Alastair Buchan

WORKING WITH THE BRAIN. Alastair Buchan is a British-Canadian doctor who specialises as a clinical neurologist. His main research interest is how to make neuroprotection a reality in the clinic.  He currently holds the Chair of Stroke Research at the University of Oxford. From 2008 until 2017, he served as the Dean of Medicine and the Head of the Medical Sciences Division at the University of Oxford, and then from 2017 on as the university’s Pro-Vice-Chancellor and Head of Brexit Strategy. Working to maintain Oxford’s continued presence in Europe he brokered partnerships with the Universities and hospitals in Berlin and  established the Oxford-Berlin Research Partnership, which includes an “Oxford in Berlin” centre for Oxford University in Berlin.

You can listen to the podcast of this interview here.

Alastair Buchan, what is neurology, this branch of medicine to which you have dedicated your life?

My field is brain health and protecting the brain against disease and ageing. Keeping the brain and nerves healthy is the job of a clinical neurologist. My basic science is about how to understand how to keep brain cells alive when they are threatened. In stroke, there’s an  acute energy crisis. You lose the cerebral blood flow supplying nutrients to the brain. Apoplexy as it was called was thought to be an act of God, those afflicted (as was Nabal in the Old Testament) were struck down, hence the term stroke.  In the Seventies when I was a medical student, there was no treatment for stroke and there was very little treatment in neurology at all, it was mainly a diagnostic speciality. As residents we were taught that once a blood vessel to the brain was blocked and the damage was done, if you tried to unblock the blockage, you would get a hemorrhage and would likely kill the patient. We were taught that our brain is what we gain when we are in our mother’s womb and the brain forms rapidly at the time we are born, and once the brain cells and the connections are formed it was fixed, immutable and if anything happened and you lost brain tissue, that was it. It turns out, that actually, none of that is true. 

What is the brain?

The brain is the organ of the mind, the essence of humanity. It is how we see, hear, think, feel, create, remember. It is how we develop our personality, how we store our experiences, ultimately memory is to be human. The on-going tragedy is the disease of dementia, when you lose the ability to remember. Neuroprotection is the desperate need to find a way to stop brain cells dying, particularly those that could serve memory and cognition. My work concerns how you look after the single biggest threat to an individual human being, which is their personality, their memory, their ability to look after themselves, but beyond physiology and day-to-day living, it’s about how you preserve intelligence, cognitive abilities, creativity, and the ability to share humanity with other humans.

Illustrating how doctors were incorrectly taught that the brain is fixed and immutable, an 1885 Golgi silver stain, hippocampal neurons as discreet cells as drawn by Santiago Ramón y Cajal, a Spanish neuroscientist, pathologist, and histologist specializing in neuroanatomy and the central nervous system. He and Camillo Golgi received the Nobel Prize in Physiology or Medicine in 1906. Ramón y Cajal was the first Spaniard to win a scientific Nobel Prize.

Alastair Buchan, what kind of protection is there against dementia, Alzheimer’s or even brain tumors?

As I said, as a young student and doing a research degree at Cambridge, I was taught that if you damaged the brain it couldn’t repair itself, that in the words of the celebrated neuro-anatomist Ramon y Cajal the brain was fixed, immutable. It’s not. It can regenerate it is plastic. I was also taught you couldn’t restart the brain by resuscitating the heart, and that too was not true. As for taking blood clots out when the block cerebral vessels – we were told never to do that. Again we’ve discovered that that’s not true. Just as in cardiology we’re learning that the heart is able to recover, now in neurology we’re learning that you can reperfuse the brain, as you do in the heart with stents to get the blood flow back to the heart. We now use stents for the brain arteries, and we use thrombolytics to dissolve the blood clots that block the flow of energy to the brain and achieve reperfusion resulting in neurological recovery for the patient.

The timing of what we do is critical. If you lose all cerebral blood flow, as in cardiac arrest  you have maybe  5, 10, 15 minutes to get it back. If you block an individual vessel, you have 1, 2, 3 hours, maybe even longer in some situations when there are collaterals,  6-12 hours and this element of timing has made neurology interventional and  acute like cardiology.

Can we now also monitor the brain in a similar way that we can monitor the heart? 

