 9: the things that commonly cause infection in these kids. But
Speaker 9: beyond that, so that's kind of like we can prevent
Speaker 9: kids from dying at a very young age from sickle
Speaker 9: cell but beyond that, we really have cruddy treatment for
Speaker 9: sickle cell disease and sickle cell anemia. If somebody comes
Speaker 9: in with one of these acute crises of pain. There's
Speaker 9: not much more to do besides pain control, which I'm
Speaker 9: sure you'll talk more about later. Is like, yeah, the problems,
Speaker 9: so many problems. You can give transfusions, so you can
Speaker 9: do an exchange transfusion where you take out their blood
Speaker 9: and give them new blood essentially, so that can decrease
Speaker 9: the amount of sickled cells in their blood, which can
Speaker 9: be very helpful. But the only actual treatment like drug
Speaker 9: that we have is hydroxyurea, which this is so fascinating.
Speaker 9: We have no idea how it does this, but what
Speaker 9: it does is it increases the amount of that fetal hemoglobin,
Speaker 9: that gamma hemoglobin. I see your confused.
Speaker 8: Face, Saran, Yeah, how why? Why is how okay?
Speaker 9: How can we have a.
Speaker 8: Normal amount Do we have, like any amount of gamma
Speaker 8: hemoglobin just circulating at any given time?
Speaker 9: Yes? So okay and great question. Potentially yes. And there's
Speaker 9: massive amounts of variation in how much fetal hemoglobin a
Speaker 9: non sickle cell disease person produces, and even within someone
Speaker 9: with sickle cell disease, how much fetal hemoglobin they have
Speaker 9: correlates to how severe their disease is. So the more
Speaker 9: fetal hemoglobin, the less severe their disease tends to be.
Speaker 9: So giving somebody hydroxyurea in increases the production of fetal hemoglobin,
Speaker 9: decreases the severity of disease.
Speaker 8: That's fascinating, fascinating, And I have a question, Okay, do
Speaker 8: you know is there any sort of elevational or altitudinal
Speaker 8: gradient in terms of like, let's say, if populations whose
Speaker 8: ancestral history has been mostly like high elevation, do they
Speaker 8: produce more gamma hemoglobin than those lower elevations.
Speaker 9: That's such a good question, and I can't remember. That
Speaker 9: is such a good questionnairein I can't remember. I don't
Speaker 9: know if people tend to have higher fetal hemoglobin, but
Speaker 9: there are certainly adaptations in populations that have lived for
Speaker 9: a long time at high altitudes where their hemoglobin has
Speaker 9: a higher affinity so it binds tighter to oxygen the
Speaker 9: way that fetal hemoglobin does the same way.
Speaker 8: Interesting.
Speaker 9: Yeah, there's there's so much more to that whole, like
Speaker 9: the whole oxygen thing and altitude get into it.
Speaker 8: But I know, I mean, there's we really should do
Speaker 8: like an episode on blood ooh, because I also want
Speaker 8: to talk about blood groups at some point.
Speaker 9: Oh, I know we've never done that. That would be super fun.
Speaker 9: I'd love to talk about blood even more. Okay, people
Speaker 9: will be experts by then because we did it in
Speaker 9: hepatitis and now we're doing hemoglobin. It's cool.
Speaker 8: Okay.
Speaker 9: So that's hydroxyurea. So that is considered a disease modifying agent.
Speaker 9: It's the only one we have because it actually improves
Speaker 9: your functioning essentially by increasing the amount of fetal hemoglobin.
Speaker 9: But the only cure, and I'm going to put that
Speaker 9: in air quotes, is bone met or chansplant.
Speaker 8: But that has its own suite of problems.
Speaker 9: Absolutely always does. Yeah, So it has to be, you know,
Speaker 9: a perfectly or very well matched donor, which is very
Speaker 9: difficult to find. It requires that you wipe out somebody's
Speaker 9: entire bone marrow first, which leads them very susceptible to infection.
Speaker 9: Then once you put in the new bone marrow, you
Speaker 9: can have auto rejection, et cetera. And so because the
Speaker 9: severity of sickle cell disease and sickle cell anemia is
Speaker 9: so it ranges so much, transplants are not generally done
Speaker 9: except in very severe cases, and even then only in
Speaker 9: high income countries like the US or the UK. So
Speaker 9: it's very rare essentially, which is problematic since that's the
Speaker 9: only curative treatment that we.
Speaker 8: Have, right, and it's like curative is in like gets
Speaker 8: done forever.
Speaker 9: Like you're if yeah, as long as your body doesn't
Speaker 9: reject it, then yes you have you have brand new
Speaker 9: bone marrows, so you no longer make these sickled cells.
Speaker 9: You could still pass that on, right, You would still
Speaker 9: be able to if you had a kid, they could
Speaker 9: have either sickle cell trait or sickle cell anemia because
Speaker 9: but but yeah, you would be cured. Yeah. I think
Speaker 9: that's all the major things I wanted to talk about
Speaker 9: for the biology.
Speaker 8: Okay, gosh, this is a big one.
Speaker 9: It's a big one, Aaron. Where did this come from?
Speaker 9: Why does anyone have to live with sickle cell disease?
Speaker 9: And what the heck is up with this mutation?
Speaker 8: Tell me about it, Okay, as soon as we take
Speaker 8: a short break. Okay, So to tell the history of
Speaker 8: sickle cell trait and sickle cell anemia. For this, I'm
Speaker 8: going to concentrate primarily on the HB S form, not
Speaker 8: talk about thalacmia. This is just about sickle cell anemia
Speaker 8: and sickle cell trait. I think that the best place
Speaker 8: to start is in the name itself, because, aside from
Speaker 8: being one of my favorite things to learn about and
Speaker 8: talk about for any disease, it can also be incredibly revealing,
Speaker 8: especially in the case of sickle cell because the name
Speaker 8: tells us not only what those who named it saw
Speaker 8: and what was important to them in describing this disease,
Speaker 8: but it also makes us consider what discovery is like,
Speaker 8: what does discovery mean, and how often that term is
Speaker 8: misapplied to something that could more accurately be called a development.
Speaker 9: Ooh.
Speaker 8: So, when the term sickle cell anemia was first used
Speaker 8: by Western medicine in nineteen twenty two, named by doctor
Speaker 8: Verna Reem Mason, the medical field was still in the
Speaker 8: midst of this big rush of new technology and new
Speaker 8: theories and new hypotheses that led to enormous leaps forward
Speaker 8: in the understanding of disease, both infectious and non infectious,
Speaker 8: and with huge improvements in microscopic, surgical and other medical tools,
Speaker 8: physicians could now get a much more detailed look at
Speaker 8: what was going on inside the human body, and among
Speaker 8: other things, this led to a shift in how diagnoses
Speaker 8: were made so previously doctors may have had to rely
Speaker 8: solely on symptoms of disease as described by the patient,
Speaker 8: but with these new tools, it allowed for measurements and observation.
Speaker 8: So the art of medicine was becoming a science, and
Speaker 8: this is something that we've kind of talked about before. Yeah,
Speaker 8: And the vast increase in knowledge of medicine and the
Speaker 8: human body also changed the medical field in terms of
Speaker 8: specialization because with the volume of information that was growing
Speaker 8: day by day, it was nearly impossible for one person
Speaker 8: to learn it all and retain it all, and so
Speaker 8: there was not only the capacity, but also the need
Speaker 8: for specialists in certain fields. Okay, interesting, and so both
Speaker 8: of these shifts were enormously beneficial to the people being
Speaker 8: treated because with an accurate diagnosis, you had a greater
Speaker 8: chance of getting appropriate treatment and care. But there were
Speaker 8: also some unintended consequences. So in some ways, medicine became
Speaker 8: more about the body and less about the person, and
Speaker 8: the heightened attention paid to measurements or direct observation could
Speaker 8: sometimes take away from the experience of the person receiving treatment,
Speaker 8: and this is reflected in the naming of sickle cell anemia.
