Hey, please take a second and leave us a review on Apple Podcasts, Spotify, or wherever you listen to the podcast. Thanks a lot. Hey, welcome to Sign Stuff or production of iHeart Radio. I'm Jorge cham and today we're answering the question is it safe to edit your DNA? In case you haven't been keeping up, humans now have the ability to change their genes. You could, for example, take a pill that will change the DNA of your eyes, or your skin, or even your brain. And it's all
due to a technology called Crisper. But how far can we take this technology? Is it safe or even ethical to use. We're gonna talk to two geneticists who work with Crisper, and we're gonna learn where it came from and how it works. So start thinking about how you would upgrade yourself and edit your genes as we answer the question is it safe to edit your DNA? Hey? Everyone, I don't know about you, but sometimes I feel like
the future arrived and I wasn't paying attention. I mean, it seems like yesterday to me that we were able to sequence the human genome, and now apparently we can basically edit it as easily as editing a word. Document. If you don't like the gene that you have inside of you, you can just cut it and paste it. So I had a lot of catching up to do.
And so before we get to the question of whether it's safe to edit your DNA, we're gonna learn where this technology came from and how it works, because to understand its limits and what makes it potentially dangerous, we're gonna eat both of those things. And the history of how crisper came to be is actually kind of interesting. It all started in a small lab in the south of Spain that was looking at tiny creatures called Archaea.
To Phillisen. Here's Professor Louis Montealieu, a geneticist and the deputy director of Spain International Center for Biotechnology in Madrid. Well, thank you, doctor Montaliu for joining us.
Thank you.
So we have a very general audience who may not have heard of crisper or even gene editing. So for people who are not familiar, can you tell us about the history of gene editing. When did this idea start becoming a reality for people?
Well, genomeediting is one of these revolutions you never know that you will be able to winness so this are tool that enable precise genetic modification of georgenome and as a matter of fact, any genome of any creature, any bacteria, any plan and including human beings. At the end of the previous century we had a first generation of geno mediating Those were called megan nucleases that were not very versatile,
so they were not used much. Then we had two different families of geneo mediting tools, and for some time there were okay, but the real revolution came across when we discover crispa. Crispa is an acronym for a cluster. Let me see I have it here because we always say, say chrispa, and we always forget this by is cluster regularly interspace short palindromic rapids.
The acronym is too catchy, it's too easy.
It is very sexy exactly so it looks like what you're having for breakfast, chrispher from Kellos and Crispa was invented, by the way, by one the young microbiologist at the University of Licante at the south of Spain. So the origin of crispa, it's actually in Spain, and this is normally forgotten.
Okay, So to get to the origin of this revolutionary technology, we have to go back even further than the turn of the millennium. Back in nineteen ninety three, a young researcher in Spain called Francis Mohika was interested in something very few people thought was important and that was completely unrelated to gene editing. He wanted to know how a very primitive form of life called urkia, which are kin of the cousins of bacteria, could survive in super salty
pools of water. So he did what everyone was doing in the early nineteen nineties, which was to sequence the DNA of these supers dirty or KaiA to see if there were any clues there. But when he looked at their DNA, he noticed something odd.
He saw repetitions the same sequence, same shot sequence, repeated many times. That was his discovery in nineteen ninety three, and this puzzled Mohika.
Why did these archaia have this stretch of genetic code all over its DNA? And while you and I might just shrug this off and move on with our lives, Mohika spent the next ten years of his life trying to figure it out.
And he did, and it took him about ten years to discover by someow of two thousand and three that this was the basis of an immune system, of a defence system the bacterias were using to fight the viruses.
Yes, even bacteria and primitive organisms like archaea have to fight viruses. What Uhika found was that the repeating sequence of DNA was part of a pretty badass system for killing viruses. Here's how it works. Whenever a virus attacks the Arkaia and the Archaea survives, it grabs a piece of the virus DNA and remembers it. It stores the little virus sequence in its own DNA.
So the bacterias that have been visited by many viruses over thousands or hundreds of millions of years, they had bits and bits and bits of different viral genomes and this was like a picture they kept from the virus. So next time the same viruses wanted to infect this bacteria, they say, hey, I know you, I know who you are, and because I know who you are, I can fight you and I can destroy your DNA.
