Medical Humanities Blog

On Gene "Therapy," and the Therapeutic Misconception

Here at MH Blog, I've posted several times on the woeful state of both public and academic discourse about genetics, and the high prevalence of reductionistic views of genetic causation.  Some particularly visible critics, like Richard Lewontin, whose work on the matter should be required reading for anyone venturing to write anything at all about the ELSI of genetic science, have charged that such reductionism proliferates even among scientists.

In this context, I wanted to note the news that

For the first time, researchers have shown that gene therapy can be used to improve vision for blind children and young adults. Two new studies document the treatment of six young people who underwent the potentially groundbreaking surgery at the Children's Hospital of Philadelphia and the University of Pennsylvania and at Moorsfields Eye Hospital in London.

The BBC news article on the story notes:

His doctors were shocked at the improvement.

Professor Robin Ali, of the Institute for Ophthalmology, who led the trial, said: "To get this indication after only three patients is hugely exciting.

"I find it difficult to remember being as excited as I am today about our science and what it might achieve."

A few comments:

First, it is wonderful that the use of these techniques improved, or at least halted the degeneration, of several people's eyesight.  The amelioration of human suffering should always be recognized, validated, and lauded.  That these successes hold promise for future efforts at healing and easing human suffering and illness is obviously significant, as well.

Second, however, note the lede to the ABC News article: "for the first time."  Yes, indeed.  One of the most obvious datum for the prevalence of the therapeutic misconception is the continued usage of the term "gene therapy" in place of the more accurate (PDF) "gene transfer research."  Gene transfer research has, thus far, been long on promise and short on therapeutic results.

In and of itself, of course, there is nothing wrong with this.  Most worthwhile scientific endeavors feature a very great deal of failure before any kind of success.  Yet to term gene transfer research "gene therapy" is to beg the question of its therapeutic nature.  The entire question, for anyone who wishes to practice any kind of evidence-based healing, is whether there is good evidence for believing a given intervention will be therapeutic. 

As such, I continue to have difficulty understanding why both lay and professionals alike continue to refer to this kind of research as "gene therapy."  This datum suggests just how deep and widespread is the therapeutic misconception, especially when we have some reason to believe that gene transfer research poses no insignificant amount of risk to the human participants.

The March/April 2008 issue of the Hastings Center Report features an article written by Paul Gelsinger (Jesse's father) and Adil Shamoo, querying whether there is good reason to believe that human participants research is any safer 8 years after Jesse Gelsinger died (PDF).  They generally answer this question in the negative (as would I), and it is worth noting that some of Paul Gelsinger's public comments after Jesse died suggest that both he and Jesse were laboring under the therapeutic misconception.  (To be more precise, Paul's comments indicate that he was misled into believing the intervention would be likely to produce individual benefit for Jesse).

My point is simply this: while it is wonderful that an application of gene transfer research has demonstrated therapeutic efficacy, there are other important lessons lurking in the background of the story that should not go unnoticed.

Finally, speaking of the University of Pennsylvania, Anita Allen has an apt article up on SSRN entitled

The Poetry of Genetics: The Pitfalls of Popularizing Science.

Hypatia: A Journal of Feminist Philosophy (forthcoming).

Abstract:

The role genetic inheritance plays in the way human beings look and behave is a question about the biology of human sexual reproduction, one that scientists connected with the Human Genome Project dashed to answer before the close of the 20th century. This is also a question about politics, and, it turns out poetry, because, as the example of Lucretius shows, poetry is an ancient tool for the popularization of science. "Popularization" is a good word for successful efforts to communicate elite science to non-scientists in non-technical languages and media. According to prominent sociobiologist E.O. Wilson, "sexual dominance is a human universal." He meant, of course that men dominate women. Like sociobiology, gene science is freighted with politics, including gender politics. Scientists have gender perspectives that may color what they "see" in nature. As the late Susan Okin Miller suggested in an unpublished paper tracing the detrimental impact of Aristotle's teleology on western thought, scientists accustomed to thinking that men naturally dominate women, might interpret genetic discoveries accordingly. Biologists have good, scientific reasons to fight the effects of bias. One must be critical of how scientists and popularizers of science, like Genome author Matt Ridley, frame truth and theory. Ridley's "battle of the sexes" metaphor and others have a doubtful place in serious explanations of science.

Recommended!

Conflicts-of-Interest-O-Sphere

The American Association of Medical Colleges has released its Report on Industry Funding of Medical Education (PDF), the result of over 2 years of work.

