Robyn Williams: Which brings me to sex. Everything eventually brings me to sex, but not always in creatures so small; fruit flies. Stephen Goodwin at Magdalen College in Oxford can't get enough of it.
Why do you study reproduction, in fact the act of reproduction in fruit flies?
Stephen Goodwin: That's a very good question. One of the reasons we look at the fly nervous system is that it's comparatively simple when you compare it to our own nervous system. So a fly has about 100,000 neurons, we have billions of neurons. So we sort of use it as a proxy for looking at more simple behaviour, although fruit flies are capable of all sorts of complex behaviours that they are probably not aware of, including learning and memory, love and hate essentially...
Robyn Williams: Love and hate?
Stephen Goodwin: Well, maybe I am being a bit extreme, but certainly flies can fly, which is something we can't do. What we are interested in is what are the differences in the nervous system and how do these give rise to characteristic differences in sexual behaviour. And this is everything from the way that the fly looks and the way that the fly behaves essentially, and the flies will, when you immediately put the male and female together they will start courting each other. And they go through a whole series of stereotypical behaviours where the male essentially woos the female, and if the male is the right species...obviously the female and the male have to recognise each other, so there is olfactory and gustatory cues and visual cues that both the male and the female respond to. But if the male likes the female he will show off to her essentially, and he actually sings to her, he vibrates one wing and sings her a love song. And if she is getting all the right cues from him and he is the right species, she will actually slow down and sanction the mating, and then the two will be locked in bliss for the next 20 minutes.
Robyn Williams: Twenty minutes is not that swift.
Stephen Goodwin: Twenty minutes is pretty good. As an Irishman I would say 20 minutes is pretty good, but anyway...20 minutes, and then within the first 10 minutes sperm and seminal fluid is transferred. And then what we are looking at is actually what the underlying neural circuitry and what the differences in those neural circuitry between males and females is, and what are the kind of differences that go on within the development of the nervous system and how that comes together in the adult to give you essentially behaviour.
Robyn Williams: But tell me, how do you get in to such a tiny nervous system to find out what's going on?
Stephen Goodwin: The way we do it is using genetics. Fly sex is determined genetically, and as such because it is innate, because it's hardwired and because a male and a female don't need any experience, there's a genetic basis to it and this allows us to look at the mutants and how mutants affect these behaviours. And two mutants that my lab and many other labs now work on as well are the gene called fruitless and a gene called double-sex. And in the fly world the name gives away the kind of behaviour that the mutant exhibits here. So with fruitless mutants...I was part of a group of people in the '90s that ended up cloning the gene responsible for this and it's kind of an interesting gene because it is largely expressed in a male nervous system. If a male is missing this gene actually his sexual orientation goes out the window and he starts courting both males and females. And on the other hand the other gene, double-sex, is actually found in both sexes, and this gene classically if you are missing this gene you are actually intersexual, you look both male and female.
Robyn Williams: You go for everybody, do you?
Stephen Goodwin: As an intersexual fly you're pretty confused because you both look and behave like a male and a female, and in addition to looking that way flies also use pheromones, and if you're an intersexual fly you have a mixed pheromone profile. So in fact in some cases you might be arousing yourself because you actually look and smell like a male and a female. So they become very difficult to work with behaviourally.
But the next step from looking at the genes that are responsible and disrupt these behavioural pathways is then to clone the genes. So what we can do genetically and how we get into manipulating these neurons is that once we've cloned these genes we can make transgenics that specifically express only in these neurons that the gene is expressed in. And then there's a whole plethora of wonderful genetic tools that allow you to disrupt that neuron. You can disrupt that neuron, switch that neuron off, or you can activate that neuron.
And in fact here at Oxford we have Gero Miesenböck who is one of the godfathers essentially of optogenetics, and optogenetics and techniques like this are widely being used now in all sorts of different nervous systems. And actually where he first pioneered this was in the fly, and this is where you have this wonderful ability to be able to activate a neuron and see the consequences of doing that. So I could show you videos here of flies that we have where we're expressing optogenetic markers in these neurons and we can make a male behave and show male behaviour even in the absence of a female. And similarly you can shut down the behaviour in an animal by inactivating the neuron as well.
Robyn Williams: I see, so what you're actually saying is that by understanding how the genes work you can, if you like, play the orchestra of the nervous system and work out how it operates. But this is a leap that you'll find uncomfortable but occurs to most of us…the insects do it that way, is there anything that you can tell from this sort of study about how we humans might operate?
Stephen Goodwin: We always get this question, it's an awkward one. Part of me get angry little bit about it because...
Robyn Williams: That's why I hesitated!
Stephen Goodwin: No, it's just everybody wants a justification; does it happen in us? Why are we so central to biology? But I guess we are fascinated in ourselves. First and foremost I'd say in the fly it's an intrinsically interesting question all of its own; how does a simple nervous system, even in a fly which, again, I repeat is capable of quite complex behaviour, how does that come about and what are the mechanisms involved? And what I should say is that whilst there are no obvious candidate genes that are like, say, fruitless...well, actually it is not true for double-sex, there are double-sex homologues in the mammalian genome, but there doesn't seem to be an obvious one for fruitless, although fruitless is a transcription factor that is a member of a large family of proteins and we do have proteins in our body that look like this. But I think the same kind of mechanisms will be operating, but I don't think anyone has looked at it in enough detail yet.
Robyn Williams: The mind boggles. But can you understand why it was that Sarah Palin actually said that she would ban fruit fly research?
Stephen Goodwin: No. No comment without saying something libellous.
Robyn Williams: You know she did.
Stephen Goodwin: I'm aware she did, but I guess if you talk to a moron you'll get a moronic answer back, so...
Robyn Williams: What's going to happen next in this line of research?
Stephen Goodwin: So the next thing is that we figured out some of the genes that are responsible for this. We've looked where they are expressed in the fly and we've started to manipulate these neurons to see what these neurons are capable of behaviourally. And the idea now is that what we're trying to figure out is this whole idea of what is called the connector, and you've probably heard mammalian people talking about the brain connector and the sort of challenges that exist, this is trying to basically map all the component elements of the nervous system and how they make connections to each other and how they come together to give behaviour essentially. So we are at the step at the moment where we're really just defining what these neurons are capable of doing. And the plan next is essentially to start to see how those kind of neurons, what the properties of those neurons are and how they talk to each other and how they are connected to one another.
And then more importantly actually is in many of the behavioural studies we do .You put two flies in a test tube and you ask them to go at it. But actually what would be really important, and colleagues of mine are actually starting to address this, where you actually look at social interactions and you put flies in groups and ask how they respond and how things change in a social context. And also there is a learned component to fly sexual behaviour too, and where does that circuitry lie in this. So whilst everything seems robotic and innate, flies actually do remember from a lousy experience or a bad sexual experience and can modify their behaviour accordingly.
Robyn Williams: They live long enough to do that, do they?
Stephen Goodwin: Oh yes, they might have a little bit of a James Dean…but in the short time that they live they pack a lot of behaviour in.
Robyn Williams: And I can't help wondering whether Stephen Goodwin at the University of Oxford will eventually be able to manipulate those flies to mate as he chooses. Now, that's a sex god, isn't it!
The fruit fly Drosophila melanogaster, has a simple nervous system which makes it an ideal subject as a proxy for more complicated animals, such as humans. Stephen Goodwin describes his work studying the genetic, developmental, and neural mechanisms that underlie sex-specific behaviours. The elaborate courtship ritual performed by the male fly has provided remarkable insights into how the neural circuitry underlying sexual behaviour, which is largely innate in flies, is built into the nervous system during development, and how this circuitry functions in the adult.