The brain surgeons hoping to transplant Groote Schuur success to solve Africa’s brain disorders

Google the word ‘brain’ and the phrase ‘the least understood organ of the body’ and ‘final frontier’ pops up time and time again. What is intriguing about neuroscience as one of the scientists at UCT’s new neuroscience institute pointed out; you use an organ, the brain, to study itself. The University of Cape Town’s Neuroscience Institute is an African first which is bringing the various fields for basic research in brain disease and disorder under roof in their quest to find African solutions. To achieve this, the Director of the Institute, Graham Fieggen says, he is going for a collaborative, global approach and who better to call on than a fellow neuroscientist, Prof Matthew Wood from Oxford University where he is not only involved in leading-edge research, but has also managed to commercialise four of the university’s innovations. Biznews founder Alec Hogg spoke to professors Fieggen and Wood at the opening of the institute which is housed in a building where a winner of a Nobel prize once tinkered away – and surprisingly, it’s not Chris Barnard. Prof Fieggen said he had been working for decades to bring together this kind of collaboration under one roof. – Linda van Tilburg

As one of our main benefactors David Barnes likes to say ‘this is an idea whose time has come but it’s been coming for a while.’ The first neuroscience institute was established probably nearly a hundred years ago. And there’s been a sense over the years that neuroscience is esoteric; it’s something that maybe rich European or Asian or North American countries need to pay attention to. But the reality is that disorders of the brain are front and centre in the 21st century and South Africa and Africa generally need to be part of that.

If you just look at the demographics and the United Nations’ very sober assessments of where the world’s population is heading by 2100; half of all children in the world will be African and the median age of most African countries is well under 20. It is about understanding the disorders that are prevalent in Africa such as HIV and TB and other infections; trauma is very prevalent in Africa, but it’s about understanding the impact of a lot of these conditions in young children and how that alters brain health. And if half the children in the world are going to be African; understanding the conditions and impact on the health of their brains is profoundly important not just for Africa but for the whole world.

And who’s paying attention to it at the moment?

I think a lot of people are and I certainly wouldn’t claim that we’re the only people that are. I think there’s been an enormous amount of attention paid to things like HIV and TB and malaria over the last couple of decades but maybe not as much attention paid to the neurological consequences. And I think that’s really what sets us apart, that we are in this environment at UCT where there’s an incredibly strong track record of research in these different areas. For example, in HIV; UCT was ranked as the most impactful institution in the world in HIV research but very little of that actually has addressed the impact of HIV on the brain which is enormous.

When people talk about dementia, obviously Alzheimer’s and conditions like that spring to mind but when you look at the global burden of HIV and recognise that 6 million people who potentially live to old age with HIV are going to have HIV dementia that really starts to alter things. So, I think there are  conditions that maybe haven’t yet been fully appreciated for their significance that we are going to be able to pay some attention to.

The whole UCT story; preparing for this trip; I learnt that UCT was the home of Chris Barnard, that is pretty well-known for the first heart transplant in the world but also a Nobel Prize winner who was based in exactly the same building that your Neuroscience Institute is now occupying.

Absolutely. Thank you for asking about that; I think it is one of the extraordinary stories. Sir Allan Cormack was a physicist who worked on our campus and really had no interest whatsoever in any medical applications of physics. And just by chance; the hospital physicist emigrated, and he was instructed to go down to the hospital and once a week to check the radiation doses for patients getting radiotherapy. I love telling this story to students because it’s one of the best examples I’ve ever heard that life takes you in directions you may never have anticipated.

Cormack never ever wanted to spend a day concerned with any form of medical application of physics but spent the time going to the hospital once a week looking at these X-rays and worked out radiation doses and had this paradigm changing idea that an X-ray is just a reflection of tissue density, which can be calculated mathematically. And he wrote a bunch of algorithms that he published in some obscure physics journal in the 1950s and nobody paid any attention until 20 years later when an English engineer called Godfrey Huntsville came up with a technical solution for what became known as a CAT scan and used Cormack’s  completely ignored publications to derive the software that would run the CAT scanner.

They both got the Nobel Prize and I think actually the most interesting part of the story is; it’s the first time that the Nobel Prize for Medicine had gone to people who had no medical qualifications and that was in 1979. That’s over 40 years ago and if you think about where progress happens in medicine today; it’s in fusing different disciplines. It’s not just about doctors having smart ideas; it’s about doctors working with people from disciplines like physics and engineering and computer science and linguistics and all sorts of other disciplines and actually thinking of new ways of tackling old problems.

Steve Jobs of Apple used to talk about design and technology meeting in the centre to produce the best products, the insanely great products he spoke about. You are doing something similar, in fact much more than that by bringing in many disciplines under the same umbrella.

So, I think Steve Jobs would have conceded that the most insanely great product in the history of the universe is the human brain and to be doing this in the context of neuroscience is tremendously exciting.

So how difficult has it been to get the collaboration together that you are now enjoying?

