In Search of Enlightenment

Pain Perception

2009-12-06T08:20:00.005-05:00

The early edition of PNAS has this interesting piece on differences in pain perception. Here is the abstract:

Pain is a highly subjective experience that can be substantially influenced by differences in individual susceptibility as well as personality. How susceptibility to pain and personality translate to brain activity is largely unknown. Here, we report that the functional connectivity of two key brain areas before a sensory event reflects the susceptibility to a subsequent noxious stimulus being perceived as painful. Specifically, the prestimulus connectivity among brain areas related to the subjective perception of the body and to the modulation of pain (anterior insular cortex and brainstem, respectively) determines whether a noxious event is perceived as painful. Further, these effects of prestimulus connectivity on pain perception covary with pain-relevant personality traits. More anxious and pain-attentive individuals display weaker descending connectivity to pain modulatory brain areas. We conclude that variations in functional connectivity underlie personality-related differences in individual susceptibility to pain.

Cheers,
Colin

The Effects of Exercise on Cognition

2009-12-06T08:12:00.006-05:00

The early edition of PNAS has this interesting study of Swedish men which suggests that cardiovascular fitness changes in early adultlife can enhance cognition. Here is the abstract:

During early adulthood, a phase in which the central nervous system displays considerable plasticity and in which important cognitive traits are shaped, the effects of exercise on cognition remain poorly understood. We performed a cohort study of all Swedish men born in 1950 through 1976 who were enlisted for military service at age 18 (N = 1,221,727). Of these, 268,496 were full-sibling pairs, 3,147 twin pairs, and 1,432 monozygotic twin pairs. Physical fitness and intelligence performance data were collected during conscription examinations and linked with other national databases for information on school achievement, socioeconomic status, and sibship. Relationships between cardiovascular fitness and intelligence at age 18 were evaluated by linear models in the total cohort and in subgroups of full-sibling pairs and twin pairs. Cardiovascular fitness, as measured by ergometer cycling, positively associated with intelligence after adjusting for relevant confounders (regression coefficient b = 0.172; 95% CI, 0.168–0.176). Similar results were obtained within monozygotic twin pairs. In contrast, muscle strength was not associated with cognitive performance. Cross-twin cross-trait analyses showed that the associations were primarily explained by individual specific, non-shared environmental influences (≥80%), whereas heritability explained <15% of covariation. Cardiovascular fitness changes between age 15 and 18 y predicted cognitive performance at 18 y. Cox proportional-hazards models showed that cardiovascular fitness at age 18 y predicted educational achievements later in life. These data substantiate that physical exercise could be an important instrument for public health initiatives to optimize educational achievements, cognitive performance, as well as disease prevention at the society level.

Cheers,
Colin

Health Innovations: Safety and Equality

2009-12-01T11:20:00.014-05:00

This post brings together a number of issues I have been working on with respect to aging research.

In particular, I am interested in why so many people tend to eschew the field of biogerontology, and often express worries or concerns that really are (upon reflection) inappropriate, inconsistent or disproportionate given the nature of the stakes typically involved (e.g. the high risks of morbidity and mortality associated with the aging "status quo"). To bring these issues to the fore consider the following...

Many scientific studies demonstrate that health innovation X (I will conceal the details of what X is until later on) can reduce our risk of disease and increase life expectancy. X reduces, for example, the risk of cardiovascular disease, the #1 killer in the United States. Some estimate that a steady intake of X can actually add between 1-4 years to a person's life expectancy.

But there is a down side. Firstly, X also has some risks of harm. Some of these risks are very low, but others are high. For the most minor of harms, like discomfort (or even mild pain), fatigue, sweating and muscle and joint pain, these usually accompany taking X (though they are not long-lasting).

But X can also cause more severe harms. There is some basis for believing that X can be addictive. Furthermore, there are thousands of cases of X causing death. X1, for example, is a very popular version of X. In the United States millions of people regularly take X1 each week. X1 is a popular and cheap form of X. Sadly, more than 500,000 people in the US who take X1 are treated in emergency departments every year, and more than 700 people die as a result of X1. (source)

Even more tragically, children are at particularly high risk of injury by taking X1. Children 15 years and younger accounted for 59% of all the X1 injuries seen in US emergency departments. Now there are things we can do to mitigate some of these harms, but X1 is intrinsically risky. The only way to prevent any deaths from X1 would be to prohibit X1. But no one would propose that.

The proper administration of X could reduce many of the risks I have outlined above. But there is no way to completely eliminate the risks associated with X.

Let me now turn, just briefly, to concerns of equality. X is not equally accessible to everyone. Some people, because of where they live, or their family situation (single parent, etc.), or their income, or their education, or their job, have greater access to X than others. And this inequality in access to X can have a profound impact on a person's risk of disease and death. Having regular and easy access to X can make the difference between suffering a heart attack and dying at 65 or enjoying a healthy retirement. So having access to X really is a matter of life and death.

OK, so what we know about X is that (a) it can have enormous health benefits for both populations and individuals. The regular utilization of X can reduce the risk of disease and increase life expectancy. We also know (b) that X has some adverse side-effects, ranging from injury (which is common) to addiction and even death. And we know (c) that X is not equally available to all people. So what should we do?

Some might think that X is only imaginary. "Surely", one might conjecture, "if X kills people, including children, it would be banned!". Or the egalitarian might argue that "X should be equally accessible to all, and if it isn't, then no one should have access to X". These are common intuitions. Let's see how they fare when I reveal that the case in hand is a real one....

OK, let me now tell you what X is.................................... X is EXERCISE!!

Regular exercise is an important health intervention that can help reduce our risks of morbidity and mortality and extend life. But exercise is intrinsically risky. As long as bikes share roads with cars (bike riding was X1) there will be bike fatalities. But even if cars didn't exist, people can still fall off of bikes, or drop weights on their heads, get hit by lightening while playing baseball, suffer a heart attack or dehydration while running a marathon, sprain ankles, pull muscles, etc., etc., etc.

Do a "google" image search for "sports injuries" to see some of the 16 000 000 images (some more graphic than others) that make this point more vivid.

But despite seeing these images, and taking stock of all of the potential harmful effects of exercise, the pros of exercise *far outweigh* the potential harms. You are much more likely to die from an inactive life than you are from an active one. Hence why we (ought to) exercise!

Secondly, we are not all equally well placed to exercise regularly. Some people work at jobs that are outside and involve physically demanding work (like being a brick layer). Others have jobs with very long hours that involve sitting in front of a computer for most of the day (like academics!). Some people live in congested cities where clean air itself is a scarce resource, while others live in beautiful countrysides with amble opportunities for hiking and biking. Some people have an education that better positions them to make long-term decisions about their health (e.g. to regularly exercise or not). Others have family situations that can make exercising more of a challenge (e.g. providing the primary care for a child or sick parent) than it is for others. And some enjoy a higher income that permits them to buy a gym membership that others could not afford.

Concerns about safety and equal access do not lead us to eschew the importance of exercise. No one declares: "Someone died riding a bike so let's ban all bikes!", or "Jimmy broke his leg playing soccer so let's ban soccer!". No one invokes the precautionary principle in the context of exercise. Perhaps we don't because we are all familiar with the risks of exercising and the risks of inactivity. We know the latter outweigh the former by far.

