Editor’s note: The following story is co-published with Matt Bivens’ Substack newsletter, The 100 Days.

“Do more reading,” I’d been told as a medical student when I worried aloud about overly liberal use of morphine (see Part I). Had I obediently done so, a thorough review of the medical literature could have turned up many studies demonstrating that a casually-written opioid prescription can wreck a person’s life.

But to find them I would have had to sift through many hundreds of peer-reviewed publications arguing the opposite: that addiction with opioid prescriptions never really happens. My medical school years (2005-2009) saw a blizzard of such academic papers, all claiming that we could relax and start slinging product. Hundreds of those papers — 439, to be exact— cited for their evidence one mysterious paper, published in the New England Journal of Medicine

Once upon a time we’d killed babies with morphine syrups, and destroyed lives by treating laryngitis with heroin. Eventually we wised up. Yet now, a single publication was being cited, over and over again, to contradict everything we’d learned through a century of tragic experience. This publication, called “Porter & Jick” after its authors, was receiving hugely respectful attention from hundreds of other doctors and scientists, writing in hundreds of other medical journals.

Porter & Jick was even enjoying glowing write-ups in mainstream media. TIME magazine called it a “landmark study,” one that showed fears of opioid addiction had been “exaggerated,” and were “basically unwarranted.” Scientific American said Porter & Jick’s “extensive study” was evidence for a new modern understanding that “morphine taken for pain is not addictive.”

Journalism from 30 years ago, helping lay the groundwork for a catastrophe.

So, what was this landmark, game-changing, extensive study?

Brace yourself: It was a letter to the editor. It’s just five sentences. 

Five sentences! 

The letter’s authors were Jane Porter, a grad student, and Hershel Jick, a physician. Porter and Jick reported reviewing 11,000 patients in “our current files” at a Boston hospital who got treated with an opioid and finding only four cases of “reasonably well-documented addiction”, whatever any of that means. As evidence goes, it’s so low-quality for decision-making purposes that it borders on useless. And that’s okay, by the way: When your research findings are too weak to merit a full publication, eking a letter to the editor out of them is a common tactic in publish-or-perish academia. Everyone understood this at the time; upon publication the Porter & Jick letter was thus promptly and appropriately ignored; and that should have been the end of it.

Then they would grin slyly, because no one ever reads the footnotes.

But no. Many years later, unscrupulous pharmaceutical companies dusted off this five-sentence letter. Their marketing departments had come up with a clever use for it. They would claim that addiction happens far less than 1% of the time (four cases out of 11,000 would be 0.036%). They would cite The New England Journal of Medicine. Then they would grin slyly, because no one ever reads the footnotes.

And if some skeptic did read the footnotes? At the dawn of the Opioid Crisis, the New England Journal’s archives weren’t even available on-line; they were only uploaded and made accessible around 2010. Before then, doubters who wondered what this Porter & Jick citation was about would have had to go to a brick-and-mortar library for a physical copy of the journal, if they wanted to be let in on the joke.

As that should suggest, the Porter & Jick letter was ancient: Like, pre-computer ancient. It was published in 1980. (When Porter and Jick described reviewing “our current files,” they meant actual paper files.) When the letter was rediscovered some 20 years later, the explosion of new academic citations stunned and distressed the letter’s authors. Dr. Jick came to wish he’d never published it. “Only years and years later, that letter was used to advertise by new companies that were pushing out new pain drugs,” Dr. Jick later told NPR. “I was sort of amazed. None of the companies came to me to talk to me about the letter.” (Dr. Jick passed away in October at age 91).

Eventually, this five-sentence letter would be cited more than 600 times, a situation so ridiculous that the New England Journal felt compelled to go into its archives and affix a warning label atop it. “For reasons of public health,” the warning said, anyone looking at this letter should know it has been “heavily and uncritically cited”. That label was recently removed, but here’s a screen shot of how it used to look:

“Heavily and uncritically cited” was a polite way of saying “used as part of a conspiracy.” This was no accident. The deceptive use of Porter & Jick — that “landmark study” — that “extensive study” from the New England Journal of Medicine supposedly proving that “morphine taken solely to control pain is not addictive” — this was one small cog of an elaborate machine, one built to tell dangerous lies to doctors and their patients. 

Deception ‘Tainted Nearly Ever Source’ a Doctor Might Consult

Many have now described aspects of that conspiracy. Few have done so more clearly than a 2015 lawsuit by the state of Mississippi against 16 of the nation’s largest opioid manufacturers.

