Chapter 33: “Black River”

1. 1. Until 1976 the DRC was Zaire.
2. 2. Donald G. McNeil, Jr., “Earlier Ebola Outbreaks, and How the World Overcame Them,” New York Times, July 17, 2019.
3. 3. Between 1908 to 1960, the Democratic Republic of the Congo was the Belgian Congo. After independence in 1960, the new country maintained close ties to Belgium, so it is not surprising that the blood sent abroad for testing went to an institute in Antwerp before any arrived at the CDC. Helen Branswell, “History credits this man with discovering Ebola on his own. History is wrong,” STAT, July 14, 2016.
4. 4. Ibid.
5. 5. Lawrence K. Altman, “The Doctor’s World; Battle-Scarred Veteran Is General in Global War on AIDS,” New York Times, July 21, 1998, F1.
6. 6. N.J. Cox et al., “Evidence for two subtypes of Ebola virus based on oligonucleotide mapping of RNA.” J Infect Dis. 1983; 147: 272–75.
7. 7. In parts of Africa, bush meat is cooked and consumed as are dried remains of wild animals, from bats to chimpanzees. It is a multigenerational tradition and also a key source of protein in a region where protein is scarce. See Abby Phillip, “Why West Africans keep hunting and eating bush meat despite Ebola concerns,” Washington Post, August 5, 2014.
8. 8. Charlie Cooper, “How the Ebola Virus Got its Name and How We Caught it From Animals,” Independent, October 2, 2014.
9. 9. Feldmann H, Geisbert TW (March 2011). “Ebola haemorrhagic fever.” Lancet. 377 (9768): 849–62. See also “Ebola Virus Disease,” World Heath Organization at http://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease.
10. 10. Cooper, “How the Ebola Virus Got its Name and How We Caught it From Animals.”
11. 11. “What happens to your body if you get Ebola,” Conversation, June 17, 2014.
12. 12. E. Stimola, Ebola (New York: Rosen Publishing, 2011), 31, 52.
13. 13. Bahar Gholipour, “How Ebola Got Its Name,” LiveScience, October 9, 2014.
14. 14. Ibid.
15. 15. In 1973, the international committee with oversight for such naming had proposed Congo-Crimean hemorrhagic fever virus. The Soviets, who had isolated the virus in Crimea, insisted on Crimean-Congo hemorrhagic fever. They prevailed. Onder Ergönül and Charles Whitehouse, Personal Reflections, Congo Hemorrhagic Fever: A Global Perspective, Netherlands: Springer, 2007, 23.
16. 16. Only later did the doctors realize the map they had picked was not very precise; Ebola was not the river nearest to the infected village. In 2005, two British medical researchers caused an uproar by publishing a thesis that the fourteenth-century Black Plague that killed some 25 million Europeans was not a flea-borne bubonic disease but rather an early version of Ebola. It took researchers five years of DNA analysis to convincingly disprove that. Peter Piot, No Time to Lose: A Life in Pursuit of Deadly Viruses (W. W. Norton & Company, 2012). Christopher J. Duncan and “Congo ebola epidemic becomes second worst outbreak ever,” SKY News, March 25, 2019.
17. 17. “A HIV/AIDS Timeline: The Origins of HIV/AIDS,” 5th Edition, An Albion Center Publication, Australia, 2007, in collection of author.
18. 18. Pneumocystis carinii was long classified as a protozoan and many journalists and authors list it as such. In fact, DNA sequencing analysis has in recent years confirmed it is a fungus. The parasitic microorganism had first been isolated in guinea pigs in 1910 by a Brazilian researcher, and then French scientists subsequently identified it in Parisian sewer rats. See Ann E Wakefield, “Pneumocystis carinii: Role in childhood respiratory infections,” British Medical Bulletin, Volume 61, Issue 1, March 1, 2002, 175–88; M. T. Cushion, “Pneumocystis carinii Pneumonia,” Transmission and Epidemiology, September 1994; 123–37.
19. 19. Altman, “The Doctor’s World.”
20. 20. Randy Shilts, And the Band Played On: Politics, People and the AIDS Epidemic (London: Souvenir Press, 2011), 6.
21. 21. Ibid., 20. See also Y. Chang et al., “Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma,” Science. 266 (5192), 1994: 1865–69. See also “A HIV/AIDS Timeline: The Origins of HIV/AIDS.”
22. 22. Some researchers believe the first case of AIDS in the U.S. was confirmed by a preserved tissue sample to be a sixteen-year-old African American who died in St. Louis in 1969. Others contest that finding, citing that the brand of test kit used was one that had a high rate of false positives, and aside from Kaposi sarcoma, none of his symptoms were typical of AIDS patients. See generally “A HIV/AIDS Timeline: The Origins of HIV/AIDS.”
23. 23. “Charles Richard Drew—‘Father of the Blood Bank,’ ” American Chemistry Society, at https://www.acs.org/content/acs/en/education/whatischemistry/african-americans-in-sciences/charles-richard-drew.html.
24. 24. Douglas P. Starr, Blood: An Epic History of Medicine and Commerce (New York: Perennial, 2002), 216.
25. 25. “The Blood, Plasma, and Related Programs in the Korean War,” Chapter 20 from “The Blood Program in World War II,” at http://hcvets.com/data/military/1948_korea_military_blood_supply.htm.
26. 26. Starr, Blood, 219.
27. 27. Paolo Caraceni et al., “Clinical use of albumin.” “Blood transfusion,” Trasfusione del Sangue Vol. 11 Suppl 4, Suppl 4 (2013): s18–25.
28. 28. Starr, Blood, chapter 12.
29. 29. Starr, Blood, 178.
30. 30. Ibid.
31. 31. D. J. Wallace, “Apheresis for lupus erythematosus,” Lupus (1999) 8, 174–80.
32. 32. Factor VIII was a glycine-precipitated plasma fraction.
33. 33. There are two types of hemophiliacs, A and B; both are mostly men whose blood fails to produce sufficient proteins required for clotting. Factor VIII treated only hemophilia A. A different treatment, Factor IX, was later developed for hemophilia B. See generally Starr, Blood, chapter 12.
34. 34. The first crude method developed around 1940 to separate plasma from blood was dubbed fractionation. When the liquid plasma was then centrifuged, the first fractionation produced a small pebble-sized piece of clotting protein (mostly fibrinogen, called Factor I).
35. 35. Hemophiliacs, who had a short life expectancy then of only forty-two years, were more than willing to pay several thousand dollars for a year’s supply.
36. 36. See Albert Farrugia and Josephine Cassar, “Plasma-derived medicines: access and usage issues,” Blood Transfusion, vol. 10,3 (2011): 273–8.
37. 37. Starr, Blood, 178, 186.
38. 38. “National Research Council Committee on AIDS Research and the Behavioral, Social, and Statistical Sciences, Chapter 5, AIDS and the Blood Supply,” in AIDS: The Second Decade, H. G. Miller, C. F. Turner, and L. E. Moses, eds. (Washington, D.C.: National Academies Press, 1990).
39. 39. JAMA, Feb 5, 1968: Vol 203, No 6.
40. 40. Starr, Blood, 256–57. In 1975 a new hepatitis screening test was 40 percent effective.
41. 41. Cutter Laboratories and Armour Labs had separated blood and plasma during World War II. Armour was a drug spinoff of the meatpacking giant. The others were Courtland Laboratories (later Alpha Therapeutics) and Hyland (owned by Baxter Labs).
42. 42. Donna Shaw, “On The Trail Of Tainted Blood—Hemophiliacs Say U.S. Could Have Prevented Their Contracting Aids,” Philadelphia Inquirer, April 16, 1995, 1.
43. 43. Gilbert M. Gaul, “How blood, the ‘gift of life,’ became a billion-dollar business,” Philadelphia Inquirer, March 12, 1989, 1.
44. 44. The U.S. drug market was largely self-regulated through the 1990s. Those three giant blood bank organizations are registered nonprofits, but all derive significant annual profits from their blood business. They simply mark it as “excess over expenses” and then bank it against future losses. Gaul, “How blood, the ‘gift of life,’ became a billion-dollar business.”
45. 45. The United Nations Organization in the Congo was the sponsor for the project. U.N. secretary-general Dag Hammarskjöld was trying to mediate the armed conflict when he was killed on September 18, 1961. His chartered DC-6 crashed in the Congo. To this day there are conflicting theories about whether the fatal crash was an accident or the result of ground fire. For those who believe it was intentional, different conspiracy theories put the blame on black nationalists, white mercenaries, Western intelligence agencies, and even colonial-era mining syndicates. Rick Gladstone and Alan Cowell, “More Clues, and Questions, in 1961 Crash That Killed Dag Hammarskjold,” New York Times, February 17, 2019.
46. 46. In the 1960s there were an estimated 4,500 and the number increased by another 1,500 in the 1970s.
47. 47. Regine Jackson, “The Failure of Categories: Haitians in the United Nations Organization in the Congo, 1960–1964,” Journal of Haitian Studies, Vol. 20, No. 1 (Spring 2014), 34–64.
48. 48. Gorinsteen had incorporated the company in Florida on August 11, 1970 (Document Number 368180). Werner H. Thill was the only technical director. See Richard Severo, “Impoverished Haitians Sell Plasma for Use in the U.S.,” New York Times, January 28, 1972; Jacques Pepin, The Origin of AIDS (Cambridge: Cambridge University Press), 2012, 201.
49. 49. Duvalier liked the nickname. He was a physician before he was elected Haiti’s president in 1957 running on a black-nationalist-populist campaign. He considered himself the father of independent Haiti and the “Doc” was a reference to his medical degree.
50. 50. Severo, “Impoverished Haitians Sell Plasma for Use in the U.S.”; Pepin, The Origin of AIDS, 201–2.
51. 51. Ibid., 202.
52. 52. Ibid., 201–2.
53. 53. Francis B. Kent, “Rising Criticism—Haiti: Jobless, Poor Line up to Sell Blood,” Los Angeles Times, January 27, 1972, 1; Severo, “Impoverished Haitians Sell Plasma for Use in the U.S.”
54. 54. Pepin, The Origin of AIDS, 201.
55. 55. The pharmaceutical/biologic companies were Armour Pharmaceutical, Cutter Laboratories, Hyland Labs, Dow Chemical, and Dade Reagent. Hemo-Caribbean also sold to pharmaceutical and biologic companies in Germany and Sweden. Severo, “Impoverished Haitians Sell Plasma for Use in the U.S.”
56. 56. Ibid. The FDA has a rule from 1984 banning cash payments in the U.S. to blood donors, but there are numerous examples of how little it is enforced; blood banks are supposed to only give small token rewards including such items as movie tickets, gift cards, and T-shirts. Elizabeth Preston, “Why You Get Paid To Donate Plasma But Not Blood,” STAT News, January 22, 2016.
57. 57. Severo, “Impoverished Haitians Sell Plasma for Use in the U.S.”
58. 58. “Haiti: Jobless, Poor Line Up to Sell Blood,” Representative Victor V. Veysey, Congressional Record, February 3, 1972, 2563–64.
59. 59. Not only was the Biologics Division unable to say whether infected Hemo-Caribbean plasma fractions were sold in the U.S., it could not track where the plasma was distributed after it entered the country. The government agency tasked with protecting the American blood did not even know how much Haitian plasma had been imported into the U.S. The National Blood Bank Act, HR 11828, that in 1975 established inspection and licensing of all blood banks and importers.
60. 60. Author interview with former assistant manager at Hemo-Caribbean, July 8, 2017.
61. 61. Francis B. Kent, “Rising Criticism—Haiti: Jobless, Poor Line up to Sell Blood,” Los Angeles Times, January 27, 1972.
62. 62. Author interview with former assistant manager at Port-au-Prince Hemo-Caribbean, November 1971 to August 1972, name withheld on request, in Miami, June 28, 2017. While it is not possible to know with certainty what caused the instances of vomiting or breathing problems, a known rare adverse effect with blood donors is “citrate reaction,” in which a donor reacts badly to the body’s temporary loss of calcium.
63. 63. Report of the United Nations AIDS report, Country: Haiti. See http://www.unaids.org/en/regionscountries/countries/haiti.
64. 64. Dr. Jacques Pepin, an infectious disease specialist who has written extensively about HIV/AIDS, believes that Hemo-Caribbean “could have been the perfect venue for the rapid parenteral amplification of a strain of HIV-1.… Hemo-Caribbean operated in 1971 and 1972, at exactly the right time, after the virus had been imported into Haiti.” Pepin, The Origin of AIDS, 205.
65. 65. B. Liautaud et al., “Kaposi’s Sarcoma In Haiti: Unknown Reservoir Or A Recent Appearance?” Ann Dermatol Venereol. 1983;110(3):213–19. There are no written records of donors from which to compare to the earliest identified HIV patients.
66. 66. Mirko Gmek, History of AIDS: Emergence and Origin of a Modern Pandemic (Princeton, NJ: Princeton University Press, 1990), 37.
67. 67. H. Luke Shaefer and Analidis Ochoa, “How Blood-Plasma Companies Target the Poorest Americans: The industry’s business model depends on there being plenty of people who need cash quickly,” Atlantic, March 15, 2018.

