What will a cure for Parkinson’s look like?

I’ve had a bit of time to think about this. I was diagnosed with Parkinson’s, the young onset variety, in late 2006. So I’m well into my 15th year of cogitation on the matter. And if you count my research career beforehand, messing about with dopamine in the basal ganglia, you can probably add another 23 years to that. Not full-time you understand. Nobody can think about any issue with that intensity. But always simmering away somewhere at the back of the stove. Of course, having the condition myself focuses the mind wonderfully. What was previously simmering, comes to the boil quickly. There is nothing like the symptoms of Parkinson’s to help drive a sense of urgency into one’s own personal agenda even if not to the same degree to a wider caucus. An academic interest in the subject – and I hope my scientific and clinical colleagues will forgive me – doesn’t quite generate the same sense of urgency. I know – I’ve been there.

Over those 37 years, I’ve listened to, interviewed, challenged, agreed and disagreed with some of the finest thinkers on the subject. And a few klutzes as well, obviously. Useful tip: if you are speaking to people with Parkinson’s about Parkinson’s you will always be asked for your thoughts on a cure. Better have your answers ready. People with Parkinson’s expect clear thinking.

I would like to be able to say that I will present you here with clear thinking. That would probably be disingenuous or at the very least overambitious. Greater minds than I have pondered this without reaching any persuasive conclusion.

It is important above all to not allow one’s thinking to be clouded by emotion. We all want a cure. Yes we do so let’s quickly brush aside any conspiracy theory nonsense about the pharmaceutical industry’s preference for long-term treatments rather than quickfire cures. Obviously pharma is not innately philanthropic but that does not render it complicit in some global conspiracy. Let’s put that aside immediately. If you are unable to do so, well I suggest you go back to playing with those unicorns.

From day one post diagnosis, the clock is running and each day, week, month and year we register some further erosion of our abilities. Each day puts distance between our old pre-diagnosis selves and our current manifestation. By the same token each day brings that dark dot on the horizon a little bit closer, makes the heart beat a little bit quicker and renders our perceived need for a cure that tiny bit more pressing.

You might think that would drive the research programme with more force and energy. Show the scientists our raw selves and perhaps they might themselves be imbued with our urgency? You might think. Many of the best scientists do cultivate relationships with patients explicitly to understand the driving forces for people with Parkinson’s. In many respects they gain hugely from those patients in the same way that the patients feel empowered. But don’t expect the scientists to walk in the patients’ shoes. And nor should they.

The best scientists will have a deeper awareness, a more visceral grasp of the condition but always ultimately be one step removed from the full Parkinson’s experience (unless of course they contract Parkinson’s themselves – oops). We, as patients, can take them just so far along the road but no further.

And that’s the way it should be in my view. Scientists do not, in the final analysis, share our gnawing fears. And nor should they. They make decisions and interpretations in the light of cold hard numbers and statistics. Their decisions are certainly informed by their contact with patients but remain or should remain emotionally neutral. The best science is not driven by panic.

That’s a long way of saying that patient input is vital but should not cloud scientific judgement. No amount of desperation changes hard facts.

I wonder how many of us were told on diagnosis that old favourite “there will be a cure in 10 years”. The kind of glib blanket reassurance that so discredits the medical profession. The substitution of measured reason by tired platitude. Ultimately this does little but breed resentment as the 10 year mark approaches, placing a further barrier between patient and physician. To raise false hopes is every bit as damaging as crushing overoptimistic expectations. Neither help.

So what is the path to a cure? Is there one? Are we still fumbling our way through the undergrowth hoping to pick up the path? These things typically only become apparent with hindsight. We only understand the link or otherwise in 20:20 hindsight. Decisions and choices which at the time seemed capricious are rationalised as logical steps along that particular path. What was a wild stab in the dark is reconceptualised as the product of linear thought.

On the whole, science isn’t like that. But it’s difficult to budget for serendipity. Science is always willing prey to serendipity. As it should be.

