Friday, February 27, 2009

PGD Paper Now Available in JMP

My paper entitled "Preimplantation Genetic Diagnosis, Reproductive Freedom, and Deliberative Democracy" is now available on the advance access site of the Journal of Medicine and Philosophy.

Here is the abstract:

In this paper I argue that the account of deliberative democracy advanced by Amy Gutmann and Dennis Thompson (1996, 2004) is a useful normative theory that can help enhance our deliberations about public policy in morally pluralistic societies. More specifically, I illustrate how the prescriptions of deliberative democracy can be applied to the issue of regulating non-medical uses of pre-implantation genetic diagnosis (PGD), such as gender selection. Deliberative democracy does not aim to win a philosophical debate among rival first-order theories, such as libertarianism, egalitarianism or feminism. Rather, it advances a second-order analysis that strives to help us determine what would constitute a reasonable balance between the conflicting fundamental values that arise in the context of regulating PGD. I outline a theoretical model (called the Reasonable Genetic Intervention Model) that brings these issues to the fore. Such a model incorporates the concern for both procedural and substantive principles; and it does so in way that takes provisionality seriously.


Thursday, February 26, 2009

Globe Story on Cancer Prevention

Some project that cancer will soon overtake heart disease as the world's leading cause of death. Today's Globe has this interesting story about a report from experts in nutrition epidemiology on the benefits of cancer prevention. The report concludes that 25% of cancers could be prevented with appropriate nutrition and physical exercise.

This report is of particular interest to me for many reasons. Firstly, as a society we should take prevention much more seriously than we do. We must encourage everyone (young and old alike) to eat a healthy diet and exercise. I have noted this many times before (here, here and here).

Secondly, this story interests me given my interest in genetic justice. This paper, for example, examines the diverse considerations that arise-- given genetic complexity-- when we think about how best to mitigate our vulnerability to diseases like cancer.

Thirdly, this story and study reveal how complex and difficult it is to appreciate what a 25% prevention of cancers actually means. It does not mean that active people will not get cancer. For most people it means they will be able to delay the time it takes them to develop a different form of cancer that is not preventable by life style, or another disease of aging. Furthermore, eliminating all cancer would not (contrary to what most people think) dramatically increase life expectancy for humans. These points are worth emphasising for they reveal the importance of aging research.

Take smokers. Smoking increases one's risk of lung cancer. There are both genetic (see this) and environmental (tobacco contains hundreds of carcinogens) reasons for this. All else being equal, smoking lowers one's life expectancy when compared to non-smokers. But never smoking doesn't mean you won't get cancer (even lung cancer). There are still another 200+ kinds of cancer that we could develop and die from.

Furthermore, people often overestimate what eliminating all cancers would mean for the life expectancy of humans. We tend to think that eliminating cancer would add decades to a person's life expectancy. But this is not the case. It would add about 3 years to life expectancy at birth. Why is the increase so small? Because of the fact of co-morbidity. If you don't die from cancer chances are you will soon die of heart disease, stroke, or one of the other afflictions associated with senescence.

Now of course exercise and proper diet can reduce your risk of these other afflictions as well. I in no way mean to trivialize these benefits or undermine the importance of lifestyle. But at the same time it is important not to hype what these benefits will be. You often hear people say that anyone could live to a 100 years with proper diet and lifestyle. But this is false. There is no credible scientific basis for believing that lifestyle changes would increase the maximal human life span (which is around age 85).

Exercise is not as effective as calorie restriction in terms of extending lifespan. Just to be clear, I am not suggesting that we pursue CR. Rather my point is that we should support the science that could develop a safe and effective pill that would mimic the effects of CR, thus reducing our risks of disease and death in later life.

So decelerating aging is the most important form of prevention for aging populations. I'm a fan of all forms of prevention. The greater their proposed benefits (in terms of quality of life) and the more likely it is that people will utilize them, the more important they are. A pill the slows aging is something everyone could take (unlike regular exercise and nutrition) and it would add significantly more health to our life prospects than exercise and diet alone. So if you are excited about the prospect of reducing your risk of 25% of cancers by exercise and diet, you should be "over the moon!" about the prospect of reducing your risk for cancer, heart disease, stroke, etc... etc... by decelerating aging.