The point of this exercise it get to us to realize what the benchmark is, in terms of safety and access, for a measure of preventative medicine that we all would applaud. Once one makes vivid the realities of exercise, then, and only then, can one begin to form considered judgements about concerns of safety and equality for a health innovation that conferred even bigger health benefits-- like a pill that retards human aging by mimicking calorie restriction.

Many people hesitate or even refuse to take drugs that could promote their health because they fear any potential adverse side-effects. Yesterday I spent 45 minutes waiting in line for the H1N1 shot. And I overheard many conversations about the fears and concerns people had after reading the info sheet about the flu vaccine. But what these people fail to reliaze is that, unlike the flu shot, getting in their car to drive home, or riding a bike, doesn't come with a small print warning label. These activities are much more risky, but they only feel safer because you do not read a warning label each time you do them.

If everything in life had a warning label they we wouldn't fixate so much on the potential adverse consequences of pharmaceuticals rather than other potentially risky interventions-- like exercise. Because the latter is considered "natural" we tend to view it as inherently safe. But the fact that one intervention is "natural" and a second "unnatural" doesn't make one safe and the other risky. The data, rather than our intuitions, ought to guide rational decision-making about health innovations.

Cheers,
Colin

Exercise and Arthritis

2009-11-30T07:36:00.005-05:00

For the past two weeks I have been working on a lengthy post about the risks associated with exercise (with the goal being to help us think more rationally and consistently about our attitudes towards different kinds of preventative medicine). So when I noticed this study this morning I wanted to link to it here.

Expect my substantive post on exercise in the next few days.

Cheers,
Colin

Main Menu (Nov. 2009)

2009-11-22T14:27:00.004-05:00

Recent posts on "In Search of Enlightenment" include:

1. 21st Century Humanism
2. David vs Goliath
3. Biogerontology Paper on Framing the Inborn Aging Process
4. Life Expectancy, Priorities and Aging Research
5. Where the Action As: On the Site of the Playful Life (as told in song)

Cheers,
Colin

Egalitarianism and Ideal/Non-Ideal Theory

2009-11-19T11:46:00.033-05:00

Suppose one considers oneself an "egalitarian". And by that I mean one who believes in distributive equality (rather than moral or political equality). And this egalitarian also has philosophical inclinations, and thus they wish to undertake the project of developing an egalitarian theory of distributive justice.

And, for the purpose of the exercise today, let us also suppose further that our egalitarian philosopher is primarily interested in developing an egalitarian theory of domestic justice for an affluent, liberal democracy like the US, Canada or England (rather than a global egalitarian theory of justice that encompasses all people in the world).

How does one go about developing such a theory? Where should one start?

One might start at the level of “ideal theory”. That is, one could begin by pondering what they think the ideal society would look like (i.e. one where everyone is equal!), and then derive some egalitarian prescriptions from that exercise (i.e. inequalities shouldn’t be tolerated).

Alternatively, one could start at the level of “non-ideal theory”. In other words, one could begin by pondering what actually causes different kinds of inequality in the real world and what has, and what might prove to be, effective ways of fairly and efficiently mitigating such inequalities.

A significant bulk of the ink spilled in political philosophy over the past few decades has taken up the first project. And a central impetus for this has been John Rawls’s theory of distributive justice, in particular Rawls’s famous difference principle- which permits socio-economic inequalities provided they are arranged to the greatest benefit of the least advantaged.

Two of the most prominent debates egalitarian philosophers have had of late concern the questions (1) Equality of What? (resources, welfare, opportunities for welfare, capabilities, etc.?), and (2) what is the scope of egalitarian principles (e.g. do they only apply to institutions, or do they also apply to the individual decisions we make in daily life?).

The latter issue receives extensive treatment in Cohen’s latest book and has now come to dominate the attention of egalitarian political philosophers. In particular, a great deal of attention has, and continues to, be paid to the concern of whether it is unjust for self-seeking highfliers to threaten to withhold their productive talents unless they receive very high incomes, incomes that promote socio-economic inequality.

An outsider who first happens upon this literature could easily form the impression that egalitarians are so concerned about the employment decisions of highfliers *because* these decisions are the major cause of inequality in real societies. That might be a natural assumption to make, but it would be mistaken.

The main reason why egalitarian philosophers spend so much time concerned about these issues stems from the fact that John Rawls wrote this book back in 1971. And in this book, Rawls developed what is called the “Pareto argument” for inequality. Rawls argued that a deviation from equality is justified so long as everyone benefits from it.

And how could a movement away from equality benefit everyone? Enter the issue of incentives. By offering the promise of a higher post-tax income to the most talented members of society we can entice them to be more productive than they would otherwise be. If their higher level of productivity brings benefits to everyone then there is no reason to insist on the initial equal division. The underlying intuition behind egalitarianism is, for Rawls, a concern for the least advantaged in society. Why object to a movement away from equality if everyone, including the least advantaged, benefit? Rawls believes that there is no reasonable reply to this question. The difference principle combines considerations of equality with those of efficiency.

The question that has always come to my mind as I read over the egalitarian literature on these debates in the past decade is this—is it true that incentives are the real cause of the inequalities that exist today? For if they aren’t (which seems to me to be the case) it is rather odd to fixate so much on the incentives issue.

But the ideal theorist can respond to my point in the following way— "but we are not (at least primarily) concerned with the real world. We are concerned with what kind of behaviour would be permissible in the ideal world. And in the ideal world, we egalitarians disagree with Rawls that the talented members of society could justly withhold their talents unless offered inequality-generating incentives".

There are many things to say in response to this reply. Firstly, why think that the kind of talented highfliers Rawls posits in the Pareto Argument would even exist in the “ideal world”? Assuming, as I think is clearly the case, that in the egalitarian society all would have access to a decent education, etc., why think that super-talented individuals who could single-handedly create a more optimal cooperative surplus if offered the right kind of financial incentive, would even exist? (in fact, I am sceptical such people exist in the real world!) That is just one of many things that has troubled me about having the debate at the level of ideal theory. It mixes real-world concerns (like Cohen’s concern that Thatcher’s tax cut could be justified by reference to these incentives) with abstract, idealized scenarios where supposedly real-world facts have no relevance or place.

If real-world facts have no relevance or place in ideal theory, then why fixate on incentives rather than some other behaviour that could possibly perpetuate inequality in the ideal society? I can't think of any examples off the top of my head, perhaps because I am sufficiently deficient in my capacity for idealization, but I'm sure the ideal theorist could come up with some. Maybe the most talented highfliers will also demand to couple and reproduce with the most talented partners, thus perpetuating genetic and social inequalities by commanding the highest family incomes and passing on the "superior" and "selfish" genetic endowments that constitute these self-seeking highfliers. Maybe if Rawls invoked that example it would have been debated for 20 years. But I'd like to think not. Deep down I think egalitarians are drawn to the incentive case because it tracks what they see as a relevant and true empirical reality-- that people often respond to incentives.

Rather than starting one’s quest for an egalitarian theory of justice with the remnants of an academic debate about a book published over 40 years ago, I would encourage the next generation of egalitarians to start at the level of non-ideal theory. This would involve, as I outlined here, developing 3 different skills.

