As I write this I am on the way back from an ‘atypical’ summer holiday with my family. We spent a week in the ‘Oude Land’, South Africa, celebrating my mother in law’s 80th Birthday and then a week in the subtropics for some warm sunshine. The internet access was dismal, which was a good thing that allowed me to switch-off, sleep, eat, exercise, think, relax and recharge my batteries.
The insights learned, or relearned, is that my family are my priority and for quality reading and thinking time you need to take yourself offline for long as possible. One consequence of the latter is that I now have two inboxes with over 3,000 unread emails (panic).
As I lay next to the pool I had ample time to contemplate life, the universe and all things MS. I came to the conclusion that the biggest threat to our field, at least in the short term, is dogma and groupthink. We are so entrenched in the MS autoimmune hypothesis that it is becoming increasingly difficult to see the light, and blue sky, because of the sheer depth of the autoimmune trench we have dug ourselves into.
In ‘Range: How Generalists Triumph in a Specialized World’, by David Epstein, one of my holiday reads, I learnt that Arturo Casadevall believes that specialisation has created a ‘system of parallel trenches‘; everyone is digging deeper into their own trench and rarely standing up to look in the next trench over, even if the solution to their problem happens to reside therein.
Using the trench analogy we are going to have to build a human scaffold several generations deep to get out of the trench the MS community has dug, or we could build a rocket. I can’t resist the rocket analogy. Whilst away I also read ‘Loonshots: How to Nurture the Crazy Ideas That Win Wars, Cure Diseases, and Transform Industries’ by Safi Bahcall, which describes how out-of-the-box thinking has the ability to transform a field.
It is clear that the autoimmunity model has many flaws or as Safi Bahcall would say warts. As a result, it is becoming increasingly difficult to support the autoimmune hypothesis intellectually. Some of the holes in the autoimmune hypothesis have been rehearsed many times before on this blog.
- Dear MSologist, why am I progressing despite being NEDA?
- What is causing my accelerated brain volume loss when my disease is in remission?
- You say I am in long term remission, and possibly cured, from MS, but my last CSF analysis shows that I am still oligoclonal band positive? Why?
- My head is full of slowly expanding blackholes. Can you please stop them expanding?
- There is an epidemic (increasing incidence) of MS in Scotland and almost every geographical area studied. Why? Is the increasing incidence explicable by the autoimmune hypothesis?
- If MS is an autoimmune disease please tell me why your immunotherapies are only partially effective at preventing disease activity and worsening disability?
- How do you explain the early Prineas MS lesion; massive oligodendrocyte apoptosis without T- and B-cell infiltration?
- Why does rebound happen post natalizumab and fingolimod? And why are anti-CD20 therapies so effective in preventing rebound? How do these observations fit into the autoimmune hypothesis?
- What about the evidence that EBV plays such a pivotal role in MS? How does this fit in with MS being an autoimmune disease?
- Is the human endogenous retroviral or HERV activation within the peripheral and CNS compartments of MSers simply a bystander phenomenon or part of the disease? Are HERVs a non-specific trigger of autoimmune disease?
- Does the memory B-cell data and hypothesis sit comfortably with MS being an autoimmune disease? Could this be explained by EBV alone?
- Does the strong MHC association with MS have to be due to autoimmunity? Could the MHC link be explained by an infection or dual-infection hypothesis?
- How does the epidemiological data on vitamin D, childhood/adolescent obesity, smoking, solvent exposure, HIV and MS, explain autoimmunity?
It seems to me that most people in the field of MS are content with fitting a square peg into a round hole. I am not. So what am I going to do about all my angst and increasing doubts? We have been trying to do something about it with our Charcot Project and our Preventive Neurology Unit, but things are happening too slowly. What we need is a turbocharge – a rocket – to accelerate our programme of work. In short, we need people, resources and money. Therefore, the 2019/2020 academic year will be a year of grant writing focusing on MS prevention and loonshots.
Brilliant deep thoughts .
Nothing new, just a sense of urgency.
“The insights learned, or relearned, is that my family are my priority”. I doubt whether anyone with a family would dispute this as their key priority. Unfortunately MS affects most aspects of life (work, finances, relationships…) so doing the best for your family is so much more challenging.
MS is all about luck / bad luck. The bad luck is getting the disease and the disease falling to a specialism that is still in the dark age in respect of the diseases covered (your questions show this).