Monday, February 23, 2009

Abuse in Childhood Impacts Brain Development in Adulthood

A few months back I posted this story about the impact poverty has on the brain development of children. This study in Nature Neuroscience sheds light on how abuse early in life can impact the biology of the brain later in life. Childhood abuse affects a gene involved in stress control even decades after the abuse. Here is the abstract from the study:

Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A–inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.

The NY Times has the scoop about this study here.


Saturday, February 21, 2009

"Framing Ageing"

This is the second installment to my post yesterday. This is a more formal attempt to raise awareness of the importance of longevity science. The presentation is entitled "Framing Ageing and Longevity Science".

You can download the video by clicking here: "Framing Ageing"


Friday, February 20, 2009

Kant, Public Sense, and a Video

In my previous post I noted that I would make an effort, in the spirit of Kant's account of the "public use" of reason, to reach a larger audience than that typical in a standard academic paper. So that is the intention of this post today.

Because academic journals require subscriptions in order to download and read the findings of academic research, most people not associated with a university do not have access to the findings being made in different disciplines. And thus the constraints of academia actually impose some limitations on the requirement of "publicity" which is essential to Kant's account of the public use of reason. Enlightenment cannot be achieved if new moral insights and empirical discoveries can only reach a limited number of people. And so the project that I "unveil" today is meant in the spirit of Kant's call for us to use "public reason".

It is also in the spirit of the 3 maxims of what Kant calls "public sense". These maxims are:

1. “Think for yourself”: the motto of the enlightenment
2. “To think from the standpoint of everyone else”
3. “always think consistently”

So please feel free to watch, debate and distribute "3 Wishes" as you see fit:

Click this: "3 WISHES"


Tuesday, February 17, 2009

Equality and Aging Paper Now Online

My paper "Equality and the Duty to Retard Human Ageing" is now available on the "Early View" section of the journal Bioethics.

This paper is my latest in a series of papers (see this, this, this, this and this) that aspire to get us to seriously address the most pressing issue facing the health prospects of humans this century-- the biological vulnerabilities inherent in the current rate of human aging. Many of the arguments made in these published papers are first expressed here at "In Search of Enlightenment". This blog serves as a useful place for me to (1) get my ideas written down and (2) ensure they are sufficiently reflective and defensible before putting them out in the "public arena" of the blogosphere.

The great thing about a blog is that one can potentially reach a much larger and more diverse audience than one can with an academic scholarly publication. And, drawing inspiration again from Kant, we should aspire to use what he calls the "public use of reason".

The public use of reason, in contrast to the private use, is, for Kant, defined in terms of the audience (i.e. the world at large) whom an act of communication may reach. By engaging in an interdisciplinary debate about aging research I have tried to exercise the public use of reason. While my new paper in Bioethics addresses a specific philosophical debate, this contribution and this one , for example, are attempts to engage a broader audience and utilize different tools to do this. And this blog itself is perhaps the best venue I have for exercising the public use of reason.

My future contributions to advocating for aging research will be much more in the spirit of invoking the public use of reason. This is imperative for a topic like aging given (a) where the science is, (b) how few the advocates of this science, and (c) the enormous benefits this science could bring to the health and economic prospects of those living in both the developed and developing world.

Here is the abstract from my Bioethics paper:

Where does the aspiration to retard human ageing fit in the 'big picture' of medical necessities and the requirements of just healthcare? Is there a duty to retard human ageing? And if so, how much should we invest in the basic science that studies the biology of ageing and could lead to interventions that modify the biological processes of human ageing? I consider two prominent accounts of equality and just healthcare – Norman Daniels's application of the principle of fair equality of opportunity and Ronald Dworkin's account of equality of resources – and conclude that, once suitably amended and revised, both actually support the conclusion that anti-ageing research is important and could lead to interventions that ought to be considered 'medical necessities'.

Tomorrow I will be giving a talk entitled "Slowing Human Aging: Ethical and Social Issues" to the Probus Club of Kingston.


Sunday, February 15, 2009

Gene Therapy for Human Arthritis

On many occasions on this blog I have urged us to seriously ponder, and prepare for, the greatest challenge facing humanity this century--- tackling the health challenges facing aging populations. This is a challenge that human societies have never had to tackle before.

Before the 19th century life expectancy in the world was below 30 years. Today it is 67 and expected to rise to 75 by 2050.

