Wednesday, October 31, 2007

Lindblom on The Market As Prison

Today the democracy reading group I am involved with at UW met to read Charles Lindblom’s very interesting article entitled “The Market as Prison” (published in The Journal of Politics in 1982). I was not familiar with Lindblom’s work so I was pleasantly surprised by this excellent paper. In fact, I have added his latest book to my list of must reads.

So what does he argue in “The Market as Prison”? He examines the way the market works in democratic societies. Many kinds of market reform automatically trigger punishments in the form of unemployment or a sluggish economy. And thus the market represses (but does not completely stop) change. Why, for example, shouldn’t the government just double the minimal wage overnight or implement the most stringent environmentally friendly regulations on industry? Such proposals might sound attractive to some voters, but why would no political party really do this? Because such policies would trigger massive punishments, and thus the costs would outweigh any potential benefits we think such reforms could achieve. Doubling the minimum wage is not desirable if the result is massive unemployment and capital flight. But why would these adverse effects happen? Why is it the case that market reform doesn’t have the desired outcome expected by those who argue passionately for it?

Lindblom argues that we must recognize that the market is an inducement system. You cannot compel people to invest in industry, employ more workers, reduce their prices, etc. They must be induced. Inducements direct and control many of the leaders in business. And thus Lindblom’s analysis reveals how complex the relation between democracy and the market really is. On the one hand, argues Lindblom, no democratic nation state has ever arisen anywhere in the world except in conjunction with a market system. And yet, because the market imprisons the policy-making process, no market society can achieve a fully developed democracy.

I think Lindblom is basically right about this. At least I think he is right that it is important to realize that there is a tradeoff involved here. If you want efficiency, economic stability and prosperity, you need a market. If you want democracy you no doubt believe that “the people” should govern society. But the principle of inclusion entailed by the latter conflicts with the elitism entailed by the former.

Lindblom’s paper helped me make a bunch of links with some other issues (like ideal theory) I have been thinking about over the past few years. Take Rawls, for example. Lindblom’s argument in many ways overlaps with the kinds of concerns that Rawls introduces when derives the difference principle. But Lindblom’s story shows how Rawls’s account is artificially constrained in many ways. For Rawls, who begins by assuming that society is closed, the role of incentives is much more constrained. And this explains why the debate between Rawls and his critics (like Cohen) have focused on things like the work attitudes of talented high fliers. “Are their attitudes just or unjust?”…and so on…

But once you relax Rawls’s idealized assumption, and recognize that the story of inducements is way more complex than the story Rawls paints in his just closed society, it is much harder to determine to what degree inequalities can be described as “just” or “unjust”. In the Rawlsian closed society industry doesn’t have the option of going somewhere else. But in the real world it does. So the inducements government will have to provide to open societies, to attract and retain business and investment , are very different than those needed in the Rawlisan closed society. Does justice demand that business leaders invest in our country rather than another country? That question doesn’t even arise when ideal theorists assume that we are talking about closed societies.

This really illustrates my central concern in this forthcoming paper. When philosophers function at the level of ideal theory they overestimate their ability to gain privileged insights into what “the best foreseeable conditions” are. Reflecting on what justice demands in an abstract, closed, fully complaint society doesn’t help us gain any truly helpful practical insights. In fact, it can impair the development of such insights. And the evidence of this is, I believe, the debate between Rawls and Cohen (and others) concerning the role of inequality-inducing incentives. Any insights derived from that debate have assumed that we are talking about closed societies. But no society in the world is like this. And once you relax that assumption our moral and pragmatic sensibilities are drastically altered. So, for me, ideal theory is a real dud.

