The following first appeared on the site, tmrwedition. It is from an email exchange between Benjamin Stecher and Prof. Andrew Lees on his latest book, on the state of Parkinson’s disease research, and on what can be done to improve medical science.
Professor Lees is a Professor of Neurology at the National Hospital for Neurology and Neurosurgery and an advisor to the UK Medical Research council. He is the most cited researcher in Parkinson’s Disease research.
His latest book is Mentored By A Madman: The William Burroughs Experiment.
“In this extraordinary memoir, neuroscientist Andrew Lees explains how William Burroughs, author of Naked Lunch and troubled drug addict, played an unlikely part in his medical career.
Lees draws on Burroughs’ search for an addiction cure to discover a ground-breaking treatment for shaking palsy, and learns how to use the deductive reasoning of Sherlock Holmes to diagnose patients. Lees follows Burroughs into the rainforest and under the influence of yagé (ayahuasca) gains insights that encourage him to pursue new lines of pharmacological research and explore new forms of science.” (Source)
Proceeds from Mentored By A Madman go to support Parkinson’s disease research.
Over the course of your career you have seen substantial progress made in our understanding of the underlying pathology of Parkinson’s disease, yet, apart from DBS and a few agonists, that knowledge has failed to translate to any substantially better therapies, what do you think accounts for this gap?
In my opinion the most important basic scientific finding in the last 30 years has been the greater understanding of the circuitry of the basal ganglia with demonstration of direct and indirect output pathways which led on to the first trials of deep brain stimulation of the subthalamic nucleus, a surgical procedure which has improved the lives of thousands of people with Parkinson’s disease.
Millions of dollars have been wasted by drug companies due to a degeneration in the quality of medical departments and benchmarking within big Pharma.
In the last twenty years clinical pharmacological studies to evaluate new compounds have almost disappeared from university departments because of legal restrictions. I think hope lies now with small companies depending on venture capital that are prepared to take risks and work closely with academics and patients. It is highly unlikely that in the present risk averse climate L-DOPA would get a licence as a medicine if it were discovered today. A sick joke is that for big drug companies the best treatment is a placebo!
Medical science has created fields of hyper-specialists, yet very few people capable of seeing the forest through the trees. What do you think needs to be done to ensure that we encourage more generalists to emerge that are capable of seeing how all the various puzzle pieces might fit together?
In my view the greater problem is that the doctors dictating research agendas in medical science see fewer and fewer patients. Many chairmen of medicine in prestigious Ivy League universities have given up clinical duties entirely.
Trying to find the cause of Parkinson’s disease may not actually be the most important question and yet for many grant giving bodies it seems to be the only one that matters . What patients want are answers to some very elementary questions such as ‘what will I be like in five years time?’ and ‘ when should I start treatment?’ There are many examples in medicine of very effective treatments being introduced into clinical practice without the underlying cause ever being determined.
In your latest book, Mentored by a Madman: The William Burroughs Experiment, you recount the lessons you learned from the life and times of William Burroughs and his experiments with ayuahasca and other psychedelic drugs, what role do you think psychedelics might have in the treatments of neurological diseases like Parkinson’s disease?
Banisteriopsis caapi (the vine of the soul), one of the two ingredients of the psychedelic herbal concoction called ayahuasca, was used in the late nineteen twenties and thirties as a treatment for stiffness and slowness in post-encephalitic Parkinsonism. When synthetic anticholinergics were marketed, ‘Merck’s harmine’ as the treatment was called withered away. I am involved in a research program to reinvestigate Banisteriopsis caapi extract as a potential treatment for Parkinsons disease but regulatory red tape has made it very difficult to embark on new clinical studies.
Lysergic acid 25 has considerable dopamine receptor stimulating effects but its hallucinogenic qualities due to its action on serotoninergic receptors has precluded its trial so far in Parkinson’s disease. There is new pre-clinical evidence that small non-hallucinogenic doses of LSD 25 may have neuroprotetive properties and trials with low doses of the drug are being considered in both Alzheimers disease and Parkinson’s disease.
You seem to admire Burroughs’ spirit of self-experimentation, what would you say to patients looking to follow this approach?
I encourage patients with Parkinson’s disease to experiment but only in the context of clinical trials. I also strongly discourage desperate patients from visiting unscrupulous charlatans who make false claims for potentially harmful unproven medicines. Life is an experiment and many patients make very interesting serendipitous observations (a good example of this was the discovery by a patient that L-DOPA did not work when taken with dietary protein.)
What is your diagnosis of the field of neurology today? What treatments would you prescribe to it?
When my new research fellows start I tell them to read everything they can about diabetes mellitus. Where the diabetic researchers go we follow ten years later. I then tell them to read the history of great medical discoveries like the discovery of penicillin, the discovery of Helicobacter pylori as a cause for peptic ulceration and the L-dopa story. The biggest mistake a neurologist can make is to try to become a scientist. This should be left to the professionals! A neurologist is a field worker and an artist who collaborates with scientists and incorporates new knowledge into his daily practice.
If you had absolute power over the field of medicine, how would you reconstruct it?
I would try to encourage every doctor to devote a day of the working week to clinical research. A great deal can be learned from observational studies. Good doctors sometimes also have to break the rules. I have learned most in my career from mistakes, preferably those of others but also sometimes my own.
If you were diagnosed with Parkinson’s disease today, what would you do to ward off progression for as long as possible?
I’d try to keep positive, happy and motivated and deal with each day as it comes rather than worrying about the imaginary disease to come. I’d increase my coffee intake and even chew some nicotine gum once or twice a week.
What do you think are the most promising branches of PD research?
I remain keen on stem cell research because I believe that if we can physiologically restore the nigrostriatal dopamine bundle almost all the problems of Parkinson’s disease could be corrected.
The selective vulnerability of dopaminergic and noradrenergic neurones in PD needs molecular biological explanation. Basic neurochemical catecholamine research remains dear to my heart even though it is now a very unfashionable area in Parkinson’s disease
I do not believe that the Lewy bodies are markers for cell death and am less enthusiastic about alpha synuclein studies/ treatment.
I have an open mind about the relevance of the microbiome to Parkinson’s disease. Over the years several of my patients have spontaneously told me they believe their illness began in their gut.