To get a sense of the human toll senescence will reap in the years to come just consider arthritis along. Arthritis covers over 100 different conditions. Here are some facts from the Arthritis Foundation:

Number of Americans with arthritis or chronic joint symptoms:

1985 - 35 million
1990 - 37.9 million
1998 - nearly 43 million (1 in 6 people)
2006 – 46 million (nearly 1 in 5 adults)
Arthritis is one of the most prevalent chronic health problems and the nation’s leading cause of disability among Americans over age 15.
Arthritis is second only to heart disease as a cause of work disability.
Arthritis limits everyday activities such as walking, dressing and bathing for more than 7 million Americans.
Arthritis results in 39 million physician visits and more than a half million hospitalizations.
Costs to the U.S. economy totals $128 billion annually.
Arthritis affects people in all age groups including nearly 300,000 children.
Baby boomers are now at prime risk. More than half those affected are under age 65.
Half of those Americans with arthritis don’t think anything can be done to help them.
Arthritis refers to more than 100 different diseases that affect areas in or around joints.
Arthritis strikes women more often than men.

The health (e.g. pain and suffering) and economic toll of arthritis is staggering. The latest issue of Human Gene Therapy offers some hope to those who currenty suffer arthritis (and those bound to in the years to come). It provides some reason for optimism that gene therapy for arthritis might offer some therapeutic benefit to those who suffer from arthritis. Here is the abstract:

This paper provides the first evidence of a clinical response to gene therapy in human arthritis. Two subjects with rheumatoid arthritis received ex vivo, intraarticular delivery of human interleukin-1 receptor antagonist (IL-1Ra) cDNA. To achieve this, autologous synovial fibroblasts were transduced with a retrovirus, MFG-IRAP, carrying IL-1Ra as the transgene, or remained as untransduced controls. Symptomatic metacarpophalangeal (MCP) joints were injected with control or transduced cells. Joints were clinically evaluated on the basis of pain; the circumference of MCP joint 1 was also measured. After 4 weeks, joints underwent surgical synovectomy. There were no adverse events in either subject. The first subject responded dramatically to gene transfer, with a marked and rapid reduction in pain and swelling that lasted for the entire 4 weeks of the study. Remarkably, joints receiving IL-1Ra cDNA were protected from flares that occurred during the study period. Analysis of RNA recovered after synovectomy revealed enhanced expression of IL-1Ra and reduced expression of matrix metalloproteinase-3 and IL-1β. The second subject also responded with reduced pain and swelling. Thus, gene transfer to human, rheumatoid joints can be accomplished safely to produce clinical benefit, at least in the short term. Using this ex vivo procedure, the transgene persisted within the joint for at least 1 month. Further clinical studies are warranted.


Saturday, February 14, 2009

Science Spending and Justice (Update)

Following on from my previous post two weeks ago.... the US stimulus bill approved last night will provide an extra $10 billion to the National Institutes of Health.

The New York Times has this fascinating story describing the behind the scenes "wheeling and dealing" that brought this about.


Thursday, February 12, 2009

Bicentenary of Darwin's Birth

Charles Robert Darwin was born 200 years ago today. As NatureNews describes Darwin's impact: "No single researcher has since matched his collective impact on the natural and social sciences; on politics, religions, and philosophy; on art and cultural relations".

A Google search for "Darwin" in today's News yields this impressive list. Here is a random sample from some of the stories:

From the BBC: Ten stamps are being issued to mark the birth of scientist Charles Darwin in Shrewsbury exactly 200 years ago.

Royal Mail said it was celebrating the studies that inspired his theories on evolution - zoology, botany, geology, ornithology and anthropology.

From the New York Times: Unlike many members of the human species, Darwin makes an easy hero. His achievements were prodigious; his science, meticulous. His work transformed our understanding of the planet and of ourselves.

At the same time, he was a humane, gentle, decent man, a loving husband and father, and a loyal friend. Judging by his letters, he was also sometimes quite funny. He was, in other words, one of those rare beings, as likeable as he was impressive.

From Nature: Although history is not made entirely, or even mostly, by prominent men and women, two great exceptions to that rule were born exactly 200 years ago today, on 12 February 1809: Charles Darwin and Abraham Lincoln.

These men shared more than just a birthday, the loss of a mother in childhood and a date with immortality. They shared a position on one of the great issues of their age: the 'peculiar and powerful interest' of their fellow humans bound in slavery. When he circled the world in the 1830s, Darwin's delight at our planet's natural riches was repeatedly poisoned by the cruelties he saw meted out to slaves. "I thank God, I shall never again visit a slave-country," he wrote at the end of the Voyage of the Beagle.

