Thursday, January 31, 2008

Gene Linked to Aging of Ovary in Mice

This incredible image is a human egg with follicle cells, provided by the Science Museum.
The latest issue of Science has this report on the findings of a study that examined the infertility of mice that lacked a particular gene (PTEN). The "News of the Week" piece nicely summarizes the study. Here is a sample:

When a woman is born, her ovaries already contain a full supply of the immature eggs she will need in her reproductive lifetime. Normally, these eggs begin ripening at about age 13 and are gradually released, usually at the rate of one per month, until she is about 50 years old. But in a small minority of women, perhaps 1 in 100, the ovaries stop releasing eggs much earlier in life, thus causing infertility and premature aging. Exactly why that happens isn't understood, but new results may help provide an explanation.

On page 611, a team led by Kui Liu of Umeå University in Sweden, reports that a gene called Pten, which is best known as a suppressor of tumor growth, is needed to keep egg development in check. In its absence, the researchers found, the egg-containing follicles of mice were activated rapidly at an early age, thus causing depletion of the animals' eggs much sooner than is normal--a situation similar to that of premature ovarian failure (POF) in humans.

"It is a very nice piece of work that shows the importance of the PTEN pathway" in controlling follicle maturation in mice, says reproductive geneticist Aleksandar Rajkovic of Baylor College of Medicine in Houston, Texas. If PTEN also controls human egg maturation, the finding may aid the design of improved infertility treatments.

Liu and his colleagues came to their conclusion by genetically engineering a mouse strain in which Pten expression was inactivated specifically in the animals' oocytes. The results showed that a functional Pten in oocytes is needed to keep egg follicles from maturing. Without it, Liu says, "all the primordial follicles were activated prematurely."

Once a follicle is activated, there's no going back. Its egg either matures and is released for fertilization or dies. As a result, the animals had one litter but were infertile by about 3 months of age, which is early adulthood for mice. By that same age, their ovaries had lost essentially all their follicles.


Wednesday, January 30, 2008

Nature Article on Evolution and Violence

The latest issue of Nature has an interesting piece on evolution and violence entitled "Human behaviour: Killer Instincts" by Dan Jones. Here is a sample:

...A growing number of psychologists, neuroscientists and anthropologists have accumulated evidence that understanding many aspects of antisocial behaviour, including violence and murder, requires the study of brains, genes and evolution, as well as the societies those factors have wrought.

At the same time, though, historians, archaeologists and criminologists have started to argue that in most places life was more violent — and more likely to end in murder — in the past than it is today. The time span of this apparent decline in violence has been too short for appeals to natural selection to be convincing. If humans have evolved to kill, then it seems that they have also evolved to live without killing, given the right circumstances.

....A key condition for an evolutionary account of homicide is an explanation of the fact that most deadly violence is committed by men. Evolutionary psychologists say that this is because men have evolved to compete more intensively than women in the race for status, material wealth and sexual partners. In terms of the by-product theory, men are more likely to suffer the consequences when competition gets out of hand. This competitive kindling, Daly and Wilson argue, is at its most combustible in men of low socioeconomic status in regions of high social inequality, suffused with a sense of everything to gain and little to lose.

....The evidence suggests that humans may indeed have what the Seville Statement called a 'violent brain', in as much as evolution may favour those who go to war. But evolution has also furnished us with a moral sense. The complexities of the relationship between morals and violence may prove a fruitful field for future research, in as much as they can be disentangled from the social and historical factors that clearly hold great sway over the ultimate levels of violence. Evolution is not destiny; but understanding it could help maintain the hard-to-discern progress of peace.

Going from our violent past to our enhanced future... this issue of Nature also has some interesting reply letters to this Commentary about cognitive-enhancing drugs published in Dec. 2007. Here is a sample of some of the replies:

From Nick Bostrom:

...Unfortunately, progress on developing effective cognitive enhancers, and on understanding their long-term effects, is hampered by a shortage of focused research in this area. In general, the potential of enhancement medicine has yet to be fully appreciated.

Prevailing patterns of medical funding and regulation are organized around the concept of disease. Every pharmaceutical on the market with alleged cognitive-enhancing effects was developed as a treatment for some pathology. Its good effects on healthy adults' brains were discovered as fortuitous side effects. This disease-centred framework impedes the development of safe and effective enhancing medicines and has several consequences.

And from John Harris and Muireann Quigley:

...Science and technology will continue to generate all sorts of new enhancers, and the quest for enhancement is not necessarily unfair or unethical. We humans are inveterate enhancers, striving to increase our intelligence and to improve our memory and powers of perception.

Consider spectacles: before they became commonplace, those who had good eyesight enjoyed an advantage over those who did not. Later, those who could afford spectacles joined those with naturally good eyesight — increasing (or decreasing?) natural unfairness. Enhancing technologies that improve eyesight are now widely available; we do not conclude that they are unethical because they are not globally accessible.

Before the invention of lamps or candles, most people went to bed at dusk; these inventions, and then electricity, enabled social life and work to continue into the night. Night owls can steal a march on their lazier or saner competitors, raising the bar and creating pressure for longer working hours. But such enhancement technologies are not considered unethical.

The same is and will continue to be true of cognitive enhancers. We must press for wider and more equitable access, turning our backs neither on technology nor on improving the human condition.

And finally, Nature also has the scoop about the Canadian government's decision to close the Office of the National Science Advisor.


Tuesday, January 29, 2008

Aging and Health Report

The National Academy on an Aging Society website has an informative report entitled The State of Aging and Health in America 2007. Here are a few excerpts from the report:

Demographic changes create an urgent need

Improved medical care and prevention efforts have contributed to dramatic increases in life expectancy in the United States over the past century. They also have produced a major shift in the leading causes of death for all age groups, including older adults, from infectious diseases and acute illnesses to chronic diseases and degenerative illnesses. Currently, about 80% of older Americans are living with at least one chronic condition.

The growth in the number and proportion of older adults is unprecedented in the history of the United States. Two factors — longer life spans and aging baby boomers — will combine to double the population of Americans aged 65 and older during the next 25 years. By 2030, there will be 71 million American older adults accounting for roughly 20% of the U.S. population.

America’s older adult population also is becoming more racially and ethnically diverse. At the same time, the health status of racial and ethnic minorities lags far behind that of non-minority populations. Th e burden of many chronic diseases and conditions — especially high blood pressure, diabetes and cancer — varies widely by race and ethnicity. Data from the 2004 National Health Interview Survey (NHIS) indicated that 39% of non-Hispanic white adults aged 65 years or older reported very good or excellent health, compared with 24% of non-Hispanic blacks and
29% of Hispanics.(5)

There is a strong economic incentive for action

The cost of providing health care for an older American is three to five times greater than the cost for someone younger than 65. As a result, by 2030, the nation’s health care spending is projected to increase by 25% due to these demographic shifts.

More than one-third of U.S. deaths are preventable

Three behaviors — smoking, poor diet, and physical inactivity — were the root causes of almost 35% of U.S. deaths in 2000. These behaviors are risk factors that often underlie the development of the nation’s leading chronic disease killers: heart disease, cancer, stroke, and diabetes.

The above statistics highlight the need to focus on improving the health of older adults by encouraging them to adopt healthier behaviors and obtain regular health screenings that can reduce the risk for many chronic diseases, help decrease health disparities, and lower health care costs.


Sleep and the Brain

In some previous posts I linked to recent studies on the importance of a good night's sleep in forming new memories and in reducing the risks of obesity and cancer.

The latest issue of Nature Neuroscience has an article by Vyazovskiy et. al entitled "Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep". The journal's News and Views piece helps describe the significance of the findings. Here is a sample:

How and why do we spend a third of our lives asleep, and why do even fruit flies do it? Although we have all experienced the poor performance that accompanies inadequate sleep, many aspects of sleep remain mysterious, or at the very least controversial. In this issue, Vyazovskiy et al. provide support for a synaptic view of sleep: namely, that it serves to enforce global homeostatic control of synapse strength, correcting the imbalances created during wakefulness.

