Medical Advances That Were Initially Ridiculed or Rejected: Introduction Although medical science most often advances incrementally on the basis of an ever-accumulating body of evidence, occasionally leaps forward are made. And quite often these leaps fly in the face of conventional wisdom. Today's standard of care was yesterday's experimental treatment, and before that, in many cases, it was one man or woman's visionary idea. The history of medicine includes many examples of ideas that were initially ridiculed or rejected by the medical establishment but that later became widely adopted. Here is a collection of some of the better known examples; in highlighting them, Medscape acknowledges the courage of researchers and clinicians who stood by their ideas, often in the face of withering criticism from their colleagues. Antiseptic Handwashing Ignaz Semmelweis may be the best known example of a physician ridiculed for an idea that is now accepted as common sense. A Hungarian physician working in the maternity ward in Vienna in the mid-19th century, Semmelweis noted that puerperal fever was contagious—students and physicians were performing autopsies and then contaminating new mothers in the maternity ward with what Semmelweis, working prior to the germ theory of disease, termed "cadaverous particles."[1] Semmelweis advocated that doctors in obstetric clinics disinfect their hands following autopsies; at the clinic in which Semmelweis's hand-washing policy was implemented, the puerperal fever mortality rates dropped 90%, from 18.3% to less than 2%, in fewer than 6 months. Despite Semmelweis's demonstration of the value of antiseptic techniques, by and large his ideas were rejected by the medical community, with a few notable exceptions. Semmelweis had believed that antiseptic hand washings would be widely adopted and save thousands of lives; when they were not, Semmelweis began publishing a series of vitriolic "open letters" against his critics.[2]Increasingly isolated and unpredictable, Semmelweis was admitted against his will to a Viennese insane asylum, where he was severely beaten; he died after 2 weeks. Newborn Incubators Incubators are standard equipment in neonatal intensive care units and have become so common that, in many ways, they are emblematic of the care given to premature babies in their first hours and weeks of life. In the United States, however, for the first decades of their use, the only place infant incubators could be found was at amusement parks and "sideshows" alongside tattooed ladies and sword swallowers. First pioneered by French obstetrician Stéphane Étienne Tarnier, infant incubators were initially used and refined throughout Europe in the late 19th century.[3] Martin Arthur Couney, who studied under one of Tarnier's assistants, first witnessed an infant incubator at the Berlin Exposition and decided to import them to the United States.[4] After they were largely rejected by the US medical establishment, Couney established a bank of incubators at Luna Park on Coney Island in New York. From 1903 to the early 1940s, Couney charged visitors 25 cents to view the premies on display, money that was used to pay for the babies' medical care so that parents did not have to. It has been estimated that Couney treated about 8000 children and saved the lives of 6500 babies during his 4 decades on the Coney Island boardwalk. In 1939, New York Hospital opened the first official training and research center for premature babies—36 years after Couney debuted his baby incubator in Luna Park. Couney died in 1950 in relative obscurity; however, the widespread adoption of infant incubators is a testament to his courage (and showmanship). Balloon Angioplasty Percutaneous transluminal coronary angioplasty (PTCA) is one of the most common procedures performed during US hospital stays. According to a report published last year by the Agency for Healthcare Research and Quality, PTCA accounted for 3.6% of all operating room procedures performed in 2011, ranked behind only cesarean section, circumcision, and knee arthroplasty.[5] It is interesting to note, then, that in 1976, when German cardiologist Andreas Roland Grüntzig first presented the idea as a poster at the annual meeting of the American Heart Association, world-renowned catheterization specialist Dr Spencer King said, "It'll never work."