Good morning,
I’m trying something different this week, a new kind of column in which I share some of what I learned by diving down a research rabbit hole. I’ve been saddened by recent news of the apparent fentanyl-related death of Marco Troper, a college student and the son of former YouTube CEO Susan Wojcicki, who joined hundreds of thousands of Americans who died from drug poisoning by fentanyl in recent years (a January 2024 report from the DEA notes that over 72,000 such deaths occurred in 2022 alone).
So, I thought I would share some findings from one of my ongoing research projects, to help provide a small bit of historical and economic context for thinking about the modern-day American opioid epidemic. On and off for the past decade or so I’ve dug into the political economy and history of drugs, including opioids but also marijuana, cocaine, crack-cocaine, and methamphetamine. Part of my focus is on how the industrialization process works to alter the drug landscape and how those changes impact humans. My approach is a little unconventional, but that is to be expected given how it was that I stumbled into opioid research in the first place...that is, with help from the Twinkie.
Many of the drugs humanity today finds most vexing, addictive, and deadly are available to us thanks to technological and scientific developments associated with advances in the fields of chemistry and chemical engineering, advances that have helped us create a mind-boggling array of highly specialized drugs designed to treat a broad range of specific ailments. Fentanyl, for example, is the outcome of more than 200 years of scientific and industrial development that started with the derivation of morphine from opium in the early 19th century. In a 2020 article in the International Journal of Drug Policy, I wrote:
Close analysis of opioid drugs has left me in awe of the accumulated bodies of industrial knowledge and practice that we subsume under the name “chemistry”. From roughly the time that the first alkaloid was isolated by early chemists of the Industrial Revolution—it was morphine, derived from raw opium in 1806—chemistry has gradually and steadily come to know and order, and thus control, broad swaths of the natural world (Breger Bush 2020, p. 4).
The influence of chemistry on how we live today is profound and certainly not limited to drugs. For example, the ways in which raw opium has been sliced and diced and refined and processed over the centuries into dozens of other drug products—from morphine and heroin to codeine and oxycodone—is not unlike the ways in which crude oil has been transformed via the petrochemical industry into a staggering array of derivative products, such as ethylene (used to make antifreeze and polyester fabric) and benzene (used to make plastics, glues, resins and other adhesives). It is also similar to the ways in which the corn plant has been processed and refined by food chemists and engineers into corn starch, cellulose, high fructose corn syrup, and other corn-derived industrial products some of which appear as ingredients in the Twinkie.
Twinkies and Carrots
I’ve been prepping this week to do a guest presentation in my son Will’s 2nd grade class. They learn social studies on Fridays and his teacher has been integrating some economics lessons into the curriculum. The last economics homework I saw helped students understand the difference between “goods” and “services”. Building on this foundation, I’m going to chat with Will and his classmates about production processes and commodity chains.
The major theme of the lesson is that every good and service has a story. Some stories, such as that of the humble carrot, are relatively simple. But other stories, such as that of the infamous Twinkie, are a lot more complex. To start, we will plant Colorado carrot seeds in Colorado dirt, and then eat some carrots from Bakersfield, California (it’s too cold here in CO to grow carrots right now). Commodity chains in which the producer and the consumer are the same person, and in which the product grows directly in the soil using minimal amendments and is only gently processed (e.g., washed in water) are some of the simplest chains there are.
Then, we will turn to the Twinkie, the popular snack cake made from more than 30 different ingredients sourced from around the world, and which some joke is sufficiently heavily processed and preserved that it could survive a nuclear winter (in truth, they only last about a month or two on the shelf). Unlike the carrot, the Twinkie is pretty complicated for amateurs making food at home, largely owing to the complexity of its ingredients. And those ingredients are themselves extremely complicated to produce. We will look at pictures of the ingredients, examine where they come from on a map, think about how raw materials like corn and crude oil are processed and turned into other goods, talk about mold and food preservation, and we will also eat some Twinkies.
(Images: Sweet dairy whey, Polysorbate 60, corn syrup and vegetable shortening are four of the more than 30 ingredients found in a Twinkie.)
Industrial food and Western diseases
Decades of research on industrial foods and industrial food production techniques has revealed that some of the heavily processed ingredients used to make foods like Twinkies can be harmful, and even toxic, to humans. For example, trans-unsaturated fatty acids (aka “trans fats”), which appear in the images above as “vegetable shortening”, have been shown to increase the risk of high cholesterol, stroke, heart disease, and type 2 diabetes.
