Friday, February 29, 2008

Is "Acceptingness" A Parental Virtue?

I just read two interesting articles by Rosalind McDougall on parental virtue and reproduction. The first is "Parental Virtue: A New Way of Thinking About the Morality of Reproductive Actions" in Bioethics Vol21(4), 2007 and "Acting Parentally: An Argument Against Sex Selection" in Journal of Medical Ethics 31, 2005.

These papers are of particular interest to me as I have argued (here) that a virtue ethics approach to reproduction can view some pre-natal interventions (like genetic enhancement) as not only morally permissible, but as *morally required*. One of the distinctive features of McDougall’s approach, which I think explains the somewhat different conclusions we arrive at, concerns what she calls the virtue of "acceptingness". She argues that it is an intrinsic feature of a child that his or her characteristics will be, to some extent, unpredictable. And "this fact renders acceptingness a parental character trait conducive to the flourishing of the child and thus a parental virtue" (PV, 185).

This is an interesting way to think of parental virtue, and I thought I would offer some of my initial thoughts about it here.

Let’s begin with the claim that it is an intrinsic feature of a child that their characteristics will be, to some extent, unpredictable. I think a lot hinges on the issue of “to some extent”. I am willing to grant this. But at the same time I think the notion of acceptingness threatens the concern for flourishing which, as McDougall acknowledges, is the cornerstone of the virtue ethics account of reproduction.

Take height. The precise height your child will reach in adulthood is somewhat unpredictable. No prenatal genetic test will give you a precise estimate of height. Environmental factors like the diet the child consumes is vital for their height. However, the genes the child inherits do impact the likelihood that the child will, with proper nourishment, fall between a certain min and max height.

Consider now cancer. The precise likelihood that your child will die of cancer before reaching the age 60 is somewhat unpredictable. No prenatal genetic test will give you a precise estimate of all cancer risk. Environmental factors like lifestyle, smoking, stress, etc. are important risk-factors for complex diseases like cancer. However, the genes the child inherits do impact the likelihood that the child will, even with proper nourishment and lifestyle, fall below or above the average risk for developing certain cancers.

Consider now intelligence. The precise IQ your child will attain during adulthood is somewhat unpredictable. No prenatal genetic test will give you a precise estimate of potential for intelligence. Environmental factors like parental care, education, diet, exercise, etc. are vital for a complex phenotype like intelligence. However, the genes the child inherits do impact the likelihood that the child will, even with a loving home, decent education, etc, fall below or above the average IQ.

Okay, so I can appreciate how invoking the notion of acceptingness as a virtue would dissuade parents from pursuing prenatal interventions that promised to deliver predictable traits that simply are not predictable. For example, if a parent believed that there was a gene for artistic expression and wanted a child with that gene so they could become the next Picasso. But it seems to me that such scenarios can be ruled out of hand by simply saying that virtuous parents would not make procreative decisions that were based on bogus assumptions about genetic determinism. So a virtuous parent would not undergo PGD to screen for the artistic embryo, or subject a fetus to a prenatal artistic enhancement, because these things would not be achievable (so virtuous parents are not stupid). Furthermore, planning the specifics of your child’s life like this would compromise a child's right to an open future. And thus a parent compromises a child’s opportunity for flourishing by having some specific lifeplan in mind (e.g. “You are going to be a great artist!"). But I don’t think we need to classify “acceptingness” as a parental virtue in order to get us to that conclusion.

Furthermore, I think the notion of acceptingness threatens genuine parental virtue (and the flourishing of one’s offspring). Part of the difficulty that I have with the notion of “accepting” a child’s characteristics is that it overlooks the central function virtuous parents are to play in their children’s lives: to help their children flourish. A child is not born with a set of “characteristics”, rather these characteristics evolve over the course of a child’s development, through adolescence and continue to develop for the rest of a person’s life. No one ever reaches a stage where this process stops, and one then has a fixed, stagnate list of characteristics.

For example, when one’s child is aged 3 they will have particular characteristics in terms of their intelligence, sociability, etc. But a virtuous parent will hope these characteristics develop, and they will play an active role in ensuring this occurs. So by the time the child reaches age 13 they have a different set of characteristics that they did not (and probably could not) possess at age 3 (reading, writing, riding a bike, etc.). And so on.

So even though a child’s characteristics are unpredictable, a virtuous parent will seek to pursue environmental interventions that reduce the likelihood of certain characteristics becoming part of their child. For example: traits like being stunted, malnourished, illiterate, impaired, etc. And they will seek to increase the likelihood that their children will come to acquire other characteristics. Namely, those that a flourishing agent possesses (e.g. friendship, health, practical reason, etc.).

I guess I remain puzzled as to why the notion of acceptingness would be construed as a trait of a virtuous parent. I can see some of the attraction, in the sense that it shows us why the “control freak” parent acts contrary to virtue. But I don’t think it is hard to see their shortcomings. Such parents impair their child’s opportunity for flourishing by enforcing a particular, detailed future on them- thus stifling a child’s individuality and imagination. But I believe a virtuous parent will play a proactive role in shaping the phenotypes of their children so that they can achieve eudaimonia. And the notion of “acceptingness” seems to run counter to what I take to be integral to virtuous parenting.

Let me conclude then by tying this up with the issue of intervening in the genotype of one’s offspring (e.g. through prenatal therapy or enhancement). Because a child’s opportunity for flourishing will be profoundly impacted by both their genes and their environment, virtuous parents should not rule out of hand the duty to intervene in either. A prenatal intervention to remedy a single-gene disease like CF, or an intervention that seeks to reduce the life-expected risk of cancer, are virtuous actions. Similarly, parents that take reasonable steps to ensure their children are physically active and don’t “hangout with the wrong crowd” are virtuous. In all these cases the parents, assuming the means pursued are not risky, ineffective or too intrusive, are acting virtuous. They are taking reasonable steps to increase the likelihood that their children will live flourishing lives. And this proactive attitude is warranted because these children are *their children*.

While I agree that there is a sense in which acceptingness can be virtuous, I don’t think it makes sense to call it a parental virtue. Primarily because a child is constantly developing and thus there is nothing that a parent can really be said to accept (other than the fact that traits are somewhat unpredictable). Sure virtuous parents will recognize the individuality of their children, even their limitations (e.g. “He’ll never be a soccer star!”), but that doesn’t mean they accept the traits their children happen to have at any given age as things beyond parental concern and involvement. Virtuous parents are a positive, formative influence on their children’s lives.


Thursday, February 28, 2008

The Brilliance of Bentham.

Many important ideas have been advanced in the history of moral and political thought- Plato on justice; Hobbes on the social contract; Locke on property; Rousseau on democracy; Mill on liberty, etc. The list goes on and on... And those lucky enough to spend their lives pondering the great thinkers of the past (and present) often forget what a luxury and privilege it is.

Here is a thought experiment: Suppose an instructor had only a 1 hour window with which to teach one idea or figure from the history of ethics. And this 1 hour class would be recorded and all future generations around the world would watch it and reflect upon and discuss what you teach.

What issue, insight or idea would you choose that would help equip future generations to meet the challenges they would face?

Hmmm, interesting question! What idea or figure would I choose? If I stop and think about it, I would probably spend that time talking about the philosopher I covered in my second year class today: Jeremy Bentham.

For the record, I am not a Bentham scholar, nor do I consider myself a utilitarian (though perhaps I am a closet consequentialist, as I believe virtuous agents- and aspiring virtuous agents- are really, deep down, sophisticated consequentialists!). So just to be clear, I’m not choosing Bentham because he figures prominently in my own research or writings.

But if there was just one idea or insight I would want the next generation of humanity to consider and reflect upon, as they face the deluge of important issues they face, it would be Bentham’s brilliant “Calculus of Happiness”.

