The Brotherhood of the Screaming Abyss (63 page)

Even then, the specimens for export had to be prepared for suboptimal conditions during transport and the horrible things that were done to them on the receiving end by the USDA plant import authorities. Our method was to buy a large woven basket at the market, about three feet tall, with a lid that could be lashed on. We cleaned and washed all the cuttings, wrapped them in damp muslin, and put those in the basket, along with packets of seeds that needed to remain moist. After lashing up the basket, I treated it as part of my luggage. In Lima, nobody even looked at it except for a young policeman with an AK-47, who took one desultory glance inside and waved me through.

In Los Angeles, it was a different story. I dropped off the collections along with our documents at the USDA import facility, where the staff unwrapped all the collections and fumigated them. I had presented phytosanitary certificates and requested that the collections not be fumigated, but the staff didn’t listen. I really believe that the USDA does its best to kill all live plant imports; that’s their job, as they see it. Once the cuttings had been unwrapped and fumigated, they were dumped back into the basket (no one bothered to wrap them again) and left to sit for about a week until we were notified that they were ready for pick-up. Luis Eduardo then flew with them to Hawaii, but by the time they arrived, nearly all the cuttings had lost their leaves and looked like dead sticks, for the most part. With careful tending from Terence and Kat, about half of the plants survived.

By then, in 1985, Terence and Kat had turned nine acres of the land they’d acquired on the Big Island into an ethnobotanical reserve. They also founded Botanical Dimensions, a nonprofit organization based in California whose mission was “to collect, protect, propagate and understand ethnomedically significant plants and their lore,” as noted on its website (Botanicaldimensions.org). As its president and project director, Kat ran the nonprofit from the start, managing the Hawaii site and applying for grants. That remains true today. Over the years, the organization has used grants and contributions to complete projects ranging from watershed restoration to ethnobotanical research in the Amazon.

Back in 1985, Botanical Dimensions provided me with the cachet and destination I needed to import the plants I had collected in Peru. Since the days when Kat and Terence first began their gene bank in the Hawaiian rainforest, many of its earliest arrivals have reached maturity, and there are now many species of rare Peruvian medicinal plants in the garden, along with specimens from elsewhere on the planet. The site has played an important role in the ethnobotany courses Kat teaches, including “Plants in Human Affairs,” which we have taught together since 2002.

Chapter 45 - The Perpetual Postdoc

I began making plans to leave the Helicon Foundation soon after I returned to San Diego. By then, the papers I’d written on the results of my thesis work had stirred quite a bit of interest. I’d gotten numerous reprint requests, including one from Dr. Juan Saavedra, a section chief in the Laboratory of Clinical Pharmacology at the National Institute of Mental Health, or NIMH.

Saavedra’s name seemed familiar to me, then I remembered: he’d been a colleague of Julius Axelrod, the Nobel Prize–winning neuroscientist who had done pioneering work elucidating the molecular basis of neurotransmission. Axelrod was one of the giants of neuroscience. He and Saavedra had published an early paper on the endogenous synthesis of DMT, characterizing the enzymes in rat brains, human brains, and other tissues that used tryptamine and serotonin to make DMT, 5-MeO-DMT, melatonin, and other neurohormones (Saavedra and Axelrod, 1972). Saavedra had requested a reprint of my paper on ayahuasca from the
Journal of Ethnopharmacology
. If he’s crazy enough to ask for that, I figured, maybe he’s crazy enough to take me on as a postdoc. I wanted to redirect my efforts toward psychedelic research, toward something that ideally would combine pharmacology, which I wanted to learn, and ethnobotany, which I had credibly done.

I sent him the reprint along with a polite letter mentioning my supervisor, Neil Towers, and my mentor, Schultes, and inquired if there might be an opportunity to work in his lab at NIMH on some aspects of ayahuasca pharmacology. At the time, I was unaware that Saavedra had been one of the scientists from the National Institutes of Health (NIH) that joined the RV
Alpha Helix
expedition to the Amazon in 1977. Schultes had been chief science officer on the expedition, and Neil had been selected to go, along with the NIH chemist John W. Daly, who achieved fame for his pioneering work on frog venom alkaloids. Saavedra had been selected because of his work on endogenous tryptamines and also because of his South American (Argentinian) heritage.

