Curved Air and The Long Road To A Sickle Cell Cure

October 27, 2026

A cure can be real and still feel out of reach. Trends from the Trenches host Allison Proffitt is joined by Kevin Davies, executive editor of The CRISPR Journal and author of Curved Air: A Biography of Sickle Cell Anemia and the Quest to Cure the First Molecular Disease. Kevin shares howsickle cell disease became both a landmark genetics story and a test of whether medicine can treat patients with dignity. He follows Victoria Gray’s CRISPR gene therapy success while facing the discrimination, underfunding, and access barriers that still shape sickle cell care.

• Why Curved Air centers sickle cell warriors as the lead characters
• Why gene therapy success does not erase racism and bias in emergency care
• Stories of mistreatment during pain crises and the cost of lost trust
• How sickle cell spread globally through malaria selection and migration
• Why the first molecular disease took decades to reach curative treatment
• Funding gaps compared with cystic fibrosis and what that changes
• How hydroxyurea helps and why better everyday treatments still matter
• What Casgevy demands from patients and why durability monitoring continues
• Why affordability and infrastructure limit global access in Africa and India
• What could come next with in vivo editing and small molecule BCL11A ideas

Please subscribe to the podcast and give us a rating. It helps other people find and join the conversation. If you've got speaker or topic ideas, we'd love to hear those too. You can send them in a podcast review.

GUEST BIOs

Kevin Davies, PhD, Executive Editor, The CRISPR Journal
Kevin Davies PhD is a British scientific editor and author specializing in the medical and societal implications of major breakthroughs in genetic technologies. His new book, published in September 2026 by Harvard University Press, is CURVED AIR: A Biography of Sickle Cell Anemia and the Quest to Cure the First Molecular Disease. The book is a sweeping account of the world’s most famous genetic mutation.

Kevin is the author or co-author of five other popular science books including Cracking the Genome and The $1,000 Genome. He was invited by Nobel laureate Jim Watson to serve as a co-author of DNA: The Story of the Genetic Revolution. In 2017, he won a Guggenheim Fellowship that led to the publication of EDITING HUMANITY: The CRISPR Revolution and the New Era of Genome Editing.

Kevin is the founding Editor of Nature Genetics (the first spin-off journal from Nature) and a former Editor-in-Chief at Cell Press. In 2002, he helped launch Bio-IT World magazine as founding Editor and organize the annual Bio-IT World Conference + Expo. In 2018, he created The CRISPR Journal, the first scientific journal devoted to gene editing.

Kevin graduated with a degree in biochemistry from Oxford University and took his PhD in human genetics from St Mary's Hospital Medical School in London. He held postdoctoral fellowships at MIT and Harvard Medical School before hanging up his lab coat for good.

TRANSCRIPT

Meet Kevin Davies And Curved Air

Hi, I'm Allison Proffitt, executive editor of BioIT World, and one of the hosts of the Trends from the Trenches podcast. Today I'm thrilled to have Kevin Davies, a friend, former boss, executive editor of the CRISPR Journal, and founding editor of Nature Genetics, and, in fact, BioIT World join me. Welcome, Kevin.

Hello, Allie. Thanks so much for having me on your show.

So, congratulations on the new book published by Harvard University Press last month's Curved Air, A Biography of Sickle Cell Anemia and the Quest to Cure the First Molecular Disease.

You got that right.

Um, one of the things that I love about your books, um, there was cracking the genome, uh, editing humanity before this, and my daughter's favorite, the thousand dollar genome. Um, you always tell a science story through a human lens, and you subtitled this book, A Biography of Sickle Cell Anemia, and I think that the language of biography reflects that you've taken this personal approach to a new level, even.

Why Tell It As Biography

Curved Air is a book about people and patients and their experiences well before it's a scientific discovery story. Was that your vision for this all along, or did the story take you somewhere you didn't expect?