...The concept of homeostasis, maintaining a system at a particular set point using feedback modulation, is an old one. More recently, the idea that neurons and neural networks exhibit homeostatic regulation has become an important partner to Hebbian learning rules. Homeostatic plasticity can take many forms, with the regulated set point involving relative synaptic strength, neuronal excitability and/or firing rate. It can also be expressed either pre- or postsynaptically. This broad view of homeostatic plasticity is relevant to the main thrust of the study by Vyazovskiy et al., which shows consistent correlations between molecular and electrophysiological markers of synaptic strength during the early phases of sleep and in wakefulness. Wakefulness increases net potentiation, which is then reduced during recovery sleep. This ensures that the potentiation process can begin anew during the next wake episode.


Friday, January 25, 2008

NICE Report on Physical Exercise

NICE (which stands for National Institute for Health and Clinical Excellence) has just released a new UK guidance report entitled "Physical Activity and Environment: Guidance".

The report highlights the harms of our inactivity and the complex challenges we face in trying to promote physical activity. Here is a sample:

Physical activity not only contributes to wellbeing, it is essential for good health (DH 2004). Increasing physical activity levels in the population will help prevent or manage over 20 conditions and diseases. This includes coronary heart disease, diabetes, some cancers and obesity. It can help to improve mental health. It can also help older people to maintain independent lives.

In 2004, the DH estimated that physical inactivity in England cost £8.2 billion annually (this included the rising cost of treating chronic diseases such as coronary heart disease and diabetes). It is estimated that a further £2.5 billion each year is spent on dealing with the consequences of obesity. Again, this can be caused, in part, by a lack of physical activity (DH 2004).

Physical activity levels vary according to age, gender, disability, ethnicity and socioeconomic status. (National data on physical activity are not broken down by faith, religious belief or sexual orientation.)

Facts and figures

Adults are recommended to undertake a minimum of 30 minutes of at least moderate-intensity activity on most days of the week (DH 2004). Around 65% of men and 76% of women in England do not achieve this (Joint Health Surveys Unit 2004). Seventy per cent of boys and 61% of girls aged 2–15 years are sufficiently active to meet the recommendations for their age (at least 60 minutes of at least moderate-intensity activity each day). Trends between health surveys for England in 1997, 1998, 2003 and 2004 found small increases in physical activity levels between 1997 and 2004. Between 1999 and 2004 (when the same physical activity questions were included for each survey) there were significant increases in the percentage of adults meeting the national recommendations. However, changes in the way physical activity is measured over time mean that no clear trends can be determined (Stamatakis et al. 2007).

Data from the ‘National travel survey’ show that the distance people walk and cycle has declined significantly in the last 3 decades (Department for Transport 2007a). The average distance walked, per person per year, has fallen from 255 miles in 1975/76 to 201 miles in 2006. Bicycle mileage for the same years fell from 51 to 39 miles per person per year. However, some of the surveys may not have captured all walking and cycling trips.

Environmental issues

Increasing levels of physical activity is a challenge, not just for those directly involved in public health but for professionals, groups and individuals in many sectors of society. Adults, young people and children can achieve the national recommended levels by including activities such as walking, cycling or climbing stairs as part of their everyday life. However, while individual interventions to promote such activity may be important, they are not the only (nor possibly the main) solution. Other issues, including environmental factors, need to be tackled. As Schmid and colleagues say (1995), ‘It is unreasonable to expect people to change their behaviours when the environment discourages such changes’.


Thursday, January 24, 2008

Cell Article on Mitochondria and Aging

As I've noted several times before (see here, here and here), a great deal of my current research concerns the moral imperative to retard human aging. This is a truly fascinating topic to examine. When I tell people I am working on this topic they react in different and interesting ways. "Could we actually do this?" "Would we want to do this?" Few topics can enliven a dull dinner party like a discussion of the ethical and social implications of aging research! And I believe that moral and political philosophers should be investing a greater portion of their energies into tackling these important and timely issues.

The latest issue of Cell has a fascinating essay by Leonard Guarente entitled "Mitochondria—A Nexus for Aging, Calorie Restriction, and Sirtuins?". This essay is a great example of the truly amazing advances that are being made in our understanding of the biology of aging. And this scientific research could lead to interventions that confer enormous health benefits. Here is the abstract:

Recent studies of calorie restriction in several organisms demonstrate an increase in mitochondrial activity that is associated with the salutary effects of this dietary restriction regimen. In this Essay, I speculate on how an increase in mitochondrial activity might provide benefit and discuss how diet, mitochondria, and sirtuins might interact in a pathway to slow aging and associated diseases.

And a sample from the Essay:

Mitochondria have long been proposed to play an important role in aging. Recent genetic findings in lower organisms have pinpointed sirtuins as antiaging genes, and at least four of the seven mammalian sirtuin homologs have mitochondria-associated functions. CR is perhaps the most robust intervention that extends mammalian life span and has been associated with an increase in SIRT1 levels in several tissues and a corresponding increase in mitochondrial components. Here, I have presented several models for how this increase in mitochondria may have the effect of slowing aging and disease. Some of the models rely on an important role of ROS in the aging process, whereas others do not. It is hoped that the next few years will see a further convergence of genetic pathways with mitochondrial function, which will provide a comprehensive view of aging and antiaging mechanisms and will also explain how CR works. It seems likely that we are on the right track of acquiring this understanding, and that it will involve mechanisms rich in new and old ideas about aging and how to counteract it.


Tuesday, January 22, 2008

Informed Consent in Gene Therapy Trials

The latest issue of Human Gene Therapy has free online Commentaries on informed consent and gene therapy trials. Here are a few samples:

From Arthur Caplan's "Informed Consent and Initial Clinical Trials of Gene Therapy":

We have not come all that far between the deaths of Jesse Gelsinger and Jolee Mohr when it comes to informed consent practices. Despite a lot of rhetoric and hand-wringing about the need to fix human subjects protections, very little has changed in the past decade in the way informed consent is obtained from prospective subjects. Nor has much changed about the process of gaining informed consent.

....There are steps that the gene therapy community could and should take to improve the consent process. Someone not affiliated with the research for which consent is being sought should be made available to prospective subjects to answer their questions and concerns (Emanuel et al., 2003). Whether that is a local physician, a nurse, or a trained subject advocate available by phone or teleconference, someone ought to be made available to ensure that therapeutic misconception—a belief that what is, in actuality, purely experimental is beneficial and therapeutic— does not take root in phase I and II trials in the fuzzy boundary between where a clinician is also a researcher.

From Suzanne Pattee's "Protections for Participants in Gene Therapy Trials:
A Patient’s Perspective":

People who participate in clinical trials are a rare breed.
Those of us with life-threatening diseases know what it feels like to live each day with a serious health condition and an uncertain future. Instead of accepting our lot in life, we choose to help others in the best way we can—by participating in clinical trials. Even if a trial does not provide a direct therapeutic benefit, we still hope that the first trial will be successful and a new product or cure will result that will help people with our disease. Participating in trials is a way we can give something back to society and others with our disease for the benefits we have received from improved medical care and treatments. After all, if others had not participated in clinical trials before me, I would not have benefited from improved CF care and new treatments, such as Pulmozyme, that have enabled me to live this long and remain relatively healthy.

And a brief excerpt from Jeffrey Kahn's piece entitled "Informed Consent in Human Gene Transfer Clinical Trials":

Human gene transfer (HGT) research raises significant issues for informed consent of the subjects who are recruited to participate in trials, calling into question whether and how HGT research can be performed ethically. My brief answer to this question is that while HGT poses challenges for the informed consent process, acceptable informed consent can be achieved through careful attention to the persistent issues that are outlined below. These challenges are hardly unique to HGT, so the analysis to follow, and the suggestions and recommendations that stem from it, apply more widely across areas of clinical research that share aspects with HGT.

....because so-called “first in human” trials for HGT often combine the goals of “traditional” phase I and II research, the terminology used in the informed consent process can only lead to confusion and misunderstanding on the part of subjects. Subjects will understandably perceive the likelihood of efficacy to be greater than is warranted when both toxicity and safety (phase I goals) and efficacy (phase II goals) are described as part of trials that are the first uses of HGT in humans and in very small groups of subjects. Both of these problems contribute to the problem of therapeutic misconception, an issue that has been widely discussed in the medical and bioethics literature (Appelbaum et al., 1982; King et al., 2005). Finally, the combination of therapeutic misconception with the confusion of overlapping roles leads to potential conflicts in the recruitment of subjects into HGT trials. There is no doubt that researchers must and do believe in the importance of their work and the need to validate the science of HGT. But they may also be “true believers” for whom it is difficult if not impossible to be objective in recruitment of subjects into their research. Their commitment to science should be unquestioned, but they are often equally invested in the ongoing success of the research. All this points to the need be more careful in recruitment, and to do better in the informed consent process.