[6] Grüntzig, who had spent years developing the concept and initial device in his kitchen, was undeterred. Croatian cardiac surgeon Marco Turina, MD, is noted to have said that Grüntzig "had the 'sacred fire,' as the French call it. It was what he thought about constantly. I have never seen somebody so centered on a single idea like Andreas was. Never in my life. Everyone was telling him his idea would never work, and had been tried before, and that he was going to fail, that there were pitfalls at every turn. But the idea was consuming him all the time."[7] Grüntzig returned to the American Heart Association 1 year later in 1977 and presented his first four cases of angioplasties in humans from the podium. When he finished, the audience of his colleagues rose as one and gave him a standing ovation. Viruses and Cancer When critics responded severely to Peyton Rous's demonstration of the viral transmission of cancer in 1911, Rous was so dismayed that he quit working with the retrovirus that now bears his name—the Rous sarcoma virus—and quit studying cancer altogether for the next 2 decades, focusing instead on research questions in support of the World War I effort.[8] At the time, viruses were not well understood and beyond the reach of contemporary microscopy; critics contended that the tumor caused by Rous's virus was not a true neoplasm but rather a reaction to the virus more akin to inflammation, such as a granuloma.[9] Nearly 60 years after Rous's initial discovery, his work was fully validated by American biologists Peter Duesberg and Peter Vogt, who discovered the gene responsible for the tumorigenic activity of the virus, the first viral oncogene v-src. Later, in 1989, J. Michael Bishop and Harold Varmus would win a Nobel Prize for extending this work yet further to discover the first proto-oncogene, suggesting that tumors may arise from defects in normal cellular genes.[10] Today we recognize that roughly 20% of human cancers have an infectious etiology. In 1966, 55 years after his discovery, Rous himself was awarded the Nobel Prize, the longest "incubation period" in the history of the Nobel Prizes in Physiology or Medicine. Helicobacter pylori "Everyone was against me. But I knew I was right."[11] This is how Dr Barry Marshall, a gastroenterologist from Western Australia, described his efforts in the mid-1980s to convince the medical establishment that ulcers were caused by bacteria and not by stress, spicy foods, and too much acid, as conventional medical wisdom held at the time. In fact, both sides were so firmly entrenched in their beliefs that Marshall himself felt compelled to drink a Petri dish containing an estimated thousand million bacteria, including cultured H pylori. Within a week Marshall began experiencing symptoms including achlorhydric (no acid) vomiting; biopsies showed severe damage to the mucosa of Marshall's stomach. Later, Marshall would link this initial infection with the development of ulcers. Marshall was given the 2005 Nobel Prize for his discovery. In his Nobel biography, he reflected on his choice to infect himself: "If I was right, then treatment for ulcer disease would be revolutionized. It would be simple, cheap, and it would be a cure. It seemed to me that for the sake of patients this research had to be fast tracked."[12] Infectious Proteins When neurologist Stanley Prusiner insisted that mad cow disease and Creutzfeldt-Jakob disease are caused not by viruses, bacteria, or fungi but by infectious proteins, which he dubbed "prions" in 1982, even he admitted that the idea was "clearly heretical."[13] It was instantly controversial, particularly among Prusiner's infectious disease and virology colleagues who had staked their entire careers on searching for and studying the pathogens behind these diseases. They simply could not accept that a mere protein, with its lack of genetic material, could transmit disease. (Some still cannot.) Prusiner himself described this first publication as setting off a "firestorm," and he suffered a series of "very vicious" personal attacks in the press.[14] Prusiner continued publishing, however, further characterizing prions and adding diseases to the list of those he believed were caused by infectious proteins. Slowly some in the medical community accepted his hypotheses. And then in 1996, more than a decade after he had initially described prions, the first cases of the human form of mad cow disease were reported in Britain. Mad cow disease, or bovine spongiform encephalopathy, had previously been identified as a prion disease by Prusiner.