Speaker 8: As you mentioned, The term sickle cell describes the shape
Speaker 8: of the affected cells, which is a direct result of
Speaker 8: the mutated allele, and it was given that name by
Speaker 8: the physicians who first observed these types of cells under
Speaker 8: a microscope. But the condition, the experience of sickle cell
Speaker 8: anemia had been known long before the nineteen hundreds, thousands
Speaker 8: of years before, and people who lived in areas of
Speaker 8: high prevalence, notably in parts of Africa, had names for
Speaker 8: the disease as well. And I have a list of
Speaker 8: these names, but I don't want to butcher them entirely.
Speaker 8: But one of the commonalities of these names is that
Speaker 8: they have sort of this onomatapia, this automatapoetic like rhythm
Speaker 8: to them, And that's because it represented the repetitive, gnawing
Speaker 8: pain of sickle cell anemia rather than the cellular morphology, right.
Speaker 9: So it's like a description of what people were going through,
Speaker 9: not just exactly this what the cell looks like, exactly fascinating.
Speaker 8: And there was also another name that was reported in
Speaker 8: the African medical literature in the late eighteen hundreds. It
Speaker 8: was a term agwanges, meaning children who come and go,
Speaker 8: which is in reference to the high childhood mortality. Yeah,
Speaker 8: and so yeah, these names describe someone's experience with the
Speaker 8: disease and perhaps how they would define it, rather than
Speaker 8: a cellular observation which was completely removed from the experience.
Speaker 8: I mean, if you think about it, if you have
Speaker 8: sickle cell anemia, you are probably familiar with these extremely
Speaker 8: painful episodes characteristic of the disease, but you may have
Speaker 8: never seen your own sickle shaped cells under a microscope. Right,
Speaker 8: So I just think that was a very yeah.
Speaker 9: Oh, I love that, Aaron. That's so so interesting and important,
Speaker 9: and I don't think I ever would have thought about
Speaker 9: about it, quite honestly.
Speaker 8: Well, and this is not my observation, this is something
Speaker 8: I've read in a book, but I think it also
Speaker 8: it did make me think about other diseases that we
Speaker 8: have talked about. And you know, there is a lot
Speaker 8: of me in a name, whether it's a specific to
Speaker 8: a location and we've talked about the issues with that,
Speaker 8: and or whether it's these this very clinical, detached way,
Speaker 8: objective way of looking at a condition. And I think that.
Speaker 8: I mean, there are some other ones that have that
Speaker 8: are more about the experience itself, like Dengey, I remember,
Speaker 8: may have some link to the painful bone breaking sensation.
Speaker 8: But yeah, it's a.
Speaker 9: That's very interesting.
Speaker 8: It's interesting.
Speaker 9: Yeah.
Speaker 8: And also, as the author of one of the books
Speaker 8: I read pointed out, the sharp contrast between the visible,
Speaker 8: the sickle shaped cells, and the invisible the excruciating pain
Speaker 8: endured in the various names of sickle cell anemia. In
Speaker 8: many ways, it mirrors the history of the disease, particularly
Speaker 8: throughout the twentieth and twenty first centuries in the US.
Speaker 8: Oh Okay, So, though there were some brief descriptions of
Speaker 8: what was likely sickle cell anemia since the eighteen hundreds
Speaker 8: the mid eighteen hundreds, the first clinical description of the
Speaker 8: disease was made in nineteen oh four by the University
Speaker 8: of Chicago physician James Herrick, who reported quote peculiar elongated
Speaker 8: and sickle shaped red blood corpuscles in a twenty year
Speaker 8: old patient of his named Walter Clement Nole, who was
Speaker 8: originally from Grenada and the only person of African descent
Speaker 8: to be accepted into the Chicago College of Dental Surgery
Speaker 8: that year.
Speaker 9: Wow.
Speaker 8: Yeah, so Noel had some I don't know if it's
Speaker 8: Noel or Nol. So I'm just saying Noel. Noel had
Speaker 8: some ulcers on his leg and described painful episodes and
Speaker 8: other symptoms of anemia, and so Herrick drew some blood
Speaker 8: and gave it to his interurn named Ernest Irons to
Speaker 8: check it out, and Irons made the actual observation like
Speaker 8: that description, but Herrick reported his findings at a conference
Speaker 8: in nineteen ten, and then Irons was given no credit
Speaker 8: as per USh as per usan And although Walter Clement
Speaker 8: Knole recovered from his illness after his visit to Herrick,
Speaker 8: he did die at a young age at thirty two
Speaker 8: of pneumonia twelve years after that visit. And this first
Speaker 8: description of sickle cell anemia was closely followed by many
Speaker 8: others who noted that it primarily affected black Americans of
Speaker 8: African descent. These were all American physicians, and that complications
Speaker 8: arising from the condition often led to death at an
Speaker 8: early age. And despite these warning bells going hey, we
Speaker 8: have a serious disease here on our hands. Maybe we
Speaker 8: should learn more about it and how to treat it,
Speaker 8: sickle cell anemia remained largely invisible for a couple of
Speaker 8: decades before finally gaining some recognition in the nineteen thirties. Wow. Okay,
Speaker 8: so why was sickle cell anemia obscured for so long?
Speaker 8: I think many reasons. Yeah. Part of it was the
Speaker 8: pre antibiotic high prevalence of acute infectious diseases, and also
Speaker 8: pre vaccine, some of which mimicked the symptoms of sickle celenemia,
Speaker 8: such as malaria, and made it more difficult to see
Speaker 8: this disease underneath. And when antibiotics, vaccines, and infectious disease
Speaker 8: control policies were implemented in the early decades of the
Speaker 8: twentieth century, other chronic diseases became much more visible.
Speaker 9: So it was like kids were just getting sick and
Speaker 9: dying from sickle cell anemia before they knew that it
Speaker 9: was because of sickle cell anemia exactly. Okay, that makes
Speaker 9: sense exactly.
Speaker 8: But of course, the other enormous component was the inherent
Speaker 8: racism in medicine.
Speaker 9: Yeah.
Speaker 8: Higher rates of disease, higher infant mortality, and lower life
Speaker 8: expectancies overall in Black Americans compared to white Americans was
Speaker 8: dismissed by the vast majority of those in the medical field,
Speaker 8: which of course were primarily white, as either evidence for
Speaker 8: a biological basis of race or they said, oh, that
Speaker 8: this is just indicating that, you know, there's large, widespread
Speaker 8: ignorance of medical practices. Oh and essentially the fact that
Speaker 8: Black Americans faced worse health outcomes was seen as normal,
Speaker 8: as an inevitability.
Speaker 9: I would say, unfortunately, that still is the bias in medicine.
Speaker 8: Oh yeah, oh yeah, yeah. And this false concept of
Speaker 8: racial superiority in biology is so longstanding and insidious and
Speaker 8: is still, like we talked about, very present today in medicine. So,
Speaker 8: following the American Civil War, some opponents of emancipation claimed
Speaker 8: that the black race would die out and that the
Speaker 8: high rates of disease and poverty among black people were
Speaker 8: evidence that enslavement was a good thing. And these paternalistic
Speaker 8: beliefs bled into policy policies which were designed to uphold
Speaker 8: these divisions of class and privilege and prevent any movements
Speaker 8: across those invisible but very real lines. In addition, there
Speaker 8: was the bigger issue of how risks of disease overall
Speaker 8: were perceived. So in much of the American South, for instance,
Speaker 8: discussions about disease were framed as the dangers posed by
Speaker 8: black people, rather than the dangers the diseases posed to
Speaker 8: black people.
Speaker 6: Wow.
Speaker 8: So this is something that, like I've talked about before
Speaker 8: in the context of syphilis, to berculosis, hookworm, and so on.
Speaker 8: So high rates of disease among black people were not
Speaker 8: seen as worrisome because they were directly damaging the health
Speaker 8: and shortening life expectancy of black people. It was more, oh, well,
Speaker 8: we don't want white people to get sick from black people.
Speaker 8: So that is where the focus primarily was.
Speaker 9: How can we prevent white people from getting sick with
Speaker 9: what the black people have? Exactly yeah, exactly yeah.
Speaker 8: And this shaped policy and attitudes toward public health and
Speaker 8: access to health care. Basically, the only way a public
Speaker 8: health policy was going to be enacted or research funds
Speaker 8: awarded was if the disease affected or threatened to affect
Speaker 8: white Americans in some way, okay. And so when antibiotics
Speaker 8: and vaccines became more widely available throughout the nineteen thirties
Speaker 8: and forties, the widespread prevalence of chronic diseases such as
Speaker 8: sickle cell anemia was revealed. At the same time, the
Speaker 8: commodification of health and people's bodies had really ramped up.