Chapter 34: “Everything Can Be Abused”

1. 1. The Sacklers had incorporated Napp Chemicals in Delaware in 1970, but its name changed by 1978. Besides its U.S. branch, the Sacklers used the name in a series of UK companies, all slight variations of the original 1966 Napp Pharmaceutical Group Limited (company #00884285). Among them are Napp Research Centre Limited, co. #01837276 (1984); Napp Pharmaceutical Research Limited, co. #4608592 (1985); Napp Pharmaceutical Holdings Limited, co. #03486244 (1997); and Napp Pharmaceuticals Limited, co. #03690299 (1998). Files in collection of author.
2. 2. The Mortimer Sackler and Sackler Family Foundations use the same address and telephone number to this day. When Michael Sonnenreich began working as an attorney for Arthur Sackler in 1973, his office was at 15 East 62nd Street. He told the author he does not remember Greene there in 1978, suggesting Greene might have only used it as a mail drop. Tax Return of Private Foundation, Mortimer D. Sackler Foundation, EIN: 23-7022461. 19 pages, Form 990-PF, 2013, in collection of author.
3. 3. Edward Shorter, A Historical Dictionary of Psychiatry (Oxford, UK: Oxford University Press, 2005).
4. 4. Carol Brennan, “Valium,” at https://www.benzo.org.uk/valium3.htm.
5. 5. Author interview with former business partner of Arthur Sackler, November 2018.
6. 6. Marilyn Goldstein, “Society Is Still Coping with Valium,” Newsday (New York), January 26, 1988, 4A.
7. 7. Barbara Gordon, I’m Dancing as Fast as I Can (New York: Harper & Row, 1979). See Tammy Faye Baker, “Mother’s Little Helper: Valium at 35,” ABC News, December 17, 1998, and for Elizabeth Taylor, Robin Marantz Henig, op-ed, “Valium’s Contribution to Our New Normal,” New York Times, September 29, 2012.
8. 8. The Memphis medical examiner concluded that Elvis died of natural causes, a cardiac arrhythmia caused by “polypharmacy” (drug interaction). That ruling eliminated any possible prosecution against Dr. Nick for murder or manslaughter. Three years after Presley’s death, the Tennessee Board of Medical Examiners gave Dr. Nick a three-month suspension but cleared him of more serious charges of unethical conduct and medical malpractice. The following year, state prosecutors filed a 14-count indictment for overprescribing thousands of stimulants, barbiturates, and painkillers to Elvis, Jerry Lee Lewis, and eight others. A jury acquitted Dr. Nick on all counts. In 1992, a tougher Tennessee Board of Medical Examiners charged him again, this time with reckless overprescribing. It took three years before the state prevailed and stripped Dr. Nick of his medical license. See “Presley’s Doctor on Trial Over Prescriptions,” New York Times, September 30, 1981, A22; Adam Higginbotham, “Doctor Feelgood,” Guardian, August 10, 2002; see Dr. Nick interviewed in Gerald Posner, “Elvis’s Doctor Speaks,” Daily Beast, August 14, 2009.
9. 9. The fourth benzodiazepine discovered by Leo Sternbach was Dalmane, which Roche released in 1970 as a sleep aid. It was marketed as a hypnotic and had little effect on Valium sales.
10. 10. “Lorazepam (Ativan),” History, Ativan Drug Project, at https://ativandrugproject.weebly.com/structure-and-history.html.
11. 11. Shahrzad Salmasi et al., “Interaction and medical inducement between pharmaceutical representatives and physicians: a meta-synthesis,” Journal of Pharmaceutical Policy and Practice, vol. 9, no. 37, November 17, 2016. See also Hneine Brax et al., “Association between physicians’ interaction with pharmaceutical companies and their clinical practices: A systematic review and meta-analysis,” PloS One (Public Library of Science), vol. 12, iss 4, April 13, 2017.
12. 12. Sackler hoped that Valium might also be helped unintentionally by the chief of the Office of Drug Abuse whom Jimmy Carter had selected earlier that year. Arthur knew Dr. Peter Bourne, a London-born, American-educated psychiatrist, who made barbiturates his number one target for the most abused prescription category in the U.S. That took the federal spotlight temporarily off benzodiazepines.
13. 13. Nicholas E Calcaterra and James C Barrow. “Classics in Chemical Neuroscience: Diazepam (Valium).” ACS Chemical Neuroscience vol. 5, no. 4 (2014): 253–60.
14. 14. Matthew Herper, “Slide Show: America’s Most Popular Psychiatric Drugs,” Forbes, September 17, 2010.
15. 15. Boyce Rensberger, “Abuse of Prescription Drugs: A Hidden but Serious Problem for Women,” New York Times, April 19, 1978, A12; also Myra MacPherson and Donnie Radcliffe, “Betty Ford Says That She Is Addicted to Alcohol,” Washington Post, April 22, 1978, 1.
16. 16. Arnie Cooper, “An Anxious History of Valium,” Wall Street Journal, November 15, 2013, 1; Dowbiggin, The Quest for Mental Health, 161.
17. 17. Stephen Cohen, “It’s a Mad, Mad Verdict: Hinckley Got Off, But the Verdict on the Insanity Defense Is Guilty,” New Republic, July 12, 1982.
18. 18. Author interview with former business associate of Arthur Sackler, November 2018.
19. 19. The generic name was triazolam.
20. 20. An Assessment of Data Adequacy and Confidence. Halcion: An Independent Assessment of Safety and Efficacy Data. Institute of Medicine (US) Committee on Halcion (Washington, D.C.: National Academies Press, 1997, introduction, 1.
21. 21. FDA Approval for “Type 1—New Molecular Entity, alprazolam,” drug application from Pharmacia and Upjohn, NDA 018276, FDA action date October 16, 1981.
22. 22. J. Angs, “Panic Disorder: History and Epidemiology,” Eur Psychiatry. 1998;13 Suppl 2:51s–55s.
23. 23. Matthew Herper, “America’s Most Popular Mind Medicines,” Forbes, September 17, 2010.
24. 24. Dowbiggin, The Quest for Mental Health, 188–89.
25. 25. The FDA approval for Xanax to treat panic disorder did not come until 1990. However, psychiatrists and general practitioners had been prescribing it off-label for that from since its 1981 introduction.
26. 26. Cooper, “An Anxious History of Valium”; Tone, Age of Anxiety, 213.
27. 27. Shorter, Before Prozac; George Stein and Brett Chase, “Pharmacia & Upjohn, Monsanto to Merge in $26.5-Billion Deal,” Los Angeles Times, December 20, 1999; Matthew Herper, “Pfizer Buys Pharmacia For $60 Billion,” Forbes, July 15, 2002.
28. 28. Dowbiggin, The Quest for Mental Health, 174–76.
29. 29. Arthur Kleinman quoted in Ashley Pettus, “Psychiatry by Prescription,” Harvard Magazine, July–August 2006.
30. 30. Peter Kramer quoted in Jonathan Rosen, “The Assault on Antidepressants,” Atlantic, July/August 2016.
31. 31. C. Karestan Koenen et al., “Persisting Posttraumatic Stress Disorder Symptoms and their Relationship to Functioning in Vietnam Veterans: A 14-Year Follow-up,” Journal of Traumatic Stress vol. 21, no. 1 (2008): 49–57.
32. 32. Smith, A Social History of the Minor Tranquilizers, 1.
33. 33. Leo Sternbach quoted in B. D. Cohen, “Valium and Health,” Washington Post, February 24, 1980.
34. 34. Author interview with former business partner of Arthur Sackler, November 2018.

    Eventually there was a scientific pushback against the offensive on Valium. Heinz Lehmann, a psychiatrist considered the “father of modern psychopharmacology,” had predicted in 1960 Senate testimony that the overprescribing of mild tranquilizers would create a dependence crisis. Two decades later he had concluded that “sensational horror stories” had unfairly maligned Valium. A JAMA editorial later asked, “Where are all the tranquilizer junkies?,” questioning whether the great scare about the addictiveness of the benzos was mostly wrong. E. R. González, “Where are all the tranquilizer junkies?,” JAMA, May 20, 1983;249(19):2603–4; Andrea Tone, “Listening to the Past: History, Psychiatry, and Anxiety,” Canadian Journal of Psychiatry, June 2005.

Chapter 35: The Age of Biotech

1. 1. Searches by the author for “valium” in LexisNexis and newspapers.com show 32,769 print articles in the United States from 1975 through 1980.
2. 2. Oversight and Review of Clinical Gene Transfer Protocols: Assessing the Role of the Recombinant DNA Advisory Committee. Committee on the Independent Review and Assessment of the Activities of the NIH Recombinant DNA Advisory Committee, Board on Health Sciences Policy, Institute of Medicine (Washington, D.C.: National Academies Press 2014).
3. 3. With the end of the moratorium, the NIH became the unofficial biotech regulator and benefactor. Its National Medical Library was an unmatched knowledge base through which researchers shared information. And, most important, it opened its peer-review pipeline for federal grants to encourage cutting-edge research and sponsored the doctoral and postdoctoral studies of young biologists and scientists. Fredrickson quoted in Nell Henderson and Michael Schrage, “The Roots of Biotechnology: Government R&D Spawns a New Industry,” Washington Post, December 16, 1984, 5.
4. 4. Ibid.
5. 5. The change was proposed in 1979 but it took until 1981 for it to become effective. Private companies were mostly uncertain about how much of what they discovered would be theirs under a patent that had been financed by the government. For the first decade, on average there were a dozen private companies that applied annually for research grants, in contrast to the approximately twenty thousand nonprofit applications every year.
6. 6. History of Congressional Appropriations, National Institutes of Health,1960–1969, at https://officeofbudget.od.nih.gov/pdfs/FY08/FY08%20COMPLETED/appic3806%20-%20transposed%20%2060%20-%2069.pdf.
7. 7. If, for some reason, the university did not patent its NIH-funded discovery, the government could patent it and the royalties would go the Treasury Department. The NIH created the Office of Medical Applications of Research in 1977 and it was responsible for recommending whether something developed by an academic research center should be patented by the government.
8. 8. Swanson called Boyer in April 1976; the moratorium was not lifted until July.
9. 9. Kleiner Perkins was the firm, based in Menlo Park. Kleiner was a cofounder of Fairchild Semiconductor.
10. 10. It was Stanford’s director of Technology Licensing that convinced a reluctant Cohen to file for the patent. Their original application was split into three parts, two of them for products produced in different cell lines and the other a process patent for the mechanics they used.
11. 11. S. S. Hughes, “Making dollars out of DNA. The first major patent in biotechnology and the commercialization of molecular biology, 1974–1980,” Isis, 92(3), September 2001: 541–75.
12. 12. Doogab Yi, “Who Owns What? Private Ownership and the Public Interest in Recombinant DNA Technology in the 1970s,” Isis, 102(3), September 2011: 446–74
13. 13. Marie Godar, “Humble Beginnings: The Origin Story of Modern Biotechnology,” LabBiotech, November 17, 2005.
14. 14. “Gobind Khorana and the Rise of Molecular Biology,” MIT School of Science/Research and Academics, at https://science.mit.edu/gobind-khorana-molecular-biology/.
15. 15. Nathan Rosenberg, Annetine Gelijns, and Holly Dawkins, ed., “Sources of Medical Technology: Universities and Industry,” Chapter 7 in vol. 5, Committee on Technological Innovation in Medicine, Institute of Medicine (Washington, D.C.: National Academy Press, 1995).
16. 16. Ibid., 168.
17. 17. Ibid., 169–70, and Biogen: Company History Overview, at https://www.biogen.com/en_us/history-overview.html.
18. 18. Stephan S. Hall, Invisible Frontiers: The Race to Synthesize a Human Gene (New York: Atlantic Monthly Press, 1987).
19. 19. Quoted in “Cloning Insulin,” Genentech, April 7, 2016, at https://www.gene.com/stories/cloning-insulin.
20. 20. There were over four thousand biotech start-ups in the coming decades. Most were one-product firms and more than 80 percent never brought a drug to market. Gary P. Pisano, “Can Science Be a Business?: Lessons from Biotech,” Harvard Business Review, October 2006.
21. 21. Henderson and Schrage, “The Roots of Biotechnology,” 5.
22. 22. Robert J. Cole, “Genentech New Issue, Up Sharply,” New York Times, October 15, 1980, D1.
23. 23. Stelios Papadopoulos, “Evolving paradigms in biotech IPO valuations,” Nature Biotechnology, Volume 19, BE18–BE19 (2001).
24. 24. A miscalculation by Wall Street was the belief that the FDA approval process for biopharmaceuticals would be much speedier than the one for traditional drugs. A 2005 study showed that over thirty years the biotech industry had attracted $300 billion in venture capital. Although the sector had gone from zero revenues in 1975 to $40 billion, only a handful of companies earned profits. The most successful firms were the earliest ones, Genentech, Amgen, Chiron, Genzyme, and Biogen. Stelios Papadopoulos, “Evolving paradigms in biotech IPO valuations”; Pisano, “Can Science Be a Business?”
25. 25. Bogle quoted in The Wall Street Reporter, May 1980; see also Wayne Duggan, “John Bogle’s Biggest Investing Mistake And What He Learned From It,” Benzinga, June 11, 2005, in which Bogle referred to market bubbles such as biotech, and later the dot-com companies, “Each stock looked really great, but anybody would know that all of them cannot succeed.”
26. 26. Activase is the brand name for the first drug to utilize tissue plasminogen activator (TPA), an enzyme that dissolves blood clots. The stock dropped from 48.25 to 36.75 for a paper loss of $930 million. Carpenter, Reputation and Power. For FDA approval, see License 1048, Application No.:103172-Supplement 1055, generic name Alteplase, tradename: Activase, June 18, 1996.
27. 27. The next rally would not happen until congressional Republicans killed Bill Clinton’s sweeping proposed health care legislation in 1995, easing concerns that there could be price controls. Biotech would suffer the most from such limits since its successful products are by a wide margin the most expensive in the industry.
28. 28. For a few examples of institutional buy recommendations followed by drops of 80 percent or more in share price within a week of bad news, see DOV Pharma in 2005; Threshold Pharmaceuticals and Valentis in 2006; Casey Murphy, “The Ups and Downs of Biotechnology,” Investopedia, updated October 16, 2019; Heidi Ledford, “Blood Money: The Biotech Debacle of Theranos on Screen,” Nature, April 2, 2019.

