James Lee and the Mysterious No. 2
Self-experimentation has played a fundamental role in the development of psychopharmacology with notable discoveries made by Albert Hofmann (LSD, psilocybin, and psilocin), Gordon Alles (MDA and amphetamine), Fredrich Sertürner (morphine), Joseph Priestley (nitrous oxide), Alexander and Ann Shulgin (too numerous to list) and countless others. In this blog, I plan to discuss a number of these fascinating cases. However, there is one lesser known and more complex case I wish to start this blog off with. It is the story of James Sidney Lee (1874-1951), born in Redcar, England, set in the late 19th and early 20th century[1]. A number of features of Lee’s story are distinct and have long fascinated me. For one, James Lee was not a trained or practicing scientist but a mining engineer. Another distinct aspect is the fact that Lee’s discoveries have never been confirmed and tragically may be lost to history- but before getting to that, let’s take a closer look at Lee’s story.
The work of James Lee comprises a single book titled “Underworld of The East: Being Eighteen Years’ Actual Experiences of the Underworlds Drug Haunts and Jungles of India, China, and the Malay Archipelago” and was first published in 1935, by Sampson, Low, Marston & Co., London[2]. One of the remarkable things of this work is Lee’s views on psychoactive drugs, their use, and many other matters. Many of his views seem to me remarkably modern, rational and progressive. With a few exceptions[A], he comes across as a well-intentioned, open-minded and caring person.
Due in part to his modern and progressive views on drugs and social matters some have even questioned the book’s authenticity. For example, author and drug historian Mike Jay[A] wrote an introduction to a modern printing of “Underworld of the East” by Green Magic Press[3] that Jay himself organized. Jay describes his initial suspicions regarding the genuineness of “Underworld of The East” when first reading an excerpt of Lee’s work in the anthology “The Drug User: Documents 1840-1960” edited by John Strausbaugh and Donald Blaise. In his introduction, Jay states his doubts as to the authenticity were ultimately allayed by locating an original “1930’s cloth-bound volume typical of travel memoirs of the period”, encouraging any skeptics to “locate the yellowing, age-spotted copy in the British Library.”[3] First edition copies of Underworld of The East can also be found for sale online. Even more convincing Jay has since managed to track down a death certificate, his will and a surviving relative[1].
“Underworld of The East” describes Lee’s captivating 18 year-long adventure traveling as a mining foreman around the British colonies of Southeast Asia from 1894-1912. His adventures are fueled by various psychoactive substances including: cocaine, morphine, opium, Cannabis indica, hashish, bhang, ganja and tobacco as well as caffeinated and ethanolic beverages. Fascinating details of the local drug scenes and local cultures are offered. As a pharmacologist I enjoy the articulate reports on the pharmacological effects of various psychoactive drugs, along with noteworthy descriptions of harm reduction tactics including cleaning of injection equipment, tapering schedules to minimize withdrawal, and cycling of specific drugs to minimize withdrawal and avoid developing too strong a habit with any one. Lee describes how he sources these substances, as well as interactions with fellow consumers. “Underworld of The East” is a fascinating account of drug use in the late 19th and early 20th century but has much more to offer including tales of malaria, man-eating tigers, motorcycles, and confrontations with greased up and half-naked criminal thugs. It is, however, his self-experimentation with various exotic plants that I personally find most remarkable. Lee’s interest in psychoactive drugs and medicine led him to seek out what he called “strange plants and roots”, which he prepares decoctions from, and then dries to powders for self-experimentation. Lee collected some of the plants himself, but also had a standing trade agreement (opium for plants) with many locals who collected plants for him. Like a one man pharmaceutical enterprise, the extracts prepared were first tested on rats and then, if all clear, on himself. Just two of these plant extracts, which he calls No. 1 and No. 2, are described in detail. Both were plants obtained in Sumatra.
