Yesterday I decided to binge on the two part HBO series “The Crime of the Century.”  It detailed the horrors inflicted on the most vulnerable of the American people – individuals who suffer from chronic pain or are about to pass away and are in extreme pain.  The culprit for these horrors was and remains the Sackler family and its company Purdue Pharma which was created when its other pharmaceutical company Purdue Frederick was making a great deal of money manufacturing items like Benedine and Senekot, but for the family led by Richard Sackler this did not produce enough profit, so it branched out into the “pain market” and took one of its products MS Contin and reoriented its composition to create Oxycontin.  The process involved pressure on the FDA, a great deal of obfuscation concerning its components, bribery, and outright lies to cause the death of over 500,000 Americans since its release in 1996.  One of the narrators for the documentary was Patrick Radden Keefe, a staff writer at The New Yorker and the author of the New York Times bestseller, SAY NOTHING: A TRUE STORY OF MURDER AND MEMORY IN NORTHERN IRELAND the winner of the 2019 National Critics Circle Award for Nonfiction.  Keefe’s newest book EMPIRE OF PAIN: THE SECRET HISTORY OF THE SACKLER DYNASTY fills in some of the gaps of the HBO expose and reaffirms the despicable actions of numerous characters in the family, Purdue Pharma employees, and individuals outside the company and family who were coopted into the process because of greed and a convoluted sense of morality.

EMPIRE OF PAIN is a multi-faceted biography of a family dynamic that produced individuals who seemed to lack empathy for others and were obsessed with the accumulation of wealth which allowed them to satisfy their pocketbooks and egos.  Secondly, it is a study that delves into the drug empire created by the Sackler family and the lengths they would go to continue to engage in practices that would enhance and maintain their wealth while ignoring the negative and at times disastrous effects of their decisions on the American people.  Some family members would argue that this accumulation of wealth is partially offset by the philanthropic ventures that the Sackler’s pursued.  The name Arthur M. Sackler, the individual most responsible for beginning the creation of its “pain empire” appears on museum walls and buildings ranging from New York’s Metropolitan Museum of Art, the Smithsonian in Washington, D.C., Harvard, Tufts, Columbia Universities, the Sackler School of Medicine in Tel Aviv, among others in London, Paris, and Berlin.  These gifts and/or donations were made possible by the fortune earned from developing and marketing drugs like Librium and valium in the 1960s and 70s with its negative effects on those patients whose doctors over prescribed the medication.

Keefe’s narrative unfolds as he explores the origins of Sackler family wealth which is estimated at about $14 billion.  He delves into the role played by three brothers; Arthur, Raymond, and Mortimer Sackler, all three physicians who developed the edifice that resulted in the hundreds of thousands of drug overdoses that have been inflicted on American society in the last few decades.  The key figure is Arthur M. Sackler who after working at Creedmoor Mental Hospital in New York along with his brothers in the 1960s concluded that the care for the mentally ill was grisly and became convinced there was a better treatment solution.  Arthur Sackler, trained as a Freudian concluded that one’s life experience could not fully account for mental illness – that there was a chemical component, and he would unlock the mystery to help these people.  Sackler would conclude that the derangement of brain chemistry was the missing link.  The brothers conducted a series of experiments on rabbits which reinforced their views of chemical changes in the brain being responsible for mental illness.

Keefe lays out the early careers of the brothers, but Arthur was the key.  He was a complicated individual who enjoyed multiple careers; physician, mental illness researcher, and advertising executive.  His strategy was to market products/medicines directly to doctors and at first took “broad spectrum anti-biotics” and revolutionized medical marketing by convincing physicians to write prescriptions for his products.  The advertising techniques used for clothing, automobiles, food, perfume etc. were now applied to medicine.  Promotion and brand differentiation were key, and Arthur’s success was built upon his purchase of the William Douglas McAdams advertising agency whose major client was Pfizer. 