So the Arkaea or bacteria remember every single virus they've ever interacted with, and they lay a trap for them. They create a molecule called CAS nine or CAST nine, which is basically like a sharp DNA scissor, And to each copy of this scissor they give it the memory of each virus they've ever met. So now the archaea has a bunch of scissors rooting around, each of them keyed to a snippet of the DNA of every virus
it's ever encountered. You can start to see how this could be used to cut your own DNA.
This is a very efficient system that was invented by bacterias. This was invented probably more than three billion years ago, so this is something that has been drunning for many years. So next time a virus wants to insert the DNA, if the virul is known by the lacteria, this will trigger a signal and the signal will start cutting the viral DNA. And if you cut the vital DNA, basically you destroy They may that you destroy the intruth.
All right. This was a discovery that eventually led to Crisper. These Archaia and bacteria basically figured out how to make a DNA scissor, and they figured out how to key the scissor to a particular sequence of DNA, So the scissors are floating around looking for a particular stretch of DNA. When it finds, it cuts the DNA, but only in the spot where it finds the sequence. Now, at first,
nobody thought this could be used at a DNA. It was just some discovery about the immune system of bacteria, and in fact, Mohika had trouble getting it polished.
He submitted this discovery to the top journal's Nature Science Cell and they all rejected because what really they all rejected because this was coming from Alicante, was not coming from Stanford, from Yale, from Oxborg, Cambridge, so he didn't include any kind of foreign researcher. It was him with his students, and eventually he took him like two years, and in two thousand and five he published his discovery in a very historical journal, but kind of very far
away from the top journals. The journal was a journal of molecular evolution, all.
Right, So Mohika publishes this in a not so prominent journal, and that could have been the end of the story. Maybe nobody would have read it or thought it could be used for anything other than understanding how bacteria work. But the two special people happened to read the paper and they had an idea.
What happens since that that paper in two thousand and
five was read by many other people. Jennifer Downa and Emmanuel Charpantier, and these two working independently, they met in San Juana, Puerto Rico in spring of twenty and eleven and they decided to collaborate because they both have read Francis paper that was published like six years before, and they had the idea to transform this defense system into a genomediting tool, into a tool that you could use to eraise and to replace letters so in order to
correct mutations. And that's exactly what they decided to do. And it took them only one year to do this collaboration, and that's the only time they collaborated. They never have collaborated again. And they published this in Science and eight years later, in October twenty twenty, they were awarded a Nobel Prize of Chemistry.
And that's how we got Crisper. From a scientists getting curious about how bacteria basically survive a cold, we get to a Nobel price and a technology that might revel uianized medicine, and even who we are.
And the beauty of this is that this was basic science. So when he was discovering how bacteria fight viruses, nobody cared. He said, what is this? Who is interested how the bacteria decide to fight viruses? Well, what happens is that the same mechanism that is used by bacteria to fight viruses is what Manuel Chaptee and Jennifer Downer transformed into
a genomeedicing tour. Basic science became an application many years later, I think, and this is the poetry behind these ideas, because he was sharing his knowledge about what the bacterias are capable of doing, and then that was illominating new ideas in the mind of all the researchers many years later.
All right, when we come back, we're going to talk to another scientist about how crisper actually works to edit your DNA, what you can do with it, and then later we'll talk about whether it's safe to edit your DNA or even morally right, So stay with us. We'll
be right back, and we're back. We're talking about whether it's safe to edit your DNA, and the main way scientists and doctors are doing this is with a technology called Crisper, which we learn is what most archaea and about half of all bacteria use to defend themselves against viruses. But around twenty twelve scientists figure it out it could be used for gene editing. Now, the basic idea of crisper is this, there's a special kind of molecule that acts like a scissor to DNA, meaning it can cut
strands of DNA. But there's a way to attach as nippit of genetic code to this scissor, so that the scissor will only cut in the places where it sees the nippet in the DNA strand. It's like imagine if you have a book and you only wanted to cut the book in places where it had the word hippopotamus
printed on it. Well, you would print the word hippopotamus on a little strip of paper, and you'd attach this strip to a special kind of scissors, and the scissors would check every word on the book, and whenever it saw the word hippopotamus, it would cut the page, breaking the flow of words. Now, the question is how do you use this to edit human DNA and is it safe.
To help explain how crisper works, I reached out to doctor Leanna Pelea, a researcher at the University of Zurich and one of the co authors of a well cited paper on Crisper titled Past, Present and Future of Crisper Genome Editing Technologies. Thank you so much, doctor Pellia.
For Joe, thank you so much for having me. It's really a pleasure.
