The "war" on cancer....retreat, defeat, or on its feet?

The BBC reported the other day that we are facing a 'tidal wave' of future cancer cases, and we had better prepare for it.

The globe is facing a "tidal wave" of cancer, and restrictions on alcohol and sugar need to be considered, say World Health Organization scientists. 

It predicts the number of cancer cases will reach 24 million a year by 2035, but half could be prevented. 

The WHO said there was now a "real need" to focus on cancer prevention by tackling smoking, obesity and drinking.

The point is that treatment isn't going to do the trick, and could even bankrupt world healthcare resources, and what is really needed is prevention.  The article doesn't really talk about whether resources pouring into things like cancer genomics and other sorts of omics should be diverted to prevention, but it's certainly a legitimate view.

And the article also doesn't point out that the rise in cancer rates is also a reflection of the fall in rates of other causes of death, like heart disease for example.  Indeed, it's not clear that that's clear to people at the WHO.

Chris Wild, the director of the WHO's International Agency for Research on Cancer, told the BBC: "The global cancer burden is increasing and quite markedly, due predominately to the ageing of the populations and population growth.

We've written a number of times before about competing causes of death: when one goes down, others must go up.

From the BBC

But this does all raise the question of whether the 'War' on cancer that was declared by President Nixon in 1971 was a waste of time.  After all, nearly 45 years on, there are more cancers and perhaps even a higher cancer rate (risk per person) than back when Tricky Dick was calling the shots.

What about all the high promises by us geneticists?  After all, cancer is a disease of cells not behaving themselves in their tissue context, and growing or not adhering as they should in their tissue type.  That is basically about the cells' use of genes, so cancer should be the very epitome of a genetic disease.

There has been much progress in identifying genes involved in cell-cycle regulation, growth control and inhibition, and genes that when mutated clearly add to cancer risk, sometimes quite dramatically.  There are also tests that, experts say, identify tumor genotypes as to whether they'll respond to particular chemotherapeutic agents.

Let's not forget the HPV vaccine that can end cervical cancer.  Also, the discovery of Helicobacter infection of the gut may lead to prevention of stomach cancers.  Likewise, viral causation of esophageal and some oral cancers or leukemias in animals if not also humans. These are purely research-discovered, reflect increases in genetic knowledge of all kinds, and thus have to count as major War-on successes. 

There still aren't many--if indeed there are any--gene-specific preventive or gene-targeting therapies and some attempts have failed or had only mixed results.  There have apparently been huge advances in some chemotherapeutic, surgical, and radiation treatments, often guided by the tumor cell type, that greatly jump the survival odds for many types of tumor.  In a sense, bone marrow transplants are dependent on knowledge of genetics and we personally know a number of people for whom such transplants have worked.

Cancer is a very complex and diverse set of diseases, some due to outright mutations, some due to failure to correct mutations, some due to viruses and chromosome rearrangements.  Some susceptibility genotypes can be inherited or can occur somatically during life, and it appears to be combinations of these that generate tumors rather than one inherited mutation or one caused during life.  We think it's fair, however, to say that a lot of trumpeting of cancer genome projects and profiling has far exceeded the successes to date.

An indicator of the state of play is the rapid building programs at the nation's major cancer research institutes: if they were doing so well, why aren't they shrinking in size--turning their buildings into apartments or office buildings?

But is this fair?
After quadzillions of dollars spent, all sorts of massive data bases and so on, one can say that the reason cancer rates are going to be overwhelming is the failure of research to win the War.  Cancer is a hugely complex problem, but the increase is not due to a failure of the researchers.  Instead, it's a failure of the patients!

We continue to live in ways that are epidemiologically known to increase cancer risk.  Smoking is the main culprit. Being overweight seems for some reason to be another.  Alcohol is, too, or so the story goes.  These and other lifestyle factors have indirect mechanisms, mostly unknown, by which they increase cancer risk.  Mainly, however, they lead to needless mutations in our cells, even if just because bad lifestyle habits increase the numbers of cell divisions we experience.

