Thursday, September 19, 2024

New early approach for Alzheimer’s – ABC listen

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Robyn Williams: Why are you in Australia?

Susan Greenfield: I’m a guest of NeuRA, that stands for Neuroscience Research Australia, which is a not-for-profit institute based in Sydney, affiliated to UNSW, and I’ve been there for three days. And I wince at what they called me, but it’s hugely complimentary; rock star in residence. 

Robyn Williams: Really? They want you to sing as well? 

Susan Greenfield: Well, luckily not because I think they would have wanted to send me home if I did that. But no, it’s been great because we’ve had a series of lectures and I think they’re available as podcasts that people can approach, and one is exactly on the Alzheimer work, and the other is a more general one about the brain, developing it and then losing it and expanding it and so on. But I’ve also had the chance to engage with the scientists, and we’re hoping to establish some collaborations so that they’ll get me back here again.

Robyn Williams: Well, there she is, or was, rock star in residence. What is science coming to? And later in this program we’ll also hear about Dirty Bertie, and then a wombat faster than Usain Bolt. What can all these fun and games represent? Why, just another Science Show. Hello again from me, Robyn Williams. 

And the residential rock star is of course also a baroness, Susan Greenfield of Oxford, whom you may have heard a couple of weeks ago talking to Norman Swan about Alzheimer’s and dementia. I mention her baroness status not to glory in another British aristo, but to note that Susan is also in Parliament and takes part in debates about the future of research. She is leading a company linked to Oxford, where she was a professor for quite a long time.

Susan Greenfield: It’s no longer the Oxford campus because, being a private sector, being a spin-out, it’s about six miles away from the university. That’s not so we don’t collaborate with the university, and in fact they have certain facilities that we use, so we’re still closely connected with the university. But they actually, and quite unusually for a spin-out, they don’t have any equity or any royalty in the company. 

Robyn Williams: But it’s a happy relationship.

Susan Greenfield: Yes, as much as one can with universities, yes, and also as much as one can given it’s such a monolith. We have good connections, I think.

Robyn Williams: And you still have students?

Susan Greenfield: We aren’t part of the teaching of the university, so we don’t run courses, we’re there to do research. But that said, we have a very vigorous program of interns, industrial placement interns that come from other universities. We have about three or four a year. They come for about nine months, and because they don’t have mortgages or kids and they’re there primarily because they want to get a good degree and they’re interested in the science, they actually work their socks off, and it’s lovely because we have this vigorous, energetic, curious, bright group of people. And because they are there for nine months, they actually learn a lot, and they’re actually valuable, rather than just being observers.

Robyn Williams: And what about a bird’s eye view of science and young people in Britain at the moment? I mention this because there was yet another article in the paper just a few days ago, that amongst teenagers, and that would be in years 6, 7, 8, 9, 10, science, they said, is flatlining in half the population, presumably in the state schools here, science is in trouble. How well is it doing in Britain? 

Susan Greenfield: When you say it’s in trouble, you mean not enough people are taking it up?

Robyn Williams: And the measured results are as low as they’ve been in ages.

Susan Greenfield: Okay, I think there’s various factors that would apply both to Australia and here. The first is the exceptional case of covid. You might be able to learn history at home and literature at home, but you can’t do science experiments at home. And I think perhaps that generation that would have suffered from being excluded from school for a year or even two years, that must have taken its toll in detracting from the excitement of going into the science labs. 

A second issue is resources. Science is expensive and requires expensive equipment, and we’ve had huge problems in state schools in the UK with infrastructure, there’s been asbestos and damage. I don’t know if it got to the Aussie news, but schools have been closed because they’ve been deemed health hazards, and therefore the kids have been learning in sheds and so on. That doesn’t play out well if you’re going to do science. 

We then have a demoralised teaching force. But that might apply to a range of subjects, but for teaching science, you can’t just wing it. You do require a certain level of expertise, and that’s a diminished constituency now. So because I don’t teach myself, and I don’t have teenage children, I can’t really speak exactly to how the situation is. But if you say (and I can believe it) that the scenario is not good and it’s deteriorated from a few years ago, I would say they’re the factors that might play in.

