Genome editing with CRISPR, Part I
Part II
Part III
Part IV
If you've been paying attention to recent news - 'recent' as in, the past six months or so - about genetic research, you might get the impression that genetic engineering as we typically (science-fictionally) think of it is coming ever closer to being a reality in the not-too-distant future. Making all of those associated ethical issues a conversation we need to be having right now.
Except, not.
Despite descriptions of the latest breakthroughs and developments in methods of genetic engineering, broadly construed, the science fiction version of genetic engineering - think, Gattaca - is still just a fanciful fabrication of our imagination. The term "designer babies" gets thrown around quite a bit in the public sphere, but this is little more than a mascot for a campaign of fear, based on either, or both, ideologically driven misunderstandings (or misrepresentations) of current science, or religious ideologies.
There are a few different methods of genetic engineering that we've been using, but the one getting all the attention as of late is CRISPR. It stands for "clustered regularly inter-spaced palindromic repeats". We've been using it for at least a couple of years now. (But still only in the lab. So, not in any people.)
One interesting historical fact is that we didn't invent CRISPR. "Nature" invented CRISPR. We noticed it, and then copied it. Because it's pretty damn clever and useful.
So I have to explain it, because it's kind of amazing. I also want to explain it and go into some more details because it's really important to have a full understanding of things like this before getting into what all the recent hype is about. Because - and you should know this by now - the media, in general, are great at misrepresenting and skewing things like this (like with most things, actually - need I go into another rant about skin color ("racial") discrimination? Or mind-reading robots? Or those infamous faster-than-light neutrinos!?). So, just bear with me a bit, and I'll get to the "designer babies" discussion. (Well, probably more than "a bit"…)
What we noticed were some interesting DNA sequences in some bacteria: a very specific pattern of nucleotides regularly spaced along a stretch of DNA that caught our attention. Given what we know about DNA, we suspected they must have some function. We ended up finding the exact same sequences in lots of other bacteria, and that's a clear indication that it had to have a very important function for it to have been so perfectly preserved in evolution. However, the spaces between the instances of that pattern along a particular stretch of DNA were always all different sequences of nucleotides. We eventually figured out that those sequences, the "spaces", were actually snippets of viral DNA.
CRISPR is a defense mechanism.
Remember: a virus attacks by getting its DNA into a host cell - in this case, a bacterium - and hijacking the host's own DNA in order to get it to replicate the viral DNA. So if the bacterium is being attacked by a virus, the viral DNA is just kind of floating around. (Let me be clear: this is a very simplistic, broad sweeping generalization based on what we currently know. But now that I've said that, I kind of have to take it back: we do know there are viruses that don't behave this way at all. (In fact, some of them are so unlike what we've understood viruses to be like, that some scientists think that maybe they should be in their own category.) It's just that most viruses we have so far observed behave this way. I won't get into it, but I'll just say this: we keep discovering that "Nature" refuses to fit into the categories we try to box her into, and she is ever more creative than we mere humans will ever be.)
The snippets of viral DNA between the CRISPR sequences serve as "mugshots" for the viruses they initially came from. The CRISPR sequences themselves code for molecular "bounty hunters", each carrying one mugshot to hunt down the virus (i.e., the invading viral DNA) and kill it. What that means is that, when a CRISPR bounty hunter finds a match to the mugshot it's carrying, it immediately slices the DNA right there.
So CRISPR cuts DNA wherever it's told to. But it doesn't need to be told how to do it. And it doesn't need to be given instructions for where on the DNA to go, because it just actively seeks out the sequence of nucleotides it's carrying a "mugshot" for, and it slices every match it finds.
Furthermore, we discovered that CRISPR seems to be universal: we haven't yet come across an organism in which it isn't functional.
The potential usefulness of CRISPR should be becoming clear by now: genome editing.
If we could cut DNA wherever we like, then we could remove pieces of DNA, such as harmful mutations, and we could prepare to insert pieces of DNA, such as replacing those harmful mutations with the right sequences of DNA.
However! It needs to be said that such an ability would not be an entirely new thing to us. We've already been able to cut up DNA, using a different method, and so we've already been doing genome editing.