Chapter 36: A “Gay Cancer”

1. 1. Randy Shilts, And the Band Played On: Politics, People, and the AIDS Epidemic, 20th-Anniversary Edition (New York: St. Martin’s Griffin, 2007), Kindle Edition, 11. See also Bill Van Niekerken, “Rainbow Gold Mine: Early SF Pride Parade Photos Rediscovered in Archive,” San Francisco Chronicle, June 26, 2019.
2. 2. The Bay Area’s burgeoning gay community had social and political influence. One of those who had arrived in the migration to San Francisco was Harvey Milk; he made history in 1977 when he ran and won a seat on the city’s board of supervisors. Milk was California’s first openly gay elected official. When he and the city’s progressive mayor were assassinated by a disgruntled former supervisor the following year, Milk’s death was a chilling reminder that although tremendous gains had been made in only a few years, homophobia still flourished. Dudley Clendinen and Adam Nagourney, Out for Good: The Struggle to Build a Gay Rights Movement in America (New York: Simon & Schuster, 1999) 151–55; Shilts, And the Band Played On, 15–17; Jennifer Robison, “What Percentage of the Population Is Gay?” Gallup Poll, October 8, 2002.
3. 3. Randy Shilts, broadcast commemorating Stonewall, June 22 1979, Bay Area Television Archive, KQED Collection, (Public Television, San Francisco), San Francisco State University.
4. 4. The Consenting Adult Sex Bill did not repeal the state’s sodomy and oral copulation laws, but instead excluded private consensual activity between adults over the age of eighteen. See Assembly Bill 489, January 15, 1975.
5. 5. Clendinen and Nagourney, Out for Good, 151.
6. 6. Among two dozen San Francisco bathhouses was the Bulldog Baths, the world’s largest in the seedy Tenderloin district. It was a two-story bondage/leather reproduction of nearby San Quentin prison. In 2012, the shuttered building was listed in the National Register of Historic Places. The decision to list the building on the federal government’s register of historic places was not without controversy. Some leaders of the San Francisco gay community thought the Bulldog’s contribution to gay history was not one that deserved historic recognition. On the other hand, Back2Stonewall, a popular online LGBT news site, wrote at the time: “The Bull Dog was an architectural playground for the fantasies of gay sexual desires. It is a historic place in gay history and it’s good to see that the National Registry of Historic Places recognizes that even though many in our own community won’t.” Will Kohler, “National Register of Historic Places Recognizes San Francisco’s Bulldog Baths With Historical Plaque,” Back2Stonewall, September 22, 2012. Miller HG, Turner CF, Moses LE, editors.
7. 7. David Cheng, “Amyl Nitrites: A Review of History, Epidemiology, and Behavioral Usage,” Journal of Student Research, vol. 2, no. 1, 2013; 17–21.
8. 8. Sevgi O Aral et al., “Sexually Transmitted Diseases In The USA: Temporal Trends,” Sexually Transmitted Infections vol. 83, no. 4 (2007): 257–66.
9. 9. Dale O’Leary, “The Syndemic of AIDS and STDS among MSM [men who have sex with men],” Linacre Quarterly, vol. 81, no. 1 (2014): 12–37.
10. 10. “AIDS and the Blood Supply,” chapter 5 in AIDS: The Second Decade (National Research Council, Committee on AIDS Research and the Behavioral, Social, and Statistical Sciences), (Washington, D.C.: The National Academies Press, 1990).
11. 11. William J. Woods et al., “Facilities and HIV Prevention in Bathhouse and Sex Club Environments,” Journal of Sex Research 38, no. 1 (2001): 68–74; see also Shilts, And the Band Played On, 19.
12. 12. Thomas R. Blair, “Safe Sex in the 1970s: Community Practitioners on the Eve of AIDS,” American Journal of Public Health 107, no. 6 (June 1, 2017): 872–79.
13. 13. Giving credence to the idea that sex acts could be considered part of the political Gay Liberation movement, a left-wing alternative Toronto newspaper hailed rimming as “a revolutionary act.”
14. 14. Shilts, And the Band Played On, 18–19.
15. 15. Janice Hopkins Tanne, “Fighting AIDS: On the Front Lines Against the Plague,” New York, January 12, 1987, 24–25.
16. 16. Donna Mildvan quoted in Ibid., 25.
17. 17. Ibid., 27.
18. 18. Harry Mobley, “How Do Antibiotics Kill Bacterial Cells But Not Human Cells?” Scientific American, March 13, 2006.
19. 19. Iulia Filip, “Avoiding the Black Plague Today,” Atlantic, April 11, 2004.
20. 20. Joan Trossman Bien, “The Swine Flu Vaccine: 1976 Casts A Giant Shadow,” Pacific Standard, December 4, 2009; “Why Can’t We Beat Viruses?,” BBC News, January 24, 2013.
21. 21. Lawrence K. Altman, “Rare Cancer Seen in 41 Homosexuals,” New York Times, July 3, 1981. In a 2014 interview, Altman told The Atlantic that he had been intending to write a story in the spring, but it got delayed to the summer because he had been assigned to cover the attempted assassination of Pope John Paul II that May. See Cari Romm, “ ‘The Disease of the Century’: Reporting on the Origin of AIDS,” Atlantic, December 5, 2014.
22. 22. Romm, “ ‘The Disease of the Century.’ ”
23. 23. Tanne, “Fighting AIDS,” 25.
24. 24. The first medical paper about the symptoms and cases that would later be identified as AIDS was in December 1981: M. S. Gottlieb et al., “Pneumocystis Carinii Pneumonia And Mucosal Candidiasis In Previously Healthy Homosexual Men: Evidence Of A New Acquired Cellular Immunodeficiency,” NEJM, December 10, 1981, 305(24):1425–31. As for the early descriptions of the mystery illness as being unique to the gay community, see André Picard, “How the Advent of AIDS Advanced Gay Rights,” Globe and Mail (Canada), August 15, 2014, updated May 12, 2018; “News From the Front Lines of the AIDS Fight,” Newscenter, Univeristy of Rochester, December 1, 2016. See Myrna Watanabe, “AIDS 20 Years Later,” Scientist, June 11, 2001. See also “July 2, 1981, Bay Area Reporter” listing in 1981 on the Timeline of HIV and AIDS at HIV.gov.
25. 25. Dr. Samuel Broder, Oral History Collection, National Institutes of Health, Historical Office, U.S. National Library of Medicine. Bethesda, MD, February 5, 1997. The medical records for that first paitent were subsequently “lost, misplaced, or something happened to them.”
26. 26. The CDC description of what was now believed to be a new virus was “A disease at least moderately predictive of a defect in cell-mediated immunity, occurring in a person with no known cause for diminished resistance to that disease.” See the September 24 listing in 1982 on the Timeline of HIV and AIDS at HIV.gov.
27. 27. Tom Curtis, “The Origin of AIDS,” Rolling Stone, issue 626, March 19, 1992; see also Tom Curtis Papers, The Wittliff Collections, Texas State University; David Secko, “Polio Vaccine-AIDS Theory Dead,” Scientist, April 21, 2004; M. Worobey et al., “Origin of AIDS: Contaminated Polio Vaccine Theory Refute; Kisangani Chimpanzees Contain a Virus Unrelated to HIV-1,” Nature, Vol. 428 [6985], April 22, 2004; Mitch Leslie, “Study Pushes AIDS Origins Back to 1930s,” Science, June 9, 2000; Jon Cohen, “Vaccine Theory of AIDS Origins Disputed at Royal Society,” Science, Vol. 289, Issue 5486, September 15, 2000; Stanley A. Plotkin and Hilary Koprowski, “Responding to The River,” Science, Vol. 286, Issue 5449, 2449, December 24, 1999; Jon Cohen, “Disputed AIDS Theory Dies its Final Death,” Science, Vol. 292, Issue 5517, April 27, 2001. And see Richard Horton, “New Data Challenge OPV Theory of AIDS Origin,” Lancet, Vol. 356, Issue 9234, September 16, 2000; Sarah Ramsay, “Cold Water Downstream from The River,” Lancet, Vol. 357, Issue 9265, April 28, 2001; Helen Branswell, “HIV’s Genetic Code, Extracted From A Nub Of Tissue, Adds To Evidence Of Virus’ Emergence In Humans A Century Ago,” STAT, July 16, 2019.
28. 28. Herpes, which was possibly the most widespread sexual disease in the 1970s, was the same DNA family from which Kaposi sarcoma and cytomegalovirus developed. High rates of parasitic infections added to the overall toll on the immune system. Infectious disease experts later concluded that unprotected anal intercourse was the highest sexual risk factor for HIV. John Tierney, “The Big City; In 80’s, Fear Spread Faster Than AIDS,” New York Times, June 15, 2001. And see Trenton Straube, “Against All Odds: What Are Your Chances of Getting HIV in These Scenarios?” POZ, March 26, 2014.
29. 29. Altman quoted in Cari Romm, “ ‘The Disease of the Century’: Reporting on the Origin of AIDS,” Atlantic, December 5, 2014.
30. 30. Another key person was Dr. Bruce Chabner, chief of the Division of Cancer Treatment.
31. 31. Broder says most scientists who steered clear of AIDS did not want to risk their reputations. They thought the pressure from HIV/AIDS activists meant they would have to rush. Instead, their attitude was, “A cure or nothing. Give me 20 years and I’ll give you a cure.” Dr. Samuel Broder, Oral History Collection, NIH.
32. 32. Tanne, “Fighting AIDS.”
33. 33. Filip, “Avoiding the Black Plague Today.”
34. 34. “Pneumocystis Carinii Pneumonia Among Persons With Hemophilia A,” Morb Mortal Wkly Rep. 1982;31:365–67; Gilbert C. White, II, “Hemophilia: An Amazing 35-Year Journey From The Depths Of HIV To The Threshold Of Cure,” Transactions of the American Clinical and Climatological Association vol. 121 (2010): 61–73; see figure 1.
35. 35. Dr. Samuel Broder, Oral History Collection, NIH.
36. 36. Renowned sex researchers William Masters and Virginia Johnson wrote a book, Crisis: Heterosexual Behavior in the Age of AIDS, in which they warned that AIDS could be potentially caught from a public toilet seat. Another pioneer sex therapist, Helen Singer Kaplan, published The Real Truth About Women and AIDS, in which she warned that condoms might not provide protection against infection and claimed even kissing was risky. Dr. Samuel Broder, Oral History Collection, NIH. See also Tierney, “The Big City; In 80’s, Fear Spread Faster Than AIDS.”
37. 37. Simon Garfield, “The Rise And Fall Of AZT,” Independent (UK), May 2, 1993.
38. 38. Broder quoted in Ibid.
39. 39. Broder quoted in Celia Farber, “AIDS and the AZT Scandal: SPIN’s 1989 Feature, ‘Sins of Omission,’ ” SPIN, October 5, 2015.
40. 40. At the peak of the AIDS epidemic, July of 1988, the New York City health commissioner, Dr. Stephen Joseph, reduced the city’s estimate of infected New Yorkers from 400,000 to 200,000. The leaders of ACT UP, the AIDS Coalition to Unleash Power, were furious, convinced he lied to cover up the gravity of the epidemic and thereby cut city funding to battle it. Activists demanded his resignation and dogged him at public appearances. They picketed at his home and spray-painted his car. Police protection was assigned after he got death threats. Dr. Joseph rescinded his reduced estimate and restored it to 400,000. Thirteen years later The New York Times reported: “Now it turns out that Dr. Joseph’s estimate [of 400,000] was actually too high. It might have been twice the actual figure, according to a new report from the American Council on Science and Health, a science advocacy group. The total number of AIDS cases diagnosed in New York City from 1981 through early 2000 was less than 120,000.” Tierney, “The Big City; In 80’s, Fear Spread Faster Than AIDS.”
41. 41. Picard, “How the Advent of AIDS Advanced Gay Rights.”
42. 42. Daniel J. DeNoon, “AIDS Worse Than Black Death,” WebMD, January 25, 2002.
43. 43. Matt Ridley, “Apocalypse Not: Here’s Why You Shouldn’t Worry About End Times,” Wired, August 17, 2012.
44. 44. The Health Department investigator was Anastasia Lekatsas, whom the New York Times journalist John Tierney dubbed “America’s most dogged street detective of AIDS.” Lekatsas had examined the New York Health Department’s NIR cases (no identified risk). “If a man claimed to have gotten AIDS from a woman, she would visit him, revisit him, interview his family and friends—and eventually she would almost always find that he’d been sharing needles or having sex with men.” Regarding the eight men listed by the New York Health Department as having been infected as heterosexuals, she told the Times, “I have doubts about seven of them, but we couldn’t prove anything.” See Tierney, “The Big City; In 80’s, Fear Spread Faster Than AIDS.” See also K. G. Castro et al., “Investigations of AIDS Patients With No Previously Identified Risk Factors,” JAMA, 259(9), 1988,1338–42.
45. 45. Tierney, “The Big City; In 80’s, Fear Spread Faster Than AIDS.”
46. 46. Patrick J. Buchanan and J. Gordon Muir, “Gay Times and Diseases,” The American Spectator, August 1984.
47. 47. Ronald Reagan, Appointment of Patrick J. Buchanan as Assistant to the President and Director of Communications Online by Gerhard Peters and John T. Woolley, The American Presidency Project, https://www.presidency.ucsb.edu/node/259289.
48. 48. Picard, “How the Advent of AIDS Advanced Gay Rights,” and see “Homophobia and HIV,” Avert, at https://www.avert.org/professionals/hiv-social-issues/homophobia.
49. 49. “Some people had hoped that AZT would be a cure,” says Broder. “No one at NIH ever said that it would be.… We always chose our words cautiously and specifically. It was simply a starting point. But without AZT… we would have been very hard pressed to make any progress in the therapy of the AIDS virus.” D. Fajardo-Ortiz et al., “The Emergence and Evolution of the Research Fronts in HIV/AIDS Research,” PLoS One. 2017;12(5); Ghobad Moradi et al., “Health Needs of People Living with HIV/AIDS: From the Perspective of Policy Makers, Physicians and Consultants, and People Living with HIV/AIDS,” Iranian Journal of Public Health vol. 43,10 (2014): 1424; Dr. Samuel Broder, Oral History Collection, NIH.
50. 50. Alice Park, “The Story Behind the First AIDS Drug,” Time, March 19, 2017.
51. 51. Farber, “AIDS and the AZT Scandal.”
52. 52. “AZT’s Inhuman Cost,” New York Times editorial, August 28, 1989, A16.
53. 53. Ibid.
54. 54. Garfield, “The Rise And Fall Of AZT.”
55. 55. Harry Jupiter, “18 Protestors Arrested at AIDS-Drug Firm,” San Francisco Examiner, January 25, 1988, B1.
56. 56. Victoria F. Zonana, “Firm to Offer AIDS Drug Free in Critical Cases,” Los Angeles Times, July 14, 1989, 1, 39.
57. 57. Mikami, “Orphans in the Market,” 609–30.
58. 58. Ibid.
59. 59. Sarah Jane Tribble and Sydney Lupkin, “Drugs For Rare Diseases Have Become Uncommonly Rich Monopolies,” NPR Morning Edition, January 17, 2017; Michael Henry Davis et al., “Rare Diseases, Drug Development and AIDS: The Impact of the Orphan Drug Act,” 73 Milbank Quarterly 231 (1995). See also Mikami, “Orphans in the Market.”
60. 60. Davis et al., “Rare Diseases, Drug Development and AIDS.”
61. 61. Malorye A. Branca, “How the Orphan Drug Act Changed the Development Landscape,” BioPharma Dive, April 10, 2017.
62. 62. Tribble and Lupkin, “Drugs For Rare Diseases Have Become Uncommonly Rich Monopolies.”
63. 63. Davis et al., “Rare Diseases, Drug Development and AIDS.”
64. 64. See generally P. S. Arno et al., “Rare Diseases, Drug Development, And AIDS: The Impact Of The Orphan Drug Act,” Milbank Q. 1995;73(2):231–52.
65. 65. Davis et al., “Rare Diseases, Drug Development and AIDS.”
66. 66. Off-label dispensing is legal, set out in the Food, Drug, and Cosmetic Act of 1938. That was the same law that empowered the FDA to regulate drugs, medical devices, food, and cosmetics. See D. C. Radley et al., “Off-Label Prescribing Among Office-Based Physicians.” Arch Intern Med 2006 May 8;166(9):1021–26.
67. 67. The generic is a combination of emtricitabine and tenofovir disoproxil fumarate. The FDA’s approved label indication for the orphan on September 28, 2017, is “DESCOVY, indicated in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg and also indicated, in combination with other antiretroviral agents other than protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection in pediatric patients weighing at least 25 kg and less than 35 kg.”
68. 68. Christopher Rowland, “An HIV Treatment Cost Taxpayers Millions. The Government Patented It. But a Pharma Giant Is Making Billions,” Washington Post, March 26, 2019.
69. 69. Robert M. Grant et al., “Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men,” NEJM, December 30, 2010, 363:2587–99.
70. 70. James Krellenstein, Aaron Lord, and Peter Staley, “Why Don’t More Americans Use PrEP?,” New York Times, July 16, 2018.
71. 71. Ibid.