Going back now to Lindblom… his argument reaffirmed my belief that a really useful normative framework will be both pluralistic (e.g. democracy doesn’t reign supreme, nor does efficiency) and provisional- our attitude concerning what the best tradeoff is will change and evolve as our circumstances and sensibilities change and evolve. And this is why I believe that a “virtue-oriented” public ethic is really the most useful and defensible one to invoke. It’s all a matter of *degree*. The just society will track reflective and balanced preferences (rather than knee-jerk reactions, etc.) and will push through market reform when the likely benefits outweigh the likely punishments, and will abandon such reforms when those punishments outweigh the proposed benefits. But this is not a simple cost-benefit analysis, because the tradeoff is complicated by the fact that the stakes at risk are often things we cannot easily compare and rank. For example: how do we compare

(a)a benefit to the environment and future Canadians WITH
(b)a benefit to those currently living in poverty (small % of population) WITH
(c)a benefit to the middle classes (vast majority of population) WITH
(d)a benefit to those in need of life-saving medical treatment WITH
(e)a harm to the economy and our ability to re-pay the debt we leave to future Canadians WITH

And add to this other non-ideal factors- like uncertainty about the likely benefits and harms, our fallibility, indeterminacy, etc.- and you begin to appreciate how hard it really is to know what the right thing to do is. Things are never as simple as they appear in the hypothetical abstract examples employed by ideal theorists who champion the supremacy of one particular value or principle (equality, democracy, liberty, etc.).

So a move from ideal to non-ideal theory, coupled with a shift from a principle-oriented ethic to a virtue-oriented ethic, is where I believe things need to go. Then we can talk sensibly about moving from where we are to a more fair and humane social arrangement.


Tuesday, October 30, 2007

Excellent Video Debate on Tackling Aging

I just came across this fascinating video of Richard Miller and John Trojanowski debating the topic “Alzheimer's Research and Basic Science of Aging: Is There a Better Balance?”. The discussion addresses a number of important issues concerning sorting out priorities in a situation of scarcity, plurality of worthy causes in need of funding, and uncertainty concerning the likely benefits of scientific advances. How much should we invest in tackling Alzheimer’s disease (AD) versus aging itself?

Here are some facts about Alzheimer’s from the Alzheimer’s Association:

There are now more than 5 million people in the United States living with Alzheimer’s.

Every 72 seconds, someone develops Alzheimer’s.

The direct and indirect costs of Alzheimer’s and other dementias amount to more than $148 billion annually.

And what facts can we amass to reveal what the costs of aging are? That is a very tall order indeed, and not something one can easily find from a vocal lobbying group or association. This article is a good place to start if one wants to get a sense of what the benefits of even modest success in slowing aging (by just 7 years) could be. We know that aging greatly increases our risk of many diseases- not only Alzheimer’s disease, but also heart disease, stroke, cancer, diabetes, etc., etc., not to mention the fact that it also makes us less resistant to infection, increases the risk of bone fracture, cognitive decline, etc.. Those interested in the impact aging has on our brain might find this lab of interest. These researchers conclude that while aging does not result in the decline of all cognitive functions, it does affect certain functions like top-down processing and use of prior knowledge.

One could go on and on, listing a variety of disadvantages that are visited upon us as we age.

So IF we could slow down the biological processes of aging we might be able to far exceed the health benefits we could confer upon the population by curing some of the most prevalent diseases.

But of course there is disagreement and skepticism concerning what is actually possible here. One might object: “Just because we can retard aging in mice (thus extending their opportunity for healthy life by 40%) doesn’t mean we can do it in humans”. That may be true, but it surely gives us a very good reason to further explore this. Doesn’t it? After all, the headlines are often filled with stories about the breakthroughs of therapeutic experiments on mice (in fact I often link to these stories). And while we should be cautious about making the leap from these experiments to the claim that we could do it in humans, we typically view such empirical evidence as very promising and worthy of further exploration. So we should adopt the same attitude towards experiments on the aging process.

One point that comes out in the interview, when John Trojanowski is pushing the point that Alzheimer’s is deserving of the lion’s share of (existing) funding, is that we are so close to developing effective treatments. And thus, because the likelihood of the benefits being realized (and realized soon) is higher, it should receive greater attention.

