Sunday, August 31, 2014

Dear Dane County Board Supervisors. Re: Resolution 275

August 31, 2014

Dear Dane County Board Supervisors,

I am writing in reply to a letter which was sent to you by the University of Wisconsin-Madison urging you not to support Resolution 275 introduced by Supervisor Matano. I hope you will find the following points helpful in coming to your decision.

The university begins its argument by presenting a false and misleading characterization of the specific research program addressed in Mr. Matano's resolution. They say that the monkeys taken from their mothers will be raised by human "caregivers." But the monkeys will not be held, comforted, or allowed to form normal emotional bonds with these so-called caregivers. They will be provided food and water by them and their isolation units will be cleaned by them, but such limited hands-off care would be judged abuse if human children were being raised in the same way.

The university says that once the infants are able to feed themselves, that they will be in the company of "other young monkeys." But they will simply be placed in a small cage with one other infant of the same age similarly deprived of psychologically important contact comfort from their mother or other nurturing caregiver.

The university falsely claims that this isolation and pair-housing is no different from what happens in zoos when infants are rejected by their mothers or even on a typical Wisconsin dairy. But even zoos try to provide a semblance of contact care and social interaction with caregivers; zoos try to ameliorate the impact of the loss of an infant's mother, the university's plan is to exacerbate that impact.

The university goes so far as to say that even infant humans are similarly separated from their mothers in neonatal intensive care units. If there is much similarity between the care provided to the infant monkeys being taken from their mothers and the level of care provided to human infants at the UW Hospital, then a thorough investigation is needed immediately because such isolation and social neglect would be a clear case of criminal child abuse.

The university isn't being honest with you.

A paper cited by Ned Kalin, the lead scientist in the research that is causing so much concern, explains that increased crying, decreased environmental exploration, and increased huddling, and lying-down are common symptoms of the despair typically seen after maternal separation in infant monkeys.
The impact of early-life stress, frequently induced by maternal separation during infancy has been extensively studied in non-human primates. Thus, rhesus macaques that grew up either alone or with peers only show several signs of behavioral despair, i.e. decreased locomotion, environmental exploration and play, disturbed sleep, decreased, or sometimes increased, food intake. These behavioral changes resemble many of the cardinal symptoms of human depression. (The role of corticotropin-releasing factor in depression and anxiety disorders. J Endocrinol. 1999. See below for one reason behind Ned Kalin's and the university's keen interest in corticotropin-releasing factor.)

The well-documented severe psychological insults of maternal deprivation (the method that the university falsely equates to the way they care for children in neonatal intensive care units) and peer-rearing are exactly why they are being employed in this project.

This is the third time I am aware of that the university has resorted to what seems to be the intentional misleading of local government officials about its actions or intent regarding the use of monkeys in its labs.

The first time was their eight years of repeatedly reporting to zoo officials that the monkeys owned by the university and housed at the zoo were exempt from being used in harmful experiments. Leaked documents revealed that their repeatedly written reaffirmations of the policy were never honored and that while claiming otherwise, the university was selling monkeys from the zoo to labs around the country and killing them in their own labs. The university's maneuvering successfully derailed the County Board's efforts to safeguard the remaining animals.

The second case was the university's response to Supervisor Matano's effort to establish a citizens' advisory committee to examine the question of whether or not the university's use of monkeys is ethical. In what seems to have been given as a promise to County Board Chair Scott McDonald and others on the County Board in exchange for killing the proposal, the university said that it would institute a public discussion about the use of animals in its labs. But that promise was never substantively fulfilled; the university did begin having speakers from around the country come in to talk about animals in society generally, but very little about the university's own use of animals was addressed, and essentially none of the specific details it said would be, were. Nearly everyone involved in or familiar with the so-called forums has admitted they have failed to meet the university's promise.

Now, yet again, the university has chosen to mislead the Board. Its characterization of what will be done to the infant monkeys and the effects those procedures will have on them is far from the truth. The university seems to think that the County Board is made up of enough people who are either good UW soldiers or awed by its authority, that it need not address the factual details of the project under discussion.

The university appeals to the possible results of Ned Kalin's project as a justification for the short abused life these infant monkeys will endure. But Kalin's prior three-and-a-half decades of identifying fearful young monkeys, frightening them, damaging their brains, and then killing them and analyzing the results have led to no discernible benefit for people suffering from depression. There is no reason that the current experiments will fare any better.

