Advice For Those With A Curiosity To Find A Cure For The Shaking Palsy
Between 1958 and 1964 the BBC broadcasted a television documentary called Your Life in their Hands. It was the first time in the United Kingdom that cameras had been taken into the operating theatre and the programme became popular prime time viewing. There was one particular episode that I filed subconsciously in my brain attic. The presenter Doctor Charles Fletcher began by informing the viewers that Parkinson’s disease was a fatal degenerative brain disease of unknown cause and for which no medical remedy had been found. A new surgical treatment called thalamotomy had recently changed the outlook for many patients although it was far from a cure. He then introduced a sixty-year-old bank clerk who the brain surgeons considered a suitable case for treatment. Mr S had been forced to retire from his work because of an intrusive trembling of his right hand.
With Mr S sedated but still conscious a vital probe was inserted deep into his brain through a metal frame that had been attached to his cranium. Once the desired target had been reached and a few thousand brain cells cooked his shaking stopped abruptly. Further footage then showed the relieved man demonstrating to his doctor how he could hold a spoon in his hand and feed himself for the first time in years.
Ten years later I made my first acquaintance with William Seward Burroughs. The hard man of hip agreed to allow me to qualify as a doctor provided I listened closely to what he had to say about the medical profession, universities, governments and the pharmaceutical business.
I used L-DOPA for the first time in 1970. Within two weeks my patient could walk again. It was a magic moment and it was at that time that the Your Life in Their Hands episode rose to the surface. The shaking palsy was now associated with the supernatural. How was it possible that making a hole in the head or administering an innocuous amino acid present in broad beans could lead to such miracles?
By the time I began my quest to find better remedies for Parkinson’s disease it was no longer considered a death sentence but L-DOPA had proved to be no panacea. I had not forgotten my Faustian pact with Burroughs and continued to read his books and letters.
Burroughs taught me to be open-minded and non-judgemental and run with what life threw my way. He looked at the literature in a slanted and unusual way and helped me to read between the lines. He believed that the time had come for the line between literature and science to be erased. He emphasised I should never miss a chance. He reminded me of the importance of single-mindedness in medical research. He wrote that scientists must find new ways to regain the power to explore independently.
Far from being rational treatments based on a slow march of scientific data accumulation with rational translation to targeted therapeutic innovation I came to realise that thalamic surgery and L-DOPA had depended to a considerable degree on providential serendipity, a random collision of a biological accident with an observer in a perceptive state.
The Yage Letters reinforced my view that the natural world and its plant kingdom held most of the secrets to understanding and manipulating the chemical systems of the human brain. Reserpine the alkaloid present in the dried Rauwolfia root caused Parkinsonism by irreversibly blocking the uptake and storage of catecholamines including dopamine. Without the snake root plant there would have been no L-DOPA. It was no coincidence that Mucuna pruriens a plant known to be rich in L-DOPA grew in close proximity to the snake root.
In 2004 with my colleague Regina Katzenschlager we demonstrated in a small double blind trial that a seed suspension of the leguminous climber Mucuna pruriens (the cowhage plant) held considerable potential as a treatment for Parkinson’s disease (Katzenschlager et al. 2004). Despite recent support for our findings (Cilia et al. 2017) the chances of this cheap herbal remedy ever being made available by governments in sub-Saharan Africa or licensed, as a medicine seems negligible.
I didn’t want to waste time repeating the mistakes of the past. I learned that whenever a really effective treatment had been introduced it was violently opposed by the experts. These people denigrated the mavericks as self-promotional prima donnas blind to the dangers and failures of their suspect therapies. They had read all there was to know about a subject and that was that. Anything outside their own knowledge was not worth hearing about.
By paying attention to what Burroughs had to say I explored the magic of apomorphine (Stibe et al. 1988) and the dreamachine as a tool to investigate visual hallucinations (Weil et al. 2016) His self-experimentation and observations on drug addiction helped me to understand the dopamine dysregulation syndrome better than anything I read in the academic literature (Giovannoni et al. 2000).