According to doctor Peleia, in just the last ten or twelve years, there have already been three generations of Crisper technologies, and each one is more advanced than the last. It's sort of like the iPhone.
Because I think Krisper twos are a bit like the iPhone. It's always like a newer version.
Each one has a better camera.
Yes, it's a better camera, better features, and it's always getting better. It's very exciting.
Okay, we're going to talk about what each of these generations that Chrisper can do, because that's going to help us when we talk about what makes these technologies risky. Here's how doctor Pellia describes what we'll call Crisper one point zero.
Yes, so the original Chrispher systems are just Cast nine or Cast TWELVEA. They cut both strands of DNA, so in human sales the DNA. We know it's like double stranded, which means it has two strands of DNA, and these enzyme cut both the top and the bottom strand of the DNA. So by producing double strand break, meaning cutting both strands of the DNA, that means that the cells
undergo damage into their DNA. So when there is a double strand break, a dour gene of interest, the DNA repair mechanism, that is something that the human cells have by themselves, would fix the brake. And in fixing the brake, it's going to introduce some small mutations. And in this way we can disrupt the activity of human genes, which is something that's very useful.
Okay, So Crisper one point zero is essentially a gene breaker. Let's say you have a gene in your DNA that has mutated or a gene that you inherited that is giving you a disease. For example, sickle cell disease, which affects about one hundred thousand people in the US, can be traced to a single mutation in your DNA that it causes red blood cells to have the wrong shape.
So to cure this disease, you want to take out this gene, Well, you can do it with Crisper by writing down this gene in that little piece of paper I described before attaching it to the cutting molecule that acts like a scissor, and then letting these scissors loose on the patient's bone marrows themselves. The scissors will then find this gene in the DNA sequence and cut the gene. Now, human DNA has a self prepaired mechanism that would normally
fix this cut. But this mechanism is not perfect. Every once in a while it makes a mistake. But if the human body fixes the break, doesn't that defeat the purpose of knocking out the gene.
So that's the thing. So the human body fixes the break, but it doesn't fix it perfectly. Sometimes it could fix it properly. But even if it's fixed properly, then it's going to be cut again by another cast nine molecule and cut again and again, so in the end it's going to be probably mutated. So that would cause disruption of the gene.
So Crisper will cut the DNA. Then the DNA will repair itself, so Crisper will cut it again, and this will repeat until the repair mechanism makes a mistake, and so you'll end up with a different version of the gene. And because it's different, it's not going to work. And because it doesn't work, the patient is not going to have the disease anymore. So that's level one of editing your DNA. You can basically kill a gene and this
has been shown to work in people. After about nine years of research and pre clinical trials and clinical studies, the FDA in December twenty twenty three approved the use of Crisper for treating sickle cell disease. Okay, now we move on to Crisper two point zero.
Yeah, so the second generation involved in engineer risper and so and these enzyme is engineered so it cannot cut both strands of DNA, but they can only cut one of the DNA strands. Okay, And instead of making a double strand DNA break, they make a single strand DNA break. And this is less toxic than the double strand break.
I see, because the cell doesn't freak out as much. Yes, okay, so then how does it work? It breaks one strand?
Yeah, it breaks one strand. But that's not all they do. So they are also fews with an enzyme called damnas, which could convert one DNA letter to another, So it makes the letter change on the strand that it doesn't break.
Okay, this is where we get to actual gene editing. The first of the second generation of Chrisper tools, called base editing, goes in, breaks one strand of DNA and then replaces one letter in your DNA sequence. So before if your gene read something like ATTAGC, it might now read adt cgc. Wow. So now this tool has two things, the cutter and something that it replaces one letter.
Yes. So these are very powerful for maybe correcting mutations that are just defecting one letter.
Okay, that's base editing, and you said there was another one.
Yes, that's prime editing, where this technology makes also a single strand break off the DNA and then it extends one of the DNA strands with a new sequence of interest. And depending on how these prime editors are engineered, one could make up to maybe one hundred nucleotide modifications into the genome.
And when you say one hundred nickelodies, you mean like one hundred letters in your DNA.
One hundred letters of DNA. You could add up to a hundred letters and also delete something in the ten two hundred range.
All right, now we're getting even more advanced. What can the second generation Crisper tools called prime editing, can go in, cut your DNA and replace up to one hundred letters in your DNA sequence, and then we get to Crisper three point zero.
