I was diagnosed with Parkinson’s disease three and a half years ago at 29 years old. Like all that hear such news, I have felt the fear, anxiety and despair that goes along with it. But, for whatever reason, at some point all that negativity gave way to a desire to understand, an almost childlike curiosity to figure out what is happening inside my head. Over the last nine months I have allowed that curiosity to be a driving force in my life and it has led me on a tour around North America visiting some of the best neuroscience labs there are and meeting with some of the top researchers in the world.
The Benefits Of Understanding
I now have the terminology needed to describe for myself what is happening to me as well as just about anyone can. Here is a brief summary of what science today has to say about my Parkinson’s disease – the N370s variant of the GBA gene I carry caused a deficiency in my lysosome which as a result can no longer clear the build up of alpha-synuclein proteins which has had a toxic effect on many of the organelles in my neurons leading to the death of over 80% of the dopaminergic cells in my substantia nigra causing the axons that innervate my striatum to no longer signal the release of dopamine in my putamen resulting in the action potentials in the receiving neurons across the post-synaptic gap to sputter stochastically rather than fire steadily leading to a cascade of misfiring neurons through my brain, down my spinal cord and out to the ends of my limbs where the muscles don’t know what to do with the jumbled message they receive and thus tremor or seize up.
But what is the use in all those words? Well, for one, it has given me an image of what is happening in my head, which, oddly enough, has been useful when meditating, which I try to squeeze in time for daily. Though in meditating the goal is to clear the mind, I allot a certain portion of that time to thinking about this cascade of events happening in my brain. I draw pictures in my head from all the neurons I have seen in illustrations and under microscopes and imagine the damage taking place. I strain to see those neurons rewiring themselves and try to map in my head the incredibly intricate interactions taking place between the millions of organelles inside each neuron in the hope that if I imagine it vividly enough they might actually be repairing and rewiring themselves. With all that we are learning about neuroplasticity and the minds ability to reshape itself, it is not inconceivable to believe that this is having some benefit. Though in reality who the hell knows, but it makes a lot more sense than some of the therapies out there and it at least gives me an effective meditative technique to use.
That knowledge also gives some semblance of reason for the symptoms I experience. Prior to I was bothered by just not being able to make sense of the tremors and rigidity I was experiencing. Now that I can at least come up with a plausible explanation it does help settle my mind and give me some clarity. However there is still a long way to go as I still don’t know exactly how this disease came about and exactly what I will need to do to stop further decline, but having walked this path so far I at least believe I am on the right track.
Exercise and a positive attitude are the best things anyone with PD can do for themselves, but when those fail at least we do have some drugs we can turn to. The best by far is levadopa, which I take three times daily. Each time it takes about an hour to enter my gut, get broken down and absorbed into my bloodstream, and then released throughout my brain. First the tremors subside, then I feel it in my toes as they loosen up and I’m able to wriggle them again. The feeling then spreads as neurons all over my body send forth a resounding trumpet that lets me know I am once again free to move as I please.
It is accompanied by a high, not only brought on by the joy of mobility, but by dopamine being released in various parts of my brain associated with our innate reward system, this I experience as a mild sense of euphoria. I then begin to ache for something to do as both my body and my mind start to feel nimble again. There is also an elevated sense of alertness and focus as well as a mild cognitive improvement that allows me, for example, to read and remember what I read better than I ever could before. I simultaneously want to go for a run and do some writing or learn something. I’ve also learned to recognize the subtle tells of dyskenisia that don’t even come up under neurological examination by a movement disorder specialist.
Do the difficult things while they are easy and do the great things while they are small.
– Lao Tzu
Figuring all this out has been a gradual ascent. It started slow, reading a patient account or journal article maybe once every couple weeks after the initial diagnosis. After a few months of that I branched out to new sources of information like YouTube and podcasts, followed soon after by buying popular science books about the brain and checking relevant subreddits like r/neuroscience daily. When that no longer felt like enough I further up’d the dosage by getting textbooks on neurobiology and subscribing to medical journals and newsletters. Now I find myself flying all over the world to talk to the people in the field that know this thing best.