When facing decisions concerning how we ought to live our lives, both as individuals and as societies, Bentham argues that we ought to consider the *consequences* of our actions. More specifically, we should seek to maximize pleasure and minimize pain. In order to sensibly think about how we could do this, Bentham believes we ought to apply the following calculus of happiness:

1. Intensity of the pleasure
2. Duration of the pleasure
3. Its certainty/uncertainty
4. Remoteness [nearness in time]
5. Fecundity [likelihood that it will be followed by sensations of the same kind]
6. Purity [likelihood that it will be followed by opposite sensations]
7. Extent [the number of persons to whom it extends]

Now, I have chosen Bentham’s calculus not because I think we should endorse it full stop. Rather, I believe that his consequentialist insights are where I think all moral agents should start their reflections (though perhaps not end!). Instead of making decisions based on religious dogma, or abstract thought experiments like Rawls’s original position or Kant’s categorical imperative, Bentham’s public ethic requires us to take seriously *empirical information*. Like the amount of happiness in question, the likelihood this happiness will be achieved, the negative consequences our action could have on others, etc.

Bentham’s concise calculus, more than any other idea I can think of in the history of ethics or political philosophy, captures what I think is one of the (if not the) most important components of living a good life and establishing and maintaining a flourishing society— knowledge.

Whatever one might take the flaws of consequentialism to be (e.g. it permits the violation of side-constraints, ignores the importance of virtue etc.), its main strength, in my opinion, is that it explicitly rules out letting dogma, superstition, ideology, etc. infest our deliberations concerning how to live our lives. And that’s a pretty big asset of a moral and political theory! An asset few contemporary normative theories possess.

Sure I would want to say a lot more, if I had more than the 1 hour window, to talk about the potential problems with Bentham’s calculus, what rival normative theories might offer, etc. But in this thought experiment I am asking us to limit ourselves to just the 1 hour window, for doing this is helpful in reflecting on what we want from our normative theories. For example, is it more important that they achieve the requisite level of precision vs proportionality? Which is more important if we want to increase the likelihood that our normative theories will lead us in the direction of living well? So if the moral compass we leave future generations is Bentham’s calculus of happiness then I think we would not, as many deontologists maintain, be doing them a disservice. Far from it.

Of course I would not want future generations to simply accept and blindly live by Bentham’s calculus (thus making it the secular equivalency of conventional religion). Rather I would want them to think about the pros and cons of Bentham’s utilitarianism. To think about the different ways their actions can impact the lives of others, to think about the uncertainty of the impact their actions can have, and the purity and impurity of their actions, etc... These are all great insights we often ignore! And so I think the brilliance of Bentham has been overlooked by contemporary moral and political philosophers. Bentham’s ideas are perhaps more important today than ever.


Wednesday, February 27, 2008

More on Risks of Death and Priority Setting

Following on from my previous post... when thinking about society’s main priorities one could focus on many different facts (e.g. economic prosperity, education, disease, etc.) and moral principles (e.g. equality, liberty, etc.). And any attempt to determine what justice requires, “many-things-considered”, will involve the Herculean task of piecing the various pieces of the justice puzzle together in a way that gives due attention to the diverse, and sometimes competing, demands of justice.

One important part of the story of getting an accurate sense of the “big picture” of what justice demands is to consider what the leading causes of human death are. Though we might not want to be reminded of this fact, the reality is that human beings are intrinsically vulnerable. We can die from starvation, conflict, natural disasters, parental neglect, car accident, choking, drowning, cancer, poisoning, obesity, aging... etc. Tragically the list goes on, and on, and on….

Okay, given that risk of death is so omnipresent, then we need to think rationally about setting some priorities for mitigating, or minimizing the risks of, these various causes of death. To do this one needs a clear sense of what the most prevalent causes of death are. And the answer to this question will vary depending on where one lives (e.g. in the developed world vs the developing world). It also depends on the timeframe we invoke. If we ask what killed most people in the world in the twentieth century then we would have to acknowledge the enormous costs of war, infant mortality, infectious diseases like smallpox, poverty, etc. Some of these things will also cause many deaths in this century, and yet others most likely will not (e.g. smallpox). Just because something has, historically, been a leading cause of death does not mean it will necessarily be so in the future.

It would however be a mistake, when setting priorities, to focus merely on those things that actually have caused human deaths. There are also things that could possibly cause human deaths- such as a nuclear war, or a new infectious disease, etc. And so reasonable risk management will require us to consider the magnitude of the harms different risks pose for us, as well as the likelihood that these harms will be realized (and the likelihood that we could take steps to avoid these harms).

Unfortunately it is really difficult to get an accurate sense of what the biggest challenges facing humanity this century will be. We do not possess a crystal ball. Furthermore, our sense of reality is often influenced by sensationalist journalism, exaggerated alarmism propagated by politicians catering to the public’s fears or special interests.

Public perception of real health risks is, especially in the post 9/11 mindset, particularly troubling. How many Americans, for example, have died of terrorist attack versus obesity? Are the fears and anxieties that Americans have about the likelihood that they will be killed by terrorists proportionate to the fears and anxieties they ought to have about the quantities of food they consume, or their inactive lifestyles? How many Americans will likely die from cancer versus climate change?

And if one considers things from the global perspective, one can ask- how many will die from war, from poverty, from HIV, from climate change, from cancer, from aging?

One way to help focus our minds on the reality of the challenges facing us, without inundating us with endless statistics, is to consider the following thought experiment: think of all the people you have known who have died. The results of this exercise will vary depending on what country you live in. But for now let's assume most of my readers are in the developed world. Ask yourself what the most common cause of death has been. Perhaps you know someone who died in a car accident. Or you know someone who died of cancer. Etc.

As you try to determine what the most common cause of death has been among your friends and family, you will start to see that the majority of these people share one thing in common: they were older than you.

This is especially true for people who are not themselves that old. The older one gets the more likely it is that many of their own contemporaries have also passed away. So the diseases (cancer, diabetes, AD, etc.) and frailty of aging are the most prevalent causes of death (though it varies depending on the affluence of one's country). Aubrey De Grey puts the toll of daily global deaths caused by aging related causes at 100 000 a day. And in the industrial world, approximately 90% of all deaths are caused by ageing (De Grey, 2007: 8).

Now gathering facts about the causes of human death is a contentious business, and such facts do not completely settle all the important issues that must be addressed when setting priorities. So I am not suggesting that tackling aging ought to be our #1 priority. But appreciating the realities of what causes human death is an important step in grasping a sense of the “big picture” of things. So does an understanding of the likelihood that we can actually do something to retard human aging. Once we combine the facts concerning the magnitude of mortality and morbidity caused by our biological vulnerabilities with the amazing scientific advances that have been made in the past decade in the science of longevity, then we cannot justify the current marginalization of aging research.

If I were a betting man, I would put money on the bet that more human beings this century will suffer disease and death from DNA damage, RNA damage, oxidation, etc. than anything else. The greatest threat to our health might in fact be our own biology- the biological vulnerabilities we have inherited from our evolutionary history. If I am right, then the costs (to our health and economies) of aging must inform our decisions concerning what our main priorities ought to be. I know hearing me say this will raise a lot of questions and concerns from my readers. And I don't pretend for a moment to presume these are easy issues for us to address and discuss. But we cannot afford to ignore them.


Tuesday, February 26, 2008

Climate Change and Death Rates

I came across two interesting stories today in UK newspapers on the issue of deaths caused by climate change. The first is this piece by Simon Lewis who asks "Climate change is killing us. So why are we still so reluctant to quantify the deaths it has caused?". Well, this story from two weeks ago in the BBC News perhaps offers an answer- because climate change may actually result in less domestic deaths for the UK.

As the story highlights, the winter weather in the UK kills approximately 20 000 people each year. Whereas an extremely hot summer (which has only a 25% chance of occuring in the next 10 years) would only claim 6000 lives. The report was commissioned by the UK Department of Health and Health Protection Agency (HPA). It also mentions that greater exposure to the sun could result in an increase in skin cancer, but it could also result in a decline of other kinds of cancer (see my recent post on that here).