I think it's it it certainly was the initial hook. You mentioned editing humanity, which some of your listeners will hopefully remember or recall or have read even. that was my attempt to tell the story of CRISPR, the CRISPR revolution in gene editing, which was, of course, incredibly exciting. The book came out six years ago in October 2020, literally on the eve of the Nobel Prize being awarded to Doudna and Charpentier. So that was that was pretty cool. And then Walter Isaacson published The Codebreaker a few months later. So any hopes I had of, you know, oh, a bestseller at last sort of fizzled almost overnight. So I got invited onto you know the occasional sort of obscure national public radio affiliates and even more obscure podcasts to talk about editing humanity and CRISPR. And every time, whatever the platform was, I would always be asked, Well, what's, Kevin, what's the most exciting application of CRISPR? And I had a stock answer, which was, well, if you ask Jennifer Doudna, she's going to tell you plants. It's editing crops, safeguarding the food supply. And I think that is the correct answer. But for me, who trained as a human geneticist, I'm always drawn to the human saga, the patient stories. And so I said, Well, for me, CRISPR DNA surgery, as I like to call it, this is about treating patients with terrible, devastating genetic

CRISPR DNA Surgery And Victoria Gray

diseases like sickle cell. And that answer I think would have sufficed in the abstract, but we could actually put a face and a name to that example, which was Victoria Gray, because in 2019, not far from you, in the Sarah Cannon Research Institute in Nashville, she had undergone the CRISPR stem cell therapy, where she'd received her gene-edited bone marrow stem cells that had been fixed to upregulate fetal hemoglobin and therefore cure her sickle cell disease. that all happened in July 2019. And she decided to go public with that. So she started giving a series of interviews to Rob Stein at National Public Radio. So, you know, HiPAA be damned, you know, now we had a face to put to the success of the trial. And even though no one necessarily would have put money on it, the success Victoria's story, which was rapidly followed by other patients following in her footsteps in the CASGEVY trial, showed that this therapy was working beyond anybody's wildest dreams. I don't even think, you know, the vertex executives and the physicians who were caring for her believed that the therapy could work this well, and that in virtually every case, not every case, but in most cases, now uh dozens upon dozens of patients who've been through this trial and similar gene therapy trials, their symptoms have essentially melted away. They've had no more pain crises, no more hospitalizations, no more blood transfusions, you could not have scripted a better therapeutic clinical outcome. And so seeing and reading about Victoria's story and then having the opportunity to meet her at the at the earliest opportunity I could I could arrange made me think this is this is an amazing feel-good story.

Success Story With A Harder Truth

But then if you just peeled the layer back one layer, you realized this is not all a success story. It's not all a feel-good story because sickle cell, the sickle cell community, about 100,000 patients in the US and millions more worldwide, have suffered from, at best, apathy, lack of investment, and at worst, uh rank discrimination, discrimination, and racism in the way that their care is managed when they go to the ER looking for medications to help alleviate their brute, their terrible pain crises. So Victoria was really the the hook that got me really thinking about sickle cell in a much wider context. And it's for that reason that the book is dedicated to her and and the rest of the sickle cell warrior community.

Yeah. So I remember when you were talking about writing this, I think it was this one, and I was like, Oh, are you coming to Nashville? Well, you know, well, I'll see you, but you didn't come to Nashville, to my knowledge. You went to visit Victoria Gray in her home in Mississippi. And in fact, you you traveled a decent amount for this book to see sickle cell warriors, as you call them, I think as they call themselves, in a bunch of different in their homes in different, you know, historic

A Church Pew Interview In Mississippi

sites. And what how did that help you shape the story in a way that just the data didn't because you you knew the science. How did spending time with these people impact your view of it?

