Monday, January 30, 2012

PLoS One Study on Genetics of Exceptional Longevity

The Jan. 2012 issue of PLoS ONE has this study on the genetics of longevity.

The abstract:

Like most complex phenotypes, exceptional longevity is thought to reflect a combined influence of environmental (e.g., lifestyle choices, where we live) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity in 801 centenarians (median age at death 104 years) and 914 genetically matched healthy controls. Using these data, we built a genetic model that includes 281 single nucleotide polymorphisms (SNPs) and discriminated between cases and controls of the discovery set with 89% sensitivity and specificity, and with 58% specificity and 60% sensitivity in an independent cohort of 341 controls and 253 genetically matched nonagenarians and centenarians (median age 100 years). Consistent with the hypothesis that the genetic contribution is largest with the oldest ages, the sensitivity of the model increased in the independent cohort with older and older ages (71% to classify subjects with an age at death>102 and 85% to classify subjects with an age at death>105). For further validation, we applied the model to an additional, unmatched 60 centenarians (median age 107 years) resulting in 78% sensitivity, and 2863 unmatched controls with 61% specificity. The 281 SNPs include the SNP rs2075650 in TOMM40/APOE that reached irrefutable genome wide significance (posterior probability of association = 1) and replicated in the independent cohort. Removal of this SNP from the model reduced the accuracy by only 1%. Further in-silico analysis suggests that 90% of centenarians can be grouped into clusters characterized by different “genetic signatures” of varying predictive values for exceptional longevity. The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity.


Friday, January 27, 2012

EMBO Reports Paper Online

My paper "'Positive Biology' as a New Paradigm for the Medical Sciences" is now published in the advance online section (for Jan. 27) of Nature's EMBO Reports.

The abstract:

Most basic and applied research in the medical sciences today is premised upon the presumption that well-ordered science requires us to prioritize what one can call “negative biology”. Negative biology is the intellectual framework that presumes the most important question to answer is- what causes pathology? Positive biology, by contrast, focuses on a different set of questions and priorities. Rather than making disease the central focus of our intellectual efforts and financial investments, positive biology seeks instead to understand exemplar examples of health and happiness. Understanding why some (rare) individuals can live a century of disease-free life, or why some individuals enjoy more well-being (e.g. positive subjective experience, optimism, perseverance, high talent) or possess greater memory or resilience than the average person could lead to new knowledge that permits us to significantly expand the opportunities today’s populations have for health and happiness.

A sample:

Most of today’s medical research could be called ‘negative biology’. It is conducted in an intellectual framework that presumes that the most important question to answer is: what causes pathology? Disease is its central focus and this explains why medical research and research funding is mainly concerned with trying to understand, prevent and treat specific diseases. The design of the US National Institutes of Health, which is largely composed of individual institutes dedicated to specific diseases such as cancer, mental illness or infectious diseases, reflects this prevalence of pathology-oriented negative biology.

Positive biology, by contrast, focuses on a different set of questions and priorities. Rather than making pathology and disease the central focus of intellectual efforts and financial investments, positive biology seeks to understand positive phenotypes: why do some individuals live more than a century without ever suffering from the chronic diseases that afflict most humans much earlier in their lives? Why are some individuals more happy, optimistic, talented, or have a better memory than most people? The paradigm of positive biology is based on the insight that the process of evolution by natural selection does not create a perfect organism in terms of life expectancy, resistance to disease or other abilities.


Wednesday, January 25, 2012

Enhancement Book (Chapter 1)

Over the coming weeks I will be making my way through Allen Buchanan's new book Beyond Humanity? I am looking forward to reading this timely book which is written by a first-rate scholar who has made substantive contributions to various debates in practical ethics and political philosophy.

My goal here on the blog is to make a few notes for each chapter, primarily for my own benefit so I can return at a later point to write something more substantive. So on to Chapter 1.

Chapter 1 begins with a very useful characterization of the "anti-enhancement" stance. This characterization resonates with me as I have encountered these kinds of objections for the past decade now when teaching these topics. Buchanan captures the "anti-enhancement" position in the following:

For the first time, human biology and even the human genome itself can be shaped by human action. But the human organism is a finely balanced whole, the product of eons of exacting evolution. It is irresponsible to tamper with the wisdom of nature, the handiwork of the Master Engineer of evolution, in order to be better than well. Our situation at present is not perfect, of course, but it is clearly satisfactory; so it is a mistake to risk it for the sake of improvement. Those who seek biomedical enhancement desire perfection; they crave mastery. But such attitudes are incompatible with a due appreciation of the given, a sense of gratitude for what we have. (1)

Buchanan notes that every single sentence in the above passage is in fact false. Let me break the paragraph down, line by line, to show why this is so (I will add some further details and points, etc. to the case Buchanan makes against this statement).