I suspect the data provided in this UK report is not the kind of info Dr. Lewis was hoping for as it would suggest that the imperative to reverse climate change is not the single biggest issue facing humanity (or at least the UK). Of course climate change is an important concern, but then there are lots of pressing issues facing humanity. And so our response to any one thing must be fair and proportionate or else we run the risk of doing more harm than good. So we must be clear on what the costs to human lives will be from climate change versus other things- like poverty, cancer, war, etc. And without sound empirical evidence that climate change will cause anything close to the costs of conflict (see this), or something like cancer, which killed 7 million people worldwide in just the year 2005 alone (see here), then it is unjust for us to treat climate change as if it is the number one priority of the world.

Now there is some overlap between issues like poverty, disease and climate change. But I have always found it odd that climate change seems to have impaired the historical sensibilities of many intelligent people, as if starvation and disease (as well as hot summer days and the hurricanes) are recent phenomena that did not occur before temperatures rose. Furthermore, if we really want to benefit the globally disadvantaged then we should advocate those things that will help the poor now (not in 50 or 100 years). No doubt tackling climate change can be a part of a global strategy, but it is only a small part of it. Unfortunately we do not hear enough about the importance of other things (e.g. like providing bed nets for malaria, tackling HIV, removing the farming subsidizes that exclude the poor from competing on the market, etc.)

For an excellent overview of the complexities involved with climate change justice I highly recommend Cass Sunstein and Eric Posner's article "Climate Change Justice"


Sunday, February 24, 2008

AD Test; Pressures of Conformity

The latest issue of Science has a number of interesting articles. The News of the Week Piece "Once Shunned, Test for Alzheimer's Risk Headed to Market" by Jennifer Couzin details a new genetic test for AD that is set to come to market:

A Pennsylvania company is preparing to market a genetic test that will tell healthy people whether they are at increased risk for developing Alzheimer's disease. The move comes more than 15 years after the critical gene, APOE, was linked to Alzheimer's, and it is getting a mixed response from researchers. Some of them point out that the test could upset people without giving any therapeutic benefit. On the other hand, as the company says, the information has its uses, and research has shown that receiving a bad result is not as devastating as once feared.

The test will be offered by Smart Genetics in Philadelphia, likely starting next month. For $399, healthy people will give a saliva sample and learn whether they have a risk of Alzheimer's that's 3 to 15 times higher than normal. The analysis is based on variations in the APOE gene, which is widely agreed to play a role in Alzheimer's risk and heart disease.

And there is also an interesting News Focus piece entitled “Crossing the Divide” which details the immense social pressures even scientists face as they attempt to square their personal beliefs with the findings of science. Which makes the case for getting serious about tackling these issues all the more important. Here is a sample from the story about paleontologist Stephen Godfrey:

On a clear January day, Stephen Godfrey is dressed for fossil-hunting: frayed baggy jeans, a puffy green vest, and a leather jacket that's seen better times. A paleontologist and curator at the modest Calvert Marine Museum here, Godfrey frequents the nearby Calvert Cliffs, which rise from the shoreline of Chesapeake Bay and hold everything from ancient shark teeth to dolphin skulls. "You start collecting them because, well, they're beautiful," he says of his beloved fossils.

It was the study of fossils that, 25 years ago, set Godfrey on an anguished path. Raised in a fundamentalist Christian family in Quebec, Canada, embracing a 6000-year-old Earth where Noah's flood laid down every fossil, Godfrey began probing the underpinnings of creationism in graduate school. The inconsistencies he found led step by step, over many years, to a staunch acceptance of evolution. With this shift came rejection from his religious community, estrangement from his parents, and, perhaps most difficult of all, a crisis of faith that endures.

Powerful emotions bind together young-Earth creationists, members of a movement making inroads from Kenya to Kentucky, where a $27 million Creation Museum opened last year. Scientists and educators have responded mainly by boosting biology's place in the classroom and building rational arguments for evolution. But reason alone is rarely enough to sway believers. That's because letting go of creationism carries enormous emotional risks, including a loss of identity and community and an agonizing, if illusory, choice: science or faith.


Friday, February 22, 2008

New Gene Therapy Targets Brain Cancer Cells

Cancer Research UK has this news update about a new gene therapy approach to GBM, an aggressive form of brain cancer. Here is a sample from the story:

Scientists are developing a new gene therapy approach that 'trains' the immune system to destroy brain cancer cells and may even restore normal brain function.

The approach is being tested on animal models with glioblastoma multiforme (GBM), an aggressive form of brain cancer that often affects concentration, memory and balance as the tumour compresses nerve cells.

Researchers at Cedars-Sinai Medical Centre used a modified virus to deliver two therapeutic proteins directly into tumour cells.

One of the proteins, 'FMS-like tyrosine kinase 3 ligand' (Flt3L), attracted a class of immune cell called dendritic cells to the brain. Dendritic cells clear up dying cells and alert the immune system to the existence of foreign objects, such as cancer cells.

The other protein, 'Herpes simplex virus type 1 thimidine kinase' (HSV1-TK), when combined with the antiviral drug gancyclovir, proved directly toxic to tumour cells.

Publishing their initial findings in the journal Molecular Therapy, the researchers revealed that around 70 per cent of animals survived, compared to just 20 per cent when the dendritic-cell inducing Flt3L was left out.
The publication of the study in Molecular Therapy is here.


Wednesday, February 20, 2008

Embryonic Stem Cells and Diabetes

Yesterday I noted an article that helped shed light on the evolutionary history of the development of metabolic disorders. Today we hear the exciting news that researchers at the biotech company Novocell have been able to convert embryonic stem cells into cells that produce insulin for mice. The NY Times has the scoop here, and here is a sample:

Scientists reported on Wednesday that they were able to control diabetes in mice by harnessing human embryonic stem cells. The work raised the prospect that the embryonic cells might one day be used to provide insulin-producing replacement cells to treat the disease in people.

The scientists, at the biotechnology company Novocell, turned the stem cells into cells that produced insulin in the mice. Those cells kept blood sugar in check after the mice’s own insulin-producing cells were destroyed.

“For those who say there is not much evidence that embryonic stem cells can cure diabetes, there you go,” said Dr. Camillo Ricordi, director of the Diabetes Research Institute at the University of Miami, who was not involved in the research.

The study is published on the advanced online publication of Nature Biotechnology. Here is the abstract:

Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo

By Evert Kroon, et. al.

Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human -cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional -cells, including expression of critical -cell transcription factors, appropriate processing of proinsulin and the presence of mature endocrine secretory granules. Finally, in a test of therapeutic potential, we demonstrate that implantation of hES cell–derived pancreatic endoderm protects against streptozotocin-induced hyperglycemia. Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.

Lets hope a story like this can revive our optimism for scientific research and help topple the dogma and arrogance that has restrained stem cell research.


(Yet) More New Insights Into Our Evolutionary History

Following on from my post yesterday, today's issue of Nature contains two interesting studies that reveal how migration has impacted the number of deleterious genetic mutations present in different populations. The two articles are "Proportionally more deleterious genetic variation in European than in African populations" by Kirk Lohmueller et. al. and "Genotype, haplotype and copy-number variation in worldwide human populations" by Mattias Jakobsson et. al. The Nature Editor's summary nicely outlines the two studies:

The analysis of genome-wide patterns of variation in human populations can provide genetic evidence of patterns of human migration and adaptation across the world. Two contrasting papers in this issue illustrate the power of the method. By combining a large number of datasets, Lohmueller et al. obtain precise estimates of the number of deleterious mutations carried by each of 15 African-Americans and 20 European-Americans, resequenced across 11,000 genes. They find that individuals with a European background have more potentially damaging mutations lurking in their genomes than those with an African background. This is interpreted as a genetic legacy from the 'out-of-Africa' bottleneck that accompanied the peopling of Europe. Jakobsson et al. take a broader snapshot of human variation by examining 29 populations in the Human Genome Diversity Project. They obtain genotype data for over 500,000 markers in the human genome. Echoing the study of Americans with African and European backgrounds, these data reveal increasing linkage disequilibrium with increasing geographic distance from Africa.

