Menu (Dec. 2006)

Blogging will probably be light for the next month as I divide my time between finishing a few research projects and spending time with the family over the holiday period. So I have put together this menu which gives the links to a few recent posts on various topics that I have been contemplating of late.

Cheers,
Colin


"The Priority View: Some Thoughts": some thoughts on priority vs sufficiency.

"The Virtue of Virtue Ethics": why I think virtue ethics is preferable to consequentialism and deontology.

"Luck Egalitarianism": some reflections on the poverty of luck egalitarianism.

And you can read my recent thoughts on genetics and justice on the two posts dealing with the presentations I made this term at Manchester and Oxford.

Cheers,
Colin

Congenital Inability To Experience Pain

The latest issue of Nature has this fascinating article about a very rare phenotype- the inability to experience pain. Congenital inability to experience pain can be caused by a single mutation of a gene. This condition causes extreme problems for the people who have this condition. The ability to experience pain is crucial for our survival, it alerts us to injuries, etc. The opening paragraph of this article emphasizes the importance of pain:

Pain is an essential sense that has evolved in all complex organisms to minimize tissue and cellular damage, and hence prolong survival. The onset of pain results in the adoption of behaviours that both remove the organism from a 'dangerous environment' and allow for tissue repair; for example, resting a broken limb so that new bone can form. Pain also protects us from our environment, by teaching us what situations and behaviours are likely to lead to injury. Pain pathways operate at numerous levels in the nervous system and are under both voluntary and involuntary control. Blockade of this system with analgesics has been a major pharmacological achievement.

The study examined families in northern Pakistan, several members of which seemed immune to pain. Here is a brief excerpt that describes the problems some of these children encountered:

The index case for the present study was a ten-year-old child, well known to the medical service after regularly performing 'street theatre'. He placed knives through his arms and walked on burning coals, but experienced no pain. He died before being seen on his fourteenth birthday, after jumping off a house roof. Subsequently, we studied three further consanguineous families in which there were individuals with similar histories of a lack of pain appreciation, each originating from northern Pakistan and part of the Qureshi birdari/clan. All six affected individuals had never felt any pain, at any time, in any part of their body. Even as babies they had shown no evidence of pain appreciation. None knew what pain felt like, although the older individuals realized what actions should elicit pain (including acting as if in pain after football tackles). All had injuries to their lips (some requiring later plastic surgery) and/or tongue (with loss of the distal third in two cases), caused by biting themselves in the first 4 yr of life. All had frequent bruises and cuts, and most had suffered fractures or osteomyelitis, which were only diagnosed in retrospect because of painless limping or lack of use of a limb. The children were considered of normal intelligence by their parents and teachers, and by the caring physicians.

News@Nature also has a story about the article here. That story concludes:

This could offer potential new ways to treat severe pain. Current methods, such as local anaesthetics, are impractical, and constantly taking opiate painkillers can lead to addiction. Targeting SCN9A, perhaps through gene therapy, could also help sufferers of constant extreme pain from injuries, arthritis, spinal conditions or cancer.

But, as the Pakistani subjects showed, the new discovery is of no use in tackling that perennial human condition, emotional pain. "They can blush and cry, and when they have flu they feel unwell," he says. "And they are hurt by rejection just the same as anyone."

Cheers,
Colin

Genome Policy

The December 2006 issue of Nature Reviews Genetics has a useful article by Susanne B. Haga and Huntington F. Willard entitled "Defining the Spectrum of Genome Policy". Here is the abstract followed by a brief excerpt:

Abstract: Many achievements in the genome sciences have been facilitated by policies that have prioritized genome research, secured funding and raised public and health-professional awareness. Such policies should address ethical, legal and social concerns, and are as important to the scientific and commercial development of the field as the science itself. On occasion, policy issues take precedence over science, particularly when impasses are encountered or when public health or money is at stake. Here we discuss the spectrum of current issues and debates in genome policy, and how to actively engage all affected stakeholders to promote effective policy making.

Genomics, the science of whole genomes, differs in approach, breadth and emphasis from genetics, which focuses on the roles and inheritance of individual genes and their variants. Genomics encompasses the development and application of technologies for the comprehensive study of the biology of cells, tissues, whole organisms and even populations. It includes genome sequence analysis, as well as studies of gene expression, protein products and metabolites. The data from such studies have advanced such diverse areas as evolution, developmental biology, drug development and clinical diagnosis. Examples of applications are as diverse as comparative sequence analysis, tumour microarray expression profiling, whole-genome analysis for disease-association studies and hand-held sensors that identify airborne pathogens.