The failure is not one of geneticists, but of the inability of society to put to work what science has discovered.  Here we include epidemiology as well as health education, not just--indeed, not mainly--genetics (even if, at the cell level, cancer is largely a genetic disease).  We don't know how to get people to stop risky behavior even when they know it's bad.

One can debate the reasons, and libertarians will differ about this from interventionists.  Unfortunately, one way or another, we all have to bear a share of the costly treatment (and research) that bad behavior occasions.

Worse is that the excess cases due to exposure to bad behaviors blurs the distinction between cases that might have clear-cut genetic causes that really could benefit from focused research.  This applies as well to heart disease, diabetes, and other quasi-pandemics of our time.

So you can wage a War-on, and be technically quite successful even in the face of daunting complexity, but if the enemy forces just keep increasing like a tsunami, you will be overwhelmed and it will seem that you've lost.  Here, the loss is in terms of prevention.  Unfortunately, preventive measures can save or spare more people from cancer than all the genetics and similar research one could throw mega-bucks at.

Playing the waiting game
Things are not as simple as is being claimed.  For example, CNN's reporting on the cancer-tsunami release is headlined "Cancer doesn't have to happen."  It says that "Most cancers in our world pandemic are preventable -- here's how."  But this is quite misleading if our understanding of cancer is true.  Because the truth is that cancers are all preventable -- but only if you die of something else first!

Cancer is caused by the accumulation of DNA changes--mutations, viral incorporation events, expression-regulation, sequence elements rearranged among chromosomes.  These are, as best we understand, probabilistic but the probability is not zero. Mutations happen by molecular chance when cells divide, even if they're not exposed to environmental carcinogens.  This means that the probability you get cancer at age x is the probability that none of your cells has by then accumulated enough 'bad' changes to start to grow out of control.

This means that if you live long enough you will get cancer, indeed basically every type of cancer.  Each has its own age of onset pattern depending on the number of cells at risk, their division rate and so on.  You can speed this up by exposure to radiation or other carcinogenic factors, or slow it down by not being exposed.  This in essence is what the news stories are about.

But eventually, you'll be unlucky, or rather, your luck will eventually run out.  Unless....unless you die of something else first.

One reason for the predicted increase in cancer is that antibiotics have reduced earlier deaths from infection, surgery and medication prevent death from other causes like heart disease, diabetes, stroke and injuries, leaving people alive longer.  So the 'War' on heart disease is a kind of battle being won at the expense of the battle on cancer being lost.

This is what is meant by competing causes (and we've blogged on it in the past).  It's a Devil's kind of trade-off.  We can only avoid this evil bargain if Francis Collins' promises of immortality (on earth--he presumably also believes you'll persist after death as well) comes to pass, which even he probably can't promise NIH massive genomics and other 'omics' research will achieve.   And then, well, you may not get cancer but you will be so demented and immobile for so long, that you won't know it but you might yearn for an end.

That's life, but it's hard to face up to it.  At least, it is one factor that adds nuance to the whole subject of the War on cancer.

On the other hand
We scientists are grabbing up a lot of resources for our relatively small Wars, compared to what might be gained by prevention, even though the latter is not glamorous and won't feed the University professor welfare system.  This is a failure of policy, not science.

And there's another thing.  Our love of technology is responsible for a major part of the coming cancer tide, if current estimates are to be believed (and in this case, projections are likely to be accurate).  That is by the gross, excessive, almost game-like over-use of radiation technology. So much overkill with CT scans and their like will cause near-epidemic scale cancer if the recent projects are accurate.  This is the result of the research-corporate-medical complexes drive for money, credit, attention, or whatever aspect of the science-religion you want to blame it on.

Worse is that some of this excess scanning doesn't just expose people to carcingens, but leads to diagnosis of cancers that would never lead to clinical disease in the first place.  Evidence shows this in relation at least to prostate cancer in men and breast cancer in women.

So stories about a tidal wave of future cancers, probably by now unavoidable because the mutational risks have already been piling up, reflect a mix of factors.  Reducing heart disease has worked to some extent, so people who don't die of a heart attack live longer, free to develop cancer. And, the War on cancer has been a success and a failure at the same time.  We know how to do better: avoid what we know are needless cases so we can focus research attention on those that really are genetic or caused by some mechanism that technical research is so very good at attacking.

