Sunday, September 28, 2014

UW-Madison: Playing with statistics

Date: 2014
To: [my redaction]
Cc: Rebecca Blank
Subject: Re: From a Bascom Hill Society member

Mr. [my redaction],

On behalf of Chancellor Blank [who doesn't actually give a shit about your concerns], I wanted to respond to your message with [pretend and misleading] detailed information about research at UW-Madison.

The planned research with young monkeys is aimed at understanding how adversity early in life influences the development of the brain [and making us lots of money for redecorating the Chancellor's office]. That knowledge -- coupled with clinical work with human patients -- could provide the basis for new and better treatments [but never has] for people suffering from anxiety, depression, bipolar disorder and other psychological conditions that lead to undue suffering for tens of millions of people in the United States alone.

Critics of this mission draw comparisons between the modern study and the important work done at UW-Madison decades ago by Harry Harlow. It is true that the current study, like Harlow's work, is aimed at better understanding how the brain and behavior change when early infant environments are disrupted [even though Harlow didn't study the brains of the baby monkeys he tortured]. But the current study is also fundamentally different from Harlow's work. The infant monkeys are reared with human contact [as they grab and manhandle them], with other [freaked out and abused] infant monkeys, with toys [?] and environment enrichment [like water and air]. And advances in brain imaging and chemistry allow modern UW-Madison researchers to address basic causes and associations between brain development and mental illness that Harlow would never have been able explore. [So, please ignore the fact that Ned Kalin is taking baby monkeys away from their mothers at birth for the same reason Harry Harlow did.]

A [misleading and not at all] detailed description of the research and its [ridiculous and obviously bullshit] rationale can be found here: [Note: The university's link might not remain active. You can read the unattributed original document here, just in case.]

The way animal research is undertaken on our campus has also changed a great deal in the decades since Harlow was active in Madison. [Now, unlike or PR colleagues from Harlow's day, we know that filming and broadcasting the animals suffering would be a mistake.] This vital anxiety research [though the term 'vital' is completely misleading and false] has been assessed by several university committees [made up of other vivisectors] tasked with making sure that [Kalin has claimed in writing that] potentially beneficial research subjects the fewest animals to the least invasive possible measures. [That sentence needed some more editing.] As with all animal research on campus, specially trained veterinarians [whose livelihood depends on them staying quite about the animals' suffering] will care for the monkeys involved and ensure that all the work is done in accordance with [the meaningless and wildly permissive] federal regulations [nominally] enforced by the National Institutes for Health and the U.S. Department of Agriculture [the two agencies in bed with us.]

We remain committed to [lying about] the humane conduct of important [sounding] biomedical research. We appreciate your willingness [to suspend all critical thought and] to consider all sides of the story before judging our work in light of rhetoric clearly intended to mislead and inflame emotions on the sensitive issue of animal-based research [that we try so hard to keep hidden.]

John Lucas
Executive Director of University Communications

The document linked to in the letter above is something other than the "detailed" description spin-meister John Lucas claims it to be. But then very little about the university's use of animals is what it claims. This is part of the linked document they sent in response to a (now previous) financial donor who wrote with alarm and disgust over psychiatrist Ned Kalin's experiments on infant rhesus monkeys:
Mental illnesses such as anxiety disorders, depression, bipolar disorder, and schizophrenia are extremely common, can be very disabling, and negatively impact physical health. Anxiety disorders are the most common mental illnesses and are frequently accompanied by depression and substance abuse. In addition to creating immeasurable suffering and dysfunction, the worst outcome of mental illness, suicide, is increasing and is among the leading causes of death in adolescents. Each year over 30,000 lives are lost to suicide in the United States, and worldwide suicide is the leading cause of violent deaths. It is estimated that in any 12 months 26% of the population suffers from a diagnosable mental illness. Forty-six percent of the American population will suffer from a mental illness at some point during their life. A study by the World Health Organization shows that of all the medical illnesses, mental illness and substance abuse are the most costly to society and the most disabling. Most mental illnesses have their beginnings during childhood and the earliest presentation of these problems frequently is increased levels of anxiety. Abnormal levels of childhood anxiety can greatly increase the risk for adolescent and adult mental illness.

This is pretty interesting. It makes me wonder how many people at the university reviewed these claims before making the document publicly available. It is a study in propaganda.

The claims in the statement are similar to Kalin's earlier explanations. I wrote about them here. I'm not going to repeat them, very much.

The university argues that Ned Kalin's cruel experiments are justified because mental illness is "extremely common" and "can be very disabling." Mental illness can be disabling. But it usually isn't. Only a tiny percentage of people with a mental illness are disabled and an even smaller number are very disabled.

