Sunday, June 15, 2014

A Skeptics guide to the mind and Montaigne: the just seem to go together

Just finished reading:

Robert Burton's: "A Skeptic's Guide to the Mind" (still have to watch this talk).

Stephen Greenblatt on Shakespeare's debt to Montaigne 
reasonably happy that 

18th century Swedish biologist Carl Linnaeus is bigger than Jesus (on Wikipedia anyway)

Thursday, April 10, 2014

Reading list

As I am working on updating the Biofundamentals course (and turning the web notes into a book), I find myself reading and rereading a number of great books.    Mostly so that I do not forget, I will list them here.   On the off chance anyone cares, I have linked them to reviews.

THE UNDERGROWTH OF SCIENCE: Delusion, Self-Deception and Human Frailty’ By Walter Gratzer, Oxford University Press  [a review here] Quite amazing how often weird ideas become accepted or accepted (at least for a time), until reason prevails.

Black Mass: Apocalyptic Religion and the Death of Utopia by John Gray Allen Lane  The main idea is that apocalyptic (religious) thinking is pervasive among people, even those who claim to be complete secularists - and it least to some truly stupid and tragic consequences (as if tragedy can be avoided in this life).

Beyond the Hoax: Science, Philosophy and Culture by Alan Sokal  An oldy but goody on how people can stop thinking and get lost in the ozone.

The fanaticism of the apocalypse by Pascal Bruckner

Religion explained by Pascal Boyer

The theory of evolution by John Maynard Smith

The age of wonder: How the romantic generation discovered the beauty and terror of science by Richard Holmes

Principles of social evolution by Andrew F.G. Bourke

The Ancestor's Tale by Richard Dawkins

The evolution of physics (yet again) by Albert Einstein and Leopold Infeld

Farewell to reality: How modern physics has betrayed the search for scientific truth by Jim Baggott

To save everything, click here: the folly of technological solutionism by Evgeny Morozov

Religion in human evolutionL from the paleolithic to the axial age by Robert Bellah

Darwin's Lost world: The hidden history of animal life by Martin Brasier:

The Rocks don't lie: A geologists investigates Noah's Flood by David Montgomery:

Microbes and evolution: the world that Darwin never sawL Stanley Maloy

The first crusade by Steven Runciman

Wednesday, April 09, 2014

Academic Freedom, Monty Python & Loretta.

Neither faculty or "Students do not shed their constitutional the schoolhouse gate." Tinker v. Des Moines Independent Community School District, 393 U.S. 503 (1969).

Having read Professor Hayward’s now notorious October 2013 blog post[1], it is clear he takes delight in rattling cages. Nevertheless, some of the issues raised could serve as interesting jumping off points for discussion. For example, I have always objected to being lumped together with other Caucasians when it comes to ethnic identity. But assuming that he maintains an atmosphere of civility, it is difficult to understand how it is even imaginable that his comments rise to the level of “hate speech”. That said, I would love to listen to the debate that might ensue if students were asked to critically consider the Loretta sketch from Monty Python’s Life of Brian []. One wonders whether this video (or even showing this video in class) is a form of hate speech? 

But really, that is not the issue here, rather there are two issues: the defense of academic freedom and the importance of training our students to learn to defend their positions, and critique the positions of others, based on empirical evidence and rigorous and logical argument.

Why does this matter?  Primarily because as faculty we are called upon to present and analyze a wide range of potentially disconcerting (and perhaps even threatening) facts, phenomena, and their implications. A short list, off the top of my head, includes the evolutionary bases and outcomes of sexual selection and the various forms of social organization[2], the dynamics of immunity and the social outcomes arising from the refusal to vaccinate children (which could be seen as a form of child abuse), the origin of the universe and the elements of life, not to mention evolutionary mechanisms in general (which could offend a range of more literalist religious groups), the generation, costs and benefits of genetically modified organisms (including, in the future, humans), as well as the implications of social policy in the context of feeding the world’s population, the ramifications, positive, negative, economic and sociopolitical of climate change. Given the importance of social biology in species as deeply socialized as humans, one might even imagine a discussion of the origins of customs ranging from “honor” killings to the personal and political subjugation of women or the origins of slavery and its modern variants (which could be seen as “disrespecting” certain cultures.)  What will the position of the BFA be if faculty are publicly denounced by a group of devout students demanding retraction or the punishment of the faculty member?  