The reason for the hype over CRISPR is that it is much, much more effective, accurate, efficient, and cheaper than the old method, which was very expensive, very time consuming, not that accurate, and you crossed your fingers that your microscopic recruits followed your instructions correctly. In other words, how much better CRISPR is over the old method cannot be overestimated.
So, we figured out how to give CRISPR a mugshot of our choosing, and then send it into the nucleus of pretty much any cell.
I should also mention that inserting (replacing) DNA is actually rather easy once we have the ability to slice the DNA. We take advantage of the presence of enzymes whose sole job it is to repair DNA: we slice the DNA where we want to make the insert, get the to-be-inserted piece next to the gap we've created in the DNA sequence, and then the repair enzymes will do the rest, i.e., detect the break, detect the piece next to the break, and then put that piece into the slot.
It's important to understand that genome editing is not necessarily something done before the organism is created. Genome editing can be performed on an adult organism - 'adult' meaning, not embryonic. But what that amounts to is that the editing only takes place in a certain type of cell into which it is specifically injected. For example, CRISPR might be injected only into liver cells, so as to, let's say, correct a mutation that affects only the liver cells; the rest of the cells in the body (minus red blood cells, of course) will still be carrying around the unedited DNA.
One specific use of CRISPR that scientists are hoping will be possible is in the lungs of victims of cystic fibrosis, in order to hopefully cure the disease. Can one really be against such a potential use of CRISPR? We already know via testing in mice that CRISPR can indeed cure a genetic disease. (I think it was a blood disease in the mice, so I think that would mean it was injected into the bone marrow.) It's hard to imagine that someone could be against bringing a cure to children and young adults suffering from a truly horrendous and painful, life-threatening disease. (According to the Cystic Fibrosis Foundation, in the U.S., amongst those regularly receiving medical care at Foundation accredited facilities, the current median life expectancy is about 40. Just to give you some perspective on how much getting the best treatments available makes a difference: in the 1950s, i.e., before treatments started becoming available, very few with CF lived to see elementary school. So the same will be true for those have no access to such treatments; and then there's a range in between for less than the best treatment.)
When it comes to the ethical considerations of the use of CRISPR, we have to be very careful about what exactly we are talking about that we think may be ethically problematic. You can't just say, "editing the genome at all is ethically problematic because…" [whatever]. For, in that statement, which genome is being referred to by the term 'the genome'? If your answer is, "the human genome", well, then the statement doesn't apply to the example above, since the DNA in the liver cells of a single human being doesn't comprise the human genome. The same could be said about the DNA in nearly all of the other types of cells in the body of an individual human.
So one thing that needs to be dealt with is getting a clear handle on what we're really talking about editing when we talk about "genome editing". Because the term "the human genome" doesn't actually refer to a concrete thing in the world that we can just point to; the human genome is an abstract concept. But that doesn't mean it's any less real; and it doesn't mean that it isn't inherently linked to and doesn't have anything to do with concrete things in the material world, because it most certainly does. After all, the human genome exists in me, and it exists in you, and everyone else in the world, and it existed in everyone who's ever been, and it will exist in everyone who ever will be.
But let me be more precise: it exists in every individual cell (w/nucleus) in each of our bodies, and it existed in every individual cell (w/nucleus) that was once in each of our bodies but has died and been replaced, and it will exist in every individual cell (w/nucleus) that has yet to be created to replace some previous cell in each of our bodies. And that was true for every human who's ever been; and it will be true of every human who ever will be.
Let's take it a step further: my genome is different from your genome; it's also different from the genomes of my parents, and it's different from that of my brother. Everyone's genome is different from everyone else's genome, minus any identical siblings of course. (Actually, identical siblings don't really have nucleotide for nucleotide identical genomes.) I know that I'm not telling you anything you don't already know, but it's crucially important to keep certain facts in mind if we hope to think and reason intelligently about issues such as these that do or will affect so many lives as well as legislation.
Given these facts, it is clear that, as I have already pointed out, one way that CRISPR can be used is ethically unproblematic. If CRISPR is used to edit the genomes of a targeted cell type in an individual person, even as an infant, then it makes no sense to say that "the human genome" has been edited. It can't even make sense to say that that person's genome has been edited, but only the genome of some of his or her cells.
Effectively, this use of CRISPR is really no different from any other form of medication, or an organ transplant. And it's not altering "the human genome" by any stretch.
