In April 2013, the drug Diclegis® (doxylamine succinate/pyridoxine hydrochloride) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of nausea and vomiting associated with pregnancy (NVP). Some readers may remember this drug when it was previously marketed in the United States under the brand name Bendectin (see “Bendectin History,” http://bendectin.com/en). Bendectin was originally developed in the 1950s containing the active ingredients doxylamine succinate (an antihistamine), pyridoxine hydrochloride (vitamin B6), and dicyclomine hydrochloride (an antispasmodic), and it was approved for the treatment of NVP by the FDA in 1956. The dicyclomine ingredient was removed from the formulation in 1976 when clinical studies found that it contributed nothing to the nausea and vomiting benefits of Bendectin.
Thirty years ago this year, Bendectin was voluntarily withdrawn from the market by its then manufacturer, Merrell Dow Pharmaceuticals, not because of its safety, but for financial reasons related to litigations and exorbitant insurance premiums tied to the drug. The FDA even published a statement in 1999 in the Federal Register that it had determined that the product was not withdrawn for reasons of safety or effectiveness (Maskin & Lacayo, 2013). Hundreds of lawsuits had been filed by 1983 claiming that Bendectin caused birth defects. An Australian obstetrician-gynecologist, William McBride, played a prominent role in the Bendectin story. He was conducting studies of the anticholinergic drug scopolamine in rabbits during the 1970s and believed that anticholinergic drugs cause birth defects. Because Bendectin contained the anticholinergic drug doxylamine, McBride believed that it was teratogenic. He appeared as a principle scientific witness for parents in several of the subsequent Bendectin lawsuits.
Bendectin litigation in the United States lasted for 10 years after the drug was withdrawn in 1983, but ultimately the manufacturer prevailed in a case (Daubert v. Merrell Dow Pharmaceuticals, 1993) decided by the Supreme Court. The extensive literature pertaining to the reproductive effects of Bendectin found no evidence the drug was teratogenic (Brent, 1995). Presentations by many of the plaintiff’s experts, including McBride, failed to meet the scientific standards expected of knowledgeable scientists, likely contributing to the inappropriate persistence of litigation for many years even after it was clear that Bendectin was not culpable in causing birth defects. To put it bluntly, much of the plaintiff’s scientific evidence was considered “junk science.” The Daubert decision is considered a landmark case in Supreme Court history, because the court changed and established the standards for determining the admissibility of expert testimony and scientific evidence in federal courts (Maskin & Lacayo, 2013; Wolsing, 2007).
In 1987, McBride was accused of scientific fraud by the coauthors of his paper on scopolamine in rabbits, and he was also accused of clinical malpractice (Skolnick, 1990). The inquiry conducted by an Australian tribunal ended in 1993, when one allegation of clinical malpractice and 24 allegations concerning medical research were proven (Loff & Cordner, 1998; McBride, 2001).
The first U.S. lawsuit involving Bendectin was filed in 1977. This lawsuit was instigated by a woman, Betty Mekdeci, whose son (born in 1975) had a foreshortened right arm and missing fingers on his right hand (Marcus, 1997). Mekdeci on her own had extensively researched possible causes of birth defects and focused on Bendectin as the cause of her son’s birth defect. In 1976, she hired the prominent celebrity attorney, Melvin Belli (known as the “King of Torts”), to represent her. No other suits were filed until after the National Enquirer (a tabloid newspaper once known for the advertising slogan “Inquiring minds want to know”) picked up on the Mekdeci case and published in October 1979 a sensationalist article about this “common drug causing deformed babies” (Brent, 1983). The National Enquirer was clued into the case by Belli, apparently as a way to generate pretrial publicity (Marcus, 1997). McBride was one of two physicians (the other was Alan Done) who were interviewed by the National Enquirer for their story (Wolsing, 2007). The story was picked up by other media within the next year, contributing to explosive adverse publicity about the drug around the world (Korcok, 1980). Large numbers of women taking Bendectin panicked, and some had unnecessary abortions (Brent, 1983).
Why was there particular interest in soliciting and highlighting the opinion of McBride about Bendectin? Indeed, McBride was already famous worldwide, having first alerted the world to the dangers of the drug thalidomide in 1961 when he published a letter in the eminent medical journal The Lancet, describing babies with unusual abnormalities whose mothers had taken thalidomide. McBride had also directly conveyed his observations to the company responsible for manufacturing thalidomide in the United Kingdom (Distillers Biochemicals), and the company withdrew the drug several weeks before McBride’s letter was actually published (Lerner & Lerner, 2006; Maxwell, 2011). After McBride’s thalidomide observations were confirmed by subsequent work, he received numerous honors and a large monetary prize (McBride, 2001). He used the prize to set up an Australian research organization (Foundation 41) devoted to studying the causes of mental and physical handicaps. McBride’s subsequent research, which included reputable studies of thalidomide as well as his fraudulent research on scopolamine, was funded by Foundation 41. In 1972, he had also claimed that the antidepressant imipramine caused birth defects, although this was never independently confirmed and did not seem to generate much attention (McBride, 2001).