Speaker 8: And what I mean by that is that basically, alongside
Speaker 8: the medical developments of the late nineteenth century and early
Speaker 8: twentieth century, people's health and bodies began to be assigned
Speaker 8: a monetary value. How much did this procedure cost, how
Speaker 8: much did that medicine cost, how much did someone's poor
Speaker 8: health limit their productive output?
Speaker 9: Disability adjusted life years and yep.
Speaker 3: Right.
Speaker 8: The medical profession contributed to this, not just through the
Speaker 8: exchange of money for treatment, but also by assigning intrinsic
Speaker 8: values to certain conditions. People with rarer diseases were seen
Speaker 8: as valuable to the medical profession. Hospitals in poverty stricken,
Speaker 8: densely populated urban areas were considered to be great places
Speaker 8: to get experience in training as a medical student, and
Speaker 8: the term clinical material was frequently used as a way
Speaker 8: to even further remove the person from the medical experience,
Speaker 8: as in whatever general hospitals supplied an adequate amount of
Speaker 8: clinical material to train students at not one, but two
Speaker 8: medical schools.
Speaker 9: I'm sorry, so that means clinical material meaning humans? Humans?
Speaker 8: Yeah, humans, or like different cases or like different surgeries.
Speaker 8: I mean, and this is like still, this is still today.
Speaker 6: People.
Speaker 8: It's very much like, oh, you should do you should
Speaker 8: you get experience there because you're likely to see more
Speaker 8: of these diseases.
Speaker 9: The amount of times I heard, oh, we've got really
Speaker 9: interesting pathology at this residency program, I'm like, Wow, that's
Speaker 9: horrible for the people in that area, but yeah, yeah.
Speaker 8: And employers also played a large role and continue to
Speaker 8: play a large role in the commodification of health. Maximize
Speaker 8: profits and productivity by ensuring that your employees are well
Speaker 8: enough to work, and of course, if your health can't
Speaker 8: be improved, consider dropping them. Against this backdrop of this
Speaker 8: enormous growth of medical knowledge, reduction of infectious disease, and
Speaker 8: commodification of health and disease awareness of sickle cell anemia
Speaker 8: rose greatly, and in the coming decades this fame would
Speaker 8: grow to become in some ways a double edged sword.
Speaker 8: So on the one hand, the adoption of sickle cell
Speaker 8: anemia throughout the nineteen fifties, sixties seventies as a cause
Speaker 8: by many social groups and the increase in research funding
Speaker 8: for it led to a great deal of important knowledge
Speaker 8: being gained and in a raising awareness overall. Researchers fascinated
Speaker 8: by the puzzle that the disease posed not necessarily by
Speaker 8: the people experiencing the disease, they had uncovered that certain
Speaker 8: conditions like low oxygen and high acidity could induce sickling
Speaker 8: of cells, and they had also observed that sickling could
Speaker 8: also result in people who did not have the disease
Speaker 8: but were relatives of those that did. In nineteen forty nine,
Speaker 8: two papers published nearly simultaneously by doctor James Neil and
Speaker 8: Colonel ea Beat presented the hypothesis that the disease was
Speaker 8: an autosomal recessive trait, meaning that it was inherited, and
Speaker 8: like you said, the two copies were required for disease
Speaker 8: to be present. I also want to note that, once
Speaker 8: again discovery versus development, that the inheritability of sickle cell
Speaker 8: anemia had long recognized in some groups where the disease
Speaker 8: was especially prevalent, such as among certain populations in GHANAA
Speaker 8: makes sense. Yeah. And also in nineteen forty nine, doctor
Speaker 8: Harvey Etano and doctor Linus Pauling demonstrated that the sickling
Speaker 8: was caused by an abnormality in the hemoglobin molecule, prompting
Speaker 8: them to call it a molecular disease. I think it
Speaker 8: might actually be the first disease described as a molecular disease.
Speaker 8: A few years later, the individual amino acid substitution leading
Speaker 8: to the structural change in hemoglobin was identified, teaching researchers
Speaker 8: that that single mutation could be responsible for this whole
Speaker 8: suite of systemic effects on the body.
Speaker 9: Yeah, which is pretty incredible.
Speaker 8: Oh yeah. But a huge shift in the notion or
Speaker 8: representation of sickle cell trait or that sickle cell that
Speaker 8: mutated allele as a disease condition came about with the
Speaker 8: hypothesis first floated in like the mid nineteen forties that
Speaker 8: the sickle cell trait so again, one copy of that
Speaker 8: mutated actually provided a level of protection against the falciparum
Speaker 8: malaria parasite, giving insight into why the allele was present
Speaker 8: at relatively high rates despite its deliterious effects. And so
Speaker 8: this is an example of what is called a balanced polymorphism.
Speaker 8: And this turned the the dichotomy or this long standing
Speaker 8: dogma of normal equals good and abnormal equals bad on
Speaker 8: its head.
Speaker 9: Yeah, it's why the term normal is stupid.
Speaker 8: Yeah, it's it's yeah, it's it's inadequate.
Speaker 9: It doesn't, it doesn't. I mean, what is normal?
Speaker 5: Like it?
Speaker 9: That's not it? And sometimes it's hard, like I'm like,
Speaker 9: I don't I don't know what other word to use,
Speaker 9: but that it's not a good word.
Speaker 8: I know, because we need to improve our vocabulary. Yeah
Speaker 8: for that. So, but these these scientific breakthroughs, particularly in
Speaker 8: its labeling as a molecular disease, and all the hype
Speaker 8: that that generated, it got a lot of researchers super
Speaker 8: excited to jump on the sickle cell train, which was
Speaker 8: also pulled forward by the increasing interconnectedness of hospitals, research institutions,
Speaker 8: public health departments, and outreach groups. And this wealth of
Speaker 8: new information about the nature of sickle cell trait and
Speaker 8: sickle cell anemia did not, though necessarily, translate directly into
Speaker 8: lives saved, because in much of the South, racial segregation
Speaker 8: still prohibited Black Americans from seeking care at the highest
Speaker 8: funded hospitals, which were of course white only.
Speaker 9: Yeah wow.
Speaker 8: In addition, and here comes the other side of that
Speaker 8: double edged sword. Despite these advancements in the understanding of
Speaker 8: the disease outside of academia, such as in political discussions
Speaker 8: or debates, clear knowledge about the exact nature of cell
Speaker 8: anemia lagged far behind, especially in understanding the difference between
Speaker 8: sickle cell trait and sickle cell anemia. For instance, during
Speaker 8: World War Two, a controversial debate arose about whether sickle
Speaker 8: cell trait, so having the one copy posed a threat
Speaker 8: to the health of soldiers who had the trait, in
Speaker 8: other words, posed a threat to war efforts. Oh gosh,
Speaker 8: suddenly this disease that had been invisible for so long
Speaker 8: was now visible and could be used to discriminate against
Speaker 8: those with the disease or even just the trait. After
Speaker 8: four people in the Marine Corps with sickle cell trait
Speaker 8: died after a training exercise at a high elevation, strict
Speaker 8: limits were placed on whether those with sickle cell trait
Speaker 8: could become pilots either in the armed forces or commercial airlines,
Speaker 8: or hold other positions. So not just in armed forces,
Speaker 8: so there was like a huge, huge restrictions placed on that,
Speaker 8: but also in other parts of the workforce, so like
Speaker 8: flight attendants. There was a lot of issues with health
Speaker 8: insurance carriers dropping people who were found to have sickle
Speaker 8: cell trait or sickle cell anemia.
Speaker 9: Oh my god.
Speaker 8: And so these restrictions were instances of racial discrimination, since
Speaker 8: the overwhelming majority of those forbidden from entering the armed forces,
Speaker 8: for instance, due to sickle cell trait were black, and
Speaker 8: class action lawsuits led to the removal of some of
Speaker 8: these restrictions, but only decades after they were first put
Speaker 8: in place.