I made an effort. I didn't even I didn't even really make an effort. I think it just their stories were so compelling that I really wanted them to be woven throughout the book in a way that none of my other books. I mean, I've always touched on patient, the odd patient story here and there, but I really wanted to make the uh sickle cell warriors, yes, that's how they self-identify as as sort of the lead characters in this book. And they certainly are that certainly at the be in the beginning and and then back towards the end. And so it started with with me inviting myself down to Mississippi. I'd never set foot in Mississippi before, but a couple of years ago went and Victoria invited me to come visit her in her home. And we spent I spent a wonderful day, a day I will never forget, with her, first in in her modest little house in Forest, about 40 miles east of Jackson. And then we went to to lunch. And I said, Victoria, her husband Earl was with her. I said, Victoria, we we I'd love to go somewhere really quiet where we can hold a proper uh interview. And and what about your church? knew from her NPR interviews what a woman of faith she was, and she sort of lit up and said, Oh, what a great idea! Yeah, let's do that. And as luck would have it, Earl was a deacon of the church, so he had the keys. So we he lets us into the church on a this was only May or April or May, but it was incredibly brutally hot. And uh, so he goes upstairs and turns on the air conditioning, and Victoria and I sit in the front pew of this beautiful Baptist denomination church. And and I made the sort of mistake in a way of asking her what examples if did she have, if any, of discrimination that she may have experienced being treated, you know, in her home state. I perhaps naively thought, no, they they would take care of her because she's one of their own.

Right.

And... The stories just kept tumbling out. And she's now a full-time patient advocate. And so I've seen her two or three times in different settings, often hosted by a biotech company. And she'll just stand in front of an audience and extemporaneously, no script, no notes, just the stories will keep tumbling out. And what's remarkable for me is that they're all that they're always different stories. It's just a different set of stories. It's whatever, you know, whatever just comes top of mind. What disturbed me, I think, the most was just the lying that goes on to her, not just the sort of the negligence uh often and the lack of care and empathy, but in in several instances, doctors and nurses just lying to her face to get rid of her, to kick her out and go.

Was hers the story where the doctor came and told her what her blood draw had shown, but they had not actually taken.

Yes. So in one particular day, one afternoon, a doctor says, so comes up with the clipboard and says, uh, Victoria, oh, great news. Your labs are looking great, kind of come back great. You're you're free to go. We'll get you, we'll get you ready to to depart. And she looked in disbelief at the doctor and said, What do you mean my labs came back great? You couldn't get the nurses, couldn't get a I'm a hard stick, she said. You couldn't get a blood draw from me this morning. So what lab results exactly are you looking at? I mean, I you can and shivers down my my spine just thinking about that scene. And there are many others like that. And it I I didn't want to paint a give a false impression that somehow, because of the success of these gene editing therapies, we've we've all we've cured sickle cell or the community's problems have gone away. And

When Care Turns Into Cruelty

so I juxtaposed Victoria's story with the story of another woman who lived in the neighboring, well, just west of her in Texas, at the same age, early 30s, named Brittany Hightower, who tragically passed away a couple of years ago, died of pneumonia, brought on from her sickle cell years of sickle cell symptoms. But in a viral episode that you can find online, she live streamed a five-minute episode where uh security guards in a in a major Dallas hospital, Dallas Fort Worth Hospital, are kicking her out in while she's in the middle of a pain crisis because they've just had enough of her and they don't want to even to attempt to treat her or make her feel better. And she's live streaming this with a voice that is so halting she can barely speak because her body is so ravaged with pain. And you would like to think, well, okay, that was then, but surely that doesn't happen now. But I go on Reddit and look at the sickle cell forums, and it's still happening. And I just earlier this week, Alli stumbled on a story of a woman, a sickle cell warrior who in her mid-twenties who died at a in Texas. Her name was Kyla Tompkins, and her mother has launched a petition because, again, the same lack of uh respect and dignity. They just see a person of color, they what I need to be careful here, some medical professionals see patients of colour, per persons of color, uh looking for narcotics. And often these are very well-educated people. They know what works for them, they know what their body needs in the middle of a pain crisis.

Right.