Monday, January 21, 2008

Canine Behavioral Genetics Article in AJHG

Back in October I posted this piece about the importance of the Dog Genome Project. The latest issue of The American Journal of Human Genetics has a fascinating article entitled "Canine Behavioral Genetics: Pointing Out the Phenotypes and Herding up the Genes" by Tyrone Spady and Elaine Ostrander that also illustrates the importance of dogs for genetic research. Here is the abstract:

An astonishing amount of behavioral variation is captured within the more than 350 breeds of dog recognized worldwide. Inherent in observations of dog behavior is the notion that much of what is observed is breed specific and will persist, even in the absence of training or motivation. Thus, herding, pointing, tracking, hunting, and so forth are likely to be controlled, at least in part, at the genetic level. Recent studies in canine genetics suggest that small numbers of genes control major morphologic phenotypes. By extension, we hypothesize that at least some canine behaviors will also be controlled by small numbers of genes that can be readily mapped. In this review, we describe our current understanding of a representative subset of canine behaviors, as well as approaches for phenotyping, genome-wide scans, and data analysis. Finally, we discuss the applicability of studies of canine behavior to human genetics.

And a sample:

The domestic dog displays greater levels of morphological and behavioral diversity than have been recorded for any land mammal and holds the unique distinction of being the first species to be domesticated.1 The phenotypic radiation of the dog has been the product of restricted gene flow and generations of intense artificial selection. These factors have generated the astounding level of diversity noted among the more than 350 breeds of dog recognized worldwide, many of which were developed for highly specialized tasks such as herding, hunting, and retrieving. Indeed, breeds are often defined by a combination of their specialized morphological and behavioral traits.

....A long-stated goal of behaviorists is to identify genes that control behavioral traits. Traits that define specific breeds, such as those associated with hunting and herding, are of interest, as are those observed in particular dogs or lineages of dog, such as obsessive-compulsive behaviors in the bull terrier. Because of its inherent complexity, developing reliable behavioral metrics for dogs has been difficult. Currently, four general approaches have been employed to study canine behavior: test battery, owner-directed survey, expert rating of breeds, and observational study,38 with test battery being the most frequently used. In this method, dogs are exposed to novel stimuli, and their responses are recorded.

....For years the dog has been suggested as an ideal system for studies of behavioral genetics. With the genome now mapped and sequenced and tools for building haplotypes and studying expression at hand, it is time to tackle the hard experiments. Why is the basset hound less effective at herding sheep or an Anatolian shepherd less effective as a hunting dog? More importantly, why do Australian shepherd dogs herd and greyhounds chase, both in the absence of instruction? Why did the domestication of dogs lead to a level of loyalty and devotion unrivaled among modern mammals?

For many geneticists, the most interesting behaviors in dogs are those that are highly breed associated, such as herding and pointing. For others, the challenge is to understand the genetic variation that contributes to the individual variation between dogs (personality). Still others see in man's best friend a mirror of our best (loyalty, steadfastness, trainability, strong work ethic) and worst (stubbornness, aggression, and anxiety) qualities. An understanding of the genetics of all of these traits is likely to produce a better understand of not only the canine species, but the human species as well.


Sunday, January 20, 2008

Menu (Jan. 2008)

Thursday, January 17, 2008

Gene Testing for Mental Illness

The latest issue of Science has two interesting "News Focus" stories on gene testing for mental illness by Jennifer Couzin. The first is entitled "Gene Tests for Psychiatric Risk Polarize Researchers". Here is a sample:

Starting a biotechnology company was not part of John Kelsoe's life plan. A respected psychiatric geneticist here at the University of California, San Diego (UCSD), he has spent 20 years patiently searching for the genes behind bipolar disorder, tracing patterns of inheritance in families from Amish Pennsylvania to Iceland. Kelsoe has now laid this solid reputation on the line: He has founded a company that last year quietly began selling the first gene test to help diagnose people with bipolar disorder, which affects about 1% of the population.

Kelsoe knows well that he is opening himself up to harsh criticism. And it has begun: Francis Collins, director of the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, was taken aback to learn that a gene test for bipolar disorder was on the market. Being diagnosed with a mental disorder carries "great significance," says Collins, who, like many in the field, thinks a test based on current knowledge is likely to be misleading. In Collins's list of accepted genes for common diseases, "there are no entries" yet for bipolar disorder, he says.

....Because of this uncertainty, not to mention concern about how test results will be interpreted, researchers and ethicists are asking difficult questions. Why test for genes whose science is shaky or that boost risk only slightly? Who will buy these tests? And how will consumers understand and cope with the genetic information they're given?

The second story is "Hoping for a Glimpse of What's Ahead". Here is a sample:

It's one of the first questions people ask about testing for a gene associated with mental illness: Who would want to know the result? One ready volunteer for testing is Holly Finn, 13, who lives in Grand Rapids, Michigan, with her parents and her 16-year-old sister, Katherine. Holly's mother, Kristin Finn, was diagnosed with bipolar disorder 3 months before her 17th birthday. She says that Katherine began showing signs of depression and difficulty concentrating in the fourth grade. Initially pegged as having attention deficit hyperactivity disorder (ADHD), Katherine received a bipolar diagnosis in July of 2004, when she was 12. It's been a rocky road: Katherine has switched schools three times and suffered taunting from her peers, says her mother, an active member of the Depression and Bipolar Support Alliance in Chicago, Illinois.

Now the younger Finn daughter, Holly, is being treated for ADHD and anxiety. Her symptoms are different from her sister's, and she is not thought to have bipolar disorder. But, Holly says, having witnessed her sister struggle for years, she would welcome testing for a bipolar gene. "I think I might have a chance of having bipolar disorder," says Holly, who writes songs she plays on her guitar to cope with her sister's ups and downs. A test could help her "get to the bottom of" her symptoms, Holly says, or at least prod her and her psychiatrist to keep an eye out for bipolar disorder down the road. "It certainly wouldn't hurt."

But hurt is exactly what many are afraid of. "Some people would say individuals have a right to this information and shouldn't be barred by the medical community from receiving it," says psychiatrist Jinger Hoop of the Medical College of Wisconsin in Milwaukee, who is studying how people with schizophrenia or at risk for it respond to genetic data. Her work has confirmed what others have seen: Consumers often react favorably to hypothetical genetic knowledge. "But we don't know a lot about what the actual risks and benefits are" of receiving genetic results, Hoop notes. "We really need empirical data to let us know how people would interpret very subtle changes in risk."


Wednesday, January 16, 2008

China Begins First Large-Scale Whole-Genome Sequencing Project

Another great example of the rapid speed of progress being made by the genetic revolution-- China has begun the first large-scale whole-genome sequencing project. Nature has the story here. Here is a sample:

Next-generation human genomics has arrived. The first large-scale whole-genome sequencing project has now begun in China, and an international multi-genome sequencing programme is hot on its heels.

The Yanhuang Project, which will sequence the entire genomes of 100 Chinese individuals over 3 years was announced by the Beijing Genomics Institute (BGI) on 8 January. Ye Jia, a spokeswoman for the project, said that once it is completed, the BGI aims to sequence the genomes of thousands more people, including ethnic groups from other Asian countries.

....The sequencing will allow scientists to add more detail to their maps of human diversity. The last large study of diversity, the HapMap, analysed only single-nucleotide polymorphisms, or SNPs — places in which DNA differs between two individuals by just one letter of the genetic code. This approach allows scientists to hunt for relatively common genetic variants. But the evidence linking disease to rare variants is growing, says Richard Myers, director of the Stanford Human Genome Center in Palo Alto, California. Whole-genome sequencing will improve detection of these rare variants, and offer a more complete understanding of the genetics of many human traits, he predicts.