As mentioned above, most of this came from tapping into that simple childhood curiosity to know, to incessantly ask why and never being completely satisfied with any answer. But it has also come from talking to dozens of different patients and trying to figure out why some are doing better than others. Those that are doing relatively well are usually the ones that have taken caring for this disease into their own hands and aren’t reliant on their doctor. Chronic illnesses, by their nature, are ever-present, constantly occupying your body and mind, and though doctors do what they can, there is only so much they can do. Most patients, if they are lucky, see a motor disease specialist for a total of one hour per year, but the symptoms of PD vary from patient to patient and moment to moment, you simply can’t convey enough information to your doctor in the time you have with them. This concept is wonderfully illustrated by Sarah Riggare, who has been living with this disease since she was 13, and in her blog 1 vs 8,765, demonstrates the need for patients to learn as much as they can so they can actively engage in their own healthcare.
Next I’ll be travelling through Europe and Asia to continue this journey and meet with as many people as I can along the way who might have a piece of this puzzle. Along the way I have also been trying to see if I might be able to fit any of these pieces together myself and am excited to say that I have been able to play a small role in furthering collaboration in the field as I have managed to connect some of the teams I have visited to learn from a each other and work together.
I’m writing this as an exercise in reflection before I embark on the next leg, to look back on all the places I have been far, to remember all of the people I have met, and try to organize all that I have learned. I also know that I am in a privileged position and that most patients don’t have the luxury to do all of this so I hope that this might allow some of them to learn vicariously through my travels. I want them to know that the world is full of people working on this thing, though I do wish there was more collaboration between them, that there are so many out there should be a boon to everyone involved.
This is also my tribute to all the scientist and and researchers and physicians and nurses and caregivers I have had the fortune to speak with along the way. Though you are constrained by budget cuts and strict grant timelines and mountains of paperwork and scores of patients to see, you have made time for me, patiently answered my questions and gave me countless lectures. I am forever grateful for all the work that they have done to get us to where we are today and I hope they understand the vital role they play in helping the millions afflicted with PD.
I have seen and met with scores of patients at all stages of this disease and I am convinced that maintaining a positive attitude in the face of such things matters more than any drug or therapy ever could. The biggest battle people with chronic illnesses such as Parkinson’s have is not the physiological symptoms, it is the daily psychological battle that one has with oneself. I have seen and heard of a number accounts of patients that lapse into apathy or just become despondent over time. They stop exercising and stop taking care of themselves, as a result the disease starts to progress even faster. For them, knowing that there are people out there working to push the science and healthcare forward inspires hope and gives them reason to get up and continue the daily grind imposed on them by PD.
The People Who Have Fueled My Curiosity
Below is a recap of some of the researchers I have met along the way and what I learned from them. I tried as faithfully as I can to succinctly record what I learned from each one but I am sure I missed some details, I hope no offense is taken.
There is one person I’d like to start this account by paying homage to, somebody who would have been at the top of my wishlist of people to meet, Dr. OliverSacks. Unfortunately my interest in the brain peaked a little too late to get a chance to meet him as he passed away in August of 2015. No one has done a better job of articulating the intrigue one can have in the confounding complexity that is the human mind. Here is just one of the many astounding talks he has given, this at the first World Parkinson’s Congress highlighted by words I wish were written above the doors of every medical school in the world, “our patients are our teachers”. (the video skips half-way through)
Dr. Mark Guttman was my introduction to this disease. He broke the news to me gently and was as good of a guiding hand as I could have asked for in helping me start this journey. He told me stories of patients who had been with him for years who water-ski and run marathons and climb mountains. I think of all the patients that don’t have the kind of doctor needed to ensure they still get the most out of life despite disease, if only more of them had someone like Dr. Guttman to see them through.
I lived in Shanghai for the first couple of years after my diagnosis and was lucky enough to find Dr. Hung at the WA clinic. A neurologist from Taiwan who also introduced me to functional medicine and hammered home the importance of looking at this disease as not just the result of dysfunction in the brain but as the result of a complex interaction of environmental, nutritional and hormonal factors that must also be considered when trying to figure out how best to treat such an illness.
