Risk Alleles for Osteoporosis Identified

The latest issue of The Lancet has this interesting article on a genome-wide association study for osteoporosis and osteoporotic fracture. Here is a sample:

Osteoporosis and its main complication, fragility fractures, incur substantial global morbidity and mortality.1 The public-health burden of this disease is US$17 billion every year in direct expenditure—and this is expected to increase dramatically as populations age.2 Osteoporosis is defined clinically through the measurement of bone mineral density, which remains the single best predictor of primary osteoporotic fractures.3 Bone mineral density is highly heritable, with estimates from a cohort study in the UK of 78% heritability of density at lumbar spine and 84% at femoral neck;4 these figures are consistent with other twin studies.5 Only a few well-replicated studies of candidate genes for osteoporosis have so far emerged,6–8 suggesting that bone mineral density is a complex polygenic trait.5

Genome-wide association studies have been facilitated by the HapMap project, and by recent advances in genome-wide genotyping arrays that provide a high degree of genome coverage.9 We therefore undertook a genome-wide association study to identify genetic loci that influence bone mineral density.

....We have identified genetic variants that decrease bone mineral density and predispose people to osteoporosis and osteoporotic fracture. The increased risk of osteoporotic fracture in people who had both risk alleles was independent of the effect of these alleles on bone mineral density.

....In conclusion, the risk alleles we have identified justifiy further clinical and biological investigations. These SNPs alone are unlikely to change current clinical practice, but as has been shown for other diseases,59 extended panels of several SNP markers could be used in the future, in addition to traditional risk factors, to better identify populations who are at high risk for osteoporotic fractures.

Cheers,
Colin

UTLJ Review Article (Now Published)

My paper entitled "The Institutional Theory of Legal Interpretation" is published in the latest issue of The University of Toronto Law Journal. This paper is a review article of Adrian Vermeule's excellent book Judging Under Uncertainty.

It was a real joy reading Vermeule's book. Legal theory has long been dominated by debates concerning the primacy of different high-level conceptual commitments, like democracy and constitutionalism. Vermeule documents the chronic condition of institutional blindness in Anglo-American interpretive theory, covering the contributions of important historical figures — like William Blackstone and Jeremy Bentham — to the most important contemporary contributions, such as the theories of H.L.A Hart, Ronald Dworkin, and Richard Posner. Rather than trying to win a debate concerning "first-best conceptualism", Vermeule makes the case for developing a second-best interpretive theory. Second-best interpretive theories ask how nonideal interpreters of law should proceed in light of widespread disagreement about competing first-best theories and given the institutional constraints and political conditions that actually obtain in the legal system.

There are a lot of important insights Canadian legal theorists can incorporate from Vermeule's institutional theory, especially for the "dialogical model" of judicial review which I am interested in (see here). And Vermeule's concerns parallel many of those I have for political philosophy more generally (esp. theories of distributive justice). I will post some more specific thoughts on these issues later. Here is the abstract of this UTLJ article:

In his provocative and masterly book Judging Under Uncertainty Adrian Vermeule seeks to displace the dominance of what he calls ‘first-best conceptualism’ in legal theory and instead argues that interpretive law needs to take an institutional turn. Vermeule’s focus on the empirical problems of institutional interpretation is a welcome and long overdue contribution to legal theory. Judging Under Uncertainty is an ambitious book and a valuable contribution to legal theory. The book deals exclusively with American law and Vermeule’s institutional approach to legal interpretation takes the existing status quo of the American system as a given. This, one might be tempted to complain, limits the scope and application of the institutional theory advanced by Vermeule. I shall raise some of these concerns towards the end of this review article when I consider some of the insights Canadian jurisprudence could contribute to the development on an institutional theory of legal interpretation (as well as the insights Canadian legal theorists can take from Vermeule’s compelling and important arguments).

Cheers,
Colin

Gene Therapy for Blindness (Update)

Back in May of last year I posted this, which linked to this BBC News story about Robert Johnson who underwent the first ever gene therapy for a sight disorder.

The "online first" section of the NEJM has the encouraging results of two preliminary clinical trials for gene therapy for retinal degeneration. Here is an excerpt from the NEJM editorial:

In both these studies, patients had severe vision loss secondary to Leber's congenital amaurosis that was documented by visual acuity and ERG, as well as by microperimetry, which measures retinal sensitivity at precise locations (carried out by Bainbridge et al.), and pupillary light reflex, measured by pupillometry (carried out by Maguire et al.). Bainbridge et al. showed no change in patients' visual acuity, whereas all three patients in the study by Maguire et al. found a gain in visual acuity. Visual acuity is a subjective measure, and since the patients could not be masked in either study, there is certainly a possibility of placebo effect for this outcome measure. Furthermore, measurement of visual acuity at such low levels of acuity is not reliable. The fact that three patients in the study by Maguire et al. showed improvement and the three patients in the study by Bainbridge et al. did not show improvement is of uncertain significance. With additional subjects and longer follow-up, this outcome may prove more informative, particularly if continued safety justifies the inclusion of patients with better baseline visual function.

As this Telegraph article notes, unfortunately the treatment was not successful for Mr Johnson. But he is quoted as saying: "For the team, I am thrilled that their hard work and dedication has paid off, with promising results in one patient allowing them to continue with this important trial,". The one patient was 18-year-old Steven Howarth, whose life has been transformed by the treatment. Here is a sample from the Telegraph story:

"Before the operation I used to rush home from college when it started to get dark because I was worried about getting around," he said.

"Now I can take my time and stay later at college if I need to, for band rehearsals and things like that."

His father, Tommy, said the change was "incredible".

"He's doing things now that he just couldn't do before," he said. "It's completely transformed the life he leads."

The teenager, of Westhoughton, near Bolton, said his eyes felt like sandpaper after the operation and he could not see anything.

"But it got much better after a week," he said. "Now my sight is definitely better when it's getting dark. It's a small change, but it makes a big difference to me."

Forbes also has an in-depth report on the two studies here.

What does gene therapy for vision involve? See this video.

Cheers,
Colin

Students' Questions from "National DNA Day"

Friday was National DNA Day. And like National Child Day, DNA Day is something I can get really excited about as the message of such a day (i.e. celebrate human curiosity, ingenuity and science!) is vital for a healthy and humane polity.

The NHGRI web site has a list of hundreds and hundreds of questions students sent in all over the U.S. on DNA Day. And reading over the very long list of questions raised by these bright students was very encouraging. Here is a sample:

Q: Kannapolis Middle School (8th grade student): How many different countries worked on the human genome project?
A: Phyllis Frosst, Ph.D.: From its inception, the HGP has been an international effort. The United States has made the largest investment, but important contributions have come from many countries, including Britain, France, Germany, Japan, China, and Canada.