No. 1
In chapter 18, Lee describes preparation of extract No. 1 from “a very peculiar plant”. Satisfied by his rodent safety studies, he carefully starts to test increasing doses of No. 1 on himself describing “a slight intoxication and a feeling of lightness and increased energy”. At a somewhat higher dose he describes “At first it made me quite drunk as far as my movements are concerned, but clear mentally.” In chapter 19, Lee continues his experiments writing “I had been steadily taking the new drug during the afternoon, and I was intoxicated in an entirely new and strange manner.” Continuing his experiments that day, Lee reports an intense hallucinogenic experience involving No.1: “The trees in the jungle alongside assumed grotesque shapes, and faces peered out at me from the foliage.” “Spirit-like faces and forms of many nations and of all periods.; men and women of noble and beautiful appearance passed before me.” “I knew they were only visions” and with eyes closed “I was living through years of time and former periods of my life returned and I lived them again not only as a memory but actually, with every long-forgotten detail returning with startling clearness.”
Lee’s account on his experience with No. 1 is fascinating, but there are confounding issues with speculating on any unique pharmacological mechanism of action. The largest confound is that his report is not just describing the experience of No.1 but rather No. 1 in combination with cocaine and morphine and later the addition of hashish. Cocaine can be hallucinogenic at high doses (and extended use periods) and in fact throughout the book Lee describes intense hallucinogenic experiences including encounters with the “spirit world” from use of cocaine combined with hashish and other drugs. Accordingly, this is not the cleanest psychological canvas to assess the clinical pharmacology of a novel drug. Still, one could argue, Lee as an experienced drug user, concluded the experience to be unique and thus likely in part the result of No. 1. However, the novelty of knowing he ingested a new plant extract, coupled with cocaine mania, could easily lead him to ascribe any inherent uniqueness of this experience to the effects of this extract. Lee himself acknowledges every drug experience is unique. Thus, I don’t think we can conclude much from this description of No. 1. That said, if it was hallucinogenic, one interesting possibility is the deliriant Datura metel. D. metel is a well-known deliriant plant containing scopolamine, used for various medicinal and ceremonial purposes by humans and has been documented to have grown and been used by humans in this region of Asia around this time.[C] Furthermore the appearance of D. metel could certainly be called “peculiar” and common names like thornapple and devil’s trumpet illustrate this. While Lee does not describe any of the common anticholinergic side effects, we would expect with consumption of a deliriant including constipation, pupil dilation, sweating, dry mouth, and urinary retention, his use of other substances with overlapping side effects could have masked these or made him less aware. A bigger issue with this hypothesis is his description of the visual hallucinations. Lee writes “I knew they were only visions”; the visual hallucinations from deliriants typically are what can be called “true hallucinations” where one lacks this awareness.
After the description of these experiments (Ch. 19), Lee describes preparing a larger stock of No. 1 by boiling the roots of the plant (a detail absent when he describes the initial preparation) which he evaporates into a powder and saves in sealed bottles. Sadly, no subsequent descriptions of experiments with No. 1 are provided after this. Ultimately, while interesting, I’m not sure what to make of the No. 1 reports.
No. 2
Like No. 1, the plant used to prepare No. 2 originated in a plants for opium trade. Lee was immediately “struck with” this plant, describing “It was a plant carrying many pods, which were full of seeds.” He collected the seeds and boiled them, straining the resulting dark brown liquor which had a “strong aromatic flavour” which he concentrated to a “dry powder”.
Next, Lee writes “I tried a little of it on my rats, mixed in their food, and carefully took note of the results.” After a few days without any notable effects with the rats, Lee tries No. 2 on himself, gradually working his way up to active levels. He continues his experiments to find No. 2 blocks the psychological and physiological effects of cocaine. He goes on to find No. 2 is a powerful antidote to the effects of alcohol, cocaine and hashish. He reports, however, “It did not seem to have so much power over morphia.” Furthermore, he describes “it would remove pain of most kinds. It would reduce the temperature if too hot, produce a feeling of warmth when too cold, and remove fatigue.” He elaborates that “It seemed to have the power of bringing the bodily condition back to normal in every case, and producing a feeling of perfect happiness and content.” He also describes using No. 2 to avoid withdrawal and cravings of drugs he was using: “No matter what drug I was using with the aid of No. 2 I could give it up quite easily.” To give you some sense of his opinion on this material, Lee refers to No. 2 as the “elixir of life”, a name for an immortalizing material long sought by alchemists.