In response to my note, Saavedra sent back a letter encouraging me to apply to a program at NIH, the Pharmacology Research Associate Traineeship, or PRAT, a fellowship for young investigators who were outside the field of pharmacology but wanted to acquire skills in that discipline. I applied in the fall of 1985. The application process involved selecting three potential supervisors in order of preference, and then visiting the NIH campus in Bethesda, Maryland for interviews. Naturally, I selected Saavedra as my first choice, followed by Axelrod and John Daly. I had an interesting interview with Axelrod, in which we discussed the function of endogenous DMT. In other words, why was DMT naturally present in the human brain? He said that he thought it had no function; it was basically metabolic “noise,” which surprised me.

It was clear from the start that my supervisor would be Saavedra. He had encouraged me to apply, he had the connection to Schultes and Towers, and he had an interest in ayahuasca. It wasn’t clear what we would work on together, but there were many possibilities. It seemed likely our project would somehow involve the endogenous synthesis of tryptamines and beta-carbolines.

I returned from my visit quite stoked; I had a dawning belief that with a little luck, and hard work, my career might actually go somewhere. In mid-February 1986, I learned I’d been accepted into the program. Sheila took a week off from her job and went out to Washington, D.C. and Bet hesda to find a position in one of the hospitals there. Going out on her own was a good experience for her. The United States was still a foreign and slightly threatening country to her at the time, but surviving her “expedition to America” was a tremendous confidence-builder. She interviewed at four or five hospitals in the Washington area and was offered positions at all of them. She elected to work at one of the area’s biggest inner-city hospitals; she thought the diversity of both the patient population and the staff would be more interesting, and she was right. The hospital’s clientele included many of the most disenfranchised of the urban poor. The health effects of violence, crack addiction, and AIDS were destined to become familiar sights in the course of her work.

Our transition to Bethesda became our American pilgrimage, a chance to discover the country together and to discover each other more in the process. During our two years in San Diego, we’d gone through one beater after another, so at the start of our journey we bought our first new car, a 1986 Honda Accord. We felt very much like upwardly mobile young marrieds, which we were. We took off in mid-May for three weeks of travel before we were due at our respective jobs.

We stopped to see the 200-inch Hale telescope at Palomar, a mecca for the kid astronomer in me still enthralled with outer space. Sheila had never seen Esalen, so we headed up Highway 1 along the coast to Big Sur and pulled in there for a look at that observatory of inner space, as well. In Santa Cruz, we dropped in on my Aunt Tress, then drove through San Francisco and across the Golden Gate Bridge, pulling in for a few days with Terence and Kat. Moving on, we reached Vancouver eager to see Expo 86 and our old friends, by then grad-school survivors and more or less gainfully employed. We spent a couple of nights with Sheila’s parents in their place outside Kamloops, and then dropped in on her sister in Slocan, a village in the pretty Kootenay region of southeastern British Columbia.

Another long leg took us through Idaho to Utah, where we gave ourselves a day to gawk at the Mormon Temple and Salt Lake, then moved on, clearing our heads in Goblin Valley State Park, a lonely, weird place with lots of mushroom-shaped rock formations carved by the wind. The opening scene of the cheesy psychedelic movie
Altered States
was shot there, the only thing good about the film. I’m sure it would be most interesting to chomp down five grams or so in the Goblin Valley around dusk, but we had miles ahead of us and shoved on. Moab, Spanish Fork, Monticello, Dove Creek, Cortez—this was familiar territory to me, evoking memories of the weekend trips our family had taken to Arches National Monument or Mesa Verde, flitting in and out like celestial beings on the shining wings of Dad’s little plane, insulated from the mundane concerns of the folks who lived in that beautiful but harsh and arid land.

