This is the third part of an ongoing series, click here for part 1 – North America and part 2 – Israel.
To Mr. James Parkinson,
It has been 200 years since you identified the ‘shaking palsy’ that now bears your name, but I regret to tell you that we haven’t made much progress. Though we have identified some of the biochemical pathway responsible for the shaking, rigidity and postural instability you identified, and have even learned to synthesize the chemical deficiency responsible for the disease, it is still very much with us, and in me, today.
But I think you’ll be delighted to learn that your countrymen have taken up the cause and are in full pursuit of ensuring that your name is finally allowed to move on from the present and become history. I have spent the last couple weeks touring your homeland and was impressed by the buzz of activity and innovation going on at the universities and medical centers I visited. The English of your day accomplished some incredible feats and ushered in the Industrial Revolution when they learned to harness steam energy to improve transportation and manufacturing. Now the fourth iteration of that revolution is making it possible for us to apply some of those same engineering principles to the biomedical sciences, and Parkinson’s disease, and England is once again at the forefront.
But what I found even more inspiring was the strength and determination of the people afflicted with your disease here. They seem impatient with the impersonal nature of large organizations and unwilling to sit around waiting for doctors to fix things for them. This spirit is something I wish more PD communities would embrace, even if it does mean having to stop for tea at every chance.
One of the first things I did after touching down in London was pick up a copy of Mentored by a Madman: The William Burroughs Experiment by Prof. Andrew Lees, who I briefly got to correspond with. Prof. Lees is a world renowned neurologist who conducted some critical clinical trials for your disease in the 1990’s. His book is a riveting account of the unconventional tales of writer William Burroughs and the lessons Prof. Lees’ gleamed from him. Prof. Lees is something of a rogue in the field himself, though he is one of the three most cited neurologists on the planet, he has grown weary of how much politics and big business has invaded medical science and seems to long for the day when doctors were free to pursue their craft unfettered. As I write this he is deep in the Amazon jungle conversing with shaman in search of medicinal herbs and psychedelic potions that may have something to offer in the treatment of this disease.
My first meeting in London was at Royal Free Hospital, where a team of about 20 PhDs are working on a specific genetic form of Parkinson’s disease associated with variants in the GBA gene. Researchers have recently identified a variety of mutations in our DNA that may account for the disease. One of them, which has catapulted to the forefront of Parkinson’s research today, and which I also carry, is called the N370s variant of the GBA gene. It’s a great boon to see that many researchers are no longer treating this as one disease and are instead now targeting specific variations of PD. Walk into any patient center and it becomes plain to see that we are dealing with a spectrum of disorder, so any serious attempt to combat this must start by identifying the different forms of the disease and developing treatments to target each unique version.
At the hospital I met Dr. Stephen Mullin and Dr. Matt Greg who are two of the principal investigators of a trial using a compound called Ambroxol to target the GBA mutation. They walked me through some of the details of their trial and why they believe their approach might work better than similar trials happening in other parts of the world. Human trials are set to commence soon and a great deal of anticipation is building surrounding their potential. Exciting times.
(What is genetics you say? About seventy years ago a team in Cambridge, lead by James Watson, Francis Crick, and Rosalind Franklin, identified a chemical structure called DNA that is found within every living cell on the planet. Human DNA is comprised of 20,000 sub-components, called genes, that contain the instruction manual responsible for determining the shape and function of every cell in our bodies. Over time random changes occur in that instruction manual as part of the process of evolution. You don’t even know what evolution is, do you? Well, a couple decades after your death, another Englishman named Charles Darwin came up with a theory of Evolution by Natural Selection. In short, according to Darwin, it is a “principle by which each slight variation [of a trait], if useful, is preserved.” This theory now forms the framework underpinning almost all of biology.)
My next meeting was with Anna Louise Smith, the research support network manager for Parkinson’s UK. Recently the organization has refocused on building a Research Support Network to connect their members to research news and opportunities to take part in research and have their say, as well as drug development through their Parkinson’s Virtual Biotech initiative. One of the more exciting developments in Parkinson’s research today is the GDNF trials that they support. GDNF(glial derived neurotrophic factor) is a protein that promotes the survival of brain cells. A lot of promise is building around it’s potential use as a therapy to slow or even stop disease progression. We will learn more very soon as results of the trials are going to be released later this year.
Next I saw Dominic Graham from the European Parkinson’s Disease Association, a collaborative body seeking to connect the different PD organizations in Europe. They are located in nearly 30 European countries and, despite all the difficulties involved in trying to organize Europeans into a coherent body, they have managed to link some of these disparate groups and provide sorely needed information to patients throughout Europe.