So they come in, you know, quoting, you know, the the trade names of different drugs, and it just raises suspicions and and biases, and often it can lead to tragedy, which and and and you know, we love to talk about American healthcare, the best in the world, and in many respects it is. So then why why is this happening?

Yeah.

Who Gets Sickle Cell Worldwide

So you you just said they see a person of color come in, and that was definitely a presupposition I had about sickle cell, that it was a a disease of African origin and affected mostly African patients, but that is not the case. And that's so I learned that from the book. Can you tell me how much broader it is?

Well, it it's the the millions of patients, the epicenter is still Western Africa, where the genetic analyses suggest the mutation arose. There's been a not a controversy, but a lively discussion amongst some geneticists as to the origins of sickle cell disease. There are various haplotypes and different genetics upon which the sickle cell mutation in the beta-globin gene is found around the world. And so for many decades, the supposition was well, the mutation probably arose several different discrete times. But most of the genetic data now suggests it arose somewhere between seven and twenty thousand years ago in sub-Saharan Africa, in the middle of the Green Sahara. So, you know, don't think of deserts and sand.

that was a new idea for me, too.

Beautiful, green, pristine, you know, water-filled, river-filled, you know, landscapes, perfect breeding grounds for malaria. And we haven't mentioned the malaria connection, but of course, this is why sickle cell has spread so rampantly around the world and of course came to the Americas during the Middle Passage. Because if you carry one copy of the sickle cell mutation, so you have so-called sickle cell trait, you are at a major advantage, uh health advantage against uh malaria. And so this provided the selective advantage that you frequently see to explain why common genetic diseases, cystic fibrosis being another example to another to some other disease, why these otherwise very deleterious mutations should become so so commonplace.

But it's also common in India. There's even a population in Greece and Turkey.

Yeah, it's it's it's spread to the Mediterranean. And so it is it can be found on other genetic backgrounds over just the way the way it's sort of bred out. So there are a small minority of patients, sickle cell patients, or with a form of sickle cell, they may have one copy of the sickle cell gene and a slightly different mutation on the other uh copy of the gene, but it still manifests to all intents and purposes as sickle cell disease, who do not present or do not may not even know that they originally are of of African ancestry. So uh you know it's a small percentage who who are of either uh largely uh Latino descent or Mediterranean descent.

The 75 Year Gap To A Cure

Okay. So Pauling called sickle cell the first molecular disease in 1949.

Yeah.

And we got our first curative therapy in December of 2023. that's crazy. Why obviously it was not an easy problem, but why the gap?

