DNA Stories


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Sarah Fourcheraud (producer)

You’re listening to Decoding Nature’s Alphabet

Prof. Turi King

Parents will have a choice as to whether or not they wish to have, have a child with that particular disease, knowing that this child would have a particular disease and the impact that would have on this putative child’s life, particularly if it’s life limiting or, you know, um, something where their quality of life would be, you know, extremely poor.

Ron McCullagh (presenter)

Hello. I’m Ron McCullagh and you’re very welcome to Expressive Minds and our first podcast series Decoding Nature’s Alphabet.

Our guest is Professor Turi King, Professor of Public Engagement and Genetics at the University of Leicester. In these next 6 podcasts, Turi will be taking us on a journey from the origins of our genes to the bones of King Richard the third, revealing along the way, how our growing knowledge of what we humans are, is now changing what we can become.

A hundred years ago we thought the DNA molecule irrelevant, today it’s both a history machine and a beacon to our future.

Welcome Turi.

Prof. Turi King

Hello

Ron McCullagh

Let’s begin with a simple question “What is DNA and where does it come from?”

Prof. Turi King

Okay, so that’s a really, really deep question. So where does DNA come from? Okay. So, we know that DNA is actually a relatively simple and straightforward molecule, and we know that, um, there must have been these molecules forming as the earth was forming. People actually think that the sort of molecules that make up the DNA molecule were actually probably being formed in the atmosphere of the earth, you know, billions of years ago, and would have been rained down onto the earth. And then slowly, what would happen is presumably you would get these molecules joining together in chains. And we think that actually DNA didn’t come first. It was a, a molecule known as RNA. So, people will know from having watched the television, that our DNA looks like a double helix structure. So, it looks like a ladder with a bit of a twist to it.

Now RNA is as if you’ve got just one side of that ladder. And at some point, there must have been a way that it started to be able to replicate itself. And with being able to replicate itself then becomes the possibility for mistakes or mutations, some of which might’ve been advantageous so, it’s, it’s able to replicate itself faster. At some point there then must have been a membrane that starts to form around this and that’s actually really good because it keeps you separate from the rest of the environment and keeps any sort of products that are being made within this little membrane close by. Uh, and then slowly we think what happened is that probably then DNA formed and DNA is much more stable than RNA. And then it starts to code for proteins which go about and carry out various chemical reactions that would be in this sort of very, very early cell. So, um, we call this cell, which seems to be the, kind of the common ancestor of all life on earth, the last universal common ancestor, so, LUCA, it has a name. And actually, the idea that this must exist was actually proposed by Darwin, um, in his, in his work that he did. And we now know that there are three domains of life. So, there’s bacteria and archaea which are quite similar and they are known as prokaryotes and they are single-celled organisms with no nucleus. And then you have got eukaryotes, So, that’s where we come in. So, these are cells that have a nucleus that has the DNA within the nucleus. And we think that the last universal common ancestor was about 4 billion years ago.

Ron McCullagh

So, DNA then is almost the definition of life?

Prof. Turi King

It is, uh, it, I mean, every sort of living organism has got DNA in it. Um, so you know, everything from sort of fungi to, you know, flies, bananas, mice, us. Um, so our DNA is this very, very long, uh, molecule that we have in ourselves. And I think the general public often think, Oh, well, it’s all made up of genes. We know that it’s not actually made up of genes, just a small percentage of it is actually made up of genes. The rest of it, we are still learning what it does. So, some of it, we don’t know what it does. Some of it may have a regulatory effect, uh, and that it will turn genes on and off. Um, and our, what our genes do is essentially it’s the, the DNA molecule, uh, is made up of what’s known as nucleotides or bases. And there are just four of these. So they are guanine, adenine, cytosine, and thymine. But as you can imagine, we just tend to use CTG and A, uh, for that. And we know that it’s the sequence of these letters, which code for proteins being made in the body. And it’s these things which, you know, make up our hair or act as enzymes or form parts of hormones and this kind of thing that allow for life essentially to occur.