As Keefe points out, Arthur was shrewd as he owned or had a partnership with McAdams and Bill Frohlich’s ad agency.  The brothers opened their medical practice in the 1950s in New York and purchased Purdue Frederick, a small company in the patent medicine business.  The expansion of their wealth was predicated on developing what they termed “a minor tranquilizer” to offset the use of Thorazine.  Roche, another major pharmaceutical company developed Librium to meet that market and Arthur was tasked to market the new drug.  In an age of Cold War anxiety, it was the perfect time to launch a new tranquilizer.  By 1963 Roche would build upon Librium and develop Valium and Arthur’s firm zeroed in on convincing doctors that it worked separately on anxiety, muscle tension and numerous other ailments.  It would become the first $100 million drug in history, further little was done to determine if the new drugs were addictive – creating a Sackler family pattern.  Valium would be used by 20 million Americans and was at that time the most widely consumed and abused drug in history.  Even the Rolling Stones wrote a song about Valium, “Mother’s Little Helper.”

Keefe encapsulates Arthur’s approach carefully correctly arguing that “he desired posterity, not publicity.  The last thing Arthur wanted to do was call attention to his own wealth and holdings, and to do so in a manner that might raise questions about his overlapping careers.”  It was quite clear that Arthur modus vivendi of helping develop drugs, fiercely marketing them to physicians, manipulating the FDA through the likes of Dr. Henry Welch, indirect gifts and bribery to the right individuals be they salespeople or doctors was unethical as well as illegal.

(Cheryl Juaire, center, of Marlborough, Massachusetts, center, leads protesters near the Arthur M Sackler Museum at Harvard University)

As Keefe lays out his arguments it is clear the groundwork for our current drug problem was fostered by the Sackler brothers approach that drugs are not addictive, and it was the patient’s personality and needs that were responsible not the drug manufacturer or the physician.  It was clear as they marketed Valium they developed the advertising approach designed to create a vast market for Oxycontin.

The main culprit among the next generation of Sackler’s was Raymond’s son Richard, and Arthur’s daughter Elizabeth (Kathe).  The family created a new company, Purdue Pharma to engage in developing a “pain” product that would create a new market since their patent for MS Contin, a morphine based drug was running out.  The Contin process contained a time released component over a twelve hour period that they argued would prevent addiction.  Kathe’s goal was to apply the Contin system to Oxycodone and Richard would micromanage its development.  At first, they stressed that the new drug Oxycontin (time released Oxycodone/morphine) should be marketed just for cancer patients to gain FDA approval, but what was never mentioned was that Oxycodone was synthesized into heroine by Bayer in Germany.  Once on the market for a period of time the target market would be expanded.

Keefe does an excellent job recounting the mindset of Richard Sackler and his cohorts in undoing the perception that Oxycontin was addictive to enhance the profitability of the drug.  This approach was implemented with a vengeance.  Mitchell Freidman who had been Head of Marketing at the FDA joined Purdue Pharma a year after he left the government and he and Richard would spearhead the idea that Oxycontin could be used for a myriad of issues from back pain, arthritis, post-surgical pain etc.  Keene has culled the evidence and shows how Richard and Freidman deliberately chose a marketing strategy to deceive doctors and their patients of the low addictive quality of Oxycontin and the mistaken belief held by doctors that the drug was less powerful than morphine.  Curtis Wright, who oversaw pain medication at the FDA, was cultivated and he helped write the drug insert for the medication that stated, “Delayed absorption, as provided by Oxycontin tablets, is believed to reduce the abuse liability of the drug.”  On December 28, 1995 the FDA approved Oxycontin.  A year later Wright earned $400,000 at Purdue Pharma.

The sales approach described by Keefe to market the new drug rested on the company’s catechism, “the delivery system is believed to reduce the abuse liability of the drug.”  Keefe dissects the sales pitch and training of the hundreds of Pharma reps.  They would target certain geographical areas like southern West Virginia and eastern Virginia and the rust belt to maximize sales as people overdosed.

Keefe’s account is stunning and based on assiduous research, confidential and original documents, and interviews.  The author follows the legal battle to unearth what the Sackler’s had done and its vast implications for the wealth and health of the American people.  Their arrogance is clear in the words of Kathe Sackler who boasted  that Oxycontin was “very good medicine” and “a safe medicine.”  She also claims credit for coming up with the “idea.”  Years later in reference to the hundreds of thousands of addicted Americans she claimed not be aware of that.  In 2007 the Bush Justice Department only delivered a slap on the wrist after investigating Purdue Pharma.  It was no coincidence that the Sackler’s were major donors to the Republican Party and Rudy Giuliani was one of their lawyers!