Speaker 9: Oh my god.
Speaker 8: But of course, just because restrictions are gone does not
Speaker 8: mean the racial discrimination and the workplace was gone. And
Speaker 8: whether it was because the parent of a child with
Speaker 8: sickle cell anemia was more likely to miswork or if
Speaker 8: they themselves were affected, there was simply no shortage of
Speaker 8: ways for people to be discriminated against. Into the nineteen
Speaker 8: sixties and nineteen seventies, sickle cell trait and sickle cell
Speaker 8: anemia moved or was pulled even for into the spotlight
Speaker 8: in academic circles. Sickle cell became the focus of narratives
Speaker 8: that interwove of biology, anthropology, and history to explain whatever
Speaker 8: story was the goal of the author, and these narratives
Speaker 8: were sometimes criticized for their tendency to make sweeping generalizations
Speaker 8: about entire groups of people or entire places, or for
Speaker 8: forcing the facts to fit the story, making it sort
Speaker 8: of a just so story. Other researchers finally began talking
Speaker 8: about how sickle cell disease and inadequate medical care may
Speaker 8: lead to poverty rather than poverty being the cause of
Speaker 8: disease and ill health, and understanding the more of the
Speaker 8: cycle of poverty and access to healthcare. And in the
Speaker 8: socio political sphere, sickle cell disease took on new meaning
Speaker 8: during the civil rights movement of the nineteen sixties. It
Speaker 8: was held by some civil rights groups to be symbolic
Speaker 8: of the long standing invisible or ignored pain and suffering
Speaker 8: experience by so many who had long been racially discriminated
Speaker 8: against and whose access to healthcare had always been restricted.
Speaker 8: Despite the increased awareness of sickle cell, it's still lagged
Speaker 8: behind other genetic diseases in terms of funding, particularly those
Speaker 8: that disproportionately affected white people, such as cystic fibrosis. Oh yeah, So,
Speaker 8: For example, in nineteen sixty seven, there were roughly the
Speaker 8: same new number of cases of cystic fibrosis and sickle
Speaker 8: cell anemia, but the difference in funding from volunteer organizations
Speaker 8: was staggering. For cystic fibrosis, these organizations raised one point
Speaker 8: nine million dollars, and for sickle cell that number was
Speaker 8: fifty thousand. Uh.
Speaker 9: Do you want some current numbers or do you want
Speaker 9: me to tell you those later?
Speaker 8: Because tell me those later but I'm yeah, I'm sure
Speaker 8: that they're not any better at all. Yep, yep. But
Speaker 8: there was a lot of charitable work being done and
Speaker 8: awareness efforts that were made. So the Black Panther Party,
Speaker 8: among other groups, organized and created a massive network of
Speaker 8: healthcare centers across the country where one of the goals
Speaker 8: was to raise sickle cell awareness and funding. Doctor Charles Witten,
Speaker 8: for whom our drink is named, started the Sickle Cell
Speaker 8: Detection and Information Center in Detroit in nineteen seventy one
Speaker 8: and also helped found the Sickle Cell Disease Association of America,
Speaker 8: which has been instrumental not only in their educational efforts,
Speaker 8: but also in assisting families who have been impacted by
Speaker 8: sickle cell disease. And also he did a lot of
Speaker 8: work in terms of lowering barriers for people who were
Speaker 8: underrepresented in medicine to be able to go to medical
Speaker 8: school and have that as an option. Federal funds also
Speaker 8: poured in as Nixon signed into law the Sickle Cell
Speaker 8: Anemia Control Act in nineteen seventy two, and so this
Speaker 8: act included increased funds for research as well as healthcare
Speaker 8: for those impacted. It also required genetic screening to be
Speaker 8: voluntary rather than mandatory, which had been a huge issue
Speaker 8: previously because that just like paved the way for discrimination,
Speaker 8: and it also included support for reproductive counseling. And during
Speaker 8: the seventies our understanding of the disease itself became more
Speaker 8: nuanced as well. So first, new research about the possible
Speaker 8: origins of the allele showed that it likely emerged in
Speaker 8: four different mutational events between seventy one hundred and fifty
Speaker 8: thousand years ago, three events that took place in Africa
Speaker 8: and a fourth that took place in either Saudi Arabia
Speaker 8: or Central India. This allele emerged in different places around
Speaker 8: the world, it's not just from one origin event. Secondly,
Speaker 8: there was the growing awareness of other hemoglobin disorders and
Speaker 8: the fact that sickle cell trade was found in non
Speaker 8: black people as well, which threw some complexity into the discussion.
Speaker 8: In the seventies, representation of sickle cell anemia and popular
Speaker 8: media also increased, as characters with the disease were featured
Speaker 8: in a couple of movies or TV episodes, and magazines
Speaker 8: featured articles about the condition. But once again, here comes
Speaker 8: the other side of that double edged sword. Yeah, The
Speaker 8: prominence of sickle cell anemia and political discussions of this
Speaker 8: time meant that some politicians felt as though they could
Speaker 8: use the disease to symbolize whatever they wanted to in
Speaker 8: order to drive their own narrative about race relations in
Speaker 8: the US, and sometimes it was used. Sometimes that was
Speaker 8: used to bring about real positive change, but other times
Speaker 8: it was twisted to halt forward progress. Let's take genetic
Speaker 8: screening and reproductive counseling as an example. Okay, the push
Speaker 8: for genetic screening for sickle cell anemia and sickle cell
Speaker 8: trait came at a time when genetic screening in general
Speaker 8: had greatly increased, and when discussion of reproductive rights was
Speaker 8: at the forefront, especially issues of birth control and abortion.
Speaker 8: Genetic screening to look for sickle cell trait or sickle
Speaker 8: cell anemia, although it was helpful in terms of getting
Speaker 8: people the medical attention that they may need, it often
Speaker 8: did an inadequate job of explaining what exactly the difference
Speaker 8: between sickle cell trait and sickle cell anemia was. And
Speaker 8: this inadequate explanation may have been unintentional or intentional at times.
Speaker 8: It appears so people who had the trait just one
Speaker 8: copy of the allele, were often openly discouraged from having
Speaker 8: children and urged to have abortions or undergo sterilization procedures
Speaker 8: that were sometimes made free as an incentive. Uh yeah.
Speaker 8: And then the concept of mandatory screening for this and
Speaker 8: other genetic disorders was floated, and Linus Pauling, the Nobel
Speaker 8: Prize winner and whose name I mentioned earlier as being
Speaker 8: the scientist yep, he suggests, did that everyone who had
Speaker 8: the sickle cell trait should have it tattooed on their
Speaker 8: forehead so that when they see another person with the tattoo,
Speaker 8: they can avoid falling in love and wanting to have
Speaker 8: children with them. What mm hmmm mm hmm.
Speaker 9: Oh.
Speaker 8: And these acts, these discussions, of course, resulted in accusations
Speaker 8: of restricting black fertility, racial genocide, and new eugenics. And rightfully, so.
Speaker 9: Yeah, that's what sounds like to me.
Speaker 8: Oh yeah, And this misleading reproductive counseling for sickle cell
Speaker 8: was just one way that reproductive restrictions were intentionally or
Speaker 8: forcefully placed upon Black people. I really recommend Killing the
Speaker 8: Black Body by Dorothy Roberts to read more about that topic.
Speaker 8: And so, before wrapping up with the history of sickle
Speaker 8: cell in the nineteen eighties and nineteen nineties. I want
Speaker 8: to read a quote by the author of Dyeing in
Speaker 8: the City of the Blues that I think does a
Speaker 8: really good job of summing up the nineteen seventies and
Speaker 8: sickle cell perfectly. The story of sickle cell disease in
Speaker 8: the early nineteen seventies also revealed the ways in which
Speaker 8: the political process both channeled and deflected the popular activism
Speaker 8: of the time. It was a time of grudging recognition
Speaker 8: of the black experience, but it proved difficult to translate
Speaker 8: that awareness directly into health policy without creating enormous new,
Speaker 8: stigmatizing burdens for Black Americans and without fostering growing cynicism
Speaker 8: about racial politics. Yep, yep. And so that brings us
Speaker 8: to the nineteen eighties and nineteen nineties. I don't want
Speaker 8: to step on your toes too much, Aaron, about whatever
Speaker 8: you're going to talk about. So I'm just going to
Speaker 8: go over a few big developments or patterns that emerge
Speaker 8: during this time with regard to sickle cell that I
Speaker 8: have a feeling you'll talk more about.
