Robyn Williams: Now another Brit-based scientist with strong Australian connections. In fact Kat Arney is here on your ABC RN station every week in The Naked Scientists on Fridays at 10pm, and Sundays at 3pm. The naked ones come from Cambridge, as does Kat Arney, and she has a new book, Herding Hemingway's Cats, which apparently had six toes.
I have a problem. Look, I've got DNA in my nose cells and I've got DNA in my belly cells, and it's the same DNA, but one lot made the nose and the other made my belly. How does that work?
Kat Arney: Well, that is basically the fundamental question of genetics because we start life as a single cell. You know, when mummy and daddy love each other very much. And you become two cells, four cells, eight cells, your cells divide, and they are copying this single set of DNA, your genome, half from mum, half from dad, that's your genome. And every single time a cell divides it copies all that DNA. So by the time you've made a baby, you have millions, billions, trillions of cells, and they all have that same set of DNA, your genome.
Clearly because you have all sorts of different types of tissue, you have nose cells and belly cells and liver cells and pancreas cells and eyeball cells, and they are all doing different things, all doing their own job, knowing what they are up to. They don't change between different functions. A liver cell doesn't just go, hey, I'm going to be brain today, I'm off. So clearly, even though you have all genes in all your cells, they are not all switched on at the same time, otherwise you'd just be this identical blob of putty and that would just be weird and gross.
Robyn Williams: Sometimes I feel like it, but go on!
Kat Arney: It would just be disgusting. So this is the fundamental challenge of genetics, and particularly developmental genetics, which is the area I used to study as a scientist, is how do you turn on the right genes at the right time in the right place. And in my book I explore a lot of things about what we know now about how our genes work. Because we hear about genes all the time in the papers and all this kind of stuff, but we don't really understand how they work. And some of the chapters that I cover are looking at these things called enhancers…well, scientists call them enhancers, I call them control switches. And they are little stretches of DNA that attract the kind of reading machinery in the cells to read a gene, to turn it on at the right time in the right place. So whether that's really early on in development to help cells decide are you head-end or bottom-end, or the really specialised decisions in development; are you a cell in the middle of the body, then are you a type of cell that we call mesoderm, and then are you going to be a muscle cell? So all of those little decisions involve enhancers, control switches, turning on certain sets of genes.
Robyn Williams: Did those stretches of DNA used to be called junk? In other words, did they not know what they were for and just assumed they were hanging about?
Kat Arney: Junk DNA is such a loaded term, and if anyone has been following any of these kind of debates…I don't really like the term 'junk DNA'…
Robyn Williams: I said 'used to be called'.
Kat Arney: Yes, I don't like the term 'junk DNA' to cover everything that's not an actual honest-to-God protein coding gene. So we can call it non-coding DNA. Some of it is junk. Like the very worst cable TV channel, most of your genome is very dull and repetitive, it's all these long dead viruses that got in the genome, copied themselves, copied themselves…
Robyn Williams: Because viruses come in and make you copy them, and so they leave their barcode behind.
Kat Arney: And repetitive DNA tends to get repeated more. It's like if you are reading a book with lots and lots of repeated words, you sort of slip and you forget where you are and you read more of them. So you end up with about half the human genome probably junk, probably more of it is actually junk. And then we have known for a long time that there are these control elements. You know, this isn't suddenly brand-new. What's kind of up for debate is some of the rest of the stuff in the genome. So we know there are stretches of the genome that seem to be read, they are read to make what's called the messenger RNA, and we're not sure is that useful, is that functional? It's very hard to prove that something is functional. And just finding evidence that something is happening doesn't mean it is functional. You could find chewing gum stuck on your shoe, it doesn't mean the function of chewing gum is to stick to shoes. So there's a lot we really, really don't understand about exactly what is going on in the genome and how it works.