The name Barry Meier, a New York Times reporter and author of the first major expose dealing with Purdue Pharma and the Sackler’s, PAIN KILLER: AN EMPIRE OF DECEIT AND THE ORIGIN OF AMERICA’S OPIOID EPIDEMIC became a thorn in the side of the opioid industry.  Keefe relies on Meier’s early work in his research and conveys the travails that the reporter had to deal with.  Purdue Pharma executives pressured the Times  to block Meier’s efforts.  They were successful for a period of time until the various trials against the corporation took place where he was “reinstated” on the topic and his incisive reporting reemerged.

Keefe and Meier argued that it is clear that Purdue Pharma had an inside man at the FDA and Paul McNulty, the deputy attorney general during the Bush administration handcuffed the prosecution and the efforts of John Brownlee, the federal prosecutor for the western district of Virginia who went after Purdue Pharma.  In 2007 Purdue would pay a $600 million fine for the $35 billion earned from Oxycontin.  Two years ago, when the Sackler’s faced their harshest legal challenge, they sold their stake in Purdue Pharma, moved their money overseas and had Purdue file for bankruptcy.  Once that strategy was implemented, no court could gain damages from the family’s personal funds.  By 2019-20 the Trump Justice Department under William Barr gave the family a reprieve and no family members or company executives would face criminal charges.

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Keefe effectively traces how finally after 2013 the Sackler family name became toxic as museums, universities, medical schools, and hospitals refused their donations and, in some cases, removed their names from their properties.  Keefe follows the family’s efforts to counter lawsuits brought by numerous state Attorneys General and their use of White Plains, NY Judge Robert D. Drain to protect the Sackler family wealth, in addition to the family realization that for the first time settlements might hit them personally.  As a result, they began to siphon off vast amounts of cash (family wealth is estimated to be $14 billion) from the company and planting it in offshore accounts.  The result is that this entitled group of “Sackler’s” had to face the fact they had become social pariahs.

Samanth Subramanian’s review of May 13, 2021, in The Guardian sums up the devastation and corruption, both government and non-government very clearly and its implications for the future: Keefe’s narrative is so lush with details that only in the chinks do we spot the story behind the story: the rotting structure of American healthcare that almost wills disasters into being. Some failures are born of lethargy or neglect. A federal government official once told me that if states had simply transitioned faster to reporting their health statistics electronically, someone might have caught a pattern: “all the drug overdose deaths, the suicides, the medical examiner events” that advertised the opioid crisis. But other failures are the results of a system maintained at a level of designed corruption.

 

(Ranbaxy plant in Mohali, India)

The other day I was chatting with my doctor and I mentioned to him that he should consider reading Katherine Eban’s recent book, BOTTLE OF LIES: THE INSIDE STORY OF THE GENERIC DRUG BOOM.  He was not familiar with the title but as we chatted about the role of India and China in reverse engineering American brand name medications his eyes lit up.  My physician is of Indian descent and he described to me what he witnessed when visiting India and the practices pursued by Indian generic drug manufacturers, particularly Ranbaxy.  He described disingenuous practices, fraud, corruption, the lack of government oversight and a myriad of illegal practices pursued by companies that went against the FDA’s best practices protocols.  Since 40% of all generic drugs are produced in India and 80% of the active ingredients in all drugs are produced in India and China his comments were eye opening and affirmed what Eban lays out in her investigative narrative of the generic drug industry and raised in my mind whether the new medication I was about to ingest was based on correct data and honest productive practices.  According to Eban, Americans should think twice when taking medications which puts people in a quandary – you need the medication, but can they be trusted?

The narrative that Eban has produced can best be described as “mind blowing.”  As one Dutch pharmaceutical executive described the generic industry as being similar to the meatpacking productive processes described by Upton Sinclair in his book, THE JUNGLE at the turn of the 20^th century.  Eban delineates the gulf that exists between what regulations require of generic drug companies and how those companies operated.  Their goal is to minimize costs and maximize profits.  To achieve this companies circumvented regulations and resorted to fraud: “manipulating tests to achieve positive results and concealing or altering data to cover their tracks.  By making the drugs cheaply without regard to safeguards and then selling them into regulated and more costly Western markets, claiming that they had followed all necessary regulations, companies could reap enormous profits.”