Tuesday, January 15, 2008

The Sun: Balancing Risks and Benefits

Few things in life fall neatly into the category of "good" or "bad" for our well being. It is often the case that something can be beneficial in one respect (e.g. enhance our mood), but it might also be potentially harmful in another respect (e.g. high in calories, etc.).

Take something as simple as physical exercise. Recall, for example, my earlier post about the benefits of physical exercise. But there is some risk of harm associated with physical exercise, especially contact sports (e.g. sprains and strains, stress fractures, etc.). Determining what constitutes a sensible course of action requires us to responsibly pursue these benefits, so that we minimize, where possible, these risks of harm (though we cannot eliminate them completely).

Another obvious example are medically prescribed drugs, for they could remedy one's alignment but it is also possible that they could cause an adverse reaction (thus creating more problems for us). But when the likelihood of the benefits far outweigh the potential harms, it is sensible to pursue them. Much of our day-to-day activity involves such judgements (though we not even consciously think of things in these terms). The decisions we make concerning getting to work (via car, bike, etc.) has potential benefits and harms. Ditto for the food we consume.

And so life involves, for us as both individuals and collectively as societies, a complex balancing exercise. And thus it is always prudent, when faced with an argument that focuses exclusively on one purported harm or benefit, to step back and adopt the "big picture" perspective concerning the potential benefits and harms, and strive for some proportionality. And so reflecting on what constitutes responsible "risk management" should increase the likelihood that our lives will, on balance, go better.

Today I came across a great example that illustrates the complexities of potential harms and benefits- exposure to the sun. "Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure" by Johan Moan et. al. is published in the latest issue of PNAS. Here is the abstract:

Solar radiation is the main cause of skin cancers. However, it also is a main source of vitamin D for humans. Because the optimal status of vitamin D protects against internal cancers and a number of other diseases, a controversy exists: Will increased sun exposure lead to net health benefits or risks? We calculated the relative yield of vitamin D photosynthesis as a function of latitude with a radiative transfer model and cylinder geometry for the human skin surface. The annual yield of vitamin D is 3.4 and 4.8 times larger below the equator than in the U.K. and Scandinavia, respectively. In populations with similar skin types, there are clear latitude gradients of all major forms of skin cancer, indicating a north–south gradient in real sun exposure. Surprisingly, the incidence rates of major internal cancers also increase from north to south. However, the survival prognosis also improves significantly from north to south. Reasons for these findings are discussed in view of the role of vitamin D. In Norway, melanoma rates increased by a factor of 6 from 1960 to 1990, while the prognosis improved in the same period. After 1990, melanoma rates have remained constant or even decreased in age groups <50 years, whereas the prognosis has not improved further. These data, together with those for internal cancers and the beneficial effects of an optimal vitamin D status, indicate that increased sun exposure may lead to improved cancer prognosis and, possibly, give more positive than adverse health effects

And here is a sample from the article:

There is a controversy as to whether increased sun exposure to Western populations would prolong or shorten lifetime expectancy, result in fewer or more cancer deaths, and, in general, lead to health benefits or risks (1, 2). For years, emphasis has been placed on the increasing time trends of incidence and mortality rates of cutaneous malignant melanoma (CMM) (3, 4) and, in contrast, on the protective role of vitamin D regarding many types of internal cancer and other diseases (5–7). Too much sun exposure has been blamed for the high and increasing incidence rates of CMM. However, solar radiation is a major, if not the main, source of vitamin D in humans. Therefore, a population's increased sun exposure leads to improved vitamin D status. The observation that the incidence and mortality of several types of internal cancers decreases with decreasing latitude in the United States and other countries initiated the research on vitamin D–cancer relationships in the 1980s and 1990s. However, in some cases, there is an inverse gradient of the rates of internal cancer with latitude (1), with the rates being higher in regions with high annual UV fluences (New Zealand and Australia) than in countries with low annual UV fluences (Northern Europe, Scandinavia, and the U.K.), despite the fact that the populations of these regions are closely related genetically or, at least, have similar skin types, which is important for the photosynthesis of vitamin D.

These issues have health consequences far beyond those of cancer because a number of diseases are associated with inadequate vitamin D levels or low sun exposure: neurological, cardiovascular, metabolic, immune, and bone diseases (2, 7). Evolutionary arguments involving skin color also should be taken into account. A dark skin color is found among Africans and, possibly, early hominids who lived close to the equator (8). This pigment may protect against skin cancer and folate photodegradation (8, 9). A white skin color developed later in our history, as humans left Africa and went north. Because dark skin needs about 6 times higher solar exposure for vitamin D photosynthesis than white skin (10, 11) and because the fluence rate of vitamin D-generating solar radiation decreases with increasing latitude (Fig. 1A), one can argue that skin whitening may be related to the need for vitamin D and the lack of sunshine at high latitudes.

....So far, epidemiological data for cancer argue for an overall positive role of sun-induced vitamin D. There may be more beneficial than adverse effects of moderately increased sun exposure, even for total cancer mortality (65). This message should be addressed to populations at risk for vitamin D deficiency. Trends need to be closely followed in the future. In view of the supposedly long latency times for cancer manifestation, decades are needed for final evaluation of the impacts of the antisun campaigns with respect to melanoma incidence, cancer prognosis, and other possible positive or adverse health effects. Authorities should pay attention not only to skin cancer research, but also to research on vitamin D–sun–health relationships occurring worldwide.

Saturday, January 12, 2008

Precision vs Proportionality: The Future Direction of Political Philosophy

I believe that contemporary political philosophy is at an important crossroads, and this makes it a very interesting and exciting time to be working in the field. In this post I will elaborate a bit on why I believe this to be the case.

In many respects this post brings together some disparate thoughts I have posted before. It is really Part 2 to my earlier entry “What Justice Requires “Many-Things-Considered”". And this post was also partly motivated by the interesting exchange that took place over at Crooked Timber a while back. Here I offer some more specific thoughts on the methodological issues that arise when we aspire to develop, and assess, theories of distributive justice.

What does justice demand of us, as both individuals and societies? One could attempt to answer this question by developing normative analyses at varying levels of abstraction, with varying degrees of precision and detail. I’ll return to this issue shortly, but first there are some preliminaries that need to be addressed.

When contemporary philosophers approach the issue of distributive justice they begin from *somewhere* (no one’s ideas exist in a vacuum), whether it be a particular liberal, egalitarian, communitarian, feminist or multicultural framework. One begins with certain theoretical commitments- like equality, freedom, inclusion, etc.- and perhaps an alliance to a particular philosophical theory (e.g. consequentialism, Rawlsian liberalism, equality of welfare, etc.)

With so many interesting and varied theories of justice on offer, who wants to spend their career trying to re-invent the wheel by developing a new theory or approach?! (note: of course the greatest scholars of the past 3 or 4 decades are, at least in my opinion, the ones who tried to do precisely this!) It's so much easier to simply begin with one of the theories already out there (whichever one takes your fancy) and then build on it, refining the theory in new and interesting ways. This is, I believe, what has mostly occurred over the past few decades in debates in political philosophy.

But suppose for a moment that we did not have the barrage of theories on offer that we actually do have. Suppose we really were starting from scratch. I know this might be a bit hard to envision but lets just see where this goes. Sometimes it is helpful to try to get some distance from the projects that preoccupy most of our thoughts and energies.

So, now that we have wiped the slate clean, suppose someone comes along and says they have what they consider to be a pretty good theory of justice. And they think that, once you hear the details of their theory, you too will be convinced that it is a good theory.

Now if we stop things there, before you hear any of the details of the potential theory on offer, lets consider first the initial expectations you have concerning what a theory is suppose to deliver. What do we want from a theory of justice?
Philosophers will have different answers to this question. And I believe the expectations we have are deeply influenced by what we think of our actual societies (e.g. their virtues and vices) and the kind of “ideal” society that we could achieve. So liberals will want a theory of justice that takes liberty seriously. Egalitarians want a theory that takes equality seriously. Feminists want a theory that takes gender seriously... You get the picture.

Now some of these convictions will reflect ideological differences. But they also reflect different perceptions of the empirical realities facing one’s society. For example, that more could be done to reduce economic inequality and improve the life prospects of the poor. Or that the government could do more to ensure that the family is not an institution that entrenches patriarchy (and that it could do this without being oppressive). Thus our expectations concerning what we want from a theory of justice will be deeply influenced by a mixture of normative and empirical considerations.

