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Hanging Out With The Molecules

Andrew Lees

 In 1953, two years after he had shot Joan Vollmer, his common-law wife, in a drunken William Tell routine at the Bounty Bar in Mexico City, William Seward Burroughs embarked on a South American quest in search of yagé, a hallucinogenic vine used by the shamans of the Upper Amazon for healing and divination. In Puerto Limon, under its hallucinogenic influence, he saw neon blue flashes, a diaspora of multi-racial travellers; and he caught his first glimpse of the “Composite City”. In letters written to Allen Ginsberg from Pucallpa on the Ucayali River he reported yagé’s capacity to extend consciousness, induce automatic obedience and alter mindset. He also warned his friend of its propensity to derange the senses and bring about acute states of sensitivity that were beyond description.

I must give up the attempt to explain, to seek any answer in terms of cause and effect and prediction, leave behind the entire structure of pragmatic, result seeking, use seeking, question asking Western thought.

I first heard about yagé as a sixteen-year-old reader of Richard Spruce’s Notes of a Botanist on the Amazon and the Andes, compiled between 1849 and 1864 and posthumously published by his friend Alfred Russel Wallace in 1908. It was five years later that I first began reading Burroughs and resolved to become a neurologist. Reading Spruce convinced me that the natural world and its plant kingdom held most of the secrets to understanding and manipulating the chemical systems of the human brain. Spruce was the first person to identify the plant source of yagé and he also documented its orgiastic use by the Tariana tribe. He even tried yagé himself “but found the taste so unpleasant that I did not venture on a second”. In fact, virtually every naturalist who wrote about yagé before the 1920s had tried it. In 1905, the Colombian naturalist and pharmaceutical chemist Rafael Zerda Bayón administered a preparation of yagé to a soldier far from home who reported visions of his sister’s death, which was confirmed by letter a few weeks later. Convinced of yagé’s power to awaken telepathic capacities, Zerda Bayón suggested the name telepathine for its active ingredient, and that name was retained when the active ingredient was first isolated in 1923 by another Colombian chemist, Guillermo Fischer Cárdenas.

From the early 1920s, the Merck pharmaceutical company in Darmstadt began to investigate the medicinal properties of a number of New World flora. Extracts from the woody stems of the yagé vine were sent to Germany by chemists at the University of Bogotá and some of this material was handed on to Louis Lewin, a Berlin pharmacologist known for his work on mescaline. Lewin discusses yagé in his magisterial book Phantastica, Narcotic and Stimulating Drugs (1924). Lewin named the active ingredient banisterine and went on to suggest that its pharmacological properties might offer hope for the treatment of some of the thousands of brain-damaged survivors of the sleepy sickness (encephalitis lethargica),which spread across the world between 1915 and 1926. Shortly before his death in 1929, Lewin delivered a paper of his own findings with banisterine at a meeting of the Berlin Medical Association. His presentation included a convincing cinematographic recording of three treated patients with neurological handicap due to sleepy sickness. Lewin’s colleague, Kurt Beringer, a neurologist and psychiatrist working in Heidelberg, followed up this suggestion by giving a subcutaneous injection of 20 mg of banisterine to each of fifteen patients with post-encephalitic Parkinsonism. Their stiffness and slowness improved for up to a week but there was no benefit to the tremors. Unfortunately not all physicians found it to be efficacious and some suggested that the early positive reports could be explained by the power of suggestion.

Burroughs’s interest in yagé seems to have arisen from his belief in the Magical Universe.  This was “a universe of many gods, often in conflict. The paradox of an all-powerful, all-seeing God who nonetheless allows suffering, evil, and death, does not arise.” The advantage of inhabiting this Magical Universe was that it enabled one to escape the confines of “Control”. Yagé offered direct access to the Magical Universe. Burroughs had read Phantastica at Harvard and knew about Spruce. In letters to Allan Ginsberg written in 1952 he hinted that he had first attempted to get hold of yagé on his first trip to South America the previous year. “Did not score for Yage [sic]’ he told his friend, ‘I think the deal is top secret. I know the Russians are working on it, and I think U.S. also. Russians trying to produce “automatic obedience,” have imported vast quantities of Yage for experiments on slave labor. I will score next trip.”