[15] One year later, in 1997, Prusiner won the Nobel Prize for his discovery of prions. Germs Cause Disease Though Louis Pasteur was not the first to propose the germ theory of disease, he is forever linked with this critical leap forward in medical science because he was the first to conduct convincing experiments that demonstrated the underlying role of micro-organisms in disease, thus firmly overturning the concept of "spontaneous generation" as their cause. Less well known is the bitter and long-running resistance to Pasteur's ideas spearheaded by Pierre Béchamp, a successful French chemist and biologist. Béchamp, a contemporary of Pasteur's, believed that tiny organisms present in all things called "microzyma" were responsible for disease, as opposed to external bacteria that invaded healthy tissue.[16] Though Béchamp was well known at the time of his public dispute with Pasteur, he died in relative obscurity and would be nothing more than a historical footnote had he not become the figurehead of a larger movement of germ theory denialists that continued throughout the 20th century.[17] Heredity Though Gregor Mendel established the laws of inheritance through plant experiments and, to a lesser degree, with mice and bees, his contributions to science are included not only because of their far-reaching effects on medicine but because Mendel also experienced so many varieties of ridicule and rejection of his work.[18] Mendel's theories were initially rejected by the scientific community because they sought to overturn a substantive body of science supporting "blending inheritance," which argued that traits from each parent were averaged together in offspring. (This was later explained through the action of multiple genes that produce "quantitative effects.") Few could believe that such a vast body of work could be incorrect. Mendel's theories were also rejected by scientific luminaries at the time—with whom he tried to correspond directly—because in their eyes he was a simple monk from a provincial town. As such, he could never address such weighty scientific questions. Finally, Mendel's presentation of his studies was criticized because it blended botany with mathematics, two disciplines that were seen as separate. The use of what are now considered simple statistical techniques was then seen as strange and obtuse to mid-19th century botanists and zoologists. Mendel's theories were not accepted until after he died, when the results were duplicated in papers published in 1900, some 35 years after he initially presented his ideas. Cancer Immunotherapy Occasionally, rejection comes in the form of well-intentioned advice. Immunotherapy is now being heralded as a revolution in cancer treatment, but when immunologist James Allison first suggested his research interest in T cells, his mentors discouraged him. "Tumor immunology had such a bad reputation," he told the New Yorker in 2012.[19] "Many people thought that the immune system didn't play any role in cancer." After wandering "in the wilderness for a while," Allison finally developed an antibody that he felt was ready for pharmaceutical development. But biotech companies repeatedly turned him away: "People were skeptical of immunology and immune therapy. They would say, 'Oh, anybody can treat cancer in mice.' Sometimes they'd say, 'You think you can treat cancer by just removing this negative signal on a T-cell?'" Allison believed precisely that, and he persevered in his pioneering work. Drugs based on Allison's initial ideas are now poised to become among the most clinically and commercially successful cancer drugs on the market[20]; he has also won a number of awards for his work, including last year's Lasker Award, often considered a shortlist for the Nobel Prize. Traumatic Brain Injuries in Sports When a purely scientific advance stands to jeopardize a very powerful interest, rejection can turn threatening. Such was the case of forensic pathologist Bennet Omalu, a native Nigerian working in the Allegheny County coroner's office. Dr Omalu had no idea just how powerful the National Football League (NFL) was when he published the first diagnosis of chronic traumatic encephalopathy in Neurosurgery.[21] The NFL immediately mobilized a cadre of physicians on the organization's payroll to attack Dr Omalu's research. Dr Omalu, however, continued publishing, and the NFL continued its attack in kind, very often through physicians with a long history of working with, and for, the NFL. "I was naive," Dr Omalu told GQ in 2009.