JB: How did you make the discovery [that a new molecule -- a little peptide, five amino acids long -- seems to be able to rescue the memory loss that occurs with the disorder of the Alzheimer proteins]?

ROSE: It came about in a rather classical scientific way. What we did first was to show that in order to make long-term memory, that is memory that persists for more than half an hour or so, you need to make a new class of proteins. Then, using standard biochemical techniques, we were able to identify what the class of proteins were. They turn out to be a group called cell adhesion molecules. That is, they're molecules whose job is to stick together the two sides of the synaptic junction, the business end of the relationship between one cell and another. And that was interesting in itself; you can discover how they work, you can show how you have to unstick them and restick them in new configurations.

I was looking at this, and then I suddenly realized that one of the key proteins which is a major risk factor for Alzheimer's Disease, is itself a cell adhesion molecule. The question was could that be involved in memory as well? And it turns out that the normal functioning of this molecule is necessary for long-term memory to be made; if we stop the molecule from functioning -- you put an antibody into the brain which binds to the molecule, or a specific bit of RNA which stops it being synthesized -- then the memories can't be made.

Then if you look at the structure of this molecule, the amyloid precursor protein, it turns out that there is a very small section of it which is just a few amino acids long which seems to have some very special properties. It's those properties which you can mimic by making an artificial peptide, and it's that it turns out will rescue the memory which is lost otherwise. Clearly that's a long way from having a drug which will cure or protect from Alzheimer's Disease. But nonetheless, being able to rescue memory in this sense seems to me to be a step which is potentially in the right direction.

JB: What steps are necessary to make this available for human use?

ROSE: There's a lot more work to be done in animals first of all, the standard sort of drug development stuff would have to be done, and then you would have to show that you can take it orally without it breaking down -- at the moment we have to get it in by injection. Or else you have to find a way of protecting it so it can get into the brain. Then there are various other bits and pieces of peptide controls that we need to do, and so on. You're talking a few years downstream, but you're moving in that direction.

JB: What has been the reaction among scientists?

ROSE: People are pretty excited about it. The formal scientific paper is just in press.

JB: When will it come out?

ROSE: Within some months from now I suspect. What we haven't done is patent it.

JB: For ideological reasons?

ROSE: I suppose so, yes.

JB: Then somebody will come and patent it.

ROSE: No, they can't once it's published. You can only patent it if it's new. Patent law is a bit different in Europe. I have to say that a fair number of my molecular neuroscience colleagues, mainly on this side of the water, have got companies in which they're trying to develop molecules which will do this sort of thing. That's fine, but I would prefer to publish in the scientific press and develop things that way.

JB: Did you see the Arnold Schwarzenegger movie Total Recall? How long will it be before you begin to implant memories?

ROSE: That's a different story. People are unclear about what we mean by a memory-enhancing drug. If you go to the smart bars in San Francisco and buy a smart drug, a memory drug (none of which work, I have to say, but they're good marketing for the health food stores and bars) what you don't get is something which will give you someone else's memory, or even bring back memories you lost when you were just a few years old. What they do is they help in the transition from short- to long-term memory.

If you take someone with Alzheimer's Disease, then the first problems that people notice are things like you don't know where you've left your car keys, whether you've done your shopping this morning, whether you know the person who's ringing your front doorbell. The early stages of the disease are stages in which you will remember things for a few minutes but then you will forget them. What we need to do is find a way of helping people in the early stages of Alzheimer's Disease to remain in the community rather than have to be in care. To do that they need to be able to hold their short-term memory. Most of the so-called smart drugs are looking at doing that.

Further downstream there's the question of why do people get Alzheimer's Disease in the first place? Is there something we can do by way of neuro protection? Is there something you can take like you take Vitamin E or half an aspirin, something like that which will build up some protection? Interestingly, the best evidence for neuro-protection comes not out of the lab but out of epidemiology. It turns out that post-menopausal women who are on HRT are much less likely to get Alzheimer's Disease than if they're not on HRT, and that has to do with estrogen, although it's probably not estrogen itself in the brain.

What happens is that the sex hormones, the steroids, are converted in the brain into things called neuro-steroids, brain steroids. My guess is that if we're going towards neuro-protection there will be an interaction between these peptides I'm looking at, the neuro-steroids, and some other growth factors in the brain. So it will be possible to get a cocktail of processes which will be able to provide neuro protection in this sort of way. That will be the long-term aim.

There are a lot of risk factors for Alzheimer's Disease. Some of them are genetic, or in other cases there are genes you've got that are risk factors, and they will interact with things in the environment. The proteins that we're looking at are the risk factors for Alzheimer's Disease. They are proteins called presenilin, the amyloid precursor protein and so on. Somehow there's an interaction between whether you've got these proteins, whether you have some problems -- for example if you've had concussion as a kid, you've been involved in a football game and banged your head or had a car accident, or you've had general anaesthesia, you are more likely to get Alzheimer's when you're old than if you've had none of those things. So there's a whole lot of environmental risk factors. How they play together no-one knows.