Q: Booth Middle School (7th grade teacher): How is DNA being used in the field of evolutionary biology?
A: Elliott Margulies, Ph.D.: Since DNA is found in every living organism, we can compare DNA from different species to see which bits are similar and which bits are different. When sequences remain similar throughout millions of years of evolution, we can deduce that the sequence is likely functional. In fact, "comparative genomics" is a major way we can determine the functions encoded genomic sequences.

Q: Holy Family Catholic High School (9th grade student): Why do people have red hair?
A: Arjun Prasad, B.S.: The genetics of hair color in humans is not very well understood, but a lot of work has been done in the hair color of horses because breeders have been very interested in breeding certain hair colors of horses. Horse hair color is controlled by a large number of genes, only some of which have been worked out. Some of the genes that control horse coat color are genes that code for the actual colored proteins behind horse coat color, and some of them are differences in when/where those genes are turned on or off to make white legs, or spots for example.

Q: John C. Fremont High School (10th grade student): Can parents choose the sex of their children?
A: Don Hadley, M.S., C.G.C.: There are ways that have been suggested to increase the chances of having a boy or girl, however, they are NOT fully reliable. This is an issue that raises many ethical and social issues of concern. Should we, as a society, be picking our children's characteristics and traits? There's no easy answer to this and it will require a lot of careful consideration.

Q: Rock Canyon High School (11th grade student): How difficult is it to turn on or turn off a persons genes once they are already an adult? (MS)
A: Greg Feero, M.D., Ph.D.: It is not, your genes turn on and off many times a day in each of your cells. Many factors affect this including your diet, your physical activity and and the medications you might take....

Q: Dennis (10th grade student): Do chimpanzees have DNA similar to humans?
A: Carla Easter, Ph.D.: Humans and chimpanzees are about 95% genetically identical.

Q: Susan (n/a grade other): Have you discovered the genes involved in depression or bipolar disorder?Once the genes are identified, how difficult is it to come up with drugs that over come the genetic deficiency?
A: Greg Feero, M.D., Ph.D.: In the last year there have been a large number of studies relating gene discoveries relevant to mental health conditions. These have come about because of a new approach to gene discovery called "genome-wide association studies". Each of these new markers provides potential new approaches to develop therapies. Discovery of new drugs is usually a long and challenging process, but with new genes in hand many scientists are excited that new therapies will come in the next few decades. For more on genome-wide association studies see the catalog of genome wide association studies on www.genome.gov

Q: Francis Howell North (11th grade student): Which genetic diseases are increasing in frequency in humans (in the past few generations)?
A: Greg Feero, M.D., Ph.D.: In the United States diseases like diabetes and heart disease are increasing in the population. These diseases result for interactions between environmental factors and a large number of genetic factors. The interesting question is why. It seems less likely that the genetic factors are becoming more common and much more likely that those disorders are becoming more common because the environmental factors (like lack of exercise and poor diet) are becoming more common.

Q: Montgomery College (Higher Education grade student): What proportion of the human genome is thought not to have a function (truly "junk" DNA)?
A: Elliott Margulies, Ph.D.: A long time ago, some people thought that all DNA that didn't code for genes was "junk". We now know that non-coding DNA plays a very important role in regulating how genes are turned on and off. We're still trying to figure out what all this non-coding DNA does, and my bet is that little to none is "junk" (though admittedly that gives me job security since my lab studies non-coding DNA!)

Q: Westview High School (9th grade student): What are major hurdles scientists are still faced with that they still have to overcome?
A: Arjun Prasad, B.S.: One fun thing about being a scientist is that the more we discover the more we realize all that we don't know. We have completed the sequencing of the human genome, but we are now trying to understand what it all means. A big hurdle now is to understand the genetic differences between people that are responsible for inheritable differences in disease susceptibility. We know that some people can smoke their whole lives and never get lung cancer, why is that? The hope is that by figuring out the genes that increase risks for disease we can also figure out how to prevent them from getting the disease in the first place and treat those diseases more effectively.

Q: Michael pointer (9th grade student): will learning this stuff actually help us in the future?
A: Alan Guttmacher, M.D.: I guess it depends what stuff you are learning - although almost anything I have learned has eventually proved useful sometime. If you mean this stuff about genetics, the answer is definitely "yes." In your lifetime, much of health care will rely on patients being knowledgeable enough about genetics to work with their doctors to devise personalized prevention strategies to avoid many of the common diseases that us old folks have fallen victim to...

Q: Shikellamy High School (10th grade student): Have you ever said "I don't know" to a genetic question?
A: Alan Guttmacher, M.D.: YES!!!!! In both research and in medicine, it is incredibly important to know when you don't know something, and to be honest about that fact with both yourself and others. In fact, much of the fun of research is to answer questions that have never had an answer before.

Q: Maple Shade High School (10th grade student): What causes bad vision?
A: Don Hadley, M.S., C.G.C.: There are a number of factors that can cause a person to have poor vision. A person's genetic make-up can be one of the factors that influence our ability to see. Many genes are being identified that influence our visual abilities on different levels, development, clarity, ability to see far and near, etc. However, there are other "non-genetic" factors that can be involved in our ability to see such as environmental factors that effect the development of the eye while the baby is growing in the mother's womb or exposures to harsh chemicals that cause destruction to functioning of the eye. Great question. I encourage you to look into this further

Q: Joe Nva Academy (9th grade student): what is the worst possible disease to get if your genomes are messed up
A: Alan Guttmacher, M.D.: There is no single answer to this question. It depends upon who you ask and what things they care about. If someone cares most about having a long life, then any of a number of diseases that often provide fateful very early in life would be the answer. If it was avoiding physical pain that was most important, that would dictate another list of diseases. If it was having a condition that leads to loss of intelligence and control over one's body, yet another group of conditions would come to mind. If it was diseases that lead to physical disfigurement that were most feared, that would be another group. So, it all depenfds upon who you ask, and what they care most about...