It's amazing to see how quickly the pieces of our evolutionary history are beginning to be put into place. And the more we understand how we arrived at where we are, the more likely we will be able to move forward to create a world with less disease and disadvantage.


Tuesday, February 19, 2008

PLOS Article on Climate, Genes and Metabolic Disorders

Metabolic disorders relate to how the body absorbs food and processes into energy. Diabetes is an example of a metabolic disorder. Here are some stats on diabetes from the World Health Organization:

Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin, or alternatively, when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood sugar. Hyperglycaemia, or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially the nerves and blood vessels.

The World Health Organization (WHO) estimates that more than 180 million people worldwide have diabetes. This number is likely to more than double by 2030.
In 2005, an estimated 1.1 million people died from diabetes.

Almost 80% of diabetes deaths occur in low and middle-income countries. Almost half of diabetes deaths occur in people under the age of 70 years; 55% of diabetes deaths are in women.

WHO projects that diabetes deaths will increase by more than 50% in the next 10 years without urgent action. Most notably, diabetes deaths are projected to increase by over 80% in upper-middle income countries between 2006 and 2015.

Prevention of type 2 diabetes can be achieved by maintaining a healthy weight and exercising.

Like my previous post on Why We Develop Cancer, one can ask why we, as a species, develop metabolic disorders? The latest issue of PLOS Genetics has a very interesting study which examines this question. And the study's conclusions are truly fascinating-- adaptations to climate might be an important part of the story.

The article is entitled "Adaptations to Climate in Candidate Genes for Common Metabolic Disorders" by Angela Hancock et. al. and you can download it for free here. Here is a summary of their findings:

The human species inhabits a wide geographical range encompassing a diversity of climates, and adaptation to these climates likely played an important role in shaping genetic and phenotypic variation among populations. We hypothesized that spatially varying selective pressures related to climate shaped the frequencies of genetic variants in the energy metabolic pathway. To test this hypothesis, we examined patterns of genetic variation in 82 candidate genes for common metabolic disorders across the 52 globally dispersed populations of the Human Genome Diversity Project. We applied a combination of statistical approaches to test whether the geographic distribution of these variants could be accounted for by differing climates, consistent with a signal of spatially varying positive selection. For several climate variables, we observed signals in excess of that expected from human population history and chance alone. Significantly, many of these signals were from genes previously shown to affect cold tolerance and disease risk. Our results provide evidence that variation among human populations in susceptibility to common metabolic diseases may be due, in part, to different histories of selective pressures on genes in these disease pathways. Furthermore, our results point to additional genes and variants that are suitable targets for follow-up disease association studies.


Monday, February 18, 2008

Academic Health Research in Canada

Recall my previous post concerning a recent editorial in the EMBO Reports on reviving our optimism for scientific research. Well, while I was searching around for some data on the state of academic health research in Canada I came across this recent editorial in the CMAJ. It is entitled "Getting Serious about Canadian Health Research". The authors argue that research is a fundamental public good. They also argue that "the research community must first persuasively explain the rationale for and evidence of a need for increased funding. Canadian taxpayers have a right to know what their hard-earned dollars will buy and how it will improve their health or the state of the economy, or both". Here is a sample from the editorial which shows how Canada lags far behind the US in terms of per capital expenditures on academic health research:

...the Canadian government needs to decide once and for all whether it is serious about being a meaningful global player in health research. To do so, it must vastly increase research outlays to the level provided by leading Organisation for Economic Co-operation and Development (OECD) nations. The United States, for example, will spend $28.9 billion on academic health research in 2007, or $95.37 per capita. Canada will spend $828 million, or $25.09 per capita. If government is not interested in being a global player, then it should give up the charade. Canada's researchers, who have proven they can do more with less, are ill-served by short-term promises followed by long-term disappointments. If the funding won't be there, our best and brightest scientists should be told honestly to shop abroad for a stable platform on which to build the careers into which so much of their hard work and our tax dollars have been invested. The Canadian public should then be disabused of expectations that our health care problems will be addressed by made-in-Canada solutions, reflecting Canadians' priorities and values.

This final sentence raises a number of issues that should be of concern to political theorists. Firstly, I believe theorists (in Canada and in general) are failing in the sense that we do not take seriously the fact that research is a fundamental public good. As I have opined before, the current divide between science and political theory is simply inexcusable. So normative theorists are partly to blame for the pitiful investment that is made in academic health research. For we ourselves often completely ignore such issues when we allegedly tackle society's most pressing problems. How many theorists in Canada, for example, are seriously engaged in theoretical work that pertains to health research?

By neglecting science we are failing our students, our citizens and our discipline. The gap between science and political theory is, in my mind, the most important gap in need of filling. Of course it is not a topic that can simply be addressed by extending the debates of the past 30 years or so in political theory. And that just reinforces the shortcomings of contemporary political theory. When we lose sight of the "big picture" of the moral and political landscape it is time for a major re-think. And we cannot afford to waste any more time. The meager investment we make in academic health research impacts not only the health prospects of Canadians, but also other values and aspects of our culture and society as a whole.

The academic work of normative theorists should not simply be "academic" work. It should help us diagnose the problems with the status quo and help inspire some sage prescriptions concerning how we ought to move forward. And theorists will be better positioned to do this if they take science more seriously.


Sunday, February 17, 2008

Family Day in Ontario

Thanks to the Ontario Liberal Party, Monday is a new public holiday- "Family Day". Dedicating a public holiday to the most important institution in society is very fitting (and long overdue!). From the Ministry of Labour web page:

There is nothing more valuable to families than time together. And yet it seems tougher than ever to find, with so many of us living such busy lives. That's why, on the third Monday of this coming February--and every February from now on--Ontarians deserve a new public holiday--Family Day.


Russell on the Point of Philosophy

I just came across this very insightful and humorous interview with the late great Bertram Russell. Russell addresses the very important methodological question of what philosophy actually is. Do philosophers simply seek to clarify the meaning of questions, or should they also try to help us answer them? Russell claims that the rise of linguistic philosophy reduces philosophy to the former. And this impoverishes philosophy. He gives the following example of how it does this:

Russell was biking to Winchester, but had gotten lost. He stopped in a small village shop and asked the clerk if he knew the shortest way to Winchester. The clerk then called to a man in a backroom that Russell couldn’t see.

Clerk: “The Gentleman wants to know the shortest way to Winchester”.

Voice in backroom: “Winchester?”

Clerk: “Aye”

Voice in back room: “Way to Winchester?”

Clerk: “Aye”

Voice in backroom: “Shortest way?”

Clerk: “Aye”

Voice in backroom: “Don’t know!”

Russell: “So I had to go on my way without an answer”.

This is great! I share Russell’s sentiment, and believe these concerns still apply, especially to contemporary political philosophy.


Saturday, February 16, 2008

NEJM Article on Genomic Variation and Personalized Medicine

The latest issue of the New England Journal of Medicine has this interesting article by Charles Lee and Cynthia Morton entitled "Structural Genomic Variation and Personalized Medicine". The article appears in the section for "Clinical Implications of Basic Research". The authors note the importance of this recent study which revealed that the almost exclusive attention given to qualitative differences in the genome is unwarranted. As Lee and Morton note, "quantitative differences, such as deleted and duplicated genomic sequences, and large-scale rearrangements (collectively referred to as structural genomic variant architecture) are just as — or more — relevant".

These empirical insights have important implications for an account of genetic justice. For example, in this recent paper I argued that genetic inequalities were qualitative rather than quantitative inequalities. Well, now I know this is not the case after all (though I think it is safe to say that this was the standard scientific view at the time I actually wrote the article!). And so this empirical fact is worth noting as it could impact our determination of what kind of intervention is required (e.g. one that remedies qualitative versus quantitative differences). And it is precisely these kinds of discoveries that have lead me in the direction of arguing that the demands of genetic justice are provisional- they are open to new moral insights and empirical discoveries. Furthermore, I don't think these issues necessarily undermine or pose a serious problem for the central principle of genetic justice I defend. That is, the lax genetic difference principle which states that genetic inequalities (important to the natural primary goods) are to be arranged so that they are to the greatest reasonable benefit of the least advantaged.