There is lots of good discussion on this: Howard Brody, Daniel Carlat, Merrill Goozner, and, in detail, Roy Poses from Health Care Renewal.

Also, please be sure to check out the horrifying details related by Clin Psyc on the newest Paxil study.  While it may be too much of a generalization to suggest that professionals in general do a poor job of self-regulation, the modern history of the medical profession (since 1847) should not inspire confidence.  As someone sympathetic to virtue ethics, I believe quite strongly that the building of professional and virtuous character should be a paramount pedagogical goal for medical education.  Yet, given the legacy of lax self-regulation, which, as CP notes, continues to this very day, it is becoming increasingly untenable to suggest that such self-regulation is sufficient to resolve the worst problems of scientific misconduct and conflicts of interest.

Thoughts?

On Moral Esperanto

Stuart Rennie, editor of the excellent Global Bioethics Blog, has an outstanding post on the dubiety of the search for universal consensus in bioethics (a subject both near and dear to my heart, and a position which I endorse whole-heartedly):

But it is -- and has always been -- precisely the lack of consensus that has driven many a moral philosopher or theologian to seek a kind of Ethical El Dorado, the one true set of ethical judgments that everyone (purely on the basis of being human) has to agree with. You can see the tendency at work in human rights documents, in international codes of research ethics, and in philosophical treatises. The desire for a universal morality (as opposed to the mores of some particular culture and tradition) seems to express a rage for order, and disgust with seemingly endless and messy ethical disagreement and conflict. Why can't we all get along?

The search for what Rennie terms the Ethical El Dorado, and what Walzer has termed "moral Esperanto," is quixotic, IMO.  It is, to borrow a Wittgensteinian metaphor, an attempt to open doors that are painted onto walls.  Ethics is an extremely messy business; we do not all speak the same moral language.  And given that languages are conceptual schemes in which we actively construct our world, that means we live our lives within divergent moral worlds (yes, yes, this is more Quine than Davidson, but there is no doubt both would agree on the notion of language as a conceptual scheme).  This is not to construct an atomistic notion of the moral life, because, again, as Wittgenstein showed, private languages do not exist.  To speak a language at all is to share some kind of weltanschauung.

We can understand each other; we can work to understand different worlds in context of the languages the inhabitants of those moral worlds speak. 

But we cannot all speak the same moral language.  Hence universal norms of morality are, IMO, chimerical.  But, the typical objection goes, what of justice? Who would disagree that justice is a crucial virtue? And if so, doesn't that show there are some kinds of universal norms? Rennie supplies one of my preferred responses to this line of argument:

The success rate [of the search], at least since Plato, has been abominable. What typically happens is that in order to become potentially universalizable, the set of judgments becomes so abstract as to become meaningless. It is almost as if one climbs a mountain top to transcend human disagreements and conflicts of value, only to find that -- while the panoramic view is great -- you have run right out of oxygen. But if more substantive content is added to the judgments, people start bickering about them again, and the reality of moral diversity comes flooding back.

It is perfectly fine to suppose that consensus could be obtained on an ethical norm at a high level of generality.  But as the tradition of virtue ethics reminds us -- in particular, see MacIntyre -- our moral lives are inherently localized and particular, because we practice our lives in these local, particular worlds.  As the Zen expression puts it, wherever you are, that's where you are.  Thus, the moral issues that arise from abstract commitments to justice only take on meaning in particular cases or contexts.  This is why Paul and Jane may agree perfectly well on the need for justice, but may understand what justice requires in any given case in diametrically opposed ways.

This is a blog post, not an essay, so I'll stop here, other than to note that these kinds of issues are at the core of the approach I plan to take in my dissertation (on pain).  Kudos to Rennie for raising the issue so thoughtfully and succintly.   

On Power, Abuse, and Disability

Kay Olson, proprietor of the outstanding disability blog, The Gimp Parade, has an absolutely phenomenal pathblogographical post up on power, abuse, and disability.  The setting is Kay's initial stint at a rehabilitation hospital following a month-long stay in an ICU.  The post details Kay's requests for help in order to avoid a pressure ulcer, made to a nurse's assistant Kay names "The Russian" (for the assistant's accent):

She understood I needed to be repositioned and she told me she needed to go get another person to help. It is commonly a two-person job in acute care settings and may even be required procedure, but when she didn't return and my butt began to ache badly from laying in one position too long, I rang the bell again.