Cerebral function is a bit like having an endogenous  heart monitor, if we are with people and we are actively talking and engaging with people, we are being (self-) monitored. The brain monitors its own function exquisitely when it is active. It is when you are asleep or dozing off watching the TV or under anesthesia and the brain is relatively  inactive that it is not being monitored. Brain activity requires all kinds of back up drawing on memory, vision, speech, movement – you are essentially monitoring and maintaining the physiology of your own brain all the time, and I believe it is absolutely true that having many interests – reading, working, interacting and when alone trying to solve puzzles – is helpful.

What have you learnt about brain activity? 

For 30 years I’ve been treating stroke patients and giving a clot remover or a thrombolytic and getting the blood flow back and seeing fantastic results. But it turns out that the brain activity during the ictus is critical. The brain in the morning, when engaged and active, is much easier to treat than the brain in the evening going into the night. Your brain being active is relatively quite protected. The blood vessels work better, the neurovascular unit is more active. It turns out that it’s a bit like Einstein and relativity; rather than space-time and gravity the brain-time continuum gets bent by metabolism depending on the hour of the day. The brain late into the evening and at night has a different brain time continuum curvature, with cells dying quickly, compared with a brain first thing in the morning.  We’re just beginning to explore what turns out to be a Circadian effect, related to the 24-hour cycle day-night, sleep-wake cycle. When you lose blood flow because the blood vessel is blocked by a clot causing a stroke, depending on when you pull the clot out, you get much better results. Chrono-therapy and Circadian hygiene are important, which makes evolutionary sense given the active brain is much better at protecting itself and it all comes back to physiology and self survival.

Is it possible to protect the brain?

It’s possible. Stopping the brain becoming too overloaded with glucose, stopping the hypoxic brain getting hot, especially if you have an infection causing fever or the environment is simply too hot. 3 to 6 to 9 hours after we had resuscitated the brain we can drop the temperature by as little as 1 to 2 degrees for 24 hours and prevent the injury that matures very slowly. Dropping temperature is a way of protecting the brain even after the insult. For 30 years I have been trying to find a way to get a drug, a small molecule to do what we achieve with low temperature or hypothermia.  To find such a small molecule that will actually result in the same protection and if we can do that in stroke, and if it works acutely in that car crash of a stroke, the question then will then be, could it be given very gently over years to prevent the insidious onset of dementia.

Just as we have pills to protect the heart and control blood pressure and cholesterol?

In cardiology we’ve learned to protect people prophylactically lowering the blood pressure, giving statins and giving aspirin to stop embolic events. Lowering the blood pressure is good for the brain too; it keeps the brain blood vessels –in the so-called neurovascular units – healthy. Interestingly, the statins, which stop you dying and having heart attacks don’t seem to stop you getting dementia. It has been a really big disappointment that in the heart protection studies we haven’t also seen concurrent brain protection.

Nevertheless, in your long career you have seen much progress? 

The only things we could do in acute neurology when I graduated, was to ventilate in polio or Guillain Barre Syndrome or by giving an iv shot of an anti-convulsant to stop an epileptic seizure. We simply had no treatments to prevent or  treat stroke. At the Montreal Neurological Institute built by Wilder Penfield, a brain surgeon, in the 1960s and 70s there was a house rule: No stroke patients! Because they had no treatment and they didn’t want the beds filled with untreatable stroke patients. 50 years on, stroke is the number one treatable disease in neurology, with extraordinary effectiveness. We have to triage, get the patients into stroke units early, diagnose them instantly, unblock the occluded vessel and get reperfusion with the blood flow carrying oxygen and glucose restored. We have made stroke very much like cardiology, and we now need to move on and take even more lessons from our cardiological colleagues  who are concentrating on heart failure so we are starting to learn how to work on brain failure, which results in dementia.

Alastairr Buchan, why do people say it will be very difficult to find a cure for Alzheimer’s or dementia? 

The problem is we don’t truly understand the actual cause of the disease. In stroke and in heart attack we know the cause: you have a blocked blood vessel, you lose oxygen, glucose and metabolism fails, and unless you unblock the vessel, the tissue will die because the cells need oxygen and glucose. In Alzheimer’s we simply don’t know what causes it so finding effective treatments is harder.