1. Ascertaining how we got to where we are and understanding why things are this way.
2. Deliberating about the kind of world we want to have.
3. Judging how far, and through what actions, and at what risk, we can realistically hope to move this world as it now stands towards the way we might excusably wish it to be. (Dunn, 1990, p. 193)

Rather than invest the bulk of one’s energies sifting through 30 some odd years of Rawlsian scholarship, the next generation of egalitarian philosophers should begin by asking “Why is there inequality?”. So this recent paper, for example, should serve as the starting place for serious egalitarians. This study concludes that “differences in the technology by which a people derive their livelihood and in the institutions and norms making up the economic system jointly contribute to this pattern [of inequality]”. This is good news for Rawlsians, in that the basic structure is indeed important. So Rawls was on the right track when he claimed that the basic structure is the primary subject of justice.

But, as I noted before, egalitarians (and Rawlsians) also need to appreciate how complex the factors that lead to inequality are. This study found that health inequality among infants in the US actually declined. However, the reasons for this include the fact that highly educated parents are more likely to utilise fertility treatments, which increase the chances of multiple births. So the narrowing of the gap was achieved, in part, by a leveling down. Rather than have the children of affluent parent’s suffer higher risks of infant mortality (which makes things more “equal”), the goal ought to be bring all up, to minimize the risk of infant mortality. Or recall my earlier post here, which addressed the concern that the behaviour of some educational elites (when it comes to choice of partners) perpetuates inequality.

Anyways, taking (1) seriously shows us that institutions *and* individual behaviour matter in terms of the complex factors that influence different kinds of inequality.

What about (2)—what is the ideal? Unfortunately most egalitarians jump straight to this. And the ideal is-- we should be *equal* in something (e.g. welfare, wealth, capabilities, etc.).

But once one takes the empirical constraints of (1) and (2) seriously, I believe one’s account of (2) would become more attractive, defensible, feasible and (most importantly) *provisional*. One can get a better sense of “what” should be equalized. Indeed, one might even temper their egalitarian ambitious and opt instead for a principle of sufficiency or priority. Indeed, this is what has happened to me.

And skill (3) is where the real action is. “What Needs to be Done?” should be the overarching concern of the egalitarian. How do we move from our unequal situation to a more just one? Unfortunately, egalitarians tend not to think much further than “take money from X (the rich) and give it to Y (the poor), thus creating more equality!”.

But appreciating the complex factors highlighted by (1) will, I believe, expand the imaginative capacities of egalitarians, providing them with a better sense of what would constitute a feasible timescale for achieving their egalitarian aspirations (given our history and circumstances) as well as a better understanding of the things that can help them realise a better world (like public health measures, such as sanitation, vaccinations, etc.). And so science would come to the fore, and egalitarians would engage in new questions concerning the role of innovation in a just society, and how to ensure the benefits of technology and medicine are efficiently and fairly dispersed.

One last point. In exercising skill (1) the egalitarian should also ask why it is that they themselves are egalitarians (or rather why they have egalitarian intuitions; I have yet to meet a self-described "egalitarian" who actually lives like an egalitarian!).

Now Cohen himself provides some autobiographical details, like his upbringing here. But I don't mean we should just ask what the proximate cause of our moral sensibilities are. I mean we should ask why we, as a species, have the moral sensibilities we have (so what are the ultimate or evolutionary causes? And this in fact links up with Cohen's point about the influence of religion in his life, so there is an important link there). And one of these sensibilities, which seems to be more prevalent in some more than others, are the egalitarian sensibilities that our egalitarian philosopher starts off with. I won't go into this topic here today, but I believe that, once the theorist critically reflects on their own starting intuitions, then it will profoundly influence the way they go about developing and assessing a theory of distributive justice. But that is an expansive topic for another day.

Cheers,
Colin

PNAS Study on Telomere Length and Centenarians

2009-11-18T09:38:00.012-05:00

Why is it that some people, who are exceptional cases, can live 100 years of disease-free life while the vast majority of their contemporaries die from cancer, heart disease or stroke 20-30 years earlier?

This is perhaps the most important question which the medical sciences should be tackling today, rather than the questions which currently dominant the "disease model" approach to health extension (e.g. what causes specific diseases, like cancer, stroke, AD, etc.).

If we had a better understanding of the things that influence "healthy aging" then we could reduce the increasing risks of morbidity and mortality which aging populations face.

Contrary to what most people might be inclined to think, exercise alone will not make the goal of a century of healthy life a reality for the vast majority of people alive today. If we are to increase the average life expectancy beyond 85 years, and do so in a way that "adds life to years, not simply years to life", we will need to find a way of modulating the aging process.

Studies like this one, published on the "Early View" of the Proceedings of the National Academy of Sciences, are where the real action is in terms of the new frontiers of the medical sciences. Here is the abstract:

Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC. We demonstrated that centenarians and their offspring maintain longer telomeres compared with controls with advancing age and that longer telomeres are associated with protection from age-related diseases, better cognitive function, and lipid profiles of healthy aging. Sequence analysis of hTERT and hTERC showed overrepresentation of synonymous and intronic mutations among centenarians relative to controls. Moreover, we identified a common hTERT haplotype that is associated with both exceptional longevity and longer telomere length. Thus, variations in human telomerase gene that are associated with better maintenance of telomere length may confer healthy aging and exceptional longevity in humans.

And an excerpt from the article:

In summary, we provide strong correlative evidence that individuals in Ashkenazi Jewish families with exceptional longevity have better maintenance of telomere length and that the telomerase genes may function as important genetic determinants of both human longevity and telomere length. Additionally, our data suggest that both telomere length and variants of telomerase genes may have a cumulative influence on lower disease prevalence and a favorable lipid profile in centenarians and their offspring. Additional comprehensive studies on genetic and genomic variation of centenarians and their offspring comprising candidate genes, especially those known to play a role in telomere maintenance in model organisms, may reveal previously undescribed genomic regions and molecules that are operative in human health and longevity.

Cheers,
Colin

David vs Goliath

2009-11-13T09:11:00.024-05:00

The story of humanity is a fascinating and inspiring one.

Despite the great adversity our species has, and continues to, face, we are capable of great compassion, imagination and inspiration. Indeed, it is perhaps these human traits that have helped us overcome the almost insurmountable obstacles we have faced in our species' evolutionary history.

What we are today reflects the challenges we have had to overcome in the past. From our two eyes and two hands, to our emotions like love, hope and fear, we are a complex history of biological and, more recently, cultural evolution. The inhospitable and unpredictable environments in which our species lived has given us aggression and compassion, emotion and reason, fear and happiness.

To help us overcome starvation we developed tools for hunting and farming. To help us overcome infectious disease we created the sanitation revolution and vaccinations. Our ability overcome diverse and complex forms of adversity is admirable.

The history of humanity is thus one of struggle (with all of its accompanying tragedy) but also one of hope (with all of its accompanying inspiration). Hope for a better state of affairs. One where humans have more opportunities to enjoy health, love and happiness. This aspiration to make things better is, I believe, what makes us truly human. And it is an aspiration that links us to our distant ancestors.