I agree that, all-else-being equal, more weight should be placed on benefits that are more likely to be realized that not, and that benefits that can be realized in 5 years count more than those that might be realized in 50 years. But of course all else isn’t equal if the comparison is between the benefits of treating just one age-related disease versus postponing all age-related diseases and disadvantages. Things are no doubt complicated by the fact that the likelihood of success and the likely timescales are contestable. But the magnitude of the current imbalance between the amount being spent on AD versus tackling aging is not, I believe, justified on the rational grounds of a cost-benefit analysis.

As Miller notes, part of the problem is that anti-aging research isn’t sexy. There are no prominent figures that can help rally public support for the cause (like Nancy Regan has for AD, or Michael J. Fox for stem cell research). This really shows how ingrained our existing skeptical prejudices are. For we all see the ravages the passage of time inflicts on the health prospects of our loved ones (as well as ourselves). And yet it is really hard to convince people that the effort to postpone these disadvantages through anti-aging research is a laudable goal. One worthy of a much greater investment of public resources.

The fact that the discussion in this interview is between funding research for AD vs research in aging is of course a reminder of how dire the situation is with funding basic scientific research. The choice shouldn’t be an either/or decision. Unfortunately it is. And thus the current generation are forfeiting potential health benefits that they and all future generations could enjoy. As Miller points out at one stage in the interview, just one day of the opening-day revenues of the movie Spider Man 2 equals the budget of 5 years scientific work on the biology of aging. That poignantly reveals who perverse our priorities really are. Miller also makes an excellent point that scientists alone can’t win this battle. And that others, like journalists, have to help get these issues on the radar of the public. I think his plea also applies to academics, especially those in the humanities and social sciences. When was the last time you sat down with your students and intelligently discussed the moral imperative to retard human aging? It’s a discussion we need to have! Especially if we are serious about Taking People as They Really Are.

So the real challenge for us is to determine what would constitute a fair and proportionate response to different kinds of disadvantages. During the video discussion it becomes evident that the funding for basic science into aging is a very small fraction of the funding spent on Alzheimer’s. Miller estimates that 6 cents from very $100 dollars that the NIH spends on scientific research is devoted to the basic science on aging. I believe that this is an injustice, to both the current and future generations. Tackling aging is, in my opinion, one of the most interesting and important issues facing us this century. The 21st century will witness an unprecedented number of human beings suffer from age-related disadvantage. And thus this is an issue normative theorists ought not ignore. If one is serious about promoting the opportunities for healthy, flourishing life, then one has to get serious about taking on aging itself.


Thursday, October 25, 2007

Science Journals Set to Tackle Poverty and Human Development (Update)

Just a brief update to my previous post on how science journals are tackling global poverty. There is an excellent editorial in the latest issue of Nature entitled "The War on Want". Here is a sample:

That concept of time is vital to understanding poverty. In 1915, the United States resembled India today on several poverty indicators, from child mortality to life expectancy, and Mexico has now achieved standards of human development equivalent on some scores to Sweden in the 1950s. Many of the countries labelled as 'Third World' are in fact well along the same trajectory to prosperity as today's wealthy nations. Yet growing prosperity means that new technologies are needed even more urgently, because as more countries escape the shackles of poverty, demand for energy, water and other resources will exacerbate the problems, such as climate change, that face our planet.

It is essential that the myths about poverty are debunked for policy-makers. Few scientists have done more in this regard than Hans Rosling, a global-health researcher at the Karolinska Institute in Stockholm. Extracting and collating vast amounts of data on poverty, he has created stunning visualizations that vividly dispel many preconceived ideas about poverty. He also highlights the importance of factors such as good governance and institutional capacity building, showing, for instance, that although economic growth is the motor of escape from poverty, that escape is achieved faster when public health is improved.

