Cancer moonshot and slow-learners

Motivated by Vice President Biden's son's death at an early age from cancer, President Obama recently announced a new health initiative which he's calling the cancer 'moonshot'.  This is like a second Nixonian 'war' on cancer but using a seemingly more benign metaphor (though cancer is so awful that treating it as a 'war' seems apt in that sense). Last week the NYTimes printed an op-ed piece that pointed out one of the major issues and illusions belied by the rhetoric of the new attack on cancer, as with the old:  Curing one cancer may extend a person's life, but it also increases his or her chances of a second cancer, since risks of cancer rise with age.

Cancers 'compete' with each other for our lives
The op-ed's main point is that the more earlier onset cancers we cure, the more late onset, less tractable tumors we'll see.  In that sense, cancers 'compete' with each other for our lives.  The first occurrence would get us unless the medical establishment stops it, thus opening the door for some subsequent Rogue Cell to generate a new tumor at some later time in the person's life.  It is entirely right and appropriate in every way to point this out, but the issues are subtle (though not at all secret).

First, the risk of some cancers slows with age.  Under normal environmental conditions, cancers increase in frequency with age because they are generally due to the accumulation of multiple mutations of various sorts, so that the more cell-years of exposure the more mutations that will arise.  At some point, one of our billions of cells acquires a set of mutational changes that lead it to stop obeying the rules of restraint in form and cell-division that are appropriate for the normal function of its particular tissue. A tumor is a combination of exposure to mutagens and mutations that occur simply by DNA replication errors--totally chance events--when cells divide.  As the tumor grows it acquires further mutations that lead it to spread or resist chemotherapy etc.

This is important but the reasons are subtle.  The attack on cells by lifestyle-related mutagens like radiation or chemicals in the environment becomes reduced in intensity as people age and simplify their lives, slowing down a lot of exposures to these risk factors. However, cell division rates, the times when mutations arise, themselves slow down, so the rate of accumulation of new mutations, whether they be by chance or by exposures, slows.  This decrease in the increase of risk with age at least tempers the caution that curing cancers in adults will leave them alive for many years and hence at risk for at least some many more cancers (though surely it will make them vulnerable to some!)

Apollo 11, first rocket to land humans on the moon; Wikipedia

Competing causes: more to the story, but nothing at all new
There's an important issue not mentioned in the article, but that is much more important in an indirect way.  This is an issue the authors of the op-ed didn't think about or for some reason didn't mention or perhaps because they are specialists they just weren't aware of.  But it's not at all secret, and indeed is something we ourselves studied for many years, and we've blogged about here before: anything that reduces early onset diseases increases the number of late onset diseases.  So, curing cancer early on (which is what the op-ed was about) increases risk for every later-onset disease, not just cancer.  In the same way as we've noted before, reducing heart disease or auto accident rates or snake bite deaths will increase dementia, heart disease, diabetes, and cancer--all other later-onset diseases--simply because more people will live to be at risk.  This is the Catch-22 of biomedical intervention.

In this sense all the marketing rhetoric about 'precision' genomic medicine is playing a game with the public, and the game is for money--research money among other things.  There's no cure for mortality or the reality of aging.  Whether due to genetic variants or lifestyle, we are at increasing risk for the panoply of diseases as we age, simply because exposure durations increase.  And every victory of medicine at earlier ages is a defeat for late-age experience.  Even were we to suppose that massive CRISPRization could cure every disease as it arose, and people's functions didn't diminish with age, the world would be so massively overpopulated as to make ghastly science fiction movies seem like Bugs Bunny cartoons.

But the conundrum is that because of the obvious and understandable fact that nobody wants major early onset diseases, it seems wholly reasonable to attack them with all the research and therapeutic vigor at our disposal. The earlier and more severe, the greater the gain in satisfactory life-years that will be made.  But the huge investment that NIH and their universities clients make in genomics and you-name-it related to late-age diseases is almost sure to backfire in these ways.  Cancer is but one example.

People should be aware of these things.  The statistical aspects of competing causes have long been part of demographic and public health theory.  Even early in the computer era many leading demographers were working on the quantitative implications of competing causes of death and disease, and similar points were very clear at the time.  The relevance to cancer, as outlined above, was also obvious.  I know this first-hand, because I was involved in this myself early in my career.  It was an important part of theorizing, superficial as well as thoughtful, about the nature of aging and species-specific lifespan, and much else.  The hard realities of competing causes have been part of the actuarial field since, well, more or less since the actuarial field began.  It is a sober lesson that apparently nobody wants to hear.  So it should not be written about as if it were a surprise, or a new discovery or realization.  Instead, the question--and it is in every way a fair question--should be why we cannot digest this lesson.  Is it because of our normal human frailty wishful thinking about death and disease, or because it is not convenient for the biomedical industries to recognize this sober reality front and center?

It's hard to accept mortality and that life is finite.  Some people want to live as long as possible, no matter the state of their health, and will reach for any life-raft at any age when we're ill.  But a growing number are signing Do Not Resuscitate documents, and the hospice movement, to aid those with terminal conditions who want to die in peace rather than wired to a hospital bed, continues to grow.  None of us wants a society like that in Anthony Trollope's 1881 dystopic novel The Fixed Period, where at age 67 everyone is given a nice comfortable exit--at least that was the policy until it hit too close to home for those who legislated it.  But we don't want uncomforable, slow deaths, either.

The problem of competing causes is a serious but subtle one, but health policy should reflect the realities of life, and of death.  I wouldn't bet on it, however, because there is nothing to suggest that humans as a collective electorate are ready or able to face up to the facts, when golden promises are being made by legislators, bureaucrats, pharmas, and so on.  But, science and scientists should be devoted to truth, even when truth isn't convenient to their interests or for the public to hear.