Robyn Williams: Hence the herding bit in the title of your book. But going back to mummy and daddy, the wonderful thing about your book is I keep being surprised by things. I did not know that the genes from mummy and daddy were actually formed in their baby cells, when they were even embryos, and they've been hanging about waiting for them to grow up and be adults.
Kat Arney: This I think is incredible. So the germline, the cells that are going to become eggs and sperm, they are laid down in the embryo very, very early on in development. These are special important cells and they need to be protected from all of the hurly-burly of development and all of the weird things that could go on. So when your mother was a foetus in your grandmother, the egg cell that made you was laid down, and the same thing for your dad. So this is incredible, that the cells that are going to make the next generation are already laid down in the grandmother and the grandfather.
Robyn Williams: And about 2 million or 10 million to one against it being me but I scored.
Kat Arney: Yes, exactly, you're here now. But I think this is fascinating, and there's so much discussion about what can be passed on then to the generation to come, the grandchildren's generation from being in these cells in the womb of the mothers and the fathers, so this is a kind of really hot topic now, it's called transgenerational epigenetic inheritance. And there's lots of interesting stuff, we know it probably happens in smaller organisms, things like fruit flies and tiny nematode worms. Plants do all kinds of wacky transgenerational stuff. I mean, plants are really weird.
But in humans there's some interesting evidence, and the best evidence that affects can go down the generations comes from something called the Dutch hunger winter, which is a very, very short period of starvation during the end of the Second World War in the Netherlands when women were starved. And some of the women who were pregnant at the time, they had babies that were a bit smaller and then they went on to have babies who were also a bit smaller. And then there is some evidence that there are health problems that have arisen from the exposure to starvation in the womb. But in terms of how it works and what's going on and whether this is really some kind of effect in the genome or whether this is just an effect of the womb, or cultural, all sorts of things, we don't really know.
Robyn Williams: But there are some clues and you go into this in the book. Epigenetic means sort of tagged on, and it's not in your original set barcode, it's extra bits, hence 'epi'. And I've got this picture of something hanging onto the scaffolding, if you like, tagged on, that came from outside. And what I'm trying to differentiate, good old Lamarck who said that you can learn new characteristics during a lifetime and pass them on, is that now possible?
Kat Arney: Yes, at the end of the book I go and talk to a woman in France who's doing some very, very interesting experiments looking at what is possibly a mechanism for this communication down the generations. And lots of people hear about epigenetics, and your listeners might have heard of things like DNA methylation or even histone modifications, and these are basically…I think of them like molecular post-it notes stuck onto DNA or onto the proteins that DNA wraps around. And that can impart information about use this gene, don't use this gene, or sort of lock-in states of this gene is on and open for business, this gene is shut. But what it's looking like is that actually the mechanism by which this information may go down the generations is through tiny, tiny fragments of RNA, which is a molecule very similar to DNA, it's the message that is read off DNA.
Robyn Williams: Yes, in fact if you go to the president of the Royal Society of London, Venkatraman Ramakrishnan, who we've had on, he showed how it actually works. He got the Nobel Prize for it I think in 2009. In other words, the ribosomes with the RNA carries it through so the interpretation can actually be transferred.
Kat Arney: Yes, there's definitely evidence that these little RNAs are important, in small organisms, in worms, in flies, definitely in plants. In humans we don't have evidence yet. A woman called Minoo Rassoulzadegan in France, she's got some really interesting evidence from mice that these RNAs may be responsible for carrying information. A guy called Oliver Rando at Massachusetts, he has just got a huge grant to look at tiny little fragments of RNA and their role in passing information and taking characteristics down the generations. It's still a very new field. Some people think it's way fringey, some people think, well, it's starting to come together.
And that's what fascinates me as well, is this is real frontier stuff, and you start to see how science is made, how paradigms are made. There's like, okay, there's Lamarckism, that's clearly wrong, but then people go, yes but some characteristics do seem to go in a way down the generations that isn't linked to the genome or directly linked to the DNA. And then, so how does that work? And then people go no, it's rubbish. And then people go but I found this evidence. And then other people go no, that's rubbish. And you start to piece together this narrative. And there are lots of fields of science where this is happening, this is active science.