What patients want to hear of course is that there is, in the pipeline, some drug or treatment that will permanently remove their symptoms. A simple definition of cure. Do I believe in such a simple definition? No, I don’t think I do. If we regard three steps as being the sequence of events towards a cure – slow, stop and reverse the pathology – we currently stand at the “slow” stage. There are reasonably plentiful indications that we can make a difference at this stage. Stopping the progression of Parkinson’s is an amplification of that. Reversal however involves a whole different sway of biochemical processes. It is not simply a reversal of neurodegeneration. It will require rebuilding the neuronal architecture as much as patching up faulty biochemistry. The paths of degeneration and regeneration are not mirror images. Regeneration will be a much tougher nut to crack.

The overwhelming problem with Parkinson’s, and a thorn in the side of every research endeavour, is the extent to which the pathology has progressed before it translates into symptomatology. We lose more than 80% of our dopaminergic neurones before we even show the slightest finger tremble. By any reckoning this is stacking the odds against us. If neurodegeneration is holding all the aces, how can we intervene and successfully expect to be able to reverse that damage?

The answer lies in biomarkers in general and early presymptomatic markers of Parkinson’s in particular. We need to know who is going to develop Parkinson’s before they do so. This is the incentive to develop drugs that will slow progress or even stop it. Let’s focus our efforts on finding those predictive markers and mass screening. I think there is every reason to hope that we can, if we catch it early enough, prevent it developing into full-blown Parkinson’s.

In other words, I think the elimination of Parkinson’s is going to come less from treatment of those already afflicted than the prevention of its occurrence. In the same way that we have eliminated conditions like smallpox not by the development of novel therapeutics but by its prevention. We will beat Parkinson’s by its prevention. Screening with reliable biomarkers, alongside the development of drugs to slow or stop progression will, over the course of a generation, eliminate Parkinson’s.

So where does this leave those already afflicted? Well certainly it’s not the solution that might be wanted but it’s fair to say that development of neuroprotective agents will benefit those already diagnosed as well as those who will be. We know so much more now about the pathway to neurodegeneration that “slow” and “stop” are parts of the usable vocabulary of Parkinson’s, not science fiction. Much has been spoken of the so-called oncoming Parkinson’s pandemic. Indubitably that will provide an impetus for research into prevention.

What of my own Parkinson’s? After all I’ve had its more than 10 years. Do I expect a cure? Truthfully, I do not expect to see a cure for myself in the course of my lifetime. Does that make me downhearted or resigned? No, it doesn’t. Because I know that the same impetus to develop neuroprotective agents in combination with a greater understanding of the presymptomatic biomarkers will benefit my generation as well. I may not live to see a cure but I will live to see benefit (touch wood). And I will know that, in whatever tiny little way, I played my part. That keeps me going.

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Doctor doctor

What’s in a title?

For many years I had an unresolved discussion with my father as to the validity of the term “Doctor” as a form of address to academics, medics and otherwise. My father, a physician (MD), held that the term Dr was reserved strictly for the medical profession and that the only way to earn the title correctly was through several gruelling years of medical school. I the other hand, being a doctor of philosophy (PhD), argued that historically the term was applied to academics and philosophers and only used as an honorary term with the medical profession, in deference to their long period of training. Needless to say the matter went unresolved and we shall doubtless take it up again when we meet next.

I earned the title through several years of tough research, a doctoral thesis of 75,000 words and a highly challenging  viva voce examination by two notable academics (who I shall not name except by their initials GC and DS). It was cut and thrust for 2 ½ hours. This was in the mid-80s when oral exams rarely lasted more than an hour. The discussion was friendly and engaging but also challenging and at times teetering on confrontational. At the end of the examination they asked me to leave the room while they reflected on their opinions. I remember at the time thinking that was a bad omen but it turned out to be nothing of the sort. After 10 minutes or so of hushed chatter – I tried to eavesdrop unsuccessfully – I was called back into the room. The examiners asked me to sit down again which automatically raised my stress level a notch or two. Then GC told me that it was a very good thesis and an excellent defence, words which stick with me even to this day. I remember asking them why, if they felt it was such a good thesis, had they given me such a grilling in the examination. DS replied “if we had not done so, you would have had less respect for the degree”. He was right, I felt I’d earned it.

