Saturday, December 30, 2017

Mindful magazine and the new age hoodwink

We just received an offer in the mail to subscribe to a new age magazine called Mindful. The piece was high-end glossy and filled with images of seemingly happy people. One image, apparently the lead off to an article from a past issue, was titled, "A Kinder, Gentler World." What really caught me eye was the image above, both on the envelope and then again as the largest image in the enclosed advert.

The universe is complex. Things that seem impossible sometimes aren't. So, it isn't absolutely impossible that a university program led by a primate vivisector could teach people to be kind, but the notion is creepy and the endeavor somehow tainted. It is sort like the faith healer Benny Hinn urging people to be charitable.

It seems to be little more than a charade, a bamboozle of sorts, a gimmick that benefits the purveyor. The benefits to the buyer, though not necessarily always zero, are secondary to the interests of the seller. Even faith healers sometimes heal people; even snake oil has had its successes; the mind is complex and the placebo effect is real.

But there is something particularly distasteful about a primate vivisector telling people that he has discovered an ancient secret from the Great Masters of the Himalayas for becoming more compassionate, and that really is Richard Davidson's schtick. And then he dresses it up in science to make it appear respectable. And boy, people really lap it up.

Of course, most of his adorers have no knowledge of his long intimate relationship with Ned Kalin or the nature of their twenty-five year collaboration into the neurobiology of fearful young monkeys' brains.

It seems to me that if someone peddling a way to be more compassionate is hurting and frightening young monkeys who they have identified as having "excessively fearful dispositions," is publishing reports on the invasive surgeries on the monkeys, is comfortable isolating newborn infant monkeys in order to induce heightened anxiety and depression, that this is proof that their claim of being able to teach someone how to be more compassionate is probably nonsense and at least suspicious.

I've written thousands of words about Davidson already, so I won't go on. If you are interested in learning more here are some resources in (almost) no particular order:

"Compassion." Chapter 11 in "We All Operate in the Same Way."

June 22, 2008 Primate research at the University of Wisconsin. Host Neil Heinen moderates the discussion on this 22, 2008 episode of For the Record, WISC-TV.

June 24, 2008 Looking at Richard Davidson's Assertions

April 13, 2008 Richard Davidson's Mushy-Headedness

Tuesday, March 6, 2007 Could You Recognize Evil if It Stared You in the Face? (Will the anti-Christ come wearing a t-shirt saying I'm the anti-Christ?)

February 3, 2009 Richard Davidson's Choices Are Evidence That Thinking Good Thoughts Won’t Make You a Good Person

November 27, 2007 A minimal amount of suffering

October 24, 2007 Compassion and Kindness Redefined

May 9, 2010 The Dalai Lama is Coming Back to Madison, or "'Callooh! Callay!' He chortled in his joy."

April 25, 2010 Center for Investigating Healthy Minds

March 20, 2009 Richard Davidson

September 3, 2010 Monsters: Lojong

And, if you want to know even more about Davidson's use of monkeys, this is a current bibliography of a his work in this area: A selected Davidson bibliography. Reports on his experimental use of monkeys:

Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Shackman AJ, Fox AS, Oler JA, Shelton SE, Oakes TR, Davidson RJ, Kalin NH. Mol Psychiatry. 2017.

Connectivity between the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the non-human primate: neuronal tract tracing and developmental neuroimaging studies. Oler, Jonathan A., Do PM Tromp, Andrew S. Fox, Rothem Kovner, Richard J. Davidson, Andrew L. Alexander, Daniel R. McFarlin et al. Brain Structure and Function. 2017.

Intergenerational neural mediators of early-life anxious temperament. Fox AS, Oler JA, Shackman AJ, Shelton SE, Raveendran M, McKay DR, Converse AK, Alexander A, Davidson RJ, Blangero J, Rogers J, Kalin NH. Proc Natl Acad Sci U S A. 2015.