The Mississippi attorney general said:

During the 1990s … In order to expand the market for opioids and realize blockbuster profits, Defendants needed to create a profound transformation in medical and public perception that would permit the use of opioids … to treat more common aches and pains, like lower back pain, arthritis, and headaches … Defendants, through a common, sophisticated, and highly deceptive marketing campaign that began in the late 1990s, deepened around 2006, and continues to the present, set out to, and did, reverse the popular and medical understanding of opioids. …

[The pharmaceutical companies created] a body of false, misleading, and unsupported medical and popular literature about opioids that … appeared to be the result of independent, objective research …

Defendants coordinated the timing and publication of manuscripts … The plans for these materials did not originate in the departments … that were responsible for research, development or any other area that would have specialized knowledge about the drugs and their effects on patients, but in Defendants’ marketing departments … their deceptive messages tainted virtually every source on which doctors could rely for information …

It seems hard to believe, doesn’t it? Yet here’s just one of oh-so-many similar documents out there confirming it, courtesy of all of those lawsuits. This one is a spread sheet from a team at Johnson & Johnson working on marketing for the opioid medication tapentadol. In it, the marketing reps document sending article outlines and first drafts (!) of proposed peer-reviewed, academic publications to the author for approval — complete with reminders under Next Steps to “create reprints for sales rep distribution.”

From the 2017 Oklahoma lawsuit against Johnson & Johnson. Accessed at the UCSF’s Library of Opioid Industry Documents. 

Or if a spread sheet is too dry for you, check out this Austin Powers-themed motivational video. It was made by the opioid manufacturer Cephalon, Inc. for its sales staff, and discusses how they will market their new dissolve-in-the-mouth fentanyl tablet. Cephalon was able to patent generic fentanyl as Fentora® by adding in Alka Seltzer®-style “plop plop fizz fizz” effervescence. It was also able to patent generic fentanyl as Actiq® by making it into a lollypop. Feel free to eye-roll in disgust, but that’s how you make a cheap drug expensive: Tweak how the medication gets delivered into the body, and claim it’s now a completely new substance, worthy of a new patent. (Remember this. It will come up again and again.)

The 2006 Fentora® motivational video, shown to a New York jury in 2021 over the strenuous objections of the Cephalon legal team, edits new audio into scenes from the cult classic movie Austin Powers: International Man of Mystery. “Gentlemen! I have a plan. It’s quite brilliant,” says Dr. Evil. “We are going to roll out a blockbuster marketing campaign, focusing on ‘effervescent speed’ — a concept so nebulous, so indecipherable, it will absolutely help drive prescriptions … to Fentora®!”

When his staff of fellow villains tell him that’s already been tried but “FDA shut it down,” a disappointed Dr. Evil quickly recovers. Punctuating his speech with frequent air quotes, he outlines his next evil plan:

We will do studies in low-back breakthrough pain, neuropathic breakthrough pain and for all non-cancer breakthrough pain — a new “pivotal study.” Using these “studies,” we will … show doctors around the world that Fentora® “works for all breakthrough pain.” 

(For those who want more, the full 5-minute video can be seen here.)

Cephalon (later taken over by Teva Pharmaceuticals) failed to get the FDA to agree that fizzy or lollypop fentanyl were safe for anyone other than a patient with terminal cancer, and in 2008 had to pay a $425 million fine for marketing fun-and-fizzy fentanyl too broadly. But at moment, I’m more interested in the frank, mocking acknowledgement of how pharmaceutical companies fund and organize “studies” — the very studies used to justify their commercially-sold products. That practice has massive implications for what we call evidence-based medicine.

Big Pharma has repeatedly been caught passing off its wishful thinking as science.

Consider that we are supposed to believe that Paxlovid®, the antiviral cocktail, is life-saving in COVID-19 — based on a single, Pfizer-run and Pfizer-controlled study filled with red flags, which Pfizer then turned in like an invoice to the U.S. government, in return for $18.9 billion in 2022. Again, that’s eighteen billions of our dollars. Meanwhile, according to the respected Cochrane Review, there are 17 other studies out there of Paxlovid® either showing no effect or oddly in limbo or “still in progress” (i.e., going nowhere). This was happening after the well-documented Porter & Jick debacle — afterBig Pharma over and over again admitted in opioid-related settlements that it lies about these sorts of things, whenever there’s real money in play.

In fact, Big Pharma has repeatedly been caught passing off its wishful thinking as science. Billions of dollars of Tamiflu® have been stockpiled by governments around the world, in deals struck years before researchers realized that the Swiss pharmaceutical company Roche had only shared some of its data — the flattering half. When the full data was finally dragged into the light of day, Tamiflu® looked pretty worthless. A storm of academic outrage ensued. All agreed that this was not the proper way to conduct scientific inquiry; that pharmaceutical money was contaminating the medical evidence base with lies.