Speaker 9: Okay, let's see.
Speaker 8: Yeah, So, as you mentioned pain management is a huge
Speaker 8: component of sickle cell anemia, and the sympathy for people
Speaker 8: with sickle cell that seemed characteristic of the nineteen sixties
Speaker 8: and nineteen seventies kind of gave way to this disturbing
Speaker 8: trend of cynicism and stigma. More and more healthcare providers
Speaker 8: seem to simply not believe that people with sickle cell
Speaker 8: anemia were experiencing a true painful episode, and there were
Speaker 8: increasing reports of healthcare providers accusing their sickle cell anemia
Speaker 8: patients of faking it, of exhibiting drug seeking behavior and
Speaker 8: correspondingly limiting the pain medication prescribed. And earlier, when you
Speaker 8: talked about the different timeline of when at different ages
Speaker 8: you experience you're more likely to experience one symptom over another,
Speaker 8: that the increase in painful episodes in late adolescents and
Speaker 8: early adulthood is something that also made this whole made
Speaker 8: this whole thing worse. They were like, oh, well, you're
Speaker 8: a young adult, you're just seeking drugs, not going to
Speaker 8: give you any Oh my god, And this is you know,
Speaker 8: this is despite the fact that there was research indicating
Speaker 8: that this wasn't going on, that people with sickle cell
Speaker 8: anemia were just as worried about their own, you know,
Speaker 8: narcotic consumption or pain medication consumption as as anyone else.
Speaker 8: And it was it's just like it didn't seem to
Speaker 8: make a difference. Yeah, it's like it seemed to be
Speaker 8: like this this belief that became so embraced and like
Speaker 8: so difficult to get rid of.
Speaker 9: It's so frustrating that in so many papers that you read,
Speaker 9: it's still something that is mentioned like, oh, you often
Speaker 9: have to use opioids to treat pain, which can lead
Speaker 9: to addiction. It's like that's true in anyone. And there's
Speaker 9: no higher rates of opioid addiction in people with sickle
Speaker 9: cellinemia than in the general population, Like there just isn't.
Speaker 9: So it's it's infuriating that you'd be like withholding treatment
Speaker 9: that is necessary.
Speaker 5: Ough.
Speaker 8: Yeah, well, and there's also there was also something that
Speaker 8: was mentioned in this book about how there was research
Speaker 8: indicating that opioid addictions starting from hospital treatments or medical
Speaker 8: treatments is extraordinarily low. That is not the way that
Speaker 8: the vast majority of opioid addictions begin. And so but
Speaker 8: despite all this, this enormous bias still remains and this
Speaker 8: is I mean, this is a larger issue. Yeah, the
Speaker 8: invisibility of pain in medicine. We can't measure it, and
Speaker 8: I think that that makes people trust it less, trust
Speaker 8: the person less. And it sort of goes back to
Speaker 8: what I was saying earlier about how like medicine became
Speaker 8: more about the body and measurements and these things that
Speaker 8: you could, you know, you could put on a chart.
Speaker 8: Then it became about the person's experience itself.
Speaker 3: Yeah.
Speaker 8: So yeah, yeah, but you know, in this context, what
Speaker 8: this meant, this this increasing you know, disbelief, was that
Speaker 8: people with sickle cell anemia were at renewed risk for
Speaker 8: their pain, their experience to once again be neglected, ignored,
Speaker 8: and made invisible. And this persists today. This issue and
Speaker 8: these decades also brought the promise of many different therapies
Speaker 8: for sickle cell anemia, such as hydroxyurea as you mentioned,
Speaker 8: and bone mirror transplantation, which didn't necessarily uphold the shiny
Speaker 8: promises that had been made about them in their first introduction.
Speaker 8: But I'm really hopeful to hear more about new approaches.
Speaker 8: But I want to end now again with another quote,
Speaker 8: again from Keith Wailu. The author of Dying in the
Speaker 8: City of the Blues. For liberals, moderates, and conservatives alike,
Speaker 8: the history of neglect and the disease's chronic, painful character
Speaker 8: seemed to reflect White America's neglect and misunderstanding of black
Speaker 8: health concerns and demanded attention. The disease became a multipurpose
Speaker 8: metaphor a proxy in social, economic, and political debates about
Speaker 8: a wide range of seemingly unrelated issues. Ye okay, erin,
Speaker 8: bring me up to speed on what's going on with
Speaker 8: sickle cell today.
Speaker 9: Okay, let's take a quick break first, all right, So
Speaker 9: we'll talk first about numbers, how many people are being
Speaker 9: affected by sickle cell in the US and in the
Speaker 9: world today, and then we'll touch a little bit more
Speaker 9: on why that is and the malaria connection, because I
Speaker 9: do think that's a really interesting part of the story.
Speaker 9: And then we'll talk about current research. Does that sound good?
Speaker 8: Sounds great?
Speaker 9: Okay? So we'll talk first about the US and then globally.
Speaker 9: So in the US, newborn screening is conducted since two
Speaker 9: thousand and six or two thousand and seven across the
Speaker 9: board in all states plus Puerto Rico, and the US
Speaker 9: Virgin Islands, so we know the rates of sickle cell
Speaker 9: allele in the population. So one copy having one copy
Speaker 9: of the sickle cell trait okay. So overall in the
Speaker 9: US in twenty ten, the incidence was fifteen per one
Speaker 9: thousand babies born trait trait okay. But this is a
Speaker 9: huge range, from seventy three per one thousand among black
Speaker 9: newborns to two per one thousand in Asian, Native, Hawaiian
Speaker 9: and Pacific Islander newborns, three in white babies, and seven
Speaker 9: per one thousand in Hispanic newborns.
Speaker 8: And this is voluntary or mandatory screening.
Speaker 9: So newborn screening is generally it's universal. I think it
Speaker 9: is possible to opt out of it, but in general
Speaker 9: it's universal and kind of recommended. I think most of
Speaker 9: the time they don't want to let you leave the
Speaker 9: hospital without newborn screening because it doesn't only screen for
Speaker 9: sickle cell. This screen's for a whole bunch of different
Speaker 9: We talked about this in the cystic fibrosis episode as well,
Speaker 9: right right, because you're also identifying then those newborns with
Speaker 9: sickle cell anemia. But what's interesting is that it's actually
Speaker 9: hard to get a number on the number of babies
Speaker 9: in the US born with sickle cell anemia, which I
Speaker 9: think is interesting. So let's talk about the whole globe.
Speaker 9: How many people are born every year with sickle cell
Speaker 9: anemia globally. Estimates are about three hundred thousand, just over
Speaker 9: three hundred thousand babies born every year with sickle cell anemia.
Speaker 8: That's a huge number.
Speaker 9: It's a massive number, and I want to point out
Speaker 9: that that number is the number of babies born with
Speaker 9: sickle cell HBSS. But remember that there are other ways
Speaker 9: that you can have sickle cell anemia, right. You could
Speaker 9: have it with one copy of HBS and one copy
Speaker 9: of beta thalacemia. You could have it with one copy
Speaker 9: of HBS and one copy of HBC. Those aren't included
Speaker 9: in that estimate of three hundred thousand. So it's thought
Speaker 9: that that total number accounts for about seventy percent of
Speaker 9: the total amount of sickle cell disease, so that whole
Speaker 9: range of clinical disease worldwide. And it's also estimated that
Speaker 9: about half of these babies worldwide are born in Nigeria,
Speaker 9: the Democratic Republic of Congo, and India, and that in
Speaker 9: many parts of Sub Saharan Africa, sickle cell anemia might
Speaker 9: be responsible for as much as six percent of all
Speaker 9: childhood mortality. Six percent, Oh my god, just from sickle
Speaker 9: cell anemia. Because in many places, in many parts of
Speaker 9: the world, under five mortality from sickle cell anemia, so
Speaker 9: dying before your fifth birthday can be as high as
Speaker 9: fifty to ninety percent, which is atrocious.