It was the convention in those days for the examiners to make their recommendations to Senate who would then in turn and in the fullness of time notify the candidate of their decision. University administrative machinery was painfully slow in those pre-fax, pre-email days. There were various codicils and caveats in the legislation which allowed Senate, theoretically at least, to overturn or modify an examiner’s opinion. In practice none of these applied. Unless there had been malpractice, the examiners opinion was taken as read. However because of this ratification by Senate, examiners were specifically asked not to pass on their opinion to the candidate in case Senate chose to reassess the matter. In theory, the examiners were not allowed to tell the candidates of their opinion. Needless to say nobody took a blind bit of notice. Examiners routinely told the candidates on the spot. I remember the wording DS used to tell me. “We are not allowed to tell you the result of your examination, Dr Stamford…” GC chipped in “…but if we were, we would tell you that you have passed”. I have been at pains over the years to repeat the very same words to candidates I have had the pleasure of examining.  

So I know what it takes to get a PhD. And in my opinion, that makes me every bit as worthy to be called Dr as any stethoscope wielding white coat!

In my case the situation is slightly more complicated. Not only do I have a PhD but I also have a DSc. This probably takes a bit of explaining. The DSc is both an honorary and earned degree. It is commonplace for universities to award a DSc as an honorary title to a senior academic or to someone who has made a significant contribution to an academic discipline whether through the University system or outside. The other category of DSc is earned and on the basis of a large body of published research in a given field along with submission of a substantial thesis. I was awarded mine in 2000 on the basis of 75 published papers on the dynamics of neurotransmission and a thesis (of my published work with introduction and discussion) of around 700,000 words. A doctorate is considered to be a higher degree. In the same way, a DSc is considered a higher doctorate. Relatively few people with a degree go on to do a PhD. A tiny fraction of PhD holders go on to do a DSc. It carries no value in terms of promotion or of career prospects. It is merely an acknowledgement by the very best of your peers of your standing within the academic community. A vanity in many ways.

A DSc is also a degree largely unknown outside the UK and the UK influenced academic communities worldwide. Very occasionally I meet people who recognise the significance of a DSc but, for the most part, people assume it to be a typo.

Not so in Germany. Germans are sticklers for detail and for achievement and will always err on the safe side. Whereas the French will always refer to even a head waiter as boy (garcon), Germans will elevate even the lowest food server to head waiter (Herr Ober…). In academia, and for absolute certainty, they will throw in Professor for good measure. I have more than once been addressed at conferences in Germany as Herr Professor Doktor Doktor Stamford.

Within medicine, the terms doctor and mister are further confused. Whereas in the outside world doctor is considered the higher term of respect, not so in medicine. Surgeons are referred to as mister or, in the case of female surgeons, Miss. This is of historic origin. Back in the 18th century or so doctors still had to undergo extensive training before they were allowed to minister to the sick. Surgeons on the other hand were largely unrelated to medicine and could practice without the need of medical training.

All you needed was adequate premises and the ability to amputate a limb as swiftly as possible. There were no anaesthetics before 1840. Speed was of the essence – the record for the fastest amputation of a leg was by Joseph Liston who performed the task in 28 seconds. Liston also held the dubious honour of being the only surgeon to have a 300% mortality from one operation. So swift was he on that occasion that not only did he remove the patient’s leg but also three fingers of an assistant and a member of the assembled crowd (operations were public events – why do you think they are called operating theatres) who had a heart attack. The patient and assistant died of subsequent infections.

This was not the only time when Liston’s penchant for speed came at a price. On another occasion whilst taking up a patient’s leg, he also removed his testicles. For these reasons surgery was felt to be not the specialisation of a highly qualified physician but as a career path entirely unrelated. Surgeons were often barber surgeons. The mind boggles. But it accounts for why, to this day, surgeons are referred to by their peers as Mr. I think I’ll stick with the German version. Just call me Prof Dr Dr Jon. I thank you.