            It is in this context that Paul Chinowsky’s remarks (presumably made as chair of the BFA rather than as an individual faculty member) - assuming that they have been accurately reported (If any (other) faculty member said this, we would find ourselves in a deans office or possibly on suspension for writing this. ... The question is, are we going to allow this or condone this from someone in our own faculty?” ), seem, at least to me, to be overtly threatening, and certainly not dispassionately supportive of faculty who hold potentially unpopular or contrarian views. 

Is this an appropriate role or position for a BFA chair to take, given that this a chair rather than a CEO position. Am I to be marched to the Deans office (perhaps even by the BFA chair) or not allowed to teach until my views become consistent with the current orthodoxy, or rather the orthodoxy imposed by a vocal subgroup of the student body?  I suggest that these are extremely serious questions that strike at the heart of faculty freedom, and the viability of intelectual life on campus, and I am shocked that they have been addressed in such a cavalier manner — when speaking for the BFA (and the faculty at large) a more circumspect and supportive stance would seem appropriate.

[2] Pity for example the poor slime mold that becomes part of the stalk rather than a spore cell, and so sacrifices itself for the good of the community.  Of course we probably should also talk about the internal and external mechanisms involved in the suppression of social cheating, but that is another course.

Sunday, March 23, 2014

Restore the balance (in Boulder and beyond)

Recently, I came across a sticker advocating "restoring the balance" by bringing back the wolf.  Great idea, I thought, but perhaps not daring enough. What about following the lead of those who refuse to vaccinate their children!  Given the complete absence of empirical evidence that vaccination increases the odds of autism or other diseases, one must conclude that these brave  souls are working to restore the balance in their own small way.  We can help them by bringing back smallpox, plague, and other potentially lethal (but currently avoidable) diseases. What right do we have to drive viruses like polio to extinction? To be perfectly consistent, however, we might also want to refuse expensive medical care to those unvaccinated children who fall ill. Of course children rarely make their own decisions about vaccination (and perhaps water and waste treatment plants as well), but it seems reasonable that they share the costs of their parents semi-religious beliefs. While we are at it, we might also outlaw antibiotics, as this would lead to a dramatic increase in avoidable deaths, another balancing move. After all, in a balanced system viruses and bacteria have as much of a right to infect us as we have avoid infection.

Friday, February 14, 2014

Emotional versus dry science

Here is an extremely interesting article, particular in the light of thinking about how to teach evolutionary biology effectively:  The science of why we don't believe science

Tuesday, January 07, 2014

Autism, Mice, and the Dangers of Scientific Hype

Another day, another PR barrage centered on a scientific paper and a real danger that people will be tempted to treat a serious human disease with untried, ineffective, and potentially harmful “cures.” The paper, published in the prestigious magazine Cell, reports that some autism-like symptoms in mice, generated by treating pregnant animals with a compound that mimics viral infection, can be ameliorated by treating their offspring with the bacteria Bacterioides fragilis (1).  Rob Knight, a major player in the “American Gut” project, claims that, “The broader potential of this research is obviously an analogous probiotic that could treat subsets of individuals with autism spectrum disorder.”(2)  This is a truly remarkable claim given the multiple inherent and substantial limitations of the original study.  

So what are these limitations and why do they lead to significant doubts about whether their “promise” is either misguided or likely to be fulfilled?  The first and most obvious issue is whether mice, no matter how experimentally manipulated, can actually be autistic or, better put, whether the symptoms such manipulated mice display are related in any useful way to developing an understanding of autism or the more general “autism spectrum disorder” (ASD) in humans, yet alone alleviate the symptoms displayed by people diagnosed with ASD.  

Let us begin with what autism is currently defined to be.  According to the National Institute of Neurological Disorders and Stroke, “The hallmark feature of ASD is impaired social interaction.”(3)   Because people are so deeply and inherently social, ASD is a serious condition. That said, it remains unclear whether ASD is one or a number of distinct diseases that produce similar symptoms.

Mice, and in fact the vast majority of animals, are very, very much less social than humans, and in so far as they are social, they are social in dramatically different ways.  Moreover, mice often differ quite dramatically from humans in their responses to various physiological insults and how diseases arise and progress.  Unless carefully taken into account, these differences can make observations in mice more or less irrelevant to humans. This has been revealed most recently in the course of comparative studies on sepsis, the life threatening consequence of a wide-spread bacterial infection, where “… researchers report evidence that the mouse has been totally misleading as a model system to investigate at least three major killers – sepsis, burns, and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.” (Kolata, 2013).