Ron McCullagh

Now, you talk about genes within the DNA. What is a gene?

Prof. Turi King

So put really simply a gene is a section of DNA, which codes for a particular protein to be made. And it’s really interesting. So, in, you know, when early starting out, we used to think, Oh, well, you know, particular genes code for particular things, and they just have one job. We know that that’s not true now that we know that a, single gene can be involved in multiple different sort of biochemical pathways in the cell. And you can have particular genes that are more active in some cells than in others. So basically, I suppose, to go back to your question in its simplest form of gene, simply codes for a protein, which takes part in chemical reactions within the body

Ron McCullagh

In the old nature versus nurture debate DNA is the nature bit then?

Prof. Turi King

Yes, that’s absolutely right. So, uh, this has been one of the really, really big questions, I suppose, uh, within, uh, genetics or within, within biology, generally. So, as I say, it used to be thought that, you know, everything was down to a particular gene, and we now know that that’s not necessarily the case, certainly for some diseases, for example, we know that if you have a, a particular version of a gene, so obviously genes can come in different versions. If you’ve got a particular version of a gene that is disease causing, and you just have to have one copy, or two copies, of that gene for this particular disease to occur, then obviously that is just down to a single gene, but we know that most things are actually down to a number of different genes working together, some of which have little sort of incremental effects, but then it’s also down to your environment as well.

For example, you might have genes that are associated with, um, a slightly higher risk of heart disease, but, you know, it’s things like if you are active, then you are less likely to develop heart disease. Then you can be somebody who has genes that are supposedly not associated with heart disease. But if you’re sitting on the sofa all day and eating donuts and not getting much exercise, you’re more likely to get heart disease. So, it’s really important to understand that actually we know that for the vast majority of things now it is actually a combination of the genes that you have and the environment.

One of the things we do know from being able to sequence genomes now is just how conserved a number of the genes that we have are across all life forms. So, for example, we know from looking in mice that we actually carry a huge number of the same genes. We might have slightly different variations of them, but we’re incredibly similar. And there’s actually very few genes that mice carry that we don’t and vice versa. And this was actually found out very, very early on when looking at things like fruit flies. So, this was at Columbia University in the early part of the 20th century, uh, where they were looking at fruit flies and they were looking for ones that had mutations. And then they were interested in having like, okay, so what’s, what’s causing those mutations. And what they found was that, um, a particular set of genes known as the Hox genes, and these are really important genes for saying which bits of your body goes where, so your head goes at the top and your feet go at the bottom and your arms go in the middle and the genes that are involved in development and working out which body bits are going to go where are actually found, not just in fruit flies, they’re found in mice, they’re found in us. So, what you find is actually, there’s a huge, huge number of genes that are conserved across all of life on the planet. And that’s really, really interesting. It’s about how we are all connected, uh, genetically, you know, through our genomes,

Ron McCullagh

I suppose that puts an end to the evolution debate. Um, this is, if proof were needed, the final evidence.

Prof. Turi King

Absolutely. I mean, you can really, really see it in, in the genetic code and you can see how, you know, mutations have occurred and they have, you know, they are then advantageous for particular reasons and you can actually watch this happening quite quickly, um, within particular organisms. And that’s, that’s something which is absolutely… we know that, evolution exists and we can actually sort of watch it happening.

Ron McCullagh

What else can we deduce about us humans from our DNA?

Prof. Turi King

Obviously the really big interest is, is disease. Um, there’s a huge amount of interest in, in doing genomic sequencing to look for genes associated with disease. And, um, some of them, as we know…there might be just a single gene involved. It might be something where like for Huntington’s disease, we know that, uh, for that particular disease, you only need to have one copy of a, of a deleterious form of the gene to go on, to develop that. Um, haemophilia, for example, we know that that the gene for that is carried on the X chromosome. Now girls have got two copies of the X chromosome, so you can have one copy that is deleterious. And the other copy, that’s fine. You won’t have haemophilia yourself, but you’re a carrier. Boys on the other hand, they have an X chromosome and a Y chromosome.