#1. For the first time, human biology and even the human genome itself can be shaped by human action. WRONG. Human biology is shaped by our environment. Creating cities, vehicles and jobs that limit human mobility helped (when combined with access to cheap, high caloric food) modulate our biology in ways conducive to an epidemic of obesity. The design of human societies and new technologies also changed the human genome. These "human" factors altered who we reproduced with, who lived long enough to reproduce, etc. Culture impacts biology. A scan of the brain of a literate child living today in the developed world, who is exposed to education and ample nourishment, for example, would look very different from the brain scan of a 10 year-old living in a small hunter-gather tribe from 80 000 years ago.

#2. But the human organism is a finely balanced whole, the product of eons of exacting evolution. WRONG. Read this. It is hard to see how an organism susceptible to chronic pain, depression, cancer, diabetes, heart disease, etc. is "finely balanced".

#3. It is irresponsible to tamper with the wisdom of nature, the handiwork of the Master Engineer of evolution, in order to be better than well. WRONG. We tamper with the wisdom of nature every single day. I put a bundle of clothes on my body before braving the deep freeze of the average winter day in Canada. I read, exercise, etc. in order to become "better". Now one might argue that the human brain itself is perhaps part of the "wisdom of nature". But this brain is capable of vice as well as virtue. Surely we don't want to defer to the wisdom of sociopaths, the weak willed, etc. So deferring to the "wisdom of nature" is a vacuous suggestion.

#4. Our situation at present is not perfect, of course, but it is clearly satisfactory; so it is a mistake to risk it for the sake of improvement. WRONG. The chronic diseases of aging will kill an unprecedented number of human beings in the next decade. The WHO estimates the number to be over 200 million people. And death by chronic disease is a slow, painful demise. Hardly a state of affairs that can be called "satisfactory". In my view, the moral imperative to tackle aging is among the greatest of moral imperatives our species has ever faced.

#5. Those who seek biomedical enhancement desire perfection; they crave mastery. WRONG (or, at least, it depends on who the target of criticism is). Wanting to improve cognition or promote healthy aging via biomedical intervention does not presuppose we want "mastery" anymore than pursuing these same aims via education and exercising does.

#6. But such attitudes are incompatible with a due appreciation of the given, a sense of gratitude for what we have. WRONG. Promoting education (an enhancement), for example, is not incompatible with gratitude. A parent that wants their child to receive a better education than what they received growing up is not necessarily ungrateful for the opportunities they received as a child. Rather such an attitude denotes an appreciation of the importance a good education has. It need not express feelings of ingratitude.

OK, back to the book.

Buchanan notes (3) that the enhancement debate, perhaps more than any other academic debate in Practical Ethics, is one largely populated by rhetoric and grandstanding and slogans rather than sound arguments. Appeals to "the given" and "normal species functioning" abound, but there is little understanding of, or engagement with, evolutionary biology. The enhancement literature, he claims, "is one of the last academic strongholds of a priori psychology and sociology. One would think that one was living in the eighteenth century, when serious intellectuals still believed they could formulate interesting and controversial generalizations about human behavior or the workings of human society from the armchair" (9). Love that passage!

A unique move Buchanan makes is the introduction of the "anti-anti-enhancement" stance versus the "pro-enhancement" stance, which helps transcend the debate between the typical "pro vs anti-enhancement" frame. He adopts the "anti-anti-enhancement" stance. Such a stance "more positively commits itself to developing the moral and institutional resources needed to pursue enhancements responsibly" (16). The case in favour of enhancements, argues Buchanan, comes to the fore once we discard the erroneous assumptions that enhancements will be predominately zero-sum, competitive goods, or expressions of bad character. What is needed is thus a re-framing (more on this later) of the ethical issues at stake with biomedical enhancements. And this is the primary goal of the book (19).

Definition of biomedical enhancement: a deliberate intervention, applying biomedical science, which aims to improve an existing capacity that most or all normal human beings typically have, or to create a new capacity, by acting directly on the body or brain. (23)

5 Types of enhancement widely discussed in debates are:

1. improvements in physical characteristics such as speed, strength, and endurance
2. improvements in cognitive capacities, such as various aspects of memory, information - processing and reasoning
3. improvements in affect, emotion, motivation, or temperament
4. improvements in immunity or resistance to disease
5. increased longevity (25)

Stay tuned for overview/outline of chapter 2 in the next few days.