The company responsible for introducing thalidomide to the United States in 1960 (Richardson-Merrell) was also the company that had introduced Bendectin to the United States in 1956. In 1980, Dow Chemical acquired Richardson-Merrell, forming Merrell Dow Pharmaceuticals. Taking advantage of this connection, the National Enquirer story on Bendectin was headlined “New Thalidomide Scandal—Experts Reveal” (Brent, 1983; Wolsing, 2007). Who would be a better expert to interview than McBride, famous for revealing the dangers of thalidomide and apparently intimately familiar with the putative dangers of Bendectin?
The philosopher, mathematician, and scientist Charles Peirce once wrote that “in order to reason well…it is absolutely necessary to possess…such virtues as intellectual honesty and sincerity and a real love of truth” (Haack, 1995, p. 57). Genuine inquiry, whether scientific or otherwise, is any inquiry that is fueled by a desire to find true answers regardless of what the answers might be. Peirce distinguished genuine inquiry from what he called “sham reasoning.” In sham reasoning, the intent is not to find true answers to the questions asked, but to find facts that will support a conclusion that is already believed. The philosopher Susan Haack (1995) further distinguished genuine inquiry and sham reasoning from what she refers to as “fake reasoning.” Fake reasoning occurs when there is no concern necessarily for finding the right answer, but there is some ulterior goal related to addressing the question at hand. Haack (1995) says that the fake reasoner is concerned to advance himself or herself in some way by making a case for some proposition while being indifferent to the truth-value of the proposition.
I am not privy to McBride’s inner motives regarding Bendectin, including publishing his fraudulent research on scopolamine, his willingness to talk to the sensationalist media, and his discredited “junk science” testimony as an expert witness. Perhaps his reputable involvement with the thalidomide case debased his thinking about the honesty of pharmaceutical companies and the supposed safety of taking drugs during pregnancy, rendering him guilty of sham reasoning about the “dangers” of Bendectin. Or, perhaps, the worldwide fame and fortune he enjoyed as a result of his involvement in the thalidomide case and his self-interest in his research and Foundation 41 led him down a path toward fake reasoning about Bendectin.
Finding Truth on the Internet
The McBride, Bendectin, and thalidomide saga may be old news, but the moral of this story resonates today. Haack (1997) believes (and I would agree with her) that we are in danger of losing our grip on the concepts of truth, evidence, objectivity, and disinterested inquiry. Large amounts of misinformation and disinformation, masquerading as genuine information, pollute cable television, talk radio, and (especially) the Internet (Mintz, 2002). Whether it is intentional or unintentional, the dissemination of false or distorted information certainly includes various forms of scientific, medical, and mental health information. The “published” medical literature, although peer reviewed, can even be considered suspect (Steen, 2011). During an era without cable television and the Internet, McBride was as famous in his day as “America’s doctor,” Mehmet Oz, is famous today (Specter, 2013). Although Oz has a distinguished academic and research background in medicine, I believe he has become a master of sham reasoning and fake reasoning, at least as it pertains to dispensing and promoting highly unconventional health advice (Belluz & Hoffman, 2013; Gorski, 2011), appealing to an audience that seems to be either irrational or unthinking.
There have been considerable efforts to develop tools to measure and evaluate the quality of health information on the Internet, but doing so meaningfully and effectively is probably futile (Deshpande & Jadad, 2009). According to the Safe Practices for Motor Vehicle Operations standard ( http://www.asse.org/publications/standards/z15/docs/Z15_1_Tech_Brief_4_2012.pdf), defensive driving is defined as “driving to save lives, time, and money, in spite of the conditions around you and the actions of others” (p. 7, Definition 2.5). Travelers on the information superhighway of the Internet, especially nurses and other health care professionals, should perhaps “drive defensively” when it comes to health and research information.
Eric Schmidt, executive chairman of Google Inc., told the journalist Jeffrey Goldberg (2012) in an interview at the Aspen Ideas Festival that Google should “rank against” disinformation. Acknowledging that doing so is not easily accomplished, however, Schmidt simply recommended that “You all have to be aware that searching for something doesn’t mean you have to believe it” (Propaganda, Facts, para. 2). As users and communicators of medical and research information, nurses should strive to be discerning when evaluating the veracity of information that is relevant to their work. There are, for example, numerous examples in nature of zombie creatures at work (van Houte, Ros, & Oers, 2013). David Stanley (2012) has further suggested, in a comprehensive peer-reviewed article for nurses, that “there is considerable…evidence to support the theoretical probability for an outbreak of Solanum virus which could result in a zombie epidemic” (p. 1612) in humans. His purpose in writing the article was to present information about the issues nurses will face when confronted with a zombie epidemic. Driving defensively and following Schmidt’s advice would seem to be the best course of action for us to follow.