Yeah. Well, I spent many, many chapters in the book trying to answer that question. And that's really, I think, one of the reasons why I felt that sickle cell disease warranted a popular science book to sort of explore this sort of huge contradiction. We've known so much about the origins of sickle cell and the protein that is mutated in sickle cell disease, which is of course hemoglobin. As you say, Linus Pauling described it as the first molecular disease because they published a paper, he and his colleagues, including a star Japanese medical student who had been uh incarcerated in one of those the Japanese-American internment camps at the beginning of World War II, Harvey Itano published a short paper in science with a beautiful series of electrophoresis experiments showing different migration patterns and and different electrical charges in the sickle cell version of hemoglobin versus the normal version of hemoglobin. And Pauling, interestingly, I quote various letters and and uh essays from him. He he somehow thought, he didn't speculate that this was necessarily a change in the in the sequence. that sort of theory really was was championed by Francis Crick and his colleagues in Cambridge a few years later. He thought it might have been a folding problem and maybe some electrical motif in the hemoglobin molecule was somehow being buried and obscured. But clearly this was a sequence issue, and it was the group in in uh Cambridge, England that was able to solve that in in 1956 and 1957 in a couple of papers in Nature. So we've known that the precise amino acid substitution in sickle cell for you know 75 years. Wow. And we've done so little to do it. And I think you can look at the pharma industry and say, was sickle cell their number one priority? And in most cases, the answer to that was a resounding no. We can look at funding and other aspects of sort of the basic foundational research. And I quote some work by a Duke University hematologist, uh John Strauss, who's published on this over the last 10 years, looking at a variety of metrics, NIH funding, patent applications, drugs that that are going to clinical trials or get approved by FDA. And if you stack up cystic uh sickle cell disease, the quintessential black disease on the one hand, and CF, the quintessential northern European genetic disease, both recessively inherited diseases. CF has a smaller population in America than sickle cell disease, but the funding and all those other metrics that I just uh summarized far outstrip sickle cell disease. And some of that you credit the foundations and their sort of the more entrepreneurial approach that they've taken. And maybe they got lucky, but that that funding led to the development and support for work by Vertex in particular to develop a whole series of small molecule drugs that have worked wonders for for cystic fibrosis patients. And I do spend a little time kind of not marveling necessarily, but it's interesting that it should be Vertex again, with a completely different set of technologies that they decided way back in 2015. Sickle cell has a huge unmet medical need. Gene editing might provide the the successful therapeutic route. We're not experts in in uh gene editing. This is Vertex now. So they partnered with CRISPR therapeutics, which had made a big bet on sickle cell very early on as the as the disease that they would focus on, one of the first CRISPR biotech companies. And that that partnership has uh has absolutely uh uh uh paid off. And of course, they took an interesting route to solving it going back even before, a year before the Linus Pauling first molecular disease discovery, an observation by Janet Watson, a pediatrician in Brooklyn, who observed that sickle cell infants aren't sick particularly when they're first born.

Fetal Hemoglobin And Drug Reality

Their symptoms only become manifest maybe six, three, six, nine months after birth. And that in that there's an inverse correlation with the levels of fetal hemoglobin, which begin to drop off during that same period. And she she speculated, based purely on clinical observations, no lab experiments, but she was spot on that fetal hemoglobin, the form of hemoglobin we all rely on before we're born, provides some sort of protective layer against the sickle cell mutation. And as the fet levels of fetal hemoglobin drop to just one, two, three percent of our total hemoglobin, whatever is causing sickle cells now becomes manifest, and all of the symptoms and all of the organ damage and the Anemia, of course, this all starts to play out, and the pain crises, of course, too. So the fetal globin connection, the seeds for that were sown back in 1948. And one of the themes of the book and this journey is that you know supporting basic research, no matter where it takes you, is so incredibly important. Right. We've learned about the different molecular players that control globin gene expression, thanks to the trailblazing work of Stu Orkin at Boston Children's Hospital and his colleagues, who were doing that work really just to better understand the biology the basic biology, not because they necessarily immediately saw the connection with sickle cell.

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So hydroxyurea is a drug that is not anywhere close to curative, but it does help and it works, it raises fetal hemoglobin. Is that right?

Yes. I I gave a talk the other day and I pulled out a a figure from the New England Journal of Medicine and and showed it it has So five different pathways. I couldn't even quote you four of them. So it's it's it seems to work in a variety of ways. It was a former chemotherapy drug, a generic drug, championed by Boston legend, David Nathan, present emeritus of the Dana Faber Cancer Institute. And that finally won FDA approval in the late 1990s. And it is another tragedy of sickle cell that that is still to this day the best small molecule drug that we have on the market. The FDA approved a trio of different drugs in the period from 2017 to 2019. One was a highly touted small molecule from a biotech in San Francisco called Global Blood Therapeutics. But each of these drugs have been withdrawn either in Europe or voluntarily taken off the market because the initial hope and hype behind these drugs, once further we had we gained further experience and further clinical observation, many of these have been withdrawn. And so the sickle cell community gets incredibly excited because they've had so little to give them hope in the form of daily pills or medications that they can take and help manage their symptoms at home. And just when they think, oh, this finally we've got something, it seems to get taken away. I know a few weeks after this podcast goes out, I believe the FDA is going to be holding a review and hopefully approval for a new drug. Well, a drug that's already on the market, but it'll be a new drug for sickle cell called MetaPVAT, developed by Agios. And uh some of the experts I've spoken to have pretty high hopes for that drug to improve a variety of sickle cell symptoms. Not again, not a cure, but you we're touching on, I think, an important point that the the success of Caschevi, the ex vivo gene therapy developed by Vertex, it's it's proven incredibly successful, but it is an