Extreme early-life anxiety is associated with an evolutionarily conserved reduction in the strength of intrinsic functional connectivity between the dorsolateral prefrontal cortex and the central nucleus of the amygdala.mBirn RM, Shackman AJ, Oler JA, Williams LE, McFarlin DR, Rogers GM, Shelton SE, Alexander AL, Pine DS, Slattery MJ, Davidson RJ, Fox AS, Kalin NH. Mol Psychiatry. 2014.

Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety. Birn RM, Shackman AJ, Oler JA, Williams LE, McFarlin DR, Rogers GM, Shelton SE, Alexander AL, Pine DS, Slattery MJ, Davidson RJ, Fox AS, Kalin NH. Mol Psychiatry. 2014.

Neuropeptide Y receptor gene expression in the primate amygdala predicts anxious temperament and brain metabolism. Roseboom PH, Nanda SA, Fox AS, Oler JA, Shackman AJ, Shelton SE, Davidson RJ, Kalin NH. Biol Psychiatry. 2014.

Neural mechanisms underlying heterogeneity in the presentation of anxious temperament. Shackman AJ, Fox AS, Oler JA, Shelton SE, Davidson RJ, Kalin NH. Proc Natl Acad Sci U S A. 2013.

CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression. Rogers J, Raveendran M, Fawcett GL, Fox AS, Shelton SE, Oler JA, Cheverud J, Muzny DM, Gibbs RA, Davidson RJ, Kalin NH. Mol Psychiatry. 2013.

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.

Evidence for coordinated functional activity within the extended amygdala of non-human and human primates. Oler JA, Birn RM, Patriat R, Fox AS, Shelton SE, Burghy CA, Stodola DE, Essex MJ, Davidson RJ, Kalin NH. Neuroimage. 2012.

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.

Orbitofrontal cortex lesions alter anxiety-related activity in the primate bed nucleus of stria terminalis. Fox AS, Shelton SE, Oakes TR, Converse AK, Davidson RJ, Kalin NH. J Neurosci. 2010.

Subgenual prefrontal cortex activity predicts individual differences in hypothalamic-pituitary-adrenal activity across different contexts. Jahn AL, Fox AS, Abercrombie HC, Shelton SE, Oakes TR, Davidson RJ, Kalin NH. Biol Psychiatry. 2010.

Serotonin transporter binding and genotype in the nonhuman primate brain using [C-11]DASB PET. Christian BT, Fox AS, Oler JA, Vandehey NT, Murali D, Rogers J, Oakes TR, Shelton SE, Davidson RJ, Kalin NH. Neuroimage. 2009.

Serotonin transporter availability in the amygdala and bed nucleus of the stria terminalis predicts anxious temperament and brain glucose metabolic activity. Oler JA, Fox AS, Shelton SE, Christian BT, Murali D, Oakes TR, Davidson RJ, Kalin NH. J Neurosci. 2009.

The distribution of D2/D3 receptor binding in the adolescent rhesus monkey using small animal PET imaging. Christian BT, Vandehey NT, Fox AS, Murali D, Oakes TR, Converse AK, Nickles RJ, Shelton SE, Davidson RJ, Kalin NH. Neuroimage. 2009.

Trait-like brain activity during adolescence predicts anxious temperament in primates. Fox AS, Shelton SE, Oakes TR, Davidson RJ, Kalin NH. PLoS One. 2008 .

Automatic physiological waveform processing for FMRI noise correction and analysis. Kelley DJ, Oakes TR, Greischar LL, Chung MK, Ollinger JM, Alexander AL, Shelton SE, Kalin NH, Davidson RJ.PLoS ONE. 2008.

The serotonin transporter genotype is associated with intermediate brain phenotypes that depend on the context of eliciting stressor. Kalin NH, Shelton SE, Fox AS, Rogers J, Oakes TR, Davidson RJ. Mol Psychiatry. 2008.

Automatic physiological waveform processing for FMRI noise correction and analysis. Kelley DJ, Oakes TR, Greischar LL, Chung MK, Ollinger JM, Alexander AL, Shelton SE, Kalin NH, Davidson RJ. PLoS One. 2008.