Chapter 37: “None of the Public’s Damned Business”

1. 1. The Martha Graham Dance Company performed before two thousand guests.
2. 2. It was a far cry from an ostentatious seventieth birthday gala that Mortimer hosted for himself a decade later at the Temple of Dendur. The highlight was a four-foot-high cake resembling a Sphinx with Mortimer’s face. In a cringe-worthy rambling speech, he said that collecting art was like masturbation, an orgasm could only be delayed so long. Arthur told another guest it “was vulgar.” His friends recalled that on his seventieth birthday a few years earlier, he had marked it with a private dinner for some close friends. Author interview with business partner of Arthur Sackler, December 2018.
3. 3. The forty-one-year-old Montebello was a surprise choice after a special committee of six trustees spent nearly six months conducting an intensive international search for a new director. He transformed the museum in his thirty-one-year tenure, the longest in the institution’s history. Leah Shanks Gordon, “Help Wanted at the Met,” New York Times, June 26, 1977; Calvin Tomkins, “The Importance of Being Élitist,” New Yorker, Nov 24, 1997, 75; Charles McGrath, “Twilight of the Sun King,” New York Times, July 29, 2007.
4. 4. Arthur complained constantly that Montebello was defiling Dendur’s “sacred” enclosure by using it as the setting for dinner parties. Arthur griped that a Diana Vreeland fete for fashion designer Valentino was “disgusting.” Worse was a dinner for designer Pierre Cardin that drew Norman Mailer, Andy Warhol, Estée Lauder, Betsy Bloomingdale, Atlantic Records president Ahmet Ertegun, and talent agent Swifty Lazar, among others. “It was an everybody-who-is-anybody guest list,” wrote John Duka in the next day’s New York Times. Duka was a style and fashion industry reporter and Sackler pointed to that as the epitome of what was wrong with how Montebello used the family’s wing. McGrath, “Twilight of the Sun King.”
5. 5. Lee Rosenbaum, “The Met’s Sackler Enclave: Public Boon or Private Reserve?” ARTnews, September 1978, 56–57; John L. Hess, “Can the Met Escape King Tut’s Curse?,” New York, November 13, 1978, 82.
6. 6. Hess, “Can the Met Escape King Tut’s Curse?,” 83.
7. 7. Ibid., 79.
8. 8. Hoving File memo, Dec. 29, 1982, and memos to Phil Herrera, Jan. 1, 2, 1983, Hoving Papers, cited in Michael Gross, Rogues’ Gallery: The Secret Story of the Lust, Lies, Greed, and Betrayals That Made the Metropolitan Museum of Art (New York: Random House, 2009), Kindle Edition, 346. The New York State attorney general ultimately found no liability for Sackler, but sharply chastised the Met for the arrangement. Testimony of Sol Chaneles, chairman of Rutgers University Department of Criminal Justice, cited in Hess, “Can the Met Escape King Tut’s Curse!,” 86. Chaneles had been on assignment for ARTnews when he uncovered the secret Sackler storage room at the Metropolitan. The Society of Silurians, a distinguished press club of veteran reporters and editors, awarded ARTnews a journalism award for Lee Rosenbaum’s two-part “The Care and Feeding of Donors” and “The Met’s Sackler Enclave.” Grace Glueck, “An Art Collector Sows Largesse and Controversy,” New York Times, June 5, 1983; “Protecting the Public Interest in Art,” The Yale Law Journal, Vol. 91, No. 1 (November 1981), 121–43. See also Milton Esterow, “Reflections on Three Decades at the Helm of ARTnews,” ARTnews, November 1, 2002.
9. 9. Gross, Rogues’ Gallery, 338–39. Also, author interview with Sonnenreich, February 23, 2019.
10. 10. Lutze, Who Can Know the Other?, 165.
11. 11. Press reports often spell the name as Gillian. The same spelling was used in court litigation in the 1990s. However, in an announcement from the Smithsonian about a $5 million endowment she made in 2012, it was Jillian. In her own public statements it is Jillian, which is the one in this book.
12. 12. “Design Notebook: A Remarkable Maisonette on Park Ave,” New York Times, July 16, 1981. Jillian Sackler lives there today. See also Christopher Gray, “The Real 666 Park Avenue,” New York Times, September 27, 2012.
13. 13. Glueck, “Art Collector Sows Largesse and Controversy.”
14. 14. George Bulanda, “The Legacy of Charles L. Freer,” Detroit Hour, February 7, 2008.
15. 15. Meyer is the author of a dozen books. He was a foreign affairs reporter before serving on the New York Times and Washington Post editorial boards.
16. 16. British architect James Stirling was retained to complete the Sackler Museum and also to renovate the Fogg Museum, directly across the street. Grace Glueck, “Sackler Art Museum To Open At Harvard,” New York Times, October 18, 1985.

Chapter 38: A Pain Management Revolution

1. 1. “John Bonica, Pain’s Champion and the Multidisciplinary Pain Clinic,” Relief of Pain and Suffering, John C. Liebeskind History of Pain Collection, Box 951798, History & Special Collections, UCLA Louise M. Darling Biomedical Library, Los Angeles, CA.
2. 2. Ibid.
3. 3. Medical historians pick that time as the unofficial beginning of the pain management field.
4. 4. Frank Brennan, “Decade on Pain Control and Research 2001–2011: A Review,” Journal of Pain & Palliative Care Pharmacotherapy, (2015) 29:3, 212–27; Edward Helmore, “Enduring Pain: How A 1996 Opioid Policy Change Had Long-Lasting Effects,” Guardian, March 30, 2018.
5. 5. Victor Cohn, “Study Lowers Estimate Of Prescription Drug Toll,” Washington Post, February 28, 1977, A3.
6. 6. “Addiction Rare in Patients Treated With Narcotics,” Correspondence, NEJM, January 10, 1980, Vol. 302, No. 2, 123.
7. 7. Sarah Zhang, “The One-Paragraph Letter From 1980 That Fueled the Opioid Crisis,” Atlantic, June 2, 2017.
8. 8. Ibid.
9. 9. The number of times it was subsequently cited is evidence of its impact. In comparison, there were eleven other letters published in that same NEJM issue; they were cited on average fewer than ten times each. Pamela T. M. Leung et al., “A 1980 Letter on the Risk of Opioid Addiction,” NEJM; June 1, 2017, 376:2194–95.
10. 10. Ibid. Before the Jick-Porter letter, a 1977 study about drugs that treated chronic headache sufferers had sometimes been cited for the thesis that powerful pain relievers were not terribly addictive. That study was not persuasive, however, since its statistics did not support the “low risk of addiction” theory. Fifty-five patients had taken a combination of nonnarcotic analgesics and barbiturates or codeine. The report listed eight as “dependent,” six physically addicted, two “psychologically dependent,” and five as “abusers.” See Jose L. Medina and Seymour Diamon, “Drug Dependency in Patients with Chronic Headaches,” presented at the eighteenth annual meeting of the American Association for the Study of Headache, Dallas, Texas, June 26, 1976.
11. 11. Leung et al., “A 1980 Letter on the Risk of Opioid Addiction,” and “Painful Words: How A 1980 Letter Fueled The Opioid Epidemic,” Associated Press, STAT News, May 31, 2017.
12. 12. Ronald Melzack, “The Tragedy of Needless Pain,” Scientific American, February 1990, Vol. 262, No. 2, 27, 29.
13. 13. Sam Allis, “Less Pain, More Gain,” Time, June 24, 2001.
14. 14. The WHO report was the product of a commission of anesthesiologists, neurologists, pharmacologists, and oncologists. It warned that “not enough is done to control pain in cancer patients” and that an underlying reason for “unsatisfactory” pain management was “fears concerning ‘addiction’ both in cancer patients and in the wider public.” Cancer Pain Relief, World Health Organization, Geneva, 1986, 79 pages, publication in collection of author.
15. 15. A UCLA researcher, John Liebeskind, coined the term “non-malignant chronic pain” to describe persistent pain in patients who did not have cancer. He contended that most doctors were “dangerously wrong” in not appreciating that “pain can devastate lives… kill by leading to suicide” and “accelerate tumor growth.” R. K. Portenoy and K. M. Foley, “Chronic Use of Opioid Analgesics in Non-Malignant Pain: Report of 38 Cases,” Pain, 25(2):171–86, May 1986; “Pain can kill!” later draft, 1990, John C. Liebeskind History of Pain Collection, History & Special Collections, UCLA Louise M. Darling Biomedical Library.
16. 16. “At Work: Neurologist Kathleen Foley,” Memorial Sloan Kettering Cancer Center, at https://www.mskcc.org/experience/physicians-at-work/kathleen-foley-work.
17. 17. Portenoy and Foley, “Chronic Use of Opioid Analgesics in Non-Malignant Pain.”
18. 18. Ibid.
19. 19. Oral history interview of Dr. Kathleen Foley, by Marcia L. Meldrum, in the Liebeskind History of Pain Collection, History & Special Collections, UCLA Louise M. Darling Biomedical Library.
20. 20. Portenoy had become acquainted with the benefits of opioid painkillers for cancer patients at Memorial Sloan Kettering Hospital in New York. Portenoy and Foley, “Chronic Use of Opioid Analgesics in Non-Malignant Pain.”
21. 21. Portenoy, as of 2019, is executive director and chief medical officer of the Institute for Innovation in Palliative Care at the MJHS, a not-for-profit Brooklyn health care organization. He is also a neurology professor at the Albert Einstein College of Medicine. Foley, after eight years running the George Soros–funded Project on Death in America, is an attending neurologist in the Pain and Palliative Care Service at Memorial Sloan Kettering Cancer Center.
22. 22. Max quoted in Joseph R. Schottenfeld et al., “Pain and Addiction in Specialty and Primary Care: The Bookends of a Crisis,” The Journal of Law, Medicine and Ethics, July 17, 2018. vol 46, no. 2: 220–37.
23. 23. That was a concept light-years removed from the early-nineteenth-century medical view that since “pain was one of God’s punishments for the wicked and purifying trials for the good,” doctors should not interfere by treating it. Natalia E Morone and Debra K Weiner, “Pain As The Fifth Vital Sign: Exposing The Vital Need For Pain Education,” Clinical Therapeutics, November 2013, vol. 35, no. 11 (2013): 1729.
24. 24. The Veterans Administration adopted it in 1999. “At Work: Neurologist Kathleen Foley,” Memorial Sloan Kettering Cancer Center, https://www.mskcc.org/experience/physicians-at-work/kathleen-foley-work. See State of Indiana v. Purdue Pharma L.P. et al.; Brennan, “Decade on Pain Control and Research 2001–2011”; Morone and Weiner, “Pain As The Fifth Vital Sign.”
25. 25. S. A. Dunbar et al., “Chronic Opioid Therapy For Nonmalignant Pain In Patients With A History Of Substance Abuse: Report of 20 Cases,” J Pain Symptom Management 1996;11:163–71; D. T. Cowan et al., “A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Pilot Study To Assess The Effects Of Long-Term Opioid Drug Consumption And Subsequent Abstinence In Chronic Noncancer Pain Patients Receiving Controlled-Release Morphine,” Pain Med 2005; 6:113–21; F. S. Tennant Jr. et al., “Narcotic Maintenance For Chronic Pain. Medical And Legal Guidelines.” Narc Maintenance 1983;73:81–94; F. S. Tennant et al., “Chronic Opioid Treatment Of Intractable, Nonmalignant Pain,” Pain Management 1988;Jan/Feb:18–26; A. Taub et al., Opioid Analgesics In The Treatment Of Chronic Intractable Pain Of Non-Neoplastic Origin,” Narcotic Analgesics in Anesthesiology 1982:199–208; R. K. Portenoy, Chronic Opioid Therapy In Nonmalignant Pain, J Pain Symptom Management 1990;5:46–62; F. S. Tennant et al., “Chronic Opioid Treatment Of Intractable, Nonmalignant Pain.” NIDA Res Monogr 1988;81:174–80; G. Schaffer-Vargas et al., “Opioid for Non-Malignant Pain Experience,” 9th World Congress on Pain, 1999;289:345; B. J. Urban et al., “Long-Term Use Of Narcotic/Antidepressant Medication In The Management Of Phantom Limb Pain,” Pain 1986;24:191–96; M. Zenz et al., “Long-Term Oral Opioid Therapy In Patients With Chronic Nonmalignant Pain,” J Pain Symptom Management 1992;7:69–77; K. Milligan et al., “Evaluation Of Long-Term Efficacy And Safety Of Transdermal Fentanyl In The Treatment Of Chronic Noncancer Pain,” J Pain 2001;2:197–204; D. E. Moulin et al., “Randomised Trial Of Oral Morphine For Chronic Non-Cancer Pain,” The Lancet 1996;347:143–47; J. Porter and H. Jick. “Addiction Rare In Patients Treated With Narcotics,” NEJM 1980; 302:123; N. Doquang-Cantagrel et al., “Tolerability And Efficacy Of Opioids In Chronic Nonmalignant Pain,” Addiction 1991; 722:129; A. J. Bouckoms et al., “Chronic Nonmalignant Pain Treated With Long-Term Oral Narcotic Analgesics,” Ann Clin Psychiatry 1992;8:185–92; R. N. Jamison et al., “Opioid Therapy For Chronic Noncancer Back Pain. A Randomized Prospective Study,” Spine 1998;23:2591–600; R. D. France et al., “Long-Term Use Of Narcotic Analgesics In Chronic Pain,” Soc Sci Med 1984;19:1379–82; M. J. Kell, “Long-Term Methadone Maintenance For Intractable, Nonmalignant Pain: Pain Control And Plasma Opioid Levels,” AJPM 1994;4:10–16; D. T. Cowan et al., “A Survey Of Chronic Noncancer Pain Patients Prescribed Opioid Analgesics,” Pain Med 2003; 4:340–51; W. S. Mullican and J. R. Lacy, “Tramadol/Acetaminophen Combination Tablets And Codeine/Acetaminophen Combination Capsules For The Management Of Chronic Pain: A Comparative Trial,” Clin Ther 2001;23:1429–44.
26. 26. Some studies were more than sixteen weeks; three followed patients for twenty-four months. Mark D Sullivan and Catherine Q Howe, “Opioid Therapy For Chronic Pain In The United States: Promises And Perils,” Pain vol. 154 Suppl 1,0 1 (2013), 94–100.
27. 27. The medical description given was “an iatrogenic syndrome resulting from poorly treated pain” where the patient exhibits behavior of “psychological dependency.” D. E. Weissman and J. D. Haddox, “Opioid Pseudoaddiction—An Iatrogenic Syndrome,” Pain 1989 Mar;36(3):363–66.
28. 28. “Definitions Related to the Use of Opioids for the Treatment of Pain,” Consensus Statement of the American Academy of Pain Medicine, the American Pain Society, and the American Society of Addiction Medicine, approved by the American Academy of Pain Medicine Board of Directors on February 13, 2001, the American Pain Society Board of Directors on February 14, 2001, and the American Society of Addiction Medicine Board of Directors on February 21, 2001 (replacing the original ASAM Statement of April 1997), published 2001.
29. 29. The study’s researchers did not find empirical data to support the pseudoaddiction theory. Marion S Greene and R. Andrew Chambers, “Pseudoaddiction: Fact Or Fiction? An Investigation Of The Medical Literature,” Curr Addict Rep (2015) 2:310–17. Other prominent pain specialists offered theories as to why opioids had what they considered an undeservedly bad reputation. Several experts in 1988 concluded that “mental disorders” of some chronic pain patients “had led to substance abuse among prescription opioid users [rather] than prescription opioids themselves.” The 2008 article has a comprehensive discussion of previous studies as well as the underlying theory. Mark J. Edlund et al., “Do Users of Regularly Prescribed Opioids Have Higher Rates of Substance Use Problems Than Nonusers?” Pain Medicine, Vol 8, no. 8, November 2007, 647–56.
30. 30. Sidney H. Wanzer et al., “The Physician’s Responsibility toward Hopelessly Ill Patients. A Second Look,” NEJM, March 30, 1989, 320(13):844–49.
31. 31. Others include federal Intractable Pain Regulation (1974); and the state laws in Virginia (1988), Texas (1989), California (1990), Colorado (1992), Washington (1993), and Florida (1994).
32. 32. R. K. Portenoy, “Appropriate Use Of Opioids For Persistent Non-Cancer Pain,” Lancet, August 28, 2004, vol. 364, no. 9436, 739–40.
33. 33. For some historical overview on the debate over whether there should be a maximum dose, see L. R. Webster and P. Fine, “Approaches To Improve Pain Relief While Minimizing Opioid Abuse Liability,” J Pain. 2010;11(7):602–11.
34. 34. The pain reevaluation proponents are similar to today’s cannabis advocates who push for much wider acceptance of medical or recreational marijuana. Will it be the panacea that some predict or will it turn into diversion to the illicit market and abuse resulting in human and financial costs from accidents, lost productivity, hospitalizations, and yet-to-be-discovered adverse effects of long-term use? As with opioids, it might take twenty years to get the definitive answer. And as with opioids, the experiment will be run with millions of patient guinea pigs. The difference is that no matter what the potential downside of the widespread dissemination of legalized marijuana, it is unlikely to be lethal on its own.
35. 35. Thomas Catan and Evan Perez, “A Pain-Drug Champion Has Second Thoughts,” Wall Street Journal, December 17, 2012; “ASPMN Backs Pain Champion: Russell Portenoy,” Pain Management Nursing, Vol. 14, Issue 1, 1–2.
36. 36. The rivals with opioid painkillers in the 1990s were Johnson & Johnson, Janssen, Mylan, and Endo.
37. 37. The American Society for Pain Management Nursing, in 2012, said: “It is not only repugnant but deeply disturbing to link Pharma monies to pro-opioid proselytizing; impugning both the science and merit of the subsidized research.” “ASPMN Backs Pain Champion: Russell Portenoy,” Pain Management Nursing, March 2013 vol. 14, no. 1, 1–2.
38. 38. Russell Portenoy on ABC’s Good Morning America, July 20, 2010.
39. 39. Catan and Perez, “A Pain-Drug Champion Has Second Thoughts.” That interview with the other physician was videotaped. Dr. Portenoy refused the author’s requests for an interview or to answer questions by email.