I recently came across the Ted Talks videos with Hans Rosling (see here and here) and they are very informative and helpful. Anyone interested in global poverty will want to watch his talks. Placing things in a "big picture" perspective like Rosling does (rather than looking at things frozen in the "snapshot" of the present) really helps one comprehend the magnitude of the challenges humanity faces. And the link between improving public health and fighting poverty is very important.

This link is the subject of a short piece that I have forthcoming in the next issue of Journal of Evolution and Technology. And that paper will help explain why I think the aspiration to retard human aging is a requirement of justice. So I will post and link to that piece, entitled "3 Wishes", when it comes out next month.


Saturday, October 20, 2007

Gene Therapy Trial for DMD

Duchenne muscular dystrophy is an inherited degenerative disease that affects voluntary muscles. Approximately 1 in every 3500 boys born have this disease. And all ethnic groups are equally susceptible to DMD. You can learn more about DMD from the "Your Genes Your Health" site, as well as the MDA website and the Muscular Dystrophy Canada site. Here are a few details about the disease from the MDA site:

Duchenne muscular dystrophy

Cause - An absence of dystrophin, a protein that helps keep muscle cells intact.

Onset - Early childhood - about 2 to 6 years.

Symptoms - Generalized weakness and muscle wasting first affecting the muscles of the hips, pelvic area, thighs and shoulders. Calves are often enlarged.

Progression - DMD eventually affects all voluntary muscles, and the heart and breathing muscles. Survival is rare beyond the early 30s.

Today's "Google Alerts" brings this encouraging story about the world's first clinical trial for gene therapy for DMD. Here are a few excerpts from the story:

A gene therapy trial for the fatal disorder Duchenne muscular dystrophy (DMD) is about to begin in London.

In a world first, a small group of patients will be injected with an experimental drug which it is hoped will extend their lives.

....The injection contains a "molecular patch" targeting the faulty gene so that it should work again.

,,,,Professor Muntoni describes the gene therapy as like a piece of molecular velcro which will form a temporary repair.

Gene therapy will work best in young children, as it cannot reverse existing muscle damage.

....The Muscular Dystrophy Campaign said it had high hopes the outcome of the study would be positive.

Dr Marita Pohlschmidt, the campaign's director of research, said: "The start of the trial is exciting news because it will provide us with the evidence of how this promising technology will prevent the wasting of muscles in boys with Duchenne muscular dystrophy.

"This is the first time that results from this type of research are so close to being translated into a treatment.

"We are proud that we were able to play a vital role in the formation of the scientific consortium and to support the preclinical work with more than £500,000."


Thursday, October 18, 2007

Science Journals Set to Tackle Poverty and Human Development

Next week will be an eventful week in the effort to eliminate global poverty. On October 22nd over 230 scientific journals will simultaneously publish articles on the topic of poverty and human development. You can read about the event on the NIH website (which will have a webcast event on Oct. 22nd) here. Here are some excerpts from the editorial in the latest issue of Science, by Nobel laureate Norman Borlaug:

"Feeding a Hungry World"
By Norman Borlaug

Next week, more than 200 science journals throughout the world will simultaneously publish papers on global poverty and human development--a collaborative effort to increase awareness, interest, and research about these important issues of our time. Some 800 million people still experience chronic and transitory hunger each year. Over the next 50 years, we face the daunting job of feeding 3.5 billion additional people, most of whom will begin life in poverty. The battle to alleviate poverty and improve human health and productivity will require dynamic agricultural development.

....Today, nearly two-thirds of the world's hungry people are farmers and pastoralists who live in marginal lands in Asia and Africa, where agro-climatic stresses and/or extreme remoteness make agricultural production especially risky and costly. Africa has been the region of greatest concern. High rates of population growth and little application of improved production technology during the past three decades have resulted in declining per capita food production, escalating food deficits, deteriorating nutritional levels among the rural poor, and devastating environmental degradation. There are signs that smallholder food production may be turning around through the application of science and technology to basic food production, but this recovery is still fragile. But African capacity in science and technology needs strengthening, and massive investments in infrastructure are required, especially for roads and transport, potable water, and electricity.