Robyn Williams: Yes, you mentioned covid, which, of course had a tremendous effect, and, okay, inflation and the economic situation. But why do you think this is happening? Do you talk about this in the House of Lords? You were going there quite often, and some tremendous debates were on, on aspects of science. So what do you think is happening these days for the state of science?

Susan Greenfield: I think any debate on science has been outplaced by debates on immigration and Rwanda and Brexit and Putin and Gaza. There’s, sadly, over the last year or two, hot on the heels of covid, there’s so many terrible things happening in the world and immediate things happening in the world that a debate on stem cells, for example, might not be the top priority in the list of things to discuss. There has been a lot of debate, but sadly I haven’t been able to myself join in too much on safety on the screen. The online safety bill is something that has gone through, thanks to Baroness Kidron, and there’s been a lot of hot debate on that. But that’s not really about science, that’s more about, I suppose, child welfare. But clearly one draws on the science in order to comment on…

Robyn Williams: Yes, but if you look at science and its place in society, or what it should be, I mean, with these terrible things happening in Papua New Guinea and the 2,000 people, and we did a program about forestry and steep slopes, and if you cut down the trees, well, what happens? Everything collapses and you get sliding of the mud, and people die. And similarly, in your field you can have advances with Alzheimer’s research, and if you can alleviate that problem, the wealth, the benefit to society, financially and with other aspects, could be colossal.

Susan Greenfield: Absolutely. And I think what people forget are the carers. So with Alzheimer’s…I’ll say how many people love you in the world? So if you’re lucky, say ten people, for the sake of argument, ten people love you, Robyn. So if, sadly, you were diagnosed, that’s ten lives that are completely upended. And actually, I did give a speech about that in the Lords relatively recently, a general debate on what to do about this and the case for early diagnosis and so on. Because unlike cancer and heart disease, which are of course very serious conditions, you can still look at pictures of your grandchildren. And I have to say, my own mother now is taking that path, and it is very distressing for the carers, and people tend to forget about the carers because they’re already undergoing a sense of bereavement, because the person they knew is no longer there. There is a person breathing in front of them, but that person doesn’t know who they are. They can’t share any memories anymore, so they go through a sense of loss as though the person had actually died, and people don’t realise that, and don’t give them the sort of care and thought and consideration that that involves.

Robyn Williams: When it comes to your own research, and Norman Swan talked to you about Alzheimer’s on the Health Report, and we heard about the tangles and the tau, in other words those signs that come with it in the brain may be consequences rather than causes. So what could possibly be the cause, do you think?

Susan Greenfield: Okay, I think the cause is the story that we unfolded in a paper…well, it’s a review actually, so it’s joining up all the dots, that came out on Saturday in Alzheimer’s & Dementia, there’s a plug for it. So the cause isn’t really the relevant factor, it’s why is it that if the brain has something happen to it, it then responds with this non-biological feed-forward snowball effect of more dying and more dying and more dying. As you appreciate, in biology it normally operates on a homeostatic principle of feedback. So, think of the old thermostat and the electric bell, if you were old enough to learn about that at school, where something happens, it feeds back and it shuts it down. 

So what happens we think in Alzheimer’s in a selectively vulnerable group of cells, what is intended as a feedback system to compensate for damage actually is a feed-forward system, it actually causes more damage. And the reason for that is that primarily cells damaged in development have the ability to grow again. But if that is mobilised in the context of a mature adult system, it actually in the context of the mature brain has the opposite effect and it’s toxic. The brain doesn’t know this, so in response to such toxicity it mobilises more of this mechanism, and more and more, and then for 10 or 20 years in these primarily vulnerable cells…which, incidentally, do not contain amyloid at that stage…

Robyn Williams: That’s the plaque. 