The Russian returned alone to tell me she was trying to get help, then left again. I don't know exactly how much time passed, though it was easily 30 minutes since my first call for assistance, and it may have been as long as an hour. My butt was throbbing painfully now, sparks of nerve pain shooting down my leg. In desperation, I spent significant energy wrestling the pillow wedged behind my back away enough that I could shift slightly and ease the sharpest of pain to buy some time.

Shortly after, The Russian returned. Again alone. She saw the pillow had been moved and began berating me: "Why you bother me? You don't need help! You did this yourself after bothering me? If I catch you ever moving by yourself again don't expect me to do anything for you!"

Kay's situation was complicated by her limited ability to speak.  She concludes:

Abuse doesn't really need much space to thrive, and it needs even less to occur only once. Probably not everyone would consider this abuse. But it was a verbal threat to deny me assistance while lying helpless in a bed from someone charged to show up if, say, my ventilator quit giving me air. Like any sort of intimate violence (domestic violence, date rape, etc.), violence against disabled people is contextual and opportunistic and can happen to anyone.

The power of narrative is exemplified in this post.  As they say, go read the whole thing. 

On BMI

The critiques over the use of BMI as a criterion for fatness/obesity are not new.  Eric Oliver's excellent book, Fat Politics, which demonstrates the arbitrariness of BMI over the decades, was published in 2005.  ("Arbitrary" is one possible description; "socially constructed" would be perhaps a more descriptive phrase).  Kate Harding has a nice slideshow at Shapely Prose entitled the BMI Project, intended to show just how flawed the measure is as an assessment of fatness and/or obesity.

While the problems with BMI, then, are hardly unknown, these difficulties have not generally translated into scholarship (aside from critical theory) or into media reporting.  In this context comes a strongly worded article in the newest Journal of Health Economics:

Beyond BMI: The value of more accurate measures of fatness and obesity in social science research

Richard V. Burkhauser, John Cawley

Abstract:

Virtually all social science research related to obesity studies a person's body mass index (BMI). Yet there is wide agreement in the medical literature that BMI is seriously flawed because it does not distinguish fat from fat-free mass such as muscle and bone.  This paper studies data that include multiple measures of fatness and finds that many important patterns, such as who is classified as obese, group rates of obesity, and correlations of obesity with social science outcomes, are all sensitive to the measure of fatness and obesity used.

We show that, relative to percent body fat, BMI misclassifies substantial fractions of individuals as obese or non-obese; in general, BMI is less accurate classifying men than women.  Furthermore, when percent body fat instead of BMI is used to define obesity, the gap in obesity between white and African American men increases substantially but the gap in obesity between African American and white women is cut in half.  Finally, total body fat is negatively correlated with employment for some groups and fat-free mass is not significantly correlated with employment for any group, a difference that was obscured in previous research that studied BMI.

In the long run, social science datasets should include more accurate measures of fatness.  In the short run, estimating more accurate measures of fatness using height and weight is not possible except by making unattractive assumptions, but there is also no reason to adhere uncritically to BMI as a measure of fatness.  Social science research on obesity would be enriched by greater consideration of alternate specifications of weight and height and more accurate measures of fatness.

____________________________

It is particularly interesting to note how the social construction of BMI affects prevalence and incidence of obesity among racial groups.  This in turn shows that prevalence and incidence are themselves irreducibly social concepts, and that our beliefs about who has what health status is irretrievably informed by all manner of social, political, and cultural factors.

Call for Papers: Victorian Disability

CALL FOR PAPERS

Special Issue: Victorian Disability

Fall 2009

Submission Date: 15 September 2008

The Victorian Review invites submissions for its forthcoming special issue devoted to Victorian Disability. From the development of new sign

systems for the blind and deaf, to the growth of eugenics, from Dickens’ one-legged man, Silas Wegg, to the disabled communities that populate the fiction of Charlotte Yonge, the Victorians were creating and consolidating ideas of ability, normalcy, difference, health, and illness. This special issue seeks to explore the constructions of ability and disability that circulated in Victorian Britain and abroad.

Recent critical work in Disability Studies has suggested disability as another mode of analysis alongside class, race, gender and sexuality in the understanding of culture. How can a focus on ableness complicate traditional readings of gender, class, race, and sexuality in the period? We particularly invite submissions that engage with the challenge that Disability Studies poses for the future of Victorian Studies. To what extent might Disability Studies pressure conventional disciplinary boundaries? How might we approach Victorian Disability Studies while recognizing that the term "disability" and the meanings we now grant to it as a general category did not exist in the Victorian period?