The title of this post is "David vs Goliath". Humanity is David, and Goliath represents all the things that have, and continue to, challenge the health and welfare of humans. The specific form of Goliath alters over time. Reflecting on the causes of death in the 20th Century, for example, we see that Goliath was warfare (including two World Wars), totalitarianism, and, most importantly, infectious disease. The Flu pandemic of 1918, for example, killed an estimated 50 000 000 people, which is more than 3 times the estimated number of deaths caused by four years of “Great War” in 1914-18. And small pox is estimated to have killed between 300 and 500 million people in just the 20th century.

In the 21st century, Goliath is CHRONIC DISEASE (e.g. cancer, heart disease, stroke, etc.). Just 1 year of chronic disease today kills as many people as 300 years of the Black Plague.

In the decade from 2005 and 2015, the World Health Organization estimates that 220 million people will die from chronic illness, 144 million of these deaths will be in lower middle income countries like China and India.

To slay the Goliath of today humanity must be more compassionate, more imaginative, and more inspiring than it has been in the past. Slaying Goliath in the 21st century will require, I believe, an aggressive effort to understand the biology of aging, and then the development of interventions that modulate the rate of aging, so that humans can enjoy more disease-free life and a compression of morbidity at the end of life.

Why we age, and become frail and diseased, is a legacy of our evolutionary history. In short, because life in the state of nature was "nasty, brutish and short" the force of natural selection does not apply to the post-reproductive period of the human lifespan. So most disease and death today are caused by evolutionary neglect. And given the size of today's aged populations, unprecedented numbers of humans will suffer the ravages of chronic disease.

The vision of David battling Goliath came to me today as I happened across the following video this morning and was deeply moved by it. It is an interview with J.M. Smith, an evolutionary biologist who died in 2004. While a student Smith studied fruit fly genetics with J.B. Haldane.

In this interview Smith discusses the illness and death of his teacher, who died of cancer. This brief video moved me in many ways. It captures the human ability to display humour and determination in the face of adversity, as well as love and friendship. It captures humanity's most redeemable qualities, as told by one the greatest scientists of the 20th century.

It is only fitting to quote a passage from Haldane's famous poem on cancer:

I wish I had the voice of Homer
To sing of rectal carcinoma
Which kills a lot more chaps in fact,
Than were bumped off when Troy was sacked

To slay Goliath this century we must build on the work of great minds like Haldane and Smith. We must transcend the "disease model" approach to the medical sciences, and develop Darwinian medicine.

And aging research is at the frontier of this more robust and ambitious vision of medicine. Modifying the biological clocks we have inherited from our Darwinian past would be this century's most important advance in public health. For age retardation would help protect the 2 billion people who will be over the age of 60 by 2050 from the chronic diseases that currently ravage unprecedented numbers of aged people in the world today. In order for this biological revolution to occur we must also undergo a cultural revolution. We need a rational and humane culture. We need more compassion, more imagination and more (new sources of) inspiration.

And we all have a moral responsibility to help spur on this cultural revolution and become 21st century humanists.

Cheers,
Colin

Biogerontology Paper Now Online

2009-11-07T14:45:00.007-05:00

My paper entitled "Framing the Inborn Aging Process and Longevity Science" is now published on the "Online First" section of the journal Biogerontology. Here is the abstract:

The medical sciences are currently dominated by the ‘‘disease-model’’ approach to health extension, an approach that prioritizes the study of pathological mechanisms with the goal of discovering treatment modalities for specific diseases. This approach has marginalized research on the aging process itself, research that could lead to an intervention that retards aging, thus conferring health dividends that would far exceed what could be expected by eliminating any specific disease of aging. This paper offers a diagnosis of how this sub-optimal approach to health extension arose and some general prescriptions concerning how progress could be made in terms of adopting a more rational approach to health extension. Drawing on empirical findings from psychology and economics, ‘‘prospect theory’’ is applied to the challenges of ‘‘framing’’ the inborn aging process given the cognitive capacities of real (rather than rational) decision-makers under conditions of risk and uncertainty. Prospect theory reveals that preferences are in fact dependent on whether particular outcomes of a choice are regarded as ‘‘a loss’’ or ‘‘a gain’’, relative to a reference point (or ‘‘aspiration level for survival’’). And this has significant consequences for the way biogerontologists ought to characterise the central aspirations of the field (i.e. to prevent disease versus extend lifespan). Furthermore, it reveals the importance of shifting the existing reference point of the medical sciences to one that is shaped by the findings of evolutionary biology and biodemography.

Cheers,
Colin

Gene Therapy Success for Brian Disease

2009-11-06T08:30:00.009-05:00

Naturenews reports on another important success for gene therapy-- treatment for ALD (adrenoleukodystrophy), a rare, inherited metabolic disorder that afflicts young males.

ALD results in severe degeneration of the structure that is crucial for brain-cell function and most die before adolescence.

Here is a sample from the news story:

Researchers have halted a fatal brain disease by delivering a therapeutic gene to the stem cells that mature into blood cells.

The gene was transferred using a virus derived from HIV, a technique that researchers have pursued for more than a decade but has not been successful in humans until now.

...."It's a huge advance," says Mark Kay, director of the Program in Human Gene Therapy at Stanford University School of Medicine in California. "If you look in general at the vectors we use for gene therapy, we've really come a long way. This is the first successful use of lentiviral vectors, and it gives me a lot more cautious optimism moving forward."

The research article of the study is published in Science (paper here).

Cheers,
Colin

Science Paper on Dynamics of Inequality

2009-11-05T07:14:00.003-05:00

The latest issue of Science has this interesting article on the intergenerational wealth transmission and the dynamics of inequality. Here is the abstract:

Small-scale human societies range from foraging bands with a strong egalitarian ethos to more economically stratified agrarian and pastoral societies. We explain this variation in inequality using a dynamic model in which a population’s long-run steady-state level of inequality depends on the extent to which its most important forms of wealth are transmitted within families across generations. We estimate the degree of intergenerational transmission of three different types of wealth (material, embodied, and relational), as well as the extent of wealth inequality in 21 historical and contemporary populations. We show that intergenerational transmission of wealth and wealth inequality are substantial among pastoral and small-scale agricultural societies (on a par with or even exceeding the most unequal modern industrial economies) but are limited among horticultural and foraging peoples (equivalent to the most egalitarian of modern industrial populations). Differences in the technology by which a people derive their livelihood and in the institutions and norms making up the economic system jointly contribute to this pattern.

Cheers,
Colin

Nature Editorial on Gene Therapy

2009-10-30T21:18:00.005-04:00

The latest issue of Nature has this insightful, and refreshing, editorial on renewing our optimism for gene therapy. Here is a sample:

In the early 1990s, when the first human trials got under way, it seemed to many that the era of gene therapy was at hand: the techniques of modern molecular biotechnology would make it possible to repair genetic defects by inserting healthy DNA directly into a patient's cells. The excitement was short-lived. Lasting effects proved difficult to obtain in early trials, and the community quickly grew sceptical. Then, in 2003, when it was announced that several gene-therapy patients in a Paris-based clinical trial had developed leukaemia, and that one of them had died, the mood became bleak. Subsequent reports of successful and effective gene-therapy trials have done little to lift the prevailing sense of doom. For most researchers, gene therapy now seems like a dead end.