To be continued…
Part III
Part IV
If you've been paying attention to recent news - 'recent' as in, the past six months or so - about genetic research, you might get the impression that genetic engineering as we typically (science-fictionally) think of it is coming ever closer to being a reality in the not-too-distant future. Making all of those associated ethical issues a conversation we need to be having right now.
Except, not.
Despite descriptions of the latest breakthroughs and developments in methods of genetic engineering, broadly construed, the science fiction version of genetic engineering - think, Gattaca - is still just a fanciful fabrication of our imagination. The term "designer babies" gets thrown around quite a bit in the public sphere, but this is little more than a mascot for a campaign of fear, based on either, or both, ideologically driven misunderstandings (or misrepresentations) of current science, or religious ideologies.
There are a few different methods of genetic engineering that we've been using, but the one getting all the attention as of late is CRISPR. It stands for "clustered regularly inter-spaced palindromic repeats". We've been using it for at least a couple of years now. (But still only in the lab. So, not in any people.)
One interesting historical fact is that we didn't invent CRISPR. "Nature" invented CRISPR. We noticed it, and then copied it. Because it's pretty damn clever and useful.
So I have to explain it, because it's kind of amazing. I also want to explain it and go into some more details because it's really important to have a full understanding of things like this before getting into what all the recent hype is about. Because - and you should know this by now - the media, in general, are great at misrepresenting and skewing things like this (like with most things, actually - need I go into another rant about skin color ("racial") discrimination? Or mind-reading robots? Or those infamous faster-than-light neutrinos!?). So, just bear with me a bit, and I'll get to the "designer babies" discussion. (Well, probably more than "a bit"…)
What we noticed were some interesting DNA sequences in some bacteria: a very specific pattern of nucleotides regularly spaced along a stretch of DNA that caught our attention. Given what we know about DNA, we suspected they must have some function. We ended up finding the exact same sequences in lots of other bacteria, and that's a clear indication that it had to have a very important function for it to have been so perfectly preserved in evolution. However, the spaces between the instances of that pattern along a particular stretch of DNA were always all different sequences of nucleotides. We eventually figured out that those sequences, the "spaces", were actually snippets of viral DNA.
CRISPR is a defense mechanism.
Remember: a virus attacks by getting its DNA into a host cell - in this case, a bacterium - and hijacking the host's own DNA in order to get it to replicate the viral DNA. So if the bacterium is being attacked by a virus, the viral DNA is just kind of floating around. (Let me be clear: this is a very simplistic, broad sweeping generalization based on what we currently know. But now that I've said that, I kind of have to take it back: we do know there are viruses that don't behave this way at all. (In fact, some of them are so unlike what we've understood viruses to be like, that some scientists think that maybe they should be in their own category.) It's just that most viruses we have so far observed behave this way. I won't get into it, but I'll just say this: we keep discovering that "Nature" refuses to fit into the categories we try to box her into, and she is ever more creative than we mere humans will ever be.)
The snippets of viral DNA between the CRISPR sequences serve as "mugshots" for the viruses they initially came from. The CRISPR sequences themselves code for molecular "bounty hunters", each carrying one mugshot to hunt down the virus (i.e., the invading viral DNA) and kill it. What that means is that, when a CRISPR bounty hunter finds a match to the mugshot it's carrying, it immediately slices the DNA right there.
So CRISPR cuts DNA wherever it's told to. But it doesn't need to be told how to do it. And it doesn't need to be given instructions for where on the DNA to go, because it just actively seeks out the sequence of nucleotides it's carrying a "mugshot" for, and it slices every match it finds.
Furthermore, we discovered that CRISPR seems to be universal: we haven't yet come across an organism in which it isn't functional.
The potential usefulness of CRISPR should be becoming clear by now: genome editing.
If we could cut DNA wherever we like, then we could remove pieces of DNA, such as harmful mutations, and we could prepare to insert pieces of DNA, such as replacing those harmful mutations with the right sequences of DNA.
However! It needs to be said that such an ability would not be an entirely new thing to us. We've already been able to cut up DNA, using a different method, and so we've already been doing genome editing.