Here is a sample from the NEJM article:

The ultimate goal of personalized medicine is to comprehensively identify genetic differences among persons and to correlate specific genetic features (or combinations of genetic features) with the differential risk of human diseases or the efficacy of certain therapeutic interventions. This goal is likely to be achieved when we are able to identify all relevant forms of genetic variation in each person and are able to interpret this information in a clinically meaningful manner.

The Human Genome Project revealed a very high degree of similarity between the DNA sequences of any two persons. These similarities unite us as a species. On the other hand, the differences in our DNA sequences (combined with the effects of our environment) make each one of us unique. Until recently, qualitative differences in the genome — in the form of single-nucleotide polymorphisms — have enjoyed the limelight. However, a recent study by Korbel and colleagues1 reinforces the notion that quantitative differences, such as deleted and duplicated genomic sequences, and large-scale rearrangements (collectively referred to as structural genomic variant architecture) are just as — or more — relevant.

....Physicians may eventually be able to use a person's genetic-variation profile to determine the optimal intervention for the patient's condition (Figure 1), although such a strategy will depend on genetically informed clinical trials. Of course, there will continue to be a struggle to provide this type of information so that a patient and a physician can make informed health-related decisions, while minimizing its effect on insurance-related discrimination. Nevertheless, we are currently witnessing an exciting discovery phase in human genetics that will undoubtedly affect the way physicians ultimately practice medicine.


Friday, February 15, 2008

The "What is Justice?" Question

I was motivated to write this post when I happened to come across this great passage from Supreme Court Justice Antonin Scalia (from A Matter of Interpretation (1997)):
What intellectual fun all this is! It explains why first-year law school is so exhilarating, because it consists of playing common-law judge, which in turn consists of playing king- devising, out of the brilliance of one's own mind, those laws that ought to govern mankind. How exciting! And no wonder so many law students, having drunk this intoxicating well, aspire for the rest of their lives to be judges.

Scalia's insights resonated with many of the concerns I have about political philosophy. So let me draw a parallel between what Scalia says about first-year law students and what I take to be problematic about the attitude of the great bulk of contemporary analytic political philosophers (who function at the level of ideal theory).

Philosophers are in the business of asking (and attempting to answer) complex, profound questions. For example, "What is Justice?". Socrates asks this question in one of the greatest philosophical works of all time- The Republic. And Socrates' question remains one of the most interesting and challenging questions in political philosophy. One of the most important works in political philosophy in the twentieth century was John Rawls's A Theory of Justice.

The question "What is Justice?" is without a doubt the single question that I have invested most of my own intellectual energies into pondering. And yet in this post I want to highlight the potential dangers of asking this question. Or more precisely, the dangers with trying to answer this question.

It might seem odd to suggest that there could be potential dangers with contemplating a philosophical question like "What is Justice?". Isn't the real danger the situation when we don't ask such a profound question?, one might reasonably retort. I agree that there are real dangers if we ignore this question, but I also believe there are dangers with becoming intoxicated by the challenge that Socrates raises for us in The Republic. And I believe many contemporary political philosophers have become intoxicated with this question. Let me explain.

One could set about answering the question "What is Justice?" in a number of different possible ways. And in The Republic we find Socrates's interlocutors presenting a number of answers that cohered with the views of Athenians. For example, that justice is giving a man his due. Or that justice is the interest of the stronger party. Socrates effectively dismantles all these answers, and then Plato sets the stage for developing his own account of justice. One where the just society is governed by (surprise, surprise!) Philosopher Kings.

Now few (if any) contemporary philosophers would endorse (at least explicitly) the conclusions Plato comes to in The Republic concerning what constitutes a just form of government. But when one tackles the "What is Justice?" question in a particular fashion one can't help but see the stark parallels between the reasoning that goes on in the philosopher's mind and the conclusions Plato reaches.

This insight is put very poignantly by Jeremy Waldron in his excellent book Law and Disagreement. When characterising most legal and political theory Waldron claims it is work of the following type: "I-expect-you’d-all-like-to-know-what-I-would-do-if-I-ruled-the-world". Now one might wonder what is wrong with such grandiose theorizing. Why not consider what the world would be like if it were ruled by Rawls, or Nozick, or Dworkin, etc.?

Well, I can think of a number of problems, problems which really undermine what I think political theory is suppose to do. For starters it compromises the value and importance of democracy. It also grossly overestimates the importance of the insights that a philosopher can give us when they are confined to the ivory tower. So generally speaking, it compromises those very things I believe political theory ought to aspire to achieve. Recall this post.

So the danger with asking the "What is Justice?" question arises when one presupposes that the best answers will be provided by what Vermeule calls "first-best conceptualism". That justice is: equality of such-and-such a kind; or liberty; or democracy, etc. Seldom are we satisfied with the answer- "Justice is a messy mix of all the above and much more!".

I guess that would be my answer, though I don't think it is likely to appear as the title of any academic paper I shall publish. The really difficult and interesting challenge is, I believe, to examine the appeal and limitations of different values, principles, institutions, etc. And so to really tackle the "What is Justice?" question we must see it as a question of real practical insight. This means the Philosopher Kings do not have privileged insights to offer us. Do philosophers have any role to play at all? Yes they do. But it is a limited role. Determining what justice requires, many-things-considered, requires much more than the tools of analytic precision or conceptual consistency could offer. It requires wisdom, which is inherently practical. And so we shouldn't attempt to answer the "What is Justice?" question by appealing to first-best conceptualism.

This takes me back to the interesting passage noted above by Scalia. Scalia's insight about the intoxicating effects legal theory has on first-year law students applies to political philosophers as well. There is nothing wrong with turning law or philosophy students on to these issues by contemplating the Philosopher King question. But when these students take this attitude to heart, so that it informs their attitudes as judges; or, in the case of political philosophy, it encompasses their identity as both citizen and scholar; this can be troubling. And so I think we need to critically reflect upon what we actually hope to achieve by asking the "What is Justice?" question. Can asking this question enlighten us? You bet. When addressed in the proper manner, it can even help us achieve phronesis. But the current state of contemporary political philosophy is one that impedes, rather than facilitates, phronesis. The longer version of that complaint is available here.


Thursday, February 14, 2008

Kant and Marley on Freedom

This term I am teaching "Classics in Political Thought 2" to around 90 undergraduate students here at UW. The course goes from Thomas Hobbes to Karl Marx. I really enjoy teaching this class, and I try to show the students that the ideas and theorists we study (e.g. property, the legitimacy of the state, democracy, equality, etc.) are still alive and relevant today.

This past week we were doing Kant's "What is Enlightenment?". Given the title of my blog it will be no surprise that I love covering this topic. Kant's motto of the Enlightenment is: "Have Courage to Use Your Own Reason!" And it is a motto that I think is just as important today as it was in the 18th Century. Moral and political progress is hampered by our own intellectual immaturity. Kant nicely summarizes this insight when he claims:

"If I have a book to serve as my understanding, a pastor to serve as my conscience, a physician to determine my diet for me, and so on, I need not exert myself at all. I need not think, if only I can pay: others will readily undertake the irksome work for me."

The Kantian aspiration to free ourselves from our own self-imposed immaturity really informs my attitude towards higher education (and my life in general). And when the opportunity arises when an educator can engage their students with a medium that transcends the typical constraints of stuffy academic writings, I believe one should do so. And this is where Bob Marley's music comes in!

In my class today we finished the section on Kant and the Enlightenment with this excellent video from Bob Marley. It is his song "Redemption Song", which is a really beautiful song. This verse from Marley really captures the Kantian ideal of enlightenment:

"Emancipate yourself from mental slavery. None but ourselves can free our minds".

Marley's message of course reflects many of his own circumstances, having grown up in Jamaica. For example, many of the lyrics address the religious beliefs of the Rastafari movement.