You know, with first generation and second generation, these are very powerful, but the range of the mutations that they can make are still relatively small. So if we imagine different patients and they all have mutations in a certain gene, maybe some patients would have a mutations more towards the beginning of the gene, some patients more towards the end of the gene, some patients more in the middle of
the gene. And with these first and second generation tools, in general, we would need a different correction strategy for different parts of a gene. But that's where the third generation tools come into place, where you could have large insertions into the genome and you could insert gene size fragments where in theory you could replace the whole mutant gene with the correct version.
So Crisper three point oh can replace whole genes at a time, that's like being able to edit several pages in a book and not just one letter or a paragraph. And scientists are even working on Crisper four point zh. Well not technically Crisper four point oh, because these new tools use a different system than Crisper, but they work the same way.
Then we have an emerging class of engineer gcombinaces. This is a bit complicated, but these enzymes allow us to make large deletions in the genome, large inversions, and large insertions in the same time. I think at this point we could make megabased mutations.
Like a million letters. So we're at the point where we can change millions of letters at a time. Yes, So then what's the next step to change whole chromosomes and things like that?
Yeah, I don't know, Like we are waiting. I think that would be quite interesting for sure.
Okay, well, we're at the stage where we're waiting for Tim Cook to announce when the next generation of iPhones are Yes, do you have to stand in line at the Apple store for a really long time, I'll say, or no.
Yes.
So basically we're almost at the point where we can change anything about our DNA. You're not happy with the genes you inherit it from your parents. You could, in theory, just cut and pay some new genes. But now the question is it safe to do this? What are the risks of this technology, and maybe more important, is it right to change your DNA? When we come back, we'll dig into the risks of using Crisper and the ethics of gene editing. Stay with us, you're listening to science stuff,
and we're back. We're talking about whether it's safe to edit or change your DNA, which is a relatively new question in the history of humanity. As we learn from our experts, we are getting close to the point where we can alter our genes in almost any way we want. And all of this has only recently come up with a new technology called Crisper. Now the question is is it safe to change your DNA. Here's how doctor Juana Pella answers that question. Now, maybe step me through it.
Let's say I want to have blue eyes. Okay, what would be the first step?
Well, I don't think that we are there yet to make you know, genome edits for these kind of features. We can edit DNA, but this comes with certain limitations and certain problems. That are actually associated with these Yeah, we can edit DNA associated with certain diseases, but we take this risk because the benefit of editing the DNA outweighs the problems caused by this disease. And having blue eyes, I mean, I don't know. I think maybe easiest is to get contact lenses that blue eyes.
That does sound easier, Yeah, it does.
I don't think that at the moment, like the benefits of having blue eyes with gene editing would justify this.
What Tarcapilla is saying is that there are still risks in editing your DNA, so at the moment, you probably don't want to use it for something as trivial as changing your eye color. Okay, what are these risks? Well, there are three things that can go wrong when using crisper. The first is that crisper might cut your DNA in
places that you don't want it to cut. I heard that one of the risks in gene editing is that the guide sequence is made to match a certain part of your DNA, but it's possible that the same sequence exists somewhere else in your DNA.
I think this is for sure one of the major problems there might be similar sequences in other parts of the genome.
Remember that the way crisper works is that you attach a sequence of DNA letters to a molecular scissor and the scissor will look through your DNA and where it finds the sequence, it will make a cut. Well, that sequence might be in more than one place in your DNA, so the scissor might end up cutting your DNA in places you didn't want it to cut. This is a problem, although according to doctor Pelea, there are ways to avoid it, like, for example, checking all three billion letters in your DNA
to make sure the sequence doesn't repeat. This is a lot of work, but it's getting cheaper to do.
So you need to check it very carefully. Make sure it's not somewhere else. Make sure that the sequence even if if you change of your nucleotizing these twenty nuclodized sequence, it's also not somewhere else, or other sequences that are very similar with these sequence are also not present into the genome.
The second risk in editing your DNA is that sometimes crisper in the different ways to use crisper don't always make the edit that you want. Sometimes it makes a mistake Okay, so you're saying the second risk is that maybe it doesn't edit it the way you want it to edit. Yes, that happens, It could happen.
Yeah, And even if it doesn't happen often, when you edit a population of sales, and even if let's say one percent or less than one percent has an edits that you don't want, let's say that edit makes the sales grow better or gives them growth advantage, this very rare population could actually take over.