The American Heart Association explains the difference between naturally occurring and “artificial” trans fats: “Naturally-occurring trans fats are produced in the gut of some animals and foods made from these animals (e.g., milk and meat products) may contain small quantities of these fats. Artificial trans fats (or trans fatty acids) are created in an industrial process that adds hydrogen to liquid vegetable oils to make them more solid.” Edible oils develop higher concentrations of trans fatty acids when they are processed at very high heats, typically in industrial facilities at temperatures much higher than those used to cook at home.
Similar relationships between heavily processed food products and negative human health outcomes have been observed with high fructose corn syrup, bleached and refined white flour, and food additives like polysorbate (an emulsifier), among other industrial ingredients that have become ubiquitous in the Western diet and are central to medical explanations of the rise of the so-called “Western diseases”. The Western diseases are a cluster of mostly chronic illnesses that have been found to disproportionately affect populations living in advanced industrial economies in North America and Europe, including obesity, cardiovascular disease, hypertension, type 2 diabetes, osteoporosis, osteopenia, and cancer. As Cordain et. al. note,
There is growing awareness that the profound environmental changes (eg, in diet and other lifestyle conditions) that began with the introduction of agriculture and animal husbandry 10 000 years ago occurred too recently on an evolutionary time scale for the human genome to adapt. In conjunction with this discordance between our ancient, genetically determined biology and the nutritional, cultural, and activity patterns in contemporary Western populations, many of the so-called diseases of civilization have emerged” (2005, p. 341).
It is partly against the backdrop of industrial food and Western diseases that I’ve been thinking and researching about drugs. As I argued with student researcher Matt Kriese in the Review of Social Economy in 2019, the line between “foods” and “drugs” is not altogether clear. Consider, for example, the tropical beverage crops: coffee, tea, and cocoa. These are plant-based products we like to think of as beverages and foods but that we love in part because of the powerful central nervous system stimulant they contain (caffeine). Is a bar of chocolate a food or a drug? Might it behave like a drug in some contexts but like a food in others? What happens if we apply what we know about food to thinking about drugs?
What happens if we think about fentanyl as the Twinkie of the drug world?
While Twinkies are made from natural things, i.e., plants and animals and rocks and the like, the final product is a great distance, in economic terms, from those natural things from which it was created. The story of the Twinkie is the story of chickens and cows, of crude oil and wheat and corn and sugarcane. But it’s hard to see the chickens and cows and corn behind the Twinkie owing to the many different industrial processes that stand between “nature” and the snack cake we see on our grocery shelves. And, the processes that shape and alter our food as it travels that long distance from the Earth into our mouths and bellies are not wholly benign. Some of those processes render our food more toxic and dangerous to our health, and they have strongly contributed to the epidemic of Western diseases (See here and here for medical write ups from NIH, if you’re interested).
Might the same be said for certain drugs, then? Might it also be the case that when we apply industrial processing techniques to natural things in order to produce “drugs” similar unintended consequences sometimes arise? To what extent should fentanyl perhaps be considered the Twinkie of the drug world? Is fentanyl poisoning rightly considered a Western disease like heart disease and type 2 diabetes? My co-author and I wrote in 2019,
[T]he most interesting thing to happen to drugs in the modern era is not that some of them ultimately came to be scorned and prohibited by states and societies, but rather that they were revolutionized in terms of their variety, availability, cost, potency and toxicity. Here, the evolution of the economy of the opium poppy or the coca plant begins to look more similar to that of corn or coffee or cotton or sugar. As with corn for example (see, e.g. Pollan 2006), the opium poppy, and our relationship to it, was transformed as it was gradually subsumed by the industrial capitalist system over the course of the 19th and 20th centuries. Just as corn was fundamentally altered by the logic and machinery of industrialism—with its transmutation into ethanol, high fructose corn syrup, and corn gluten meal, among other feats of chemistry and engineering—so too runs the story of the poppy, and, it could be argued, with strikingly similar effects on humanity (Breger Bush and Kriese 2019, p. 13).
Opioid industrialization: Facts and findings
My research on this topic is exploratory and ongoing and has proceeded over the years in fits and starts (one needs to come up for air after spending time in a rabbit hole). I don’t have any hard conclusions yet, but I did learn some interesting stuff about opioids and the industrialization process.
For example, check out the table below from my 2020 article about opioids. It shows the many historical medical uses of raw opium compared to the highly specialized uses to which chemical derivatives of opium are put today. All of the slicing and dicing and refining and processing associated with 200 years of advancements in chemistry and chemical engineering has turned a single plant product that formerly served many purposes for humans into an array of refined chemical products each of which serves really only one singular medical purpose. This kind of processing and specialization is a hallmark of the industrialization process more generally, and has historically generated a lot of negative, unintended consequences.
