Shekerah Primus 0:00
What can you do with your love of science? We'll tell you
Hello everyone and welcome back to another episode of We Love science, the show where we discuss all the things that you can do with your love of science. We are your hosts, I'm Shekerah,
Fatu Badiane-Markey 1:19
and I'm Fatu, and today we're talking CRISPR and if you haven't heard about it yet, well, you will today. I don't know what rock you've been sleeping under though. I do have to say, but you know, we'll we'll let it slide. We'll let it go. You'll hear about it today.
Shekerah Primus 1:38
Today, it's time to get out from under your rock, right Fatu?
Fatu Badiane-Markey 1:42
Yes, yes. Yeah.
Shekerah Primus 1:45
Yes, ma'am. So CRISPR is the hottest gene engineering tool in science. And it's so hot that it's even reached mainstream media, right. Everyone's been talking about it. We had the CRISPR babies scandal where a scientist you know unethically created babies using this technique. So it's been out into the world, and well known. So it hit the global stage back in 2012, when two scientists, not two scientists but two groups of scientists, right working together, published their work, showing just how simple and powerful this system was for genetic engineering. So those two scientists, Jennifer Doudna, and Emmanuelle Char Char. Fatu how do you say that cause I know I'm not saying it right?
Fatu Badiane-Markey 2:45
I would say Emmanuelle Charpentier
Shekerah Primus 2:51
Emmanuelle Charpentier so they both they quickly gained worldwide attention for discovery of this technique, and they won the nobel prize in 2020 for this work, and this was so significant because this was the very first time in history that two women only won the Nobel Prize in Chemistry.
Fatu Badiane-Markey 3:15
Yeah, Yeah. breaking boundaries, which is so awesome. And I love hearing about these firsts. So Shekerah Why is CRISPR so important? Like is it really worth the hype? Or is it just you know, like, the hot new thing and you know, it's not it's not all always live lives up to be I guess
Shekerah Primus 3:35
everyone wants to hear all about the hot new thing. But yes, it is definitely worth the hype. so what is CRISPR? CRISPR is a tool that scientists use to change DNA and as we know, DNA is basically the instruction manual for every living thing. Right? And so for humans, say for humans, our DNA is the instruction manual that determines how to build a human and also how a human works right what is the proper way for all of our bodily functions to function together to make a well working human being? And so DNA is divided into smaller segments called genes. And every gene has a specific function. So think of it as a car for those of you who are not so scientifically inclined. Think of it as a car, right with all the different parts, you got the brakes, you got the transmission, you got the steering wheel, right, etc, etc. And each part has its different function, right, but it all works together as a whole. But unlike a brand new car, which usually comes off the manufacturing line, in perfect condition without any problems. You know, we've got to put some, we gotta put some stars there because sometimes there can be recalls and Things like that, but for the most part when you buy a new car you don't expect it to have any problems. Unlike that, humans we're often born with mistakes in our DNA. And those mistakes can cause the body to malfunction. So say for example, if a gene in the eye is incorrect, then that person may be born blind. Or if a gene important for red blood cell function has a mistake, then that person might have sickle cell anemia, right some sort of blood illness, genetic disorder. And this is true for every living thing, right that there can be mistakes in the DNA that causes diseases and even death. Now, the power of CRISPR and why it's such a big deal, Fatu, is that scientists can use it to fix these errors in our DNA. Right? So these mistakes in DNA are called mutations. And what scientists can do is program the CRISPR system to specifically target a mutation of choice and voila, it's like it's like having the best mechanic ever, right? The problem is fixed, right? So it's, it's so amazing that you can go from a genetic disorder with DNA that has some mistakes to completely fixed DNA and this person has been cured.
Fatu Badiane-Markey 6:35
Yeah, that's so amazing. And I just had a quick question just to make it a little bit more, more clear in my head. The mistakes in the DNA are those usually found in genes? Also?
Shekerah Primus 6:48
Right Yeah, so in genes. It can also be in regulatory parts of genes, which we're not going to get into because that's a lot right but it's gonna be in yeah in genes and that causes the gene to basically malfunction and not not function not do its work properly. Right. If you need a gene to be able to carry oxygen properly, right? you need, hemoglobin, and if the gene is not functioning properly, then you have some problems with your blood cells and oxygen transport in your body. Right. So these people end up suffering from some type of genetic disorder because of this mistake in their DNA.