And the Guardian has an excellent mix of items on Darwin here.


Wednesday, February 11, 2009

Annual Review of Medicine Article on Life Extension

The latest issue of the Annual Review of Medicine has this excellent article on the prospects of life extension. This paper addresses many of the issues I have been pondering for the past few years. I would like to do a substantial post on these issues by am swamped at the moment. For now, here is a sample from the article:

The large increase in life expectancy observed during the last century was achieved without much increase in our understanding of the ultimate causes of aging and age-related diseases. Although lifestyle changes and the taming of age-related disease are likely to continue increasing human life span (see Figure 1), it remains an intriguing possibility that a major increase in life expectancy could be achieved through an understanding and manipulation of the basic principles governing the progressive loss of function and fitness that accompanies aging.

…. The age trajectory of mortality rates was initially thought to be exponential, with risk of death increasing progressively with age, but a decline in mortality at the extreme of age has been observed in medflies (4), as has a slowing in humans (5). There are several possible explanations for the slowing of mortality at older ages, including genetic factors; indeed, siblings of centenarians also enjoy significantly unusual longevity (6).

…. Human studies on interventions intended to extend life span or health span may stem from findings in laboratory animals or in humans. Several considerations relate to the potential human applicability of such an intervention, e.g.,
▪ Is it available, feasible, and safe for testing in humans?
▪ What would be its profile of positive and negative effects in people?
▪ At what age would it need to be started to be effective, and for how long would it need to be administered?
▪ If it needs to be started relatively early in life, would there be any differences in beneficial versus adverse effects at different stages of the life span?
▪ How would environmental factors affect its efficacy and safety?
▪ Would it be suitable for the general population or only for particular subgroups?
▪ Should it be administered systemically or only to certain tissues?

.... Over time, because of the compounding effects, small increases in average life expectancy can lead to very large increases in the size of a population. Some analyses suggest that improvements in health and longevity have resulted in enormous gains in economic welfare over the past century (81–83). Indeed, one estimate of the economic impact of post-1970 gains in life expectancy suggested that they might have added as much as $3.2 trillion annually to the U.S. economy, equal to 50% of GDP! These calculations depend heavily on the assumed economic value of a statistical year of life, but even if the gains were only a fraction of that amount, they would still be huge.

Great stuff!


Thursday, February 05, 2009

The Parallels Between Apologism and Theism

This term, like last term, I am teaching my favourite class "Genetics and Justice" here at Queen's. And today's topic is one that always stimulates much debate-- aging research. Last term I offered a number of substantive points on the imperative to get people to discard their "aging blinders". Here I want to elaborate a bit more on a point I made in that earlier post.

Let me start by re-stating something I posted last term:

Consider what I will call “Key Value Premise”: Suffering disease and death is bad. If you agree with Key Value Premise, then you must also come to grips with the reality of aging. Let’s call this “Key Empirical Premise”: aging increases our risk of morbidity and mortality; not just by a small amount- these risks increase *exponentially* with age (until around age 95, when late-life mortality plateaus).

So if suffering disease and death is bad, and aging dramatically increases these risks, then we ought to be seriously considering ways of tackling aging. When things are clearly laid out like this, it is hard to see how anyone could object to making longevity science more of a priority (who can deny the value and/or empirical premises noted above?)

Today I was struck by the parallel between how I justify my belief that aging (more specifically the biological aging of adults) is a significant problem that we should strive to mitigate and my atheism. These two beliefs I have, which I admit are in the minority among my contemporaries, are ones I think no rational person ought to deny. Here I will draw a parallel between those that deny both. The former we can call (following Overall) "apologists" and the latter are "theists".

Let us start with what I will call "Conventional Belief #1": this is the belief that death and disease are significant harms and things we should aspire to prevent and avoid if possible (providing certain conditions hold- like the mitigation is cost-effective, etc.).

So most rational people hold Conventional Belief #1. If you ask them if they think we should strive to reduce the deaths caused by poverty, malaria, HIV, cancer, car accidents, smoking, war, etc.... etc... they would say "YES!". Things that cause disease and end our lives are bad. We should try to prevent them from happening. OK, so far nothing very controversial.

So now I ask: is there any cause of disease or death you would object to trying to minimize?...... long silence..... anyone out there opposed to trying to reduce our risk of morbidity and mortality?..... anyone.... last call for objections.....