Although policy issues can be categorized in different ways, we consider five main areas of genome policy: research issues; legal issues; economic issues; educational issues; and acceptance and implementation. The natural history of any genome advance or application, from the discovery stage through to translation, production and both professional and public acceptance, can be considered in terms of these broad categories. Many policy issues have arisen in response to genetic advances and applications, but the broader scale of genome sciences expands and potentially exacerbates them, and gives rise to new issues. Although presented here in discrete categories, genome policy is actually a complex network of issues, whereby one issue can influence or be dependent on another.

Cheers,
Colin

Public Perception of Nanotechnology

The latest issue of Nature Nanotechnology has an important commentary entitled "What Drives Public Acceptance of Nanotechnology" by Steven C. Currall, Eden B. King, Neal Lane, Juan Madera and Stacey Turner.

Unfortunately neither of my two institutions have a subscription to the journal so I cannot read it myself (let alone post a few excerpts). I suspect this is due to the fact that the journal is relatively new.

The brief outline on the journal webpage has the following description of the piece: "The first large-scale empirical study of how consumers view the risks and benefits of nanotechnology shows that nano-based products are viewed as relatively neutral, and as less risky and more beneficial than GMO".

After a little more digging I did come across this site for the Project of Emerging Nanotechnologies. It has an interview (and a podcast should also be posted eventually... keep an eye on this) with one of the authors of the article. Here is an excerpt from that interview:

“A recent poll by the Project on Emerging Nanotechnologies shows that while public awareness of nanotechnology is increasing, fully 69 percent of Americans have heard little or nothing about nanotechnology,” said Lane. “More young people are seeing nanotechnology in advertisements for MP3 players than are learning about nanotechnology in schools.”

“In my view, given what’s at stake, this situation is unacceptable. I fear that nanotechnology may be heading for a fall. A major environmental, medical or safety problem—real or bogus—with a product or application that’s labeled ‘nanotechnology’—whether it actually is nanotechnology or not—could dampen public confidence and financial investment in nanotechnology’s future, and could even lead to unwise regulation. We should not let this happen,” stated Dr. Lane.

He called on government, corporations and the science and engineering community to take urgently three steps to avert this possible occurrence. “First is a major effort to set aside the resources necessary to investigate nanotechnology’s possible environmental, health, and safety risks.”

A “second step critical to the success of nanotechnology is to infuse nanotechnology education into the curriculum in every school and teacher education program.” Dr. Lane highlighted the huge investment the U.S. made to science and engineering education almost fifty years ago when Russia launched Sputnik—the world’s first artificial satellite. He stressed that America’s “children and workforce need that same level of national commitment to lead and keep them competitive in the Nano Age.”

Finally, Lane called for “a deliberate effort to provide the public with balanced and easily understood information about nanotechnology’s potential benefits and its possible risks and for more public engagement”—led by government, industry and the science and engineering community working together.

Cheers,
Colin

The Limits of State Neutrality

Originally posted June 9th, 2006

The principle of state neutrality enjoys great prominence in contemporary liberal thought. It is espoused, perhaps most persuasively, by the political philosopher John Rawls. There are of course many different ways in which the principle of state neutrality can be stated, so it is important to first clarify what the principle entails before I address its limitations.

The kind of neutrality that liberals like Rawls have in mind is called “neutrality of aim” or justificatory neutrality. This version of neutrality maintains that the justification for a law or policy should be neutral. It should not presuppose, for example, values particular to one conception of the good. Piety is a clear example of a value which would violate justificatory neutrality. The religious state is the archetype of the non-neutral state.

Why do liberals argue for justificatory neutrality? In Beyond Neutrality George Sher (p. 15) identifies three reasons why liberals defend state neutrality. These are:

1. because non-neutral government decisions violate the autonomy of citizens.

2. because non-neutral government decisions pose unacceptable risks of oppression, instability, or error.

3. because non-neutral government decisions rest on value-premises that cannot be rationally defended.

By requiring the justification for a law or policy be neutral, the neutrality constraint ensures that only those laws or policies that rest on value-premises reasonable citizens of a pluralist society could accept are legitimate. The neutrality constraint thus rules out many intolerant measures. For example, it rules out laws against religious heresy. The religious state is non-neutral because its laws and policies are based on values (e.g. piety) particular to one conception of the good. A non-neutral value like piety should not trump the political values of liberty and equality.