Fatu Badiane-Markey 7:29
Got it. Okay.
Shekerah Primus 7:30
Yeah, so CRISPR can fix that which is so amazing and powerful.
Fatu Badiane-Markey 7:35
It is.
And I also just love this analogy that you had about a mechanic and you know, like, automobile. I think that's such a clever way to describe DNA. And it just it makes so much sense, right? If if the DNA is I mean, it was obviously it's there. But you know, if all the genes are correct in their aren't mutations, then it functions as it should, like a car should function as it should. But if you have some issues and you have mutations, and you need a mechanic to fix it, and in this case, our little bio-mechanic is CRISPR.
Shekerah Primus 8:10
Yeah exactly, our biomechanic is CRISPR and the hands on mechanic. Those are the scientists right? Those are the people who are actually telling CRISPR what to target and what to do. So. Yeah, go scientists. So imagine, you know, just to just to give the impact of CRISPR in the world already since it was first discovered a little over 10 years ago. Imagine living all your life with a particular disease, right? Just because of some mutation in your DNA because of something that happened You know, before you were born, not even before you're born when you were formed. The first couple cells right when you were formed, by your mom's and your dad's right, when you're first formed, there's this mutation. And now you're living with this disease your entire life, that might be an incredibly painful, debilitating type of disease. Right. So there may be treatments that are available to help to manage the symptoms, like in the case of sickle cell disease, but there's really no cure. Right? And sickle cell disease, as we know is an incredibly debilitating disease, right. It just takes it out of you. And then you find out that you can be cured by CRISPR gene therapy. Right. Imagine how amazing that would feel? Right?
Fatu Badiane-Markey 9:41
Yeah, that's basically a dream come true. And in fact, that dream has already come true. Is that right? For people who participated in the sickle cell disease Gene therapy clinical trial, right. I think I heard something about that in the news a little while ago. So there are patients who have already been cured. This is so amazing.
Shekerah Primus 10:01
I know. I know. It's so amazing and just so inspiring. And I think it just gives a lot of hope to people who are out there suffering with genetic disorders and things that there are no cures for, right. So I've heard just both from Victoria gray and Jimi Olaghere speak out, they have been giving interviews. So those are the two of the patients who were involved in that sickle cell disease clinical trial. And, you know, they have spoken out about how this gene therapy treatment has just saved their lives and just changed their lives so much for the better. So Victoria in particular said that she went from having to have an in home caregiver to give her baths and take care of her take care of her house, to basically being able after the treatment to live a normal, independent life where she can take care of herself. She can take care of her children, and she even has a full time job. Right? So imagine the change in her life and that's, that's just such a miraculous recovery to me. I mean, can you imagine hoping for a cure in your lifetime and then having it actually happened to you? Right? It's just so inspiring the possibilities that have opened up with CRISPR. They are vast. And so we'll put links for in the show notes for you know, so people can listen to Victoria and Jimi, talking in some of the interviews that they've given and hear directly from these patients. hear them speak about basically being cured from a previously incurable disease.
Fatu Badiane-Markey 10:03
Oh my gosh, Shekerah, I literally got chills like all the way up and down. My jaw is just rolling on the floor. This is it's I think it's just so incredible and you know, now, I'm not only impressed by the power of right of this, like, I guess like, you know, bio editing technology. But also just if you think about how long like the human history of living with sickle cell anemia has been, you know how just like we've taken like baby steps just gradually, gradually, gradually help improve people's lives and help them manage the disease. And now it's like, we can cure it baby like that. I have no words. I literally have no words.
Shekerah Primus 12:35
Yeah, you no longer have to spend so much of your time in the hospital. You can have you can have a job. Right. You can have a job. You can take care of yourself. You can take care of a family, you can manage your life in just a normal independent way. And that's just so powerful to be able to give those people back their lives like that. Yeah, I love it. I'm so excited. Yeah.
