“If you want something done right, do it yourself.”[1]
Most current research is published with multiple authors, a mean of 11-18 in three of the top medical journals during 2016 (Journal of the American Medical Association, The Lancet, and New England Journal of Medicine). Scientists working in teams published as group authors in 30-45% of these three journal publications in 2015[2]. The idea of a modern-day Edward Jenner or Alexander Fleming, working and publishing mostly alone and uncovering startling and world changing findings, is almost a romantic fantasy. And yet, the 2005 Nobel Prize for research in Medicine and Physiology was awarded to two men, working alone and in relative clinical obscurity, who believed in their data and hypotheses so strongly they even experimented on one of themselves. As a result, they overturned conventional theory and standard treatment.
Though armed with observational data that pointed to the Helicobacter pylori (H pylori) bacterium as a common cause of gastritis, peptic ulcer disease and gastric cancer[3], Barry Marshall, MD, and Robin Warren, MD, met with stiff resistance from the medical community about their hypothesis[4]. The prevailing theory prior to their research was that these conditions were caused by stress and excessive stomach acid. Treatment was chronic with generally poor results. Convinced of the validity of their observations, but unable to prove their hypothesis in animal models, Dr. Marshall eventually turned himself into a single experimental subject[5].
Having had some luck discovering how to culture H pylori, the two clinical scientists were able to create a sample for Marshall to ingest, following an endoscopy to demonstrate he did not have H pylori infection to begin with. Shortly after ingestion of the bacteria, Marshall developed clinical symptoms consistent with gastritis and then repeated the endoscopy to show it had developed. He treated himself with antibiotics and his symptoms and the pathological changes resolved.
This satisfied Koch’s postulates – four steps that must be followed to demonstrate a certain microorganism causes a specific disease. Step 1: The bacterium must always be present with the disease. Step 2: The bacterium must be isolated from the organism with the disease and grown in culture. Step 3: The disease must be reproduced when the cultured bacteria are introduced into a healthy but susceptible host. Step 4: The bacteria must be found with the disease in the new host.
Even though Drs. Marshall and Warren utilized the unconventional process of self-experimentation, they nevertheless adhered to the traditional scientific method, utilizing Koch’s postulates to demonstrate that H pylori could be a common and treatable cause of gastritis and peptic ulcer disease. Their belief in the scientific process is what motivated them to take what might be considered drastic, yet valid, methods to prove their hypothesis. Society is better off for it: a 50% decline in the incidence of gastric ulcer for both men and women occurred between 1992 and 2003 in the Netherlands[6], for example, and a 47% reduction in the age-adjusted US hospitalization rate for H pylori infection (ulcers and inflammation) was measured between 1998-2005[7].
Courage, belief in data over conventional theory and, in this case, self-reliance, sustained Marshall and Warren and led them to prove to a skeptical world that it was heavily invested in the wrong theory and treatment of a major world-wide health problem. Observation and data usually, and must, precede theory. The great researchers fit theories to data, not the other way around.
[1] Attributed to Charles-Guillaume Etienne [2] Fontanarosa P, Bauchner H, Flanagin A. Authorship and Team Science. JAMA. 2017;318(24):2433–2437. doi:10.1001/jama.2017.19341 [3] Wroblewski LE, Peek RM Jr, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev. 2010;23(4):713-739. doi:10.1128/CMR.00011-10 [4] Marshall B. Helicobacter pylori--a Nobel pursuit?. Can J Gastroenterol. 2008;22(11):895-896. doi:10.1155/2008/459810 [5] Watts G. Nobel prize is awarded to doctors who discovered H pylori. BMJ. 2005;331(7520):795. doi:10.1136/bmj.331.7520.795 [6] Post PN, Kuipers EJ, Meijer GA. Declining incidence of peptic ulcer but not of its complications: a nation‐wide study in The Netherlands. Alimentary Pharmacology & Therapeutics. 2006, 23: 1587-1593. https://doi.org/10.1111/j.1365-2036.2006.02918.x [7] Feinstein LB, Holman RC, Yorita Christensen KL, Steiner CA, Swerdlow DL. Trends in hospitalizations for peptic ulcer disease, United States, 1998-2005. Emerg Infect Dis. 2010;16(9):1410-1418. doi:10.3201/eid1609.091126