- Belluz, J. & Hoffman, S.J. (2013, January1). Dr. Oz’s miraculous medical advice. Retrieved from http://www.slate.com/articles/health_and_science/medical_examiner/2013/01/can_you_trust_dr_oz_his_medical_advice_often_conflicts_with_the_best_science.html
- Brent, R.L. (1983). The Bendectin saga: Another American tragedy. Teratology, 27, 283–286. doi:10.1002/tera.1420270217 [CrossRef]
- Brent, R.L. (1995). Bendectin: Review of the medical literature of a comprehensively studied human nonteratogen and the most prevalent tortogenlitigen. Reproductive Toxicology, 9, 337–349. doi:10.1016/0890-6238(95)00020-B [CrossRef]
- Daubert, v.Merrell Dow Pharmaceuticals, 509 U.S. 579, 589 (1993).
- Deshpande, A. & Jadad, A.R. (2009). Trying to measure the quality of health information on the Internet: Is it time to move on?Journal of Rheumatology, 36, 1–3. doi:10.3899/jrheum.081101 [CrossRef]
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- Gorski, D. (2011, February3). Dr. Mehmet Oz completes his journey to the dark side. Retrieved from http://www.sciencebasedmedicine.org/dr-oz-once-the-learner-now-the-master-of-woo
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- Haack, S. (1997). Science, scientism, and anti-science in the age of preposterism. Skeptical Inquirer, 21, 37–42.
- Korcok, M. (1980). The Bendectin debate. Canadian Medical Association Journal, 123, 922–928.
- Lerner, K.L. & Lerner, B.W. (2006). Medicine, health, and bioethics: Essential primary sources. Detroit, MI: Thompson/Gale.
- Loff, B. & Cordner, S. (1998). McBride reregistered. Lancet, 352, 1690. doi:10.1016/S0140-6736(05)61473-0 [CrossRef]
- Marcus, R.L. (1997). Reexamining the Bendectin litigation story: Bendectin and birth defects: The challenges of mass toxic substances litigation. Iowa Law Review, 83, 231–253.
- Maskin, A. & Lacayo, I.C. (2013). Expert evidence in the federal courts: A historical perspective. Retrieved from http://www.weil.com/files/upload/Expert_Evidence_Federal_Courts.pdf
- Maxwell, M.W. (2011). Autism ideas–Pt 6: The thalidomide doctor who got struck off. Retrieved from http://rense.com/general94/aut6.htm
- McBride, W. (2001). Specialist life-William McBride. European Journal of Obstetrics, Gynecology and Reproductive Biology, 95, 139–140. doi:10.1016/S0301-2115(01)00302-5 [CrossRef]
- McBride, W.G. (1961). Thalidomide and congenital abnormalities. Lancet, 2, 1358. doi:10.1016/S0140-6736(61)90927-8 [CrossRef]
- Mintz, A.P. (2002). Web of deception: Misinformation on the Internet. Medford, NJ: CyberAge Books.
- Skolnick, A. (1990). Key witness against morning sickness drug faces scientific fraud charges. Journal of the American Medical Association, 263, 1468–1469, 1473. doi:10.1001/jama.1990.03440110020003 [CrossRef]
- Specter, M. (2013, February4). The operator: Is the most trusted doctor in America doing more harm than good? Retrieved from http://www.newyorker.com/reporting/2013/02/04/130204fa_fact_specter
- Stanley, D. (2012). The nurses’ role in the prevention of Solanum infection: Dealing with a zombie epidemic. Journal of Clinical Nursing, 21, 1606–1613. doi:10.1111/j.1365-2702.2011.03920.x [CrossRef]
- Steen, R.G. (2011). Misinformation in the medical literature: What role do error and fraud play?Journal of Medical Ethics, 37, 498–503. doi:10.1136/jme.2010.041830 [CrossRef]
- van Houte, S., Ros, V.I. & van Oers, M.M. (2013). Walking with insects: Molecular mechanisms behind parasitic manipulation of host behaviour. Molecular Ecology, 22, 3458–3475. doi:10.1111/mec.12307 [CrossRef]
- Wolsing, J.M. (2007). Daubert’s Erie problem. Indiana Law Journal. Retrieved from http://www.re-pository.law.indiana.edu/ilj/vol82/iss1/7