Enormous assumptions are frequently made concerning what the state can and cannot successfully do. But these empirical assumptions are seldom made explicit. This is, in my opinion, one of the biggest problems with the state of contemporary political philosophy. We have yet to take seriously what Adrian Vermeule calls “the institutional turn”. I’ll link this point to the general question raised earlier towards the end of this post.

But lets return now to my general methodological question: what do we want from a theory of justice? How would we know if the theory someone is offering us is real gold or just fool’s gold? Two of the richest and most influential (and I think probably among the greatest works in political philosophy in the 20th Century) theories of justice shed light on these methodological issues- Rawls’s A Theory of Justice (1971) and Gauthier’s Morals by Agreement (1986).

For Rawls, the main criterion for success is reflective equilibrium. And for Gauthier, the criterion is that a theory must be premised on rational self-interest.

So the Rawlsian believes you have a good account of justice when it coheres with your considered judgments and the Hobbesian contractarian believes you have a good account of morality/justice when you can convince the moral skeptic that they too should be just.

Rawls’s approach captures both motivational and guiding requirements. His contractarian account of justice (like the original position) is premised upon moral sentiments he believes no reasonable person could reject (e.g. impartiality, the equality of all persons). And he also believes that the conclusions yielded by his theory are a good guide for liberal democracies (or at least they are a better guide than its main rival utilitarianism).

Although Gauthier presents his approach as primarily being concerned with providing a rational foundation for morality, he also brings in moral premises that make his conclusions more palatable (e.g. the Lockean proviso), thus permitting him to offer some guiding prescriptions.

What would the ideal Rawlsian and Gauthierian society look like? Well, for Rawls it is a society that satisfies his three serially ordered principles of justice. See my post “Are You a Fully Fledged Rawlsian?” to see if you agree with Rawls’s basic prescriptions. With respect to Gauthier’s theory, well, that’s even harder to determine. While his principle of minimax relative concession might make some sense in two-person examples, how one goes about applying it to the real world has always puzzled me. And other parts of Gauthier’s theory, like his commitment to the rough equality clause, leads his theory to some very counterintuitive results (e.g. what Allen Buchanan calls the “reciprocity thesis”).

OK, so let’s return to the motivation and guiding requirements. These two requirements remind us of what a theory of justice is primarily for: it’s for us! I don’t mean just you and me. I mean for us as a society. Those of us living in the “here and now”- in the societies we find ourselves, with the pressing moral and practical dilemmas that face us. It is a theory for the biological, temporal, social beings we are. We don’t want a theory of justice for people who might live on Mars in 10 000 years. Or a theory for beings that have a very different biology than ours (e.g. beings that do not need to eat to be nourished, that are not susceptible to disease and disability). We are not interested in what a theory might look like for beings that did not progress through the different life cycles that real, temporal, finite beings progress through. (For an account of what we do want, rather than what we don’t want, see “Taking People For What They Really Are”)

As the example of Rawls and Gauthier illustrate, the motivation/guiding requirements of justice could be (and have been) spun in a number of different ways. Keeping things a level of generality then, we can ask: how adequate are these criteria for a philosophical account of justice? Of course much depends on what one takes the *philosophical* part to mean. It can be cut two different ways, depending on what one takes “philosophy” to mean.

The first way is to view the philosopher as what I will call a “conceptual surgeon”. This means the philosopher is someone who views concepts (like equality) as something they need to dissect, analyze, then refine and polish before churning out a pristine and comprehensive account of what justice requires.

The second way is to view the political philosopher as someone who longs for *wisdom* (see this post) concerning how we ought to live collectively. Can the conceptual surgeon help impart wisdom? To some degree I think the answer is “yes”. Take Isaiah Berlin’s masterful “Two Concepts of Liberty”. If one wants to create a free polity then it is imperative that one gets clear on what freedom actually means. Pursuing negative or positive freedom will take one in different directions. And so achieving some conceptual clarity will help one on their journey towards creating a free society.

But while it is important to recognize that some conceptual clarify is necessary and useful, it is also important to realize that conceptual surgery has its limits. If we invest most of our intellectual energies into conceptual surgery then we risk missing the boat.

To push the surgeon analogy further- while some minor conceptual surgery can be therapeutic, if one goes too far they run the risk of doing more harm than good. Like a skilled surgeon, the political philosopher should not subject her patient to unnecessary surgery. I believe that a good deal of what currently passes for political philosophy is in fact unnecessary surgery; procedures that will not increase the health prospects of the patient. In fact, such conceptual surgery can actually be harmful to the patient as we end up spending all our time and energies on the intricacies of our conceptual surgery and thus miss other obvious things that could be beneficial to the patient (like sterilizing our utensils, checking the patient’s blood pressure, etc.). OK, I don’t want to take the medical analogy too far. But hopefully you get my point!

So if conceptual surgery is part, but *only* part, of what is involved in being a good political philosopher, what else do we need if we hope to create and impart wisdom? (at least the kind of wisdom that a political philosopher could hope to achieve and impart). This takes me to the second theme in my title: proportionality. What the philosopher should really strive for, if they hope to convey some wisdom, is a sense of what the “big picture” perspective of the moral and political landscape looks like. And to do this we must take seriously the issue of proportions. And this is something that conceptual surgery cannot provide. Let me give you two examples, from different ends of the political spectrum, concerning how conceptual rigor can stifle proportionality (and thus wisdom).

My two examples come from two of the most influential philosophers from the past 30 years- Robert Nozick and G.A. Cohen. Nozick’s entitlement theory of justice contains three principles- the principle of transfer, the principle of just initial acquisition and the principle of rectification. The bulk of Anarchy, State and Utopia concerns the first two principles. So Nozick introduces examples like the “eye lottery” and his famous Wilt Chamberlain example to illustrate his point that “taxation is on a moral par with forced labour”. But once one gets to the principle of rectification, and one reflects on how wealth and income have, over human history, been acquired and transferred, one realizes that they must qualify Nozick’s motto so that it reads “taxation is on a moral par with forced labour…if and only if no considerations of injustice could apply to justify such taxation”.

Given the actual history of the world it is puzzling why Nozick did not spend the bulk of his book on rectification, and then just have a small chapter entitled “Why Libertarianism is Required After You Rectify All Past Injustice”. So Nozick’s account of justice gets the proportions wrong. The principles of transfer and just initial acquisition are not vital components of a theory of justice for the world as it actually is. And once he gets the proportions wrong, Nozick is unable to generate any sage prescriptions concerning what constitutes a just government.

The “big picture” story of justice is, according to Nozickians, “get your hands off my income!”. It is not “Hey, let’s rectify past injustices!”. Clarifying what the requirements of self-ownership are in the ideal scenario did not help right libertarians figure out what justice required in the real world. Thus Nozick’s theory was wisdom-impairing rather than wisdom-enhancing.

OK, now an example from the other end of the spectrum- G.A. Cohen’s egalitarianism. I’ve posted my objections to luck egalitarianism before, so I’ll keep this brief. My discontents with luck egalitarianism were reaffirmed after hearing Cohen’s recent interview here. At one stage in the interview the discussion focuses on the central insight of luck egalitarianism- that inequalities we are not responsible for should be mitigated, but those we are responsible for should be tolerated. When the presenter asks Cohen to elaborate on the latter, Cohen says “nothing is ever merely the result human responsible action”. This empirical fact is, in my view, more than a sufficient reason to reject luck egalitarianism. For it shows that the theory has nothing interesting to say about the real world. Given that no inequalities satisfy the Cohenian account of “chosen inequalities”, then one does not need to be a luck egalitarian.

Now of course one might say that there could be a counterfactual society where such inequalities could arise. And thus it is imperative that we clarify precisely what we mean by “egalitarian”. But why should we want to do that? The fervor that many egalitarians get themselves worked up into in this respect reminds me of the medieval theological disputes concerning how many angels could dance on the head of a pin. I can’t see what the point of resolving such a dispute is, especially considering that Cohen himself admits that the second component of luck egalitarianism does not apply in the real world. So I think this is another example of how conceptual surgery can distort proportions and thus impair wisdom. In the “big picture” of things, justice does not require us to ensure we do not compensate chosen inequalities as such inequalities cannot be said to exist in the first place! The real action to be had is not on the site of precision, it is on the site proportions. And luck egalitarianism is of no real help on that front.