....To reverse this trend, it is time for researchers and industry to refresh their perspective on gene therapy and to consider its successes with as much intensity as its setbacks. The focus on adverse events has had positive consequences: researchers dissected the exact molecular mechanisms that led to cancer, designed better vectors, devised animal models to test these vectors and developed sophisticated assays for monitoring patients. As a result, both scientists and clinicians now have a battery of extraordinarily refined tools for preclinical and clinical studies of gene therapy. The field is ripe for further successes.

Cheers,
Colin

21st Century Humanism

2009-10-29T13:17:00.031-04:00

As a humanist I believe in the equal worth of all human beings. My humanist sentiments open my eyes to the problem of global poverty, the pervasiveness of patriarchy and the dangers of extremism.

My humanist sentiments also open my eyes to the shortcomings of evolution (evident by the prevalence of chronic disease in late life) and the prevalence of "ageism". In this post I will address these latter concerns.

If humanists reflected critically and consistently upon their basic moral convictions, I believe they would become strong advocates of aging research and the aspiration to decelerate human aging. However, most humanists are not (at least yet) strong advocates of this scientific research; indeed many probably oppose this research or at the least do not think it an important priority. In this post I will explain why this is a mistake given the foundational moral premises of humanism.

What separates me from those humanists who ignore or eschew aging research is that I am a 21st century humanist, while they are 20th century humanists. A 21st century humanist endorses the aspirations of 20th century humanists (e.g. racial equality, the elimination of gender, the elimination of world poverty, etc.), but we go one step further by incorporating the challenges of an aging world and the rapid advances in biomedical science into our purview of the demands of justice (see this excellent article which played a major role in bringing me around to thinking more rationally about these issues).

A 21st century humanist recognizes the fact that no person, regardless of race, gender, nationality or *age*, deserves to suffer morbidity and mortality. And thus we ought to aspire to reduce these risks when it is feasible to do so, whether it be by providing access to clear drinking water, bed nets to protect against malaria or developing new drugs that re-programme our metabolism and help protect against chronic diseases.

For the first time in human history, most disease and death this century will occur in late life. Aging will cause hundreds of millions of cancer deaths, strokes, bone fractures, infections, etc. Furthermore, these chronic diseases are extremely costly. The Centre for Disease control estimates that chronic diseases account for 70% of all deaths in the United States and the medical care for people with chronic diseases account for more than 75% of the nation’s $2 trillion medical care costs. (source)

20th century humanists seek to mitigate socially created harm and oppression, whereas 21st century humanism extends the concern for the equal worth of all beyond the harms created by social institutions. 21st century humanism also seeks to mitigate the adverse consequences of natural selection- in particular, the evolutionary neglect that leaves humans vulnerable to late-life morbidity and mortality.

The average age of life expectancy, at birth, in the world today is 67. This means that most people born today will live long enough to suffer one of the chronic diseases of aging, like cancer or heart disease. This is a fate suffered by millions every year now, especially in the developing world (contrary to what most people in the developed world think).

21st humanists ought to be among the strongest and loudest advocates of biogerontology. For the goal of "healthy aging" is one that follows from the core humanist sentiment that the worth of all human life, regardless of chronological age, is equal. Once humanists open their eyes to the reality of today's aging world, appreciate the incredible advances that are being made in the biomedical sciences, and discard their ageism, perhaps they will embrace a public philosophy well suited for meeting the full range of challenges we face in the "here and now" (and in the years to come).

Cheers,
Colin

Biogerontology Paper on Framing the Inborn Aging Process

2009-10-23T09:50:00.015-04:00

My paper entitled "Framing the Inborn Aging Process and Longevity Science" has been accepted for publication in the journal Biogerontology.

This paper integrates insights from economics, psychology, evolutionary biology, demography, and epidemiology in an effort to help equip us for tackling this century's greatest challenge-- the rapid rise of chronic disease that accompanies population aging.

This paper is probably my most ambitious paper to date, and was a real labour of love. Here is the abstract:

The medical sciences are currently dominated by the “disease-model” approach to health extension, an approach that prioritizes the study of pathological mechanisms with the goal of discovering treatment modalities for specific diseases. This approach has marginalized research on the aging process itself, research that could lead to an intervention that retards aging, thus conferring health dividends that would far exceed what could be expected by eliminating any specific disease of aging. This paper offers a diagnosis of how this sub-optimal approach to health extension arose and some general prescriptions concerning how progress could be made in terms of adopting a more rational approach to health extension. Drawing on empirical findings from psychology and economics, “prospect theory” is applied to the challenges of “framing” the inborn aging process given the cognitive capacities of real (rather than rational) decision-makers under conditions of risk and uncertainty. Prospect theory reveals that preferences are in fact dependent on whether particular outcomes of a choice are regarded as “a loss” or “a gain”, relative to a reference point (or “aspiration level for survival”). And this has significant consequences for the way biogerontologists ought to characterise the central aspirations of the field (i.e. to prevent disease versus extend lifespan). Furthermore, it reveals the importance of shifting the existing reference point of the medical sciences to one that is shaped by the findings of evolutionary biology and biodemography.

Cheers,
Colin

Cancer Funding in Canada

2009-10-21T17:08:00.017-04:00

Today's Globe has this interesting piece on how small the portion of cancer research spent on childhood illness is. A sample:

One dollar in every $30 invested in cancer research goes specifically to research on childhood and adolescent cancers, according to a new report.

In 2007, $13.2-million of the $402.4-million that was invested in cancer research in Canada was aimed at understanding the causes and improving the cancer of younger patients, the study from the Canadian Cancer Research Alliance shows

Now the fact that only 3% of cancer research focuses on childhood illnesses will surprise, and no doubt trouble, many people.

Let me first address the sensibility that spending only 3% of cancer funding on childhood and adolescent cancers is unfair. What most people don't realise is the fact that cancer is predominately a disease of aging. Like other chronic diseases (heart disease, AD, etc.), most people who die of cancer are over the age of 65. So if one wants to spend money on things that will help save more young lives then one should support tackling more prevalent risks. Look here, for example, to see what kills more young people than cancer. For every young person ages 14-24 that dies of cancer, 6 die in accidents, and 3 die from suicide.

Furthermore, the death rates for the young in Canada are very low, especially compared to the morbidity and mortality rates of the aged. This is not to suggest that we shouldn't do more to reduce early life morbidity and mortality (we should), but that any response should be proportionate to the risk. A 20 year-old smoker has a much lower risk of cancer and death than a 75 year-old active, non-smoker. Why? Because aging is the major risk factor for disease and death in Canada.

So while the intuition that it is unfair to spend so much on cancer research for the aged rather than the young misses the mark, there is a legitimate complaint to make here. Once we make explicit the point that cancer research aims, primarily, at benefiting people in late life, how much bang for the buck will it actually yield? Would we be better served investing more money in aging research rather than cancer research?

Imagine, as fantastical as it is, there was no cancer in Canada. That all 200+ types of cancer were eliminated overnight, just like that. How much longer could Canadians expect to live? 10 years? 20 years? 40 years? The answer will no doubt surprise you. If there were no cancer to kill us the *average* life expectancy would rise by about 3 years.