How Casgevy Works And Unknowns

arduous process. Even the developers would would freely admit that. The patients have to give their blood cells, then they're that those cells have to be taken, shipped off to a special facility, a C DMO, where they are edited. Months of quality control and growth, and finally the patient is called back. They then have have to undergo chemotherapy to evacuate their bone marrow to make room for the newly gene-edited supercells, as Victoria calls them, to be reinfused into the bodies. And then, of course, you have a nervous few weeks as you hope that they they take and start pumping out red blood cells full of the fetal hemoglobin, which is the route that Casgevy, the Casgevy developers have taken. Eventually, we might be able to learn from the the point of attack of Casgevy and develop a small molecule that can sort of mimic that approach. that that would be a I think a long-term hope for the single cell community.

Um so Casgevy doesn't turn off the adult hemoglobin, it just turns back on the fetal hemoglobin, which and those cells live longer and they kind of overpower the Yeah.

Yeah, because they're healthier red blood cells, and so they stay in the circulation much longer than any cells that are primarily comparing the beta-globin, uh the sickle form of globin. But I think you you've touched on an interesting point, which is you know, Victoria is the eldest patient in the sense that her therapy was the first to be to be performed. So she's seven years out now, just past the seven-year point. But Vertex and her doctors will be monitoring her at least through year 15. And I'm sure her doctors will want to keep monitoring her, you know, for many years beyond that. Because, you know, with every passing week and month, she's you know, it's a further vent venturing into the unknown. We've never observed what the durability and the so we uh and I'm not a stem cell biologist, so I think we just have to keep an eye and make sure that everything is going well, but everything does seem to be going, going great uh for her. So there's a there's a molecule that was discovered about 25 years ago, and then 20 years ago, BCL11A, it's a transcription factor. It was seen to be one of the key regulators of fetal globin levels in in adults. And so the strategy was how can we unclamp BCL11A from the DNA that it's binding to? Because if we can just remove it or decouple it, then that should free up other promoters to land in on in that region of the DNA and switch on the fetal globin, the gamma globin gene. And there was all kinds of experimental evidence, mouse models and other things to show that this should work. And of course, that there was no substitute for you know trying this in humans. And it's worked, it's worked beautifully. Now, that doesn't mean there won't be other approaches that can be tried. Editas Medicine, a well-known biotech company in the CRISPR world, was trying a different approach. Its early clinical results looked every bit as good as the vertex data, but they couldn't find a pharmaceutical partner to carry this through. So they've they've even though they did the hard part, they got the CRISPR therapy working, you know, chef's kiss, but they they have had to shelve that that program, which is which is so sad. And it's just shows that, you know, economically this is a this is a tough disease to crack.

Yeah. So I think you said there's a hundred thousand, is that right? A hundred thousand civil cell patients in the US, millions outside of the US,

Cost Insurance And Global Access

many of them in geographic areas that are not Sarah Cannon, that cannot do what Sarah Cannon could do for Victoria in terms of the chemo and the support to her during that process.