Role of the Primate Orbitofrontal Cortex in Mediating Anxious Temperament. Kalin NH, Shelton SE, Davidson RJ. Biol Psychiatry. 2007.

Brain Regions Associated with the Expression and Contextual Regulation of Anxiety in Primates. Kalin NH, Shelton SE, Fox AS, Oakes TR, Davidson RJ. Biol Psychiatry. 2005.

Calling for help is independently modulated by brain systems underlying goal-directed behavior and threat perception. Fox AS, Oakes TR, Shelton SE, Converse AK, Davidson RJ, Kalin NH. Proc Natl Acad Sci U S A. 2005.

The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. Kalin NH, Shelton SE, Davidson RJ. J Neurosci. 2004.

The primate amygdala mediates acute fear but not the behavioral and physiological components of anxious temperament. Kalin NH, Shelton SE, Davidson RJ, Kelley AE. Related Articles, J Neurosci. 2001.

Cerebrospinal fluid corticotropin-releasing hormone levels are elevated in monkeys with patterns of brain activity associated with fearful temperament. Kalin NH, Shelton SE, Davidson RJ. Biol Psychiatry. 2000

Asymmetric frontal brain activity, cortisol, and behavior associated with fearful temperament in rhesus monkeys. Kalin NH, Larson C, Shelton SE, Davidson RJ. Behav Neurosci. 1998.

Individual differences in freezing and cortisol in infant and mother rhesus monkeys. Kalin NH, Shelton SE, Rickman M, Davidson RJ. Behav Neurosci. 1998.

A new method for aversive Pavlovian conditioning of heart rate in rhesus monkeys. Kalin NH, Shelton SE, Davidson RJ, Lynn DE. Physiol Behav. 1996.

Lateralized response to diazepam predicts temperamental style in rhesus monkeys. Davidson RJ, Kalin NH, Shelton SE. Behav Neurosci. 1993.

Lateralized effects of diazepam on frontal brain electrical asymmetries in rhesus monkeys. Davidson RJ, Kalin NH, Shelton SE. Biol Psychiatry. 1992.

Monday, December 25, 2017

This Little Mutant Pig Might be Seriously Impaired

Wisconsin miniature pigs, an image used in both articles mentioned below.

To help kids battling a rare disease, scientists forge a genetic link between people and pigs []
December 19, 2017 By Kelly April Tyrrell

This is a recent PR piece from UW-Madison. If you don't read it very carefully, you will come away with the belief that creating mutant pigs has in some way helped children suffering from a rare genetic disease. But a careful reader will learn that no children have been helped. The article is the same sort hype that has filled newspapers ever since the mid 1930s as a result of the wildly successful fundraising for polio, the first commercialization of medical research. (See Polio: An American Story. David M. Oshinsky. Oxford University Press. 2005.)

The author, a UW-Madison news writer (aka propagandist) is a past mouse vivisector, so it makes some sense she gets giddy about "advances" in the scientific use of animals. In this article she describes symptoms children with neurofibromatosis type 1, or NF1, can experience; she makes no mention of the symptoms in the pigs.

Oddly, perhaps not, a version of the article was published in The Atlantic a week earlier: "Turning Piglets Into Personalized Avatars for Sick Kids." The author was Ed Yong, he also left out any description of the disease in the pigs.

It may be that neither author plagiarized the other. They are after all telling the same story, but the parallels are suggestive, For instance:

Ed Yong: "... Once Mason’s diagnosis was in, [Charles “Chuck” Konsitzke, Mason's father] started asking around about NF-1 research. In particular, he wanted to know where the bottlenecks are. What was the single thing he could do that would most accelerate research into his son’s condition? And the answer that he kept hearing was: Find better animals to experiment on."

Kelly April Tyrrell: "Upon Mason’s diagnosis [Charles “Chuck” Konsitzke, Mason's father] began to delve into published NF1 research. He wanted to know where it was happening, who was doing it and how he might be able to help. He sought opinions from experts, wondering how the field could be improved. Many identified the same bottleneck: the lack of a good research model."