Wednesday, October 17, 2007

We are Losing the Battle Against Childhood Obesity (Part 2)

Following on from my post last night... today's issue of Nature has an interesting Science and Politics essay entitled "Big lessons for a healthy future" by David King and Sandy Thomas. Here is an excerpt:

One of the most important findings of the Foresight obesity project is that individuals have much less choice in the matter of their weight than we may often assume. Our analysis shows that the current epidemic of obesity does not arise from individual over-indulgence or laziness. Instead, human biology has become out of step with the structure of society.

We evolved to respond to hunger by eating; we are only weakly able to notice, and stop when we have had enough. This was an effective survival strategy in prehistoric times when food was scarce. Now high-energy, cheap foods abound, as do labour-saving devices, motorized transport, sedentary work and the association of eating with indulgence. These conspire to create an 'obesogenic' environment. The increasing prevalence of obesity is a consequence of modern life.

These points reinforce the importance of "Taking People as They Really Are". The social contract for the 21st Century must be updated to include the new insights we have made concerning the factors (both environmental and genetic) that have an important impact on our health prospects.


Tuesday, October 16, 2007

We are Losing the Battle Against Childhood Obesity

I believe something like the following moral precept is a sensible one that should inform our individual and collective decision-making: "Parents, and society in general, have a moral obligation to provide our children with the opportunities necessary for living a flourishing life" (let's call this MP).

I know, I know...many will contest the "perfectionism" explicit in this precept (what constitutes human "flourishing"?!). So let me water it down to a less contentious precept (so that this post does not go astray).

Here is the watered down ("non-perfectionist") version of MP, what we can call MP': "we have a moral obligation not to harm our children".

Some behaviours obviously violate MP'. For example, when a parent abuses their child, or severely neglects them (e.g. starvation). Such behaviour is criminal and can result in the parent losing custody of their child. But other kinds of neglect are less subtle, and the harms less immediate (though still severe).

This story in today's Guardian is a wake up call for all parents and society in general. We are losing the battle against childhood obesity and this has devastating consequences for our children and society. Here are a few excerpts from the story:

The government has quietly abandoned its target to halt childhood obesity by 2010, setting instead the goal of reducing it by 2020 - a decade further on.
The move comes in the response today of the public health minister, Dawn Primarolo, to the Foresight report, a two-year trawl through the evidence by scientists which concluded that the problem was huge, could cost the UK £45bn a year and could take 30 years to turn round.

While it was acknowledged the government target was ambitious when it was set in 2004, many critics say that to take the pressure off by allowing the childhood obesity goal to slip by 10 years is unwise.

....It is neither entirely the fault of the individual nor of society, Foresight says. There is no magic bullet solution, and no wonder diet drug will do the trick. Foresight draws many parallels with climate change, saying that changes in many different areas of society are necessary, from the design of towns and transport systems to encouraging healthier food production and consumption. If current obesity levels continue, about 60% of men, 50% of women and 25% of children in the UK will be obese by 2050.

As the story notes, that there are no easy solutions to the problem. But hopefully greater awareness of how severe the problem of childhood obesity is will inspire greater reflection, and action, on this dire situation. A virtuous parent is one that will be proactive in promoting the health opportunities of their children (and setting a good example by living a healthy lifestyle themselves).

Going back to my previous post on "Is Healthcare Special? Part 2", whatever one thinks about the priority society should place on healthcare services, if anything is deserving of the title "special" it is the health prospects of our children. And parents and society are failing our children- those we are entrusted to love and care for. So the moral and political discourse needs to get more serious about tackling the epidemic of childhood obesity.


P.S.- some info on the epidemic of childhood obesity in Canada is available here.

