The Resilient Brain (great example of Positive Biology)

In general, I'm not a betting man. Intellectual humility cautions against sticking one's neck out too far into terrain that is too complex to understand, let alone reasonably predict with any confidence.

But some bets are unavoidable. You must gamble on an outcome as inaction or hesitation itself is a bet, and a potentially worse bet (namely, certain disaster). The gamble on which areas of scientific research will yield the greatest health benefits for human populations this century is one such bet. Should we invest most research dollars into research on cancer, heart disease, Alzheimer's disease, etc.?

I am willing to go out on a limb here and make the following bet: I bet that, in the year 2100, when my grandchildren's generation reflects upon the greatest advances in science and medicine in the 21st century, they will say that the most significant advances in medicine came from research that studies "positive" rather than "negative biology".

I have expounded upon positive biology before (see this presentation, and this paper and this paper, and finally this post).

When, in the year 2100, society reflects back on the scientific and medical accomplishments of the 21st century, I predict they will take the view that the greatest innovations that improved human health came from not from the study of pathology itself (e.g. any specific chronic disease, like heart disease or stroke, or any of the 200+ types of cancer). Instead, the real "game changers" came from research on exemplar examples of health. Research that examined why some rare individuals (who engage in risky behavior) are immune to HIV, why some rare individuals can live a century free from the chronic diseases that afflict most decades earlier, why some individuals possess exceptional resilience to overcome adversity, why some experience more optimism, gratitude and flow than others, etc.

If I am correct about this prediction, it means that we must shift away from the fixation on the study of pathology, and tackle, with the same about of zeal, resources, talent and energy, the study of health and happiness. We must shift from the paradigm of negative biology to a more balanced approach which places equal importance on positive biology.

I was inspired to write this post when I came across this story in Scientific American about "super agers", individuals whose brains possess a special resiliency which protects their memory from the decline of aging. The original study mentioned in the article is here. And the abstract from the study is below:

It is “normal” for old age to be associated with gradual decline in memory and brain mass. However, there are anecdotal reports of individuals who seem immune to age-related memory impairment, but these individuals have not been studied systematically. This study sought to establish that such cognitive SuperAgers exist and to determine if they were also resistant to age-related loss of cortical brain volume. SuperAgers were defined as individuals over age 80 with episodic memory performance at least as good as normative values for 50- to 65-year-olds. Cortical morphometry of the SuperAgers was compared to two cognitively normal cohorts: age-matched elderly and 50- to 65-year-olds. The SuperAgers’ cerebral cortex was significantly thicker than their healthy age-matched peers and displayed no atrophy compared to the 50- to 65-year-old healthy group. Unexpectedly, a region of left anterior cingulate cortex was significantly thicker in the SuperAgers than in both elderly and middle-aged controls. Our findings identify cognitive and neuroanatomical features of a cohort that appears to resist average age-related changes of memory capacity and cortical volume. A better understanding of the underlying factors promoting this potential trajectory of unusually successful aging may provide insight for preventing age-related cognitive impairments or the more severe changes associated with Alzheimer's disease.

Cheers,
Colin

Major Medical Breakthroughs Video: Past and Future

I just came across this excellent video by demographer Jay Olshanksy, someone whose work has greatly influenced my thinking about the health challenges of the world's aging populations.

Reflecting on the successes of the past can help us better understand the challenges we now face today, and tomorrow.

Cheers,
colin

Nature Study of the Genetics of Burrowing

NatureNews has this interesting story about this recent study on the genetics of burrowing in mice.

A sample from the news story:

Oldfield mice are native to the southeastern United States, where they burrow in soils ranging from sandy beaches to silt-rich clays. Wherever they dig, their holes look much the same, with a long entrance tunnel and a second tunnel that stops short of the surface and allows them to escape predators. Such invariability hints that the trait is encoded in DNA, says Hoekstra.

To find out where, she and her Harvard colleagues Jesse Weber and Brant Peterson cross-bred oldfield mice with deer mice, whose burrows are shallow and lack escape routes. The offspring continued to build complex tunnels, suggesting that the oldfield burrowing genes were dominant.

And the summary of the study:

Relative to morphological traits, we know little about how genetics influence the evolution of complex behavioural differences in nature1. It is unclear how the environment influences natural variation in heritable behaviour2, and whether complex behavioural differences evolve through few genetic changes, each affecting many aspects of behaviour, or through the accumulation of several genetic changes that, when combined, give rise to behavioural complexity3. Here we show that in nature, oldfield mice (Peromyscus polionotus) build complex burrows with long entrance and escape tunnels, and that burrow length is consistent across populations, although burrow depth varies with soil composition. This burrow architecture is in contrast with the small, simple burrows of its sister species, deer mice (P. maniculatus). When investigated under laboratory conditions, both species recapitulate their natural burrowing behaviour. Genetic crosses between the two species reveal that the derived burrows of oldfield mice are dominant and evolved through the addition of multiple genetic changes. In burrows built by first-generation backcross mice, entrance-tunnel length and the presence of an escape tunnel can be uncoupled, suggesting that these traits are modular. Quantitative trait locus analysis also indicates that tunnel length segregates as a complex trait, affected by at least three independent genetic regions, whereas the presence of an escape tunnel is associated with only a single locus. Together, these results suggest that complex behaviours—in this case, a classic ‘extended phenotype’4—can evolve through multiple genetic changes each affecting distinct behaviour modules.

Cheers,
Colin

Arizona Conference

I just returned from this excellent conference in Tucson, Arizona. Tucson is a beautiful city. And I had a very enjoyable time listening to a variety of talks in moral philosophy and had many interesting discussions with participants over lunch and dinner. I gave the presentation above on the duty to extend the biological warranty period.

Cheers,
Colin

Winter Term (POLS 250)

Tomorrow I embark, along with the 250 students in my second year political theory course, on the second half of our year long study of the history of western political thought from Plato to Marx.

The trailer above captures the key figures and topics we shall cover. Should be fun.

Cheers,
Colin

Science NextGen VOICES Submission

My submission to Science's NextGen Voices competition was selected as one of the top online essay submissions.

The competition asked you to imagine you had been elected President, and in your inaugural address you had to announce the biggest challenge facing the country today and how you will use science to address it. Here was my entry:

The biggest challenge facing the United States is promoting the health prospects of an aging population. By the year 2030, the number of people aged 65 or older will double to approximately 71 million. Age is a major risk factor for chronic disease and disability, and a healthcare system originally designed to attend to acute illness and injury is ill-equipped for addressing the challenges of a growing, older population with multimorbidity. Promoting the health prospects of those late in life is both a moral duty and an economic necessity. How can science help us meet these novel challenges? In recent years the biology of aging has helped unlock the mysteries of healthy longevity. For example, the genome of the longest living rodent, the naked mole rat, was sequenced in 2011. It has a maximum life span exceeding 30 years and an exceptional resistance to cancer. A variety of experiments on fruit flies, mice, and other species have demonstrated that the rate of aging can be manipulated, either by calorie restriction or by activating particular genes. Research on centenarians (age >100) and supercentenarians (age > 110) suggests there are "longevity genes" that protect these rare individuals from the diseases that afflict their contemporaries decades earlier. The development of a drug that would help the average person replicate the biology of these exceptionally healthy older persons would be among this century's greatest advances in medicine. Thus the field of biogerontology ought to be an integral component of "well-ordered" science for the 21st century.

Cheers,
Colin