Tuesday, January 24, 2012

PSR Paper Published

My paper "Virtue Epistemology and the ‘Epistemic Fitness’ of Democracy" is now out in print in the latest issue of the journal Political Studies Review.

The abstract:

In this article I explore three distinct advantages of linking virtue epistemology to an epistemic defence of democracy. First, because intellectual agents and communities are the primary focus of epistemic evaluation, virtue epistemology offers political theorists the opportunity to develop an epistemic defence of democracy that takes ‘realism’ seriously (e.g. the cognitive limitations and biases of humans). Second, because virtue epistemology conceives of epistemology as a normative discipline, it builds normative criteria into the exercise of assessing the ‘epistemic fitness’ of a political arrangement (e.g. democracy vs. epistocracy).Third, by assessing the epistemic powers of democracy from a virtue- epistemological perspective, a more robust (Deweyan) conception of democracy needs to be employed and assessed than the minimalist conception employed by the Condorcet Jury Theorem.


Wednesday, January 18, 2012

The Imperative to Relieve Pain

The latest issue of the NEJM has this interesting Perspective piece on pain in the US. Here is a sample:

The magnitude of pain in the United States is astounding. More than 116 million Americans have pain that persists for weeks to years. The total financial costs of this epidemic are $560 billion to $635 billion per year, according to Relieving Pain in America, 1 the recent report of an Institute of Medicine (IOM) committee that we cochaired. And these figures don't include pain in children or people in long-term care facilities, the military, or prison. The annual U.S. expenditures related to pain (including direct medical costs and lost wages) are higher than those for cancer, heart disease, and diabetes combined. They include nearly $100 billion annually from state and federal budgets. Yet the treatment covered by these expenditures doesn't fully alleviate Americans' pain. Indeed, our committee reviewed the scientific and clinical evidence, held public workshops, received testimony from more than 2000 Americans, commissioned a review on pain's economic burden, and concluded that relieving acute and chronic pain is a significant overlooked problem in the United States.


Sunday, January 15, 2012

5 Musicians, 1 Guitar

Just discovered this band from Burlington. The video above is a real treat.


Monday, January 09, 2012

Distributive Justice and Genetics in ELS (updated and expanded version)

An expanded and updated version of my entry "Distributive Justice and Genetics" in Wiley's Encyclopedia of Life Sciences has been accepted for publication and is now forthcoming.

The abstract:

What will the demands of distributive justice be in the postgenetic revolutionary world? Will genetic inheritance be regarded as socially distributed goods? This may seem a more reasonable position to assert as biotechnology progresses further toward human genetic manipulation. Advances in human genetics raise a number of unique considerations for theories of justice, ranging from the realization of egalitarian ideals and the therapy/enhancement distinction to the scope and limits of reproductive freedom. As new empirical discoveries are made concerning the environmental and natural determinants of human welfare, theories of justice must re-conceptualize what the demands of justice are and how society can fairly distribute the natural and social goods which influence the life prospects of humans.

Keywords: distributive justice; equality; genes; John Rawls; natural lottery of life; reproductive freedom


Friday, January 06, 2012

POLS 250 Trailer... Part II

Monday I continue on with my year long intro theory course for some 250 students here at Queen's. This term we go from Rousseau through to Marx (having already covered Plato through to Hume in the Fall term).

I have found music and visual imagery to an effective way to tap the emotive sensibilities of my students and help sustain their interests (as well as my own!) over this year long theory course.

The trailer above is the intro for part 2 of the course, and it attempts to make vivid the importance of the study of ideas.


Wednesday, January 04, 2012

Journals of Gerontology Paper (Advance Access)

My perspectives article titled "Biogerontology and the Intellectual Virtues" is now available via the advance access for Journals of Gerontology: Biological Sciences.

The abstract:

The case for prioritizing the study of the biology of aging can be persuasively made by making explicit its connection to the exercise of the intellectual virtues needed to realize well-ordered science. These intellectual virtues include a range of attitudes and dispositions integral to all areas of science (e.g. sensitivity to details, adaptability of intellect, the detective's virtues), but the so-called “teaching virtues” are especially important for biogerontology. Without the foresight to anticipate how their audience will likely respond, biogerontologists risk marginalizing the field's importance to well-ordered science as the general public are likely to dismiss, or underestimate, the health and economic benefits of an intervention that retards the rate of biological aging.