One goal of Ned Kalin's work not mentioned by the university is his identification of patentable gene sequences thought by him to be implicated in a greater susceptibility to the development of clinical depression. Kalin is the founder and principal owner of a company, Promoter Neuroscience, which is "focused on developing tools and finding drugs that affect expression of genes in the CRH family." (CHR is shorthand for the brain chemical: corticotropin-releasing factor.) He and WARF hold at least four patents on these gene sequences identified by Kalin in his invasive rat and monkey brain experiments.

It looks as though he and his company are focused on patenting gene sequences that they believe might one day be part of a genetic pathway affected by a drug used for the treatment of depression, and thus could be leveraged into a share of potential profit should someone invent an antidepressant that acted through those promoter gene sequences.

The university continues to mislead the Board with its claim that the study was approved only after rigorous scrutiny. This study was the subject of more scrutiny by university oversight committees that any previous project because it is an affront to any notion of the humane use of animals. But when changes were demanded, the resulting rewrite was approved by only two unnamed people, both of whom are likely to have supported the project earlier or who are also using animals in their own research. That's the opposite of rigor.

The university closes its argument by claiming wildly that if the County Board condemns Kalin's project that it could lead to an end of all basic research and that progress against disease would slow drastically. But a growing body of respected scientific evidence suggests that the opposite may be more likely.

Over the past decade or two, researchers have undertaken a number of very large meta-analyses of the results of animal-based models of human disease and illness, and the results have not been encouraging to the industry. Overwhelmingly, these very large analyses have found that the results from experiments on animals are not translating into treatments for humans. Proffered explanations for this sweeping failure have included the less than rigorous design of the projects and the underlying genetic differences that plague cross-species applications. But no matter the reason, the failure of animal models to productively mimic human biology is the subject of much and increased scientific discussion.

See for instance:

Comparison of treatment effects between animal experiments and clinical trials: systematic review. Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P, Macleod M, Mignini LE, Jayaram P, Khan KS. BMJ. 2007.

Where Are the Cures? Sharon Begley. Newsweek. 2008.

Translation of Research Evidence From Animals to Humans. Daniel G. Hackam, Donald A. Redelmeier, 2006, JAMA.

Why Most Published Research Findings Are False. John P. A. Ioannidis. PLoS Med. 2005.

Where is the evidence that animal research benefits humans? Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I. BMJ. 2004.

Does animal experimentation inform human healthcare? Observations from a systematic review of international animal experiments on fluid resuscitation. Roberts I, Kwan I, Evans P & Haig S. BMJ 2002.

Evolution and translation of research findings: from bench to where? Ioannidis JP. PLoS Clin Trials. 2006.

Survey of the quality of experimental design, statistical analysis and reporting of research using animals. Kilkenny C, Parsons N, Kadyszewski E, Festing MF, Cuthill IC, Fry D, Hutton J, Altman DG. PLoS One. 2009.

The university has shown itself unwilling to engage is substantive dialog regarding its use of animals. It has misled the Dane Count Board in the past. It has destroyed public records concerning its use of monkeys to keep them out of the public eye. It builds barriers to public scrutiny of its operations. It worries now that if the Dane County Board condemns Ned Kalin's use of maternal deprivation, that it may lead to more questioning from the public.

Undoubtedly, County Board Supervisors are being lobbied by people on one or the other side of this issue. I imagine that they generally fall into one of two camps: people who are concerned for the monkeys and are outraged at having to pay for these cruel dead-end experiments, and people who have a professional or financial interest in basic research using animals. I do think it is that simple.

I hope you will not let yourself and the County Board be again convinced to shelter the university and to hold them harmless for their past lies, manipulations, and cover-ups. Taken as a single instance of the research underway at the university, Kalin's maternal deprivation project warrants great condemnation.

Sincerely,

Rick Bogle
5133 Maher Ave.
Madison, WI 53716
Dane County, District 24

Sunday, August 17, 2014

University experts stumble over facts

Cue the spin doctors.

True to form, UW-Madison's experts responded with a cacophony of either ignorant or calculated false claims in response to the recent article in Madison's somewhat progressive weekly, the Isthmus.

Where to start? Well, let's see...

First, there was yet another paroxysm of confusion from Dr. Robert N. Golden. I replied earlier to his first error-laden letter to the editor defending the torture of young monkeys by his his colleague Dr. Ned Kalin after Dr. Murry Cohen criticized Dr. Kalin's methods(all three of the doctors are psychiatrists)in a letter to the editor in the Capital Times (Monkey studies vital...), another of Madison's progressive weeklies, The Capital Times. [Wisconsin is the birthplace of the Progressive Party, in case you didn't know.]