Chapter 39: Enter Generics

1. 1. Ron A. Bouchard et al., “Empirical Analysis of Drug Approval-Drug Patenting Linkage for High Value Pharmaceuticals,” 8 Nw. J. Tech. & Intell. Prop. 174 (2010). See also Austin Frakt, “How Patent Law Can Block Even Lifesaving Drugs,” New York Times, September 28, 2015.
2. 2. The Hatch-Waxman Act of 1984 attempted to correct some of the time lost while drugs were pending approval, but it gave five additional years only when a drug qualified as a “new chemical entity,” words that sometimes got mired in years of litigation. Garth Boehma, LixinYaoa Liang, Hanab Qiang Zhengac, “Development of the generic drug industry in the US after the Hatch-Waxman Act of 1984,” Acta Pharmaceutica Sinica B, Volume 3, Issue 5, September 2013; Kesselheim, “The High Cost of Prescription Drugs in the United States: Origins and Prospects for Reform,” JAMA, 861.
3. 3. Kesselheim, “The High Cost of Prescription Drugs in the United States.” As of 2018 it was as high as twelve years. Katherine Ellen Foley, “Big Pharma Is Taking Advantage of Patent Law to Keep OxyContin From Ever Dying,” Quartz, November 18, 2017.
4. 4. It has ballooned to $2.7 billion on average in 2018.
5. 5. It is the same in the U.K., a twenty-year patent protection from the date of discovery, and instances in which some drugs took a decade or more before approval and the start of public sales. See “Briefing for the Public Relations Committee,” Subject: Wholly Owned National Private Pharmaceuticals, PE1608, August 16, 2016, Scottish Parliament Information Centre. See also T. H. Stanley, “The History Of Opioid Use In Anesthetic Delivery,” Chapter 48 in Eger EI II, Saidman LJ, Westhorpe RN (eds): The Wondrous Story of Anesthesia (New York: Springer, 2014).
6. 6. Matthew Herper, “Solving The Drug Patent Problem,” Forbes, May 2, 2002.
7. 7. Katie Thomas, “Pfizer Races to Reinvent Itself,” New York Times, May 1, 2012.
8. 8. Those were Pfizer, Abbott Laboratories, Johnson & Johnson, Eli Lilly, Merck, and Bristol-Myers Squibb.
9. 9. The pharma firms that were the most active buyers of biotech companies were Novartis, Pharmacia & Upjohn, Warner-Lambert, Glaxo-Wellcome, SmithKline Beecham, and Hoechst-Marion Roussel. “Conference Proceedings—Consolidation in the Pharmaceutical Industry,” Semantic Scholar, 2001.
10. 10. Kelli Miller, “Off-Label Drug Use: What You Need to Know,” WebMD, June 2009.
11. 11. Darshak Sanghavi, “Cooking The Books: The Statistical Games Behind ‘Off-Label’ Prescription Drug Use,” Slate, December 21, 2009.
12. 12. That becomes somewhat alarming in light of a study that later demonstrated more than half of the off-label use “may have insufficient scientific support… [and] may result in inadequate efficacy or an unjustified risk of harm to the patient.” D. C. Radley et al., “Off-Label Prescribing Among Office-Based Physicians,” Arch Intern Med 2006;166: 1021–26.
13. 13. Meyers, Happy Accidents, 4688 of 6459; Henry Grabowski, “The Evolution of the Pharmaceutical Industry Over the Past 50 Years: A Personal Reflection,” Int. J. of the Economics of Business vol. 18, no. 2, July 2011, 16.
14. 14. A. S. Kesselheim and J. Avorn, “Pharmaceutical Promotion to Physicians and First Amendment Rights,” NEJM, 2008;358(16): 1730.
15. 15. M. S. Kinch et al., “An Overview Of FDA-Approved New Molecular Entities: 1827–2013,” Drug Discovery Today. 2014 Aug;19(8):1033–39; Kesselheim, “Pharmaceutical Promotion to Physicians,” 1730.
16. 16. Kesselheim, “Pharmaceutical Promotion to Physicians.”
17. 17. See Rebecca Dresser and Joel Frader, “Off-Label Prescribing: A Call For Heightened Professional And Government Oversight,” The Journal Of Law, Medicine & Ethics (The American Society Of Law, Medicine & Ethics) vol. 37,3 (2009): 476–86, 396. See also Kesselheim, “Pharmaceutical Promotion to Physicians.”.
18. 18. Ajaj Raj, “How A Doctor’s Chance Appointment With A Hairy Woman Led To The Discovery of Rogaine,” Business Insider, September 26, 2014.
19. 19. Gina Kolata, “Hair-Growth Drug Approved, The First Cleared in the U.S.,” New York Times, August 18, 1988, A1. Author interview with Bill Winkowski, retired pharmacist, about the standard practice of extracting minoxidil by crushing hundreds of Loniten tablets, April 2, 2019.
20. 20. Abraham Morgentaler, The Viagra Myth: The Surprising Impact On Love And Relationships (San Francisco: Jossey Bass, 2003).
21. 21. Lisa Beebe, “Viagra Turns 20: The History Of The ‘Little Blue Pill,’ ” Romanhood, February 12, 2018.
22. 22. Ibid., and see “Rogaine—Pharma’s Biggest Flops,” Fierce Pharma.
23. 23. A pharmacist, Gavin Herbert Sr., had started Allergan in 1950 in a room above his drugstore. It was named after an anti-allergy nose drop developed by his business partner, Stan Bly, a chemist. “Taking A Chance On Botox Paid Off For Allergan,” Ocular Surgery News, U.S. Edition, June 10, 2018.
24. 24. Dr. Alan Scott quoted in “Botox: A Story With a Few Wrinkles,” CBS News, April 15, 2002.
25. 25. “The Government has approved a type of food poisoning bacteria for use as a treatment for two eye muscle disorders.” “Eye Drug Approved By F.D.A.,” New York Times, January 9, 1990, C6.
26. 26. Lucy Rock, “Is America Developing a ‘Crack-Like Addiction’ to Botox Beauty?” Observer (UK), January 7, 2017.
27. 27. It is such a powerful toxin that even today powdered botulinum toxin the size of a pea is enough to supply all the Botox dispensed worldwide. Cynthia Koons, “The Wonder Drug for Aging (Made From One of the Deadliest Toxins on Earth),” Businessweek, October 26, 2017.
28. 28. See generally “Pharmacia & Upjohn Company to pay the largest criminal fine ever imposed in the U.S.,” Medical Life Sciences, October 19, 2009.
29. 29. Joseph G. Contrera, “The Food and Drug Administration and the International Conference on Harmonization: How Harmonious Will International Pharmaceutical Regulations Become?” 8 Admin. L.J. Am. U. 1995; (927), 934 n.26.
30. 30. E. Colman, “Anorectics on Trial: A Half Century of Federal Regulation of Prescription Appetite Suppressants,” Annals of Internal Medicine 2005;143(5):380–85.
31. 31. “The future of Pfizer’s $5bn Lyrica brand is in jeopardy,” Pharmaceutical Technology, November 21, 2018; Ben Hirschler, “Pfizer Loses Drug Patent Fight in UK Top Court, May Face Claims,” Reuters, November 14, 2018.
32. 32. C. W. Goodman and A. S. Brett, “A Clinical Overview of Off-label Use of Gabapentinoid Drugs,” JAMA Intern Med. 2019;179(5):695–701.
33. 33. Jane Brody, “Millions Take Gabapentin for Pain. But There’s Scant Evidence It Works,” New York Times, May 20, 2019.
34. 34. As for its worldwide ranking, it was at #9 for 2012–2014, #10 in 2017 and 2018, #11 in 2011, #12 in 2016, and #13 in 2015. See “Lyrica, The Top Pharma List: Top 50 pharmaceutical products by global sales ranking is compiled from GlobalData.” PMLive.
35. 35. See generally Comprehensive Drug Abuse Prevention and Control Act, Pub. L. 91-513, 84 Stat. 1242 (1970) (codified as amended at 21 U.S.C. §§ 801-971).
36. 36. Robin Feldman et al., “Empirical Evidence of Drug Pricing Games—A Citizen’s Pathway Gone Astray,” (September 1, 2016). 20 Stan. Tech. L. Rev. 39 (2017).
37. 37. “How Much Haven for Drug Pioneers?,” Editorial, New York Times, June 25, 1984, 33.
38. 38. William Haddad, president of the Generic Trade Association, quoted in Philip M. Boffey, “Accord May Lead to Cheaper Drugs,” New York Times, June 2, 1994.
39. 39. Ibid.
40. 40. Richard Lyons, “Demoralized FDA Struggles to Cope,” New York Times, March 14, 1977.
41. 41. Thomas Ascik, “Report: The Drug Regulation Act, (S.2755–H.R. 11611), The Heritage Foundation, June 21, 1978.
42. 42. Philip J. Hilts, “F.D.A. Commissioner Reassigned In Aftermath of Agency Scandals,” New York Times, November 14, 1989, B13.
43. 43. Harry Low and Tom Heyden, “The Rise and Fall of Quaaludes,” BBC News Magazine, July 9, 2015.
44. 44. Lee Linder, “Quaalude Manufacturer: Image Hurt By Street Use,” Lawrence Journal-World (Lawrence, KS), May 28, 1981, 6.
45. 45. Boffey, “Accord May Lead to Cheaper Drugs.”
46. 46. Roche Prods. Inc. v. Bolar Pharm. Co., 733 F.2d 858 (Fed. Cir. 1984), cert. denied, 469 U.S. 856 (1984), 860. See also Hoffmann-La Roche, Inc. v. Weinberger, 425 F. Supp. 890, 892–93 (D.D.C.) 1975.
47. 47. Stuart Diamond, “Upjohn Cuts Price of Top-Selling Drug,” New York Times, July 12, 1984; Boffey, “Accord May Lead to Cheaper Drugs.”
48. 48. FDA Consumer Vol. 19, U.S. Department of Health, Education and Welfare, Public Health Service, FDA, (Washington, D.C.: Government Printing Office, 1985), 28.
49. 49. Tamar Levin, “Drug Makers Fighting Back Against Advance of Generics,” New York Times, July 28, 1987, 1.
50. 50. Boffey, “Accord May Lead to Cheaper Drugs.”
51. 51. Milt Freudenheim, “Executive Changes at LaRoche,” New York Times, December 5, 1992.
52. 52. Levin, “Drug Makers Fighting Back.”
53. 53. Stuart Diamond, “Upjohn Cuts Price of Top-Selling Drug,” D5.
54. 54. Public Law 98-417. It passed 362–0 in the House, and in the Senate by a voice vote, with a notation of not a single “nay” vote.
55. 55. Nearly twenty years later (2013), the percentage of physicians with a negative opinion of generics was still at 50 percent. Katie Thomas, “Why the Bad Rap on Generic Drugs,” New York Times, October 5, 2013.
56. 56. Aaron S. Kesselheim et al., “Clinical Equivalence Of Generic And Brand-Name Drugs Used In Cardiovascular Disease: A Systematic Review And Meta-Analysis.” JAMA vol. 300,21 (2008): 2514–26.
57. 57. Levin, “Drug Makers Fighting Back.”
58. 58. Sales dropped from $294 million in 1984 to $185 million in 1986. Ibid.
59. 59. The figures are from Arthur D. Little.
60. 60. “We’re not anti-generic,” said Martin Brodie, the director of the Epilepsy Institute, “we believe that people who start on generics should stay on them. But based on the anecdotes we’ve heard, we are concerned about switching.” Levin, “Drug Makers Fighting Back.”
61. 61. “Seminar Briefs Lawmakers On How Prescription Drug Reimbursement Affects Access To Care,” American Journal of Hospital Pharmacy, Vol 44, no. 10, October 1, 1987, 2197–98.
62. 62. M. J. Grinfeld, “Ex-Profs Charged in Psych Department Research Scam,” Vol. 14, no. 4, Psychiatric Times, April 1, 1997; “Drug Money: Medical Trials Run Without Real Doctors,” reported by Laura Spencer, 48 Hours, CBS News, July 31, 2000. See also Steve Stecklow and Laura Johannes, “Drug Makers Relied on Two Researchers Who Now Await Trial,” Wall Street Journal, August 18, 1997, A1.
63. 63. Ibid.
64. 64. Borison’s colleague, pharmacologist Bruce Diamond, was convicted and given a five-year sentence, and CBS’s 48 Hours dubbed Borison “the mastermind.” “Drug Money,” CBS News.
65. 65. When generics are available, patients select them 94 percent of the time. Two of the largest ten generic manufacturers are subdivisions of traditional drug firms, the Sandoz division of Novartis is third and Pfizer is fourth. See generally Kathlyn Stone, “Top Generic Drug Companies,” The Balance, May 10, 2018. Author interview with former business partner of Arthur Sackler, November 2018.