I then took a trip out to the English countryside to visit Gaynor Edwards who put together Spotlight YOPD, one of the only organizations in the world designed specifically for young onset Parkinson’s disease. This disease affects people of all ages and those who get the diagnosis at a younger age have very different needs than the older onset group. There is also a growing belief that the underlying mechanisms of YOPD and ‘normal’ PD are different, with many now believing that they should not be lumped together under the same heading. Gaynor saw this and set about to create a group specifically to meet the needs of younger onset people. Later I would also meet Brian Lowe who is the chief blogger of a similar group called South London’s Younger Parkinson’s Network. Both are a bold step forward in improving awareness and care for young onset PD.
With Gaynor I took a trip through the lush English countryside to see Dr. Jon Stamford and Dr. Pete Langman, where I sat perplexed trying to make sense of the cricket game Dr. Langman was playing. Dr. Stamford is a rare case, he was a neuroscientist who studied PD for decades in a dish only to eventually get diagnosed with it himself. This certainly gives him a unique perspective and makes his take on Parkinson’s worth reading. Dr. Langman’s book, Slender Threads, is a hilarious yet brutally honest patient account of this disease, perfect for anyone wanting to know what it is actually like to live with it. Watching his determination to play the game he grew up with, despite what this disease was doing to him, was a testament to the kind of spirit people diagnosed need to foster to live through it.
Back in London I met with Andy Butler, whose father passed away from PD a few years ago. In the last years of his father’s life Andy took care of him and watched the day by day toll PD has on a person. He resolved to do something about it and began reaching out to people all around the world. Perhaps no single person has done more to connect Parkinson’s people from around the globe than Andy. Through his advocacy and his Facebook page, Parkinson’s People, he has built a network of almost 40,000 people connected to this disease. He has provided a place for people to come together to try and ensure that no one has to face this thing alone.
(The biggest change in PD research over the last few decades, and the world for that matter, has been the internet, a world wide network of information processing machines. Through it, every human on the planet (we are at 7.5 billion now) has access to all of human knowledge on devices that fit inside their pant pockets. It is how I have been able to connect to all the researchers I have visited, it has allowed Andy to build his network, and it makes it possible this blog you are reading to be seen by people in 178 different countries. It also enables research to spread much faster and wider than ever before and gives scientists the ability to collaborate with researchers on every corner of the planet. It is an integral part of why science has made such immense progress over the last few decades.)
In London I also got an introduction to the Linked Clinical Trials, the brain-child of Dr. Richard Wyse at The Cure Parkinson’s Trust. Through it Dr. Wyse is trying to usher in the age of personalized medicine(see picture above) by re-purposing a spectrum of existing drugs. The trial is also trying to determine which cohort of patients each drug, or combination of drugs, would be best suited for. It is a shining example of the kind of concerted effort that is needed in devising novel therapies for chronic diseases as he is developing it in collaboration with clinics and labs around the world. This could be a model for the era of personalized medicine, a time when we finally move away from the one size fits all approach to medicine to tailored treatments for patients’ unique genetic and physiological makeup.
I can’t mention The Cure Parkinson’s Trust without noting its founder, the late Tom Isaacs. His story is often repeated in the PD community but is always worth retelling. After his own diagnosis(like me at 29), he walked the entire 4,500 mile coast of Britain to raise money, it also provided the impetus for the creation of The Cure Parkinson’s Trust.
Tom was one of a kind and his performance at the World Parkinson’s Congress last September was the highlight of the entire event for me. Despite his advanced state, he got up on stage and sang about the need to bridge the divide between patients and researchers, something he had spent his life advocating for through the Cure Parkinson’s Trust. I’ve come across too many researchers that only see the diseases they study in a dish and never bother to meet the people afflicted by it, let alone get their input. Tom believed in the role patients play in the study of disease, not simply as lab rats, but as active participants in shaping research and clinical trials. Scientists may have a better understanding of the mechanisms underlying the disease, but patients have a more visceral understanding of what the disease does to the body and the mind. Both branches of knowledge need to be part of devising therapies to tackle this disease.
I was further emboldened visiting The Cure Parkinson’s Trust and seeing all that he had built. In addition to the Linked Clinical Trials, CPT also supports a wide array of other research initiatives including the GDNF and Ambroxol trials mentioned above. It was also inspiring to meet Dr. Wyse, Helen Matthews and Leah Mursaleen, who run the organization and seem determined to carry on Tom’s legacy and bring an end to this disease. In the words of Dr. Wyse, Tom was “intolerant of this disease” and spent his life doing his part to eradicate it from the face of the earth. On May 31st I sent him an email asking if I could meet him on my tour of the UK, later I found out that he had unexpectedly passed away that same day. Though I never got the chance to meet him, he was a great source of motivation and I thank him for showing the way.