Robyn Williams: Yes, and you've been around the world and you've seen most of these people, you've asked them recently exactly what the state of the nation is. And we are so far on from, say, Watson and Crick, or even the publication of the human genome project, which is a generation ago. So your book encompasses the latest people saying the latest things.
Kat Arney: Absolutely. I mean, when I got the idea for this book I was sitting in a meeting at the Royal Society in London, which is a great place to be inspired to write a book, I have to say, and it was a meeting about these control switches in the genome; how do you turn genes on and off at the right time and the right place? And that's where I learned about the Hemingway cats, and that's why my book is called Herding Hemingway's Cats, because Ernest Hemingway had these six-toed cats. And you look at a six-toed cat and you think that's a fault in the toe gene, right? And it's not, it's a fault in a control switch.
And so I just got thinking that we hear about genes all the time in the papers, the things that make your eyes brown, they give us cancer, and so, how do they work? And I talked to my friends and they'd go, like, 'I dunno.' And so I went to talk to all these incredible scientists, Nobel Prize winners, people working on the frontiers, and I said I'm going to write a book about how genes work. And they all said, well, when you find out, let me know. And that's kind of where I've ended up. There is huge amounts that we do know.
Robyn Williams: Yes, but it's a slim book in fact, that's the nice thing, it's not off-putting and hundreds and hundreds of pages long. I want to ask you one last question that might require a bit of a bigger answer but kind of sums it up, the herding part. When you've got DNA that is metres long, frankly, or wound up with so much in the way of code, a lot of it is bound to go wrong even in your lifetime, and there are repair mechanisms to fix it. How do these repair mechanisms work. How does the DNA stay mainly, in my case for decades and decades, intact?
Kat Arney: Well, I think the answer is it doesn't, but often the damage doesn't matter. So we know that every single day your DNA is under assault. It's being damaged by the processes of life, copying DNA. Actually the most damaging thing for DNA in the environment is the oxygen you breathe. You are making free radicals of oxygen in your body and it damages your DNA. And then there's things like ultraviolet light from the Sun, chemicals in tobacco smoke, all the carcinogens, the bad stuff that can damage our cells. So all the time our cells are being damaged. Most of the time that doesn't matter. A lot of the time your cells are not that important. The cells in your skin, most of them just get shed off and become the dust in your house. And like I said, about half the genome is probably junk. It doesn't really matter if that gets damaged.
There's going to be a few really crucial genes where damage does matter, and if those go wrong then you get diseases like cancer. But a lot of the time this damage is patched up, it's repaired. You have two copies of every gene. Sometimes one is used as a template for the other to repair it. There are all of these molecules that spot and patrol and flag up damage and repair it. It's not perfect, and this is why cancer is mainly a disease of older people, you just pick up typos in your genome as you get older. But the really incredible thing is that we don't get cancer all the time, that actually we've got very good at repairing our DNA and getting through this thing that we call life.
Robyn Williams: Well, it's a lovely book, congratulations. And I can hear you again Friday evenings just after 10 o'clock on Radio National, RN, on Sunday afternoons at 3pm on The Naked Scientists.
Kat Arney: Exactly. It is always a pleasure to talk to you, and it's always a pleasure to talk to the listeners in Australia too.
Robyn Williams: Kat Arney's book is called Herding Hemingway's Cats: Understanding how our genes work, it's published by Bloomsbury.
Most people are familiar with genes, their effects, and some common terminology such as DNA, but little is known even amongst scientists about how genes actually work. If our entire genetic makeup is present in each cell, what determines when a gene is activated? Or the place of activation? What happens when genes are damaged? These are questions Kat Arney addresses in her book, Herding Hemingway’s Cats, Understanding how our genes work. Kat Arney is heard as a co-presenter of The Naked Scientists and The Naked Genetics Monthly Podcast.
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