[22] "There are times I wish I never looked at [former professional NFL player] Mike Webster's brain. It has dragged me into worldly affairs I do not want to be associated with. Human meanness, wickedness, and selfishness. People trying to cover up, to control how information is released. I started this not knowing I was walking into a minefield. That is my only regret." Even experts without any ties to the NFL initially discounted Dr Omalu's work. "The credit must go to Bennet Omalu," neuropathologist Peter Davies, of the Albert Einstein College of Medicine in New York, said, "because he first reported this, and nobody believed him, nobody in the field, and I'm included in that. I did not think there was anything there. But when I looked at the stuff, he was absolutely right. I was wrong to be skeptical." Because of Dr Omalu's persistence, the NFL has been forced to acknowledge chronic traumatic encephalopathy, and the wider sports culture has begun questioning the costs of repeated brain injuries in sports, both professional and recreational. References Semmelweis I, Carter KC (translator and editor). The Etiology, Concept, and Prophylaxis of Childbed Fever. Madison, WI and London: University of Wisconsin Press; 1983. Carter KC, Carter BR. Childbed Fever. A Scientific Biography of Ignaz Semmelweis. Herndon, VA: Transaction Publishers; 2005. Dunn PM. Stéphane Tarnier (1828-1897), the architect of perinatology in France. Arch Dis Child Fetal Neonatal Ed. 2002;86:F137-F139. Field C. Boardwalk babes: the strange story of the incubator. The Blaze. November 19, 2014. http://www.theblaze.com/stories/2014/11/19/boardwalk-babes-the-strange-story-of-the-incubator/Accessed November 9, 2015. Weiss AJ, Elixhauser A, Andrews RM. Characteristics of operating room procedures in U.S. hospitals, 2011. Agency for Healthcare Research and Quality. February 2014. http://hcup-us.ahrq.gov/reports/statbriefs/sb170-Operating-Room-Procedures-United-States-2011.jsp Accessed November 9, 2015. Forrester JS. The Heart Healers: The Misfits, Mavericks, and Rebels Who Created the Greatest Medical Breakthrough of Our Lives. New York City, NY: St. Martin's Press; 2015. Barton M, Grüntzig J, Husmann M, Rösch J. Balloon angioplasty—the legacy of Andreas Grüntzig, M.D. (1939-1985). Front Cardiovasc Med. December 29, 2014. http://journal.frontiersin.org/article/10.3389/fcvm.2014.00015/full Accessed November 9, 2015. Hudnall SD. Human cancer virology: an historical review. In: Hudnall SD, ed. Viruses and Human Cancer. New York, NY: Springer; 2014. Morris J, ed. Rethinking Risk and the Precautionary Principle. Oxford, UK: Butterworth-Heinemann; 2000. Weiss RA, Vogt PK. 100 years of Rous sarcoma virus. J Exp Med. 2011;208:2351-2355. Academy of Achievement. Interview: Barry Marshall. May 23, 1998. http://www.achievement.org/autodoc/printmember/mar1int-1 Accessed November 9, 2015. Nobelprize.org. Barry J. Marshall - Biographical. The Nobel Foundation. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2005/marshall-bio.html Accessed November 9, 2015. Ingram J. Fatal Flaws: How a Misfolded Protein Baffled Scientists and Changed the Way We Look at the Brain. New Haven, CT: Yale University Press; 2013. Nobelprize.org. Stanley B. Prusiner - Biographical. The Nobel Foundation. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1997/prusiner-bio.html Accessed November 9, 2015. Prusiner SB. Prion diseases and the BSE crisis. Science. 1997;278:245-251. Hess DJ. Can Bacteria Cause Cancer?: Alternative Medicine Confronts Big Science. New York, NY: NYU Press; 1997. Hume D. Bechamp or Pasteur: A Lost Chapter in the History of Biology. Whitefish, MT: Kessinger Publishing; 2010. Barber B. Resistance by scientists to scientific discovery. Science. 1961;134:596-602. Groopman J. The T-cell army. New Yorker. April 23, 2012. http://www.newyorker.com/magazine/2012/04/23/the-t-cell-army Accessed November 9, 2015. King S. The biggest selling cancer drugs in 2020 show significant change expected in five short years. Forbes. June 1, 2015. http://www.forbes.com/sites/simonki...nificant-change-expected-in-five-short-years/ Accessed November 9, 2015. Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH. Chronic traumatic encephalopathy in a National Football League player. Neurosurgery. 2005;57:128-134. Laskas JM. Game brain. GQ. September 14, 2009. http://www.gq.com/story/nfl-players-brain-dementia-study-memory-concussions Accessed November 9, 2015. Source