So, if they’ve got a deleterious version of that gene on the X chromosome, they haven’t got another one to protect them. So, they will go on to have haemophilia. And that was very, very famously shown, um, with, you know, Queen Victoria and her children and, and how this form of haemophilia was, was spread throughout the royal houses of Europe. But for the vast majority of disease and conditions, we know that actually it’s a number of genes that are involved, um, or, you know, even for, for traits like height, we know that it’s a number of genes that seem to each have a little incremental effects, but then again, it’s down to environment. So, for example, with height, it will be things like, you know, what’s your, what’s your diet? So, we know, for example, the Dutch are the tallest population on earth, and that’s thought to be because, in part, they have such a high dairy as part of their diet.

So, they’re getting lots and lots of calcium. Um, and so that’s really, really affecting and interacting with these genes and giving them this, this height that they have, obviously you inherit half of your genes from each parent. So, you get one half from mum, one half from dad. So, it’s that combination of genes that you get from each of your parents plus your environment. And exactly the same is true for, um, disease or various conditions. So, things like obesity, we know that there are certain genes that will have quite a high impact on whether or not somebody is going to go on to develop, um, obesity. But for the majority of cases, we know that it seems to be a number of genes that are involved. Again, it’s this usual story, lots of little incremental effects, but then it’s also down to your environment.

The same is true for things like Type 2 diabetes, um, and what we’re really showing with being able to look at, uh, in being able to sequence our, our genomes and look for genes that are associated with particular things, is really just how complex it is. So, for example some of the, the direct-to-consumer testing companies will do things like they will tell you, um, whether or not you’re able to tolerate caffeine. So how, how are you going to be with your coffee? Uh, you know, are you going to be able to metabolise it quickly? Which means that you can drink more of it, or, you know, there’s others who have the other version of a gene that means that you metabolise it more slowly so, you’re a bit more wired for longer sort of thing. Now, obviously you can get two copies of the gene, which kind of processes caffeine quickly, or you could get two versions of the slow one, or you could get one version of the slow and one version of the fast, but it’s, it’s not as simple as that because we know that there’s also another gene, which then affects how much of the protein from the first gene is actually made. It’s complex, it’s much more complex than we ever even really imagined when we first started out on this road.

Ron McCullagh

You’ll remember the 1997 film, Gatica, which explored the idea of a superior class of gene edited humans. With the recent discovery of actual gene editing – CRISPR, genome engineering is now possible, so Turi, is it the case that we have only our laws and our morality between us and the race to produce someone’s idea of the perfect human being?

Prof. Turi King

So, this, I mean, the biggest news for this was obviously… so CRISPR, this amazing new technology, which allows for particular genes to be edited.  It’s still actually in its relatively early stages. And that’s been shown in particular by this case of He Jiankui who’s a geneticist who tried to, well, who did try to genetically engineer two embryos prior to implantation. That is not allowed, not in China where he was working, uh, not in, in this country, not in many, many countries around the world.  

This is a couple where the father has got HIV and the mother doesn’t. And what he’s trying to do is protect the potential offspring from HIV, even though they were at virtually no risk of getting HIV and the way he, he tried to do this, that we know, is there’s a particular version of a gene on Chromosome 3 with a deletion in it. And if you have got two copies of this version, you are less likely to be infected with HIV because it’s known that the normal version, the non-deleted version of this particular gene, is part of an entry pathway for HIV to get into cells. Now the experiment did not go to plan. He didn’t introduce the intended deletion in either of the embryos. He introduced a completely different mutation in one of the embryos and in the other embryo, he introduced two mutations. On top of this, he didn’t manage to do the deletion on both of the chromosomes 3s so, in one embryo there are cells where one chromosome has a mutation and the other does not, and he appears to have introduced, what’s known as Mosaciscm. So, this is where, um, some of the cells have one version and some of the cells have another version. And one of the big worries with CRISPR, because it’s still, you know, relatively early in its use and development is that you get what’s known as off target mutations. So, where you affect the genetic code in an area that you really were not intending to do this. And this doesn’t matter if you’re doing this as an experiment and the embryos are not going to be implanted to go on to become babies. But that is actually what he did. He implanted them and now there are two girls alive living with the consequence of his actions.