The neutrality principle may be of some use in helping us avoid the oppression of a perfectionist state but it is important to recognise that it is principle whose usefulness tends to be overemphasised by liberals who make it the cornerstone of a liberal public ethic. Consider, for example, a repressive policy like the criminalization of homosexuality. Neutralist liberals might believe that the principle of neutrality can easily dismiss such policies as they will be premised on perfectionist values (e.g. religion). But the most influential arguments for such a prohibition are not usually framed in such a way that its violation of the neutrality constraint is so obvious.

In The Enforcement of Morals Lord Devlin (p. 10) criticised the Wolfenden Report (1957) which recommended that homosexual acts between consenting adults in private be decriminalised. Devlin’s argument for such a prohibition was premised on a conception of legal moralism. He argued:

If men and women try to create a society in which there is no fundamental agreement about good and evil they will fail; if, having based it on common agreement, the agreement goes, the society will disintegrate. For society is not something that is kept together physically; it is held by the invisible bonds of common thought. If the bonds were too far relaxed the members would drift apart. A common morality is part of the bondage. The bondage is part of the price of society; and mankind, which needs society, must pay its price.

Neutralist liberals might dismiss Devlin’s argument on grounds that a prohibition on homosexuality is non-neutral. So liberals might argue that the real aim of such a measure is to promote a particular conception of the good life (i.e. heterosexuality). But such a characterisation of Devlin’s argument would be misleading. Devlin did not justify his argument on the grounds that heterosexuality is the good life or that homosexuality is merely offensive. His argument was that the decriminalisation of such behaviour would be harmful to society. His argument could thus be framed in terms more congenial with the neutrality constraint. Neutralist liberals themselves recognise that the state should not be neutral between all conceptions of the good, but only between permissible conceptions of the good. Devlin would argue that the behaviour targeted by such legislation is impermissible because it threatens the social cohesion necessary to maintain stability. By prohibiting homosexual behaviour the state is taking the steps necessary to establish and secure the minimal standards of behaviour necessary for society to be stable.

Framed in these terms, Devlin’s argument is perhaps more formidable to the neutralist liberal than one might have initially expected. But one does not have to establish that a prohibition on homosexuality violates the neutrality constraint in order to establish a persuasive case against such a provision. Emphasising this point is important for it highlights the other demands of public reason. Namely, that not only must the objectives of legislation be neutral, but the means chosen must be reasonable and demonstrably justified. Prohibitions on homosexuality fail these requirements. In order to substantiate that the means chosen in this instance are reasonable and demonstrably justified Devlin would have to support a number of claims he failed to substantiate. Firstly, he would have to provide evidence to show that decriminalising homosexuality would cause the harm he claims it would cause. Devlin’s failure to do this is more than sufficient grounds for rejecting the call for a prohibition on homosexuality. Secondly, Devlin would also have to show that less restrictive measures (e.g. education) are insufficient for establishing and securing the minimal standards of behaviour necessary for society to be stable. And thirdly, even if Devlin could substantiate his claim that such behaviour harms society, such a policy would only be reasonable if the benefits of the prohibition clearly outweighed its costs (this is the requirement of proportionality). Given the gross violation of individual liberty such a prohibition entails, the harm at issue would have to be very substantial. Devlin’s failure to establish these points reveals the different ways his proposal fails to satisfy the demands of public reason. The requirements of public reason go well beyond the requirements of the neutrality constraint.

The neutral state could pursue a number of oppressive measures in the name of promoting ‘neutral aims’. It could enforce, for example, overly stringent traffic laws or unreasonable building regulations, etc. Such laws or policies are legitimate, the neutralist liberal might argue, because they are premised on values no one could reasonably reject (e.g. public safety). But does the fact that they are neutral necessarily mean that these policies are publicly justified? There is nothing in the ideal of neutrality itself that ensures that measures be reasonable as well as premised on neutral values. The state could justify a number of repressive measures that are consistent with neutrality of aim. For example, the government could justify a prohibition on motorised vehicles on grounds of public safety. In this case we have a neutral aim but an unreasonable policy.

Two features of such a law are worth emphasising to reveal how, despite its being neutral, it is unreasonable. Firstly, while we recognise that the aim of public safety will require limitations on our freedom we also expect legislators to take a responsible approach to pursuing such an aim. Comparable levels of public safety can be secured by varying degrees of restrictive policies and we expect law-makers to opt for those measures that impair our freedom as little as possible. Opting for the most extreme form of restriction in the name of public safety is unjustified if a less restricted policy, say one that permitted motorised vehicles but imposed a number of various traffic laws, would secure a comparable level of public safety. Furthermore, even if a prohibition on motorised vehicles secured a substantially higher degree of public safety such a proposal would still qualify as unreasonable and unfair. Public reason demands that there be a proportionality between the effects of the measure and the objective in question (i.e. public safety). In the case of prohibiting motorised vehicles there is no such proportionality. The gains secured in public safety do not outweigh the burdens imposed on freedom and efficiency. People prefer to live with the higher degree of risk which comes with permitting motorised vehicles because it also brings with it benefits which outweigh these risks (e.g. greater mobility).