I am glad you have had the opportunity to recharge your batteries relax by the pool. For many people with MS these luxuries are distant memories and the future looks pretty grim (slowly expanding lesions….). I came across this story recently about a 46 year old woman with MS stuck in an elderly care home –
https://www.dailymail.co.uk/health/article-7317591/Why-multiple-sclerosis-sufferer-Nina-left-rot-old-peoples-home-just-46.html
I imagine the Barts MS mob will point to the age of austerity and the need for residential care for younger people with MS / other disabling diseases. I would take this from a different angle and ask why MS research has failed a patient like this (and many others). Your list of questions is a sad indictment of where we are with understanding the disease. Coming up with questions is easy, answering them seems to be near impossible for those who work in MS research.
So I don’t want to put a damper on your new enthusiasm, but I have seen this before over the last ten years since I’ve been following this blog. I would suggest that you / your research colleagues spend a day visiting a few care homes where young people with MS reside. Ask yourself would I want my partner, son, daughter.. to be in this position? Then find a quick solution without the usual excuse of science takes time. It’s been 150 years+ since Charcot and I’m not sure we’ve come that far (evidenced by the woman in the elderly care home).
The question to answer is finding a safe / effective drug to stop progression / cell death.
PS please don’t use the term turbocharge again. This seems to be doing the rounds after Boris Johnson used it.
For the record – you’re a nice guy and caring doctor, but being nice / caring isn’t finding a solution to this disabling / cruel disease.
While a keen reader of this blog I have to agree with Bridget’s comments
Me too.
Bridget,
Thanks for putting an alternative view across. Many posters will praise Prof G for his creative thinking / brilliant mind, but the lady in the story shows the terrible impact MS can have on young lives. I’ve had MS for c.20 years and have lost track of the various drives / fundraising/ programmes to end MS / cure MS / remyelinate exposed axons… in my modest view, the researchers went for the low hanging fruit = relapses / focal inflammation. The work showed benefits, but did not address the real disease = virus / slow burn inflammation / neuro-degeneration. A poster some time ago called MS ‘MND light’. The final destination is the same, but MS is generally a slower journey. Too many questions remain unanswered for us to be patting the MS researchers on the back. I’m guessing I’ve got c.20 years left in this world. Prof G’s questions will take that long to get an answer (given grant applications, trials, licensing…). I not expecting the results of this work to benefit me. At least it keeps the researchers in full time employment and the MS conferences chugging along.
I recommend not listening to Boris. He’s full of sh*t.
Focusing on MSers with the established disease and its consequences is not what I am referring to, but the next generation of MSers who don’t need to develop MS. I am faced with young people with MS in wheelchairs week after week, which is part of the motivation to prevent MS.
Looks like the game is up once you have the disease ie the disease will just run its course regardless of what treatment you have. I appreciate your honesty that the focus is on those yet to develop the disease and to prevent them from developing it. Good luck.
Hang on, I thought many of your points in your post also refer to people with established disease? As a slow/standstill PwPPMS, I was heartened to read them!
Yes, they do but they challenge the autoimmune dogma. They all need to be addressed but prevention is for those who are at risk.
Best response I have ever read Bridget!
I don’t think the Barts team need any more convincing about the effects os MS on young people. And my impression is that they are working very hard to make meaningful progress in their research. I too am impacted by my ability to do things by my PPMS, but I don’t therefore start to resent other people for not having my disability.
Anon,
I think it is important to challenge the status quo. Every year there is a new impetus, renewed focus….. yet the questions being posed in Prof G’s piece are so fundamental that you have to wonder what progress has been made. My aunt died of MS at 52 in the mid 1990s. I got MS and went for a highly effective treatment- the treatment came with big risks but the possibility of long term remission / stability. Now I get the impression that MS will still progress despite me being NEDA. I fully acknowledge that I am bitter. I had one life, saw my aunt be destroyed by this disease and now face an uncertain future. The story of the woman in the care home was heartbreaking. I read this blog to keep updated on breakthroughs. But I’m not here to stay silent and praise the researchers when I can see that as we approach 2020 young people’s lives are being destroyed by this disease. The dogma and intransigence of some key members of the MS research world has stifled innovation and real progress in beating this disease. The major conferences are still mostly run by grey haired white men in their 60s. Look at the technology sector and it is people under 35 who drive the innovation. Things need to change. The pace of research is way too slow. The sector could learn much from the way AIDS was tackled (and it’snot just money).
