From H. pylori to Spanish colonialism: the scales of cancer.

IMO2014Yesterday was the first day of the 4th Integrated Mathematical Oncology Workshop here at Moffitt. This year, it is run jointly with the Center for Infection Research in Cancer and is thus focused on the interaction of infection disease and cancer. This is a topic that I have not focused much attention on — except for the post on canine transmissible venereal tumor and passing mentions of Human papillomavirus (HPV) — so I am excited for the opportunity to learn. The workshop opened with a half-day focused on getting to know the external visitors, Alexander Anderson’s introduction, and our team assignments. I will be teammates with Heiko Enderling, Domenico Coppola, Jose M. Pimiento, and others. We will be looking at Helicobacter pylori. Go team blue! If you are curious, the more popularly known HPV went to David Basanta’s team, it will be great to compete against my team leader from last year. As you can expect, the friendly trash talking and subtle intimidation has already begun.

To be frank, before yesterday, I’ve only ever heard of H. pylori once and knew nothing of its links to stomach cancer. The story I heard was associated with Barry J. Marshall and J. Robin Warren’s award of the 2005 Nobel Prize in Physiology and Medicine “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”. In 1984, Marshall was confident in the connection between H. pylori, inflammation, and ulcers, but the common knowledge of the day was that ulcers were caused by things like stress and smoking, not bacteria. The drug companies even happened to have an expensive drug that could manage the associated stomach inflammation, and given the money it was bringing in, nobody was concerned with finding some bacterium that could be cured with cheap antibiotics. Having difficulty convincing his colleagues (apart from Warren), Marshall decided to drink a Petri dish of cultured H. pylori, and within a few days grew sick, developing severe inflammation of the stomach before finally (two weeks after the ingestion) going on antibiotics and curing himself. This dramatic display was sufficient to push for bigger studies that eventually lead to the Nobel prize; I recommend listening to Warren’s podcast with Nobel Prize Talks or his acceptance speech for the whole story.

This is a fascinating tale, but from the modeling perspective, the real excitement of H. pylori and its role in stomach cancer is the multitude of scales that are central to the development of disease. We see important players from the scale of molecules involved in changing stomach acidity, to the single-cell scale of the bacteria and stomach lining, to the changes across the stomach as a whole organ, and the role of the individual patient’s life style and nutrition. These are the usual scales we see when modeling cancer, and dovetail nicely with Anderson’s opening remarks on the centrality of mathematics in helping us bridge the gaps. However, in the case of H. pylori, the scales go beyond the single individual at which Anderson stops and extend to the level of populations of humans in the co-evolution of host and pathogen, and even populations of groups of humans in a speculative connection to a topic familiar to TheEGG readers — the evolution of ethnocentrism. In preparation for the second half of the second day and the intense task of finding a specific question for team blue to focus on, I wanted to give a quick overview of these scales.
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