Isn’t it just normal to lose a bit of memory as we age? 

Like most things we’re all on a spectrum. Some people get to age 100 or even 105 with no cancer, no vascular disease, no dementia; and some people sadly get cancers in their 20s, 30s and 40s, and heart attacks, strokes and the onset of dementia in their 50s and 60s. We’ve learnt to stop people smoking. We’ve learnt to control blood pressure and cholesterol, and some of that is also helpful with stroke, but the evidence that it prevents dementia is still not completely clear. There are two types of dementia. One is so-called Alzheimer’s, where toxic proteins called Amyloid and Tau are deposited in the brain, and getting the amyloid out looks like it might be helpful but that’s the waste product result of the brain tissue being damaged, not necessarily the cause. So it may not prevent the disease, but it might help improve cognition. The second type is vascular dementia, which is like mini-strokes when the neurovascular units get blocked, and with the right treatments, so-called vasculoprotective that’s more likely to result in success.

What sort of treatments?

Hopefully relatively simple: controlling blood pressure, keeping the blood clean, keeping the cholesterol down, using anti-platelet agents to stop blockages, and possibly reducing the inflammation in the body as we get older by being healthy with diet and exercise. If there’s a reason for the inflammation, like arthritis for example, by controlling age related inflammation with anti-inflammatory drugs. Inflammation is something that creeps up on everybody, and controlling inflammation may buy more time and reduce the risk of ill-health, particularly as it affects the brain.

Don’t these issues arise simply because nowadays we are living to excessive old age?  

No, no, no. As recorded in the Bible, people lived to 100 or 110. Many people such as women that weren’t dying prematurely in childbirth or for all of us not dying from starvation, trauma, or infection during pandemics would live for a very long time. It is possible to live to 100 or 110 and still be perfectly healthy and perfectly intelligent. The risk as we get older is that inflammation will damage the vessels, will damage the brain, and this will lead to poor health. The only point in living, as you say “to excessive old age” is if you live healthy and fulfilled.

How should we regulate our sleep to keep healthy?

We need to sleep in such a way that our physiology is optimized, to go to bed at a regular time. We need to avoid eating late and having a big glucose surge just before we go to sleep. We should eat a bigger meal at lunchtime and perhaps be more careful with dinner. In Oxford, we provide all the staff and all of the Fellows with a very ample college lunch, that’s their main meal of the day. The windows at night probably need to be open to lower the ambient temperature by 1 or 2 degrees, and we need to keep the nights dark. Light is really toxic to the brain at night, and you do not want to be looking at a computer screen late at night.

People spend much of their lives in front of one screen or another. Is that bad for the brain?

I personally think the most protective thing to do is to be sufficiently disciplined to make the evening a very healthy evening and to maybe physically hand-write a diary or to read on paper with proper reading illumination but not excessive light. I worry that all of the information overload coming through the Internet on screens is possibly not allowing the brain to prepare for a proper Circadian rhythm. Screens and the interaction first thing in the morning is fine, but in the evening you need a period of transition.

Often when you start to fall asleep you think of something, then that something brings you to something else, and then you start worrying.

Yes. This is where circadian hygiene is important, how your day finishes. You have dinner, you have some time to listen to music, to relax, you maybe write a diary. You need to have that rhythmicity. If you suddenly late at night open a hostile email or a letter from a lawyer or perhaps look at your tax return this is not a good thing to do. You need to avoid stresses that are predictable. My parents like most people in Europe in the latter part of the 20^th century, if the phone went after 9pm, they simply didn’t answer.

Your parents were British, but weren’t you born in Germany?

Yes, my father was a doctor and my mother a teacher, and they grew up in North East England. After the war, because my father had to do national service he was sent during the “Aftermath” to be a doctor in the Royal Army Medical Corps of the British Army of the Rhine. So I was born in Rinteln, near Hanover in the then West Germany.

In your view has the NHS, the English public National Health Service, degenerated a lot?  