I believe Prof G is challenging the status quo with this very post.
With time we will have more and more people turning from rrms to spms Despite all the medication , because to be honest I don’t think there is a drug that is gonna stop ms. Then the numbers “ hopefully “ will be big enough to make a high impact in trying to find a cure . I believe people with SPMS have just given up and no one can hear them .
Sleep, Resting, Sunshine on your mind is So Therapeutic,
Even for Rocket Scientists.
If anyone can get us out of our Trenches,
You can,
Dr. G.
Thanks; all hands onboard is our battle cry.
Great Article Prof G. There’s plot in new scifi series called Another life. Where the cast start experiencing never damage, resulting in blindness, muscle zpasns, dementia, etc. They try to fgute out what’s causing the damage. I thought to myself that’s ms. No it’s alien virus attacking the cns. Instead of taking anti inflammatkdies. They fly to nearest star to sterilise the ship with gamma rays which kills the alien virus. Coincidently the show stars selma Blair. Point is the damage being done by external entity. Immune is trying to target the virus and in doing so is blanket bombing the infected Area? Hence smouldering. Brain.
I have many daydreams along these lines, but that is not the solution. Hard work, slog and more slog are what is needed.
Building a rocket: a huge database with MS patients.
Can’t we start on-line research. People with MS could register for a topic for instance fasting or a diet and compare the outcome after 3, 6, 9, 12 months or longer.
Yesterday Science Daily published the results of a diet for MS, it took them 10 years… , that is simply too long.
Citizen science, could there be a way of doing citizen science on the subject of MS?
Citizen science has been used for public health.
I agree 10 years is too long. The problem is controlling for biases with online observational studies. There may be ways of doing randomised studies this way, but again it will need some thought.
Pleased you’ve had reconnecting time with your family as part of a well deserved holiday to SA.
The MS community needs the likes of you to recharge and feel reenergised to return to the never-ending fray of trying to tackle the beast that is MS. Tho over 3000 emails will no doubt make a dint in that!😳
Thanks too MD for the holding the fort.
Good luck with trying to make further progress and inroads.
Fi,
I’d like the opportunity to reconnect with my family and take a well deserved holiday. Unfortunately like many MSers, I lost my job and have financial and mobility issues so no luxury breaks for me (EVER). Surely the losers are people with this disease not those who have made a career from it? I’d gladly swap my life with overworked Prof G, but I’m guessing he wouldn’t swap his with mine! There’s c100,000 people with MS in the U.K. I pray Prof G can fastrack some of his ideas so they can make an actual difference to people with MS (halting progression should be the aim). Until then, talk is cheap. Too much procrastinating / navel gazing over the last 50 years. We need some Young Turks to rattle the cage of MS research. Is Prof G a Young Turk or part of the current establishment / dogma? With pharma making billions from MS will an establishment figure bite the hands that feeds them?
Re: “With pharma making billions from MS will an establishment figure bite the hands that feeds them?”
We need Pharma they are the only show in town when it comes to commercialising vaccines and drugs for that matter. The NIH may develop the vaccine, but we will need a Pharma company with big pockets to deliver an EBV vaccine for MS prevention. The estimate for developing and marketing an EBV vaccine is close to $1.5-2.0 billion., which needs to backed-up by at least $2 billion of global annual sales.
A lot of vaccine development and deployment relates to politics and getting public health behind the strategy.
Hi Suzie,
I’m sorry that my reply to Gavin post has been the cause of such consternation for you. In supporting him in his endeavours and respecting his needs as a person, it is definitely the case that I’ve inadvertently caused you a negative reaction. My position is influenced by the benefit I’ve gained from this site. I see the drive and commitment evidenced by the blog team as an additional positive. I’m also conscious of the fact that ms is the only neurological disease for which there are any treatments that evidence a degree of efficacy for some of those who receive them.
I’m also impacted by my MS such that I’m unable to go on holidays that involve long distance travel, including here in the UK.
I’m also frustrated that progress isn’t anything like what we want it to be, exacerbated by financially driven Pharma and an number of dodgy studies.
However, I can’t take away from our need for researchers to keep slogging away, or for the potential benefits to PwMS from clinicians such as Gavin.