The reason for the hype over CRISPR is that it is much, much more effective, accurate, efficient, and cheaper than the old method, which was very expensive, very time consuming, not that accurate, and you crossed your fingers that your microscopic recruits followed your instructions correctly. In other words, how much better CRISPR is over the old method cannot be overestimated.
So, we figured out how to give CRISPR a mugshot of our choosing, and then send it into the nucleus of pretty much any cell.
I should also mention that inserting (replacing) DNA is actually rather easy once we have the ability to slice the DNA. We take advantage of the presence of enzymes whose sole job it is to repair DNA: we slice the DNA where we want to make the insert, get the to-be-inserted piece next to the gap we've created in the DNA sequence, and then the repair enzymes will do the rest, i.e., detect the break, detect the piece next to the break, and then put that piece into the slot.
It's important to understand that genome editing is not necessarily something done before the organism is created. Genome editing can be performed on an adult organism - 'adult' meaning, not embryonic. But what that amounts to is that the editing only takes place in a certain type of cell into which it is specifically injected. For example, CRISPR might be injected only into liver cells, so as to, let's say, correct a mutation that affects only the liver cells; the rest of the cells in the body (minus red blood cells, of course) will still be carrying around the unedited DNA.
One specific use of CRISPR that scientists are hoping will be possible is in the lungs of victims of cystic fibrosis, in order to hopefully cure the disease. Can one really be against such a potential use of CRISPR? We already know via testing in mice that CRISPR can indeed cure a genetic disease. (I think it was a blood disease in the mice, so I think that would mean it was injected into the bone marrow.) It's hard to imagine that someone could be against bringing a cure to children and young adults suffering from a truly horrendous and painful, life-threatening disease. (According to the Cystic Fibrosis Foundation, in the U.S., amongst those regularly receiving medical care at Foundation accredited facilities, the current median life expectancy is about 40. Just to give you some perspective on how much getting the best treatments available makes a difference: in the 1950s, i.e., before treatments started becoming available, very few with CF lived to see elementary school. So the same will be true for those have no access to such treatments; and then there's a range in between for less than the best treatment.)
When it comes to the ethical considerations of the use of CRISPR, we have to be very careful about what exactly we are talking about that we think may be ethically problematic. You can't just say, "editing the genome at all is ethically problematic because…" [whatever]. For, in that statement, which genome is being referred to by the term 'the genome'? If your answer is, "the human genome", well, then the statement doesn't apply to the example above, since the DNA in the liver cells of a single human being doesn't comprise the human genome. The same could be said about the DNA in nearly all of the other types of cells in the body of an individual human.
So one thing that needs to be dealt with is getting a clear handle on what we're really talking about editing when we talk about "genome editing". Because the term "the human genome" doesn't actually refer to a concrete thing in the world that we can just point to; the human genome is an abstract concept. But that doesn't mean it's any less real; and it doesn't mean that it isn't inherently linked to and doesn't have anything to do with concrete things in the material world, because it most certainly does. After all, the human genome exists in me, and it exists in you, and everyone else in the world, and it existed in everyone who's ever been, and it will exist in everyone who ever will be.
But let me be more precise: it exists in every individual cell (w/nucleus) in each of our bodies, and it existed in every individual cell (w/nucleus) that was once in each of our bodies but has died and been replaced, and it will exist in every individual cell (w/nucleus) that has yet to be created to replace some previous cell in each of our bodies. And that was true for every human who's ever been; and it will be true of every human who ever will be.
Let's take it a step further: my genome is different from your genome; it's also different from the genomes of my parents, and it's different from that of my brother. Everyone's genome is different from everyone else's genome, minus any identical siblings of course. (Actually, identical siblings don't really have nucleotide for nucleotide identical genomes.) I know that I'm not telling you anything you don't already know, but it's crucially important to keep certain facts in mind if we hope to think and reason intelligently about issues such as these that do or will affect so many lives as well as legislation.
Given these facts, it is clear that, as I have already pointed out, one way that CRISPR can be used is ethically unproblematic. If CRISPR is used to edit the genomes of a targeted cell type in an individual person, even as an infant, then it makes no sense to say that "the human genome" has been edited. It can't even make sense to say that that person's genome has been edited, but only the genome of some of his or her cells.
Effectively, this use of CRISPR is really no different from any other form of medication, or an organ transplant. And it's not altering "the human genome" by any stretch.
To be continued…