Monday, August 12, 2013

Biomedical Research: A View From the Deep Past

By Jim Wood

A recurrent theme of this bog has been about how best to invest the limited resources available for biomedical research.  I have a peculiar (but I think useful) perspective on this question that grows out of my professional interest in long-term population history.

I study the population dynamics of preindustrial societies.  Some of my work involves historical demography, some of it involves working with traditional farming communities in remote parts of the developing world, all of it involves asking questions about the relationship between the ecology of food production and health/morbidity/mortality, especially among the very young.  So my view of the contemporary scene in the U.S. tends to be that of someone peering out from the Neolithic or some other long-dead period of the past.  And from that point of view, my take on the modern health care crisis in the developed world is:  “Crisis?!  We should only have such crises!”  Let me explain.

Since the eighteenth century, average human life span (or rather life expectancy at birth, which is not necessarily the same thing) in the Western World has roughly doubled – that is, it’s increased by about 40 years.  How can we now achieve a comparable, further increase in U.S. life span based on the kinds of new medical research that are currently being touted?  My answer:  We can’t.  And we probably shouldn’t even try.

The dramatic increase in life expectancy in European and European-derived populations during the nineteenth and the first half of the twentieth centuries had to do almost exclusively with a decrease in early childhood mortality.  It had very little to do with health and survival among the elderly or what we would now (fashionably) call “life span extension”.  In addition, the historical decline in mortality was attributable entirely to changes in environmental conditions, especially exposure to infectious diseases and the ability to fight off such diseases, reflecting (among other things) the immunological effects of under-nutrition and thus the sufficiency and reliability of the food supply.  (In America today we may have lousy diets from many points of view, but nobody can claim that most of us ever go hungry.)  Past medical advances had surprisingly limited effects on this dramatic drop in mortality at the aggregate (population) level.  The “wonder drugs” of my youth – penicillin, streptomycin, etc. – certainly saved lives, but most of the historical decline in mortality had already occurred by the time those antibiotics and most vaccines came onto the scene.  (Note: I am not disparaging vaccines, which I think are a blessing.)  Thanks in part to the evolution of drug-resistant strains of pathogens, infectious diseases are making a bit of a comeback these days, but they are very far indeed from dominating human mortality patterns the way they once did – except, of course, in parts of the present-day developing world.

Since the 1950s, there have certainly been improvements in life expectancy in the West, mostly having to do with the ongoing campaign against smoking and, probably, with a better understanding of the role of dietary factors in cardiovascular disease (again, environmental exposures).  But the improvements have been small, and they have been getting smaller and smaller – despite the ever-spiraling costs of medical research and health care.

But now we are entering (supposedly) a Brave New World of genomic medicine and life span extension – a Brave and Unbelievably Expensive New World in terms of both research dollars and medical care costs.  This investment will, we are reliably informed, lead to our living active, healthy lives until age 120 or older.  In the future, 120-year olds will be hard to distinguish from present-day 45-year olds.  And much of this advance will come from research on the genetics of life span.

As is frequently pointed out on this blog, there are a few major genetic diseases having substantial effects on mortality, and these diseases have long been known and have mostly already been mapped, at least approximately, using what would now be regarded as pretty old-fashioned, low-tech methods.  While treating these diseases can certainly improve individual health and survival, they are mostly so rare that even the most effective treatments would have little effect at the demographic level.  And, because they’re so rare, there’s little economic incentive to invest in their further study.  There’s something else worth noting about these major genetic diseases: they mostly kill at comparatively young ages, so even their total elimination would have basically zero effect on the overall human life span.

Beyond that, genomic medicine has, as Anne Buchanan and Ken Weiss regularly point out here on MT, contributed pretty much nothing to aggregate human health and is unlikely to do so in the future.  I would say the same is true of gerontological science (hang on to those telomeres, kids!).  Recent increases in life expectancy at birth, while real, have been nugatory compared to the historical shift in rates and causes of death.  The idea that we can achieve another 40-year increase in life expectancy is delusional.

Interestingly, a new Pew Charitable Trust poll shows that most Americans are not particularly attracted by the idea of living to 120, even if they are assured of being active, healthy, and alert at that age.  As it happens, I am only one degree of separation from the world’s only well-documented case of human survival past age 120 – Jeanne Louise Calment, who died in southern France about fifteen years ago aged 122.  My colleague Jim Vaupel, who was part of the team of demographers who verified the paper trail linking Madame Calment to her birth records, was invited to her 120th birthday party.  Afterwards I asked how she was.  His reply: “REALLY OLD!!!”  She sure as hell didn’t look 45.  She was blind and deaf, slipping into dementia, and in general extremely decrepit.  As is the case of most of the oldest old today, her extraordinary longevity had doomed her to years of physical disability and severely impaired functionality.  For my part, I’ll pass on such a medical miracle.