In his newest attempt to defend the indefensible, he criticizes the Isthmus for "promulgating the animal activists' claims" that the university is "reviving" Harry Harlow's work. He put quotation marks around the word for some odd reason. He must not have reviewed the minutes of the committee meetings when the project was discussed. Some decidedly not-animal-rights-activists university staff also see it that way.

He must not have reviewed the information at uwnotinourname.org.

No one has claimed that Kalin is isolating monkeys for as long as Harlow and his students did, or that they are being placed in the vertical chamber, but Golden is uninformed apparently about Harlow's work. The reason Kalin is isolating infant monkeys at birth, isolating them for month or so, pairing them with a similarly traumatized infant, and frightening them with novel experiences is that doing so was shown by Harlow to cause behavioral changes that he and visitors to his lab thought to be evidence of severe depression. Golden apparently hasn't spend much time reviewing Harlow's many publications.

Golden says that Kalin is "following the current state-of-the-art guidelines for the ethical use of of nonhuman primates in research." He's right. Sort of. In a misleading way. First, there aren't any enforceable ethical guidelines, if you use the term to mean what most people commonly believe the word to mean. There are some enforceable rules that regulate to some degree the care and use of primates and other animals, but only one of the rules really matters and can get you into trouble if you break it, that's the one that says researchers have to have permission from their institutional animal care and use committee before proceeding. As long as they have permission, they can do anything to an animal. There is no regulatory limit on what can be done to an animal with permission. That's the state of the art. Moreover, the researcher needs only to get the permission of those who like themselves are using animals and who know that their colleagues may be on the committee when their own project comes up for re-approval. That's the state-of-the-art ethics governing the oversight of experiments on primates today at the university and almost everywhere else in the U.S.

Golden says that Kalin is focusing "on key clinical issues in the treatment of children who have been exposed to early life stresses, including neglect."

This is additionally misleading. Kalin's project design does a poor job at emulating early life stresses of human children. Essentially no children are raised alone and then put in a box with another infant, kept there for a year (actually, because of the differences in maturity rates, you'd have to keep the humans in the box for about three years to approximate the same degree of normal development), and occasionally frightened.

Abuse and neglect are frequently mentioned in tandem. The Federal Child Abuse Prevention and Treatment Act (CAPTA), (42 U.S.C.A. §5106g), as amended and reauthorized by the CAPTA Reauthorization Act of 2010 spells out legal definitions of these terms. A helpful fact sheet on this law is available on line from the Department of Health and Human Services.

Almost nothing about Kalin's project is at all similar to the real life experiences of an abused and/or neglected child. Claims to the contrary must be based on a blunted notion of the complexities of genetics, neurobiology, and chemistry.

Golden repeats the craziest whackiest claim in Kalin's project, that the goal is to: "identify new molecular targets for preventing the emergence of psychiatric illness in children who are exposed to early life trauma."

Think about this. Six year-old Johnny is removed from his home after authorities discover that he wasn't being adequately fed, was sometimes locked in his room for days at a time, and was shaken and slapped frequently. A pediatric psychiatrist examines him and notes that he is underweight, very withdrawn, bites his nails, bites his arms, and still sucks his thumb. No problem. Johnny can simply get an injection of some magic serum or maybe take a couple of pills every day for a few years, and there won't be any serious lasting psychological consequence of his early adversity. Heck, maybe criminals can take it and not have to feel any guilt after their misdeeds. Maybe the military will want to vaccinate soldiers so they won't be bothered by the memories of killing people. Goofy indeed.

Golden says the project was approved only after it was approved by two committees, but again he's either confused or being intentionally misleading. The article reported that most of the members of the College of Letters and Sciences Animal Care and Use Committee were excluded from participating in the final decision. Two people were given the task of making the final approval. I'll wager that both of them experiment on animals themselves.

Eric Sandgren, the university's head vivisector also had a letter printed and tries to change what he told the reporter, but since he pretty much always says whatever seems to sound good at the time, who cares?

There was a sad little letter from from a student named Parker David Tenpas who works at the primate center. Sad and little in the sense that he imagines he has a clue. Maybe his embarrassment at trying to sound informed, heck, maybe he thinks he is, is what led to him blocking public access to his web site? It's no wonder. He writes, "My lab is focused on primate well-being, and we study how these animals interact with toys, television, music, each other and their environment. We care about these animals." Right. I'm sure he tells himself that he cares. In his CV, a once-public document on his now hidden website (see above), he says that his academic(?) mentor is the creepy Peter J. Pierre who has nothing in his CV that suggests he ought to be the Behavioral Management Unit Head. (His CV.) Parker also has the fringe extremist vivisection group Speaking of Research on his short list of important links which makes sense because of Pierre's close connection to the group's not-so-interested-in-speaking darling, Allyson Bennett. The saddest part of his letter was his blind and obedient Sieg heil: "Many perspectives are needed to get the full picture, but as long as irrelevant ones are perpetuated, scientific progress and solutions will be stalled." Apparently, he feels that concerns about suffering and cruelty are irrelevant. He's definitely primate center material. His decision to hide from public view fits the vivisector profile.