Possible topics may include (but are not limited to):

• The Representation of Disability in Victorian Literature
• Disability and Cultural Production (blind poets, deaf artists)
• Disability and the Practice of Reading Disability
• Communities and Cultures
• Medicine and Disability
• Social Darwinism and Eugenics
• Industrialization and Disability
• The Materiality of Disability (canes, wheelchairs, ear trumpets)
• The Languages of Disability (Braille, Sign)
• Celebrity and Disability
• The Spectacularisation of Disability
• Health, Disability and Invalidism
• The Institutionalization of Disability (educational, governmental and charitable)

Essays must be between 5000 and 8000 words and formatted according to MLA guidelines. Please submit electronic copies of essays to both of the issue’s guest editors by September 15, 2008:

Christopher Keep

Department of English

The University of Western Ontario

ckeep@uwo.ca 

Jennifer Esmail

Department of English

Queen’s University

3je@queensu.ca 

(h/t H-NET-DISABILITY)

Health Wonk Review

Maggie Mahar and Niko Karvounis over at Health Beat Blog have compiled a wonderful Health Wonk Review, replete with commentary and chock full of excellent transitions.  Check it out.

We at MH Blog have the honor of hosting the next Health Wonk Review, so submit away.

On Fatness & Stigma

The inimitable Kate Harding over at Shapely Prose (a leading blog in the Fatosphere, and one which I have finally added to our blogroll) has some excellent commentary on the results of a study on discrimination against obese people.  Excerpts:

I’m kind of stunned that a bunch of researchers not only noticed that discrimination against fat people exists, they correctly identified a major cause of it. (Did hell freeze over while I was neglecting the blog last week?) I am so fucking sick of the phrase “personal responsibility,” which always seems to be used by people who want to justify their prejudices, so I LOVE that they identify that phrase–and the thinking behind it–as the hate-fueling horseshit it is.

And that, I might add, is why this blog continues to work toward busting the myth that all fat people eat non-stop and never exercise. Sure, some fat people do, and they deserve the same respect as any other human beings, but as long as the culture keeps insisting that fatness is a failure of “personal responsibility,” I’m going to keep screaming that there are fat people who live “healthy lifestyles,” and thin people who live “unhealthy lifestyles” (see below for more on that odious framing) and you just can’t know how much “personal responsibility” any given person is taking by looking at them.

Well said.  In addition, as we have noted on this blog before, the problem with the lifestyle model of disease is that it often permits interlocutors to ignore the tremendous effects social and economic conditions have in shaping lifestyles.  It should be obvious that it is harder to eat right and exercise when unacceptable levels of violence in a community discourage persons from exercising outside, when supermarkets and fresh foods are either entirely absent or located far away from certain neighborhoods, and when 2 hours of commuting time is required to enable someone to get to work.

This is not to deny the effect of human agency, but to note instead that social and economic conditions are powerful determinants in shaping individual choices.  Thus, telling obese persons that they "just" need to exercise and eat less is not only deeply stigmatizing and often erroneous -- because, as Kate points out, many fat people do in fact exercise and watch what they eat -- but also obscures the importance of social and economic conditions in shaping the range of options available to us, and our ability to exercise those options.

Thoughts?

Call for Papers: American Association for the History of Medicine

Fresh off of its 2008 Annual Meeting (which I was sadly unable to attend), the American Association for the History of Medicine has wasted no time in announcing its Call for Papers for the 2009 Annual Meeting, to be held in Cleveland, OH April 23-26, 2009:

The American Association for the History of Medicine invites submissions in any area of medical history for its 82nd annual meeting, to be held in Cleveland, OH, April 23-26, 2009. The Association welcomes submissions on the history of health and healing; history of medical ideas, practices, and institutions; and histories of illness, disease, and public health. Submissions from all eras and regions of the world are welcome. Besides single-paper proposals, the Program Committee accepts abstracts for sessions and for luncheon workshops. Please alert the Program Committee Chair if you are planning a session proposal. Individual papers for these submissions will be judged on their own merits.

Abstracts must be received by September 15, 2008, to be eligible for consideration.  Further details are available on H-Net.