I’d have to say it’s been embarrassingly easy, actually, because it’s just so obvious that it’s the right thing to do and just to give you a sort of a personal example… I trained as a neurosurgeon at UCT after a few years in Canada and the UK, and the neurosurgery that we were taught 20 years ago; it’s different. Things move so fast in in these very dynamic and rapidly changing areas of practice that you realise that what’s important is the patient in front of you, not the sort of false divisions that we have into surgery and medicine and psychiatry, and those sorts of disciplines; they’re completely artificial.

And I think the focus is increasingly that somebody has a brain disorder and that might be a brain tumour, dementia, a previous injury, infection or whatever. How that manifests, is different at different times and at certain points may require those highly developed skills of a neurosurgeon and at other times may require incredibly sophisticated help from a psychiatrist or a neurologist. But the point of the matter it’s a human brain you’re talking about; different conditions manifest in different ways ,but ultimately, it’s about the human brain.

How confident are you that what you’re going to do today is 100% the right thing, or is there still a lot of, not guesswork, but mystique around this incredible thing that we call the brain?

One of the really rewarding things about working in an academic institution such as Groote Schuur or Red Cross Children’s Hospital is that you know we’re part of the global neurosurgical community. Every single time we go to the operating theatre; we’re going there to do something that colleagues in New York, Moscow or Delhi would be looking to do. Neurosurgery is a small community and we’re part of that international community. So, it’s not like we’re doing things differently in some way or we’re kind of behind the curve.  I think the real opportunity is that there are many things that we haven’t yet figured out. So, for example brain tumours; such incredible progress has been made in the treating of most forms of adult brain cancer. When you’re working in a field where there are such huge scientific challenges and there is a massive need to make progress in offering treatment wherever in the world you are, that’s got to be a good field to pick for your career. It’s no good going to do something where all the difficult questions have been solved and it is certainly not the case for neurosurgery.

Is there a chance then that there could be some global breakthrough at the Neuroscience Institute; in other words, you have as much chance as anybody else to break down or find solutions to these questions that still remain?

I think that’s a really thought provoking question. I guess the answer I would like to give you – what would please us most would be to be part of solving some of these really big problems collaboratively because I do think the fundamental nature of science is changing and there’s sort of the arms race between different institutions all wanting to be first and to be the person to make the breakthrough that is really important. And there’s no doubt that it is still an important driving factor in a lot of people’s work and their research, but the really big questions today are being tackled in a very collaborative way.

And I think for me the immediate challenge is to know that we’re as good as anybody else and we can lead in a certain area. So, for example, the areas where we have huge local opportunity, is trauma. Huge numbers of Africans sadly sustain traumatic injuries to the brain. We know about the devastation caused by infections such as TB and HIV. Epilepsy in developing countries is still very understudied; the causes of stroke that we see in African countries and there probably are genetic components of brain tumours that are unique to African populations.

So, there are definitely competitive advantages that one could describe related to being in South Africa and there are huge institutional advantages to being in Cape Town in particular at the University of Cape Town. But as I say, I think a lot of the really big, challenging and exciting questions that need to be answered are going to be answered in collaborative ways, where you get institutions in different countries on different continents working together to tackle them.

The worldwide collaboration that Professor Fieggen is striving for at the Neuroscience Institute includes working with former university pal Matthew Wood. He is a professor in neuroscience at Oxford University and is originally from Zimbabwe, and although he is also a surgeon, he does not operate on brains anymore and is concentrating on science and research. As biomedical sciences are increasing in investment potential; he has been involved in spinning out several companies from Oxford University. He told Alec he’s planning to spend considerable time at the Cape Town Neuroscience Institute.

Over the last decade with the developments of the various types of technologies that could be used for repairing genetic and other brain disorders; I’ve been involved in setting up four different companies that have now received investments. It is the principal mechanism by which we’re developing these new treatments and new technologies. So, I think a lot of this has emerged just from very basic science. Oxford, which has created the basic science, own a lot of the intellectual property and it’s been something that we’ve been doing now pretty successfully in Oxford but really following examples from California and particular Boston.

The way to develop these is to get investors to be interested and develop small companies and get investment into those. It’s the quickest way to develop the technology, the quickest way to be able to test to see whether these ideas are likely to be useful in patients before you really have to embark on a much longer piece of work to develop these drugs proper. The four companies are all in Oxford.

You’re also very involved at UCT and at the Neuroscience Institute. Why?

Well, I think for a couple of reasons. Having grown up in Africa; I have always been very committed in trying to think about how the work I do and how it could be of benefit back here within African populations. So that’s one. One strong reason is Graham (Fieggen). He was a close colleague of mine and I’ve been very willing to help him develop ideas for this institute, but I think in many ways probably the most important reason is the importance, or the way that Africa is going to develop in the next 50 years. We know that probably by about 2050 half the world’s children will actually be living in Africa, which is a stunning thing to think about on the planet of ten or twelve billion people; there are going to be four billion children and half of those 2 billion children will live in Africa. Many of these children will probably be suffering not from the traditional types of diseases which are infectious diseases; many of them will have neurological problems, mental health problems and it’s almost going to be the most important place on the planet to be able to have treatments and medical interventions that will benefit enormous population of children that’s going to exist here in 30 years’ time.