At the beginning of the video Marley notes that music is a vehicle that can liberate the people. And to find this message of enlightenment and freedom freely available on something like You Tube, one can't help but be struck by the fact that Marley's message satisfies the Kantian requirements for political progress- that communication be both publicizable and made public.

Redemption song is an inspirational song, one that offers the message of hope to those who face the legacies of slavery and colonialism. And to have such a liberating message song by such a beautiful voice, it is hard not to feel the attraction of Kant's (and Marley's) call for enlightenment.

Here are the verses for the song, but be sure to download the video as well and crank up the volume, and help join in in singing for freedom!

Redemption Song by Bob Marley

Old pirates, yes, they rob I;
Sold I to the merchant ships,
Minutes after they took I
From the bottomless pit.

But my hand was made strong
By the 'and of the Almighty.
We forward in this generation

Won't you help to sing
These songs of freedom? -
'Cause all I ever have:
Redemption songs
Redemption songs.

Emancipate yourselves from mental slavery;
None but ourselves can free our minds.
Have no fear for atomic energy,
'Cause none of them can stop the time.

How long shall they kill our prophets,
While we stand aside and look? Ooh!
Some say it's just a part of it:
We've got to fulfil de book.

Won't you help to sing
These songs of freedom? -
'Cause all I ever have:
Redemption songs
Redemption songs
Redemption songs


Wednesday, February 13, 2008

The Decline of Nature-Based Recreation

The PNAS has this early online study which reports that, over the past 20 years, the United States has undergone a fundamental shift away from nature-based recreation. Here is the abstract:

"Evidence for a fundamental and pervasive shift away from nature-based recreation"
by Oliver Pergams and Patricia Zaradic


After 50 years of steady increase, per capita visits to U.S. National Parks have declined since 1987. To evaluate whether we are seeing a fundamental shift away from people's interest in nature, we tested for similar longitudinal declines in 16 time series representing four classes of nature participation variables: (i) visitation to various types of public lands in the U.S. and National Parks in Japan and Spain, (ii) number of various types of U.S. game licenses issued, (iii) indicators of time spent camping, and (iv) indicators of time spent backpacking or hiking. The four variables with the greatest per capita participation were visits to Japanese National Parks, U.S. State Parks, U.S. National Parks, and U.S. National Forests, with an average individual participating 0.74–2.75 times per year. All four time series are in downtrends, with linear regressions showing ongoing losses of –1.0% to –3.1% per year. The longest and most complete time series tested suggest that typical declines in per capita nature recreation began between 1981 and 1991, are proceeding at rates of –1.0% to –1.3% per year, and total to date –18% to –25%. Spearman correlation analyses were performed on untransformed time series and on transformed percentage year-to-year changes. Results showed very highly significant correlations between many of the highest per capita participation variables in both untransformed and in difference models, further corroborating the general downtrend in nature recreation. In conclusion, all major lines of evidence point to an ongoing and fundamental shift away from nature-based recreation.


Genetic NonDiscrimination Bill

During a visit to the National Institutes of Health (NIH) on Jan. 17th 2007, President George W. Bush urged Congress to pass long-stalled legislation to safeguard genetic privacy (see here). The Genetic Information Nondiscrimination Act of 2005 (S.306) passed unanimously in the U.S. Senate by a vote of 98-0 but has been stalled in Congress. The Genetic Information Nondiscrimination Act of 2007 was passed in the U.S. House of Representatives, by a vote of 420-3.

When urging Congress to pass this legislation Bush declared that “if a person is willing to share his or her genetic information, it is important that that information not be exploited in improper ways…We want medical research to go forward without an individual fearing personal discrimination.”

The latest issue of Nature has an editorial on the imperative to pass the Genetic Information Nondiscrimination Act. Here is a sample:

Technology development guru George Church — aka the information exhibitionist — is playing a salutary social role with his Personal Genome Project. Church is in the process of gathering phenotypic data and sequencing portions of the genomes of ten volunteers, including himself (see page 763). He intends to study how the genes of these people — all but one of whom have revealed their identities — influence their phenotypes, and to make those data public. Church's point is simple: information, including genetic information, can and should be freely available.

Whether or not one agrees with him, society had better be ready to deal with the results of such research, which is occurring against a background of explosive growth in the availability of genetic information. Consider that, in the five-and-a-half months since Nature last opined about this topic (see Nature 448, 969; doi:10.1038/448969a 2007), the number of diseases for which genetic tests are available to patients has grown by 8.4%, to 1,236.

This makes it all the more urgent that the US Congress enact the Genetic Information Nondiscrimination Act, which would protect people from being discriminated against by health insurers or employers on the basis of their genetic information. The entire scientific and medical community is adamantly supportive of this bill — as is the House, which passed it on a vote of 420:3 last April. In previous Congresses, the Senate has twice passed it unanimously. These are sure signs of an idea whose time has come, given that no less powerful a lobby than the US Chamber of Commerce had twisted arms to try to prevent its passage.

....the enormous research and clinical progress being made in the nascent era of personalized medicine will come crashing to a halt because people — despite the efforts of George Church — will remain rightly wary of taking genetic tests.


Sunday, February 10, 2008

Reving Our Optimism For Scientific Research

The latest issue of EMBO Reports contains two very interesting items pertaining to science and ethics. The first is Frank Gannon's excellent editorial entitled "The End of Optimism?". Frank notes that back in the 1950's and 60's "citizens believed that scientists could free humanity from the constraints of Earth and reach for new frontiers". But now this optimism is gone. Advances in genetics have been met with concerns that scientists are "playing God"; advances in genetically modified crops have been met with enormous suspicion, etc. What has caused this transformation in the public's attitudes? Frank notes that there are many causes, like the media's tendency to reduce scientific research into a sensational "sound-bite", and scientists themselves are partly to blame when they exaggerate the implications of their research.

Frank effectively illustrates how science is on the retreat when he claims "a clear sign of the lack of optimism is the continued trust in alternative 'natural' cures, and the fact that scientists and politicians need to reiterate constantly the message that research is our best strategy to meet the needs of society". The latter insight is particularly apt for Canadians given that our Prime Minister recently abolished the national science advisor post! Frank finishes the editorial with this paragraph:

As a community, scientists must therefore work hard to counter this creeping cynicism and instill a healthy dose of optimism about what science can do—albeit in a fair and balanced way. We have to do this for ourselves as well as society at large. We have to explain the complexities of the tasks that lie ahead and, at the same time, highlight the genuine successes that scientific research has achieved. We must counter the cheap shots directed against honest and determined scientists, and reign in those who overstate their work and its implications. But more than anything else, we have to stress time and again that rigorous research is the only way to discover the cures and solutions needed for the twenty-first century. This optimistic message must also encourage the younger generation to join the quest for understanding and help to develop the new services and products that come from it. Sputnik was a huge technological and scientific breakthrough; it was a testament to human ingenuity that led all societies to invest more in education and research. Today, that optimism is waning, and we are facing an even bigger and more universal challenge; one that we must meet with optimism for exciting and successful scientific research.

The EMBO Report also has this interesting article entitled "A Question of Method: The Ethics of Managing Conflicts of Interest" by Samia Hurst and Alex Mauron. Potential conflicts of interest raise a number of pressing issues that must be addressed if we hope to protect the integrity of biomedical research. The author's argue that a "conflict of interest is acceptable if the joint activity is motivated by at least one shared primary interest, if regulation is possible to protect primary interests and if there is an exit strategy in case the partners' aims diverge too far".

Here are a few samples from the article:

Conflicts of interest in biomedical research can endanger the independent judgement of researchers and, in a worst-case scenario, can result in harm to humans, animals or the environment, or avoidable damage to scientifically validated truths. Highly publicized cases of scientists who have downplayed the risk of passive smoking—while receiving funding from the tobacco industry—or researchers who have questioned anthropogenic global climate change—yet are supported by the coal or oil industries—(LaDou et al, 2007) have attracted persistent, and often appropriate, criticism.