What doctor Pillar is saying is that even if mistakes happen very rarely with Crisper, those stakes could be crucial. It might result in mutant cells that take over or have bad effects on your health. Then, the last risk in editing your genes is that the human body is really complicated. Changing a gene might have consequences you didn't expect.
There might be other consequences in the cell that we still don't understand fully how the affects later generations of cells, for example, like how the selle might get stressed, or how this could affect the future of the cell. Or if we make an edit, would the cell behave exactly like a normal cell. There are many things that we know about, but there are also many things that we don't know that we don't know. It's always good to research these from every possible avenue.
So those are the risks in editing your DNA. Now, a question I was also interested in is whether it's right to edit your DNA? What are the ethics of gene editing? As it turns out, this is also something that your Louis Want to You has written about. When I heard about the ethics of gene editing, what it brought to mind was the question should we be editing our genes? Like, is it something that we should be doing philosophically? Is it something that seems right to you,
to me, to the average person. Does it seem right to change we are in this way? Is that something that's in the discussion. Oh?
Absolutely, And I'll tell you there are different opinions on this. So there are some people that consider that the human genome as a psychred thing, so something that should not be touched. We should not be messing around with our geno. There are all the opinions in which they say, well, if we find a way to cure the congenital disease that is affecting this person, we have an ethical imperative. If we can't solve the question, we should do this.
What if there's a third category of people who just want edit their genes to be thin or to be smarter.
Oh well, this is the other aspect, which is enhancement. So you want to enhance your gena, you want to see better, you want to be thinner, you want to be taller.
So there are people that might reject gene editing out of principle, others who say it's a no brainer in the case of serious diseases, and there are others who might use it to change who they are. For example, in sports, you might change a gene so your body makes more glucose so you can run faster or longer. Or you might change a gene to have better lung capacity or even better eyesight.
All this is called enhancement, and this is very controversial.
Well, what's the ethical argument against that.
The ethic or undergoment against do this? You increasing the difference, you're increasing inequity, you increasing injustice. And basically you have to want that who is able to go down this road, who is want to be paying for them, Those that are wealthy, those that are wealthy are the ones that can be afforded the cost of such a treatment.
So the argument against is that it gives people an unfair advantage and that will probably reject it, maybe the same way that we reject steroids and sports.
Yeah, this is like dopy, So this is biodopy.
If I edit my genes, is it possible for me to edit them back?
Well, I mean it shouldn't be a problem. Modifying a gene can be in both directions. You can clean a mutation, you can rain certain mutation I see, and actually, if you think it carefully, this is also a biological weapon because if you're distributing this and you're killing some important genes,
you might be affecting the health of your enemy. So this is why there is also some biosafety concerns and by your security concerns regarding CRISPA, because eventually you can spray nanoparticles with CRISPA that will be inactivating a gene that is fundamental for cell cycle regulation until the body will stop functioning.
Wow, you can use it as a weapon exactly.
We always talk about anapetics. Now we started talking about enhancement. But there is also the evil side and the evil side is that you can use it as a web.
So this is definitely uncharted territory for human ethics. Okay, to summarize, I asked our experts how they would answer the main question of the episode. If I asked you is it safe to edit your DNA? How would you answer that question?
I would say it depends. I think it depends on the reasons why you would want to edit your DNA. And if the reason is because of a rare disease or because the editor would really benefit the quality of life, then we bring a better life. Then I think there are instances where this might be a good idea.
It's worth for those people that have no cure, have no read man, and they might be dying or they might be suffering. But if it's not for a CBA disease, I will think it twice. Because the technique at the current moment is not one hundred percent safe.
It's always that the risk of editing should be smaller than the risk of not editing. For these two makes sense.
All right, Well, if you do end up editing your genes, don't forget to make a backup, you know, just in case. Thanks for joining us, see you next time you've been listening to Science Stuff. Production of iHeartRadio written and produced by me or Hm, credited by Rose Seguda, Executive producer Jerry Rowland, an audio engineer and mixer. Kasey Pegram Tacapillia
participating in this interviewing in a personal capacity. If you use an opinions expressed by her in this interview or her own and do not necessarily reflect those of her employer or affiliated institutions, and you can follow me on social media to search for pH comics and the name of your favorite platform. Be sure to subscribe to Sign Stuff on the iHeartRadio app, Apple Podcasts, or wherever you get your podcasts, and please tell your friends we'll be back next Wednesday with another episode.