The key figure in the first half of the narrative was Dinesh S. Thakur, who was employed by Bristol-Myers, Squibb in Hopewell, NJ where he ran a department that built robots and other automated products designed to make drug testing more efficient and reliable.  Thakur’s problems began when he decided to leave his position in the United States and took one at Ranbaxy Laboratories located in India.  Almost immediately Thakur witnessed extensive fraud and a lack of transparency at the company.  Within two years Thakur’s friend, Rashmi Barbhaiya who convinced him to accept a position at Ranbaxy left the company leaving Thakur to fend for himself.  The first issue was HIV medications for South Africa which had a number of defects and the company refused to recall them.  As time went on Thakur would soon learn that Ranbaxy faked over 50% of its dossiers to the Food and Drug Administration (FDA); 100% for India; and 50% for Europe.  Thakur ordered a breakdown of every product, year by year of each dossier.  Ranbaxy used data as a fungible marketing tool without consideration for the impact its drugs had on patients.  “The company manipulated almost every aspect of the manufacturing process to quickly produce impressive looking data that would bolster its bottom line.”  Ranbaxy’s approach was to do whatever it could get away with the patients be damned.

Eban unravels the crimes and conspiracies involved in Ranbaxy’s approach to developing and producing generic drugs, layer by layer.  The company had no written protocols for investigating physician and patient complaints and viewed FDA regulations as an obstacle to be gamed.  When Dr. Kathy Spreen, Ranbaxy’s American Executive Director of Clinical Medicine uncovered the fraud dealing with Aids drugs she expressed her concerns to a company executive who responded, “Who Cares…It’s only blacks dying.”  When another friend of Thakur, Rajinder Kumar resigned because of company practices, Thakur was targeted by executives because of his complaints and when executives threatened him and his family, he also left the company. Eban’s focus on Thakur’s experiences reads like a crime novel.  He smuggled out damning evidence against the company and became a whistleblower for the FDA.  His life was a mess and his experience were chilling as he feared he would be outed, and his family would pay the price.

Thakur is not the only one to experience the deceit of the Indian generic industry.  Eban describes how Dr. Harry Lever, a Cleveland Clinic cardiologist discovered that when his patients switched from brand name drugs to generics their health greatly deteriorated.  Dr. Randall Starling, a member of the Cleveland Clinic Heart Failure and Cardiac Transplant Medicine team uncovered that the generic version of tacrolimus, made by Dr. Reddy’s Laboratories, an Indian company caused major issues with his transplant patients.  Eban’s discussion of Joe and Jerry Graedon who for over thirty years had a syndicated newspaper column and a patient advocate NPR program realized through their own research that FDA standards in approving generic medication were extremely flawed and eye opening.  All of these examples lead one to believe that the generic industry produces one horror show after another and the under funded and understaffed FDA with little access to the truth in India can not protect American patients, or for that matter foreign markets that Indian companies supply with medications.

Aside from Thakur there are a number of important personages in Eban’s expose and the one that stands out the most is Peter Baker.  In 2008 Baker joined the FDA and soon became its most important foreign investigator.  A no nonsense individual who thought nothing of jumping into a dumpster to find evidence of fraud and god knows what else as he became the bane of Ranbaxy and other companies’ existence.  His work in India and China, the threats he dealt with from foreign companies, and even opposition within the FDA who at times saw him as a “cowboy” probably resulted in saving countless lives.  Baker’s discoveries boggle the mind and provide unbelievable insights into the minds of foreign generic executives and their approach to the manufacturing process and the frauds they engaged in.

The further one reads Eban’s expose the more distressing the information becomes.  It seemed it was standard practice for the generic companies to make different versions of the same product, high quality drugs for the Western markets, and low-quality ones for lower income countries which was highlighted by Eban’s reportage of the drug Lipitor.  Eban’s work is very important and I found myself checking the labels on my own medication and where they were manufactured as I became immersed in the book producing a great deal of anxiety on my part.  It seems that what started in Mahatma Gandhi’s ashram as a campaign of Indian self-reliance had morphed into a pharmaceutical rescue mission for the world’s most unfortunate patients. It is obvious that Eban’s work is extremely one sided which can be seen as a criticism, but in reality, how could it be anything different based on her findings especially since her research is impeccable.  The book should have a label for patients on the cover because it will create extreme angst in anyone who reads it.