A good friend of mine did her training at Baragwanath Hospital in Johannesburg and said that during her time; there were students from all over the world. It was like raw material, Bara being a place where occasionally people would walk in with an axe in the head and stuff like that. Oxford is a very peaceful, calm place… brain trauma and some of the diseases that exist in Africa, might be different to what you have come across over there.

I suppose in many ways it is. A lot of the real expertise here in Africa is the clinical expertise; it’s the people who really understand the patients, the diseases. What is lacking here is often investment, funding or other types of expertise based on, for example, technology which has been developed in the Far East or Europe or North America. So, there are ways that we can help future work here by providing expertise, by providing access to technology. This is not the natural place to develop computational technology or genetic technology, but it is absolutely the natural place to be using that technology to benefit patients.

And I think there is potentially a very productive working relationship between a place like Oxford, which is a very vibrant place but really developing fundamental science and technology and how you would think about applying that in the real world to problems that could really have a huge impact. And I think the other element of the childhood neurological challenge, which is going to exist here in 20 years’ time is the economic potential of the continent of providing a good answer to that problem.

Instead of having half of 2 billion children not developing their full potential and having neurological diseases, having infectious diseases; if you suddenly have a billion children that are healthy, that can contribute economically, that can develop professionally; you have a completely different future for sub-Saharan Africa. So, I think potentially, this is almost the most important place in the world to be thinking about how you’d apply computational technologies and genetic technologies. It is the only continent where our population is growing over the next 50 years or so. So, there’s potentially a huge amount of benefit that could be got here.

If we can get this right;  it’s also a huge benefit to this organisation, UCT that they got you as a professor of neuroscience at Oxford. It’s at the top of the tree isn’t it. Or is there another university that you could go to?

I mean Oxford for the last six years; you measure these things in different ways, but in at least two of the three ways we measure how good universities are in terms of their medical research; Oxford is the number one for six years. So, we’re very good at what we do in Oxford. But I mean; this is a tremendously exciting effort and institution. Oxford would love to be much more involved here and there’s some very obvious ways that Oxford can support this by giving people opportunities to spend time in Oxford when they’re in Europe, by developing collaborative links, by helping to get funding, by providing access to technology and resources that we take for granted in Oxford that are not necessarily here.

Oxford is a very global university. We have research bases and institutes all over the world, Southeast Asia, all over Africa, Central America. So, it’s not unusual for Oxford to be supporting things like this but I think the potential and the challenge that Africa faces in the next 50 years is enormous. And I think the potential to be able to contribute to solutions to that, is something that  great universities should be doing wherever they are. And so, it’s a privilege to be involved.

Your African roots have certainly played a big part in this. How much time will you be able to devote to the Neurosciences Institute?

Well, I think that remains to be seen but I think I could potentially devote most of my time to supporting it. It is a live discussion at this point. I think it depends. Actually, a lot of the work that I talked about earlier today as we begin to develop that research in Oxford; a lot of that work could be tested in patients that are based here. So, for example, we could make a decision that we don’t test these new medicines in patients in Boston, Massachusetts; we test them in patients in Cape Town, South Africa and we can bring some of our research here and train people here to do that work.

So, there are decisions we could make that would make it much easier for me to spend a lot of my time and…

Making this into a centre of excellence, not just ideas for African countries but perhaps global

Yes, if this really is going to be successful, which we really hope it will be; I think it’s going to require a couple of ingredients. David Barnes last night sort of alluded to some of those crucial things. The one is, the goodwill here from all the various elements in the university, in the hospitals to work together productively so the environment has got to be right.

You have to have individuals and scientific and medical qualities. There’s abundant talent here. So I don’t think that’s the issue, but one of the issues really will be the future of how we develop more people with expertise in brain science and neuroscience here and really develop African people with a passion and the skills to be addressing these problems because if we’re looking 50 years ahead it’s not going to be the current generation of doctors and scientists, however good they are. It’s going to be the subsequent generation that will really need to be an exceptional group of people who are well trained, who are committed to solving some of these problems.

So, I think as much as we can contribute by establishing research and help with investment and funding and build collaborative links around the world, first places around the world; one of the crucial elements will be training and finding and persuading the next generation of medical scientists to come here and work on the brain instead of working on infectious diseases or working on cancer.

You know, attract them to the challenge of coming here to this new institute and working on brain science and building the links in sub-Saharan Africa that means that whatever is done here can be rapidly translated into benefit in West, East or other parts of Africa that may be facing exactly the same problems over the next 50 years that South Africa is dealing with.

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