In the final chapter, Lee describes giving up his drug use for good with the assistance of No. 2. This final farewell was in response to the passage of the Dangerous Drug Act (1920) in the UK where he was living at that time. A potentially smart move as this act led to, like all attempts at small molecule prohibition, a self-fulfilling prophecy of harm maximization. I wish to try to explain the well-meaning disaster of (some) small molecule prohibition to future readers, whom I hope have had a spark of rationalism and view such efforts in the way most Americans today view the disastrous attempts of US alcohol prohibition. The best way I can describe the harmful consequence of small molecule prohibitions is through analogy.
Picture a group of firefighters, armed to the teeth with weaponry, blinded by an amalgamation of well-intentioned confidence and an insatiable fear and loathing for fire. They tramp around in a chest thumping rampage searching for and attempting to extinguish fires. The only issue is they are attempting to use gasoline as an extinguishing agent. Predictably the flames rise in response and people at the wrong place and time get burned. The firefighters and their supporters point to the growing flames and their victims as a monument to justify more fear, more loathing, and the obviousness and urgency for more firefighters, heavier weaponry, and of course more gasoline. This positive feedback loop of destruction repeats until nearly everyone gets scorched to some degree or another. The only hope is society eventually wakes up to this absurdity, when they finally hear the voices from the growing chorus of victims and their allies crying out through the crackling flames. At that point society can move on to hunting witches, satanists, immigrants, religious minorities, or some other scapegoat. Hey, it's not my view of a productive game, but journalists, politicians, and bureaucrats need to make a living too. And as long as we all act like fiddles can we really blame them for playing us?
But wait, incredibly, the reality of this situation is even more desolate, bizarre and senseless. We must also imagine these firefighters themselves enjoy certain forms of sanctioned fire while insatiably fearing and wishing to stamp out other forms. This distinction is not based in logic, science or rational discourse – rather historical gobbledygook, devised from the passionate delusions of a few wide-eyed arrogant lunatics with their own agendas. Thus, we can picture a typical night where a group of firefighters relax from a long day of eradication, warming themselves around a properly regulated fireplace, discussing the evils of those who enjoy the dangerous illicit fires like candles and bonfires. Above the fireplace on the mantle sits a small sign with the phrase ‘Shoot Your Local Candle Dealer” and another just next to it that reads “Land of the Free”.
Ok, back to James Lee. We are just about done, I promise. Lee’s descriptions of No. 2 are captivating and raise several questions. First, are the effects of No. 2 described, a true pharmacological response or a placebo response? There are reasons that the reports of No. 2 are more convincing to me than No. 1. Unlike No. 1, Lee describes repeated use of No. 2 in detail, including its use alone without other substances, in multiple contexts and importantly with what appears to be consistent effects. Lee writes “I have proved the power of this drug conclusively to my own satisfaction”. While we cannot be confident without additional experimentation, it very well may be that No. 2 has real pharmacological effects. Humans have certainly discovered the pharmacological effects of substances with self-experiments or without double blind studies (every first in class antidepressant for that matter was a serendipitous observation). I thus believe we should take Lee’s claims seriously here and consider the possibility that No. 2 has some interesting therapeutic potential should we ever encounter some.
Taking Lee’s descriptions as accurate we must then accept that there is a broad-spectrum treatment for intoxication, substance use disorders, a powerful non-addictive painkiller, a “contentogen” and a possible thermoregulating medication out there contained in a plant growing deep in the Sumatran jungle. The next obvious question is what is the “elixir of life” plant described by Lee?! Unfortunately, we have very little to go on aside from a description of “notable seed pods” and an “aromatic flavour” of the extract. Interestingly Mike Jay wrote of an individual named James Gilman who had tried unsuccessfully to track down the plant source of No. 2 [3]. To any ethnobotanists out there it is surely worth continuing this pursuit, although it may be difficult. Still, I can’t help but wonder if this plant has since gone extinct. The last of it hacked down or burned to ashes to clear space for another palm tree monoculture or cattle ranch. Billions of years of evolution, gone forever, in a flash, along with No. 3, No. 4, ….and No. 9,999. How many No. Xs have been lost all over the planet in exchange for a smear of Vegan butter on our avocado toast, a tasty burger, or some other minor convenience?
This brings us to a few final thoughts. One I think Lee would appreciate is on the value of the natural world to humanity. In Chapter 8, Lee expounds on the importance of natural products to medicine: “In the great islands of Borneo, Sumatra and New Guinea, there are thousands of square miles of unexplored territory. What secrets must there be hidden in those jungles? The Pharmacopeia will never be complete until every plant and flower and root has been tested.” I couldn’t agree more, though I would extend this to include all life on our planet. Nature, by any conceivable measure, holds the crown for greatest organic chemist of all time; having synthesized every other organic chemist herself it's hardly a real competition (even for EJ Corey).
Which brings me to one final point, we humans and our creations are arguably “natural”. The distinction we make between natural and synthetic is an anthropomorphic construct that I doubt would be immediately recognized by alien zoologists upon first observing us. But in no way should this justify the belligerent destruction of the rich diversity of other species, for convenience, comfort, power and whatever else drives us to produce and create. How do we improve our behavior? I wish I had the answers, but sadly I don’t. And I’m not pointing fingers; we are all guilty. What I do know is we should each be doing everything we can to recognize, preserve and facilitate investigations into the diversity of biological life. In addition to the ethical aspects (these are all our relatives after all), there is a selfish reason – these species contain powerful biochemical and chemical tools, along with scientific secrets of incalculable value to us. We can and must strive to improve life for all on this plant. Ultimately, this cosmic blue spaceship we call home won’t last forever. The future role of our species and all life on earth in the greater universe will ultimately depend on the knowledge and tools hidden within us all and thus our ability to access these secrets. It seems a bit reckless to destroy that future for some avocado toast.
Footnotes:
[A] I highly recommend Mike Jay’s work on James Lee which can be found in the references list. I also recommend everything else Mike Jay has written.
[B] Mike Jay has discussed this fact in his introduction to the modern printing of Underworld of the East. In general, despite some language used that is typical of the time, Lee comes across as having notably progressive views on his fellow humans for the time (which let’s be honest is not a very high bar). That said there are a few unfortunate instances of clear racism (e.g., in Chapter 31 while describing his travels to the West Coast of Africa) which to put it mildly is repulsive to read. While I suspect despite being fairly progressive, Lee was still a product of his time, which does not excuse this. It's unfortunate and I feel it must be acknowledged.
[C] While there has been some debate, the current leading theory is that D. metel originated in the New World Americas and traveled to Asia sometime prior to Columbus’s voyage to the New World in 1492. It has been speculated this oceanic journey was facilitated by early human explorers. In this case the distribution of D. metel would be similar to that of the sweet potato Ipomoea batatas which is believed to have made its way from the new world to Polynesian Islands on human ships around 1,000 AD.
References:
[1] Jay, Mike. The Lost World of James Lee. https://mikejay.net. 2024. Link: https://mikejay.net/the-lost-world-of-james-lee/?utm_source=rss&utm_medium=rss&utm_campaign=the-lost-world-of-james-lee
[2] Lee, James. Underworld of the East: Being Eighteen Years’ Actual Experiences of the Underworlds Drug Haunts and Jungles of India, China, and the Malay Archipelago. Sampson, Low, Marston & Co. London. 1935
No. 1: Chapter 1, 18, 19 and 25
No. 2: Chapter 22, 23, 25, 30, 31, 37 and 38
[3] Lee, James. Underworld of the East: Being Eighteen Years’ Actual Experiences of the Underworlds Drug Haunts and Jungles of India, China, and the Malay Archipelago. Green Magic. London. 2000.
Additional publications discussing James Lee:
Jay, Mike. Orient Excess: James S Lee’s Drug Memoir Underworld of the East. The Quietus. 2022. Link: https://thequietus.com/articles/31007-underworld-james-lee
Jay, Mike. Psychonauts: Drugs and the Making of the Modern Mind. United Kingdom, Yale University Press, 2023