Yes. To my absolute sadness, while there are still truly excellent specialists, doctors and hospitals, especially the specialty hospitals, the NHS itself has ceased to be the all-encompassing  service that it was. As a result of the Lansley reform in 2011 the National Health Service has become the purchaser, National Health England, and it is not providing people the care they need for preventative disease and the best treatments for cancer, rheumatology, vascular disease, neurological disease – because the services and the district general and even the University teaching hospitals are all completely overloaded with providing social care for the elderly who are not being properly supported in the community. The whole point of providing medical and surgical care has been displaced by the fact that social care is using up all the resources of what was the National Health Service, to look after a community that’s no longer being looked after in the community by families or local councils. Andrew Dilnot, is absolutely right, successive governments have not dealt with this very pressing need and now the new Labour Government is suggesting another report, one that will not report till 2008-2029 i.e. the next election.

Recently there was Covid and there are threats of new pandemics. Are vaccines the saving grace for the NHS?

The bigger pandemic in my clinical lifetime was actually HIV. When I was a young doctor, we started to see cases with very strange infections in the brain, strange skin tumours. Patients, including people I knew, were getting ill in a way that we simply didn’t understand, and it was thought to be because they were gay and unsympathetic opinion suggested (like stroke) that it was an act of God, Gay-man’s syndrome. It took maybe two- three years to understand that this was a virus and this retro-virus, HIV was identified as the cause of what was then called AIDS. That has yet to lead to a really effective vaccine. It’s led to retroviral treatments, and people are now being kept alive and are healthy in much the same way that insulin stops people dying from diabetes, but there is no vaccine for HIV. My real worry with Covid was that when it broke-out we were all looking to see an influenza epidemic and it was a corona epidemic, one that was especially fatal for very elderly people. The governments got into a panic, and there’s going to be a very difficult analysis of what was really necessary, whether the lockdowns did more harm than good. What happened to the NHS is that it stopped its provision of care for heart attacks, for cancer, for all the diseases that needed to be taken care of, and after 2 or 3 years there’s now a tsunami of people with untreated disease that hadn’t been taken care of in the 2020 21 22 pandemic and the recovery from pandemic years.

Was Covid vaccination very effective?

The amazing success of discovering the virus and its molecular structure very quickly was phenomenal. Getting a vaccine developed, particularly with the novel mRNA vaccines, has been revolutionary because now the mRNA vaccines are very easy to dial up. In Covid the infection spread really very rapidly and the vaccines looked very good, but in fact an awful lot of people had already developed immunity by the time the vaccines came around. The vaccines did help prevent people getting really ill, but what they didn’t do, ever, was to stop people getting the disease. Unlike the vaccine that we still need for HIV, the Covid vaccines, while really important in reducing its severity, do not stop you getting the disease. Everybody who’s been vaccinated against Covid is still getting Covid. We haven’t figured out how to make true vaccines, as we did for polio and for smallpox, to actually stop the disease infecting people. That’s what a vaccine needs to do.

Academic Health Science Centres (AHSCs) are designated by NHS England and the National Institute for Health Research (NIHR) for demonstrating excellence in health research, health education and patient care.

When William Osler died in 1919, The Lancet medical journal described him as ‘the greatest personality in the medical world at this time’. More than any other single figure, William Osler defined the framework for medicine in the 20th century.

Alastair Buchan, is the medicine good at Oxford University where for ten years you were Dean of Medicine? 

I worked in Canada for 20 years, where the hospitals and the universities were very integrated as they are in Holland, in Germany, and at the big hospitals in the United States such as at Harvard, Johns Hopkins, Stanford the integration of the university and the hospital is absolutely tight. This is extremely important. The problem in the UK is the universities developed separately from the NHS district general hospitals. You go to university for medical school and they then partner with the local hospitals for clinical training, but the hospital runs the hospital and the university runs the university, and I think that Berlin Wall style administration is a disaster.

What were you running as the Dean of Medicine at Oxford University?

I was running the university’s Medical Science Division, and I tried very hard for ten years to integrate American or Canadian style/ Berlin style, so that for instance our University heads of Department of neurology, of surgery, of cancer, of pediatrics, was also the head of the practice at the hospital for surgery, medicine, pediatrics, obstetrics and gynecology. My model was to integrate the leadership of the department in the university so the department of the University and the department of the hospital was one and the same. The University of Oxford as a medical school, as a University, is as good as anywhere in the world, but the hospital is not operating at the same level. Medicine at Oxford in the university is exceptional, fantastic, and the hospital gets the benefit of the university, but it doesn’t let the university run the hospital and I think that is a pity. Importantly while there are some fantastic specialty services the overall provision of acute general care needs improvement to integrate general practice with hospital care.