Why is the number so low? Because removing cancer as a cause of death will simply delay, by only a few years for most people, one of the other chronic diseases of aging. So a 75 year-old who doesn't die of cancer will probably suffer a stroke or heart attack a few years later. See this paper in Science for an overview of the estimates of the upper limits of human longevity.

Aging limits average life expectancy to around 85 years. To add real quality of life in late life we need to tackle the major cause of chronic diseases--- aging itself.

So the real problem with the current approach is that by aggressively going after each specific disease of aging, rather than the aging process itself, we pursue a sub-optimal approach to health extension. One that requires much more funding and yields smaller health dividends. Retarding aging would help delay, simultaneously, most these afflictions, thus freeing up more money to spend on improving the lives of young Canadians.

Thus everyone, young and old alike, would benefit from a more inclusive approach to medicine. To get there we need doctors and medical researchers (and politicians and the general public!) to adopt a Darwinian-based approach to health and disease.

The funding numbers for cancer research reveal that cancer research is really striving to help the aged. But the problem is it focuses only on the proximate cause, rather than the ultimate cause, of mortality. If you really want to improve the health prospects of people in late life we should search for ways to modulate the biological clocks we have inherited from our Darwinian past.

Cheers,
Colin

Surfing Web Good for Older Brain

2009-10-19T22:09:00.008-04:00

This EurekAlert! notes a recent study that found that middle-aged and older adults with little Internet experience were able to trigger key centers in the brain after just one week of surfing the Web. A sample:

The findings, presented Oct. 19 at the 2009 meeting of the Society for Neuroscience, suggest that Internet training can stimulate neural activation patterns and could potentially enhance brain function and cognition in older adults.

As the brain ages, a number of structural and functional changes occur, including atrophy, reductions in cell activity and increases in deposits of amyloid plaques and tau tangles, which can impact cognitive function.

Research has shown that mental stimulation similar to that which occurs in individuals who frequently use the Internet may affect the efficiency of cognitive processing and alter the way the brain encodes new information.

"We found that for older people with minimal experience, performing Internet searches for even a relatively short period of time can change brain activity patterns and enhance function," said study author Dr. Gary Small, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and the author of "iBrain," a book that describes the impact of new technology on the brain and behavior.

Cheers,
Colin

Nature News Feature on Cognitive Enhancement

2009-10-18T07:45:00.005-04:00

The latest issue of Nature has this interesting "News Feature" story on the current state of neuroscience and the goal of enhanced cognition. Here is a sample:

Researchers have now created or identified at least 33 mutant mouse strains that, like Doogie, have enhanced cognitive abilities. The animals tend to learn faster, remember events longer and solve complex mazes better than ordinary mice. And because the molecular pathways used in the brain to form long-term memories are almost identical in humans and rodents, the hope is that the work will inform research into treatments for a wide variety of learning and memory problems, from dyslexia to dementia.

Much of the work involves making an adult brain behave more like a younger, more flexible version of itself by increasing the organ's plasticity. This, in turn, means that some problems, long believed to have been made permanent during development, might actually be reversed.

....Many scientists are concerned that the animal models of enhanced cognition might obscure subtle side effects, which can't be studied in rodents or primates. Farah is currently looking at the trade-off between enhanced attention — she gives human subjects a mild amphetamine — and performance on creative tasks. Other researchers have used computer models to show that memory is actually optimized by slight imperfections, as they allow one to see connections between different but related events9. "The brain seems to have made a compromise in that having a more accurate memory interferes with the ability to generalize," Farah says. "You need a little noise in order to be able to think abstractly, to get beyond the concrete and literal."

....Although Silva recognizes the risks of enhancement, he remains hopeful that the performance of the normal human brain can be improved by neuroscience. "We're getting to a point where we almost need these enhancements," he says. "We don't have enough attention, we don't have enough memory, we don't have enough awake hours. There's clearly a demand to optimize the human brain given what it needs to do in the information age."

Cheers,
Colin

Interesting Globe Article

2009-10-17T13:39:00.015-04:00

I seldom write anything on Canadian politics on this blog, but this article in today's Globe is very insightful and explains why, if I were a betting man, I would wager that there will be a Conservative majority government in Canada this time next year (unless the Liberals can come up some truly helpful and creative ideas and do so quickly, which I think is unlikely).

It all feels like a case of déjà vu.

The simplistic lesson to be learned from all this?

The combination of

(1) Liberty Party = Green Party
AND
(2) Conservative Party = Old Liberal Party
RESULTS IN
(3) Conservative Party = Governing Party.

Can the Liberals come up with some new ideas to give the Conservatives a real run for their money? Only time will tell.

Cheers,
Colin

Chronic Disease in the United States (and the World)

2009-10-16T14:02:00.032-04:00

When media headlines are dominated by the economy, global warming and terrorism, it is imperative that we step back from "the hype" and turn to actual data to reveal what really are the greatest challenges we face.

This chart from the Centers For Disease Control and Prevention ought to make the headlines of the evening news every single evening (since it doesn't, it headlines this blog for tonight!).

Reporting on reality is not entertaining, hence why little attention is paid to chronic disease. But this blog does not aspire to entertain (which no doubt severely limits its readership! :)). So I will provide us with "the facts". And hopefully this will stimulate new insights to help us get serious about today's challenges.

Consider this-- in the year 2005 the total deaths caused by the three leading causes of death in the United States (heart disease, cancer and stroke) far outnumber the complete category of "unintentional deaths". For every person who dies in a car crash, plane crash or workplace accident, etc., 100 people die from one of these three chronic diseases. The next time you see a media story about a hiker who died in a remote mountain, or a person being malled by a tiger at a zoo, just bear in mind how many more deaths occur from chronic disease every single day and go unreported.

Furthermore, and it is imperative that we recognise this, most chronic diseases afflict the aged.

So most of the people who died from heart disease, cancer or stroke were over the age of 65. More than three quarters of cancer deaths (76%) occur in people aged 65 years and over (source). According to the American Heart Association, over 83 percent of Americans who die of coronary heart disease are age 65 or older (source).

Aging causes most disease and death and yet we spend a minute fraction of public funds studying the biological processes of aging compared to the vast amounts spent on national defence and trying to control the climate and the economy. Gaining some control over the biological clocks we have inherited from our evolutionary past would yield enormous health and economic dividends. Age retardation might prove to be one of the most optimal ways to prevent chronic disease. Yet the social and political obstacles that impede this vision of preventative medicine are perhaps even bigger obstacles than the scientific ones aging researchers face.

One last point. Many of you are probably thinking "yeah, yeah, aging and chronic disease are problems in rich America. But what about the rest of the world? Surely infectious diseases like HIV and malaria and poverty kill more people than chronic disease". Well, if you are inclined to think that you should think again. Yes, HIV, malaria and poverty are very serious problems in poorer countries. But chronic diseases kill far more people. In lower middle income countries like China and India the World Health Organization estimates that chronic diseases are estimated to account for 75% of all deaths over the coming decade (source). And chronic diseases are on the rise in the poorest countries in the world (see here).