Speaker 8: Wow.
Speaker 9: Yeah, wow, yeah yeah. And that's because if babies aren't
Speaker 9: identified by newborn screening, then they don't receive penicillin prophylaxis,
Speaker 9: or they don't receive adequate vaccinations, then it's very common
Speaker 9: that they will die from overwhelming infection before they turn five.
Speaker 9: So that's why newborn screening is so important and has
Speaker 9: been so helpful. Like it's only worth screening if you
Speaker 9: can do something about it, right, So we screen for
Speaker 9: things that we can prevent death if we identify them early.
Speaker 9: And so that's what we can do with newborn screening.
Speaker 8: Yeah, I think it's just been It's like I mean,
Speaker 8: and this is in general. Newborn screening or any kind
Speaker 8: of genetic screening is such a touchy issue because it
Speaker 8: can so easily lead to you know, who has that
Speaker 8: information and how can I use it against you absolutely.
Speaker 9: I mean, plus it gets into so many things of
Speaker 9: So if you identify a newborn with a genetic trait,
Speaker 9: that had to come from either mom or dad, right,
Speaker 9: so now you know that either mom or dad has this.
Speaker 9: Maybe they didn't want to know that. Like, there's a
Speaker 9: whole the ethics of all of that is wide ranging
Speaker 9: and more than we can talk about in this episode. Yes,
Speaker 9: but identifying babies with sickle cell anemia prevents them from dying,
Speaker 9: So in that way it's extremely important and helpful. But
Speaker 9: despite the fact that this is a very common disease
Speaker 9: and a very common trait among the population, like you said,
Speaker 9: funding discrepancies remain, which is why to date we have
Speaker 9: only one disease modifying treatment, that is hydroxyurea. So I
Speaker 9: want to talk I want to give some more specific numbers.
Speaker 9: You mentioned them from I think the sixties and seventies,
Speaker 9: so let's talk about the last decade, from two thousand
Speaker 9: and eight to twenty eighteen.
Speaker 8: Is that I was hoping you would do this.
Speaker 9: This paper just came out in March of this year.
Speaker 9: So we'll compare federal funding per person between cystic fibrosis,
Speaker 9: which we did an episode on and sickle cell disease. So,
Speaker 9: cystic fibrosis is another genetic disorder. It's also identified on
Speaker 9: newborn screens. It's also like the most common genetic disorder
Speaker 9: among white babies. So compared with cystic fibrosis, per person
Speaker 9: with the disease. In the US, cystic fibrosis received two thousand,
Speaker 9: eight hundred dollars in federal funding compared to eight hundred
Speaker 9: for sickle cell. Wow, that's two thousand dollars more. And
Speaker 9: it's even worse if you look at charitable foundation expenditures
Speaker 9: cystic fibrosis seven thousand, six hundred dollars per person with
Speaker 9: cystic fibrosis compared to one hundred.
Speaker 8: Oh my god, oh my for sickle cell.
Speaker 9: Which I mean this directly leads to a discrepancy in
Speaker 9: the number of new drug approvals. In that same time period,
Speaker 9: four new drugs were approved for cystic fibrosis, one for
Speaker 9: sickle cell.
Speaker 8: I mean, it just it just trickles down and down
Speaker 8: and down. Like you have the research money, you have
Speaker 8: treatment accessibility, you have new treatments being developed, you have healthcare,
Speaker 8: access to healthcare, like all of these different components to it,
Speaker 8: which is yeah.
Speaker 9: And so to put like a specific number two on
Speaker 9: the difference in terms of overall prevalence of sickle cell
Speaker 9: versus cystic fibrosis in the US. This paper reported the
Speaker 9: US birth rate of stickle cell disease is one in
Speaker 9: three hundred and sixty five black babies. For cystic fibrosis,
Speaker 9: it's one. It's very high. That's scary high. For cystic fibrosis.
Speaker 9: It's one in twenty five hundred white babies, which is
Speaker 9: also you could say, very high, but one in three
Speaker 9: sixty five is a lot higher.
Speaker 8: But yeah, when you when you put the numbers side
Speaker 8: by side, it is very I mean, it's not surprising,
Speaker 8: but it is appalling that I know there's such unequal support, yeah, funds.
Speaker 9: And so I think it kind of leads to a
Speaker 9: really important question about why is it that this is
Speaker 9: such a prevalent disease. Because a lot of times when
Speaker 9: we have genetic diseases that are recessive, so you have
Speaker 9: to have two copies of that allele in theory evolutionarily
Speaker 9: that that allele that mutation should die out right if
Speaker 9: it's so bad that if you have two copies of
Speaker 9: it you end up dying before the age of five,
Speaker 9: You're not going to be reproducing, so you're not going
Speaker 9: to be passing on that allele. So why is it
Speaker 9: at such high prevalence in the black population. Here's why,
Speaker 9: or at least what we think. It turns out that
Speaker 9: if you have one copy of this allele, it's very
Speaker 9: protective against dying from malaria. It's very protective against infection
Speaker 9: severe infection with Plasmodium falciparum malaria. So in regions where
Speaker 9: Plasmodium falciparum malaria, so that one species of malaria is
Speaker 9: very very prevalent, the prevalence of this specific mutation is
Speaker 9: also very prevalent. What I think is so interesting is
Speaker 9: like this has been kind of an epidemial. We've shown
Speaker 9: this epidemiologically in so many many studies just how massive
Speaker 9: the protection is. But there's still not a clear molecular
Speaker 9: answer as to how one copy of this allele protects
Speaker 9: you against dying from malaria. Overall, it seems like if
Speaker 9: you have some of that HBS beta hemoglobin, then your
Speaker 9: cells can eventually sickle, and then those cells that are
Speaker 9: infected with plasmodium, the plasmodium doesn't replicate, so essentially malaria
Speaker 9: can't grow as well in those cells for like a
Speaker 9: number of different reasons that we still don't fully understand.
Speaker 8: Right, But it's it's only in the cells that have sickled.
Speaker 9: Yeah, And so it turns out that infected cells tend
Speaker 9: to sequester in certain organs that have low oxygen concentration. Right,
Speaker 9: So then those cells something yeah, spleen and liver. So
Speaker 9: then those cells end up sickling because of that. So
Speaker 9: whereas normally, if you just have one copy, your cells
Speaker 9: wouldn't sickle very often, but these infected cells get sequestered
Speaker 9: under low oxygen concentration and then end up sickling, and
Speaker 9: then the plasmodium can't replicate.
Speaker 8: That's really interesting.
Speaker 9: Yeah, it's pretty interesting. So I'll post a paper, one
Speaker 9: of the more recent papers I found, going into more
Speaker 9: detail on that if you're interested. But yeah, so then
Speaker 9: I guess the question is where do we go from here?
Speaker 9: And even though we only get what one hundred or
Speaker 9: eight hundred research dollars per twenty eight hundred versystic virosis,
Speaker 9: is their research going on about more treatments? And the
Speaker 9: answer is yes, there's actually some pretty exciting in terms
Speaker 9: of technology treatments on the Horizon. So we have a
Speaker 9: very special guest on today to talk about the wonderful
Speaker 9: world of genome editing and specifically CRISPER as it relates
Speaker 9: to treatment options for sickle cell disease and other genetic disorders.
Speaker 9: So let me introduce doctor Meghan Hawkstrasser, the Education Programs
Speaker 9: Manager at Innovative Genomics Institute in Berkeley, who's here to
Speaker 9: tell us in much greater detail than I ever could,
Speaker 9: what CRISPER is, a little bit about genome editing, and
Speaker 9: what that even means, how we can use it for
Speaker 9: diseases like sickle cell, what some of the drawbacks might be,
Speaker 9: and how far away we are from technology like this
Speaker 9: being in everyone's life.
Speaker 8: Excellent.