A conflict of interest occurs when someone in a position of trust—for example, an academic researcher, lawyer or physician—has competing private and professional interests that make it more difficult to fulfil his or her professional duties without bias. However, a conflict of interest in itself is not necessarily bad, as long as the 'right' interests prevail.

Nevertheless, conflicts of interest can create an impression of impropriety that, in the long run, might undermine the credibility of an individual or even an entire profession. At a time when policy-makers, politicians and the public increasingly rely on scientific advice about controversial issues—for example, human embryonic stem cells, genetically modified crops or global climate change—conflicts of interest diminish the public's trust in the independence and unbiased judgement of academic scientists. To maintain trust, researchers must remain visibly trustworthy, which requires a careful and explicit management of conflicts of interest.

....Academics ought to give priority to their primary interests—generating knowledge, integrity, transparency and openness—and make it clear to all their partners that they will stick to these. Organizational structures should support and enable them to assess their priorities as if the conflict of interest did not exist.

The EMBO Report editorial, coupled with the article about the importance of managing conflict of interests in scientific research, effectively show why we cannot remain complacent about science. To create a more humane world we must remain vigilantly committed to the importance of science, both at the level of public policy and in our culture as a whole. The health of a polity's science policy is only as good as the health of a society's attitude towards science more generally. And I believe that science needs more champions if we are to stand a chance of creating a better future. From politicians and journalists to academics and parents, we all need to take a serious reflective look at our attitude towards science. To those who remain sceptical about what science might offer us, just consider what kind of world our children will inherit if we don't embrace and celebrate science. A world with more dogma, more poverty, more disease, etc. The stakes are very high indeed. And it's about time that we all got more serious about protecting the role of science in our culture.


Saturday, February 09, 2008

Science Focuses on Cities

The latest issue of Science is a special issue on the topic of cities. There are a number of interesting articles, like Ruth Mace's "Reproducing in Cities" and Christopher Dye's "Health and Urban Living". Here are a few samples:

"Reproducing in Cities" by Ruth Mace

ABSTRACT: Reproducing in cities has always been costly, leading to lower fertility (that is, lower birth rates) in urban than in rural areas. Historically, although cities provided job opportunities, initially residents incurred the penalty of higher infant mortality, but as mortality rates fell at the end of the 19th century, European birth rates began to plummet. Fertility decline in Africa only started recently and has been dramatic in some cities. Here it is argued that both historical and evolutionary demographers are interpreting fertility declines across the globe in terms of the relative costs of child rearing, which increase to allow children to outcompete their peers. Now largely free from the fear of early death, postindustrial societies may create an environment that generates runaway parental investment, which will continue to drive fertility ever lower.

And from Dye's "Health and Urban Living":

For the citizens of 18th century London and Paris, it was the worst of times. As far as public health was concerned, the best of times would be for future generations. By modern health standards, London in the 1700s was a slum: Between 10% and 30% of infants died before their first birthdays, and although the death rate of young children was lower in richer parts of the city, there was little variation in life expectancy across social classes. Edwin Chadwick's "sanitation revolution" gained momentum in the early 1800s and was given greater impetus by the Public Health Act of 1848, but even in 1858, the River Thames brought "the sewage of three millions of seethe and one vast open cloaca.". Conditions were no better in 19th century Paris: Relatively high food prices and poor sanitation left Parisian men more stunted than men elsewhere in France. In Europe today, about 70% of people live in urban areas. In the Europe of 1800, only 10 to 15% of people did so, partly because of the atrocious living conditions. Cholera, dysentery, measles, plague, smallpox, tuberculosis, typhus, and other infections, exacerbated by undernourishment, imposed an "urban penalty" such that deaths, mostly of children, exceeded births. London, Paris, and other European cities could only grow by immigration from the countryside.

The 1848 act focused on sanitation—piping clean water to homes and safely disposing of human waste—but led on to a wider range of environmental improvements that had benefits for health, including ventilation of dwellings and streets, the preservation of green spaces, and the upgrading of road surfaces (6). By the start of the 20th century, urban health was typically improving faster than rural health in the industrialized world, and towns and cities grew faster than their hinterlands. As cities expanded, they started to provide a variety of indirect benefits to health: large markets with a steady and diverse food supply, economies of scale with low transportation costs, organized public services, and a critical mass of educated people that was needed to establish centers of enterprise, learning, and innovation.

Today, more than half the world's population—about 3.3 billion people—lives in urban areas, including roughly 50,000 settlements of at least 50,000 people. By 2015, and for the foreseeable future beyond, population growth will be mainly urban, mainly in the 500 or so cities that have 1 million to 10 million inhabitants, and mainly in poorer countries. Although three-quarters of the people who earn less than a dollar a day still live in rural areas, the proportion and number of poor people living in urban areas are rising. About one in three urban inhabitants—roughly one billion people—now live in slums, but the proportions are much higher than this average in sub-Saharan Africa and South Asia.

....Many of the prescriptions for better urban health are in fact self-evident and are often inexpensive: healthy housing, primary health care, communicable disease control through sanitation and vaccination, safe roads, and targeted assistance to women. They are also not specific to urban areas. The tough problem is that technical solutions need a framework in which they can be executed. Hence, the call for "healthy governance," regulated land ownership, probity in financial investment, social cohesion, the empowerment of civil society, and foresight in planning the physical environment. The right structure is hard to create because there are no recipes for social cohesion and good governance. Yet there is an imperative to succeed: If cities are the "defining artifacts of civilisation", a nation may now be judged by the health of its urban majority.


Friday, February 08, 2008

NBT Article on Supreme Court and Licensing Power

The issue of gene patents is a central concern for a theory of genetic justice. The regulatory framework a society implements for intellectual property rights will have a profound impact on the pace and shape of innovation, as well as the distribution of the potential benefits and burdens of biomedical research.

My earlier post on the "Google Alerts" for gene patents helps give one a sample of some of the complex legal and social issues that arise in this context. And my forthcoming paper "Gene Patents and Justice", which should be out in the next issue of The Journal of Value Inquiry, attempts to bring to the fore some of the complex empirical concerns that arise in this context. And these empirical concerns muddy the water for conceptual normative analyses of IP.

The latest issue of Nature Biotechnology has a very useful piece by Jennifer Giordano-Coltart and Charles Calkins entitled "Recent Supreme Court decisions and Licensing Power". They focus on two recent Supreme Court decisions- eBay Inc. v. MercExchange and MedImmune, Inc. v. Genentech, Inc. These decisions effectively reveal (1) how intricate and complex IP law can be and (2) how judicial decisions on such issues can impact (for better or worse) research. Here is a sample from the Nature Biotechnology article:

Perhaps more so than in any other area of business, intellectual property, particularly patents, is the key asset of companies in the pharmaceutical and biotechnology industries. Universities, emerging pharmaceutical and biotechnology companies, and the research and development units of larger pharmaceutical and biotechnology companies protect their investments in research, and their investors, by filing for patents. Companies' stock prices rise and fall on the issuance and expiration of patent rights. Market share and selling price—and therefore a company's profits—for pharmaceutical products are maintained and protected against generic competition during the lives of patents covering the products.

Like other forms of property, the rights granted by patents can be sold or exchanged between and among companies through legal contracts, referred to as licenses. Universities can license their patent rights in their research to life science companies that will attempt to develop commercial products from the research. Emerging life science companies may license their small- or large-molecule platforms to joint venture partners to collaborate on clinical trials and commercialization. Life science companies of every size seek to in-license product lines for commercialization and to out-license product lines that do not fit within their current market strategy. As a result, licenses have a major role in the pharma and biotech industries.

....The legal landscape, however, was altered by the Supreme Court's decision in eBay Inc. v. MercExchange, LLC1. The Court held that a patentee should be entitled to a permanent injunction only if it satisfies the traditional equity-based test for injunctive relief by showing that (i) it has suffered irreparable injury; (ii) the remedies available at law, such as money damages, are inadequate to compensate it for the injury; (iii) the balance of hardships between the patentee and the infringing party favors an equitable remedy; and (iv) the public interest would not be disserved by an injunction.

