What is Cancer?

In toxic tort cases plaintiffs’ attorneys and their experts tend to rely on one of two theories about the cause of cancer. The first is the "one-hit" model in which a single mutagenic molecule, particle or fiber causes DNA damage leading to a malignant cell that self-replicates uncontrollably. The second theory imagines that the damage leading to the malignancy is the result, somehow (the hypothesis is never set out in any great detail) of the cumulative effect of exposure to many molecules, particles or fibers. They say "it’s like a glass of water that finally overflows when one last drop is added, each drop in the glass was a necessary cause of the overflow."

The one-hit theory is rolled out in low dose cases involving from one to a handful of exposure sources. Here the idea is that carcinogenesis is like playing the skull and crossbones lottery. The more tickets you buy (i.e. exposures you encounter) the more likely you are to wind up with the losing ticket. "All it takes is one bullet and they shot trillions of bullets at my client".

The cumulative dose theory is deployed when there are many sources of exposure and where those responsible for the biggest portion of the exposures are bankrupt or have already settled. Here the idea is that once the individual’s defenses are overtopped a malignant clone is born (initiation) or conditions for propelling the spread of an existing malignant clone are created (promotion). The most odious example of this argument was directed, despite my objection, against a client in an asbestos trial in state court in Galveston – "It takes several men to have a lynching. One to hold the man, one to get the horse; one to get the rope, etc. They (meaning my client) want you to believe that each and every man in the lynch mob must go free just because the act of each man alone would not have resulted in my client’s death. I know that’s wrong and you know that’s wrong!"

Either way, whether it’s a matter of each cell playing the cancer lottery one molecule at a time or of each cell slowly filling over the years it’s carcinogenic reservoir you’d think that the more cells you have in your body the more likely you’d be to hit the losing ticket or see a chemoprotective dam collapse. Even for cancers thought to be caused by mishaps during normal cell division you’d think that if you had a lot more cells you’d have a lot more opportunity for mishaps.

But you’d think wrong. People don’t get cancer more often than mice and neither do whales – even though they (obviously) have a lot more cells and also live long enough to have them and their progeny divide many many more times. See "The Mere Existence of Whales" and "Why Don’t All Whales Have Cancer? A Novel Hypothesis Resolving Peto’s Paradox". Hat tip Marginal Revolution.

So what’s going on? Do bigger organisms have better cancer defenses? Does size confer some advantage as suggested by the hypertumor hypothesis?

Maybe it’s the underlying deterministic model that needs tweaking. Maybe cancer rates scale up with physical size because cancer is a system, or a subystem, rather than a simple switch, Indeed there’s a growing body of literature showing a tight association between reproductive optimization, energy availability, aging and cancer. Maybe the 30% cancer rate seen across mammalian species represents an evolutionarily determined risk-of-cancer/benefit-of-plasticity ratio that holds true from mice to whales.

If so, that would mean that we’re programmed to run a high risk of cancer. Not exactly the "cancer is a man-made problem" meme in which labor, environmentalists and their lawyers found a common purpose and a common tool.