Cheers,
Colin

Aging Cell Article on Longevity Genes

The latest issue of Aging Cell has this excellent Review piece which is currently available online for free. It's titled "Genes encoding longevity: from model organisms to humans" by Maris Kuningas et. al. Here is the summary:

Ample evidence from model organisms has indicated that subtle variation in genes can dramatically influence lifespan. The key genes and molecular pathways that have been identified so far encode for metabolism, maintenance and repair mechanisms that minimize age-related accumulation of permanent damage. Here, we describe the evolutionary conserved genes that are involved in lifespan regulation of model organisms and humans, and explore the reasons of discrepancies that exist between the results found in the various species. In general, the accumulated data have revealed that when moving up the evolutionary ladder, together with an increase of genome complexity, the impact of candidate genes on lifespan becomes smaller. The presence of genetic networks makes it more likely to expect impact of variation in several interacting genes to affect lifespan in humans. Extrapolation of findings from experimental models to humans is further complicated as phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar. Finally, currently used methodologies may have only little power and validity to reveal genetic variation in the population. In conclusion, although the study of model organisms has revealed potential candidate genetic mechanisms determining aging and lifespan, to what extent they explain variation in human populations is still uncertain.

And here is a sample from the article:

Over the last century, the mean life expectancy in Western societies has increased dramatically (Oeppen & Vaupel, 2002). In Japan, for instance, the mean life expectancy has increased from 50 years to 80 years in no more than six decades. It is unlikely that changes in the population genome over this time-period can explain for the observed increase in lifespan which is more likely to be attributable to the improvement of environmental conditions and medical care. The increase in mean life expectancy of the total population, however, has left the marked interindividual variance in lifespan unaltered. Socio-economic factors can in part explain this phenomenon, but ample evidence suggests that genetic factors are also at play. Studies of twins and long-lived families have estimated that 20–30% of the variation in human lifespan is determined by genetic factors, which impact becomes more important for survival at older ages (Herskind et al., 1996; Mitchell et al., 2001; Hjelmborg et al., 2006). Furthermore, siblings of centenarians have a significantly higher chance of becoming a centenarian themselves when compared to other members of their birth cohort (Perls et al., 2002). The survival benefits of family members of these long-lived subjects are lifelong and persist up to the highest age categories (Perls et al., 2002; Hjelmborg et al., 2006). Offspring of long-lived sibling pairs have a lower mortality risk already at middle age, whereas their spouses, with whom they have shared in part a common environment, do not show this survival benefit (Schoenmaker et al., 2006).

As for lifespan, aging is under moderate genetic control influencing the rate at which stochastically induced damaged molecules accumulate. Such damage is caused by various endogenous and exogenous biological and biochemical stresses. As a result, over the life course there is a constant rise in vulnerability of the body, leading to a continuously increasing risk of disease and death. Longevity and the maintenance of health in old age can be ensured via two principally different strategies that minimize the risk of permanent damage to occur, that is, by a decrease of environmental hazards or an increase of the durability of the body. Pathways that influence metabolism, maintenance and repair mechanisms, and prevent the accumulation of permanent damage thus represent key molecular candidates for the preservation of health and longevity.

Experiments in model organisms have demonstrated that a series of induced mutations in various genes that make up an integrated molecular pathway can dramatically increase lifespan. The most prominent example includes the Caenorhabditis elegans daf-2 and clk double mutants that live nearly five times longer than wild-type worms (Lakowski & Hekimi, 1996). Most of the genes of model organisms are evolutionarily conserved and present in humans.

Fascinating stuff!

Cheers,
Colin

How Scepticism About Science Harms the Least Advantaged

In some previous posts (e.g. here and here) I lamented about the harms of dogma and ignorance. Popular opposition to genetically modified crops is another perfect example of this. It's easy for those in the richest countries to demand organic produce, even when it costs more than perfectly healthy, cheaper food (it's the same as our irrational aversion to drinking tap water).

But our scepticism about the science of genetically modified crops has harmful consequences for those in the poorest parts of the world where the costs of food are much higher. Many in the West like to think they are helping to combat global poverty by riding their bike to work, or having less children (indeed, perhaps none!), thus minimizing their carbon footprint. And yet many of these same people fiercely oppose what they view as "frankenstein" food; when the reality is that support for these technologies could actually help the most vulnerable people in the world. This reinforces a point I've made before: that good intentions themselves are not enough. Good intentions, when coupled with dogma or ignorance, can be just as harmful (sometimes even more harmful) that malicious intentions. True Wisdom is only achieved when we act in accordance with both our hearts and our heads.

While many people might intuitively feel that the idea of genetically modified crops sounds risky and dangerous, the reality is there is no scientific evidence to suggest they are unsafe (and yet many people still smoke and obesity is an epidemic, despite the overwhelming scientific evidence of their harms...so it you are really worried about our health, protest against smoking and physical inactivity!).

But don't take just my word for it. Here is what Health Canada says about consuming genetically modified foods:

Is there any scientific evidence to suggest that genetically modified foods are less safe that those foods produced using conventional techniques?

After twelve years of reviewing the safety of novel foods, Health Canada is not aware of any published scientific evidence demonstrating that novel foods are any less safe than traditional foods. The regulatory framework put in place by the federal government ensures that new and modified foods can be safely introduced into the Canadian diet. Safety assessment approaches are well established to address the potential risks associated with foods.

This NY Times article suggests that perhaps people in the developed world will come around to their senses now that we have set the fight against poverty back by 7 years. Here is a sample:

Soaring food prices and global grain shortages are bringing new pressures on governments, food companies and consumers to relax their longstanding resistance to genetically engineered crops.

....Genetically modified crops contain genes from other organisms to make the plants resistance to insects, herbicides or disease. Opponents continue to worry that such crops have not been studied enough and that they might pose risks to health and the environment.

“I think it’s pretty clear that price and supply concerns have people thinking a little bit differently today,” said Steve Mercer, a spokesman for U.S. Wheat Associates, a federally supported cooperative that promotes American wheat abroad.

The group, which once cautioned farmers about growing biotech wheat, is working to get seed companies to restart development of genetically modified wheat and to get foreign buyers to accept it.

...Through gene splicing, the modified crops now grown — mainly canola, corn, cotton and soybeans — typically contain bacterial genes that help the plants resist insects or tolerate a herbicide that can be sprayed to kill weeds while leaving the crop unscathed. Biotechnology companies are also working on crops that might need less water or fertilizer, which could have a bigger impact on improving yield.

Cheers,
Colin

Inequalities That Really Matter (but we seldom think about)

Human beings can be unequal in a variety of different ways.

For example, one person may be taller than another. Or one person may be more intelligent than another person. Some people have more friends and loved ones in their lives than other people. Others might be fluent in more than one language, while some struggle to even read and write in their native tongue.

Given there are innumerable ways in which human beings differ, it is worth pondering which inequalities or differences are the most important and in need of redressing. And in this post I limit my reflections to issues that arise in the case of domestic justice (things look a bit different when we move to considerations of global justice).