What does all this tell us? Lets return now to my initial question: What does justice demand of us, as both individuals and societies? The conceptual surgeons would have us believe that we could capture the requirements of justice in a nifty slogan like “Liberty upsets Patterns!”. But such mottos do not convey wisdom. If forced to come up with a slogan I suppose mine would be “Justice is about proportionality”. This is not a novel suggestion, as it goes all the way back to insights made by Aristotle. And I guess I long for a return to seeing philosophy as an activity primarily concerned with phronesis. Of course I believe precision does have a role to play here. For there is lots of work to be done in terms of clarifying what the stakes are that are in need of balancing. And so I would like to see the conceptual surgeons investing more of their time tackling the notion of proportionality. Doing this will shift us away from trying to win a “first best conceptualism” debate and propel us towards seriously engaging with the empirical and the “institutional turn”.

So the title of this post- “Precision Vs Proportionality”-is, at the end of the day, a false dichotomy. We need both. But given how much time political philosophers have spent on precision, it is not surprising that we have messed up on the proportions!


Friday, January 11, 2008

NEJM Article on "Letting the Genome out of the Bottle"

This week's New England Journal of Medicine has an interesting Perspectives article by David Hunter et. al. entitled "Letting the Genome out of the Bottle — Will We Get Our Wish". Here is a sample:

It may happen soon. A patient, perhaps one you have known for years, who is overweight and does not exercise regularly, shows up in your office with an analysis of his whole genome at multiple single-nucleotide polymorphisms (SNPs). His children, who were concerned about his health, spent $1,000 to give him the analysis as a holiday gift. The test report states that his genomic profile is consistent with an increased risk of both heart disease and diabetes, and because the company that performed the analysis stated that the test was "not a clinical service to be used as the basis for making medical decisions," he is in the office for some "medical direction." What should you do?

This year has seen a dizzying number of genomewide association studies demonstrating associations between novel gene variants or chromosomal loci and common diseases and phenotypes. These studies rely on microarrays that can assess 300,000 or more SNPs in each DNA sample; researchers use these microarrays to examine interpersonal differences in inherited genetic variability and to compare the prevalence of gene variants among patients who have a given disease with that among controls. Such studies have identified associations with many gene variants that were not previously suspected to be related to the phenotypes under consideration. The new technologies involved have been a boon to researchers who needed unbiased clues as to the causation of diseases that may be used to develop new therapeutic and preventive interventions. The test undergone by the patient described above is one of the products of this new knowledge.

....So what advice should a physician offer patients? For the patient who appears with a genome map and printouts of risk estimates in hand, a general statement about the poor sensitivity and positive predictive value of such results is appropriate, but a detailed consumer report may be beyond most physicians' skill sets. For the patient asking whether these services provide information that is useful for disease avoidance, the prudent answer is "Not now — ask again in a few years." More information is needed on the clinical utility of this information in the light of existing disease-specific opportunities for prevention or early detection and the potential value that genomic profiles can add to that of simpler tools, such as the family health history. Finally, given the risk of commercial exploitation, if patients are determined to proceed, perhaps because they are simply curious, are genetic hobbyists, or are "early adopters" of new technology, it would make sense to encourage them to enroll in formal scientific studies.

Now that the genome is out of the bottle, how will our wish for better health be granted? Just as the emergence of a commercial entity (Celera) with ambitions to sequence the human genome spurred public projects to accelerate their efforts, perhaps the emergence of commercial personalized genomic services will galvanize efforts to plan and conduct the necessary translational research5 for the rational integration of genomic information into medical training and practice. Until the genome can be put to useful work, the children of the man described above would have been better off spending their money on a gym membership or a personal trainer so that their father could follow a diet and exercise regimen that we know will decrease his risk of heart disease and diabetes.


Thursday, January 10, 2008

Genetic Justice Must Track Genetic Complexity (Now Published)

My paper "Genetic Justice Must Track Genetic Complexity" is now available in the latest issue of the Cambridge Quarterly of Healthcare Ethics. Here is a sample:

Genetic inequalities permeate our societies. These inequalities are not quantitative inequalities; rather they are qualitative inequalities. Justice is concerned with both kinds of inequalities. Economic inequalities are the most common form of quantitative inequalities. People can have differing amounts of wealth and income. But this does not exhaust the scope on inequalities justice seeks to address. Inequalities in opportunities for education, for example, are typically qualitative inequalities rather than quantitative ones. Children may receive the same number of hours of instruction but the quality of instruction they receive could be very unequal. Similarly, although all citizens have approximately the same quantity of genes (estimates suggest there are between 20,000 and 25,000 protein-coding genes), the quality of our genetic constitutions can vary significantly.

Unlike socioeconomic inequalities, which are a mix of both brute luck factors (e.g., natural endowments, social position, etc.) and choice (e.g., consumption habits, attitudes toward saving and work, etc.), genetic inequalities are 100% brute luck. We inherit our genetic endowments from our parents, and they inherit theirs from their parents, and so forth. No individual is responsible for the genetic endowments he or she is born with. Furthermore, the life prospects for the least advantaged in the “genetic lottery” of life are often extremely grim.

Consider, for example, that in America the average life expectancy is around 77 years of age. That number will vary depending on factors like gender, race, and wealth. Although these factors influence the life prospects of Americans, none of them come close to the extent to which genetic variations impact the life expectancy of the worst endowed. Americans born with average genetic constitutions can expect much greater life prospects for things like health, longevity, and intelligence than those born with the worst genes. Children born with infantile Tay-Sachs will die by five years of age. People born with a mutation of the FMR1 gene will develop Fragile X Syndrome, the symptoms of which can vary from slight learning disabilities to mental impairment. No one deserves the genes they are born with. The results of the “genetic lottery” are arbitrary, and they are often tragic, both for the victims themselves and their loved ones and families.

The prevalence of the worst genetic disorders, like infantile Tay-Sachs, is extremely small. But there are over 6000 known single-gene disorders, which occur in 1 out of every 200 births. “A single-gene disease is a disease caused by a single malfunctioning allele. Such diseases typically can develop in practically all usual environments.”

The most prevalent diseases—like heart disease, cancer, and diabetes—are not caused by a single malfunctioning allele. These more common diseases are multifactorial diseases. Their development depends on a variety of factors beyond our genetic constitutions. Environmental factors like diet and lifestyle (e.g., exercise, smoking, stress levels, etc.) often play a more important role in determining our risk of developing multifactorial diseases. The American Heart Association estimates that, in the year 2001, 64,400,000 Americans had one or more forms of cardiovascular disease. Cardiovascular diseases are responsible for 1 out of every 2.6 deaths. Coronary heart disease caused 502,189 deaths in 2001 and is the single leading cause of death in America today. This is followed closely by cancer. Taken together, heart diseases and cancer account for over half of all deaths in America. Our genes do play a role in our susceptibility to multifactorial genetic disorders. For instance, inheriting faulty BRCA genes gives women a greater risk of developing breast cancer. But for many debilitating conditions, environmental factors play a much greater role in our susceptibility to disadvantage.

What will the demands of distributive justice be in the postgenetic revolutionary society? Where do the current and possible future benefits of biomedical research figure in an account of justice? These are questions we must begin to grapple with if we hope to institute a just regulation of new genetic technologies. But we must ensure that our desire to mitigate genetic disadvantage is tempered by an appreciation of the fact of genetic complexity as well as a recognition of the other demands of justice (e.g., the duty to mitigate other forms of disadvantage, respect for reproductive freedom, etc.).


Tuesday, January 08, 2008

The Human Lifecycle and Our Cognitive Capacities

The latest issue of Psychological Science has two very interesting studies that illustrate how our cognitive capacities are influenced by our development through different stages of the lifecycle. The first study is the Research Report "Bright Children Become Enlightened Adults" by Ian Deary et. al. Here is the abstract:

We examined the prospective association between general intelligence (g) at age 10 and liberal and antitraditional social attitudes at age 30 in a large (N = 7,070), representative sample of the British population born in 1970. Statistical analyses identified a general latent trait underlying attitudes that are antiracist, pro-working women, socially liberal, and trusting in the democratic political system. There was a strong association between higher g at age 10 and more liberal and antitraditional attitudes at age 30; this association was mediated partly via educational qualifications, but not at all via occupational social class. Very similar results were obtained for men and women. People in less professional occupations—and whose parents had been in less professional occupations—were less trusting of the democratic political system. This study confirms social attitudes as a major, novel field of adult human activity that is related to childhood intelligence differences.