The 21st century is set to be the century of chronic disease. To meet the challenges of chronic disease we need to understand the ultimate (or evolutionary) and not just proximate causes, of these diseases. Hence why aging research should be among our top priorities for a new global health initiative. One with more health, less disease, disability and suffering, and greater economic prosperity for all. That's a world worth fighting for! To achieve it we must overcome the vulnerabilities of evolutionary neglect.

Cheers,
Colin

New Journal: Translational Medicine

2009-10-14T20:58:00.012-04:00

Science has just launched a new exciting journal entitled Translational Medicine. See the details here.

The latest issue of Science has this insightful editorial about the journal by Bruce Alberts. Here is a sample:

Knowledge accumulates as science advances, and science and technology are generating new knowledge at an increasing pace. The acceleration becomes understandable once one recognizes that new knowledge is formed by creatively combining old knowledge in new ways, and that, for example, 100 pieces of knowledge can be combined in 100 times more ways than can 10 pieces of knowledge. The most striking innovations often come from combining knowledge across disparate domains, but only a tiny fraction of such combinations will be useful, making research strategies ever more critical as science proceeds. Great science therefore resembles great art in the sense that an outstanding scientist has carefully selected a "subject" (the unsolved problem to attack) and the "brushes and paints" (the research strategy and techniques), using them to skillfully create a pleasing original "painting" (a new explanation of some aspect of the natural world).

The opportunities and the challenges in translational medicine are enormous, and constant waves of innovation will be needed to meet them. New ideas and approaches are essential. Too often, information with the potential to improve human quality of life is available only through silo-like channels. For example, cardiologists who only attend specialized meetings and read the cardiology literature, but not the physics or computer science literature, can miss an important breakthrough that could advance their own research. To stimulate innovation, we must intentionally catalyze the mixing of scientists and clinicians from different disciplines, knowing that new approaches will emerge from their interactions. Science Translational Medicine strives to increase such mixing by keeping researchers informed about relevant advances across all disciplines.

And the video below details the how journal aspires to translate the incredible advances being made in our understanding of biology into benefits for human health. Such an aspiration is vital if we are to meet the challenges we face today in the 21st century.

Cheers,
Colin

Is Retirement Actually Bad for Your Health?

2009-10-13T16:18:00.006-04:00

...this interesting study in the latest issue of Journal of Occupational Health Psychology suggests that it might be, at least when compared to the retiree health outcomes of those who take on "bridge employment". Here is the abstract:

The present study examined the relationship between bridge employment and retirees’ health outcomes (i.e., major diseases, functional limitations, and mental health). We used a nationally representative sample of 12,189 retirees from the first 4 waves of the Health and Retirement Study. Hierarchical regression analyses showed that compared with full retirement, engaging in bridge employment either in a career field or in a different field was associated with fewer major diseases and functional limitations, whereas engaging in career bridge employment was associated with better mental health. The findings highlight the health benefits of engaging in bridge employment for retirees. The practical implications of this study are discussed at both the individual and policy levels. Limitations of the current findings are also noted in conjunction with future research directions.

Cheers,
Colin

Cell PaperFlick Video on Lifespan Extension

2009-10-13T06:49:00.004-04:00

The latest issue of Cell has this paper which examines the mechanism involved with lifespan extension via dietary restriction. The video above (Cell's PaperFlick file) summarizes the paper's findings and here is the abstract:

Dietary restriction (DR) extends lifespan in multiple species. To examine the mechanisms of lifespan extension upon DR, we assayed genome-wide translational changes in Drosophila. A number of nuclear encoded mitochondrial genes, including those in Complex I and IV of the electron transport chain, showed increased ribosomal loading and enhanced overall activity upon DR. We found that various mitochondrial genes possessed shorter and less structured 5′UTRs, which were important for their enhanced mRNA translation. The translational repressor 4E-BP, the eukaryotic translation initiation factor 4E binding protein, was upregulated upon DR and mediated DR dependent changes in mitochondrial activity and lifespan extension. Inhibition of individual mitochondrial subunits from Complex I and IV diminished the lifespan extension obtained upon DR, reflecting the importance of enhanced mitochondrial function during DR. Our results imply that translational regulation of nuclear-encoded mitochondrial gene expression by 4E-BP plays an important role in lifespan extension upon DR.For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.

Cheers,
Colin

NEJM Review on Aging and Cancer

2009-10-09T08:09:00.006-04:00

The latest issue of the New England Journal of Medicine has this interesting review article on aging and cancer. Here is a sample:

DNA damage has emerged as a major culprit in cancer and many diseases related to aging. The stability of the genome is supported by an intricate machinery of repair, damage tolerance, and checkpoint pathways that counteracts DNA damage. In addition, DNA damage and other stresses can trigger a highly conserved, anticancer, antiaging survival response that suppresses metabolism and growth and boosts defenses that maintain the integrity of the cell. Induction of the survival response may allow interventions that improve health and extend the life span. Recently, the first candidate for such interventions, rapamycin (also known as sirolimus), has been identified.1 Compromised repair systems in tumors also offer opportunities for intervention, making it possible to attack malignant cells in which maintenance of the genome has been weakened.

Time-dependent accumulation of damage in cells and organs is associated with gradual functional decline and aging.2 The molecular basis of this phenomenon is unclear,3,4,5 whereas in cancer, DNA alterations are the major culprit. In this review, I present evidence that cancer and diseases of aging are two sides of the DNA-damage problem. An examination of the importance of DNA damage and the systems of genome maintenance in relation to aging is followed by an account of the derailment of genome guardian mechanisms in cancer and of how this cancer-specific phenomenon can be exploited for treatment.

....DNA damage can trigger the development of cancer, accelerate aging, or both, depending on the type, amount, and location of the damage; the type of cell sustaining the damage and its stage in the cell cycle; and the specific repair, checkpoint, and effector systems involved. When the damage is not repaired, the outcome may be cancer or, if cell death or senescence occurs, protection from cancer, but the trade-off is acceleration of the aging process. The development of cancer and the process of aging can be delayed by reducing the load of DNA damage — by avoiding or limiting exposure to exogenous genotoxins and by suppressing metabolism — thereby producing fewer reactive species. However, DNA damage, like caloric restriction, can also elicit a protective survival response that promotes longevity and healthy aging. Recently, the use of sirolimus in mice was found to extend their life span and delay the development of conditions associated with aging, including cancer.1 Sirolimus is one of presumably many compounds that may elicit the survival response. The frequent derailment of DNA damage-response systems in tumors presents another possible route by which new treatments can act selectively on the tumor.

Cheers,
Colin

Statins and Health Inequalities: Some Thoughts

2009-10-08T09:07:00.020-04:00

Last week I read this article on statins and health disparities which provoked a few different thoughts which I wanted to note here, especially as they pertain to similar concerns that arise with respect to aging interventions and debates in biogerontology.

Before addressing the article let me say a bit about "egalitarianism". My understanding of the term "egalitarian", at least as that term is commonly utilized in contemporary debates in political philosophy, is that it is a term attributed to one who believes that distributional equality of some good or goods (like wealth or health) has considerable moral value in itself (and, conversely, that (unchosen) inequality is unjust).

As I have noted before, I myself am not an egalitarian. When it comes to the issue of how much weight to attribute to equality, the devil is really in the detail (not the abstract concept!). Much depends on the good in question, the level of disparity, and the causes of the inequality and the different challenges that often impede the realization of a more equal (or rather optimal) situation.