Sheila and I visited some of the earliest attempts at building a life there: the Anasazi ruins at Mesa Verde and Hovenweep. We then turned north and stayed a few days with my Aunt Mayme in Paonia, my first chance to introduce Sheila to my extended family. With our time growing short, we surmounted the Rockies and dashed to St. Louis, and then on from there, finally reaching greater Washington, D.C. in sweltering rush-hour traffic like neither of us had ever seen before.

Within a few days, we’d found a funky place on a nice dead-end, leafy street lined with older townhouse-style quadriplexes, about half a block from the Bethesda Metro. The NIH was one stop north. Bethesda is a nice place to live, especially if you like good food. Our two-year stint there was destined to be one of the best times of our lives.

When I had applied for the fellowship at NIMH, Saavedra and I had discussed doing some research related to tryptamines and beta-carbolines, and building on the research he’d done years earlier on the endogenous synthesis of DMT. He was interested in ayahuasca. We thought that endogenous ayahuasca analogs involving both tryptamines and beta-carbolines might be produced in the brain under some circumstances, and this seemed like a promising avenue for investigation. As it turned out, I ended up working on an entirely different problem, unrelated to ayahuasca or natural products, but it was still a useful experience.

At the time, there was a lot of interest in neuroscience in characterizing neurotransmitter receptor subtypes using subtype-selective drugs. For example, a compound that selectively bound to a particular subtype of a receptor for the neurotransmitter serotonin, or 5HT, could be labeled with radioactive isotopes like tritium or iodine 125. Equipped with these radioactive labels, a researcher could use receptor-binding assays to do some interesting things. One could characterize the molecular properties of receptors in brain tissue, for instance, or compare the affinity of an unlabeled drug for a particular receptor type by determining how much of it was needed to displace a labeled drug from the binding site. The technique had been developed by Solomon Snyder and his student Candace Pert, whose landmark work on opiate receptors led to the isolation of the brain’s own morphine—the endogenous opiate peptides known as enkephalins and endorphins. Snyder and Pert had developed this methodology in the early seventies at Johns Hopkins, and it had since revolutionized neuroscience.

Sheila and Dennis, about 1993.

During my time at NIMH, and later at Stanford, many investigators were busy using these radioactively “hot” molecular probes to fish for new receptor subtypes of the major known neurotransmitters. Serotonin receptors were getting a lot of attention because of their known or suspected role in brain disorders such as depression and schizophrenia.

Serotonin receptors also appeared to play a role in the psychedelic response. Research dating back to the fifties had demonstrated that drugs like LSD acted on serotonin receptors; but no one knew exactly which receptor subtypes LSD and other psychedelics targeted, let alone how these subtypes were affected. The “hallucinogen receptor” became the object of a quest. Various subtypes were proposed as the likely culprits. By the time I arrived at NIMH, in 1986, a consensus was emerging that the hallucinogens acted as “agonists,” at one particular serotonin subtype, the so-called 5HT
_2A
receptors. (In pharmacology, an “agonist” is a drug that binds to a receptor and initiates an effect, often acting in a way that is similar to the native neurotransmitter. The opposite type, “antagonists” block the binding of the native neurotransmitter but do not have any effect themselves.)

As luck had it, some of the so-called “psychedelic amphetamines” developed by my colleague and mentor, Sasha Shulgin, happened to display extraordinary selectivity for the 5HT
_2A
receptor subtypes. Shulgin’s compounds were called amphetamines because they relied on a basic amphetamine structure, but they did not act as stimulants. They were really mescaline analogs, and some were almost pure 5HT
_2A
receptor agonists. Conveniently, one of the most effective in this regard was an “iodinated” analog of the mega-hallucinogen known to pharmacologists as DOM, and more widely as STP after its notorious appearance on the street in the late sixties. Its iodinated derivative was known as DOI. Because DOI included an iodine atom, highly radioactive forms of the compound could be synthesized using isotopes like iodine 125. This “hot” tag or label would allow us to track where this compound bound in neural tissue.