V Day

It’s barely 6 am and I’m wide awake.  It feels like Christmas. I am jittery. I can’t sleep properly because today is the day I am to be vaccinated. Well the first jab at least. I’m that excited. My appointment is at 9:05 and I am sufficiently fearful of oversleeping that I have set no fewer than three alarm clocks to ring at staggered intervals and at different distances from the bed to ensure  that I am not only awake but out of bed. This cunning plan works well. Too well perhaps as one of the alarms is still ringing intermittently four hours later when I return to the house. In my haste I have pressed ‘snooze’ rather than ‘cancel’. Still it has served its purpose. I am out of bed albeit without the slightest idea of where I am. Or who I am for that matter. But the clocks have fulfilled their part of the bargain. I am up at 5:58, standing bewildered on the landing and wondering where the the last alarm clock although it’s surely loud enough to wake the neighbours. They don’t call them thunder clocks for nothing.  I briefly entertain the notion of going back to bed for an extra few winks but fortunately am sufficiently compos mentis to acknowledge the folly of such action.

For a minute or two I stare blankly into my wardrobe in search of inspiration. What is the etiquette for a mass vaccination? It’s not exactly black tie. A bit like going to work then – commuter train chic? Perhaps more casual? Or should one try to scale sartorial pinnacles? I plump for a pair of forest green cords, my t-shirt with the joke about the 2010 Icelandic volcano and a Fair Isle jumper. A quick glance outside and the sight of my crisply frosted car adds my father’s Crombie and a dark blue trilby/fedora to complete the ensemble. Throw in my brown suede Chelsea boots and I am good to go. I blow my reflection a kiss, instantly embarrassing myself. 

Out of the front door and into the car. Then out of the car and back into the house when I realise it is still only 6:30 and my appointment, only some 5 miles away, is not until 9:05. Even allowing for the most event-ridden journey – avalanche in Sevenoaks, escaped panther at Capel, plague of frogs in Southborough – this is still not going to take me over 2 ½ hours.

Cornflakes and coffee I decide.

It’s still only 7 am even after a couple of weapons-grade espressos.

I turn on the wireless to catch the news and just as quickly switch it off – more Royal family shenanigans. I have a limited interest in such nonsense at the best of times. Royal intrigues simply do not hold my attention. More than I can handle at this hour. Whatever happened to the shipping forecast? 

I find myself pacing the living room. Until I remember that these are the boots I was wearing the previous week when I trod in some undisclosed cat poo in the garden. Probably not my best thinking to pace the living room. I hastily check the living room carpet. Fortunately all is well  with the rug and the shoes pass a brief olfactory inspection.

7:30 a.m. It suddenly dawns on me that the schools are back today and therefore the roads will potentially be choc-a-bloc with school buses, cyclists who haven’t cycled in months and schoolchildren with the road sense of hedgehogs. Plus the usual monday morning mayhem. Better get on the road I decide.

Ten minutes later I am in Tonbridge, parked at the vaccination centre and wondering how I’m going to kill 90 minutes or so in the Sports Centre car park. The cafe is closed –   obviously – and it has never dawned on me to take a thermos or a book. Not that it would have done anyway. My bladder is on a hair trigger these days. Challenging it with a flask of coffee would be supremely ill judged. 

The only reading matter to hand is the car handbook. It turns out to be one of the least compelling reads ever. Not exactly a page turner. On the other hand it fills the time until the vaccination centre opens. And I now know how to do a full annual service, refill the aircon and change all the bulb units. Still a little bit shaky on the electrics.

Still half an hour before my my allotted time slot. I overhear one elderly gentleman saying that there is no strict regulation of appointment times. Sheepishly, I join the queue hoping nobody will notice my early arrival. It turns out they notice but evidently do not care. As long as the system has you detected, directed, consented and punctured, all is well.