So of the various inequalities we could attend to in our society, which ones should we give serious attention to? Inequalities in wealth? Inequalities in opportunities for education? Inequalities in health? Etc. etc.

Well, such questions are ones that often weigh on my own deliberations (e.g. here and here) as I attempt to try to get an accurate sense of the most pressing issues we face. As I’ve noted many times before, I do not consider myself an “egalitarian” in the way that that label is used by most contemporary political philosophers who count themselves as “egalitarians”. But I am interested in the story of why different kinds of inequalities exist, and what, if anything, we could (and ought to) do to redress them. And I usually prefer to classify this in prioritarian rather than egalitarian terms (see this post). But today I feel like exploring these thoughts from an egalitarian standpoint. So please allow me to indulge myself in seeing where these thoughts lead me.

Here is one inequality that you seldom hear anything about, but it is an inequality that I think is actually very important and worth thinking seriously about. Let’s compare the life prospects of the following two individuals- Claire and Katherine.

Both Claire and Katherine live in the same, relatively affluent, city in Canada. In fact, Claire and Katherine are neighbours. And they have known each other for about 10 years now, from the time Claire’s family moved into the house beside Katherine.

But Claire and Katherine are unequal in many respects. Claire is the head cheerleader at her college. She also plays basketball and enjoys running. Claire is a straight “A” student, and recently wrote on article on women and politics for the local newspaper.

Claire’s situation stands in stark contrast to the situation of Katherine. Katherine’s mobility is severely limited. She can barely sit up on her own, and is unable to walk. She relies on others to help feed and bath her. Katherine finds it hard to concentrate for long periods of time and she often forgets who her loved ones and friends are.

If we look at things through a *synchronic lens*, the life prospects of Claire and Katherine as thus very unequal. Claire has a very low risk of developing disease in the next twenty years of her life. Katherine, however, is not expected to live more than five more years. Katherine already suffers dementia, among many other aliments (e.g. high blood pressure, weak bones, poor vision, infertility, etc.).

The case of Claire and Katherine is not an unusual one. It is a scenario typical of many neighbourhoods all around the country (indeed, around the world). You might be wondering what explains the vast difference between the life prospects of Claire and Katherine. Well, the most relevant fact is that Katherine is actually 65 years *older* than Claire. Claire is 20 years old, Katherine is 85 years old.

Now once I give you this further bit of information your moral sensibilities might start to alter. Perhaps you were initially concerned about the inequality between Claire and Katherine, but now that I have revealed their age you are not concerned (or are less concerned then you were before I mentioned this fact). You might feel that the afflictions that Katherine suffers are “natural” and there is nothing we can do about them. Alternatively, you might feel that there is no real inequality between Claire and Katherine when we measure their health prospects over their expected lifetimes, rather than at a particular moment in time. And so perhaps you feel that a comparison of their lives should really be made through a diachronic, rather than synchronic, lens.

But luck egalitarians cannot, I believe, easily cast aside this kind of inequality. Recall that luck egalitarians maintain:

Inequalities in the advantages that people enjoy are just if they derive from the choices people have voluntarily made; however, inequalities deriving from unchosen features of people's circumstances are unjust.

Katherine’s debilitating condition is not the result of her choice (she didn’t choose to experience the cellular damage that comes with aging), but rather it is the result of brute luck. Well, the story is more complex (and interesting) than saying it is just brute luck. Katherine’s condition is the result of our species’ evolutionary history. Why do human’s age the way we do? Why don’t we age like turtles (see this)?

The question of why we age is a very interesting, important and complex question. One influential answer among scientists is that the level of extrinsic mortality is a principal determinant in the evolution of longevity. So in many respects Hobbes was correct when he said that life in the state of nature was “nasty, brutish and short”. Not only was it short in the state of nature, but also in societies that instituted a government. It was only in the twentieth century that real substantive gains were made in life expectancy.

This Time website, for example, has a useful comparison of life expectancy (among other things) in the United States, Italy, Japan and Mexico, from 1900 to 1998. During the last century life expectancy in the US rose by 29 years, Italy by 34 years, Japan by 36 years, and Mexico by 41 years. Nothing like these dramatic increases has ever occurred in the history of humanity! The vast majority of human beings born over 200 years ago would have died before my current age (38).

And so the disadvantages visited upon Katherine are really a legacy of the challenges her (and our) distant ancestors faced. Because very few humans that have ever lived on this planet died from age-related causes (versus poverty, violence, infection, infectious disease, etc.), Katherine’s biology was not designed to protect her from the ravages of time itself.

But the fact that the passage of time killed a very low percentage of human beings in the past does not mean this will necessarily be the case in the future. And while there are many possible things that could kill the world’s existing population (which is currently 6.5+ billion people), the vast majority of these people will most likely suffer age-related morbidity and mortality. And so I think it is accurate to label senescence is the real “scourge” of the 21st century. To say this doesn’t mean we could actually eliminate senescence, but even if we just retard human aging, so that people can enjoy more years of disease-free life, then it would be a very laudable accomplishment.

So if, as many scientists who work on longevity science believe, there might actually be a way to redress the inequality between people in the kind of situation described by Katherine and Claire, then we need to think seriously about what justice requires.

Just a brief point to avoid some likely confusion. I am not suggesting that science will permit us to reverse or undo the disadvantage that Katherine currently suffers (though advances in regenerative medicine might make that possible); rather I am suggesting that it is likely that we may be able to intervene in our biology so that by the time a person reaches their 85th birthday their risk of mortality and morbidity could be significantly reduced compared to what it is for today’s average 85 year-old . While such an intervention would not result in such a person having the health profile of today's 20 year-old, if it just reduces the risk of disease and disability to the level enjoyed by today’s 60 year-old that would be very significant. And if there is a sound basis for believing this could be achieved, then I think egalitarians should favor investing public funds in this science. For anti-aging interventions would not only benefit people like Katherine, they would also benefit Claire (and every other person in the world who is susceptible to senescence!). So everyone wins when society suffers less age-related morbidity.

To fail to invest in the science that could help confer extra disease-free years on humans is irrational and morally indefensible. Contrary to the intuitions of most egalitarians, I believe that tacking human aging is actually a requirement of equality. It is not the only requirement, but it is a requirement none-the-less. Tackling human aging is simply a subset of the more general goal of keeping humans healthy. If we want to prevent cancer, diabetes, AD, bone fractures, infection, age-related macular degeneration, age-related hearing loss, etc. etc., then we should also want to minimize the damage caused by senescence. For these things are the result of this damage. Aging is by far the biggest cause of disease (at least in the developed world, if not the world as a whole). Modifying the biological processes of aging could turn out to be one of the most cost-effective ways of ensuring quality of life for those in the later stages of life.