Last but certainly not least in its errors was the letter from rat and mouse vivisector Craig Berridge. Berridge is clearly confused. He writes, "... reference is made to earlier work of Dr. Kalin's in which monkeys' amygdalae were 'damaged with acid.' instead, the amygdalae were 'lesioned'/damaged using microinfusions of a specific amino acid to overstimulate glutamate receptors using modern neurosurgical techniques." He sounds so scientific and knowledgeable doesn't he? How could the average reader know that he is full of crap?

In fact, in past experiments, Kalin's methods are crude at best. In one study he sent images of monkeys' acid-damaged brains to a researcher at UC-Davis and had him circle the area that he imagined was the amygdala. That's not very high tech. Moreover, Berridge is wrong about Kalin's use of acid to damage the monkeys' brains. He cites his use of the neurotoxin ibotenic acid in his publications. I don't know whether Berridge is just ignorant and opining about things he doesn't know about or rather is just following in Eric Sandgren's footsteps and making shit up as he goes. Either way, he isn't a reliable source of information about the university's use of animals.

Saturday, August 2, 2014

A New UW-Madison Vivisection Spokesperson

You may have read this by now: Motherless monkeys: UW-Madison to revive controversial primate experiments
Researchers will deprive infants of maternal contact to study anxiety and depression
Noah Phillips. Isthmus 07/31/2014.

I've debunked Kalin's claims here: A Response to Ned Kalin.

This is a response to the sidebar that accompanied the main article: UW-Madison animal research oversight committees strive for consensus.

The title belies the twin facts that there wasn't a consensus among the members of the oversight committee on Kalin's maternal deprivation project, and that the decision to let him proceed was made by only two unnamed people, who I will wager were both vivisectors, demolishing the worn and repeated contention that members of the public are involved in the decision-making. What a joke.

Mostly though, I am writing because a new University voice in support of hurting and killing animals for hire has emerged from within the cloistered animal labs: Craig Berridge. The sidebar's author paraphrases Berridge and says that he "is comfortable with the scrutiny given animal research on campus."

Berridge is quoted saying that: "Animal research is a heavily regulated and overseen process... I think everyone who does animal research feels they're balancing the need for and desire to alleviate human suffering and to minimize animal suffering."

Animal research isn't heavily regulated. See my essay The Ethics Underpinning Oversight. I suspect that at least some of the members of his lab believe that the things they are doing to rats might in someway alleviate human suffering, but in any other setting with similarly remote odds of success, they would probably say that the odds are so slight that the costs could not be justified. And the odds of alleviating human suffering as a result of what they are doing to the rats are vanishingly small. For one of the many examples of the failure of using other animals to model human biology see: "Mice Fall Short as Test Subjects for Humans’ Deadly Ills." Gina Kolata. New York Times. February 11, 2013.

Anyway, it isn't any surprise that someone riding the public funding gravy train to wealth thinks that oversight of what they are doing is adequate. Here's a passage for one of Berrige's papers that gives some idea of just what it is that we are paying him to do:
When exposed to an inescapable stressor, animals may engage in a limited set of “coping” behaviors, often involving oral behavior such as chewing, which act to attenuate certain components of the stress response (Berridge et al., 2002). For example, mice and rats exposed to an inescapable, novel, and brightly lit environment (novelty-stress) chew inedible material (wood, foil, etc) preferentially over highly palatable food (Berridge et al., 1999; Hennessy and Foy, 1987). Under these conditions, chewing suppresses the glucocorticoid stress response (Hennessy and Foy, 1987). Moreover, chewing also attenuates stress-related DA utilization preferentially within the mPFC, having no noticeable effect on stressor-induced increases in DA utilization outside this region (Berridge et al., 1999). Interestingly, chewing-induced suppression of [medial prefrontal cortex dopamine] utilization is largely confined to the right hemisphere (Berridge et al., 1999).

It probably cost us millions in tax dollars to find that out. That's why I go to work. You too?

But, that passage doesn't give a us much insight into the suffering he and his staff cause the rats they consume. Before reading any further, just in case you have a false impression of who rats are, you ought to check out these links. Here, here, and here.