Fatu Badiane-Markey 12:59
So what's the update then for that therapy, you know, has it been like FDA approved is it still in clinical trials like what, what is going on with it?
Shekerah Primus 13:09
Yeah. Yeah. So there are several different sickle cell disease clinical trials that have been going on this particular one that I mentioned, including Victoria and Jimi. It was done. By CRISPR therapeutics in collaboration with Vertex pharmaceuticals. And the the gene therapy is actually called exa-cell. And back in June, the companies, June of this year, so we're in 2023, the companies released they gave an update released a press release, that the FDA has accepted the application to review exa-cell for approval as gene therapy treatment for sickle cell disease, as well as another disease called beta thalassemia, which is also another blood disorder. But they they're going to review it and you know, it's if it's approved, then this will be available to the public. I mean, the only thing that I would say is how much is this going to cost? Right? We don't know yet. Definitely going to be expensive but that would be amazing. And not only have they accepted the application, to review for approval. But for sickle cell disease in particular. They've given it priority review status, as well as some other designations like fast track and orphan drug and rare pediatric disease and the FDA usually does this kind of thing, giving you know fast tracking and priority review, when the potential therapy that they're reviewing is to treat a serious illness and will fill an unmet need for a treatment or cure for a disease that basically causes great harm and does not currently have viable therapies available. And so sickle cell disease definitely fits this description. And this is similar to what they did during the COVID 19 pandemic. Right because they fast-tracked approval for vaccines because of their immense life saving potential right and it definitely filled a dire need, right? A global pandemic. Yeah, that's a dire need. So it's a similar type of thing where there aren't treatments available out there that are as good as this one. And we need it so badly because people are really suffering from from this disease.
Fatu Badiane-Markey 15:44
Okay, got it. So when do we expect to know for sure if it's approved?
Shekerah Primus 15:50
Yeah. Yeah. So because of the priority review status, we can expect a decision for sickle cell disease by December of this year. That's just in a few months, right. In a few months, we can have a CRISPR therapy on the market to treat this serious disease. And I mean, just a little over 10 years ago, think about it. It's been just a little over 10 years ago after that pivotal paper by Doudna and Charpentier, tell me again,
Fatu Badiane-Markey 16:25
Uh-huh you got it
Shekerah Primus 16:26
Oh my god. Did I get it?
Fatu Badiane-Markey 16:29
You got it
Shekerah Primus 16:31
OK, Doudna and Charpentier about the technique, right. So that tells you how fast the field has moved just latching on to that power of this technique to save lives and ease suffering.
Fatu Badiane-Markey 16:46
Yeah, that is so amazing. Only three years after they received the Nobel Prize for it Right?
Shekerah Primus 16:55
mm-hmm Exactly.
Fatu Badiane-Markey 16:57
Yeah and then literally to have that taken from, you know, bench work or like theory biology where it's just used in the lab and then you know, tested in mice to use in actual human beings that I feel like it's warp speed. It's so fast.
Shekerah Primus 17:13
Yeah. It is right. preclinical to clinical to approval like that alone, like clinical trials alone could take 10 years.
Fatu Badiane-Markey 17:22
Oh, yeah.
Shekerah Primus 17:22
Right so to go from discovery to you know, a cure on the market. That's amazing. That is so amazing.
Fatu Badiane-Markey 17:31
So when we talk about when we talked about sickle cell disease, earlier the intro, you also mentioned beta thalassemia. And that's like another type of blood disorder. Are there any other clinical trials currently underway to use CRISPR technology for that treatment?
Shekerah Primus 17:51
Oh, my gosh, yes. Yes, yes. And yes, there are so many, and they're multiplying, right? So we'll have a whole show actually dedicated to sickle cell disease, and discussing exactly what is it? How does this you know gene therapy work? And just more info about the outcome of the clinical trials that the company has put out there. And the clinical trials are still ongoing, right, because they are following the original patients long term to look for any long term effects, of course, of this therapy, and they're also expanding the trials to include more people, as well as different age groups. But other trials underway right now include cancers, specifically in blood cancers, like leukemia and lymphoma, solid tumor cancers, and these are tougher to target and that's something that we'll also talk about in later episodes. So for example, lung, colorectal ovarian cancers to name a few, genetic blindness, and so a form of childhood blindness called Leber congenital amaurosis is also in clinical trials right now. Type one diabetes, even infectious diseases that are chronic like HIV, chronic urinary tract infections, protein folding diseases, inflammatory diseases, cardiovascular disease, muscular dystrophy, the list goes on and on. Right there is such a great, great, great potential here to help right such great potential and I mean, just the sheer volume of these clinical trials going on right now. And the ones that are poised to start goes to show not only the power of this technique, but also how much simpler it is compared to the previous gene therapy techniques that have been discovered.