But this is a worrying post to write, and we need a smoke and a couple of scotches to calm ourselves down.

Can the grant system be overhauled?

Gina Kolata writes in today's New York Times that $105 billion dollars have been spent on cancer research since 1971 when Richard Nixon declared 'war on cancer', but, measuring progress in death rates, we're not a whole lot better off now than we were then. Indeed, cancer is good business, and cancer specialty clinics are opening or expanding all over the country (and advertising about how good they are, to promote sales). Cancer treatments are long and costly to our health care system, so it's a serious problem, both economically and for anyone who has cancer.

Ms Kolata correctly attributes much of this to the conservative nature of the grant system. Researchers don't even apply for money for new ideas because they know the system doesn't reward innovation, so what does get funded is research that doesn't even attempt to go beyond incremental progress. And researchers' careers, prestige, even salaries depend on grants.

Kolata's article is specifically about cancer, but the conservative nature of the grant system is true for all fields. It's partly because 'peer review'--the judging of grants by people who do similar work--keeps it that way. People can only evaluate what they already know. And it's partly because the system demands that the researcher demonstrate that the work can be done, which requires pilot data. And as with any large establishment, it learns how to protect and perpetuate its own interests.

It is not easy to say what to do about it. What kind of accountability for grant recipients would be appropriate? The research questions being asked are tough, so 'cures' cannot be promised in advance, and the more basic the research the less clear what the criteria for success could be. The idea of accountability is that if your research is paid by a health institute it should make notable contributions to health, not just journal articles or to the researcher's career. A candid observer could quickly eliminate a high fraction of grant applications on the grounds that, even if successful as promised, their contribution would be very minor, as Kolata illustrates. Perhaps there should be a penalty for making promises that aren't kept--at least, that could help make the system more honest.

Limits on the size or length of projects or of an investigator's total grants would help spread funds around. But what about the role, sometimes legitimate and sometimes mainly based on a love of technology, of very expensive equipment and approaches? Is there a way to identify less technically flashy, but perhaps more efficacious work? It's easy to see that this can be true: lifestyle changes could prevent vastly more cancer than, say, identifying genetic susceptibility causes, yet we spend much money on cancer genetics research compared to environmental change.

Speaking of lifestyles, one cannot order up innovations the way one can order a burger with fries. Might there be 'meta' approaches that would increase the odds that someone, somewhere will make a key finding or have a penetrating idea? Would that more likely come from someone in a big lab working on long-term projects, or someone in a small lab working in relative obscurity?

Or is it OK to perpetuate the system, assuming good will come of it here and there, meanwhile a lot of people are employed to manage big labs, run the experiments, collect data, make machinery and lab equipment, and sweep the floors in large lab buildings?

These reflections apply to much that is happening in the life (and other) sciences today. They drive the system in particular directions, including fads and technologically rather than conceptually based approaches, and in that sense some things are studied while other approaches may not be considered (or funded because they're out of the mainstream). An example relevant to our blog and work is the way that genetic determinism and, more broadly, a genome-centered focus, drives so much of life and health sciences. By no means irrelevant or all bad! But it is a gravitational force that pulls resources away from other areas that might be equally important.

Clearly major findings are generated by this way of doing science, even if false promises go unsanctioned (indeed, those making them usually continue to do that and continue to be funded with major grants). Life sciences certainly do increase our knowledge, in many clearly important ways. Yet disease rates are not dropping in proportionate ways relative to grandiose promises.

Is there a solution to all this? Could the system be dramatically overhauled, with, say, research money being parceled out equally to anyone a university has deemed worthy of employment? Could the peer review system be changed, so that some non-experts are on review panels, ensuring that the system doesn't simply perpetuate the insider network? Or would they not know enough to act independently? Universities encourage and reward grant success not because it allows important work to be done by their brilliant professors but because it brings prestige, score-counting, and 'overhead' money to campus--can university dependence on overhead or faculty's on salary be lessened? Is there a way to encourage and reward innovation?