Susan Greenfield: Yeah. So, heaven forfend, you and I might even now as we speak have this happening deep down in our brains, you don’t know. So what you need, and one of the problems, is to actually have that readout before you have memory problems, because by the time you get to the memory problem stage, you are closing the door after the horse has bolted because the core cells have already gone on this relentless snowball effect. So what we think we have done is to identify the primary mechanism in responding to what neurologists call an insult, that’s to say, a blow to the head or decline in protective mechanisms, it doesn’t matter. The actual trigger doesn’t matter. But if it’s in these vulnerable cells, that’s what matters, it’s site specific, such that you set in train this mechanism that you can read out. 

So we could measure this in nasal fluids, for example, as well as cerebral spinal fluid that bathes the brain and spinal cord. We can measure it in saliva. So what we are working on is development of what here is called a RAT test, so you could have some kind of screen that told you things perhaps were disrupted in these primary vulnerable cells that sent you to the doctor, you would have a further test that was sent off for precise quantification. And if all this happened in the 10-to-20-year time window before the symptoms came on, and if our drug works in humans, as we know it does in mice, then it would stop any more cells dying. So if, again, you took it in that magic window, then you would never get the symptoms.

Robyn Williams: I’m reminded, to some extent, of multiple sclerosis, where the body reacts to what might be a virus, but it turns out to be one of your own mechanisms, and you get this shutdown effect. And similarly, as I was growing up and everyone else, you have various cells that need to be knocked off, it’s called apoptosis. In other words, you’ve got to kill off stuff that you don’t necessarily need anymore, and those mechanisms are around and if they get, as you said, badly triggered, then you’ve got a problem. But it’s quite interesting, if you can have that kind of early warning system, that’d be wonderful.

Susan Greenfield: Indeed, well, that’s what we’re working on. And because we believe we’ve identified the primary mechanism upstream of amyloid, it means that this evil molecule, we can use that directly as a readout that the problem is underway, and we can also target it specifically as a therapy. And our therapy, and we’re quite proud of this, is the evil molecule itself, but just bent into a circle. It’s bit like tying your hands behind your back. So it will occupy the site that the evil molecule would normally occupy, but because its hands have been tied behind its back, it can no longer have any effect.

Robyn Williams: That’s very interesting, isn’t it. What do the people in Melbourne, where one of the centres of the Alzheimer’s research happens to be, what do they say about this idea?

Susan Greenfield: I haven’t spoken to them directly. I think there are some people there who understandably have followed the traditional path. Because this paper, this review, was only appearing on Saturday, I don’t know what the reaction will be. But what I will say about it, and I’m very proud, is, apart from myself and my wonderful colleague Sara, all the other authors are external to the company, and three of them are Alzheimer clinicians. So one’s a neuropathologist, one’s a geriatrician, one’s a neurologist, and the fact that this has been co-authored by three independent experts gives us, I think, a certain credibility that perhaps, had we just done it internally, wouldn’t have had.

Robyn Williams: Well, there’s science, science in the future, and you have an election coming. In the best of all possible worlds, what do you hope might happen? 

Susan Greenfield: Oh, I would like to think that people saw that the answer to our very terrible crisis, economic crisis and cost of living crisis, that in the long term the answer has to be we have to generate our own wealth. We can’t just not tax people; that seems to me, as a non-economist, a rather short-term way. I would like to think that Britain (and I’m sure you’ll say the same for Australia) really promoted science and technology, because if you can have innovative science and innovative technology, you are automatically creating wealth and you’re creating jobs and you’re making society better anyway. So I would like to see, if I ruled the world, which you may have noticed I don’t, if I ruled the world, I’ll have the ear of the Prime Minister, which I don’t, I would like to think that they would put a premium on science education. Back to what you were saying, ways in which one can excite young people to do science, ways in which you can encourage more women to do science and technology, and then putting more money into companies such as mine, which are struggling with innovative ideas such that it could actually be given the fast pace that is required to really get there. 

Robyn Williams: Good luck. I hope you do get there.

Susan Greenfield: Thank you so much, thank you. 

Robyn Williams: Professor Susan Greenfield in Oxford once more, this time as a rock star with the University of New South Wales.

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