There is a lot more to be said here. But for now I just wanted to float a few of these ideas out there.

Cheers,
Colin

Genetic NonDiscrimination Bill (Update)

This CNN story suggests that the long-awaited Genetic Information Nondiscrimination Act (see here and here) might soon become law. Here is an excerpt from the story:

Lawmakers have agreed to make it illegal for employers and insurance companies to deny applicants jobs and health care coverage because DNA tests show they are genetically disposed to a disease.

Supporters of the Genetic Information Nondiscrimination Act said Wednesday that the Senate planned to vote on it Thursday. The House also is likely to give quick approval to the bill, sending it to President Bush for his signature.

A similar bill passed the House by a 420-3 vote a year ago. The White House, at the time, indicated its support for the legislation.

Sponsors reached an agreement Tuesday with Sen. Tom Coburn, R-Oklahoma, who had been blocking Senate action on the bill.

The compromise tightens language to ensure there is a "firewall" between the part dealing with health plans and the section regarding employment so as to discourage inappropriate claims.

It also makes clear that, while individuals are protected from discrimination based on genetic predisposition, insurance companies still have the right to base coverage and pricing on the actual presence of a disease.

Cheers,
Colin

Main Menu (April 2008)

Some recent posts on "In Search of Enlightenment" include:

(1) Science Editorial on Importance of Science Education

(2) Bad Government 101: Lessons to be Learned from the Bush Administration

(3) Risk of Harm in Sport

(4) Thinking Outside the Box

(5) Genes and Our Evolutionary History

Cheers,
Colin

The "Dictator" Gene?

Advances in genetics are helping us gain a better understanding of the role genes play in different, complex behavioral traits and characteristics.

And the latest issue of the journal Genes, Brain and Behavior has this article which nicely illustrates the kinds of insights being made. The lengthy title is "Individual differences in allocation of funds in the dictator game associated with length of the arginine vasopressin 1a receptor RS3 promoter region and correlation between RS3 length and hippocampal mRNA" by Knafo A et. al. Naturenews has a story about the study's findings here.

The study suggests that there is a genetic link to "ruthlessness", which is tested in an economic exercise called the "Dictator Game". Here is an excerpt from the Naturenews story:

Ebstein and his colleagues decided to look at AVPR1a because it is known to produce receptors in the brain that detect vasopressin, a hormone involved in altruism and 'prosocial' behaviour. Studies of prairie voles have previously shown that this hormone is important for binding together these rodents' tight-knit social groups.

Ebstein's team wondered whether differences in how this receptor is expressed in the human brain may make different people more or less likely to behave generously.

To find out, they tested DNA samples from more than 200 student volunteers, before asking the students to play the dictator game (volunteers were not told the name of the game, lest it influence their behaviour). Students were divided into two groups: 'dictators' and 'receivers' (called 'A' and 'B' to the participants). Each dictator was told that they would receive 50 shekels (worth about US$14), but were free to share as much or as little of this with a receiver, whom they would never have to meet. The receiver's fortunes thus depended entirely on the dictator's generosity.

About 18% of all dictators kept all of the money, Ebstein and his colleagues report in the journal Genes, Brain and Behavior. About one-third split the money down the middle, and a generous 6% gave the whole lot away.

....There was no connection between the participants' gender and their behaviour, the team reports. But there was a link to the length of the AVPR1a gene: people were more likely to behave selfishly the shorter their version of this gene.

....Though the mechanism is unclear, Ebstein says, he is fairly sure that selfish, greedy dictatorship has a genetic component. It would be easier to confirm this if history's infamous dictators conveniently had living identical twins, he says, so we could see if they were just as ruthless as each other.

Cheers,
Colin

Watson's Genome

Back in September I posted this story about the sequencing of Craig Venter's genome. NatureNews reports about the exciting progress being made with sequencing technology. The cost of sequencing Venter's Genome was $100 million. But now James Watson's genome has been sequenced (in just 4 months) with the next generation of technology for less than $1.5 million. This makes the prospect of achieving a $1000 human genome look like something that could be achieved in the near future.

Here is the abstract of the actual Nature article entitled "The complete genome of an individual by massively parallel DNA sequencing":

The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome1, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2–40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual2 by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'.

Cheers,
Colin

NEJM Piece on Global Health Challenges

The latest issue of the New England Journal of Medicine has this interesting article by Tadataka Yamada, who is the President of the Global Health Program for the Bill and Melinda Gates Foundation. The essay is entitled "In Search of New Ideas for Global Health". Here is a sample:

The recent failure of another potential vaccine against human immunodeficiency virus (HIV) underscores the enormous challenges of tackling diseases whose heaviest burden falls on the developing world. A quarter of a century after the first report of AIDS, our knowledge about how an HIV vaccine might work is still distressingly limited. It seems clear that neither current dogma nor traditional thinking is likely to get us to the next step. Truly creative ideas will be required.

....New ideas should not have to battle so hard for oxygen. Unfortunately, they must often do so. Even if we recognize the need to embrace new thinking — because one never knows when a totally radical idea can help us tackle a problem from a completely different angle — it takes humility to let go of old concepts and familiar methods. We have seemed to lack such humility in the field of global health, where the projects related to diseases, such as HIV, malaria, and tuberculosis, that get the most funding tend to reflect consensus views, avoid controversy, and have a high probability of success, if "success" is defined as the production of a meaningful but limited increase in knowledge. As a result, we gamble that a relatively small number of ideas will solve the world's greatest global health challenges. That's not a bet we can afford to continue making for much longer.

....To help promote a more adventurous approach to research, the Bill and Melinda Gates Foundation, where I am president of the Global Health Program, is willing to take risks as well. We are launching a $100 million initiative called Grand Challenges Explorations, which will supplement our current grant making by funding hundreds of innovative early-stage projects over the course of 5 years, investing $100,000 in each one. We want bold ideas — even seemingly wacky ones — that need just a little help to get tested. Proposals will require creative thinking but no preliminary data. The applications are only two pages long, and we'll make a funding decision within about 3 months after the May 30 submission deadline. We'll run each idea past two groups of reviewers — one composed of internal scientists, and another of partners and advisers with a history of identifying creative solutions to difficult problems. We expect many of these projects to fail, but we stand ready to put substantial funding behind those that succeed.

Details about the Grand Challenges initiative are available here.

Cheers,
Colin

Yet More on Priorities and Proportionality

In my earlier posts Bad Government 101 and More on Risks and Priority Setting I detailed some of the important lessons we can learn from the US response to the threat of terrorism.