Fatu Badiane-Markey 19:50
Wow. So CRISPR is really just a powerhouse tool like the mitochondria is the powerhouse of the cell. CRISPR is the powerhouse Bio-tool I love it.
Shekerah Primus 20:00
I like that, I like that analogy
Fatu Badiane-Markey 20:03
This is and honestly you know, this is I don't even know how much you can emphasize like how not even like life changing but world changing all this is going to be, you know, like, it really is gonna have an impact for every single human being on the planet. And I think that's just like, so incredibly amazing. And one of the things that I absolutely love about biology, you know, it's just like, wow, is too small of a Word.
Shekerah Primus 20:39
Wow is too small of a word, we need a better word, it's just it's too amazing for words, words cannot express. Right? And I mean, I did CRISPR back in grad school, that would have been maybe, I think 2014 is when I did it, you know, so just a few years after it was first published. And you know, I just did it with my you know, and Drosophila, my fruit flies just changing and mutating one of the genes to study the effect of the gene and the gene was called Sex lethal. You know, I don't have to like that was a big deal for me to do that. But it's it's come such a long way. Even since then. We've made so many advancements and the more and more I learn about it, the more I'm in awe over how much we have achieved already, and just the potential for more, you know, for it to go even further and further, and not just in medical treatments, right, but also, as you said, world changing. So also, it has been used in other fields and applications as well, including food, pest control, environmental issues, tackling some of those, diagnostic tests and other things, right. So the opportunities here really seem limitless. They seem limitless, and I think it's probably going to be you know, human ingenuity and you know, our imagination, how can we imagine this happening and can we make it even better than it is and I think we can, we can do it? We can do it. So we'll have a whole CRISPR series, running all throughout season 3, as I said, and we'll expand on the sickle cell disease clinical trials and have an entire episode about that. Since that's sort of like the first one. And we'll touch on some of the other clinical trials as well. But we'll also delve deeper into how exactly CRISPR works, why is it better than the other genetic engineering techniques that have come before it. And also how did it all start? You know, we love origin stories, right? you and me, we love to ask you know, how did it all start? So, we'll all we'll go to how did it all start? And I really love this story for CRISPR because the first time the CRISPR like sequence was noticed and published. It was by a scientist who was doing a completely different research, right. So this is another example where it kind of like was discovered by accident, right? And of course, other scientists, you know, found it later on, but he was doing completely different type of research and what I love is that they described it, literally it was one paragraph at the end of the paper is where they said oh, we also saw this sequence so they describe the sequence and they literally just say we don't know what it is. We don't know what it is. We don't know what the significance is, you know if it has one, but we found this really interesting sequence and we're gonna put it out there and I love that they did that. You know, I think so many scientists now might be afraid to put something out there if they don't have an explanation for you know what it is, but they were brave enough to just, I think back then, you know, just be like, Yeah, we saw this is interesting, but we don't know what it is. And, you know, I just love that story. So we're going to talk a little bit about that. So, just so so cool. Lots to talk about it's going to be an amazing series.
Fatu Badiane-Markey 20:42
Yes, I agree. 150%. I remember when we were thinking about what we're going to do next for our short series and you were like I really want to talk about CRISPR. And initially I was like, Okay, I guess CRISPR's cool and all. But for real for real. It's lived up to the hype. So I look forward to learning more from you, Shekerah and have our audience learn more also, about CRISPR, how it started, what it's doing where it's going. It's going to be so interesting. So listeners stay tuned. And until next time,
Shekerah Primus 24:51
Bye, everybody.
Fatu Badiane-Markey 24:52
Bye, everybody.