Kalin's work is funded by the National Institute of Mental Health (NIMH), one of the twenty-seven Institutes and Centers that comprise the National Institutes of Health. NIMH keeps statistics and provides some explanation of the terms it uses in the course of reporting on mental health problems.

NIMH notes: "While mental disorders are common in the United States, their burden of illness is particularly concentrated among those who experience disability due to serious mental illness (SMI)." This suggests that not all people with serious mental illnesses experience disability as a result.

According to NIMH, about 4.1 percent of all U.S. adults have a serious mental illness and some of those will be disabled as a result. But the university says: "Forty-six percent of the American population will suffer from a mental illness at some point during their life." The university's claim is off by more than 131 million people.

The university says: "A study by the World Health Organization shows that of all the medical illnesses, mental illness and substance abuse are the most costly to society and the most disabling." I wrote to Mr. Lucas and asked for the title of that WHO report, but alas, he never replied. Why didn't they supply the title of the report in the letter? And Kalin doesn't claim to be studying substance abuse, so why would the university have appealed to substance abuse in its defense of Kalin's cruelty?

The university says that over 30,000 people kill themselves in the United States each year and that worldwide, suicide is the leading cause of violent deaths." That's sad, but torturing baby monkeys won't change those statistics. World Health Organization statistics help put the university's numbers in perspective: WHO, in its "The top 10 causes of death" reports that:
Ischaemic heart disease, stroke, lower respiratory infections and chronic obstructive lung disease have remained the top major killers during the past decade.

HIV deaths decreased slightly from 1.7 million (3.2%) deaths in 2000 to 1.5 million (2.7%) deaths in 2012. Diarrhoea is no longer among the 5 leading causes of death, but is still among the top 10, killing 1.5 million people in 2012.

Chronic diseases cause increasing numbers of deaths worldwide. Lung cancers (along with trachea and bronchus cancers) caused 1.6 million (2.9%) deaths in 2012, up from 1.2 million (2.2%) deaths in 2000. Similarly, diabetes caused 1.5 million (2.7%) deaths in 2012, up from 1.0 million (2.0%) deaths in 2000.

WHO makes no mention of mental illness in that report,

Quite simply, the claims made by the university, while not outright lies, are misleading and are probably knowingly misleading. After all, misleading people about the use of animals on campus is part of the PR department's job. Their claims are doubly bad because the university has a much greater than normal duty than most to verify that its claims are accurate and not misleading when communicating with the public. The university has an overwhelming responsibility to the citizens of Wisconsin to be honest, forthcoming, and to make the facts plain. The university is violating its public trust.

The university writes: "Based on work performed at the University of Wisconsin with young rhesus monkeys born into UW-Madison’s primate research colonies, we now know that brain alterations are at the root of early abnormal anxiety." But like the misleadingly reported statistics cited by the university, this is also misleading.

Much of Ned Kalin's NIH-funded work has been based largely on his discovery that it is possible to identify some rhesus monkeys who are more anxious and fearful than others by injecting them with them diazapam (Valium) and then scanning their brains. (See Lateralized response to diazepam predicts temperamental style in rhesus monkeys. Davidson RJ, Kalin NH, Shelton SE. Behav Neurosci. 1993.) But they did not and have not demonstrated that the monkeys without the lateralized response to Valium don't develop abnormal anxiety.

One confounding factor among a symphony of confounding factors in his experiments, is that anxiety is epidemic in the monkey labs. (See: Stereotypic and self-injurious behavior in rhesus macaques: a survey and retrospective analysis of environment and early experience. Lutz C, Well A, Novak M. Am J Primatol. 2003; and Risk factors and remediation of self-injurious and self-abuse behavior in rhesus macaques. Rommeck I, Anderson K, Heagerty A, Cameron A, McCowan B. J Appl Anim Welf Sci. 2009.) In Lutz. et al., the researchers found that essentially all the monkeys -- 321 out of the 362 animals surveyed -- had at least one abnormal behavior.

And who wouldn't be anxious in that setting? You are powerless; confined to a small space, occasionally, sometimes regularly hurt, hear others screaming, are socially isolated, and have no support group. Exactly what is the university referring to when it mentions "abnormal anxiety"? Was any of the anxiety experienced by the people in the Nazi camps abnormal? Do Kalin and the university believe that monkeys in its labs ought not be worried?

The university asserts that Kalin's prior work on young fearful monkeys not only: "demonstrates the specific parts of the brain that have altered function, but also shows that this altered brain function that is important for anxiety can be inherited &"

Kalin has always claimed prudently that the fearfulness he has been studying is a "trait-like" phenomena. The university tries to support its claim by pointing to two press releases linked above. The first starts out with an important qualifying remark:
A new study focused on anxiety and brain activity pinpoints the brain regions that are relevant to developing childhood anxiety. The findings, published in the August 12 edition of the journal Nature, may lead to new strategies for early detection and treatment of at-risk children.