Monday, October 15, 2007

Globe Story on HD

Today's Globe has this moving story about Canadian scientist Jeffrey Carroll. Carroll, who is only 30 years old, has Huntington's Disease and is working on cure for it. You can learn more about HD from this site. Here are a few excerpts from the story:

No one knows this better than Mr. Carroll, a slender, fit man who looks like the poster child for good health. He knows what awaits him: Huntington's disease killed his grandmother and, more recently, his mother, Cindy Carroll, who died in December at the age of 54. Near the end, she had to be placed on floor mats in the nursing home in a Washington state town, so severe was her violent, involuntary thrashing.

This is the inherent viciousness of the disease: A child who watches it slowly kill a parent has a 50-per-cent chance of developing it, creating this perpetual cycle of grief and suffering.

....Jeffrey Carroll decided to undergo the test in 2003, wanting the certainty of knowing what the future held. He had already been through the physical – he had no neurological symptoms of the disease – and he had undergone psychological counselling. He was 25, married and an undergraduate biology student working in a laboratory. He was as ready as he ever would be.

On July 21, 2003, on a clear Vancouver day, Mr. Carroll showed up for his appointment with his wife, Megan Carroll, then 28.

The physician unfolded the piece of paper and read the test result out loud. In one brief moment, he learned he tested positive for the gene. Megan let out a noise she described as something between a gasp and a sob.

“And Jeff,” she recalls, “asked for a job.”

Mr. Carroll told the doctor that he was keen to be involved in finding a treatment. He wanted to help.

.......Life has been particularly sweet for Mr. Carroll over the past 15 months. When he learned he carried the Huntington's gene, he thought that fatherhood was out of the question. But when he heard about pre-implantation genetic diagnosis, which combines genetic screening with in-vitro fertilization, that all changed.

He and his wife decided to tackle this high-tech fertility treatment as a way to ensure they do not have a child who would ultimately carry the disease. It all worked – two unaffected embryos that did not carry the genetic mutation were implanted and twins, a boy and a girl, were born on June 27, 2006.


Thursday, October 11, 2007

The Cost of Conflict in Africa

Today Oxfam released a new study entitled "Africa's Missing Billions". Analysts estimate that the cost of conflict, across the continent, is a staggering $300 billion dollars for the past 15 years. The Oxfam press release is here, and the full report here. Here is an excerpt from the report:

Compared to peaceful countries, African countries in conflict have, on average:

• 50 per cent more infant deaths;
• 15 per cent more undernourished people;
• Life expectancy reduced by five years;
• 20 per cent more adult illiteracy;
• 2.5 times fewer doctors per patient; and
• 12.4 per cent less food per person.

....Thus there is an urgent need to address the international supply of arms and ammunition. An effective ATT, based on the ‘golden rule’, is vital to reduce the human and economic costs of armed violence in Africa and across the world. Such an ATT would need to come with support and capacity-building to ensure effective implementation.

Economic growth and the lives and livelihoods of people in Africa are being held back by armed violence. In failing to control the arms trade, the international community has let Africa down. The disarmament community must play its part to help Africa achieve the MDGs and lift people out of poverty.

We are now at a crucial stage. As well as sustaining dynamic arms control efforts at national and regional levels, African governments, arms-producing countries, and the rest of the international community, must vigorously and proactively support international discussions to achieve a robust ATT, to protect Africans from the daily effects of armed violence.


Tuesday, October 09, 2007

The Challenges Facing Pharmacogenomics

Sometimes the things we believe will help us (e.g. a drug) can have the opposite effect. One reason for this is that current medical practice is largely premised on a "one size fits all" mentality. But the rise of pharmacogenomics promises to help us bring about more safe and effective treatments. This NCBI website describes the potential benefits of pharmacogenomics:


Adverse Drug Reaction. These three simple words convey little of the horror of a severe negative reaction to a prescribed drug. But such negative reactions can nonetheless occur. A 1998 study of hospitalized patients published in the Journal of the American Medical Association reported that in 1994, adverse drug reactions accounted for more than 2.2 million serious cases and over 100,000 deaths, making adverse drug reactions (ADRs) one of the leading causes of hospitalization and death in the United States. Currently, there is no simple way to determine whether people will respond well, badly, or not at all to a medication; therefore, pharmaceutical companies are limited to developing drugs using a "one size fits all" system. This system allows for the development of drugs to which the "average" patient will respond. But, as the statistics above show, one size does NOT fit all, sometimes with devastating results. What is needed is a way to solve the problem of ADRs before they happen. The solution is in sight though, and it is called pharmacogenomics.

What Is Pharmacogenomics?

The way a person responds to a drug (this includes both positive and negative reactions) is a complex trait that is influenced by many different genes. Without knowing all of the genes involved in drug response, scientists have found it difficult to develop genetic tests that could predict a person's response to a particular drug. Once scientists discovered that people's genes show small variations (or changes) in their nucleotide (DNA base) content, all of that changed—genetic testing for predicting drug response is now possible. Pharmacogenomics is a science that examines the inherited variations in genes that dictate drug response and explores the ways these variations can be used to predict whether a patient will have a good response to a drug, a bad response to a drug, or no response at all.

So what challenges must pharmoacgenomics overcome before we can reap its purported benefits? The latest issue of PLOS Medicine has an informative paper on that topic (here) by Jesse J. Swen et. al., entitled "Translating Pharmacogenomics: Challenges on the Road to the Clinic". Here is a sample:

Because variation in drug responses is, at least to some extent, related to genetic variation, PGx testing has the potential to result in safer and more effective use of drugs by permitting individualized therapy. In recent years FDA-approved PGx tests have become available, but the use of PGx testing has remained limited, largely by a lack of scientific evidence for improved patient care by PGx testing. Providing this scientific evidence presents a significant challenge. The development of novel tests should be aimed at solving important clinical problems. To demonstrate potential for clinical use, PGx studies should report diagnostic test criteria. For PGx tests shown to improve patient care, guidelines directing the clinical use of PGx test results should be developed. Information on cost-effectiveness and cost-consequences of PGx testing should be provided to facilitate reimbursement by insurance companies. Finally, uptake in clinical practice will be given a stimulus if regulatory agencies recommend testing prior to prescribing the drug, and if pharmaceutical companies or patient groups advocate for use of the test. If the outlined challenges can be met, the incorporation of PGx in routine clinical practice may prove an achievable goal in the near future.


Monday, October 08, 2007

Noble Prize in Medicine 2007

The Noble Foundation has announced this year's recipients of the Noble Prize in Medicine- Mario R. Capecchi, Martin J. Evans and Oliver Smithies. They received the award for their discoveries of "principles for introducing specific gene modifications in mice by the use of embryonic stem cells". Here is an excerpt from the press release (and the NY Times has the story here):

They were honored for a technique called gene targeting, which lets scientists inactivate or modify particular genes in mice. That in turn lets them study how those genes affect health and disease.

To use this technique, researchers introduce a genetic change into mouse embryonic stem cells. These cells are then injected into mouse embryos. The mice born from these embryos are bred with others, to produce offspring with altered genes.

The first mice with genes manipulated in this way were announced in 1989. More than 10,000 different genes in mice have been studied with the technique, the Nobel committee said. That's about half the genes the rodents have.

''Gene targeting has pervaded all fields of biomedicine. Its impact on the understanding of gene function and its benefits to mankind will continue to increase over many years to come,'' the award citation said.

The Noble Foundation also has an informative video detailing the research of last year's winners (who discovered RNA interference) here.