In altering the almost automatic standard for injunctive relief, the Court decreased the leverage of a patent holder during licensing negotiations, as potential licensees can now worry less about being enjoined. The Court did recognize a difference between patentees who practice their patented technology and those who do not, finding that it would be more likely that patentees who practice their technology would be able to meet the standard for injunctive relief. Fortunately for universities and emerging technology companies, the Court further recognized a need to differentiate between those patentees who do not practice their invention because of inadequate capacity or insufficient capital, such as independent inventors or university researchers, and patent trolls who exist solely to license their technology to those who are already using the technology in the market place as a means of extracting fees. A critical distinction between these types of patentees is that the former are using licensing programs toward the goal of developing their inventions into marketable products, and use their patents as a shield to protect their right to exclude, market share, reputation, goodwill or name recognition, whereas the latter use their patents as a sword, seeking only to maximize fees from market participants.

....The recent Supreme Court cases eBay and MedImmune interject both reassurance and uncertainty into the present scheme of patent licensing, the latter of which will need to be addressed in future negotiations. Because of the uncertainty raised by these cases, it is unclear whether these decisions, particularly MedImmune, will really benefit either party in achieving the desirable win-win license agreement. On the front end, MedImmune seems to have eliminated the finality of a negotiated agreement, which changes the dynamics of the negotiations and potentially makes the entire labor-intensive program fruitless, while on the back end the decision may lead to iron-clad contracts that may result in more onerous circumstances than would have arisen from just breaching the licensing contract before MedImmune. Now, with the dispute in Quanta, the patent community is waiting to see how much control licensors will be able to exert on the downstream uses of their technology. Over time, courts will determine which terms licensors may impose on licensees and, hopefully, the result of this process will be stronger patents that can be marketed effectively as useful products and services, as was the original intent of the patent system.


Wednesday, February 06, 2008

Nature Article on Aging

This week's issue of Nature has an excellent piece by Thomas Kirkwood entitled "A Systematic Look at an Old Problem". The paper addresses one of the most pressing and challenging issues humanity faces this century- tackling aging. As I've noted many times before (e.g. see here), the imperative to retard human aging occupies a great deal of my current research. And so it was with much interest that I read Kirkwood's interesting article. Here is a sample:

The continuing increase in life expectancy, which in many countries advances by several hours per day, is one of humanity's most astonishing successes. But as the population ages, new approaches are required to unravel the complex biology of ageing and understand its links with frailty and disease.

The increase in human life expectancy over the past ten years has taken both scientists and the population generally by surprise. Until recently, demographers were confidently predicting that once the gains made by reducing mortality in early and middle life had reached completion, growth in longevity would stop and we would see the fixed reality of the ageing process. This has not happened1. In much of the developed world, life expectancy continues to increase at the rate of five or more hours per day; in some developing countries, which have some catching up to do, the rate is even faster.

The continuing increase in life expectancy, which in many countries advances by several hours per day, is one of humanity's most astonishing successes. But as the population ages, new approaches are required to unravel the complex biology of ageing and understand its links with frailty and disease.

....The idea that ageing is programmed was dismissed long ago by evolutionary gerontologists who recognized that natural selection could not, and would not, bring about such a fate (except in very special circumstances)4, 5. Even for those who spurned such logic, the idea of programmed ageing began to seem rather odd when it was found that the genes that affect longevity do so not by changing the timing of a mechanism for self-destruction, but by adjusting hundreds of mechanisms for maintenance and repair6, 7. If ageing were programmed, this would be a clumsy way to do it.

....Age is by far the biggest risk factor for a wide range of clinical conditions that are prevalent today. One might therefore presume that a major effort is being made to understand the ways in which ageing renders the elderly more vulnerable to pathology. Nothing could be further from the truth. There is a large number of medical research institutes around the world, many with a focus on one or more of the major age-related diseases — cancer, heart disease, arthritis or dementia. Yet only a tiny fraction of these carries out any research on the intrinsic contribution from the ageing process itself.

The point Kirkwood notes in the final paragraph above- that age is by far the biggest risk factor for a range of prevalent clinical conditions- is more than sufficient grounds for taking seriously the duty to retard human aging. Once we add to this the fact that incredible advances have been made in our understanding of the biology of aging (like the fact that aging is not immutable, and that particular genes can extend longevity), one realizes that there is no justification for the current neglect of aging research. To get serious about promoting our health prospects we have to get serious about retarding human aging. It's great to see premier science journals like Nature taking these issues seriously.


Tuesday, February 05, 2008

PNAS Study on Autism in Mice

The Proceedings of the National Academy of Sciences has an interesting early online study entitled "Reduced Social Interaction and Ultrasonic Communication in a Mouse Model of Monogenic Heritable Autism" by Stephane Jamain et. al. Their findings, based on research on mice, suggest that a protein network that regulates the maturation and function of synapses in the brain is at the core of a major ASC susceptibility pathway. Here is the abstract:

Autism spectrum conditions (ASCs) are heritable conditions characterized by impaired reciprocal social interactions, deficits in language acquisition, and repetitive and restricted behaviors and interests. In addition to more complex genetic susceptibilities, even mutation of a single gene can lead to ASC. Several such monogenic heritable ASC forms are caused by loss-of-function mutations in genes encoding regulators of synapse function in neurons, including NLGN4. We report that mice with a loss-of-function mutation in the murine NLGN4 ortholog Nlgn4, which encodes the synaptic cell adhesion protein Neuroligin-4, exhibit highly selective deficits in reciprocal social interactions and communication that are reminiscent of ASCs in humans. Our findings indicate that a protein network that regulates the maturation and function of synapses in the brain is at the core of a major ASC susceptibility pathway, and establish Neuroligin-4-deficient mice as genetic models for the exploration of the complex neurobiological disorders in ASCs.


Editorial on In Utero Gene Therapy

The journal Molecular Therapy has an interesting editorial on In Utero Gene Therapy by Charles Coutelle. Here is a sample:

In utero gene therapy in humans remains controversial, despite the increasing use of fetal gene delivery in animals. Advantages of in utero gene therapy include the beneficial vector-to-cell ratio, the presence of expanding and developing stem cell populations during fetal life, the possibility of achieving tolerance against vector and transgenic proteins, and the prospect of preventing irreparable tissue damage associated with early-onset inherited disease. Therapeutic proof of principle by this approach has been demonstrated in several rodent models of human genetic conditions. Recent advances in fetal medicine—particularly in imaging and minimally invasive intervention—have opened the way, in large animal models, for clinically relevant delivery of gene therapy vectors to virtually any fetal organ. However, although postnatal gene therapy has seen its first successful clinical applications, no trials are planned for human gene therapy in utero, now or in the near future. Indeed, many view the concept as having only academic value, with no potential for translation into the clinic.

At present, the options for a couple at risk of having a child with a serious mendelian disease are preimplantation genetic diagnosis and embryo selection, abortion, or caring for an affected child. Safe, effective, and curative gene therapy in utero would be by far a better option. Research toward this goal may also facilitate postnatal gene therapy by providing insights into the problems associated with stem cells and immunologic rejection later in life.

The most frequent objection to in utero therapy is that, if a fetus is shown to be affected by a serious inherited disease, abortion is a logical and clinically safe procedure that should not be rejected in favor of the initially unproven outcome that would result from a gene therapy approach in utero. However, it is not rare for a family to decide against abortion, even though this may mean assuming the burden of caring for an affected child. Prenatal gene therapy may offer an answer to this dilemma, although the first families to choose this option would certainly face a difficult decision because of the perceived and real dangers, and the unproven reliability of the procedure.

....We are only at the beginning of the development of effective therapeutic approaches for severe human genetic diseases. These conditions are so varied and complex that each will require a specific approach by drug, cell, or gene therapy. None of these approaches will provide a "magic bullet," and, until we have clinically proven results, no one can predict which approach will be successful for which disease. In utero gene therapy should thus have a place in our potential arsenal.