Today I read this interesting piece in the Guardian on the tragic consequences of biofuel policies. In many ways I think an important analogy can be made between the insights of my post on the war on terror and the threat of global warming. While I have a great amount of respect for Al Gore (as noted before and here), I believe there are some (disturbing) parallels between the alarmist message that he champions with respect to climate change and G.W. Bush's stance on the threat of terror.

And just as few were willing to speak up against policies like the USA Patriot Act in the immediate aftermath of 9/11, very few are willing to raise concerns against environmental policies for fear that they might be construed as "environmental skeptics". I am not such a sceptic. But I know that good intentions alone are not enough to make a positive, lasting improvement to humanity. And anyone who believes the answers are obvious or simple is not giving these issues enough attention. Good intentions alone can often result in bringing about the very tragic consequences one is trying desperately to avoid or mitigate-- like harming those already vulnerable and impoverished.

In the Guardian article Robert Zoellick, president of the World Bank, claims that rocketing food prices had set back the fight against poverty by seven years.

What are the costs of a 7 year set back in the war on poverty versus the likely gains to be had from biofuel policies? A failure to take these issues seriously will likely result in our doing more harm than good. What's more important-- *feeling* like we are actually doing good in the world, or actually doing good? I wish more people took the latter more seriously.

Cheers,
Colin

Heading to Queen's

Those at UW may have already heard this news, but I am leaving this summer to join the Dept of Political Studies at Queen’s University as a Queen’s National Scholar.

Leaving UW was not an easy decision as my colleagues here have been very supportive and collegial during the five years I have been here. But Queen’s offers me new exciting intellectual challenges that I am really keen to pursue. With their strengths in political theory (as well as the discipline as a whole), plus a first-rate philosophy dept with expertise in both bioethics and political philosophy (not to mention a Law School, School of Medicine, School of Policy Studies, etc.!), I can’t think of a more engaging environment for pursuing the kind of interdisciplinary research I believe is needed to meet the pressing ethical and social challenges that we face this century. So I am very excited about the move to Queen's.

I have really enjoyed my time here at Waterloo. I have had the privilege of teaching a number of truly first rate students. I want to thank those students who have, over the years, eagerly participated in my fourth year/MA seminar on “Genetics and Justice”. (This is a course I will continue to offer at Queen’s. Indeed I expect to develop that course even further over the coming years). And I am especially grateful to the democracy reading group here at Waterloo. Together we have debated almost every important issue one can think of. And Jan Narveson has proven to be a very generous and engaging intellectual companion. While we (still!) disagree on many things, I have learned so much from Jan. Having such a collegial and sharp critic at hand to attack one’s ideas is one of the most valuable resources a scholar could hope to have. If only I had half the energy that Jan possesses! While he has been officially “retired” for a few years now, one wouldn’t know it by the very busy schedule he maintains (which included teaching a few of my courses while I was on sabbatical).

The move to Kingston will be the sixth move for my wife and I over the past decade. Our journey began back here (from 1996-99 while I was doing my PhD), then here for a year (where son #1 was born), then here for two years (where son #2 was born), then here for a year, then to Waterloo in 2003, and a special year here and here in 2006/7 (and son #3 was born 2 weeks early back in Waterloo while I was tying up some loose ends in Oxford!).

And now we are all headed here.

It’s been an amazing journey! One I couldn’t have taken on without the love and support of my wife and kids.

So while we are sad to be leaving our friends in Waterloo, we have many fond memories of both the city and the University. And we are all looking forward to the next chapter of our lives in Kingston.

Cheers,
Colin

The Speedo "Enhancement" ?

I've posted a few thoughts before about the role of "enhancements" in sport (see here and here).

Well, this issue is in the news again as the Speedo LZR Racer swimsuit has come out with this new swimsuit which some argue will result in many world records being broken.

Here is a snippet from the CNN story:

Since the suit was unveiled in February, 19 long-course world records have been set and four short-course marks. The new Speedo suit has been worn in all but one of the 23 records.

At this point in 2004 -- the last Olympic year -- five world records had been set.

Swimming's world governing body decided last weekend not to ban the new high-tech suit, despite claims of buoyancy and "technological doping" by some critics.

"I wouldn't be surprised to see every world record broken at the games, and hopefully we'll get a big percentage of those," said Schubert, one of the most outspoken supporters of the new swimsuit.

Cheers,
Colin

Sinclear Interview in RR

I've posted a few things before about the important aging research of Harvard's David Sinclair. The latest issue of Rejuvenation Research has an interesting interview with Sinclair on his research and the anti-aging molecule resveratrol (which is found in red wine).

Here is a sample from the interview:

RR: a high-profile biogerontologist with a clearly stated agenda to combat aging—a controversial goal. How do you maximize the benefits of the public’s interest in such work while minimizing the drawbacks?

DAS: There are two schools of thought. One is that it is dangerous to talk to the media. The other view is that the public has a right to have the research they fund explained to them in a way they can understand, without hyping it. I am in the latter camp. I have not sought media attention, but I feel it is my duty as a scientist to explain to the public what their money is being used for and why this is an important area that deserves to be funded more than it is currently, and to correct any myths whenever possible. I often do interviews in which I do my best to explain how important and how cutting edge this field is, and what its benefits could be for society. I am not always successful in getting my message across, and many times I have been misquoted and misinterpreted. But that is worth the risk in my view.

Some people are against extending lifespan, and I have debated, for example, Leon Kass (who was chairman of President Bush’s Council on Bioethics from 2002–2005). We have disagreed on many things. My goal is to convince the opposition that what we are trying to do is no different than any other type of medical research. We are trying to improve people’s lives, and in doing so the cost savings to society, not just in terms of people’s well-being, but also the economic benefits, will be in the trillions of dollars.Therefore, we cannot afford not to try to advance this area of science as quickly as possible.

My stated goal is to keep people out of nursing homes for as long as possible. It is known that the longer a person lives, the shorter the period of his or her chronic disability or illness. People who live a very long time die relatively quickly. Thus, the goal would be to reach 90 years of age, feel well, still be a productive member of society, be able to play tennis, and see your grandchildren graduate from college. Then, in a matter of weeks, go through the final stages of life and die. In that way we would suffer less and be less of a burden on our families and society.

I like the way Sinclair summarizes the goal of his research-- "to keep people out of nursing homes as long as possible". So the motto of anti-aging science should be "Live long and die fast!". Or, to borrow a phrase from this Neil Young classic--"It's better to burn out then to fade away!" And such an aspiration is one I think everyone should agree is a laudable goal.