On Neuroreductionism

Alice Ristroph has an excellent post over at CoOp on the relationship between criminal law and neuroscience.  She writes:

But I’m skeptical that more knowledge of the brain is going to unsettle retributive arguments and the associated attributions of responsibility. (Here, I think I'm in agreement with Jeff Lipshaw's take on experimental philosophy: many moral claims are just not provable or disprovable.) I suspect that whatever we learn about the brain processes of criminals, some persons will look at those brain processes and say, “this criminal deserves to be held responsible; this criminal deserves to be punished.” Put differently, one might say that “responsibility” is a normative judgment, not a fact about the causal mechanisms of the human brain. Whether a defendant “is” responsible depends on whether we (the punishers) decide to hold him responsible. To take an example raised last night, did new facts about the juvenile brain, or about developmentally disabled persons, dictate the outcomes in Roper v. Simmons and Atkins v. Virginia? I don’t think so. It is still the case that some will look at all the empirical information available about Daryl Atkins—IQ tests, medical records, brain scans, whatever—and say he deserves to die, and others will look at the same information, and say he does not.

[ . . . ]

All in all, I think it’s pretty hard to unseat the belief in deserved punishment by introducing new facts.

This is right on, in my view.  Violence, like any other complex social phenomena, is just that -- irreducibly social.  To homogenize all violence as analysable under the same category and to reduce it to brain dysfunction is both patently reductionist and quite dubious, in my view.  Not to mention which, it is also exceedingly dangerous.  In the comments to Ristroph's post, guest-blogger extraordinaire Frank Pasquale points to a truly brilliant article by Amanda Pustilnik, entitled Violence on the Brain: A Critique of Neuroscience in Criminal Law.

Here is the Abstract:

Is there such a thing as a criminally violent brain? Does it make sense to speak of the neurobiology of violence or the psychopathology of crime? Is it possible to answer on a physiological level what makes one person engage in criminal violence and another not, under similar circumstances?

Current research in law and neuroscience is promising to answer these questions with a yes. Legal scholars working in this area claim that we are close to realizing the early criminologists' dream of identifying the biological roots of criminality. In the grip of a neuroeverything craze, legal scholars, practitioners, and lawmakers have already begun incorporating new neurolaw into criminal adjudications, lawmaking, and criminal law scholarship. These breathless hopes for a neuroscientific transformation of the criminal law, although based in the newest research, are part of a very old story. Criminal law and neuroscience have been engaged in an ill-fated and sometimes tragic affair for over two hundred years. Two failures have appeared in current work that mirror precisely the prior failures. First is the claim is that the various phenomena we call criminal violence comprise a single entity, which arises causally from dysfunction within specific locations in the brain (localization). Second is that violent crimes are committed by people who are essentially biologically different from typical people (otherization). This Article first demonstrates the parallels between current neurolaw claims and past movements in law and neuroscience: phrenology, Lombrosian biological criminology, and lobotomy. It then engages in a scientific critique of the shortcomings of current neurolaw claims about the neurological bases of criminal violence. Drawing on research and interviews with leading neuroscientists, this Article shows that causally localizing what we call criminal violence to bits of the brain is highly scientifically contestable and epistemologically untenable. In viewing the criminal law-neuroscience relationship through the lens of history of science, this Article hopes to offer caveats to legal users of neurolaw and a realistic and constructive portrait of how current neuroscience might inform criminal law discourse about regulating violence.

This paper is brilliant, and is sorely needed.  Weaving together historical, legal, social, and cultural analyses, Pustilnik provides a contextualized and devastating critique of our continued penchant to reduce complex social phenomena to individual brains.  Not content with merely explaining the history, Pustilnik engages the neuroscience on its own terms, illustrating the divergence and dissent within the praxis of neuroscience, and thereby seriously undermining the excessive reliance on localization that rests at the heart of neuroreductionism (which actually can be traced to the early 19th century, and is relevant to my own work on pain.  Contrary to what some scholars have suggested, I quite firmly believe that we are still enthralled with a specificity theory of disease as relates to mental phenomena).

Pustilnik's critique also touches on the dangers of using "biology" to other, though there is obviously a great deal more that can be side of the importance of using neuroscience to stigmatize.  Indeed, American eugenics and scientific racism did just that, and relied heavily on then prevailing neuroscientific theories of crime and race.  We would be well-advised to exercise extreme caution before skipping down such paths again.

In any case, for those interested in the intersection of criminal law and neuroscience, Pustilnik's paper is a must-read.