Ed Yong: "When studying diseases, scientists often turn to laboratory animals like mice and zebrafish. They can use these so-called model organisms to work out how mutations cause diseases, and to find and test possible treatments. But the usual lab animals aren’t a good fit for NF-1. They’re too small, and they don’t react in the same way to the mutations that cause the disease in humans. For example, studies in mice suggested that a drug called lovastatin might help to address the learning and attentional problems that accompany NF-1. But when the drug was tested on actual children, in a large clinical trial, it did nothing.

"To better understand NF-1, Konsitzke learned, you need a species that’s closer in both size and biology to a person, and yet is still relatively easy to raise and study. That is, you need pigs. “Pigs closely represent humans,” says Neha Patel, who directs the UW neurofibromatosis clinic. “People with NF-1 have varied cognitive deficits, from severe learning issues to subtle problems. If you imagine studying those in a rat, you’d only get a crude picture of how that translates to humans. But pigs are intellectual animals."

Kelly April Tyrrell: "In biology, research models are animals, cells, plants, microbes and other living things that allow scientists to study biological processes and recreate diseases in order to better understand them. Good models yield information relevant to humans, but the right model can sometimes be difficult to find.

"NF1 is especially complex, affects many systems of the body and touches many areas of scientific inquiry, from cancer research to neurobiology. Chuck began to search for a better model and in 2013, when Mason was 3, he settled on pigs. Pigs are similar to humans in many ways that other common research animals, such as mice and flies, are not. That includes their size, which means drugs and devices that work on humans can also be tested on pigs. They have a robust immune system, which rodents lack. And they’re intelligent, so scientists can study changes to their cognition."

In any case, there at least seem to be some prepared talking points that both authors heard from some of the people they interviewed.

One thing that caught my eye in both articles was the bit about Charles “Chuck” Konsitzke being told that no one was making progress on treating the disease because their was not a good animal model. Ed Yong describes Konsitzke as an "administrator at the University of Wisconsin’s Biotechnology Center." Kelly April Tyrrell is less vague, she notes that he is the associate director of universit’s Biotechnology Center, "a sort of one-stop shop for scientists in need of DNA sequencing, genome editing and other services."

Konsitzke may have gotten a different answer to his questions if he had spoken with someone outside the animal research bubble. The Biotechnology Center he helps direct is deeply involved in promoting and facilitating animal use. His intimate involvement in this part of the university helps explain the talking points repeated in both articles.

A significant difference between The Atlantic and the UW-Madison articles is that the university article implies that individual children's disease will be modeled by a group of pigs with the gene defect from the child, and that the course of the disease in the pigs will inform doctors about the disease course in the children. The Atlantic article quotes the researchers saying that ethical problems might arise if they do do that, so the researchers might blind themselves to the source of the pigs' mutations, which eliminates one potential benefit claimed in the university article.

Missing from both articles was mention of the need for genetic counseling for couples intending to have children. The prudent course would be to forego breeding in cases with a likelihood of producing children with genetic illnesses. I suspect most readers will come away from the articles thinking that making pigs sick is a good thing.

And who knew that UW-Madison has a 1,500-pig research facility? I learn new things every day.

Monday, December 18, 2017

APHIS-AC, the Vivisectors' New Confessor

Oversight and enforcement of compliance with the Animal Welfare Act (Title 7 – Agriculture. Chapter 54 – Transportation, Sale, and Handling of Certain Animals Sections 2131 - 2159) is largely the responsibility of a unit of the United States Department of Agriculture’s Animal and Plant Health Inspection Service, named Animal Care. The usual abbreviation in the literature is APHIS-AC. AWA is shorthand for the Animal Welfare Act.

APHIS-AC has become a sort of guard dog for those who use animals, an version of what is known as regulatory capture, defined by Wikipedia as a form of corruption:
Specifically, it is a government failure which occurs when a regulatory agency, created to act in the public interest, instead advances the commercial or political concerns of special interest groups that dominate the industry or sector it is charged with regulating.