My last stop in London was with Dr. John Hardy, a geneticist whose lab has spawned some of the world’s leading minds in genetics. The stories he told me were a sobering reminder of the complexity involved in trying to unravel the code that makes us who we are. For instance, the first disease identified as having a direct genetic cause was cystic fibrosis, which mainly affects the lungs. The gene for CS was identified in 1989 by Dr. Lap-Chee Tsui in Toronto and it was believed that this would soon lead to a cure. Unfortunately the only thing that did was highlight how little we really know about genetics. Though we have discovered all sorts of methods for improving care for people with CS, none of those treatments have to do with the gene.
The same may be true for Parkinson’s disease. We now have over 40 known genetic variants associated with PD, and that list is growing quickly. However there is still no practical use to any of that information for patients. I have one of those variants, but so does my mother and a couple cousins yet none of them have any signs of the disease and nobody can say with any degree of certainty why. But it is early days and genetics still holds a lot of promise, though progress might be slower than we like, the work Dr. Hardy and other such modern day wizards are doing may soon open the door to a brave new world of healthcare.
Another recent giant leap forward has come from research into pluripotent stem cells, cells capable of becoming any cell in the body. Recently we have learned how to extract stem cells from developing embryos and turn them into any cell we want. Even more incredible, eleven years ago a scientist in Japan named Shinya Yamanaka discovered how to take skin cells and reprogram them so they can revert back to their embryonic form. These are called induced pluripotent stem cells(IPSCs) and scientists around the world are now using IPSCs to work all sorts of wonders that might have had them burned at the stake in your times. If that isn’t enough, we now also have a technique called direct programming that skips the stem cell phase all together and directly converts one cell type into another.
One of the first applications of these techniques has been in Parkinson’s disease as we discovered that it is attributed to the death of a very specific type of cell in a tiny part of the mid brain. Many now believe that we may be able to use stem cells to replace these dead cells, reversing the disease progression. Similar trials were conducted in the 1990’s with mixed results, to learn more about those trials read Dr. Curt Freed and Simon Levay’s gripping account, Healing The Brain.
Accompanied by Prof. Gerold Riempp, a professor of information systems who was diagnosed with PD 16 years ago, I next traveled to one of the labs leading the world in this new age of Parkinson’s stem cell therapy run by Prof. Roger Barker at Cambridge. Prof. Barker embodies the cautious optimism that him and his colleagues carry as they walk the fine line between hope and hype surrounding this therapy. But it is a highly contentious issue that is further complicated by the dozens of labs around the world already claiming to be able to cure this disease using stem cells. While living in China I got several offers to have either pig’s eye cells implanted into my brain or to have stem cells taken from my fat dripped into my veins. A team in central China recently implanted 10 patients with neural progenitor cells and Prof. Barker was among those to voice his concern over these trials as neural progenitor cells can grow to become any number of different kinds of cells. The Chinese have little qualms about using people as lab rats, while unfortunate for the patients involved, at least we will learn more about what happens when you throw these kinds of cells into human brains.
But such ill-advised trials may ultimately do more harm than good for the global PD community as the results influence not only public perception over the use of stem cells, but they also affect the opinions of neurologists around the world. This betrays all the knowledge that Prof. Barker and a few others have acquired by thoroughly studying both the successes and failures of trials of the past. We now have a much better understanding of what kind of cells to use, how to culture and store these cells, how best to implant them and what kind of patient this therapy would be best suited for. This is why Prof. Barker and a few of his colleagues are confidently moving forward with a new batch of trials set to commence soon.
I also was in attendance for this brilliant talk he gave the next day outlining the development and potential of this therapy… (recorded by Prof. Riempp)
While visiting Prof. Barker’s lab I also met with Dr. Simon Stott who runs the excellent blog, Science Of Parkinson’s Disease. Not only is he a part of all the incredible work going on at Prof. Barker’s lab, but his blog also plays a vital role in the PD community. One of the biggest problems we face today is misinformation, and at times, outright deceit from our news sources. The internet, though it has done a tremendous amount of good in connecting the world, has also made it possible for anyone to have a voice, and if those voices are outlandish enough they can draw an audience and shape narratives. Celebrity matters more than truth these days and what too often spreads are stories that appeal to our base emotions and shrinking attention spans. Dr. Stott’s blog is an attempt to cut through all that and present pertinent information that is scientifically sound.