Chapter 40: Selling Hearts and Minds

1. 1. Roy Vagelos and Louis Galambos. Medicine, Science, and Merck (New York: Cambridge University Press, 2004), 142.
2. 2. Gambardella, Science and Innovation, 95.
3. 3. Ibid.
4. 4. From $570.1 million to $229.2 million. Moody’s Industrial Manual, 1989.
5. 5. In 1991, for instance, Zantac was the top selling drug in America, with $3 billion in revenues and a 10 percent annual growth rate. Tagamet was still a big seller, the seventh best with $1 billion. It had a negative growth rate, however, of 2.2 percent. The gap between the two grew during the 1990s. “Top Ten Pharmaceutical Products in 1991,” Financial Times, 1992.
6. 6. As Smith Kline cut back, it no longer attracted the best research scientists. Another blow came when Dr. James Black, a Scottish pharmacologist who led the team that developed Tagamet, and later won a Nobel for that breakthrough, left the company.
7. 7. Don Kazak, “Syntex Lays Off 1,000 Employees,” Palo Alto Online, January 18, 1995; see also Gambardella, Science and Innovation, 93–102.
8. 8. Vagelos and Galambos, Medicine, Science, and Merck, 56–57, 208–9.
9. 9. His full name was Pindaros Herodotus Vagelos. Roy is the anglicized version of his middle name. He liked pointing out that he was born only three weeks before the 1929 stock market crash, so his parents were under financial distress from his birth. While he was at the University of Pennsylvania, he interned at the Merck laboratory in Rahway, New Jersey, for what he later described as “one unexciting summer.”
10. 10. Vagelos and Galambos, Medicine, Science, and Merck, 101.
11. 11. John Simon, “The $10 Billion Pill: Hold the fries, please: Lipitor, the cholesterol-lowering drug, has become the bestselling pharmaceutical in history. Here’s how Pfizer did it,” Fortune, January 20, 2003.
12. 12. It was Aspergillus terreus.
13. 13. Merck licensed the active drug in Pepcid, the first time the company had not released a drug that was developed from inception inside its lab. It had lost several years of getting into the ulcer treatment field by pursuing a different line of research that proved fruitless. Vagelos and Galambos, Medicine, Science, and Merck, 130–31. Its one billion a year in revenue included later OTC sales in a partnership with consumer goods giant Procter & Gamble.
14. 14. Peter A. Kreckel, “The First Billion-Dollar Drug,” Vol. 162, no. 1, MJH Life Sciences, January 11, 2018.
15. 15. Gina Kolata, “Companies Search for Next $1 Billion Drug,” New York Times, November 28, 1988, D1.
16. 16. John A. Byrne, “The Miracle Company,” Businessweek, October 19, 1987, 88.
17. 17. Vagelos and Galambos, Medicine, Science, and Merck, 250.
18. 18. Transcript of speech by George W. Merck, “Medicine Is for the Patient, Not for Profits,” December 1, 1950, available in full at https://www.merck.com/about/our-people/gw-merck-doc.pdf.
19. 19. Luke Whelan, “This Company Gave Away a Drug That Just Won the Nobel Prize and Helped Millions,” Mother Jones, October 5, 2015.
20. 20. Vagelos and Galambos, Medicine, Science, and Merck, 193–94.
21. 21. Kolata, “Companies Search for Next $1 Billion Drug.”
22. 22. “Mega-Merger Mania Hits Pharmaceutical Industry,” The Pharma Letter (TPL), March 2, 1998; Melody Petersen, “Pfizer Gets Its Deal to Buy Warner-Lambert for $90.2 Billion,” New York Times, February 8, 2000.
23. 23. Vagelos and Galambos, Medicine, Science, and Merck, 208–9.
24. 24. Ibid., 200.
25. 25. Scott Holleran, “The History of HMOs,” Capitalism Magazine, November 1, 1999.
26. 26. Transcript of taped conversation between Richard Nixon and John Ehrlichman (1971), University of Virginia—February 17, 1971, 5:26 pm–5:53 pm, Oval Office Conversation 450-23. Tape rmn_e450c.
27. 27. The idea of partial coverage for a limited number of medications was borrowed from inpatient prescription formulary lists developed originally by hospitals. Robert Goldberg, “Managing the Pharmacy Benefit: The Formulary System,” Journal of Managed Care Pharmacy, Vol. 3, No. 5, September/October 1992, 565.
28. 28. N. R. Kleinfield, “The King of the H.M.O Mountain,” New York Times, July 31, 1983, 132, 153.
29. 29. “History of the Kaiser Permanente Medical Care Program,” Kaiser Thrive at http://www.kaiserthrive.org/kaiser-permanente-history/.
30. 30. Vagelos and Galambos, Medicine, Science, and Merck, 201.
31. 31. Helene L. Lipton et al., “Pharmacy Benefit Management Companies: Dimensions of Performance,” Annual Review of Public Health 1999 20:1, 361–401.
32. 32. Ellen Schultz, “Merck Is No. 1 For The Second Year In A Row, IBM Falls Out Of The Magic Circle To No. 32, And Two Tobacco Companies Make It Into The Top Ten For The First Time,” Fortune, January 18, 1988.
33. 33. Jennifer Reese, “America’s Most Admired Corporations: What Lies Behind A Company’s Good Name?” CNN Money, February 8, 1993.
34. 34. Carpenter, Reputation and Power, 666. Gardiner Harris, “How Merck Survived While Others Merged—Drug Maker Relied on Inspired Research,” Wall Street Journal, January 12, 2001.
35. 35. Barry Werth, The Billion-Dollar Molecule (New York: Simon & Schuster, 1995).

Chapter 41: “No One Likes Airing Dirty Laundry in Public”

1. 1. In fact, by the time MS Contin went on sale, there was already competition from a rival morphine pill boasting its version of a time release delivery. Fortunately for Purdue, an independent clinical trial compared the two and concluded that MS Contin was by far the more effective drug. L. M. Sherman, “The use of sustained-release morphine in a hospice setting.” Pharmatherapeutica, 1987;5(2):99–102.
2. 2. In the U.K., Napp’s exclusive patent was issued in 1980 and was set to expire in 1992. The drug accounted for more than half of Napp’s income, although it had (and would) release seven other painkillers. See “Decision Of The Director General Of Fair Trading No Ca98/2/2001 in the matter of Napp Pharmaceutical Holdings Limited And Subsidiaries (Napp),” pursuant to the Competition Act 1998, March 30, 2001, 72 pages, in collection of author; Katherine Ellen Foley, “Big Pharma Is Taking Advantage of Patent Law to Keep OxyContin From Ever Dying,” Quartz, November 18, 2017.
3. 3. Herper, “Solving The Drug Patent Problem.”
4. 4. Kesselheim et al., “The High Cost of Prescription Drugs in the United States,” 861. See also Joanna Shepherd, “The Prescription for Rising Drug Prices: Competition or Price Controls?” 27 Health Matrix 315 (2017).
5. 5. The cost of discovering, developing, testing, and getting approval for a new class of drugs was prohibitively expensive. Large pharmaceutical firms avoided medications they thought had potential sales of less than $200 million. That was the market Purdue and smaller drug firms targeted. Stanley, “The History Of Opioid Use In Anesthetic Delivery”; Deposition of Richard Sackler, Commonwealth of KY v. Purdue Pharma L.P., August 28, 2015, 14–17 (hereinafter Richard Sackler Deposition). See also Theodore H. Stanley, “The Fentanyl Story,” The Journal of Pain, vol 15, no 12 (December), 2014: 1215–26.
6. 6. City of Jersey City, New Jersey v. Purdue Pharma L.P. et al., District of New Jersey, njd-2:2018-cv-11210, Complaint, filed June 28, 2018, 13.
7. 7. Deposition of Richard Sackler, 17.
8. 8. Ibid., 17–18.
9. 9. One had settled on morphine and the other utilized hydromorphone, a semisynthetic opioid.
10. 10. On the patent applications reviewed by the author, in the instances in which rights were assigned to Euro-Celtique (sometimes spelled Euroceltique), the assignors were Mortimer and Raymond Sackler, joined sometimes by Dr. Alfred Halpern, and occasionally Sackler-owned companies also assigned their interests. Those firms included Purdue Frederick, Gray Pharmaceutical, and Synergistics. The eighteen patents located by the author for the Mundipharma or Euro-Celtique transfers included five from U.S. See generally U.S Patent Office applications 3440320, 4954351, 3325472, 3471617, 3360535.
11. 11. FDA Statement quoted in Miranda Hitti, “Palladone Pain Drug Pulled Off the Market,” WebMD, July 14, 2005. Besides Palladone, other Napp painkillers consisted of oxycodone and dihydrocodeine, a weaker synthetic opioid based on codeine as well as buprenorphine, which has antagonist properties that can wean addicts from opioids. Napp also produced nonnarcotic painkillers, Remedeine and Remedeine Forte, a combination of acetaminophen and dihydrocodeine. Decision Of The Director General Of Fair Trading No Ca98/2/2001 in the matter of Napp Pharmaceutical Holdings Limited.
12. 12. R. F. Kaiko et al., “The United States Experience With Oral Controlled-Release Morphine (MS Contin Tablets). Parts I And II. Review Of Nine Dose Titration Studies And Clinical Pharmacology Of 15-Mg, 30-Mg, 60-Mg, And 100-Mg Tablet Strengths In Normal Subjects,” Cancer, 1989 Jun 1;63(11 Suppl):2348–54.
13. 13. Deposition of Richard Sackler, 20.
14. 14. Author interview with former Purdue assistant marketing manager, February 2017 and July 2018.
15. 15. Philip J. Hilts, “F.D.A. Commissioner Reassigned In Aftermath of Agency Scandals,” New York Times, November 14, 1989, B13.
16. 16. Starr, Blood, 317.
17. 17. Ibid.
18. 18. Author interview with former Purdue assistant marketing manager, Feburary 2017.
19. 19. Marie Curie was the only other person to win Nobels in two different fields (chemistry and physics). Frederick Sanger and John Bardeen were awarded two Nobels each, but in the same field, Sanger in chemistry and Bardeen in physics.
20. 20. Michael Sonnenreich told the author that Sackler never complained about his health and seemed to be one “of the healthiest guys I knew.” In the few weeks before his death, Sonnenreich recounted that Arthur was depressed and agitated over scathing reviews of a jewelry exhibition he held in London. Sonnenreich believes the stress from Sackler’s first ever bad reviews contributed to his unexpected death. Sonnenreich interview 2-23-2019; Grace Glueck, “Dr. Arthur Sackler Dies at 73; Philanthropist and Art Patron,” New York Times, May 27, 1987, B8.
21. 21. Although the sales of SSRIs were double that of antianxiety medications in the 1990s, some firms bent the rules to sell even more. In 2010, Forest Laboratories pled guilty to a criminal count that it illegally promoted Celexa, its best-selling antidepressant, to children despite the FDA having blocked it for such use. Forest paid $313 million to settle those claims, and others against its successor SSRI, Lexapro. That fine was a fraction of what Forest had earned in profits on the two SSRIs. Herper, “America’s Most Popular Mind Medicines.” Sonnenreich interview 2-23-2019; Shorter, Before Prozac, 1383–87).
22. 22. Arthur Sackler Probate Litigation; author interview with Sonnenreich, February 23, 2019.
23. 23. Ibid.
24. 24. Deirdre Carmody, “The Media Business; Springer’s Medical Tribune To Start Publishing Today,” New York Times, April 5, 1990, D22.
25. 25. In The Matter Of The Estate Of Arthur M. Sackler, Deceased, Surrogate’s Court, Nassau County, 145 Misc.2d 950 (N.Y. Misc. 1989).
26. 26. Ibid.
27. 27. In The Matter Of The Estate Of Arthur M. Sackler, Deceased, Surrogate’s Court, Nassau County, 149 Misc.2d 734 (N.Y. Misc. 1990).
28. 28. In The Matter Of The Estate Of Arthur M. Sackler, Deceased. Gillian T. Sackler, Respondent; Else Sackler, Appellant, Et Al., Respondent, Appellate Division of the Supreme Court of New York, Second Department.·193 A.D.2d 806 (N.Y. App. Div. 1993). Note that all litigation files have Jillian Sackler spelled as Gillian Sackler.
29. 29. In The Matter Of The Estate Of Arthur M. Sackler, Deceased. Gillian T. Sackler, Respondent; Else Sackler, Appellant, Et Al., Respondent, Appellate Division of the Supreme Court of New York, Second Department.·192 A.D.2d 660 (N.Y. App. Div. 1993).
30. 30. In The Matter Of The Estate Of Arthur M. Sackler, Deceased. Gillian T. Sackler, As Executor Of Arthur M. Sackler, Deceased, Appellant; Breed, Abbott Morgan, Respondent, Et Al., Respondents, 222 A.D.2d 9 (N.Y. App. Div. 1996).
31. 31. In The Matter Of The Estate Of Arthur M. Sackler, Deceased. Gillian T. Sackler, Respondent; Else Sackler, Appellant, Et Al., Respondent, Appellate Division of the Supreme Court of New York, Second Department.·192 A.D.2d 536 (N.Y. App. Div. 1993).
32. 32. In The Matter Of The Application Of The Final Account And Supplemental Account Of Carol Master, Arthur F. Sackler, Gillian T. Sackler And Michael R. Sonnenreich, And Carol Master And Elizabeth A. Sackler, As Executors Of The Estate Of Arthur M. Sackler, Deceased, John B. Riordan, Judge. 2008 [This case is unpublished, copy in collection of author]. See also Dec. No. 466, same judge, in 2007.
33. 33. In The Matter Of The Settlement Of The Final Account And Supplemental Account Of Carol Master, Arthur F. Sackler, Gillian T. Sackler And Michael R. Sonnenreich, And Carol Master And Elizabeth A. Sackler, As Executors Of The Estate Of Else Sackler, As Executors Of The Estate Of Arthur M. Sackler, Deceased, Surrogate’s Court, Nassau County, 2007 NY Slip Op 33226(U) (N.Y. Misc. 2007).
34. 34. Author interview with Sonnenreich, Febraury 23, 2019.
35. 35. Ibid.
36. 36. “Arthur would have expected that Mortie and Ray would do the right thing,” Sonnenreich believes. “He had always taken care of them since they were kids. He expected they would have been fair with his children, no question in my opinion that he would have done it for them.” Author interview with Sonnenreich, February 23, 2019.
37. 37. As quoted by Barry Meier in Pain Killer and confirmed to the author by Sonnenreich.
38. 38. The details only became public in an Audited Combined Financial statement of Purdue LP and associated companies, PRA holdings, Inc. and subsidiaries, Purdue Pharma Inc., AB Generics LP, Purdue Associates Inc., Purdue Associates LP, and Norwell Land Company, years ended Dec 31 1997 and 1996.