And I might purchase the winning lottery ticket. And while it might be understandable that people working in the public relations office are somewhat ignorant about many things scientific, even they should know that a press release hyping a newly published paper isn't evidence of genuine merit. I suspect that at least some of them know that, but their actual goal isn't public education, its all about muddying the water and keeping the details and ethical implications as murky as possible.

The university's announcement from 08/11/2010 about the "new study" doesn't provide a citation or a link to the actual paper. Maybe they didn't want people reading it, or just knew that few reporters would take to the time to review it or care what it said. It's all about sound bites. The unidentified paper was Amygdalar and hippocampal substrates of anxious temperament differ in their heritability. Oler JA, Fox AS, Shelton SE, Rogers J, Dyer TD, Davidson RJ, Shelledy W, Oakes TR, Blangero J, Kalin NH. Nature. 2010 Aug 12.

Like most of Kalin's work with monkeys and rats, there doesn't seem to be much insight into what it might be like to be one of the animals he uses. The paper starts out by implying that the things they did to the monkeys used in the study were mild: "Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli."

Given that the paper's few readers are most likely other vivisectors, his characterization might make some sense given the spectrum of terrible things they do to animals. But from the animals' perspective, mild is probably just a sick joke.

Here's the gist:
... monkey AT was assessed using measures of threat-induced freezing behaviour and inhibited vocalizations, as well as plasma cortisol concentrations.... AT and brain metabolism were assessed when monkeys freely behaved in a test cage by themselves for 30 minutes in a potentially threatening situation in which a human “intruder” entered the room and stood 2.5 meters from the cage. During this time the intruder presented his profile to the monkey ensuring that he avoided eye contact with the animal (No Eye Contact; NEC). Animals with the greatest AT froze longer, vocalized less, and had elevated plasma cortisol levels. ....

The authors also explain it this way:
Each monkey was injected with FDG immediately preceding the No Eye Contact (NEC) challenge. During the experimental paradigm, FDG-uptake occurred and behaviors were monitored non-invasively. During NEC the animals were placed in a test-cage and a male human (the “intruder”) entered the room and stood still at a distance of 2.5 meters presenting his profile to the animal. Following 30-minutes of exposure to the experimental condition, animals were anesthetized and blood samples were taken.

From the monkey's vantage, the entire episode was probably something other than mildly threatening. Consider who the monkeys were. This is the description from Kalin et al:
All animals were mother-reared, and pair-housed at the Harlow Primate Laboratory and the Wisconsin National Primate Research Center. At the time of behavioural testing/brain scans, the mean age was 2.4 years (range = 0.74 – 4.2 years), the median age was 2.34 years, there were only four animals that had reached the age of 4 years, and there were only nine animals less than 1 year of age. The typical life span of a rhesus macaque is approximately 25 years. Females reach puberty around three years old, and males reach puberty between three and 3.5 years of age (cf. Wisconsin Primate Research Center). This would correspond to a human sample of mostly prepubescent children with some peri-adolescents.

The youngest monkeys were the victims of recent trauma. It appears to be the standard practice at the university to take babies from their mothers at 6 months of age and place them with a similarly aged monkey. This is a dramatic departure from the millennia-old normal course of a rhesus macaque's life. Behavior is largely gene-mediated, a foundational claim in all of Kalin's experiments on animals. Millions of years of evolution have molded the behavior of rhesus macaques. These animals are adapted to live in large multi-generational family groups in complex environments and societies. Mothers and a single infant in a small barren metal box are profound deviations from the norm. It is a near certainty that the normal course of development, particularly emotional reactivity is profoundly altered by the near complete absence of normal social stimuli. Mothers and their daughters typically remain together for their entire lives. Mothers and their sons sometimes do as well. In the lab, the isolated mother-child pair are torn apart; the infant is put with a similarly traumatized infant. The cause of their misery is clear; giants in white coats and face masks who have them cornered and who must be recognized and reacted to by every other monkeys in the room as a threat, in fact, the only threat most of them will face.

I wonder if the Jews in the camps felt that a guard looking them was merely a mild threat?

Kalin et al claim that the "anxious temperament" they have identified is trait-like. That is, they can't identify the genes responsible for the monkeys' anxiety, but because the offspring of highly anxious monkeys are also anxious, ergo it must be genetic.

But another possibility exists. Perhaps it is simply a matter of modeling. If my mother was frightened by the approach of one of the white-clad monsters, why wouldn't I learn to be frightened too?