And so this study reinforces some of the points I expressed earlier (here) concerning the importance of parental love and virtue.

The second paper in Psychological Science that I want to mention is "Age-Related Changes in the Episodic Simulation of Future Events" by Donna Addis et. al. Here is the abstract:

Episodic memory enables individuals to recollect past events as well as imagine possible future scenarios. Although the episodic specificity of past events declines as people grow older, it is unknown whether the same is true for future events. In an adapted version of the Autobiographical Interview, young and older participants generated past and future events. Transcriptions were segmented into distinct details that were classified as either internal (episodic) or external. Older adults generated fewer internal details than younger adults for past events, a result replicating previous findings; more important, we show that this deficit extends to future events. Furthermore, the number of internal details and the number of external details both showed correlations between past and future events. Finally, the number of internal details generated by older adults correlated with their relational memory abilities, a finding consistent with the constructive-episodic-simulation hypothesis, which holds that simulation of future episodes requires a system that can flexibly recombine details from past events into novel scenarios.

This study is also featured in NatureNews, and here is an excerpt from their story entitled "Ageing Makes the Imagination Wither":

Old age does more than stealthily steal away our most cherished memories: it also seems to diminish our ability to imagine things....

The researchers speculate that personal memories are particularly susceptible to ageing because they rely heavily on 'relational processing', the ability to mentally summon and join unique pieces of information, such as where and when an experience occurred. Stitching the particulars of a scene together — be it real or imagined — gets more difficult with age.

Over the past year, the prospective brain hypothesis has gained steady support among neuroscientists. An intriguing possibility raised by the hypothesis is that the primary role of human memory may not be to remember the past, but to imagine and prepare for the future.

“Once things in the past are finished, there’s nothing you can do about them,” Levine says.

Both studies illustrate the importance of taking seriously those factors (be it childhood education or aging) that have an important bearing on our opportunities for flourishing.


Monday, January 07, 2008

Who are the Least Advantaged?

Theories of justice strive to help elucidate what we owe to each other. What rights and opportunities (e.g. for education, healthcare, etc.) should we provide to our citizenry and why? Over the past 4 decades or so there has emerged a number of competing accounts of distributive justice that champion a range of diverse principles to govern the distribution of different goods and opportunities. A sample of the main contenders often discussed include a principle of liberty, equality, desert, democracy, sufficiency, etc.

Some argue that justice requires wealth and income to be distributed in accordance with liberty (as Robert Nozick famously argued: “From each as they choose, to each as they are chosen” ); others defend some version of equality (e.g. equality of resources, complex equality, equality of opportunity for welfare) or sufficiency.

Today was the first class for my “Genetics and Justice” seminar. In the beginning of the class I had them answer a range of questions concerning their views about justice. Here is the very first question I had them consider:

It is often claimed that a fair society should be judged by how well it treats its least advantaged members. How would you describe who the “least advantaged” members of Canadian society are?

Most students in the class identified the poor as the least advantaged. Some noted that cultural inequalities were pressing concerns and thus aboriginals formed part of the category of the least advantaged. One student mentioned people with severe cognitive impairments.

I suspect the responses from my students would probably cohere with the attitudes of most people in Canadian society. They certainly reinforce the assumptions of contemporary philosophers working in the area of distributive justice. John Rawls, who is arguably one of the most (if not the most) important political philosophers of the twentieth century, argued that justice requires (amongst other things) that we maximize the life prospects of the least advantaged. And he offered two interpretations of this group:

(1) The least advantaged are all those with approximately the income and wealth of the unskilled worker, or less.


(2) All persons with less than half of the median income and wealth.

Rawls’s theory of “justice as fairness” focuses exclusively (though in some footnotes in Political Liberalism he tries to quality this to some degree) on the distribution of what he calls the social primary goods.

These goods are: Rights and liberties, powers and opportunities, income and wealth and self-respect.

The distribution of the social primary goods, argues Rawls, are influenced by what he calls the “basic structure” of society (e.g. the Constitution, political economy, etc.). But what Rawls ignores are what he calls the “natural primary goods”- health and vigour, intelligence and imagination. These goods are not, Rawls contends, influenced by the basic structure of society. Or at least not to the same extent as the social primary goods are.

To help probe the moral sensibilities of my students, and to help steer them towards adopting a wider lens concerning what constitutes serious disadvantage in our society, I mentioned a few facts concerning the impact the genetic lottery of life has on the victims of genetic disease. How inheriting a particular genetic mutation could drastically influence one’s expected life-time acquisition of both natural and social primary goods.

I showed my class the compassionate and moving video by Ian Brown called “The Boy in the Moon”.

Rapid advances in the field of human genetics means that Rawls’s assumption that the distribution of natural endowments themselves are beyond the reach of the basic structure has to be re-evaluated. This was the subject of a paper I published 6 years ago in Bioethics. The decisions we make concerning the safety standards for gene therapy, how robust genomic intellectual property rights are, and how much to invest in basic biomedical research (among many other things) will have a profound impact on the life prospects of some of our most vulnerable citizens.

And so I believe that the interests of the genetically disadvantaged have not yet been given their due. They have largely remained absent from both theoretical/philosophical debates about justice, and in the more general public discourse concerning pressing societal priorities. If we hope to respond, in a fair and proportionate manner, to genetic disadvantage then educators must begin to take seriously the difficult, interdisciplinary research and dialogue needed to put genetic justice on the moral and political radar. In higher education this will mean transcending some of the traditional intellectual barriers that have been erected in recent decades. But in my experience it is the scholars themselves, not the students, who erect these artificial divides. Once given the opportunity to consider the pressing and important issues raised by the genetic revolution, students are inclined to approach these issues in innovative and interdisciplinary ways. And that makes teaching this course all the more enjoyable for me.

So when it comes to adopting a “big picture perspective” concerning who the least advantaged are, we cannot justify excluding those who fair the worst in terms of natural primary goods. And this thus raises the important issue of genetic justice. And then many fascinating, complex ethical, social and legal issues arise. I couldn’t think of a better topic to spend my career contemplating than these challenges, challenges that we have only begun to comprehend.


Friday, January 04, 2008

Exercise, Genes and Depression

Physical exercise has many health benefits. We often hear about the physical benefits of exercise (e.g. weight reduction, stronger muscles, lower risk of heart disease, etc.) but exercise is also extremely important to your mental health. Recall, for example, this earlier post.

The latest issue of Nature Medicine has a fascinating study on how exercise-regulated genes can induce an antidepressant response. The article is "Antidepressant Actions of the Exercise-Regulated Gene VGF" by Joshua G Hunsberger et. al. So if one needed yet another good reason to make good on one's New Year's resolution to exercise more then read this article. Not only will you likely live a longer, healthier life, you will also be more happy! And you owe it to yourself to promote your physical and mental well being. Here is a sample from the Nature Medicine article:

Exercise has well known cardiovascular benefits; however, it has only recently been documented that exercise also augments brain function and mental health. For instance, exercise enhances hippocampal learning and improves executive functioning in aging humans, while also providing protection from brain insults and disease. In addition, recent studies have shown that exercise produces antidepressant responses in rodent models and mood-elevating actions in humans. The mechanisms underlying the beneficial effects of exercise are not fully understood and could be targets for new therapies that are different from traditional chemical antidepressants.

The antidepressant actions of exercise are particularly noteworthy because of the prevalence of depression (16% in the US population), its enormous economic burden ($83.1 billion per year in the US) and a tremendous need for more effective treatments. Current antidepressant medications are effective for approximately 65% of depressed patients and require long-term treatment for weeks to months before a therapeutic response is achieved.