Over the years, the agency has removed evidence of AWA violations and then grudgingly restored the records only when forced to do so by threats of lawsuits or legal settlements. The records have typically been restored in a significantly degraded form.

Over the years, the agency has occasionally taken steps to impede the public’s access to the records it has been forced to provide. Today, on the agency’s web page, “AWA Inspection and Annual Reports,” one can review a limited set of records. The agency has been captured by those it is supposed to be regulating.

The agency did at one time seem to honor its responsibility to the public. Now, not so much. It hasn’t always been like this. At one time the records were kept for years and easily searched. Why should purportedly public records be password protected and non-searchable? Moreover, available electronic data storage space is now essentially unlimited. And yet, APHIS-AC deletes records after only three years. Some animals in labs are used for decades; repeated violations that cause them harm are expunged. This is not much different than police destroying records of child abuse to protect the abusing parents. Records demonstrating a pattern of federal law violations are routinely destroyed.

Over the years, the USDA’s Office of the Inspector General has evaluated APHIS-AC’s enforcement of the AWA. The OIG has reported that the agency does a very poor job of monitoring and enforcing the AWA. See:

1/1995 - APHIS Animal Care Program Inspection and Enforcement of the Animal Welfare Act.
(Report No. 33600-1-Ch.)

10/20/2005 - APHIS Animal Care Program Inspection and Enforcement Activities.
(Report No: 33002-03-SF.)

05/25/2010 - Animal and Plant Health Inspection Service, Animal Care Program, Inspections of Problematic Dealers.
(Report No: 33002-4-SF.)

12/18/2014 - Animal and Plant Health Inspection Service Oversight of Research Facilities.
(Report No. 33601-0001-41.)

06/02/2017 - APHIS: Animal Welfare Act - Marine Mammals (Cetaceans).
(Report No. 33601-0001-31.)

The NIH Office of Laboratory Welfare (OLAW) is responsible for overseeing and enforcing compliance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals. Enforcement is pro forma. OLAW almost never inspects a lab or verifies claims made by NIH-funded institutions. When the local oversight committee, the Institutional Animal Care and Use Committee (IACUC) discovers a violation of the policy, it is reported in a letter or phone call to OLAW along with a statement briefly explaining what the institution is doing to avoid a repeat violation. OLAW seems to always say, “Sounds good.” And that’s the end of it.

Not too long ago, it was discovered that OLAW was not sharing this information with APHIS-AC. A well-known watchdog organization began using the Freedom of Information Act to obtain copies of OLAW’s correspondence with the labs and then filing complaints about the violations with APHIS-AC which is legally required to investigate allegations of violations of the AWA. And, when they did, they found records of the violations which in turn required them to cite the institutions. This did not sit well with the vivisectors or APHIS-AC. The agency was unhappy at being forced to do its job.

A couple interagency agreements resulted, but still, the labs’ animal welfare violations were at risk of public exposure. Now, APHIS seems to have come up with a plan to better shield the labs; they call it: “Incentives for Identifying, Reporting, Correcting, and Preventing Noncompliance with the Animal Welfare Act.”

Those incentives? Not being cited in writing. It appears that the agency has come up with a plan to collude with the industry to make it even harder for the public to find out what is happening to the animals. A friend likened the new system to the Catholic confessional -- what’s said remains confidential and absolution is all but certain.

It seems to work like this: A lab official learns that a violation has occurred. A call is made to APHIS, just as a call will be made to OLAW. APHIS makes a record of the call without mentioning the name of the facility. The violation will not show up on an inspection report. When an annual inspection occurs, a violation will not be mentioned in the inspection report if there was no mention of a violation in the last inspection report and the lab had previously self-reported it.

Additionally, apparently, unless the inspector witnesses the violation during the actual inspection, the violation will not be recorded in the inspection report.

One thing is clear: the animal welfare records of the labs are going to show improvement, it will be much more difficult to recognize a pattern of violations, and the apparent reduction of recorded violations will make APHIS look like it is doing a better job. Yes sir, its win-win for everyone except the few people who take the time to try and find out what’s really going on in the labs and the animals.