Ron McCullagh

We’re probably going to get better at this though. And I suppose a concern must be that you’re going to have human DNA, excuse the expression, chop shops in the future, where, you know, one has this sort of dystopian idea of, in some back street in some far away country, there’s going to be some technician who will offer the service of, of tailor-made human beings…

Prof. Turi King

All you can do is try and regulate as much as possible. I mean, He Jiankui has gone to jail, for what he’s done, because in China, creating a gene edited baby is against the law coming under illegal medical practice. And, and quite rightly too.

Ron McCullagh

On a more positive note. What do you think are the opportunities that will open up as we advance our knowledge of DNA?

Prof. Turi King

Well, obviously I think disease; the more, the more we learn about what genetics are involved in particular diseases, the more that we can obviously start to think about ways that we can help people with those particular diseases and through things like pre-implantation diagnostics, it’s, it means that we can, um, parents will have a choice as to whether or not they wish to have, have a child with, that particular disease, knowing that this child would have a particular disease and the impact that that would have on this putative child’s life, particularly if it’s life limiting or, you know, um, something where their quality of life would be, you know, extremely poor. Really lovely stuff that’s coming out of some of the genetic testing that is going on are things that are done by these, uh, direct to consumer testing companies… and that is things like being able to find distant relatives.

So genetic genealogy has been really, really fantastic. Um, so this is where you are able to get your DNA tested and what the companies do is they take your DNA and they compare it against other people in their database, and they can do things like say something about your ancestry, which can be absolutely fantastic for people who say were adopted, or they’ve got a bit of a family mystery like, you know, we always thought that grandma was actually from this part of the world and you can actually look at that within the DNA, but also for things like if somebody is adopted and they want to see if they can find, you know, distant family members, that’s quite a…that can be quite a lovely thing to do, though it does have the flip side in that if, you know, you’ve given up a child for adoption, you may not want to be found.

So, it, again, it introduces some really interesting ethical questions into that. Um, but it can be really nice for people who want to be sort of building their, their family trees. I always say that you would do a mixture of sort of standard genealogy research and use DNA to help you build your family tree.  Um, so, some of the other really interesting things about these new direct to consumer testing companies is some of the claims that some of them make. So, and, and it comes with a note of caution, so some of the, the genetics testing companies will test for genes that are associated with potentially quite serious diseases. So, some of the testing companies will test for things like BRACA 1, BRACA 2.

So, these are two genes that are known to be, um, you know, heavily involved in, um, predicting whether or not somebody is going to go on to develop breast cancer or ovarian cancer. And what they don’t come with is the expert advice. If you test positive for a particular version of a gene, which means that you’re more likely to go on and develop this disease, which is why, I mean, the NHS testing services absolutely brilliant, because when they do the testing for this particular thing, you are, are given genetic counselling and I’ve got a wonderful colleague, actually who’s a genetic counsellor and they, they take the person very carefully through each of the steps. And you’re not getting that if you go to one of the genetic testing company. So, it’s a little bit of a note of caution on that one. And the other thing is they don’t necessarily test…you know, they’re there for things like breast cancer.

It is not just a single, allele uh, you know, version of a particular gene that’s involved. So, if they are not testing all of them or they are not giving you enough information about the particular version that they’re testing and therefore your likelihood, your risk of going on to develop the disease, you’re not getting that expert advice about what this genetic result actually means. So, as I say, that’s a bit of a, a bit of a note of caution on there. And often some of the testing companies, they will tell you things like how likely you are to be able to smell certain flowers and whether or not you’ve got freckles and what hair colour you’ve got, which presumably, you know, by looking in the, in the mirror, things like, things like that. And some of them, some of the claims of what, uh, some companies seem to be able to do, uh, you know, some of them will look at things like genes associated with sport.

