Of Helicobacter, Cancer and the Medical Establishment

The 2005 Nobel Prize in physiology was awarded to Barry Marshall and Robin Warren. These two practicing physicians made the discovery that peptic ulcer disease resulted, not from excess acid production, the prevailing theory, but instead from infection with an enteric pathogen – helicobacter pylori. In 1982, Marshall and Warren identified this organism in the stomach of an ulcer patient. When they proposed the causative relationship with ulcers they were virtually laughed off the stage. First, no organism could withstand the high concentration of acid found in the stomach. Second, excess acid, not infections caused ulcers.

These investigators wrote letters to the Lancet describing their early findings, while they continued to accumulate supporting documentation that correlated the presence of these spiral shaped organisms with gastric ulceration. This led other gastroenterologists and pathologists to more closely inspect gastric biopsy specimens for the presence of these pathogens.

What seemed so obvious to Warren and Marshall met with enormous resistance. After all, the acid causation theory had been in place for almost a century. The treatment of peptic ulcer disease had spawned an industry. From Maalox to Mylanta to Tums, sodium bicarbonate and even to Coca Cola and dairy products, soothing patient’s gastric symptoms had become a cause celebré for Western medicine. Ulcer surgery in the form of the vagotomy and pyloroplasties (V&P), Bilroth1 and Bilroth2, even gastrectomies, had come to constitute the most widely practiced surgical procedures in the United States. Gastric ulcers were good for business and no one from the pharmaceutical industry, to the hospitals, or the operating surgeons, were very interested in changing that.

Frustrated by their lack of traction amongst their colleagues, Marshall consumed a flask filled with helicobacter, thereby inflicting himself with an ulcer that was confirmed at the time of an endoscopy 10 days later. Treating the ulcer successfully with antibiotics still left little impact on his doubting Thomas colleagues. But clearly some were listening. By 1987, the first triple therapy cocktail had been developed. The success of this medical treatment became increasingly irrefutable. Slowly, but surely, these two unsung heroes were recognized for their fundamental and practice-altering observations.

These two physicians represent the very best of medical scientists. They began with an observation and painstakingly worked back to an etiology. This is how most medical discoveries are made. Yet, this is not the model for today’s oncologic investigation wherein, scientists conceive of novel theories and then demand that physicians test them, rarely to good effect. These Australian physicians were not highly acclaimed academics, or senior professors. Instead, they practiced their art and unceremoniously made important observations. . Confronting immense inertia in an entrenched medical community, they stood their ground and ultimately carried the day. Aided by the invention of the fiber-optic gastroscope, they were able to prove correlations, repeat experiments and ultimately confirm their results. It took 20 years, but the Nobel committee finally recognized their contribution.

Cancer research today is inhabited by these same entrenched forces, which are convinced of certain principles and unwilling to reconsider their positions. Like the environment in which Warren and Marshall found themselves 30 years ago, the academic community eschew any idea that disrupts their hegemony However, similar paradigm shifts are occurring today in oncology: Yesterday’s gastric acid theory is akin to today’s cell proliferation model. The development of the fiberoptic endoscope in the 1980s is the equivalent of today’s advance in primary culture laboratory platforms. Marshall and Warren changed  medical history. Do we really need to wait another 30 years to do the same for cancer patients?