Dr. Alfonso Fasano was exceedingly gracious in responding to my initial inquiry and for his continued interest in my case. He gave me many of my first lessons on the neuroscience behind Parkinson’s, carefully sketching out neurons and identifying the cell body, the axon, the dendrites and the synapses. These lessons formed the base that has allowed me to soak up all of the knowledge I have gained about my brain. The PD community at large also owes a huge debt of gratitude to him and many of his colleagues at Toronto Western for pioneering many of the techniques used in deep brain stimulation, after levadopa (and exercise) it is the most effective therapeutic tool we have. Also grateful to Dr. Andres Lozano and the brief exchange I had with him that inspired hope for me in the future of such neuromodulation techniques, which some people are going to use to try and do some pretty crazy things.
At the invitation of Sherrie Gould, a nurse practitioner who I had never met, I went down to San Diego to learn about the latest stem cell therapies being developed for Parkinson’s disease. While there I got to meet the head of the lab working on this project, Dr. Jeanne Loring and the lead scientist Dr. Andres Bratt-Leal. It was in San Diego where I got my first real sense of the immense progress science has made lately towards one day putting an end to neurodegeneration. The team there introduced me to the medical marvel that is IPS cells, and the idea that one day soon stem cells will be used to restore dopamine producing neurons to patients. Sherrie is a true inspiration in putting together the Summit for Stem Cells and the community that has built up around it is a model that all PD communities should learn from. Too often there is a disconnect between researchers, physicians and patients, no center I have visited does a better job of integrating all three and that is due in large part to the work of Sherrie, Jeanne and Andres.
I next went to the World Parkinson’s Congress in Portland last year, held every three years, it is a mixing of worlds as patients, physicians, clinicians, media members, scientists, researchers, and big pharma all mingled in a giant conference center for three days to learn from each other. There were 5000 people in attendance and over the three days at any given moment there were at least 8 separate seminars or discussions being run. I attended as many of the science talks as I could, and though much of it went way over my head, it did give me some clear insights into which areas I need to read up on. I hope that by the next congress in Japan in 2019 (which I have been just been chosen to be an official blogger for) I will be able to keep up with all the lectures.
I saw Dr. Stephen Finkbeiner speak at the World Parkinson’s Congress and I was enthralled by the work he is doing to come up with better disease models and by his application of machine learning to our understanding of disease. The biggest limitation we have when studying the brain is that it’s not see easy to crack open people’s heads and see what is going on inside, so we use models like rodent brains, or neurons in petri dishes to test new therapies on but they just aren’t able to mimic the incredible complexity of the human brain. Thankfully, there are people working on better disease models by integrating robotics and machine learning and at the forefront of this new line of research is Dr. Finkbeiner. I went down to his lab at the Gladstone Institute in San Francisco to see this work for myself where I also met with Dr. Gaia Skibinski and Dr. Julia Kaye who showed me around. The work they are doing to help us better characterize dopaminergic cells and understand the process by which they differentiate from stem cells is ground-breaking and will be integral to developing better treatments. I would also like to thank Gaia for her willingness to collaborate with a wide variety of researchers, she is a true testament to the kind of interdisciplinary approach we need in the study of diseases.
For all the complexity surrounding Parkinson’s disease, it is a relatively easy disease to define as it is primarily the death of dopamine producing neurons, so, it makes sense to develop therapies to try and replace these neurons. There are currently five labs around the world working on stem cell therapies to do exactly that and the lab that is closest to bringing this to human trial is run by Dr. Lorenz Studer who was very generous with his time and patiently answered my barrage of questions in his office at the Rockefeller labs. It can be hard for researchers and patients alike to walk the fine line between hope and hype with any promising new therapy, which especially true with these new stem cell therapies. This tight-rope walking is on the minds of all of the scientists working to bring this therapy to patients and is embodied in the cautious optimism of Dr. Studer, whose human trials are set to begin at the end of this year.