Cheers,
Colin

Nature Poll on Cognition-Enhancing Drugs

Nature ran a poll on the use of cognition-enhancing drugs and the results are now posted here. One in five respondents said they had used drugs for non-medical reasons to stimulate their focus, concentration or memory. Here is a sample:

All participants who took part in the survey were asked 10 questions designed to gauge their attitudes towards neuroenhancing drugs. Almost all respondents (96%) thought people with neuropsychiatric disorders who have severe memory and concentration problems should be given cognition-enhancing drugs. But perhaps surprisingly, a high four-fifths thought that healthy adults should be able to take the drugs if they want to. And 69% reported that they would risk mild side effects to take such drugs themselves.

Cheers,
Colin

NG Paper on Mitochondrial DNA and Aging

One of the rapidly growing areas of interest in aging research is the role played by mitochondria DNA. What are mitochondria? This site explains:

Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. This genetic material is known as mitochondrial DNA or mtDNA. In humans, mitochondrial DNA spans about 16,500 DNA building blocks (base pairs), representing a fraction of the total DNA in cells.

Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. Oxidative phosphorylation is a process that uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell's main energy source. The remaining genes provide instructions for making molecules called transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), which are chemical cousins of DNA. These types of RNA help assemble protein building blocks (amino acids) into functioning proteins.

Mitochondrial genes are among the estimated 20,000 to 25,000 total genes in the human genome.

The latest issue of Nature Genetics has this Brief Communication piece which further illustrates the impressive and exciting advances that are being made in aging research. Here is the abstract:

"DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice" by Marc Vermulst et. al.

Mitochondrial DNA (mtDNA) mutations are thought to have a causal role in many age-related pathologies. Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA deletions. In addition, our results demonstrate that the rate at which mtDNA mutations reach phenotypic expression differs markedly among tissues, which may be an important factor in determining the tolerance of a tissue to random mitochondrial mutagenesis.

Cheers,
Colin

P.S. the image of the "anatomy of the cell" is provided via the Lucile Packard Children’s Hospital website at Stanford.

Aging Research and Aggregation

This post is, in many respects, the latest update to my series of “Genetic Justice” posts (so this would be update #3, here are #1 and #2)

As I’ve noted many times before (e.g. here and here), a great deal of my current research concerns the moral imperative to retard human aging. This aspect of my research sprung out of my ongoing work on genetic justice, a topic I have been working on for about the past 8 years now.

In fact, digging up some old blog posts, I can actually track down the *precise moment* when I started thinking more seriously about aging research. It started at this event at Stanford. In particular, I was really impressed by Aubrey De Grey’s JME paper on “Life extension, Human Rights, and the Rational Refinement of Repugnance”. And so it was Aubrey’s presentation that got me first thinking seriously about these issues.

I was so impressed by Aubrey that I knew I just had to include him in the event I organized last summer at Oxford on “Genetic Justice”.

Indeed, at that conference it was interesting to hear some arguing that we need to do more to tackle cystic fibrosis and then others arguing for tackling aging. Of course we ought to tackle both, but how do we go about determining priorities in such a scenario? The imperative to tackle any one disease is complicated by many factors. Those born with CF can only expect to live to their 30’s. When compared to individuals with CF, those that suffer age-related afflictions are fortunate. However, age-related afflictions are much more *prevalent* in the population. And so how do we compare the imperative to treat a rare, early onset condition with the duty to treat cancer or retard human aging? I think such questions are very important, and yet extremely complex and difficult to answer.

When I tell people I am working on justice and aging research they are often very puzzled. And here is how I would summarize the common response: “Justice may impose many different obligations on us— like eliminating world poverty, combating climate change, respect for cultural equality, eliminating gender inequality, etc. etc..- but how on earth can you say that justice requires us to modify the biological processes of aging so that we retard human aging?

This question is a very valid question. Indeed, it is something that has preoccupied most of my thoughts for the past two years! And over the past few days an important piece of this puzzle fell into place for me. So I wanted to post this blog to capture my initial thoughts about this “eureka moment!” in my thinking about these issues.

As I was revising one of my latest papers on justice and aging research (which builds on this previous post), I came across an excellent and very helpful discussion on Aggregation in chapter 5 of Scanlon’s excellent book What We Owe To Each Other.

In this chapter Scanlon explores how the contractualist could incorporate some room for aggregation without leading to the counterintuitive consequences of utilitarianism. These counterintuitive scenarios are typically ones where we have the option of preventing a large number of people from suffering a very minor harm (e.g. like a headache) or help a smaller number of people who will suffer a serious harm (e.g. premature death). In such cases a standard cost-benefit analysis would prescribe we should help the larger numbers because, once we add up the large amount of small benefits, they *outweigh* the large benefits that would only be conferred upon a small number of people.

But the important part of Scanlon’s chapter that I am particularly interested in is his acknowledgement that much hinges on the broad categories of moral seriousness. Let me explain how I think this can be very helpful to those championing aging research.

To suffer disease and disability is to suffer disadvantage that rates on the broad category of “moral seriousness”. Of course some diseases and disabilities are more serious than others. And the *Priority View* would prescribe that, all-else-being-equal, more weight should be placed on benefits to those who suffer the worst forms of disadvantage.

So let’s illustrate this with an easy two person example. Suppose there are two individuals in need of life-saving medical intervention. Person A suffers from an early onset disease (let’s say CF) and will die by age 35 if we do not help them. Person B suffers from a late onset condition (let’s say cancer) and will die at age 70 if we do not help them. We can only afford to help one of these two patients. What are we to do?

If one takes the Priority View to entail (as I think it does) that we look a person’s *expected life-time acquisition* of the natural primary goods (like health), then it clearly is the case that person A is in need of more urgent aid. Without intervention A will only live half the number of years of B. And so if we had to decide between A and B we should go with aiding A. Person B cannot reasonably reject a principle that gives greater moral weight to the interests of a person who is much worse off in terms of their expected life-time acquisition of health.

Now in this first case the problem of aggregation does not arise because there are only 2 people. So let’s add in some further facts to the example to see how the numbers complicate things. We now have 2 categories of individuals- those with an early onset disease and those with a late onset disease. Those in the first group (A) can expect to live to 35 (without treatment); those in the second category (B) will die at 70. The number of people in the two groups is very unequal. There are only 4 people in A and 10 000 in B. We can only provide treatment to one group, which group should we aid?