    A footnote on page 9 of a twenty-two page report of the independent auditors, Ernst & Young, dated April 9, 1998, states: “The note payable to the Estate of A.M. Sackler, MD bore interest at approximately 14% per annum, payable quarterly through November 13, 1996, at which time the interest rate decreased to 11.75% per annum through November 13, 1997. The note was secured by 250 shares of PRA Holdings, Inc.’s common stock and Mortimer D Sackler M.D. and Raymond R. Sackler M.D. each guaranteed one-half of all amounts due. The balance of the note was paid off on November 14, 1997.” This footnote refers to a line item below “Number 6, Debt,” showing a debt as of December 31, 1996 to AM Sackler estate of $19,654,000 and then nothing due as of the end of December 31, 1997.

    Some opioid case plaintiffs tried bringing Arthur Sackler’s estate into the litigation by contending it profited from some Oxy money since the $22 million installment buyout of his Purdue share extended a year past the drug’s sale date. However, the author has verified there was more than enough profit from other Purdue Frederick products to make the final installments to the estate without the need to rely on any OxyContin profits.

Chapter 42: “The Sales Department on Steroids”

1. 1. Deposition of Richard Sackler, 19.
2. 2. “Purdue Pharma Inc.’s 1991 filings with the Secretary of State of Connecticut state that it was incorporated in New York on October 2, 1990. Richard, Ilene, Jonathan, and Kathe Sackler are all listed as directors on the earliest (1991) report. Ilene and Kathe are Mortimer’s daughters with his first wife. Dr. Muriel Lazarus Sackler. Beverly, Mortimer, and Theresa all appear on the 1995 report. Commonwealth of Massachusetts v. Purdue Pharma L.P., et al. Superior Court, C.A. 1884-cv-01808 (BLS2) (hereinafter Massachusetts v. Purdue). See also Jared S. Hopkins, “OxyContin Made The Sacklers Rich. Now It’s Tearing Them Apart,” Wall Street Journal, July 13, 2019, 1.
3. 3. Purdue paid for and directed the trial on women recovering from gynecological and abdominal surgeries at two hospitals in Puerto Rico. Ninety women received one dose of OxyContin while the other patients got immediate release painkillers or placebos. Ryan, Harriet, Lisa Girion, and Scott Glover, “ ‘You Want A Description Of Hell?’ OxyContin’s 12-Hour Problem,” Los Angeles Times, May 5, 2016.
4. 4. Deposition of Richard Sackler, 20–21.
5. 5. Starting with this chapter, unless specified otherwise, Purdue refers to both Purdue Pharma Inc. and Purdue Pharma LP. Purdue Pharma Inc. is a New York company with its principal place of business in Stamford, Connecticut. Purdue Pharma LP is a Delaware limited partnership with its operating office at the same Connecticut address. As for Purdue Frederick acting as the holding company for Purdue Pharma Inc. and Purdue Pharma LP, see Deposition of Richard Sackler, 20.
6. 6. Deposition of Richard Sackler, 22.
7. 7. Ibid., 22–24.
8. 8. Ibid., 20.
9. 9. Incorporation documents and Articles of Incorporation in collection of author.
10. 10. A review by the author of the company’s audited financial statements for the year in which the family members assumed director’s positions reveals they held control over a consortium of companies beyond those with “Purdue” in the title. Some associated companies over which they exerted control through PRA Holding Company included AB Generics, Norwell Land, PF Laboratories, and Blair Labs. See Audited Combined Financial statements, Purdue LP and associated companies, PRA holdings, Inc. and subsidiaries, Purdue Pharma Inc., AB generics LP, Purdue Associates Inc., Purdue Associates LP, and Norwell Land Company, years ended Dec 31 1997 and 1996, Report of the independent auditors Ernst & Young dated April 9, 1998, 22 pages, in collection of author.

    Richard Sperber, himself a marketing executive at publicly traded pharmaceutical companies, did business with many privately held drug and biotech firms. “Purdue was always tightly controlled,” he told the author. “However, almost all those family-held companies were like that, they always thought they knew how to run it better than anyone else.” Sperber says that based on his experience, the most control was usually exerted when the companies were run by doctors, as was the case with the Sackler brothers and Richard Sackler taking the lead for the next generation of the family. “They are the worst because they are obnoxious and think they know how to do marketing,” Sperber says. Colleagues of his at private companies often shared stories about how the founders micromanaged the business. Author interview with Richard Sperber, March 26, 2019.