In addition to the five labs that will be going to human trial soon, there are a number of other labs also working to ensure the safe and effective transplant of the cells. Dr. Tilo Kunath and his lab in Edinburgh are working diligently on just that. Stem cells have a lot of potential to be the next big breakthrough therapy in PD but without groups like his testing and refining the techniques being applied we may fall short of our goal. I am also thankful for his openness and willingness to work with other researchers, I wish more scientists shared his enthusiasm for collaboration. He was also the first one that alerted me of the prospect of in-vivo direct programming, though still in its infancy, it is a technique by which we may one day be able to change any cell in the body from one cell to another and may be the closest thing we get one day to a cure.
Dr. Scott Ryan and his team at the University of Guelph are also playing a critical role in unraveling the intracellular mechanisms behind degeneration in transplanted stem cells. Though him and his team are quite a bit younger than some of the others out there, it was exciting to see how each disparate group is developing their own niche in PD research that will hopefully one day all be able to pieced together to help us solve this incredibly complex riddle.
The team of researchers I met in Vancouver left an indelible impression on me, starting with Dr. Katie Dinelle who was kind enough to organize my tour around their facility. The Center for Brain Health in Vancouver does an excellent job of providing an interdisciplinary approach to the study of Parkinson’s, another shining example of exactly the kind of facility that is needed to tackle complex chronic diseases. Dr. Dinelle also took the time to take me through the inner working of fMRI and SPECT scans and elucidated the hope surrounding a new line of such machines coming out soon that will blend these techniques together and give us new tools to peer into the inner-workings of the brain.
Later that day I met Dr. Matt Farrer, who chose as his calling in life the daunting task of trying to figure out the role our genes play in neuronal development. Matt is a fitting character to tackle a field as complex as neurogenetics, the sheer complexity involved is mind-boggling as any truly comprehensive understanding would involve knowing the roles of all the various neurochemicals, all the different kinds of cells that make up the brain, the internal structure and composition of each of those different kinds of cells, all the factors that lead to both neurogenesis and neurodegradation, all the genes that regulate the proteins the brain uses, all the different parts of the brain, and how all the different neurons are connected to one another. The brain is the most complex arrangement of atoms in the universe, and yet there are people like Matt that decided for some crazy reason to spend their days trying to figure it out. Wind him up and he can talk for hours about the history of single genes and the role they play inside your head. I let slip my own gene mutation and his eyes lit up, before long I was spitting into a tube for him to analyze and play with.
I’d also like to thank a round table of talks given for me by half a dozen grad students at UBC who were just beginning their careers in brain science research. They were an enthusiastic bunch, eager to show off what they had been working. Most were working on various brain machine interfaces that have the potential to offer novel therapeutic approaches to a variety of brain disorders. Feels good to see that the future of the brain is in good hands.
Through the PPMI study run by the Michael J. Fox Foundation I was put under the care of Debra Smejdir and Dr. David Russell in New Haven. Debra is an impeccably warm-hearted healthcare provider who really goes all out in ensuring that patients get treated with the dignity and respect they deserve and Dr. Russell humored me to no end by allowing our conversations to veer off into evolutionary neuroscience and artificial intelligence. The PPMI study itself is the best run clinical trial I have been a part of due in large part to the patient-centered approach they take to running their study. I am also very hopeful that the mountains of data they are collecting on the patients involved in the study will reveal something soon about the biomarkers involved in PD.
I can’t get out of my head what Dr. Thomas Schwarz at Harvard told me about the role mitochondria play in our neurons. I am left dumbfounded thinking about the numbers he gave me, how in some neurons in your brain there are 2 million mitochondria that each live for at most 2 months and are thus somehow constantly being repopulated at the rate of about 33000 per day. Though malfunction of organelles such as mitochondria do play a role in neurodegeneration, given the incredible complexity inherent in biology, the fact that more does not go wrong is astounding. I should count myself lucky that my brain has stayed more or less in tact for the first 30 years of my life and that though there are some nuisances that I now experience, it still does the vast majority of what I want it to do.