Dr Lewis Wohlberg, one of his former psychiatrists, seems to have encouraged this interest. He wondered if the Cold War superpowers hoped to have “armies of telepathy-controlled zombies marching around”. By May 1952 he wrote again to Ginsberg: ‘No doubt about it. Yage is a deal of tremendous implications, and I’m the man who can dig it.” In 1953 he announced triumphantly: “Yage is it.” The seven-months-long expedition he undertook in 1953 issued in a book of notes and letters to Ginsberg subsequently published as The Yagé Letters, which has since gone through multiple editions. In these letters he presented himself not only as a mystic and spiritual quester but also as a whistleblower on the activities of the Cold War superpowers.

All of this came back to me in 1977 when a drug called Deprenyl was smuggled in from Budapest by Merton Sandler, a professor in chemical pathology at Queen Charlotte’s Hospital in West London. I was a young neurologist with an interest in Parkinson’s disease and with two colleagues I agreed to be a guinea pig to explore the effects of Deprenyl. Self-experimentation at that time was unorthodox but not unacceptable practice. It was a way of achieving medical fame and avoiding mind-numbing red tape. Deprenyl, like yagé, prevented the breakdown of cerebral chemical messengers by inhibiting the action of a brain enzyme called monoamine oxidase. It was particularly effective at preserving dopamine, the chemical that fails in Parkinson’s disease. We all took 10 mg of Deprenyl each morning for a week and experienced fragmented sleep with vivid waking dreams, feelings of boundless energy and subtle aphrodisiac effects. We then took escalating doses of tyramine to show that it could be used safely without the dietary restrictions of cheese, pickled herrings, Chianti wine and fava beans needed with some similar drugs used to treat depression. In contrast to yagé we experienced no hallucinations and were sufficiently pleased with the results to proceed to clinical trials and demonstrate its efficacy and safety in the treatment of Parkinson’s disease. From this moment on, Burroughs became a kind of bad angel at my shoulder, repeatedly luring me into dialogue with him. Here was a self-experimenter who documented his experiences with a range of psychoactive substances with no small degree of rigour. At the same time, Burroughs’s status as an addict, his investment in his own esoteric cosmology and his often-expressed hostility to medicine were warnings. But the shadow of a different part of his history fell over my next major piece of Parkinson’s research.

In the spring of 1956, Burroughs had travelled from Tangier to England to be treated for opiate dependence. He sought out a physician called John Yerbury Dent (1888-1962). Dent was famous for using a drug called apomorphine in the treatment of alcoholism. Boiling morphine with hydrochloric acid in the absence of oxygen creates the apomorphine molecule, but the drug is free from narcotic effects. At first Dent had thought that it worked aversively by inducing vomiting whenever it was combined with alcohol. But by the time Burroughs came to see him he understood that it actually worked by stimulating the brain stem. Burroughs’s treatment began with injections of one-twentieth grain of apomorphine every two hours day and night. He found he was able to give up the thirty grains of morphine he was taking and with relatively little discomfort apart from insomnia. After five days he was discharged from the clinic to his West London flat with three tubes of apomorphine tablets in case of delayed withdrawal symptoms. Apomorphine had dissolved away his dependency on morphine and led to an intensified perspective and increased libido.

Burroughs later wrote enthusiastically in Naked Lunch about Dent’s integrity and empathy and his innovative drug rehabilitation programme:

The vaccine that can relegate the junk virus to a land-locked past is in existence. This vaccine is the Apomorphine treatment discovered by an English doctor … I found this vaccine at the end of the junk line … suddenly my habit began to jump and jump. Forty, sixty grains a day. And it still was not enough. And I could not pay … The doctor explained to me that apomorphine acts on the back brain to regulate the metabolism and normalize the blood stream in such a way that the enzyme system of addiction is destroyed over a period of four or five days … I saw the apomorphine treatment really work.