But again: It’s one thing to nudge-wink people into buying Paxlovid® or Tamiflu® — stuff that’s questionably effective, yet basically harmless. It’s something else entirely to con people into prescribing, buying or ingesting the world’s most dangerous and addictive substances. We are looking at hundreds of thousands of opioid overdose deaths so far, with models predicting we’ll chalk up the millionth opioid-specific overdose death sometime in the next 2-3 years. Tens of millions of families have been ravaged by the tragedy of an avoidable opioid addiction. In just one 10-year period of this 25-plus-years nightmare (2011-2021), more than 320,000 children lost a parent to an opioid.

And yet, to this day, the House of Medicine simply can’t be bothered to look into how it happened. Everyone knows we serenely and calmly let deception-based scientific “studies” (Dr. Evil air quotes) — lie, after lie, after dishonest lie — lead us doctors into bringing about a public health catastrophe. But there’s no reckoning. The House of Medicine says: “Well, the lawyers will take care of it.” Did our collective screw-up kill the mother or father of more than 300,000 children? Medicine whistles nervously, and looks away.

Pseudoscience and Pseudoaddiction

So, an opioid maker’s marketing department would draw up most of a review article, lecture program, or “study” (Dr. Evil air quotes). This would invariably state that addiction doesn’t really happen when the doctor prescribes the opioid, and cite The New England Journal of Medicine (i.e., “Porter & Jick”.) And then they’d go find a physician willing to slap his or her name on the top. 

Dr. Russell Portenoy was, by his own frank admission, one such physician. A medical school professor who believed opioids could be used more liberally, he for a time chaired the Department of Pain Management and Palliative Care at New York’s Beth Israel Medical Center — and simultaneously worked as a well-paid consultant or collaborator with multiple opioid manufacturers, including Purdue Pharma, Endo, Janssen and Cephalon. The Mississippi lawsuit says:

“As described by Dr. Portenoy, drug companies would approach him with a study that was well underway and ask if he would serve as the study’s author. Dr. Portenoy regularly agreed.”

In the midst of the opioid crisis, when opioid sales were soaring and patients were dying by the tens of thousands, Portenoy went on national television’s Good Morning America to claim that “addiction, when treating pain, is distinctly uncommon,” unless a person already has a history of it or “a very major psychiatric disorder.” Otherwise, “most doctors can feel very assured that that person [they just started on opioids] is not going to become addicted.”

Again: This is a medical school professor, the chair of a department at a major New York Hospital, on national television in 2010. What was his evidence? He didn’t have any — other than the notorious five sentences of “Porter & Jick”, which by the time Portenoy went on television that morning were already 30 years old. As Portenoy later told the New York attorney general:

From paragraph 176, pg. 52, of New York’s 2019 lawsuit against the opioid industry.

As the opioid crisis continued to spin out of control, Dr. Portenoy later told The Wall Street Journal that he “gave innumerable lectures in the late 1980s and 90s about addiction that weren’t true.” He came to describe his promotion of opioids as based on “pseudoscience.” He’s now had a change of heart and has testified for the prosecution in some of the opioid lawsuits. (He did not reply to my e-mails.)

As the opioid crisis continued to spin out of control, Dr. Portenoy later told The Wall Street Journal that he “gave innumerable lectures in the late 1980s and 90s about addiction that weren’t true.”

Another vocally pro-opioid physician, Dr. David Haddox, did not even bother with the fig leaf of a consulting contract, and was straight-up hired by Purdue Pharma. They made him a company Vice President. “If you are taking OxyContin® for legitimate pain, you have nothing to worry about,” Haddox once told a newspaper reporter, before comparing it to a vegetable that would only be unhealthy if misused: “If I gave you a stalk of celery and you ate that, it would be healthy for you. But if you put it in a blender and tried to shoot it into your veins, it would not be good.”

Haddox was hired by Purdue after he’d coined the concept of “pseudoaddiction” — the idea that people might act like they have a drug addiction, but really only have uncontrolled pain.

Haddox and a co-author introduced this “pseudoaddiction” concept in a 1989 publication about a single patient: a 17-year-old admitted to hospital with leukemia, who after a few days of being on morphine started to want more, and got restless and unpleasant when denied. So, was this a new, healthcare-acquired morphine addiction, of the kind doctors had been seeing literally since the Civil War? Or was it “pseudoaddiction”? The best way to figure out, according to Haddox and his disciples, would be to give more drugs and see what happens. 

It sounds like garbage to me. Did people really advocate to radically change medical practice based on an anecdote about a single 17-year-old acting out for morphine? Yes they did. Like that five-sentence “Porter & Jick” letter, the “pseudoaddiction” concept was marketing gold. Haddox was to become what the pharmaceutical business calls a KOL — a “Key Opinion Leader” — someone to fund and support. More than 200 articles would rapidly be pushed out to solemnly discuss “pseudoaddiction.” Many of these “studies” (Dr. Evil air quotes) were no doubt conceived, written and placed by marketing departments, as part of the ongoing conspiracy to keep doctors pushing product.

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