Why did you create an Oxford University in Berlin? 

Because we felt that we were going to lose a lot with Brexit and gain nothing. In Oxford, 30 to 40% of the students were coming from Europe. You were more likely to get a first-class undergraduate degree in Oxford if you came from a German high school than if you came from Eton or Winchester or St Paul’s. These students were exceptional. We had maybe 30 to 40% of our academic researchers bringing what was European Research Council money to Oxford. They brought it, Oxford did not competitively win the European money. Oxford was very attractive to European scholars who got European research funding, which made them mobile, and they came to Oxford because it’s a great university, with excellent global networking and an exciting place to be. After Brexit they left, and Oxford all of a sudden risked becoming a university up the Thames Valley. But Oxford is a global university. It’s been a European university since it was founded 900 years ago, and when I went to the House of Commons as the representative for the university I got myself and probably the university into some difficulty when I went off script.

What happened?

They challenged me and said, why was Brexit not good for Oxford? We would be able to get the best students from all over the world and they would pay more. And I said, because we are a European university, and the truth of the matter is that the one thing you don’t do in a university is to put up a wall. Bologna, the first European University, was founded on the principle of national borders being open to scholars and students and ideas. The Bologna charter was about allowing students from all over Europe  come to Bologna. That charter embraced the revolutionary principle that scholars (and so ideas) should be free to pass without hindrance, they should not be oppressed by national borders this was important as it allowed the mobility of students, scholars ideas. Many of the students and scholars originally in Oxford at the foundation came from Europe. Oxford, I said to the House of Commons, is a bit like a Premier Football team it is a Manchester United  problem we are completely integrated with Europe. The money, the players come from all over the world, and we play or in our case collaborate, with integrated research networks that stretch all over the world. Brexit defied the Bologna Charter. It is a disaster. And there was a big row.

What was the result?

They said, no, no, by walling Oxford off, it would become much better for people in the UK. So the only way I could protect Oxford was to open a European entity, and we created Oxford in Berlin. I went to the mayor and the universities in Berlin and we established an open laboratory and office space in the Museum for Nature, and we funded it, and we had an open access so people could come, be there and collaborate. We had workshops, seminars, student mobility, and partnered with not just the Charité – where I worked in Berlin – but with Humboldt University, with the Free University, and with the Technical University, which formed the Berlin University Alliance in 2019.

This is the exact reverse of what happened in the 1930s?

Yes, and I created the model. The paradox to me was that in the 1930s scholars came from Berlin to Oxford to Cambridge, some stayed but many were on their way to North America, to Harvard, to Princeton to California.  Post Brexit we had the ability to create an open border, a channel between Oxford and Berlin.  When I talked to the French government and to the Federal Government, Angela Merkel’s German government, they said, no, you’re in England, the UK is in the middle of Brexit, and you must talk to Brussels. But if we took it down a level to the Länder, to the Governing Mayor of Berlin, at the time Michael Mueller we were welcomed with open arms. As a result of Oxford’s Berlin architype, Cambridge partnered with Munich’s LMU, Birmingham partnered with Frankfurt, Kings with Dresden and Imperial with the Technical University in Munich.

How many students do you have between Oxford and Berlin?

In three years we had over a thousand people working between Oxford and Berlin, people going backwards and forwards across the Brexit wall, and we had funding for workshops. We then got research grant seed funding and I had hoped that we would develop a virtual college. The mayor of Berlin persuaded the Prussian Cultural Heritage Foundation to make Glienicke Palace available, so we might use it as a conference centre. I had managed to get 20 senior academics, funded as Fellows, and each Fellow might have 5-10 students and then a virtual college shared between Oxford and Berlin could be envisaged, where we might have12-20 Oxford Fellows, partnering with 12-20 Berlin Fellows, and together we would share 100 to 200 students and the virtual college would be a modern university – one without restrictions from national borders. Critically, what we learned from Covid is that we can work virtually on the Internet, with Zoom and with Teams, and we can teach, research, collaborate, investigate, and write papers, virtually. And that’s all new. The future of universities is that they will be integrated transnationally in a way that we’ve never thought of before.