OK, I assume there are not many objectors to Conventional Belief #1. But, and this is were one opens the floodgates of "Gerontologiphobia", how many people think it is desirable to try to prevent disease and death by retarding human aging? Well, that changes everything!! Now the apologists come out in full force. People who agreed with me so far will all of a sudden do an about face and raise objections to the goal of keeping people healthy and alive. "That is unnatural!" they might say. Or they worry "This will cause overpopulation!" or "There will be massive unemployment!" etc., etc....

There is almost no end to the reasons people will give to justify why the current rate of aging, and its ever growing disease burden, is actually a good (rather than bad) thing! This is particularly frustrating giving that aging causes most disease in the world today. If people tried to rationalize why death by being decapitated by an elevator was desirable and should be tolerated at least that would not make a big difference to the health prospects of most people. But to tolerate the main cause of disease and death in the world today is the last thing we should be tolerating given our commitment to Conventional Belief #1. Those who believe, as I do, that there is a moral duty to retard human aging, just take Belief #1 one extra step.... we believe it is important to try to prevent the most common causes of disease and death-- the chronic diseases associated with aging. It is irrational to not extend Belief #1 to aging itself given the role aging plays in our susceptibility to disease.

So how does this link up with the issues of theism and atheism? Here is another conventional belief that many rational adults will accept- "Conventional Belief #2": there is no such thing as magic. In other words, we don't believe in things that have 0% empirical evidence to support them. We don't seriously entertain the belief in the existence of the tooth fairy, pixies, dragons or unicorns. These things are not real. And yet, many people want to make at least one exemption to Belief #2, just as apologists do with Belief #1. That is, they are willing to believe in a god.

Dawkins has a great line that we are all atheists about most of the gods humans have believed in (thor, zeus, etc.)... some of us just go one god further. Likewise, we are all "pro-longevity" for most things that kill humans (war, cancer, poverty), champions of aging research just go one step further by acknowledging that aging itself is a big problem we should strive to mitigate.

So when I reflect on my own belief system I appreciate the influence that respect for logic and a philosophical apptitude have had on my own personal beliefs. I cannot permit myself to just grant exemptions to core rational beliefs like Belief #1 and Belief #2.

Having said that, I can also appreciate why it is hard for so many people to abandon their "pro-aging" or "pro-magic" belief system. Indeed, I myself used to hold those beliefs and it has been a long and sometimes difficult journey to go from the beliefs I once held as a young adult to those I have today. Giving up these beliefs requires a major re-orientation of one's perception of the world, something few people are keen to undertake. Indeed, I would describe my own transformation as one that involved a good deal of cognitive dissonance, as I sought to reconcile my desire for some logical consistency between Belief #1 and #2 with my attitudes towards aging and magic. So I can understand why people are not keen to being reminded that aging increases their risk of disease and death (it's not a pleasant thought!). Nor do theists enjoy hearing that this life "here and now" is all there is to their existence (indeed, they often wonder why atheists even bother going on with life if they don't believe in some higher purpose).

The tendency to grant exemptions to Belief #1 and Belief #2, like apologists and theists do, are perhaps adaptations or a byproduct of our evolution. They are a form of cognitive bias, and as such they lead people to hold beliefs that are irrational and contradict the way they tend to live their lives on a daily basis (i.e. trying to avoid disease and death and not believing in magic).

The two issues of longevity science and religion are related in other ways. I actually believe the latter impedes the advancement of the former. It is much harder to make the case for modifying the rate of aging natural selection has given us when people think that death actually brings eternal bliss (rather than an end to life) and that evolution is "just a theory" or wrong. To meet the challenges of the 21st century we must have the courage to strive for a 21st century intellect. To do this we must emphasis the importance of science education.

So let me finish with the sage comments from a recent editorial by Bruce Alberts in the journal Science :

Rather than only conveying what science has discovered about the natural world, as is done now in most countries, a top priority should be to empower all students with the knowledge and practice of how to think like a scientist.

Scientists share a common way of reaching conclusions that is based not only on evidence and logic, but also requires honesty, creativity, and openness to new ideas. The scientific community can thus often work together across cultures, bridging political divides. Such collaborations have mostly focused on the discovery of new knowledge about the natural world. But scientists can also collaborate effectively on developing and promulgating a form of science education for all students that builds scientific habits of mind.