From my Neolithic point of view, only a few pieces of health advice have ever made much difference at the population level: eat as much food as you can (as Michael Pollan would add, mostly plant material), avoid famines and plagues, don’t smoke tobacco (or at least don’t inhale), and keep your latrines as far away from your sources of drinking water as you reasonably can.  Oh yeah, and think about maybe using mosquito nets if they’re available.  “Don’t live in swamps” is also pretty good advice.  Everything else is hype.

My overall conclusion is that the only truly important – and potentially solvable – health problems in the world today are found overwhelmingly in developing countries.  Genomics and gerontology are not going to help solve those problems.  Mind you, the right kind of medical research can certainly contribute toward finding solutions, but only if it can attract funding in today’s market.  And much good work can be done on the cheap.  Think of what would happen if we diverted the money currently invested in, say, genome-wide association studies and used it to buy mosquito nets or oral rehydration packs for the tropics.  Why, then, are we investing all our resources in the kinds of “modern” ailments that only affect the well-off and already long-lived?  As my Neolithic (or Third World) farmer would say, “Crisis?!  We should only have such crises!”


Ken Weiss said...

This is your usual thoughtful work, Jim. And I think you didn't even touch on the ancillary issues. There is the resesrch-industrial-university-government complex that leads to widespread institutionalization and vested interests in the momentum of science; these days that's in the direction of "Big Data" (the new cachet phrase). Too many peoples' jobs and too much pride to be lost if we recognized the truths of what is happening (and, now, 23andMe is even advertising to increase their Googling of the gene metaphor).

But what about the 120-year lifespan? If there are 7 billion of us now, how many billions will there be in the rather near future? And if still living like 45-year-olds, think of the consumption, demand for food and energy and living space?

But wait, what happens at 120th birthday parties? Sudden death? History shows, I think (at least, it seemed to when I was working on such issues some years ago) that what would ensue would be longer years of decrepitude than we experience today, which means greater healthcare costs, higher dependency ratios (young having to pay for the care of their elders) and so on.

We all know this, if we think about it. These would be among the real subjects to discuss and form policy around, but our culture is not structured in a way that leads such kinds of discussions to take center stage and affect policy. But thinking can be dangerous.

So, Onward Genomics, Big Data, and the Brain Map!

Holly Dunsworth said...

How much or how little can we credit c-sections for the increase in life expectancy?

Ken Weiss said...

That kind of thing could be estimated: how many (what percent of births) c-sections are done. In what fraction would the mothers or babies die or have lasting damage that would shorten their lives (here, we're not considering quality of life, just length)?

If babies were to die at birth or before term, then one can ask whether they should count as 'people' in data asking how long the average person lived.

Presumably c-sections give better chances for normal survival to both mother and child, and would thus add to mean length of life relative to the average if the procedure weren't done and either person died more quickly as a result.

But globally, it's probably a miniscule effect, and my guess is that it's probably not that great even in the industrialized world.

A separate set of questions has to do with the quality rather than just the length of life. That becomes more subjective, among other things.

And if c-sections became really, really common would they divert health-care resources away from other things that might affect length of life?

These questions are never easy for all sorts of reasons like these.

Holly Dunsworth said...

By my comment, I was mostly just hoping that if a paper came to Jim's mind, one with an approach he liked, he'd mention it.

Ken Weiss said...

My over-long response was only intended to point out how the nuances make even clear-sounding questions challenging to answer.

Jim's post essentially points out that, for example, McBurger diets may 'cause' heart disease in the sense that they wouldn't occur if people ate more, say, broccoli, but in fact McBurgers are nutritional wonders relative to under-nutrition. So are they 'healthy' to eat or not? It has to do with one's comparison base, etc.

One can ask, for example, whether it's true that many c-sections are done for convenience, expedience, fashion or cosmetic reasons, which would have no effect on life expectancy (unless the costs of the procedures made some other healthcare programs less available).

Jim Wood said...

Actually, Holly, c-sections became frequent only long after the decline in early childhood mortality.

Holly Dunsworth said...

Thanks probably in large part to you, Jim, I've seen it this way. But I think you'd be surprised at how many people think they're an important part of this story. I thought that if there was an article that came to mind that explicitly took this on, I'd jog it out of you.

Ken Weiss said...

I won't keep chiming in, except to say that there is a difference between asking whether c-sections save or extend or improve _indivdiual_ lives, and whether c-sections are responsible for the _average_ length of life in a population, for which they would have to be both common and consistently effective enough to make a material difference.

I think that is Jim's point. Now I'm done, since he'll know much more about it than I do!

Holly Dunsworth said...

There is definitely a difference between whether they reduce perinatal mortality or not and whether they contribute to an increase in a population's life expectancy overall. I was merely hoping that if something good came to mind about research on c-sections (or just childbirth in general) from a demographic perspective, it could be shared and I could go to there and read it :).

Jim Wood said...