The coercive power of the state is not necessarily legitimate when it is consistent with the requirements of the neutrality constraint. In addition to pursuing neutral aims, the government must consider a diverse range of concerns which the neutrality constraint itself is silent about. The threat of oppression in liberal democracies often comes, not from perfectionism, by from an overzealous pursuit of neutral aims (e.g. public safety). In order to ensure that we pursue a reasonable balance between conflicting fundamental values, like liberty and safety, we need a public ethic that goes much further than simply prescribing justificatory neutrality. I say more about this topic in my paper "Neutrality, Toleration and Reasonable Agreement".

Cheers,
Colin

CF Gene Therapy Trial

The Sunday Times has an article on a new gene therapy trial for Cystic Fibrosis in the UK. Here are some excerpts:

BRITISH researchers are to trial a new gene therapy for cystic fibrosis in which sufferers simply inhale a spray laden with DNA.

....If it works, the £20m programme could lead to a treatment that will improve and extend the lives of thousands of cystic fibrosis sufferers around the world.

....About 10,000 people in Britain have cystic fibrosis. Most can expect to live no more than 31 years and much of their life will be spent struggling to control the symptoms, which can include liver failure and diabetes. Researchers emphasise that such trials must be treated and publicised with caution for fear of raising false hopes among sufferers. It will also take at least three years for the early results to emerge. However, the large-scale medical trials follow studies in animals and smaller trials in humans that have already hinted at powerful benefits.

....The technique being tested involves the use of a nebuliser that injects a fine spray into the airways. Within the spray are tiny soap-like bubbles called liposomes containing DNA without the cystic fibrosis defect. The liposomes fuse with the outer surfaces of cells lining the lungs and the DNA passes by natural processes into their nuclei. Once installed, it is hoped the DNA will prompt the cells to make the essential protein lacking in cystic fibrosis sufferers.

You can learn more about CF from the Cystic Fibrosis Foundation website and CF Trust site. Below is some useful information from the former's webpage:

What is cystic fibrosis?
Cystic fibrosis (CF) is a life-threatening disease that causes mucus to build up and clog some of the organs in the body, particularly in the lungs and pancreas. When mucus clogs the lungs, it can make breathing very difficult. The thick mucus also causes bacteria (or germs) to get stuck in the airways, which causes inflammation (or swelling) and infections that leads to lung damage.

Mucus also can block the digestive tract and pancreas. The mucus stops digestive enzymes from getting to the intestines. The body needs these enzymes to break down food, which provides important nutrients to help us grow and stay healthy. People with cystic fibrosis often need to replace these enzymes with capsules they take with their meals and snacks to help digest the food and get the proper nutrition.

How do people get cystic fibrosis?
Cystic fibrosis is a genetic disease. That means people inherit it from their parents through genes (or DNA), which also determine a lot of other characteristics including height, hair color and eye color. Genes, found in the nucleus of all the body's cells, control cell function by serving as the blueprint for the production of proteins.

The defective gene that is responsible for causing cystic fibrosis is on chromosome 7. To have cystic fibrosis, a person must inherit two copies of the defective CF gene—one copy from each parent. If both parents are carriers of the CF gene (i.e., they each have one copy of the defective gene), their child will have a 25% chance of inheriting both defective copies and having cystic fibrosis, a 50% chance of inheriting one defective copy and being a carrier, and a 25% chance of not having CF or carrying the gene.

Cheers,
Colin

Liberal Leadership

After the Conservatives won a minority government back in January I made the decision to join the Liberal Party of Canada. After spending 7 years (now going on 8) of the past decade living outside of Canada I have been more of a spectator of Canadian politics than a participant. And I had hoped to get more involved as the Liberals re-built themselves into a Party that could topple the Conservatives and inspire Canadians. However my move to Oxford this year has meant that I have had to settle for being more of a spectator again so I was anxious to read the results of the Liberal Leadership race this weekend. This morning I woke up to read the news that Stéphane Dion has won the race for the Liberal Party of Canada.