11. 11. By 2000, only three of the top ten pharma companies had not been involved in any mergers or acquisitions. Anna Bonomi and Oana Pop, “Implications of Consolidation in the Pharma & Biotech Sector,” Sustainalytics, December 12, 2018.
12. 12. On average, $138 million in the 1970s and approximately $800 million in the early 1990s.
13. 13. Pisano, “Can Science be a Business?”
14. 14. “1980s: Arteries, AIDS and Engineering,” part of “Ten Decades of Drug Discovery, The Pharmaceutical Century,” ACS Publications.
15. 15. Grabowski, “The Evolution of the Pharmaceutical Industry,” 169.
16. 16. Ibid.
17. 17. Raymond had persuasively made the case that the name should include “contin” since MS Contin had earned a good reputation among dispensing doctors and was recognized as a Purdue product. “Oxy” was an abbreviated way of signaling the active ingredient was oxycodone, not morphine.
18. 18. Paul Goldenheim sworn declaration, 2003, cited in Ryan, Girion, and Glover, “You Want A Description Of Hell?”
19. 19. Patent 5,549,912, filed November 25, 1992, granted on August 27, 1996, in collection of author.
20. 20. In 2001, The Medical Letter on Drugs and Therapeutics concluded OxyContin offered no therapeutic advantage over equivalent doses of immediate release opioids. In 2003, that was confirmed in randomized double-blind studies that compared OxyContin and comparable opioids for chronic back pain and cancer pain. R. Kaplan et al., “Comparison Of Controlled-Release And Immediate-Release Oxycodone In Cancer Pain,” J Clin Oncol 1998;16:3230–37; T. Heiskanen et al., “Controlled-Release Oxycodone And Morphine In Cancer Related Pain,” Pain 1997;73:37–43; P. Mucci-LoRusso et al., “Controlled-Release Oxycodone Compared With Controlled-Release Morphine In Treatment Of Cancer Pain: A Randomized, Double-Blind, Parallel-Group Study,” Eur J Pain 1998;2:239–249; B. S. Berman et al., “Randomized, Double-Blind, Cross-Over Trial Comparing Safety And Efficacy Of Oral Controlled-Release Oxycodone With Controlled-Release Morphine In Patients With Cancer Pain,” J Clin Oncol 1998;16:3222–29; J. E. Staumbaugh et al., “Double-Blind, Randomized Comparison Of The Analgesic And Pharmacokinetic Profiles Of Controlled- And Immediate-Release Oral Oxycodone In Cancer Pain Patient,” J Clin Pharmacol 2001;41:500–506; “Oxycodone and OxyContin,” Med Lett Drugs Ther 2001, 43:80–81; “New Drug Application for OxyContin.” Purdue Pharma, Stamford, CT, December 1995.
21. 21. In addition to the six controlled clinical trials, the company did four less rigorous studies and fourteen pharmacokinetic studies. More than seven hundred subjects were involved in all. See “Approval Package for: Application Number: NDA 20-553/S-002, Trade Name: OXYCONTIN 80 mg, Generic Name: (oxycodone hydrochloride controlled release tablets), Sponsor: Purdue Pharma LP, Approval Date: December 9, 1996, Indication: Provides for 80 mg green colored tablets as a line extension to the approved 10, 20 and 40 mg tablets,” Center For Drug Evaluation And Research, FDA. See also Ryan, Girion, and Glover, “You Want A Description Of Hell?”
22. 22. Pat Beall, “Purdue Pharma Plants The Seeds Of The Opioid Epidemic In A Tiny Virginia Town And Others,” Investigation: “Igniting the Heroin Epidemic,” The Palm Beach Post, January 31, 2019.
23. 23. Raymond Sackler, the author learned, liked to say, only partly in jest, that Purdue’s marketing department would have been hard pressed to outdo the persuasive presentations of their star lecturers. United Food and Commercial Workers Health Fund of Northeastern Pennsylvania v. Purdue Pharma et al., case 2:17-cv-05078-TJS, filed 11/09/17, Document 1, 42–46.
24. 24. “Prescription Drugs: OxyContin Abuse and Diversion and Efforts to Address the Problem,” Washington, DC: General Accounting Office; December 2003. Publication GAO-04-110.
25. 25. Andrew Joseph, “Purdue Cemented Ties With Universities And Hospitals To Expand Opioid Sales, Documents Contend,” STAT, January 16, 2019.
26. 26. “In 1980, three Sackler brothers, through a very large payment, established the Sackler School of Graduate Biomedical Sciences. Later, in 1999, the Sackler family made a more targeted gift, establishing Tufts Masters of Science in Pain Research, Education, and Policy.” Massachusetts v. Purdue, 93; Rick Seltzer, “ ‘Deeply Troubling’ Allegations,” Inside Higher Ed, January 21, 2019.
27. 27. In March 2019, Tufts retained Donald Stern, a former U.S. attorney, to conduct an independent investigation of whether Purdue had manipulated Tufts to promote its narcotic painkillers. Andrew Joseph, “ ‘We Owe Much to the Sackler Family’: How gifts to a top medical school advanced the interests of Purdue Pharma,” STAT, April 9, 2019. In December, the school announced it would remove the Sackler name from all buildings and programs.
28. 28. Michael Joyce, “Pharma Backing of Advocacy Groups: A Call for Transparency,” Health News Review, March 7, 2018.
29. 29. County Of Wayne and Country of Oakland v. Purdue Pharma, USDC Eastern District of Michigan, 17-cv-13334-JCO-EAS, Exhibit 57, General Financial Information for the American Pain Foundation.
30. 30. John Fauber, “Academics Profit By Making the Case for Opioid Painkillers,” MedPage Today, April 3, 2011.
31. 31. Ibid. From 2009 to 2012, Purdue gave the American Pain Society nearly $500,000 and the American Academy of Pain Medicine more than $400,000. Purdue gave APS another $500,000 and AAPM more than $700,000 between 2012 and 2017.
32. 32. ProPublica’s database is at https://projects.propublica.org/docdollars/. The partial listing of 2009 to 2013 payments is at https://projects.propublica.org/d4d-archive/.
33. 33. In 2019, a respected group of international researchers proposed a revised definition of pain. The International Association for the Study of Pain suggested changes that would cover situations in which the discomfort was not simply from a physical cause but might also be the result of “an aversive sensory and emotional experience.” Emotional or mental connections to pain would not need opioid medications for treatment, a goal of the proposed changes. See Dawn Rae Downtown, “Who Is Really Behind a Proposed New Definition of Pain?” STAT, September 5, 2019.
34. 34. Gigen Mammoser, “Is OxyContin Losing Its Luster?” Healthline, February 21, 2018.
35. 35. Tony Dokoupil, “America’s Long Love Affair With Anti-Anxiety Drugs,” Newsweek, January 21, 2009.
36. 36. They were all men then; the first detail women started in the late 1950s. Carl Elliott, “The Drug Pushers,” The Atlantic, April 2006; see Tone, Age of Anxiety, 72,
37. 37. Goldacre, Bad Pharma, 89 of 7421.
38. 38. Email from Russell Gasdia, Purdue vice president, 02-07-2012, Massachusetts v. Purdue, document LPC012000368569.
39. 39. Ryan, Girion, and Glover, “You Want A Description Of Hell?”.
40. 40. Ibid.
41. 41. Holcomb B. Noble, “A Shift in the Treatment of Chronic Pain,” New York Times, August 9, 1999.
42. 42. Urging patients to “overcome” any “concerns about addiction” was the main message on the Purdue-sponsored website, In The Face of Pain, 14.
43. 43. Purdue internal strategy presentation, Massachusetts v. Purdue, 2009-11 FACETS, slide 9, document PTN000006436.
44. 44. “Website capture, In the Face of Pain, 2011-10-24,” Massachusetts v. Purdue, document PVT0033890–891.
45. 45. “Exit Wounds (2009), pg. 107,” and “Opioid Prescribing: Clinical Tools and Risk Management Strategies (2009), pg. 12,” Massachusetts v. Purdue, documents PTN000023114 and WG000242087.
46. 46. Art Van Zee, “The Promotion And Marketing Of OxyContin: Commercial Triumph, Public Health Tragedy,” American Journal Of Public Health vol. 99,2 (2009): 221–27.
47. 47. Sales reps told doctors that in instances in which some patients “became physiologically dependent… addiction is rare.” Massachusetts v. Purdue, “Opioid Prescribing: Clinical Tools and Risk Management Strategies (2009), pg. 12,” document PWG000242087.
48. 48. See for instance, “I Got My Life Back,” Purdue Pharma LP, transcript of video presentation by Dr. Alan Spanos, 1998; Massachusetts v. Purdue, document PDD9521403504. See also Barry Meier, Pain Killer, 99.
49. 49. The Anatomy of Sleep, Roche Laboratories, Div of Hoffmann-LaRoche Inc (Roche: Nutley, NY, 1966), 111, in collection of author.
50. 50. Resource Guide for People with Pain (2009), pg. 8, Massachusetts v. Purdue, document PVT0037321.
51. 51. Beall, “Purdue Pharma Plants The Seeds Of The Opioid Epidemic.”
52. 52. See email from John Stewart, senior Purdue executive, later CEO, 2008-02, Massachusetts v. Purdue, document PPLPC012000172201. See also two Purdue studies published in 2013 regarding “abuse potential” of crushed or altered OxyContin, documents PTN000002031-2034 and PTN000002031-2044. Purdue revised its OxyContin label to refer to those studies.
53. 53. Kelly R. Cohen et al., “Relationship Between Drug Company Funding And Outcomes Of Clinical Psychiatric Research,” Psychological Medicine, 36(11), 1647–56, 2006.
54. 54. Ibid. And see L. Bero et al., “Factors Associated with Findings of Published Trials of Drug–Drug Comparisons: Why Some Statins Appear More Efficacious than Others,” PLOS Medicine 2007 Jun 5;4(6): e184.
55. 55. Handwritten interview notes of Purdue sales manager Bill Gergely obtained by investigators for the Attorney General of Florida, Interview Notes 2/21/2003, 2 pages, included in litigation files in “Purdue And The OxyContin Files,” Kaiser Health News, June 23, 2018.
56. 56. The study David Sackler referred to was a meta-analysis of 6,164 articles and 12 studies involving more than 300,000 participants. The surprising conclusion was that when opioids were dispensed to treat pain, the “incidence of opioid dependence or abuse [was] 4.7%.” C. Higgins et al., “Incidence Of Iatrogenic Opioid Dependence Or Abuse In Patients With Pain Who Were Exposed To Opioid Analgesic Therapy: A Systematic Review And Meta-Analysis,” British Journal of Anaesthesia, vol 120, no. 6, 1335–44. In any case, David Sackler said “the FDA approved this medication,” so it was their responsibility to protect patients, not an obligation of Purdue. See also Bethany McLean, “ ‘We Didn’t Cause The Crisis’: David Sackler Pleads His Case On The Opioid Epidemic,” Vanity Fair, August 2019.
57. 57. Author interview with assistant marketing manager, July 2018.
58. 58. P. R. Chelminski et al., “A Primary Care, Multi-Disciplinary Disease Management Program For Opioid-Treated Patients With Chronic Non-Cancer Pain And A High Burden Of Psychiatric Comorbidity,” BMC Health Serv Res. 2005;5(1):3; M. F. Fleming et al., “Reported Lifetime Aberrant Drug-Taking Behaviors Are Predictive Of Current Substance Use And Mental Health Problems In Primary Care Patients,” Pain Med, 2008;9(8):1098–1106.
59. 59. See joint statement, “Use of Opioids For The Treatment Of Chronic Pain. A Consensus Statement From The American Academy Of Pain Medicine And The American Pain Society,” Clin J Pain. 1997;13(1):6–8.
60. 60. Joyce, “Pharma Backing of Advocacy Groups: A Call for Transparency.”
61. 61. That incredibly low figure was simply a calculation of the numbers in the letter to the NEJM sixteen years earlier (four cases of addiction out of 11,882 patients). By the time of the joint statement, while the details of the NEJM letter had been forgotten, what stuck was its dramatic conclusion. It had become so enshrined as an accepted fact inside the emerging pain management field that no one challenged it. Dr. J. David Haddox, the inventor of pseudoaddiction, chaired a joint commission. By this time, Haddox, with dual specialities in anesthesiology and behavioral medicine and psychiatry, was one of the most successful lecturers in Purdue’s speaker’s bureau. Another successful Purdue-sponsored lecturer, Dr. Portenoy, was retained by the two pain societies as their single consultant to help draft the joint language.
62. 62. Zoe Matthews, “AG: North Andover doctor was top prescriber of OxyContin,” Eagle Tribune (North Andover, MA), February 6, 2019. See also Patrick D. Wall and Ronald Melzack. Textbook of Pain. 3rd ed. Edinburgh; Churchill Livingstone, 1994, 341; Dennis C. Turk and Ronald Melzack, eds. Handbook of Pain Assessment. New York, Guilford Press, 1992, 262.
63. 63. The contract was between Purdue Pharma LP and IMS Health Strategic Technologies, a wholly owned subsidiary of IMS. See “Purdue Pharma Selects IMS HEALTH Strategic Technologies to Enhance Sales and Marketing Effectiveness, CORNERSTONE(TM) 3.0 Automation Solution to Support Purdue Pharma Sales Representatives,” PR Newswire, September 14, 1998.
64. 64. Elliott, “The Drug Pushers.”
65. 65. Also included in the prescribing habits was a new drug, Ultram, released the previous year by Ortho-McNeil. It was a weaker chemical cousin to oxycodone.
66. 66. “OxyContin Marketing Plan, 1996,” Purdue Pharma, Stamford, CT; Stolberg S, Gerth J., “High-tech stealth being used to sway doctor prescriptions,” New York Times, November 16, 2000; Van Zee, “The Promotion and Marketing of OxyContin.”
67. 67. Massachusetts v. Purdue, paragraph 113, 39.
68. 68. “Purdue Pharma Selects IMS HEALTH Strategic Technologies.”
69. 69. Author interview with assistant marketing manager, July 2018. Also, the Sacklers were irked that IMS sold its much more accurate prescribing info to any drug company that paid its asking price. “The result was an arms race of pharmaceutical gift-giving,” wrote Carl Elliott, a physician and distinguished professor of bioethics, “in which reps were forced to devise ever-new ways to exert influence.” Elliott, “The Drug Pushers.”
70. 70. “Treatment Options: A Guide for People Living with Pain,” pg. 15, Massachusetts v. Purdue, document PWG000243995.
71. 71. If pressed, the sales reps were instructed to backpedal slightly and declare that OxyContin provided a “quality of life we deserve.” See “Treatment Options: A Guide for People Living with Pain,” pg. 15, Massachusetts v. Purdue, document PWG000243995.
72. 72. The marketing team developed some “reminder items” for the detail force visits to nursing and long-term-care facilities. For patients who had previous problems with opioids or were too ill for OxyContin, the sales reps were told to push Ryzolt, Purdue’s brand name for tramadol, a less potent narcotic-like medication. Finally, since one of the most common side effects from opioids is constipation, the sales reps were reminded to sell Purdue Frederick’s Senokot laxatives and Colace stool softener.
73. 73. Purdue also underwrote a website promoting the book and its central theses. The author was a decorated Iraq combat veteran, Derek McGinnis, who had lost a leg in combat and suffered himself from chronic pain. The book was Exit Wounds: A Survival Guide to Pain Management for Returning Veterans and Their Families.
74. 74. Jenni B. Teeters, “Substance Use Disorders In Military Veterans: Prevalence And Treatment Challenges,” Subst Abuse Rehabil 2017: 8: 69–77.
75. 75. Some of the publications included Providing Relief, Preventing Abuse: A Reference Guide to Controlled Substance Prescribing Practices; Resource Guide for People with Pain; Clinical Issues in Opioid Prescribing; Opioid Prescribing: Clinical Tools and Risk Management Strategies; Responsible Opioid Prescribing. One of their main websites was In the Face of Pain. As for the curriculums at schools, some included Purdue’s underwriting of the Massachusetts General Hospital Purdue Pharma Pain Program and a complete degree program at Tufts University. See Joseph, “Purdue Cemented Ties With Universities And Hospitals To Expand Opioid Sales, Documents Contend,” and Seltzer, “ ‘Deeply Troubling’ Allegations.”
76. 76. An executive director of a leading California treatment center noted that medical schools spent so little time on the subject that “if you miss the three hours they spend on pain management, you’ve missed the entire curriculum.” Kathryn Weiner, Executive Director of the American Academy of Pain Management, quoted in Doris Bloodsworth, “Pain Pill Leaves Death Trail,” Orlando Sentinel, October 19, 2003, A19, A22.
77. 77. Pat Anson, “Purdue Pharma’s ‘Misleading’ Websites,” Pain News Network, August 21, 2015; NY State AG filing on 2015. After the New York attorney general filed a complaint against Purdue for the misleading information on its In the Face of Pain website, Purdue subsequently closed it. All that remains as of 2019 is a single page that says in full: “Dear Pain Advocates: In the Face of Pain has been proud to serve the pain community since 2001. Please note that we have deactivated the website on October 1, 2015. It is our sincere hope that the information and materials available on this website have informed, equipped, and inspired you on your pain advocacy journey. With gratitude, Your Patient & Professional Relations Team at Purdue Pharma L.P.”

    The date of the rollout, 2001, was early in what would become the dominance of the internet for consumers who wanted to quickly obtain information about health-related matters. There were more than thirty thousand websites devoted to health as of 2000 and by 2002, two thirds of respondents to a nationwide poll reported they went online to get health information. Fox and Fallows, 2003, Internet Health Resources, Pew Internet and American Life Project, Washington DC, July 16, 2004.

78. 78. “Partners Against Pain’s Pain Management Kit,” HCP Live Network, August 21, 2011.
79. 79. Review of five thousand pages of Purdue marketing documents released pursuant to Orlando Sentinel Freedom of Information lawsuit, detailed in Bloodsworth, “Pain Pill Leaves Death Trail,”
80. 80. Sergey Motov, “Is There a Limit to the Analgesic Effect of Pain Medications?” Medscape, June 17, 2008.
81. 81. Scott E. Hadland, “Association of Pharmaceutical Industry Marketing of Opioid Products to Physicians With Subsequent Opioid Prescribing,” JAMA Intern Med. 2018;178(6):861–63. Seven hundred and thirty thousand Americans have died of drug overdoses from 1999 through 2018. That includes everything from heroin to mixtures of barbiturates and cocaine. The lethal overdoses involving only opioids account for about two thirds of the total. About half of all the opioid-related fatalities are from legally dispensed prescriptions. “Overdose Death Rates,” National Institute on Drug Abuse, National Institutes of Health, revised January 2019. German Lopez and Sarah Frostenson, “How The Opioid Epidemic Became America’s Worst Drug Crisis Ever, In 15 Maps And Charts,” Vox, March 29, 2017.
82. 82. 2011-10 Guidelines on Product Promotion: Comparative Claims Workshop, slide 12, Massachusetts v. Purdue, 67, 68.
83. 83. “Partners Against Pain’s Pain Management Kit.”
84. 84. Olga Khazan, “The New Heroin Epidemic,” The Atlantic, October 30, 2014, and Beall, “Purdue Pharma Plants The Seeds Of The Opioid Epidemic.” According to Dopesick: “$300,000 worth of OxyContin-branded scroll pens, $225,000 worth of OxyContin resource binders, and $290,000 worth of ‘Pain: The Fifth Vital Sign’ wall charts and clipboards,” 28. See Purdue budgets in Massachusetts v. Purdue, each year presented with original slides at board meetings for which the Sackler-family directors voted to approve them. For example, 2015-11 budget for 2016, slides 24, 26, 49, documents PPLPC011000069975, -69977, -70000.
85. 85. Bert Spilker, “The Benefits And Risks Of A Pack Of M&Ms,” Narrative Matters, Health Affairs, March/April 2002; Goldacre, Bad Pharma, 4277 and 4291 of 7421. See also Elliott, “The Drug Pushers”; A. Fugh-Berman et al., “Following The Script: How Drug Reps Make Friends And Influence Doctors,” PLoS Med 4(4): e150 (2007).
86. 86. “Follow the Money: Pharmaceutical Manufacturer Payments and Opioid Prescribing Patterns in New York State,” Report, New York State Health Foundation, June 12, 2018.
87. 87. Hadland, “Association of Pharmaceutical Industry Marketing of Opioid Products to Physicians With Subsequent Opioid Prescribing.”
88. 88. Kanner was the chairman of Long Island Jewish Medical Center’s Department of Neurology.
89. 89. Portenoy and four other doctors are cited as “KOL, Key Opinion Leaders” in many of the lawsuits filed against Purdue. The theory is that their prominence helped make OxyContin widely acceptable to dispensing physicians. As of 2019, Portenoy had evidently agreed to help the plaintiffs in the litigation against Purdue in the hope he would be excluded as a party in any litigation. Larry McShane, “How Big Tobacco-Style Marketing Propels U.S. Opioid Crisis—And Powers $400B Pharma Industry,” New York Daily News, June 24, 2017, and “Portenoy Opioid Talk Sparks Controversy,” Medpage Today, September 29, 2014.
90. 90. The authors revealed that in a recent survey more than half of physicians said they had decided not to dispense opioids since they were controlled substances. They worried that prescribing opioids might subject them to “regulatory scrutiny or… possibility of investigation.” Portenoy and Kanner, Pain Management: Theory and Practice, 253, 254, 364–65.
91. 91. In concluding a discussion about whether the drugs should be dispensed more widely, the two doctors admitted “this approach… is controversial.” That did not prevent them from a “tentative” endorsement of “long-term opioid therapy for chronic nonmalignant pain.” Their only caveat was the need for “appropriate controlled clinical trials.” Portenoy and Kanner, Pain Management, 258–59, 268.
92. 92. Ibid., 258–59.
93. 93. “Pain and the Dying: The Hospice Movement and the Work of Cicely Saunders,” Relief of Pain and Suffering, John C. Liebeskind History of Pain Collection.