Apomorphine took away the biological need for morphine without inducing dependence. It steadied the system, leaving no trace. In Burroughs’s words it was like a dutiful policeman that did its job and then left. Soon after Burroughs’s treatment programme was completed, Dent’s hunch that apomorphine had specific chemical actions in the brain was scientifically confirmed, but it never took hold as a routine treatment for addiction. Crucially for neurologists, it was shown to act on the brain by opening the dopamine receptor lock, which meant that Parkinson’s patients could use more of their own dopamine for longer. My hope was that in time apomorphine would become part of the clinical armoury against Parkinson’s symptoms.

More and more people with Parkinson’s disease were noticing that their drug response had become brittle. The shakes were back and some described spells during the day when it felt as if they were clad in a suit of armour. They clumped through treacle, their faces froze and their speech would fade to a monotonous slur. New approaches were urgently needed to relieve their distress.

Burroughs had described how apomorphine had dissolved “the layers of grey junk rooming house smell” and led to an intensified perspective and increased libido. It was with some trepidation that I returned to self-experiment and injected myself with 1 mg of apomorphine combined with domperidone, a substance known to prevent the vomiting associated with apomorphine. It was with surprise and bemusement that I experienced a drawn-out yawn and an erection, two phenomena I had not linked with dopamine, and some mild sedation and lightheadedness. Trials then began on McAlpine ward at the Middlesex Hospital, where we were able to show that intermittent rescue injections and continuous infusions of apomorphine dramatically alleviated Parkinsonian “switch offs”. Not long afterwards, the drug was licensed for the routine treatment of Parkinson’s disease.

In Deposition: Testimony Concerning a Sickness, Burroughs explores the machinery of addiction. He writes about monopolies and controls and a pyramid of dependencies created by the consumerism of modern America:

I am not an addict. I am the addict. The addict I invented to keep this show on the junk road. I am all the addicts and all the junk in the world. I am junk and I am hooked forever. Now, I am using junk as a basic illustration. Extend it. I am reality and I am hooked, on, reality.

In 1999 the wife of a patient with Parkinson’s disease accused me of turning her husband into a drug addict. At first, the suggestion that dopamine replacement prescribed for a neurodegenerative disorder could lead to misuse seemed absurd. Deep brain dopamine circuits in the limbic brain were now known to be the final common pathway for habit formation but in my research I had remained fixated on motor programmes and was oblivious to Burroughs’s “algebra of need”. Her husband was a 46-year-old university lecturer who was taking high doses of l-dopa (the precursor amino acid that acts to replenish dopamine in the brain) with apomorphine rescue injections for Parkinson’s disease. She complained that in the last year it had been like living with a horrible deceitful stranger, obsessed with the euphoric effects of his drugs. He binged on food, spent money irresponsibly; cross-dressed and acted out sexual fantasies with a sex therapist. Sometimes he disappeared and was brought home hallucinating by the police or a concerned member of the public. I attributed her husband’s behaviour to his terror of “switching off”. When a second similar case occurred a colleague and I took more notice and started to specifically enquire about drug overuse among the patients attending the out-patient clinic. Over the next year we identified a further thirteen individuals who, despite escalating doses of l-dopa, complained that their treatment was becoming less and less effective. Panic attacks, autonomic storms of profuse sweating and episodes of profound incapacity occurred in these individuals many times a day. They became slaves to their medication. When their craving for higher and higher doses of medication was thwarted we learned that they visited other doctors’ surgeries. Distraught families complained of patients’ Jekyll and Hyde mood changes, their morbid jealousy, reckless gambling and compulsive sexual behaviour and their intense and idiosyncratic fascination with repetitive tasks and stereotyped rituals (similar to “crack dancing” after cocaine). Some patients became estranged or divorced from their spouses and one ended up in jail.