So, whether or not you’ve got a version of a gene that’s associated with being able to be a fast sprinter, for example, but as I always tell people, these are genes that are associated with…so it’s not causative, you have, this you will definitely be able to do this it’s associated with. And we know that there’s zillions of factors that are involved in being able to run fast. So, it’s going to be things like diet and body shape, as you know, as well as your genetic makeup, which are going to be involved with whether you can run fast. Like, uh, like I said before, if you’re sitting on the sofa, eating donuts all day, you’re not gonna be running fast anywhere, so, it’s, it’s knowing what these, the results that you’re getting back…What does that actually mean? And that doesn’t necessarily come back with some of these genetic testing companies.

Ron McCullagh

Well, one of the things we’re going to do in this series is I, I’m going through a number of DNA tests, uh, from a number of websites. One of the things that worries me Turi, is that when I do these tests, I’m basically giving my DNA code to be put into a database. I slightly worry about that, but I’m sure this, I know this database has proven to be, not just one, there’s the number of them now, has proven to be very useful in things like discovering who’s committed a crime 30, 40 years ago, and so on.

Prof. Turi King

Absolutely. So, this is something known as forensic genealogy, and you’re absolutely right. So, my understanding is that when you take these tests, you can tick various boxes of how you want your genetic data to be used – for example for research, and I know that for example, in the UK there is a code on genetic testing and insurance that’s an agreement between the government and the association of British insurers who automatically sign up to that code, and they cannot ask for or take into account a predictive genetic test other than if you’re applying for life insurance over a specific level and have a positive predictive test for Huntington’s.  But you’re right, there’ve been some sort of slightly unexpected uses. There’s a very, very famous case around this. And, and this is the one where it sort of really kicked this off and it’s the, the Golden State Killer case. Now this is a chap who committed a number of sort of burglaries and rapes and murders in California in the 1970s and eighties. And then they stopped.

And what happened was, some investigators decided to go back and see if they could use any of the DNA from these cases and go back and use this sort of modern technology. And fortunately for them, there was still some, you know, DNA that was still left from some of these cases. So, they, they had it tested in such a way that you can actually then upload it to one of these databases. And when they did that, they found these DNA matches. So, these DNA databases, which are fantastic for being able to find that you share chunks of your DNA with particular people. Now you share half of your DNA with each of your parents. You share about a half of your DNA with each of your siblings. You share about 25% with uncle nephew, uh, aunt niece, um, about 12 and a half percent with your cousins and so on and so on.

So, what, what happened was they put this DNA into the database from this crime scene and they got a number of hits with people who must be his relatives. And then this is where standard genealogical, research went on, and they were able to trace these people back to a set of great, great, great grandparents. So, the perpetrator must be descended from this set of great, great, great grandparents. So, then what they do is again, more genealogical research and they work their way back down and they, you know, they come up with a, uh, a huge family tree where they know these are the people who are descendant from this couple, and then they start to go through it. Well, this is a woman. We know it was a man who perpetrated the crime. Uh, this person was too old. This person was too young.

This person didn’t live in the right area. And you start to use the DNA with lots and lots of other strands of evidence, including things like they knew what this person’s eye colour was. They can then go to the driving license registries and things like this. And then that allowed them to narrow down to this one individual. And they then went and got a DNA sample, um, from a tissue that he’d thrown into his bin. Um, this is in the U S and they were able to get the DNA from that and it matched, and then they can go and arrest the individual. And that has absolutely opened the floodgates. This is forensic genealogy. It’s been an interesting thing because some people, the people who are on this database that was used, they obviously didn’t know it was being used for this particular purpose.