I take a diachronic, rather than synchronic, view of justice. Telling me that inequality X is present at time 1 tells me little (if anything) about the justness of a situation. But for those inclined to adopt a synrchonic view of justice, one that is premised on our abstract intuitions concerning what is fair, hearing that an inequality exists is all they need to hear before they are inclined to demand that we mitigate such inequalities (even possibly by levelling down, depending on how strict of an egalitarian one is).

Even though I am not an egalitarian, I am interested in learning why so many (at least academics) hold such a view and what follows from their position. In this earlier post, for example, I argued that if one is an egalitarian of the kind Cohen defends then one ought to take seriously the issue of how inclusive your choice of partner is (which I actually think is a tenable conclusion, but not by appeal to egalitarian concerns).

And in this post I brought attention to the fact that the infant health inequality among the rich and poor has narrowed. To an egalitarian, the information that the gap between the neonatal and infant mortality of rich and poor infants has narrowed might be cause for celebration. Less inequality is inherently good. However, once one notes the reason why this is so-- namely, that part of the reduction in infant health inequality is due to the fact that children of highly educated parents now have an increased risk of complications and death because mothers are more likely to utilise fertility treatments, and hence have a higher change of multiple births-- the intuition "less inequality is good" looks perverse. When it comes to health, "leveling down" is not the goal. What we really want is to bring everyone up. So prioritarianism, or sufficiency, probably underpins most the sensibilities of those who claim to be egalitarian.

This brings me to the article on statins and health inequalities. My interest in this article stems from my interest in the egalitarian objection to aging interventions. Many critics dismiss the prospect of an aging intervention because such a medical intervention, when it arrives (and I think it is really a question of when, not if) will not (at least immediately) be available to all people on the planet. And from this they form the judgement that, "all-things-considered", such a technology will exacerbate injustice and do more harm than good. And thus these kinds of sentiments impede the development of biogerontology, perhaps this century's most important science.

But such a judgement is very naive and misguided. In fact, one can only arrive at such a judgement if one develops a judgement of what justice requires "only-one-thing-considered"-- and that one thing is what weight ought we to place on the abstract value of equality? But if we insist on subjecting our moral sensibilities to a determination of what justice requires "many-things-considered"-- then we will not eschew medical innovations that might have some adverse (at least) short-term impact on relational considerations but, in absolute terms (and in the long run), will improve the situation of all.

It is important to recognise that health is not a zero-sum game- that is, a game where the total amount of health available is fixed and redistributed, so that extra health for X comes at the price of less health for Y. Of course in some cases, like rationing scarce medical resources, things are like this. Either we fund treatment for disease A or for disease B. But we should not generalize from these cases to health in general.

Health itself is not a zero-sum game. If you achieve more health via exercise and diet that benefit does not come at the cost of someone else who thus suffers more disease and an earlier death. Your remaining healthy for longer need not reduce the amount of health available to me. Indeed, by remaining healthy and productive you can increase the likelihood that health dividends will also come my way by helping to reduce the strains on medical resources that are scarce and need to be rationed.

This brings us then to the study on statins. Statins are cholesterol lowering drugs that can reduce the risk of cardiovascular disease. But statins are not freely available. And thus those who can afford them enjoy a reduced risk of heart disease. A sample from the paper:

As an innovation, statins have a number of attributes favoring effective diffusion and adoption. Classical diffusion theory considers the following factors: “relative advantage” (e.g., effectiveness relative to alternatives), lack of “complexity” (e.g., simplicity of use), “compatibility” (fit with existing values and practices), “observability” (outcomes can be observed), and “trialability” (users can experiment on a limited basis) (Rogers 2003). Statins possess, to some degree, all of these attributes, and each can be considered from the standpoint of both physician and patient as the adopter. Empirical data suggest that the diffusion of statins has indeed been rapid.

....Statins are far more powerful than prior cholesterol-lowering drugs and, of particular importance, are highly effective in lowering low density lipoprotein (LDL), the fraction of total cholesterol that is most closely associated with heart disease and the principal target of treatment guidelines (NCEP 2002). Statins can achieve reductions of up to 50 percent or more in LDL (Jones et al. 1998), but they are expensive. Simvastatin (brand name “Zocor”) is one of the most effective and frequently prescribed statins, and its cost was over $120 a month in 2003 for a starting dose of 20 milligrams per day (The Medical Letter 2003). In addition to being costly, statin use requires access to lab services and physicians who prioritize prevention, adhering to guidelines for cholesterol screening and treatment. It also requires resources such as patient willingness and ability to fast overnight and present for a scheduled blood draw. Blood analysis is essential for diagnosis, drug titration, and monitoring side effects.

....While the more advantaged were once more likely to have high levels of cholesterol and LDL, they are now definitively less likely. Additionally, exploratory analyses suggest that income is positively associated with statin use accounting for clinical need. While statins hold great promise for improving cardiovascular health, it appears that they may have contributed to expanding social disparities in cardiovascular risk.

....The influence of technologies on socioeconomic disparities is subject to two important modifiers: (1) the nature of the technological change and (2) the extent of its diffusion and adoption. While resources affect access to technologies, some technologies can also affect resources, lessening the productivity of various health inputs. In our case, statins could have helped to equalize cholesterol levels by overtaking the value of lifestyle inputs. Significant disparities in diffusion and adoption, however, resulted in a net effect of gradients favoring the wealthy. It is important to note that average cholesterol levels declined during this period at all income levels. Hence, statins have contributed to an overall improvement, yielding absolute health benefits at all incomes. Health enhancing innovations, however, are typically implemented in a context of inequalities, and an innovation that raises average health can nevertheless create new links between social factors and disease pathways.

So what to make of this? Well, if what one really wants to argue is that everyone, and not just the rich, should have access to statins, then we should invoke a prioritarian or sufficiency or even utilitarian framework. An egalitarian framework distracts us from the real concern (i.e. access to statins) and often leads people to endorse the conclusion "then none should have access to X". There is much more to be said here. But I will leave things there as this is a complex issue which requires more reflection that I can offer here at the moment. But I want to leave things with this final thought:

I believe the prevalence of egalitarian intuitions helps explain (at least in part) the dominance of the "disease model" approach to the medical sciences. People eschew aging research and positive psychology because they believe it is inappropriate to worry about improving the health and happiness of those they consider "the advantaged", when there are those who suffer early onset disease and mental illness. But we should reject this simple dichotomy and its conclusion that we should only use science to help those with the worst afflictions.

To overcome the exclusive vision of the medical sciences (namely, that medicine should only aid those who are sick and ill) we need to overcome these misplaced moral sensibilities. Fairness is much more complex than invoking simple egalitarian intuitions.

Cheers,
Colin

Inhibition of S6K1 Gene Increases Lifespan

2009-10-06T15:25:00.005-04:00

This study in the latest issue of Science is yet another reason why aging research is among the most exciting, and important, areas of scientific research today.

Researchers from UCL, the Wellcome Trust, Imperial College, the University of Cincinnati and Aberdeen University have identified a gene, S6K1, that influences healthy mammalian life-span. Here is the abstract:

Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)–activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.

Cheers,
Colin