His blog also helps bridge the gap between researchers and patients. Science has made enormous strides in the past 200 years but it has become nearly impossible for any non-specialist to discern the relevant from the snake oil. Additionally, while you had the luxury of pursuing several disciplines and could apply yourself as a surgeon, apothecary, geologist, palaeontologist, and political activist, today researchers are forced to pigeonhole themselves into one tiny branch of knowledge and spend their entire career trying to carve out a name for themselves in that narrow space. This has produced fields of specialists with very few capable of seeing and analyzing the entirety of it. Parkinson’s research, for instance, has become so multifaceted that it has left us with almost nobody capable of taking it all in and giving sound advice on the various aspects of it. Dr. Stott, through the work he has put into his blog, is one of a few researchers trying to take into account as many different avenues of research as possible and look at the big picture, making him and his blog invaluable resources.
Finally, while in Cambridge I also got to meet with Prof. Maria Grazia Spillantini and Jessica Santivanez-Perez. The most impactful development in the last twenty years in Parkinson’s disease research has come from the identification of a protein called alpha-synuclein that comes together in toxic clumps, which kills brain cells, resulting in the disease. Prof. Spillantini played a critical role in identifying alpha-synuclein in Lewy Bodies, the harmful protein aggregates that develop in the nerve cells of people with Parkinson’s disease. Now her lab is trying to find the mechanisms behind the formation of these alpha-synuclein bodies and they are working on methods to clear the brain of these toxic clumps. Jessica, a doctoral student, studies these protein formations by growing neurons from patient derived skin cells and studying under microscope the formation and neuronal effects of these toxic clumps.
(One great advantage of the connected world today is that prestigious institutions such as Cambridge are able to draw from not only the best minds in Britain but the best minds in the world. Jessica is from Peru, a South American nation in the Andes. Prof. Spillantini comes from the Italian peninsula, in the 1870’s the Italians finally managed to put their irascible personalities aside and form a united nation. In fact, for the last half century all of Europe has been drifting closer and closer together (The French are now one of your allies!) and have even formed a united governmental organization called the European Union that has presided over the longest period of peace Europe has ever seen. (Though bear in mind that it did require two world wars that killed almost a hundred million people and nearly resulted in the destruction of the entire planet.) However recently some of your countrymen may have cast the die that will end this whole arrangement when they decided to pull out of the European Union. Oh you intractable Brits.)
Well Mr. Parkinson, there it is. Though we haven’t made as much progress over the last 200 years as you might have hoped, we have come a long way and are currently living through the most exciting time in the history of your disease. From one Canadian, I thank you for getting the ball rolling, and thank England for your unpredictable weather, your tea with milk, and your dogged determination in the fight against this disease.
(By the way, I have some bad news you, the British empire long ago crumbled and Canada is now an independent nation. Also that backwater republic called The United States of America that was made up of slaves, refugees and the religiously persecuted in your day now runs the world. It is lead by a bombastic man-boy who seems determined to piss off as many of his fellow world leaders as possible, though that might not be too far removed a description from your own tyrannical King George III. However America might be in the last throws of its reign as it is now having its supremacy challenged by China, the same China that Britain subjugated with a couple gun boats just after your death. Yup, geopolitics is still a quagmire of turbulence and stupidity, here’s hoping we will one day figure out how to put all that petty squabbling aside and focus on the real sources of progress in society, education, the arts, and science.)
Next Up: Edinburgh
Fantastic! Love your writing. Have you read Atul Gawande’s Being Mortal? FANTASTIC book that analyzes the role of medicine in human-kind’s quest for worthwhile living. Great, thought-provoking questions about life choices and the partnership between “patients” and their medical advisors!
Keep blogging. All the best.
Thanks for the recommendation, I have not read it yet but have been meaning to pick it up. Will do so soon.
There is a lot to be learned from your blogs as I watch them get more complex as you integrate what you have learned from past travels to what you are learning today. Really fascinating and informative. Excellent writing Ben.
Good luck in Scotland!
Ben – I LMAO at your complete pithy, punchy understanding of the Brits and EU’s historical complexities – bang on! And yes… the ‘Empire’ is still bandied about (neglecting to mention all those sired that now rightly have come home to suckle on the sagging teats of the wonderful NHS….oops!). I always said ‘give the Brits guns and we’ll all be dead in 3 days’ 🙂
But this is also a brilliant and thorough report of the state of research for Parkinson’s now; I agree that stem cells or IPSCs are the future.
A true pleasure to read and learn! Thanks dude!