This is from Stress-induced impairment of a working memory task: role of spiking rate and spiking history predicted discharge. Devilbiss DM, Jenison RL, Berridge CW. PLoS Comput Biol. 2012:
Materials and Methods
Animals
Five male Sprague-Dawley rats (300–400 g; Charles River, Wilmington MA) were individually housed in an enriched environment (Nylabone® chews) on a 13/11-hour light-dark cycle (light 0600-2000). Animals were maintained on a restricted feeding schedule (15–20 g of standard chow available immediately after training/testing). All procedures were in accordance with NIH guidelines and were approved by the University of Wisconsin Institutional Animal Care and Use Committee.

If you watched the videos linked to above, you ought to have noticed that Berridge and people who care about the rats have a much different idea of what "enrichment" means. A Nylabone is sparse enrichment. Devilbiss, Jenison, and Berridge continue:
Animals were trained in a T-maze delayed-non-match to position task as described previously .... Initial training was complete when animals entered the T-maze arm opposite from the last one visited for food rewards (chocolate chips 1.6 gm) delivered by the experimenter's hand with 90% accuracy on 10 trials (0 seconds delay, 1 session/day). Animals were then surgically implanted with recording electrodes and returned to ad lib feeding for the duration of recovery (7–10 days). Following recovery, training continued until animals performed two sessions of 41 trials at criterion of 90–100% correct for 2 consecutive days.... During training sessions, animals were tethered to a dummy wire harness of identical weight and flexibly as the harness used for electrophysiological recording on testing days. After acclimation to the tether, animals showed no differences in maze performance or overt behaviors from prior reports....

On the morning of testing, an animal was placed in his home cage, on top of the T-maze, 2 hours before the first session began to allow the animal to habituate to the tether and the recording arena and allowed the experimenter to discriminate neural activity. Although animals had access to water and were able to freely move about their cage, during this period animals predominantly slept.... During the second testing session of the day, presentation of the white noise (93 db) stressor was begun immediately prior to testing and presented continuously throughout the duration of the 41 trials. White noise as stressor has been shown previously to impair PFC-dependent functions in rats, monkeys, and humans and activate the stress-related circuits within the brain as well as the hypothalamic-pituitary axis of rats. Testing with noise stress was permitted at most 1/week.

93 db is like the sound of a jackhammer 50 feet away, or the sound of a lawnmower when you are standing next to it.

This is their description of the surgery (Can you imagine a psychologist being permitted to perform brain surgery on a human?):
Under halothane anesthesia (Halocarbon Laboratories, River Edge, New Jersey; 1%–4% in air), animals were implanted bilaterally with linear electrode arrays (n = 8 electrodes/array; 250 µm separation; SB103, NB Labs, Dennison, TX) targeting layer V of the prelimbic region of the PFC (plPFC) as previously described. Electrode arrays contained 50 µm stainless-steel electrodes orientated in a rostral-caudal direction. Electrodes were attached to skull screws (MX-0080-16B-C, Small Parts, Inc.) with dental acrylic (Plastics One, Roanoke, Virginia), the wound was closed with wound clips (9 mm Autoclip; BD Diagnostic Systems, Sparks, Maryland), and animals were allowed to recover for 7–10 days.

There is no mention of post-surgical analgesia. Humans describe pain after a craniotomy -- the surgical removal of part of the skull to expose the brain -- as being moderate to severe. Research has found that many patients do not receive adequate treatment for their pain. [Perioperative pain management in the neurosurgical patient. Ortiz-Cardona J1, Bendo AA. Anesthesiol Clin. 2007.] But hey, I'm sure an psychologist doing brain surgery on rats does a better job treating his rats' pain than do trained brain surgeons caring for their human patients.
On testing days, animals were brought into the T-maze testing room and tethered to the Multichannel electrophysiology Acquisition Processor. During the 2 hour habituation period, ... animals remained tethered to recording hardware and the quality of the discrimination was monitored throughout the remainder of the day.

[You can watch a video here.]

And then they were killed and their brains analyzed.

I though too that it was interesting that Berridge defended the oversight system that sanctioned Kalin's experiments on the effects of stress -- in many ways not too different from Berridge's, and yet Kalin says that he simply must use monkeys because rats' brains are so different from humans'. Inconsistency is probably common in situations where people are indirectly paid to ignore it.

I can't conclude this short missive without at least mentioning the deep thinking exhibited in the article by the University's head vivisector, Eric Sandgren who says all is well with the oversight system in place; after all, 9 of the 12,000 animal research protocols submitted since 2004, have been denied outright. And who but an extremist like me would see anything but success in the fact that the University has approved all but .075% of its vivisectors' proposed experiments?