Thursday, October 04, 2007

Sequencing Genomes Related to Research on Aging

Flipping through some recent issues of the Journal of Gerontology: Biological Science, I was struck by the number of fascinating studies being done on the biology of aging. One piece in particular seemed a nice complement to my previous post. It was "A Proposal to Sequence Genomes of Unique Interest for Research on Aging" in Volume 62A, Number 6, June 2007 by João Pedro de Magalhães et. al. Below are some excerpts:

THE recent sequencing of genomes, including the human genome, has revolutionized biomedical research. The projected genome sequencing of a large number of mammalian species, such as several primates, will offer extraordinary opportunities for studying genome evolution and to better understand the structure and dynamics of the human genome. Most target organisms for sequencing were chosen because of their usefulness as biomedical models or because of their phylogeny in relation to the human genome to address comparative and evolutionary issues. The biology of longevity, however, has been neglected in these considerations. Yet one of the most striking and mysterious differences among mammals is the wide variability in longevity. Understanding the differences in aging rates among species is a major biological puzzle. Herein we argue that studying genome evolution across species with different life spans has the potential to change our understanding of aging processes. Thus, longevity should also be taken into consideration when selecting target organisms for sequencing. As a first step, we propose the sequencing of three organisms of unique interest for aging research: the naked mole-rat (Heterocephalus glaber) whose record longevity of 28.3 years makes it the longest-lived rodent (2), the white-faced capuchin monkey (Cebus capucinus) which can live > 50 years (3), and the bowhead whale (Balaena mysticetus), the longest-lived mammal with estimates suggesting that it may live > 200 years.

...In the same way it is possible to analyze sequence data from species with different brain sizes to obtain candidate genes, we think it is now computationally possible to analyze genome sequence data from species with different life spans for candidate genes that can be experimentally tested. Computational strategies to understand the genetic basis of differences in aging between humans and closely-related species would define a new paradigm for gerontological research. For example, nearly all vertebrates share the amyloid-ß peptide sequence associated with Alzheimer's disease in humans, yet the accumulation of Alzheimer-like changes varies widely among species. What other gene differences, one may ask, modulate the effect of the amyloid gene during aging? Mammals also show major species differences in cancer type and incidence, which may be traced to specific gene differences. As humans, and one of the longest-lived animal species, it is in our keen interest to study the genetic features that contribute to the evolution of longevity and that determine our susceptibility to age-related diseases.


Dog Genome Project

The Broad Institute, which was created in 2003, aspires to construct new powerful tools for genomic medicine. It is a collaborative project between MIT and Harvard, and the Institute's researchers are involved in the Dog Genome Sequencing Project. Here is a brief description of that project from their website:

The genome of the domesticated dog, a close evolutionary relation to human, is a powerful new tool for understanding the human genome. Comparison of the dog with human and other mammals reveals key information about the structure and evolution of genes and genomes. The unique breeding history of dogs, with their extraordinary behavioral and physical diversity, offers the opportunity to find important genes underlying diseases shared between dogs and humans, such as cancer, diabetes and epilepsy.

The latest issue of Nature has an interesting News item on the Institute's research entitled "Dogs help sniff out genes". Here is a brief excerpt:

Man's best friend is becoming the geneticist's too. Researchers have made good on the dog genome's promise: a quick-and-dirty way to find the genes responsible for physical traits using just a couple of dozen pooches and a gene chip.

Kerstin Lindblad-Toh, of the Broad Institute of Harvard and Massachusetts Institute of Technology in Cambridge, Massachusetts, and her colleagues have devised a method of locating the genes responsible for specific traits that requires as few as 10 animals with the feature and 10 without — as long as they are all the same breed. The team has also identified the genes that give the Rhodesian ridgeback breed its ridge but additionally predispose the dogs to a crippling developmental disease called dermoid sinus. Such feats were predicted when Lindblad-Toh's team mapped the dog genome but this is the first time they have been achieved.

....Dogs lacking the duplication of genes are unridged; those with one copy have a normal ridge; but having two copies also carries an 80% risk of dermoid sinus. The mechanism paves the way for geneticists to use the dog genome to help identify genes involved in disorders such as diabetes that also affect humans.