Thank-you for saying what I have been thinking. All of us with MS are frustrated by the slow pace of progress but lets not beat up the researchers trying to make a difference. They are doing their best and that is all we can ask.
What a refreshing post. Thank you for thinking, not being content with ploughing on in the same old ruts with blinkers on.
As someone with slow “PPMS”, I find myself very dissatisfied with much of the MS research field and certainly with the therapies currently available.
Thank you again.
Schools could help with educating children and parents about mono. GP’s could help by advising that children with mono do not return to school until the child is recovered, so less chance of passing it on. I had mono at secondary school and was given no/ little advice at the time.
As about 95% of the population have Epstein Barr virus (the cause of mono/glandular fever) and the infection is for life, so keeping people who show symptoms of infection away from others will not help. In most infection causes no symptoms. A vaccine is the only way forward. Epstein Bar virus also causes some lymphomas.
But it seems to be those who get mono in the high school years are the ones that develop MS more. It seems to be at this time in life and when being unwell with mono, the immune system possibly hits a tipping point of some type. That’s why I gave my suggestion. Those that get mono before or after this point in life seem to not go on to develop MS as much.
That’s what I understand anyway.
Is this what Bart’s MS recognise too?
You can get Epstein Barr at the age of 1 from your mother when she sucks the dummy you just dropped on the pavement to “clean” it for you. You can get it from your friend at 5 when you try their lollipop. Or from your first kiss in your teens. And the second, third… And never know you have it. That’s why most people have the virus.
From what I read those that get mono in secondary school years seem to experience more severe symptoms, than at other times in life.
Indicating mono might have a more intense impact on the immune system, in the secondary school years possibly.
There’s also a theory that as people in developing countries get exposure to EBV at a much younger age, this is/could be a factor in why they do not go on to develop MS.
So thinking along these lines… if people in developed countries like the UK, if they were to be exposed to EBV on purpose at a very young age, could this influence less chance of developing MS??
A risky research project but an interesting theory.
I agree that the scientific community has a problem with trenches. We’ve been firmly working in the EBV trenches. Every time we write a grant that attempts to bridge over to the MS trenches, we are soundly rejected. The last reviews we received were nasty. It is also a chicken-and-egg problem, where we can’t get preliminary data without a grant and we can’t get a grant without having everything worked out, it seems.
It is disappointing because we also have an interesting drug that targets latent EBV infection. This drug is in the early stages of clinical development in patients with EBV-positive cancer. It also has a pretty good safety profile so far because we are targeting an EBV-specific protein. It would be interesting to explore using this drug as a prophylactic treatment to prevent MS in high risk individuals.
But these structural barriers that we have erected between different sub-disciplines in life sciences are vexing and prevent collaborative work that need to be employed to make significant breakthroughs for MS patients.
ProfG a Looney:-)
Surely part of this breakthrough is repurposing drugs – MS-Stat2 is such a potential example as well as Cladribine
Collaborative breakthroughs sound a very good idea but sadly I suspect there is a lot of luck to make the link from one area of medicine to another
‘To prevent MS in high risk individuals’…, how would you distinguish who is high risk other than individuals who have MS in the family?
There are certain geographical regions that have a high incidence of MS in the UK–Orkney, for example. You could start there. Certainly, family members of someone diagnosed with MS are higher risk.
But it’s also requires a risk-benefit analysis: Is the risk (side-effects) worth the benefits (potential prevention of MS)?
Dr Ruth did this as her PhD project; i.e. to define an MS endophenotype to try and predict who will go onto develop MS. The area under the ROC (receiver operating curve) was just shy of 80% and therefore not good enough for use at a population level.
The best we have is 1st, 2nd and possible 3rd-degree relatives of MSers.
” everyone is digging deeper into their own trench and rarely standing up to look in the next trench over”
Are ´nt Barts team doing exactly this ?
Our trenches aint that deep we can’t climb out:-)
🙂
OhOhOh I got a rocket..Goldfrapp
How do you explain the early Prineas MS lesion; massive oligodendrocyte apoptosis without T- and B-cell infiltration?
These observations plausibly explain the findings of Barnett and Prineas and further support the concept of interindividual heterogeneity in MS. ANN NEUROL 2012;72:385–394
https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.23621
Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate