Opinion, Berkeley Blogs

Hail and farewell to a legendary Cal grad

By David Presti

Alexander "Sasha" Shulgin, renowned graduate of UC Berkeley, died on June 2, 2014, a few days short of his 89th birthday. Shulgin was born in Berkeley on June 17, 1925. Both his parents were teachers. He received his bachelor’s degree (1949) and his doctorate in biochemistry (1955) from UC Berkeley. Except for some time spent as an undergraduate at Harvard and a stint in the US Navy during World War II, he lived his entire life either in Berkeley or nearby in the East Bay.

Shulgin’s doctoral research developed methods for the synthesis of amino acids containing chemical isotopes of carbon and nitrogen; such isotopically labeled molecules are useful for investigating details of metabolic pathways.

Title page of Shulgin's UC Berkeley doctoral dissertation.
Title page of Shulgin’s UC Berkeley doctoral dissertation (click for larger view).

Following his PhD, he pursued the study of pharmacology at UCSF, and worked for a few years in industry, first at Bio-Rad Laboratories and then at Dow Chemical. In 1960, in his 35th year, Shulgin experienced the powerful psychoactive effects of mescaline, a psychedelic chemical that had been identified from the peyote cactus in 1897 by German pharmacologist Arthur Heffter.

A century ago mescaline was the only chemical substance known to science that today would unequivocally be called a psychedelic. By 1960, when Shulgin experienced its effects, there were but a handful of additional psychedelically-active chemicals known: LSD (lysergic acid diethylamide) had been characterized by Albert Hofmann in 1943; psilocybin and psilocin were identified from Psilocybe mushrooms in 1958, again by Hofmann; lysergic acid amide had been identified, again by Hofmann, from the seeds of morning glories, used for shamanic healing ceremonies in Mexico; and DMT (dimethyltryptamine) had been characterized from several species of plants employed for their psychoactive effects by Amazonian shamans.

Now, in the early 21st century, there are well over a hundred chemicals known to be psychedelically active. Some say over two hundred. The majority of these were discovered through the investigations of Alexander Shulgin.

Shulgin’s initial encounter with mescaline was one of the most powerful and interesting experiences he ever had. Being a chemist, he was intrigued by the question of how a chemical could have such a profound effect on the mind, and decided that the study of how molecular structure relates to a chemical’s effects on body and mind was a topic deserving rigorous scientific investigation.

Taking the chemical structure of mescaline as his starting point, he made, over a period of years, numerous molecular modifications, and very carefully tested the effects of each one on himself. He published the results of his investigations in scientific journals – several hundred chemically unique compounds that had never before been synthesized and investigated, or even imagined.

This was truly heroic work. For the most part he worked alone, or with a very small number of close friends and colleagues. He used his own resources – supporting his work via lecturing and consulting - and did his chemical syntheses in a small laboratory he constructed behind his home.

Alexander Shulgin in his laboratory in 2007.
Alexander Shulgin in his laboratory, 2005

Neurochemists and psychopharmacologists appreciate the pioneering nature of Shulgin’s work. Practitioners of these disciplines in years to come are likely to have an even greater appreciation for his contributions. Work of this nature may never again be possible. Shulgin so thoroughly explored such a vast array of chemical structures related to the neurotransmitters serotonin, dopamine, and norepinephrine, that the field is to a large extent fully cultivated.

Many discoveries in science happen when a confluence of ideas and technological capabilities make it ripe for them to happen. If such-and-such an individual or individuals had not made a particular discovery, then someone else perhaps would have sometime soon. Joseph Priestley and Antoine Lavoisier both appreciated around the same time that there must be a previously unrecognized elemental substance involved in combustion – the discovery of oxygen. Charles Darwin and Alfred Russel Wallace independently came up with the notion of evolution through natural selection. If Albert Einstein had not created the special theory of relativity, some other brilliant physicist of the day probably would have. If a cadre of physicists working at Los Alamos in the 1940s had not built the world’s first fission bomb, it would have been done elsewhere at some point. If Francis Crick and James Watson had not discovered the double-helical structure of DNA, someone else (Rosalind Franklin or Linus Pauling, for starters) soon would have.

For other discoveries it is not so clear. If Einstein had not come up with the general theory of relativity – the description of gravity in terms of a non-Euclidean geometry of spacetime – it’s not at all clear that someone else would have thought of this. If Albert Hofmann had not synthesized and then tested on himself the diethylamide derivative of lysergic acid obtained from an extract of ergot alkaloids, it is likely that the world today would not know the effects of LSD. If Sasha Shulgin had not shuffled methoxy groups around the phenethylamine ring of mescaline and then had the wit to place substituents like bromine, iodine, and alkylthios in what he called the “magical 4-position” of the 6-carbon ring, followed by careful adventurousness and focus of intention in the testing of these molecules on himself, many interesting chemicals with novel effects on the mind would have gone undiscovered. It is possible no one else would have done these things in the way required to make the discoveries Shulgin made.

These discoveries concerning relationships between specific chemical compounds, brain physiology, and mental experience are, by all objective criteria, worthy of the very highest academic kudos: National Academy, Royal Society, Nobel Prize kind of stuff.

A very well deserved Nobel Prize in Chemistry would have been one shared by Albert Hofmann and Alexander Shulgin: Hofmann for his discovery of LSD and its effects, contributing to kick-starting the field of biological psychiatry, and a whole lot of other things; and Shulgin, for pioneering the study of chemical-structure relationships to biological activity and mental experience in humans.

However, due to the complex social and legal circumstances that followed the emergence of the use of psychedelic chemicals in the wider culture, such honorific considerations are off limits. The institutions of academic honors, and the larger society in which they are embedded, have not yet figured out how to balance such complexities.

Shulgin’s work in pharmaceutical chemistry – the logic of his molecular modifications and his chemical syntheses – published in academic journals of medicinal chemistry and collected together in books (1), has influenced and will continue to influence others in the continuation of this kind of scientific work. Insights of his that may inspire whole trajectories of structure-activity research soon enough become anonymous, melting into the stream of knowledge of the field. Thus is generally the way of scientific progress.

However, there is an iconic cultural presence to Shulgin and his work that transcends that which happens in most cases of scientific endeavor. He is revered not only as a genius of pharmaceutical chemistry, but also as a chemical artist of the highest caliber. In his conversations and lectures about chemistry, he generated enthusiasm for the subject, speaking of molecules as having personalities, and describing the doing of laboratory chemistry as a meditation (2). His molecular creations will continue to unfold in inspiring new directions of neurochemical exploration, and very importantly, application in clinical therapeutics (3). Happily, research in psychotherapeutics is returning anew to the powerful capacities of the class of chemicals Shulgin spent his life investigating.

Also very importantly, Shulgin was and is revered as a warm, joyful, and considerate human being, giving of his time and energy to his community, locally and globally. His science and his humanity were impeccable. There is a largeness to Sasha Shulgin’s legacy of contribution to science and society that is beautiful and wonderful to witness. Ave atque vale.

Notes and references:

(1) Alexander Shulgin & Ann Shulgin (1991) PiHKAL (Phenethylamines I Have Known and Loved). Transform Press, Berkeley CA; Alexander Shulgin & Ann Shulgin (1994) TiHKAL (Tryptamines I Have Known and Loved). Transform Press, Berkeley, CA.

(2) Alexander Shulgin speaking on chemistry as meditation in 2006 (YouTube video).

(3) MC Mithoefer et al. (2011) The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology, 25: 439-452.

MC Mithoefer et al. (2013) Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine-assisted psychotherapy: a prospective long-term follow-up study. Journal of Psychopharmacology, 27: 28-39.

T Shroder (2014) Acid Test: LSD, Ecstasy, and the Power to Heal. Blue Rider Press, Penguin.

See also:

Many obituaries of Alexander Shulgin have been written. An excellent one can be found at erowid.org.

Photo credits: David Presti.