Speaker 5: My name is Megan Hawkstrasser, and I work for the
Speaker 5: Innovative Genomics Institute or IGI, at UC Berkeley. I am
Speaker 5: the education program Manager, so I basically try to talk
Speaker 5: to people about all of the research that our institute
Speaker 5: does and the science behind it and help them understand
Speaker 5: what it means and what it's all about. So the IGI,
Speaker 5: or the Innovative Genomics Institute, is a partnership between UC
Speaker 5: Berkeley and you see San Francisco, So we're a nonprofit
Speaker 5: research group doing academic research trying to use genetic engineering
Speaker 5: tools like Crisper to solve big world problems. So we
Speaker 5: work in biomedicine and human health. We work in sustainable agriculture,
Speaker 5: and we basically try to improve based and other technologies
Speaker 5: that are used to manipulate DNA in different ways, improve
Speaker 5: the tools and then apply them to solve different problems.
Speaker 9: Oh my gosh, that's amazing good. Oh that is so cool. Well,
Speaker 9: so could you start off just by telling us what
Speaker 9: exactly CRISPER is. I think that people have heard that term,
Speaker 9: but a lot of us don't know what it means.
Speaker 5: Sure, I mean I got my PhD study in CRISPER,
Speaker 5: and I still am behind the times and understanding every
Speaker 5: little bit about it. It's really complicated, and actually there's
Speaker 5: new Crisper tools and Crisper news like every other day,
Speaker 5: so it's hard to keep up with. But at the core, Crisper,
Speaker 5: in the most basic terms, is a way of changing DNA.
Speaker 5: So it's a tool that scientists can use to make targeted,
Speaker 5: precise changes in the sequence of DNA that's in a
Speaker 5: living cell or organism. So this is really impactful because
Speaker 5: previously we were kind of limited to, you know, making
Speaker 5: synthetic DNA in a tube or something in the lab
Speaker 5: and kind of adding that to a cell, or breeding
Speaker 5: two plants together to try to change the DNA in
Speaker 5: the plant, the progeny plant, the child plant. But now
Speaker 5: we can take something that is alive, like a human being,
Speaker 5: make changes in their cells to change the DNA sequence,
Speaker 5: and they will continue to be alive. So that's a
Speaker 5: really amazing advancement. Actually, so genome editing is actually the
Speaker 5: bigger category. So crisper is one type of genome editing tool.
Speaker 8: It is. So it's like, I feel like I'm living
Speaker 8: in the future.
Speaker 6: It is.
Speaker 8: It's incredible. So specifically, you know this in this episode,
Speaker 8: we're focusing on sickle cell disease, and recently in the
Speaker 8: news there was you know, stories about using genome editing
Speaker 8: to treat sickle cell disease, and could you maybe walk
Speaker 8: us through how that is done, Like what in the
Speaker 8: case of sickle cell how crisper was used to treat
Speaker 8: the disease.
Speaker 5: Sure. Yeah, So it's been a really exciting time to
Speaker 5: be in the crisper field because I was there kind
Speaker 5: of before it was used as a genomeediting tool, and
Speaker 5: I was just interested in what it's normally doing, which
Speaker 5: I don't have to get into because it's a long story.
Speaker 5: But crisper actually comes from bacteria, and it's just this
Speaker 5: system that bacteria used to fend off viruses that infect them,
Speaker 5: which sounds so obscure and not interesting, but we were
Speaker 5: able to take this tool from bacteria and kind of
Speaker 5: steal it and use it for our own purposes. So
Speaker 5: I've been watching the development of this field since the
Speaker 5: very beginning, and it's been amazing actually to see when
Speaker 5: patients like the person who's been covered in NPR who
Speaker 5: has sickle cell talking about how they have been essentially
Speaker 5: cured fingers crossed. It seems like she's really been cured
Speaker 5: of the disease. So it's been incredible to watch from
Speaker 5: the beginning, so it's very exciting. I guess I would
Speaker 5: say there are two general approaches to using crisper to
Speaker 5: treat sickle cell disease, and they're really different in a
Speaker 5: conceptual way. So the most straightforward way you can imagine
Speaker 5: to fix a genetic disease would be to go in
Speaker 5: and change whatever the mutated letter is in the DNA
Speaker 5: to the correct letter, right, And that's what our institute
Speaker 5: is trying to do for sickle cell disease. That's our approach.
Speaker 5: It's kind of conceptually straightforward and understandable. The approach being
Speaker 5: used to treat the patients who are now in the
Speaker 5: news being treated for sickle cell disease with Crisper is
Speaker 5: a little bit different. So instead of trying to fix
Speaker 5: the mutation in the hemoglobin gene that is causing their disease,
Speaker 5: instead those clinicians are editing cells to start producing something
Speaker 5: called fetal hemoglobin. So instead of fixing the broken hemoglobin,
Speaker 5: they actually turn back on this other hemoglobin that all
Speaker 5: of our cells have the instructions to make but is
Speaker 5: turned off, and that hemoglobin can compensate for the damaged one.
Speaker 8: That is so amazing, it's so incredible. Wow. And is
Speaker 8: this like a treatment like Crisper? Does it fall under
Speaker 8: the category of treatment or cure?
Speaker 1: Right?
Speaker 5: So, in theory, Crisper could be a one time fix
Speaker 5: for something like sickle cell disease. I think we're not
Speaker 5: going to know how long things like this last until
Speaker 5: we actually try them in a person, because we can
Speaker 5: test something in a mouse, but mice live for a
Speaker 5: couple of years and then you don't know right. So
Speaker 5: I think it remains to be seen how long lasting
Speaker 5: the effects are, and it also remains to be seen
Speaker 5: whether or not there are side effects that will pop
Speaker 5: up later that we haven't been able to detect early on.
Speaker 5: But so far it seems like things are going well. Again,
Speaker 5: this is only like two patients for which there are data,
Speaker 5: but I think it's really promising. And that's what's exciting
Speaker 5: about genomediting in general to me, is that you could
Speaker 5: do a one time treatment because you're not treating the
Speaker 5: symptoms of a disease. You're not doing some kind of
Speaker 5: lateral approach to kind of helping the person but not
Speaker 5: actually fixing the underlying cause. With genomeeditting, we can in theory,
Speaker 5: correct the underlying mutations. We can change someone's DNA in
Speaker 5: their cells and keep them from having any kind of symptoms,
Speaker 5: basically wiping out whatever the disease is. So it's super promising.
Speaker 5: I think one thing to note is that for some
Speaker 5: conditions you've already done damage, Like just living with some
Speaker 5: of the genetic diseases that are out there, like sickle
Speaker 5: cell causes a lot of damage to your tissues, and
Speaker 5: there are things that you can't change once they've already happened.
Speaker 5: They're irreversible. But in theory, with sickle cell, you could
Speaker 5: stop future crises like pain crises where the cells pile
Speaker 5: up and get stuck in a cell and cause really
Speaker 5: horrible pain and more damage. So you could kind of
Speaker 5: halt the progression of the disease permanently. But that still
Speaker 5: remains to be tested.
Speaker 9: So I guess that kind of leads into our next question,
Speaker 9: which is how close are we to this being something
Speaker 9: that you know is more commonly used beyond just a
Speaker 9: couple of patients.
Speaker 5: I think we're farther away than I would want to be,
Speaker 5: So I think it's going to be a slow process.
Speaker 5: And this is something I have to deal with all
Speaker 5: the time when I'm talking to people I know who
Speaker 5: have various diseases or I'm giving public talks, is that
Speaker 5: everyone wants their disease to be cured today or yesterday,
Speaker 5: and it's just a very slow process. So sickle cell
Speaker 5: is one of the most mechanically treatable diseases, so there's
Speaker 5: just details about the way it works that make it
Speaker 5: treatable using genetic engineering or genome editing, and there are
Speaker 5: a couple of other conditions that are also possible to
Speaker 5: do with our current technologies, and so they're coming first.
Speaker 5: But there are thousands of genetic diseases out there, and
Speaker 5: all of those deserve to have some sort of treatment.
Speaker 5: So I think it's going to be probably a couple
Speaker 5: decades before we start having really common treatments using genome editing.
Speaker 5: Right now, we have I guess maybe three or four
Speaker 5: genetic diseases are in clinical trials using CRISPER, and the
Speaker 5: clinical trial process us takes years. But I think I
Speaker 5: would be shocked if you had told me when I
Speaker 5: was in graduate school that just, you know, six years later,
Speaker 5: basically someone would be cured of a disease using CRISPER.
Speaker 5: I would be stunned. I wouldn't have thought that was possible.