At the end of the day, what makes the best doctor?

The great Canadian physician Sir William Osler, long dead, used to say, it is not the patient that has a disease, it, is the disease that has a patient. It’s really important that you become very knowledgeable about what the disease is doing to the individual, the person. You can’t do that through data or with computerized images. The best doctors are the are those very connected on a human level to the patient, the person who is suffering a disease. The best surgeons are the surgeons that are very selective and don’t operate because they have the confidence, when it is right to say you don’t need surgery. The best oncologists are the oncologists who are very well informed but will say, no, you don’t need that, you don’t need that chemotherapy, that radiotherapy, and they are guided by objective evidence and the individual’s response to treatment. Often the best doctors are the ones that provide or obtain secondary consultation and may agree that you don’t need the treatment that’s perhaps being pushed by people who’ve got perhaps a motive or are running a service to provide that treatment. It is through rose-coloured spectacles but the best doctor is the family doctor the one that looks after you and your family for the whole of their career.

Today, people have no time to get ill, and when they do nobody takes the time to go to a sanatorium to convalesce? 

Yes, but this is wrong. Just on a personal level, my wife had orthopedic surgery in August, and they tried to send her home the very same day. While we kept her in the hospital for 2 or 3 days for all kinds of practical reasons, there was no planned hospital stay to ensure recovery, no physiotherapy, no occupational therapy or rehabilitation. A colleague had the same surgery in Switzerland, was in the acute hospital two weeks, had intensive physiotherapy and occupational therapy, was then sent for a month to a rehabilitation facility and at the end of six weeks was back on their feet. We have lost that ability because of the reduction of beds.

But this is because that way of treating costs too much money.

I don’t know if I agree with that. Where I work in Berlin the Charité has exactly the same budget as the Oxford University hospitals in Oxford even though the Charité has three times the number of beds. Their length of stay is three times our length of stay. They provide the same amount of care much more gently with much better discharges home than the hospital in Oxford where people go home the same day. We’re in too much of a hurry in Oxford to get people out (because we have way too few beds), and the reason we’re doing that is because the hospitals are looking after all those patients who are in the wrong place at the wrong time, i.e. they should be in social care. Technically you’re right, it is increasingly expensive, but it’s increasingly effective. The stroke treatment that I’m talking about maybe costs £20 to £30,000, which is expensive, but if each patient we treat is cured and goes home the savings are massive. The truth is that the cost of a stroke that you don’t treat is more than £100,000, while the cost of treatment and if you get better it is £30,000. You only need to treat one person badly compared to three that you treat well. So this is a false economy.

The problem comes of course because medicine is effective and therefore people end up not dying, and so then you have the cost of people ageing more slowly.

One of my big upsets about Covid was, of course, it was very cost effective for governments because very elderly people were dying. The problem in the UK now is because the wait lists are long and because the NHS access is poor, more and more people are paying for private care because they need it, and that undermines the state’s provision of care and more and more of my colleagues, more and more of the students and resident doctors that we train, are reverting to providing private care.

They don’t want to go into the NHS?

Correct. And in 1948 when my father was a medical student, this switch to providing care to all, free at the point of delivery, absolutely transformed people’s expectation of medical care. They were providing care for people with infection, with heart attacks, in child birth, with those needing acute abdominal surgery who had before the NHS been unable to access care. Gradually, the NHS has been providing more and more social care, and it’s been diluted from its primary purpose. The new Labour government has somehow got to get the National Health Service providing health care, and not social care.

Are you optimistic?

No. I wish. I really wish I was.  At interview, at the end I like to ask the candidate what are their three wishes. So if, in turn I was granted three wishes going forward; I would put the Universities in charge of health care as in Europe and North America, for the UK I would reverse Brexit and see us back in Europe, and if I could, I would help discover a true neuroprotection, one discovered from Stroke research, that would prevent dementia.

Alastair Buchan, thank you very much indeed.

All images courtesy of Alastair Buchan.

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