To be honest, I must admit I was both stunned and disappointed by this result. Dion was not my first choice, or even second, (…OK not even my third!) choice. When the Liberals lost back in January I think the message Canadians were sending was that they were discontent with the “status quo” of the Liberal party. So discontent that they elected Harper and the Conservative government. Perhaps Dion can lead a re-newed Party that can dispel this popular perception but I myself have serious doubts. Listening to Dion’s online video message on the Liberal website (here) was flat and uninspiring to say the least.

So what does this mean for Canadian politics? I would not be surprised if this results in a much stronger Conservative government eventually coming to power. If Canadians were unwilling to re-elect a Liberal government under Paul Martin, who I think had all the qualifications of Dion and much, much more, then I don’t think the Liberals will win unless the Conservatives suffer a really major blunder. Maybe that will happen. Maybe the pragmatic strategy for the Liberals is to go with the status quo (which historically has been successful) and wait for the Conservatives to make major mistakes. But I think this strategy is misguided. I think Harper is much more astute then his critics assume. And I think Canadian politics as a whole would have been much better off with a charismatic visionary like Ignatieff (or even Rae, my second choice). I can’t help but feel we squandered a really unique opportunity here.

Cheers,
Colin

Gene Therapy Clinical Trials: A Snapshot

Worldwide there are over a 1000 clinical trials for gene therapy. Gene therapy is a technique for correcting defective genes responsible for disease (see here).

I came across this site a few days ago which gives us a fascinating snapshot of the diversity of the potential applications of human gene therapy. It provides information on 421 clinical trials that are currently recruiting patients. The search for "gene therapy" trials also contains some of those recruiting for genetic tests (like this one, this one and this one).

Here I provide a brief snapshot of these fascinating developments with a sample of 3 of the therapy trials currently recruiting.

(1) The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is sponsoring the follow gene therapy trial for chronic leg wounds:

Most chronic (long-lasting) wounds of the leg (also known as venous ulcers) fail to heal in a reasonable period of time. Although researchers have made great progress in understanding how the body repairs wounds, attempts to develop new treatments have been disappointing. In general, treatments based on recent findings about the details of wound repair have not greatly reduced the number of people who have chronic wounds. The long-term goal of this study is to evaluate a new approach for healing a chronic wound. Current methods of directly applying substances that are involved in wound healing to a chronic wound do not cause enough healing. We think that PDGF-B (platelet-derived growth factor B), a factor associated with wound healing, will dramatically enhance healing if we inject a genetically engineered virus into the wound that causes cells in the wound to produce PDGF-B in large quantities.

(2) Providence Health Care is sponsoring the following trial for prostate cancer patients:

Androgen (a male sex hormone) deprivation is the standard therapy for metastatic prostate cancer and results in regression or control of disease in 80-85% of patients. This hormone therapy results in a progression-free survival of 12-18 months and overall survival of 24-30 months. However, all patients ultimately develop hormone-refractory prostate cancer (HRPC). Management of HRPC patients is a significant challenge for both patient and physician. Neither past nor current chemotherapy regimens have shown curative potential in patients with HRPC. Thus new treatment strategies are a high priority.
A major focus of new treatment strategies is to enlist the aid of the immune system, particularly the development of prostate cancer vaccines. There has been a number of studies using dendritic cell based vaccines and the treatment has been well tolerated. Specific T-cell immune responses have been observed and occasional evidence for tumor regression. A reduction in serum prostate-specific antigen (PSA) has been observed as well. Lengthening the time-to-progression and delays in the onset of bone pain have been observed in subsets of patients with HRPC.

The initial preclinical observations suggesting that a granulocyte-macrophage colony-stimulating factor (GM-CSF) gene transduced allogeneic (GVAX) prostate cancer vaccine may be efficacious in poorly immunogenic cancers were reported.

The objective of this study is to evaluate the safety and immunologic effects of vaccinations with Allogeneic Prostate GVAX® (CG1940 & CG8711) in patients made lymphopenic by treatment with chemotherapy and infused with autologous peripheral blood mononuclear cells (PBMC). Clinical observations and laboratory measurements will be monitored to evaluate safety, toxicity and immune responses. Additionally, the effects of treatment on serum PSA levels and tumor response will be evaluated.

(3) The Southwest Oncology Group is sponsoring this trial for breast cancer:

RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and prevent or delay the recurrence of cancer.

PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with stage IIIB or stage IV breast cancer in remission.

Going through the list of these various trials for tests and therapies one cannot help but be amazed at the rapid pace with which our new knowledge about our biology is being applied (in diverse ways) to improve our health.

Cheers,

Colin