Further inquiry led us to an Internet demi-monde of blogs where contributors described a dream world of “dopamine highs”. Body-builders were using herbal sources of dopa and describing manic aphrodisiac effects. Recreational drug users were describing enhanced colour vision and pain sensitivity and a “return to childhood”, where the world was seen with enhanced beauty and innocence. On a patient message board one of our patients had written:

Had an insane high on 250mg l-dopa, felt like I was king of the earth, sex drive way above my normal levels and feels as if it is still increasing, sensations all take longer and the feel is multiplied, fantastic dreams that are so amazingly vivid that makes it feel as if I have another world to go to when I sleep.

Burroughs had described a situation where a drug was badly wanted but no longer made him feel better. Something similar was happening to our patients with l-dopa. Halving the dose over two weeks in our first patient reduced his risky behaviour but led to profound unhappiness:

I have stopped cross-dressing since I reduced my daily dose of dopa and find this to be much more socially acceptable. But privately I must admit that I rather miss my skirts as I used to get a blast of ‘feel good factor’ when I put them on, that overrode any aches and pains I may have had at that time.

The maladaptive sensitisation of the brain’s reward circuits in these susceptible individuals has provided a new and as yet largely unexplored paradigm for the understanding of addiction. It is not just a matter of the pharmacological properties of drugs.

Burroughs’s space-time travel in search of a magical universe sustained me on those days when treating the neurologically handicapped was not enough to fill my heart and mind. The Beach Press edition of his Apo-33 Bulletin: A Metabolic Regulator (1966) is a grand remonstrance against all the false information spread by pharmaceutical companies. Burroughs’s barely legible mark-ups, scrawled in the margins, read like his prescription for society’s ills. In The Job, a series of interviews by Daniel Odier, Burroughs explains why he believed his pleas for the apomorphine “cure” had fallen on deaf ears:

Pharmaceutical researchers are told what research to pursue by vested interest, which gives orders to the American Narcotics Department. Billions for variations on the Benzedrine formula, for tranquilizers of dubious value, not ten cents for a drug that has unlimited potentials not only in treating addiction but in handling the whole problem of anxiety.

Burroughs came to see most academic medical journals, including the British Journal of Addiction, as part of the conspiracy of vested interests that would bend the truth. Institutional corruption by Pharma is now a matter of grave concern. The successful hijacking of academic journals means that it is no longer possible to take the results of many clinical trials at face value or to believe the conclusions of authoritative treatment guidelines. Burroughs was right to say that sex, food and money acted on the same brain reward circuits as heroin. Even compulsive water drinking is now recognised as a disease.

Successive British governments have attempted to curb the explosive increase in the use of Class A drugs with more and more punitive and draconian legislation. Obstructive bureaucracy, an adversarial culture and empty governmental promises of more funding have eroded the creative freedom in which Dent flourished and which later allowed me to make breakthroughs in the field of Parkinson’s disease. Even before he met Burroughs, Dent sensed this might soon be coming to an end. “Soon,” he wrote to his illustrious patient, “we [British doctors] will only be able to prescribe what is seen to be permissible by Whitehall and Anslinger’ [the first commissioner of the US Federal Bureau of Narcotics].”

The heroic era of neuropharmacological research ended long ago and self-experimentation is now denigrated for its danger and lack of objectivity. But Burroughs’s writings taught me that there are specific things that first-hand experience can lay hold of that are therapeutically important. His hope that other aporphines more potent and less toxic than apomorphine could be synthesised and find wider medical application has continued to inspire me. The “hard man of Hip” helped me to understand that if I was to make my mark in science I would need to be a lamp unto myself, ride my luck and stick to my guns. He taught me to fly crookedly in my curiosity for cures.

I wish to acknowledge the help of Neil Vickers, Warwick Sweeney, James Grauerholz, Mike Jay, Peter Kempster, Isabelle Aubert-Baudron, Susie Sainsbury and Bill Morgan.


Andrew Lees is professor of neurology at the National Hospital for Neurology and Neurosurgery, Queen Square, London and University College London. His most recent books include The Hurricane Port: A Social History of Liverpool (Random House, 2011), William Richard Gowers 1845-1915: Exploring the Victorian Brain (OUP, 2012) and Alzheimer’s: The Silent Plague (Penguin E-book, 2012.)