Meeting with Dr. John Quackenbush while at Harvard was also incredibly enlightening. He is a cancer geneticist applying a range of bioinformatic techniques to help us better understand the role of genetics in cell formation. He walked me through which aspects might be helpful in applying to Parkinson’s disease and also engaged me in a riveting talk on evolutionary genetics and the incredible complexity involved in understanding all the interactions genes have within us. He reminded me that though we have made a lot of progress of late, we are still only at the beginning of developing any kind of comprehensive understanding of our biology.
I am also thankful for the machine learning specialists I have come across who have not only helped me better understand AI and the role it will have in society, but who are also eager to apply the techniques they have learned to help us better understand Parkinon’s disease. In particular Dr. Ben Goertzel in Hong Kong and Dr. Joseph Geraci in Toronto who’s teams are working hard to parse and better make sense of the mountains of data that biologists have amassed. We will certainly need artificially intelligent systems if we are ever going to get to the bottom of many of the diseases we still face.
I’d also like to extend my appreciation to all the patients I have had a chance to share parts of this journey with; John Pepper, Gerold Riempp, Sara Riggare, Lisa Vanderburg, Gaynor Edwards, Gina Lupino, Bob Dulich, Tom Walter, Harry McMurty and Jon Palferman. Each contributed their stories and gave me invaluable insight into what is happening between my ears.
One other guy I have yet to thank is Michael J. Fox. Though I only met him briefly at a research talk put on by his foundation, he has been an inspiration to everyone involved in this struggle and has probably done more than anyone to raise awareness and to push research and advocacy for PD forward.
The reality of brain health is that much of this does not just apply to those diagnosed with disease. Once you’ve been around for about 20 years, neurons in your brain start to die, and unlike other cells in your body, neurons don’t grow back. But there are a hundred million neurons in your head with one hundred trillion connections between them so you don’t notice when a few go, it’s only when they cross a certain threshold that we call it disease. But its not like anything really changes either before or after that threshold is crossed, we just give it the name disease because now symptoms of that cell death are visible, but what led to that disease is usually decades of accumulated degeneration that doesn’t stop.
The good news is, we might be able to figure out, stop, and possibly reverse all that death. We live in amazing times and it seems today like anything is possible. In PD for instance, more progress has been made in the past two decades than in all of history combined, and that progress is speeding up, meaning the next two decades will see far more progress than the last two. But it requires work, progress does not just happen, it is the result of human labor and human ingenuity (for now at least) and these scientists and researchers and doctors and nurses and everyone involved in health care need money, time and resources to continue pushing the science forward. Science is the engine responsible for everything we have ever accomplished but it is also the fuel driving our collective curiosities and it should be the responsibility of society to give the men and women in the trenches the help they need to do their work. In the words of Edmund Burke…
“Society is indeed a contract. … It is a partnership in all science; a partnership in all art; a partnership in every virtue, and in all perfection. As the ends of such a partnership cannot be obtained in many generations, it becomes a partnership not only between those who are living, but between those who are living, those who are dead, and those who are to be born.”
However it also important to remember what Freeman Dyson had to say…
“In the modern world, science and society often interact in a perverse way. We live in a technological society, and technology causes political problems. The politicians and the public expect science to provide answers to the problems. Scientific experts are paid and encouraged to provide answers. The public does not have much use for a scientist who says, “Sorry, but we don’t know.” The public prefers to listen to scientists who give confident answers to questions and make confident predictions of what will happen as a result of human activities. So it happens that the experts who talk publicly about politically contentious questions tend to speak more clearly than they think. They make confident predictions about the future, and end up believing their own predictions. Their predictions become dogmas which they do not question. The public is led to believe that the fashionable scientific dogmas are true, and it may sometimes happen that they are wrong. That is why heretics who question the dogmas are needed.”
A final thank you to my parents, none of this would have been possible without your support and without the urge to explore that I certainly inherited from both of you. (For your sakes I’ll try to resist the desire to go back to North Korea on this journey, no promises though).