Ken, you've made two important points that I'd like to emphasize: First, just because medical interventions have trivial effects at the population level (e.g. on average length of life) doesn't mean they can't be profoundly important at the individual level (e.g. a non-elective c-section to save a mother's life). Second, your view of, say, the typical American diet depends in large part on what other diet you're comparing it to. Compared to the diet of a scrupulously healthocentric American, McBurgers are a horror. Compared to the diet of most people in the preindustrial past and in much of the developing world, McBurgers are a medical miracle. I guess the underlying message of my post is that, when Americans think about the U.S. health situation, they almost never look beyond their own borders (including temporal borders) to see how we stack up.

Holly Dunsworth said...

Thanks for today's post. It got me googling and I found this treasure trove I hadn't come across yet.

Jim Wood said...

Interesting, Holly. Thanks. The cross-population pattern (and history) of the sex difference in mortality is complicated, as this article suggests. By the way, I realize I've ducked your original question about c-sections, precisely because I don't know of any reference that specifically addresses the contribution of c-sections to average length of life. My confident (arrogant?) assertion that the contribution was trivial comes from my general knowledge of what specific causes of death were involved in the historical decline in mortality -- infectious diseases were of overwhelming importance.

Holly Dunsworth said...

Thanks Jim. I get the feeling that there's enough we know about relatively recent history, demographically speaking, to take on evolutionary assumptions of the obstetrical dilemma (specifically addressing that school of thought) but I just don't think anyone has and was hoping maybe I'd just missed it.

Anonymous said...

Great essay Jim. Had me thinking about age-specific mortality rates though: I take your point that most of the increase in "life expectancy" is due to reduce childhood mortality. But hasn't life expectancy at 60 (for example) increased over the last century or two? That wouldn't need to mean that maximum lifespan is limitless, or that max (possible) lifespan is changing or changeable, just that more 60 year olds get closer to that max than they did in previous years.

If that's the case, then there's good reason to invest in research to get older folks healthier. And data from traditional populations (Tsimane, Hadza, etc) indicates that the incidence of heart disease, diabetes, etc could be reduced by changing environmental variables (e.g., diet and activity) as elderly folks in those populations don't get our set of chronic diseases.

Perhaps the potential contribution of genetics/ genomics is small here, but seems to me there's reason to think more research into aging and health could mean happier healthier 70 and 80-year olds.

Or perhaps you'll argue that older people in traditional groups have already been through a serious selective filter, and their health outcomes are indicative of what we can expect population-wide in the West? Interested to hear your thoughts.

-Herman Pontzer

Jim Wood said...

Thanks, Herman, for the thought-provoking questions. I do mention that life expectancy in the U.S. has been increasing since, say, 1950, but the increases have been tiny compared to the earlier increase associated with lowering childhood mortality. In fact, the recent increases have mostly been getting smaller and smaller with time. I don't especially think there's a fixed maximal human life span (i.e. written into our genome), but it seems pretty clear that recent advances in survival among the elderly have been subject to rapidly declining marginal "productivity".

To my mind, the best way to increase average life expectancy in the U.S. is to reduce or eliminate the social and economic disparities in access to health care. I don't think genomic medicine and the genetics of aging are going to help with that goal.

Oh, and I agree completely with you that the Tsimane, Hadza, !Kung, Gainj, and similar groups are under threat of being harmed by the chronic "diseases of civilization" as their traditional life ways change, but right at the moment they have greater threats, mostly from infectious diseases. Besides we know how to treat and prevent things like heart disease and diabetes. All we need is the political will to help folks like these.

And of course none of this has anything to do with goal of living to age 120.

The question you raise about older people in traditional societies having already been through a selective filter is a complicated one -- see the demographic literature on heterogeneous frailty and selective mortality. I would only point out that the heterogeneity that selective mortality works on need not be genetic -- in fact, if the selection has been going on for many generations, the heterogeneity is exceedingly unlikely to be genetic since natural selection (in the usual sense) tends to eliminate additive genetic variance. But, as I say, it's a complicated question.

Ed Hollox said...

Tangentially related to this, linking perinatal survival to a human genetics, is the development of anti-RhD Ig eradicating Rhesus disease. Its an unusual case (unfortunately) and a direct benefit of human genetics, from quite a long time ago... I suspect that this might have substantially improved population level life expectancy over the past 50 years but have absolutely no data to back this up! Would be interesting to look into.

Jim Wood said...

Betcha five bucks it had next to no measurable effect on life expectancy. (I too have absolutely no data, so I'm probably not at much risk of having to pay out!) This gets us into the whole issue of competing causes of death (see below). In the past, newborn babies who managed not to die from anti-Rh syndrome despite being susceptible were still likely to die from something else.

Ed's lab Conference Blogs said...

Jim, the bets on!

Jim Wood said...

Yikes, I had no idea I stood to lose money by posting comments! Okay, Ed -- or maybe I should just send you the five smackers up front.