The time lag in the therapeutic response, in spite of the rapid (hours to days) increase in monoamine levels, has lead to the hypothesis that neural adaptations or plasticity are required. One of the adaptations that may contribute to the actions of antidepressants is the upregulation of neurotrophic factors, most notably brain-derived neurotrophic factor (BDNF), in limbic structures that have been implicated in depression. Notably, exercise also increases the expression of BDNF.

Here we extend these results by using a focused microarray to show that exercise upregulates a primary signaling cascade for neurotrophic factors and a peptide precursor, VGF, that has strong antidepressant efficacy in behavioral models.

....A role for neurotrophic factor signaling and its downstream gene targets in the antidepressant actions of exercise is consistent with a large body of literature showing opposing actions of this pathway in the pathophysiology versus the treatment of depression. The selective induction of VGF by exercise, as well as by ECS, also indicates that there are differences in the molecular mechanisms underlying these treatments in comparison to chemical antidepressants. This highlights the potential importance of VGF as a new endogenous, exercise-regulated target for drug development that could have complementary and possibly even superior efficacy to chemical antidepressants.


Thursday, January 03, 2008

Virtue Ethics and Enhancement Paper (now online)

My paper "Virtue Ethics and Prenatal Genetic Enhancement" is now available in the first issue of the new journal Studies in Ethics, Law, and Technology. The issue is dedicated to the topic of human enhancement. Here is a lengthy sample of my argument:

In this paper I argue that the virtue ethics tradition can enhance the moral discourse on genetic enhancements in distinctive and valuable ways. Virtue ethics prescribes we adopt a much more provisional stance on the issue of the moral permissibility of prenatal genetic enhancement. This means great care will be placed on differentiating between the different stakes involved with developing different phenotypes in our children and the different possible means (environmental vs genetic manipulation) available to parents for pursuing legitimate concerns of parental love and virtue.

Key components of the virtue ethics account of morality, such as the Aristotelian account of happiness, love and the doctrine of the mean, provide an adequate basis for rejecting the claim that it is morally impermissible for parents to pursue (safe and effective) prenatal enhancements. Furthermore, there is good reason to believe that a virtue ethics account of morality could actually support the stronger claim that utilising such interventions can (in certain contexts) be morally required.

....So our question is: would virtuous parents pursue prenatal enhancement of a child who is expected, assuming they are exposed to a particular bundle of environmental interventions (e.g. nutritious diet, safe home environment, education, etc.), to fall within “normal species functioning”? As I shall emphasise shortly, much of course hinges on the assumption concerning the available environmental interventions a parent will (likely) have at their avail.

....Virtuous parents will recognise that many formative environmental interventions are multifaceted. That is, they serve many laudable aims at once. So parents read to their children, not only as a way to develop the cognitive capabilities of their children, but also as a way of spending time with a child, forging the psychological connectedness and continuity necessary for true love and friendship. Reading stories together provides the child and parent with shared experiences (e.g. the adventures of Pooh Bear, etc.) from which they can have further discussions and reflections. These stories will relate, in different ways, to the ups and down of real life. Sharing such stories helps a parent and child address issues like friendship, morality, happiness, human history, etc.

Sharing these experiences with one’s child not only enriches a child’s cognitive capabilities and moral development, and the bond between the parent and child, but it also enhances the parent’s own practical deliberation. It permits the parent to re-visit, in intimate ways, the psychology of childhood again; its naivety, fears and optimism. And this enhances a parent’s practical deliberation and better positions them to relate in virtuous ways with their children as well as others.

Virtuous parents will not pursue genetic enhancements as a substitute for providing the formative environmental interventions necessary for human flourishing. Virtuous parents know that a child’s needs change over time, as the circumstances influencing their lives (e.g. their school, friends, diet, hobbies, etc.)change. No “one-off” prenatal genetic enhancement will replace the judicious judgement of fine-tuned environmental interventions that are shaped and developed to meet a child’s particular needs over the course of their physical, psychological and moral development...

As the father of three I really enjoyed writing this paper and thinking about these issues. And the argument developed in the paper actually expresses my own (not yet fully developed) perfectionist conception of the good life. And this account of ethics is something I have only recently come to endorse. I plan on doing a future post on how I switched from being a non-perfectionist liberal to a perfectionist liberal. But this paper captures some of the central ideas that have helped me re-shape my thoughts about what constitutes the good life. And forging caring, loving relationships is the cornerstone of this vision of ethics. And so I think the issue of enhancing one's offspring (whether through biological or environmental intervention) is a useful way of getting to the heart of some very important moral issues.

As I noted earlier, my argument is not quite "The Case in Favour of Perfection". A more accurate description would be "The Case for Not Prejudging How Parents Can Best Help Their Children Flourish!".


Wednesday, January 02, 2008

The Complex Challenges of Mitigating Disadvantage

Two of my main research projects address the general issue of the moral duty to prevent/mitigate disadvantage. My recently published book Justice, Democracy and Reasonable Agreement defends a virtue-oriented account of justice in non-ideal theory. And my ongoing research on genetic justice addresses some of the ethical, social and legal implications of the genetic revolution.

Any fair and humane society will aspire to prevent and mitigate disadvantage/suffering/etc. But many things complicate the story of how we move from this general moral aspiration to comprehensive practical strategies for improving people's life prospects.

Consider for a moment just the complexities of addressing domestic justice within an affluent liberal democratic country like Canada. Many might feel inclined to say that this is an easy case; that the real important and challenging issues are ones that raise global concerns (e.g. global poverty, climate change). That may be true, but I think reflecting on what justice requires in the case of domestic justice is still an important and insightful exercise in its own right. For it can help us realize (1) how intrinsically vulnerable human beings are to different kinds of disadvantage, and (2) how diverse, flexible and yet also limited the instruments of government can be in promoting the life prospects of a population. So please permit me to expand a little on the case of domestic justice.

Suppose we know that something bad will happen to some of our compatriots and that we might prevent this from happening by pursuing a particular course of action (Action X). Should we pursue Action X? From the very vague and general information I provide here it is hard to know whether it would be wise and just to pursue Action X. So what kind of information would help us in this context? Well, firstly it would be useful to know the severity and magnitude of the harm in question (e.g. death, disease, unemployment, etc.). It would also be useful to know what the likelihood of success would be for intervening (e.g. is Action X 99% effective in preventing this harm or only effective 50% of the time? etc.). And finally, we might also want to know what the cost of pursuing Action X is. Not only in financial terms, but also in terms of other important values we might care about. Perhaps Action X limits the liberty of others, or it would divert scarce public funding from another laudable social policy.

Bringing these empirical considerations to the fore makes us appreciate how difficult it is to implement and discharge responsible risk-management policies at the level of just domestic justice. It is often the case that we do not have all of the pertinent information at hand (indeed such info may not even exist) regarding the likelihood of success, costs, etc. When is it fair and responsible to act in the absence of such information? And how do we determine how we should prioritize among the almost infinite list of things we could try to protect ourselves against?

Suppose, for example, that the probability and cost of success for a range of interventions are roughly comparable. But the harms they could prevent or mitigate are very different. So Action A would reduce the number of innocent persons wrongly incarnated for criminal offenses by n, Action B would lower the number of traffic fatalities by n. And Action C would reduce by n the number of people who die from a particular disease.

All three of these outcomes would be important outcomes to achieve. But what if we cannot afford to pursue them all? How do we go about prioritizing them? And even more challenging, how do we prioritize them when we have imperfect and incomplete information concerning the cost-effective measures available to actually mitigate the disadvantages in question?

I think these are very pressing questions that should play a much more prominent role in the deliberations of political theorists who aspire to give us a “big picture perspective” of the moral and political landscape. There is a danger with generating a priority list from a purely conceptual analysis of political values (e.g. liberty trumps equality, etc.). I think it is also a mistake to endorse something stronger than a provisional attitude about these issues. The more we learn about the things that influence our wellbeing- including the impact of our individual actions and the apparatus of government- our priorities and the prescriptions of government will no doubt change and alter. And how one conveys all of these things in a coherent, defensible public ethic is, I believe, an interesting and important project. And that is why I hope the tide is turning away from ideal theory towards a vision of political theory/philosophy that integrates normative theory with a richer appreciation and understanding of the importance of the empirical. Sensible deliberations about the kind of society we want must be informed by an appreciation of how we got to where we are and the challenges we face in moving from the "here and now" to a better society.