And some people have decided they want to come off of it. So, you have to opt out of it with one of the genetic testing companies, if you don’t want to be any part of any forensic investigation, whereas other companies do not allow the use for this without a warrant but it’s absolutely opened the floodgates. And it’s now happened, there’s been a case in Sweden earlier this year, but it is a really, really interesting thing because ordinarily with sort of police databases, it has to be either you on that database or a very, very close relative like a sibling or a parent. Um, with this, it doesn’t have to be, it can be second cousin, third cousins, people you’ve never met before and don’t necessarily even know exist. And that DNA from them can be used to track the individual down. So it’s, it’s really, really interesting stuff that the power of DNA when it’s, when it’s used within these databases is, is really quite incredible.

Ron McCullagh

I know you’re a mother to Turi, and when it came to having children, this must’ve been an interesting moment for you considering your knowledge of DNA.

Prof. Turi King

It was and it wasn’t because I know just how complex DNA is and our genetic makeup is, and that it isn’t everything that, that we are. But I mean, I do have a particularly interesting, I suppose thing to think about is that my mum is schizophrenic. And so, we know that there, there is, does seem to be a genetic component to that, but it doesn’t seem to necessarily be huge. So, we know from looking at twin studies so identical twins, so they are genetically identical. And if we have a look at them, then if one has schizophrenia, there is, you know, a certain percentage chance that the other one will, but it’s not a hundred percent. In fact, I think it’s somewhere around a third, so genes are not the entire picture. There’s other stuff that’s going on. There’s some thinking that there may be epigenetic changes that happen.

So, epigenetics is that we know that there’s not just the genetic code that is involved in, in DNA. So that’s the sort of the underlying sort of hardware, which, which are the particular proteins that are being made. But there’s another layer of information on top of that, which acts a bit like a dimmer switch. So, it turns genes on, turns genes off, this kind of thing, and that’s affected by your environment. Um, so there’s, there’s definitely environmental factors that come into it. And it’s interesting. So, my mom has schizophrenia, but neither I nor my siblings do. And so, it’s always been something which has been vaguely in the back of my mind in that I know that this is in, this is in my mum. So would any of the children go on to develop… and so far, no signs of any of it, which is fantastic. And I suppose that just kind of really underlines just how much of it, that, that DNA is not everything about who we are. It’s, uh, so much of it is also about environment and everything’s far more complex than we ever really thought, but it also really fun because having had four children, I can do things like an Ooh you look, way more like my dad than this one does and things like that. So, it’s fun in that way. For sure.

Ron McCullagh

Now I began this podcast by saying that a hundred years ago, we thought the DNA molecule irrelevant. It’s been such a journey in a hundred years, hasn’t it?

Prof. Turi King

It really, really has been. I mean, it, it’s, we’ve gone from, understanding that there, there must be DNA. There must be something that’s affecting inheritance to obviously, you know, 1953, we start to, we understand the structure of DNA, jump into the two thousands where we’ve been able to sequence the entire human genome. We are sequencing genomes of other organisms all of the time, and they are being uploaded, uh, to act as resources for, for researchers, um, through to sort of direct-to-consumer genetic testing, which goes on and, and all of the information that we are learning about particular diseases. Uh, it, it is such an amazing time to be in the field. I absolutely love it because it’s moving so, so quickly and we’re learning so much all of the time. It’s just incredibly exciting field to be in.

Music

Sarah Fourcheraud

You’ve been listening to Decoding Nature’s Alphabet presented by Ron McCullagh and produced by me, Sarah Fourcheraud. In episode 5 of this series, Unchained, Turi will delve deeper into the science of DNA and the ethics and morality of editing our genes. In the next episode, Africa in Britain, Turi describes the history of Africa’s long involvement in Britain’s national identity. To get transcripts, or contact us and say nice things, please visit our website www.expressivemindsmedia.com If you’ve enjoyed this podcast, please share to help us produce more. All our episodes are on Apple Podcasts or your favourite podcast platform.