In this case the numbers are stacked in favour of aiding B rather than A. However, this conclusion is not arrived at by a simple aggregation of benefits across lives. For the contractualist, aggregation *within* each person’s life can justify why helping B rather than A is justified. Aiding A would mean that all 10 000 people in B would suffer premature death by disease. While dying of disease at age 70 might not be as serious as dying of disease at age 35, it is “morally relevant” in this case. And so the Complaint Model (which insists that the justifiability of a moral principle depends only on various individuals’ reasons for objecting to that principle and alternatives) could be satisfied in this instance. The four individuals in A, if they protest, could only respond in the following fashion: “The principle that prescribes aiding B (rather than A) will result in our premature death. Granted aiding us rather than B would also result in premature death for the people in B, but at least they have enjoyed a longer life than we have had the opportunity to enjoy”.

But when the numbers in this case are so unequal, so that for every life we could save/extend in A we could save/extend 2500 lives in B, and the benefits at stake are “morally relevant” (even though not equal), the decision to aid B is justified. And this in fact justifies why funding for cancer research dwarfs funding for rare (yet early onset) diseases. (Though this is not to say that the current levels of funding for medical research in general are fair and reasonable, I will leave that issue open for now)

So this then sets the stage for talking about aging research. Now consider the following two examples. People in Group A will die from cancer. People in Group B will die from the diseases of aging. This latter category includes most people in Group A, *plus* most people who die from heart disease, AD, diabetes, stroke, infection, bone fracture, etc., etc.

And thus once one clarifies what retarding human aging would actually mean to an individual’s life, we see how it passes Scanlon’s test for being “morally relevant”. As the author’s of the excellent paper “In Pursuit of the Longevity Dividend” argue, slowing aging by just 7 years would reduce, by approximately half at every age, our risk of death, frailty and disability. So retarding aging is not about prolonging the number of years we spend in the latest stages of the human lifespan; it is about increasing the number of *disease-free years* individuals can expect to enjoy. And once we realize this, we see that the current neglect of aging research is unjustified. For the goal of extending the number of disease-free years is what justifies our funding of medical research into cancer, heart disease, diabetes, etc. But the strategy of tackling one disease at a time is an inefficient and narrow approach to health extension. We should also explore the prospects of intervening in the biological processes of aging itself. This could confer significant health benefits on individuals (and enormous socio-economic benefits on society as a whole).

And so if I go back to the central principle of genetic justice I have defended elsewhere (the lax GDP) I think modifying our biology to retard human aging can be justified to the least advantaged (even though we have not yet developed therapeutic interventions for all early onset diseases). While these scientific advances would exacerbate genetic inequality between the "worst off" and those better off, they would create greater equality between the second least advantaged and the better off. And this is very important (even though it might exacerbate some level of inequality) as it would reduce the most prevalent diseases that afflict people in society.

Furthermore, aging research could actually help research into more rare conditions, for our understanding of the biology of aging is bound to confer some benefits to our understanding of early onset disorders (like pregoria).

And finally, I am not suggesting that funds be diverted from medical research into cures for rare early onset conditions into tackling aging. Rather I am suggesting that a greater portion of the funding we currently invest into tackling each age-related disease could be better spent on aging itself. And while we’re at it, we should also consider how much we invest in health related research in the first place, for we may be neglecting the interests of those who suffer both early onset and late onset disease.

Cheers,
Colin

Cancer Risk and Genes

The latest issue of Nature has this important study on the discovery of a genetic link for lung cancer.

The study is titled "A variant associated with nicotine dependence, lung cancer and peripheral arterial disease" by Thorgeir E. Thorgeirsson et. al. Here is the abstract:

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene–environment interaction20, highlighting the role of nicotine addiction in the pathology of other serious diseases.

And here are a few samples from the NatureNews report about the study.

Three independent genetic studies have found some of the strongest evidence yet that your genes influence your risk of developing lung cancer.

....About 50% of the general population carries a single copy of this cancer gene variant, members of the three research groups suggest. Data from all three studies — some of which did not include non-smokers — show that possessing this single copy raises the risk of lung cancer by about 30%.

What's more, another 10% of the population is likely to carry two copies of this set of mutations, raising cancer risk by as much as 80% relative to people with equivalent lifestyles without the cancer-linked gene variant.

A typical smoker who refuses or fails to give up has a roughly 15% risk of lung cancer over their lifetime. But with two copies of the genetic variant, this rises to 23%. In contrast, someone who has smoked fewer than 100 cigarettes in their entire life has a less-than-1% chance of developing the disease.

These stats provide yet more reasons for taking seriously the most fundamental moral requirement you owe yourself- looking after your health. Help reduce the 5 million annual death toll caused by smoking, quit today!

Cheers,
Colin

JAMA Article on Genomic Medicine

The latest issue of the Journal of the American Medical Association has an interesting article by Maren Scheuner et. al. entitled "Delivery of Genomic Medicine for Common Chronic Adult Diseases". Here is a sample:

The greatest public health benefit of advances in understanding the human genome will likely occur as genomic medicine expands its focus from rare genetic disorders to inclusion of more common chronic diseases, such as coronary heart disease, stroke, diabetes mellitus, and cancer. These diseases are generally due to complex interactions between variations in multiple genes and the environment and only rarely are due to single-gene forms of the disease. With genomics discoveries relating to common chronic diseases, numerous genetic tests may emerge that hold promise for significant changes in the delivery of health care, particularly in preventive medicine and in tailoring drug treatment.

Attempts to integrate genetic/genomic knowledge of common chronic conditions into clinical practice are in the early stages, and as a result, many questions surround the current state of this translation. These questions include, what are the outcomes of genomic medicine? What is the current level of consumer understanding about genomic medicine, and what information do consumers need before they seek services? How is genomic medicine best delivered? What are the challenges and barriers to integrating genomic medicine into clinical practice? By examining studies relevant to these questions, this systematic review attempts to synthesize available information on the delivery of genomic medicine for common adult-onset conditions.

.... The most important and consistent finding from our literature review is that the primary care workforce, which will be required to be on the front lines of the integration of genomics into the regular practice of medicine, feels woefully underprepared to do so. Remediation of this deficiency should be a top priority, and more studies are needed to test models for how this can be feasibly accomplished.

A second theme we identified is that consumers have unclear and dissonant notions about the value of genetic testing for common chronic disease. In general, consumers knew little about genetics/genomics but were interested in the prospect of this technology helping to better identify diseases for which they and their family members were at increased risk. Consumers were also worried about the possible adverse consequences of genetic testing, particularly the privacy issues and discrimination in health insurance and employment. Therefore, another research need is the development and testing of interventions to promote greater understanding of genomic medicine among consumers. Such interventions may need to be tailored for the needs of specific populations.

This article touches on a number of the challenges we must meet if we hope to effectively harness the important health benefits the genetic revolution could yield.

Cheers,
Colin