Governments, in the name of protecting the public against dangerous doctors and mad scientists, have imposed more and more restrictive regulations. Twenty-five years after its introduction in Europe apomorphine pump therapy remains unavailable in America. Apomorphine has no patent and costs a few cents to manufacture. It has side effects but none that could deny it a licence. Up until 2010 The California Uniform Controlled Substances Act listed it inaccurately as a Schedule II substance.
Meanwhile new drugs with astronomically high price tags or ‘me-too’ formulations with no demonstrable superiority over existing cheaper medicines pour onto the market and are sold for large profits. Burroughs saw this coming.
I believe that all neurologists in the Western world, irrespective of whether they have an academic appointment should devote a little of their working week to research. Private practice and burgeoning bureaucracy are impediments to this aspiration but never a viable excuse. When I speak of research I am not talking about dedicated molecular biological investigation in a ‘wet laboratory’ or crunching big numbers in front of computer screens to determine risk factors
What I mean is willingness and a curiosity to answer with more precision the questions every doctor is asked by patients and to acknowledge that patients can inspire valid research through their own observations.
Medical researchers are often reluctant to reveal their sources of inspiration in case it reduces the impact of their contribution. Patients have always been my main teachers. It is from listening carefully to what they have to say that my best research ideas have flowed. Teachers like Gerald Stern and William Gooddy have also been extremely influential in my discoveries. They never ceased to encourage me to search for meaning in my daily work.
My choice of William Burroughs as an independent literary mentor reflects in part my ambivalence to my own profession and my sixties adolescence. Burroughs led me down the rabbit hole and opened my eyes. I hope my book will encourage young neurologists to chose their mentors carefully and include at least one from outside medicine.
Mentored by a Madman: The William Burroughs Experiment by A.J Lees is to be published by New York Review of Books in September 2017. Professor Lees will give readings from his book at City Lights Bookshop San Francisco in November
He will also be reading at Howl Arts at 6 East 1st Street in New York on September 27th at 19:00 hours.
Royalties will go to Cure Parkinson’s Trust.
Cilia, R., J. Laguna, E. Cassani, E. Cereda, N. G. Pozzi, I. U. Isaias, M. Contin, M. Barichella, and G. Pezzoli. 2017. "Mucuna pruriens in Parkinson disease: A double-blind, randomized, controlled, crossover study." Neurology 89 (5):432-438. doi: 10.1212/WNL.0000000000004175.
Giovannoni, G., J. D. O'Sullivan, K. Turner, A. J. Manson, and A. J. Lees. 2000. "Hedonistic homeostatic dysregulation in patients with Parkinson's disease on dopamine replacement therapies." J Neurol Neurosurg Psychiatry 68 (4):423-8.
Katzenschlager, R., A. Evans, A. Manson, P. N. Patsalos, N. Ratnaraj, H. Watt, L. Timmermann, R. Van der Giessen, and A. J. Lees. 2004. "Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study." J Neurol Neurosurg Psychiatry 75 (12):1672-7. doi: 75/12/1672 [pii] 10.1136/jnnp.2003.028761.
Stibe, C. M., A. J. Lees, P. A. Kempster, and G. M. Stern. 1988. "Subcutaneous apomorphine in parkinsonian on-off oscillations." Lancet 1 (8582):403-6. doi: S0140-6736(88)91193-2 [pii].
Weil, R. S., A. E. Schrag, J. D. Warren, S. J. Crutch, A. J. Lees, and H. R. Morris. 2016. "Visual dysfunction in Parkinson's disease." Brain. doi: 10.1093/brain/aww175.
Andrew J. Lees MD, FRCP, FMedSci presented at the second World Parkinson Congress in Glasgow Scotland and the third World Parkinson Congress in Montreal, Canada. He is currently Professor of Neurology at the National Hospital for Neurology and Neurosurgery, Queen Square, London and University College London.
Ideas and opinions expressed in this post reflect that of the authors solely. They do not reflect the opinions or positions of the World Parkinson Coalition®