(Image: Table 1 from Breger Bush 2020, p. 7. “Over the past roughly two hundred years, beginning with the derivation of morphine in 1806, the opium poppy has been systematically deconstructed and disassembled, with each of its component parts isolated, named, categorized and specialized for use, each used for an ever-narrower range of ailments…”, p. 6).
Different opioids are produced in different ways, with simpler processing and production methods used to produce opium relative to those used produce morphine and heroin. Opium is collected from the immature seed pods of middle-aged opium poppy plants. Slits are made in the seed pod and over the course of several days, the opium leaks out of the slits and is gently collected by hand. It is then sun dried before it is ready for consumption. While addiction and long-term use of opium is historically fairly common, overdose deaths are relatively rare (Breger Bush 2020, p. 10).
Making morphine is more complicated, requiring the addition of other ingredients and tools as well as the application of heat, though it is a process that can be performed at home by non-experts. The result is a more refined substance that is more potent and more toxic to humans than opium and is used to treat fewer ailments:
After raw opium is collected and dried…the opium is put into boiling water and cooked for a while in a pot. It is mixed with calcium hydroxide (slaked lime), which causes the morphine molecule to form a solution with the lime. This solution is filtered to remove any bits of plant matter or other impurities. Then, it is mixed with ammonium chloride and reheated. The morphine separates from the rest of the mix, and the solid white chunks of morphine base (morphine class 1) accumulates on the bottom of the pot. The base is then filtered out from the rest of the mix using a cloth (Breger Bush 2020, p. 8).
Heroin production starts with morphine and results in a more toxic substance that is 2-3 times as potent as morphine. While the process is a bit more complicated, heroin, too, can be produced relatively easily at home and without much expertise, assuming one can obtain the necessary ingredients:
Morphine can be easily converted to heroin with the same simple tools—a pot, a burner, and a filter/cloth—and a few more ingredients. Heroin, also known as diamorphine, is assembled from morphine base, which is mixed with acetic anhydride and cooked at 85°C for two hours. The morphine dissolves during this process, and after two hours, the mixture is left to cool, over which time the acid bonds with the morphine to form a new assemblage: heroin. Water is added to the mix, which dissolves the heroin, and then sodium carbonate is added. The result is called “heroin base”. Heroin base is converted to “smoking heroin” by adding hydrochloric acid. Purer heroin is made by adding ether along with the hydrochloric acid. These various pasty compounds are dried before packaging and sale (Breger Bush 2020, p. 8).
But the production of fentanyl, developed more than 70 years after the invention of heroin, is a different matter entirely, showcasing well the huge advances in chemistry and chemical engineering during the 20th century. Fentanyl is a synthetic opioid (i.e., it contains no opium derivatives), is produced via a series of extremely complex and high-tech processes, and is about 50-125 times more potent than morphine. The production process takes a lot of words to explain, so I’ll provide only a few highlights:
Fentanyl is synthesized from a precursor chemical called 4-anilino-N-phenethylpiperidine (4ANPP), which is itself a derivative of piperidine, which can be derived from piperine (an alkaloid commonly found in pepper plants, like those that produce peppercorns) but is most commonly derived from pyridine (a coal tar derivative, but more commonly synthesized from other chemicals)…
By the time Janssen developed his process for creating fentanyl in 1964, chemistry had advanced significantly, such that chemists could by this time create in a laboratory from wild lists of ingredients using more advanced tools and techniques compounds that mimicked the effects of opiate drugs. Importantly, Janssen's recipe begins with a series of industrial chemicals: N-(4-piperidyl)-propionanilide, sodium carbonate, potassium iodide, hexone, Ɓ-phenylethyl chloride, and 4-methyl-2-pentanone. This mixture is to be stirred and “refluxed” for 27 hours (USPO #3,141,823, 1962).
Reflux is a process typically employed in industrial chemical plants and other high-tech chemical operations and is part of a process by which materials in a solution are separated from one another by leveraging the different boiling/evaporation points for different compounds in the solution… At the time Janssen was developing fentanyl, reflux would have likely been achieved using some kind of fractionation device (Breger Bush 2020, pp. 5 and 8).
I’ll stop there, and for the sake of symmetry, sign off with another image. The picture below is of a petrochemical production plant in Texas. Perhaps this plant produced the oil derivatives required to make the Polysorbate 60 or Yellow #5 found in the Twinkies I’m bringing to Will’s class.
(Image: Petrochemical production plant in Texas, courtesy of ResourceWise, here.)