Speaker 5: So I think it is moving very fast in scientific terms,
Speaker 5: but it can be kind of slow in human terms.
Speaker 8: Mm hm, that makes sense, yeah, yeah, And so I guess,
Speaker 8: speaking of clinical trials and you know why, there might
Speaker 8: be potential for this to take a little bit longer
Speaker 8: than other traditional treatments. Are there or have there been
Speaker 8: observed any downsides to Crisper either in the technology itself,
Speaker 8: whether it's like expensive or in sort of like the
Speaker 8: you know, side effect kind of way.
Speaker 5: Yes, for sure. So I think as fast as we
Speaker 5: can move scientifically, we're still a long way from figuring
Speaker 5: out a societal level solution to rolling out Crisper based therapies.
Speaker 5: There's a big gap between a scientific solution to a
Speaker 5: disease and a societal solution. Because we can make the
Speaker 5: greatest scientific tool we can come up with that works
Speaker 5: really efficiently and it's accurate and there's no side effects,
Speaker 5: but if we can't make that affordable or accessible to people,
Speaker 5: it's not going to have any impact. So the cost
Speaker 5: in particular of genetic therapies is a huge issue, and
Speaker 5: it's something we talk about all the time at our
Speaker 5: institute and are trying to strategize and come up with
Speaker 5: ways to get around this. But it's enormously expensive. So
Speaker 5: there's a similar technology called gene therapy that is a
Speaker 5: little bit different from crisper. You could kind of call
Speaker 5: crisper a gene therapy, but at its base, a gene
Speaker 5: therapy is using a virus to add in a gene.
Speaker 5: So instead of making a precise change in DNA like Crisper,
Speaker 5: you're just throwing a gene in somewhere into the genome
Speaker 5: that will be helpful, and actually you can't. There's a
Speaker 5: gene therapy for sickle cell disease. You could throw in
Speaker 5: a copy, a healthy copy of the beta globin or
Speaker 5: hemoglobin gene to help people, and that's under development. But
Speaker 5: gene therapies are kind of an emerging approach to genetic
Speaker 5: disease that have only recently started being approved by the FDA.
Speaker 5: So they've been in development for a couple decades now
Speaker 5: and are finally starting to reach patients or real people.
Speaker 5: But their price tags have been whopping, So they've been
Speaker 5: a couple hundred thousand dollars to millions of dollars per treatment,
Speaker 5: which is more money than I have. I don't know
Speaker 5: about you, but that's a lot of money. And I think,
Speaker 5: on the one hand, we talked about how these approaches,
Speaker 5: since they're fixing the underlying cause of a disease, could
Speaker 5: be a single treatment. So if you compare the lifetime
Speaker 5: cost of treating something like sickle cell disease or data
Speaker 5: th allacmia or these other blood disorders, that's going to
Speaker 5: be a lot of money, and then in theory, perhaps
Speaker 5: paying half a million dollars once is actually going to
Speaker 5: be cheaper than the long term cost, But if you
Speaker 5: can't afford that upfront, it's a moot point. And I
Speaker 5: think right now we're kind of trying to figure out
Speaker 5: if this is something that's going to be covered by
Speaker 5: insurance companies. I think it's an issue in America that
Speaker 5: is kind of broader than the science. But we've been
Speaker 5: trying to think if there are scientific solutions, So hopefully
Speaker 5: someone will figure out some social solutions to healthcare. But
Speaker 5: in the meantime, we're trying to figure out if there
Speaker 5: are ways that we can change the way we do
Speaker 5: the science that will actually change the outcome when things
Speaker 5: are priced eventually. So that's one thing that we're working
Speaker 5: on that I'm kind of hopeful about. One of the
Speaker 5: big issues with sickle cell disease that's going to make
Speaker 5: this so expensive is that we're doing all of this
Speaker 5: gene editing. I'm talking about in patient cells that we've
Speaker 5: taken out of a patient, So we're not putting a
Speaker 5: shot in someone's arm or giving them a pill, we're
Speaker 5: taking their cells, extracting cells from their bone, marrow editing
Speaker 5: them in the last and then putting them back into
Speaker 5: the patient's body. And that's really complicated and expensive. It
Speaker 5: requires people with a lot of expertise to handle the cells,
Speaker 5: and it just jacks up the price by a lot.
Speaker 5: And there's also this requirement in a lot of these
Speaker 5: cases for using a virus to deliver the crisper tools
Speaker 5: and manufacturing this virus is really expensive and difficult as well,
Speaker 5: So there are a lot of steps and compounding steps
Speaker 5: potentially that add costs. So we've been trying to think,
Speaker 5: are there ways to do this in vivo? So instead
Speaker 5: of having to take cells out and put them back,
Speaker 5: can we just do the fix directly in a patient's body.
Speaker 5: So I think there are potential scientific solutions to some
Speaker 5: of these problems, but they're really really hard problems and
Speaker 5: they'll take a lot of investment. You said you've talked
Speaker 5: in this episode about kind of historic marginalization of people
Speaker 5: with sickle cell and the way there's racism and medicine
Speaker 5: manifests and this disease. I think one of the promising
Speaker 5: things that's been happening lately is one this kind of
Speaker 5: reckoning amongst the white scientific community and others about how
Speaker 5: black communities have been affected by the practice of science
Speaker 5: and government funding and medicine and all of that. And two,
Speaker 5: we were recently told that the nih and Gates Foundation
Speaker 5: are now investing one hundred million dollars towards doing in
Speaker 5: vivo therapies or potentially other therapies, but particularly in vivo
Speaker 5: therapy is using genomediting for sickle cell So that's a
Speaker 5: huge investment of money that I think could make a
Speaker 5: really big difference in how we're able to treat this
Speaker 5: disease and actually making it an affordable treatment for people.
Speaker 8: What an awesome interview. Thanks again so much Megan for
Speaker 8: taking the time to chat Crisper and genome editing with us.
Speaker 8: We loved it, and Aarin, we should definitely do an
Speaker 8: entire episode on Crisper someday. Oh yeah, all right, should
Speaker 8: we do sources? Yes? Absolutely? Okay, So for my sources,
Speaker 8: I read a few books. One is called Body and Soul,
Speaker 8: The Black Panther Party and the Fight Against Medical Discrimination
Speaker 8: by Alandra Nelson. Also, as I mentioned earlier, Killing the
Speaker 8: Black Body by Dorothy Roberts and Dying in the City
Speaker 8: of the Blues by Keith Waylou and also I have
Speaker 8: a few other books and papers that I will link to.
Speaker 8: A couple of papers I want to shout out are
Speaker 8: by Steinsma at all, Walter Clement Nole, first patient described
Speaker 8: with sickle cell disease, and by Barrash in nineteen ninety
Speaker 8: eight Sickle Cell Trait Policy and Research Paradigms awesome.
Speaker 9: I read a few good book chapters that I will
Speaker 9: link to as well as there is a great sickle
Speaker 9: cell disease in Nature Reviewed Disease Primers that was from
Speaker 9: twenty eighteen if you want just kind of a nice
Speaker 9: overview of the biology of sickle cell disease. And then
Speaker 9: if you want that paper on the comparison of funding
Speaker 9: between sickle cell and cystic fibrosis was by Fahim Farak
Speaker 9: at All published in jama in twenty twenty. Just earlier
Speaker 9: this year. We post all of these sources, as well
Speaker 9: as the sources from every one of our episodes on
Speaker 9: our website This Podcast will Kill You dot Com. Just
Speaker 9: click on the episodes tab.
Speaker 3: Well.
Speaker 8: Thank you again so much to the amazing Marsha and
Speaker 8: Shari for sharing your experiences with us, and also to
Speaker 8: Megan for walking us through the incredibly cool world of
Speaker 8: Crisper technology.
Speaker 9: Yeah, thank you all so much, and thank you to
Speaker 9: Blood will Be for providing the music for this episode
Speaker 9: and all of our episodes.
Speaker 8: And thank you to you listeners for listening. We love you,
Speaker 8: we appreciate you. We hope you liked this episode.
Speaker 9: Yeah, it was really fun, so we hope you had
Speaker 9: fun too.
Speaker 8: Until next time, wash your hands
Speaker 9: You filthy animals.