Ralph and his iPad identifies me, logs me into the system and then passes me over to Celine whose role is to point left or right depending on which is the shorter of the two queues. I turn out to be a Lefty and am greeted by Jean whose job it is to consent me and satisfy herself that I really want the vaccine. She starts by asking me if I know why I’m here. “Is this not beginners yoga?” I ask. Eventually she is satisfied that am a safe bet on anaphylaxis and passes me on to another pointing person. “Cubicle number 8” she announces in a tone that fleetingly reminds me of Argos. I’m greeted by Janine, the nurse, in a manner that is disproportionately enthusiastic for such an early hour of the day. “Which arm?” she asks “We need to leave you with one good arm”. I quickly check that we are talking about vaccination and not amputation. My meds have not really kicked in this morning and I am slow in baring my arm. Janine wrestles me out of my coat with the kind of fevered urgency of newlyweds. I toy with the idea of mentioning this to her but fortunately think better of it. She is after all holding a syringe. “A little scratch” she says and it’s all done. Nurses no longer say “a little prick”. Apparently some patients take it personally.

Janine’s assistant passes me a card with my next appointment and a sticker saying “I’ve been brave”. OK I made the last bit up. A quick thankyou and I am I shown out via the tradesman’s entrance so to speak, past huge skips of rodent-riddled rubbish with the instruction not to drive for 15 minutes ringing in my ears. Fair enough – I can brush up on the car’s electrics.

Home 10 am. Job done.

2020 – return to sender.

I don’t think I’m alone in saying that I will be glad to see the back of 2020. Normally when it reaches the end of the year I find myself in reflective post-Christmas bonhomie, buoyed by the occasional glass of sherry and mince pie. Through the rose tinted optics of hindsight I find myself mulling over the year and its many joys. A warm fire, a Val Doonican jumper and grandad slippers and the illusion is complete. Gosh, is that snow outside?

Not this year. Not in 2020.

If ever there was a year to see the back of, this is it. Australian bushfires to start with. Huge news story in any other year but this. Climate change as a global emergency. Wasn’t that enough to be going on with? We are in a full tilt race to save the planet. A full-time job in its own you might think. But no, the media circus moves on. And what happened to little Greta? Nowhere to be seen. Or, more accurately I think, avoided by the press who have other fish to fry. Never mind the planet frying. As far as I’m concerned that’s high enough on the apocalypse-o-meter

But apparently not.

You can be forgiven for missing it but there it was, some tiny little news item, buried in between the Wichita under 30s Bake off challenge and the list of unpaid parking tickets. Something about a virus crossing over from wild animals to man. Hardly a news item really. Within a month there was cause for concern in China. Another month and the rest of the world was beginning to wake up to the defining news story of the year. Suddenly attention was focused on China and its food markets. And before you know it, it is ‘traced’ to bats. Specifically people eating bats. I ask you.

For goodness sake what kind of a person eats bats? There are no bat recipes, no bat cookbooks and not a single Internet bat bistro devoted to the bat gourmet.

Perhaps I’m mistaken. Perhaps, in the Far East, the Burger King Bat Super Whopper is competing for the stomachs and minds of the Chinese with the McDonald’s Big Bat combo platter?

And to follow? The bat pavlova, bat cobbler, sorbet de bat? And then there are the canapés – bat goujons, pate de bat, bat fricassee, bats on horseback? No, the reason there are no bat recipes is because we are not meant to eat them. It’s not discrimination. It’s not being Battist. It’s just common sense. Besides, they’re very crunchy.

Back in China, some clown ignores common sense and tucks into the bat sushi platter. All well and good (even if rather disgusting). Unfortunately his particular selection of choice bat cuts contains a previously unknown respiratory virus.

Viruses don’t normally cross species barriers. They snuggle up to the same species. But when they do cross species, they do so with a vengeance. Before you know it, we have an epidemic in China. It turns out to be such a hit that other adjacent countries take it as well. Another couple of weeks and it’s a pandemic. Short for panic epidemic. (No it isn’t but it sounds good). People start filling hospital beds. Then they start dying. Some wear face masks, some don’t. Panic breeds more panic. World leaders, used to fluffing news about a new national traffic management scheme, or a regional document archive plough their collective ostrich heads into the sand. Then there is a vaccine. Then there are two. Then more. Then the virus hits the gas pedal, reluctant to be outdone by mere humans. A feeling of déjà vu? Wait till the third wave.

And to think that we were concerned about forest fires in January. At the end of December, we are virtually praying for forest fires – to kill the virus or kill the news stories.

Dear Sir, my year 2020 is faulty. Can I have my money back please.