Can American Medicine Learn from Past Mistakes?
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COMMENTARY To Err is Human: Can American Medicine Learn from Past Mistakes? Jeffrey B Ritterman, MD Perm J 2017;21:16-181 E-pub: 06/14/2017 https://doi.org/10.7812/TPP/16-181 ABSTRACT seasoned researchers in overcoming a “set infants would be put to bed and found The history of medicine includes of well entrenched beliefs that conflicted dead in the morning. In 1830, patholo- many errors. Some persisted for decades with the new ideas.”3 gists noted that SIDS-affected infants had and caused great harm. Several are It took a generation for Marshall and enlarged thymus glands compared with highlighted in this article, including the Warren’s pioneering work to be recognized “normal” autopsy specimens.7 It seemed mythical thymic diseases: thymic asthma and acknowledged. They first published logical to conclude that these “enlarged” and status thymicolymphaticus. Some their findings onH pylori in 1984. More glands were in some way responsible for medical mistakes, such as the diet-heart than a decade later, in 1995, only 5% of the deaths. hypothesis of Ancel Keys, continue to American physicians were prescribing anti- In 1830, Kopp introduced the term cause harm. To avoid future errors and biotics for treatment of peptic ulcer disease.3 thymic asthma, suggesting that the “en- their associated harm, I suggest a cultural In 2005, Marshall and Warren received the larged” thymus occluded the trachea.8 The shift encouraging professional humil- Nobel Prize in Medicine for their discovery, existence of this fictitious disease became ity and greater questioning of medical 26 years after Warren discovered H pylori.2 widely and quickly accepted, and persisted dogma. Medical education focused on This problem of mistaken ideas per- for at least a century. The thymic syndrome teaching students this history may help sisting despite scientific evidence to the underwent an additional modification by with this cultural shift. contrary has been present since the onset the Austrian physician, Paltauf, who added of the scientific method. In 1633, Galileo the term status thymicolymphaticus to the INTRODUCTION was sentenced to house arrest for the crime medical lexicon in 1889.8 Paltauf believed During my medical training, we were of proclaiming that the sun, not the earth, that a systemic disorder leading to vascular taught that stress and lifestyle factors was the center of our planetary system.4 collapse caused the sudden deaths. The caused gastritis and peptic ulcer disease. Three hundred years later, Nobel prize- enlarged thymus, it was believed, caused We accepted without question the idea winning physicist Max Planck5 stated: “A this unexplained vascular collapse, often that bacteria could not live in the highly new scientific truth does not triumph by precipitated by minor stress. acidic environment of the stomach. Pa- convincing its opponents and making Descriptions and case reports of these tients with severe ulcer disease would be them see the light, but rather because its thymus “diseases” appeared in medical offered surgery. We now know, thanks opponents eventually die, and a new gen- articles and textbooks.9,10 There was even to the pioneering work of Marshall and eration grows up that is familiar with it.” a list of physical characteristics that ac- Warren,1 that peptic ulcer is caused by a Or more succinctly: “Science advances companied these syndromes, including bacterium, Helicobacter pylori. one funeral at a time.”6 changes in incisor teeth, heart size, and Warren discovered the curved bacteria in This problem is of particular concern skin color. The 1924 edition ofManage - the stomachs of patients with peptic ulcer in medical science, where outmoded ideas ment of the Sick Infant claimed that the disease and gastritis in 1979.2 But it wasn’t translate into excess morbidity and mortal- clinical picture of thymic asthma was “so until his research partner, Marshall, delib- ity. How can medicine learn from its mis- characteristic that once seen, it is unlikely erately infected himself with the bacterium takes and make these timely corrections? to be mistaken.”8 and gastritis developed that their findings Perhaps a few additional examples will help If an enlarged thymus was leading to were taken seriously. make clear the importance of doing so. sudden infant death, removal of the thy- Marshall’s ability to take a fresh look at mus might be of preventive value. Radi- these gastric bacteria as etiologic agents, A CAUTIONARY TALE: SUDDEN ology had advanced to the point at which rather than to uncritically accept the stress INFANT DEATH SYNDROME AND THE physicians began making the diagnosis theory of ulcer disease, was in part because “ENLARGED” THYMUS GLAND of thymic enlargement from x-ray films. of his lack of experience. Having started In the first half of the 19th century, phy- After radiographic diagnosis, thymec- his study of gastroenterology in 1981, sicians were becoming alarmed by sudden tomy was initially recommended, but