that's right. I think everyone who's celebrating Casgevy, and I certainly try to make this point myself in the book, is this is not a therapy that's going to translate or transfer easily to the African continent and beyond. Now, there are certainly um experts in Africa who take umbrage, if I was to say that publicly, and would say, look, you're, you know, if you if you're a patient in America or a Sarah Cannon, you're still shipping the the stem cells from your patient to some specialized facility, quite possibly one in in Scotland, affiliated with the with the Roslyn Institute, where Dolly the Sheep was cloned nearly 30 years ago. You know, we have FedEx too, we can ship cells to Scotland too, and and you know, they have a point. They absolutely have a point. And so I think we would love to see some of these some of these therapies uh now being performed in Africa. Of course, they've got the other challenge of paying for it. These therapies were priced at two and three million dollars. And that's when that was announced back in on the day of approval, back in 2023, you thought, oh, well, this is ridiculous. Who on earth is going to be able to afford that? I think one of the happy uh side stories of this is that many private insurance companies and much of the Medicare statewide system is supporting this, the these high costs because they know, and studies have shown that yes, $2 million is a heck of a lot of money, but that's still over the course of a sickle cell patient's lifetime, that's still less than they are than is likely to be incurred covering all of their hospital visits, all of their transfusions, all of the sometimes a lot major organ transplant, you know, hip surgeries, lung surgeries.

Necrosis is something that's that commonly happens. And so I'm assuming if we could do this earlier, then those patients would not have the damage to their systems that even Victoria, she has damage from the years that she has sickle cell. I don't know what that looks like for her, but the earlier we could intervene, then the longer healthy life these patients could endure.

Totally. Yeah, you can't you can't just start a clinical trial on children for obvious reasons, but the the the age eligibility has now been slashed dramatically so that children are now semi- able to to uh enroll in in trials, and I think eventually we'll we'll be able to qualify for these for these for these therapies. So that's that's good. But the therapies can't reverse the years or decades of uh damage to different organs and the the vascular lining and so on that that years of living with sickle cell disease has incurred.

So is there, in your opinion, is there a hope that the Casgevy when would at least prompt new attention to the disease so that maybe this is not where we end in terms of therapeutic offerings that maybe we'll people will get excited? Because this was this is ex vivo editing. What about in vivo editing? What about other drugs? Like maybe we can get some attention and more excitement around it?

Yes.

In Vivo Editing And Small Molecule Goals

Casgevy and the the other gene therapy that was approved at the same time. lyfgenia, yeah. It's really that I see that as just the beginning, I see that as just the beginning of the end of the first chapter, really. You mentioned in vivo editing. So the next big step would be to take what we've learned from from targeting BCL11A and engineer a system whereby we wouldn't need to take the stem cells out of the body. If we could find a way and a delivery mechanism using lipid nanoparticles or or some such vehicle to get to target the right stem cells while they are residing in the bone marrow, that that's that's a big ask, but that would be a huge step forward. And then it's clear that the the some of the key players in the story to date, Vertex Pharmaceuticals, Stuart Orkins' team at uh Boston Children's, they're very interested in looking at small molecules. So whether ex vivo or in vivo, this is only going to have a very limited impact on the on the burden of sickle cell disease across Africa and India. Obviously, the Holy Grail is a small molecule, a small molecule that could target BCL11A. that's easier said than done. But Stew's team and others have learned we've learned a lot about the biochemistry of BCL11A. It seems to work as a tetramer. So if you could stop it from forming a tetramer, then you know you may be one major step closer to keeping fetal globin uh switched on. So that would be a huge step forward. But it's gonna be uh several years, I think, before we learn about progress in terms of a curative small molecule drug for sickle cell disease. But I'm happy that there are some very smart people already working on it and they're doing it for the right reasons.

Yeah, and your book can raise awareness. And those of us that didn't know much about it, not gonna develop any drugs, but now I can talk about it to all my friends.

that's right. that's right. Well, yes, raising awareness is is certainly one of the main, the main objectives. You know, I it it it's a disease that hasn't had it, doesn't it hasn't had a lot of role models. I think for good reason, it's very hard to to succeed in