JB: How does this line of research play into Darwinian ideas?

ROSE: It depends what you mean by Darwinian ideas, which is one of the problems. Darwin's basic idea is very straightforward. What is not controversial is that evolution occurs. What is at issue is the mechanism of evolutionary change. And the Darwinian evolutionary process says something which is also incontrovertible, that like breeds like with variations, that all organisms produce more offspring than can survive into adulthood and reproduce themselves. Those variations which are best able to survive are more likely to survive into adulthood and breed in their turn, so you get evolutionary change like that. No question. That's one of the fundamental mechanisms of evolutionary change.

But if you read Darwin himself, he was very clear that there are others as well. Sexual selection is one, random changes are another. And chance -- the issues that Steve Gould calls contingency -- becomes very important here as well. Darwinian mechanisms are very good for species getting better at what species do, but they're not good at making new species. Darwin himself was very well able to recognize this, which is why the Galapagos became very important. Here were islands very close together populated by species which seemed similar but had particular differences from island to island.

Much later when he was looking at the specimens that he'd got from the different islands, particularly at finches of which there are generally agreed to be 13 different species in the different islands, Darwin came to the conclusion that what must have happened is that the original parents of all these finches had come from the mainland, from Ecuador, which is about 400 miles to the east. Once they were on the islands, they bred and they radiated out. In the different islands there were different potential foods available and the finches became more specialized accordingly -- some of them are cactus eaters, some of them are insect eaters, some of them are ground finches, there's a woodpecker finch, there's an insect eating warbler finch, and so on. All which probably came from the same original stock. This is one way in which new species were produced, by arriving in a virgin territory and then radiating out from there. So all these mechanisms become very important as far as evolution is concerned.

Now we come to the question that you were asking, which is about the evolution of humans, and the relationship between our brains and our brain processes and evolutionary mechanisms. We are evolutionary products. The particular evolutionary line which has led to humans has been one which has achieved species success by the individuals developing bigger and bigger brains. Now brains aren't necessarily the only way to evolutionary success -- bacteria (Lynn Margulis would say proctista) outnumber us, and will probably outsurvive us in the world. But once you start on the evolutionary line which leads to brains, once you're an omnivore, you have to hunt your prey, or you have to learn to escape from prey, then there's an evolutionary pressure to get smarter -- that's the route that led to humans.

What our evolution has given us is brains which are enormously powerful and adaptive, capable of enabling us to live in the very complicated social circumstances in which we do, and capable of creating our own history and our own technology. There's a lot of debate which you get from the ultra-Darwinians about free will.

Richard Dawkins ends one of his books by talking about the power of humans, that only we can escape the tyranny of our selfish genes. Somehow free will rescues us from the sort of determinism which is given by our genes. I don't look at it like that.

I don't take free will very seriously. I would say something different, and that is that we have to get rid of this whole attempt to create dichotomies between nature and nurture. The real thing about our brain development, our development as organisms, is not a dichotomy between nature and nurture, but a dichotomy between specificity and plasticity or perhaps between process and outcome. What is required is a developmental system which is partly not modified by the environment and partly capable of responding to the environment.

Why must it not be modified by the environment? To take a very simple example, a new-born baby's eyes are connected via other brain regions to the visual cortex, at the back of the brain. As the child develops, the eye grows, the different brain regions grow, and the visual cortex grows -- but they grow at different rates. What you've got to do is keep an orderly relationship between the inputs from the eyes finally to the inputs to the visual cortex. Otherwise you'd cease to be able to see or make sense of what you saw. And you don't really want that to be too much screwed around by the environment. So you've got to have specific developmental mechanisms which hold that wiring and make sure that the connections are made and broken in an orderly way. That's specificity.

On the other hand, you've also got to have plasticity, the ability to modify your response to the environment by depending on experience. Take the visual system again as an example -- how the visual system is finally fine-tuned depends very much on the shapes and patterns that you experience as a young and developing child. Equally we have to learn, and learning means that we have to make and break and remold connections in our brains the whole time.

This intense dynamism which is fundamental to understanding developmental processes, is lost in the argument that the ultra-Darwinians have that there is, if you like, almost a direct line between a gene and a phenotype, unmodifiable by environmental change. The crucial thing we have to understand, or that I want to understand as a scientist, theoretically and experimentally, is the way that this interplay occurs during development. And that's in a sense what memory is a special case of. Pat Bateson discusses this at some length in his new book Design for a Life.

Read on for Part Two: A Trip To The Galapagos.