Marshall had an easier time than more infant death syndrome (SIDS). Healthy the mortality rate was unacceptably high. Jeffrey B Ritterman, MD, is the retired Chief of Cardiology of the Kaiser Richmond Medical Center; he is the Clinical Coordinator and Associate Professor in the Joint MSPAS/MPH Program at Touro University in Vallejo, CA. E-mail: [email protected]. The Permanente Journal/Perm J 2017;21:16-181 1 COMMENTARY To Err is Human: Can American Medicine Learn from Past Mistakes? Thymus irradiation became the treatment A CAUTIONARY TALE: FAT new knowledge seemed to fit well with of choice.8 Perhaps there is no better modern medi- Keys’ “dietary fat hypothesis” as the cause The first “successful” use of irradia- cal example of our capacity for serious error of CVD. Because LDL cholesterol corre- tion to shrink the thymus was reported than the fact that we have given the wrong lated with the risk of CVD and dietary fat by Friedländer in 1907.11 Thousands of dietary advice since shortly after President increased blood LDL cholesterol levels, it children eventually received radiation to Eisenhower’s heart attack in 1955. Not seemed logical to conclude that dietary fat prevent status thymicolymphaticus. Some only has our advice been wrong, it has was the cause of CVD. physicians advocated prophylactic irradia- been dangerously wrong.18 Once again, incomplete knowledge tion for all neonates.8 As in the case of the supposed thymic led to the pursuit of a dangerous path. In There was only one slight problem. It disorders, once again a mistake has led to the dietary guidelines case, epidemiologic turned out to be deadly.7 great harm. research that showed an association was The cadavers used by anatomists to Ancel Keys, PhD, a physiologist, studied wrongly assumed to prove causality. In determine the “normal” thymus size the American and European diets after addition, the contrary evidence to Keys’ were from the poor, most having died World War II. He studied the epidemiol- diet-heart hypothesis was ignored. There of highly stressful chronic illnesses such ogy of cardiovascular disease (CVD) and never was any association between dietary as tuberculosis, infectious diarrhea, and noted that American business executives fat and all-cause mortality. Certainly, if di- malnutrition. What was not appreciated had high rates of CVD,19,20 whereas the etary fat was the cause of CVD, one would at the time was that chronic stress shrinks heart disease rates in postwar Europe had expect such an association. In the single the thymus gland. The “normal” thymus fallen sharply, presumably from reduced randomized controlled trial that compared glands of the poor were abnormally small. food supplies. He postulated that the a 10% saturated fat intake vs a diet with Here is where the fatal mistake occurred: different rates of CVD were owing to unrestricted saturated fat, the subjects with because the autopsied thymus glands of markedly different rates of dietary fat con- low-fat intake had a higher death rate due the poor were regarded as normal in size, sumption. Keys was convinced that dietary to all causes, including heart disease.26 the SIDS-affected infants were erroneous- fat led to elevated cholesterol levels, which In 1977, the McGovern Commission, ly believed to have thymic enlargement.7,8 then caused CVD.21 Keys presented his chaired by then Senator George McGov- The thyroid gland, which is highly diet-heart hypothesis to the World Health ern, issued dietary guidelines in keeping sensitive to irradiation, sits close to the Organization in 1955. His research was with the diet-heart hypothesis.27 Decades thymus. The increased risk of thyroid epidemiologic and could only prove an later, we have continued to follow these malignancy in the patients who had un- association, not causality. But Keys was a guidelines.28 Americans have been repeat- dergone thymic irradiation was first rec- convincing salesman at a time when the edly told to consume no more than 30% ognized in 1949.12 The patients subjected country was searching for solutions to pre- of total calories from fat and no more than to thymic radiation “therapy” also expe- vent the sudden deaths resulting from this 10% from saturated fat.28 rienced higher rates of breast cancer.13-15 newly recognized killer. In January 1961, When the food companies responded The regular practice of thymic irra- Keys became a cultural hero, his picture to the guidelines by removing the fat from diation was finally halted in the 1940s, gracing the cover of Time Magazine, and food, the taste went with it. The solution: almost four decades after Friedländer irra- the diet-heart hypothesis was accepted.22 add sugar, and lots of it. This worked well diated the first patient. In the first edition In 1978, Keys published his data in sup- economically, as the invention of high- of his radiology textbook in 1945,16 John port of dietary fat as the cause of CVD, fructose corn syrup provided an endless Caffey, MD, a pioneer in pediatric radi- in the Seven Countries Study.23 Unfortu- supply of cheap sugar.