Role Models Media And Patient Advocacy

any chosen career when you have sickle cell disease. Victoria talked movingly about having to give up on her dreams so many times. She wanted to enlist in the Navy. Nope, can't do that. You've got sickle cell disease. She wanted to be a nurse, couldn't, couldn't keep up with the with the education and had to drop out of college. So it's hard to to to to do that. Her role model growing up was uh T-Boz, one of the members of the TLC uh rap group. I know it's a favorite in your household, Alli. So, but you know, it's uh that it's not the same, or it's not pretty comparable to, you know, Angelina Jolie talking about her breast cancer diagnosis, or Michael J. Fox, or the the viral movement about, you know, the ice bucket challenge from a few years ago. You know, other disease communities have got their their international iconic star uh challenges. And so I think that's sort of one sort of reason why perhaps sickle cell has been left behind a little bit. It's good to see it beginning to gain some traction in the main popular media. There was a great episode of The Pit, this new HBO uh hospital drama starring Noah Wiley. The second episode of that had an electrifying storyline about a sickle cell patient coming into the ER. And there was a great, a really good uh Netflix series from a few years back uh called Supercells, set in South London, made with a lot of a lot of verve and and and flair, and with these five young South Londoners each developing sort of a random superpower who they didn't know each other, but what connected them was that they all had a family history of sickle cell disease and it's trying to sort of paint sickle cell in a in a different light. Yeah, we need more of that.

Yeah. All right. Well, maybe Victoria, she has taken a bit of a banner, hasn't she? I mean, she speaks and she shared her story far and wide.

So she's doing a fantastic job. Yeah, she quit her job at Walmart to become a full-time patient advocate. She's written a children's book, she is giving talks at biotech companies, she's hiking mountains. I know she's been in training to climb Mount Kilimanjaro and may well have already uh reached the summit, as far as we'll we'll find out soon enough. Uh and that's and it's not just sort of you know, as a new alternative career, it's it's first and foremost, she's trying to inform the community about what it's like. It's so, you know, from from your the bio IT conference over many years, every anytime you can bring a patient in, it just changes the whole tenor of the conference. You know, we we all ad admire great scientists and technology developers talking about the progress that they've made. But until you hear from a patient's, you know, a patient's own voice, it's it's it doesn't really come to life. So, and what it's what's inspiring is that Victoria's story has literally influenced and persuaded several other warriors to to join her trial, to come to Nashville and meet uh Dr. Haydar Frangoul, the brilliant bone marrow transplant physician who led Victoria's work and is still treating sickle cell patients to this day, and has been the lead author on

Trust In Care And The CRISPR Offer

most of the key Vertex publications over the last six, seven years.

Yeah. He was definitely one of my favorites in the book. He just seems to have such an incredible rapport and treat every one of his patients so kindly and personally. They all seemed to feel so known by him, not at all.

Yeah, I'm so glad you picked up on that. They they all revere him. And uh every sickle cell patient I interviewed said the same thing. You know, the care they received as a pediatric patient up to 18 was it wasn't great, but it wasn't terrible. But the moment you cross over and as are now seen as an adult and you're going to different centers and different wards and so on, the whole tenor changes and not for the better. So, and Victoria said something pretty striking, which was after 30 years of being treated at many hospitals in and in and around Mississippi, she said if somebody had presented her with the idea of some experimental therapy in her home state, she would have declined. She was so burned out. It was the fact that she was going out of state to Tennessee to, and she had one nurse in Jackson who she really bonded with and she trusted. And when this nurse told her, Victoria, you know, this guy is the real deal, he's he's look he can offer you hope. Initially for a bone marrow transplant, that was what really that was what first took her to Nashville. And then there were complications with doing that. And one day, while she was recovering from a pain crisis, Haydar went up to her bedside and said, uh, Victoria, I've got a new opportunity I would like to discuss with you. Have you ever heard about CRISPR? And of course, she hadn't, but the rest is history.

The rest is history. Well, Kevin, thank you so much for sharing so many of those stories. Um, I thoroughly enjoyed it. Um, I recommend you go get Curved Air, a Biography of Sickle Cell Anemia and the Quest to Cure the First Molecular Disease. Kevin, thank you for joining us in the trenches.

Thank you, Alli. Great to be with you.

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