Our ward, Mickey, is a designer dog bred at a puppy mill in a nearby town. We adopted him from the local shelter. Once, when we had two other dogs staying over for a weekend, there was an electrical storm with lots of thunder, something fairly common in our area of the country. Prior to that weekend, Mickey had seemed relatively unconcerned by the thunder claps. But the two visiting dogs were visibly frightened. Their behavior and fear resulted in Mickey adopting a similar opinion. Now, he too is frightened by thunder. After one night of seeing other dogs being afraid. I'm not surprised that a young monkey would quickly learn from their mother to be very worried about visits from lab workers. That's not trait-like, it's simply learned and warranted wariness.

The second press release is from 10/18/2012. It starts out like this:
Decreased activity of a group of genes may explain why in young children the “fear center” of the anxious brain can’t learn to distinguish real threats from the imaginary, according to a new University of Wisconsin study.

The paper referred in the press release is Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates. Fox AS, Oler JA, Shelton SE, Nanda SA, Davidson RJ, Roseboom PH, Kalin NH. Proc Natl Acad Sci U S A. 2012, Oct 30.

I'm always amazed at the gibberish that is passed off as science among vivisectors. Kalin et al: "The rhesus monkey is ideal for studying the origin of human AT because these species share the genetic, neural, and phenotypic underpinnings of complex social and emotional functioning (5–10)."

First, we actually have only the most sparse understanding of the genetics underpinning complexities like social and emotional functioning. Complexity and complicated are not synonyms. Complex systems are not good models of each other. But, as I mentioned above, the realities of laboratory incarceration negate the expression of the complex social and emotional functioning in humans that Kalin mistakenly claims are modeled by profoundly deprived rhesus monkeys.

In the six citations provided by Kalin et al as supporting evidence for their claims, not one of them supports their claim of some shared genetic underpinning of social or emotional functioning. None. Not one. Kalin makes claims apparently, and then points to 'evidence' that he must assume no one will review.

--- Let me pause here for a moment to mention that this phenomena is apparently widespread and fully understood and accepted by insiders. One of the times I debated primate vivisector Paul Kaufman, UW-Madison's Ophthalmology department head, I called attention to his wild claims about the need and importance for finding better treatments for near-sightedness. Reading glasses do a pretty good job already, I said, and experimenting on the eyes of monkeys was needlessly cruel. Kaufman replied that his claims, which I had quoted from his grant, should not be taken seriously; they were mere grantsmanship. When I pushed the point, moderator Robert Streiffer, "bio-ethicist" and critic of the Kalin project, stopped further discussion. He and the rest of the panel of "experts" asking us questions seemed to fully understand that the rhetoric used in grants (and publications?) is just so much blather. ---

Equally silly is their next claim: Importantly, the rhesus developmental model bridges the critical gap between human psychopathology and rodent models, allowing for translation to humans by using in vivo imaging measures and translation to rodents by using ex vivo molecular methods. Thus, the unique hypotheses that can be generated from the rhesus model are invaluable in guiding both imaging studies in children and mechanistic efforts in rodents.

You can be excused for not noticing the spin and absurdity in that statement.

After a scathing 2003 editorial in the Journal of the American Medical Association titled "Translating Biomedical Research to the Bedside: A National Crisis and a Call to Action," the term "translation" quickly became a buzz word among those tying to justify the use of animals. Numerous "Centers" and "Institutes" for the translation of basic science -- a euphemism for animal experimentation -- have been started around the country, as if doing so could improve the translation rate. The UW Institute for Clinical and Translational Research, created in 2007 apparently, is a local example. "Translation" has become a sort of talisman; if it is chanted long enough, maybe it will come to pass. See too: Evolution and translation of research findings: from bench to where? Ioannidis JP. PLoS Clin Trials. 2006.

The primary purported justification of Kalin's experiments on monkeys, written by him, one of his collaborating students, or a university PR hack, is based on statistics regarding the incidence of mental illnesses. Their purported justifications rest on claims about the incidence of mental illness that do not withstand even cursory inspection. They are not being honest. It appears to me that they are knowingly dishonest. Money has a well known corrupting influence on people's behavior. In this case, the millions of dollars of other people's given to Kalin and the university by the other vivisectors who comprise the NIH committee that sanctions his projects is a mere data point in the flood of taxpayer dollars pouring into the university coffers from NIH. The university defends every funded project because they fear that even one admission of error could be the hole in the dam that leads to a financial catastrophe for them.

The simple fact that they have written a PR piece to foist off on donors who contact them about Kalin et al's cruelty is an indication that many people are writing in alarm and disgust. But the university can't back down. NIH can't back down. It would be like the Nazis having said that they had made a mistake about trying to achieve racial purity.

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