Let us consider the mouse as a model for autism/ASD used in the Cell study.  The investigators used an inbred line called C57BL/6N. To induce autism/ASD-like symptoms, pregnant mice were injected on embryonic day 12.5 (birth occurs between 19-21 days) with the compound poly(I:C); this treatment mimics an acute viral infection.  Administration of this compound hyper-stimulates the mother’s immune system, leading to a condition known as “maternal immune activation” (MIA) associated with elevated levels of inflammatory factors in the maternal blood, placenta, and amniotic fluid.  These changes have dramatic effects on fetal development and the affected offspring often display behaviors seemingly analogous to some of those displayed by people with ASD. Of course, since mice never display the types of social behaviors that normal people do, whether the symptoms mice from MIA mothers display are relevant to individuals diagnosed with ASD is speculative at best. 

What the authors of the Cell paper focused on were changes in the behavior of the gut, that is primarily changes in cellular behavior affecting the gut’s permeability in MIA-derived mice and the possibility of repairing these behaviors through treatment of afflicted mice with bacteria. There have been some reports that humans with autism/ASD have gastrointestinal abnormalities, but the data is unclear. A small study, published in the British Medical Journal, found no relationship between an ASD diagnosis and gastrointestinal symptoms (4) while a larger study by the Autism Microbiome Consortium reported “significant enrichment of bowel symptoms and disorders in patients with ASD (11.74% vs. 4.5%, p<0.0001 by chi-square test)”, perhaps not a completely unexpected result from a project centered on the relationship between autism and gut bacteria, but these authors note that their conclusions “may well be affected by the limitations of our study,” which relate to the specific population of patients examined. Here it is worth noting that only a minority (~12%) of individuals with ASD appeared to display gastrointestinal symptoms.

The authors of the Cell paper pursued the hypothesis that autistic/ASD-like symptoms displayed by mice might well arise directly from the defects in their gastrointestinal tract associated with MIA treatment. They found changes in the relative abundance of intestinal microbes between normal and MIA mice. We know that the interaction between intestinal microbes and gut is critical for the normal “development, maintenance, and repair of the intestinal epithelium.”  Following on they tested whether feeding mice B. fragilis, a microbe also found in humans and previously shown to ameliorate experimental colitis, could influence the effects of MIA. Their observation was a striking yes. This treatment also corrected some, but not all of the autism/ASD-linked behavioral effects found in MIA offspring mice. Most interestingly, however, from the perspective of the defining social aspects of autism and ASD, “they (the B. fragilis treated MIA mice) retain deficits in sociability and social preference” (emphasis added). Now given that autism/ASD is primarily a disease of social interactions, together with the rather dramatic differences between human and mouse immune systems brought to our attention by the sepsis studies, these observations suggest that this study’s results may well not be relevant to ASD. Moreover, from a practical perspective “B. fragilis, which accounts for only 0.5% of the human colonic flora, is the most commonly isolated anaerobic pathogen due, in part, to its potent virulence factors. Species of the genus Bacteroides have the most antibiotic resistance mechanisms and the highest resistance rates of all anaerobic pathogens. Clinically, Bacteroides species have exhibited increasing resistance to many antibiotics.” (6)  This suggests that the use of B. fragilis as a “probiotic” treatment in humans might be actively dangerous.    
Based on the lack of compelling evidence i) that mice really can, in any meaningful sense, be made to be autistic, ii) that there are substantial differences between mice and humans, particularly with respect to their immune systems, which is critical to these studies, and iii) that treatment of mice with B. fragilis fails to reverse the social symptoms of MIA mice, one might well have expected that objective, disinterested scientists would refrain from excessive hyperbole until more relevant and DEFINITIVE data is available. This would not be of great concern if confined to the scientific community but the danger is that such sanguine interpretations in the public press will lead parents or caretakers of people with ASD  to “medicate” affected children with unproven, ineffective, and potentially hazardous  “probiotic” treatments.  This concern is not a theoretical one when one considers how ubiquitous self-medication is in our society.  Any trip to the grocery store or Costco will reveal the widespread availability of dietary supplements including probiotics and other “alternative” medicines that claimed to prevent or treat a wide array of disorders, real or imagined, including gastrointestinal ailments. In the absence of a sober evaluation of the soundness of the observations made in mice and, more importantly, their relevance to humans, the essential question is whether it is socially irresponsible not to include clear and appropriate caveats directed to a scientifically-na├»ve population who may rightly assume the experiments described represent established fact and therefore, give license to self-directed probiotic treatment of affected individuals, or included in diets of unaffected children as a prophylactic measure.   
1. “Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders,” 
5. Kohane et al., 2012. PLoS One DOI: 10.1371/journal.pone.0033224

Further reading.

Kolata, G. 2013. Mice Fall Short as Test Subjects for Some of Humans’ Deadly Ills. New York Times.