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?

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

2 Responses to Of Helicobacter, Cancer and the Medical Establishment

  1. Frank Wiewel says:

    In 2012 it is expected that 1,500,000 Americans will be diagnosed with cancer and 750,000 will die notwithstanding the best conventional treatment. Increasingly we see our family members dying of devastating illness after ineffective treatments feared more than the disease itself. Clearly, we are losing the war on cancer. As a nation we can not afford to overlook any alternatives for any reason.

    Dr Robert Nagourney has made a significant advance in identifying the best cancer treatments for each individual, we can not afford to overlook this remarkable advance.

  2. I remember reading about Drs. Barry J. Marshall and Robin Warren, both Australians, winning the Nobel Prize in medicine for proving, partly by accident, that bacteria and not stress was the main cause of painful ulcers of the stomach and intestine. Yes, a general practioner proved that ulcers are not caused by stress, spicy foods, or even cigarettes and alcohol, but rather by a bacterium. It was one of the most richly deserved Nobel Prizes in Medicine ever awarded.

    Prior to the discovery, the number one surgical operation (in terms of revenue produced for the surgeons and hospitals) was the vagotomy and antrectomy. Prior to the discovery, the number one drugs were H2 receptor blockers like Tagamet and the then up and coming proton pump inhibitors like omeprazole. Single handedly, he got rid of both the number one surgical operation and the largest part of the market for the number one drugs, dealing a huge blow to both big surgery and big pharma, and making the lives of tens of millions much more pain free and enjoyable.

    How many loved-ones had died of a bleeding ulcer? Today, they would have been cured permanently by a two week course of antibiotics. Oh! How having that big mug of thick black coffee without having to chase it with a half bottle of Maalox!

    And the Aussie did it without any research grants and over the dead body opposition of the entire world of medicine, gastroenterology, surgery, the NIH, and the pharmaceutical industry. And, for gosh sakes, he used himself as the definitive guinea pig!

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